2023 TDDW摘要手冊

Theme: Future Perspectives in Digestive Disease Post Covid-19 Era

Date: September 23rd (Sat) ~ 24th (Sun), 2023

Venue: National Sun Yat-sen University 國立中山大學

2023 Taiwan Digestive Disease Week, TDDW

Chairman’s Lecture

Toward HCV Elimination: Does Domestic Epidemiology Matter?

Sheng-Nan Lu

Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

WHO proposes to elimination viral hepatitis by 2030. And our health administer tends to complete hepatitis C virus (HCV) elimination by 2025. Can Taiwan meet the WHO criteria of elimination on time? There are general principals or structured guidelines for the control of viral hepatitis by international organizations. Can Taiwan well control hepatitis C according to these general guidelines?

Epidemiology is always in the beginning in chapter of each disease. Dose domestic epidemiology matter for HCV control in Taiwan? Since first 3 HCV-endemic area, i.e. Paisha in Penghu, Tzukuang in Kaohsiung and Mashago in Taiwan, were noted in 1990s, we began to explore epidemiology of HCV-endemic areas. Series studies clarified, the characteristics of HCV-endemic areas, such high incidence of HCC, high incidence of female HCC, high proportion of HCVrelated HCC, high rate of ALT elevation and high rate of thrombocytopenia. Incorporation of large data from a None Government Organization, the Bood Donor Center and the National Health Insurance, the National Hepatitis C Program Office published the risk map of HCV infection. It is the useful guide in the beginning of HCV control in HCV endemic. The national hepatitis B and C screening confirmed geographic aggregation and provide new information.

Besides of HCV-endemic areas, HCV-endemic birth cohort is also noted in the series. Communitybased survey in Tainan and in whole Taiwan reveals the endemic birth cohort. Iatrogenic transmission should be the major transmission routes. Other blood borne diseases also endemic in these areas. Following improvement of public health, the prevalence decreased overtimes, people born after 1960 have relative low prevalence. The national hepatitis B and C screening also confirmed birth cohort aggregation. Hepatitis C for people born before 1960 is an emic disease with geographic aggregation but for younger population it is sporadic diseases. According to

genotype study, patient number and age decrease from genotypes1b & 2, followed genotypes 1a & 6 to genotype 3. Newly introduced high risk populations infected majorly by young genotypes.

Natural history of chronic hepatitis C showed some subjects will clear virus spontaneously. while some other subjects progresses to end stage liver diseases. According to FIB-4 of anti-HCV-positive adults in a large-scale community-based survey, the proportion of F0: F1: F2 and above F3 were 3: 3: 3: 2. Roughly, about half of them were with clinical significance. Some community-based study mentioned prevalence of viremia, it was 80% in the earlier study, and decreased in the latest studies. The current HCV RNA positive rates should be 50% or less. HCV endemic area have high HCC incidence and mortality. In HCV-positive subjects have high chance to die of HCC. During 1990 to 2010 proportion of HBV-related HCC decreased due to HCVrelated HCC increased. However, the proportion of HCV-related HCC decreased after 2011.

Since majority of patients were from elder people in endemic community, it is the priority of HCV controlled. Post-screening questionnaire interview reported that low awareness of diseases and poor accessibility of medical resources resulted in low treatment rate. Outreach or accessible post-screening medical care were provided. For counties lacking of local endemicity information, village-specific endemic maps established by pooling both hospital and community data together. Using anti-HCV reflex HCV Ag test as screening tools to decrease unnecessary referral. Cooperation with local governments and local hospitals, these endemic areas are becoming models of HCV controls. These unique strategies make HCV elimination possible even in remote or indigenous endemic areas. This models also as a national reference.

Domestic epidemiology dose matter in HCV control. It is the reference to design control program for different areas.

Special Lecture (I)

Probiotics in the Prevention and Treatment of Cancer

Jun Yu

Institute

of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong

Colorectal cancer (CRC) is the third most common cancer in the world. To reduce CRC burden, it is important to identify agents to prevent progression at early cancer stage or reduce recurrence following disease remission. Moreover, development of agents that can enhance efficacies of therapy which are currently used for treating patients with CRC is also highly warranted. Gut microbiota plays key roles in many aspects of tumorigenesis and holds great potential for clinical application (Nat Reviews Gastroentero Hepatol 2019). We discovered CRC-depleted bacteria (i.e. Streptococcus thermophilus, Lactobacillus gallinarum) that are capable of producing anti-CRC enzymes (e.g. β-galactosidase) or metabolites (e.g. indole-3lactic acid, 7-dehydrocholesterol) (Gastro 2021b, Gut 2022b) to inhibit CRC and some bacteria/metabolites modulate cancer immune therapy. We have recently

demonstrated that Carnobacterium maltaromaticum colonizes the gut in an estrogen-dependent manner and acts along with other microbes to augment the intestinal vitamin D production to activate the host VDR for suppressing CRC (Cancer Cell 2023). In cancer therapy, Roseburia intestinalis generated butyrate boosts anti-PD-1 efficacy in CRC by activating cytotoxic CD8+ T cells (Gut 2023). Lactobacillus gallinarum derived metabolites boost anti-PD1 efficacy in colorectal cancer by inhibiting regulatory T cells through modulating IDO1/Kyn/AHR axis (Gut in press). Thus R. intestinalis and L. gallinarum are potential adjuvants to augment anti-PD-1 efficacy against CRC. These findings have highlighted the potential of leveraging probiotics or bacteria-based therapeutics as an adjuvant to prevent CRC formation and to improve cancer immunotherapy.

Special Lecture (II)

How Can We Improve the Prognosis of Pancreatic Cancer?

Masayuki Sho

Department of Surgery, Nara Medical University, Nara, Japan

Much progress have been made in the treatment of pancreatic cancer. However, the overall prognosis remains unsatisfactory. It is now widely recognized that multidisciplinary treatment is required to improve prognosis and to further achieve a complete cure for resectable pancreatic cancer. To this end, there are some possible therapeutic strategies. Among them, adjuvant and neoadjuvant therapies play critical roles. Indeed, a number of clinical trials have been attempted, and some of which have shown a significant impact on patient survival. Furthermore, some other trials especially in neoadjuvant settings are underway. Previous studies have also demonstrated

that completion of adjuvant therapy, which is often difficult to achieve after pancreatectomy, is a significant prognostic factor. Therefore, perioperative nutritional support and physical rehabilitation may be suggested.

We have also been trying to improve the patient prognosis for the last two decades. During this time, we have constantly reviewed our own data and changed our strategies. In this lecture, we would like to discuss the current status and future perspective for the optimal treatment of resectable pancreatic cancer.

Special Lecture (III)

Non-invasive Test for Metabolic Dysfunction Associated Fatty Liver Disease: An Important Piece of the Puzzle

Wah Kheong Chan

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common cause of chronic liver disease, contributing substantially to the burden of liver-related complications, including hepatocellular carcinoma. The presence of steatohepatitis indicates more severe liver disease that is associated with a higher risk of progression to fibrosis and cirrhosis, while fibrosis stage is the most important predictor of adverse clinical outcomes. Liver biopsy is the reference standard for the diagnosis of steatohepatitis and fibrosis, but it is invasive, associated with a small risk of serious complications, limited by sampling and observer variability, and not feasible for routine clinical use for diagnosis, guiding treatment decision and monitoring of response. Various non-invasive tests have been developed, from simple and freely available fibrosis scores that use readily available parameters, to proprietary ones that may use non-routine blood biomarkers, and from clinic-based vibration-controlled transient elastography (VCTE), to magnetic resonance imaging-

based techniques and scores. Current guidelines recommend the use of a two-step approach for risk stratification i.e., simple fibrosis score (e.g., fibrosis-4 index) followed by a second test (e.g., liver stiffness measurement) for selected patients. Furthermore, the use of VCTE to stratify patients according to the risk of compensated advanced chronic liver disease and clinically significant portal hypertension for initiation of downstream management is practical and appealing. On the other hand, there is currently no FDA approved treatment for steatohepatitis. Ongoing clinical trials are facing various challenges in enrolment, including the requirement for liver biopsy and the high screen failure rate due to unmet histological criteria. However, evidence is emerging on the potential use of non-invasive tests for risk stratification (therefore guiding treatment decision) and for monitoring of response. The use of non-invasive tests will continue to evolve and they represent an important piece of the puzzle in the management of patients with MAFLD.

Special Lecture (IV)

Update

on Pathophysiology of Functional Dyspepsia

Hiroto Miwa

President, Kawanishi City Medical Hospital, Hyogo, Japan

Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

Functional dyspepsia (FD) is an extremely common disorder in which upper abdominal symptoms such as stomachache and heavy feeling in the stomach occur despite the absence of organic disease. FD decreases the quality of life of patients suffering from it and the productivity of society. The pathophysiology of functional dyspepsia has been investigated over these 30 years, and it is already known that the pathophysiology is a multifactorial and complicated. The factors contributing to symptom manifestation in FD probably should be divided into 3 categories:

1) physiological abnormalities that directly induce symptoms, 2) factors that modify those physiological abnormalities, and 3) factors that govern abnormal responses to stress. The FD symptoms are directly caused by two major physiological abnormalities—abnormal gastric motility and visceral hypersensitivity—occurring in patients who have acquired excessive responsiveness

to stress. Namely, gastric motility abnormalities and gastric hypersensitivity are main factors in inducing the symptoms. The involvement of other causative factors including acid, Helicobacter pylori, psychological factors, and diet has been debated, but how they are involved in the manifestation of dyspeptic symptoms remains unclear. We believe that most of those factors cause FD symptoms by inducing gastric motility abnormalities and gastric hypersensitivity via the duodenum. In this paper, I will present the role of duodenum as the pathogenic center of FD, where the following points were mainly discussed, which are 1) how the duodenum of patients with FD differ from those of healthy persons, 2) why such difference cause the symptoms in patients with FD, and 3) why such difference is brought to the FD patients. Hope my talk would inspire the research interests of the participants of Taiwan Digestive Disease Week.

Special Lecture (V)

Novel Biomarkers in Natural Course of HBV Infection

Yasuhito Tanaka

Department of Gastroenterology and Hepatology, Kumamoto University, Kumamoto, Japan

Liver Disease Center, Kumamoto University Hospital, Kumamoto, Japan

The hepatitis B core-related antigen (HBcrAg) is a novel HBV serum biomarker that plays an essential role in reflecting intrahepatic covalently closed circular DNA (cccDNA) in chronic hepatitis B (CHB). (1) HBcrAg can be detected in clinical cases where serum HBV DNA is undetectable during anti-HBV therapy such as nucleos(t)ide analogues (NAs). (2) Low levels of HBcrAg and HBsAg were correlated with favorable outcomes, including sustained virological responses after NA treatment cessation. (3) Decreased HBcrAg levels have been significantly associated with promising outcomes in CHB patients, reducing the risk of progression or recurrence of hepatocellular carcinoma. (4) Recently, a fully automated, novel high-sensitivity hepatitis B core-related antigen assay (iTACT-HBcrAg) has been developed (J Hepatol 2021). The sensitivity of iTACT-HBcrAg (2.1 Log U/mL) was approximately 10-fold greater than that of the conventional G-HBcrAg. The iTACT-HBcrAg should be of increased benefit for monitoring anti-HBV treatments for HBeAg-negative patients and early detection of HBV reactivation, as an alternative to HBV DNA. Additionally, monitoring HBcrAg may be useful for determining the therapeutic efficacies of novel anti-HBV drugs targeting HBV-RNA and its related-

proteins. We also introduce our novel compound destabilizing HBV-RNA.

(5) Finally, international guidelines showed that anti-HBV prophylaxis is recommended for pregnant women with high viral loads to prevent mother-tochild transmission of HBV. However, >95% of HBVinfected individuals live in countries where HBV DNA quantification is not available. Based on this situation, we show the clinical application of a rapid and easy HBcrAg assay as a POCT.

References:

1. Inoue T, Kusumoto S, Tanaka Y (Corresponding), et al. J Hepatol. 2021,75(2):302-310.

2. Kusumoto S, Tanaka Y (equal contribution), et al. J Hepatol. 2020;73:285-293.

3. Hayashi S., McMahon BJ, Tanaka Y(Corresponding), et al. Hepatology. 2019;69:19-33.

4. Matsuura K, Tanaka Y (Corresponding), et al. Gastroenterology. 2017;152(6):1383-1394.

5. Takamatsu Y, Tanaka Y (equal contribution), et al. Hepatology. 2015;62:1024-1036.

6. Tanaka Y, Nishida N, Sugiyama M, et al. Nature Genetics. 2009;41(10):1105-1109.

Special Lecture (VI)

Optimizing Conventional Treatment and Biologic Therapies in IBD

John Y Kao

Division of Gastroenterology & Hepatology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA

The incidence of IBD is rapidly rising in Asia Pacific and the treatment options are also rapidly evolving but the goals of IBD management remain largely the same with the initial goal to induce disease remission followed by maintenance of remission. The art of IBD

care rests on balancing the aggressiveness of the therapy with the severity of the disease but also on knowing how to optimize conventional therapies and choosing the appropriate biologic therapies.

Special Lecture (VII)

Development of GI Disease Treatment Due to Advances in Science and Technology

Masaki Mori

Tokai University School of Medicine, Kanagawa, Japan

Recent advances in science and technology are astounding. In the life sciences, the speed of analyzing samples has become extremely fast, and as a result, the amount of accumulated knowledge and data has become enormous. In addition, progress in communication tools such as video distribution is remarkable, and online medical care is expected to spread. In this talk, I will present two themes brought about by these advances.

One is the application of liquid biopsy using the whole genome sequence. Early diagnosis of cancer is an important theme, and attempts are being made to achieve it by detecting cancer cell derived DNA, RNA, or exosomes flowing in the blood. We performed whole genome sequencing of cancer cells and normal cells from individual patients and extracted 16 genes with significant differences. PCR of blood samples was performed on these 16. The 16 genes are patient specific. Preoperative and postoperative analyzes were performed on more than 1,000 colorectal cancer patients, and it was found to be extremely useful in predicting cancer recurrence and determining postoperative anticancer drug administration. We expect it to become a model for precision medicine

in the future.

The second is about tele-surgery. Telemedicine is used for medical diseases, skin diseases, pathological diagnosis, image diagnosis, etc., but telesurgery has lagged behind. With the Japan Surgical Society playing a central role, robot companies, telecommunications companies, academia, government agencies such as the Ministry of Internal Affairs and Communications and the Ministry of Health, Labor and Welfare formed a community and started a project to realize remote surgery. More than 10 experiments have been conducted, from demonstration experiments between hospitals 100 km apart to demonstration experiments between hospitals 2000 km apart. As a result, it was shown that there were no problems with time lag or video distribution. Although there are problems to be cleared, such as dealing with troubles and ethical issues, it was shown that the practical application of remote surgery is possible.

I would appreciate it if you could deepen your understanding of the reforms in the medical field that are being brought about by recent advances in science and technology.

Special Lecture (VIII)

Application of Gastric 3D in Vitro Models in Regenerative Medicine

Kazushige K. Yokoyama

Cell Therapy and Research Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Three dimensional (3D) in vitro model systems are the newly developed techniques that can simulate the 3D structure of tissues in vivo, thus reproducing the physio pathological characteristics of the original tissues.These models can restore the complex structure of the tumor, preserve tumor heterogeneity as well as epi-genotypic and phenotypic characteristics. This technology is represented by organoids and spheroid model, but also includes air-liquid interface culture model, microfluidic culture model, tissue engineering based 3D-bioprinting model. Recently, FDA can agree the proposal of such biosystem and enforce these 3D more. In this presentation, we present on the gastric cancer (GC) organoids generated by Helicobacter pylori and studied the role of growth factors for progression of GC, and the role of antioxidative drugs for inhibiting the GC development.

We found that the independent signaling of HDGF and TNFalpha, which were previously identified

as the cancer progression. In addition, we also found that the heterogeneity of antioxidant functions in proliferation of GC and reactive oxygen species generation through p53-Nrf2 axis. The different outputs are sometimes detected between 3D and 2D in vitro models and thus, we have to reinvestigate and identify the interaction between cancer stem cells and stem cells niches in response to the therapeutic agents to avoid the confusions of the xenotransplantation animal models and 2D systems.

References:

1. K Wuputra et al., Stem Cell Res Ther 12, 492, 2021.

2. J Pers Med, 12, 929, 2022.

3. CC Ku et al., Cells 11, 184, 2022.

4. Saito et al., Advances in stem cell biology, Vol 5, chapter 4, pp87-105, Springer Nature, 2021.

5. K Wuputra et al., Int J Mol Sci 24, 6567, 2023.

Special Lecture (IX)

Roadmap of Biomarkers for Hepatitis B Virus

Man-Fung Yuen

Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong

In the life cycle of hepatitis B virus (HBV), there are production of viral nucleic acids including HBV DNA and intermediate HBV RNA. Translation of different genomic regions of HBV also generate different mRNAs which would be transcribed into different viral antigens including HBsAg, HBcAg and HBeAg. Conventional measurements of viral biomarkers in the blood of patients with chronic hepatitis B (CHB) include HBsAg, HBeAg and HBV DNA. Although HBsAg can also be produced by integrated HBV DNA, measuring serum HBsAg has predictive value for spontaneous HBsAg seroclearance. Existing nucleos(t)ide analog (NA) treatment has minimal effect on HBsAg level. Whereas baseline HBsAg levels before initiation of novel treatment predicts antiviral response including HBsAg seroclearance. Recently, a new entity of measuring several viral antigens, collectively named as hepatitis B core-related antigen (HBcrAg) which

include HBcAg, HBeAg and p22cr becomes more readily available. It was found that HBcrAg correlated well with covalently closed circular (ccc) DNA. HBcrAg profile also relates to the development of CHB complications including hepatocellular carcinoma and cirrhosis, treatment outcome, and chance of HBV reactivation in occult HBV patients receiving immunosuppressive therapy and CHB patients who stopped NA treatment. In addition, a certain proportion of occult HBV patients could be identified by the detectable HBcrAg levels in the blood where both HBsAg and HBV DNA were undetectable. HBV RNA is another novel HBV biomarkers, its roles were very similar to HBcrAg. HBV RNA measurement also correlates with disease outcome, treatment response and HBV reactivation. In conclusions, HBV biomarkers could provide essential information in different aspects for CHB management.

Prof. Teh-Hong Wang Memorial Lecture

ChatGPT in Healthcare and Research: Fact or Fiction?

Jaw-Town Lin

Vice Superintendent, E-Da Hospital, Kaohsiung, Taiwan

Professor Emeritus, National Taiwan University, Taipei, Taiwan

Honorary President, The Digestive Endoscopy Society of Taiwan (DEST)

Honorary President, The Gastroenterological Society of Taiwan (GEST)

ChatGPT is an artificial intelligence (AI) chatbot program developed by OpenAI in November 2022. It is a large-scale language model designed to achieve natural conversations with humans. The full name of ChatGPT is “Chat Generative Pre-trained Transformer”. When ChatGPT talks to humans, it can understand the human context and answer naturally and fluently according to the context. ChatGPT can be applied in many different scenarios, such as customer service, question answering system, chat room, etc., which can effectively improve efficiency and satisfaction. Conversational artificial intelligence service similar to ChatGPT

ChatGPT is a set of tools developed by Open AI in San Francisco, USA, among which Musk, the founder of Tesla, is also one of the founders. On February 7, 2023, Microsoft used its partnership with OpenAI to launch a preview version of “Bing AI”. In February 2023, Google launched a conversational artificial intelligence service “Bard” similar to ChatGPT. Baidu also launched it in February 2023. Monthly

confirmation ChatGPT chat robot, project name “Wen Xin Yi Yan”. On April 7, 2023, Alibaba Cloud developed the language model “Tongyi Qianwen”

ChatGPT can be used in the fields of healthcare: virtual medical assistant, analyzing medical data, creating medical documents, recruiting clinical trial subjects, medical education, and medical translation. Chatbot ChatGPT helps you diagnose and treat patients. Chatbot ChatGPT helps you with medical research.

What the chatbot ChatGPT cannot do: ChatGPT has no right to decide the fate of the paper. ChatGPT does not meet the status of “author”. ChatGPT will not conduct experiments, so there will be no data and results after the experiments. ChatGPT only has medical literature before September 2021. ChatGPT lacks the ability to analyze, evaluate, or reason. The various references or information provided by ChatGPT need to be re-verified, and such literature may not exist. Some documents do not exist at all, and some are the result of self-judgment and inference.

Prof. Juei-Low Sung’s Research Foundation 36th Annual Academic Meeting

Impaired Chromatin Remodeling Predicts Better Survival to Modified Gemcitabine and S-1 plus Nivolumab in Advanced Biliary Tract Cancer: A Phase II T1219 Study

Nai-Jung Chiang

Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan

National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan

Background:

Modified gemcitabine and S-1 (GS) is an active regimen for patients with advanced biliary tract cancer (ABTC) in our previous study. Herein, we report the results of a single-arm phase II of nivolumab plus modified GS (NGS) as first-line treatment in ABTC.

Methods:

Patients received nivolumab 240 mg and 800 mg/m2 gemcitabine on day 1 plus daily 80/100/120 mg of S-1 (based on body surface area) on days 1 to 10, in a 2-week cycle. The primary endpoint was the objective response rate (ORR). Thirty-nine out of 48 subjects who had sufficient formalin-fixed, paraffinembedded tumor tissue were subject to NGS using the 440-gene panel ACTOnco® (ACT Genomics) and sequenced on the Ion Torrent platform (Thermo Fisher Scientific). Genomic alterations and features, including single nucleotide variations, short insertions and deletions, copy number variations, tumor mutation burden (TMB) and microsatellite instability (MSI) were analyzed. The correlation between therapeutic efficacy and genetic alterations with signatures identified by targeted next-generation sequencing panels was explored.

Results:

Between December 2019 and December 2020, 48 eligible patients were enrolled. After a median of 17.6 months of follow-up, the ORR was 45.9% [95% confidence interval (CI), 31.4%-60.8%]. The median

progression-free survival (PFS) and overall survival (OS) was 9.1 (95% CI, 5.8-9.6) and 19.2 (95% CI, 11.6not reached) months, respectively. All grade 3/4 treatment-related adverse events (AE) were less than 10%, except fatigue (14.6%) and skin rash (10.4%). Eighteen patients (35.4%) experienced immunerelated AEs without treatment-related death. High TMB (top 20%; ≥7.1 mut/Mb) only predicted prolonged median PFS but not OS. One MSI-high patient who had a high mutation load of 9.7 mut/ Mb and deleterious B2M mutations as predicted by in silico only achieved 2.7 months of stable disease, possibly due to acquired biallelic loss of B2M gene. Up to 28.9% of patients who harbored loss-offunction mutations in chromatin remodeling genes demonstrated significantly longer median PFS and OS than those without alterations.

Conclusions:

NGS is a safe and promising regimen in ABTC. Impaired functions of chromatin remodeling genes may be a potential surrogate biomarker with predictive value in this study.

Prof. Juei-Low Sung’s Research Foundation 36th Annual Academic Meeting

LINC01348 Suppresses Hepatocellular Carcinoma Metastasis through Inhibition of SF3B3-mediated EZH2 pre-mRNA Splicing

Yang-Hsiang Lin

Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Long non-coding RNAs (lncRNA) play crucial roles in hepatocellular carcinoma (HCC) progression. However, the specific functions of lncRNAs in (AS) and the metastatic cascade in liver cancer remain largely unclear. In this study, we identified a novel lncRNA, LINC01348, which was significantly downregulated in HCC and correlated with survival functions in HCC patients. Ectopic expression of LINC01348 induced marked inhibition of cell growth, and metastasis in vitro and in vivo. Conversely, these phenotypes were reversed upon knockdown of LINC01348. Mechanistically, LINC01348 complexed with splicing

factor 3b subunit 3 (SF3B3) acted as a modulator of EZH2 pre-mRNA AS, and induced alterations in JNK/c-Jun activity and expression of Snail. Notably, C-terminal truncated HBx (Ct-HBx) negatively regulated LINC01348 through c-Jun signaling. Our data collectively highlight those novel regulatory associations involving LINC01348/SF3B3/EZH2/ JNK/c-Jun/Snail are an important determinant of metastasis in HCC cells and support the potential utility of targeting LINC01348 as a therapeutic strategy for HCC.

Prof. Juei-Low Sung’s Research Foundation

36th Annual Academic Meeting

Personalized Treatment and Long-term Safety Issues of H. pylori Eradication for Gastric Cancer Prevention

Jyh-Ming Liou

Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

The development of modern sequencing technology has enabled us to gain insight into GI microbes. Helicobacter pylori (H. pylori) colonization significantly affects the gastric microenvironment, which in turn affects gastric microbiota and may be correlated with colonic microbiota changes. Crosstalk between H. pylori and GI commensal flora may play a role in H. pylori-related carcinogenicity and extragastric manifestations. Antibiotic may cause short-term perturbation of gut microbiota and emergence of antibiotic resistance. Significant perturbation of the diversity and composition of gut microbiota develops soon after H. pylori eradication. There is a reduction in Actinobacteria, relative to baseline, throughout the follow-up. Proteobacteria have a higher relative abundance at the short-term follow-up, which then returns to normal. The relative abundances of all phyla were restored at months after treatment. Our previous randomized trial showed

that the diversity of gut microbiota was significantly perturbed immediately after triple, concomitant, and quadruple therapies, but to a greater extent for concomitant therapy and quadruple therapy. The diversity was restored at week 8 and 1 year for triple therapy, but was not yet fully recovered at 1 year for concomitant and quadruple therapies. We also observed some potential beneficial effects on metabolic parameters, such as reduction of insulin resistance, after H. pylori eradication. More recently, we showed that the short-term increase of antibiotic resistome could be restored to basal state 2 months after levofloxacin sequential or bismuth quadruple therapy. The results collectively support the longterm safety of H. pylori eradication on the diversity, composition, and antibiotic resistome. More welldesigned randomized controlled studies from other populations are warranted to confirm these findings.

Prof. Juei-Low Sung’s Research Foundation 36th Annual Academic Meeting

Serum Biomarkers Predictive of Liver Fibrosis and Survival in Viral and Non-viral Hepatitis Patients

Naoya Sakamoto

Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Hokkaido, Japan

With the development of DAA for hepatitis C, HCV can be cured at a high rate. However even after SVR, liver fibrosis did not improve in 45% of patients, 48% remained unchanged, and 6% developed fibrosis, indicating that fibrosis progression after SVR is an independent risk factor for the development of HCC.

Angiopoietin-2 (Ang-2) is an antagonist of TIE2 signaling, which is expressed on the vascular endothelium and regulates vascular stabilization. Ang-2 production from stromal cells due to hypoxia or inflammation in the liver leads to increased vascular

permeability, angiogenesis, and inflammatory cell infiltration. Recently, it has been reported that high Ang-2 expression is associated with the risk of hepatocarcinogenesis and recurrence after DAA treatment and with the prognosis of cirrhosis. We have reported that Ang-2 is a biomarker associated with the efficacy of lenvatinib therapy in hepatocarcinoma. In the present study, we investigated the association between serum Ang-2 and non-improvement of liver fibrosis and hepatocarcinogenesis after HCV elimination.

Symposium (I)

Precision Surveillance for the High-risk Population of Gastrointestinal Cancers

Esophageal Cancer: Head & Neck Cancer, Heavy Smoker-heavy Drinker and Betel Nut Chewers

I-Chen Wu

Digestive Disease Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Esophageal cancer is notably prevalent in the Asian esophageal Cancer belt, ranking 8th in global incidence and 6th in mortality, with over 100 esophageal squamous cell carcinoma (ESCC) cases per 100,000 person-year. From 1992 to 2012, ESCC’s incidence showed an annual 1.5% decline, while adenocarcinoma’s (EAC) surged by 5.2% annually. The risk factors for ESCC includes alcohol consumption, smoking, betel quid chewing, specific genetic polymorphisms, high-temperature food intake, and a history of head and neck squamous cell carcinoma (HNSCC). This association with HNSCC is explained through field cancerization: 2.4-5% of HNSCC patients develop synchronous esophageal neoplasia and 0.783% experience metachronous esophageal neoplasia within five years. The ALDH2 polymorphism exhibits limited ability to metabolize ethanol-derived acetaldehyde, leading to DNA interactions that blocks translation DNA synthesis and increases cancer risks.

International Agency for Research on Cancer (IARC) cited our work in Kaohsiung Medical University to recognize Betel quid as a group I carcinogen for ESCC in 2009. Later on, one of the carcinogenic alkaloids in Betel quid, arecoline has been recognized as a Class 2B carcinogen by IARC in 2020. Concurrently, smoking is identified as a universal risk amplifier for both ESCC and EAC. There is a dose-dependent effect of the cumulative amount of consumption of alcohol, cigarette and betel nut on ESCC risk. Collectively, the interplay of these risk factors heightens the carcinogenic pathways, escalating the chances of developing esophageal cancer and HNSCC. It is now a common practice to use image-enhanced endoscopy to screen for esophageal squamous cell neoplasm (ESCN) among HNSCC patients. Heavy drinkers with alcohol flush response has been identified at highest risk for synchronous ESCN among incident HNSCC patients.

Symposium (I)

Precision Surveillance for the High-risk Population of Gastrointestinal Cancers

Gastric Cancer: Intestinal Metaplasia, Atrophic Gastritis

Hsiu-Chi Cheng

Department of Internal Medicine, Institute of Clinical Medicine and Molecular Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan

It is important to apply the concept of precision medicine to cancer surveillance. We should move away from a “one-size-fits-all” approach to tailoring the surveillance intensity to individual risk profiles. Accordingly, accurate risk stratification models are necessary. The models may include clinical presentations, genetic data, biomarkers, and others.

Some patients are still at risk of gastric cancer even though H. pylori infection is eradicated. Atrophic gastritis and intestinal metaplasia are known as gastric pre-cancers. The incidence rates of gastric cancer in patients with atrophic gastritis and intestinal metaplasia are 2.25 (95% CI, 1.67–2.90) and 7.58 (4.10–1.91) per 1000 person-years, respectively, in East Asia. The risk to develop gastric cancer could be stratified further by histological analyses and endoscopic mucosal visualization. Histological analyses are performed by target biopsies using the Sydney protocol and evaluated by the Operative Link for Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM). The disease severity and risk could also be evaluated by the Kimura-Takemoto classification and endoscopic grading of gastric intestinal metaplasia (EGGIM) under white-light or image-enhanced endoscopy. A systematic review and meta-analysis suggests that OLGA or OLGIM stages III–IV predict higher risk of gastric cancer than stages 0–II, and the odds ratios (OR) are 2.64 (1.84–3.79) for OLGA and 3.99 (3.05–5.21) for OLGIM. The severe-type (O-2 and O-3) and opentype (O-1, O-2, and O-3) of the Kimura-Takemoto classification have increased risk of gastric cancer,

and the pooled risk ratios are 3.89 (2.92–5.17) and 8.02 (2.39–26.88), respectively. EGGIM scores > 4 has 0.89 (0.77–0.97) of sensitivity and 0.95 (0.91–0.97) of specificity to diagnose OLGIM stages III-IV. In Taiwan, the gastric cancer incidence rates (per 1000 personyears) after H. pylori eradication are 0 (0–12.05) in subjects with normal gastric mucosa, 0 (0–29.66) in those with corpus-predominant gastritis, 4.61 (0.94–13.53) in those with stages I-II of OLGA/OLGIM, and 11.13 (4.05–24.35) in those with stages III-IV of OLGA/ OLGIM.

Biomarkers, i.e., serum pepsinogen (PG) I and I/II ratio, are also useful to assess the risk of gastric cancer and pre-cancer. Serum PG I ≤ 70 ng/mL and PG I/II ratio ≤ 3 could be used to predict subjects developing non-cardiac gastric cancer and the adjusted hazard ratio is 18.8 (5.1–68.7). A systematic review and metaanalysis shows that serum PG I ≤ 70 μg/L and PG I/ II ratio ≤ 3 have low sensitivity (59% [38%–78%]) but high specificity (89% [70%–97%] to diagnose chronic atrophic gastritis; moreover, low sensitivity (59% [50%–67%]) and borderline specificity (73% [64%–81%]) to diagnose gastric cancer. In Taiwan, serum PG I < 45 ng/mL and PG I/II ratio < 6 have borderline sensitivity (60% [36%–80%]) and specificity (71% [65%–76%]) to predict subjects with OLGA/OLGIM stages III-IV or gastric cancer.

In order to down-stage gastric cancer at diagnosis, endoscopy surveillance is suggested. The balance between effectiveness and costs of endoscopic surveillance should be considered. A cost-utility analysis reports the optimal interval of

surveillance may be dependent on gastric cancer risk. Annual surveillance is optimal for subjects with OR 5.46–21.5 of gastric cancer and biennial surveillance is optimal for those with OR 2.4–5.46.

Based on the concept of precision medicine, we should tailor the surveillance intensity to individual risk profiles. In Taiwan, for no-risk subjects, observation instead of surveillance until risk profiles change is suggested; moreover, for subjects who have atrophic gastritis or intestinal metaplasia, endoscopic surveillance is suggested. Furthermore, we should consider “complex” precision approaches for subjects at different risk of gastric cancer. For example, for

subjects with high-risk atrophic gastritis or intestinal metaplasia, 2- or 3- yearly endoscopic surveillance should be optimal now. However, surveillance strategies for subjects with low-risk gastric precancers, such as stages I-II of OLGA or OLGIM, the mild-to-moderate-type or closed-type of the KimuraTakemoto classification, or EGGIM scores 1–4, should be studied further. Moreover, the role of genetic data in gastric cancer surveillance should be studied further. As these data are validated, the concept of precision gastric cancer surveillance should achieve an aspirational goal.

Symposium (I)

Precision Surveillance for the High-risk Population of Gastrointestinal Cancers

Colorectal Cancer: Hereditary Colorectal Cancer

Yu-Min Lin

Division of Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

Precision surveillance is a vital component in the comprehensive management of gastrointestinal cancers, especially for individuals at high risk of hereditary colorectal cancer (HCRC). HCRC is characterized by a strong familial component and inherited genetic mutations, requiring specific and focused surveillance approaches for early detection, timely interventions, and improved outcomes. This targeted surveillance approach significantly impacts reducing cancer incidence, mortality, and improving survival rates.

Tailoring surveillance intervals and starting age based on specific genetic mutations and family history further enhances the precision of surveillance efforts. Different hereditary colorectal cancer syndromes, such as Lynch syndrome with DNA mismatch repair gene mutations, and familial adenomatous polyposis (FAP) with APC gene mutations, may exhibit distinct patterns of tumor development and progression. Therefore, individual variations in disease susceptibility must be considered to ensure the most effective surveillance approach for each high-risk individual. This tailored approach not only improves patient outcomes but also reduces the burden of hereditary gastrointestinal cancers on affected individuals and their families.

Understanding the effectiveness of precision surveillance is critical, especially in terms of its impact on colorectal cancer incidence, mortality, and survival rates. Compared to a “one size fits all” strategy, precision surveillance offers advantages in early detection, timely interventions, and potentially higher survival rates. By tailoring surveillance based on individual risk factors, precision surveillance optimizes the chances of detecting cancer at an early stage, leading to better outcomes.

In conclusion, precision surveillance is a pivotal tool in managing hereditary colorectal cancer and other gastrointestinal cancers in high-risk populations. Identifying individuals with genetic mutations predisposing them to HCRC, such as Lynch syndrome and FAP, and implementing personalized surveillance can achieve early detection and preventive measures. As research and technology continue to advance, precision surveillance hold the promise of further enhancing our ability to effectively prevent, detect, and manage gastrointestinal cancers. Advocating for increased awareness and support for precision surveillance will be essential in achieving a future with fewer cancer-related deaths and improved quality of life for individuals at risk.

Symposium (I)

Precision Surveillance for the High-risk Population of Gastrointestinal Cancers

Pancreatic Cancer: Chronic Pancreatitis, Cystic Tumors

Wei-Chih Liao

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Pancreatic adenocarcinoma is the most lethal cancer and comprises approximately 90% of pancreatic malignancies. Screening for PDAC in high-risk individuals including carriers of germline susceptibility gene variants and familial pancreatic cancer kindred enables early detection and may improve survival. However, the role and benefit of screening/surveillance in patients with pancreatic cystic lesions and chronic pancreatitis are less clear.

Pancreatic cystic lesions (PCLs), including intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN), carry malignant potential. A meta-analysis of 18 studies showed that the incidence of advanced neoplasia was 0.6% and 1.0% patient-years within the initial 5 years and thereafter, respectively. The Fukuoka guideline recommends endoscopic ultrasound (EUS) in patients with worrisome features (cyst ≥3 cm, enhancing mural nodule <5 mm, thickened/enhancing wall, main pancreatic duct (MPD) 5-9 mm, change in MPD diameter with distal atrophy, lymphadenopathy, increased serum CA 19-9, growth ≥5 mm in 2 years) without high-risk stigmata suggesting surgery (obstructive jaundice, enhancing mural nodule ≥5 mm, MPD ≥10 mm), and that surgery should be considered if definite mural nodule ≥5 mm, suspicious MPD involvement, or positive/suspicious cytology is noted after EUS. The American Gastroenterological Association (AGA) guideline recommends EUS-FNA if 2 or more of the following features are present: cyst ≥3 cm, dilated MPD, or solid component, and surgery should be considered if both a solid component

and a dilated pancreatic duct are noted or positive cytology. The European evidence-based guidelines recommend that EUS should be performed when concerning clinical or radiologic features are noted and contrast harmonic enhanced EUS (CH-EUS) should be considered for detection of mural nodules. EUS-FNA is suggested if the differentiation between mucinous vs non-mucinous and benign vs malignant PCLs are unclear on CT or MRI, or if hyperenhancement of mural nodules, solid masses, or septation is noted on CH-EUS, and the results are expected to change management. Any solid component or thickened cyst wall should be targeted for cytology, and cyst fluid CEA and lipase levels should also be analyzed.

Chronic pancreatitis was associated with an increased risk of pancreatic cancer, with relative risk estimates ranging between 2.7 and 13.3. The incidence of pancreatic cancer in sporadic chronic pancreatitis is not high enough to justify screening or surveillance. However, patients with autosomal dominant hereditary chronic pancreatitis resulting from gain-of-function mutations in the protease serine 1 (PRSS1) gene carry a particularly high risk of pancreatic cancer. Therefore, surveillance starting from the age of 40 has been recommended in this high-risk group patients, with CT and MRI as the recommended surveillance method. On the other hand, EUS is not recommend as the first-line method for surveillance as early tumors may be obscured by inflammation, fibrosis and calcification in the background for chronic pancreatitis. However, the optimal screening interval remains to be determined.

Symposium (II)

Advances in the Management of Early Esophageal Neoplasia in Asia

Current Status of Barrett’s Esophagus in Asia

Fu-Jen Lee

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Fu-Jen Catholic University Hospital, New Taipei City, Taiwan

Barrett’s esophagus, a premalignant condition characterized by the metaplastic transformation of the esophageal mucosa, has garnered increasing attention in Asia. This topic provides an overview of the current status of Barrett’s esophagus in the region as of 2023. Through a comprehensive analysis of the available literature and medical data, it highlights the prevalence, risk factors, diagnostic modalities, and management approaches utilized in

Asian populations. Additionally, we delves into the challenges faced in the early detection and treatment of Barrett’s esophagus, along with ongoing research efforts to improve outcomes and reduce the burden of this condition in Asia. The findings underscore the importance of continued research and collaboration to address the specific nuances of Barrett’s esophagus in the Asian context and enhance patient care and outcomes.

Symposium (II)

Advances in the Management of Early Esophageal Neoplasia in Asia

Screening Strategies of Early Esophageal Cancer for High-risk Population

Chen-Shuan Chung

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

Esophageal cancer is ranking the 8th most common cancer and the 6th leading cause of cancer death worldwide. Esophageal adenocarcinoma (EAC) is the predominant histological subtype in Western countries whereas the majority in Eastern countries are esophageal squamous cell carcinoma (ESCC), particularly in the region, so-called “Asian Esophageal Cancer Belt” stretching from Turkey, Iran to the East Asia. Therefore, the clinical manifestations, risk factors and prognosis for esophageal cancer vary between Western and Eastern data. Meanwhile, the

population at risk for screening of early esophageal cancer are different for the main two histological subtypes. Nowadays, endoscopic, particularly image-enhanced endoscopy techniques, and non-endoscopic screening modalities, such as cell collection devices, body fluid (blood, saliva and urine) or breathing biomarkers, are available for screening and surveillance for esophageal cancer. In this lecture, I will present the advances in the preventive medicine for esophageal cancer.

Symposium (II)

Advances in the Management of Early Esophageal Neoplasia in Asia

Computer-aided Diagnosis of Early Esophageal Cancer

I-Chen Wu

Digestive Disease Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Diagnosis of early esophageal cancer is crucial to improve patients’ prognosis; however, most esophageal cancer is diagnosed at advanced stages because typical symptoms usually do not develop during early stages. Although image-enhanced endoscopy is the most sensitive approach, accurate diagnosis of esophageal precancerous lesions and superficial cancer is still difficult. A few studies have shown the feasibility of artificial intelligence (AI)-assisted screening and characterizing of early esophageal neoplasms based on traditional whitelight images, narrow-band images or magnifying

images. Computer-added diagnosis combining methods such as sponge cytology have been applied to identify high-risk population for image-enhanced endoscopy. Moreover, in cooperation with Professor Hsiang-Chen Wang from National Chung Cheng University of Taiwan, the hyperspectral imaging technology has been applied to our magnifying endoscopic red, green, and blue (RGB) images for better diagnostic performance. Our data showed that the AI diagnostic model incorporating hyperspectral imaging system could improve the diagnostic rate of early esophageal cancer.

Symposium (II)

Advances in the Management of Early Esophageal Neoplasia in Asia

Endoluminal Therapies for Early Esophageal Neoplasia: Resection or Ablation

Tze-Yu Shieh

Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan

Early esophageal neoplasm (ESCN) can be treated by endoscopic submucosal resection (ESD) or endoscopic radiofrequency ablation (RFA). The advantages of ESD including deeper tissue removal (submucosal layer), complete specimen examination, less recurrent rate. However, the disadvantages of ESD including long learning curve, more procedure

time and more complications. RFA provides an easy way to treat pre-cancerous lesions, but it is limited in flat lesions. The relationship between ESD and RFA is not competitive but cooperative. For circumferential lesion, RFA follows by ESD may have better effect and less complication.

Symposium (III)

Learning from the Past: Rethinking Colonoscopy Practice and Looking into the Future

Colonoscopy Screening Trials – From NPS to NordlCC: Is Colonoscopy Still in the Frontline of Screening?

Wei-Yuan Chang

Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan

From 1980, the National Polyp Study (NPS), a nation-wide prospective study in USA, had tried to discover the role of colonoscopy in reducing the incidence of morality of colorectal cancer (CRC).

After the effort in 40 years, NPS not only showed us the efficacy of colonoscopy as the best tool of preventing CRC, but also helped us explore several important knowledge regarding of CRC prevention. Such as the proof of important assumption of adenoma-carcinoma sequence, determining optimal surveillance interval by evident based study and reducing CRC mortality by removal of precancerous adenoma. However, nowadays, with the emerging

of non-invasive CRC screening demand, such as fecal immunochemical test (FIT), the efficacy of using colonoscopy as the first-line CRC screening tool need to be established. Therefore, a European multi-countries prospective study by the NordicEuropean Initiative on Colorectal Cancer (NordICC) had launched in 2009 to demonstrate the effects of population-based colonoscopy screening on the risks of colorectal cancer and related death at 10 years. With the publishment of the surprising result of NordICC, an old and important question has revealed: Is colonoscopy still in the frontline of screening?

Symposium (III)

Learning from the Past: Rethinking Colonoscopy Practice and Looking into the Future

Non-polypoid Colorectal Neoplasm: Old Story, New Perspective

Wen-Hsin Hsu

Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan

Non-polypoid colorectal neoplasm was thought to be an unique illness in Japan for a long time. Although it has been accepted as a worldwide illness gradually, recognition and detection remained difficult during colonoscopy. Non-polypoid colorectal neoplasm may progress to invasive cancer in a shorter interval than protruded lesion. Neglect of such

lesions was considered a contributing factor for postcolonoscopy colorectal cancer. With the progress of endoscopy resection technique, most non-polypoid colorectal neoplasm could be resected endoscopically. However, which is the best or appropriate endoscopy technique remained a debate.

Symposium (III)

Learning from the Past: Rethinking Colonoscopy Practice and Looking into the Future

Image Enhancement to Artificial Intelligence: Are They the Magic Bullets in Colonoscopy Practice?

Chen-Ya Kuo

Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei City, Taiwan

Colonoscopy is widely recognized as the gold standard for accurate colorectal cancer (CRC) screening. However, it has limitations, with studies indicating that it may miss about 30% of colorectal adenomas and contribute to a significant proportion of post-colonoscopy colorectal cancers (52-57%).

Increasing the adenoma detection rate by 1% could potentially reduce interval cancer incidence by 3%.

Image-enhanced endoscopy has shown promise in improving adenoma detection rates, yet its adoption is hindered by unnatural light source coloration. Recent trends in national CRC screening programs have led to the discovery of early-stage cancers, such as superficial T1 cancer, with lower lymph node metastasis risks. Endoscopic complete resection yields comparable outcomes to traditional surgery while preserving organs. Image-enhanced endoscopy aids treatment decisions by assessing tumor invasion depth, but interobserver variability poses diagnostic challenges, relying heavily on the endoscopist’s experience.

AI advancements have produced computeraided detection (CADe) systems to detect colorectal polyps. While prospective trials demonstrate

enhanced adenoma detection rates, retrospective pragmatic trials show inconsistent results. CADe is more effective in identifying low-risk polyps, yet its impact on reducing CRC incidence and mortality remains uncertain, potentially increasing the number of surveillance colonoscopies and costs. Factors affecting adenoma detection extend beyond image interpretation, encompassing cecal intubation rate, withdrawal speed, mucosal exposure, and colon cleanliness, areas where AI assistance remains limited.

Computer-aided diagnosis (CADx) systems aid endoscopists in classifying polyps as neoplastic or non-neoplastic and determining the extent of invasiveness. CADx may further enable a “diagnoseand-leave” strategy for non-neoplastic polyps and a “resect-and-discard” strategy for low-risk adenomas, potentially reducing pathological examination costs by up to 80%.

Current AI applications in colonoscopy primarily focus on CADe and CADx for polyps, requiring further validation in reducing cancer incidence and mortality. Developing a comprehensive computer-aided quality monitoring system (CADq) is crucial for overall colonoscopy effectiveness.

Symposium (III)

Learning from the Past: Rethinking Colonoscopy Practice and Looking into the Future

Polypectomy Techniques: Evolution and Revolution

Yutaka Saito

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan

Polypectomy continues to play a main portion in colonoscopy, even in the era of ESD. Most adenomatous polyps < 2 cm can be treated by polypectomy. Even at NCCH, there were 4,500 colorectal polypectomies/ EMRs and 267 ESDs in 2022, with polypectomy being performed 20 times more frequently than ESD.

In the past, polypectomy was performed with electric current, but recently the safety of cold snare polypectomy (CSP) has been reported, and CSP without electric current is rapidly gaining popularity. However, it has been reported that CSP should not be applied to cancer because of its shallow resection depth. Therefore, the Japan Gastroenterological Endoscopy Society (JGES) guidelines1 states that CSP should be limited to definite adenomas < 1 cm in size, and IEE with magnification by JNET classification or Pit pattern diagnosis may be mandatory for CSP. In the West, there are reports of piecemeal CSP (p-CSP)

for the treatment of adenomas ≥ 1 cm and, in some cases, LSTs ≥ 2 cm.

The JGES, which encourages en-bloc resection including ESD for LSTs ≥ 2 cm, is cautious about easily expanding the use of CSP, but there is a possibility that p-CSP can be used for lesions ≥ 2 cm, such as SSL without dysplasia, and its use is expected to increase in the future. The advantages of CSP are its simplicity and safety, and we believe that outpatient endoscopic treatment will become increasingly popular in the future.

Reference:

1. Uraoka T, Takizawa K, Tanaka S, et al. Guidelines for Colorectal Cold Polypectomy (supplement to “Guidelines for Colorectal Endoscopic Submucosal Dissection/Endoscopic Mucosal Resection”). Dig Endosc. 2022;34:668-675.

Symposium (IV)

GI Motility Disorders and Systemic Diseases: An Update

Mucosal Permeability and Functional GI Disorders

Hiroto Miwa

President, Kawanishi City Medical Hospital, Hyogo, Japan

Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan

It is interesting to recognize that the inside of GI tract is outside of human body as GI tract is a long tube that penetrates the center of our body. In order to prevent the unfavorable forging bodies coming into our body, we need the barrier function at the GI mucosa. On the other hand, we need to incorporate the necessary digested nutritional stuffs and liquids, and we need to dispose unnecessary materials from our body. Therefore, the ability of GI mucosa to allow the passage of the materials between inside and outside of human body is significant. In other word, the intercourse between outside and inside of our body to some extent is necessary. We need the smart barrier function. The degree of the passage between inside and outside of our body is called “permeability”.

In order to maintain the function of human body, the permeability should be well controlled. There are several machineries that control the barrier function and permeability, and among them tight junction is known as the most important machinery. It is well known that mucosal barrier function is impaired and the mucosal permeability in increased in many GI diseases, such as GI infection including Helicobacter gastritis, inflammatory bowel diseases, and NSAIDs gastroduodenal injuries. In my talk, I will review the mucosal permeability and discuss whether barrier function is impaired also in functional GI disorders, such as irritable bowel disease and functional dyspepsia.

Symposium (IV)

GI Motility Disorders and Systemic Diseases: An Update

Gastrointestinal Motility Disorders in Obesity

Wei-Yi Lei

Division of Gastroenterology & Hepatology, Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

Obesity is a complex disease in which the excess of adiposity results in increased health risks and disease. Various gastrointestinal and hepatic disorders can be directly linked to obesity or considered substantial risk factors. Motility of gastrointestinal tract may be affected by obesity. Recent investigations reveal that adipocyte-secreted peptides can modulate GI motility, exerting influence, both in the central and peripheral aspects. In esophagus, obesity comes along with increased intraabdominal pressure, leading to decreased pressure in the lower esophageal sphincter (LES), a rise in the frequency of transient lower esophageal sphincter relaxations (tLESR), the occurrence of hiatal hernia, and compromised esophageal motor functions. These changes in physiology heighten the occurrence of gastroesophageal reflux disease (GERD), potentially progressing to Barrett’s esophagus or even esophageal adenocarcinoma. Studies demonstrate that obesity is linked to a greater fasting gastric volume and an accelerated rate of gastric emptying

for both solids and liquids. In obese individuals, symptoms of irritable bowel syndrome (IBS) may be attributable to alterations in small bowel and colonic motility, dietary patterns rich in carbohydrates and lacking in fiber, as well as changes in intestinal microbiota. However, the available evidence is insufficient to definitively establish a cause-andeffect connection between obesity and disorders of gut-brain interaction. Additionally, studies on the changes in the intestinal transit are limited, but it suggests increased transit in the proximal intestines and delayed transit in the distal small intestine and colon among those with obesity. In summary, obesity is linked to impaired motor function in the gastrointestinal tract. Nevertheless, comprehensive studies designed with care are necessary to delve into the underlying mechanisms connecting obesity with gastrointestinal dysmotility. These investigations will also be instrumental in identifying potential obesity treatments that could ameliorate symptoms of these gastrointestinal motility disorders.

Symposium (IV)

GI Motility Disorders and Systemic Diseases: An Update

Gut Dysfunction in Diabetes

Yen-Po Wang

Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan

As the prevalence of diabetes increases, gastrointestinal complications also become more common. Gastrointestinal manifestations include upper GI symptoms (heartburn, dysphagia, dyspepsia, nausea, vomiting, gastroparesis) and lower GI symptoms (diarrhea, constipation, and fecal incontinence). The prevalence of GI symptoms can be as high as 10-20%. Disordered gastrointestinal motor and sensory functions in diabetes, as a consequence of diabetic autonomic neuropathy, have been suggested to be related to these GI symptoms.

Patients with diabetes are more likely to experience altered gastric emptying, impaired gastric accommodation, and abnormal gastric sensation. Delayed gastric emptying can be found in 30-50% of outpatients with long-standing type 1 or type 2 diabetes. The risk of developing gastroparesis is higher in individuals with Type 1 diabetes, followed by those with Type 2 diabetes and control subjects. Small bowel and colonic dysmotility, as well as anorectal

dysfunction, are also frequently encountered. The development of GI symptoms is linked with chronicity and hyperglycemia. In a recent rodent study, hyperglycemia was found to induce apoptosis of enteric neurons in the myenteric plexus, leading to delayed gastric emptying and more rapid intestinal transit.

Dysbiosis of the gut microbiome has also been found to be related to increased intestinal permeability, inflammatory modulation, and insulin homeostasis. The management of gastrointestinal manifestations in diabetes primarily involves symptomatic medical treatment. Additionally, maintaining glycemic control and managing fluid/nutritional status are important. For patients with severe gastroparesis refractory to medication, enteral feeding, gastric peroral endoscopic myotomy (G-POEM), or gastric electrical stimulation may be considered as potential management options.

Symposium (IV)

GI Motility Disorders and Systemic Diseases: An Update

Esophageal Motility Disorders in Connective Tissue Diseases

Jiunn-Wei Wang

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Esophageal motility disorders are a group of conditions characterized by abnormal contractions and coordination of the esophageal muscles, leading to swallowing difficulties and related symptoms. These disorders often occur in the context of connective tissue diseases (CTDs), a diverse group of autoimmune disorders that affect connective tissues throughout the body. The association between esophageal motility disorders and CTDs poses unique challenges for diagnosis and management, requiring a comprehensive understanding of the underlying mechanisms and tailored treatment approaches.

Connective tissue diseases encompass various autoimmune conditions, including systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, Sjögren’s syndrome, and mixed connective tissue disease. Autoimmune processes in these diseases can lead to inflammation and fibrosis in the esophageal wall, affecting its muscular function and motility. Esophageal motility disorders commonly observed in CTDs include ineffective esophageal motility, gastroesophageal reflux disease (GERD), and esophageal dysmotility. Patients with these disorders often experience dysphagia, regurgitation, chest pain, and heartburn, which can significantly impact their quality of life.

The diagnosis of esophageal motility disorders in the context of CTDs is complex, as symptoms may overlap with other gastrointestinal conditions. Esophageal manometry is a key diagnostic tool

used to assess esophageal motility and identify abnormalities in contraction patterns. However, the presence of fibrosis and structural changes in the esophagus due to CTDs can complicate the interpretation of manometric findings.

Management of esophageal motility disorders in CTDs focuses on symptom relief, prevention of complications, and improving esophageal function. Treatment options may include medications like proton pump inhibitors to reduce acid reflux and protect the esophagus. Smooth muscle relaxants and prokinetic agents may also be prescribed to improve esophageal motility and alleviate dysphagia. In severe cases with strictures caused by fibrosis, esophageal dilation or surgical interventions might be considered to restore swallowing function. Lifestyle modifications, such as dietary adjustments and postural changes during meals, can also complement medical treatment.

In conclusion, esophageal motility disorders in connective tissue diseases represent a complex and multifaceted clinical challenge. Early recognition and accurate diagnosis are essential for developing tailored treatment plans and improving the overall wellbeing of affected individuals. Further research and collaboration among specialists in gastroenterology and rheumatology will advance our understanding and management of esophageal motility disorders in the context of CTDs.

Symposium (V)

Microbiota from Bench to Bedside

Microbiota State-of-art Basic Research

Jun Yu

Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong

Gastrointestinal (GI) cancers are a major disease burden globally. Gut microbiota plays key roles in many aspects of GI tumorigenesis and holds great potential for clinical application (Nat Reviews Gastroentero Hepatol 2019). We depicted the microbiota signature of colorectal cancer (CRC) by identifying the ectopic overgrowth of a network of oral microbes (Nat Comm 2015), and discerned the oncogenic effects of specific CRC-enriched microbes, including Peptostreptococcus anaerobius (Gastro 2017b, Nat Microbiol 2019), hemolytic Escherichia coli (Cancer Res, 2016), Hungatella hathewayi (Microbiome 2020), and Aspergillus rambellii (Gastro 2022a). These microbes were found to promote CRC via key oncogenic mechanisms, including upregulating cholesterol biosynthesis (Gastro 2017b), inducing the expansion of myeloid-derived suppressor cells (Nat Microbiol 2019), activating hypoxia-inducible factor 1α to induce GLUT-1 expression (Cancer Res, 2016), inducing DNA hypermethylation to silence tumor-suppressor genes (Microbiome 2020), and enhancing Th17 cell infiltration and cytokine release.

Intratumoral microbiota heterogeneity correlates with mutational features (i.e. KRAS mutation and microsatellite instability) (Gastro 2021a) and unveiled the roles of gut microbiota in mediating high-fat diet- and cigarette smoke-promoted CRC (Gastro 2022b, Gut 2022a). In gastric cancer, we revealed the alterations of mucosaassociated bacteriome across stages of gastric cancer (Gut 2018) and identified specific bacteria (e.g. Acinetobacter lwoffii, Streptococcus anginosus) that are associated with persistent inflammation, gastric atrophy or intestinal metaplasia after eradication of Helicobacter pylori (Gut 2020). In liver cancer, Bifidobacterium pseudolongumgenerated acetate suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma (J Hepatol 2023). Parabacteroides distasonis uses dietary inulin to suppress NASH via its metabolite pentadecanoic acid (Nat Microbiol 2023). These findings thus provide new insights for the function and mechanism of microbiome in GI and liver carcinogenesis.

Symposium (V)

Microbiota from Bench to Bedside

Microbiota State-of-art Bioinformatics Advances

Yu-Wei Wu

Graduate Institute of Biomedical Informatics, Taipei Medical University, Taipei, Taiwan

Microbiome sequencing and analysis techniques are advancing very rapidly in recent years. The popularity of 3rd-generation sequencing technologies allows more comprehensive views for a variety of microbiota-mediated studies. The plethora of microbiome studies also allows in-depth comparative analysis for addressing important questions such as how the microbes affect the residing environments or how microbes cause diseases. In this talk I will introduce the computational advances that I observed in the microbiome world. I

will first introduce why 3rd-generation sequencing matters and how it changes the analysis. I will also talk about new computational challenges introduced by the 3rd-generation sequencing technology and how we may possibly deal with them. Lastly I will discuss other important topics including strain-recovery, comparative metagenomics, and non-prokaryotic species (including viruses and eukaryotes) identification. I hope this talk can provide clues into how we may

Symposium (V)

Microbiota from Bench to Bedside

Microbiota State-of-art Translational Studies

– Lessons Learned from Animal Models of Heart Repair, Wound Healing and Cancer Nanomedicine

Ching-Ho Hsieh

Division of Cardiovascular and Metabolic Diseases, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

The gut microbiota plays a vital role in maintaining tissue homeostasis and regulating disease pathophysiology; however, the underlying mechanisms remain to be elucidated. We previously showed that mice depleted of gut microbiota with antibiotics (ABX mice) were more prone to cardiac rupture after infarction (Tang et al. Circulation 2019), suggesting that the gut microbiota impacts cardiac structural remodeling following injury. Thus, we carried out to determine whether the gut microbiota is required for adaptive cardiac remodeling in response to pressure overload stress.

By a transverse aortic constriction (TAC) surgery, we found that cardiac hypertrophy and dysfunction were more severe in ABX-TAC mice compared to the controls. Moreover, TAC-induced fibrosis was more profound in ABX hearts, which was accompanied by disrupted ECM structure making the heart tissues mechanically weaker and more brittle. Reconstruction of healthy gut microbiota in germfree mice successfully restored cardiac function and prevented excessive fibrosis and ECM disarray under stress. Furthermore, functional prediction identified acetate and propionate as critical mediators in the gut microbiota-modulated cardiac mechanics. Supplementation of acetate and propionate improved heart function, attenuated fibrosis, and

reversed ECM disarray after TAC. We conclude that the gut microbiota is a potential therapeutic target for cardiac ECM remodeling and heart structural integrity. By establishing a healthy gut microbiome or replenishing the derived metabolites, we could improve cardiac health under dysbiosis after pressureoverload stress (Lin et al. Theranostics 2022).

To test if the host microbiome may influence foreign body responses following biomaterial implantation, we implanted a variety of clinically relevant biomaterials into germ-free or antibiotictreated mice or in pigs. Surprisingly, these animals displayed less fibrous tissue deposition, reduced host cell recruitment to the site, and differential expression of angiogenic and inflammatory markers (Chen et al. Biomaterials 2022). Furthermore, to understand the potential impact of the gut microbiota on cancer nanomedicine, we showed that ABX-treated or germ-free mice had improved therapeutic efficacy of liposomal doxorubicin (LipoDox) against triple-negative breast cancer (Prajnamitra et al. Theranostics 2022). Together these results suggest that gut microbiota modulation may be exploited in combination with available nanomedicine-based therapeutics to improve cancer diagnosis, therapeutic efficacy and outcome.

Symposium (VI)

Strategies of Conversion Surgery for GI Cancers

Pancreatic Cancer

Conversion Pancreatectomty – NTUH’s Experience

Yu-Wen Tien

Division of Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

At time of diagnosis, most pancreatic ductal cell adenocarcinomas (PDACs) are unresectable or metastatic. With recent advancement in chemotherapy, many reported good clinical outcome of conversion pancreatectomy for advanced PDAC after preoperative chemo(radio) therapy. Here, we reported 42 conversion pancreatectomies

(29 pancreaticoduodenectomies and 13 distal pancreatectomies with splenectomies) for 35 locally advanced and 7 metastatic PDACs with emphases on preoperative chemotherapy, reevaluation after chemotherapy, operative and postoperative, pathologic, and survival outcomes.

Symposium (VI)

Strategies of Conversion Surgery for GI Cancers

Pancreatic Cancer

What Is the Optimal Treatment Strategy for Conversion Surgery in Pancreatic Cancer?

Masayuki Sho

Department of Surgery, Nara Medical University, Nara, Japan

It is well known that pancreatic cancer is the most intractable malignancy in humans. However, due to recent advances in the treatment of pancreatic cancer, we occasionally encounter unexpected therapeutic effects in daily clinical practice. In highly selected patients who had a favorable or stable response to chemotherapy or chemoradiotherapy, conversion surgery may be considered. However, at present, there is very limited evidence to recommend the optimal indication, duration of pretreatment, and preferred regimens regarding conversion surgery. Furthermore,

there are significant differences in various aspects between unresectable locally advanced (LPC) and metastatic (MPC) pancreatic cancer. Indeed, conversion surgery appears to be generally accepted in clinical practice for LPC, while it is rarely performed for MPC. In this lecture, we would like to discuss the current status and several issues in clinical practice for initially unresectable pancreatic cancer. We will also present our data of conversion surgery to discuss the optimal therapeutic strategy.

Symposium (VI)

Strategies of Conversion Surgery for GI Cancers

Hepatocellular Cancer

Ming-Chih Ho

Department of Surgery, National Taiwan University College of Medicine and National Taiwan University Hospital Hsin-Chu Biomedical Park Branch, Hsinchu, Taiwan

For some intermediate and advanced stage hepatocellular carcinoma (HCC), surgical resection and transplantation still provide the best chance of cure. Those patients successfully underwent conversion surgery has been reported to have similar survival with those patients received primary surgical treatments. In addition, complete surgical resection reduces prolonged and repeat HCC treatments, which have significantly negative impact on the liver function and life quality.

Before the introduction of sorafenib, transarterial chemo-embolization (TACE) and hepatic artery infusion chemotherapy (HAIC) were the most frequent treatments used to convert unresectable HCC into resectable disease. TACE can be used to treat small simple nodular HCCs, but it is not effective for large tumors or microscopic metastasis. Repeat TACE and HAIC usually leads to the deterioration of liver function, which makes surgical resection more difficult and riskier.

Systemic therapy has the advantage of treating

microscopic metastasis with less liver damage. Longterm survival has been reported when salvage liver resection can be performed after the treatments. With the introduction of immune check point inhibitors (ICI), the response rate has been significantly improved. In the Japanese prospective registered multicenter study, the objective response rate was 43.8%. The hepatic reserve was maintained after the start of treatment in the patients received atezolizumab plus bevacizumab (Atezo + Bev). Conversion surgery after ICI based treatments is becoming more possible. Unresectable intermediate stage and advanced HCCs have been thought to be uncurable when they could not undergo surgical resection. ICI based systemic therapies followed by curative treatments, such as resection, RFA or highly selective TACE provided better chance of cure and reduce the need of prolonged repeated treatments. The advancement of conversion treatment strategies may significantly improve the survival of intermediate stage to advanced stage HCCs in the future.

Symposium (VI)

Strategies of Conversion Surgery for GI Cancers

Gastric Cancer

Hiroya Takeuchi

Department of Surgery, Hamamatsu University School of Medicine, Shizuoka, Japan

Due to remarkable advancements in the development of anticancer drugs, including recent molecular targeted therapies, there has been significant progress in the field of cancer therapy. Chemotherapy has led to the eradication of noncurable factors, allowing for cases who undergo curative resection, thereby enabling long-term survival. Consequently, there is an increasing number of cases, even in Stage IV gastric cancer, in which surgical conversion therapy aimed at curative resection after chemotherapy has become promising.

In the 6th edition of the Gastric Cancer Treatment Guidelines by the Japanese Gastric Cancer Association, it is stated that “performing conversion surgery for Stage IV gastric cancer cases is weakly recommended under the condition that a certain antitumor effect is achieved through chemotherapy, response is maintained, and R0 resection is deemed

feasible.”

On the other hand, for the question of whether surgical treatment is recommended for oligometastasis, the guidelines stated that “weak recommendations are made for surgical resection after preoperative chemotherapy for a limited number of paraaortic lymph node metastases (No.16a2/b1). Additionally, for solitary liver metastases without other non-curative resection factors, weak recommendations for surgical resection are made.”

While the conversion surgery is characterized by extremely limited evidence, the emergence of immune checkpoint inhibitors is expected to further expand the indications for conversion surgery. Future developments, including biomarker research using techniques like liquid biopsy, are anticipated to shed light on the types of cases that can achieve cure and long-term survival through conversion surgery.

Symposium (VI)

Strategies of Conversion Surgery for GI Cancers

Stage IV Gastric Cancer

I-Shu Chen

Health Management Center, Kaoshiung Veterans General Hospital, Kaoshiung, Taiwan

Stage IV gastric cancer consists of heterogenous conditions with mixture of distant hematogenous metastasis, distant L/N metastasis, and the most troublesome peritoneal dissemination. Because of its diversity, it is very difficult to classify these patients and establish the treatment policy.

In the past decades, there were no good chemotherapy, so palliative surgery was done with very poor prognosis and dismal result. With the development of better chemotherapy regimens, not only median survival of stage IV GC was prolonged, but conversion therapy was engaged. Many studies tried to do conversion surgery after neoadjuvant

chemotherapy with good response in some patients. Conversion surgery should be done under the curative intent of R0 resection, and these patients can get long-term survival.

Conversion surgery is a promising option for improving the survival of stage IV GC, but many issues should be clarified, such as definition, patient selection, chemotherapy regimens, timing of the operation, and the postoperative chemotherapy. Anyway, conversion therapy for stage IV GC patients might be one of the main roles of surgical oncologist in the near future.

Symposium (VI)

Strategies of Conversion Surgery for GI Cancers

Colorectal Cancer

Jaw-Yuan Wang

Department of Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan

Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

In the past two decades, we have witnessed dramatic improvements in the outcomes of patients with rectal cancer. Advances in surgical pathology, refinements in surgical techniques and instrumentation (robotic surgery), new imaging modalities, and the widespread use of neoadjuvant therapy have all contributed to these improvements. Concurrent chemoradiotherapy (CCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer (LARC). Preoperative CCRT substantially improves local control and sphincter preservation rates, decreasing treatment-related toxicity compared with that in a postoperative setting. Additionally, locally advanced colon cancer (LACC) is clinically defined as primary colon cancer with direct invasion to the adjacent structures or extensive regional lymph node involvement. Approximately 15% of colon cancers are LACC without distant metastasis (DM), which involves invasion to other organs or lymph node metastasis encasing the root of the main feeding artery. In these cancers, curative surgical resection followed by adjuvant chemotherapy may be a treatment option. However, achieving R0 resection can be challenging, and this type of resection is associated with high morbidity rates, with an incidence of up to 20% for postoperative complications

The multidisciplinary approach of neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) and postoperative adjuvant chemotherapy has been accepted worldwide as the standard treatment for patients with LARC. Poor patient compliance with adjuvant chemotherapy is also a serious concern in clinical practice; therefore, the efficacy of adjuvant chemotherapy in rectal cancer treatment remains controversial. As expected, the treatment outcome of LACC is unsatisfactory. The 5-year overall survival (OS) rate is low and ranges from 13% to 73% depending on the invasion depth

and lymph node metastasis. Therefore, recently, neoadjuvant CCRT followed by surgical resection has also been proposed to treat LACC. Total neoadjuvant therapy (TNT) offers a chance to deliver aggressive treatment against the development and progression of micrometastases, potentially increasing survival rates in LARC. Furthermore, there is tremendous interest and desire for organ preservation in rectal cancer partly driven by patients who want to preserve a decent quality of life in the modern era. The TNT approach may facilitate a greater number of patients having the potential for organ preservation.

Conventionally, high ligation of the inferior mesenteric artery (IMA) is one of the important surgical steps in rectal or sigmoid colon cancer surgery. However, this technique may reduce blood flow in the bowel and increase the risk of ischemia and anastomosis leakage. Recently, some surgeons suggest the technique of low ligation of the IMA with preservation of the LCA. In addition, the metastatic rate of lymph nodes around the IMA was reported to be 0.3%–8.6% in patients with rectal cancer. Therefore, the routine ligation of IMA might be re-considered if it remained as a standard operative procedure. Herein, we will present our robotic-assisted high dissection and selective ligation of the IMA method, of which it leads to low postoperative complication rates, enables the harvesting of sufficient lymph nodes, and provides equivalent oncologic outcome compared with the conventional high ligation technique. Compared with laparoscopic surgery, robotics rectal cancer surgery is more favorable in regarding to clinical and short-term oncological outcomes and is suggested in several studies. Even in patients of LARC or mid to low rectal cancer received CCRT, robotic rectal surgery is still associated with at least comparable short-term surgical outcomes.

Symposium (VII)

Update of Chronic Liver Disease in Childhood

Early Biomarkers of Chronic HBV Infection

Jia-Feng Wu

Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

Hepatitis B virus (HBV) infection remains a global health hazard. Nearly 300 million people are chronically infected with HBV in the world, and approximately one million chronic HBV-infected people die annually from HBV-related causes. Noninvasive biomarkers are key to the development of curative HBV therapies in the future. Currently, only a few biomarkers are available for the prediction of HBV disease course and the treatment response. As some novel therapeutics become available in phase II and III trials, novel biomarkers for the monitoring of viral and host responses are urgently needed. The International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) held a virtual and interactive workshop on HBV biomarkers in 2020. The clinical utility of both classic and emerging viral and immunological serum biomarkers for the course of infection, disease progression, and response to current and emerging treatments was appraised. However, the majority of these biomarkers focused on chronic HBV-infected adults.

In an endemic area, such as Taiwan, the majority of chronic HBV infections started in childhood or even in infants. Early biomarkers in childhood play a pivotal

role in the life-long journey of chronic HBV infection. Our very-long term cohort followed from childhood till adulthood offers solution to the knowledge gaps from childhood to young adulthood. Our serial studies demonstrated the early entrance of the immune inflammatory phase and HBeAg seroconversion under 10 years of age are predictors of HBsAg loss in chronic HBV-infected children. The proportion of BCP mutation is positively correlated with HBeAgseroconversion age, which solves the puzzle about the ominous role late of HBeAg-seroconversion. HBeAg-seroconversion beyond childhood serves as an important risk factor for HBeAg-seroconversion and liver fibrosis in adulthood. Our recent study further demonstrated HBsAg titers in childhood, a surrogate marker of HBV cccDNA, is predictive of liver cirrhosis in adulthood.

With the identification of very early biomarkers of chronic HBV infection, we may further stratify the risk of chronic HBV infection from the very beginning of the life-long infection. Prompt monitoring and timely management of chronic HBV infection according to their specific risk is important in the precision medicine of chronic HBV.

Symposium (VII)

Update of Chronic Liver Disease in Childhood

Patient Centered Care of Wilson’s Diseases: Role of Pediatric Hepatologists

Ching-Feng Huang

Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan

Wilson’s disease, also known as hepatolenticular degeneration, arises from an autosomal recessive genetic disorder resulting from a mutation in the ATP7B gene. This mutation impairs hepatic copper excretion, leading to copper accumulation in various tissues. The condition is marked by cirrhosis, neurological manifestations, and the detection of Kayser-Fleischer rings in the eyes. However, the clinical presentation can vary significantly, encompassing incidental discoveries of abnormal liver enzymes to acute liver failure necessitating a liver transplant.

Pediatric patients may exhibit subtle findings, such as asymptomatic hepatomegaly, transaminitis, alterations in behavior, movement disorders, or difficulties in school performance. Pediatric hepatologists may often be the first specialists to recognize these symptoms and include Wilson’s disease as a crucial consideration in their differential diagnoses. Treatment for Wilson’s disease necessitates

lifelong dietary and medical management. Pediatric hepatologists possess strong communication skills that enable effective interaction with children and their families, a vital aspect in ensuring consistent treatment compliance.

Moreover, they have extensive knowledge in pediatric nutrition and development, allowing them to monitor and adapt treatment plans for medical control, including drug indications and appropriate dosages, tailored to each patient’s unique needs. With the long-term and meticulous care provided by pediatric hepatologists, many adolescents may be hesitant to transition to adult medical services.

Pediatric hepatologists not only deliver delicate and long-term care to children with Wilson’s disease but also earn the trust and confidence of their families. These factors contribute to providing the best therapeutic outcomes.

Symposium (VII)

Update of Chronic Liver Disease in Childhood

The Care of Biliary Atresia Infants after Hepatoportoenterostomy: From Bench to Bedside

Mao-Meng Tiao

Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Biliary atresia is a rare but severe disease and the most common cause for children to receive liver transplantation in Taiwan. We will discuss biliary atresia incidence and diagnosis using sonogram and stool color card. A case study on cystic biliary atresia history and operation. Molecular diagnosis using Matrix Metalloproteinase-7, Osteopontin and IL10, the prediction of jaundice-free outcome. Kasai

operation and redo kasai operation with two studies to share. The impact of post reperfusion syndrome on liver transplant outcome. The complications of post-kasai including Intussusception, diaphragmatic hernia post-liver transplant, and gastroesophageal varices. We will also discuss the psychological journey of biliary atresia families.

Symposium (VIII)

Beyond Fatty Liver in MAFLD

MAFLD in Lean Subjects and Impact of Chronic HBV Infection

Chih-Lin Lin

Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan

The clinical profile, natural history and pathophysiology of MAFLD in lean subjects are not well characterized. It can be caused by factors such as insulin resistance, genetic predisposition, or certain lifestyle choices. In a meta-analysis with 85 study showed that the prevalence of MAFLD in lean were 13.11% of the global population and 14.55% in Asia. The degree of metabolic dysfunction was significantly less in lean-NAFLD in lean subjects as compared with obese-NAFLD. In our recent study with 572 patients with histologically confirmed NAFLD, the prevalence of nonalcoholic steatohepatitis (NASH) were 22.5%, 25.93% and 36.19% in lean, overweight and obese NAFLD patients, respectively. Lean NAFLD patients had a higher proportion of no fibrosis (F0) than overweight and obese NAFLD patients (P=0.018). In both lean and obese patients with NAFLD, the fibrosis stage tends to increase in patients with definite NASH. Patients with NASH had a higher proportion of significant fibrosis (F2-F4) than non-NASH patients.

Regarding the impact of chronic HBV infection on MAFLD, chronic HBV infection can contribute to the progression of MAFLD. For example, in a communitybased cohort study reveal that concomitant steatosis in CHB patients was significantly associated with a higher risk of type 2 DM. However, whether concurrent MAFLD aggravates the disease severity in CHB patients remains controversial. In the prospective cohort studies with more than two-thousand male CHB patients in Taiwan, fatty liver at baseline was an independent protective factor for HCC development. In addition, CHB patient with MAFLD had higher HBsAg seroclearance rate than those with MAFLD. In summary, a proportion of lean patients with NAFLD have advanced fibrosis and liver cirrhosis. Regardless of the BMI, patients with NAFLD need to be closely followed to monitor the progression of fibrosis. Further research is needed to clarify the impact of concurrent MAFLD on long-term outcomes of patients with CHB.

Symposium (VIII)

Beyond Fatty Liver in MAFLD

Risk of Extrahepatic Diseases in MAFLD

Ming-Lun Yeh

Division of Hepatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a multisystemic disease. A wide spectrum of extrahepatic manifestations including type 2 diabetes mellitus (T2DM), metabolic syndrome, cardiovascular disease (CVD), chronic kidney disease (CKD), extrahepatic malignancies, obstructive sleep apnea, cognitive disorders, hypothyroidism, and polycystic ovarian syndrome are associated with MAFLD. The leading causes of mortality of MAFLD are CVD, followed by extrahepatic malignancies, diabetes, and liver-related mortality. The severity of extrahepatic diseases is correlated to the severity of MAFLD. It is important to identify high-risk patients earlier and be aware of the extrahepatic manifestations for initiating prompt and timely screening and management of the disease spectrum. Though

the current guidelines do not provide guidance on the management of extrahepatic manifestation of MAFLD, lifestyle modification especially weight loss remains the foundation of treatment for many of the extrahepatic manifestations associated with MAFLD. Meanwhile, MAFLD patients not only have an increased risk of hepatocellular carcinoma but of extrahepatic malignancies as well. Therefore, MAFLD patients should also be kept up to date on cancer screening. In conclusion, MAFLD must be evaluated as a multisystemic disease affecting many extrahepatic organs. Patients who were diagnosed as MAFLD should be evaluated for these extrahepatic diseases, especially the evaluation of CVD risk. Furthermore, treatment of dyslipidemia, T2DM, and hypertension is recommended to decrease the risk of CVD and CKD.

Symposium (VIII)

Beyond Fatty Liver in MAFLD

Reduction of CVD and DM Risk in MAFLD

Chia-Chi Wang

Department of Gastroenterology and Hepatology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan School of Medicine, Tzu Chi University, Hualien, Taiwan

Metabolic (dysfunction) associated fatty liver disease (MAFLD) is currently the most common chronic liver disease, and its prevalence is increasing due to the rising rates of obesity and diabetes. It was previously known as non-alcoholic fatty liver disease (NAFLD), but in 2020, new nomenclature and diagnostic criteria were proposed, renaming it as MAFLD. The diagnostic criteria are based on the evidence of hepatic steatosis by either imaging or histologic examinations, plus any of the following three conditions: overweight/obesity, presence of type 2 diabetes mellitus (DM), or evidence of metabolic dysfunction. It can lead to chronic hepatitis, fibrosis, cirrhosis, and even hepatocellular carcinoma. Additionally, it is associated with various extra-hepatic

manifestations, such as DM, cardiovascular diseases (CVD), osteoporosis etc. The top three causes of mortality in MAFLD patients are CVD, cancer, and liverrelated diseases. Therefore, reducing the risk of CVD and DM is crucial in managing patients with MAFLD. This presentation will focus on the incidence and potential mechanisms of CVD and DM development in MAFLD patients. It will also discuss strategies to decrease the risk of CVD and DM including lifestyle modification, pharmacological and surgical therapies. Additionally, we will introduce a new disease name and diagnostic criteria of metabolic associated steatotic liver disease (MASLD), proposed by the American Association for the Study of Liver Diseases recently.

Symposium (VIII)

Beyond Fatty Liver in MAFLD

Biomarkers of NASH and Advanced Liver Fibrosis

Wah Kheong Chan

Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the most common cause of chronic liver disease, contributing substantially to the burden of liver-related complications, including hepatocellular carcinoma. The presence of steatohepatitis indicates more severe liver disease that is associated with a higher risk of progression to fibrosis and cirrhosis, while fibrosis stage is the most important predictor of adverse clinical outcomes, with the risk increasing exponentially with increasing fibrosis stage. Liver biopsy is the reference standard for the diagnosis of steatohepatitis and fibrosis, but it is invasive, associated with a small risk of serious complications, and not feasible for routine clinical use for diagnosis, guiding treatment decision and monitoring of response. Therefore, various non-invasive tests have been developed for the diagnosis of steatohepatitis, especially fibrotic or at-risk steatohepatitis [defined histologically as steatohepatitis with non-alcoholic fatty liver disease (NAFLD) activity score ≥4 and

fibrosis stage ≥2], and advanced liver fibrosis. There are several notable prediction models for steatohepatitis, including models that are based on machine learning. Non-invasive tests for diagnosis of at-risk steatohepatitis include MACK-3, NIS2+ (optimized from NIS4), a composite model comprising four proteins (ADAMTSL2, AKR1B10, CFHR4 and TREM 2), SomaSignal, FAST and MAST. Non-invasive tests for diagnosis of advanced fibrosis include simple fibrosis scores (e.g., fibrosis-4 index, the NAFLD fibrosis score), the Hepamet fibrosis score, the Enhanced Liver Fibrosis test, FibroTest, FibroMeter, ADAPT, LSM-VCTE, Agile 3+ and MRE. Non-invasive tests have also been developed for the diagnosis of significant liver fibrosis (fibrosis stage ≥F2), for example the fibrosis-8 score, and the combination of MRE and FIB-4, called MEFIB. An understanding of the strength and weaknesses of the various non-invasive tests will enable us to use them effectively in day-to-day clinical practise for better patient care.

Symposium (IX)

Advance in the Microbial Therapeutic Interventions: From Next Generation Sequencing to Next Generation Probiotics

Gut-heart Therapeutics

Wei-Kai Wu

Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

Current understanding of the gut microbiota’s role in human health and disease has deepened, revealing its significant impact on the human body. The gut microbiota is implicated in the development of chronic inflammation, vascular plaque formation, and heightened thrombotic potential, all of which are crucial factors for cardiovascular health. Several metabolites, produced by gut bacteria breaking down food, are connected to conditions like atherosclerosis, hypertension, heart failure, chronic kidney disease, obesity, and type 2 diabetes. This suggests that the gut microbiome behaves similarly

to an endocrine organ, producing compounds that influence host health. In recent years, our research has centered on metabolic pathways of gut microbiota, especially the L-carnitine-mediated trimethylamine N-oxide production and identifying its associated gut microbes. This offers a potential explanation for the connection between red meat consumption and cardiovascular diseases. Furthermore, we propose a microbial gene-centric approach to precision nutrition and highlight emerging microbiome-based therapeutics for cardiovascular disease and explore their potential applications.

Symposium (IX)

Advance in the Microbial Therapeutic Interventions: From Next Generation Sequencing to Next Generation Probiotics

Gut-metabolism Therapeutics

Hsin-Chih Lai

Revive Biotechnology co., Taipei, Taiwan

The gut microbiome is a very important coordinator that closely interacts with the host. During the process of symbiosis, the gut commensals produce a repertoire of metabolites. This is achieved by using either exogenous dietary ingredients or endogenous host components. Alterations in the structure and function of the gut microbiota may result in change of the metabolites production, leading to initiation of many chronic inflammation related disorders. Important and functional metabolites may be produced in both extra- and intracellular manner. Important groups of microbiotaderived metabolites that affect host physiology comprise of proteins/amino acids, carbohydrates and lipids derived chemical components, secondary bile acids, as well as bacterial cell wall derived functional

proteins, glycolipids and polysaccharides. Among these, short-chain fatty acids, branched-chain amino acids, trimethylamine N-oxide, tyrosine, glutamate, and tryptophan derivatives etc. have been implicated in the modulation of host immunity together with metabolism. Production of aberrant metabolites may result in pathogenesis of metabolic disorders. In this presentation, the key groups of microbiotaderived metabolites whose concentrations are changed in association with metabolic diseases will be characterized. Their role in amelioration of host pathogenesis as well as for the development of new therapeutic intervention agents will be discussed.

Keywords: gut microbiome, metabolites, signaling, immune modulation, pathogenesis

Symposium (IX)

Advance in the Microbial Therapeutic Interventions: From Next Generation Sequencing to Next Generation Probiotics

Gut-brain Therapeutics

Chin-Hsien Lin

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan

Disturbances in the brain-gut axis are involved in the pathogenesis of many neurological disorders, including Parkinson’s disease (PD), one of the most common neurodegenerative disorders. Recent evidence indicates that the pathognomonic hallmark of PD, Lewy bodies, may start in the enteric nervous system and then spread to the central dopaminergic neurons through the vagus nerve. Another non-vagal route from gut microenvironmental changes also contributes to PD process. Consistently, the onset of gastrointestinal dysfunction may precede the motor symptoms of PD by decades. With the advent of metagenomic sequencing and metabolomic analysis, a plethora of evidence has revealed different gut microbiomes and gut metabolites in patients with

PD compared with unaffected controls. Currently, although dopaminergic treatments and deep brain stimulation can provide some symptomatic benefits for motor symptoms of the disease, their long-term use is problematic. A mechanism-targeted therapy to halt the neurodegeneration is lacking. The recently observed gut microenvironmental changes in the early stages of the disease play a vital role in the PD pathogenesis. Patients whose disease begins in the gut may benefit most from interventions that target the gut microenvironments. This talk will summarize the currently available evidence for targeting the gut microbiota as a novel approach as a potential diseasemodifying therapy for PD.

Symposium (X)

Advances in Treatment of Biliary Tract Cancer

Optimized Surgical Management of Perihilar Cholangiocarcinoma

Chun-Yi Tsai

Department of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

College of Medicine, Chang Gung University, Taoyuan, Taiwan

The prevalence of cholangiocarcinoma is increasing globally, yet the prognosis remains devastating stemming from tumor biology and the lack of specific signs for early diagnoses. Cholangiocarcinoma is categorized into intrahepatic, extrahepatic, and perihilar cholangiocarcinoma based on its anatomical location, which also determines the fashion of surgical management ranging from hepatectomy to pancreaticoduodenectomy (PD). Curative resection remains the most promising modality to provide long-term survival for cholangiocarcinoma; however, less than 40% of patients diagnosed of perihilar cholangiocarcioma (pCC) were feasible for curative resection owing to disseminated disease at diagnosis, unrelieved jaundice, insufficient future liver remnant (FLR), and invasion of the vital vessels.

To expand the resectability of pCCs, or, to optimize the preoperative conditions, various interventions were applied including aggressive biliary drainages, augmentation of FLR by percutaneous transhepatic portal vein embolization (PTPE), thorough review of perihilar anatomy, and administration of neoadjuvant chemotherapy in selective clinical scenarios. Above all, a multi-disciplined team is warranted. The surgical procedures were also standardized and integrated based on the primal Bismuth classification. For the laterally extended tumors, combined PD is warranted to achieve R0 resection. In the past 6 years, we performed 39 curative-intent resections for pCCs based on our established settings. We would like to share our surgical experiences, and your precious comments are welcomed to make the treatment to perfection in the future.

Symposium (X)

Advances in Treatment of Biliary Tract Cancer

Immunotherapy in Biliary Tract Cancers: Current Evidence and Future Perspectives

Wen-Kuan Huang

Division of Hematology/Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Cholangiocarcinoma (CCA) has a complex and immunosuppressive tumor microenvironment, with an abundance of myeloid cells like tumor-associated macrophages and myeloid-derived suppressor cells.

Four distinct “immune subtypes” of intrahepatic cholangiocarcinoma in the tumor microenvironment included immune desert (48%) with low infiltration and activity of immune cells, immunogenic type (11%) with massive infiltration of T cells and high immune checkpoint expression, myeloid type (13%) with enrichment of myeloid cells like macrophages and fewer T cells, and mesenchymal type (28%) with high abundance of cancer-associated fibroblasts. Monotherapy with PD-1/PD-L1 immune checkpoint inhibitors has shown very modest efficacy (5-10% response rates) in unselected CCA populations. Combining immunotherapy with chemotherapy

has shown improved outcomes compared to chemotherapy alone in phase 3 trials. The TOPAZ-1 trial showed improved overall survival, progressionfree survival, and response rate with durvalumab plus gemcitabine/cisplatin versus chemotherapy alone in previously untreated advanced CCA. The

KEYNOTE-966 trial demonstrated improved overall survival with pembrolizumab plus gemcitabine/ cisplatin versus chemotherapy alone in previously untreated advanced CCA. Based on these trials, the FDA approved durvalumab plus chemotherapy in 2022 and pembrolizumab plus chemotherapy in 2023 as first-line treatments for advanced CCA, providing a new standard of care. Ongoing studies are evaluating immunotherapy combinations with other anticancer agents and identifying predictors of immune response to guide patient selection.

Symposium (X)

Advances in Treatment of Biliary Tract Cancer

Molecular Testing and Targeted Therapy for Biliary Tract Cancers: Current Status and Perspectives

Nai-Jung Chiang

Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan

National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan

Biliary tract cancer (BTC) is an uncommon condition arising from the biliary epithelium found in the small ducts within the liver periphery (intrahepatic) and the primary ducts of the hilum (extrahepatic). In the Western world, the occurrence of intrahepatic carcinoma is on the rise, while gallbladder cancer is on the decline. Only a limited number of patients are eligible candidates for surgical intervention. For individuals with advanced or metastatic cases, systemic chemotherapy plus immune checkpoint inhibitors serve as the standard treatment. The median overall survival was around 12 months after first line systemic treatment. Nevertheless, there is a gradual shift in the treatment paradigm due to targeted therapy aimed at tumors harboring fusion

mutations in genes such as fibroblast growth factor receptor (FGFR), isocitrate dehydrogenase (IDH) 1 and 2, B-Raf protein (BRAF), BRCA1/2, epidermal growth factor receptor 2 (HER2), and neurotrophic receptor tyrosine kinase gene (NTRK). This transformation is particularly noticeable in the approach to managing BTC, especially for intrahepatic cholangiocarcinoma, which frequently presents with a high incidence of mutations/fusions. The objective of this talk is to present the most recent scientific evidence regarding the use of targeted therapy in the treatment of BTC and to have introduction of the T3221 study (the registry of genetic alterations of Taiwan BTC; NCT05036486) and currently available clinical trials in Taiwan.

Symposium (X)

Advances in Treatment of Biliary Tract Cancer

Personalized Endoscopic Treatment in Complex Malignant Hilar Biliary Strictures

Takao Itoi

Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan

Malignant hilar biliary stricture is a serious complication resulting from biliary tract cancer or other liver disease and is considered difficult to treat. Recent advances in endoscopic therapy have revolutionized the management of this disease, but treatment strategies have not yet been

standardized. In particular, endoscopic ultrasound enables better biliary drainage for complicated hilar biliary strictures in combination with endoscopic retrograde cholangiopancreatography. This talk will present videos and discuss individualized drainage techniques for complex, hilar strictures.

Symposium (XI)

Forum of Small Intestinal Disease: Immune-mediated Gastrointestinal Disorders

Immune-Checkpoint Inhibitor-Induced Enterocolitis

John Y Kao

Division of Gastroenterology & Hepatology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, Michigan, USA

With the promising results of immune checkpoint inhibitors (ICI) for the treatment of various types of cancer, gastroenterologists are increasingly

encountering immune-related adverse events (irAEs). This lecture will review the clinical presentation, diagnosis, and management of ICI colitis.

Symposium (XI)

Forum of Small Intestinal Disease: Immune-mediated Gastrointestinal Disorders

Eosinophilic Enterocolitis

Chen-Shuan Chung

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

Eosinophilic enterocolitis is a rare disease entity with an unclear pathogenesis. It is caused by an intestinal infiltration of eosinophils into gastrointestinal wall that can cause clinical manifestations, such as abdominal pain, diarrhea, malabsorption and less frequently, ascites or obstructive symptoms. The diagnosis is sometimes challenging but mainly based on combination of

information from clinical and histological findings as well as the exclusion of other common causes of intestinal eosinophilia, for example, infection, inflammatory disease, drug reaction or food allergies. In this lecture, I will briefly introduce the diagnosis and management of eosinophilic enterocolitis and present some case sharing.

Symposium (XI)

Forum of Small Intestinal Disease: Immune-mediated Gastrointestinal Disorders

Celiac Disease

Tien-Yu Huang

Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Celiac disease, an autoimmune disorder triggered by the consumption of gluten, presents a complex and evolving landscape of diagnosis and treatment. This presentation aims to provide a comprehensive overview of the latest insights into the diagnosis and treatment of this condition.

Celiac disease diagnosis has seen significant advancements in recent years. We will explore the various diagnostic methods, including serological tests measuring specific antibodies like antitissue transglutaminase (tTG) and anti-endomysial antibodies (EMA). Additionally, genetic testing for HLADQ2 and HLA-DQ8 markers plays a role in identifying individuals at risk. However, a definitive diagnosis still relies on histopathological examination of small intestinal biopsies, highlighting the importance of collaboration between clinicians and pathologists.

The cornerstone of Celiac disease management

remains a strict gluten-free diet. We will delve into the challenges patients face in maintaining this diet and discuss strategies for dietary compliance, such as education, support groups, and access to glutenfree products. Furthermore, we will address the importance of monitoring nutritional deficiencies that can arise due to malabsorption.

Emerging therapies offer hope to those with refractory Celiac disease or those who struggle with dietary adherence. These treatments include glutendegrading enzymes and immunomodulatory drugs. We will explore the potential benefits and limitations of these approaches.

Finally, we will touch upon the necessity of regular follow-up and monitoring for patients with Celiac disease. This involves assessing symptom control, nutritional status, and the resolution of mucosal damage through repeat biopsies if necessary.

Symposium (XI)

Forum of Small Intestinal Disease: Immune-mediated Gastrointestinal Disorders

Intestinal Behçet’s Disease

Chia-Jung Kuo

Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Behçet’s disease (BD) is an idiopathic, chronic, relapsing, multi-systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, ocular disease and skin lesions. BD with predominant gastrointestinal manifestations is diagnosed as intestinal BD, which is associated with severe complications such as massive gastrointestinal hemorrhage, perforation, and obstruction. Any part of the gastrointestinal tract can be involved. The most common location of intestinal BD is the ileocecal area.

Intestinal BD and CD commonly have a young age of onset, nonspecific GI symptoms, similar extraintestinal manifestations. These lesions of intestinal BD may involve the terminal ileum and

cecum and may therefore be difficult to differentiate from CD. The ulcers in intestinal BD tend to be larger and deeper than those in Crohn’s disease, whereas stricture formation and fistulae are more frequently observed in cases of Crohn’s disease. Giant ovalshaped deep punched-out ulcer in the ileocecal area is characteristic endoscopic findings of intestinal BD. Currently, there is no single gold standard test or pathognomonic finding of intestinal BD. As intestinal BD shares a lot of characteristics with inflammatory bowel disease, distinguishing between the two diseases in clinical practice is quite difficult but important.

Symposium (XII)

Update on Colorectal Cancer Screening and Prevention

Age to Start and Stop Colorectal Cancer Screening: What Has Been Changed?

Su Young Kim

Division of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea

Regarding colorectal cancer (CRC) screening, several factors must be considered, with age being the most significant. Traditionally, the starting age of CRC screening has been known to be 50 years old. However, according to the recently revised contents of the US Preventive Services Task Force (USPSTF), it is recommended to lower the starting age of CRC screening to 45 years old. There are a number of causes for this shift, but the most significant is thought to be an increase in the incidence of early-onset CRC. In addition, the rates of advanced colorectal neoplasia in 45 to 49 year olds at average risk are comparable to those observed in 50 to 59 year olds screening populations. To begin CRC screening at such a young age, however, evaluation of cost-effectiveness and regional characteristics must be considered, and additional follow-up studies are required. Concerning

the age at which CRC screening is discontinued, there have been few studies and a circumspect approach is being taken. There are updated recommendations for the age at which to begin screening, but there are limited recommendations for determining when to cease. According to USPSTF recommendations, it is recommended to selectively screen adults aged 76 to 85 years. For patients older than 85 years, screening is discouraged because the risks outweigh the benefits. The overall benefit of screening in elderly population is decreases, and it is necessary to individualize screening recommendations based on comorbidities, functional status, and screening history, rather than basing them solely on age. In this presentation, we’d like to discuss changes in CRC screening recommendations based on age, as well as unresolved issues.

Symposium (XII)

Update on Colorectal Cancer Screening and Prevention

Stool-Based Tests Versus Colonoscopy for Colon Cancer Screening

Wen-Feng Hsu

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Colorectal cancer is one of the most common cancers globally, underscoring the need for effective screening strategies for early detection and subsequent treatment. Both colonoscopy and stool-based tests have been empirically validated as cost-effective modalities for colorectal cancer screening. Nevertheless, there is a notable discrepancy in participation rates between these two methods. A comparative analysis of the efficacy, cost-effectiveness, and patient compliance of stoolbased tests and colonoscopies is crucial, particularly as these factors can vary significantly across different countries. Colonoscopy is often regarded as the gold standard due to its high diagnostic accuracy;

however, stool-based tests provide a less invasive and more convenient alternative, which may be more palatable to certain patient demographics. Factors contributing to the variance in participation rates include the invasiveness of the procedure, preparatory requirements, and the level of discomfort associated with colonoscopy. Moreover, the availability and cost of medical resources differ internationally, potentially affecting the relative effectiveness of each screening approach. A comprehensive evaluation of these variables is essential for guiding healthcare providers and policymakers in the development of optimized colorectal cancer screening protocols that are tailored to specific demographic and healthcare contexts.

Symposium (XII)

Update on Colorectal Cancer Screening and Prevention

Post-colonoscopy Colorectal Cancer: How to Predict and Reduce

Jae Myung Cha

Gastroenterology Division, Kyung Hee University Hospital at Gang Dong, Seoul, Korea

Introduction

Colonoscopy is the gold standard for colorectal cancer (CRC) screening. However, as demonstrated in studies with tandem colonoscopy and CT colonography, high miss rate is a weak point of colonoscopy. According to the World Endoscopy Organization (WEO) consensus statement, postcolonoscopy CRC (PCCRC) can be defined as a CRC detected after a negative colonoscopy, in which no cancer was diagnosed.1 It can be subcategorized into interval cancer and non-interval cancer. PCCRC rate for an interval of 3 years is recommended for consistency and to permit benchmarking. In National Health Registry of Denmark, 80.5% was missed lesion, prior examination adequate and 4.7% was also missed lesion, prior examination inadequate for root causes of 762 PCCRC cases. In addition, 3.4% was detected lesion, not resected and 11% was detected lesion, incompletely resected. Compared detected CRC, PCCRC group were more likely to be old age, female sex, rural residence, higher Charlson comorbidity score, more colon location, more emergency presentation, more no resection and higher perioperative mortality in the Canadian study. In addition, compared with detected CRC, PCCRC was associated with a higher risk of stage IV disease and worse 5-year survival. In a population-based study from South Korea, clinical characteristics and overall survival were very similar to those of Canadian data.2 Compared with the detected CRC, PCCRC group were more likely to be old age, more proximal tumor location, and more no surgical resection. In addition, 5-year survival rate of PCCRC was worse than those of screening based detected CRC. Previous survival data of PCCRC 3years was duplicated in this Veterans Affairs

Medi-care data. In this study, all-cause mortality as well as CRC specific mortality were significantly worse in PCCRC group than those of detected CRC group.

Main body

• Endoscopist specialty

In the multivariate model generalized estimating equation logistic predicting PCCRC, the endoscopist specialty, such as non-gastroenterologist, and setting of a colonoscopy, such as non-hospital-based colonoscopy, were associated with the development of PCCRC. However, endoscopist volume was not associated with the risk of PCCRC. In a Canadian study,3 annual endoscopist colonoscopy volume was not associated with the risk of interval cancer. However, endoscopist specialty, such as non-gastroenterologist at hospital setting, was at increased risk of interval cancer. In a population-based study from Ontario, colonoscopy performed by general surgery, internal medicine, or family practice compared with gastroenterology and colonoscopy setting at office rather than hospital setting was independent risk factors for interval cancer. Similar to previous studies, surgical endoscopist is a predictive factor for PCCRC3yr compared with medical endoscopist in Hong Kong study. These studies showed us that endoscopist specialty is essential to reduce PCCRC.

• Endoscopy quality

In a recent US study, physicians with higher adenoma detection rate (ADR) had significantly lower risk of PCCRC.4 It was similar to previous study in that the risk of PCCRC and PCCRC related death were lower in physicians with higher ADR, when compared with physician with lower ADR less than

20%. In comparison to endoscopists in the lowest ADR quintile, endoscopists with highest ADR quintile had 48% less risk of interval cancer, 57% less risk of advanced stage interval cancers, and 62% less risk of fatal interval cancers. There was a 3% reduction in PCCRC incidence and a 5% reduction in PCCRC mortality with each 1% increase in ADR. ADR may be increased with optimal withdrawal time, monitoring withdrawal time, optimal withdrawal technique and new withdrawal technology. When withdrawal time is less than 6 minutes compared with withdrawal time more than 6 minutes, 2.3 times more interval cancers are encountered during colonoscopy. In a Minnesota Cancer Surveillance System, however, the incidence of interval cancer increased when the withdrawal time is less than 8 minutes as well as 6 minutes. So, withdrawal time 6 minutes should be considered as a minimal requirement. When ADR was compared between endoscopists unware of being monitored versus aware of being monitored the withdrawal time, awareness of withdrawal time monitoring itself significantly increased ADR from 21% to 36%, and monitoring was the strongest factor associated with ADR in the multivariate analysis. Optimal withdrawal time is not just about increasing time, but, it’s more about how to use withdrawal time!! Therefore, withdrawal time should be combined with optimal withdrawal technique, such as 1) fold examination, 2) distension, and 3) cleansing. Low ADR group had a lower withdrawal technique score compared with the moderate and high ADR group. In addition, new withdrawal technology such as Endocuff, Endoring and Computer Aided Detection may more increase ADR than standard colonoscopy.

How about cecal intubation rate? The endoscopists with high completion rate are less likely to have proximal and distal PCCRC. Therefore, cecal intubation rate as well as ADR may decrease the risk of PCCRC. Recently, proximal serrated polyp detection rate (PSPDR), has been proposed as a quality indicator for PCCRC. In a recent study, hazard ratios for PCCRC was adjusted according to quintile of PSPDR, cancer stage, sex, and location. In this study, PSPDR was inversely associated with the incidence of PCCRC, and PCCRC rate was 7% lower for each 1% increase in PSPDR. PCCRCs were more often proximally located, smaller in size, and more often flat than prevalent CRCs. To reduce PCCRC, we should

carefully examine the flat, small lesions at proximal colon. In many studies, interval cancers were more frequently detected in the right-sided colon, and flat, non-polypoid neoplasia was a risk factor of PCCRC. One of the most typical flat, non-polypoid lesion is a sessile serrated lesion (SSL). They could be missed during colonoscopy, potential for rapid progression, and incompletely resected during polypectomy. So, SSL likely contribute to the development of PCCRC. In patients with suboptimal bowel preparation, perpatient adenoma miss rate was significantly higher in the right colon than the left colon. To reduce PCCRC, to optimize bowel preparation not to miss adenoma in the right colon. To optimize preparation, a lower fiber diet, enhanced instruction, golden timing with 2-5 hours interval, and split dose regimen is essential.

• Complete resection

In the famous CARE study, the rate of incomplete resection for neoplastic polyps ranged from 6.5% up to 22.7%. Incomplete resection may contribute to the development of interval cancers.5 Similarly, 31% of interval cancers occurred in segment of colon with prior polypectomy, which means that incomplete resection at index colonoscopy may contribute to development of PCCRC. In addition, 27% of PCCRCs developed at the same segment of colon where previous polypectomy was done, and 67% of them were located at the right colon. According to CARE study, large, flat, and sessile serrated lesions are risk factors of incomplete resection. In the European study, tubulovillous/villous histology and high grade dysplasia were risk factors of PCCRC due to incomplete adenoma resection.

Conclusions

Endoscopist specialty is essential to reduce PCCRC. Colonoscopy quality, such as ADR, optimal preparation, optimal withdrawal time and technique is matter to reduce PCCRC. Complete resection is also necessary to reduce PCCRC.

References:

1. Rutter MD, Beintaris L, Valori R, et al. World Endoscopy Organization consensus statements on post-colonoscopy and post-imaging colorectal cancer. Gastroenterology. 2018;155:909-925.

2. Cha JM, Kim HS, Kwak MS, et al. Features of

postcolonoscopy colorectal cancer and survival times of patients in Korea. Clin Gastroenterol Hepatol. 2019;17:786-788.

3. Rebeneck L, Paszat LF, Saskin R. Endoscopist specialty is associated with incident colorectal cancer after a negative colonoscopy. Clin Gastroenterol Hepatol. 2010;8:275-279.

4. Schottinger JE, Jensen CD, Ghai NR, et al.

Association of physician adenoma detection rates with postcolonoscopy colorectal cancer. JAMA. 2022;327:2114-2122.

5. Pohl H, Srivastava A, Bensen SP, et al. Incomplete polyp resection during colonoscopy results of the complete adenoma resection (CARE) study. Gastroenterology. 2013;144:74-80.

Symposium (XII)

Update on Colorectal Cancer Screening and Prevention

Lifestyle Intervention for Preventing Colorectal Cancer

Hao-Yu Wu

Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan

Outline

• Introduction to colorectal cancer

• Common risk factors for colorectal cancer

• Protective factors for colorectal cancer

• Healthstyle connection with colorectal cancer

• Preventive strategies

• Conclusions

Introduction

• “Colorectal cancer” (CRC) – progressive cancer, slow onset, tumor on the inner lining of the rectum or large intestine

• It is the 3rd commonest malignancy after cancer of the prostate and lungs in males and after breast and lung in females in the US

• Rare in 1950, predominant cancer now, Accounts for 10% of cancers in males, 9.4% in females. Cancer mortality of 8%

• Worldwide incidence is 1.2million annually and half die of the disease.

Common Risk Factors for CRC

• Obesity

• Diet – Red and processed meat

• Smoking

• Alcohol

Protective Factors for CRC

• Physical activity

• Diet – Calcium, fiber, milk, and whole grains are associated with a lower CRC risk

Conclusions

• Colorectal cancer – one of the most common, deadly carcinomas; incidence and prevalence likely to increase in the coming years

• CRC is exacerbated by obesity, poor dietary habits, a sedentary lifestyle, smoking and alcohol consumption

• Current data support healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention

• Lifestyle modifications, screening, and early diagnosis – major decrease in mortality and will do so in the future

Symposium (XIII)

Novel and Optimizing Therapy on HCC

How to Use TKI for Long-term Administration

Yuan-Hung Kuo

Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death globally and the second leading one in Taiwan. Symptomatic HCC patients are usually diagnosed in an advanced stage with major vascular invasion or extrahepatic metastasis, so that most of them are unsuitable for curative treatments and possess an unfavorable prognosis. For patients with unresectable advanced HCC, systemic therapies are the main recommended treatment option.

According to the solid findings of clinical trials, atezolizumab plus bevacizumab or durvalumab plus tremelimumab are currently the recommended firstline systemic treatment options, while tyrosine kinase inhibitors (TKI) including sorafenib or lenvatinib are used as first-line treatment options only in cases where immunotherapeutic agents are not feasible. However, the high cost of combined immunotherapies confines its clinical application, leaving sorafenib or lenvatinib as the most common treatment for advanced HCC in clinical real life.

Therefore, understanding how to use TKIs for long-term administration is important for patients with advanced HCC. Several viewpoints exist regarding long-term TKI administration, including adequate patient selection, multidisciplinary teamwork, intensive monitoring of treatment response or treatment-related adverse effects (TRAEs), timely management of TRAEs, combination strategies with other immunotherapies or locoregional treatments, maintaining adherence and patient support, and encouraging participation in new clinical trials, among others.

In conclusion, the long-term administration of TKI for patients with advanced HCC is a critical issue that requires a multidisciplinary approach. By closely monitoring patients, personalizing treatment plans, exploring combination therapies, providing patient support, and addressing financial concerns, it is possible to optimize treatment outcomes and improve the overall survival of patients living with advanced HCC.

Symposium (XIII)

Novel and Optimizing Therapy on HCC

How to Use ICI-based Therapy for Long-term Administration

Teng-Yu Lee

Division of Gastroenterology& Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

Immunotherapy, i.e. immune checkpoint inhibitor (ICI), has been the standard of treatment for advanced hepatocellular carcinoma (HCC), and the median overall survival time has been expected to be as long as two years in the management prospective of the BCLC guidelines. Moreover, a small proportion of patients may achieve a complete response to ICI therapy, and a long-term patient survival is not just a dream. However, the ideal or cost-effective duration of ICI therapy remains undetermined. On the other hand, even though ICI-based therapy can produce a more durable response than those treated with other medical therapies, only around 30% of patients may obtain an objective response to current ICI-based regimens. Therefore, for the long-term administration in patients with advanced HCC, a following-line, i.e., second-line, third-line, or even higher-line systemic therapy, should be promptly and adequately chosen after a failed ICI therapy. Nonetheless, even though we can observe that the mean patient survival time of the control arms using the same medication in the different clinical trials has been prolonged, which may indicate a more and more effective treatment by the

following-line HCC therapies after tumor progression, strong evidence to recommend a standard followingline treatment after ICI-based therapy failure remains lacking. Therefore, except expecting new data from the clinical trials in the future, a more effective treatment strategy by using current treatment weapons in hands should be developed in the realworld practice. Nowadays, more and more weapons for the treatment of HCC, such as tyrosine kinase inhibitor (TKI), locoregional treatment (LRT), and surgical interventions, have been developed and experienced, and a proportion of patients, who received ICI combination or sequential treatments have been reported to achieve a tumor-free status, socalled “curative conversion”, after ICI-based therapy. In patients with a curative conversion response, both tumor progression-free survival and overall patient survival can be significantly prolonged. However, the ideal combination or subsequence of treatment choice remains undetermined. In this talk, the strategy of IObased treatment for the long-term administration in advanced HCC will be comprehensively reviewed and discussed.

Symposium (XIII)

Novel and Optimizing Therapy on HCC

Proton-bean Therapy for HCC

Bing-Shen Huang

Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan

Hepatocellular carcinoma (HCC) is one of the most common cancers in the world. Most HCC patients have impaired liver function because of hepatitis or liver cirrhosis, and only approximately 2040% of patients are candidates for resection. Maximal preservation of normal liver volume and function is an important consideration in the choice of treatment.

Proton beam therapy (PBT) for HCC treatment has been applied for decades, and many clinical results have shown excellent 3-year to 5-year local control (LC) rate ranging from 85-95% and nearly no major complications.

From 2015 to 2023, more than 6000 patients were treated with PBT at Chang-Gung Memorial

Hospital. More than a quarter of patients have liver cancers. The PBT was considered in the patients that were not suitable for surgery or radiofrequency (RFA) and discussed in the multidisciplinary conference. The PBT dose were 72.6CGE/22fx and 66CGE/10fx, depending on tumor location. The largest tumor diameter was more than 5 cm, and more than 30% of tumors are larger than 10 cm in diameter. More than 40% were major tumor vascular invasion. The in-field control rate was was more than 90%.

According to previous clinical results and our experiences, PBT can be a good alternative treatment for patients unsuitable for surgery.

Symposium (XIII)

Novel and Optimizing Therapy on HCC

Adjuvant Therapy for HCC after Curative Therapies

Yu-Yun Shao

Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan

Multiple new systemic therapies, mainly combination immunotherapy, have been proven effective for advanced hepatocellular carcinoma (HCC) with improved treatment efficacies compared with previous single-agent multikinase inhibitors. It is reasonable to consider these effective treatments in patients with earlier stage HCC. The interim analysis results of the phase 3 clinical trial IMbrave050 showed that bevacizumab plus atezolizumab treatment for

1 year after curative surgery of high-risk HCC could reduce the 1-year recurrence-free survival (RFS) rate but the 2-year RFS rate was similar between the experimental and the control group. Updated results of the IMbrave050 study and the results of other phase 3 clinical trials testing immunotherapy with or without targeted therapy as adjuvant treatment will confirm whether adjuvant therapy is truly required for patients with high-risk HCC after curative surgery.

Symposium (XIV)

Quantitation Imaging Study for Digestive Disease

MR Elastography for Evaluation of Liver Fibrosis

Chen-Te Chou

Department of Medical Imaging, Changhua Christian Hospital, Changhua, Taiwan

Liver fibrosis causes an alteration of liver parenchyma with the progressive deposition of extracellular matrix proteins in the liver that is an important cause of morbidity and mortality for patients with chronic liver disease. Liver fibrosis may progress to cirrhosis, which constitutes a highrisk factor of hepatocellular carcinoma and hepatic decompensation. Because fibrosis is a dynamic and potentially reversible process, early diagnosis and continual monitoring disease progression are imperative to initiate therapy and halt progression, respectively. Liver biopsy has been the standard for evaluating the stage of liver fibrosis8. However, this method is costly, suffering from interobserver variability, sampling errors, and low patient

acceptance with risks of pain and complications. As such, there is a need for non-invasive methods to precisely identify fibrosis stages, quantify disease severity and can potentially provide insight into prognosis and treatment response.

Magnetic resonance elastography (MRE) has been applied in liver fibrosis staging. This imaging technique can potentially offer an important means to measure liver fibrosis and severity of chronic liver disease. It is a modified phase-contrast technique which is developed for characterizing the elasticity of tissues. MRE can assess liver fibrosis using an elastography method by making the propagation of shear waves through tissues to measure liver stiffness.

Symposium (XIV)

Quantitation Imaging Study for Digestive Disease

Computed Tomography–based Gastric Volumetry for Morbid Obesity to Assess Weight Loss and Fatty Liver Change

Chih-Horng Wu

Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

Laparoscopic sleeve gastrectomy (LSG) is an effective treatment for patients with morbid obesity, but the optimal gastric volume (GV) for resection remains unclear. Accordingly, we aimed to determine the optimal percentage of excised stomach that could engender significant weight loss and improve fatty liver.

This prospective study included 63 patients. Computed tomography (CT) scans were performed before and 1 year after LSG to evaluate the gastric lumen (GL) and GV. Specifically, the stomach was distended with effervescent powder, following water–contrast mixture (20:1) and assessed by threedimensional reconstruction. The correlations of reduced gastric lumen/volume (RGL/RGV) with total body weight (BW) loss and liver–spleen density ratio (LSDR) changes were analyzed, and optimal RGL/RGV associated with significant BW and fatty liver changes were determined.

We noted a positive correlation between

the percentage of RGV/RGL (%RGV/%RGL) and percentage of total weight loss (%TWL; r = 0.359, p = 0.004 and r = 0.271, p = 0.032). Furthermore, a %RGL value of >78.2% and %RGV value of >75.3% were associated with more significant BW loss than did limited excision (both p < 0.01). On the other hand, LSDR values increased significantly after LSG, corresponding to the improvement of fatty liver disease at %RGL and %RGV values of >59.1% and >56.4% (both p < 0.01), respectively.

%RGV and %RGL were determined to be factors affecting LSG outcomes. LSG engendered significantly more BW loss when %RGV was >75.3% and resulted in fatty liver disease improvement when %RGV was >56.4%.

Keywords: Computed tomography, Volumetry, Morbid obesity, Laparoscopic sleeve gastrectomy, Fatty liver

Symposium (XV)

Advances in Endoscopic Treatment for GI Neoplasia

Endoscopic Resection for Gastric Submucosal Tumor

Noriya Uedo

Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan

Although endoscopic resection of early gastric cancer is extremely popular in Japan, there is limited evidence regarding the safety and efficacy of endoscopic resection of gastric submucosal tumors (SMT). To elucidate safety and efficacy of endoscopic full-thickness resection (EFTR) for gastric SMTs, a prospective multicenter study was conducted in seven Japanese tertiary centers. Indicated of EFTR for SMT was size 11–30 mm, either histologically proven Gastrointestinal stromal tumors (GIST) or clinically suspicious GIST (irregular margin, increasing size, or internal heterogeneity), with no ulceration, and intraluminal growth. A total of 46 patients with 46 lesions were enrolled from September 2020 to May 2023. The mean (range) endoscopic tumor size was 19 ± 4.5 (11–28) mm. The mean resection and

wound closure times were 54 ± 26 (22–125) min and 33 ± 28 (12–186) min, respectively. Complete endoscopic resection was achieved in all 46 lesions (100%). The full-thickness resection rate was 93%, and 21 patients (46%) required abdominal paracentesis for decompression. Endoscopic resection was completed for all lesions without the need for surgical intervention. One patient had delayed perforation and was managed endoscopically. GIST accounted for 76% of the lesions. R0, R1, and RX rates were 33 (77%), 3 (6.5%), and 7 (15%), respectively. EFTR for gastric SMT size ≤ 3 cm is technically feasible as evidenced in Japanese clinical practice. This warrants further validation in a large-scale prospective cohort study to determine the effectiveness of this treatment for gastric GIST.

Symposium (XV)

Advances in Endoscopic Treatment for GI Neoplasia

Device-assisted Endoscopic Resection in the GI Tract

Wei-Chen Tai

Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gang Memorial Hospital, Kaohsiung, Taiwan

During advanced endoscopic resection (ESD and EMR), gravity and the hood attached to the endoscope tip are always to be used to achieve traction and obtain the visual field. However, especially in difficult cases with insufficient methods, a prolonged procedure time of ESD may result in high perforation risk and operation related complications. Many traction devices have been developed to resolve these issues.

Device-assisted ESD may shorter the procedure time than in conventional ESD. Traction device-assisted ESD with traction methods such as the clip-with-line method, Spring-and-loop with clip method (S-O clip, Zeon Medical, Tokyo, Japan), or the clip pulley method (modified clip-with -line method) are all effective for upper GI and lower GI tract ESD.

Symposium (XV)

Advances in Endoscopic Treatment for GI Neoplasia

Cold versus Hot Snare Polypectomy for Small Colorectal Polyps: The Efficacy and Safety

Li-Chun Chang

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Colorectal cancer (CRC), globally recognized as the third most common cancer, often originates from colorectal polyps. The timely removal of these polyps through polypectomy plays a pivotal role in curbing the progression to CRC. Historically, the go-to technique has been hot snare polypectomy, utilizing electrocautery to encircle and remove the lesion. While its efficacy is established, due to its thermal nature, the method sometimes results in complications like perforation and delayed bleeding.

It is emerging as a promising alternative to cold snare polypectomy. This method bypasses electrocautery, relying instead on mechanical resection. It’s conceivable to lower the occurrence of related complications by eliminating the thermal aspect. A flurry of recent studies has delved into this technique, comparing it with the conventional hot snare method regarding safety, effectiveness, procedure time, and specimen retrieval.

Initial findings have been encouraging. Cold snare polypectomy not only showcases a favorable safety profile, potentially reducing risks of delayed bleeding but also seems effective in ensuring complete histological eradication of polyps. Moreover, in a demanding clinical setting where time is of the essence, cold snare polypectomy appears efficient, with procedure durations and specimen retrieval rates comparable to the hot snare technique.

Given the substantial occurence of small and diminutive colorectal polyps, choosing the right removal strategy is crucial. The debate surrounding cold snare polypectomy isn’t just academic but holds tangible implications for patient care. As more evidence surfaces, clinicians are poised to refine their approach, optimizing polyp treatment to ensure enhanced patient outcomes. The momentum behind cold snare polypectomy suggests it might soon become a primary method in the fight against CRC.

Symposium (XV)

Advances in Endoscopic Treatment for GI Neoplasia

Underwater Endoscopic Mucosal Resection for Large Colorectal Lesions: A Bridge Between Conventional Endoscopic Mucosal Resection and Endoscopic Submucosal Dissection

Yutaka Saito

Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan

Underwater EMR (UEMR) is rapidly becoming popular these days. It was first reported by Binmoeller KF et al. and has since spread mainly in the West. Meta-analyses and RCTs have reported higher en bloc resection and R0 resection rates for UEMR compared to conventional EMR, and there have been several reports of its usefulness from Japan.

However, the en bloc resection rate is not satisfactory for tumors larger than 2 cm, especially for LSTs ≥ 3 cm. Therefore, the utility of UEMR as a bridge between EMR and ESD for 2-3 cm lesions that are usually difficult to resect en bloc by EMR and for which ESD may or may be too much, is attracting attention. On the other hand, hybrid ESD or precutting EMR1 is available for similar targets. This method is also expected to shorten the time required for en bloc resection by not dissecting until the end, but the en bloc resection rate decreases when the tumor diameter exceeds 3 cm. Therefore, UEMR and hybrid ESD are expected to bridge the gap between EMR and ESD. One concern with UEMR is the ability to perform R0 resection of early-stage cancers and NPG-

type tumors, especially those with negative deep margins.2

We have developed a underwater EMR with submucosal injection (UIEMR),3 which is an EMR technique with submucosal injection under water condition, to address these concerns. In this session, I would like to show the actual application of UIEMR.

References:

1. Sakamoto T, Matsuda T, Nakajima T, et al. Efficacy of endoscopic mucosal resection with circumferential incision for patients with large colorectal tumors. Clin Gastroenterol Hepatol. 2012;10:22-6.

2. Saito Y, Takamaru H, Toyoshima N. Resection depth: a very important advantage for underwater EMR. Endosc Int Open. 2022;10:E729-e730.

3. Hirata S, Toyoshima N, Takamaru H, et al. Underwater endoscopic mucosal resection with submucosal injection. Endoscopy. 2023;55:E70-e71.

Symposium (XVI)

Updating Progress of Management for Hepatitis B Virus

Promising Novel Treatment for HBV Infection

Man-Fung Yuen

Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong

At present, nucleos(t)ide analogue (NA) is the mainstay treatment for chronic hepatitis B (CHB) infection. Long-term NA treatment is able to suppress HBV DNA level, and hence reduces the rate of development of end-staged liver disease including hepatocellular carcinoma and cirrhosis. Currently, the advanced aim for CHB treatment is to enhance the rate of functional cure which is defined as HBsAg seroclearance and undetectable HBV DNA for at least 24 weeks after all-treatment cessation. This target however, requires HBsAg reducing property from novel antiviral agents.

Small interfering RNAs (siRNA) or anti-sense oligonucleotides (ASO) are effective in knocking down the viral mRNA transcriptional activities. Rapid, profound and sustained suppression of HBV DNA levels, HBV RNA levels and HBsAg, HBeAg, HBcrAg levels are observed in patients receiving different regimens of these two groups of agents. Achievement of functional cure has been observed in 9 – 10% patients receiving ASO. Around 60 to 80% of patients could achieve HBsAg level < 100 IU/mL. Further improvement of the rate of functional cure has been shown by using combination of siRNA with pegylated interferon alpha.

Core protein allosteric modulators (CpAM)/ core inhibitors is another class of novel antiviral agent. These compounds are able to interfere the HBV encapsidation process and hence affects the multiple important functions of the HBV core protein including intranuclear cccDNA replenishment. Fourweek treatment of the newest CpAM is able to reduce

the HBV DNA by > 3 logs with a similar magnitude of reduction of HBV RNA levels. Recently, 4-week treatment of more potent CpAM used in HBeAgpositive patients was found to have promising effect on reduction of HBsAg. It is anticipated that more long-term treatment using CpAM would not only reduce HBV DNA and HBV RNA, it would also reduce the HBsAg levels especially in HBeAg positive patients.

By blocking the exit of subviral particles and degrading them intracellularly, HBsAg release inhibitors have been shown to achieve a high rate of HBsAg seroclearance and a good chance of achieving positive antibody against HBsAg (anti-HBs). More evidence is eagerly awaited from other studies.

Anti-PDL1 treatment has been proven to be associated with HBsAg reduction and HBsAg loss particularly observed in patients with low baseline HBsAg levels. However, non-selective anti-PDL1 was associated with a fairly high rate of thyroid disorders. Therapeutic vaccines particularly combined with antiPDL1 also showed some initial promising results. Liver selective/targeting anti-PDL1 is expected to have higher benefit to risk ratio for CHB disease.

In conclusion, many new agents have shown initial promising antiviral effects by targeting against different steps of the HBV life cycle. The future challenge would be on the design of treatment strategy using these new agents once their long-term efficacy and safety have been established. Important considerations would be patient populations, different drug combinations, sequences of administration and duration of treatment.

Symposium (XVI)

Updating Progress of Management for Hepatitis B Virus

Prediction Value of Non-invasive Biomarkers in HBV Natural and Treatment Outcomes

Tai-Chung Tseng

Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

Accurate prediction of hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) infection is crucial, aiding timely decisions on antiviral treatment for chronic hepatitis B (CHB) patients. Current guidelines recommend antiviral treatment for immune-active CHB patients, but not for inactive CHB patients. Yet, over half of HBeAg-negative patients fall into the “grey zone” (GZ).

In the early phase of chronic HBV infection, HBeAg-positive patients are “immune-tolerant” due to active viral replication without significant liver damage. Recent data present conflicting HCC risk for immune-tolerant patients, placing them in GZ. We combined ERADICATE-B and REVEAL-HBV cohort data, using high serum hepatitis B surface antigen (HBsAg) levels to identify genuine immunetolerant patients. Over a median 20-year follow-up, we observed distinct HCC risk pattern based on serum HBsAg levels. Patients with high serum HBsAg levels (>10,000 IU/mL) showed negligible HCC risk within the first decade, challenging the initiation of prolonged antiviral therapy. Conversely, patients with low serum HBsAg levels (<10,000 IU/mL) had an early

surge in HCC risk, advocating for preemptive antiviral intervention.

Another group of HBeAg-negative patients falls into the grey zone. We developed a new GZ-HCC risk score that considers age, sex, platelet count, ALT levels, and hepatitis B core-related antigen (EXPLORE). This is the first risk prediction model demonstrating that an HBcrAg-based HCC score outperforms HBV DNAbased HCC scores in HBeAg-negative GZ patients. It has been validated in an independent Japanese cohort. Furthermore, we propose a GZ-HCC score of 8 to categorize GZ patients into high- and lowrisk groups, with HCC risk levels are close to those of immune-active CHB and inactive CHB patients, respectively.

In conclusion, distinct viral biomarkers are essential for predicting HCC risk in various CHB populations, such as HBsAg levels in immune-tolerant patients and HBcrAg levels in HBeAg-negative GZ patients. By stratifying HCC risk in different clinical settings using different viral markers, these findings may pave the way for tailored therapeutic strategies based on individualized risk profiles.

Symposium (XVI)

Updating Progress of Management for Hepatitis B Virus

The Role Innate CD8+T Cells in Chronic Hepatitis B

Chun-Yen Lin

Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

The immunopathogenesis of chronic HBV hepatitis presents an intriguing challenge as the liver damage and development of cirrhosis and hepatoma occur despite the presence of few and exhausted HBVspecific T cells. A recent focus in research has been on understanding the detrimental effects of innate-like T cells in chronic inflammation, particularly in cases

of chronic hepatitis B and C, with the investigation utilizing single-cell approaches. This presentation will offer an overview of the most recent advancements in these research fields and propose perspectives on the role of innate-like T cells in hepatitis and virus-related HCC.

Symposium (XVI)

Updating Progress of Management for Hepatitis B Virus

The Potential of CRISPR Gene Therapy for HBV Cure

Hung-Chih Yang

Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Hepatitis B virus (HBV) infection continues to pose a significant challenge to global public health. Although current antiviral treatments have significantly reduced the mortality and morbidity associated with chronic hepatitis B (CHB), they do not provide a cure. Frequently, HBV replication rebounds after discontinuing antiviral therapy. Under antiviral therapy, the persistence of HBV covalently closed circular DNA (cccDNA) and integrated DNA remains the principal obstacle to completely eradicating HBV infection. CRISPR-mediated genome editing has emerged as a promising therapeutic approach for the targeted elimination of persistent HBV genomes, including both cccDNA and integrated DNA. Nevertheless, the cleavage of integrated HBV DNA by CRISPR-Cas9 can result in double-strand breaks (DSBs) in the host genome, raising significant safety concerns regarding genome stability and the risk for carcinogenesis. The newly developed CRISPR-derived base editors (BEs), which combine a catalytically disabled nuclease with a nucleobase deaminase enzyme, offer an alternative solution. These BEs

can be employed to permanently deactivate the HBV genome by introducing permanent point mutations, ultimately leading to the creation of premature stop codons, all without causing DSBs in the host genome. While CRISPR-mediated base editing holds great promise, it still faces formidable challenges before it can be clinically applied. These challenges encompass issues related to the efficacy of base editing, the potential for off-target effects, the difficulty in identifying conserved target sequences within the HBV genome, and the need for efficient in vivo delivery methods. Various strategies have been employed to enhance the efficiency and precision of CRISPR-BEs. Additionally, efforts have been made to improve in vivo delivery efficiency through innovative approaches involving both viral and non-viral delivery systems. Notably, the non-viral delivery of Cas9 mRNA and ribonucleoproteins using lipid nanoparticles demonstrates compelling potential for liver-targeted delivery in clinical settings. With these advancements, CRISPR-mediated gene therapy holds the promise of ultimately achieving a cure for HBV infection.

Symposium (XVII)

Diagnosis and Treatment of Pancreatic Cancer – An Update

AI Diagnosis of Pancreatic Cancer

Wei-Chih Liao

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

The application of artificial intelligence (AI) in medicine has increased rapidly with respect to tasks including disease detection/diagnosis, risk stratification, and prognosis prediction. With recent advances in computing power and algorithms, AI has shown promise in taking advantage of vast electronic health data and imaging studies to supplement clinicians. Machine learning and deep learning are the most widely used AI methodologies for medical research and have been applied in pancreatic diseases for which diagnosis and treatment selection are often complicated and require joint consideration of data from multiple sources.

Our group recently trained and tested a convolutional neural network (CNN) to distinguish pancreatic ductal adenocarcinoma (PDAC) and normal pancreas in CT images of 370 PDAC patients and 320 normal controls from Taiwan. In the local (Taiwanese) test sets, the CNN-based analysis

achieved 98.6-98.9% accuracy (AUC 0.997–0.999), with a higher sensitivity compared with radiologist interpretation (98.3% vs 92.9%, difference 5.4% [95% CI 1.1%–9.8%]; p = 0.014). Notably, CNN-based analysis achieved 92.1% sensitivity for PDACs smaller than 2 cm and correctly classified 92% of PDACs missed by radiologists. We have also investigated the potential usefulness of radiometer analysis with machine learning in detecting PDAC on CT, and identified a panel of distinguishing radiomic features of PDAC. Radiomic analysis with a machine learning model trained with predominantly Taiwanese images could differentiate between patients with PDAC and controls in Taiwanese (accuracy 95.0%) and U.S. (accuracy 86.5%) test images, with 96.9% and 90.9% sensitivity, respectively, for PDACs smaller than 2 cm. Our studies support that AI may supplement radiologist interpretation to facilitate early detection and diagnosis of pancreatic cancer.

Symposium (XVII)

Diagnosis and Treatment of Pancreatic Cancer – An Update

Robotic Surgery for Pancreatic Cancer

Yi-Ming Shyr

Departments of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

Robotic pancreaticoduodenectomy (RPD) working inside the abdominal cavity with a close and limited space raises the concerns of survival and oncological outcomes in the absence of randomized trials. This study is to clarify the feasibility and justification of robotic pancreaticoduodenectomy (RPD) on survival and oncological outcomes for pancreatic adenocarcinoma. In this presentation, we will share with you our experience in RPD and studies regarding the RPD in pancreatic cancer.

A propensity score-matched study comparing RPD and open ancreaticoduodenectomy (OPD) was conducted, based on 6 covariates commonly used to predict survival outcomes. A total of 130 patients with pancreatic adenocarcinoma were recruited after 1 : 1 propensity score-matching. RPD took longer operation time than OPD, with a median of 8.3 vs. 7.0

hours, P = 0.002. RPD was associated with less blood loss, lower overall surgical complication rate and lower incidence of delayed gastric emptying. Oncologically, radicality of resection was similar between RPD and OPD, and RPD harvested more lymph nodes, with a median lymph node yield of 18, vs. 16, P = 0.038. Before propensity score matching, survival outcome was better in RPD group than OPD, with 5-year survival of 27.0% vs. 17.6%, P = 0.006. After propensity score matching, there was still a trend towards improved overall survival in RPD although difference between RPD and OPD was not significant, with 5-year survival of 24.5% vs. 19.7%, P = 0.088.

RPD is not only feasible but also justified without increasing the surgical risk and with improved survival outcome. The survival and oncological outcomes by RPD is not inferior to OPD.

Symposium (XVII)

Diagnosis and Treatment of Pancreatic Cancer – An Update

Systemic Treatments in Pancreatic Cancer: Taiwan Pancreas Society Recommendation

Jen-Shi Chen

Division of Hematology/Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Pancreatic cancer is a malignant tumor with the worst prognosis. Taiwan Cancer Registry Annual Report 2020 found that the number of new cases of pancreatic cancer was estimated to be 3012 which accounts for 4.88% of all new cancer cases (13th). The incidence ranks 12th among males and 13th among females; but the ranking of mortality ranks 8th among males and fifth among females.1 The poor prognoses of pancreatic cancers are attributable to their late diagnosis and low sensitivity to systemic chemotherapy.

Gemcitabine alone became a standard treatment since 1997 which could have better clinical benefit but low response rate with median survival 6 months only.2 Currently, FOLFIRINOX or Gemcitabine and nab-paclitaxel is the first-line therapy for metastatic pancreatic cancer worldwide. The survival data was confirmed better than the convention Gemcitabine group.3,4 Oral TS1 also is an alternative regimen in late-stage pancreatic cancer in East Asia and Taiwan.5 In recent years. 2nd line treatment with CPT11 Liposome with 5-FU/LV was recommended by NCCN guideline and also was approved by Taiwan National Health Insurance.6 The median overall survival is still around one year with either treatment. Furthermore, post-operative adjuvant chemotherapy also demonstrated survival benefit to compare with placebo group in resectable cases.7 Induction chemotherapy also been investigated in patient with locally advanced or resectable pancreatic cancer and followed by concurrent chemoradiation therapy or conversion surgery are also been investigated.8,9 The role of chemotherapy has already become one of

importance modalities in multidisciplinary approach in each stage of pancreatic cancer.

In recent years, with the advancements in the next-generation sequencing (NGS) technology, the genome profiles of a considerable number of tumor specimens have been markedly improved, thereby making it an era wherein therapeutic targets can be explored based on these data, in a so-called tumoragnostic or histology-agnostic manner.10 Evidently, few mutations exist across organs, and basket trials targeting driver mutations regardless of the primary organ are being actively conducted. Such basket trials not only focus on the gate keeper-type oncogene mutations, such as HER2 and BRAF, but also focus on the caretaker-type tumor suppressor genes, such as BRCA1/2,11 mismatch repair-related genes, which cause hereditary cancer syndrome. As oncogene panel testing is a vital approach in routine oncologic practice, clinicians should devise a strategy for improved understanding of the cancer genome. Moreover, recent rapid advance cancer research to have several novel agents for variable cancer types in world. Selected suitable patient to join a good-designed clinical trial also is a good option for advanced pancreatic cancer patients.

Now, clinical oncologists are facing so much treatments modality and rapid advanced cancer research. Clinical oncologist should select a good and suitable treatment in this lethal cancer type. Herein, Taiwan Pancreas Society aims to organize Taiwan experts to make a consensus to guide Taiwan clinical oncologist for pancreatic cancer patients.

References:

1. Health Promotion Administration, Ministry of Health & Welfare, Taiwan: December, 2022; https:// www.hpa.gov.tw/Pages/List.aspx?nodeid=269

2. Burris HA, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15(6):2403–2413.

3. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–1825.

4. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. New England Journal of Medicine. 2013;369(18):1691–703.

5. Ueno H, Ioka T, Ikeda M, Ohkawa S, et, al. Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study. J Clin Oncol. 2013 May 1;31(13):1640–8.

6. Wang-Gillam A, Li CP, Bodoky G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after

previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial. Lancet. 2016 Feb 6;387(10018):545–55.

7. Oettle H, Post S, Neuhaus P et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–277.

8. Assifi MM, Lu X, Eibl G et al. Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery. 2011; 150: 466–473.

9. Landry J, Catalano PJ, Staley C et al. Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. J Surg Oncol. 2010;101:587–592.

10. Bailey P, Chang DK, Nones K, et al. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016 Mar 3;531(7592):47–52.

11. Golan T, et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. 2019;381(4):317–327.

Young Investigator Award (YIA)

①

PRE-EXISTING AND NEWLYDEVELOPED METABOLIC DYSFUNCTIONS INCREASE THE RISKS OF CIRRHOSIS AND ITS COMPLICATIONS IN CHRONIC HEPATITIS B PATIENTS

Shang-Chin Huang1,2,3,4, Tung-Hung Su2,3, Tai-Chung Tseng3,5, Chi-Ling Chen4, Shih-Jer Hsu2,3, Chen-Hua Liu2,3, Sih-Han Liao6, Chun-Ming Hong7, Ting-Yuan Lan8, Hung-Chih Yang2,3, Chun-Jen Liu2,3,4, Pei-Jer Chen2,3,4, Jia-Horng Kao2,3,4

1Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

3Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

4Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

5Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

6National Taiwan University Cancer Center, Taipei, Taiwan

7Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

8Division of Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan

既存及新發生之代謝異常增加慢性 B 型 肝炎患者發生肝硬化及其併發症風險

黃上秦1,2,3,4 蘇東弘2,3 曾岱宗3,5 陳祈玲4 徐士哲2,3 劉振驊2,3 廖思涵6 洪俊銘7 藍鼎淵8 楊宏志2,3 劉俊人2,3,4 陳培哲2,3,4 高嘉宏2,3,4

1 國立臺灣大學醫學院附設醫院北護分院胃腸肝膽科

2 國立臺灣大學醫學院附設醫院胃腸肝膽科

3 國立臺灣大學醫學院附設醫院肝炎研究中心

4 國立臺灣大學醫學院臨床醫學研究所

5 國立臺灣大學醫學院附設醫院醫學研究部

6 國立臺灣大學醫學院附設醫院癌醫中心分院

7 國立臺灣大學醫學院附設醫院內整合醫學科

8 國立臺灣大學醫學院附設醫院新竹分院風濕免疫科

Background: Cirrhosis and its complications are the major adverse outcomes of chronic hepatitis B (CHB). The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) is increasing among the CHB population, but the exact impact is unknown.

Aims: We aimed to explore the impacts of MAFLD, pre-existing and newly-developed metabolic comorbidities on the risks of cirrhosis and its complications in CHB patients.

Methods: Patients with CHB were consecutively recruited at the National Taiwan University Hospital from 2006 to 2021. The presence of metabolic dysfunction (MD) was based on the criteria of type 2 diabetes mellitus (DM), overweight/obesity, or ≥ two other metabolic risk abnormalities. Patients were categorized into MD and non-MD groups based on these criteria.

Results: 11,502 treatment-naïve non-cirrhotic CHB patients were included with a median follow of 5.2 years. Patients in the MD group (n = 6,250) had older age and lower HBV DNA levels than non-MD patients (n = 5,252). After adjustment for clinical and viral factors, MD patients had significantly higher risks of cirrhosis (adjusted hazard ratio [aHR]: 1.72, 95% confidence interval [CI]: 1.36 – 2.17, p < 0.001) and cirrhotic complications (aHR: 2.51, 95% CI: 1.31 –4.84, p = 0.006) than non-MD patients, with a dosedependent effect of MD on cirrhosis (aHR: 1.45 per MD increase, 95% CI: 1.31 – 1.60, p < 0.001) and the complications (aHR: 1.51 per MD increase, 95% CI: 1.08 – 2.11, p < 0.001). Furthermore, in patients without pre-existing DM, the newly-developed DM during the follow-up additively increased the risk of cirrhotic complications (aHR: 2.87, 95% CI: 1.34 – 6.11, p = 0.006). Among those with hepatic steatosis, The MD group (MAFLD patients) had a higher risk of cirrhosis than the non-MD group (non-MAFLD steatosis-only patients) in a dose-dependent manner (aHR: 1.46 per MD increase, 95% CI: 1.23 – 1.72, p < 0.001). Sensitivity analyses, including the inverse probability of treatment weighting (IPTW) between groups and multiple imputation for the missing data, confirmed the robustness of these results.

Conclusions: Concurrent and newly-developed metabolic dysfunctions increase the risks of cirrhosis and cirrhotic complications in CHB patients, independent of hepatic steatosis. Identifying and managing metabolic comorbidities in CHB are thus critical to prevent liver disease progression.

②

PRECISE APPLICATION OF TOPICAL TRANEXAMIC ACID TO ENHANCE ENDOSCOPIC HEMOSTASIS FOR PEPTIC ULCER BLEEDING: A RANDOMIZED CONTROLLED STUDY

Hsueh-Chien Chiang1, Po-Jun Chen1, Er-Hsiang Yang1, Ming-Tsung Hsieh1, I-Cheng Shih2, Hsiu-Chi Cheng2, Wei-Lun Chang1, Wei-Ying Chen1, Wei-Chu Tsai1, Yi-Ning Lo1, Kai-Chun Yang1, Chien-Ming Chiang1, Wei-Chih Chen1, Kuan-Kai Huang1, Hsu-Huan Tseng1, Chiung-Yu Chen1, Chiao-Hsiung Chuang1, Xi-Zhang Lin1

1Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

2Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan

經內視鏡精準投予傳明酸於消化性潰瘍 以增強止血效果之隨機分派臨床試驗

1 黃冠凱1 曾勗桓1 陳炯瑜1 莊喬雄1 林錫璋1

1 國立成功大學醫學院附設醫院消化內科

2 衛生福利部臺南醫院消化內科

Background: Peptic ulcer rebleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis.

Aims: This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis.

Methods: This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either a TXA group or standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose, (8 mg/h) continuous infusion proton-pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary endpoint of early treatment failure was defined as ulcer rebleeding within 4 days or major stigmata of

recent hemorrhage on the second-look endoscopy.

Results: Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to treatment groups. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P = .042). The freedom from treatment failure periods for 4 and 28 days were significantly longer in the TXA group than in the standard group (P = .023). No adverse events from TXA were recorded.

Conclusions: The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers.

③

HEALTH RELATED QUALITY OF LIFE IN COLORECTAL CANCER OVER THE FIRST YEAR OF TREATMENT FROM DIAGNOSIS IN MULTIRACIAL SINGAPORE: A PROSPECTIVE, MULTICENTRE AND LONGITUDINAL STUDY

Jarrod KH Tan1, Jing Yu Ng1, Norman S Lin1, Jerrald Lau2,3, Athena Ming-Gui Khoo2, Wei-Ling Koh2, Alyssa Isabelle Ng2, Cherie Peh2, Daphne Lee2, Ker-Kan Tan1,2,3

1Division of Colorectal Surgery, Department of Surgery, National University Health System, Singapore

2Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

3Saw Swee Hock School of Public Health, National University of Singapore, Singapore

Background: Colorectal cancer (CRC) accounted for 1,104,100 incident cases (6.1%) and 874,000 deaths (9.2%) globally in 2018, and impacts health related quality of life (HRQOL) of patients. Most existing studies examining HRQOL utilise cross-sectional or pre-post designs, but these may not fully reflect the long term effects of CRC diagnosis and treatment on HRQOL. There is also a lack of such longitudinal studies in Asian CRC patient populations.

Aims: The aim of this study was to identify factors predicting HRQOL over time in a multi-institutional cohort of curative CRC patients from diagnosis to 12 months post-surgery.

Methods: Newly diagnosed CRC patients were recruited from five public tertiary hospitals in Singapore between February 2018 and August 2021. Patients were administered the EORTC QLQ-C30 at five timepoints: diagnosis, 1-, 3-, 6- and 12 months post-surgery. Baseline sociodemographic and clinical data for each patient were extracted from the relevant hospital’s electronic medical records system using a standardised data collection form. Longitudinal analysis was conducted via generalised estimating equations (GEE) using Gaussian family with identity link, robust standard errors and unstructured withingroup correlational structure. QLQ-C30 scores with clinically significant changes across the study period were used as the outcome of interest for each GEE model. Clinically relevant changes in QLQ-C30 outcome scores were derived from interpretive guidelines established by Cooks and colleagues.

Results: The final sample was N = 233 (mean age 67.36 years; 58.8% male). Most HRQOL outcomes significantly deteriorated from baseline to 1st month post-surgery but experienced clinically relevant improvement to baseline levels by 12th month. Emotional functioning followed more linear trends of recovery from baseline to 12-month (81.79 to 90.59; higher scores denote better functioning), as did perceived financial difficulties (17.75 to 14.42; lower scores denote less severe difficulties). Stoma creation, having rectal cancer, requiring open surgery and a higher ASA score predicted poorer HRQOL outcomes over time (p < 0.05). Sociodemographic factors additionally associated with poorer HRQOL included older age, male gender, and non-Chinese ethnicity.

Conclusions: Surgery is impactful on HRQOL with clinically significant deteriorations within the first three months, but most patients can expect to recover to baseline by the end of the first year of treatment. A “one size fits all” approach to patient intervention does not do justice to improving HRQOL and future studies should seek to better understand the trajectories of certain at-risk CRC subpopulations.

④EFFICACY AND SAFETY OF 1L PEG/ASC VS 2L PEG/ASC IN THE HEMATOCHEZIA PATIENTS: A PROSPECTIVE MULTICENTER STUDY

Hyun Woo Park1, Su Young Kim1, Sang Hoon Lee2, Jundeok Lee1, Young Cheol Lee1, Jong Wan Lim1, Chang Hyun Kim1, Hyeon Min Ahn1, Dong Kyun Koh1, Hyunil Kim1, Hong Jun Park1, Yongsoo Kwon1, Byung Chul Lim1, Giho Ko1, Hyun-Soo Kim1

1Division of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea

2Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea

Background: Hematochezia is a risk factor of inadequate bowel preparation and low compliance for colonoscopy. To date, however, there has been no comparison investigation of low volume (2L) polyethylene glycol (PEG) and extremely low volume (1L) PEG in hematochezia patients.

Aims: Therefore, the purpose of this study is to conduct a prospective evaluation of the efficacy and safety of 1L PEG/ascorbic acid (Asc) in hematochezia patients undergoing colonoscopy.

Methods: This was a prospective, randomized, multicenter, non-inferiority study. Patients with hematochezia undergoing colonoscopy were randomly allocated to 2L PEG/Asc group or 1L PEG/Asc group, taken as regular regimens before colonoscopy. Quality of bowel preparation was assessed by the Boston Bowel Preparation Scale (BBPS). Patient’s satisfaction, adverse events, and polyp detection rate were also measured.

Results: A total of 184 patients were finally analyzed. There was no significant difference in successful bowel cleansing: 76.1% in the 2L PEG/Asc group vs. 78.3% in the 1L PEG/Asc group. Additionally, the noninferiority test revealed that the 1L PEG/Asc group was not inferior to the 2L PEG/Asc group. When comparing the two groups with the sum of BBPS, the 1L PEG/Asc group had a score of 6.87 and the 2L PEG/Asc group had a score of 6.30, indicating that the 1L PEG/Asc group was superior, with a marginally significant difference (P = 0.053). In terms of patient satisfaction, the 1L PEG/Asc group performed better than the 2L PEG/Asc group, but the difference was

not statistically significant. There was no difference in the polyp detection rate, intake of all solution, and adverse events between the two groups.

Conclusions: 1L PEG/Asc was not inferior to 2L PEG/ Asc for colonoscopy bowel cleansing in patients with hematochezia. In addition, 1L PEG/Asc is safe, and patient satisfaction and bowel clearing are slightly better than 2L PEG/Asc.

⑤

BODY COMPOSITION ANALYSIS OF PATIENTS WITH METABOLIC DYSFUNCTION ASSOCIATED STEATOTIC LIVER DISEASE

Karl Paolo Dillera1,2, Yen-Cheng Chiu1, Hung-Chih Chiu1, Pin-Nan Cheng1

1Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan

2Southern Philippines Medical Center, Davao City, Philippines

Background: Patients with metabolic dysfunction associated steatotic liver disease (MASLD) are at risk of co-existence of sarcopenia and osteopenia/ osteoporosis.

Aims: This study aimed to investigate factors associated with sarcopenia and osteopenia/ osteoporosis in patients with MASLD.

Methods: Patients with MASLD were prospectively enrolled. The diagnosis of MASLD was based on the multi-society Delphi consensus statement on new fatty liver disease nomenclature. Baseline characteristics, lipid and sugar profiles, and dual-energy x-ray absorptiometry to determine body composition were performed for each patient. Appendicular skeletal muscle mass index (ASMI) and bone mineral density (BMD) were measured. Sarcopenia was defined as ASMI < 0.789 for men and < 0.521 for women whereas osteopenia/osteoporosis was defined as BMD T-score between -1.0 to -2.5 for osteopenia and T-score of at or below -2.5 for osteoporosis, respectively. Factors associated with sarcopenia and osteopenia/ osteoporosis were examined through univariate and multivariate analysis.

Results: In total, 194 MASLD subjects were enrolled from March 2021 to April 2023. Twenty-five of them (12.9%) had sarcopenia and 43 (22.2%) had osteopenia/osteoporosis. Under univariate and multivariate analysis, FIB-4 score was consistently associated with sarcopenia (adjusted odds ratio, aOR = 1.86, 95% CI: 1.04-3.35, p = 0.037) and osteopenia (aOR = 1.86, 95% CI: 1.11-3.13, p = 0.02). Body mass index (BMI), presence of hypertension, and presence of cancer were positively associated with sarcopenia. Factors associated with osteopenia/osteoporosis included lower BMI, higher serum alkaline phosphatase, and lower serum creatinine.

Conclusions: A substantial proportion of MASLD patients exhibited sarcopenia and osteopenia/

osteoporosis. Liver fibrosis may associate with occurrence of sarcopenia and osteopenia/ osteoporosis. BMI was positively associated with the risk of sarcopenia but inversely linked to the risk of osteopenia/osteoporosis in MASLD patients.

⑥

SEVERITY OF FATTY LIVER IS HIGHLY CORRELATED WITH THE RISK OF HYPERTENSION AND DIABETES: A CROSS-SECTIONAL AND LONGITUDINAL COHORT STUDY

Chin-I Shih1,2, Kuan-Ta Wu3, Meng-Hsuan Hsieh3,5,6, Jeng-Fu Yang3, Yi-Yu Chen3, Wei-Lun Tsai2,4, Wen-Chi Chen2,4, Po-Cheng Liang5, Yu-Ju Wei5, Pei-Chien Tsai5, Po-Yao Hsu5, Ming-Yen Hsieh5, Yi-Hung Lin5, Tyng-Yuan Jang5, Chih-Wen Wang5,6, Ming-Lun Yeh5,6, Chung-Feng Huan5,6, Jee-Fu Huang5,6, Chia-Yen Dai5,6, Chi-Kung Ho3, Wan-Long Chuang5,6, Ming-Lung Yu2,5,6

1Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

2School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan

3Department of Preventive Medicine, and Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

4Division of Gastroenterology, Department of Internal Medicine Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

5Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

6School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan

脂肪肝的嚴重程度與高血壓和糖尿病的 風險高度相關：一橫斷式與縱向式研究

施瑾沂1,2 吳冠達3 謝孟軒3,5,6 楊正福3 陳藝祐3 蔡維倫 2,4 陳文誌2,4 梁博程5 魏鈺儒5 蔡佩倩5 許博堯5 謝明彥5 林宜竑5 張庭遠5 王志文5,6 葉明倫5,6 黃釧峰5,6 黃志富5,6 戴嘉言5,6 何啟功3 莊萬龍5,6 余明隆2,5,6

1 高雄榮民總醫院內科部

2 國立中山大學代謝異常脂肪肝卓越研究中心

3 高雄醫學大學附設中和紀念醫院健康管理中心

4 高雄榮民總醫院胃腸肝膽科

5 高雄醫學大學附設中和紀念醫院肝膽胰內科

6 高雄醫學大學肝炎研究中心與液態生物檢體暨世代 研究中心

Background: Fatty liver disease (FLD) is a hepatic component of insulin resistance, which is associated with several metabolic derangements.

Aims: We conducted a cross-sectional and longitudinal study to evaluate the role of FL severity in the risk of new-onset and co-existing hypertension (HTN) and diabetes mellitus (DM).

Methods: The cross-sectional cohort consisted of 41,888 adults who received health checkups in a tertiary hospital of Taiwan from 1999 to 2013. Of them, 34,865 without HTN and/or DM at baseline and within 1 year after enrollment were included as a longitudinal cohort (mean, 6.45 years for HTN; 6.75 years for DM). FL severity based on the degree or hepatic steatosis was assessed by ultrasound sonography.

Results: In cross-sectional cohort, 22,852 (54.6%) subjects had FL (18,203 [43.46%] mild FL and 4,649 [11.10%] moderate/severe FL); 13.5% (n = 5,668) had HTN; and 3.4% (n = 1,411) had DM. Moderate/ severe FL and mild FL had significantly higher risks of existing HTN (adjusted odds ratio/95% confidence interval [CI]: 1.59/1.43–1.77 and 1.22/1.13–1.32, respectively). In longitudinal cohort, 3,209 and 822 subjects developed new-onset HTN and DM, respectively (annual incidence, 14.3 and 3.5 per 1,000 person-years; 10-year cumulative incidence, 14.35% and 3.89%, respectively). Moderate/severe and mild FL had significantly higher risks of new-onset HTN (adjusted hazard ratio [aHR]/CI: 1.54/1.34–1.77 and 1.26/1.16–1.37, respectively) and DM (aHR/CI: 5.88/4.44–7.81 and 3.22/2.56–4.07, respectively). Resolved FL during follow-up decreased the risk of HTN and/or DM.

Conclusions: Patients with FL are at high risk of prevalent and incident HTN and/or DM. The risk increases with the severity of FL.

⑦

PREVALENCE AND RISK FACTORS OF YOUNGER AGE COLORECTAL SESSILE SERRATED LESIONS

Jen-Hao Yeh1, Chih-Wen Lin2, Po-Jen Hsiao1, Kuo-Tung Hung1, Chuan-Pin Lin1, Wen-Shuo Yeh1

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA DaChang Hospital/I-Shou University, Kaohsiung, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan 年輕型大腸鋸齒狀腺瘤之盛行率與危險

因子

葉人豪1 林志文2 蕭博仁1 洪國棟1 林詮斌1 葉文碩1

1 義大大昌醫院胃腸肝膽科

2 義大醫院胃腸肝膽科

Background: Sessile serrated lesions (SSL) are obscured lesions associated with interval colorectal cancer. Although the detection and management of SSL is gaining attention, the prevalence and risk factors of younger age (< 50 years) SSL is still largely unknown.

Aims: To determine prevalence and risk factors of younger age SSL.

Methods: A retrospective cross‐sectional study was conducted at E‐Da Dachang Hospital from 2018/06 to 2022/06. Individuals receiving index colonoscopy at outpatient service or during health check-up were included. Primary outcomes were detection rates of SSL, SSL with dysplasia and clinically significant serrated polyp between younger and elder age (< 50 and ≥ 50 years, respectively). Logistic regression was used to determine the predictive factor of SSL in the younger age group and expressed with odds ratio (OR) and 95% confidence interval (CI).

Results: 11309 individuals (3907 from health checkup) were included in the study and 5308 (46.9%) belonged to younger age group. Although individuals in younger age group had significantly less adenomas (22.7% vs. 47.0%, p < 0.001), advanced adenomas (3.9% vs. 14.3%, p < 0.001) and right-sided adenomas (11.2% vs. 28.3%, p < 0.001) compared to those of elder age group, similar occurrence of SSL was noted in both groups (7.4% vs. 6.7%, p = 0.142). Moreover, SSL with dysplasia, which has been considered rare

but high-risk precancer lesions, were more prevalent in elder age group (2.5% vs. 5.0%, p = 0.072). Logistic regression with clinical, metabolic and endoscopic risk factors revealed lower withdrawal time (each minute: OR 0.79, 95% CI 0.76 – 0.82) and presence of hyperplastic polyps (OR 0.20, 95% CI 0.11 – 0.37) were only independent and negative risk factors for SSL in younger age group.

Conclusions: SSL is not uncommon in younger age individuals compared to elder counterparts. However, the dysplasia and transformation may be less likely in the former population. While adequate withdrawal time is associated with higher detection of SSL, the association of SSL and hyperplastic polyps is worth to be explored in future studies.

⑧

SHOULD RUPTURED

HEPATOCELLULAR CARCINOMA BE CLASSIFIED AS BCLC STAGE C? A CASE SERIES

Yung-Hsin Lu1, Te-Sheng Chang1,2, Sheng-Nan Lu2,3

1Department of Gastroenterology and Hepatology, Division of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Department of Gastroenterology and Hepatology, Division of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

破裂的肝細胞癌患者是否應歸類在巴塞 隆納分期 C ？一個病例系列的分析

呂詠昕1 張德生1,2 盧勝男2,3

1 嘉義長庚紀念醫院胃腸肝膽科系

2 長庚大學醫學院

3 高雄長庚紀念醫院胃腸肝膽科系

Background: Extrahepatic spread and portal vein invasion are defined as BCLC stage C. HCC rupture is considered T4 according to 8th AJCC guidelines. However, whether HCC rupture should be classified as BCLC C or not remains controversial.

Aims: The real-world data of a tertiary referral hospital from Taiwan was utilized to conduct a retrospective study to evaluate the characteristic, risk factors and overall survival of these pure HCC rupture patients.

Methods: Eighteen Child-Pugh Class A, treatmentnaïve, ruptured HCC patients from January 1, 2011, to February 28, 2023 at Chiayi Chang Gung Memorial Hospital with AJCC stage T1b~T2 (without consideration of HCC rupture) and BCLC, stage C (presumed peritoneal spreading) were enrolled. The baseline clinical, laboratory, and image characteristics of these 18 patients were analyzed. The statistical methods used in this work included univariate analysis, Kaplan-Meier survival analysis, and multivariate analysis.

Results: Following the initial TAE treatment for hemostasis, one patient underwent hepatectomy with an overall survival of 41 months, 11 patients underwent TACE with an overall survival of 44.2 months, 3 patients received systemic therapy within 6 months after HCC diagnosis with an overall

survival of 31.3 months, and 3 patients received best supportive care with an overall survival of 15 months. The 50% probability of survival for the 18 ruptured HCC patients at is about 32 months (2.6 years). The univariate analysis of factors associated with overall survival revealed that diabetes mellitus and alcohol were associated with overall survival rates in patients with HCC rupture. Multivariate analysis revealed that diabetes mellitus has association with overall survivals. The univariate and multivariate analysis of factors associated with peritoneal seeding showed no significant.

Conclusions: The choice of treatment and survival outcomes of our HCC rupture patients differed from the BCLC stage C or TNM stage IV patients. Less than a quarter of the patients have peritoneal seeding, and whether early initiation of systemic therapy should be recommended remains debatable. It is suggested that in clinical guidelines, there should be clearer descriptions regarding the staging and treatment of HCC rupture.

Free Paper

Section: HCV

①

THE PERFORMANCE OF THE COLLAGEN PROPORTIONATE AREA (CPA), ENHANCED LIVER FIBROSIS (ELF) TEST, FIB-4, AND MAC-2 BINDING PROTEIN GLYCOSYLATION ISOMER (M2BPGI) IN PREDICTING THE LIVER FIBROSIS STAGE IN PATIENTS WITH CHRONIC HEPATITIS C WHO RECEIVED PAIRED BIOPSIES BEFORE AND AFTER ANTIVIRAL THERAPY

Hung-Wei Wang1, Hsueh-Chou Lai1, I-Ping Chiang2, Wei-Fan Hsu1, Sheng-Hung Chen1, Cheng-Yuan Peng1

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

2Department of Pathology, China Medical University Hospital, China Medical University, Taichung, Taiwan

膠原蛋白比例面積（CPA）、增強型肝纖 維化檢測（ELF）、FIB-4 和 MAC-2 結合 蛋白糖基化異構體（M2BPGI）在預測治 療前後慢性 C 型肝炎患者肝纖維化分期 之效能

王鴻偉1 賴學洲1 江宜平2 許偉帆1 陳昇弘1 彭成元1

1 中國醫藥大學附設醫院消化醫學中心 2 中國醫藥大學附設醫院病理部

Background: Accurate assessment of the fibrosis status is important for the management of hepatitis C virus (HCV) infection.

Aims: The purpose of this study was to determine the ability of various indices to predict the stage of liver fibrosis in patients with chronic hepatitis C who received paired liver biopsies before and after HCV eradication. The indices evaluated were the fibrosis index based on the collagen proportionate area (CPA), the enhanced liver fibrosis (ELF) index, the Fibrosis-4 (FIB-4) index, and the Mac-2 binding protein glycosylation isomer (M2BPGi).

Methods: The quantitative measurement of fibrotic tissue was calculated as the CPA using digital image analysis. The ELF index was determined using commercial ELISA assays for the constituent elements of the index. The Pearson correlation measures the

strength of the linear relationship between two variables. The Area Under the Receiver Operating Characteristic Curve (AUROC) was used to evaluate the predictive performance of CPA, ELF, FIB-4, and M2BPGi for different dichotomized stages of liver fibrosis, as determined by liver histology (METAVIR stage), and their predictive performance of liver fibrosis was compared by the DeLong test.

Results: A total of 197 patients who received paired biopsies were enrolled. The numbers of patients before and after HCV eradication with F1, F2, F3, and F4 were 17, 77, 58 and 45, and 73, 64, 25 and 35, respectively. The CPA increased with the histological stage of liver fibrosis and exhibited a linear relationship with the METAVIR score in all subjects before and after HCV eradication (r = 0.656, p < 0.001 and r = 0.702, p < 0.001, respectively). The median values of CPA, ELF, FIB-4, and M2BPGi after HCV eradication declined in each METAVIR stage compared to those before HCV eradication. The AUROCs for predicting significant fibrosis (F234), advanced fibrosis (F34), and cirrhosis (F4) in 197 participants before HCV eradication were 0.923, 0.919, and 0.850 for CPA; 0.685, 0.753, and 0.742 for ELF; 0.770, 0.785, and 0.771 for FIB-4; 0.653, 0.718, and 0.751 for M2BPGi, respectively. The AUROCs for predicting significant fibrosis (F234), advanced fibrosis (F34), and cirrhosis (F4) in these patients after HCV eradication were 0.854, 0.878, and 0.807 for CPA; 0.611, 0.688, and 0.727 for ELF; 0.716, 0.791, and 0.828 for FIB-4; 0.636, 0.682, and 0.727 for M2BPGi, respectively. The AUROCs of CPA were significantly higher in general than those of ELF, FIB4, and M2BPGi in predicting significant fibrosis (F234), advanced fibrosis (F34), and cirrhosis (F4) before and after HCV eradication, except for FIB-4’s AUROC in predicting cirrhosis (F4) after HCV eradication, which were numerically higher than that of CPA.

Conclusions: CPA increases with liver fibrosis stage and correlates with METAVIR score. Median values of CPA, ELF, FIB-4, and M2BPGi decrease in each METAVIR stage after HCV eradication. The fibrosis content is lower after HCV eradication compared to before HCV eradication for each METAVIR fibrosis stage. CPA has higher AUROCs than ELF, FIB-4, and M2BPGi in predicting fibrosis and cirrhosis, except for FIB-4’s prediction of cirrhosis after HCV eradication.

②

THE UTILITY OF DIABETES

MELLITUS DIAGNOSIS AND POSTSUSTAINED VIROLOGIC RESPONSE LIVER STIFFNESS VALUES IN PREDICTING THE RISK OF POST-SVR HEPATOCELLULAR CARCINOMA IN PATIENTS WITH CHRONIC HEPATITIS C

Sheng-Hung Chen1,2, Hsueh-Chou Lai1,3, Wei-Fan Hsu1,3, Hung-Wei Wang1,2, Jung-Ta Kao1,2, Hung-Yao Chen1,2, Cheng-Yuan Peng1,2

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

2School of Medicine, China Medical University, Taichung, Taiwan

3College of Chinese Medicine, China Medical University, Taichung, Taiwan

慢性 C 型肝炎患者糖尿病診斷和持續病 毒學反應後肝硬度值在預測持續病毒學 反應後肝細胞癌風險中的意義和效用

陳昇弘1,2 賴學洲1,3 許偉帆1,3 王鴻偉1,2 高榮達1,2 陳浤燿1,2 彭成元1,2

1 中國醫藥大學附設醫院消化醫學中心

2 中國醫藥大學醫學系

3 中國醫藥大學中醫學系

Background: Emerging evidence reveals a strong association between metabolic associated fatty liver disease (MAFLD) and chronic hepatitis C (CHC). Studies have shown that eradicating viremia can improve metabolic outcomes in patients with MAFLD, highlighting the importance of HCV screening among patients with MAFLD. Studies revealed that viral eradication through direct-acting antiviral (DAA) therapy is associated with a significant decline in fasting and long-term glucose levels, independent of the body mass index. MAFLD including DM has been associated with an increased risk of hepatocellular carcinoma (HCC), particularly in those with CHC. Consensus advises that patients with MAFLD who achieve sustained virologic response (SVR) following DAA therapy should be monitored for liver-related adverse events. Those with pretreatment cirrhosis and/or a FIB-4 score ≥3.25 should undergo indefinite HCC surveillance, including ultrasound examination

and testing for alpha-fetoprotein levels. DAA therapy can also lead to significant decreases in liver stiffness (LS) and fibrosis burden after achieving SVR. However, few studies have analyzed the utility of combining MAFLD and post-SVR liver fibrosis burden measured through elastography as predictors of post-SVR HCC risk at the SVR baseline.

Aims: The objective of this study was to investigate the significance and utility of MAFLD and DM diagnoses and post-SVR LS values in predicting the risk of post-SVR HCC in patients with CHC.

Methods: This retrospective study was conducted at China Medical University Hospital between 2015 and 2023. The study population consisted of patients with CHC who received DAA-based therapy and completed baseline and SVR visits for LS measurement. De novo HCC was diagnosed according to American Association for the Study of Liver Diseases guidelines, either through histopathological examination or based on the presence of liver nodules with a diameter of 1 cm or greater, observed using imaging techniques such as contrast-enhanced computed tomography, contrast-enhanced magnetic resonance imaging, or contrast-enhanced ultrasound in patients with CHC. Cox regression models were used to determine significant predictors of post-SVR HCC risk during follow-up. LS through point shear wave elastography was assessed as a predictor. Kaplan-Meier survival analysis was used to evaluate the clinical significance of risk stratification between groups using cut-off values maximizing the Youden index.

Results: Of the entire eligible cohort (n = 818), the median age was 59 years (interquartile range [IQR], 51–67), and 483 (59.0%) participants were male. Over a median follow-up duration of 29.9 months (IQR = 11.5–45.8) after SVR, 36 (4.4%) patients developed post-SVR HCC with an incidence rate of 1.74 per 100 person-years. Delta checks revealed that LS values were 1.12 m/s (IQR = 1.37–1.96) at baseline, 1.10 m/s (IQR = 1.27–1.63) at the end of treatment, and 1.07 m/s (IQR = 1.21–1.56) at SVR visit. While MAFLD status at SVR showed a nonsignificant result in the univariate analysis, multivariable Cox regression analysis identified four significant predictors of postSVR HCC: DM, adjusted hazard ratio (aHR): 2.206, 95% confidence interval (CI): 1.114–4.369, P = 0.023; α-fetoprotein (SVR), aHR: 1.044, 95% CI: 1.029–1.060, P <0.001; platelet (SVR), aHR: 0.988, 95% CI: 0.9800–0.996, P = 0.003; and LS (SVR), aHR: 2.104, 95% CI: 1.060–4.177, P = 0.034. To predict the risk of HCC after SVR, the optimal cut-off value for LS at SVR was

determined to be 1.485 m/s. According to KaplanMeier survival analysis (Log-rank P <0.001), subgroups with higher LS values at SVR or with DM exhibited a higher risk of HCC development post-SVR.

Conclusions: According to the present CHC cohort receiving DAAs, it is recommended to incorporate LS values at SVR and DM status in future post-SVR risk stratification models for predicting HCC. While MAFLD was considered in this study, it was not found to be a significant predictor at the SVR baseline of HCC risk in this cohort.

③

POST-TREATMENT FACTORS PREDICT HEPATOCELLULAR CARCINOMA AND LIVER-RELATED EVENTS IN CURED HEPATITIS C PATIENTS: A MULTICENTER STUDY

Wei-Fan Hsu1,2,3, Ching-Chu Lo4, Hsueh-Chou Lai1,3, Kuo-Chih Tseng5, Chi-Yi Chen6, Cheng-Yuan Peng1,7

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

2Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan

3School of Chinese Medicine, China Medical University, Taichung, Taiwan

4Department of Internal Medicine, St. Martin De Porres Hospital-Daya, Chiayi, Taiwan

5Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan

6Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan

7School of Medicine, China Medical University, Taichung, Taiwan

治癒 C 型肝炎患者肝細胞癌和肝臟相關 併發症的治療後預測因子：一個多中心 研究

許偉帆1,2,3 羅清池4 賴學洲1,3 曾國枝5 陳啟益6 彭成元1,7

1 中國醫藥大學附設醫院消化醫學中心

2 中國醫藥大學生物醫學研究所

3 中國醫藥大學中醫系

4 天主教聖馬爾定醫院內科部

5 大林慈濟醫院腸胃內科

6 嘉義基督教醫院內科部

7 中國醫藥大學醫學系

Background: Chronic hepatitis C (CHC) is a significant liver disease because it may lead to several liverrelated events (LREs), including esophageal or gastric varices, ascites, hepatic encephalopathy, hepatorenal syndrome, and even hepatocellular carcinoma (HCC). Direct-acting antiviral agents (DAAs) show high efficacy and excellent safety profile and are the standard of care for patients with CHC. However, a proportion of patients develop these complications despite achieving a sustained virologic response (SVR) to DAA therapy. Therefore, it is important to

investigate factors predictive of LREs and HCC in patients with an SVR to DAA therapy.

Aims: To investigate predictors of LREs and HCC in patients with CHC and an SVR to DAA therapy.

Methods: From September 2012 to March 2022, 4511 patients with cured CHC from China Medical University Hospital, Chiayi Christian Hospital, Dalin Tzu Chi Hospital, and St. Martin De Porres HospitalDaya were included in the analysis. Exclusion criteria included hepatitis B or human immunodeficiency virus infection, non-SVR, preexisting LREs, and endstage renal disease. Factors associated with LREs at baseline and 12 or 24 weeks after DAA therapy (PW12) were collected.

Results: Of 4511 patients, 2028 (45.0%) patients were male, and 818 (18.1%) and 910 (20.2%) patients had diabetes mellitus (DM) and liver cirrhosis, respectively. The median age was 62.0 (52.2–70.8) years (first–third quartile). The median follow-up duration after the end of DAA therapy was 27.53 (13.30–36.83) months. Eighty-eight (2.0%) and 124 (2.7%) patients developed incident HCC and LREs, respectively. The multivariable Cox regression analysis showed that age, DM (hazard ratio [HR]: 2.367, 95% confidence interval [CI]: 1.480–3.787, P < 0.001), albumin at baseline, post-treatment (PW12) platelet (<100 × 103/μL vs. ≥200 × 103/μL, HR: 3.902, 95% CI: 1.361–11.183, P = 0.011; 100–199 × 103/μL vs. ≥200 × 103/μL, HR: 2.218, 95% CI: 1.022–4.813, P = 0.044), alanine aminotransferase, albumin, and α-fetoprotein (AFP) >4.6 ng/mL (HR: 5.000, 95% CI: 2.957–8.543, P < 0.001) were the independent predictors of HCC in CHC patients with an SVR to DAA therapy. Another multivariable Cox regression analysis identified age, DM (HR: 1.991, 95% CI: 1.333–2.973, P = 0.001), albumin at baseline, post-treatment (PW12) platelet (<100 × 103/μL vs. ≥200 × 103/μL, HR: 3.806, 95% CI: 1.663–8.713, P = 0.002), albumin, total bilirubin, and AFP >4.6 ng/mL (HR: 3.220, 95% CI: 2.121–4.890, P < 0.001) as the independent predictors of LREs in these patients.

Conclusions: Post-treatment (PW12) platelet count (<100 × 103/μL), albumin, and AFP (>4.6 ng/mL) were predictors of LREs and HCC in CHC patients with an SVR to DAA therapy.

④ARTIFICIAL INTELLIGENCE PREDICTS

DIRECT-ACTING ANTIVIRALS TREATMENT FAILURE AMONG CHRONIC HEPATITIS C PATIENTS: A NATIONWIDE HCV REGISTRY PROGRAM (TACR)

Ming-Ying Lu1, Chung-Feng Huang2,3, Chao-Hung Hung4, Chi‐Ming Tai5,6, Lein-Ray Mo7, Hsing-Tao Kuo8, Chi-Yi Chen9, Ming-Lung Yu1,2,3,4

1College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan

2Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

3College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

4Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

5Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan

6College of Medicine, I-Shou University, Kaohsiung, Taiwan

7Division of Gastroenterology, Tainan Municipal Hospital (Managed By Show Chwan Medical Care Corporation), Tainan, Taiwan

8Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan

9Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan

4 高雄長庚紀念醫院胃腸肝膽科

5 義大醫院胃腸肝膽科

6 義守大學醫學院

7 台南巿立醫院胃腸肝膽科

8 奇美醫院胃腸肝膽科

9 嘉義基督教醫院胃腸肝膽科

Background: Despite the high efficacy of directacting antivirals (DAAs), approximately 1–3% of HCV patients fail to achieve a sustained virological response (SVR). Artificial intelligence (AI) emerged as a powerful tool for disease diagnosis and risk assessment in health care. We conducted a nationwide study to investigate the risk factors associated with DAA treatment failure. Machine learning algorithms were applied to discriminate the potential subjects who may fail DAA therapy.

Aims: (1) To explore the risk factors associated with DAA failure. (2) To establish an AI-based predictive model for risk stratification in virological failure.

Methods: We analyzed the Taiwan HCV Registry program (TACR) database to explore the predictors of virological failure among HCV patients receiving DAA therapy. A total of 55 host and virological features were assessed by multivariate logistic regression as well as decision tree (DT), random forest (RF), eXtreme Gradient Boosting (XGBoost), and artificial neural network (ANN). The primary outcome was SVR12 (i.e., undetectable HCV RNA 12 weeks after end-oftreatment).

Results: The training (n = 23955) and validation dataset (n = 10346) had similar baseline demographics, and the overall DAA failure rate was 1.6%. The multivariate logistic regression analysis revealed liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher HbA1c were significantly associated with virological failure. XGBoost outperformed other algorithms with an area under the receiver operator characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset for predicting DAA failure, respectively. The top five predictors of treatment failure were body mass index, HCV RNA, α-fetoprotein, bilirubin, and platelets. The XGBoost predictive model could capture 69.7% of subjects who fail to achieve SVR among the top five decile subgroups.

Conclusions: Machine learning algorithms provided risk stratification of DAA treatment failure effectively. Identifying and correcting modifiable factors of DAA failure will reduce the burden of retreatment for HCV elimination.

⑤

IDENTIFYING THE POPULATION AT RISK OF HCC IN NON-ACLD CHRONIC HEPATITIS C PATIENTS CURED BY DIRECT-ACTING AGENTS: A STRATEGIC APPROACH

Yu-Ting Kao, Yen-Chun Liu, Ya-Ting Cheng, Yi-Cheng Chen, Yi-Chung Hsieh, Wen-Juei Jeng, Chun-Yen Lin, Rong-Nan Chien, Dar-In Tai, I-Shyan Sheen

Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

在非晚期肝病並經治療的慢性丙型肝炎 患者中探討肝癌的風險因子

高毓婷 劉彥君 鄭雅婷 陳益程 謝彝中 鄭文睿 林俊彥 簡榮南 戴達英 沈一嫻

林口長庚紀念醫院胃腸肝膽科系

Background: HCC surveillance is recommended for chronic hepatitis C (CHC) patients with advanced fibrosis (F3) or cirrhosis (F4) after successful viral eradication, according to clinical guidelines. However, the risk of hepatocellular carcinoma (HCC) persists in CHC patients without advanced fibrosis or cirrhosis. The objective of this study is to identify the risk factors for HCC in patients with pre-treatment FIB-4 scores below 3.25 and develop a scoring system to stratify the population that would benefit from HCC surveillance after achieving sustained virological response (SVR).

Aims: Identifying the risk of HCC in non-ACLD chronic hepatitis C patients who had cured by direct-acting agents.

Methods: We enrolled chronic hepatitis C patients from Chang Gung Memorial Hospital who achieved HCV eradication using direct-acting antiviral agents (DAA) during 2015 to 2020 and had pretherapy FIB-4 scores available. Patients with a history of prior HCC before DAA therapy were excluded. Cox regression analysis was performed to assess the occurrence of HCC, and predictive scores were derived based on adjusted hazard ratios. The cumulative incidences of de novo HCC were calculated using the Kaplan-Meier method.

Results: Out of the 1597 patients enrolled, 1065 (67%) had pre-DAA FIB-4 <3.25, with a mean age of 59 years and 43% being male. Over a median follow-up period of 43 (IQR: 31-52) months, 27 of the

1065 non-ACLD patients developed de-novo HCC, resulting in an annual incidence of 0.76% personyear. By multivariate Cox regression analysis, it was revealed that male [adjusted hazard ratio (aHR): 4.262 (95% CI: 1.781-10.198), p = 0.001] and FIB-4 ≥2.5 [aHR: 4.125 (1.864-9.126), p < 0.001] were two independent factors associated with HCC in patients with FIB-4 <3.25. We derived a non-ACLD-HCC score = 1 x (Male: 1, Female: 0) + 1 x (FIB-4 ≥2.5: 1, <2.5: 0), which ranged from 0-2. The 5-year cumulative HCC incidences for scores 0, 1 and 2 were 0.6%, 4.1% and 17.8%, respectively (annual incidences: 0.18%, 0.71%, 3.76% person-year; log-rank p < 0.001). Applying the same annual incidence threshold for HCC surveillance in CHB (0.2%/year), patients with a predictive score ≥1 should undergo HCC surveillance even after SVR. Notably, 10% of non-ACLD patients with a predictive score of 2 (FIB-4 ≥2.5 plus male) had significantly higher HCC risks compared to those with predictive scores <2 (annual incidence: score = 2 vs. <2: 3.76% vs. 0.43% person-year, p < 0.01).

Conclusions: A simple scoring system utilizing the FIB-4 cut-off of 2.5 and gender can identify 10% of non-ACLD CHC-SVR patients with a predictive score of 2 who are at higher risk of HCC. These patients should be considered for inclusion in an HCC surveillance program.

⑥ IMPROVEMENT OF NUTRITION STATUS AND QUALITY OF LIFE AMONG MAINTENANCE

HEMODIALYSIS PATIENTS WITH CHRONIC HEPATITIS C AFTER VIRAL ERADICATION

Yu-Ju Wei1,2,3, Yu Ming-Lung1,4

1Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

2Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Municipal TaTung Hospital, Kaohsiung, Taiwan

3Graduate Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

4School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan

血液透析患者清除 C 型肝炎後改善營養 狀態和生活品質

魏鈺儒1,2,3 余明隆1,4

1 高雄醫學大學附設中和紀念醫院肝膽胰內科

2 高雄市立大同醫院肝膽內科

3 國立中山大學生物醫學研究所

4 國立中山大學醫學院

Background: HCV infection frequently leads to liver and non-liver complications, such as anemia and cardiovascular disease. Some HCV infected uremia patients were not treated due to side effects and lower efficacy of interferon. In the DAA era, more patients were cured of hepatitis C virus (HCV) infection, but long-term outcome after SVR12 in uremia population was unknown.

Aims: The aim of this study is to evaluate the impact of HCV eradication on nutrition status and quality of life of uremia patients on maintenance hemodialysis

Methods: We included 93 uremia patients with SVR12 from the 18 hemodialysis centers of the outreach onsite treatment program of HCV. The serum biochemical testing, non-invasive liver fibrosis measurement and quality of life (QoL) by SF-36 questionnaire were evaluated at EOT, M3 and Y1 after DAA therapy course. Albumin was the marker of nutrition status.

Results: Among 93 HCV infected uremia patients with SVR12, the baseline hemoglobin was 10.05 ± 1.27 (g/dL), the mean erythropoietin (EPO) consumption per week was 16538.17 ± 9750 (U) and the mean albumin was 3.74 ± 0.25 (g/dL). The EPO (EPO) consumption per week increased to 16581.40 ± 11779.81 (U) at 6th months aftter DAA treatment (P = 0.91) The Albumin (g/dL) increased in 3 and 12 months after DAA treatment: 3.81 ± 0.32 (P = 0.02), 3.98 ± 0.39 (P < 0.001), respectively. Age (P = 0.05), BMI (P = 0.02) and liver fibrosis stage (P = 0.03) was associated with albumin improvement one year after DAA treatment in univariate analysis. In multivariate analysis, liver fibrosis stage (F0-F2) was associated with albumin improvement after DAA treatment with SVR. HbA1c (P = 0.04) and age (P = 0.01) were associated with change of albumin level in univariate analysis, but only age was associated with change of albumin in multivariate analysis. Mean liver stiffness measurement (LSM) by the transient elastography (TE) was 9.12 ± 4.18 kPa, 7.77 ± 3.71 kPa (P < 0.001) and 6.92 ± 3.556 kPa (P < 0.001) at baseline, M3 and Y1, respectively. Both physical component summary (PCS) and mental component summary (MCS) improved significantly after HCV eradication at EOT and M3 (P < 0.001).

Conclusions: The nutrition status, quality of life and severity of liver fibrosis improved among uremia patients under maintenance hemodialysis after HCV eradication.

Section: LGI

A

PROSPECTIVE, LONGITUDINAL AND MULTI-CENTRE STUDY OF CHEMOTHERAPY-INDUCED COGNITIVE IMPAIRMENT IN COLORECTAL CANCER PATIENTS FOLLOWING ADJUVANT CHEMOTHERAPY

Jarrod KH Tan1, Jing Yu Ng1, Norman S Lin1, Jerrald Lau2,3, Athena Ming-Gui Khoo2, Wei-Ling Koh2, Alyssa Isabelle Ng2, Cherie Peh2, Daphne Lee2, Ker-Kan Tan1,2,3

1Division of Colorectal Surgery, Department of Surgery, National University Health System, Singapore

2Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

3Saw Swee Hock School of Public Health, National University of Singapore, Singapore

Background: Surgery followed by adjuvant chemotherapy (AC) is recommended for patients with advanced colorectal malignancy. However, chemotherapy is associated with a poorer quality of life (QOL) and increasing attention is being placed on cognitive deficits as a result of the chemo-brain effect. Aims: Given the paucity of longitudinal studies in Asian samples, the current study aims to examine the impact of chemotherapy on the cognitive functioning of CRC patients at various time points during treatment course.

Methods: Newly diagnosed CRC patient were recruited from five public tertiary hospitals in Singapore between February 2018 to August 2021. Patients were administered the EORTC QLQ-C30 at 1-, 3- and 6- months post-surgery. Baseline sociodemographic and clinical data were collected from medical records. Multiple linear regression was used to identify factors associated with cognitive changes and potential confounders were controlled for.

Results: A total of 208 CRC patients underwent surgery, of which 87 (42.9%) received AC. There was no difference in cognitive function between patients with and without AC at the 1-month interval. During the course of treatment, AC patients had worse cognitive scores at the 3-month mark with a mean difference of 3.23 (p = 0.038) as compared to patients without AC. Nonetheless, the cognition of AC patients returned to near baseline at the completion

of treatment (6-month) and cognitive scores were also found to be comparable to patients who did not undergo AC. Within patients who underwent AC, Malay ethnicity (β = -17.92, p < 0.01) and male gender (β = -6.03, p = 0.039) were associated with poorer cognitive function at 3-months, while being married (β = 11.40, p = 0.015) was associated with better cognitive functioning at 6-months.

Conclusions: AC resulted in significant cognitive impairment in CRC patients during the treatment course but these deficits were reversible upon treatment completion. While the development and severity of chemotherapy-induced cognitive impairment is likely multifactorial, sociodemographic factors may play an important role and should be evaluated in future qualitative studies.

COMPARISON OF RIGHT COLON ADENOMA AND SERRATED POLYP MISS RATES BETWEEN WATER EXCHANGE AND CARBON DIOXIDE INSUFFLATION: A PROSPECTIVE MULTICENTER RANDOMIZED TANDEM STUDY

Chi-Liang Cheng1, Jui-Hsiang Tang2,3, Yu-Hsi Hsieh4, Yen-Lin Kuo1, Kuan-Chieh Fang2, Chun-Chao Chang2, Chih-Wei Tseng4, I-Chia Su1,2, Ke-Yun Zou5, Yun-Shien Lee5, Felix W. Leung6,7

1Division of Gastroenterology, Evergreen General Hospital, Taoyuan, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

3Division of Gastroenterology and Hepatology, Department of Internal Medicine, New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan

4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Tzu Chi Medical Foundation, Chiayi, Taiwan

5Department of Biotechnology, School of Health Technology, Ming Chuan University, Taoyuan, Taiwan

6Sepulveda Ambulatory Care Center, Veterans Affairs Greater Los Angeles Healthcare System, North Hills, California, USA

7David Geffen School of Medicine at UCLA, Los Angeles, California, USA

比較換水大腸鏡與二氧化碳灌氣大腸鏡 對右側大腸腺瘤型息肉與鋸齒狀息肉漏 檢率的影響：一項前瞻性多中心同日進 行兩次右側大腸檢查的隨機分組試驗 鄭吉良1 唐瑞祥2,3 謝毓錫4 郭彥麟1 方冠傑2 張君照2 曾志偉4 蘇怡佳1,2 鄒可芸5 李御賢5 Felix W. Leung6,7

1 中壢長榮醫院胃腸科

2 臺北醫學大學附設醫院胃腸肝膽科

3 新北市立土城醫院胃腸肝膽科

4 大林慈濟醫院胃腸肝膽科

5 銘傳大學健康科技學院生物科技學系

6Sepulveda Ambulatory Care Center, Veterans Affairs

Greater Los Angeles Healthcare System, North Hills, California, USA

7David Geffen School of Medicine at UCLA, Los Angeles, California, USA

Background: The NordICC randomized controlled trial (RCT) showed completion of an invited screening colonoscopy reduced the risk of colorectal cancer (CRC) incidence and death. Non-RCTs showed protection was less in the proximal/right colon (PRC) where postcolonoscopy CRC (PCCRC) occurred. 85% of PCCRCs were due to missed lesions. An independent predictor of PCCRC is the PRC location with considerable variability of proximal serrated polyps (SPs) detection rate (SPDR). Water exchange (WE) colonoscopy maximizes cleanliness and improves right colon adenoma detection rate and SPDR which may reduce missed lesions.

Aims: The primary outcome of this study was to compare the combined right colon adenoma and SP miss rates (rAMR and rSPMR) between WE and standard colonoscopy.

Methods: During November 2019 and December 2022, patients aged 45-75 years undergoing screening and surveillance colonoscopy were randomized to WE or CO2 insufflation during insertion at 3 hospitals. During the first withdrawal, polypectomies were performed to the hepatic flexure. The right colon was then reexamined by a second blinded endoscopist for missed polyps. The miss rate was the number of additional adenomas and SPs divided by the total number detected in both examinations, respectively.

Results: A total of 386 patients were randomized with similar baseline characteristics and detection rates. Compared to CO2, WE significantly decreased the combined rAMR and rSPMR (22.2% vs. 32.2%, P = 0.0007), as well as the rSPMR (22.5% vs. 37.1%, P = 0.0018) and diminutive rAMR (23.2% vs. 33.3%, P = 0.04). Multivariate logistic regression showed that ≥2 SPs in the right colon was an independent predictor of the rSPMR (odds ratio [OR], 3.47; 95% confidence interval [CI], 1.89 to 6.38), along with a higher right colon Boston Bowel Preparation Scale score (OR, 0.55; 95% CI, 0.32 to 0.94). The variability in the proximal SP detection rate was similar between the WE and CO2 groups. The right colon inspection times were similar, confirming equivalent withdrawal technique.

Conclusions: Compared to CO2, WE significantly decreased the rSPMR. Variability in proximal SPDR was similar between WE and CO2-insufflated colonoscopy. Future studies should address the hypothesis that a significant reduction in the rSPMR by WE prevents PCCRC.

⑨REAL-WORLD PRACTICE OF DOCTORS IN THE TREATMENT OF ULCERATIVE COLITIS IN TAIWAN: A PILOT SURVEY

Yoen Young Chuah1,14, Deng-Chyang Wu2,14, Shu-Chen Wei3, Chiao-Hsiung Chuang4, Seng-Kee Chuah5,14, Feng-Woei Tsay6,14, Kuan-Yang Chen7,14, Chia-Long Lee8,14, Chien-Lin Chen9,14, Yu-Hwa Liu10,14, Jyh-Chin Yang3,14, Sz-Iuan Shiu11,14, Chih An Shih12,14, Hsi-Chang Lee7,14, Wei-Chen Tai5,14, Ping-I Hsu13,14

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ping Tung Christian Hospital, Pingtung, Taiwan; 2Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 3Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 4Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 5Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 6Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 7Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei City Hospital, Renai Branch, Taipei, Taiwan; 8Division of Gastroenterology and Hepatology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan; 9Division of Gastroenterology, Department of Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan; 10Division of Gastroenterology, Department of Internal Medicine, Shin Kong Wu Huo-Shih Memorial Hospital, Taipei, Taiwan; 11Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 12Division of Gastroenterology and Hepatology, Department of Internal Medicine, Antai Medical Care Corporation, Antai Tian-Sheng Memorial Hospital, Pingtung, Taiwan; 13Division

of Gastroenterology, Department of Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan; 14Taiwan Acid-related Disease & Microbiota (TARD-M) Consortium

台灣醫師對於潰瘍性結腸炎之治療在真 實世界醫療行為的普查：一個前導性研 究

蔡元榮1,14 吳登強2,14 魏淑鉁3 莊喬雄4 蔡成枝5,14

蔡峯偉6,14 陳冠仰7,14 李嘉龍8,14 陳健麟9,14 劉玉華10,14

楊智欽3,14 許斯淵11,14 石志安12,14 李熹昌7,14 戴維震5,14

許秉毅13,14

1 屏東基督教醫院胃腸肝膽科；2 高雄醫學大學附設 醫院胃腸內科；3 國立臺灣大學醫學院附設醫院內科 部；4 國立成功大學醫學院附設醫院內科部；5 高雄 長庚紀念醫院胃腸肝膽科；6 高雄榮民總醫院胃腸肝 膽科；7 臺北市立聯合醫院仁愛院區消化內科；8 國 泰綜合醫院腸胃內科；9 花蓮慈濟醫院肝膽胃腸科； 10 新光吳火獅紀念醫院胃腸肝膽科；11 臺中榮民總醫 院胃腸肝膽科；12 東港安泰醫院胃腸肝膽科；13 臺南 市立安南醫院胃腸肝膽科；14 台灣胃酸相關疾病暨 微菌叢聯盟

Background: Epidemiological data from the last four decades have shown 1.5-fold to almost 20fold increases in the incidence and prevalence of ulcerative colitis in some Asian countries. However, the prevalence of ulcerative colitis in Asia remains generally lower than that in the West. Currently, the gastroenterologists in Asia face unique challenges in how best to use available resources, including selection from a growing number of emerging treatment options for their patients with ulcerative colitis.

Aims: (1) To investigate the therapeutic target and real-world practice of doctors in Taiwan for the treatment of ulcerative colitis, and (2) To compare the differences in the practice for ulcerative colitis of doctors in medical centers and regional hospitals in Taiwan.

Methods: A questionnaire focusing on the treatment target, therapeutic strategies, and medicine use for the patients with different severities of ulcerative colitis was distributed to the doctors who attended the Taiwan Digestive Disease Week 2023 on March 25–26. The options of the treatment target, therapeutic strategy and medicine use for the treatment of ulcerative colitis in the doctors from medical centers and regional hospitals were compared.

Results: A total of 238 doctors for the medical centers (n = 136) and regional hospitals (n = 102) participated in the ulcerative colitis treatment survey. Among them, the leading therapeutic target for the treatment of ulcerative colitis was steroid-free mucosal healing (41.2%; 95% confidence interval: 35.0% – 47.5%). However, the leading therapeutic target in the doctors from medical centers was mucosal healing (34%), and that in the regional hospital was steroidfree mucosal healing (68%). There were significantly differences in the therapeutic targets between groups (P < 0.001). With regard the real-world practice, the most commonly adopted strategy for the treatment of mild ulcerative colitis in all the participants was step-up approach (76%), while that for the treatment of severe life-threatening ulcerative colitis was top-down approach (93%). In this survey, the most commonly used biological agents in medical centers were TNF-α blocker (100%), while that in regional hospitals was integrin blockers (85%). Differences in the most commonly used biological agents existed between groups (P < 0.001).

Conclusions: The leading therapeutic target for the treatment of ulcerative colitis among the doctors in Taiwan is steroid-free mucosal healing. Significant differences in the preferred therapeutic targets and most commonly adopted biological agents for the treatment of ulcerative colitis exist between the doctors from medical centers and regional hospitals.

⑩

ASSOCIATION OF HORMONE REPLACEMENT THERAPY AND INFLAMMATORY BOWEL DISEASEIN POST-MENOPAUSAL WOMEN: A POPULATION-BASED RETROSPECTIVE COHORT STUDY

I-I Chen1, Yuan-Tsung Tseng2, Lein-Ray Mo1, Kuo-Kuan Chang1, Ruey-Chang Lin1, Chun-Hsiang Wang1, Yuan-Chi Mao1

1Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan

2Department of Medical Research, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan 停經後婦女荷爾蒙替代療法與發炎性腸 道疾病的關聯：全國人口之回溯性研究

陳一毅1 曾元聰2 牟聯瑞1 張國寬1 林瑞昌1 王俊雄1 毛元治1

1 台南市立醫院（委託秀傳醫療社團法人經營）肝膽

胃腸科

2 台南市立醫院（委託秀傳醫療社團法人經營）醫學 研究部

Background: Comprehensive research study on the correlation between menopause and inflammatory bowel disease (IBD) among Taiwanese women is yet to be conducted.

Aims: This study aimed to compare the association of ulcerative colitis and Crohn’s disease among postmenopausal women in Taiwan who have received hormone replacement therapy (HRT group) versus those who have not (non-HRT group).

Methods: In this retrospective cohort study, a 1:1 new user design using the Taiwan’s National Health Insurance Research Database spanning from 2001 to 2018 was employed. The study focused on postmenopausal women and compared those who in the HRT group versus those in the non-HRT group. Clinical diagnoses were determined based on ICD 9 and ICD 10 codes. Participants were followed from their initial treatment or non-treatment until the end of 2018 with symptoms, disease progression, and mortality recorded. The primary assessments indicated ulcerative colitis and Crohn’s disease. For the study, Cox regression models were utilized, adjusting

for comorbidities and medical history, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During the 18-year follow-up study, 10,126 post-menopausal women were enrolled with 5,063 receiving HRT and 5,063 not receiving HRT. The mean follow-up duration was 11.1 ± 5.1 years. The incidence rate of ulcerative colitis was calculated as 0.14 per 1,000 person-years (95% CI 0.07–0.28) in the HRT group, while it was 0.11 per 1,000 person-years (95% CI 0.04–0.24) in the non-HRT group. Meanwhile, there was no significant difference in the incidence of ulcerative colitis between the two groups. However, A lower cumulative incidence of Crohn’s disease was observed in the HRT(hormone replacement therapy) group compared to the non-HRT group. The ulcerative colitis HR between the HRT and non-HRT groups was 1.33 [95% CI 0.46–3.83, P = 0.600]. The Crohn’s disease HR between the HRT and non-HRT groups was 0.72 [95% CI 0.45–1.16, P = 0.177].

Conclusions: This study provides longitudinal evidence that HRT prescriptions do not increase the risk of IBD in post-menopausal women. Despite conflicting literature on the association between HRT and IBD development, limitations in previous studies have made it difficult to establish a clear understanding of the relationship between these two. Our findings suggest that estrogen may not have a significant anti-inflammatory effect, but further investigation is needed to understand the underlying mechanisms involved.

⑪

GENOME-WIDE ASSOCIATION STUDY RESULT FOR INFLAMMATORY BOWEL DISEASE: A SINGLE INSTITUTE EXPERIENCE IN TAIWAN

Po-Ju Huang1, Chu-Ping Wang1, Yi-Hua Wu1, Ken-Sheng Cheng1,2, Jen-Wei Chou1,2,3

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University Hospital, Taichung, Taiwan

2School of Medicine, China Medical University, Taichung, Taiwan

3Taiwan Association for the Study of Small Intestinal Diseases (TASSID)

發炎性腸道疾病的全基因組關聯分析 : 中 台灣一醫學中心之經驗

黃柏儒1 王楚評1 吳宜樺1 鄭庚申1,2 周仁偉1,2,3

1 中國醫藥大學附設醫院消化醫學中心

2 中國醫藥大學醫學系

3 台灣小腸醫學會

Background: Inflammatory bowel disease (IBD) have two major subtype disease, including Crohn’s disease (CD) and Ulcerative colitis (UC). These two diseases of IBD in which abnormal reactions of the immune system induced inflammation and ulcers in any part of gastrointestinal tract from oral cavity to rectum, especially in colon and small intestine. Now, IBD still not have an identifiable cause and many articles that discussion about risk loci of IBD was published in recent years. Hence, we try to identify the risky locus related with IBD.

Aims: The aim of this study was to identify the genomic loci associated with these patient with inflammatory bowel disease.

Methods: From January 1992 to December 2023, we retrospectively reviewed the medical records of patients diagnosed as inflammatory bowel disease at our hospital. Then, we used the our hospital’s genetic data warehouse to assay these patient’s genome for identifying the specific loci associated with inflammatory bowel disease.

Results: A total of 286 patients with inflammatory bowel disease from January 1992 to December 2023 was in medical record. The number of Crohn’s disease and ulcerative colitis were 102 and 184 respectively. However, only 85 patient with CD and 145 patient with UC were in our hospital’s genetic data warehouse. So

far, around 200 genomic loci have been associated with IBD was reported. We also review these papers that totally 201 loci including 163 IBD general loci and 38 newly IBD risk loci was selected. The totally imputed SNP (Single-Nucleotide Polymorphism) count is 184. The result of Genome-wide association study (GWAS) for inflammatory bowel disease sample that showed only one genetic locus: CRY2 had statistically significant difference and vaule of -log10(p) is more than 6. But, no similar thesis was reported after we review other published papers about loci associated with inflammatory bowel disease. The relationship between CRY2 and inflammatory bowel disease is still pending investigation.

Conclusions: Although, around 200 genomic loci was considered to be associated with inflammatory bowel disease. But, the precise mechanism by which these loci contribute to IBD were still being investigated. However, more genetic loci associated with IBD was identified can lead us to approach the understanding of the underlying biology of the disease.

⑫

EXPLORING THE UTILIZATION OF LARGE LANGUAGE MODEL (CHATGPT) IN SHARED-DECISION MAKING: PATIENT COMMON QUESTIONS ABOUT COLONOSCOPY

Tsung-Chun Lee1,2,3, Kyle Staller4,5,6, Vlaicu Botoman4,5,6, Mythili P. Pathipati4,5,6, Sanskriti Varma4,5,6, Braden Kuo4,5,6

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan

2Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

3TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan

4Center for Neurointestinal Health, Massachusetts General Hospital, Boston, Massachusetts, USA

5Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA

6Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA

探索 ChatGPT 新穎大型語言模型人工智 慧於醫療共享決策之應用：以病患常問 大腸鏡相關問題為例

郭大猷4,5,6

1 臺北醫學大學部立雙和醫院消化內科

2 臺北醫學大學醫學院醫學系內科

3 臺北醫學大學消化醫學研究中心

4 美國麻州總醫院神經腸道健康研究中心

5 美國麻州總醫院消化內科

6 美國哈佛大學醫學院醫學系內科

Background: ChatGPT is a large language model (LLM) artificial intelligence which demonstrated its capability in conversational artificial intelligence. One potential application of ChatGPT is answering patients’ medical questions as part of shared-decision making. Colonoscopy has been the topic of discussion between physicians and patients in digestive health.

Aims: We aim to examine the quality of ChatGPTgenerated answers to common questions (CQs) about colonoscopy.

Methods: We retrieved eight common questions and

answers about colonoscopy from publicly available webpages of three randomly-selected US top-tier hospitals. We inputted these questions as prompts for ChatGPT (January 30, 2023 version) for two times on the same day and recorded the ChatGPT-generated answers, respectively. To objectively interpret the quality of ChatGPT-generated answers, four gastroenterologists (two senior gastroenterologists, two fellows) rated randomly-displayed 36 pairs of CQs and answers (including non-AI webpage Q&As and AI Q&As) for the following quality indicators on a 7-point Likert Scale: (1) ease of understanding, (2) scientific adequacy, and (3) satisfaction with the answer. Raters were also requested to interpret whether the answers were AI-generated or not.

Results: We found that ChatGPT answers were rated similarly by gastroenterologists to Non-AI answers in ease of understanding (AI 5.0 – 6.4 vs Non-AI 4.8 - 5.8, P all > 0.00089 comparing means after Bonferroni adjustment for 56 multiple comparisons), with the AI mean scores higher than non-AI scores. Scientific adequacy scores were also similar (AI 5.4 – 6.5 vs NonAI 5.1 - 6.3, non-significant), with the AI mean score higher than Non-AI 63% of the time. AI and Non-AI answers received similar ratings regarding satisfaction with the answers (AI 4.9 – 6.3 vs Non-AI 4.8 – 5.8, non-significant) The raters demonstrated only 48% accuracy in identifying AI-generated answers with 41% sensitivity and 54% specificity. Three raters had an accuracy of less than 50%, while one (a fellow) had 81% accuracy.

Conclusions: This study is the first-of-its-kind to demonstrate that ChaGPT is able to provide easy to understand, scientifically adequate, and generally satisfactory answers to CQs about colonoscopy, as determined by gastroenterologists. This study shows that a conversational AI program has the potential to facilitate shared-decision making. (published in Gastroenterology. https://doi.org/10.1053/j. gastro.2023.04.033)

Section: HBV

⑬

KINETICS OF HBV VIRAL LOAD IN HBSAG-POSITIVE RHEUMATIC PATIENTS UNDERGOING BIOLOGICAL DMARDS (BDMARDS) TREATMENT

Yi-Hsiang Huang1,2,3, Ming-Han Chen4, Chieh-Ju Lee1, Wei-Sheng Chen4, Chang-Te Chou4

1Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan

2Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan

3Institute of Clinical Medicine, Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

4Division of allergy, immunology, rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

B 型肝炎患者接受生物性疾病調節抗風濕 藥物（bDMARDs）治療之病毒動態分析

黃怡翔1,2,3 陳明翰4 李杰如1 陳瑋昇4 周昌德4

1 臺北榮民總醫院健康管理中心

2 臺北榮民總醫院胃腸肝膽科

3 國立陽明交通大學臨床醫學研究所

4 臺北榮民總醫院過敏免疫風濕科

Background: There is potential risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)–positive patients undergoing biologic disease-modifying antirheumatic drugs (bDMARDs). However, the kinetics of HBV viral load by different types of bDMARDs treatment were not clear.

Aims: To clarify the kinetics of HBV viral load by different types of bDMARDs treatment.

Methods: We conducted a prospective randomized controlled trial to define the efficacy of prophylactic Tenofovir alafenamide (TAF) in HBsAg-positive patients with inflammatory arthritis (IA) undergoing bDMARDs treatment. Patients were randomized into prophyiatic-TAF arm or observation arm by 1:1 ratio. For observation arm, TAF will be provided one year after bDMARDs treatment or at the time of HBV reactivation. HBsAg levels and HBV viral loads were closely monitored every three months for the observation arm.

Results: This is the summary report for the first 24 patients in the observation arm from June 2022 to

June 2023. The median observation period was 37.0 weeks (Min.-Max.: 13.0-66.0). Of them, 8 received anti-TNF-alpha treatment, 7 received abatacept, 2 received tocilizumab, 5 received JAK inhibitor (baricitinib, certolizumab, tofacitinib), and the other 2 received IL-17 inhibitor (secukinumab, ixekizumab). Till the data lock for the analysis, four patients (16.7%) (2 tocilizumab, 1 abatacept, and 1 anti-TNF-alpha) met the criteria of HBVr, including 3 with ≥ 100-fold increase in HBV DNA level, and 1 with HBV DNA ≥ 1,000 IU/mL from undetectable at baseline. For the rest of patients without HBVr, 4 cases (16.7%) experienced more than 1 log elevation in HBV DNA. Interestingly, 4 cases (16.7%) had more than 1 log decline in HBV viral load.

Conclusions: The kinetics of HBV viral loads were diverse during bDMARDs treatment. The risk of HBV reactivation was 16.7% in this preliminary finding. This study is still on recruitment.

⑭

PHASE TRANSITION IN CHRONIC HEPATITIS B PATIENTS AFTER CESSATION OF ENTECAVIR OR TENOFOVIR TREATMENT

Chien-Hung Chen, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung, Sheng-Nan Lu

Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

慢性 B 型肝炎病人停止貝樂克或惠立妥 治療後的相位轉變

陳建宏 胡琮輝 王景弘 洪肇宏 盧勝男 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 暨長庚大學醫學系

Background: Phase transition remains unknown after cessation of nucleot(s)ide analogues (NA) therapy in patients without clinical relapse.

Aims: To investigate the phase transition in patients without clinical relapse within 2 years after entecavir or tenofovir disoproxil fumarate (TDF) cessation.

Methods: A total of 364 patients (248 HBeAg-positive and 116 HBeAg-negative patients at initial treatment) who received entecavir (n = 245) or TDF (n = 119) therapy previously and had post-treatment followup for at least 36 months were included in this study. All patients did not experience clinical relapse and retreatment within 2 years after entecavir or TDF cessation.

Results: Inactive phase (phase I) was defined as HBV DNA < 2000 IU/mL and persistent ALT < 40 U/mL. Intermediate phase (phase II) was defined as HBV DNA > 2000 IU/mL and persistent ALT < 40 U/L, and mildly active phase (phase III) was defined as HBV DNA > 2000 IU/mL and persistent or intermittent ALT 40-80 IU/mL, and active phase (phase IV) was defined as HBV DNA > 2000 IU/mL and ALT > 80 U/mL. Of the 364 patients, 232 were inactive phase, 46 was mildly active phase and 86 were intermediate phase in the first 2 years after cessation of entecavir or TDF therapy. Of the 232 patients with inactive phase, 200 (86.2%) remained in the same phase, 17 transitioned to phase II or III and 15 transitioned to phase IV during follow-up after the first 2 years. Of the 46 patients in phase II, 9 (19.6%) transitioned to phase I, 19

remained in phase II or III, and 18 (39.1%) transitioned to phase IV. Of the 86 patients in phase III, 21 (24.4%) transitioned to phase I, 39 remained in phase II or III, and 26 (30.2%) transitioned to phase IV. Multivariate analysis showed that older age, genotype B, higher ALT levels at initial treatment and higher HBsAg levels at 2 years after entecavir or TDF cessation were factors independently associated with phase I, II or III transition to phase IV beyond 2 years after entecavir or TDF cessation. The cumulative incidences of HBsAg loss at 10 years after entecavir or TDF cessation in patients with phase I who remained in phase I and patients who transitioned phase II or III to phase I were 56.2% and 61.4%, respectively.

Conclusions: Patients who remained or transitioned to inactive phase had high HBsAg loss rates in patients who did not meet treatment criteria in the first 2 years after entecavir or TDF cessation.

⑮

IMPACT OF HBV INFECTION ON CLINICAL OUTCOMES IN PATIENTS WITH METABOLIC ASSOCIATED FATTY LIVER DISEASE

Kun-Lin Cheng1, Yu-Ming Cheng2, Tsung-Han Hsieh3, Chia-Chi Wang1

1Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan

3Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan

B 型肝炎病毒感染對代謝相關脂肪肝患者 臨床預後的影響

鄭坤霖1 鄭煜明2 謝宗翰3 王嘉齊1

1 台北慈濟醫院肝膽腸胃科

2 童綜合醫療社團法人童綜合醫院胃腸肝膽科

3 台北慈濟醫院研究部

Background: The new name and diagnostic criteria of metabolic associated fatty liver disease (MAFLD) was proposed in 2020.

Aims: Although chronic hepatitis B virus (HBV) infection has protective effects on lipid profiles and hepatic steatosis, the impact of chronic HBV infection on clinical outcomes of MAFLD requires further investigation.

Methods: The participants from Taiwan bio-bank cohort were included. MAFLD is defined as the presence of hepatic steatosis plus any of the following three conditions: overweight/obesity, type 2 diabetes mellitus (DM), and metabolic dysfunction. The patients with positive hepatitis B surface antigen (HBsAg) were considered as chronic HBV infection. Atherosclerosis was determined as having carotid plaques of duplex ultrasounds. Advanced liver fibrosis was defined as FIB-4 > 2.67. Based on the status of MAFLD and HBV infection, the participants were distributed into four groups: “dual etiology”, “MAFLD alone”, “HBV alone”, and “healthy controls”.

Results: A total of 20,460 participants (age 55.51 ± 10.37; males 32.67%) were included for final analysis. The prevalence of MAFLD and chronic HBV infections

were 38.8% and 10.3%, respectively. According to univariate analysis, “HBV alone” group had lower levels of HbA1C, lipid profiles, IMT than healthy controls. “Dual etiology” group had lower levels of TG, CHO, GGT, IMT, and the percentage of carotid plaques than “MAFLD alone” group. Using binary logistic regression, chronic HBV infection increased the overall risk of advanced liver fibrosis; and had a lesser probability of carotid plaques in MAFLD patients, but not in those without MAFLD.

Conclusions: The large population-based study revealed chronic HBV infection increases the overall risk of liver fibrosis, but protects from atherosclerosis in MAFLD patients.

⑯

ELEVATED NEUTROPHIL-TOLYMPHOCYTE RATIO COMBINED WITH DECREASED LYMPHOCYTE-TOMONOCYTE RATIO IS ASSOCIATED WITH SMALL AIRWAY DYSFUNCTION IN PATIENTS WITH HEPATIC STEATOSIS

Hsiao-Chin Shen1, Ching-hsiang Wang1, Ching-Wen Yang1, Yi-Hsuan Lin1,2, Hsiao-Yun Yeh1,2, Ying-Ying Yang1,2, Ming-Chih Hou1,2,3

1Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan

2School of Medicine, College of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan

3Department of Internal Medicine, Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan

結合升高的中性粒細胞至淋巴細胞比值 與降低的淋巴細胞至單核球比值，與脂 肪肝患者的小氣道功能障礙有關

1 臺北榮民總醫院教學部

2 國立陽明交通大學醫學系

3 臺北榮民總醫院胃腸肝膽科

Background: Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on large airways. Studies connecting hepatic steatosis and small airway dysfunction (SAD) remain scarce, with the immunological aspects largely uninvestigated. Known markers of immunological dysfunction, high neutrophil-to-lymphocyte ratio (NLR) and low lymphocyte-to-monocyte ratio (LMR), have been linked to both SAD and hepatic steatosis.

Aims: This study aims to evaluate the association between immunological dysfunction (elevated NLr and diminished LMR) and the co-occurrence of hepatic steatosis and small airway dysfunction.

Methods: In this retrospective study, chest, or abdomen CT scans and spirometry/ Impulse oscillometry (IOS) from 2018 to 2019 were used to identify hepatic steatosis and small airway dysfunction in patients. Comprehensive patient demographic and

clinical data, including lipid profiles, glucose levels, and proteinuria, were collected for comparison. Results: A total of 1391 participants who underwent chest or abdominal CT scans were included in the study, among whom 169 (12.1%) were diagnosed with hepatic steatosis. Following propensity matching based on age and abnormal ALT, a comparison was made between 169 patients with hepatic steatosis and 169 patients without hepatic steatosis. A higher proportion of patients in the hepatic steatosis group exhibited small airway dysfunction. The presence of high NLR or low LMR emerged as an independent risk factor for small airway dysfunction in patients with hepatic steatosis (aOR 2.23, 95% CI, 1.09–4.57, p = 0.029).

Conclusions: The presence of hepatic steatosis is associated with small airway dysfunction. Immunerelated markers, such as high NLR or low LMR, is independently correlated with small airway dysfunction in patients with hepatic steatosis.

⑰

METABOLIC-ASSOCIATED FATTY LIVER DISEASE AND LONGTERM RISK OF HEPATOCELLULAR CARCINOMA IN TREATED CHRONIC HEPATITIS B

Hung-Wei Wang, Hsueh-Chou Lai, Wei-Fan Hsu, Sheng-Hung Chen, Cheng-Yuan Peng

Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

代謝相關脂肪肝病對於慢性 B 型肝炎治 療後之肝細胞癌的長期風險

王鴻偉 賴學洲 許偉帆 陳昇弘 彭成元

中國醫藥大學附設醫院消化醫學中心

Background: Chronic hepatitis B (CHB) stands as the primary factor contributing to the development of hepatocellular carcinoma (HCC). Nevertheless, untreated CHB does not exhibit an association with an escalated incidence of HCC in the context of metabolic dysfunction-associated fatty liver disease (MAFLD).

Aims: We aimed to explore the impact of concurrent MAFLD on the risk of HCC in CHB patients undergoing oral antiviral therapy.

Methods: Patients with CHB who received oral antiviral therapy were consecutively recruited from 2004 to 2022. MAFLD was diagnosed when hepatic steatosis was observed on ultrasound along with obesity (BMI ≥23), diabetes, or metabolic dysfunction at the time of treatment initiation. Metabolic dysfunction was defined as the presence of at least two of the five metabolic risk abnormalities proposed by the international experts. The study compared the cumulative incidences of HCC and its associated factors between the MAFLD and non-MAFLD groups.

Results: A total of 1012 CHB patients who had undergone oral antiviral therapy were enrolled. During a median treatment duration of 5.5 years, 73 HCC events occurred. CHB patients with MAFLD (n = 436) had similar hepatitis B e antigen (HBeAg) positivity, similar HBV DNA levels, but a lower proportion of cirrhosis, a lower Fibrosis-4 value and HDL-C level, and a higher proportion of male, hypertension, diabetes and alcohol consumption, and a higher BMI, ALT, platelet, AC sugar, and TG levels at baseline compared to the non-MAFLD group (n = 576). MAFLD was independently associated with

a 41% reduced risk of HCC (adjusted hazard ratio [aHR] 0.59, 95% confidence interval [CI] 0.36–0.98, p = 0.042). On the other hand, alcohol (aHR = 1.67), AFP ≥5 ng/mL (aHR = 1.76), and FIB-4 ≥2.33 (aHR = 1.99) increased the risk of HCC. Furthermore, steatosis and metabolic dysfunction had distinct effects on HCC. Steatosis (yes vs. no) was protective against HCC (aHR 0.41, 95% CI 0.25–0.67, p < 0.001), while metabolic dysfunction (yes vs. no) increased the risk of HCC (aHR 2.21, 95% CI 1.22–4.00, p = 0.009).

Conclusions: Concurrent hepatic steatosis is independently associated with a reduced risk of HCC, whereas metabolic dysfunction exacerbates the risk of HCC in CHB patients receiving antiviral therapy.

⑱

SELF-DISCONTINUATION DURING NUC THERAPY IN HBEAG-NEGATIVE CHRONIC HEPATITIS B PATIENTS: A NOT UNCOMMON BUT PERILOUS SITUATION

Wen-Juei Jeng1,2, Cheng-Er Hsu2, Chia-Ling Wu2, Chung-Wei Su2, Yen-Chun Liu2, Rong-Nan Chien1,2, Yun-Fan Liaw1,3

1College of Medicine, Chang Gung University, Taoyuan, Taiwan

2Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

3Liver Research Unit, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

E 抗原陰性患者使用抗病毒藥物病患自行 停藥：一個非罕見卻危險的情境

鄭文睿1,2 徐正二2 吳佳玲2 蘇崇維2 劉彥君2 簡榮南1,2 廖運範1,3

1 長庚大學醫學系

2 林口長庚紀念醫院胃腸肝膽科系

3 林口長庚紀念肝臟研究中心

Background: In real-world practice, selfdiscontinuation and loss to follow-up (LTFU) during long-term antiviral treatment are not uncommon. Chronic hepatitis B (CHB) patients who selfdiscontinue treatment without proper monitoring face risks of delayed retreatment and hepatic decompensation/hepatic failure. Limited information exists on the incidence and factors associated with self- discontinuation/LTFU.

Aims: This study explores the issue using a multiinstitutional electronic medical record database (CGRD).

Methods: We recruited HBeAg-negative CHB patients who received ETV or TDF for ≥3 months between Jan 2004 and Nov 2021 at Chang Gung Memorial Hospital’s branches in Taipei, Linkou, and Taoyuan, selected from CGRD. Exclusions included patients on Nuc for prophylaxis related to chemotherapy or immunosuppressants, with co-infections (HCV, HIV, or HDV), or diagnosed with HCC within 5 years before antiviral treatment. Self-discontinuation/LTFU was identified as patients failing to refill medication for ≥2 consecutive months, verified through medical

chart review. Logistic regression analysis identified factors associated with self-discontinuation. Hepatic decompensation (HD) was determined using ICD codes (ICD-9: 572.2, 789.5, 578.0, 578.9, 456.0, 456.2 or ICD-10: K72.9, K72.91, R18.8, K92, K92.2, I85.01, I85.11, I86.4). HD events after Nuc discontinuation in nonretreated patients or within 1 year during retreatment were considered associated with Nuc discontinuation. Comparison was made between self-discontinuation and scheduled withdrawal.

Results: A total of 3358 HBeAg-negative CHB patients with 4217 treatment courses were included. Over a median treatment duration of 2.4 (IQR: 1.1-3) years, 341 self-discontinuation/LTFU events were identified, with annual incidence rates of 3.02% and cumulative rates of 8.61%, 13.23%, and 19.97% at 3, 5, and 10 years. Most self-discontinuation events (38.4%) occurred within the first year. Factors associated with self-discontinuation events included age (<40 or ≥70) [age 40-69 as referent: <40, aOR: 2.10; ≥70, aOR: 1.65], liver cirrhosis (aOR: 2.04), prior treatment experienced (aOR: 0.61), pretherapy ALT levels (<2X ULN as referent, 2-5X ULN: aOR: 0.72, >5X ULN: aOR: 0.78), and use of ETV (TDF as referent, aOR: 1.36). During median follow-up of 2.5 years (IQR: 1.3-5.4), 49 (2.1%) of 2,321 patients who stopped Nuc experienced off-Nuc HD events, primarily among cirrhosis patients (96%). Self-stop/LTFU patients had significantly higher HD incidence (7.3% vs. 1.2%, P < 0.0001) than scheduled stopped patients.

Conclusions: Self-discontinuation/LTFU increased with the duration of Nuc therapy, reaching 8.61% and 19.97% within 3 and 10 years, respectively. Among these cases, 7.3% were complicated by HD. It is crucial to prioritize education and establish a tele-call back service to prevent such events and mitigate the associated adverse outcomes.

Section: Pancreas / Biliary ⑲

THE IMPACT OF METABOLIC FACTORS AND LIPID LOWERING DRUGS ON COMMON BILE DUCT STONE RECURRENCE AFTER ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY

Sheng-Fu Wang, Chi-Huan Wu, Yung-Kuan Tsou, Kai-Feng Sung, Cheng-Hui Lin, Nai-Jen Liu, Mu-Hsien Lee

Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan 代謝因子與降血脂藥物對於在逆行性膽 胰攝影後膽管結石復發的影響

王昇富 吳季桓 鄒永寬 宋皚峰 林政輝 劉乃仁 李沐憲 林口長庚紀念醫院胃腸肝膽科

Background: Recurrent common bile duct stone after endoscopic retrograde cholangiopancreatography is an undesired problem although following cholecystectomy is done. An important factor is composition and properties of stones that results in recurrent common bile duct stone and the most significant etiology among these is the lipid level. Although many studies had proved the association between the serum lipid level and gallstones formation, not any study previously reported about the recurrent common bile duct stone after endoscopic retrograde cholangiopancreatography.

Aims: Aim 1: the association between serum lipid profile and recurrent common bile duct stone after endoscopic retrograde cholangiopancreatography. Aim 2: the association between lipid lowering drugs and recurrent common bile duct stone after endoscopic retrograde cholangiopancreatography.

Methods: We retrospectively collected 2016 patients underwent endoscopic sphincterotomy from 20152017 in Linkou Chang Gung Memorial Hospital. After excluding patients with malignant stricture, benign stricture, bile leakage and altered anatomy, we included 438 patients had cholangitis with common bile duct stone who had checked serum lipid profile after the first ERCP. Among these patients, 303 patients had cholecystectomy after first endoscopic retrograde cholangiopancreatography were finally included for analysis. We analyze if the metabolic factors including body weight, BMI, HbA1C and serum lipid profile may impact the rate of common

bile duct stone recurrence and also the different lipid lowering drugs.

Results: We found serum HDL level ≥40 (p = 0.000, OR = 0.207, 95% CI = 0.114-0.376) is a protective factor and total cholesterol level ≥200 (p = 0.004, OR = 4.558, 95% CI = 1.625-12.787) is a risk factor of recurrent common bile duct stone after endoscopic retrograde cholangiopancreatography although cholecystectomy was done. Of lipid lowering drugs, statin seems could reduce the risk of recurrence (p = 0.003, OR = 0.297, 95% CI = 0.132-0.665).

Conclusions: Serum lipid level could impact recurrent common bile duct stone after endoscopic retrograde cholangiopancreatography although cholecystectomy was done and statin seems can reduce the risk of recurrence.

⑳

CLINICAL

CHARACTERISTICS OF PRIMARY BILIARY CHOLANGITIS PATIENTS AND ASSOCIATED ENDOSCOPIC FINDINGS: ONECENTER EXPERIENCE IN TAIWAN

Pei-Tzu Chen, Hsuan-Hwai Lin, Tien-Yu Huang, Yu-Lueng Shih, Wei-Kuo Chang, Tsai-Yuan Hsieh, Peng-Jen Chen, Hsuan-Wei Chen

Division of Gastroenterology, Department of Internal Medicine, Tri-service General Hospital, Taipei, Taiwan

原發性膽汁性膽管炎病人的臨床特徵以 及相關內視鏡檢查發現：單一醫學中心

經驗分享

陳培慈 林煊淮 黃天祐 施宇隆 張維國 謝財源 陳鵬仁 陳宣位

三軍總醫院胃腸肝膽科

Background: Patients with cirrhosis are suggested to receive endoscopic screen for esophageal varices because of portal hypertension. However, patients with primary biliary cholangitis (PBC) did not routinely undergo endoscopic examinations. Nevertheless, although it is widely discussed that bile acids may increase the incidence rate of colon polyps by inducing colonic epithelium cell damage, there are only few studies in discussing colonic findings in PBC patients, which was assumed to be related to cholestasis. The issues of PBC patients’ endoscopic characteristics are still unclear.

Aims: Our study aims to evaluate the esophagogastroduodenoscopy (EGD) and colonoscopy findings in the primary biliary cholangitis (PBC) patients, which was assumed to be related to cholestasis condition.

Methods: The retrospective study was conducted at the Tri-Service General Hospital, Taiwan, and comprised data of patients aged >20 years diagnosed with primary biliary cholangitis between January 2000 and December 2018 after approval from the institutional review board. In PBC patients, the endoscopic findings including esophagogastroduodenoscopy (EGD) and colonoscopy were recorded.

Results: In PBC group, only 28 patients received EGD examinations. Among the 28 PBC patients who underwent EGD, 13 (46.4%) patients had EV and there

were no varices findings in control group (p < 0.05). Patients with PBC also presented higher incidence rate of colon polyps (50% vs. 14%; p < 0.001).

Conclusions: The findings of higher risks of esophageal varices and colon polyps supported the rationale of endoscopic examination in PBC patients.

㉑

HOW A WEAKLY SUPERVISED CONVOLUTIONAL NEURAL NETWORK ASSISTS RADIOLOGISTS INTERPRETING CHOLEDOCHOLITHIASIS ON CT IMAGE? A REAL-WORLD VALIDATION COHORT

Meng-Ying Lin1, Yi-Shen Liu2, Chia-Hsing Lu2, Ming-Ching Ou2, Chun-Rong Huang3, Wei-Lun Chang1

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nation Cheng Kung University Hospital, Tainan, Taiwan

2Department of Medical image, Nation Cheng Kung University Hospital, Tainan, Taiwan

3Department of Computer Science and Engineering, National Chung Hsing University, Taichung, Taiwan

一個弱監督式的卷積神經網路在現實世 界之世代中如何輔助放射科醫師判讀總 膽管結石

林孟穎1 劉益勝2 呂嘉興2 歐明靜2 黃春融3 張維倫1

1 國立成功大學醫學院附設醫院胃腸肝膽科

2 國立成功大學醫學院附設醫院影像醫學部

3 國立中興大學資訊工程研究學系

Background: Common bile duct stones are usually symptomatic and need to be detected earlier. CT is a convenient modality for diagnosing choledocholithiasis with acceptable accuracy. However, it takes time to review CT images thoroughly and make a diagnosis.

Aims: We aimed to evaluate whether our previously designed artificial intelligence system can assist radiologists in interpreting choledocholithiasis on CT scans.

Methods: We retrospectively enrolled patient data from October 2019 to June 2020 whose tentative diagnosis was cholangitis and interpreted their CT images with our previously published artificial intelligence system. Two experienced radiologists were invited to interpret the same images. The ground truth (stone positive on CT scan) was defined by the combined opinion of three experienced radiologists. The diagnostic performance was compared after interpretation was completed.

Results: A total of 176 patients with 12,320 non-

contrast CT images were enrolled for evaluation. The diagnostic sensitivity, specificity, and accuracy by applying a rigorous definition were 78.8%, 97.1%, and 96.5%, respectively. However, if we used a flexible definition (ignoring misinterpretation within continuous images), the diagnostic sensitivity, specificity, and accuracy could reach 94.9%, 97.5%, and 97.4%, respectively. The Kappa value between AI and radiologists was 0.68 and 0.69, respectively, without significant differences in sensitivity. The NPV of this AI system reached 99.82% in a total of 11,629 image interpretations. Of the 302 images recognized as false positive images, 207 did not contain CBD in the picture and could be quickly withdrawn.

Conclusions: A weakly supervised artificial intelligence system for diagnosing choledocholithiasis has a high negative predictive value in a real-world validation cohort and can assist radiologists in selecting images that need to be interpreted.

㉒SINGLE-OPERATOR

CHOLANGIOSCOPY-GUIDED LITHOTRIPSY IN PATIENTS WITH CYSTIC DUCT STONE AND CYSTIC DUCT STUMP STONE: EXPERIENCE OF A MEDICAL CENTER

Chi-Ying Yang, Wen-Hsin Huang, Shih-Chieh Chuang, Hsing-Hung Cheng, Tsung-Lin Hsieh

Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan 單人膽管鏡引導碎石術治療膽囊管結石 及膽囊管殘端結石：一醫學中心的經驗 楊其穎 黃文信 莊世杰 鄭幸弘 謝宗霖

中國醫藥大學附設醫院消化系內科

Background: The cystic duct stone can cause inflammation, infection, and obstruction of the biliary tract. Diagnosis of the cystic duct is often difficult and challenging, even with surgical management. It is difficult to remove cystic duct or cystic duct stump stone by conventional Endoscopic retrograde cholangiopancreatography (ERCP) technique because of small diameter and tortuous of cystic duct. A single-operator cholangioscopy system involves the insertion of a thin, flexible endoscope through an ERCP catheter, providing direct visualization of the biliary tree. Studies have shown favorable clinical outcomes when merging cholangioscopy with electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) for biliary stones. However, data on the efficacy and safety of cholangioscopy guided lithotripsy for cystic duct and cystic duct stump stones are limited. Aims: We aimed to evaluate the clinical outcomes and safety of cholangioscopy-assisted lithotripsy in patients with cystic duct and cystic stump stone.

Methods: The cystic duct stone or cystic duct stump stone was confirmed by abdominal computed tomography or cholangiogram of ERCP. All the cases were received ERCP and cystic duct stone or cystic stump stone was difficult to remove by ERCP method. From April 2016 to June 2023, patients underwent cholangioscopy-assisted lithotripsy with electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) at China Medical University Hospital, and data were retrospectively collected, including age, gender, stone size, lithotripsy, cystic duct stone clearance

rate, number of required sessions, and procedure complications.

Results: A total of 14 patients were included and the median age of patients was 61 years (range 4380 years). Six patients were female (6/14, 43%). Ten patients present as Mirizzi syndrome and 5 patients had common bile duct stones. Fifty percent patients (n = 7) were cystic duct stone and others were cystic duct stump stones. The median stone size was 11 mm (range 6-20 mm). Twelve patients have one stone and two patients suffered from three stones. Eleven (11/14; 79%) patients were successfully treated in 1 (range 1-2) sessions including LL (n = 9) and EHL (n = 6) to achieve stone clearance. Ten patients (10/14, 71%) were successful stone clearance on first session cholangioscopy with LL (n = 5) and EHL (n = 5). Three patients were technical failure. In two of the patients, the cholangioscopy could not enter the cystic duct due to the angle of the cystic duct and common bile duct; one patient was failed to remove stones from the cystic duct after lithotripsy. Adverse events after the procedure occurred in 2 (14.3%) patients, including fever (n = 2) without hemodynamic instability, bacteremia or other severe complications.

Conclusions: Cholangioscopy-assisted lithotripsy is an effective and safe treatment for management of cystic duct or cystic duct stump stone. Most of cases were successful stone clearance in one session.

㉓COMPARISON OF INCIDENCE OF CHOLECYSTITIS ASSOCIATED WITH BILATERAL STENT-IN-STENT OR SIDE-BY-SIDE STENT PLACEMENT IN PATIENTS WITH MALIGNANT HILAR OBSTRUCTION PATIENTS

Hyeon-Tae Cho, Jong-Hyun Lee, Dong-Uk Kim, Moon-Won Lee, Jeong-gil Park, Cheol-Ung Kim

Department of Internal Medicine, Pusan National University School of Medicine, Busan, Korea

Background: The malignant obstruction of the hilar bile duct is a factor that affects the patient’s survival due to various complications such as cholangitis and sepsis. Bilateral placement of the metal stents is often used to solve this problem. However, cholecystitis can be caused by cystic duct obstruction because the stents are located at the common bile duct. We would like to compare the occurrence of cholecystitis in the two methods of stent placement used to manage malignant hilar obstruction.

Aims: We conducted a study to compare the two stent placement methods used for the treatment of malignant hilar obstruction in order to determine which one is more effective

Methods: 49 patients were treated with stent-instent or side-by-side manners for malignant hilar obstruction from 2011 to 2020 in a tertiary hospital. We retrospectively compared the incidence of cholecystitis, early-onset (less than 7 days), and lateonset (7 days or more) cholecystitis according to the methods of stent placement.

Results: Side-by-side stent placement was administered in 23 patients, and stent-in-stent placement was administered in 24 patients. The average age of the side-by-side stent placement group was 75.5 ± 9.3, and the average age of the stent-instent placement group was 80.3 ± 10.3. The incidence of cholecystitis was not significantly different from 5 in the side-by-side stent placement group and 5 in the stent-in-stent placement group (p = 0.940). Each group had no patients and 3 patients with early-onset cholecystitis(p = 0.080). In late-onset cholecystitis, there were 5 patients and 2 patients(p = 0.197). Stent obstruction was not significantly different between 10 patients and 13 patients (p = 0.464). However, the duration was on average 148 days to 131 days and the survival period was on average 210 to 184 days, which was slightly longer in the side-by-side stent

placement group.

Conclusions: The stent patent and patient survival period were longer in the side-by-side stent placement group than in the stent-in-stent placement group. Cholecystitis had no statistically significant difference between the side-by-side stent and the stent-in-stent placement groups. However, no patients suffered from early-onset cholecystitis in the side-by-side stent placement group, and its p-value was 0.080. More research can be helpful to evaluate the relationship.

Section: Cirrhosis & HCC ㉔

IMPACT OF ADDITION OF ANNUAL GADOXETIC ACIDENHANCED ABBREVIATED MAGNETIC RESONANCE IMAGING ON ULTRASOUND HEPATOMA SURVEILLANCE FOR LIVER CIRRHOSIS – A RANDOMIZED STUDY

Jing-Houng Wang1, Hsin-You Ou2, Yi-Hao Yen1, Chao-Hung Hung1, Sheng-Nan Lu1

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Departments of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan

增加每年一次卜邁維斯簡短核振共振檢 查對肝硬化病患定期超音波肝癌篩檢的 影響 隨機對照研究

王景弘1 歐信佑2 顏毅豪1 洪肇宏1 盧勝男1

1 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 2 長庚醫療財團法人高雄長庚紀念醫院放射診斷科系

Background: Hepatoma (HCC) surveillance with semi-annual ultrasound (US) is recommended for high-risk patients.

Aims: The purpose of this study is to investigate the impact of addition of annual gadoxetic acidenhanced abbreviated magnetic resonance imaging (aMRI) on the recommended US surveillance.

Methods: Patients with compensated liver cirrhosis at regular HCC surveillance using US and alphafetoprotein (AFP), with adequate renal function and without HCC diagnosis were enrolled. The enrolled patients were randomized to either addition of annual aMRI or continuous US surveillance group. For patient in aMRI group, gadoxetic acid-enhanced aMRI was performed at enrollment and annually. We compared liver nodule detection, HCC development, and HCC diagnosis procedures including dynamic imaging or biopsy performances during the surveillance.

Results: There were 104 patients enrolled to this study with 15 patients excluded for loss of regular follow-up. A total of 89 patients (aMRI: 45 and US: 44) was analyzed in a median follow-up of 33.6

months. There were no significant differences in baseline characteristics between two groups. There were no statistical differences in hepatic nodule detections (aMRI: 10 and US: 18, p = 0.074) and HCC developments (aMRI: 1 and US: 6, p = 0.058) between two groups. While one HCC with 1.2 cm in size (BCLC stage: 0) was diagnosed in aMRI group, six HCC with mean size of 2.4 cm (BCLC stage 0: 2, A: 3, B: 1) in US group. For patients in US group, there were 18 (40.9%) undergoing HCC diagnosis procedures including dynamic imagings and/or biopsy, which was higher than 9 (20%) in aMRI group (p = 0.032). Curative treatments were performed, including one resection and 6 radiofrequency ablations.

Conclusions: For patients with compensated liver cirrhosis at HCC surveillance using regular US and AFP, addition of annual gadoxetic acid-enhanced aMRI might reduce HCC diagnosis procedures.

㉕

M2BPGI CORRELATED WITH IMMUNOLOGICAL BIOMARKERS AND FURTHER STRATIFIED RECURRENCE RISK IN PATIENTS WITH HEPATOCELLULAR CARCINOMA

I-Cheng Lee1,2, Hao-Jan Lei3, Gar-Yang Chau3, Ming-Chih Hou1,2, Yi-Hsiang Huang1,2,4,5

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2School of Medicine, National Yang Ming Chiao

Tung University, Taipei, Taiwan

3Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

4Healthcare and Service Center, Taipei Veterans General Hospital, Taipei, Taiwan

5Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

M2BPGI 與免疫生物標記相關並可進一步 區分肝癌復發風險

李懿宬1,2 雷浩然3 周嘉揚3 侯明志1,2 黃怡翔1,2,4,5

1 臺北榮民總醫院胃腸肝膽科

2 國立陽明交通大學醫學系

3 臺北榮民總醫院外科部

4 國立陽明交通大學臨床醫學研究所

5 臺北榮民總醫院健康管理中心

Background: The current criteria to select candidates with high risk features for adjuvant immunotherapy for hepatocellular carcinoma (HCC) remains unsatisfactory. Novel surrogate biomarkers reflect liver fibrosis and immuology might correlate with the risk of HCC recurrence.

Aims: The aim of this study was to evaluate the prognostic value of serum biomarkers in predicting HCC recurrence after curative resection.

Methods: Serum biomarkers including M2BPGi, IL-6, IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM-3 and LAG-3 in 248 patients with HCC receiving surgical resection were measured. Factors associated with recurrence-free survival (RFS) were evaluated. We used IMbrave 050 criteria to define low- and high-risk of HCC recurrence.

Results: Serum M2BPGi level significantly correlated with FIB-4 score, Ishak fibrosis stage, ALBI score, and serum IL-10, CCL5, VEGF-A, soluble PD-1, PD-L1, TIM3 and LAG-3 levels. M2BPGi, VEGF-A, soluble PD-1,

and TIM-3 levels significantly correlated with RFS. By multivariate analysis, M2BPGi >1.5 COI (hazard ratio (HR) = 1.607, p = 0.020), AFP >7 ng/mL (HR = 1.659, p = 0.018), tumor size >5 cm (HR = 1.664, p = 0.017), microvascular invasion (HR = 1.643, p = 0.046) and BCLC stage B or C (HR = 2.287, p < 0.001) were independent predictors of RFS. M2BPGi level significantly stratified the recurrence risk in IMbrave 050 low- (RFS 87.8 vs 57.6 months, p = 0.030) and high-risk groups (36.8 vs 11.4 months, p < 0.001). In the IMbrave 050 high-risk group, an M2BPGi-based model could further stratify the recurrence risk into low-, intermediate-, high- and very high-risk groups (2-year RFS of 78.3%, 64.7%, 47.6% and 15.6%, respectively, p < 0.001).

Conclusions: Serum M2BPGi level significantly correlated with surrogate markers of liver fibrosis, liver function and immunological biomarkers. M2BPGi further stratified the risk of HCC recurrence after resection, especially in the IMbrave 050 high-risk group.

㉖

LOW ATG4B EXPRESSION CORRELATED WITH TUMOR MALIGNANCY AND POOR PROGNOSIS OF HEPATOCELLULAR CARCINOMA

Po-Lin Tseng1, Ming-Hong Tai2, Chih-Wen Shu3, Chao-Cheng Huang4, Li-Na Yi1, Kuo-Chin Chang1, Tsung-Hui Hu1

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan

3Institute of BioPharmaceutical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan

4Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

自噬相關蛋白 4B 低表現量與肝癌惡性度 與不良預後有關

曾柏霖1 戴明泓2 徐志文3 黃昭誠4 易麗娜1 張國欽1 胡琮輝1

1 高雄長庚紀念醫院胃腸肝膽科系暨長庚大學醫學系 2 國立中山大學生物醫學研究所

3 國立中山大學生技醫藥研究所

4 高雄長庚紀念醫院病理科暨長庚大學醫學系

Background: Autophagy–related (ATG) proteins may play different roles in not only suppressing tumor initiation, but also promoting cancer malignancy. ATG4B expression is higher in tumor cells than that in adjacent normal cells in colorectal cancer, CD34+ chronic myeloid leukemia and HER2 positive breast cancer patients. However, the role of ATG4B in hepatocellular carcinoma (HCC) remains unclear.

Aims: To investigate the ATG4B expression in HCC tumor tissues and normal adjacent part and the correlations with clinicopathological features of HCC.

Methods: A total of 90 HCC surgical resection specimens were collected from the Department of Pathology at Kaohsiung Chang Gung Memorial Hospital for western immunoblotting. Ten HCC (2010-2013) paraffin tissues after liver resection was

obtained for immunohistochemical staining. The ATG4B expression level was defined as high when ATG4B total protein level calculated by total intensity of normal tissues and tumor samples is higher than median (1.362) intensity. The correlations between ATG expression levels and clinicopathologic features of HCC, including histologic tumor grades, stages, survival outcome, serum levels of AFP, cirrhotic background, hepatitis markers, and tumor sizes were analyzed.

Results: Low ATG4B expression in patients with HCC was correlated with increased tumor grades (P = 0.026), advanced tumor stages (P = 0.003), high serum AFP levels (P = 0.003), larger tumor size (P = 0.004), positive vascular invasion (P= 0.001) and low P62 expression (P = 0. 003). Patients with low ATG4B expression had a significant lower overall survival rate and significant higher recurrent rate. Univariate analysis showed AFP level > 200 ng/mL, TNM stage III and IV, poor histology grade (II and III), AST level > 40 U/L, liver cirrhosis, fibrosis III and IV, vascular invasion and low ATG4B expression were risk factors for recurrence HCC. Multivariate analysis showed fibrosis III and IV (P = 0.008), vascular invasion (P < 0.001) were significantly associated with HCC recurrence. In survival analysis, univariate analysis showed that tumor size > 5 cm, TNM stage III and IV, poor histology grade (II and III), vascular invasion and low ATG4B expression were risk factors for mortality. Multivariate analysis showed TNM stage III and IV (P < 0.001) and low ATG4B expression (P = 0.006) were significantly associated with mortality.

Conclusions: Low ATG4B expression is correlated with poor HCC differentiation, advanced tumor stage, higher tumor recurrence and poor overall survival.

㉗

THIRD VACCINE BOOSTERS

AND ANTI-S-IGG LEVELS: A COMPARISON OF HOMOLOGOUS AND HETEROLOGOUS RESPONSES AND POOR IMMUNOGENICITY IN HEPATOCELLULAR CARCINOMA

Chih-Wen Wang1, Chung-Feng Huang2, Tyng-Yuan Jang2, Ming-Lun Yeh2, Po-Cheng Liang2, Po-Yao Hsu2, Ching-I Huang2, Yi-Hung Lin1, Jee-Fu Huang2, Chia-Yen Dai2, Wan-Long Chuang2, Ming‐Lung Yu2

1Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan

2Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

第三劑疫苗增強劑抗 S-IgG 濃度：同源和

異源反應的比較以及肝細胞癌的低免疫 反應

王志文1 黃釧峰2 張庭遠2 葉明倫2 梁博程2 許博堯2 黃駿逸2 林宜紘1 黃志富2 戴嘉言2 莊萬龍2 余明隆2

1 高雄市立小港醫院內科部

2 高雄醫學大學附設中和紀念醫院肝膽胰內科

Background: The immune response of patients with chronic liver disease tends to be lower after receiving their second COVID-19 vaccine dose, but it is currently unknown how their immune response will be affected by a third vaccine dose.

Aims: The objective of this study was to investigate the anti-spike protein (anti-S) IgG response in patients with HBV, HCV, NAFLD, liver cirrhosis, and HCC following the administration of a third dose of either a homologous or heterologous vaccine.

Methods: A total of 722 patients without previous SARS-CoV-2 infection were recruited from three hospitals. A total of 132 individuals without chronic liver disease were included in the sensitivity analysis as controls. The study administered homologous (MMM) and heterologous (AZAZBNT, AZAZM) boosters, where AZ, BNT, and M denoted the AZD1222, BNT162b2, and mRNA-1273 vaccines. Serum IgG spike antibody levels were measured mean 1.5 ± 0.7 (visit 1) and 5.0 ± 0.5 months (visit 2) after the third vaccine booster. A threshold of 4160 AU/mL was considered significant antibody activity.

Results: In both visits, the MMM booster had higher anti-S-IgG levels than the AZAZBNT and AZAZM boosters. Patients with active hepatocellular carcinoma (HCC) had lower anti-S-IgG levels than the control group (761.6 vs. 1498.2; p = 0.019) in visit 1. The anti-S-IgG levels decreased significantly in visit 2. Individuals with significant antibody activity had a lower proportion of liver cirrhosis with decompensation (0.7% decompensation versus 8.0% non-decompensation and 91.3% non-liver cirrhosis, p = 0.015), and active HCC (1.5% active HCC versus 3.7% non-active HCC and 94.7% non-HCC, p < 0.001). Receiving the MMM booster (OR = 10.67, 95% CI 5.20–21.91, p < 0.001) significantly increased odds of having significant antibody activity compared with AZAZBNT booster.

Conclusions: Patients who have active HCC exhibit a reduced immune response to the third COVID-19 vaccine booster. However, in patients with chronic liver disease, receiving a homologous mRNA-1273 booster significantly increased the likelihood of having a notable antibody response.

㉘

PROGNOSTIC GENE SIGNATURES OF CIRCULATING TUMOR CELLS/ CIRCULATING EPITHELIAL CELLS IN LIVER CANCER

Ching-Chih Lin1,2, Po-Yao Hsu1, Yi-Shan Tsai1, Ming-Ying Lu1, Ming-Lun Yeh1,2, Chung-Feng Huang1,2, Chia-Yen Dai1,2, Jee-Fu Huang1,2, Wan-Long Chuang1,2, Ming-Lung Yu1,2,3

1Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

2Center for Liquid biopsy and Cohort Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

3School of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan

肝癌循環腫瘤細胞∕循環上皮細胞的預 後基因特徵

林敬智1,2 許博堯1 蔡易珊1 呂明穎1 葉明倫1,2 黃釧峰1,2 戴嘉言1,2 黃志富1,2 莊萬龍1,2 余明隆1,2,3

1 高雄醫學大學附設中和紀念醫院肝膽胰內科

2 高雄醫學大學液態生物檢體暨世代研究中心

3 國立中山大學學士後醫學系

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in human beings and serves as the third leading cause of cancer mortality worldwide. Early surveillance of liver disease progression to HCC in CLD is very important for further treatment and management. Liquid biopsies may serve as a surrogate of invasive biopsies because circulating tumor cells (CTCs) / circulating epithelial cells (CECs) harbor molecular features that are associated with cancers.

Aims: In this study, we utilize RNA-sequencing of CTCs/CECs purified from the blood of patients with CLD or HCC to explore the gene signature of liver disease progression and analyze its association with clinicopathologic features and prognosis of HCC patients.

Methods: A total of 190 patients were included in this study, including 60 patients with primary liver cancer, 120 patients with chronic liver disease, and 10 healthy people. As a proof of concept for the possible phenotypes of CTCs/CECs according to the underlying

disease state, we performed gene expression profiling by RNA-seq. The selected genes further validated by quantitative real-time PCR (RT-qPCR) in paired tumor and adjacent liver tissue samples of 200 HCC cases from TLCN.

Results: Our data showed that there were 624 genes overexpressed in CTC/CEC of CLD or HCC compared to healthy controls. In addition, we created a 14-gene signature including MKI67, TMC5, KIF18B, BCAM, BUB1, ATAD2, ANLN, CENPF, KIF14, FBLIM1, DKK1, DLGAP5, TTC39A and KIF23 using The Cancer Genome Atlas (TCGA) database. In our case, six of the 14 selected genes were highly expressed in HCC compared to the CLD group, including FBLIM1, BCAM, DKK1, TTC39A, CENPF and KIF18B (p < 0.05). Notably, higher FBLIM1, BCAM and DKK1 expression was associated with age > 60 years (p < 0.05) and the worse clinicopathologic characteristics including AFP >100 ng/ml (p < 0.05), and AST ≤ 40 IU/L (p < 0.05), which were linked with poorer prognosis of HCC. The mRNA level of these three candidate genes (FBLIM1, BCAM and DKK1) were significantly higher in HCC tissues than corresponding adjacent non-tumorous liver tissues, indicating that higher expression levels of these candidate genes had great risk for HCC progression.

Conclusions: Taken together, our study suggests that the significant overexpression of these candidate genes, FBLIM1, BCAM, and DKK1, is a novel independent factor for the progression of CLD to HCC.

PERSONALIZED TREATMENT FOR HEPATOCELLULAR CARCINOMA USING ARTIFICIAL INTELLIGENCE

Chih-Wen Lin1,2,3, Pojen Hsiao2,3, Chen-Wen Yen4, James Yu Lin1,2,4,7, Steven Yu Lin1,2,4,5,7, Ming-Lung Yu6,7,8,9

1Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan

2School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan

3Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan

4Department of Mechanical and ElectroMechanical Engineering, National Sun Yat-Sen University, Kaohsiung, Taiwan

5Kaohsiung American School, Kaohsiung, Taiwan

6School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan

7Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

8Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

9National Pingtung University of Science and Technology, Pingtung, Taiwan 人工智慧在肝癌個人化醫療的使用 林志文1,2,3

1 義大醫院胃腸肝膽科

2 義守大學醫學系

3 義大大昌醫院胃腸肝膽科

4 國立中山大學機械與電機工程系

5 高雄美國學校

6 國立中山大學學士後醫學系

7 高雄醫學大學醫學院肝炎研究中心

8 高雄醫學大學附設中和紀念醫院肝膽胰內科及肝炎 中心

9 國立屏東科技大學

Background: The Barcelona Clinic Liver Cancer (BCLC) stage patients are often quite heterogeneous, but different prognostic factors are generally considered

to be of similar degree of impact in the current staging system. Recent attempts on applying the artificial intelligence (AI) and machine learning (ML) technique to clinical practice have focused on using AI to develop clinical decision care system (CDCS). The AI in clinical decision for HCC prognosis remained largely unknown.

Aims: This study aims to investigate the personalized treatment using AI based on CDCS for HCC treatment and prognosis.

Methods: We respectively collect 10292 new diagnosis HCC patients and their relevant clinical data between 2006 and 2021 from E-DA hospital and Kaohsiung Medical University hospital. We develop the new model by ML using that data was randomly divided into training set (80%) and validation set (20%) and got predictive results (repeat 100 times and get average results). Cox proportional hazards model was analyzed by concordance index (C-index). Survival time for all patients in applying the ML based XGBoost survival regression model.

Results: Of the 10218 patients, the mean age was 62.6 years and 73.6% were male. 38.3%, 32.5%, and 24.3% of patients had hepatitis B virus infection (HBV), hepatitis C virus infection (HCV), and alcohol history, respectively. 3578 (35%) and 6640 (65%) patients were survival and mortality during the median follow-up time of 39.2 (range, 1.0-301) and 10.6 (range, 0.6-218), respectively. We achieved a good C-index 0.80 using Cox regression model to predict survival outcomes. To explore personized medicine in the impact of change the treatment method on survival, we change the treatment method and fix the other factors. First, the survival was significantly reduced from 70 to 91 months when we change the transplantation to other treatments. Only 2% of patients had better survival when patients underwent transplantation change to resection and other patients had worse survival when patients underwent transplantation change to other treatment. Second, the survival was significantly increased 25 months when we change the resection to transplantation, and the survival was significantly reduced from 12 to 29 months when we change the resection to other treatments except transplantation. 96% of patients had better survival when patients underwent resection change to transplantation and 2% to 14% of patients had better when patients underwent resection change to other treatment.

Conclusions: Our new CDCS model can provide personized treatment and predict the clinical outcomes for individual patients using AI. We offered the important information with shared decision making for individual patient to choice the optimal therapies.

Section: UGI

㉚

THE MOST PREFERRED ERADICATION REGIMEN AND EXPECTATIONS OF PATIENTS FOR FIRST-LINE ANTI-H. PYLORI THERAPY: A PILOT SHARED DECISION-MAKING SURVEY IN TAIWAN

I-Ting Wu1, Deng-Chyang Wu2, Yoen-Young Chuah3, Hsi-Chang Lee4, Kuan-Yang Chen4, Chao-Hung Kuo2, Chang-Bih Shie1, Kun-Feng Tsai1, Wen-Wei Huang1, Sheng-Yeh Tang1, Li-Fu Kuo1, Ping-I Hsu1

1Division of Gastroenterology, Department of Medicine, Tainan Municipal An Nan Hospital, China Medical University, Tainan, Taiwan

2Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

3Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ping Tung Christian Hospital, Pingtung, Taiwan

4Division of Gastroenterology and Hepatology, Department of Internal Medicine Taipei City Hospital, Renai Branch, Taipei, Taiwan

台灣病患在第一線幽門螺旋桿菌除菌治 療時最偏好之處方與對除菌之期待：一 醫病共享之前導普查

1 黃文威1 湯昇燁1 郭立夫1 許秉毅1

1 臺南市立安南醫院暨中國醫藥大學消化內科

2 高雄醫學大學附設醫院胃腸內科

3 屏東基督教醫院胃腸肝膽科

4 臺北市立聯合醫院仁愛院區消化內科

Background: Helicobacter pylori (H. pylori) infection is the leading cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and gastric adenocarcinoma. Eradicating H. pylori has become the standard treatment for peptic ulcer disease. The REAP-HP 2020 survey showed that 14-day standard triple therapy, 7-day standard triple therapy and 14-day reverse hybrid therapy were the three most commonly used anti-H. pylori regimen by gastroenterologists in Taiwan. Currently, medical practice emphasizes shared decision making with patients. It remains unclear which eradication regimen is preferred by infected patients.

Aims: (1) To investigate the preferred first-line anti-H. pylori regimens among infected patients in Taiwan, and (2) To compare the differences in preferred anti-H. pylori therapies and expectations concerning eradication treatments among patients in different hospitals in Taiwan.

Methods: A questionnaire for the H. pylori eradication survey of patients was distributed to patients who had previously received anti-H. pylori therapy or who were to be prescribed eradication regimens for H. pylori infection in the Ping Tung Christian Hospital (PTCH), Kaohsiung Medical University Hospital (KMUH), and Tainan municipal An Nan hospital (TMANH) from January 2019 to December 2022. In the survey, the characteristics of all eradication therapies including regimens, eradication rate, adverse effects and cost were introduced to the participants. Then, the participants were asked about their preferred eradication regimens, most concerning factors, and minimum acceptable eradication rate during eradication treatment.

Results: A total of 503 patients from the PTCH (n = 300), KMUH (n = 103) and TMANH (n = 100) participated in the survey. The leading three most preferred anti-H. pylori regimens in these patients were 14-day reverse hybrid therapy (73%; n = 365). 7-day standard triple therapy (17%, n = 86) and 14-day bismuth quadruple therapy (5%, n = 23). There were no differences in the preferred anti-H. pylori therapies among the patients in the three hospital. With regarding the concerning factors when choosing eradication regimen, the combination of 1. eradication rate, 2. side effects, and 3. medical cost was the leading one in all the three hospital (PTCH, KMUH and TMANH: 71%, 78% and 71%, respectively). The average minimal accepted eradication rates for the first-line regimen anticipated by patients in the three hospitals were 86%, 90% and 91%, respectively.

Conclusions: 14-day reverse hybrid therapy appears to be the most preferred anti-H. pylori regimen of infected patients in Taiwan. Eradication rate, side effects and medical cost are the top three concerning factors of H. pylori-infected patients when receiving eradication therapy.

㉛SCALP AND AURICULAR ACUPUNCTURE ATTENUATE RECURRENT GASTROESOPHAGEAL REFLUX DISEASE AND RELATED INFLAMMATORY CYTOKINES

Ming-Shun Wu, Chun-Nan Chen, Sheng-Jie Shiue, Tze-Sian Chan, Fat-Moon Suk, Gi-Shih Lien

Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

頭皮針與耳針降低胃食道逆流的復發與 相關的發炎性細胞激素

吳明順 陳俊男 薛聖潔 張智翔 粟發滿 連吉時 臺北市立萬芳醫院消化內科

Background: Gastroesophageal reflux disease (GERD) is an emerging disorder in developed countries. The pathogenesis involved in the symptoms includes gastric acid, esophageal or gastric motility disorder, visceral hypersensitivity, and anatomical or autonomic dysfunction of the lower esophageal sphincter (LES). Proton pump inhibitor (PPI) is the most potent therapy for gastroesophageal reflux disease (GERD). However, long-term administration may cause gastric hypoacidity and complications of nutrient deficiency.

Aims: Triggering meridian acupoint has been studied to achieve its effect by modulating visceral hypersensitivity and LES tone in patients dependent or failed of PPI. Since scalp acupuncture stimulates trigeminal-parasympathetic reflex while auricular acupuncture evokes vagus nerve and subsequently interacts with the autonomic nervous system (ANS) of the viscera, thus it may restore the LES dysfunction and reduce visceral hypersensitivity. Despite the findings, it is not clear that acupuncture could attenuate the symptoms of patients with recurrent and PPI-dependent GERD.

Methods: We enrolled patients suffering from recurrent GERD dependent on PPI for at least 6 months. The interventional protocol was four sessions in 2-week treatment by Wen’s modern scalp and auricular acupuncture (WMA) versus seed acupressure (SAP). The reflux disease questionnaire (RDQ) scores, serum Gamma-aminobutyric acid (GABA), and serum inflammatory cytokines were evaluated before and after treatment.

Results: Total RDQ scores, on-demand PPI use,

esophageal epithelial cell-derived cytokines, tight junction-modulating cytokines, and recurrent GERD markers showed significant reduction after WMA. In addition, in patients with increasing GABA after WMA, the RDQ scores and on-demand PPI use were significantly decreased.

Conclusions: WMA relieves the symptoms of recurrent, PPI-dependent GERD may possibly through modulating ANS, thus concomitant reduction of either systemic or local inflammatory cytokines of the epithelial barrier of the lower esophagus.

㉜CORRELATION BETWEEN PSYCHOSOMATIC ASSESSMENT, HEART RATE VARIABILITY, AND REFRACTORY GERD: A PROSPECTIVE STUDY IN PATIENTS WITH ACID REFLUX ESOPHAGITIS

Hsin-Ming Wang1,2, Pao-Yuan Huang1, Shih-Cheng Yang1, Ming-Kung Wu3, Wei-Chen Tai1, Chih-Hung Chen1, Chih-Chien Yao1, Lung-Sheng Lu1, Seng-Kee Chuah1, Yu-Chi Lee1, Chih-Ming Liang1

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Department of Internal Medicine, Kaohsiung Municipal Feng Shan Hospital - Under the Management of Chang Gung Medical Foundation, Kaohsiung, Taiwan

3Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

心理身體評估、心率變異性和難治性胃 食道逆流病之間的相關性：一項對酸性 反流食道炎患者的前瞻性研究

王心明1,2 黃寳源1 楊世正1 吳明恭3 戴維震1 陳志弘1 姚志謙1 盧龍生1 蔡成枝1 李育騏1 梁志明1

1 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 暨長庚大學醫學系

2 高雄市立鳳山醫院（委託長庚醫療財團法人經營） 內科部

3 長庚醫療財團法人高雄長庚紀念醫院精神科系

Background: Gastroesophageal reflux disease (GERD) affects a significant proportion of individuals, with life stress being a contributing factor. This study aimed to investigate the correlation between psychosomatic evaluations, heart rate variability (HRV), and GERD in a cohort of individuals.

Aims: The study aimed to analyze the sequencing changes following proton pump inhibitor (PPI) treatment and identify predictive factors associated with refractory GERD.

Methods: A prospective cohort of 105 individuals

with reflux esophagitis and a control group of 50 participants without acid reflux symptoms were enrolled. Psychosomatic evaluations, including GERDQ, GERDQLQ, RSI, BAI, BDI, and SSS-8, were assessed at baseline and during treatment. HRV parameters were also evaluated. Multivariate analysis was used to identify predictive factors for refractory GERD. PPIs were administered regularly for the initial 2 months and then used on-demand. Refractory GERD was defined as less than 50% improvement in symptom relief or GERDQLQ score ≥20 after 8 weeks of PPI treatment.

Results: The GERD group had higher scores in all psychosomatic evaluations compared to the control group (all p-values < 0.001). Significant differences in HRV parameters were observed between the groups before treatment. Sequential reductions in GERD symptom scores and psychosomatic evaluations were observed during the initial eight weeks of treatment. Higher GERDQ (≥10) and SSS-8 (≥12) scores were predictive of refractory GERD (p = 0.004 and p = 0.009, respectively).

Conclusions: This study emphasizes the importance of considering physiological and psychological factors in the management of GERD. Psychosomatic evaluations provide valuable insights for assessing and treating GERD patients. Integrating stress management and comprehensive assessments into personalized treatment strategies is crucial.

㉝

SHORT-TERM VERSUS LONGTERM PROPRANOLOL USE DURING LIGATION PROGRAM FOR SECONDARY PROPHYLAXIS OF ESOPHAGEAL VARICEAL BLEEDING

Wen-Chi Chen1, Tsung-Chieh Yang2, Pei-Chang Lee2, Yen-Po Wang2, Ming-Chih Hou2, Fa-Yauh Lee2

1Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

2Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

以結紮術預防食道靜脈曲張再出血時， 併用短期與長期 Propranolol 之比較

陳文誌1 楊宗杰2 李沛璋2 王彥博2 侯明志2 李發耀2

1 高雄榮民總醫院胃腸肝膽科

2 臺北榮民總醫院胃腸肝膽科

Background: Endoscopic variceal ligation (EVL) plus non-selective beta-blockers (NSBBs) is the standard of care for secondary prophylaxis of esophageal variceal bleeding (EVB).

Aims: The aim of this trial was to compare the rebleeding rates between EVL plus NSBBs till eradication of esophageal varices (EEV) and EVL plus long-term NSBBs.

Methods: After control of acute EVB, patients with cirrhosis were randomized to two groups, with Group A patients receiving EVL plus propranolol till EEV, while Group B patients received standard of care with continuation of propranolol. Recurrent varices were ligated at follow-up endoscopy in both groups.

Results: The median follow-up period was 23.0 months in Group A (n = 106) and 23.6 months in Group B (n = 106). Twelve patients (11.3%) in Group A and 11 (10.4%) in Group B had recurrent EVB. The difference in rebleeding rates and the 95% confidence interval (CI) was .9% (-7.5%, 9.3%). The upper 95% CI bound of the difference was within the margin of 13.2% and the non-inferiority of Group A to Group B was established. Thirty-eight patients (35.8%) in Group A and 40 (37.7%) in Group B had further decompensation, with the difference (95% CI) of -1.9% (-14.9%, 11.1%). Twenty-four patients (22.6%) in Group A and 26 (24.5%) in Group B expired, with the difference (95% CI) in mortality rates of -1.9% (-13.3%, 9.5%).

Conclusions: EVL plus propranolol till EEV was non-inferior to EVL plus continuing propranolol in secondary prophylaxis of EVB in terms of recurrent bleeding.

㉞

CLINICAL OUTCOMES OF DIFFERENT TYPES OF METALLIC STENTS IN MALIGNANT DISTAL DUODENUM STENOSIS: A RETROSPECTIVE STUDY

Hau-Jyun Su1, Chieh-Chang Chen2, Yu-Ting Kuo3, Ming-Chang Tsai1, Ming-Lun Han3, Hsiu-Po Wang2

1Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

3Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei, Taiwan

不同金屬支架在惡性遠端十二指腸狹窄 的臨床預後探討：一篇回顧性研究

蘇浩俊1 陳介章2 郭雨庭3 蔡明璋1 韓明倫3 王秀伯2

1 中山醫學大學附設醫院內科部

2 國立臺灣大學醫學院附設醫院內科部

3 國立臺灣大學醫學院附設醫院綜合診療部

Background: Endoscopic management with selfexpandable metallic stents (SEMSs) for advanced malignant gastroduodenal obstruction is widely used, however stenting in patients with malignant distal duodenal stenosis (MDDS) is challenging because of the length and flexibility of the endoscope, the curved configuration of the duodenal C-loop, and the angle of the duodenojejunal flexure. Studies focusing on the outcomes of stenting in patients with MDDS are lacking.

Aims: This study aimed to investigate the clinical outcomes of stenting MDDS with different types of metallic stents.

Methods: From January 2012 to December 2020, fiftysix patients with MDDS who underwent duodenal stenting were enrolled. Thirty-five patients received uncovered self-expandable metallic stent (UC-SEMS), and twenty-one patients received partially covered self-expandable metallic stent (PC-SEMS). All patients were followed for 18 months. The clinical success rate, stent dysfunction rate, and stent patency were compared between the groups.

Results: The clinical success rates were 85.7% in both the UC-SEMS and PC-SEMS groups. Stent dysfunction rates (UC-SEMS: 34.3%, PC-SEMS: 38.1%, p = 0.77) and the average stent patency (UC-SEMS: 117.2 days, PC-SEMS: 100.0 days, p = 0.58) were not statistically

different between the groups. Multivariate analysis disclosed age ≥ 65 years was a significant risk factor for stent dysfunction (odds ratio: 5.0, p = 0.03).

Conclusions: Both UC-SEMS and PC-SEMS are safe and effective treatment options for MDDS. However, the stent dysfunction remains a significant issue, particularly in the elderly.

㉟EFFICACY OF TEGOPRAZAN-BASED HELICOBACTER PYLORI ERADICATION THERAPY IN KOREA

Moon Won Lee, Gwang Ha Kim, Dong Chan Joo, Bong Eun Lee, Cho hyeon-tae, Cheolung Kim, Jeong-gil Park

Department of Internal Medicine, Pusan National University College of Medicine and Biomedical Research Institute, Pusan National University Hospital, Pusan, Korea

Background: Tegoprazan is a novel potassiumcompetitive acid blocker developed in Korea. Several studies have shown a superior efficacy of vonoprazanbased Helicobacter pylori (H. pylori) eradication therapy; however, there have been few reports on tegoprazan-based H. pylori eradication therapy.

Aims: The aim of this study was to retrospectively evaluate the efficacy of tegoprazan-based H. pylori eradication therapy in Korea.

Methods: From January 2021 to February 2022, 72 patients underwent tegoprazan-based 1st-line concomitant and/or 2nd-line bismuth quadruple therapy in Pusan National University Hospital. Successful eradication was defined as a negative 13C-urea breath test 4-6 weeks after completion of the treatment.

Results: Seventy-two patients received tegoprazanbased 1st-line concomitant therapy for 7 or 10 days; the infection was eradicated in 67 patients (93.1%). Five patients that eradication was failed in tegoprazan-based 1st-line concomitant therapy received tegoprazan-based 2nd-line bismuth quadruple therapy for 7 or 10 days; H. pylori infection was eradicated in all these five patients (100%). In subgroup analysis, we found no significant difference in eradication rate according to treatment duration (7 days vs. 10 days) in both 1st- and 2nd-line tegoprazanbased therapies (Table). There were no significant adverse events during the treatment.

Conclusions: Tegoprazan-based 1st-line concomitant therapy and 2nd-line bismuth quadruple therapy showed excellent H. pylori eradication rates in Korea.

Poster

Section: Liver

P.01

5-MTP MAY HAVE THERAPEUTIC EFFECTS ON INFLAMMATION AND FIBROSIS IN NAFLD/NASH BY MODULATING MITOCHONDRIAL DYNAMICS

Szu-Jen Wang1,2, Shu-Chi Wang3, Chung-Feng Huang4, Ming-Lun Yeh4, Chia-Yen Dai4, Jee-Fu Huang4, Wan-Long Chuang4, Ming-Lung Yu1,4

1Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

2Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan

3Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan

4Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

5-MTP 可能通過調節粒腺體動力學改善 NAFLD/NASH 的發炎及纖維化

王嗣仁1,2 王述綺3 黃釧峰4 葉明倫4 蔡青陽2 戴嘉言4 黃志富4 莊萬龍4 余明隆1,4

1 高雄醫學大學臨床醫學研究所

2 阮綜合醫院消化內科

3 高雄醫學大學醫學檢驗生物技術學系

4 高雄醫學大學附設中和紀念醫院肝膽胰內科

Background: Mitochondria play a critical role in energy production and undergo dynamic fusion and fission processes. Dysregulation of mitochondrial dynamics is associated with diseases like NASH, characterized by impaired mitochondrial function, oxidative stress, and liver fibrosis. Hepatic stellate cells (HSCs) also contribute to liver fibrosis in response to chronic liver injury. Previous findings suggest that 5-methoxytryptophan (5-MTP) may have preventive and therapeutic effects on inflammation and fibrosis in NAFLD/NASH animal models. However, the impact of 5-MTP on mitochondrial function in NAFLD/NASH remains unclear.

Aims: 1. Investigate the effects of 5-MTP on shifting HSC status. 2. Evaluate the effects of 5-MTP on dynamic mitochondrial function

Methods: For the “Human HSC cell model to mimic

the WD mice” experiments, LX-2 cells were treated with L-5-MTP or DMSO solvent, followed by adipocyte differentiated condition medium. qPCR, Western blot, and activity/function assays were performed for HSC markers, mitochondrial markers, and function analysis.

Results: The effects of 5-MTP on COX2 expression and HSC activation were assessed. COX-2 expression was decreased in the liver tissue of 5-MTP-treated animals. Similarly, activation marker GFAP expression in HSCs was reduced after 5-MTP treatment. These findings suggest that 5-MTP may target HSC cells and contribute to fibrosis regression. Mitochondrial analysis showed that 5-MTP treatment decreased the expression of biogenesis-related genes, increased fusion-related genes, and mildly decreased fissionrelated genes. This indicates a reduction in oxidative stress, improved mitochondrial dynamics, and functions in lipid-rich HSCs.

Conclusions: 5-MTP may target HSC cells and contribute to fibrosis regression. It alleviates oxidative stress and improves mitochondrial dynamics and functions in lipid-rich HSCs. 5-MTP may have therapeutic potential in NAFLD/NASH.

P.02

THE CLINICAL SIGNIFICANCE OF GPC3-POSITIVE AND CK7-POSITIVE CIRCULATING TUMOR CELLS IN HEPATOCELLULAR CARCINOMA DIAGNOSIS AND RECURRENCE

Szu-Jen Wang1, Hsi-Jung Chen1, Ching-Yang Tsai1, Chung-Er Huang2, Kuan-Yeh Huang2

1Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan

2CytoAurora Biotechologies Inc., Hsinchu, Taiwan

GPC3 與 CK7 表現的循環腫瘤細胞對於 HCC 的診斷與復發之臨床特性

王嗣仁1 陳錫榮1 蔡青陽1 黃忠諤2 黃冠曄2

1 阮綜合醫療社團法人阮綜合醫院消化內科

2 醫華生技股份有限公司

Background: Hepatocellular carcinoma belongs to primary liver cancer which is the sixth diagnosed and third leading death cancer in the worldwide. Early diagnosis of HCC can increase the survival rate of patients. Circulating tumor cells shedding from the primary tumor site and spreading into the blood stream are currently used as an indicator for cancer detection. Herein, we used glypican 3 (GPC3) and cytokeratin 7 (CK7) as markers for early diagnosis and recurrence respectively.

Aims: To elucidate the specific makers of circulating tumor cells in HCC detection and prognosis.

Methods: There were twenty-eight patients and seventeen healthy donors enrolled in 2020 to 2021. 8 ml blood of each participant were collected into ACD blood collection tube. PBMCs were isolated by density gradient centrifugation. CTCs were detected by CellRevealTM system. CTCs captured on the chips were stained by the antibodies of anti-PanCK, antiCK20, anti-CK7, anti-GPC3. All the data was analyzed by Mann-Whitney test and ROC curve.

Results: The number of GPC3-positive CTCs in HCC patients was significantly higher than in healthy donor. There was no significant difference between HCC patients and healthy donors in the amount of PanCK-, CK20-, and CK7-positive CTCs. While the cut off value of GPC3-positive cells was 2 CTCs/2ml, the sensitivity and specificity was 76.2% and 71.4%

respectively. The area under the curve (AUC) was 0.84. The CTC positive rate (≥2 CTCs/2ml) showed significance difference between patients in HCC BCLC 0/A and healthy donors. However, there was no difference between BCLC-0/A and BCLC-B/C. Dividing HCC patient into new-diagnosis and recurrence, CK7positive CTCs were significantly higher in recurrence patients.

Conclusions: In this study, the value GPC3-postive CTCs can be used as early diagnostic marker for HCC. The number of CK7-postive marker can be served as prognosis marker for HCC recurrency.

P.03

INTRA-TUMORAL MICROBIOME PROMOTES HEPATOCELLULAR CARCINOMA CELL PROLIFERATION AND IS ASSOCIATED WITH DISEASE PROGNOSIS

Ming-Lun Yeh1,2, Yi-Shan Tsai1, Po-Cheng Liang1, Po-Yau Hsu1,2, Tyng-Yuan Jang1,2, Yu-Ju Wei1, Ching-I Huang1,2, Zu-Yau Lin1,2, Chung-Feng Huang1,2, Jee-Fu Huang1,2, Chia-Yen Dai1,2, Wan-Long Chuang1,2, Ming-Lung Yu1,2,3

1Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

2School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

3School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan

腫瘤內微菌促進肝癌細胞增長且與疾病 預後相關

葉明倫1,2 蔡易珊1 梁博程1 許博堯1,2 張庭遠1,2 魏鈺儒1 黃駿逸1,2 林子堯1,2 黃釧峰1,2 黃志富1,2 戴嘉言1,2 莊萬龍1,2 余明隆1,2,3

1 高雄醫學大學附設醫院肝膽胰內科

2 高雄醫學大學醫學系

3 國立中山大學醫學院及代謝異常脂肪肝卓越研究中 心

Background: Cancer-specific intra-tumoral microbiome had been identified. We observed abundant microbiome infiltration in the cultured primary hepatoma cells of some patients. The primary hepatoma cells with abundant microbiome infiltration showed a more rapid cell growth in vitro, and the cell growth slowed after the remove of the microbiome. We therefore hypothesized that intra-tumoral microbiome promotes hepatoma cell proliferation and differentiation.

Aims: We aimed to explore the role of intra-tumoral microbiome in the pathogenesis and disease prognosis of hepatocellular carcinoma (HCC).

Methods: The method to harvest and culture primary hepatoma cells had been reported previously. Primary hepatoma cells were cultured with 10% FBS/DMEM

medium. The culture medium was replaced every 3-4 days and collected when replaced. The microbiome infiltration was identified under the microscope. We defined abundant microbiome infiltration as microbiome infiltration in more than 20% of area under high-power field. Microbiome compositions were analyzed by 16s rRNA sequencing. Hepatoma cell lines including Huh7, HA22T and Hep3B cell line were cultured with different concentrations of microbiome medium and WST-1 assay was performed for in vitro cell proliferation experiments. Total cellular proteins were quantified by BCA assay, and the expression of individual proteins was determined by immunoblot analyses. The clinical characteristics were compared between HCC patients with and without abundant intra-tumoral microbiome.

Results: Abundant microbiome infiltration was found in 56 (30.9%) of the 181 HCC patients. HCC patients with abundant microbiome demonstrated a larger tumor size. A significantly higher proportion of microbiomeinfiltrated hepatoma cells showed rapid cell growth as compared to hepatoma cells without microbiome infiltration. Meanwhile, HCC patients with abundant microbiome also demonstrated a decreased overall survival. Regarding the compositions of intratumoral microbiome, the most dominant microbes at phylum level were Proteobacteria, then Firmicutes, Actinobacteria, and Bacteroidetes. Xanthomonas and Acetobacter were the most dominant microbes at genus level. We then conducted the in vitro cell proliferation experiments. We found hepatoma cells cultured with the medium of abundant microbiome showed a higher cell proliferation as compared to culture with the medium of less microbiome. Furthermore, the effect of increased cell proliferation diminished when hepatoma cells were cultured with medium removal of microbiome. We further found hepatoma cells cultured with the medium of abundant microbiome exhibited higher expression levels of total/phosphorylated YAP1. And the YAP1 expression levels decreased after removal of microbiome.

Conclusions: Intra-tumoral microbiome was associated with poor HCC survival. In vitro study demonstrated that intra-tumor microbiome promotes HCC cell proliferation perhaps through Hippo/YAP pathway. The results implicate a future therapeutic target of HCC.

IMPACT OF HCV ERADICATION ON SYMPTOMS OF EXTRAHEPATIC MANIFESTATIONS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS TREATED WITH SOF/VEL

Chung-Feng Huang2,3, Chi-Yi Chen45, Chao-Hung Hung4, Hsing-Tao Kuo8, Chi-Ming Tai5,6, Lein-Ray Mo7, Kuo-Chih Tseng10,11, Ching-Chu Lo12, Ming-Jong Bair13,14, Szu-Jen Wang15, Jee-Fu Huang2,3, Ming-Lun Yeh2,3, Chun-Ting Chen16,17, Ming-Chang Tsai18, Chien-Wei Huang19, Pei-Lun Lee20, Tzeng-Huey Yang21, Yi-Hsiang Huang22,23, Lee-Won Chong24,25, Chien-Lin Chen26, Chi-Chieh Yang27, Sheng-Shun Yang28, Pin-Nan Cheng29, Tsai-Yuan Hsieh16, Jui-Ting Hu30, Wen-Chih Wu31, Chien-Yu Cheng32, Guei-Ying Chen33, Kwok-Hsiung Chou34, Wei-Lun Tsai35, Chien-Neng Kao36, Chih-Lang Lin37, Chia-Chi Wang38, Ta-Ya Lin39, Chih-Lin Lin40, Wei-Wen Su41, Tzong-Hsi Lee42, Te-Sheng Chang43, Chun-Jen Liu44, Chia-Yen Dai2,3, Cheng-Yuan Peng46,47, Jia-Horng Kao44, Han-Chieh Lin22,23, Wan-Long Chuang2,3, Ming-Lung Yu1,2,3,4

2 型糖尿病患者使用 SOF/VEL 根除 C 肝 對肝外表現症狀的影響

黃釧峰2,3 陳啟益45 洪肇宏4 郭行道8 戴啟明5,6 牟聯瑞7 曾國枝10,11 羅清池12 白明忠13,14 王嗣仁15 黃志富2,3 葉明倫2,3 陳軍廷16,17 蔡明璋18 黃健維19 李佩倫20 楊增慧21 黃怡翔22,23 張麗文24,25 陳健麟26 楊基滐27 楊勝舜28 鄭斌男29 謝財源16 胡瑞庭30 吳文誌31 鄭健禹32 陳桂英33 周國雄34 蔡維倫35 高健能36 林志郎37 王嘉齊38 林大雅39 林志陵40 蘇維文41 李宗熙42 張德生43 劉俊人44 戴嘉言2,3 彭成元46,47 高嘉宏44 林漢傑22,23 莊萬龍2,3 余明隆1,2,3,4

1National Sun Yat-sen University, Kaohsiung, Taiwan; 2Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 3Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 4Kaohsiung Chang Gang Memorial Hospital, Kaohsiung, Taiwan; 5EDa Hospital, Kaohsiung, Taiwan; 6College of Medicine, I-Shou University, Kaohsiung, Taiwan; 7Tainan Municipal Hospital, Tainan, Taiwan; 8Chi Mei Medical Center, Tainan, Taiwan; 9Kaohsiung Medical University, Kaohsiung, Taiwan; 10Dalin Tzu Chi Hospital, Chiayi, Taiwan; 11College of Medicine, Tzu Chi University, Hualien, Taiwan; 12St. Martin De Porres Hospital, Chiayi, Taiwan; 13Taitung Mackay Memorial Hospital, Taitung, Taiwan; 14Mackay Memorial Hospital, Taipei, Taiwan; 15Yuan’s General Hospital, Kaohsiung, Taiwan; 16Tri-Service General Hospital, Taipei, Taiwan; 17Tri-Service General Hospital Penghu Branch, Penghu, Taiwan; 18Chung Shan Medical University Hospital, Taichung, Taiwan; 19Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan; 20Chi Mei Hospital, Liouying, Tainan, Taiwan; 21Lotung Poh-Ai Hospital, Yilan, Taiwan; 22Taipei Veterans General Hospital, Taipei, Taiwan; 23National Yang Ming Chiao Tung University, Taipei, Taiwan; 24Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; 25College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; 26Hualien Tzu Chi Hospital, Hualien, Taiwan; 27Show Show Memorial Hospital, Changhua, Taiwan; 28Taichung Veterans General Hospital, Taichung, Taiwan; 29National Cheng Kung University Hospital, Tainan, Taiwan; 30Cathay General Hospital, Taipei, Taiwan; 31Wen-Chih Wu Clinic, Kaohsiung, Taiwan; 32Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan; 33Penghu Hospital, Ministry of Health and Welfare, Penghu, Taiwan; 34Kwok-Hsiung Chou Clinic, Penghu, Taiwan; 35Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 36Taiwan University Hsin-Chu Hospital, Hsinchu, Taiwan; 37Liver Unit, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 38Taipei Tzu Chi Hospital, Taipei, Taiwan; 39Cishan Hospital, Ministry of Health and Welfare, Kaohsiung, Taiwan; 40Taipei City Hospital, Renai Branch, Taipei, Taiwan; 41Changhua Christian Hospital, Changhua, Taiwan; 42Far Eastern Memorial Hospital, New Taipei City, Taiwan; 43Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan; 44Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan; 45Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan; 46China Medical University Hospital, Taichung, Taiwan; 47China Medical University, Taichung, Taiwan

1 國立中山大學；2 高雄醫學大學附設醫院；3 高雄醫 學大學附設醫院肝炎中心；4 高雄長庚紀念醫院；5 義大醫院；6 義守大學醫學院；7 台南市立醫院；8 奇 美醫學中心；9 高雄醫學大學；10 大林慈濟醫院；11 花蓮慈濟大學醫學院；12 天主教聖馬爾定醫院；13 台 東馬偕紀念醫院；14 淡水馬偕紀念醫院；15 阮綜合醫 院；16 三軍總醫院；17 三軍總醫院澎湖分院；18 中山 醫學大學附設醫院；19 國軍高雄總醫院；20 柳營奇美 醫院；21 羅東博愛醫院；22 臺北榮民總醫院；23 國立 陽明交通大學；24 新光吳火獅紀念醫院；25 天主教輔 仁大學醫學院；26 花蓮慈濟醫院；27 秀傳紀念醫院； 28 臺中榮民總醫院；29 國立成功大學醫學院附設醫 院；30 國泰綜合醫院；31 吳文誌診所；32 衛生福利部 桃園醫院；33 衛生福利部澎湖醫院；34 周國雄診所； 35 高雄榮民總醫院；36 台大醫院新竹分院；37 基隆長 庚紀念醫院肝炎中心；38 台北慈濟醫院；39 衛生福利 部旗山醫院；40 臺北市立聯合醫院仁愛院區；41 彰化 基督教醫院；42 亞東紀念醫院；43 嘉義長庚紀念醫 院；44 台大醫院肝炎中心；45 嘉義基督教醫院；46 中 國醫藥大學附設醫院；47 中國醫藥大學

Background: Type 2 diabetes mellitus (T2DM) is considered an extrahepatic manifestation of chronic hepatitis C (CHC). Studies have shown early identification and treatment of CHC in T2DM may reduce diabetic complications through improved glycemic control.

Aims: The goal of this study was to investigate whether eradication of HCV infection with SOF/VEL is associated with improved glycemic control and renal function in patients with T2DM using TACR database.

Methods: This is a retrospective analysis of adult patients cured with SOF/VEL from Aug 2019 to Dec 2022. Patients with SVR results, HbA1c at baseline and SVR 12, without use of ribavirin, or without prior DAA treatment were included in this analysis. Change in glycated hemoglobin (HbA1c) levels were assessed at treatment baseline and SVR 12. Independent predictors of HbA1c improvements were assessed using multivariate analysis.

Results: 9,187 HCV patients were reviewed, of which 2,180 patients met inclusion criteria, 2,162 achieved SVR12. 695 patients with T2DM (DM group) and 1,485 patients without T2DM (non-DM group) were included in this analysis. HbA1c were significantly decreased from 7.32 ± 1.72% at baseline to 6.87 ± 1.34% at SVR in DM group (p < 0.001); while no HbA1c change was observed in non-DM. The mean decrease of A1c were 0.02 ± 0.59, 0.17 ± 0.74, 0.37 ± 1.20, 2.17 ± 2.09 in baseline HbA1c of 5.7-6.4, 6.5-7.5, 7.6-8.5

and >8.5. The decrease of HbA1c were higher in DM with cirrhosis than without cirrhosis (0.62 ± 1.76 vs. 0.41 ± 1.43). Multivariate analysis showed DM and male gender are independent predictors of HbA1c improvement. eGFR of DM patients remains stable and significant improvement of FIB 4 and albumin were observed.

Conclusions: Eradication of HCV with SOF/VEL resulted in a significant decrease in HbA1c, particularly in DM patients with a high pretreatment HbA1c. This study suggests treating HCV improves symptoms of both hepatic and extrahepatic manifestations and should motivate non-GI-hepatology specialties to engage in HCV care.

P.05

RETREATMENT WITH TENOFOVIR ALAFENAMIDE FOR 48 WEEKS SIGNIFICANTLY REDUCES LIVER FIBROSIS, QUANTITATIVE HBSAG AND HBCRAG LEVELS

Tung-Hung Su1, Yao-Chun Hsu2, Yu-Jen Fang3, Chih-Lin Lin4, Chia-Chi Wang5, Kuo-Chih Tseng6, Chi-Yi Chen7, Jia-Horng Kao1

1Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan

3Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan

4Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan

5Division of Gastroenterology, Department of Internal Medicine, Taipei Tzuchi Hospital, the Buddhist Tzuchi Medical Foundation, Taipei, Taiwan

6Department of Hepatology, Buddhist Tzu Chi General Hospital, Da-Lin Branch, Chiayi, Taiwan

7Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan

慢性 B 型肝炎復發使用韋立得再治療 48 周顯著降低肝纖維化、B 型肝炎表面抗原 及核心相關抗原

蘇東弘1 許耀峻2 方佑仁3 林志陵4 王嘉齊5 曾國枝6 陳啟益7 高嘉宏1

1 台大醫院內科部胃腸肝膽科

2 義大醫院胃腸肝膽科

3 台大醫院雲林分院內科部

4 臺北市立聯合醫院仁愛院區消化內科

5 臺北慈濟醫院胃腸肝膽科

6 嘉義大林慈濟醫院腸胃內科

7 嘉義基督教醫院胃腸肝膽科

Background: Achieving function cure and reducing liver fibrosis are essential goals in managing chronic hepatitis B. Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel marker for liver fibrosis. Hepatitis B core-related antigen (HBcrAg) reflects intrahepatic cccDNA of HBV and its transcriptional activity. Little is known about the dynamic change of these two markers after retreatment by tenofovir alafenamide (TAF) at hepatitis relapse after

discontinuing prior entecavir or tenofovir disoproxil fumarate (TDF) therapy.

Aims: To evaluate the efficacy of TAF retreatment on the change of liver fibrosis and HBcrAg.

Methods: This prospective multicenter CHANGE (Chronic Hepatitis b patients switch to tAf after discontinuation of Nucleoside analoGuE) study (NCT04496882) is enrolling patients who experienced off-therapy (TDF or entecavir) clinical relapse and switched them to TAF for retreatment for 48 weeks in Taiwan. The primary endpoint was the rate of virological remission (HBV DNA <20 IU/mL), and the secondary endpoints included the change of HBsAg, HBcrAg, and M2BPGi levels.

Results: As of April 30, 2023, 47 patients were enrolled, and 42 patients were included in this biomarker evaluation (discontinuation of prior TDF:entecavir = 21:21). At retreatment, the median age was 49 years, and five were HBeAg positive. After 48 weeks of therapy, the rates of virological remission and ALT normalization (<41 U/L) were 77% and 88%, respectively. Among 30 patients who completed 48week TAF therapy, there was a significant decline of HBsAg (0.6 log10 IU/mL, P < 0.001), and six patients (6/30, 20%) had achieved a favorable HBsAg response (≤100 IU/mL). There was a significant reduction of liver stiffness measured by M2BPGi (0.93 to 0.59 C.O.I., P < 0.001), FIB-4 index (1.62 to 1.20, P < 0.001), and HBcrAg levels (6.05 to 3.50 log10 IU/mL, P < 0.001), especially in HBeAg-negative patients (5.70 to 3.20 log10 IU/mL, P < 0.001).

Conclusions: Switching to TAF retreatment for 48 weeks after off-TDF or entecavir relapse is effective in viral suppression, reduction of quantitative HBsAg and HBcrAg levels, ALT normalization, and liver stiffness improvement.

P.06

LONG-TERM HEPATITIS B SURFACE ANTIGEN PROFILE AND SEROCLEARANCE FOLLOWING ANTIVIRAL TREATMENT: A SINGLECENTER, REAL-WORLD COHORT STUDY

Chih-Wen Huang, Hsu-Heng Yen, Pei-Yuan Su, Yang-Yuan Chen

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

長期抗病毒治療後的 B 型肝炎表面抗原 狀況和清除情況：單一醫學中心的回溯 性研究

黃稚雯 顏旭亨 蘇培元 陳洋源 彰化基督教醫院肝膽腸胃科

Background: Hepatitis B surface antigen (HBsAg) seroclearance, an indicator of recovery from hepatitis B virus (HBV)infection, is uncommon in long-term nucleos(t)ide analog (NUC) therapy.

Aims: We compared the incidence of HBsAg seroclearance in patients with and without NUC discontinuation to identify predictors of HBsAg seroclearance.

Methods: This retrospective study enrolled adult patients with chronic HBV infection followed for ≥12 months after NUC discontinuation (finite group) and those treated with NUCs for >3 years (non-finite group). Demographic, clinical, and laboratory data were analyzed.

Results: The study cohort included 978 patients, including 509 and 469 patients in the finite and non-finite groups, respectively. Cumulative HBsAg seroclearance incidence was significantly higher in the finite group than in the non-finite group (p = .006).

The 5- and 10-year cumulative HBsAg seroclearance incidence were 6.6% and 18.9% in the finite group and 3% and 14.6%, in the non-finite group, respectively.

The likelihood of HBsAg seroclearance was higher in those with end of treatment (EOT) HBsAg levels of <100 IU/mL and in those without clinical relapse (CR).

The cumulative 3-year CR incidence was 16.8%. The incidence of liver decompensation and hepatocellular carcinoma were 4.1 and 0.4 per 1000 person-years, respectively. The hepatocellular carcinoma incidence did not significant differ between the finite and non-

finite groups (p = .941).

Conclusions: The higher HBsAg seroclearance incidence in patients receiving finite therapy, and the increased likelihood of HBsAg seroclearance in those with EOT HBsAg levels of <100 IU/mL and in those without CR should be considered during decisionmaking of treatment options.

P.07

COMPARISON

OF HBV RELAPSE RATES IN PATIENTS WHO DISCONTINUE TENOFOVIR ALAFENAMIDE VERSUS ENTECAVIR OR TENOFOVIR DISOPROXIL FUMARATE

Hsin-Wei Fang, Chien-Hung Chen, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung, Sheng-Nan Lu

Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

慢性 B 型肝炎病人停止韋立德治療和停 止貝樂克或惠立妥治療其慢性 B 型肝炎 病毒復發率的比較

方信為 陳建宏 胡琮輝 王景弘 洪肇宏 盧勝男 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 暨長庚大學醫學系

Background: The incidence and relapse pattern in CHB patients stopping tenofovir alafenamide (TAF) monotherapy are unknown.

Aims: To compare HBV relapse rate in HBeAg-negative CHB patients without cirrhosis who discontinued TAF versus entecavir or tenofovir disoproxil fumarate (TDF).

Methods: A total of 690 HBeAg-negative patients without cirrhosis who received entecavir (n=390), TDF (n=248) and TAF (n=52) therapy previously and had post-treatment follow-up for at least 6 months were included in this study. The propensity score-matching method (PSM) was used by creating a ratio of 1:4 between the off-TAF group versus off-entecavir group or the off-TDF group to adjust associated factors.

Results: The cumulative incidences of virological relapse at 13, 26 and 52 weeks in the entecavir, TDF and TAF groups were 3.3%, 27.8% and 53.8%, 29.5%, 50% and 71.7%, and 53.7%, 64.9% and 78.7%, respectively, and clinical relapse rates at 13, 26 and 52 weeks were 1.2%, 13.7% and 29.9%, 9.5%, 30.3% and 48.2%, and 27.4%, 39.7%, and 58.1%, respectively. In the analysis of entecavir and TAF groups, multivariate analysis showed that TAF was an independent factor for virological (HR: 2.132, 95% CI: 1.782-2.550, P < 0.001) and clinical relapse (HR: 2.082, 95% CI: 1.676-

2.587, P < 0.001). In the analysis of TDF and TAF groups, multivariate analysis showed that TAF was an independent factor for virological relapse (HR: 1.469, 95% CI: 1.017-2.123, P = 0.041), but not clinical relapse. After PSM, patients in the off-TAF group had significantly higher rates of virological and clinical relapse than those in the off-entecavir group (both P < 0.001). In contrast, patients in the off-TAF group had significantly higher rates of virological relapse (P = 0.002) and clinical relapse (P = 0.006) than those in the off-TDF group.

Conclusions: The off-TAF group had significantly higher HBV relapse rates than the off-entecavir or off-TDF group in HBeAg-negative patients without cirrhosis.

P.08

ELECTRIC NOTIFICATION SYSTEM

HELPS WITH HCV SCREENING OF OUTPATIENTS IN A LARGE HOSPITAL

Cheng-Kuan Lin1, Ya-Li Shih1, Kuei-Fen Chang1, Yu-Sen Peng2

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

2Deputy Superintendent, Far Eastern Memorial Hospital, New Taipei City, Taiwan

電子提示系統輔助大型醫院門診病人 C 型肝炎篩檢

林政寬1 施雅麗1 張桂芬1 彭渝森2 1 亞東紀念醫院肝膽胃腸科 2 亞東紀念醫院院長室

Background: The government of Taiwan has set the goal of HCV elimination in 2025. Extended screening of unawareness HCV-infected patients is important for the achievement of the target.

Aims: We conduct an extended HCV screening program using an electronic notification system in the Far Eastern Memorial Hospital. The high-risk patients without previous checkups of anti-HCV were reminded during visiting the outpatient department.

Methods: From December 2022 to March 2023, the patients with a higher prevalence of HCV infection (45 to 79 years old, DM, and CKD/pre-CKD) were enrolled. The patients in pediatrics, self-paid clinics, examination rooms, traditional medicine, and nursing homes were excluded. If the patients had no previous anti-HCV data in the hospital information system, the pop-up window alerted the physicians and they could choose with (1) Agree to checkup: direct ordering blood test, or refer to integrated preventive care center for B/C hepatitis screening; (2) Disagree to checkup, due to the patient has finishing therapy, refuses to checkup, unsuits for therapy, or patient saying no HCV infection; (3) Exit.

Results: Totally 75523 notifications (17.2%) were activated in 440343 person-times of clinic visits. There were 5769 patients (7.6%) in the diabetes care program, and 650 patients in the pre-CKD/CKD program (0.9%). The patients without previous checkups were more in cardiovascular surgery (31.1%), cardiology (27.4%), and neurology department (25.3%). The physicians answered 63.7% of the notification, especially higher in proctology (97%), ID (95%), psychiatric (93.4%),

oncology (93.3%), and GI (92.8%). There were 22656 patients (30%) with direct ordering blood tests, and 14216 patients (18.8%) referring to B/C hepatitis screening. The most used ordering blood tests were in metabolism (85.1%), general medicine (71%), and nephrology department (66%). The most use of referring to B/C hepatitis screening was in psychiatry (71.4%) and the radio-oncology department (59.4%). The completion of blood tests was higher by direct ordering blood tests than by referring to B/C hepatitis screening (87.8% vs 6.5, P < 0.01). During 4 months period, 20822 patients were screened with 437 patients (2.1%) of HCV seropositivity. More patients were in cardiology (101 patients), metabolism (101 patients), GI (66 patients), urology (27 patients), and neurology department (26 patients). The higher rate was in psychiatry (16.6%), trauma (7.7%), radiooncology (4.6%), GI, and ID departments (4%). During the notification, 196 patients (0.3%) had to finish therapy, 7035 patients (9.3%) refused to checkup, 652 patients (0.9%) had unsuitable conditions for therapy, and 3349 patients (4.4%) had known without HCV infection.

Conclusions: Using an electric notification system can promote HCV screening in a large hospital. The completion of blood tests was higher by direct ordering tests in the clinic than by referring to a B/C hepatitis screening service. Realization of the department with more patients without previous testing, and anti-HCV seropositivity is important to guide further hotspots for screening in the hospital.

DEVELOPMENT OF A HBSCONJUGATED ANTI-PD-L1 SCFV THERAPEUTIC AGENT FOR IMMUNE REACTIVATION TO ERADICATE LUNG CANCER

Huei-Hsiu Lin1, Chun-Chia Cheng2, Zong-Lin Sie2, Ai-Sheng Ho1

1Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan

2Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University, Taoyuan, Taiwan

發展 HBs 抗原鍵結 PD-L1 scFv 活化免疫 作為抗肺癌藥物

林慧秀1 程俊嘉2 謝宗霖2 何愛生1

1 振興醫院胃腸肝膽科

2 長庚大學放射醫學研究院

Background: HBV vaccination has been widely administered to prevent HBV infection, resulting in the development of anti-HBs immunity in the general population. We intend to utilize this existing immunity for suppressing tumors since immunotherapy is a promising approach for cancer treatment, such as the PD-(L)1 blockade. We hypothesize that expressing the HBs antigen on the tumors may serve as a potential strategy to harness HBs vaccination-derived immunity for tumor eradication.

Aims: The aim of this study was to develop a novel therapeutic agent by conjugating HBs antigen with an anti-PD-L1 single-chain variable fragment (scFv), and investigate its potential for immune reactivation and the anti-lung cancer efficacy in vitro.

Methods: We constructed the HBs-conjugated antiPD-L1 scFv agent (HBs-αPD-L1scFv) by inserting HBs and Atezolizumab scFv sequences into the pET28a plasmid. The purified protein from BL21 (DE3) was evaluated by silver stain and Western blots. The binding specificity with lung cancer A549 and LL/2 cells was measured using flow cytometry. The internalization capacity was assessed in lung cancer A549 cells. The immune reactivation was evaluated by measuring activation markers in CD8+ T cells and nonCD8+ PBMCs using qPCR and ELISA, whereas PBMCs were isolated from anti-HBsAb-positive healthy volunteers. The anti-tumor activity of the agent was assessed by examining A549 cell viability and colony formation in vitro.

Results: We found that a rigid linker (EAAAK) conjugated between HBs and anti-PD-L1 scFv ensured the integrity of the HBs-αPD-L1scFv. Furthermore, HBs-αPD-L1scFv exhibited specific binding to lung cancer A549 and LL/2 cells in vitro. We observed the internalization of HBs-αPD-L1scFv within A549 cells after 24h incubation, which was attenuated by 1 μg/ mL of endocytosis inhibitors, filipin and chloroquine. In addition, the treatment with the HBs-αPD-L1scFv led to increased production of IFNG in CD8+ T cells and elevated levels of IFNG, IL-2, and CXCL10 in non-CD8+ PBMCs compared to treatment with αPD-L1scFv. The elevated levels of IFNG and CXCL10 were evaluated in the cultured medium using ELISA. We furthermore demonstrated that the PBMCs with HBs-αPD-L1scFv significantly suppressed A549 cell viability and colony formation compared to PBMCs with αPD-L1scFv, indicating the potent capacity to reactivate immunity of HBs-αPD-L1scFv to suppress lung tumor cells.

Conclusions: Our findings suggest that the HBs-αPDL1scFv exhibits specific binding to lung cancer cells and can reactivate immune responses, including CD8+ T cells and nonCD8+ PBMCs. This innovative approach, combining HBV-vaccinated immunity and immune checkpoint blockade, offers a potential strategy for eradicating PD-L1-positive lung cancer.

P.10

FACTORS ASSOCIATED CLINICAL RELAPSE AFTER CESSATION OF ENTECAVIR OR TENOFOVIR IN PATIENTS WITH CHRONIC HEPATITIS B IN PING-TUNG COUNTY

Shi-Chi Wen1, Wu-Hsien Kuo2, Chao-Wen Hsueh1, Hsin-Wen Lai1, Jyan-Wei Huang3, Chou-Yuan Ko3, Chieh-Yu Wang4, Wei-Le Du5

1Division of Gastroenterology, Department of Internal Medicine, Pao-Chien Hospital, Pingtung, Taiwan

2Division of Gastroenterology, Department of Internal Medicine, Yuan-Sheng Branch, YuanZuong Hospital, Changhua, Taiwan

3Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan

4Case Manager, Nursing Department, PaoChien Hospital, Pingtung, Taiwan

5Endoscopy Room, Nursing Department, PaoChien Hospital, Pingtung, Taiwan

屏東地區以核 苷 酸類似物惠立妥貝樂克 治療慢性 B 型肝炎停藥後臨床復發之因 素分析

文士祺1 郭武憲2 薛肇文1 賴欣汶1 黃健維3 柯朝元3 王潔瑜4 杜維勒5

1 屏東寶建醫院胃腸肝膽科

2 員榮醫院員生院區胃腸肝膽科

3 國軍高雄總醫院胃腸肝膽科

4 屏東寶建醫院護理部個管師

5 屏東寶建醫院護理部內視鏡室技術員

Background: Chronic hepatitis B infection is currently incurable. Nucleus(t)ide analogue (NUC) treatment with entecavir (ETV) or tenofovir (TDF) can reduce hepatocecullar carcinoma and cirrhosis-related complications. Because seroclearance of hepatitis B surface antigen is not easily achievable, criteria to stop NUC treatment is undetectable HBV DNA level with normalization of ALT. Cessation of treatment is associated with rates of virological relapse (VR)/ clinical relapse (CR) up to 70%. More than 40% of NUC stopper eventually receive retreatment.

Aims: Recent studies suggested that decreasing HBsAg level at the end-of-treaetment (EOT) to less than 100-200 IU/mL seemed be a useful marker for

deciding when to discontinue NUC therapy. We aimed to explore viral and host factors for these potent roles in predicting clinical relapse.

Methods: We conducted a retrospective study. This efficacy of NUC with 3 years cumulative rates of HBeAg loss, HBV DNA negativity, ALT normalization in patients with chronic hepatitis B (CHB) in Ping-Tung County was evaluated. The treatment and follow-up period for each patient was calculated. All patients who met eligibility criteria at baseline were included in the analysis. We explored those factors associated with clinical relapse among patient groups with overall, HBeAg-positive, HBeAg -negative and HBsAg <100 IU/mL.

Results: We evaluated the clinical outcome by intention-to-treated analyses. Between Jan 2014 and Sep 2021, we consecutively enrolled total of 110 CHB patients with 10% (11) HBeAg (+), 90% (99) HBeAg (-), cirrhosis of liver 11.8% (13) and decompensation 32.7% (36) treated with TDF or ETV for 2.35 ± 0.5 years, followed for 8.07 ± 4.63 years. It had male predominant 77.3%, body mass index (BMI) 25.5 ± 3.7, a mean age (57.1.9 ± 12.3) years, HBV DNA level (5.5 ± 1.6) IU/ml by log10. The rates of undetectable HBV DNA were 67.3%, 85.5%, 92.7% and 100% in 0.5, 1, 2 and 3 years, respectively. The rates of ALT normalization were 70.0%, 80.7% and 86.4% in 1, 2, and 3 years, respectively. HBeAg loss cumulative rates were 81.9%, 90.9% and 100% after 1, 2, and 3 years of treatment. Occurrence of clinical relapse and HBsAg loss was observed in 52.7% (58) and 7.3% (8). In overall patients, cox-regression univariated analysis identified high HBV level log10 (HR 0.716, CI 0.579-0.885, P = 0.002), high EOT HBsAg (HR 0.997, CI 0.996-0.998, P < 0.001), HBsAg >150 IU/mL (HR 7.043, CI 3.635-3.648, P < 0.001), HBsAg >200 IU/mL (HR 10.231, CI 4.34424.098, P < 0.001) and no HBsAg loss (HR 0.220, CI 0.101-0.477, P < 0.001) were independent risk factors for clinical relapse. By multivariate analysis, EOT >200 IU/mL was independently associated with significant risk of clinical relapse (HR 5.676, CI 1.822-17.681, P = 0.005). In patients with HBeAg-positive, no factor associated with clinical relapse was found. In patient with HBeAg-negative, univariate analysis identified old age (HR 1.032, CI 1.004-1.061, P = 0.027), age more than aged55 (HR 0.452, CI 0.235-0.866, P = 0.017), high HBV DNA level log (HR 0.708, CI 0.564-0.889, P = 0.003), HBV DNA more than 200,000 IU/mL (HR 1.814 CI 1.002-3.285, P = 0.049), high EOT HBsAg (HR 0.997, CI 0.996-0.998, P < 0.001), HBsAg >150 IU/mL (HR 8.268, CI 3.920-17.437, P < 0.001) and HBsAg >200 IU/mL (HR

10.761, CI 4.234-27.346, P < 0.001) were independent risk factors for clinical relapse. By multivariate analysis, EOT >200 IU/mL was independently associated with significant risk of clinical relapse (HR 5.676, CI 1.82217.681, P = 0.005). By multivariate analysis, EOT >200 IU/mL was independently associated with significant risk of clinical relapse (HR 4.676, CI 1.229-17.782, P = 0.024). In patients with HBsAg less than 100 IU/mL, univariate analysis revealed age (HR 0.707, CI 0.5001.000, P = 0.05), cirrhosis (HR 0.094, CI 0.018-0.490, P = 0.005), alcoholism (HR 0.064, CI 0.012-0.341, P = 0.001), decompensation (HR 0.095, CI 0.011-0.789, P = 0.029) were independent risk factors for clinical relapse. By multivariate analysis, cirrhosis (HR 0.140, CI 0.026-0.749, P = 0.022) was independently associated with significant risk for clinical relapse.

Conclusions: Lower EOT HBsAg level is associated with risk of relapse and high HBsAg loss. EOT HBsAg level <200 IU/mL is associated with a lower risk of clinical relapse in patients with HBsAg-negative. It may have proposed a rule to stop NUC and subsequent followup. However, cirrhosis of liver remained associated with high relapse rates in patient with HBsAg less than 100 IU/mL. Long-term NUC therapy may be a favorable option for cirrhosis of liver, particular with alcoholism and decompensated liver reserve.

P.11

CLINICAL OUTCOMES IN DECOMPENSATED HEPATITIS B CIRRHOSIS INITIATING ANTIVIRAL TREATMENT: A RETROSPECTIVE STUDY IN A TERTIARY MEDICAL CENTER IN CENTRAL TAIWAN

Cheng-Che Chen1, Hsin-Ju Tsai1, I-Da Lu1, Show-Wu Lee1, Teng-Yu Lee1, Yi-Hsiang Huang2, Sheng-Shun Yang1

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

2Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

B 型肝炎肝硬化病人使用抗病毒藥物的臨 床預後：中台灣一家醫學中心的回溯性 研究

陳正哲1 蔡炘儒1 呂宜達1 李少武1 李騰裕1 黃怡翔2 楊勝舜1

1 臺中榮民總醫院胃腸肝膽科

2 臺北榮民總醫院腸胃肝膽科

Background: Decompensated cirrhosis in chronic hepatitis B virus (HBV) infected patients is associated with poor outcome with a 5-year survival rate ranging from 14-35%. Mortality and incidence of hepatocellular carcinoma (HCC) decreased significantly when antiviral agent was given. Recompensation, achieved after the administration of nucleos(t)ide analogs (NUC), is associated with an improved quality of life and prolonged survival time.

Aims: To evaluate the biochemical factors associated with recompensation among the patients with decompensated hepatitis B cirrhosis initiating antiviral treatment.

Methods: We retrospectively analyzed 1480 patients with HBV-related cirrhosis who initiated entecavir (ETV) or tenofovir disoproxil fumarate (TDF) between December 2001 and December 2021 at our hospital, one tertiary medical center in central Taiwan. The primary outcome was recompensation, defined as a sustained decrease of modified Albumin-Bilirubin (ALBI) level for at least 3 months. The secondary outcomes included subsequent hepatocellular carcinoma (HCC) occurrence, liver transplantation (LT), and mortality.

Results: Among the 92 patients with decompensated cirrhosis, recompensation occurred in 27 patients, accounting for 29% of the total. In the nonrecompensation group, 51 patients (78%) were men, while in the recompensation group, 19 patients (70%) were men. In both groups, more than 90% of the patients were treated with ETV. There were no significant statistical differences in baseline BMI, ALT, prothrombin time, platelet count, ascites grade, and severity of esophageal varices between the two groups. We identified that baseline albumin level was the most relevant indicator of recompensation, with a threshold of 3.05 g/dL. The cumulative incidence of mortality rate was 44% in the non-recompensation group, while no mortality was observed in the recompensation group. Furthermore, the occurrence of HCC and the need for LT were higher in the recompensation group (non-recompensation 15% vs. recompensation 37%, p = 0.022).

Conclusions: Baseline albumin level is an indicator for predicting recompensation among decompensated HBV-cirrhosis patients initiating antiviral treatment. Decompensated HBV-cirrhosis is associated with the occurrence of HCC and the need for LT, even in antiviral-treated recompensation cases.

P.12

IMPLEMENTATION OF AN ORDERBASED REMINDING SYSTEM AGAINST HBV REACTIVATION IN PATIENTS RECEIVING CHEMOTHERAPY

Wei-Hsiang Lan1, Tung-Hung Su2, Chun-Jen Liu2, Jia-Horng Kao2

1School of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University, Taipei, Taiwan

醫囑警示系統用於預防接受癌症化學療 法後之 B 型肝炎再復發

藍韋翔1 蘇東弘2 劉俊人2 高嘉宏2

1 國立臺灣大學醫學系

2 國立臺灣大學醫學院附設醫院胃腸肝膽科

Background: HBV carriers who underwent chemotherapy are exposed to a high risk of HBV reactivation and developing liver failure or death. The National Taiwan University Hospital (NTUH) conducted an order-based reminding system from September 2019 to March 2022 to warrant that HBV serological profiles are checked and prophylactic anti-HBV therapy is prescribed before receiving chemotherapy.

Aims: This retrospective study aimed to assess the screening rate for HBV serological profiles and HBV prophylactic treatment rate in the system-designing stage, the order-reminding stage, and the mandatory order stage to evaluate the effectiveness of this computerized order-based reminding system.

Methods: In September 2019, the reminding system was constructed after approval from the Cancer Prevention & Control Policy Commission and initially implemented in the Department of Oncology of NTUH in March 2020. Subsequently, it extended to all specialties in August 2020. The mandatory order stage for anti-HBV therapy started in May 2021, ensuring HBsAg-positive patients receive HBV prophylaxis.

Results: A total of 128,110 chemotherapy orders were prescribed from January 2019 to September 2022 with 3 stages in the period, including the system-designing, order-reminding, and mandatory order stages with 50566, 35926, and 41618 orders, respectively. The overall screening rates for HBsAg

were 82.9%, 90.0%, and 99.5% in these stages, and the HBV prophylactic treatment rates were 97.3%, 98.9%, and 100%, respectively. Both rates increased to 100% at the end of March 2022.

Conclusions: The rate of HBsAg screening and HBV prophylactic treatment raised substantially in the order-reminding stage and achieved 100% after the mandatory order stage. This computerized orderbased reminding system is crucial for patients with HBV infection to receive chemotherapy.

P.13

THE EFFICACY OF HEPATITIS B VACCINATION IN PATIENTS UNDERGOING HEMODIALYSIS

Chiuan-Bo Huang1,2, Tung-Hung Su1,2,3, Tai-chung Tseng1,2,3, Jia-Horng Kao1,2,3

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

3Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

4Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

B 型肝炎疫苗施用在洗腎病人上的效力 黃詮博1,2 蘇東弘1,2,3 曾岱宗1,2,3 高嘉宏1,2,3

1 國立臺灣大學醫學院附設醫院胃腸肝膽科

2 國立臺灣大學醫學院附設醫院內科部

3 國立臺灣大學醫學院附設醫院肝炎研究中心

4 國立臺灣大學醫學院臨床醫學研究所

Background: Hepatitis B is a public health issue in Taiwan. The most effective way to prevent hepatitis B transmission is HBV vaccination; however, patients on hemodialysis have impaired immunity, and the optimized vaccination strategy has not been established.

Aims: To understand the efficacy of HBV vaccine protection among patients undergoing hemodialysis. Methods: We conducted a prospective cohort study to include patients on hemodialysis without protective anti-HBs antibodies (>10 mIU/mL) at National Taiwan University Hospital, its Bei-Hu Branch, and several hemodialysis clinics since 2021. Their hepatitis B virus status was checked, and patients naïve to hepatitis B or with resolved hepatitis B were included. Engerix-B (GlaxoSmithKline, Belgium) 40 mg would be administered intramuscularly at the standard 0, 1, 2, and 6-month schedules. If the patient has positive anti-HBs before, a booster 40 mg vaccination would be given. After vaccination, anti-HBs Ab would be checked regularly. A vaccine responder is a positive serum anti-HBs antibody 12 months after vaccination. Results: A total of 59 patients were enrolled in the study accepted vaccination. 48 people completed vaccination and accepted serum tests for anti-HBs antibodies. Among them, 29 were HBV-naive, while 19 had resolved hepatitis B. 4 participants (7%) have

positive anti-HBs antibodies before vaccination. Among 24 HBV-naive patients to receive the complete 4-dose schedule (0, 1, 2, 6) of HBV vaccination, the anti-HBs positive rates were 70% (14/20), 67% (4/6), 65% (11/17), and 60% (9/15) at 1, 6, 12, and more than 12 months after completion of vaccination. Among 18 patients with resolved HBV who received the complete 4-dose schedule (0, 1, 2, 6), the antiHBs positive rates were 79% (11/14), 67% (10/15), 80% (4/5), and 33% (2/6) at 1, 6, 12, and more than 12 months after completion of vaccination. For 6 patients to receive a booster vaccination, anti-HBs positive rate was 100% in both HBV-naïve participants and resolved HBV patient during the annual followup. However, after 12 months, the anti-HBs positive rate declines to 75% in HBV-naïve participants.

Conclusions: The vaccine response rate was acceptable in hemodialysis patients, with 65% and 80% in HBV-naïve and HBV-resolved patients 12 months after the standard 4-dose vaccination schedule. For resolved HBV patients, the HBV vaccine did increase their anti-HBs titer, and so did the HBV booster vaccination. HBV vaccination program for hemodialysis patients without protective anti-HBs is feasible and should be further explored.

P.14

UNAWARENESS OF HEPATITIS B INFECTION AND LACK OF SURVEILLANCE ARE ASSOCIATED WITH SEVERITY OF HEPATOCELLULAR CARCINOMA

Kuan-I Lee1, Po-Cheng Liang2, Po-Yau Hsu1,2, Tyng-Yuan Jang1,2, Yu-Ju Wei2, Ching-I Huang1,2, Ming-Yen Hsieh2, Zu-Yau Lin1,2, Ming-Lun Yeh1,2, Chung-Feng Huang1,2, Jee-Fu Huang1,2, Chia-Yen Dai1,2, Wan-Long Chuang1,2, Ming-Lung Yu1,2,3

1School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

2Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

3School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan

B 型肝炎未自知及未接受篩檢與肝癌嚴重 度相關

李冠儀1 梁博程2 許博堯1,2 張庭遠1,2 魏鈺儒2 黃駿逸1,2 謝明彥2 林子堯1,2 葉明倫1,2 黃釧峰1,2 黃志富1,2 戴嘉言1,2 莊萬龍1,2 余明隆1,2,3

1 高雄醫學大學醫學系

2 高雄醫學大學附設醫院肝膽胰內科

3 國立中山大學醫學院及代謝異常脂肪肝卓越研究中 心

Background: Unawareness of Hepatitis B virus (HBV) infection and lack of surveillance may serve as major barriers to HBV control and contributors to severe hepatocellular carcinoma (HCC) at presentation.

Aims: This study evaluated the risk of HBV unawareness, and its relationship with HCC severity.

Methods: This retrospective study was conducted in a tertiary hospital in Taiwan. Patients with HBV-related HCC diagnosed from 2011 to 2021 were enrolled. The demographic, clinical, and HCC characteristics were collected and compared between patients of HBV unawareness and awareness, with and without surveillance.

Results: Of 501 HBV-related HCC patients enrolled, 105 (21%) patients were unaware of HBV infection at diagnosis of HCC. Patients of HBV unawareness

were significantly younger and with poorer liver function than those with HBV awareness. Patients of HBV unawareness also had a significantly higher rate of detectable HBV DNA and advanced stage of HCC. Ninety-one (23%) of the HBV-aware patients did not receive regular surveillance. Patients of HBV unawareness, and awareness without surveillance shared similar clinical characteristics with more severe HCC status. Further regression analysis demonstrated HBV awareness with periodic surveillance was associated with early-stage HCC. Meanwhile, we observed that there was no change in the proportion of HBV awareness over the past ten years. Patients with surveillance also had better HCC survival than patients without surveillance or unawareness.

Conclusions: HBV unawareness and lack of regular surveillance correlated to advanced HCC at presentation. Efforts on HBV education to improve disease awareness and HCC surveillance are needed.

P.15

HEPATIC FLARES AFTER COVID-19 VACCINATION IN CHRONIC HEPATITIS B PATIENTS – A SERIAL REPORT IN TAIWAN

Po-Cheng Liang, Chung-Feng Huang, Ming-Lun Yeh, Chia-Yen Dai, Jee-Fu Huang, Zu-Yau Lin, Wan-Long Chuang, Ming-Lung Yu

Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

新冠肺炎疫苗後之 B 型肝炎復發 台灣 病例系列報告

梁博程 黃釧峰 葉明倫 戴嘉言 黃志富 林子堯 莊萬龍 余明隆

高雄醫學大學附設中和紀念醫院肝膽胰內科

Background: Coronavirus disease 2019 (COVID-19) vaccination is the key strategy to fight against severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) infection.

Aims: Vaccine-induced hepatitis and hepatitis B virus (HBV) reactivation in chronic hepatitis B (CHB) patients is elusive.

Methods: CHB patients with or without nucleoside/ nucleotide analogues (NUCs) were retrospectiveprospectively recruited. After excluding other potential causes, serum alanine aminotransferase flares (clinical flare, CF) greater than 2 folds of baseline level or/and virological reactivation (VR) within 90 days after the last dose of COVID-19 vaccination was viewed as vaccine-related events.

Results: A total of 48 CHB patients who met the criteria for CF/VR were included in this study. The mean age was 55.8 years, with 6 (12.5%) testing positive for eAg, 4 (8.3%) with cirrhosis, and 11 (22%) receiving NUCs therapy at the time of the first vaccine. The median timing of the liver events after the last dose of vaccine was 5.8 weeks. Of the study patients, 29 (56.9%) experienced a combination of CF and VR, and 6 (11.8%) had VR without CF. Of the 35 patients with VR, 9 (25.7%) experienced an increase of more than 2 log10 in HBV DNA levels, 11 (31.4%) had DNA levels greater than 1000 IU/mL from an undetectable baseline, 11 (31.4%) had viral loads greater than 10,000 IU/mL if baseline values were unavailable, and 4 (11.4%) had more than 1 log elevation in HBsAg. Among the 11 cases with baseline NUCs, 7 (63.6%) underwent discontinuation and all of them had VR

(±CF). Overall, 9 (18.8%) cases were complicated by liver decompensation, one of which resulted in fatality. After the liver events, 29 (56.9%) cases received NUC treatment. One case with liver biopsy-suspected autoimmune hepatitis was successfully treated with steroids. Multivariate analysis indicated that baseline BMI and cirrhotic status were the only factors associated with decompensation, and vaccination doses or types were not predictive factors.

Conclusions: It is important to clarify the relationship between COVID-19 vaccination and HBV flares, and to be aware of the potential for HBV reactivation in CHB patients with advanced liver fibrosis and recent cessation of NUCs therapy.

P.16

IMPROVED LIVER FUNCTION AND FIBROSIS REDUCTION IN HCVRELATED CIRRHOSIS PATIENTS FOLLOWING DIRECT-ACTING ANTIVIRALS AGENT

Hsuan-Yuan Chang, Chun-Chi Yang, Hsing-Tao Kuo, Chi-Shu Sun, I-Che Feng, Ming-Jen Sheu

Division of Hepatogastroenterology, Chi Mei Medical Center, Tainan, Taiwan

接受直接型抗病毒藥物治療後之丙型肝 炎相關肝硬化病人的肝功能改善與纖維 化程度降低

張瑄元 楊畯棋 郭行道 孫啟書 馮意哲 許銘仁 奇美醫院胃腸肝膽科

Background: The eradication of the Hepatitis C Virus (HCV) through the use of direct-acting antivirals (DAA) has been associated with improved liver functions and mortality across all stages of liver disease.

Aims: The objective of this study was to evaluate the alterations in liver function and degree of fibrosis in patients with cirrhosis who achieved hepatitis C virus (HCV) eradication through direct-acting antiviral (DAA) therapy.

Methods: We conducted a prospective assessment to evaluate the changes in Child-Pugh (C-P) class, fibrosis degree, and other baseline characteristics before and after the completion of DAA therapy.

Results: Following the achievement of complete HCV eradication, defined as sustained viral response at week 12 (SVR12), C-P class improved in 15/24 (62.5%) patients (from B to A and from C to B). C-P class worsened in 4/71 patients (5.6%) (from A to B and B to C).

Conclusions: Our study provides evidence that DAA therapy can effectively improve liver function and reduce fibrosis stage in patients with HCV-related cirrhosis.

P.17

HEPATITIS C ELIMINATION MODEL IN TAIWAN’S COMMUNITY CARE HOMES

Shih-Tien Chen

Division of Gastroenterology, Department of Internal Medicine, Chia-Yi Hospital, Ministry of Health and Welfare, Chiayi, Taiwan

住宿型養護機構住民 C 肝滅除模式 陳詩典

衛生福利部嘉義醫院胃腸肝膽科

Background: WHO’s global hepatitis control strategy aims to reduce incidence by 90% and mortality by 65% during the period 2016-2030. Hepatitis C Virus (HCV) can cause cirrhosis and hepatoma, while DAA (Directacting antiviral) can cure more than 95% of cases and thus prevent progressing to cirrhosis and hepatoma. However, access to HCV diagnosis and treatment remains insufficient in rural Taiwan, especially for the residents of non-urban community care homes.

Aims: Yunlin and Chiayi counties and cities are high-prevalence areas for hepatitis C in Taiwan, with an antibody-positive rate of 7.3%, higher than the national average of 4.2%. The Hepatitis care team of the Chiayi Hospital of the Ministry of Health and Welfare proactively screened residents of 22 community care homes for hepatitis B and C in Yunlin and Chiayi counties and cities. By doing so, this plan aims to eliminate hepatitis C from the residents of community care homes, through organization and delivery integration among regional hospitals and community care homes.

Methods: Since 2017, the Taiwanese government has successively complied with financial resources for free hepatitis C screening and cure programs. From September 2021 to December 2022, An HCV elimination program was planned and implemented for a total of 450 residences of 22 community care homes based on the paradigm of integrated care, which include patient-centered principles, team resource management approach, proactive countermeasures, and innovative thinking design. The positive cases of HCV screening were then sent to the Chiayi Hospital for further blood and ultrasound tests and physician consultations. The confirmed HCVRNA positive cases were then treated and examined periodically by antivirus medications and blood tests, prospectively, delivered by Chiayi Hospital for all cases

in community care homes. At the end of the course of treatment, the physicians issue a treatment result certification for each included case.

Results: Among the 353 aged 45-79 residents, 320 (91%) participated in this HCV screening program. The number of positive cases of HCV Ab and HCVRNA was 48 (15%) and 23 (7%), respectively. Among the confirmed cares, 20 people received HCV antivirus medication treatment, while 3 of them people did not receive any treatment due to death or unwillingness to be treated. The Fibrosis-4 score, which reveals the degree of fibrosis, showed that the number of cases with F0 to F4 are 6, 7, 2, 4, and 1, respectively. The average age of cases receiving DAA treatment was 59 years; the treatment rate was 83%; the complete treatment rate, follow-up rate, and SVR rate was all 100%.

Conclusions: Among the 450 residents, 320 (71%) aged 45-79 participated in the HCV screening. The number of positive cases of HCV Ab and HCV-RNA was 48 (15%) and 23 (7%), respectively. Among the confirmed cares, 20 people received HCV antivirus medication treatment, while 3 of them people did not receive any treatment due to death or unwillingness to be treated. The Fibrosis-4 score, which reveals the degree of fibrosis, showed that the number of cases with F0 to F4 are 6, 7, 2, 4, and 1, respectively. The average age of cases receiving DAA treatment was 59 years; the treatment rate was 83%; the complete treatment rate, follow-up rate, and SVR rate was all 100%.

P.18

CHEMPREVETION OF HCC AMONG HCV PATIENTS WHO FAILED PRIOR ANTIVIRAL THERAPY

Pei-Chien Tsai1, Chung-Feng Huang1, Ming-Lung Yu1,2,3

1Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

2School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan

3Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan

探討 C 型肝炎治療失敗之肝癌化學預防

蔡佩倩1 黃釧峰1 余明隆1,2,3

1 高雄醫學大學附設中和紀念醫院肝膽胰內科

2 國立中山大學學士後醫學系

3 國立中山大學代謝異常脂肪肝卓越研究中心

Background: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at high risk of hepatocellular carcinoma (HCC), especially among patients with diabetes mellitus (DM).

Aims: We aimed to investigate if metformin or/and statin can reduce HCC risk among CHC patients with DM and/or hyperlipidemia (HLP) who failed antiviral therapy.

Methods: CHC patients who failed interferon-based therapy were enrolled in a large-scale, multicenter cohort in Taiwan (T-COACH). HCC 1.5-year after interferon-based therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplant as competing risks, Gray’s cumulative incidence method and Cox subdistribution hazards for HCC development were used.

Results: Of 2,779 CHC interferon-failed patients, 480 (17.3%) developed new-onset HCC after antiviral therapy. Patients with DM who did not use metformin had a 1.5-fold higher risk of HCC, while those with HLP who used statins had a 47% lower risk of HCC. We redefined HCC risk levels as high-, intermediate-, and low-risk based on the risk number of DM risk [DM non-metformin] and lipid risk [HLP non-statin or non-HLP]. Annual incidence rates of HCC were 519.7 per 10,000 person-years for patients with both risks, 275.2 for patients with only lipid risk, and 117.7 for

patients with only sugar risk or no risk. After adjusting for confounding factors, patients with both risks had a 3-fold higher risk of developing HCC, while patients with only lipid risk had a 2-fold higher risk compared to patients with only sugar risk or no risk.

Conclusions: Among non-SVR CHC patients, metformin use in DM patients or statin use in HLP patients significantly reduced HCC risk after antiviral therapy. A simple risk score based on DMnonmetformin use at high risk and HLP statin use at low risk could predict the new-onset HCC among those patients.

P.19

RISK FACTORS FOR HEPATOCELLULAR CARCINOMA DEVELOPMENT IN CHRONIC KIDNEY DISEASE PATIENTS WITH CHRONIC HEPATITIS C

INFECTION AFTER ANTIVIRAL TREATMENT

Kuo-Chin Chang1, Jing-Houng Wang1, Chao-Hung Hung1, Chien-Hung Chen1, Sherry Yueh-Hsia Chiu1,2, Tsung-Hui Hu1

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Department of Health Care Management and Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan

慢性腎臟病患者合併 C 型肝炎抗病毒治 療後發生肝細胞癌的危險因子

張國欽1 王景弘1 洪肇宏1 陳建宏1 邱月暇1,2 胡琮輝1

1 高雄長庚紀念醫院胃腸肝膽科系

2 長庚大學醫務管理學系暨健康老化研究中心

Background: Hepatitis C virus (HCV)-infected individuals treated with direct-acting antivirals (DAAs) are at risk for hepatocellular carcinoma (HCC) after achieving sustain virological response (SVR).

Aims: This study explored the risk factors for HCC in chronic kidney disease (CKD) patients with HCV infection receiving DAA therapy.

Methods: From March 2014 to December 2021, 738 patients with HCV-positive CKD who were regularly followed up at Kaohsiung Chang Gung Memorial Hospital for DAA treatment were included in the study.

Results: 738 patients with anti-HCV positive CKD patients were included in this study. Of these 738 patients, 542 patients who had achieved SVR without HCC before DAA treatment were analyzed. Univariate analysis showed that age (≥70.5 years), AFP (≥20 ng/ ml) and cirrhosis were risk factors for the development of hepatocellular carcinoma. Multivariate analysis showed that cirrhosis only (HR: 4.34, 95% CI: 1.4213.27, p = 0.01) was an independent risk factor for the development of HCC.

Conclusions: In HCV-infected patients with CKD, cirrhosis was an independent risk factor for new HCC after DAA treatment.

P.20

IN-HOSPITAL CALL-BACK PROGRAM OF HEPATITIS C INFECTED PATIENTS: EXPERIENCE IN A HOSPITAL IN NORTHERN TAIWAN

Cheng-Kuan Lin, Ya-Li Shih, Kuei-Fen Chang

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

實施院內 C 型肝炎病人召回計畫：台灣 北部一醫院經驗

林政寬 施雅麗 張桂芬 亞東紀念醫院肝膽胃腸科

Background: The government of Taiwan has set the goal of HCV elimination in 2025. However, the COVID-19 pandemic slows down the screening and treatment of HCV-infected patients. Some patients in the hospital are still unaware of the disease and the benefits of treatment.

Aims: We conduct an in-hospital call-back program for previously confirmed HCV-infected patients. The patients are contacted and advised to visit GI OPD for an HCV RNA checkup and evaluation of DAA therapy.

Methods: From January 2017 to March 2022, the patients with seropositivity of anti-HCV in the hospital information system were searched at Far Eastern Memorial Hospital. The patients with age <18 years old, and HIV patients were excluded. The medical chart and history were reviewed. Two times of telephone call in the daytime of Monday to Friday was performed. If the patient agreed, a scheduled GI OPD was arranged.

Results: Totally 3987 patients with seropositivity of anti-HCV were detected during 5.25 years period. After the exclusion of the patients who had finished therapy, expired, and were without HCV viremia, 1401 patients were enrolled in the call-back program. There were 280 patients (20%) returning hospital for the study. The loss of contact rate was 30.4% (381 patients who cannot be contacted and 46 patients with absence in scheduled OPD). There were 259 patients (18.4%) receiving therapy at another hospital, 177 patients (12.6%) refusing therapy, 176 patients (12.6%) dying, and 82 patients (5.9%) replying unsuitable for therapy. Among the 282 patients coming back for workup, there were 135 male patients and 148 female patients. The median age was 64 years old (range: 32 to 95). HCV viremia was detected in 82 patients

(29.3%). The age of the patients with viremia was younger than without viremia (60.3 ± 1.1 vs 62.9 ± 0.8, p = 0.05), and more male patients (59% vs 42.3%, p = 0.012). There were 80 patients (97.6%) who received DAA therapy. The SVR was 100% (ITT)/ 97.5% (PP).

Conclusions: In-hospital call-back programs can remind HCV-infected patients to receive RNA checkups and further therapy. However, only onefifth of patients come back to the hospital after telephone contact. Further intervention is necessary to encourage those patients of loss of follow-up to receive checkups.

P.21

THE EFFECIACY BETWEEN DIRECTLY ACTING ANTIVIRALS AND CHRONIC HCV PATIENTS WITH DIFFERENT STAGES OF RENAL AFFECTION

Pei-Lun Lee, Jyh-Jou Chen, Hung-Da Tung, Chun-Ta Cheng, Tang-Wei Chuang

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Hospital, Liouying, Tainan, Taiwan

直接抗病毒藥物對與不同階段腎病變的 慢性 C 型肝炎患者的療效

李佩倫 陳志州 董宏達 鄭俊達 莊棠惟

奇美醫療財團法人柳營奇美醫院胃腸肝膽科

Background: The approval of different direct-acting antivirals (DAAs) improved the clinical outcomes in patients infected with HCV worldwide and could be used in patients with chronic kidney disease (CKD). Aims: We aimed to assess the efficacy and safety of different DAAs regimens in HCV patients with various estimated glomerular filtration rates (eGFR).

Methods: This retrospective study was conducted at Liouying ChiMei hospital. Adult patients aged 18 y/o above who had been treated at the Out-Patient Departments (OPD) of the hospital during July, 2014 to Dec., 2022 in southern Taiwan. Patients were classified according to their eGFR into five groups (>80 ml/min, 60-79 ml/min, 30-59 ml/min, 15-29 & <15 ml/min). Sustained virologic response (SVR) 12 weeks after treatment was evaluated in all groups, in addition to reporting treatment side effects.

Results: The study included 2840 patients (age; 64.7 ± 12.9 years, 45.4% males). Most involved patients (87.3%, n = 2479) were treatment-naïve, and 18.4% (n = 523) had liver cirrhosis. Different DAAs regimens were used, while most of the patients (n = 3586) received Sofosbuvir (SOF) based regimen ± RBV and Maviret®. SVR rates were 98.1%, 97.7%, 97.6%, 97.8%, & 92% in eGFR (>80 ml/min, 60-79 ml/min, 30-59 ml/min, 1529 ml/min & <15 ml/min), respectively. Patients with eGFR & <15 ml/min had the lowest SVR, which was statistically significant compared to other groups, while patients with eGFR <30 ml/min had a higher risk of adverse events than patients with eGFR > 30.

Conclusions: Different DAAs regimens are highly effective and safe for treating chronic HCV patients with different kidney functions and/or impairment stages. Advanced kidney disease can impair the response to DAAs and increase the incidence of side effects.

FUNCTIONAL АND MORPHOLOGICAL ABNORMALITY OF LIVER AMONG DIABETIC PATIENTS WITH VIRAL HEPATITIS

Altantuya Idkhuu, Davaadorj Duger, Elbegzaya Erdene, Delgertsog Gantumur, Tuvshinzul Battogtokh, Sainbileg Sonomtseren, Bira Namdag, Otgonbayar Radnaa

Mongolian Gastroenterology Federation, Mongolian Endoscopy Association, Ulaanbaatar, Mongolian

Background: The management of chronic liver disease depends on the degree of liver fibrosis. Therefore, assessment of the degree of liver fibrosis is important for choosing a therapeutic strategy and for determining the prognosis.

Aims: Diabetic patients with viral hepatitis has high risk of having liver cirrhosis. Therefore, screening of fatty liver and liver fibrosis in diabetic patients is more important. The main diagnosing method of fatty liver and liver fibrosis is liver biopsy and histology but so far, we are able to detect viral infection using viral marker and determine fibrosis stage of NAFLD in patients who has diabetes mellitus type 2.

Methods: We collected 320 serums samples of diabet mellitus, HCV (-) and diabet mellitus, HCV (+) different groups. It was an matched population based case control study which included 123 adults (46.5% male, 53.5% female) aged 28-80 years old who diagnosed Diabetes mellitus in National University Hospital. The variables were measured using a conventional automated analyzer at the respective hospitals. We analyzed the serum levels for the following; platelet count, prothrombin time, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma- glutamyltranspeptidase, albumin, cholesterol, triglyceride, fasting plasma glucose. The AST-to-platelet ratio index (APRI) and FIB-4 and NAFLD fibrosis score.Statistical analysis were conducted using the SPSS version 19.0 software package.

Results: There were 350 patients in immunology tests anti-HCV 32.34% of the patients were diagnosed with Hepatitis B and C, 26.83% of viral hepatitis patients were infected with HCV, 4.94% were infected with HBV, and 0.57% were infected with both HCV and HBV. There were 123 patients and by WHO classification of ages 20-29 aged patient (n = 4), 30-39 aged (n = 19), 40-49 aged (n = 65), 50-59 aged (n = 126), 60-70 aged (n = 48), over 70 aged (n = 14) or 53.24 ± 9.43.

146 patients are male,148 patients are female. By BMI 29.9 ± 1.14. By blood test, thrombocytes counted 256.6 ± 11.7; in coagulogramm the prothrombin time was 111.7 ± 31.4; in biochemistry test total bilirubin 16.46 ± 10.6; AP 364.7 ± 192.3; AST 35.7 ± 45.7; ALT 42.8 ± 45.5; GGT 86.53 ± 123.4; albumin 42.06 ± 23.95; total cholesterol 6.04 ± 2.47; triglyceride 5.72 ± 34.5; HbA1c 8.83 ± 5.92; in immunology tests anti-HCV 29.37 ± 18.87 (n = 58); HBsAg 590.134 ± 1013.7 (n = 23); M2BPGI (COI) counted 2.24 ± 2.19. relationship of fibrosis test associated with DM, HCV (-) and DM, HCV (+) patients. HCV (+), diabetes patients’ M2BPGi and NAFLD fibrosis score was 0.7 unit higher than HCV (-), diabetes patients. Moreover, HCV (+), diabetes patients’ fibroscan was 3.4kpa higher, fib-4 was 0.4 unit higher and APRI was 0.3 unit higher than HCV (-), diabetes patients. M2BPGi was decreased by 16.1% in HCV (+), diabetes patients’ group after the treatment. Despite, the M2BPGi was dropped by 4.7% in HCV (+), non-diabetes group. As a result of the treatment liver fibrosis rate were improved in both group. HCV (+), diabetes patient fibrosis rate was upgraded from F4 to F3. Besides, fibrosis rate was improved F3 to F2 in HCV (+), non- diabetes patients.

Conclusions: 1. In our study population, 32.3% of the patients were diagnosed with Hepatitis B and C, 26.8% of viral hepatitis patients were infected with HCV, 4.9% were infected with HBV, and 0.6% were infected with both HCV and HBV. 2. Diabetes, HCV (+) the indicators of liver fibrosis such as fibroscan, M2BPGI, NAFLD fibrosis score were 0.3-0.7 unit higher than in people with diabetes, HCV (-). 3. M2BPGi was decreased by 19.4% in HCV (+), diabetes patients’ group after the treatment. Despite, the M2BPGi was dropped by 6.6% in HCV (+), non-diabetes group. As a result of the treatment liver fibrosis rate were improved in both group. HCV (+), diabetes patient fibrosis rate was upgraded from F4 to F3. Besides, fibrosis rate was improved F3 to F2 in HCV (+), nondiabetes patients.

P.23

ALPHA-FETOPROTEIN COMBINED WITH RADIOGRAPHIC TUMOR BURDEN SCORE TO PREDICT OVERALL SURVIVAL AFTER LIVER RESECTION IN HEPATOCELLULAR CARCINOMA

Yi-Hao Yen1, Yueh-Wei Liu2, Wei-Feng Li2, Chih-Chi Wang2

1Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

甲型胎兒蛋白合併腫瘤負荷分數可以預 測整體存活率在肝細胞癌病患接受手術 切除

顏毅豪1 劉約維2 李韋鋒2 王植熙2

1 高雄長庚紀念醫院胃腸肝膽科

2 高雄長庚紀念醫院一般外科

Background: The tumor burden score (TBS) is calculated using the Pythagorean theorem based on the largest tumor size and tumor number.

Aims: We evaluated whether combining the radiographic tumor burden score (TBS) and alphafetoprotein (AFP) level could be used to stratify overall survival (OS) among hepatocellular carcinoma (HCC) patients after liver resection (LR).

Methods: Patients who underwent LR for Barcelona Clinic Liver Cancer stage 0, A, or B HCC between 2011 and 2018 were enrolled. TBS scores were calculated using the following equation: TBS2 = (largest tumor size (in cm))2 + (tumor number)2.

Results: Among 743 patients, 193 (26.0%) patients had a low TBS (<2.6), 474 (63.8%) had a moderate TBS (2.6–7.9), and 75 (10.1%) had a high TBS (>7.9). Those with a TBS 7.9 and AFP < 400 ng/mL had a significantly better OS than those with a TBS > 7.9 and an AFP < 400 ng/mL (p = 0.003) or 400 ng/mL (p < 0.001). A multivariate analysis using TBS 7.9 and AFP < 400 ng/mL as the reference values showed that a TBS > 7.9 and an AFP < 400 ng/mL (hazard ratio (HR): 2.063; 95% confidence interval [CI]: 1.175–3.623; p = 0.012) or 400 ng/mL (HR: 6.570; 95% CI: 3.684–11.719;

p < 0.001) were independent predictors of OS.

Conclusions: In conclusion, combining radiographic TBSs and AFP levels could stratify OS among HCC patients undergoing LR.

P.24

PREDICTORS

OF MORTALITY IN

HOSPITALIZED

CHRONIC LIVER DISEASE FOLLOWING COVID-19: A RETROSPECTIVE SINGLE-CENTER STUDY

Pei-Jui Wu1, Hsing-Tao Kuo1, Chi-Shu Sun1, I-Che Feng1, Chung-Han Ho2, Ming-Jen Sheu1

1Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

2Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan

住院之慢性肝病患者感染 COVID-19 後的 死亡預測因子：單一醫學中心回顧性研 究

吳佩叡1 郭行道1 孫啟書1 馮意哲1 何宗翰2 許銘仁1 1 奇美醫療財團法人奇美醫院胃腸肝膽科

2 奇美醫療財團法人奇美醫院醫學研究部

Background: Chronic liver disease (CLD) is a common comorbidity among patients with COVID-19. Early recognition of high-risk individuals with comorbidities such as CLD, is important for preventing mortality. Aims: We addressed the group of CLD patients and aimed to analyze whether the clinical features, laboratory data can predict mortality in hospitalized patients with COVID-19.

Methods: We retrospectively enrolled all hospitalized patients diagnosed with COVID-19 comorbid with CLD between January 1, 2022, and September 30, 2022. We compared basic characteristics, laboratory data, treatment, clinical course, severity between survivors and non-survivors.

Results: The mortality rate of all patients was 12.79%. The all-cause mortality rates of patients with noncirrhotic CLD and cirrhosis were 11.26% and 16.39%, respectively. Compared to survivors, non-survivors had significantly higher Platelet, PT-INR, total bilirubin, AST levels, and lower albumin levels.

Conclusions: Our study found that albumin, ACLF, decompensation of cirrhosis, and vasopressor use were identified as independent risk factors for allcause mortality.

P.25

AIR POLLUTION AS A POTENTIAL A RISK FACTOR FOR HEPATOCELLULAR CARCINOMA IN TAIWANESE PATIENTS AFTER ADJUSTING FOR CHRONIC VIRAL HEPATITIS

Tyng-Yuan Jang, Chia-Yen Dai

Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

空氣污染是肝癌的潛在危險因子

張庭遠 戴嘉言 高雄醫學大學附設醫院肝膽胰內科

Background: Air pollution is a risk factor for hepatocellular carcinoma (HCC).

Aims: However, the effect of air pollution on HCC risk in patients with hepatitis remains unclear.

Methods: This cross-sectional study recruited 348 CHB patients who were tested for serum hepatitis B surface antigen (HBsAg) and for antibodies against hepatitis B core antigen (HBcIgG) and hepatitis C virus (anti-HCV) in 2022. The diagnosis of HCC was based on the International Classification of Diseases, 10th revision (ICD-10). Daily estimates of air pollutants were aggregated into mean estimates for the previous year based on the date of recruitment or HCC diagnosis. Results: Out of 348 patients, twelve had HCC (3.4%). Patients with HCC were older (71.7 years vs 50.9 year; P = 0.004), had higher proportion of HBsAg seropositivity (41.7% vs 5.1%; P < 0.001), and substantially higher levels of particulate matter 2.5 (PM2.5) (21.5 μg/m3 vs 18.2 μg/m3; P = 0.05). Logistic regression analysis revealed that the factors associated with HCC were age (OR: 1.10; CI: 1.03–1.17; P = 0.01), PM2.5 level (OR: 1.51; CI: 1.02–2.23; P = 0.04), and HBsAg seropositivity (OR: 6.60; CI: 1.51–28.85; P = 0.01). There was a combined effect of PM2.5 and HBsAg seropositivity on the risk of HCC development (OR: 22.17; CI: 3.33–147.45; P = 0.001).

Conclusions: In this study, we demonstrated that PM2.5 and HBsAg seropositivity were associated with HCC occurrence and had synergistic effects after adjusting for confounding factors.

P.26

SORAFENIB OR LENVATINIB

COMBINING PD-1 INHIBITORS IN UNRESECTABLE HEPATOCELLULAR CARCINOMA: A RETROSPECTIVE ANALYSIS

Kuan-Kai Huang1, Hsueh-Chien Chiang1, Chien-Ming Chiang1, Tzu-Chun Hong1, Wei-Ting Chen1, Juei-Seng Wu1, Ming-Tsung Hsieh1, Po-Jun Chen1, I-Chin Wu1, Yih-Jyh Lin2, Chiung-Yu Chen1, Chiao-Hsiung Chuang1, Ting-Tsung Chang1, Hsin-Yu Kuo1

1Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

2Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

以 Sorafenib 或 Lenvatinib 合併 PD-1 抑 製劑於不可切除的肝細胞癌：回顧性分 析

黃冠凱1 姜學謙1 江健銘1 洪子鈞1 陳威廷1 吳叡森1 謝名宗1 陳柏潤1 吳毅晉1 林毅志2 陳炯瑜1 莊喬雄1 張定宗1 郭欣瑜1

1 國立成功大學醫學院附設醫院內科部

2 國立成功大學醫學院附設醫院外科部

Background: Systemic therapy is currently reserved for patients with unresectable HCC, including immune checkpoint inhibitors (ICIs) and multitarget tyrosine kinase inhibitors (MTKIs). However, optimal combination therapies in uHCC are yet to be determined.

Aims: This study compared the treatment efficacy of sorafenib versus lenvatinib in combination with programmed cell death protein-1 (PD-1) inhibitors in patients with uHCC in a single university medical center.

Methods: Among 208 patients with uHCC treated with PD-1 inhibitors, 88 were administered with ICIs in combination with sorafenib or lenvatinib. The treatment response and survival outcomes were evaluated. Predictors of survival were assessed by multivariate analysis.

Results: A total of 49 patients were treated with PD-1 inhibitors combined with sorafenib, and 39 patients

were treated with PD-1 inhibitors combined with lenvatinib. The lenvatinib group exhibited a stronger objective response rate (ORR) (20.51% vs. 16.33%) and had a higher disease control rate (41.03% vs. 28.57%) than did the sorafenib group. The median overall survival was longer in the lenvatinib group than the sorafenib group (13.1 vs. 7.8 months; hazard ratio = 0.39, p = 0.017). The incidence of treatment-related adverse events was similar.

Conclusions: Combination of PD-1 inhibitors with lenvatinib could be an effective treatment strategy for HCC patients receiving MTKI-based combination therapy. PD-1 inhibitors combined with lenvatinib resulted in more favorable survival outcomes without increased adverse effects compared with PD-1 inhibitors with sorafenib. Further larger-scale and prospective studies should be conducted to verify the study results.

P.27

LENVATINIB IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA WHO DO NOT MEET THE REFLECT CRITERIA

Yu-Chen Chang, Hung-Wei Wang, Hsueh-Chou Lai, Wei-Fan Hsu, Che-Wei Chang, Cheng-Yuan Peng

Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan

於未符合 REFLECT 標準之無法切除性肝 細胞癌患者的 Lenvatinib 治療效果

張育誠 王鴻偉 賴學洲 許偉帆 張哲維 彭成元

中國醫藥大學附設醫院消化醫學中心

Background: Lenvatinib, a multitargeted tyrosine kinase inhibitor, has shown promising results as a systemic treatment option for unresectable hepatocellular carcinoma (HCC). However, its efficacy specifically in patients who do not meet the inclusion criteria outlined in the REFLECT trial remains unclear.

Aims: This study aimed to determine the efficacy of lenvatinib for patients with unresectable HCC who did not meet the REFLECT criteria.

Methods: We enrolled patients with unresectable HCC who were treated with lenvatinib as the firstline systemic therapy. Progression-free survival (PFS), overall survival (OS), and the best treatment response (objective response rate, ORR, and disease control rate, DCR) were evaluated based on whether the patients met the REFLECT criteria or not, as well as according to the criteria of the REFLECT trial.

Results: A total of 53 patients with unresectable HCC were treated with lenvatinib as the first-line systemic therapy. None of them had a history of tyrosine kinase inhibitor treatment, HCC in ≥50% of the liver, or bile duct invasion. Among the patients who did not meet the criteria, 2, 7, and 3 had ChildPugh score B, Eastern Cooperative Oncology Group (ECOG) performance status 2 or 3, and main portal vein invasion, respectively. Ultimately, 18.9% (10 out of 53) of the patients did not meet the REFLECT criteria. The median treatment duration was 7 versus 8 months for patients without or within REFLECT criteria, respectively. Their progression-free survival was similar to those who met the REFLECT criteria (P = 0.251). However, their overall survival was significantly lower than that of the patients who met the criteria (P = 0.017). Both ECOG and main portal vein invasion

were significant factors in stratifying overall survival (P = 0.029 and P = 0.003, respectively). The efficacy of lenvatinib for patients without or within REFLECT criteria was similar, with an ORR of 20% and 33.3% (P = 0.705), and a DCR of 80% and 95.2% (P = 0.163), respectively.

Conclusions: Lenvatinib demonstrated efficacy in treating patients who did not meet the inclusion criteria of the REFLECT study. Nonetheless, the overall survival may be subject to variability influenced by various factors, including the ECOG and the presence of main portal vein invasion.

P.28

REAL WORLD EXPERIENCE OF NIVOLUMAB IN THE TREATMENT OF ADVANCED HEPATOCELLULAR CARCINOMA IN A DISTRICT HOSPITAL

Pi-Teh Huang1, Yu-Ming Cheng1, Kuan-Chun Hsueh2

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan

2Division of General Surgery, Department of Surgery, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan

晚期肝癌病人在區域醫院使用

Nivolumab 的臨床經驗

黃彼得1 鄭煜明1 薛冠群2

1 童綜合醫院胃腸肝膽科 2 童綜合醫院一般外科

Background: Hepatocellular carcinoma is one of the leading causes of cancer-related death worldwide and in Taiwan. Nivolumab, an anti-PD-1 monoclonal antibody, has been proven to have clinical benefit with meaningful improvements in response rate and survival for advanced hepatocellular carcinoma.

Aims: To assess the clinical and survival outcomes of patients with advanced hepatocellular carcinoma treated with nivolumab in the real world setting in a district hospital.

Methods: This retrospective cohort enrolled 24 patients diagnosed with advanced hepatocellular carcinoma and treated with nivolumab at our hospital from January 2019 to December 2022. All patients had received prior treatment for hepatocellular carcinoma except for 2 patients (first line). All study subjects received nivolumab 2-2.5 mg/kg administered once every 2 weeks intravenously for at least 10 weeks. Treatment continued until disease progression, severe adverse events, or death. Treatment response was evaluated by mRECIST tool.

Results: Twenty-four patients were enrolled in our study with 20 males and 4 females. The median age was 63.1 ± 12.1 years. The risk factors of HCC were as follow: HBV (n = 10, 41.7%), HCV (n = 6, 25%), HBV + HCV (n = 7, 29.2%). Baseline median AFP was 30.5 ng/ ml (2-241065). BCLC staging were: B (n = 8, 33.3%), C

(n = 16, 66.7%). mALBI grades were: I (n = 15, 62.5%), IIa (n = 6, 25%), IIb (n = 3, 12.5%), III (n = 0, 0%). The median treatment duration was 4.5 months (2.023.4 months). Concurrent treatment included: TACE (n = 7, 29.2%), RFA (n = 4, 16.7%), RT (n = 3, 12.5%), TKI (n = 7, 29.2%), HAIC (n = 2, 8.3%) and IO (n = 1, 4.2%). The median OS for the whole cohort was 21.5 months (14.5-28.4 months) and the median PFS was 5.0 months (4.3-5.7 months). ORR was 34.8% and DCR was 56%.

Conclusions: Our real world experience of nivolumab in the treatment of advanced hepatocellular carcinoma showed improved clinical outcomes with good OS and PFS.

P.29

MAC-2 BINDING PROTEIN GLYCOSYLATION ISOMER TO ALBUMIN RATIO PREDICTS BACTERIAL INFECTIONS IN CIRRHOTIC PATIENTS

Pei-Shan Wu1,3, Kuei-Chuan Lee2,3, Yun-Cheng Hsieh2,3, Pei-Chang Lee2,3, Hui-Chun Huang2,3, Han-Chieh Lin2,3, Ming-Chih Hou1,2,3

1Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan

2Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

3Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

MAC-2 結合蛋白糖基化異構物與白蛋白 之比例可以預測肝硬化患者細菌感染之 風險

吳佩珊1,3 李癸汌2,3 謝昀蓁2,3 李沛璋2,3 黃惠君2,3

林漢傑2,3 侯明志1,2,3

1 臺北榮民總醫院內視鏡診斷暨治療中心

2 臺北榮民總醫院胃腸肝膽科

3 國立陽明交通大學內科學科

Background: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-related clinical outcomes.

Aims: This study aimed to investigate the predictive role of M2BPGi in cirrhosis-related complications.

Methods: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for one year and cirrhosis- related clinical events were recorded. Cox proportional hazards regression models were used to identify predictors of clinical outcomes, and receiver operating characteristic curve (ROC) analysis was used to establish the predictive value of these outcomes.

Results: Sixty (40.3%) patients experienced cirrhosisrelated clinical events and had higher M2BPGi levels compared to those without events (8.9 ± 4.2 vs. 6.2 ± 4.3 cut-off index, p < 0.001). The most common cirrhosis-related complications were bacterial infections (24.2%). Cox regression analysis revealed

that the M2BPGi to albumin ratio (M2BPGi/albumin) independently predicted all cirrhosis-related [Hazar ratio (HR) = 1.25, p = 0.034] and all bacterial infectious events (HR = 1.38, p = 0.043) within one year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant free survival. On ROC analysis, M2BPGi/albumin had superior values of area under the ROC curve (AUC) for all cirrhosis-associated (AUC = 0.74, p < 0.001) and all bacterial infectious events (AUC = 0.80, p < 0.001) compared with M2BPGi alone, Child-Pugh, MELD, ALBI scores, and NLR, with cut-off values of 1.82 and 2.31, respectively.

Conclusions: M2BPGi/albumin could serve as a prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections.

P.30

PRIMARY PREVENTION OF VARICEAL BLEEDING IN PATIENTS WITH UNRESECTABLE HCC AND PORTAL VEIN TUMOR THROMBOSIS: A SINGLE CENTER RETROSPECTIVE STUDY

Yu-Jen Chen1,2, Ming-Chih Hou1,2, Yi-Hsiang Huang1,2,3,4, Tsung-Chieh Yang1,2, Pei-Chang Lee1,2, Chien-Wei Su1,2,3,5, Jiing-Chyuan Luo1,2

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan

3Institute of Clinical Medicine, National Yang-Ming University Chiao-Tung School of Medicine, Taipei, Taiwan

4Healthcare & Services Center, Taipei Veterans General Hospital, Taipei, Taiwan

5Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

靜脈瘤之初級預防於無法切除併門脈腫 瘤侵犯之肝癌病患：單一醫學中心回溯 性研究

1 臺北榮民總醫院胃腸肝膽科

2 國立陽明交通大學醫學系

3 國立陽明交通大學臨床醫學研究所

4 臺北榮民總醫院健康管理中心

5 臺北榮民總醫院一般內科

Background: The prevalence of esophageal varices (EV) is high in patients with hepatocellular carcinoma (HCC) and portal vein thrombosis (PVT). However, the prevention strategy and outcomes in HCC patients with PVT and EV is not well studied.

Aims: The present study aimed to investigate the clinical prognoses and prevention strategy of HCC patients with PVT and EV.

Methods: A total of 445 patients with HCC and PVT, who received esophagogastroduodenoscopy (EGD) while HCC been diagnosed, were retrospectively enrolled between Jan 2013 to Jan 2023. The

diagnosis and severity of EV were reviewed by three gastroenterologists. Prognostic factors were analyzed using the competing risk analysis and Cox proportional hazards model.

Results: EV was noted in 273 (60%) patients. High risk varices (HRV) was noted in 170 (38.2%) patients, 19 patients experienced acute variceal bleeding (AVB) before or upon index EGD. Of the 151 patients with HRV, 89 (58.9%) of them received primary prevention with non-selective beta blocker (NSBB) or esophageal variceal ligation (EVL). Fifty-two patients (21.8%) experienced in a follow-up period of 108 days, with median bleeding free survival (BFS) of 79 days. Primary prevention of EV is associated with longer BFS (hazard ratio = 0.359, p = 0.007), but not overall survival (OS). There was no difference in BFS and OS between NSBB or EVL group. Of the 44 patients received EVL for primary prevention, three (6.8%) of them experienced variceal ulcer bleeding in 1 week.

Conclusions: Primary prevention with NSBB or EVL in HCC patients with PVT and HRV is associated with better BFS, but not OS. The primary prevention method is not associated with OS or BFS in patients with HRV.

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EFFECTIVENESS AND SAFETY BETWEEN ENDOSCOPIC ULTRASOUND GUIDED- FINE NEEDLE ASPIRATION AND FINE NEEDLE BIOPSY

Chung-Hsiang Wu1, Jiann-Hwa Chen1,3, Pei-Shan Tsai1, Yu-Ming Cheng2, Wei-Chih Su1, Lung-Yuan Hsu1,3, You-Chen Chao1,3

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei TzuChi Hospital, Taipei, Taiwan

23Division of Gastroenterology and Hepatology, Tung’s Taichung MetroHarbor Hospital

3School of Medicine, Tzu Chi University, Hualien, Taiwan

內視鏡超音波導引下細針穿刺與切片的 效度與安全性分析

吳仲翔1 陳建華1,3 蔡佩珊1 鄭煜明2 蘇偉志1 徐榮源1,3 趙有誠1,3

1 台北慈濟醫院胃腸肝膽科

2 童綜合醫院胃腸肝膽科

3 慈濟大學醫學院

Background: Endoscopic ultrasound (EUS) guided fine needle aspiration (FNA) is the primary method of pancreatic or gastrointestinal peri-luminal tissue acquisition. Fine needle biopsy (FNB) has been developed and allow collection of core samples. It is plausible that cutting needles will improve diagnostic accuracy as well as provide tissue with conserved architecture, enabling histological analysis. However, literature showed no definite result.

Aims: To improve our yield of EUS-guided tissue acquisition, we use FNB needle for tissue acquisition and assessed the diagnostic yield of FNA and FNB.

Methods: This was a retrospective review of our collected data since 2007 to 2022/12/31 from consecutive patients who received FNA/B due to pancreatic or gastrointestinal peri-luminal lesions. A total of 216 patients was recruited and 24 patients underwent FNA from 2007 to 2016, whereas 192 patients received FNB in the following years until the end of 2023/04/25. FNA needles included 19G or 22G (EZ shot II®, Olympus, Inc., Tokyo, Japan or Echotip Ultra®, Cook, Inc., Bloomington, IN, U.S.A.). FNB was performed with a new dedicated core needle

(Echotip ProCore® 20G, Cook, Inc., Bloomington, IN, U.S.A. or Acquire®, Boston Sci., Marlborough, MA). FNA samples were assessed by cytopathologists; FNB samples were sent for smear cytology, cell block and analyzed by surgical pathologists for the core tissue. Results: FNB needle established a diagnosis with higher sensitivity (83.4% vs. 72.2% respectively). The procedure time of FNB was in nonsignificant difference with FNA. Diagnostic accuracy was comparable between FNB and FNA (85.9% vs 79.2%). The safety of FNB was non-inferior to FNA with lower adverse event (AE) rate.

Conclusions: FNB using a newly designed dedicated core needle showed a better sensitivity than FNA, with similar procedure time, number of passes and lower AE rate. FNB was comparable with FNA in most characteristics. In addition, FNB provided qualitative information not reported on FNA, such as degree of differentiation in malignancy, metastatic origin, and rate of proliferation in neuroendocrine tumors.

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PROGNOSTIC NUTRITIONAL INDEX AS A PROGNOSTIC FACTOR FOR VERY EARLY STAGE HEPATOCELLULAR CARCINOMA

Kuan-Jung Huang1, Pei-Chang Lee1, Chun-Ting Ho2, Chien-Wei Su1,2,3,4, Yi-Hsiang Huang1,4, Teh-Ia Huo5, Ming-Chih Hou1,3, Jaw-Ching Wu4

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

3Department of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

4Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

5Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

以 Prognostic Nutritional Index 作為早 期肝細胞癌的預後指標

黃冠榕1 李沛璋1 何俊廷2 蘇建維1,2,3,4 黃怡翔1,4 霍德義5 侯明志1,3 吳肇卿4

1 臺北榮民總醫院胃腸肝膽科

2 國立陽明交通大學醫學系

3 臺北榮民總醫院一般內科

4 國立陽明交通大學臨床醫學研究所

5 臺北榮民總醫院醫學研究部基礎研究科

Background: Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of modern non-invasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined.

Aims: To investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC.

Methods: A total of 450 patients with the Barcelona Clinic Liver Cancer (BCLC) classification stage 0 HCC diagnosed at Taipei Veterans General Hospital from 2012 to 2022 were retrospectively enrolled. Serum

biomarkers and prognostic scores determining poor overall survival (OS) were analyzed by Cox proportional hazards model and logistic regression. We compared the homogeneity and Akaike information criterion (AIC) among the prognostic nutritional index (PNI), AST to Platelet Ratio Index (APRI), albumin-bilirubin (ALBI) score, EZ (easy)-ALBI score, fibrosis (FIB)-4 score and lymphocyte-to-monocyte ratio (LMR) to determine the predictability on the OS of patients.

Results: After a median follow-up of 35.0 months (interquartile range IQR 19.0-60.0 months), 81 patients died, with a 5-year OS rate of 76.9%. Among the non-invasive serum marker scores, PNI had the best performance in predicting the OS of patients with the highest homogeneity and lowest AIC compared to other scores. Moreover, we stratified the patients into high-risk (PNI < 45) and low-risk (PNI ≥ 45) groups. It showed that the 5-year OS rates were 83.3% and 63.1% in the low-risk and high-risk PNI groups, respectively (p < 0.001).

Conclusions: PNI had the best performance in predicting the OS for patients with very early-stage HCC.

EVALUATION OF CEACAMS AS THE SPECIFIC PROGNOSTIC MARKERS IN COLORECTAL, LUNG, AND LIVER CANCER

Chien-Wen Whang1, Chun-Chia Cheng2, Zong-Lin Sie2, Ai-Sheng Ho1

1Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan

2Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University, Taoyuan, Taiwan

評估 CEACAMS 作為大腸癌、肺癌、及肝 癌專一性生物標記之研究

黃建文1 程俊嘉2 謝宗霖2 何愛生1

1 振興醫院胃腸肝膽科

2 長庚大學放射醫學研究院

Background: CEACAMs are cell adhesion molecules that have been implicated in various cancers. In this study, we investigated their expression patterns and their correlation with survival rates in colorectal, lung, and liver cancer.

Aims: The aim of this study was to investigate the expression patterns of CEACAM1, 3, 4, 5, 6, 7, and 8 in colorectal, lung, and liver cancer, and evaluate the differential CEACAMs as the prognostic markers.

Methods: Using the GEPIA database, we analyzed the expression levels of CEACAM1, 3, 4, 5, 6, 7, and 8 in colorectal, lung, and liver cancer. Additionally, we utilized the Interactive Bodymap in GEPIA to determine the specific expression profiles of these genes in the different cancer types. Furthermore, we employed the Kaplan-Meier plotter to assess the association between gene expression and overall survival (OS)/progress-free survival (PFS) rates in lung and rectum adenocarcinoma.

Results: We found that CEACAM1, CEACAM5, and CEACAM6 significantly overexpressed in the tumor tissues of patients with colorectal and lung cancer based on the analysis in GEPIA database (http:// gepia.cancer-pku.cn/). CEACAM1 and CEACAM5 specifically expressed in colorectal cancer based on the Interactive Bodymap in GEPIA, whereas CEACAM6 specifically expressed in lung, pancreatic, gastric, and colorectal cancer. Further analysis for the correlation between gene expression and survival rate, KaplanMeier plotter was used (https://kmplot.com/analysis/), which indicated that high expression of CEACAM5

was correlated with poor progress-free survival (PFS) rates in lung cancer (p = 0.024). Meanwhile, high expression of CEACAM6 was correlated with poor PFS in lung and rectum adenocarcinoma (p = 0.062 and 0.034, respectively). We then demonstrated the elevated levels of CEACAM1, CEACAM5, and CEACAM6 in selective colorectal HT29, lung A549, and Hepatic PLC5 tumor cells using qPCR. We also demonstrated the expression of surface CEACAM5 in HT29 cells detected using flow cytometry by a truncated T84.66 scFv targeting CEACAM5.

Conclusions: Our study highlights the significant overexpression of CEACAM1, CEACAM5, and CEACAM6 in colorectal and lung cancer tissues. The correlation between their expression and PFS rates suggests their potential as prognostic markers. Our findings provide valuable insights into the role of these CEACAM family members in colorectal and lung cancer.

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STAT3 MEDIATES CANCER STEMLIKE TUMORSPHERE FORMATION AND PD-L1 EXPRESSION TO CONTRIBUTE RADIORESISTANCE IN HBV-POSITIVE HEPATOCELLULAR CARCINOMA

Ai-Sheng Ho1, Chun-Chia Cheng2, Cheng-Liang Peng3, Zong-Lin Sie2, Chun Yeh1, Shou-Dong Lee1

1Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan

2Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University, Guishan, Taiwan

3Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, Taiwan

STAT3 調控 HBV 肝癌類癌幹細胞及 PD-L1 的表現造成放療抗性

何愛生1 程俊嘉2 彭正良3 謝宗霖2 葉淳1 李壽東1

1 振興醫院胃腸肝膽科

2 長庚大學放射醫學研究院

3 行政院原子能委員會核能研究所

Background: We proposed that cancer stem cells (CSCs) survived and presented resistance to radiotherapy (RT) in hepatocellular carcinoma cells (HCC). IL-6 has been reported to be particularly involved in HCC tumorigenesis.

Aims: Therefore, we intended to validate that IL-6 downstream STAT3 mediated CSCs formation and immune checkpoint PD-L1 expression in HCC, thus contributing radioresistance.

Methods: HBV-positive HCC tumorspheres were formed and exposed with X-ray irradiation, cell viability of which was measured consequently. Specific inhibitors targeting EGFR (by gefitinib), STAT3 (by BBI608), and HCC-targeted therapy sorafenib were investigated to suppress tumorsphere formation. RT-qPCR was used for detecting STAT3-downstream PD-L1 and anti-apoptosis MCL1 and BCL2 gene expression in the PLC5-derived tumorspheres and STAT3-knockdowned PLC5.

Results: We found that RT significantly inhibited HBV-positive Hep3B and PLC5 cell viability but not for HCC-derived stem-like tumorspheres cultured by EGF, IL-6, bFGF, and HGF. It revealed that tumorspheres presented radioresistance compared with the

parental cells. Specifically, RT induces IFNs, EGF, and IL-6 expression, resulting in STAT3 phosphorylation. Kaplan-Meier plotter indicated that highly EGF (p = 0.0024), IL-6 (p = 0.12), and FGF2 (p = 0.0041) were associated with poor survival probability in patients with HBV-positive HCC. We further demonstrated that BBI608 and sorafenib significantly suppressed PLC5 cell viability and PLC5-derived tumorsphere formation. To investigate the mechanism of CSCs-presented radioresistance, STAT3 and STAT3-downstream genes, including PD-L1 and anti-apoptosis MCL1 and BCL2 were detected using qPCR. We demonstrated higher STAT3, PD-L1, MCL1, and BCL2 in Hep3B- and PLC5-derived CSCs compared to PLC5. In addition, knockdown of STAT3 reduced cell proliferation in PLC5 cells, resulting in down-regulation of IL-6mediated PD-L1 and BCL-2. Meanwhile, we found that knockdown of STAT3 significantly improved RTmediated suppression of tumorsphere formation.

Conclusions: We found that CSCs presented radioresistance and figured out which may be mediated by STAT3 in HBV-positive HCC.

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THE EFFICACY OF SECOND-LINE TREATMENTS AFTER FAILURE OF SORAFENIB IN PATIENTS WITH UNRESCTABLE HEPATOCELLULAR CARCINOMA: ONE CENTER EXPERIENCE

Shou-Wu Lee1,2,3, Teng-Yu Lee1,2, Sheng-Shun Yang1,2,4

1Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan

2Department of Internal Medicine, Chung Shan Medical University, Taichung, Taiwan

3Department of Post-Baccalaureate Medicine, Chung Hsing University, Taichung, Taiwan

4Department of Internal Medicine, Yang Ming Chiao Tung University, Taipei, Taiwan

蕾莎瓦治療失敗後使用二線肝癌治療藥 物的療效評估之一項單中心研究

李少武1,2,3 李騰裕1,2 楊勝舜1,2,4

1 臺中榮民總醫院胃腸肝膽科

2 中山醫學大學醫學系

3 國立中興大學後醫學系

4 國立陽明交通大學醫學系

Background: Currently, there is approved agents in patients with unresctable hepatocellular carcinoma (uHCC) who have developed resistance to treatment with sorafenib.

Aims: The aim of this real-world study was to investigate the therapeutic effects in patients with uHCC after progression on treatment with sorafenib.

Methods: Patients with BCLC stage B/C HCC and Child-Pugh A who received sorafenib as first-line treatment from January 2020 to December 2022 were enrolled. Second-line agents were initiated while progression on sorafenib. The outcomes of the sequential therapies, with started with sorafenib, were collected.

Results: Among the 44 enrolled patients who received sorafenib as first-line treatment, median PFS was 5.35 months. ORR and DCR were 18.2 and 59.1% respectively. 31 patients had progressive tumor within following period, and 20 patients (64.5%) had a chance to receive second-line treatments. 14, 2, 2, 1 and 1 case received regorafenib, ramucrimab, nivolumab, Atezolimab/Bevacizumab

and conventional chemotherapy as second-line treatment. The mean time of initiating second-line treatment was 7.05 months. Among the 31 patients received second-line treatments, the mOS was longer in patients with regorafenib (23.62 months) than those with other agents (13.82 months). The mOS of patients with progressive tumor but without secondline treatments was 11.50 months.

Conclusions: The rate of received second-line treatments in patients with uHCC and using sorafenib as first-line treatgment was 64.5%. The sequential therapy of sorafenib and regorafenib provided more favorable therapeutic outcomes.

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PM2.5 AND MAFLD IN COMMUNITY

Tyng-Yuan Jang1, Chia-Yen Dai1, Ming-Lung Yu1, Pau-Chung Chen2

1Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

2Institute of Environmental and Occupational Health Sciences, National Taiwan University, Taipei, Taiwan

空氣污染和肝纖維化關係

張庭遠1 戴嘉言1 余明隆1 陳保中2

1 高雄醫學大學附設中和紀念醫院肝膽胰內科

2 國立臺灣大學環境及職業醫學部

Background: Air pollution was associated with liver cirrhosis.

Aims: We aimed to investigate the association between air pollution and advanced fibrosis among patients with metabolic associated fatty liver disease (MAFLD) and chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections.

Methods: A total of 1,376 participants who were seropositive for HBV surface antigen (HBsAg) or antibodies to HCV (anti-HCV) or had abnormal liver function in a community screening program from 2019 to 2021 were enrolled for the assessment of liver fibrosis using transient elastography.Daily estimates of air pollutants (particulate matter ≤ 2.5 µm in diameter (PM2.5), nitrogen dioxide (NO2), ozone (O3) and benzene) were aggregated into mean estimates for the previous year based on the date of enrolment.

Results: Of the 1,376 participants, 767 (52.8%) and 187 (13.6) had MAFLD and advanced fibrosis, respectively. A logistic regression analysis revealed that the factors associated with advanced liver fibrosis were HCV viremia (odds ratio [OR], 3.13; 95% confidence interval (CI), 2.05–4.77; P < 0.001), smoking (OR, 1.79; 95% CI, 1.16–2.74; P = 0.01), age (OR, 1.04; 95% CI, 1.02–1.05; P < 0.001) and PM2.5 (OR, 1.10; 95% CI, 1.05–1.16; P < 0.001). Linear regression analysis revealed that LSM was independently correlated with PM2.5 (β: 0.134; 95% CI: 0.025, 0.243; P = 0.02). There was a dosedependent relationship between different fibrotic stages and the PM2.5 level (the PM2.5 level in patients with fibrotic stages 0, 1-2 and 3-4:27.9, 28.4, 29.3 ug/ m3, respectively; trend P < 0.001).

Conclusions: Exposure to PM2.5, as well as HBV and HCV infections, is associated with advanced liver fibrosis in patients with MAFLD. There was a dosedependent correlation between PM2.5 levels and the severity of hepatic fibrosis.

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COMPARING GUT MICROBIOTA IN HEPATOCELLULAR CARCINOMA PATIENTS PRE- AND POSTRESECTION

Ming-Chao Tsai1,2, Yuan-Hung Kuo1, Chien-Hung Chen1, Chih-Chi Wang3

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan

3Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

比較肝細胞癌患者手術前後腸道菌群的 變化

蔡明釗1,2 郭垣宏1 陳建宏1 王植熙

3

1 高雄長庚紀念醫院胃腸肝膽科

2 國立中山大學學士後醫學系

3 高雄長庚紀念醫院一般外科

Background: Recent studies have highlighted the association between gut microbiota and the development of hepatocellular carcinoma (HCC), indicating an imbalance in intestinal ecology known as dysbiosis. However, limited research has been conducted on the longitudinal changes in gut microbiota in HCC patients after resection.

Aims: The aim of this study was to compare the changes in gut microbiota before and after HCC resection.

Methods: A total of 69 HCC patients who underwent resection at Chang Gung Hospital in Kaohsiung from September 2021 to June 2023 were enrolled. Stool samples were collected before the surgery and one year after the surgery for analysis of gut microbiota. The taxonomic composition of the gut microbiota was determined by sequencing the 16S ribosomal RNA gene in the stool samples.

Results: The average age of the 69 HCC patients was 61 years, with 18 (53%) being over 60 years old. The distribution of BCLC stages was as follows: 6 patients in stage 0, 35 patients in stage A, and 28 patients in

stage B. Analysis of the gut microbiota showed no significant differences in the alpha-diversity and betadiversity before and one year after HCC resection. Conclusions: The removal of HCC did not result in significant changes in the composition of the gut microbiota.

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PROGRESSION OF PORTAL HYPERTENSION AFTER ATEZOLIZUMAB PLUS BEVACIZUMAB IMMUNOTHERAPY FOR HEPATOCELLULAR CARCINOMA: REPORT A CASE AND LITERATURE REVIEW

Tung-Yen Lin1, Tung-Hung Su1,2

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

肝癌免疫治療後增加門脈高壓：個案報

告與文獻回顧

林東彥1 蘇東弘1,2

1 國立臺灣大學醫學院附設醫院胃腸肝膽科

2 國立臺灣大學醫學院附設醫院肝炎研究中心

Background: Immune checkpoint inhibitor therapy becomes the first-line therapy for advanced hepatocellular carcinoma (HCC). Gastric or esophageal varices should be monitored and managed closely during therapy because bevacizumab is a vascular endothelial growth factor inhibitor. The progression of gastric or esophageal varices and portal hypertension during therapy is unclear.

Aims: To report a case and review the literature on the progression of esophageal varices and summarize the potential mechanisms

Methods: A case of portal hypertension progression (e.g., development of esophageal varices, ascites, and hepatic hydrothorax after atezolizumab and bevacizumab therapy at National Taiwan University Hospital was reported, and the relevant literature from Pubmed were reviewed.

Results: We present an 83-year-old male with resolved hepatitis B without cirrhosis. He had an 18cm hepatocellular carcinoma (HCC) at BCLC stage C and received tri-weekly atezolizumab 1200mg plus bevacizumab 500mg therapy for 34 cycles (26 months) with sustained partial responses and tumor reduction to 10.8cm. However, progressive ascites, esophageal varices and left hepatic hydrothorax developed after proton therapy for the residual tumor, even though his portal vein was patent and the tumor was under control. After the literature review, we found 3 case

reports and one case series with 5 cases of HCC (BCLC B/C: n = 3/2). Among them, three had cirrhosis and all had small esophageal varices identified before treatment. One had portal vein invasion. After the administration of 1~15 cycles of atezolizumab plus bevacizumab therapy, progression of varices was found in 1 patient, and the other 4 patients developed esophageal variceal bleeding. None of these patients received beta blocker for prophylaxis. The association between atezolizumab/bevacizumab and portal hypertension was possible and multifactorial, which might involved vascular endothelial growth factor (VEGF) pathway and immune-related adverse events with hepatic fibrosis.

Conclusions: Atezolizumab plus bevacizumab treatment might be associated with exacerbation of portal hypertension. Thus, monitoring signs of portal hypertension and varices should be considered during treatment.

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THE ASSOCIATION OF GUT MICROBIOTA WITH TREATMENT RESPONSE IN HEPATOCELLULAR CARCINOMA

Pao-Yuan Huang1, Ming-Chao Tsai1,2, Chih-Chien Yao1, Yuan-Hung Kuo1,2, Kwong-Ming Kee1,2, Seng-Kee Chuah1, Chien-Hung Chen1,2

1Division of Hepato-gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan

腸道菌群與肝癌治療反應的關係

黃寳源1 蔡明釗1,2 姚志謙1 郭垣宏1,2 紀廣明1,2 蔡成枝1 陳建宏1,2

1 高雄長庚紀念醫院胃腸肝膽科

2 長庚大學臨床醫學研究所

Background: Gut microbiota can influence systemic immune responses, and immune responses are directly related to the efficacy of tumor treatment. Research has shown that gut microbiota is also associated with tumor development and treatment response.

Aims: Our study primarily investigates the differences in gut microbiota among different treatment responses in patients with hepatocellular carcinoma (HCC).

Methods: This is a prospective study at Kaohsiung Chung-Gung memorial hospital, Taiwan, from October 2019 and September 2021. We recruited patients with advanced HCC (BCLC stage C) receiving target therapy (sorafenib, lenvatinib, or regorafenib). Fecal samples were collected before target treatment. The taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples.

Results: A total of 35 patients with advanced HCC were included in the study. Out of these patients, 21 presented with progression disease (PD), while the remaining 14 had stable disease (SD) at the 3-month mark. The alpha diversity indices did not show a significant difference between the two groups, but the beta-diversity indices exhibited a significant difference (p<0.001). Among the PD group and the

SD group, two families, 13 genera, and one species (Leuconostoc lactis) displayed differential abundance. Conclusions: There is variation in gut microbiota among different populations that exhibit different responses to target therapy. However, further research is needed to support the use of gut microbiota as a predictive factor for treatment response.

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REAL-WORLD EXPERIENCE IN ATEZOLIZUMAB PLUS BEVACIZUMAB FOR HIGH-RISK ADVANCED HEPATOCELLULAR CARCINOMA WITH VP4 PORTAL VEIN THROMBOSIS OR MORE THAN 50% LIVER OCCUPATION

Chung-Wei Su1,2, Chen-Chun Lin1,2, Wei Teng1,2, Po-Ting Lin1,2, Yi- Chung Hsieh1,2, Wei-Ting Chen1,2, Chun-Yen Lin1,2, Shi-Ming Lin1,2

1Department of Gastroenterology and Hepatology, Linkuo Chang Gung Memorial Hospital, Taoyuan, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

癌自癒併用癌思停用於高風險肝癌之現 實世界的使用經驗

蘇崇維1,2 林成俊1,2 滕威1,2 林伯庭1,2 謝彝中1,2 陳威廷1,2 林俊彥1,2 林錫銘1,2

1 林口長庚紀念醫院胃腸肝膽科系

2 長庚大學醫學院

Background: Hepatocellular carcinoma (HCC) patients complicated with Vp4 portal vein thrombosis or more than 50% liver occupancy (TO ≥50%) had a poor prognosis. Atezolizumab plus bevacizumab (atezo/bev) had some therapeutic efficacy for the high-risk subgroup patients in the IMbrave150 trial.

Aims: The details of real-world experience and prognostic factors are not reported.

Methods: High-risk advanced HCC was defined as HCC with Vp4 portal vein thrombosis (occlusion of the trunk or bilateral branches) or TO ≥50%. We retrospectively included 64 high-risk HCC patients who received atezo/bev in a medical center to evaluate their overall response rate (ORR), overall survival (OS), and prognostic factors.

Results: The included high-risk advanced HCC patients were 31 with Vp4 and 50 with TO ≥50%. The safety profile showed any grade and ≥ grade 3 AEs were 59.4% and 14.1%, respectively, after atezo/bev therapy. The ORR was 23.5% according to mRECIST criteria, and the estimated median OS was 7.8 months after a median follow-up of 5.5 months. In the cox-regression multivariate model, both of Vp4 and TO>50% (HR: 4.349, P=0.0051), concurrent

radiotherapy (HR: 0.158, P=0.0051), and objective response (HR: 0.086, P= 0.0168) were independent factors of OS. The patients who achieved objective response had significantly better overall survival (median: not reached. vs. 6.1 months, P = 0.0002).

Conclusions: In conclusion, atezo/bev could safely apply for the high-risk advanced HCC. The patients who had both Vp4 and TO ≥50% had extremely poor prognoses. An objective response may have benefits for a longer overall survival for the high-risk advanced HCCs.

P.41

DYSREGULATED EXPRESSION OF SLINGSHOT PROTEIN PHOSPHATASE 1 (SSH1) DISRUPTS CIRCADIAN RHYTHM AND WNT SIGNALING ASSOCIATED TO HEPATOCELLULAR CARCINOMA PATHOGENESIS

Da-Wei Chu1, Chi-Tai Yeh2,3, Ming-Yao Chen1,4

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University - Shuang-Ho Hospital, New Taipei City, Taiwan

2Department of Medical Research & Education, Taipei Medical University - Shuang-Ho Hospital, New Taipei City, Taiwan

3Continuing Education Program of Food Biotechnology Applications, College of Science and Engineering, National Taitung University, Taitung, Taiwan

4TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan

SSH1 的調節失調會擾亂與肝細胞癌發病 機制相關的晝夜節律和 WNT 信號傳導

邱大維1 葉淇臺2,3 陳明堯1,4

1 衛生福利部雙和醫院（委託臺北醫學大學興建經 營）消化內科

2 衛生福利部雙和醫院（委託臺北醫學大學興建經 營）研究部

3 國立臺東大學理工學院食品生物技術應用繼續教育 學程

4 臺北醫學大學消化醫學研究中心

Background: Cumulative evidence indicate that the circadian rhythm plays a vital role in hepatic homeostasis and pathophysiology, with its dysregulation increasingly associated with metabolic disorders, oncogene activation, and increased cancer risk. Several studies have suggested that a cofilin-1 (CFL-1) modulator, slingshot protein phosphatase 1 (SSH1), facilitates actin cytoskeleton reorganization, thus playing a critical role in invasiveness of various cancer types. However, the mechanism underlying SSH1-regulated hepatocellular stemness and circadian rhythm is largely unknown.

Aims: To evaluate the role of SSH1 in hepatocellular carcinoma.

Methods: Combining bioinformatics, tissue staining,

and functional assays in HCC clinical samples and their non-tumor counterpart.

Results: Combining bioinformatics, tissue staining, and functional assays, we demonstrated that SSH1 is significantly upregulated in HCC clinical samples, compared to their non-tumor counterpart, across six HCC platforms with acceptable AUC of 0.62 to 0.77 (p < 0.01). This aberrant expression of SSH1 was associated with worse overall (HR = 1.70, p = 0.0063) and progression-free (HR = 1.477, p = 0.0187) survival rates. Pharmacological (Sennoside A) or CRISPR targeting of SSH1 in Huh7 cells (Huh7-SSH1-/-) significantly suppressed cell viability, migration, invasion, colony and tumorsphere formation of the Huh7-SSH1-/- cells. Mechanistically, we showed that downregulated SSH1 expression suppressed CLOCK, BMAL1, WNT3, β-catenin, LRP5/6, BCL2, VIM and Snail, with concomitant upregulated CFL-1/2, and CRY1 expression, indicating dysregulated circadian rhythm and WNT/β-catenin oncogenic pathway deactivation. Consistent with these findings, significantly reduced tumor volume was observed in the mice treated with SenAlight (1.76-fold, p < 0.01) and SenAdark (3.79-fold, p < 0.01). The expression of SSH1, CLOCK, BMAL1 and β-catenin proteins were significantly downregulated in the SenAlight and SenAdark mice; this was more so in the SenAdark mice.

Conclusions: In conclusion, our results indicate that SSH1-driven oncogenicity is mediated by CSCs activities with concomitant activation of the WNT/βcatenin signaling and circadian rhythm dysregulation in the HCC microenvironment, thus uncovering a novel molecular target and a potential new therapeutic strategy to treat HCC patients.

P.42

ANALYSIS OF ALPHA-FETOPROTEIN KINETICS IN REGORAFENIBTREATED PATIENTS WITH AFP ABOVE 400 NG/ML

Yu-Jui Chang, Hung-Wei Wang, Hsueh-Chou Lai, Wei-Fan Hsu, Che-Wei Chang, Cheng-Yuan Peng

1Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan

探討使用 Regorafenib 治療 AFP 超過 400 ng/mL 的肝癌患者，甲胎蛋白的分 析結果

張育瑞 王鴻偉 賴學洲 許偉帆 張哲維 彭成元

中國醫藥大學附設醫院消化醫學中心

Background: In the Phase III REACH-2 study, it was found that changes in alpha-fetoprotein (AFP) levels were associated with the time to tumor progression. However, the relationship between AFP response or progression, and their correlation with objective measures of response and survival remains unclear in patients with unresectable hepatocellular carcinoma (HCC) who had an AFP level ≥ 400 ng/mL before initiating regorafenib therapy.

Aims: This study aimed to explore the relationship between AFP kinetics and radiographic response in unresectable HCC patients treated with regorafenib who had an AFP level of ≥ 400 ng/mL.

Methods: Serum AFP and radiographic studies were conducted at baseline and every 3 months. Pearson’s correlation coefficient was used to evaluate the statistical association between changes in AFP levels and radiographic progression. AFP response or progression was defined as a decrease or increase of ≥20% from baseline, respectively. The objective measure of radiographic response was assessed according to mRECIST.

Results: A total of 20.1% (31/154) of patients had AFP ≥ 400 ng/mL at the initiation of regorafenib therapy after sorafenib treatment failure. After excluding patients with incomplete data, the final number of patients for AFP and radiographic progression analysis was 28 and 27, respectively, and they were enrolled into the analysis. The median time to AFP progression and time to radiographic progression with regorafenib therapy were 4.0 (95% CI: 2.1–5.9) months and 3.9 (95% CI: 2.5–5.4) months, respectively. The survival probability showed no significant difference between

AFP progression and radiographic progression (P = 0.380) according to Kaplan-Meier survival analysis. The association between AFP progression and radiographic progression was negligible at up to 3 months (r = 0.246; P = 0.208) and highly positive at 3-6 months (r = 0.854; P < 0.001). A total of 46.4% (13/28) of patients had an AFP response. The median time to AFP progression was longer in patients with AFP response (not reached) than in patients without (2.8 months) (P < 0.001).

Conclusions: There is an association between AFP progression and radiographic progression in patients with unresectable HCC receiving regorafenib therapy. The potential relationship between the changes in AFP levels during treatment and survival probability warrants further investigation.

P.43

REGORAFENIB AFTER PROGRESSION ON SORAFENIB FOR ELDERLY PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA

Yen-Wun Huang1, Chi-Yu Lee1, Tsang-En Wang1,2,3, Shih-Ting Huang1, Chia-Yuan Liu1,2,3,4, Ming-Jen Chen1,2,3, Hung-Yuan Wang1,2,3, Ching-Wei Chang1,2,3

1Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan

2MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan

3MacKay Medical College, New Taipei, Taiwan

4Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan

65 歲以上長者在 Sorafenib 治療失敗後 使用 Regorafenib 之分析

黃彥文1 李騏宇1 王蒼恩1,2,3 黃詩婷1 劉家源1,2,3,4 陳銘仁1,2,3 王鴻源1,2,3 張經緯1,2,3

1 馬偕紀念醫院肝膽腸胃內科

2 馬偕醫護管理專科學校

3 馬偕醫學院

4 馬偕紀念醫院醫學研究部

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers and the leading cause of cancer-related mortality worldwide. In the RESORCE trial, regorafenib significantly improved overall survival (OS) and progression-free survival (PFS) for patients with advanced HCC who progressed on first-line sorafenib, compared to the placebo. The determinants of survival after sorafenib followed by regorafenib in elderly patients with HCC, remain unclear in the daily practice in Taiwan.

Aims: This study aims to evaluate the safety and efficacy of regorafenib after the progression of sorafenib in elderly patients with unresectable HCC. Methods: We retrospectively analyzed the medical records of 55 patients with unresectable HCC receiving regorafenib after sorafenib failure between 2017 and 2022 at MacKay Memorial Hospital in Taiwan. Patients aged 65 years or more at the time of diagnosis of HCC were defined as the elderly group. Response evaluation was based on mRECIST every two to four months after treatment. Kaplan-Meier method was

.

used for PFS and OS analysis.

Results: Twenty-seven of 55 patients (49%) were included in the elderly group. The mean age of the patients at the time of diagnosis was 70.59 ± 4.49 years. Compared to the patient characteristics of the young and elderly group, there was no significance in age, gender, etiology, Child-Pugh class, ALBI grade, up-to-seven/eleven criteria, macrovascular invasion, extrahepatic metastasis, BCLC stage, AFP > 400 ng/ mL, pretreatment and concurrent therapy. There was no significant difference in PFS after regorafenib treatment between the young and the elderly group (p = 0.709). The median PFS was three months in both groups. Furthermore, there was no significant difference in OS of sorafenib-regorafenib sequential treatment and after regorafenib treatment between the young and the elderly group (p = 0.588 and 0.574, respectively). The median OS of sorafenibregorafenib sequential treatment was 38 months in the young group and 35 months in the elderly group. The median OS after regorafenib treatment was 28 months in the young group and 19 months in the elderly group.

Conclusions: The real-world data results showed no significant difference in outcomes based on age for patients treated with either sorafenib-regorafenib sequential treatment or regorafenib after progression on sorafenib. Further study with a prospective protocol and larger sample sizes may be necessary to draw a definitive conclusion.

P.44 ATEZOLIZUMAB PLUS BEVACIZUMAB IN UNRESECTABLE HEPATOCELLULAR CARCINOMA: SINGLE

HOSPITAL EXPERIENCE

Yi-Hsing Chen1, Chien-Heng Shen1, Hui-Ling Huang2, Te-Sheng Chang1

1Devision of Gastroenterology and Hepatology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

2Department of Nursing, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

癌自禦合併癌思停於不可手術切除之肝

癌：單一醫院經驗

陳奕行1 沈建亨1 黃惠玲2 張德生1

1 嘉義長庚紀念醫院胃腸肝膽科

2 嘉義長庚紀念醫院護理部

Background: Systemic treatment of unresectable hepatocellular carcinoma (uHCC) has advanced markedly in recent years. Since the result of IMbrave 150 Phase III clinical trial has been launched in 2019, atezolizumab plus bevacizumab (Atezo/Beva) show better overall survival (OS) and progressionfree survival (PFS) than sorafenib in uHCC patients. This combination has been approved as a first line systemic option for uHCC rapidly. The efficacy of this combination in non-first line patients is still lacking. Aims: The study aims to compare the therapeutic efficacy of Atezo/Beva treated as first and non-first line therapy for patients with uHCC.

Methods: The retrospective study included a total of twenty-five patients with uHCC treated with Atezo/ Beva from March 2020 to March 2023 at Chiayi Chang Gung Memorial Hospital. Eleven patients were treated as first line therapy and the other fourteen were treated as non-first line therapy.

Results: The baseline characteristics of both groups were similar. In the non-first line group, nine (64.3%) patients were treated as second line therapy, two (14.3%) were treated as third line, and three (21.4%) were treated as fourth line. The prior therapy in the non-first line group included sorfenib, lenvatinib, regorafenib, nivolumab and even clinical trial. The objective response rate (ORR) by mRECIST criteria is 45.5% and 21.4% in the first line and non-first line group. The median OS was 14.3 and 11.6 month (p = 0.521) in the first line and non-first line group. The median PFS was 4.2 and 2 months (p = 0.186) in both

groups. The median OS and PFS increased to notreached (p = 0.261) and 7.9 months (p = 0.02) in the first line group with Child-Pugh score A.

Conclusions: Our data showed similar median OS and PFS compared with IMbrave 150 trial in uHCC patients who received Atezo/Beva as first line therapy with good liver reserve. The non-first line group or patients with decompensation still had poor outcome.

P.45

PRE-SACROPENIA PREDICTS THE OUTCOME IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA UNDERGOING FIRST LINE LENVATINIB

Yuan-Hung Kuo1, Hsing-Yun Lee2, Ching-Di Chang3, Jing-Houng Wang1, Sheng-Nan Lu1, Tsung-Hui Hu1, Ming-Chao Tsai1, Chao-Hung Hung1, Chien-Hung Chen1

1Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung

Chang Gung Memorial Hospital and Chang

Gung University College of Medicine, Kaohsiung, Taiwan

2Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang

Gung University College of Medicine, Kaohsiung, Taiwan

3Department of Radiology, Kaohsiung Chang

Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

肌少症可以預測無法切除肝癌病人使用 一線樂衛瑪的預後

郭垣宏1 李興昀2 常景棣3 王景弘1 盧勝男1 胡琮輝1 蔡明釗1 洪肇宏1 陳建宏1

1 高雄長庚紀念醫院胃腸肝膽科系

2 高雄長庚紀念醫院內科部

3 高雄長庚紀念醫院放射診斷科

Background: Muscle volume loss (pre‐sarcopenia) has been reported associate with the outcome of hepatocellular carcinoma (HCC), however, its survival impact on those patients with lenvatinib treatment is not well-established.

Aims: To elucidate the clinical importance of pre‐sarcopenia in patients receiving lenvatinib as first-line treatment for unresectable hepatocellular carcinoma (u‐HCC) in real world.

Methods: We retrospectively evaluated patients with unresectable HCC who had undergone lenvatinib treatment between January 2018 and Dec 2021. Patients were excluded if they had previously received other systemic therapy or had become lost to follow-up during treatment. Pre‐sarcopenia was diagnosed based on a previously reported cut‐off value calculation formula [psoas muscle area at

level of middle of third lumbar vertebra (cm2)/height (m)2]. Treatment response was assessed by radiologic imaging according to the Response Evaluation Criteria in Solid Tumors vesions 1.1. (RECIST1.1)

Results: A total of 171 patients (Male/Female: 124/47, mean age: 65.9 years) were recruited including 23 (13.5%) patients with sarcopenia and 148 (86.5%) patients with non-sacropenia. The Kaplan-Meier estimate of overall survival (OS) and progression free survival (PFS) was 18.2 months and 6.5 months, respectively. The overall objective response rate (ORR) and disease control rate (DCR) was 18.4% and 70.7%, respectively. There was no difference of PFS between patients with sarcopenia and non-sacropenia (4.3 vs 6.6 months, p = 0.128). However, sarcopenia group had a significantly poorer OS than non-sacropenia group (6.2 vs 18.6 months, p = 0.002) Also, the frequency of the treatment related adverse event (any grade) was greater in the sarcopenia group than in the non-sacropenia group (43.9% vs 18.2%, p = 0.003). Moreover, multivariate analysis showed sarcopenia (HR: 2.776 (1.527–5.047); p = .001) was associated with mortality after adjusting macrovascular invasion, post-treatment and alpha-fetoprotein.

Conclusions: In real world practice, pre‐sarcopenia was shown to be a significant prognostic factor in patients treated with first-line lenvatinib for u‐HCC.

P.46

ASSOCIATION BETWEEN HOMAIR AND HEPATIC FIBROSIS IN NONALCOHOLIC FATTY LIVER DISEASE

Shiang-Lin Tsai1, Hsin-Yi Chen1, Sien-Sing Yang1,2, Chia-Long Lee1,3, Jui-Ting Hu1,2

1Division of Digestive Medicine, Cathay General Hospital, Taipei, Taiwan

2School of Medicine, College of Medicine, FuJen Catholic University, New Taipei City, Taiwan

3School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

HOMA-IR

在非酒精性脂肪肝疾病中與肝 纖維化的關聯

蔡翔霖1 陳信宜1 楊賢馨1,2 李嘉龍1,3 胡瑞庭1,2

1 國泰綜合醫院消化內科

2 天主教輔仁大學醫學系

3 臺北醫學大學醫學系

Background: Insulin resistance is a common metabolic abnormality observed in non-alcoholic fatty liver disease (NAFLD) and has been implicated in the development of hepatic fibrosis. However, the association between HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) and hepatic fibrosis in NAFLD remains inconsistent.

Aims: The aim of this study was to evaluate the relationship between HOMA-IR and hepatic fibrosis in NAFLD and explore its predictive ability for the degree of fibrosis.

Methods: We conducted a study involving 73 patients with NAFLD. All patients were enrolled since January to June in 2023 in Cathay General Hospital. The degree of hepatic fibrosis was measured using Fibroscan. The severity of insulin resistance, the HOMA-IR index was calculated using the following formula: HOMAIR = [Fasting insulin (uIU/mL) * Fasting glucose (mg/ dL)]/405.

Results: Our study results demonstrated a positive correlation between HOMA-IR index and the degree of hepatic fibrosis in NAFLD (r = 0.297, p = 0.011). Patients with higher HOMA-IR values exhibited more severe hepatic fibrosis on Fibroscan measurement.

Conclusions: This study indicates a positive association between HOMA-IR and the degree of hepatic fibrosis in NAFLD. And HOMA-IR can serve as an independent predictor of hepatic fibrosis in NAFLD. Our finding emphasize the metabolic nature of NAFLD and suggest identifying metabolic dysregulation in NAFLD patient. Besides, improving insulin sensitivity may serve as a therapeutic approach for NAFLD.

P.47

ATHEROGENIC INDEX OF PLASMA CORRELATES WITH DISEASE ACTIVITY IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE

Jung-Chun Lin, Tsai-Yuan Hsieh, Tien-Yu Huang, Hsuan-Hwai Lin, Peng-Jen Chen, Yu-Lueng Shih

Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

非酒精性脂肪肝患者血漿致動脈粥樣硬 化指數與疾病活動度之相關性

林榮鈞 謝財源 黃天祐 林煊淮 陳鵬仁 施宇隆

國防醫學院三軍總醫院胃腸科

Background: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of liver disease that can ultimately lead to cirrhosis. Identifying a screening marker for early diagnosis of NAFLD in patients can reduce the risk of morbidity and mortality.

Aims: We investigated the role of the atherogenic index of plasma (AIP) as an index for NAFLD-related liver damage.

Methods: We assessed the plasma levels of AIP and their association with NAFLD-related scores in 62 patients with NAFLD.

Results: The mean levels of AIP were higher in NAFLD patients with high hepatic steatosis index (HSI) than in those with low HSI (0.5030 ± 0.04409 N = 40 vs 0.3528 ± 0.05477 N = 22, p = 0.0412). But AIP level was not correlated with fibrosis score in NAFLD patients.

Conclusions: In conclusion, our data suggested AIP as a suitable index of steatosis rather than hepatic fibrosis in the NAFLD population. However, our findings need external validation in other cohorts.

P.48

PREVALENCE OF STEATOTIC LIVER DISEASE IN PATIENTS WITH HEMOPHILIA USING CONTROLLED ATTENUATION PARAMETER: A SINGLE-CENTER STUDY

Yu-Chuan Chuang1, Hsuan-Hwai Lin1,3, Yeu-Chin Chen2,3

1Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

2Division of Hematology & Oncology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

3Hemophilia Care and Research Center, TriService General Hospital, Taipei, Taiwan

血友病患者使用肝臟纖維掃描檢測脂肪 肝疾病的盛行率：單一中心研究

莊淯全1 林煊淮1,3 陳宇欽2,3

1 三軍總醫院胃腸肝膽科

2 三軍總醫院血液腫瘤科

3 三軍總醫院三軍總醫院血友病照護及研究中心

Background: Steatotic liver disease affects approximately 30% of the global population and continues to increase. Metabolic dysfunctionassociated fatty liver disease (MAFLD) is known to be associated with obesity, hyperlipidemia, metabolic syndrome, diabetes, and hypertension. MAFLD can progress to chronic liver disease and hepatocellular carcinoma (HCC). Patients with hemophilia exhibit an elevated prevalence of obesity and previous study had shown that higher prevalence of steatosis in this population.

Aims: The aim of this study was to investigate the relationship between fatty liver disease and patients with hemophilia in a single-center setting. Additionally, the study aimed to explore the potential correlation between Controlled Attenuation Parameter (CAP) values.

Methods: A retrospective review was conducted between January 2021 and April 2023 at a single center. All patients underwent Fibroscan® and Controlled Attenuation Parameter (CAP) was measured. The CAP score was recorded, with values <215 dB/m defined as S0, >215 dB/m defined as S1, >252 dB/m defined as S2, and >296 dB/m defined as S3.

Results: A total of 73 patients with hemophilia were enrolled in the study. Among them, 89.0% had hemophilia A, 5.4% had hemophilia B, and 5.4% had von Willebrand disease. The age range was 18 to 80 years, with a mean age of 43.4 years. 52 patients (71.2%) accept prophylactic therapy. 27 patients (36.7%) are overweight and 18 patients (18.6%) are obesity. 30 patients (41.1%) have positive of antiHCV, 6 patients (8.2%) have chronic hepatitis B and 3 patients (4.1%) has HIV infection. Sixty patients (82.1%) with hemophilia were diagnosed with fatty liver using Fibroscan®. 17 patients (23.3%) were diagnosed mild fatty liver, 17 patients (23.3%) had moderate fatty liver and 26 patients (35.6%) were found severe fatty liver. Participants with overweight or obesity exhibit higher CAP values (Mean: 283.8) compared to participants without excess weight (Mean: 237.8, P=0.003). Regression analysis reveals a modest positive correlation between CAP values and BMI among patients with hemophilia (R-squared: 0.219). Additionally, we also compared the potential correlation between Controlled Attenuation Parameter (CAP) values and Hemophilia Early Arthropathy Detection with Ultrasound (HEADUS) scores.

Conclusions: This study revealed a higher prevalence of steatotic liver disease in patients with hemophilia. Additionally, the analysis indicated a weak positive correlation between CAP values and HEADUS scores, although it was not statistically significant. Further investigation with a larger sample size and additional variables may provide a more comprehensive understanding of the relationship between fatty liver disease and early arthropathy in patients with hemophilia.

P.49

THE ROLE OF TRYPTOPHAN METABOLITE IN THE PATHOGENESIS OF NAFLD/NASH

Szu-Jen Wang1,2, Shu-Chi Wang3, Chung-Feng Huang4, Ming-Lun Yeh4, Chia-Yen Dai4, Jee-Fu Huang4, Wan-Long Chuang4, Ming-Lung Yu1,4

1Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

2Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan

3Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan

4Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

色氨酸代謝物在 NAFLD/NASH 發病機制 中的作用

王嗣仁1,2 王述綺3 黃釧峰4 葉明倫4 戴嘉言4 黃志富4 莊萬龍4 余明隆1,4

1 高雄醫學大學臨床醫學研究所

2 阮綜合醫院消化內科

3 高雄醫學大學醫學檢驗生物技術學系

4 高雄醫學大學附設中和紀念醫院肝膽胰內科

Background: NAFLD is a prevalent liver condition that can progress to NASH and end-stage liver diseases. Liver fibrosis, associated with tissue inflammation, is a key factor in NAFLD-related complications. 5-Methoxytryptophan (5-MTP), a tryptophan metabolite, has shown anti-inflammatory properties but its specific role in NAFLD/NASH pathogenesis remains unclear.

Aims: (1) Analyze the correlation between tryptophan metabolites and fibrosis severity in nonalcoholic fatty liver mice. (2) Investigate the role of endogenous 5-MTP in liver fibrosis of NAFLD/NASH.

Methods: We used an animal model to study NAFLD/ NASH. Mice were sacrificed at the 16th and 28th weeks, and liver tissues were evaluated using staining methods and immunohistochemistry. Serum 5-MTP concentration was measured using LC-MS due to its small molecular weight.

Results: In the 28-week animal model, significant

obesity, liver index, lobular inflammation, steatosis pattern, ballooning pattern, and liver fibrosis were observed. Serum levels of tryptophan metabolites, including 5-MTP, decreased in ND mice at the end of 28 weeks, potentially due to aging. WD mice exhibited decreased tryptophan metabolite levels, indicating disease progression. Furthermore, mRNA expression of TPH-1 and HIOMT slightly decreased in hepatocytes and Kupffer cells but significantly increased in HSCs of WD mice at 28 weeks.

Conclusions: The concentration of 5-MTP may decrease with NAFLD/NASH progression. 5-MTP likely plays a critical role, particularly in hepatic stellate cells, in the pathogenesis of NAFLD/NASH.

P.50

TREATMENT OF NASH WITH CYTOGUARDIN – 5-MTP

Szu-Jen Wang1,2, Shu-Chi Wang3, Chung-Feng Huang4, Ming-Lun Yeh4, Chia-Yen Dai4, Jee-Fu Huang4, Wan-Long Chuang4, Ming-Lung Yu1,4

1Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

2Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan

3Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan

4Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

細胞保護素 5-MTP 對於脂肪性肝炎的 治療角色

王嗣仁1,2 王述綺3 黃釧峰4 葉明倫4 戴嘉言4 黃志富4 莊萬龍4 余明隆1,4

1 高雄醫學大學臨床醫學研究所 2 阮綜合醫院消化內科

3 高雄醫學大學醫學檢驗生物技術學系

4 高雄醫學大學附設中和紀念醫院肝膽胰內科

Background: NAFLD is a prevalent liver condition that can progress to NASH and end-stage liver diseases. Liver cirrhosis, associated with tissue fibrosis and inflammation, is a significant complication. 5-Methoxytryptophan (5-MTP), also known as cytoguardin, has been identified as a potent inhibitor of COX-2 and inflammation. Recent studies suggest its effectiveness in inhibiting tumor growth and metastasis, as well as attenuating fibrosis in various organs. However, the therapeutic role of 5-MTP in liver fibrosis, cirrhosis, and hepatocellular carcinoma remains unclear.

Aims: (1) Evaluate the preventive effect of 5-MTP in an NAFLD/NASH animal model. (2) Investigate the therapeutic effect of 5-MTP in an NAFLD/NASH animal model.

Methods: To assess the preventive effect, 5-MTP was administered every 2 days, three times per week (dose: 32.4 mg/kg), to WD mice from 0 to 16 weeks. To examine the therapeutic effect, the same regimen

was administered from 24 to 28 weeks. Liver organ, tissue, and blood biochemical data were compared with control mice. Sirius Red staining and other methods were used to evaluate inflammation and fibrosis levels.

Results: In the 16-week prevention model, obesity, liver index, lobular inflammation, steatosis pattern, and fibrosis were observed. At the end of 16 weeks, WD mice exhibited significant liver index, lobular inflammation, steatosis pattern, and liver fibrosis. Treatment with 5-MTP significantly attenuated inflammation and fibrosis at 16 weeks but had no effect on liver index and steatosis. Additionally, the fibrosis and inflammation conditions were similar between control and WD + 5-MTP mice. In the latestage NASH mice, 5-MTP significantly reduced inflammation and fibrosis but did not affect steatosis and ballooning.

Conclusions: These findings suggest that 5-MTP may have a preventive and therapeutic effect on inflammation and fibrosis in NAFLD/NASH animal models. However, it may not have a preventive or therapeutic effect on lipid accumulation.

P.51

IMPACT OF COMORBIDITIES ON THE SEROLOGICAL RESPONSE TO COVID-19 VACCINATION

Chung-Feng Huang, Tyng-Yuan Jang, Chih-Wen Wang, Ming-Lun Yeh, Po-Yao Hsu, Po-Cheng Liang, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Ming-Lung Yu

Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

共病對新冠肺炎疫苗抗體反應的影響

黃釧峰 張庭遠 王志文 葉明倫 許博堯 梁博程 戴嘉言 黃志富 莊萬龍 余明隆 高雄醫學大學附設醫院肝膽胰內科

Background: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive.

Aims: The study aims to explore the impact of comorbidities on the serological response to COVID-19 vaccination.

Methods: Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities.

Results: A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0-1, 2-3 and >4 were 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ-AZ-Moderna (39.2%), followed by Moderna-Moderna-Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/ mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity (IgG level ≥4160 AU/mL) included an age ≥60 years (odds ratio [OR]/95% confidence interval [CI], 0.49/0.34–0.72; P < 0.001), female gender (OR/

CI, 1.78/1.26–2.53; P = 0.001), Moderna-based vaccination (compared to AZ-based vaccination; OR/ CI, 6.49/3.90–10.82; P < 0.001) and a CCI score ≥4 (OR/ CI, 0.55/0.35–0.85; P = 0.01). There was a decreasing trend in antibody titers with increasing CCI scores (trend P< 0.001). Linear regression analysis revealed that AZ-based vaccination (β: 0.341, CI: 0.144, 0.21, P < 0.001) and higher CCI scores (β: -0.055, CI: -0.096, -0.014, P = 0.009) independently correlated with low IgG spike antibody levels.

Conclusions: Subjects with more comorbidities had a poor serological response to 3 doses of COVID-19 vaccination.

Section: GI

P.52

SYSTEMATIC REVIEW AND METAANALYSIS: THE EFFICACY AND SAFETY OF RADIOFREQUENCY ABLATION FOR EARLY SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL NEOPLASIA

Hsu-En Cheng1, Chung-Wang Ko1,2, Chung-hsin Chang1,2, Sheng-Shun Yang1,2, Sz-Iuan Shiu1,2

1Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

射頻消融療法對於食道早期鱗狀上皮細 胞癌的治療效果和安全性：系統性文獻 回顧和統合分析

鄭旭恩1 柯忠旺1,2 張崇信1,2 楊勝舜1,2 許斯淵1,2

1 臺中榮民總醫院內科部

2 臺中榮民總醫院肝膽胃腸科

Background: Esophageal squamous cell neoplasia (ESCN) is predominant in Asia, accounting for more than 90% of esophageal cancers. The prognosis of early superficial ESCN is generally good if treated promptly. Endoscopic mucosal resection and endoscopic submucosal dissection (ESD) have been recommended worldwide, but the application of endoscopic radiofrequency ablation (RFA) for early superficial ESCN remains inconclusive.

Aims: Our focus was on the 12-months histological complete response (CR), 3-months histological CR, acute and late postoperative adverse events (AEs) including bleeding, laceration, perforation, and stricture at follow-up periods.

Methods: We conducted a meta-analysis to inspect the effectiveness of RFA for early superficial ESCN. Three major bibliographic databases were reviewed for enrollment of case series and cohort trials prior to January 27, 2023. We included adults with early superficial ESCN receiving endoscopic RFA or ESD followed by RFA if available.

Results: Eight studies were enrolled for qualitative synthesis of narrative review and seven trials involved a total of 342 participants for analysis. The pooled 12-months and 3-months histological CR were 0.83 (95% CI, 0.59-0.94, I2 = 80%) and 0.74 (95% CI, 0.67-

0.80, I2 = 0%) respectively. As for safety, the acute and late postoperative AEs were 0.11 (95% CI, 0.05-0.26, I2 = 68%) and 0.19 (95% CI, 0.14-0.26, I2 = 0%) separately. In subgroup analysis the incidence of bleeding, laceration, and perforation after endoscopic RFA showed 0.06, 0.06, and 0.02 respectively. When compared with ESD, RFA showed lower 12-months CR (RR 0.57, 95% CI: 0.06-5.51, p = 0.63), lower acute AEs (RR 0.60, 95% CI: 0.08-4.58, p = 0.62) and higher late AEs (RR 1.67, 95% CI: 0.16-17.67, p = 0.67) without significance.

Conclusions: For early superficial ESCN, endoscopic RFA achieved both higher 12-months complete remission and late complication postoperatively while the stricture was encountered most commonly, followed by bleeding/laceration, and perforation. The choice between endoscopic RFA and ESD remains inconclusive.

P.53

GENDER AND THE CHARLSON COMORBIDITY INDEX ARE THE RISK FACTORS OF ERADICATION FAILURE AND NONADHERENCE TREATED BY SEQUENTIAL THERAPY AS THE FIRST-LINE ANTI-H. PYLORI TREATMENT IN REAL-WORLD PRACTICE

Chun-Te Lee1, Ming-Tsung Hsieh1, Wei-Lun Chang1,2, Bor-Shyang Sheu1,2, Hsiu-Chi Cheng1,2,3,4

1Department of Internal Medicine, National Cheng Kung University, Tainan, Taiwan

2Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan

4Institute of Molecular Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan

5Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan

真實世界中，女性及查爾森共病症指標 為影響系列性治療作為第一線幽門桿菌 除菌治療效果之風險因子

李俊德1 謝名宗1 張維倫1,2 許博翔1,2 鄭修琦1,2,3,4

1 國立成功大學醫學院附設醫院內科部

2 國立成功大學臨床醫學研究所

4 國立成功大學分子醫學研究所

5 衛生福利部臺南醫院內科部

Background: Eradication rates of sequential therapy were high in clinical trials; however, adherence for follow-up or patient population in the real-world setting might be different.

Aims: This study aimed to investigate the effectiveness of sequential therapy in the real world and the factors of treatment failure.

Methods: This retrospective study was conducted to review patients receiving sequential therapy for first-line anti-H. pylori treatment in a real-world setting. The Charlson Comorbidity Index and baseline variety of medications were reviewed to investigate factors correlating to H. pylori eradication failure and nonadherence for post-treatment testing.

Results: A total of 1053 patients were reviewed and 579 receiving sequential therapy were eligible for

analyses. Among them, 462 received post-treatment testing and were divided into the follow-up group. Thus, the post-treatment testing rate was 79.8%. Stroke was an independent factor of nonadherence for post-treatment testing. In the follow-up group, the eradication failure rate was 8.2%. Female sex (OR: 2.43 [95% CI: 1.18–5.04], P = 0.017) and Charlson indexes ≥2 (OR: 3.27 [1.09–9.79], P = 0.034) were two indenpendent factors of H. pylori eradication failure. The eradication failure rates were 14.4%, 7.8%, 7.1%, and 3.1% in the females with Charlson indexes ≥2, females with Charlson indexes <2, males with Charlson indexes ≥2, and males with Charlson indexes <2 subgroups, respectively (P = 0.027).

Conclusions: In the real-world setting, the adherence rate of post-treatment testing by sequential therapy for first-line anti-H. pylori treatment was suboptimal. Female sex and Charlson indexes ≥2 were two independent factors of eradication failure.

P.54

SCREENING AND SURVEILLANCE OF ESOPHAGEAL CANCER BY MAGNIFYING ENDOSCOPY WITH NARROW BAND IMAGING IMPROVES THE SURVIVAL OF HYPOPHARYNGEAL

CANCER PATIENTS

Hung-Yi Lin1, Chen-Shuan Chung1,2, Chia-Yun Wu3,4, Wu-Chia Lo3,5, Li-Jen Liao3,5,6

1Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei City, Taiwan

2College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

3Department of Oncology and Hematology, Far Eastern Memorial Hospital, New Taipei City, Taiwan

4Head and Neck Cancer Surveillance & Research Group, Far Eastern Memorial Hospital, New Taipei City, Taiwan

5Department of Otolaryngology, Far Eastern Memorial Hospital, New Taipei City, Taiwan

6Department of Electrical Engineering, Yuan Ze University, Taoyuan, Taiwan

藉由窄頻光波內視鏡檢查篩檢及監測食 道癌提高下咽癌患者的生存率

林宏益1 鍾承軒1,2 吳佳芸3,4 羅武嘉3,5 廖立人3,5,6

1 亞東紀念醫院肝膽腸胃科

2 天主教輔仁大學醫學院

3 亞東紀念醫院腫瘤科暨血液科

4 亞東紀念醫院頭頸癌監測暨研究小組

5 亞東紀念醫院耳鼻喉科暨頭頸外科

6 元智大學電機工程學系

Background: Patients with head and neck cancer may develop a second primary neoplasm (SPN) of the esophagus due to field cancerization.

Aims: This study investigated the impacts of esophageal cancer screening using magnifying endoscopy with narrow-band imaging (ME-NBI) on the outcomes of hypopharyngeal cancer patients.

Methods: Patients with hypopharyngeal cancer diagnosed from 2008 to 2021 in atertiary hospital were reviewed retrospectively. Screening and surveillance using ME-NBI examination of the esophagus were divided into three patterns: (1) ME-NBI never

performed or more than 6 months after diagnosis of index primary hypopharyngeal cancer, (2) ME-NBI within 6 months only, and (3) ME-NBI within 6 months and regular surveillance.

Results: A total of 261 were reviewed and 21 (8%) patients were in stage I, 20 (8%) in stage II, 27 (10%) in stage III, 116 (44%) in stage IVA, 65 (25%) in stage IVB, and 12 (5%) in stage IVC. Sixty-seven (26%) patients had SPN (50 esophagus, 10 oral cavity, 3 oropharynx, 2 nasopharynx, 1 larynx and 1 lung). Among esophageal SPN, 35 (70%) and 15 (30%) patients developed synchronous and metachronous neoplasia, respectively. In multivariate Cox regression analysis, advanced stages III and IV (compared with stages I and II, HR: 1.86, 1.18-2.95, p = 0.008), MENBI examination of the esophagus received within 6 months and regular surveillance (HR: 0.53, 0.360.78, p = 0.001) were independent factors affecting the overall survival of patients with hypopharyngeal cancer.

Conclusions: Our findings demonstrated that screening and surveillance of esophageal SPN by ME-NBI improves the survival of patients with hypopharyngeal cancer.

P.55

C-REACTIVE PROTEIN (CRP) IN PREDICTING MORTALITY AMONG PATIENTS FOR PERCUTANEOUS ENDOSCOPIC GASTROSTOMY (PEG) TUBE INSERTION: A RETROSPECTIVE COHORT STUDY

Gillie Anne D. Domingo, Gerardo Pedregosa

Department of Medicine - Section of Gastroenterology Makati Medical Center, Maynila, Philippines

Background: Gastroenterologists receive referrals for Percutaneous endoscopic gastrostomy (PEG) tube insertion in patients with conditions like stroke, dementia, or cancer who cannot maintain sufficient oral intake for over a month. Despite being a minimally invasive and relatively safe procedure, mortality rates post-PEG range from 3.3% to 23.9%. C-reactive protein (CRP), a marker of inflammation, has been considered as a predictor of mortality, with levels typically ranging from 0.5 to 0.7 mg/dL. Requiring patients to wait until CRP normalizes and then readmitting them for the procedure adds financial burden and delays plans to improve enteral nutrition.

Aims: Currently, there is still a demand for a rapid, efficient, affordable, and readily available marker that can predict mortality in patients undergoing PEG insertion. The objective of this study is to investigate whether elevated CRP levels can assist endoscopists in making decisions regarding the procedure, even if the patient has received clearances from other medical specialties.

Methods: This retrospective cohort study took place in a single center (Makati Medical Center) and included adult patients aged 18 years and older who underwent PEG insertion between January 2020 and June 2023. Out of the total 366 patients who underwent the procedure, 273 were excluded from the analysis. CRP values of patients within one week prior to PEG insertion were reviewed and categorized as normal or elevated (>0.5 mg/dL). The thresholds for categorization were defined as two times the upper limit of normal (up to 1 mg/dL), three times the upper limit of normal (up to 1.5 mg/dL), and four times the upper limit of normal (2 mg/dL and above).

Results: Among the 93 eligible patients, 7 (7.5%) died within 1 month post-procedure. Of these deceased patients, the majority (57%) had CRP values four times higher than the upper limit of normal. Additionally, 79% of the surviving patients had elevated CRP levels,

with 71% of them having CRP values as high as four times the upper limit of normal.

Conclusions: There was no significant association between CRP levels and 30-day mortality following PEG, which challenges the belief that CRP serves as a prognostic marker. Further research is warranted to explore alternative biomarkers or risk factors that may better predict patient outcomes post PEG.

P.56

DECODING HEREDITARY COLORECTAL CANCER: A CANCER REGISTRY DATABASE ANALYSIS USING THE GAPC CRITERIA

Yu-Min Lin1,4, Lee-Won Chong1,4, Wei-Mei Chen2, Tsung-I Hung3, Cheuk-Kay Sun1,4, Kou-Ching Yang1

1Department of Gastroenterology and Hepatology, Shin Kong Wu Ho‐Su Memorial Hospital, Taipei, Taiwan

2Cancer Prevention and Management Center, Shin Kong Wu Ho‐Su Memorial Hospital, Taipei, Taiwan

3Department of General Surgery, Shin Kong Wu Ho‐Su Memorial Hospital, Taipei, Taiwan

4School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

解碼遺傳性大腸癌：利用「 G-APC 」準 則，進行癌登資料庫分析

林裕民1,4 張麗文1,4 陳㻰玫2 洪宗義3 孫灼基1,4 楊國卿1

1 新光吳火獅紀念醫院胃腸肝膽科

2 新光吳火獅紀念醫院癌症防治中心

3 新光吳火獅紀念醫院一般外科

4 天主教輔仁大學醫學系

Background: Identifying hereditary colorectal cancer (HCRC) can feel like looking for a needle in a haystack due to the extensive data, complex genetic interactions, and variable clinical presentations involved. Despite the challenges, advanced data analysis and genetic understanding can aid in effectively pinpointing HCRC cases.

Aims: The aim would be to investigate the feasibility and effectiveness of using cancer registry databases for tracking and identifying cases of Lynch syndrome. Methods: Data was compiled from the “Cancer Registry Database” of a single medical center with the goal of identifying potential Lynch Syndrome probands. The “G-APC” (Genetic, Age, Period, Cohort) criteria guided our selection process, requiring candidates to exhibit Microsatellite Instability-high (MSI-high) status (G), and meet one or more of the following conditions: A: Age under 50, P: Diagnosed with tumors associated with Lynch syndrome either simultaneously (synchronous) or at different times (metachronous), C: Clustered from the same birthplace, demonstrating a higher proportion

compared to those with MSI-low status. The Chi-square test was utilized to establish statistical significance, with a p-value of less than 0.05 considered significant. Individuals identified as potential candidates were then referred to a multidisciplinary cancer team for further diagnostic confirmation.

Results: Between 2015 and 2022, we recorded a total of 1365 CRC cases in our database. MSI testing was conducted on 461 of these patients, with 51 (11.1%) exhibiting MSI-high status. Compared to MSIlow individuals, of the 51 MSI-high patients, 11 were under 50 years of age (p < 0.05). Two patients had synchronous cancers, and 9 were clustered from the same registered birthplace at a higher proportion (p < 0.05). The identified patients were then referred to the multidisciplinary cancer team for further evaluation. Following a thorough examination, two of these patients were conclusively diagnosed with Lynch syndrome.

Conclusions: Our study highlights the potential of utilizing data from a “Cancer Registry Database” in identifying potential probands of Lynch syndrome. The criteria we used, termed G-APC (Genetic, Age, Period, Cohort), proved effective in singling out potential candidates from a pool of 1365 registered CRC cases. Further refinement of selection criteria and enhancements in genetic testing could improve identification and management of Lynch syndrome in the future.

P.57

EARLY DOUBLE-BALLOON ENTEROSCOPY WAS NOT RELATED TO BETTER CLINICAL OUTCOMES IN PATIENTS

WITH SUSPECTED OVERT SMALL BOWEL BLEEDING

Yong-Cheng Ye1,2,4, Kuan-Yi Sung1,2,4, Tien-En Chang1,2,4, Pei-Shan Wu1,2,4, Yen-Po Wang1,2,3,4, Ming-Chih Hou1,2,4, Ching-Liang Lu1,2,3,4

1Endoscopy Center for Diagnosis and Treatment, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

3Institute of Brain Science, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

4Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

在疑似明顯小腸出血的病人早期雙氣囊 小腸鏡與較好的臨床結果無關

葉勇呈1,2,4 宋寬益1,2,4 張天恩1,2,4 吳佩珊1,2,4 王彥博1,2,3,4 侯明志1,2,4 盧俊良1,2,3,4

1 臺北榮民總醫院內視鏡診斷與治療中心

2 臺北榮民總醫院胃腸肝膽科

3 國立陽明大學腦科學研究所

4 國立陽明大學醫學系

Background: Device-assisted balloon enteroscopy has been used for over 20 years for the management of patients with suspected small bowel bleeding. Unlike esophagogastroduodenoscopy and colonoscopy, the appropriate timing of enteroscopy is still unknown. In recent guidelines, early enteroscopy is suggested to maximize diagnostic yield and therapeutic yield in patients with suspected small bowel bleeding. However, few studies have identified its influence on clinical outcomes, including mortality or rebleeding rate.

Aims: This study is aimed to evaluate the influence of the timing of double-balloon enteroscopy on clinical outcomes in patients with suspected small bowel bleeding.

Methods: Data on patients with overt small bowel bleeding who underwent double-balloon

enteroscopy from January 2013 to February 2021 were retrospectively reviewed. Patients were categorized into an early enteroscopy group (≤14 days) and a nonearly enteroscopy group (>14 days). Clinical outcomes, including short-term mortality and rebleeding rate, long-term mortality and rebleeding rate, diagnostic yield and therapeutic yield, were analyzed.

Results: A total of 100 patients (mean age, 66.2 years; 53% male) were included, and 44 patients were stratified into the early enteroscopy group. The diagnostic yield, therapeutic yield, mortality, and rebleeding rate were similar between the two groups. In multivariate conditional logistic regression analysis, there were no significant differences between the two groups regarding the 30-day rebleeding rate (adjusted odds ratio [aOR], 1.28; 95% CI, 0.44-3.75), 90-day rebleeding rate (aOR, 1.03; 95% CI, 0.42-2.49), 30-day mortality rate (aOR, 1.33; 95% CI, 0.21-8.6), 90day mortality rate (aOR, 1.88; 95% CI, 0.46-7.59) and 90-day bleeding-related mortality (aOR, 2.15; 95% CI, 0.25-18.13). The Kaplan-Meier survival curve analysis showed that the timing of DBE was not associated with the long-term rebleeding rate or mortality rate (p = 0.57 and 0.83, respectively).

Conclusions: The timing of enteroscopy did not influence the clinical outcomes, including the shortterm mortality rate, short-term rebleeding rate, longterm mortality rate and rebleeding rate, in patients with suspected overt small bowel bleeding.

P.58

THE CLINICAL PRESENTATIONS OF LIVER ABSCESS DEVELOPMENT AFTER ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATICOGRAPHY WITH CHOLEDOCHOLITHIASIS: A 17-YEAR FOLLOW-UP

An-Che Liu, Wei-Chen Tai, Shao-Ming Chiu, Fai-Meng Sou, Shih-Cheng Yang, Lung-Sheng Lu, Chung-Mou Kuo, Yi-Chun Chiu, Seng-Kee Chuah, Chih-Ming Liang, Cheng-Kun Wu

Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

內視鏡逆行性膽胰攝影治療膽管結石術 後引發肝膿瘍患者的臨床表現： 17 年追 蹤研究

劉安哲 戴維震 邱紹銘 蘇輝明 楊世正 盧龍生 郭仲謀 邱逸群 蔡成枝 梁志明 吳鎮琨

長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系 暨長庚大學醫學系

Background: ERCP, used for choledocholithiasis treatment, carries a risk of pyogenic liver abscess (PLA) due to communication between the biliary system and bowel contents. However, limited data exists on this issue.

Aims: We aim to investigate the clinical presentations of liver abscess after ERCP for treatment of Choledocholithias.

Methods: We conducted a retrospective case series across multiple centers to evaluate patients who developed PLA after ERCP for choledocholithiasis. Data was obtained from the Chang Gung Research Database (January 2001 to December 2018). Out of 220 enrolled patients, 195 were categorized in the endoscopic sphincterotomy (ES) group, while 25 were in the non-ES group for further analysis.

Results: The non-ES group had significantly higher total bilirubin levels compared to the ES group (4.3 ± 5.8 vs. 1.9 ± 2.0, p < 0.001). Abscess size, location, and distribution (single or multiple) were similar between the two groups. The most common pathogens were Klebsiella pneumoniae and Escherichia coli. Pseudomonas infection was significantly less

prevalent in the ES group compared to the nonES group (3.6% vs. 16.7%, p = 0.007). Patients with concurrent malignancies (HR: 9.529, 95% CI: 2.66734.048, p = 0.001), elevated total bilirubin levels (HR: 1.246, 95% CI: 1.062-1.461, p = 0.007), multiple abscess lesions (HR: 5.146, 95% CI: 1.777-14.903, p = 0.003), and growth of enterococcus pathogens (HR: 4.518, 95% CI: 1.290-15.823, p = 0.001) faced a significantly higher risk of in-hospital mortality.

Conclusions: PLA incidence was higher in the ES group compared to the non-ES group following ERCP for choledocholithiasis. Attention should be given to significant risk factors, including concurrent malignancies, elevated total bilirubin levels, multiple abscess lesions, and growth of enterococcus pathogens, to reduce in-hospital mortality.

P.59

CAN THE HEALTH BELIEF MODEL EXPLAIN LOW COLORECTAL CANCER SCREENING UPTAKE IN SINGAPOREAN MALAYS? A CROSSSECTIONAL STUDY

Jarrod KH Tan1, Jing Yu Ng1, Norman S Lin1, Jerrald Lau2,3, Gretel JL Wong2, Ker-Kan Tan1,2,3

1Division of Colorectal Surgery, Department of Surgery, National University Health System, Singapore

2Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

3Saw Swee Hock School of Public Health, National University of Singapore, Singapore

Background: Singapore has a national colorectal cancer (CRC) screening programme, but uptake rates are low and vary across ethnicities (27.4% Chinese, 24.8% Indians, 10.1% Malays). Ethnic cultural differences impact one’s health beliefs, which in turn influence intention to screen, but few Asian studies have explored these differences.

Aims: This cross-sectional study aimed to uncover ethnic differences in CRC screening in Singapore using the health belief model (HBM).

Methods: Average-risk individuals without CRC were recruited from a public primary care institution from January 2020 – February 2023, with purposive sampling of ethnic minorities. A locally validated questionnaire with the 5 HBM constructs was administered. Participants’ CRC screening intention was the outcome of interest.

Results: 531 participants (median age 55 years, range 45–65 years) were recruited; there were 252 (47.5%) Chinese, 146 (27.5%) Malays, and 133 (25.0%) Indians. Chinese (OR = 1.21, 95% CI: 1.02–1.43) and Indians (OR = 1.36, 95% CI: 1.05–1.75) who intended to screen were more likely to have received cues to action. Perceived susceptibility was only significantly associated with intention to screen in Chinese (OR = 1.53, 95% CI: 1.09–2.14) while perceived severity was only significant for Indians (OR = 1.40, 95% CI: 1.07–1.85). Scores for perceived barriers were highest for Malays, but none of the HBM scales significantly associated with screening intention.

Conclusions: HBM was associated with CRC screening intention, but different constructs are more pertinent across ethnicities. Health promotion campaigns

should continue to be underpinned by behavioural health theoretical bases but must also consider more culturally sensitive approaches. Future studies should employ qualitative methods to explore other sociocultural and religious determinants of CRC screening in the Malay community.

P.60

CAN THE HEALTH BELIEF MODEL EXPLAIN LOW COLORECTAL CANCER SCREENING UPTAKE IN SINGAPOREAN MALAYS? A CROSSSECTIONAL STUDY

Jarrod KH Tan1, Jing Yu Ng1, Norman S Lin1, Jerrald Lau2,3, Gretel JL Wong2, Ker-Kan Tan1,2,3

1Division of Colorectal Surgery, Department of Surgery, National University Health System, Singapore

2Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore

3Saw Swee Hock School of Public Health, National University of Singapore, Singapore

Background: Singapore has a national colorectal cancer (CRC) screening programme, but uptake rates are low and vary across ethnicities (27.4% Chinese, 24.8% Indians, 10.1% Malays). Ethnic cultural differences impact one’s health beliefs, which in turn influence intention to screen, but few Asian studies have explored these differences.

Aims: This cross-sectional study aimed to uncover ethnic differences in CRC screening in Singapore using the health belief model (HBM).

Methods: Average-risk individuals without CRC were recruited from a public primary care institution from January 2020 – February 2023, with purposive sampling of ethnic minorities. A locally validated questionnaire with the 5 HBM constructs was administered. Participants’ CRC screening intention was the outcome of interest.

Results: 531 participants (median age 55 years, range 45–65 years) were recruited; there were 252 (47.5%) Chinese, 146 (27.5%) Malays, and 133 (25.0%) Indians. Chinese (OR = 1.21, 95% CI: 1.02–1.43) and Indians (OR = 1.36, 95% CI: 1.05–1.75) who intended to screen were more likely to have received cues to action. Perceived susceptibility was only significantly associated with intention to screen in Chinese (OR = 1.53, 95% CI: 1.09–2.14) while perceived severity was only significant for Indians (OR = 1.40, 95% CI: 1.07–1.85). Scores for perceived barriers were highest for Malays, but none of the HBM scales significantly associated with screening intention.

Conclusions: HBM was associated with CRC screening intention, but different constructs are more pertinent across ethnicities. Health promotion campaigns

should continue to be underpinned by behavioural health theoretical bases but must also consider more culturally sensitive approaches. Future studies should employ qualitative methods to explore other sociocultural and religious determinants of CRC screening in the Malay community.

P.61

THE EFFECT OF ANTI-REFLUX MUCOSAL ABLATION ON LOWER ESOPHAGEAL SPHINCTER PRESSURE: A RETROSPECTIVE STUDY

Tung-Lung Wu1, Kun-Ching Chou1, Hsu-Heng Yen1,2

1Department of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan

2College of Medicine, National Chung Hsing University, Taichung, Taiwan

抗胃食道逆流黏膜灼燒術與下食道括約 肌壓力之影響：一個回顧性研究

吳東龍1 周昆慶1 顏旭亨1,2

1 彰化基督教醫院胃腸肝膽科

2 國立中興大學醫學院

Background: Esophageal reflux is a common condition that affects many individuals. Anti-reflux mucosal ablation (ARMA) is an endoscopic procedure that shows promise in treating gastroesophageal reflux disease (GERD). However, research on the relationship between high-resolution esophageal manometry and the effectiveness of ARMA is limited. Aims: to relaize the effect of ARMA and LES pressure change.

Methods: We conducted a retrospective study of 5 cases who received ARMA therapy between June 2022 and June 2023. These cases had refractory acid reflux and had undergone at least 8 weeks of PPI therapy. Manometry studies were performed before and after ARMA therapy.

Results: The differences between pre-ARMA and postARMA LES pressure were -7.9 mmHg, -1.3 mmHg, 13.1 mmHg, and 3.6 mmHg. LES pressure increased by less than 10 mmHg before ARMA in some cases. In other cases, LES pressure was higher than 10 mmHg before ARMA and decreased after ARMA treatment.

Conclusions: The ARMA procedure can affect LES pressure before and after treatment. In particular, LES pressure less than 10 mmHg may increase after ARMA treatment. Although our results show changes in LES pressure after ARMA treatment, our sample size is small. Further studies with more cases are needed.

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OUTCOMES OF THE PADLOCK PROCEDURE FOR RESECTION OF GASTRIC SUBMUCOSAL TUMORS: A PRELIMINARY ANALYSIS

Chun-Chung Lu, Wen-Chun Yeh, Chia-Jen Hsiao, Hong-Yun Chen

Division of Gastroenterology and Hepatology, Department of Internal Medicine, New Taipei City Hospital, Taipei, Taiwan

PADLOCK 手術治療胃黏膜下腫瘤的結 果：初步分析

盧俊仲 葉文俊 蕭家仁 陳鴻運 新北市立聯合醫院肝膽腸胃科

Background: The increased use of endoscopic examinations and the availability of advanced endoscopic equipment have led to an increased detection rate of gastric or duodenal subepithelial tumors (SETs) smaller than 2 cm in size in recent years. EUS may not always be able to differentiate between a Gastrointestinal Stromal Tumor (GIST) and a leiomyoma or schwannoma. Due to the low risk of disease progression, surveillance endoscopy is recommended. However, patient compliance with this recommendation is often low. Besides regardless of size, if a SET in the stomach or duodenum is identified as a gastrointestinal stromal tumor (GIST), there is a possibility that these tumors may undergo malignant transformation in the future.

Aims: Various endoscopic resection techniques have been proposed for managing small subepithelial tumors in the stomach or duodenum. However, these techniques often present technical challenges and carry a significant risk of perforation. The objective of our study is to assess the effectiveness of over-thescope padlock clip closure in the treatment of these lesions.

Methods: We extracted data on gastric or duodenal SETs smaller than 2 cm, which were resected using over-the-scope padlock clip closure, from New Taipei City Hospital between 2021 and 2023. The rate of complete resection and the incidence of complications were evaluated.

Results: These results provide an overview of the patients who underwent PADLOCK procedure for the resection of gastric submucosal tumors. The majority of the tumors were leiomyomas, and the procedure was successful without any reported intraoperative

complications. Further long-term follow-up and analysis are necessary to evaluate the effectiveness and outcomes of the PADLOCK procedure in these patients.

Conclusions: These preliminary findings support the potential efficacy and safety of the PADLOCK procedure for the resection of gastric submucosal tumors. Further research with a larger sample size and long-term follow-up is warranted to validate these findings and assess the long-term outcomes and recurrence rates associated with the PADLOCK procedure.

P.63

THE IMPACT OF PRACTICE AND EQUIPMENT ON THE EFFICIENCY AND EFFICACY OF SINGLEBALLOON ENTEROSCOPY

Chi-Yu Lee1, Wei-Chen Lin1,2,3, Horng-Yuan Wang1,2,3,4, Ching-Wei Chang1,2,3, Ming-Jen Chen1,2,3,4, Chen-Wang Chang1,2,3,4

1Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan

2MacKay Medicine, Nursing and Management College, Taipei, Taiwan

3Department of Medicine, MacKay Medical College, New Taipei, Taiwan

4Taiwan Association for the Study of Small Intestinal Diseases (TASSID)

臨床操作和儀器設備在單氣囊小腸鏡效 率和療效上的影響

李騏宇1 林煒晟1,2,3 王鴻源1,2,3,4 張經緯1,2,3 陳銘仁1,2,3,4 章振旺1,2,3,4

1 台灣基督長老教會馬偕醫療財團法人馬偕紀念醫院 胃腸肝膽科

2 馬偕醫護管理專科學校

3 馬偕醫學院

4 台灣小腸醫學會

Background: In recent years, deep enteroscopy, including double balloon enteroscopy, single balloon enteroscopy (SBE), or spiral enteroscopy, has revolutionized the diagnosis and management of small intestinal disease. These procedures are extremely valuable, but may be technically challenging to perform. The efficiency and efficacy of SBE may be related to practice and device, but the learning curve for SBE has not yet been described. Few studies have discussed the association between the efficacy and efficacy of SBE and more practices and appropriate equipment.

Aims: To investigate whether the efficiency and efficacy of SBE increase with increased practice and the availability of appropriate equipment.

Methods: We performed a retrospective analysis of all patients with suspected of small bowel diseases, who underwent SBE at MacKay Memorial Hospital, a tertiary medical center in Taiwan, from November 2008 to April 2023. All procedures were performed by one experienced gastroenterologist. We used a

cap for mucosal hooking and CO2 as insufflation gas during SBE since 2019. The patients were divided into 3 groups (group A: 2008-2012, group B: 20132017, group C: 2018-2023) based on different period. We compared the diagnostic yield, therapeutics yield, depth of insertion, procedure time, complete enteroscopy rate and complication rate among 3 groups.

Results: We totally performed SBE for 619 times in a total of 438 patients with suspected small bowel disease. The diagnostic yield and therapeutics yield increased over time (diagnostic yield: group A: 67%, group B: 68.4%, group C: 71.4%, p = 0.706; therapeutic yield: group A: 24.5%, group B: 44.1%, group C: 77.1%, p < 0.001). There was no significant difference in mean depth of insertion among 3 groups, but insertion time declined significantly, whether in the anterograde SBE or retrograde SBE (anterograde SBE: group A: 86.3 minutes, group B: 59.6 minutes, group C: 54.8 minutes, p < 0.001; retrograde SBE: group A: 92.2 minutes, group B: 73.1 minutes, group C: 64.3 minutes, p < 0.001). The complete enteroscopy rate increased over time but there was no significant difference among 3 groups (group A: 45.5%, group B: 74.0%, group C: 82.1%, p = 0.203). The complication rate decreased significantly (group A: 6.4%, group B: 0.7%, group C: 0%, p < 0.001) over time. All cases made recovery after conservative treatment.

Conclusions: The diagnostic yield, therapeutic yield, depth of insertion, and complete enteroscopy rate increased over time, while insertion time and complication rate decreased. These findings suggest that increased training, more practices, and the use of appropriate equipment may improve the efficacy and efficiency of SBE.

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THE ASSOCIATION BETWEEN COMORBIDITIES INCIDENCE, BIOCHEMISTRY PROFILE, AND BARIATRIC SURGERY: A POPULATION-BASED, CASE CONTROL STUDY

Pei-Huan Ho1, Wey-Ran Lin1,2,3

1Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

2Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

3College of Medicine, Chang Gung University, Taoyuan, Taiwan

病例對照研究：減重手術與胃腸道症狀

及生化因子之關係

何沛桓1 林蔚然1,2,3

1 林口長庚紀念醫院胃腸肝膽科系

2 林口長庚紀念醫院肝臟研究中心

3 長庚大學醫學系

Background: The rate of obesity, associated with many comorbidities, keeps growing in recent years. In Taiwan, obesity accounted for 47.9% of the adult population, which cause a great burden to the health system. Bariatric surgery was an appropriate treatment for morbid obesity, and several metabolic improvements were reported after the procedure. Though, few research was conducted in Taiwan.

Aims: We aimed to analyze the comorbidities incidence and biochemistry profile of the patients undergo bariatric surgery or not.

Methods: A retrospective case-control study of 76,552 cases of morbid obesity, based on the Chang Gung Research Database from 2002 to 2019 was performed. These cases were classified into two groups, undergo bariatric surgery or not. The comorbidities incidence and biochemistry profile were followed for 1 year, 2 year and 3 years, respectively.

Results: Our study suggests that bariatric procedures can reduce the incidence of functional gastrointestinal disorder (OR: 0.50; 95% CI: 0.27-1.02), but they may increase the risk of gastrointestinal ulcer (OR: 2.04; 95% CI: 1.04-4.01) and gastrointestinal reflux disease (OR: 7.30; 95% CI: 4.54-11.75) during the first year of followup. The associations between bariatric procedures and gastrointestinal reflux disease (OR: 1.36 in 2nd

year; 1.25 in 3rd year) and gastrointestinal ulcer (OR: 4.48 in 2nd year, 3.83 in 3rd year) appear to decrease over time. In contrast, the decrease risk of functional GI disorder remains relatively stable over time (OR: 0.40 in 2nd year, 0.42 in 3rd year). No significant correlation between changes in BMI and the presence of gastrointestinal comorbidities was observed in the study. Decrease in BMI and blood pressure after the bariatric procedure were also observed. For the biochemistry profile, the group that underwent bariatric procedures demonstrated an enhancement in high-density lipoprotein (HDL) levels, a decrease in triglyceride levels, as well as improvements in fasting glucose, glycated hemoglobin, and glutamate pyruvate transaminase (ALT) levels, compared to the group that did not undergo the procedure. A trend towards lower levels of low-density lipoprotein (LDL) and total cholesterol was also observed. The most prominent metabolic improvements were observed in the first year following the bariatric procedures.

Conclusions: In this Asian population-based study, bariatric surgery increases the risk of ulcer and reflux disease but decrease the incidence of functional GI disorder. Besides, several metabolic improvements were observed after the bariatric procedures, with the most significant changes occurring within the first year after the procedure.

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INITIAL DIAGNOSIS RATE OF YOUNG DOCTORS IN INDEPENDENT EUSFNB FOLLOWING TRAINING: ONE SINGLE-CENTER EXPERIENCE

Bo-Yan Chen, Hsin-Yu Chen, Chi-Kun Chiang, Chih-Sheng Hung, Ting-Chun Huang

Division of Digestive Medicine, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan

內視鏡超音波細針穿刺切片在年輕醫師 開始獨立操作後的診斷成功率：單一醫

學中心經驗

陳柏諺 陳信佑 江技坤 洪志聖 黃鼎鈞 國泰綜合醫院消化內科

Background: The current recommendations propose a minimum requirement of 225-250 cases for EUS (Endoscopic Ultrasound) and 50-75 cases for EUS FNA/B (Endoscopic Ultrasound-Guided Fine Needle Aspiration/Biopsy). However, there is a paucity of data concerning the proficiency of young doctors in independently performing EUS-FNB (Endoscopic Ultrasound-Guided Fine Needle Biopsy) during their initial cases.

Aims: Our objective is to investigate the initial performance of young doctors in independently conducting EUS-FNB following completion of their training program. The primary outcome is the diagnosis rate.

Methods: We retrospectively collected the data for the period between August 2019 and May 2023. A definitive diagnosis of EUS-FNB was based on the following criteria:

1. positive cytologic or histologic diagnosis obtained by EUS-FNB for malignancy with a compatible clinical course; 2. negative FNB diagnosis of malignancy with no deterioration on imaging studies for a minimum clinical follow-up time of 3 months. The failed EUS-FNB diagnosis was defined as :1. Cytologic or histologic report told NONE MADE or no definite tissue obtained; 2. negative FNB diagnosis of malignancy but following surgical intervention yield malignancy.

Results: The study included 33 patients, with 28 having pancreatic lesions and 5 having extrapancreatic lesions. The participants consisted of 14 men and 19 women. The patients had a mean age of 62 years (range: 41-87 years), and the average tumor size was 3.7 cm (range: 1.3-10 cm) in diameter.

The pancreatic lesions included 9 cases in the head region, 1 case in the uncinate process, 1 case in the neck region, 9 cases in the body region, and 8 cases in the tail region. The extra-pancreatic lesions included 1 case of stomach subepithelial lesion (SEL), 1 case of esophageal SEL, 2 cases of lymph node, and 1 case involving the ampulla. The primary outcome in terms of overall diagnosis rate was approximately 72.7% (24/33 cases). Non-diagnostic cases were predominantly observed during the initial procedures. Specifically, the diagnosis rate was 53.3% (8/15 cases) in the first 15 cases, which increased to 88.9% (16/18 cases) in subsequent cases.

Conclusions: We may provide additional support to young doctors during their first 10-15 cases of EUSFNB to achieve a better diagnosis yield rate. More data is needed to draw a conclusion.

COMPARISON OF HYBRID THERAPY AND REVERSE HYBRID THERAPY IN THE FIRST-LINE TREATMENT OF HELICOBACTER PYLORI INFECTION

Chang-Bih Shie1,12, Ping-I Hsu1,12, Chih-An Shih2,12, Chien-Lin Chen3,12, Kuan-Yang Chen4,12, Seng-Kee Chuah5,12, Chia-Long Lee6,12, Feng-Woei Tsay7,12, Jyh-Chin Yang8,12, Yu-Hwa Liu9,12, Sz-Iuan Shiu10,12, Chao-Hung Kuo11,12, Hsi-Chang Lee4,12, Wei-Yi Lei3,12, Wei-Chen Tai5,12, Deng-Chyang Wu11,12

1Division of Gastroenterology, Department of Medicine, Tainan Municipal An Nan Hospital, China Medical University, Tainan, Taiwan; 2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Antai Medical Care Corporation, Antai TianSheng Memorial Hospital, Pingtung, Taiwan; 3Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan; 4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei City Hospital, Renai Branch, Taipei, Taiwan; 5Division of Hepatogastroenterology, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 6Division of Gastroenterology and Hepatology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan; 7Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 8Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 9Division of Gastroenterology, Department of Internal Medicine, Shin Kong Wu Huo-Shih Memorial Hospital, Taipei, Taiwan; 10Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 11Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 12Taiwan Acid-related Disease & Microbiota (TARD-M) Consortium

混合療法與反轉式混合療法在第一線幽

門螺旋桿菌除菌治療之比較

施長碧1,12 許秉毅1,12 石志安2,12 陳健麟3,12 陳冠仰4,12

蔡成枝5,12 李嘉龍6,12 蔡峯偉7,12 楊智欽8,12 劉玉華9,12

許斯淵10,12 郭昭宏11,12 李熹昌4,12 雷尉毅3,12 戴維震5,12

吳登強11,12

1 臺南市立安南醫院暨中國醫藥大學消化內科；2 東 港安泰醫院胃腸肝膽科；3 花蓮慈濟醫院肝膽胃腸 科；4 臺北市立聯合醫院仁愛院區消化內科；5 高雄 長庚紀念醫院胃腸肝膽科；6 國泰綜合醫院腸胃內 科；7 高雄榮民總醫院胃腸肝膽科；8 國立臺灣大學 醫學院附設醫院胃腸肝膽科；9 新光吳火獅紀念醫院 胃腸肝膽科；10 臺中榮民總醫院胃腸肝膽科；11 高雄 醫學大學附設醫院胃腸內科；12 台灣胃酸相關疾病 暨微菌叢聯盟

Background: Reverse hybrid therapy is a simplified hybrid treatment for Helicobacter pylori (H. pylori) infection. It achieves a higher eradication rate than standard triple therapy.

Aims: To compare the efficacies of reverse hybrid and hybrid therapies in the first-line treatment of H. pylori infection.

Methods: To compare the efficacies of reverse hybrid and hybrid therapies in the first-line treatment of H. pylori infection.

Results: The eradication rates of the reverse hybrid and hybrid therapies by intention-to-treat analysis were comparable (91.5% vs 92.2%; p = 0.713). Perprotocol analysis yielded similar results (94.3% vs 94.5%). There were no differences in the efficacy of eradication between therapies for clarithromycinsensitive strains (97.3% vs 96.6%) and clarithromycinresistant strains (80.4% vs 84.1%). In addition, there were comparable frequencies of adverse events (19.3% vs 26.7%) and drug adherence (97.5% vs 97.4%) between groups.

Conclusions: Reverse hybrid therapy can achieve a similar eradication rate to hybrid therapy for the firstline treatment of H. pylori infection.

SPARKLING WATER IMPROVE INEFFECTIVE ESOPHAGEAL MOTILITY, HIGH-RESOLUTION MANOMETRY STUDY

Kun-Ching Chou, Dong-Long Wu, Hsu-Heng Yen

Division of Gastroenterology, Department of Internal Medicine, Changhua Christian hospital, Changhua, Taiwan

氣泡水改善食道蠕動不良，高解析壓力 檢查研究

周昆慶 吳東龍 顏旭亨

彰化基督教醫院胃腸肝膽科

Background: About 30% of patients who received high-resolution manometry (HRM) examinations had ineffective esophageal motility (IEM). Because IEM affects the emptying of the esophagus, it is the pathophysiology of GERD. It is related to the severity of erosive esophagitis and Barrett’s esophagus. Chronic cough is also associated with poor esophageal motility. The first glass of artificial sparkling water in history is made by a British chemist, Joseph Priestley in 1767. In 1783, a Swiss jeweler, Jacob Schweppes, developed Schweppes sparkling water, mainly It was intended to treat stomach ailments and other infectious diseases at that time.

Aims: To evaluate the influence of sparkling water in IEM.

Methods: From 2021-12 to 2023-03 in Changhua Christian Hospital, a total of 139 patients underwent HRM study. 115 people had sparkling water as paste swallows. IEM diagnostic criteria: Normal median integrated relaxation pressure (IRP), with >70% ineffective swallows or ≥50% failed peristalsis. Supine position or upright position, either match is counted. Ineffective swallows are defined as failed peristalsis or weak contraction. Equipments and software MMS/ Laborie Solar GI High Resolution Manometry system, Laborie stationary measurement & analysis software, 36 pressure solid state HRM with 16 impedance channels.

Results: A total of 62 patients with IEM, male to female ratio is 50:50, age distribution 22-90 years old, average 50 years old. Acid reflux was the most common symptom, accounting for 82%. The second is foreign body sensation in the throat, accounting for 63%, followed by night symptoms in 48%, and cough

in 39%. Compare the data of drinking sparkling water, sparkling water prolongs distal latency (DL) (from 6.6 seconds to 7.4 seconds in supine position, and from 6.1 seconds to 6.6 seconds in upright position); it increases distal contractile integral (DCI) (from 466 to 487 in supine position, and from 163 to 271 in upright position); reduce peristaltic disturbance, especially in the upright position (≥50% failed peristalsis: supine position from 37% to 35%; upright position from 85% to 65%; >70% ineffective swallows: supine position from 42% to 40%; upright position from 94% to 69%); And improving the diagnosis of IEM (in the data of sparkling water, there are 12 patients no longer meet the diagnostic criteria of IEM, and the number of IEM has dropped from 62 to 50, improving by 19%). We divided patients into two groups: Reserved supine peristalsis and ineffective supine peristalsis. The improvement in the supine reserved group was even more obvious. The DCI increased from 190 to 320, the proportion of ≥50% failed peristalsis decreased from 81% to 56%, and the proportion of >70% ineffective swallows decreased from 94% to 63%. Number of IEM reduced from 32 to 22, improved by 31%.

Conclusions: Sparkling water prolongs DL, increases DCI, reduces ineffective peristalsis, and reverses the diagnosis of IEM by 19%. Sparkling water can be a method of treatment for IEM, especially for patients with reserved supine peristalsis.

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CLINICAL MANIFESTATIONS OF CERVICAL INLET PATCHES (CIP): A SINGLE ENDOSCOPIST OBSERVATION IN A COMMUNITY HOSPITAL

Yoen-Young Chuah1,2, Lian-Feng Lin1, Chia-Jung Kuo1, Seng-Howe Nguang1, Yi-Chun Chan1, Chung-Fong Lin1, Lin-Suei Jhang1

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ping Tung Christian Hospital, Pingtung, Taiwan

2Department of Nursing, Meiho University, Pingtung, Taiwan

食道入口斑的臨床表現：一個社區醫院 內視鏡醫師的臨床觀察

蔡元榮1,2 林連豐1 郭志榮1 阮盛豪1 詹益群1 林群峰1 張琳遂1

1 屏東基督教醫院胃腸肝膽科

2 美和科技大學護理系

Background: The cervical inlet patch (CIP) is an islet of heterotopic gastric mucosa, most commonly found in the upper esophagus just below the esophageal sphincter. The cause of CIP remains unclear. It might represent embryonic gastric tissue that did not convert into squamous tissue in the upper esophagus. The clinical manifestations in the Taiwanese population remain unknown, which leads to the investigation of the current study.

Aims: To investigate the baseline characteristics and clinical manifestations of cervical inlet patches by a single endoscopist in a community hospital.

Methods: Twenty-two patients from the outpatient department who were confirmed endoscopically to have cervical inlet patches by a single gastroenterologist were recruited from May 5, 2022, to June 30, 2023. The baseline characteristics, clinical symptoms, location and number of patches, and endoscopic findings were analyzed.

Results: A total of 22 patients from Ping Tung Christian Hospital were recruited in the observational study by a single endoscopist. Female gender was slightly predominant (55.5%, n = 12) with mean age of 53 years old (33-89). Majority of patients has reflux sensation or throat discomfort (36.4%, n = 8), epigastric pain (22.7%, n = 5) and dyspepsia (18.2%, n

= 4) were at second and third place respectively. The mean position of the patches at upper esophagus was at 17 cm from incisors (15-20 cm). Most of patient had only single patch (81.8%, n = 18). In addition of the cervical inlet patch, gastric or duodenal ulcers (45%, n = 10), gastroesophageal reflux (22.7%, n = 5) and gastritis or duodenitis (22.7%, n = 5) were the three most accompanied endoscopic findings in these patients.

Conclusions: Most of the cervical inlet patch patients have reflux sensation or throat discomfort as their major clinical manifestations, with gastric or duodenal ulcers as their most common finding endoscopically.

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THE EFFICACY OF JING SI HERBAL TEA IN ALLEVIATING PSYCHOPHYSICAL MANIFESTATIONS AND GUT METABOLITE IMBALANCES IN FUNCTIONAL DYSPEPSIA PATIENTS: A DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED TRIAL

Tsung-Ching Lee, Ming-Wun Wong, Jui-Sheng Hung, Tso-Tsai Liu, Chih-Hsun Yi, Wei-Yi Lei, Chien-Lin Chen

Division of Gastroenterology & Hepatology, Department of Internal Medicine, Hualien

Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

探討靜思本草飲在緩解功能性消化不良 患者生理心理性表徵和腸道代謝失衡方 面的功效：雙盲、隨機、安慰劑對照試 驗

李宗晉 翁銘彣 洪睿勝 劉作財 易志勳 雷尉毅 陳健麟 佛教慈濟醫療財團法人花蓮慈濟醫院肝膽腸胃科

Background: Functional dyspepsia (FD) is a globally widespread disorder characterized by meal-induced discomforts. The potential mechanisms underlying FD include gastrointestinal inflammation, mucosal anomalies, and alterations in the microbiota and their metabolites, particularly short-chain fatty acids (SCFAs), which play a crucial role. Current research indicates the potential efficacy of Traditional Chinese Medicine in alleviating the symptoms of FD. Jing Si Herbal Tea (JSHT), a concoction derived from eight different herbs, has demonstrated potential in mitigating inflammation, promoting endothelial integrity, and reducing associated depressive manifestations.

Aims: This research aims to investigate the efficacy of JSHT in mitigating the symptoms of FD, alleviating psychological distress, and inducing metabolite alterations.

Methods: This study included adult patients diagnosed with FD based on the Rome IV criteria. A comprehensive protocol was followed, involving extensive physical and psychological evaluations, pretreatment blood sampling, and random assignment to either JSHT concentrate or placebo groups in a double-blind manner for a period of four weeks. Upon

completion of the treatment, repeated assessments were performed, including Liquid ChromatographyMass Spectrometry (LC-MS) for gut bacterial metabolites. A successful response was determined by a 50% reduction in dyspeptic symptoms. Symptom severity, sleep quality, depression, anxiety, and stress were evaluated at every visit using validated questionnaires.

Results: The study incorporated 26 patients (mean age 51.6, 60.6% females). The baseline characteristics were similar for both the JSHT and placebo groups, which were assigned randomly. The JSHT treatment group demonstrated a significantly higher response rate (69.2%) than the placebo group (23.1%, P = 0.018). Following JSHT treatment, patients exhibited a significant reduction in the severity of upper GI symptoms and anxiety levels (PAGI-SYM: from 28.8 to 13.6, P = 0.001; STAI: from 40.9 to 35.1, P = 0.037). An elevation in serum butyrate levels was observed in patients who showed an improvement in symptoms (P = 0.043). Conversely, no significant alterations were noted in the placebo group pre- and post-treatment (P > 0.05).

Conclusions: The four-week treatment with JSHT improved dyspeptic symptoms and anxiety, possibly correlating with increased serum butyrate levels. These findings demonstrate the therapeutic potential of JSHT in the management of FD.

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DIAGNOSIS OF ESOPHAGEAL SUBEPITHELIAL LESIONS BY USING ENDOSCOPIC BIOPSY, A RETROSPECTIVE STUDY OF A REGIONAL TEACHING HOSPITAL IN SOUTHERN TAIWAN

Yu-Chieh Tsai1, Wen-Hsin Hsu1, Wei-Shing Chang1, Yu-Chou Tsai1, Chang-Che Wu2, Shih-Cheng Chou2, Meng-Shun Sun1

1Division of Gastroenterology, Department of Internal Medicin, Yuan’s General Hospital, Kaohsiung, Taiwan

2Department of Pathology, Yuan General Hospital, Kaohsiung, Taiwan

利用內視鏡切片來診斷食道黏膜下腫瘤

區域醫院之經驗

蔡雨潔1 許文欣1 張維興1 蔡毓洲1 吳長哲2 周士程2 孫盟舜1

1 阮綜合醫療社團法人阮綜合醫院肝膽胃腸科

2 阮綜合醫療社團法人阮綜合醫院病理科

Background: Endoscopic ultrasonography (EUS) is a diagnostic examination based on cross-sectional imaging, which is different from conventional endoscopy. Esophageal wall is detected as five-layer structure. Then, EUS has become possible to diagnose subepithelial lesions by evaluate the echogenic component and the originate layer. However, some SELs lesions with potential malignancy change mimic benign lesions. Biopsy is still important for final diagnosis.

Aims: We retrospectively investigated the 92 patients who underwent EUS for esophageal lesions from Aug. 2018 to July 2023 and receiving biopsy. We analyzed the pathology from the different layer.

Methods: There were total 918 patients receiving miniprobe endoscopic ultrasound between Aug. 2018 and July 2023 at Yuan’s General Hospital. We analyzed 92 patients with a total of 102 esophageal lesions.

Results: The mean age of all esophageal lesions who underwent EUS was 58.5 ± 12 year-old. 14 cases were esophageal cancers, including 12 cases of esophageal squamous cell carcinoma and 2 cases of esophageal adenocarcinoma. 12 patients were male and 2 were female. 78 patients had total 88 esophageal SELs.

The mean age was 58.4 ± 12.8 year-old. Male was predominant (n = 53, 67.9%). 6 cases had more then one esophageal SELs. The mean distance from incisor tooth to SELs was 31.6 ± 9 cm. Two cases cannot identify layer due to poor quality. The most common origin wall layer of the SET was muscularis mucosa (n = 53, 60.2%), followed by submucosa (n = 18, 20.4%) and muscularis propria (n = 15, 21.6%). 50 esophageal lesions originated from the second layer receiving biopsy. 3 cases cannot perform biopsy due to patient intolerance. There were 24 leiomyoma (45.2%), 16 inflammation (30.1%), 5 squamous hyperplasia (9.4%), 2 granular cell tumor (5.6%), 1 adenoma (2.8%). There were two cystic lesions including 1 ductal cyst and 1 retention cyst. 18 esophageal lesions originated from the third layer but only 10 patient receiving biopsy. There were 5 leiomyoma, 3 inflammation, 1 lipoma and 1 bronchogenic cyst.

Conclusions: Esophageal SEL is mostly benign nature and misdiagnosed as extrinsic compression or normal variation easily. EUS is a good modality to examine esophageal SEL. Leiomyoma is the most common SELs from the second layer and biopsy is seldom performed if the lesion is typical homogenous hypoechoic lesion. However, in our experience, granular cell tumor and adenoma, both had malignancy potential and resection is recommended from previous reports. As a result, tissue analysis is still essential for accurate diagnosis.

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CAMERON LESIONS: A RARE CAUSE OF SEVERE ANEMIA

Aprille Joy T. Tordesillas, Roberto Jr. De Guzman

Our Lady of Lourdes Hospital, Manila, Philippines

Background: Cameron and Higgins first described Cameron lesions in 1986. The prevalence rates of hiatal hernia range from 0.8 to 2.9 in all patients undergoing upper gastrointestinal endoscopy. A Cameron lesion is a rare cause of overt upper GI bleed. Cameron lesions can be round or ellipsoid, but linear forms are most common. They are usually found on the lesser curvature of the stomach at the level of the diaphragmatic hernia. Clinically, Cameron lesions are relevant due to their ability to cause gastrointestinal bleeding resulting in substantial anemia requiring blood transfusions. The diagnosis is usually confirmed with esophagogastroduodenoscopy but is often missed and may be underdiagnosed. Meticulous search and knowledge of this lesion is necessary for prompt diagnosis.

Aims: To describe a rare cause of severe anemia secondary to Cameron Lesions.

Methods: The patient is a 52-year-old, Filipino female, who came in due to three week history of easy fatigability, exertional dyspnea, light headedness with episode of cold clammy skin. Symptoms worsened accompanied by generalized body weakness and frequent palpitations. Her past medical history is significant for Bronchial Asthma maintained on Salmeterol/Fluticasone (Seretide) inhaler 250 mcg 1 puff BID, Salbutamol MDI as needed, Gastroesophageal Reflux Disease S/P Esopaphagogastroduodenoscopy, Vertebral Spine Dislocation C4 and C5. She smoked socially (2-3 sticks a session 1-2 x a year) with the last cigarette 16 years, occasional alcoholic beverage drinker. Upon examination at the Emergency Department, vital signs were stable with BP of 110/70 mmHg, heart rate of 90 bpm, respiratory rate of 20, afebrile. Patient was noted to be obese with body mass index of 29.43 kg/m2. She was noted to be weak looking with pale palpebral conjunctivae, dry lips and oral mucosa, clear breath sounds, normal rate regular rhythm with no murmurs appreciated, soft non-tender abdomen, no bipedal edema with pale nail beds. On digital rectal examination, no skin tags, no external masses, intact sphincter tone, no internal masses palpated, no blood per examination finger. Substantial anemia was noted on complete blood count with a hemoglobin

of 45 g/L, hematocrit of 17%, with a peripheral blood smear showing normocytic, normochromic, mild poikiloanisocytosis with adequate platelets. Other work up all deemed normal: LDH, Coomb’s test, liver enzymes, fecal occult blood test. Iron profile showed: serum ferritin of 5.21 showing low iron storage and a reticulocyte count of 3.3 showing adequate bone marrow response. The patient initially underwent three units of packed RBC transfusion, but on repeat complete blood count hemoglobin and hematocrit was noted to 71g/dL and 25% respectively. She had an additional two units packed RBC transfusion. Subsequently a bone marrow aspiration and biopsy was done which revealed normal findings. Bone marrow biopsy results showed mildly hypercellular bone marrow, moderate Tri-lineage dyspoiesis. The marrow aspirate is cellular and polymorphous. Bone marrow findings shows insignificant results for her symptoms of anemia. The patient then underwent endoscopy, which revealed slightly irregular with a small mucosal area of mucosal erythema with a hiatal hernia approximately 3 cm. This may be the source of chronic occult gastrointestinal bleeding leading to severe anemia attributed to Cameron Lesions. Also noted sessile gastric polyps seen at the gastric side. On colonoscopy, noted sessile polyp at the rectum, polypectomy was done specimen sent for histopathalogy which showed villoglandular polyp. Esophagogastroduodenoscopy performed during that admission revealed hiatal hernia, with erosions and minimal bleeding. The patient was then treated and discharged with intravenous proton pump inhibitors and iron supplementation. B Results: We have a 52-year-old obese, Filipino female, with history of Gastroesophageal reflux disease who came in due to generalized body weakness, easy fatigability and palpations. On work up, noted substantial anemia with a hemoglobin of 45g/L, hematocrit of 17%, with a peripheral blood smear showing normocytic, normochromic, mild poikiloanisocytosis with adequate platelets. On further investigation for source of anemia, noted fecal occult blood test negative, iron profile showing iron deficiency anemia and unremarkable bone marrow aspiration and biopsy results. Hence, the need for evaluation of gastrointestinal for any source of occult bleeding. On gastroscopy, there were erosions at the hiatal hernia attributed to Cameron lesions, and other findings on endoscopy were d not significant to cause bleeding. The patient eventually underwent Laparoscopic Nissen Fundoplication due to recurrent symptoms of anemia secondary to Cameron lesions.

Cameron and Higgins first described Cameron lesions in 1986, and it was described as linear gastric erosions located at the edges of the mucosal folds located near or at the diaphragm. Both erosions and ulcers are two entities that form part of the same disease, called Cameron lesions. The prevalence rates of hiatal hernia range from 0.8 to 2.9 in all patients undergoing upper gastrointestinal endoscopy. According to Camus et al., of 3960 endoscopies, only 0.6% cases were found to have Cameron lesions. Cameron lesions are found in 5% of the patients known with hiatal hernia who undergo upper endoscopy. The size of the hiatal hernia has a proportional relationship to the risk of lesion because in hernias larger than 5 cm the prevalence is 10-20%.

Gray et al., classified hiatal hernia according to size as follows: small (<3 cm), medium (3-4.9 cm) and large (≥5 cm). Of all the Cameron lesions they found, 23.2% occurred in small, 32.6% occurred in medium and 44.2% occurred in large hiatal hernias. In our case, the patient is classified to have a large hiatal hernia. There is no clear pathophysiology of Cameron lesions. Though there are some predisposing factors such as mechanical trauma of the diaphragmatic impingement, hiatal hernia, acid reflux, infection by Helicobacter pylori, gastric stasis and vascular stasis. According to Mozkovitz et al. ischemia as can also be a causal factor where they found through biopsy histopathologic findings consistent focal ischemic gastropathy in coagulative necrosis. However all these theories are inconclusive, but we can ensure multifactorial etiology for developing of Cameron lesions. Treatment is primarily medical with proton pump inhibitors as the first line of therapy. Laparoscopic or open fundoplication is reserved for refractory cases to remove the trigger, the hiatal hernia.

Conclusions: Severe anemia necessitating blood transfusion is rarely seen in patients with Cameron lesion. Often overlooked during endoscopy, careful examination is needed to identify lesions especially if other causes of gastrointestinal bleeding and anemia have been ruled out. Medical treatment should be based on inhibition of acid secretion and refractory cases should undergo surgery. Cameron lesions are linear gastric erosions on the mucosal folds at the diaphragmatic impression in patients with a large hiatal hernia. Lesions are often overlooked during gastroscopy, hence, it is often underdiagnosed. Meticulous search and knowledge of this lesion is necessary for prompt diagnosis, treatment and to prevent recurrence of anemia.

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ESOPHAGEAL GRANULAR CELL TUMORS: CLINICAL OUTCOMES OF DIFFERENT METHODS OF ENDOSCOPIC RESECTION

Cheol-Woong Choi, Dae-Gon Ryu, Jin-Ook Jang, Min-Chae Jeon, Woo-Jin Kim, Won-Jun Jang, Cheolmin Lee, Hyunmyung Cho, Geonwoo Lee, Hojune Lee

Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea

Background: Esophageal granular cell tumors (GCTs), the second most common subepithelial tumors (SETs) of the esophagus, are potentially malignant. Currently, no definite management guidelines exist, despite endoscopic resection being a valuable treatment option.

Aims: We evaluated the clinical outcomes of different methods of endoscopic resection of esophageal GCTs.

Methods: A total of 35 patients with endoscopically resected esophageal GCTs were retrospectively enrolled between December 2008 and October 2021. Several modified endoscopic mucosal resections (EMRs) were performed for treating esophageal GCTs. Clinical and endoscopic outcomes including complete histologic resection rate, and associated postoperative complications, were evaluated.

Results: The mean age of the 35 patients with endoscopically resected esophageal GCTs was 55.8 ± 8.2; the majority were men (57.1%). Mean tumor size was 7.2 mm ± 2.6, most (80.0%) were asymptomatic and present in the distal third of the esophagus (77.1%). Endoscopic characteristics predominantly included broad-based (85.7%) and whitish-to-yellowish color changes (97.1%). Endoscopic ultrasound (EUS) of 82.9% of the tumors revealed homogeneous hypoechoic SETs originating from the submucosa. The five endoscopic treatment methods used were: ligation-assisted (77.1%), conventional (8.7%), capassisted (5.7%), and underwater (5.7%) EMRs and ESD (2.9%). Mean surgery time was 6.6 minutes ± 2.1, and no procedure-associated complications were noted. The en-bloc and complete histologic resection rates were 100% and 94.3%, respectively.

Conclusions: No local recurrences were evident during follow-up, and no significant differences in the clinical outcomes of the different methods of endoscopic resection were found. Based on tumor characteristics and therapeutic outcomes, modified EMR methods can be effective and safe. However, there were no significant differences in the clinical outcomes of the different methods of endoscopic resection.

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PROPER SIZE AND TIMING OF ENDOSCOPIC DILATION IN ANASTOMOTIC STRICTURE AFTER NEAR-TOTAL ESOPHAGECTOMY

Dae-Gon Ryu, Cheol-Woong Choi, Jin-Ook Jang, Min-Chae Jeon, Woo-Jin Kim, Won-Jun Jang, Cheolmin Lee, Hyunmyung Cho, Geonwoo Lee, Hojune Lee

Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea

Background: The size or timing of endoscopic dilatation for anastomotic stricture after near-total esophagectomy is not clear.

Aims: The purpose of this study is to find out the target size and the timing of endoscopic dilatation for stenosis after near-total esophagectomy.

Methods: Medical records of patients with endoscopic dilatation for anastomotic stricture after near-total esophagectomy between January 2015 and April 2021 were reviewed. We analyzed the stricture recurrence rate and dilation-free period according to each diameter of dilation.

Results: In the study period, 78 endoscopic dilations in 24 patients were enrolled. The stricture recurrence rate was 91.4% in 13.5 mm or less group, 57.9% in 15 mm group, and 0% in 16.5 mm group. The dilationfree period had a mean of 48.2 (range 14-679) days in 13.5 mm or less group and 109.3 (range 14-347) days in 15 mm group (p = 0.045). No perforation occurred in this study.

Conclusions: In patients with anastomotic stricture after near-total esophagectomy, safely consider 15 mm as the target diameter of dilation, and if this is achieved, follow-up endoscopy and dilation can be considered after 3 months.

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ACTIVE EXERCISE AFTER POLYPECTOMY REDUCES THE RISK OF METACHRONOUS

ADVANCED COLORECTAL NEOPLASM MORE SIGNIFICANTLY IN SUBJECTS WITH METABOLIC DERANGEMENTS

Wei-Yuan Chang1,3, Hsuan-Ho Lin2,3, Li-Chun Chang3, Wen-Feng Hsu3, Ming-Shiang Wu3, Han-Mo Chiu3

1National Taiwan University Cancer Center, Taipei, Taiwan

2National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan

3National Taiwan University Hospital, Taipei, Taiwan

接受大腸息肉切除後積極運動可針對性 地降低代謝失調患者產生異時性高風險 息肉之風險

張為淵1,3 林宣合2,3 張立群3 許文峰3 吳明賢3 邱瀚模

3

1 國立臺灣大學醫學院附設醫院癌醫中心分院

2 國立臺灣大學醫學院附設醫院新竹臺大分院

3 國立臺灣大學醫學院附設醫院

Background: Metachronous colorectal neoplasm (meta-CRN) may occur after colonoscopic polypectomy and subjects with metabolic derangements are associated with a higher risk of meta-CRN. Active exercise after polypectomy can reduce the risk of metachronous advanced colorectal neoplasm (meta-ACRN) but how it acts in high-risk subjects remains unclear.

Aims: The aim of this study is to elucidate whether exercise is an effective and specific preventive strategy against meta-ACRN among subjects with metabolic derangements.

Methods: We retrospectively analyzed subjects who underwent screening colonoscopy with polypectomy and subsequent surveillance colonoscopy between January 2009 and December 2019. The subjects’ baseline metabolic status was obtained at the date of screening colonoscopy and the cohort was grouped by each subject’s status of metabolic derangements (metabolically healthy; metabolically unhealthy; metabolic syndrome or NAFLD). The subjects’ exercise status after screening polypectomy were queried by questionnaires on the date of surveillance colonoscopy and the impact of exercise status on risk

of meta-ACRN was explored stratified by the subjects’ metabolic derangement status using Kaplan-Meier analysis. Cox regression models were constructed for multivariate analysis.

Results: Of those 3,231 who were enrolled, the average age was 56 years old and 2247 (65.5%) were men. A total of 1,365 (42.2%) subjects developed at least one meta-CRN including 166 (5.1%) subjects with meta-ACRN during a mean follow-up time of 3.4 years. Subjects adopting a more active exercise habit (≥14.9 metabolic equivalent of tasks/week) after polypectomy was associated with a significantly lower risk of meta-ACRN (4.3% vs. 5.8%, p < 0.05). In the multivariable analysis, the adjusted hazard ratio (aHR) of developing meta-ACRN after engaging active exercise after polypectomy was 0.52 (95% confidence interval (CI) = 0.63–0.75) for those being metabolically unhealthy, 0.48 (95% CI = 0.24–0.95) for those with metabolic syndrome and 0.24 (95% CI = 0.13–0.44) for those with NAFLD. The impact of exercise on the risk of meta-ACRN was not significant in metabolically healthy subjects (aHR: 0.65; 95% CI = 0.32–1.33).

Conclusions: The study results confirmed the protective effect of active exercise after polypectomy in preventing meta-ACRN and further demonstrated that such an effect was mediated by the subjects’ metabolic status. Active exercise should be encouraged after polypectomy to subjects with metabolic derangements.

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PATIENTS WITH CROHN’S DISEASE HAVE AN INCREASED RISK OF CHRONIC KIDNEY DISEASE

Ming-Che Chuang1, Tzu-Ju Hsu2, Tsung-Yu Tsai1,3

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

2Management Office for Health Data (DryLab), Clinical Trial Research Center (CTC), China Medical University Hospital, Taichung, Taiwan

3School of Medicine, China Medical University, Taichung, Taiwan

克隆氏症病患的慢性腎臟病風險有所增 加

莊明哲1 徐子茹2 蔡宗佑1,3

1 中國醫藥大學附設醫院消化醫學中心

2 中國醫藥大學附設醫院臨床試驗研究中心健康數據 管理辦公室

3 中國醫藥大學醫學系

Background: Recent studies suggest the association between inflammatory bowel disease and ESRD. In this study, we evaluated the risk of CKD in patients with inflammatory bowel disease.

Aims: Evaluate the risk of chronic kidney disease (CKD) in patients with inflammatory bowel disease (IBD).

Methods: Using the National Health Insurance database in Taiwan, we compared 3203 patients who were diagnosed with IBD with 3203 matched controls during 2008-2018. We applied Cox regression analysis to estimate hazard ratios (HRs) for CKD in IBD.

Results: During a mean follow-up of 5.41 and 5.72 years, 45 events developed in 17339 person-year in patient with IBD compared with 31 event in 18310 person-year in matched controls (adjusted HR, 1.16; 95% confidence interval [95% CI], 0.72 to 1.89). However, 18 events developed in 4295 person-year in patient with Crohn’s disease compared with 58 event in 31354 person-year in matched controls (adjusted HR, 2.60; 95% confidence interval [95% CI], 1.51 to 4.46).

Conclusions: CKD was more common in patient with Crohn’s disease.

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WHITE-LIGHT IMAGE SURFACE ENHANCEMENT NET: A NOVEL MODEL FOR WHITE-LIGHT COLON POLYP MULTI-CLASSIFICATION USING TEXTURE FEATURES

Wei-Lun Hsu1,2, Tzu-Ying Tsai1, Mu-Chun Su3, Wei-Jen Lin1

1Department of Computer Science and Information Engineering, National Central University, Taoyuan, Taiwan

2Division of Gastroenterology and Hepatology, Department of Medical Affairs, Landseed International Hospital, Taoyuan, Taiwan

3College of Electrical Engineering and Computer Science, National Central University, Taoyuan, Taiwan

白光影像表層增強網路：基於紋理特徵 的白光結腸息肉分類模型

徐偉倫1,2 蔡姿瑩1 蘇木春3 林烕任1

1 國立中央大學資訊工程研究所

2 聯新國際醫院腸胃肝膽科

3 國立中央大學資訊電機學院

Background: Colorectal cancer is one of the most prevalent malignant diseases worldwide. Research indicates that early polypectomy can prevent the majority of colorectal cancers. Therefore, accurate differentiation of colon polyp types and informed decision-making regarding their management are crucial. Image-enhanced endoscopy techniques, such as chromoendoscopy and narrow-band imaging (NBI), are used to enhance the pit pattern or microvascular appearance of polyps. However, the availability of NBI equipment may be limited in some clinical settings due to cost considerations.

Aims: To provide cost-effective and efficient evaluation for endoscopists and address the limited predictive capability of convolutional neural network (CNN) models caused by the blurring of texture features in white light imaging (WLI) of polyp lesions, this paper proposes a novel model called White-light Image Surface Enhancement Net (WISENet).

Methods: WISENet is based on the AlexNet architecture with several crucial modifications. Additionally, a new input feature representation method is proposed, which combines texture features, frequency domain features, and a high-

boost filter, for multi-class classification of colonic polyps based on WLI. We enrolled a total of 170 unique polyps, comprising 71 hyperplastic polyps, 90 adenomas, and 9 adenocarcinomas. These images were collected from four public datasets, including PICOOLO, PolypGen, Colonoscopy Dataset, and Set-1.

Results: Experimental results demonstrate a significant impact of the proposed texture features on the performance of CNNs for white-light polyp image classification (p < 0.05), resulting in an average increase of 13.2% in the F1 scores across multiple models (i.e. MobileNet, ResNet50, VGG19 and GoogLeNet). The accuracy was 82.3%, F1 score was 81.7% and the precision was 83.0%.

Conclusions: The findings highlight the potential of the WISENet model and the importance of incorporating texture features in improving the accuracy of colon polyp classification using WLI.

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APTAMER/DOXORUBICINCONJUGATED NANOPARTICLES

TARGET MEMBRANOUS CEMIP2 IN COLORECTAL CANCER

Maryam Kianpour1, Ching-Wen Huang2,3, Pichpisith Pierre Vejvisithsakul1,4, Jaw-Yuan Wang2,3,5,6,7,8, Chien-Feng Li9,10,11, Meng-Shin Shiao12, Cheng-Tang Pan13,14, Yow-Ling Shiue1,14

1Institute of Biomedical Sciences, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; 2Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 4Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 5Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan; 6Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Graduate Institute of Medicine, College of Medicine, Kaohsiung, Medical University, Kaohsiung, Taiwan; 8Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan; 9Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan; 10Department of Pathology, Chi Mei Medical Center, Tainan, Taiwan; 11National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; 12Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 13Institute of Precision Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; 14Department of Mechanical and Electro-Mechanical Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan

適體∕阿黴素綴合納米顆粒靶向結直腸

癌中的膜 CEMIP2

Maryam Kianpour1 黃敬文2,3 Pichpisith Pierre Vejvisithsakul1,4 王照元2,3,5,6,7,8 李健逢9,10,11 蕭孟昕12 潘正堂13,14 薛佑玲1,14

1 國立中山大學生物醫學研究所；2 高雄醫學大學 附設醫院結直腸外科；3 高雄醫學大學醫學院外科 系；4Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand；5 衛生福利部屏東醫院；6 高雄 醫學大學臨床醫學研究所；7 高雄醫學大學醫學研 究所；8 高雄醫學大學癌症研究中心；9 奇美醫學中 心醫學研究部；10 奇美醫學中心病理部；11 國家衛 生研究院癌症研究所；12Research Center, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand；13 國立中山大學精準醫學研究 所；14 國立中山大學機電學系

Background: Colorectal cancer (CRC) is one of the most deadly and the second cause of cancer-related mortality. The incidence is continually increasing worldwide. CRC evolves from precancerous lesions and adenomatous polyps through sequentially genetic and epigenetic mutations. Several internal and external factors, including age, gender, racial group, risk exposure, demographic variations, genetic susceptibility, and gene mutations, involve CRC development and treatment responses. Screening can notably reduce CRC incidence and mortality, however, missed screening opportunities, or early detection causes most deaths. Recent emerging molecular subtypes in CRC contribute to early diagnosis, prevention, prognosis, clinical stratification, and subtype-based targeted therapies. Accordingly, recognizing and incorporating CRC heterogeneity as a determining factor in current clinical practice will be greatly helpful in early diagnosis and targeted medication.

Aims: The objectives were to identify the functional domains of a potential oncoprotein, cell migration inducing hyaluronidase 2 (CEMIP2), evaluate its expression levels and roles in colorectal cancer (CRC), and develop an aptamer-based nanoparticle for targeted therapy.

Methods: Data mining, quantitative RT-PCR, immunoblot, hyaluronan assays on CRC tissues and patients sera, cell culture, gene manipulation, in vitro functional assays, Cell-SELEX, immunofluorescence, fabrication of amine-functionalized nesoporous silica nanopartilces (MSN), preparation of MSNaptCEMIP2(101) and Dox@MSN, characterization of MSN, Dox@MSN, and Dox@MSN-aptCEMIP2(101), and statistical analysis.

Results: Data mining on TCGA identified that CEMIP2 might play oncogenic roles in CRC. In a local cohort, CEMIP2 mRNA levels significantly stepwise increase

in CRC patients with higher stages, and high CEMIP2 confers worse disease-free survival. In addition, CEMIP2 mRNA levels significantly correlated to hyaluronan levels in sera from CRC patients. Deletion mapping identified that CEMIP2 containing G8 and PANDER-like domains preserved hyaluronidase activity and oncogenic roles, including cell proliferation, anchorage-independent cell growth, cell migration and invasion, and human umbilical vein endothelial cell (HUVEC) tube formation in CRC-derived cells. A customized monoclonal mouse anti-human CEMIP2 antibody probing the PANDER-like domain (anti-289307) counteracted CEMIP2-mediated carcinogenesis in vitro. Cell-SELEX pinpointed an aptamer, aptCEMIP2(101), specifically interacted with the full-length CEMIP2, potentially involving its 3D structure.

Conclusions: Treatments with aptCEMIP2(101) significantly reduced CEMIP2-mediated tumorigenesis in vitro. Mesoporous silica nanoparticles (MSN) carrying atpCEMIP2(101) and Dox were fabricated. Dox@MSN, MSN-aptCEMIP2(101), and Dox@ MSN-aptCEMIP2(101) significantly suppressed tumorigenesis in vitro compared to the Mock, while Dox@MSN-aptCEMIP2(101) showed substantially higher effects compared to Dox@MSN and MSNaptCEMIP2(101) in CRC-derived cells. Our study identified a novel oncogene and developed an effective aptamer-based targeted therapeutic strategy.

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EVALUATION OF A COMPUTERAIDED DETECTION DEVICE DURING WATER EXCHANGE COLONOSCOPY: A PRAGMATIC IMPLEMENTATION PERFORMANCE

IMPROVEMENT STUDY

I-Chia Su1, Chi-Liang Cheng1, Yen-Lin Kuo1, Ke-Yun Zou2, Yun-Shien Lee2, Sergio Cadoni3, Felix W. Leung4,5

1Division of Gastroenterology, Evergreen General Hospital, Taoyuan, Taiwan

2Department of Biotechnology, School of Health Technology, Ming Chuan University, Taoyuan, Taiwan

3Digestive Endoscopy Unit, CTO Hospital, Iglesias, Italy

4Sepulveda Ambulatory Care Center, Veterans Affairs Greater Los Angeles Healthcare System, North Hills, California, USA

5David Geffen School of Medicine at UCLA, Los Angeles, California, USA

人工智慧息肉偵測系統於換水大腸鏡的 效用評估：一項臨床實際運用人工智慧 輔助系統的大腸鏡品質提升研究

蘇怡佳1 鄭吉良1 郭彥麟1 鄒可芸2 李御賢2 Sergio Cadoni3 Felix W. Leung4,5

1 中壢長榮醫院胃腸科

2 銘傳大學健康科技學院生物科技學系

3Digestive Endoscopy Unit, CTO Hospital, Iglesias, Italy

4Sepulveda Ambulatory Care Center, Veterans Affairs Greater Los Angeles Healthcare System, North Hills, California, USA

5David Geffen School of Medicine at UCLA, Los Angeles, California, USA

Background: Real-time computer-aided detection (CADe) devices showed increased adenoma detection rate (ADR) and adenoma per colonoscopy (APC) in randomized controlled trials (RCTs) using gasinsufflated colonoscopy. Real-life implementation studies, e.g., AI-DETECT and AI-SEE trials, failed to find significant performance improvement. Water exchange (WE) colonoscopy increases bowel cleanliness and may optimize polyp detection with CADe. We hypothesized that WE with CADe would detect more adenomas than WE alone in a performance improvement study.

Aims: Our aim was to evaluate the detection rates with the use of CADe during WE colonoscopy.

Methods: This was a pragmatic implementation study conducted in Evergreen General Hospital, Taoyuan, Taiwan. Our endoscopy suite was equipped with a CADe device (CAD EYE, Fujifilm, Japan) on Feb 2, 2023. We collected the detection data on all WE colonoscopies performed in ≥45 y/o patients of all indications with the use of CADe between Feb 3 and May 15, 2023 (CADe group) and compared them with a corresponding 3-month period (Nov 2022Jan 2023) before CADe implementation (non-CADe group). The false positives (FPs) were evaluated and classified using NOISE classification in all patients. An FP was defined as any activation of the CADe system not due to any polypoid or nonpolypoid lesion. The primary outcomes were ADR and APC. Secondary outcomes included serrated polyp (SP) detection, procedural times, and real-time FP results.

Results: A total of 395 patients (206 with CADe) aged ≥45 years were enrolled in the detection study, with similar baseline demographics except more patients were active smokers in the CADe group. All procedural times were comparable. There were no significant differences in the ADR and APC between the CADe and non-CADe groups (51.5% vs. 61.9%, P = 0.365 [ADR]; 1.25 vs. 1.31, P = 0.714 [APC]). The use of CADe significantly increased the SP detection rates in the right and proximal colon (51.5% vs. 35.9%, P = 0.002 [right]; 62.6% vs. 49.7%, P = 0.01 [proximal]). A total of 242 patients of all age range (mean age 53.2 years; 48% male) were enrolled in the FP study and 3199 real-time FP activations were registered. The mean number of real-time FPs per colonoscopy was 13.2 ± 6.9, of which 11.7 ± 6.4 (88%) and 1.5 ± 1.6 (12%) were due to artifacts in the bowel wall and bowel content, respectively.

Conclusions: WE uniquely enhanced the performance of CADe in detecting proximal/right colon SP. The use of CADe with WE did not improve ADR or APC consistent with prior pragmatic implementation trials. Aligned with reported analyses of video recordings, most real-time FPs, that might be annoying or distract the non-expert endoscopists, were due to artifacts from the bowel wall. The complimentary benefits of combining WE and CADe on SP detection and potential impact of FP deserves further study.

P.79

THE CLINICAL EFFICACY AND SAFETY OF SNARE-TIPPED ENDOSCOPIC RADICAL INCISION AND CUTTING (STERIC) FOR POSTOPERATIVE BENIGN COLORECTAL ANASTOMOTIC STRICTURE OR TOTAL OCCLUSION

Chung-Ying Lee1,2,3, Hung-Ta Tsai1, Min-Hsuan Yen4, Kee-Thai Kiu4, Tung-Cheng Chang4,5, Ming-Yao Chen1,2,3

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

3TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan

4Division of Colorectal Surgery, Department of Surgery, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan

5Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

傳統線圈型電刀尖端內視鏡根治性切開 術（ STERIC ）治療術後良性結直腸吻合 口狹窄或完全閉塞的臨床療效和安全性 李宗頴1,2,3 蔡宏達1 顏珉玄4 丘基泰4 張東晟4,5 陳明堯1,2,3

1 衛生福利部雙和醫院（委託臺北醫學大學興建經 營）消化內科

2 臺北醫學大學醫學院肝膽腸胃內科

3 臺北醫學大學消化醫學研究中心

4 衛生福利部雙和醫院（委託臺北醫學大學興建經 營）大腸直腸外科

5 臺北醫學大學醫學院外科部

Background: Benign anastomotic strictures following colorectal surgery are not uncommon and often require endoscopic or surgical intervention. Endoscopic balloon dilatation (EBD) is commonly used, but multiple sessions may be needed for long-term patency. Endoscopic radical incision and cutting (RIC) is an alternative treatment for refractory

strictures, but data on its efficacy and safety are limited.

Aims: This study aimed to evaluate the clinical efficacy and outcome of snare-tipped endoscopic radical incision and cutting (STERIC) for postoperative benign colorectal anastomotic strictures or total occlusion.

Methods: A retrospective study was conducted on patients with post-operative benign colorectal anastomotic strictures treated with STERIC at ShunagHo Hospital between January 2018 and December 2022. Data on patient characteristics, including sex, age, etiology and types of colorectal surgery, anastomotic stricture location, stricture diameters, procedure time of STERIC, adverse events, successful rate of STERIC, and follow-up period were collected.

Results: A total of 7 consecutive patients received STERIC for post-operative benign colorectal anastomotic strictures. The median diameter of the strictures was 3mm (range, 0-10 mm), with two patients presenting total anastomotic occlusion. The median procedure time was 19 minutes (range, 5-34 minutes). All patients achieved clinical success and underwent closure of temporary colostomy without adverse events. The median follow-up period following STERIC was 21 months (range, 2-51 months). All patients underwent only one session of STERIC and none of them experienced clinical symptoms of restenosis during the follow-up period.

Conclusions: STERIC for post-operative benign colorectal anastomotic strictures or total occlusion was supposed to be an effective, cost-effective and safe treatment option.

P.80

COMPUTER AIDED DIAGNOSIS IN COLON POLYP CLASSIFICATION

Bou-Zenn Lin, Tsung-Jung Lin, Chih-Lin Lin, Kuan-Yang Chen

Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan

電腦輔助診斷應用於大腸瘜肉之分類

林柏任 林聰蓉 林志陵 陳冠仰

臺北市立聯合醫院仁愛院區消化內科

Background: Colon cancer is the second most common cancer in Taiwan and was derived from adenomatous polyps in the colon. Early detection and resection of these polyps can decrease the incidence and mortality rate of colon cancer in an efficient way. Colonoscope is the most important and primary way for colon cancer screening and polyp resection. Current researches on artificial intelligence assisted image recognition system in colonoscopy mainly focus on polyp detection and aid physicians to detect polyps accurately. These studies show promising result and do raise adenoma detection rate and decrease inter-observer variability, even in experienced endoscopists. However, most studies classify polyps into two simple classes, benign and malignant, without detailed classification. While discovering a polyp during the colonoscopic exam, an endoscopist must predict the class as hyperplastic, adenomatous or carcinomatous without any pathological prove and choose the most appropriate treatment. Though there are some proven effective and accurate clinical polyp classification systems to aid endoscopist to make right decisions, these classification systems are highly dependent on the knowledge and experience of the clinical members, which needs a lot of training time.

Aims: This study aims to design a competitive polyp classification model by using deep transfer learning, applying well trained convolutional neural network model to colon polyp classification.

Methods: Total 1325 polyp images were enrolled in our study, including 680 white light images and 645 narrow band images. We separated all the images into two datasets, training and internal validation set and independent test set, both datasets had white light images and narrow band images. Both sets were divided into three groups, white light image group, narrow band image group and mixed

group, which were used to re-train seven selected pretrained models. Ground truth of the images were based on pathological report, separating polyps into hyperplastic polyp, adenoma and colon cancer. Independent test set was used for external validation.

Results: Among all the models, AlexNet has the best classifying performance in the condition of white light images, test accuracy up to 80.53%. It has good sensitivity in classifying adenoma, up to 87.32%, high specificity in differentiating hyperplastic polyp, up to 98.09%, and excellent sensitivity, specificity, positive predictive value and negative predictive value in classifying colon cancer, up to 96.51%, 94.23%, 93.26% and 97.03% respectively.

Conclusions: Though the total accuracy of the model is slightly inferior to clinical classification system by human observers, it has outstanding performance on the sensitivity of adenoma class, specificity of hyperplastic polyp class and total accuracy of cancer, which can partially assist endoscopist to classify colon polyps.

P.81

ENDOSCOPIC FEATURES OF COLITIS: A CLINICAL EXPERIENCE IN ONE MEDICAL CENTER

Fui-Jun Yee1, Tze-Sian Chan1,2, Min-Shung Wu1,2, Fat-Moon Suk1,2, Gi-Shih Lien1,2, Chun-Nan Chen1

1Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

2Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

大腸炎的內視鏡特徵：一個醫學中心的 臨床經驗

余惠君1 張智翔1,2 吳明順1,2 粟發滿1,2 連吉時1,2 陳俊男1

1 臺北市立萬芳醫院消化內科

2 臺北醫學大學醫學系內科

Background: Colitis is inflammatory changes of colon caused by many different etiologies, some colitis have specific endoscopic presentations. We collected clinical data and endoscopic pictures of patients with colitis in our hospital. Analysis of the endoscopic pictures of some colitis was done.

Aims: We analyzed the endoscopic presentations of tuberculosis colitis, cytomegalovirus colitis, amebic colitis, ischemic colitis and pseudomenbraneous colitis, with emphasis on morphological presentations and patterns, which may assist on the endoscopic diagnosis of colitis.

Methods: Patients were collected from January 1, 2000 to January 1 2023. Endoscopic data such as color, shape, length, segments involvement, and other morphological change were collected.

Results: A total of 79 patients were enrolled. We found 8 tuberculosis colitis patients, 11 cytomegalovirus colitis patients, 8 amebic colitis patients, 18 ischemic colitis patients, 34 pseudomenbraneous colitis patients. In 8 tuberculosis colitis patients, 5/8 have terminal ileum involvement, 8/8 have cecal involvement, 4/8 have circular ulcers, 4/8 have deformed ileocecal valve. In 11 cytomegalovirus colitis patients, 11/11 are immunocompromised patients, 11/11 have left side colon involvement, 6/11 have geographic-shape ulcers. In 8 amebic colitis patients, 8/8 have cecal involvement, 0/8 has terminal ileum involvement, 8/8 have normal intervening mucosa. In 18 ischemic colitis patients, 15/18 have sigmoid colon involvement. In 34 pseudomenbranous colitis

patients, 32/34, there are yellowish plaques at sigmoid colon and rectum.

Conclusions: Tuberculosis colitis patients may have the presentations of circular ulcers at cecum and terminal ileum, also may have deformed ileocecal valve. Cytomegalovirus colitis patients may have geographic-shape ulcers at left side colon. Amebic colitis patients may have cecal ulcers, do not have terminal ileum involvement, and have normal intervening mucosa. Ischemic colitis patients may have sigmoid colon ulcers. Pseudomenbraneous colitis patients typically may have yellowish plaques at sigmoid colon and rectum.

P.82

THE DIFFERENCE IN ADENOMA DETECTION RATE AFTER THE IMPLEMENTATION OF AN AI MODEL IN EXPERIENCED PHYSICIANS: A RETROSPECTIVE STUDY

David Wu, Hsin-Yu Chen

Division of Gastroenterology and Hepatology, Cathay General Hospital, Taipei, Taiwan

導入人工智能輔助對於資深主治醫師大 腸腺瘤偵測率的影響：一個回朔性研究 吳大衛 陳信佑 國泰綜合醫院消化內科

Background: Worldwide, colorectal cancer (CRC) ranks as the third most common cancer and the second leading cause of cancer-related deaths. The adenoma detection rate (ADR) during colonoscopy has been shown to have an inverse correlation with the incidence of subsequent colorectal cancer. Studies have demonstrated that a 1% increase in the ADR is associated with a 3% decrease in the subsequent CRC incidence over a 10-year period. In order to reduce the rate of missed polyps, several computer-aided detection (CADe) systems have been developed for polyp detection during colonoscopy. These systems are based on convolutional neural networks or deep learning techniques. Previously, we successfully developed a CADe system named aetherAI for the detection of adenomas during colonoscopy procedures.

Aims: Our objective was to determine whether there is a difference in the adenoma detection rate following the implementation of an AI model during colonoscopy procedures.

Methods: To test the difference in ADR between the pre-implementation and post-implementation periods of aetherAI, colonoscopies performed by four experienced physicians from April 2022 to August 2022 are considered the pre-implementation period, while colonoscopies performed from December 2022 to April 2023 are considered the post-implementation period. Colonoscopies were conducted due to positive Stool Occult Blood Test results. Statistical analyses were conducted to assess the differences in ADR using a chi-square test. A two-tailed P-value of less than 0.05 was considered statistically significant. All analyses and graphical representations were performed using the Statistical Analysis System (SAS).

Results: During the pre-implementation period, a total of 3,089 patients underwent colonoscopy, while during the post-implementation period, 2,598 patients underwent the procedure. Among patients who underwent colonoscopy due to positive Stool Occult Blood Test results or other clinical purposes, there was no significant difference observed in the ADR between procedures performed without AI and those performed with AI. When comparing the ADR among the four experienced physicians, none of them exhibited a significant difference in ADR after the implementation of the AI model. (A: 59.8% vs 45.2%, B: 38.3% vs 42.4%, C: 46.8% vs 51.4%, D: 27.8% vs 41.7%) The overall analysis showed no significant difference between the pre- and post-implementation periods of the AI model. (All: 47.1% vs 44.3%)

Conclusions: In our study, we did not find a significant difference in the ADR after the implementation of the AI model in experienced physicians. This suggests that the AI model may provide relatively little assistance to more experienced physicians. However, it remains unknown whether the AI model is helpful for young physicians or training fellows. To draw a more comprehensive conclusion, further prospective randomized controlled trials should be conducted, including both experienced and young physicians. This would provide better insights into the potential benefits of the AI model in different physician groups.

P.83

SUSPECTED SMALLBOWEL BLEEDING PATIENT CHARACTERISTIC MAY RELATED TO CAPSULE ENDOSCOPY DIAGNOSTIC YIELD RATE?

Jui-Hsiang Kuo1, Yi-Shen Wei1, Shi-Chang Li1, Tsung-Rung Lin1, Chih-Ling Ling1, Guan-Yang Chen1,2

1Department of Gastroenterology and Hepatology, Taipei City Hall Hospital, Renai Branch, Taipei, Taiwan

2Department of Gastroenterology and Hepatology, Taipei City Hall Hospital, Yangming Branch, Taipei, Taiwan

疑似小腸出血病人特徵與膠囊內視鏡出 血診斷率之相關性

郭睿祥1 魏亦伸1 李熹昌1 林聰蓉1 林志陵1 陳冠仰1,2

1 臺北市立聯合醫院仁愛院區消化內科

2 臺北市立聯合醫院陽明院區消化內科

Background: Capsule endoscopy is a safe and less invasive diagnostic method for patient of suspect small bowel bleeding (SSBB). However, capsule endoscopy is expensive and reading video of capsule endoscopy is time consuming.

Aims: The diagnostic yield of small-bowel capsule endoscopy (SBCE) in patients with SSBB ranges from 55-62%. We suggest careful patient selection may improve the diagnostic yield of SBCE in patients with SSBB.

Methods: We retrospective reviewed cases of SSBB received SBCE from April 2019 to March 2023 in our hospital. Positive diagnostic yield is defined as overt bleeding finding in capsule endoscopy. We reviewed medical record of history of GI tract bleeding, age, gender, height, weight, antithrombotic agents, comorbidity. Data analysis use IBM SPSS statistics software, version 25. Statistics methods as Chi-square test, Fisher’s extract test.

Results: 36 cases of SSBB received SBCE were included. Positive diagnostic yield rate of SBCE in our hospital is 22.22%. We found diagnostic yield rate of SBCE had no significant statistically related to age [P = 0.461], weight [P = 0.751], height [P = 0.298], gender (male over female) [OR 3.24 (95% CI 0.05–1.75); P = 0.25], chief complaint (tarry stool, bloody stool, anemia, abdominal pain) [P = 0.657], comorbidity (end stage

renal disease under dialysis) [OR 0.35 (95% CI 0.56–13.83); P = 0.22], anti-coagulant or anti thrombotic drug use [OR 0.70 (95% CI 0.27–7.30); P = 0.68].

Conclusions: In our study, patient characteristics (including: age, gender, height, weight, chief complaint, antithrombotic agents, comorbidity) may not related to positive diagnostic yield rate of SBCE in patients of SSBB.

THE CORRELATION BETWEEN ENDOSCOPIC MORPHOLOGY, AND THE RESULT OF 18F-FDG PET/CT SCAN IN PATIENT WITH COLORECTAL LYMPHOMA

Jia-Kuo Chen, Yu-Ting Kuo, Hsiu-Po Wang

Division of Gastroenterology, National Taiwan University Hospital, Taipei, Taiwan

大腸淋巴癌患者內視鏡下型態與正子攝

影之相關性

陳嘉國 郭雨庭 王秀伯 台大醫院胃腸肝膽科

Background: Occurrence of colorectal lymphoma is rare in the GI tract. Its association between endoscopic morphology and 18F-FDG PET/CT scan results has not yet been fully established.

Aims: The objective of this study was to examine the endoscopic characteristics in patients diagnosed with colorectal lymphoma and investigate their relationship with the histological type of colorectal lymphoma as well as 18F-FDG PET/CT scan results.

Methods: We retrospectively analyzed patients with colorectal lymphoma who were diagnosed using colonoscopy and biopsy specimens, from 2010 to 2023 at the National Taiwan University Hospital, Taiwan. The lesions were classified into the following types via colonoscopy: polypoid, ulcerative, multiple lymphomatous polyposis, and mixed. Additionally, data from patients who underwent 18F-FDG PET/CT scans for staging purposes were also reviewed.

Results: A total of 89 lesions were identified in 66 patients enrolled in this study. Of these, 25 (28%) were located in the ileocecal region, 18 (20%) in the ascending colon, 16 (18%) in the rectum, 15 (17%) in the sigmoid colon, 12 (14%) in the descending colon, and 3 (3%) in the descending colon. Moreover, the most common histological subtypes were diffuse large B-cell lymphoma (DLBCL) in 25 patients (38%) and mantle cell lymphoma (MCL) in 17 patients (26%), followed by follicular lymphoma (FL; 11%), Extranodal marginal zone lymphoma (9%). As for endoscopic morphology the most common presentation was ulcerative lesion (36%), followed by polypoid lesions (24%), and multiple polyposis lesions (22%). Additionally, the DLBCL (62%), was endoscopically classified as ulcerative lesion while MCL was classified as polypoid or others. Besides, total 41 patient, 58

lesions were conducted by 18F-FDG PET/CT scan. Of note, 36 patient (87%) was correlated with endoscopic finding. However, it is worth mentioning that the 5 patients diagnosed with colorectal lymphoma showed a negative result on the 18F-FDG PET/CT scans, 3 of them were diagnosed with MCL showed positive findings during endoscopy.

Conclusions: Colorectal lymphomas exhibit distinct endoscopic features that vary depending on their histological type. Analyzing the classification and distribution of lesions through colonoscopy, correlated with 18F-FDG PET/CT scans provided further in formation in patient with colorectal lymphomas.

P.85

MALIGNANT TUMOURS OF THE SMALL INTESTINE DIAGNOSED BY DOUBLE-BALLOON ENTEROSCOPY: A FIFTEEN-YEAR EXPERIENCE AT A HOSPITAL-BASED STUDY IN CENTRAL TAIWAN

Yi-Hua Wu1,3, Po-Ju Huang1,2, Chu-Ping Wang1,2, Ken-Sheng Cheng1,2,3, Jen-Wei Chou1,2,3

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University Hospital, Taichung, Taiwan

2School of Medicine, China Medical University, Taichung, Taiwan

3Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taipei, Taiwan

使用雙氣囊小腸鏡診斷小腸惡性腫瘤之 統計研究：一間中台灣醫學中心之 15 年 經驗

吳宜樺1,3 黃柏儒1,2 王楚評1,2 鄭庚申1,2,3 周仁偉1,2,3

1 中國醫藥大學附設醫院消化醫學中心

2 中國醫藥大學醫學系

3 台灣小腸醫學會

Background: The malignant tumours of the small intestine are relatively rare, and their pre-operative diagnosis is usually difficult.

Aims: This study was aimed to investigate the clinical characteristics of patients with the malignant tumors of the small bowel who underwent double-balloon enteroscopy. Secondary end points were to evaluate the usefulness and safety of DBE for the diagnosis of patients with suspected small bowel tumors derived from other previous procedures.

Methods: From January 2008 to January 2023, we retrospectively analyzed consecutive patients who underwent double-balloon enteroscopy examinations in a single center over a 10-year period. Results: Double-balloon enteroscopy procedures examinations were performed in 892 patients. Small bowel tumors were diagnosed in 14.1% of patients which 53.9% of patients (mean age 61.89 years) had malignant tumors: 49.0% had gastrointestinal stromal tumors, 10.9% had lymphoma, 21.8% had adenocarcinoma, 0.18% had angiosarcoma, 0.18% had carcinoid, 0.18% had desmoid, 12.7% had metastatic cancer. The indications for DBE among

patients with malignanct small bowel tumors were obscure gastrointestinal bleeding (69.0%). The concordance rate of diagnoses based on DBE with diagnoses based on small bowel barium study, CT, and capsule endoscopy among patients with small bowel tumors. Therapeutic plans were changed to surgery due to the DBE results in 67.5% of patients with small bowel tumors and treatment was add chemotherapy due to the DBE results in 25.8% of patients with small bowel tumors.

Conclusions: In our present study, we found approximately 14.5% of patients who underwent double-balloon enteroscopy had small bowel tumors, 53.9% of small bowel tumors are malignant. Besides, the most common indication for doubleballoon enteroscopy among patients with the malignant tumors of the small intestine was obscure gastrointestinal bleeding. DBE is a very useful modality in diagnosing small bowel tumors and has an important impact on therapeutic plans and shortterm clinical results.

P.86 LOW-GRADE APPENDICEAL MUCINOUS NEOPLASM AND PSEUDOMYXOMA PERITONEI

Mai-Gio Pang, Hung-Da Tung, Pei-Lun Lee, Cheng-Heng Lin, Chien-Hung Chen, Jyh-Jou Chen

Division of Gastroenterology & Hepatobiliary, Department of Internal Medicine, Chimei Hospital, Liouying, Tainan, Taiwan

闌尾低惡性度黏液瘤和腹膜偽黏液瘤

彭美杰 董宏達 李佩倫 林政衡 陳建宏 陳志州

柳營奇美醫院胃腸肝膽科

Background: Low-grade appendiceal mucinous neoplasm (LAMN) is a rare appendix neoplasm and incidentally found in about 1% of appendectomy specimen. Most patients with LAMN presented with acute abdominal pain such as appendicitis. If left untreated and ruptured, LAMN can cause bothering pseudomyxoma peritonei (PMP).

Aims: To understand the clinical presentation and treatment outcome of LMANs with or without PMP, we retrospectively reviewed pathological diagnosis with LAMN from 01 Jan. 2022 to 31 May 2023.

Methods: Six cases of LAMNs were retrospectively collected, including 2 cases with PMP. Their demographic, clinical, radiological, pathological data and treatment outcome were collected and analyzed. Results: The age range was 43-83 (average: 56.8). Four patients were female, and two were male. Five presented with abdominal pain, including three with suspected ruptured appendicitis. The other patient was asymptomatic and was detected by CT during routine follow-up for HBV-related liver cirrhosis and HCC. Only three patients received colonoscopy before surgery, with one showing negative findings, one showing a bulging appendix orifice (volcano sign), and one showing a submucosal mucocele. All six patients had a CT scan, and pre-operative CT correctly diagnosed one case as LAMN with PMP and three cases with suspected ruptured appendicitis. The lesion sizes ranged from 2.8 to 5.2 cm. Two patients underwent laparoscopic appendectomy, which was converted to open appendectomy, two underwent laparoscopic right hemicolectomy, and two underwent open right hemicolectomy. The pathological staging was Tis in two patients, T4a in two patients, and T4aN0M1b/c in each of one patient.

One of the patients with T4a but a fragmented appendix received laparoscopic right hemicolectomy with acellular mucin but no neoplastic cells 2 months later and remained free from PMP. Notably, one patient with PMP had received pigtail drainage of an abscess of suspected ruptured appendicitis 6 months earlier, but he declined appendectomy after discharge. Two patients with PMP received chemotherapy, but the disease progressed, and they finally underwent cytoreductive surgery and hyperthermia intraperitoneal chemotherapy (HIPEC).

Conclusions: Low-grade appendiceal mucinous neoplasm may not be as rare as previously reported because 6 cases were diagnosed within less than one and a half years in our institute. LAMN is difficult to diagnose preoperatively, and its definitive diagnosis often relies on direct observation during surgery and postoperative histopathological analysis of the specimen. Although surgical resection is the most direct treatment method, it is very important to crucially maintain the integrity of the tumor to avoid tumor rupture and the dissemination of neoplastic cells which can cause PMP.

P.87

PATIENT’S AGE AND AGE AT DIAGNOSIS ARE ASSOCIATED WITH INCONSISTENT ADHERENCE TO SURVEILLANCE COLONOSCOPIES IN IBD PATIENTS

Chang-Hung Liao, Tien-Yu Huang

Division of Gastroenterology, Department of Internal Medicine, Tri-service General Hospital, Taipei, Taiwan

病患年齡跟疾病診斷年齡影響發炎性腸 道疾病病患施行大腸鏡檢查意願

廖昶虹 黃天祐

三軍總醫院胃腸肝膽科

Background: Inflammatory bowel disease (IBD) is an umbrella term used to describe disorders that involve ulcerative colitis (UC) and Crohn’s disease (CD). Both of these diseases are characterized by chronic inflammation of the gastrointestinal (GI) tract and affect the patient’s quality of life. Colonoscopy or ileocolonoscopy is well established as the mainstay procedure for diagnosing IBD or monitoring the disease severity of IBD. Otherwise, there is no cure for IBD currently, so the goals of IBD management are to induce and maintain clinical and endoscopic remission, reduce the risk of complications, and improve quality of life. According to the STRIDE II consensus, endoscopic remission is the log-term target for IBD treatment. Therefore, the evaluation of mucosal status is crucial for IBD treatment, colonoscopy is essential for mucosal detection and tissue taking currently. Previous literature mentioned that cumulative extent of colonic inflammatory lesions and disease duration are risk factors for colorectal cancer in patients with inflammatory bowel disease. In Taiwan, patients with UC and CD have higher incidence rate of colorectal cancer (CRC) than general population. 0.19% of CD had incident colorectal cancers and 0.24% of UC had incident colorectal cancers. On the other hand, the cumulative probability of CRC is estimated at 0% after 10 years, 6% after 20 years, and 12.3% after 30 years of disease. Long term of colonoscopy surveillance is necessary for IBD patients in purpose of monitoring the severity of mucosal inflammation and surveilling the colitis-associated dysplasia or cancer. Many international gastroenterological societies and guidelines recommend that IBD patients need periodic colonoscopy. But colonoscopy

demonstrated the lowest acceptability among the IBD monitoring tools (including venipuncture, stools collection, ultrasonography, MRI and wireless capsule endoscopy). Painful sensation during colonoscopy is an inevitable problem for IBD patients and general patients. Previous literature had found that IBD patients had more discomfort than general population. Besides, bowel preparation is required before colonoscopy. Well bowel preparation is necessary for physicians to operate colonoscopy for patient especially for detecting lesions and observing mucosal healing. IBD patients reported significantly more burden during the bowel preparation phase than other patient group. Otherwise, only 62% of IBD patients had their colonoscopies at the recommended time. Sex, age of diagnosis, medications and insurance are associated with inconsistent adherence to surveillance colonoscopies.

Aims: The aim of this study was to analyze the IBD patient’s perception about bowel preparation, colonoscopy and attitude to examination interval. We compared the frequency between physician’s recommendation and patient’s tendency to evaluate the possible cause of inconsistent adherence to surveillance colonoscopies for IBD patients.

Methods: The study was conducted from July 2020 to May 2022. All patients with IBD scheduled for colonoscopy (including patient selecting painless colonoscopy) in Tri-Service General Hospital in Taiwan were invited to participate. Consenting participants were asked to complete questionnaires after the colonoscopy. The questionnaire was selfadministered by each patient and took approximately 20 minutes to complete.

Results: We further evaluated the correlation between the difference which was between doctor’s advice interval and patient acceptable frequency and the characteristics of the patients. We found that age, age at diagnosis and the difference between the two kinds of intervals had significantly negative correlation, and the correlation coefficient could reach -0.394 and -0.343 in patients selecting usual colonoscopy last time. Experience of previous of painless Colonoscopy had significantly positive correlation in the difference between the two kinds of intervals, in overall patients, west food and previous of painless Colonoscopy had significantly positive correlation with the difference between the two kinds of intervals but no significantly negative correlation was observed.

Conclusions: In conclusion, the study provides insights into patients’ experiences and attitudes

towards colonoscopy, bowel preparation and interval of examinations. Younger Age and younger Age at diagnosis would have more burden of bowel preparation and painful sensation after colonoscopy. Patients with longer disease duration tend to have less painful sensation when colonoscopy introduced and during examinations. Painless colonoscopy would be the option for group of younger Age and younger Age at diagnosis to adherence to colonoscopy recommend interval but extra expenses would be an affecting factor for patients. It also awarded doctors of IBD patients to establish appropriate colonoscopy following-up program for patients to reduce further complication and early diagnosis of CRC.

P.88

THE MANAGEMENT OF ACUTE MALIGNANT COLONIC OBSTRUCTION WITH SELFEXPANDABLE METAL STENTS

Chun-Nan Chen1, Chao-Lin Cheng1, Fat-Moon Suk1,2, Gi-Shih Lien1,2, Min-Shung Wu1,2, Tze-Sian Chan1,2

1Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

2Division of Gastroenterology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

以自膨式金屬支架治療急性惡性結腸阻 塞

陳俊男1 鄭照霖1 粟發滿1,2 連吉時1,2 吳明順1,2 張智翔1,2

1 臺北市立萬芳醫院消化內科

2 臺北醫學大學醫學系內科學科

Background: Acute colonic obstruction is encountered in 7-29% of patients with colorectal cancers. As emergency surgery carries high morbidity and mortality, stoma creations are usually done, but this represents a tremendous negative psychological impact and largely deteriorates the quality of life of the patients. Recently, self-expandable metal stents (SEMS) have emerged as alternative management. The European Society of Gastrointestinal Endoscopy recommends colonic stenting as a bridge to surgery strategy, as well as the treatment for palliation of malignant colonic obstruction. The National Health Insurance Bureau also approved the use of SEMS in patients with acute malignant colonic obstruction.

Aims: This study aims to evaluate the efficacy and safety of stent placement in obstructive colorectal cancer in a medical center in Nothern Taiwan.

Methods: Patients with acute colonic obstructive lesions due to malignant diseases who underwent endoscopic stent placement between April 2012 and June 2023 were enrolled. Data such as demographic characteristics, procedure indications, procedure time, complications, and outcomes were retrospectively analyzed.

Results: Eleven patients (6 female and 5 male) were enrolled in this clinical study. Most of the patients were referred by colorectal surgeons (6 patients,

54.5%), gastroenterologists (3 patients, 27.2%), and medical oncologists (2 patients, 18.2%). The mean age was 71.5 years old (range, 42-98 years). While all the patients suffered from malignant diseases causing colonic obstruction, interestingly, one of them was a patient with lung adenocarcinoma with colonic involvement (9%). Fifty-five percent of patients were stage IV patients. Most of the obstructing lesions were located in the sigmoid colon (63.6%), followed by descending colon (18.2%), descending colon (9.1%), and distal transverse colon (9.1%). Stent placement as a bridge to elective surgery was performed in 18.2% (n = 2) of patients and with palliation intent in 81.8% (n = 9). The time elapsed to surgery was 28 and 14 days. The stent implantation was successful in 9 of 11 attempts; the two cases with failure were due to technical difficulty in identifying the residual lumen for the guidewire to pass through (in one of them, the guidewire caused micro perforation). The average time required for the procedure was 34.44 minutes (range, 24-50 minutes). Complications related to the procedure included procedure failure in 2 cases (18.2%), perforation in 1 case (9.1%), and inadequate stent positioning requiring two stents in 1 case (9.1%). When stents were placed as a bridge to surgery, the average time between endoscopic procedure and surgery was 19.5 (13-26) days. In the palliative group, the stents lasted 172 days (range, 16-462 days).

Conclusions: SEMS placement in patients with acute colonic malignant obstruction is a safe procedure that can quickly palliate patients’ acute colonic distention, and improve patients’ quality of life. The majority of the patients received SEMS for palliative purposes in our group.

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THE CAPSULE RETENTION RATE IN PATIENTS WITH CROHN’S DISEASE UNDERGOING SMALL BOWEL CAPSULE ENDOSCOPY: A SINGLECENTER EXPERIENCE IN TAIWAN

Chu-Ping Wang1, Jen-Wei Chou1,2, Po-Ju Huang1, Yi-Hua Wu1

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University Hospital, Taichung, Taiwan

2School of Medicine, China Medical University, Taichung, Taiwan

克隆氏症患者膠囊內視鏡滯留率：中部 一醫學中心之經驗

王楚評1 周仁偉1,2 黃柏儒1 吳宜樺1

1 中國醫藥大學附設醫院消化醫學中心

2 中國醫藥大學醫學系

Background: Inflammatory bowel disease (IBD) is a condition of chronic inflammation of intestine which includes two kinds of disease, ulcerative colitis (UC) and Crohn’s disease (CD). Unlike UC, which mainly affects large intestine, CD can cause inflammation of any part of the gastrointestinal tract. Thus, the investigation of small intestine for patients with CD is important. Capsule endoscopy (CE) is a non-invasive procedure and makes the exploration of the small intestine easier than before. The main complication of the CE is capsule retention, and the retention rate was 4.6% to 8.2% in patients with established Crohn’s Disease underwent small bowel capsule endoscopy in published data.

Aims: The aim of this study was to investigate the retention rate of CE in patients who had CD in a teaching hospital in the middle of Taiwan.

Methods: We retrospectively reviewed the medical records from 1980 to September 2022. There were 105 cases diagnosed of CD and 40 cases had CE.

Results: We had reviewed 40 cases and none of them had patency capsule (PC) before the CE. There was 29 males and 11 females, with a male-to-female ratio of 1: 0.38. The mean age of first diagnosis was 35.9 years (range, 17-76 years). The mean initial Crohn’s Disease Activity Index (CDAI) was 368.2, ranged from 222.2 to 542.6 (2 missing data). All of them received at least of one of the following medications including

steroid, azathioprine, mesalazine, cyclosporine and MTX. 37 cases (92.5%) received at least one kind of biologic agents as treatment; 16 cases received adalimumab (40%), 9 cases vedolizumab (22.5%), 2 cases Infliximab (remicade) (5%), 3 cases Infliximab (remsima) (7.5%), 5 cases ustekinumab (12.5%), and 2 cases underwent clinical trial (5%). 22 patients (55%) received operation (small bowel resection, colectomy, repair of fistula, and one of them had total colectomy) before underwent CE. There were 36 patients (90%) had the capsule endoscopy pass through smoothly and 4 cases undertook capsule retention (10%). Among the 4 cases of capsule retention, they were all males and 3 cases had surgery before this procedure and one had not. (3 of 22 cases, 13.6%; 1 of 18 case, 6%; Odd ratios = 2.68). Three cases who had surgery included two had small bowel resection, and one had colectomy, and all of them had surgery 6 months before underwent capsule endoscopy, and one of them had Computed Tomography (CT) within six months before the CE study and showed mild bowel swelling without obstruction. For capsule removal, one patient received laparoscopic sugery for adhesiolysis, strictureplasty and CE removal. Other three patients received deep enteroscopy and the CE was successfully removed in 2 of them.

Conclusions: According to the results of our present study, the rate of CE retention in patient with CD was about 10%. The retention rate was higher than general population. The patient with CD had previously operation had higher retention rate than those who had no surgery before.

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THE EFFICACY OF BUDESONIDE MMX VERSUS PREDNISOLONE FOR ULCERATIVE COLITIS: A HOSPITALBASED STUDY

Wei-Chen Lin1, Chen-Wang Chang1, Horng-Yuan Wang1, Tzu-Chi Hsu2, Ming-Jen Chen1

1Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan

2Division of Colon and Rectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan

傳統類固醇與 Budesonide 在治療潰瘍性 結腸炎的療效：一項以醫院為基礎的研

究

林煒晟1 章振旺1 王鴻源1 許自齊2 陳銘仁1

1 台北馬偕紀念醫院胃腸肝膽科

2 台北馬偕紀念醫院大腸直腸科

Background: Budesonide MMX is superior to placebo for mild to moderate ulcerative colitis (UC) flares and has a favorable side effect profile. In routine clinical practice, budesonide-MMX is commonly used in combination with other therapies, both for disease flares and for partial response to therapy. It has been reimbursed in UC patients with catastrophic illness since 2019 in Taiwan.

Aims: The aim of this study was to assess the use of budesonide or prednisolone in real-life UC practice.

Methods: We performed a retrospective cohort study of patients with UC treated with oral steroid therapy at a tertiary medical center from January 2020 to October 2022. Demographic and clinical features of patients, disease course and concomitant therapy were recorded.

Results: In total, there were 47 UC patients received steroid therapy and 19 patients of them received Budesonide. In budesonide group, the mean age of 49.1 years and a mean partial Mayo Score of 4.8. Overall, 8 patients had extensive colitis, and 11 patients were left-sided colitis. After a mean duration of 1.8 months therapy, clinical remission was achieved in 6 out of 19 patients (31.6%) and clinical response in 11 patients (57.9%), whereas no response was reported in 2 patients (10.5%). When comparing with the prednisolone group, there were no difference in age, gender, comorbidity, disease

location and duration. The Budesonide group has less disease activity (P < 0.001) and previous prednisolone use (57.8% vs 89.2%, P = 0.013). The most common reasons of budesonide use were alternative use to biologics (36.8%) and partial response to previous therapy (31.6%).

Conclusions: In this real-life study, budesonide is commonly used in combination with other therapies in the mild to moderate UC patients. The effectiveness of budesonide in this study appears consistent with previously published trials.

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IDENTIFICATION OF POTENTIAL PROGNOSTIC GENETIC BIOMARKERS IN COLORECTAL CANCER PATIENTS UNDERGOING SURGICAL RESECTION AND 5-FLUOROURACIL-BASED ADJUVANT CHEMOTHERAPY

Hao Chien1, Yu-De Chu2, Wey-Ran Lin1,2

1Department of Hepatology and Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

大腸癌患者接受手術切除及 5- 氟尿嘧啶 為基礎的輔助化療潛在預後遺傳標誌物 鑑定

簡皜1 朱育德2 林蔚然1,2

1 林口長庚紀念醫院胃腸肝膽科 2 林口長庚紀念醫院肝臟研究中心

Background: Colorectal cancer (CRC) is the third most prevalent cancer worldwide and is commonly treated with surgical resection followed by adjuvant chemotherapy, typically utilizing a 5-fluorouracil (5-FU)-based regimen. However, there is a lack of reliable predictive markers, specifically single nucleotide polymorphisms (SNPs), for CRC patients who have undergone surgery and received 5-FUbased adjuvant chemotherapy.

Aims: This study aims to identify specific SNPs that can serve as predictive markers for the prognosis of CRC patients who have undergone surgical resection and received adjuvant chemotherapy based on 5-FU.

Methods: The study included an exploration cohort of 30 CRC patients, with 15 patients in each group representing good prognosis (no progression and no death for at least 5 years post-surgery and adjuvant chemotherapy) and poor prognosis (progression within 1 year post surgery and adjuvant chemotherapy). Genomic DNA was extracted from their samples and subjected to DNA microarray analysis for a genome-wide association study (GWAS).

Additionally, a validation cohort of 243 CRC patients who underwent surgical resection and adjuvant chemotherapy was included. SNP genotyping was performed using PCR and Sanger sequencing. The genotypes of the SNPs and clinicopathological

parameters were correlated with the patients’ clinical outcomes.

Results: The GWAS analysis revealed two independent SNPs, DNMBP-rs10786578 and GALNT14-rs62139523, that displayed potential associations with the prognosis of CRC patients who underwent surgical resection and received 5-FU-based adjuvant chemotherapy. In the validation cohort, the DNMBPrs10786578 “CC” genotype was identified in 27.7% of patients, the “CT” genotype in 54.4%, and the “TT” genotype in 17.9%. Regarding GALNT14rs62139523, the “AA” genotype was present in 14.2% of patients, the “AG” genotype in 53.3%, and the “GG” genotype in 32.5%. Univariate and multivariate Cox proportional hazard models demonstrated that the DNMBP-rs10786578 “CT” genotype, along with the level of carcinoembryonic antigen (CEA), could independently predict overall and progression-free survival. However, no significant difference in clinical outcome was observed among patients with different GALNT14-rs62139523 genotypes.

Conclusions: The DNMBP-rs10786578 “CT” genotype is associated with a favorable prognosis in CRC patients who have undergone surgical resection and received adjuvant chemotherapy based on 5-FU.

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TWO CASES OF THIERSCH’S PROCEDURE UNDER LOCAL ANESTHESIA FOR SUPER-ELDERLY PATIENTS WITH COMPLETE RECTAL PROLAPSE

Kazunari

Mado, Akiko Sugo, Yoko Mado

Mado Clinic, Tokyo, Japan

Background: Thiersch’s procedure (TP) is an old treatment first reported in 1891 by Carl Thiersch, it remains an important technique. We experienced two cases of TP under local anesthesia for super-elderly patients with complete rectal prolapse.

Aims: First case was 98-years old female, she had chronic heart failure, myelodysplastic syndrome, and chronic respiratory failure duo to bronchial asthma. Second case was bedridden 88-years old female with terminal dementia, cerebral infarction, and chronic heart failure. After several manual repositioning, it was no longer possible. Due to concerns regarding hospitalization and surgical safety, decided not to radical treat with general anesthesia, TP was performed under local anesthesia to recover various symptoms.

Methods: Following local anesthesia with 10 ml of 1% xylocaine in the right lateral position, four small incisions were made 1 cm outside the subcutaneous anal sphincter in the 5, 2, 11, and 8 o’clock positions; the subcutaneous tissue was then detached. Using curved Pean forceps, two nylon threads were passed through the outer perimeter of the external anal sphincter from the 5 o’clock incision. The threads were ligated so that the anal diameter was about 2 cm. The operation time was 10 minutes.

Results: Surgery successfully improved symptoms and recovered activities of daily living. Both patients had recurrence of rectal prolapse several months later and underwent the same procedure. After the second surgery, there was no recurrence until they died at home.

Conclusions: Due to the high recurrence rate associated with TP alone, it is often performed in combination with other procedures. TP can be performed anywhere under local anesthesia with simple surgical instruments. It is considered to be a good alternative in elderly and high-risk patients, in whom highly-invasive treatments and hospitalization are difficult. TP alone for high-risk patients with shortterm prognosis is considered appropriate treatment, especially in home medical care.

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CLINICAL OUTCOMES OF LATE CAPSULE ENDOSCOPY IN INPATIENTS WITH SMALL BOWEL BLEEDING: PROPENSITY SCORE MATCHING ANALYSIS

Cheolung Kim, Seung Min Hong, Dong Hoon Baek, Geun Am Song, Hyeon Tae Cho, Jeong Gil Park, Gwang Ha Kim, Bong Eun Lee, Moon Won Lee, Dong Chan Joo

Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea

Background: Capsule endoscopy is sometimes difficult to perform early due to various clinical situations. Aims: This study analyzed the clinical outcomes of late capsule endoscopy in inpatients with small bowel bleeding.

Methods: From 2010 to 2020, we retrospectively reviewed the medical records of 100 patients who underwent capsule endoscopy among inpatients hospitalized for small bowel bleeding. All patients were divided into two groups: the Early-48 group (n = 46), who underwent capsule endoscopy within 48 hours of the bleeding episode, and the Late-48 group (n = 54), who underwent capsule endoscopy more than 48 hours later. Using 1:1 propensity score matching (PSM) analyses, 34 pairs were made.

Results: In the unmatched cohort, there was no difference in baseline characteristics in both groups except for the number of cases requiring blood transfusion (82.6% vs. 61.1%, p = 0.032). There were no bleeding-related deaths in both groups. After the 1:1 PSM, there was no difference in yield for both groups to detect positive findings on capsule endoscopy (88.2% vs. 79.4%, p = 0.510), the need for intensive care unit (ICU) care (8.8% vs. 5.9%, p = 1.000), the amount of blood transfusion (4.2 ± 5.5 units vs. 3.6 ± 6.9 units, p = 0.698), and the number of recurrent bleeding episodes (0.5 ± 0.9 times vs. 0.8 ± 1.5 times, p = 0.279). When the patients were divided into two groups based on 72 hours and performed 1:1 PSM, the < 72 hour group showed a significantly higher yield to detect positive findings than the > 72 hour group (95.5% vs. 68.2%, p = 0.046). But there was no difference in other clinical outcomes.

Conclusions: Except for yield to detect positive findings, late capsule endoscopy in inpatients with small bowel bleeding is feasible in terms of patient survival and bleeding treatment.

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INVESTIGATING THE ASSOCIATION BETWEEN NON-ALCOHOLIC FATTY PANCREAS DISEASE AND METABOLIC SYNDROMES FROM A SINGLE MEDICAL CENTER AND REGIONAL HOSPITAL

Kuo-Chang Lee1,2,3, Hsu-Heng Yen2, Chien-Ning Huang3, Chih-Li Lin3

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Erlin Christian Hospital, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

3Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

於單一醫學中心與區域醫院經驗中，探

討分析非酒精性脂肪胰疾病與代謝症候 群之關聯性

李國彰1,2,3 顏旭亨2 黃建寧3 林志立3

1 二林基督教醫院肝膽胃腸科

2 彰化基督教醫院肝膽胃腸科

3 中山醫學大學醫學研究所

Background: Studies have shown the associations of non-alcoholic fatty pancreas disease with obesity, diabetes, hypertension, hyperlipidemia, hyperglycemia, pancreatic adenocarcinoma, and non-alcoholic fatty liver disease. A recent study demonstrated the strong associations in metabolic disorders, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic fatty pancreas disease. In recent consequences, non-alcoholic fatty liver disease (NAFLD) has been recommended as a metabolic parameter in the definition of metabolic associated fatty liver disease (MAFLD). The prevalence of fatty pancreas ranges from 11% to 35% in Asian populations. However, the prevalence of nonalcoholic fatty pancreas disease and its relations with metabolic syndromes remain unclear in the Taiwan population. The aim of this study was to investigate the association between non-alcoholic fatty pancreas disease and metabolic syndromes.

Aims: To investigate the relation between nonalcoholic fatty pancreas disease and metabolic syndromes.

Methods: This research is a prospective study, by

case-control design, in Changhua Christian Hospital and Erlin Branch Hospital. The date is November 2022 to 2023. The total number of patients is 39. The case number of non-alcoholic fatty pancreas disease (FP) is 27, and the case number for healthy control (NFP) is 12. We used the abdominal sonography to distinguish the fatty pancreas and the normal pancreas, exclude the group with chronic kidney disease or impaired renal function. Data from leukocytes, medical chart, age, gender, waist circumference, BMI, and biochemistry were analyzed.

Results: The mean age of non-alcoholic fatty pancreas disease patients (FP) is 51.8 years, the mean age of healthy control patients (NFP) is 38.5 years. In table 1, we compared with non-alcoholic fatty pancreas disease patients (FP) and healthy control patients (NFP). There is statistically significant in waist circumference (WC: 90.7 cm versus 72.9 cm), body weight (BW: 73 kg versus 53 kg), BMI (28.4 vs 21.4), systemic pressure (SP: 134 mmHg versus 113 mmHg), glucose AC (101 mg/dL versus 90 mg/dL), HbA1c (5.7% versus 5.3%), triglyceride (TG: 107 mg/ dL versus 55 mg/dL). In the group of non-alcoholic fatty pancreas disease (FP), 14 patients (51.9%) with diagnosed metabolic syndromes. In the group of healthy control patients (NFP), only 1 patient (8.3%) with diagnosed metabolic syndromes. In Figure 1, compared to the groups between FP and NFP, which showed the statistically significant difference in waist circumference (WC) and body weight (BW).

Conclusions: In this research, the prevalence of metabolic syndromes in patients with non-alcoholic fatty pancreas disease is relatively high. There is a close association between NAFPD and MetS in the Taiwan population. In the future, we need to collect more samples to analyze the association between non-alcoholic fatty pancreas disease and metabolic syndromes to find out the real mechanism.

P.95

CLINICAL MANIFESTATION OF PATIENTS WITH GALLBLADDER CANCER DIAGNOSED BY PATHOHISTOLOGY: EXPERIENCE OF ONE MEDICAL CENTER

Zhi-Che Chen1, Ming-Lun Han2, Hsiu-Po Wang3, Yao-Ming Wu4

1Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan

3Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

4Department of Surgery, National Taiwan University Cancer Center, Taipei, Taiwan

經由病理組織學診斷膽囊癌之臨床表 現：單一醫學中心的經驗

陳知澈1 韓明倫2 王秀伯3 吳耀銘4

1 國立臺灣大學醫學院附設醫院內科部

2 國立臺灣大學醫學院附設醫院綜合診療部

3 國立臺灣大學醫學院附設醫院外科部

4 國立臺灣大學醫學院附設醫院癌醫中心分院外科部

Background: Progressive growth of gallbladder polyps is previously thought to be a risk factor of gallbladder cancer. However, emerging data have shown that gallbladder polyps, despite their nature of slow growth, do not appear to be associated with future development of gallbladder cancer. The initial presentation and clinical manifestation of gallbladder cancer patients in Taiwanese population is not clear.

Aims: The aim of this pilot study is to evaluate the most common manifestation of gallbladder cancers, and if gallbladder polyps are identified prior to pathohistological diagnosis of gallbladder cancers.

Methods: Consecutive pathology reports showing gallbladder cancers from pathohistology between 2020 and 2022 in National Taiwan University Hospital were retrospectively analyzed. Cases diagnosed as gallbladder cancer due to invasion of gallbladder from nearby malignancies were excluded. The clinical presentation, lab data, and abdominal sonography findings before pathohistology proof were collected from electric medical records.

Results: In total, 28 patients with primary gallbladder cancers were included; 7 (25%) of which are

intracholecystic papillary neoplasms, and the others are adenocarcinomas. The most common clinical presentations are abdominal pain (14 cases, 50%) followed by obstructive jaundice (5 patients, 17.9%) and incidental finding (4 patients, 14.3%). Sonography reports could be found in 20 patients (71.4%) prior to pathohistology proof, with the most common findings being GB stone(s) (7 patients, 25%) followed by gallbladder wall thickening (6 patients, 21.4%) and gallbladder polypoid lesions or mass, at least 2.2 cm in size (6 patients, 21.4%). Six of the 28 patients had abdominal sonography at least 3 months before the diagnosis of gallbladder cancer, but only 1 presented with a gallbladder polyp (initially 1.0 cm in size). Of the 18 patients tested with serum CEA and CA19-9, 5 (27.8%) show elevation in both CEA and CA19-9, 11 (61.1%) show elevation in either CEA or CA19-9, and 2 (11.1%) show neither elevation in CEA nor CA19-9.

Conclusions: Our retrospective study shows the most common clinical presentation of gallbladder cancer diagnosed from pathohistology is abdominal pain. Gallbladder cancers resulting from gallbladder polyp(s) progression, identified by regular follow-up of abdominal ultrasonography, are uncommon.

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PANCREATIC FIBROSIS PRECEDING AND PREVALENT IN PANCREATIC ADENOCARCINOMA POPULATION: A STUDY BASED ON COMPUTED TOMOGRAPHY

Chung-Tsui Huang1, Jian-Ling Chen2, Tzong-His Lee1, Cheng-Kuan Lin1

1Division of Gasteroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei City, Taiwan

2Department of Radiology, Far Eastern Memorial Hospital, New Taipei City, Taiwan

胰臟纖維化早先於且盛行於胰臟腺癌族 群：以電腦斷層為主的研究

黃種粹1 陳健翎2 李宗熙1 林政寬1

1 亞東紀念醫院肝膽胃腸科

2 亞東紀念醫院影像醫學科

Background: Pancreatic fibrosis is common in pancreatic duct adenocarcinoma studied by image method or surgical specimen. Theoretically, pancreatic fibrosis is an oncogenic organic status. However, there was few evidence proving pancreatic fibrosis preceding the pancreatic adenocarcinoma.

Aims: The primary aim of this study is to investigate patients with comparable computed tomography images to show pancreatic fibrosis existing prior to pancreatic adenocarcinoma and survey its prevalence in pancreatic adenocarcinoma population. The secondary aim is to characterize the pancreatic adenocarcinoma patients with pancreatic fibrosis.

Methods: The method is retrospectively to survey pancreatic adenocarcinoma population between 2018 and 2020. The computed tomography and medical charts were reviewed. The pancreatic fibrosis is defined by non-contrast computed tomography number (Hounsfield unit) of pancreatic non-tumoral part at least 40 or pancreas extreme atrophy that computed tomography number unmeasurable.

Results: 112 patients registered as pancreatic adenocarcinoma in Far-Eastern Memorial Hospital between 2018 and 2020 were enrolled. Five patients had comparable previous computed tomography and four of them (80 percent) showed pancreatic fibrosis long (21 to 46 months, median 38 months) before the diagnosis of pancreatic adenocarcinoma. The prevalence of pancreatic fibrosis was 70.5% (N

= 79) in pancreatic adenocarcinoma population. The proportion of pancreatic fibrosis is statistically not different between early (I, II) and late (III, IV) stages of pancreatic adenocarcinoma. In pancreatic fibrosis subgroup, CA 19-9, diabetes mellitus and alcohol history are higher as comparing to non-fibrosis counterpart.

Conclusions: In conclusion, the pancreatic fibrosis existed long before the pancreatic adenocarcinoma in some patients. Pancreatic fibrosis is prevalent in 70.5% of pancreatic adenocarcinoma population. Pancreatic adenocarcinoma patients with pancreatic fibrosis are with higher CA 19-9 level, diabetes mellitus and alcohol history ratios.

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TREATMENT RESULTS OF ERCP USING SMALL-CALIBER LONG COLONOSCOPY FOR CHOLEDOCHOLITHIASIS AND CHOLANGITIS IN PATIENTS WITH ROUX-EN-Y ANASTOMOSIS

Hikaru Kakimoto, Maki Matsui, Takeo Watanabe, Nagisa Noborikawa, Shigeyuki Kurosaki, Toru Arano, Kazuaki Tejima

Department of Gastroenterology, The Fraternity Memorial Hospital, Tokyo, Japan

Background: Balloon enteroscopy are often used for treatment for choledocholithiasis and cholangitis. However many hospitals do not have a balloon enteroscopy. In such cases, it is difficult to treat using endoscopy.The other, there have been reports of attempts to perform ERCP using small-calibre colonoscopy for patients with Roux-en-Y anastomosis.

Aims: To investigate whether it is possible to treat choledocholithiasis and cholangitis in patients with Roux-en-Y anastomosis using small-caliber long colonoscopy.

Methods: From January 2021 to June 2023 in our hospital, 17 cases were treated for choledocholithiasis and cholangitis in patients with Roux-en-Y anastomosis using small-caliber long colonoscopy. The success rate of reaching the major papilla, the technical success and the complication rate were retrospectively evaluated for these cases.

Results: The success rate of reaching the major papilla was 94% (15/16) and the success rate of the technical success was 81% (13/16). The complication rate was 6% (1/16). One case was mild pancreatitis.

Conclusions: With a success rate of over 80%, it can be first choice to perform ERCP using smallcalibre long colonoscopy for choledocholithiasis and cholangitis in patients with Roux-en-Y anastomosis at the hospital that do not have a balloon endoscope.

P.98

ANALYZING FACTORS OF RESECTED PANCREATIC SEROUS CYSTADENOMA: A MULTICENTER ANALYSIS

Jeong Gil Park, Moonwon Lee, Hyeon Tae Cho, Cheolung Kim, Jonghyun Lee, Hyeong Seok Nam, Hoonsub So, Dong Kyun Kim, Jung Wook Lee, Byung Soo Kwan, Choi Jung Sik, Geun Am Song, Seun Ja Park, Dong Uk Kim

Pusan National University Hospital, Ulsam National University Hospital, Inje University

Haeundae Paik Hospital, Gosin University Gospel Hospital

Background: About 30% of patients who were treated by resection as pancreatic tumors are evaluated as pancreatic cystic neoplasm. These include serous cystadenoma (SCA), Mucinous cystic neoplasm (MCN), and Intraductal papillary mucinous neoplasm (IPMN). Among them, SCA had a very low cancer progression rate of less than 0.1% in multi-organ studies. Therefore, patients without symptoms do not undergo surgery. However, surgery is sometimes performed because SCA is difficult to distinguish from other cystic lesions and malignant tumors.

Aims: This study evaluated factors that help differentiate pancreatic cystic tumors.

Methods: A total of 55 patients were retrospectively studied at 7 hospitals (6 tertiary hospitals and 1 secondary hospital) for 10 years from 2012 to 2021. All patients were diagnosed with SCA after surgery.

Results: Of a total of 55 patients, only 13 were diagnosed with preoperative SCA by evaluation. As for the cause of the surgery, 34 (61.81%) were uncertain about the diagnosis, and 12 (21.82%) increased the size of the cyst. Among the radiologic differences between patients diagnosed with SCA and those diagnosed with non-SCA, there were significant differences in septation (p = 0.029), enhancement (p = 0.003), and sclerosis (p = 0.045). There were no significant differences in the size, number, shape, location of cysts, radiologic properties of the pancreas (calcification, solid portion, pancreatic or bile duct dilatation, wall thickness, atrophy), and laboratory tests (blood CEA, CA 19-9, Amylase, Lipase).

Conclusions: There are ongoing efforts to identify SCA patients who do not need surgery. In this study, septation, enhancement, and sclerosis were helpful in discrimination, but the distinguishment is still

difficult. Although this study has the advantage of being conducted in multiple institutions, more additional studies are needed due to the small number of patients included.

P.99

EFFICACY OF RECOMBINANT HUMAN SOLUBLE THROMBOMODULIN IN TREATMENT FOR SEVERE ACUTE PANCREATITIS PATIENTS WITH DIC

Takeo Watanabe, Maki Matsui, Hikaru Kakimoto, Nagisa Noborikawa, Shigeyuki Kurosaki, Toru Arano, Kazuaki Tejima

Department of Gastroenterology, The Fraternity Memorial Hospital, Tokyo, Japan

Background: Imaging evaluation (CT) is used as a method for evaluating severity of acute pancreatitis (AP) and disseminated intravascular coagulation (DIC) is another indicator. DIC means worse condition. If AP becomes severe, early diagnosis and appropriate treatment can improve the condition. In Japan, recombinant human soluble thrombomodulin (rTM) are used for DIC.

Aims: We evaluated the therapeutic effects of rTM for severe AP.

Methods: We retrospectively evaluated 85 patients with AP who were admitted to our hospital from September 2020 to May 2023. We examined causes of AP, CT grade and DIC score on the admission day, and with or without DIC during hospitalization by Japanese guidelines. We compared the time until the start of diet resumption as an indicator of recovery from AP.

Results: Twenty-four patients (28%) were diagnosed with DIC in hospitalization (DIC group). DIC was diagnosed an average of 1.5 days after admission, and 22 (92%) were diagnosed within 2 days. The average DIC score at admission was significantly higher in the DIC group than in the non-DIC group (1.8 vs. 0.6 (p < 0.01)). The score at the diagnosis of DIC was 4.2. CT showed grade 1 (mild) in 42 patients, of which 3 (7%) developed DIC. Grade 3 (very severe) cases were 6 patients, of which 3 were DIC (50%). Of the 37 grade 2 (severe), 18 developed DIC (49%). When comparing the DIC and non-DIC groups, the causes were gallstones (10 vs. 6), alcohol (7 vs. 8), idiopathic (0 vs. 4), and others (1 vs. 1). No significant differences were observed. There were no significant differences in the number of days until resumption of meals, with a mean of 8.3 days vs. 6.2 days (p = 0.20).

Conclusions: In severe CT grade 2 AP, the diagnosis of DIC is important. We suggest that rTM may prevent progression of pancreatitis.