九 ) Impacts of the Tumor Microenvironment on GI-cancer Therapy

專題討論（九）

Impacts of the Tumor Microenvironment on GI-cancer Therapy

IMPACTS OF THE PANCREATIC MICROENVIRONMENT ON ANTIPANCREATIC CANCER THERAPY 陳立宗 國家衛生研究院

Pancreatic cancer is a detrimental malignant disease. Aggressive tumor biology, relatively lack of specific symptoms/signs in early stage, the difficulty in detection by regular in-hand imaging facilities, such as abdominal ultrasonography, and the lack of awareness of the disease are all potential causes for the delay diagnosis of this highly malignant tumor. At time of diagnosis 80-85% of patients presented with unresectable locally advanced or metastatic diseases, while majority of the rest 15-20% of patients who underwent curative surgical resection would suffer from systemic and/or local relapse. However, in the era of precision medicine, only a small proportion of pancreatic cancer patients could benefit modern targeted and/or immunotherapy, such as those with tumor harboring germ-line BRCA1/2 mutation (maintenance PARP-1 inhibitor), and MSI-H or TMB-H(second-line anti-PD-1 inhibitor) Systemic chemotherapy, front-line FOLFIRINOX, nalpaclitaxel plus gemcitabine and S-1-based regimens, and second-line liposomal irinotecan plus infusion 5-FU/LV, remain the main treatment strategies for advanced pancreatic cancer in clinical practice setting. Without breakthrough improvement in the screening, diagnosis and management strategies, the progress in managing pancreatic cancer was slow with an overall 5-year survival rate of 8% globally.

One of the unique pathological features of pancreatic cancer is the presence of a highly fibrotic tissue surrounding cancer cells, the desmoplastic stroma, which is conceived to attribute significantly to the aggressive biological behavior and chemo-/ radiotherapy resistance of the tumor. Unfortunately, several stromal targeting therapies, such as matrix metalloproteinases, hedgehog inhibitor, hyaluronidase, hypoxia-activating chemotherapy, and a bunch of immunotherapy have failed to demonstrate survival benefit for advanced pancreatic cancer in phase 3 trials. With the advance of modern biomedical technologies, the interactions among various stromal cells, immune cells and cancer cells are dissected more dedicatedly, which may provide the second chance for developing stromal-targeting therapy in pancreatic cancer.

專題討論（九）

Impacts of the Tumor Microenvironment on GI-cancer Therapy

IMPACTS OF THE LIVER MICROENVIRONMENT ON ANTI-HCC THERAPY 許 駿 臺大醫院

Research of HCC microenvironment used to focus on how liver inflammation caused by different etiologies promoted carcinogenesis and tumor progression. The advance in immune checkpoint inhibitor (ICI)-based combination therapy opened a new territory of research focusing on immune modulation in the tumor microenvironment to identify relevant mechanisms of drug resistance and to explore new therapeutic targets. In this presentation, the potential impact of HCC etiologies on immune modulation of HCC microenvironment will be discussed. Results from biomarker exploration using data from clinical trials of ICI-based therapy will be used to illustrate how our knowledge of the HCC microenvironment may lead to a new era of precision medicine for patients with different stages of HCC.

專題討論（九）

Impacts of the Tumor Microenvironment on GI-cancer Therapy

TARGETING CANCER STEM CELLS FOR HCC CONTROL 戴明泓 國立中山大學

Hepatocellular carcinoma (HCC) accounts for about 80% of liver cancers and is one of the most common malignancies worldwide. The prognosis for patients with advanced HCC remains poor despite the advancement of target therapies such as sorafenib. Recent evidence indicates the emergence of hepatic cancer stem cells (hCSC) may account for the resistance of HCC to sorafenib. In this study, we will explore the feasibility of using Celecoxib, a COX-2 inhibitor and non-steroidal anti-inflammatory drug, as a hCSC-targeting strategy to enhance the therapeutic efficacy of sorafenib. Celecoxib potently suppressed the self-renewal and drug-pumping functions in HCC cells by depleting hCSC population. Celecoxib therapy inhibited progression of rat Novikoff hepatoma and prolonged the survival rate of rats with hepatoma. Histological analysis revealed that celecoxib therapy reduced the abundance of CD44+/CD133+ hCSCs in hepatoma tissues. Besides, the hCSCs depletion was associated with elevated apoptosis and blunted proliferation and angiogenesis in hepatoma. Finally, it was delineated that activation of peroxisome proliferator-activated receptor γ/PTEN signaling contributed to Celecoxib-induced hCSC suppression. Thus, celecoxib-mediated PTEN upregultion may represent a novel hCSC-targeting strategy for HCC therapy.

專題討論（九）

Impacts of the Tumor Microenvironment on GI-cancer Therapy

INTERPLAY BETWEEN COLORECTAL CANCER STEM CELLS AND THE TUMOR MICROENVIRONMENT 楊慕華 國立陽明交通大學

Cancer stem cells (CSCs) have been shown to be responsible for the tumor initiation, metastasis, and therapeutic resistance of colorectal cancer (CRC). In recent year, we focus on the mechanisms for engendering stemness of CRC and the interplay between tumor microenvironments and colorectal cancer stem cells (CRCSC). We found that the EMT transcriptional factor Snail upregulates IL-8 to induce stem-like properties of CRC. Snail coordinates symmetrical division of CRCSC for expanding the stem cell pool of late-stage CRC. Furthermore, we found that the chromatin modifier ARID3B activates

the expression of intestinal stem cells genes and PD-L1 through a noncanonical Notch pathway. Regarding the communications between CRCSC and microenvironments, we demonstrate that the CRCSCderived exosomal miR-146a is a major exosomal miRNA for enriching tumor-infiltrated neutrophils. CRCSC-secreted exosomal tri-phosphate RNAs induced the expression of IL-1β to sustain neutrophil survival. CRCSC-secreted CXCL1 and CXCL2 attracted CRCSC-primed neutrophils to promote tumorigenesis of CRC cells. In summary, our studies demonstrate the interplay between CRCSC and tumor-infiltrated neutrophil through tumor-derived exosomes, which sustains the immunosuppressive microenvironment of CRC for tumor progression.

消化系基層醫療論壇

腸胃科執業的臨床陷阱 PITFALLS IN GI PRACTICE 張延亙 永安診所

Small hepatocellular carcinoma may not be correct diagnosis in non-cirrhotic HBV infection; therefore, regular sonography follows up every 6 months is recommended in GI primary care. Alfafetoprotein, as the tumor marker of HCC, defined as normal range below 10~20 ng/ml. however, alfafetoprotein was found elevation in some hepatitis exacerbation. Abdominal CT may be necessary in certain condition, but the actual value of alfafetoprotein is not clear. We present an young women with HBV infection, who had mild elevation of alfafetoprotein, but sonography can’t found any Hepatic tumor, we suggest abdominal CT in Cheng-Ching Hospital, small hepatic tumor, found at the right lobe near surface. Surgical intervention was done immediately.

Antivirus treatment for HBV reduced the risk of HCC, ESAL recommend entecavir may be discontinued until HBsAg loose. Here, we present a 56 year old male received entecavir for 8 years and HBsAg loose was detected. Therefore, we decided to discontinued entecavir. However, sonography showed HCC after 12 month later. Intensive follow up include abdominal sonography and CT scan may be necessary in high risk group, even HBsAg loose is achieved.

一般演講

主題：C 型肝炎（一） ①

全口服抗病毒藥治癒之慢性 C 肝進階性纖 維化患者在使用不同非侵入工具定義纖維化 有不一樣的肝癌風險 DISTINCT HEPATOCELLULAR CARCINOMA RISKS IN TREATED CHRONIC HEPATITIS C PATIENTS WITH DIFFERENT DEFINITIONS OF ADVANCED CHRONIC LIVER DISEASE

劉彥君1,2 徐正二1,2 鄭雅婷1,2 蘇崇維1,2 戴佳虹1,2 陳益程1,2 謝彝中1,2 滕威1,2 鄭文睿1,2 林俊彥1,2 簡榮南1,2 戴達英1,2 沈一嫻1,2 林口長庚紀念醫院1 長庚大學2

Background: To identify target population for hepatocellular carcinoma (HCC) is an important issue in chronic hepatitis C (CHC) patients after antiviral treatment. Advanced chronic liver disease (ACLD) patients have been suggested by the guideline as the target surveillance group for their remnant HCC risk after sustained virological response (SVR). However, the definition of ACLD composed of different diagnostic tools including liver stiffness measurement (LSM), FIB-4 or both or by ultrasonography image. Aims: This study aims to compare the predictability of HCC among CHC patients with SVR who meet ACLD criteria by different diagnostic measurements. Methods: CHC achieved SVR by interferon-free direct acting anti-viral agents (DAA), whose LSM by transient elastography (TE, Fibroscan) and FIB-4 index were both available before DAA therapy were enrolled. The ACLD was defined as LSM >10 kPa and/or FIB-4 >3.25 and/or ultrasound signs of cirrhosis. Predictabilities for HCC and 3-year cumulative HCC incidences were compared among four groups of ACLD patients diagnosed by different noninvasive assessments (group A: FIB-4>3.25 but LSM ≦ 10; group B: FIB-4 ≦ 3.25 but LSM>10; group C: FIB-4 >3.25 + LSM>10; group D: FIB-4 ≦ 3.25 and LSM ≦ 10 but ultrasonography showed cirrhosis.). Results: Among 1600 enrolled patients, 922 (58%) patients met criteria of ACLD (group A, N=128; group B, N=369; group C, N=406; group D, N=19). The mean age was 62 years old, 41% was male and 63% was genotype 1. The annual incidence and 3-year cumulative HCC incidences showed 0.3% and 0.8%, 2.2% and 4.6%, 3.8% and 9.1% and 3.9% and 10.5% in patients with group A, group B, group C and group D (Log-rank p<0.01), respectively (Figure). The negative predictive values (NPVs) for HCC were all the above 95% among these four groups with different ACLD definitions, while the sensitivity was much higher in group C of 62.5% compared to group A (1.4%), B (27.8%) and D (2.8%). Conclusions: LSM >10 kPa or/and FIB-4 >3.25 are more appropriate criteria for ACLD than FIB-4 >3.25 alone which PPV is only 0.8% and its 3-year HCC cumulative incidence be approximate to that of the non-ACLD (0.4%). Those with echo appeared cirrhotic features but not fit the criteria of ACLD due to LSM<10kPA and FIB-4<3.25 were still at high risk of HCC and also shall be under HCC surveillance program.

②

C 型肝炎血液透析患者經抗病毒治療後達成 持續性病毒反應後 (SVR) 再度感染 C 型肝 炎之風險研究 HEPATITIS C VIRUS REINFECTION IN PATIENTS ON HAEMODIALYSIS AFTER ACHIEVING SUSTAINED VIROLOGIC RESPONSE WITH ANTIVIRAL TREATMENT

陳嘉國1 劉振驊1,2 彭成元3 高偉育1 楊勝舜3 施宇隆1 林志陵1 蔡孟昆1,4 李志元1 張君照1 吳若玄5 劉俊人1 蘇東弘1 曾岱宗1 陳培哲1 高嘉宏1 臺大醫院內科部1 臺大醫院雲林分院內科部2 中國醫藥大學消化內科3 臺大醫院外科部4 美國加州大學聖地牙哥分校5

Background: Data are limited regarding the risk of hepatitis C virus (HCV) reinfection after treatmentinduced sustained virologic response (SVR) in patients on haemodialysis Aims: To assess the risk of HCV reinfection among patients on haemodialysis with treatment-induced SVR Methods: Patients on haemodialysis patients who achieved SVR12 with interferon (IFN) or direct-acting antiviral (DAA)-based treatment received followup at SVR24 and then biannually with HCV RNA measurements. HCV reinfection was defined as the resurgence of viremia by different viral strains beyond SVR12. The low-risk general population who achieved SVR12 and who underwent the same post-SVR12 surveillance served as the reference group. Crude reinfection rates per 100 person-years (PYs) were calculated. Multivariate Cox regression analysis was performed to estimate the relative risk of HCV reinfection between the two groups. Results: We recruited 374 patients on haemodialysis and 1571 reference patients with a mean post-SVR12 followup of 4.7 and 6.1 years. All haemodialysis patients who achieved SVR12 a lso a chieved S VR24. The incidence rates of HCV reinfection were 0.23 per 100 PYs (95% confidence interval [CI]: 0.09-0.59) in haemodialysis patients and 0.16 per 100 PYs (95% CI: 0.10-0.26) in the reference group. The risk of HCV reinfection in patients on haemodialysis was comparable to that in the reference patients (hazard ratio [HR]: 1.39; 95% CI: 0.44-4.38, P = 0.57). Conclusions: The risk of HCV reinfection in patients on haemodialysis who achieve SVR12 is low and comparable to that in the low-risk general population. HCV microelimination in this special population is feasible once universal screening and scaled-up treatment are implemented.

③

在 COVID-19 流行期間經由轉診模式達到美 沙酮治療患者 C 肝微根除 EMPOWERING METHADONE MAINTENANCE TREATMENT PATIENTS FOR HCV MICROELIMINATION WITH ADVANCED REFERRAL MODEL DURING THE COVID-19 ENDEMIC

戴啟明1 陳志城1 陳子皓1 曾政豪1 許耀峻1 余明隆2 義大醫院胃腸肝膽科1 高雄醫學大學附設中和紀念醫院肝膽胰內科2

Background: Although HCV prevails in methadone maintenance treatment (MMT) patients, the majority of MMT patients do not receive anti-HCV therapy. Aims: This study aimed to achieve HCV micro-elimination in MMT center through an integrated referral model during Coronavirus disease 2019 (COVID-19) endemic. Methods: Our referral model comprised two stages, conventional referral and on-site HCV RNA testing. On-site HCV RNA testing was applied to patients after conventional referral failure. According to the endemic status of COVID-19 in Taiwan, study period was divided into endemic period (from February 2020 to June 2020) and non-endemic period (from July 2020 to December 2020). HCV micro-elimination was defined as >90% of the HCV-infected patients diagnosed and >80% of the HCVviremic patients treated in MMT center. Results: Between January 2020 and January 2021, a total of 305 MMT patients were enrolled. At the screening, 275 (90.2%) patients were anti-HCV seropositivite. Of the 275 anti-HCV-seropositive patients, 86 (31.3%) did not need referral, including 12 were HCV RNA-seronegative and 74 had successful antiviral therapy (22 interferonbased therapy and 52 direct-acting antiviral (DAA) therapy). Of the 189 HCV-infected patients who needed referral, accumulative percentage of patients receiving HCV RNA testing increased from 93 (49.2%) patients by conventional referral to 168 (88.9%) patients by on-site HCV RNA testing (p<0.001). Of the 138 HCV-viremic patients, accumulative percentage of patients receiving DAA therapy increased from 77 (55.8%) patients by conventional referral to 129 (93.5%) patients by on-site HCV RNA testing (p<0.001). Eventually, the overall rates of HCV RNA testing, HCV treatment uptake and sustained virological response in 275 HCV-infected subjects were 92.4% (254/275), 95.8% (203/212) and 94.1% (191/203), respectively. In contrast to fewer non-MMT patients with successful linkage to care in endemic period, monthly HCV case number with successful linkage to care from MMT patients was significantly higher in endemic period than that in non-endemic period (15.2± 5.2 vs 9.2±2.9; P=0.036). Conclusions: Our integrated referral model could overcome the impact of COVID-19 and achieve HCV micro-elimination in MMT center in DAA era. On-site HCV RNA testing significantly increased HCV treatment uptake after conventional referral failure.

④

台灣原住民鄉慢性 C 型肝炎的根除 - 逐村肝 病篩檢及連結外展肝病專科醫生門診的照護 模式 HEPATITIS C VIRUS ELIMINATION IN TAIWAN RURAL INDIGENOUS TOWNSHIPS: VILLAGE-BY-VILLAGE SCREENING AND LINKING TO OUTREACH HEPATOLOGY CARE

田惠民1 鄭泰春2 連筱筑1 楊貴妃2 施丞貴3 陳柚陵4,5

許念慈4,5 盧勝男4,5 王景弘4,5 來義鄉衛生所1 牡丹鄉衛生所2 屏東縣政府衛生局3

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4 高雄市肝病防治協會5

Background: Medical resources are limited for hepatitis C virus (HCV) elimination in rural indigenous areas of Taiwan. Aims: The study aimed to investigate liver disease risk and conduct HCV elimination program in two rural indigenous townships. Methods: A program of village-by-village screening tests was conducted including hepatitis B virus surface antigen (HBsAg), antibody to HCV (anti-HCV) and gammaglutamyl transferase (GGT), and linking to outreach hepatology care at two indigenous townships (Laiyi and Mudan). Adult residents were invited to join this program. One hepatology specialist assessed liver disease risk, provided HCV treatment counselling and initiated direct acting antivirals (DAA) at outreach hepatology clinic in primary health centers. Results: A total of 3503 residents attended this program with a screening coverage of 73.5%. The prevalence of HBsAg, anti-HCV, and high GGT level was 8.2%, 10.0% and 19.5%, respectively. Laiyi had significantly higher prevalence of anti-HCV than did in Mudan. While males had significantly higher prevalence of HBsAg and high GGT in both townships, females in Laiyi had higher antiHCV prevalence. HBsAg and high GGT prevalence were peaked at 40-59 years of age and anti-HCV prevalence increased significantly by age. Two hundred and sixtythree residents visited outreach hepatology clinic for HCV treatment evaluation, with 121 (46%) residents having active HCV while 116 received DAA with 111 (95.7%) achieving HCV elimination. Conclusions: For rural indigenous townships, HCV infection and alcohol consumption were two major liver disease risks, and HCV elimination was achieved by the model of village-by-village screening and linking to outreach hepatology care.

⑤

慢性 C 肝在全口服抗病毒藥物治癒後纖維 化改變之肝癌風險變化 HEPATOCELLULAR CARCINOMA RISKS OF LIVER FIBROSIS CHANGES AFTER VIRAL ERADICATION IN CHRONIC HEPATITIS C PATIENTS

劉彥君1,2 徐正二1,2 鄭雅婷1,2 蘇崇維1,2 戴佳虹1,2 陳益程1,2 謝彝中1,2 滕威1,2 鄭文睿1,2 林俊彥1,2 簡榮南1,2 戴達英1,2 沈一嫻1,2 林口長庚紀念醫院1 長庚大學2

Background: Hepatocellular carcinoma surveillance is suggested for chronic hepatitis C (CHC) patients with advanced chronic liver disease (ACLD) by the guideline. It is reported liver fibrosis in patients with advanced fibrosis or cirrhosis can be reversed after viral eradication by direct acting antivirals (DAA). Aims: The study aims to investigate the HCC risks among CHC sustained virological response (SVR) patients with fibrosis regression, stationary or progression after SVR, and predictors for ACLD regression. Methods: CHC achieved SVR by interferon-free DAA, whose LSM by transient elastography (TE, Fibroscan) and FIB-4 index were both available before DAA therapy and after SVR were enrolled. The ACLD was defined as LSM >10 kPa and/or FIB-4 >3.25 and/or ultrasound signs of cirrhosis. The 3-year cumulative HCC incidences were compared among four groups of dynamic fibrotic changes (group A: both pre-DAA and post-SVR timepoints: nonACLD; group B: pre-DAA non-ACLD progressed to postSVR ACLD; group C: pre-DAA ACLD regressed to postSVR non-ACLD; group D: both pre-DAA and post-SVR: ACLD). Logistic regression was applied to find predictors for ACLD regression. Results: There were 906 patients (group A: 378 (42%), group B: 18 (2%), group C: 153 (17%), group D: 357 (39%) enrolling into the study with mean age of 62 years old, 38% of male and 92% of genotype 1. The 3-year cumulative HCC incidences showed 0.5%, 0%, 2.6% and 10.4% in patients with group A, group B, group C and group D (Logrank p<0.01), respectively (Figure). Logistic model showed that higher baseline ALT [adjusted OR (aOR): 1.006 (95% CI: 1.002-1.010), p=0.007] was a predictor for ACLD regression, while higher baseline LSM [aOR:0.870 (0.8250.917), p<0.001] and FIB-4 [aOR:0.655 (0.496-0.864), p=0.003] were unfavorable factors for post-SVR ACLD regression. Conclusions: Patients with persistent ACLD after SVR posed the highest HCC risks, followed by those with ACLD regression. Those progressed from pre-therapy non-ACLD to post SVR ACLD occurred in 2% of all population with minimal HCC risk as that in the persistent non-ACLD group.

主題：B 型肝炎（一） ⑥

慢性 B 型肝炎肝硬化患者發生表面抗原消 失後比未發生表面抗原消失而持續使用口服 抗病毒藥物者有較低肝癌發生率 HEPATOCELLULAR CARCINOMA INCIDENCE IS REDUCED IN CIRRHOTIC CHRONIC HEPATITIS B PATIENTS WITH HBSAG SEROCLEARANCE COMPARING TO THOSE WITH VIRAL SUPPRESSION

鄭文睿1,2,3 陳建宏1,4 楊懷壹5 陳益程1,2,3 劉彥君1,2,3 吳佳穎2,3 簡榮南1,2,3 廖運範1,2 長庚大學醫學院1 林口長庚紀念醫院肝臟研究中心2 林口長庚紀念醫院胃腸肝膽科系3 高雄長庚紀念醫院內科部胃腸肝膽科4 中央研究院基因體中心5

Background: Cirrhosis is a major risk factor for hepatocellular carcinoma (HCC) development in chronic hepatitis B patients. It remains unknown whether HBsAg seroclearance in cirrhotic patients reduces the risk of HCC compared to those under long-term Nuc treatment. Aims: This study aims to investigate the HCC incidence between these two groups. Methods: The study recruited chronic hepatitis B patients with cirrhosis undergoing Nuc therapy with viral suppression (Nuc arm, N=805) and cirrhotic CHB patients with HBsAg seroclearance (S-loss arm, N=165, 65 untreated, 90 off-therapy, 10 on-treatment HBsAg loss) from two medical centers and REVEAL-HBV cohort. The baseline in the Nuc arm was set since HBV DNA being undetectable (complete viral suppression) while in the S-loss arm was set since HBsAg loss. Those with HCC occurred prior to the baseline or within 6 months after the baseline were excluded from this analysis. Kaplan Meier analysis and log rank test were done for the cumulative HCC incidence comparison Results: Comparing the baseline features between Nuc arm and S-loss arm, the mean age (55.5 vs. 56.8, P=0.14), gender (male: 74.5% vs. 81.2%, P=0.07) and HBV genotype (P=0.27) were comparable. The median ALT (29 vs. 20 U/L, P<0.001) and AFP (4.16 vs. 3.0 mg/dL, P<0.001) level were higher in the Nuc arm while followup duration was longer in the S-loss arm (median: 7.9 vs. 4.3 years, P<0.001). In univariate analysis, older age [crude HR(cHR): 1.04, P<0.0001], higher FIB-4 level [cHR: 1.1, P=0.0004], higher AFP level [cHR: 1.02, P<0.001] were positively associated with HCC occurrence while HBsAg loss is a protective factor for HCC [cHR: 0.502, P=0.0314]. In multivariate analysis, older age [adjusted HR(aHR): 1.04 (1.02-1.06), P<0.0001] and HBsAg loss [aHR: 0.19 (0.050.76), P=0.0193] are the two independent predictor for HCC. The annual incidence and 8-year cumulative HCC incidence in cirrhotic patients in Nuc arm versus S-loss arm were 2.43% and 16% versus 1.16% and 8%, respectively (Log tank test, P=0.0282). After propensity score matching with age, gender and FIB-4 at 1 to 1 ratio with 77 patients at each arm. HBsAg loss arm still had much lower HCC incidence than those under Nuc arm (annual incidence: 0.46% vs. 3.2%, log rank test, P=0.0035). Conclusions: This is the first study proved the HBsAg seroclearance, reflecting the inactive transcriptional activity of cccDNA, is a protective factor for HCC in cirrhotic chronic hepatitis B patients

⑦

慢性 B 型肝炎 E 抗原陰性無肝硬化病人停 止貝樂克或惠立妥治療後沒有接受再治療其 表面抗原消失的長期發生率和預測因子 THE LONG-TERM INCIDENCES AND PREDICTORS OF HBSAG LOSS AFTER ENTECAVIR OR TENOFOVIR CESSATION IN HBEAG-NEGATIVE CHRONIC HEPATITIS B PATIENTS WITHOUT CIRRHOSIS WHO DID NOT RECEIVE RETREATMENT

陳建宏1 胡琮輝1 王景弘1 洪肇宏1 盧勝男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1

Background: The long-term incidence of HBsAg loss after cessation of entecavir or tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients who did not receive retreatment remains unclear. Aims: To investigate the incidence and predictors of HBsAg loss after entecavir or TDF cessation in HBeAgnegative CHB patients without cirrhosis who did not receive retreatment. Methods: This study included 265 HBeAg-negative CHB patients without cirrhosis who received entecavir or TDF treatment. All patients enrolled had post-treatment followup for at least 24 months and did not received retreatment until last visit. Of the 265 patients, 125 were sustained responders (Group I), 90 experienced virological relapse without clinical relapse (Group II) and 50 experienced clinical relapse (Group III). Results: The cumulative rates of HBsAg loss at 5 and 8 years after entecavir or TDF cessation were 40.2% and 57% in the Group A, 5.5% and 22.7% in the Group B and 18.9% and 43.2% in the Group C, respectively. Cox regression analysis showed that NA-experienced status, lower end-oftreatment (EOT) HBsAg levels and higher HBsAg decline at post-treatment 6 months from EOT were independent factors of HBsAg loss in the Group A and Group B plus C. EOT HBsAg of 40 IU/mL and HBsAg decline at posttreatment 6 months of 0.2 log IU/mL were optimal cut-off for predicting HBsAg loss in the Group A. Among patients with EOT HBsAg ≤40 IU/mL and HBsAg decline at posttreatment 6 month ≥0.2 log IU/mL (n=30) and EOT HBsAg >40 IU/mL and HBsAg decline at post-treatment 6 month <0.2 log IU/mL (n=52), the 5-year cumulative rates of HBsAg loss were 88.7% and 4%, respectively, in the Group A. Among patients with HBsAg decline >0.2 and ≤0.2 log IU/mL at post-treatment 6 months, the 6-year cumulative rates of HBsAg loss were 77.6% and 10.8 % in the Group B plus C, respectively (p <0.001). Conclusions: HBsAg loss rates are relative high in patients with sustained responders or HBV relapsers who did not need retreatment. In addition to EOT HBsAg levels, HBsAg decline at post-treatment 6 months was a useful predictor of HBsAg loss after entecavir or TDF cessation in HBeAg-negative patients without retreatment.

⑧

ENTECAVIR 與 TENOFOVIR 對 B 型肝炎 病毒相關肝細胞癌肝切除術後復發的影響： 一項全國性世代研究 ENTECAVIR VS TENOFOVIR ON RECURRENCE OF HEPATITIS B VIRUS-RELATED HEPATOCELLULAR CARCINOMA AFTER HEPATIC RESECTION: A NATIONWIDE COHORT STUDY

潘俊良1 高偉育1,2 蘇建維3,4 譚家惠5 張君照1,2 臺北醫學大學附設醫院內科部胃腸科1 臺北醫學大學醫學院內科學科2 臺北榮民總醫院內科部胃腸科3 陽明大學醫學院醫學系4 衛生福利部國家中醫藥研究所5

Background: Previous studies reported that tenofovir disoproxil fumarate (TDF) treatment has lower risk of hepatocellular carcinoma (HCC) than entecavir (ETV) treatment in patients with chronic hepatitis B virus (HBV) infection. Aims: This study aims to compare the efficacy of ETV and TDF in terms of HCC recurrence and survival in patients with HBV−related HCC after hepatic resection. Methods: By analyzing data from the Taiwan National Health Insurance Research Database between year 20112016, we identified 7,107 patients with HBV-related HCC after hepatic resection after excluding patients who had other cancers, advanced HCC, received liver transplantation, HCC recurrence within 90 days after surgery and follow-up duration less than 90 days. ETV or TDF group was defined as patients receiving entecavir ≥ 90 cumulative defined daily doses. After overlap propensity score weighting by gender, age, follow-up time, comorbidity and medication, 1,797 patients treated with ETV (n = 1,365) or TDF (n = 432) were enrolled for analyses, respectively. The Kaplan-Meier method and Cox proportional hazards models were performed for multivariable and stratified analyses to compare the efficacy of ETV and TDF for recurrent-free survival, overall survival, early recurrence and late recurrence. Results: The mean age of study patients was 56.9 years and 1,510 patients (84.0%) were male. During the median follow-up of 4.2 (interquartile range, 2.8-5.5) person-year, there was no significant difference between ETV and TDF in terms of recurrent-free survival, overall survival, early recurrence and late recurrence. Subgroup analysis also confirmed no significant difference between ETV and TDF for recurrent-free survival and overall survival. Conclusions: Based on a retrospective, nationwide population-based cohort study in Taiwan, the efficacy of ETV and TDF was not significant difference in terms of HCC recurrence and survival in patients with HBV−related HCC after hepatic resection.

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比較慢性 B 型肝炎非肝硬化病人停藥後或 持續貝樂克或惠立妥治療發生肝癌和死亡的 發生率 COMPARISON OF INCIDENCES OF HEPATOCELLULAR CARCINOMA AND MORTALITY BETWEEN PATIENTS WHO CONTINUED AND DISCONTINUED ENTECAVIR OR TENOFOVIR TREATMENT IN CHRONIC HEPATITIS B PATIENTS WITHOUT CIRRHOSIS

陳建宏1 彭成元2 胡琮輝1 頼學洲2 王景弘1 洪肇宏1 盧勝男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1 中國醫藥大學附設醫院內科部消化系2

Background: It remains unclear whether chronic hepatitis B (CHB) patients who discontinued nucleot(s)ide analuge (NA) therapy have higher risk of hepatocellular carcinoma (HCC) and mortality. Aims: To compare the incidences of HCC and mortality between patients who discontinued and continued entecavir or tenofovir disoproxil fumarate (TDF) treatment in CHB patients without cirrhosis. Methods: Patients who had received entecavir or TDF treatment for 3 years and discontinued treatment for at least 12 months (Group A: discontinuing group; n=826) and patients who had received continuous entecavir or TDF treatment for at least 4 years (Group B, continuing group; n=640) were recruited. Patients who developed HCC within the first 12 months after entecavir or TDF cessation (Group A) or 4 year of treatment (Group B) were excluded. Propensity score (PS) 1:1 matching was applied to adjust for age, sex, DM, NA-naïve, ETV or TDF use, FIB-4, HBV DNA level and HBeAg status at treatment initiation. Results: Of 826 patients in Group A, 406 patients received NA retreatment. Patients in Group B received further entecavir or TDF treatment after Year 3 (median duration: 48 months). The cumulative incidences of HCC and allcause mortality at 5 and 10 years after entecavir or TDF cessation were 1.5% and 0.7%, and 3.5% and 0.7%, respectively in Group A. The cumulative incidences of HCC and all-cause mortality at 5 and 10 years after 3 years of entecavir or TDF treatment were 0.7% and 0.04%, and 2.9% and 0.04%, respectively in Group B. There were no significant differences in HCC (p=0.299) or all-cause mortality (p=0.447) between Group A and Group B. A Cox regression analysis showed that age at treatment initiation was an independent predictor of HCC (HR: 1.100, 95% CI: 1.025-1.180, p=0.008), and that age at treatment initiation (HR: 1.109, 95% CI: 1.038-1.185, p=0.042) and DM (HR: 4.780, 95% CI: 1.060-21.561, p=0.001) were independent predictors of all-cause mortality. In 902 PS-matched patients (451 in Group A and 451 in Group B), there were no significant differences in HCC (p=0.585) or all-cause mortality (p=0.093) between Group A and Group B. Conclusions: Chronic hepatitis B patients without cirrhosis who discontinued entecavir or TDF treatment was not associated with increased risk of HCC or mortality compared with patients who received long-term entecavir or TDF treatment.

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E 抗原陰性慢性 B 肝肝硬化以及非肝硬化病 人停藥後病毒上升速率是造成嚴重肝炎復發 的重要因素 OFF-THERAPY HBV SURGE KINETICS IS THE KEY FACTOR FOR SEVERE FLARE IN BOTH CIRRHOTIC AND NONCIRRHOTIC HEPATITIS B E ANTIGENNEGATIVE CHRONIC HEPATITIS B PATIENTS

劉彥君1,2 鄭文睿1,2 彭建維1,2 簡榮南1,2,3 廖運範1,3 林口長庚紀念醫院1 長庚大學2 長庚紀念醫院肝臟研究中心3

Background: Stopping tenofovir (off-TDF) and cirrhosis are the two already known factors for off-therapy severe flare and early flare. It remains unknown whether offtherapy HBV upsurge or cirrhosis with less liver reserve would be the determinant affecting flare severity after stopping TDF and ETV. Aims: To investigate the interreleationship between HBV kinetics and severity among patients with or without cirrhosis. Methods: HBeAg-negative chronic hepatitis B (CHB) patients who encountered off-ETV or off-TDF hepatitis flare, ALT>5 upper limit of normal(ULN), were recruited. HBV DNA levels were assessed at EOT, EOT 3, 6, 9, and 12 months, as the referent level for calculating the magnitude of HBV DNA surge ( △ HBV DNA) prior to flare. HBV upsurge kinetics was calculated as △ HBV DNA/months. Propensity score matching (PSM) was performed 1:1 ratio adjusting age, gender, cirrhosis and end-of-treatment HBsAg between off-TDF and off-ETV flares. Severe flare was defined as serum ALT >=1000 U/L or ALT<1000 U/L plus total bilirubin >=3.5 or INR >=1.5. Results: After PSM, each off-TDF and off-ETV arm had 107 patients. In off-TDF arm, cirrhotic patients had higher proportion of △ HBV DNA/month >1 log10 IU/mL/month (85% vs. 52%, P<0.001) and higher incidence of severe flare (28% vs. 12%, P=0.035) than non-cirrhotic patients. In off-ETV arm, similar phenomenon was shown (cirrhosis versus non-cirrhosis: △ HBV DNA/month >1: 49% vs. 15%, P<0.001, severe flare: 25% vs. 8%, P=0.016). When stratified by cirrhotic status, multivariate cox regression showed △ HBV DNA/month >1 log10 IU/mL/month is the common independent risk factor for severe flare [aHR: 4.59, P=0.027 for non-cirrhotic; aHR: 3.12, P=0.011 for cirrhotic] while the impact of TDF on severe flare mainly shown in the cirrhotic patients [aHR: 3.12, P=0.011]. Conclusions: Greater HBV DNA upsurge rate ( △ HBV DNA/month) >1 log10IU/mL/month is an important factor for severe flare in off-ETV or off-TDF flare patients. Cirrhotic patients are more likely to have higher proportion of △ HBV DNA/month >1 log10 IU/mL/month than noncirrhotic patients, especially when stopping TDF. ETV is the preferred drug of choice if finite therapy be considered in cirrhotic patients. More stringent monitoring in those with △ HBV DNA/month > 1 log10IU/mL/month at time of flare is mandatory for safety concern of severe flare and timely retreatment to prevent hepatic decompensation, especially in patients with cirrhosis.

主題：B 型肝炎（二） ⑪

B 型肝炎警示系統與化療病患 B 型肝炎發作 探討 EVALUATION OF THE HEPATITIS B WARNING SYSTEM AND THE HEPATITIS B FLARE IN PATIENTS UNDERGOING CHEMOTHERAPY

胡彥佶1, 2 李君陽1, 2 黃怡翔1, 2, 3 侯明志1, 3 李重賓1, 2, 4 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學醫學院醫學系2 國立陽明交通大學醫學院臨床醫學研究所3 臺北榮民總醫院教學部臨床技術訓練科4

Background: Hepatitis B virus (HBV) is an endemic disease in Asia, especially in the west Pacific. More than 8% of the population in Taiwan had chronic hepatitis B infection. Reactivation of HBV is always a concern when treating hematological diseases with chemotherapy. It may lead to fulminant hepatitis and liver decompensation, and even to death. Prophylaxis of HBV by anti-HBV nucleos(t) ide analogues during chemotherapy had been advocated for many years; however, the hematologists may miss to survey the HBV infection status, and even the prescription for prophylaxis. Aims: To investigate that with the advent of the automatic reminding system for HBsAg and prescription of the antiHBV nucleos(t)ide analogues, whether or not the chance of missing HBV survey and lacking adequate HBV prophylaxis can be avoided. Methods: During Jan. 2015 – Mar. 2021, the patients who were newly diagnosed with hematological diseases and received chemotherapy in Taipei Veterans General Hospital were enrolled into this retrospective study, and the patients were separated into two groups by the day of the automatic reminding system operated. By chart review, the HBVrelated antigens and antibodies were checked, and the use of anti-viral medication as well. Events of the HBV flare up related hepatitis, severe hepatitis, and liver decompensation were recorded, and the rates were calculated. Results: A total 1,516 patients were enrolled into this study. 266 patients had acute myelogenous leukemia; 95 patients had acute lymphoblastic leukemia; 47 patients had chronic myelogenous leukemia; 40 patients had chronic lymphocytic leukemia; 65 patients had myeloproliferative neoplasm; 155 patients had plasma cell dyscrasias; and 129 patients had myelodysplastic syndrome. The HBsAg screening rate was improved after the program launched. (84.4% versus 90.9%, p < 0.001) The anti-HBc screening rate was also improved. (65.1% versus 77.8%, p < 0.001). HBV prophylaxis rate to HBV carrier or resolved HBV status increased after the introduction of the reminding system.(23.3% versus 31.9%, p = 0.045) The rate of HBV flare up related hepatitis, severe hepatitis, and HBV-related liver decompensation did not differ. (3.2% versus 3.7%, p = 0.667; 1.6% versus 1.5%, p = 1, 1.1% versus 1.1%, p = 1) Conclusions: With the advent of the automatic reminding system, the detection for HBV infection status before chemotherapy got much improvement. The prophylaxis for HBV in patients receiving chemotherapy had a better performance as well.

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在目前 B 型肝炎治療準則中的灰色區域患 者用藥效益的風險評估 RISK SCORES TO PREDICT HCC AND THE BENEFITS OF ANTIVIRAL THERAPY FOR CHB PATIENTS IN GRAY ZONE OF TREATMENT GUIDELINE

滕威1,2 張定宗3 楊懷壹4 彭成元5 蘇建維2,6 蘇東弘7 胡琮輝8 余明隆9 楊宏志7 吳肇卿2,10,11 林口長庚紀念醫院胃腸肝膽科系1 國立陽明交通大學臨床醫學研究所2 國立成功大學附設醫院內科部3 中央研究院基因體研究中心4 中國醫藥大學附設醫院消化內科5 臺北榮民總醫院胃腸肝膽科系6 國立臺灣大學附設醫院胃腸肝膽科系7 高雄長庚紀念醫院胃腸肝膽科系8 高雄醫學大學附設中和紀念醫院肝膽胰內科9 臺北榮民總醫院醫學研究部轉譯醫學科10 國立陽明交通大學腫瘤惡化卓越研究中心11

Background: ALT ≥ 80 U/L and HBV DNA ≥ 2000 IU/ml are treatment criteria of APASL guideline for chronic hepatitis B (CHB) patients. The need of antiviral therapy for patients in gray zone (ALT <80 U/L or HBV DNA<2000 IU/ml) is controversial. Aims: This study aimed to develop a scoring system to predict hepatocellular carcinoma (HCC) and evaluate the benefit of antiviral therapy in these patients. Methods: Seven hundred and forty-nine patients were analyzed. Significant variables were weighted to develop a scoring system for HCC prediction. The area under receiver operating curves (AUROC) were estimated and validated by REVEAL-HBV cohort (n=3527). Results: Older age (p< 0.001), male sex (p=0.036), family history of HCC (p=0.002), and HBV DNA ≥ 2000 IU/ ml (p=0.045) were independently associated with HCC. A 14-point risk score system predicts 3 and 5-years HCC risk to be 0.866 and 0.868 of AUROC, respectively in the derivation cohort; 0.821 and 0.820, in the REVEAL-HBV cohort. The cumulative HCC incidence was higher in the high-risk (score ≥ 8) group both in derivation and validation cohorts (p<0.001). Patients with antiviral therapy had lower HCC incidence compared to those without (p=0.016). Of note, antiviral therapy significantly decreased HCC in the high-risk group (p=0.005), but not in the low-risk group (p=0.705). Conclusions: A risk scoring system is established and validated. Of CHB patients in gray zone of APASL guidelines, those with risk scores ≥ 8 had higher risk of HCC, but the risk could be significantly reduced by antiviral therapy.

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慢性 B 型肝炎患者之膠原蛋白比例面積 （CPA）與非侵入性肝纖維化指標評估纖維 化分期的比較及相關性：一先導性研究 COMPARISON AND CORRELATION OF FIBROSIS STAGE ASSESSMENT BY COLLAGEN PROPORTIONATE AREA (CPA) AND NONINVASIVE FIBROSIS INDICES IN PATIENTS WITH CHRONIC HEPATITIS B: A PILOT STUDY

王鴻偉1 賴學洲1 莊伯恒1 陳昇弘1 許偉帆1 彭成元1 中國醫藥大學附設醫院消化醫學中心1

Background: Nucleos(t)ide analogue (NA) therapy is effective in suppressing hepatitis B virus DNA replication and resolving hepatic necroinflammation. Long-term NA treatment can also lead to the regression of liver fibrosis and cirrhosis. Aims: We aimed to investigate the association between noninvasive indirect fibrosis indices (APRI, FIB-4, modified FIB-4[mFIB-4]) and METAVIR fibrosis stages (F1, F2, F3, and F4) or collagen proportionate area (CPA) before anti-viral therapy (treatment baseline) and at ontreatment time points. Methods: We conducted a pilot study for chronic hepatitis B patients and 48 patients who had received paired liver biopsy were enrolled. Baseline and on-treatment clinical characteristics, laboratory data and image report were collected. Results: A total of 48 patients with paired biopsy were evaluated. Their age (median ± IQR) was 47±16.3 years and 35 patients were male (72.9%). Median time period (median ± IQR) between two biopsies were 7.5±4 years. A moderate correlation was observed between CPA and METAVIR fibrosis stages in paired biopsies (1st biopsy: r = 0.479, p = 0.001; 2nd biopsy: r = 0.484, p < 0.001, respectively), while APRI, FIB-4 showed low correlation with METAVIR fibrosis stages. Modified FIB-4 had a moderate correlation with METAVIR fibrosis stages only at baseline (r = 0.430, p = 0.003). After anti-viral treatment, a decreased CPA value was observed in each METAVIR fibrosis stage. Most patients (23/48, 47.9%) had improved METAVIR fibrosis stage, while 20.8% patients had deteriorated fibrosis status. CPA showed numerically higher diagnostic performance (AUC: 1st biopsy, 0.777 and 2nd biopsy, 0.783) and higher accuracy (1st biopsy, 78.9% and 2nd biopsy, 75.0%) in predicting advanced fibrosis than APRI, FIB-4 and mFIB-4 in CHB cohort.

Conclusions: These findings demonstrate that CPA might have better correlation with METAVIR fibrosis stage than noninvasive indirect fibrosis indices (APRI, FIB-4 and mFIB-4) before anti-viral therapy (baseline) and at ontreatment time points. Due to low correlation between indirect fibrosis indices and METAVIR stage, direct serum fibrosis marker might be considered for future study.

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貝樂克和惠立妥在慢性 B 型肝炎併嚴重急 性惡化之療效比較 ENTECAVIR VS. TENOFOVIR DISOPROXIL FUMARATE IN CHRONIC HEPATITIS B PATIENTS WITH SEVERE ACUTE EXACERBATION

林馳揚1 蔡維倫2 陳文誌3 孫煒智3 呂家名3 高雄榮民總醫院內科部1 高雄榮民總醫院一般內科2 高雄榮民總醫院腸胃科3

Background: Tnofovir disoproxil fumarate (TDF) and entecavir (ETV) are both effective antivirals recommended as first-line monotherapies for the treatment of chronic hepatitis B (CHB) infection. However the efficacy of different nucleos(t)ide analogues in the treatment of CHB with severe acute exacerbation (SAE) remained unclear. Aims: We aimed to compare the short term efficacy of TDF and ETV in CHB patients with SAE. Methods: We analyzed 101 treatment-naïve patients with severe acute CHB exacerbation treated with TDF 300 mg (n = 36) or ETV 0.5mg (n = 65). The primary endpoint was overall mortality or receipt of liver transplantation (LT) by 24 weeks. The secondary endpoints were virologic, biochemical and renal function responses by 48 weeks. Results: The baseline characteristics were comparable between the two groups. By week 24, 8 (22%) patients in the TDF group and 10 (15%) patients in the ETV group had either died (n= 15) or received liver transplantation (n= 3) (P= 0.367). Cox-regression multivariate analysis showed that age (p = 0.009) and PT (INR) (p = 0.008) were independent factors associated with mortality or liver transplantation by week 24. The two groups of patients achieved similar biochemical and virological responses at week 48. There was also no significant difference in the estimated glomerular filtration rate (eGFR) between the TDF and the ETV groups at 48 weeks. However a significant reduction in the eGFR at 48 weeks compared with baseline were found in each group (P= 0.003 for TDF and 0.006 for ETV group). Conclusions: TDF and ETV achieved a similar short-term clinical outcome in patients with severe acute exacerbation of CHB.

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慢性 B 型肝炎患者轉換從 TDF 到 TAF 的真 實世界經驗：一個回溯性研究 REAL-WORLD EXPERIENCE OF SWITCHING FROM TENOFOVIR DISOPROXIL FUMARATE TO TENOFOVIR ALAFENAMIDE IN PATIENTS WITH CHRONIC HEPATITIS B: A RETROSPECTIVE STUDY

蘇培元1 蘇維文1 徐友春1 黃秀萍1 顏旭亨1 彰化基督教醫院胃腸肝膽科1

Background: Tenofovir alafenamide (TAF) has good viral suppression efficacy and less adverse effect than tenofovir disoproxil fumarate (TDF). Real-world studies on the antiviral efficacy and safety of switching from TDF to TAF in patients with chronic hepatitis B (CHB) are limited. Aims: To compare the antiviral effect and changes in renal function, weight, and body mass index (BMI) before and after switching from TDF to TAF in a real-world setting. Methods: This retrospective study included 167 nucleos(t)ide analogue (NA)-naive patients with CHB. All the patients received TDF at least 12 months before switching and TAF at least 12 months after switching at a single medical center. The Friedman test with DunnBonferroni post hoc tests and repeated-measures analysis of variance was used to analyze the effect of complete viral suppression, alanine aminotransferase (ALT) level normalization, renal function changes, body weight, and body mass index in the periods before and after switching. Results: The mean age and TDF treatment duration were 52 ± 11 years and 2.8 years (interquartile range, 1.51–5.15 years), respectively. The complete viral suppression rate was similar between the time of switching and 48 weeks after switching to TAF (77.8% vs 76%, P = 1.000). The percentage of alanine aminotransferase (ALT) normalization increased from 26.3% at TDF start to 81.4% (P < 0.001) at time of switching and 89.2% at 48 weeks after switching to TAF (P = 0.428). The median estimated glomerular filtration rate decreased from 100.09 mL/ min/1.73 m² at TDF start to 91.97 mL/min/1.73 m² (P < 0.001) at the time of switching and stabilized at 48 weeks after switching to TAF (93.47 mL/min/1.73m², P = 1.000). The body weight decreased from 69.2 ± 12.2 kg at TDF start to 67.4 ± 12.1 kg (P < 0.001) at the time of switching to TAF and returned to 68.7 ± 12.7 kg (P < 0.001) 48 weeks thereafter. The body mass index (BMI) decreased from 25 ± 3.3 kg/m² at TDF start to 24.5 ± 3.3 kg/m² (P = 0.002) at the time of switching to TAF and returned to 25.1 ± 3.6 kg/ m² (P < 0.001) 48 weeks thereafter. Conclusions: Our study showed that switching to TAF from TDF had good antiviral effectiveness and stabilized renal function. The body weight and BMI decreased during TDF therapy and regained after switching to TAF.

主題：肝腫瘤（一）

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結合 CRAFITY SCORE 和治療中 AFP 變化 做為預測肝癌患者接受癌自癒和癌思停治療 預後評估 COMBINATION OF CRAFITY SCORE WITH ALPHA-FETOPROTEIN RESPONSE PREDICTS A FAVORABLE OUTCOME OF ATEZOLIZUMAB PLUS BEVACIZUMAB FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA

滕威1 林成俊1 蘇崇維1 林伯庭1 謝彞中1 陳威廷1 侯明模2 謝佳訓3 林俊彥1 林錫銘1 林口長庚紀念醫院胃腸肝膽科1 林口長庚紀念醫院腫瘤科2 新北市立土城醫院腫瘤科3

Background: Immune checkpoint inhibitors (ICIs) with atezolizumab plus bevacizumab are promising agents for unresectable hepatocellular carcinoma (HCC). Aims: We tried to guide the treatment based on recent developed CRAFITY score combining with on-treatment AFP response. Methods: Seventy-two patients who received atezolizumab plus bevacizumab regardless of as a first-line therapy or not for unresectable HCC in Chang Gung Memorial Hospital, Linkou Medical center were enrolled for analyses. Radiologic evaluation was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). Results: The objective response rate (ORR) and disease control rate (DCR) were 23.4% and 57.8%, respectively. Multivariate analysis showed that low CRAFITY score (AFP < 100 ng/ml or CRP < 10 mg/l) and satisfactory AFP response at 6 weeks (≥ 75% decrease or ≤ 10% increase from baseline) were independent factors associated with good overall survival (OS) (hazard ratio [HR]=0.263, p=0.041 & HR=0.102, p=0.004), progression-free survival (PFS) (HR=0.681, p=0.046 & HR=0.326, p=0.008) and good responder (odds ratio [OR]=4.354, p=0.044 & OR=6.406, p=0.017). Patients were further divided into three classes by combination of CRAFITY score and AFP response at 6 weeks [The CAR (CRAFITY score and AFP-Response) classification)]: low CRAFITY score with satisfactory AFP response at 6 weeks (class I), either high CRAFITY score or unsatisfactory AFP response at 6 weeks (class II) and high CRAFITY score together with unsatisfactory AFP response at 6 weeks (class III). ORR was 41.7%, 15.4%, and 0% in class I, II and III patients, respectively (overall p=0.033). Patients in the class I had the best OS and PFS, followed by class II and class III (median OS: not reached vs. 8.6 vs. 4.3 months, log-rank p<0.001; median PFS: 5.9 vs. 4.7 vs. 2.7 months, logrank p=0.014). Combination CRAFITY score and AFP response at 6 weeks with AUROC predicts OS and tumor response to be 0.809 and 0.816, respectively, better than either CRAFITY score (0.771 & 0.767) or AFP response at 6 weeks (0.725 & 0.729) alone. Conclusions: The CAR classification which combining CRAFITY score and AFP response at 6 weeks provides a practical guidance for atezolizumab plus bevacizumab therapy in unresectable HCC patients.

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以階層式融合策略深度學習網路自動偵測與 分割電腦斷層肝癌影像 A NOVEL HIERARCHICAL FUSION STRATEGY OF DEEP LEARNING NETWORKS FOR DETECTION AND SEGMENTATION OF HEPATOCELLULAR CARCINOMA FROM DYNAMIC COMPUTED TOMOGRAPHY IMAGES

李懿宬1 蔡詠平2 李潤川3 何信瑩2 黃怡翔1,4 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學生物資訊及系統生物研究所2 臺北榮民總醫院放射線部3 國立陽明交通大學臨床醫學研究所4

Background: Automatic segmentation of hepatocellular carcinoma (HCC) on computed tomography (CT) scans is in urgent need to assist diagnosis and radiomics analysis. Most existing methods including deep learning for HCC segmentation used single-phase CT images or from small datasets. Aims: This study aimed develop a deep learning based network to detect HCC using a large dataset of dynamic CT images. Methods: Dynamic CT images of 595 patients with HCC before resection or radiofrequency ablation from Taipei Veterans General Hospital, Taiwan were used. Tumors in triple phase CT images, including non-contrast, arterial and portal venous phases, were labeled by radiologists. Patients were randomly divided into training, validation and test sets in a ratio of 5:2:3, respectively. The proposed hierarchical fusion strategy of deep learning networks (HFS-Net) consists of three stages based on U-Net and DenseU-Net. The first stage segments tumors in a slice and estimates the tumor size. The second stage uses customized networks for segmenting small and large tumors adaptively. The third stage integrates the outcomes of the first two stages and uses a 3D U-Net to segment 3D liver tumors. Global dice, sensitivity, precision and F1 score were used to measure the performance of HFS-Net model. Results: The 2D DenseU-Net using triple phase images was more effective for segmenting small tumors, whereas the 2D U-Net using portal venous phase images was more effective for segmenting large tumors. The HFS-Net performed better, compared with the single-strategy deep learning model in segmenting small and large tumors. In the test set, the HFS-Net model achieved good performance in identifying HCC on dynamic CT images, with global dice of 82.8%. The overall sensitivity, precision and F1 score were 84.3%, 75.7% and 0.796 per slice, respectively, and 92.2%, 93.2% and 0.927 per patient, respectively. The sensitivity in tumors <2 cm, 2-5 cm and >5 cm were 57%, 79.2% and 89.5% per slice, respectively, and 72.7%, 93.8% and 100% per patient, respectively. Conclusions: The HFS-Net model achieved good performance in the detection and segmentation of HCC from dynamic CT images. Automatic 3D tumor segmentation from dynamic CT scans using HFS-Net can support radiologic diagnosis and facilitate automatic radiomics analysis.

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合併代謝疾病相關脂肪肝對接受無線射頻電 燒治療之肝細胞癌預後影響 IMPACT OF CONCURRENT METABOLIC ASSOCIATED FATTY LIVER DISEASE ON OUTCOMES OF HEPATOCELLULAR CARCINOMA RECEIVING RADIOFREQUENCY ABLATION

蔡豐百1 蘇東弘1, 2 黃上秦3, 4 曾岱宗1, 2 徐士哲1, 2 廖思涵5 洪俊銘6 劉振驊1, 2 楊宏志1 劉俊人1, 2 陳培哲1, 2, 4 高嘉宏1, 2, 4 國立臺灣大學醫學院附設醫院胃腸肝膽科1 國立臺灣大學醫學院附設醫院肝炎研究中心2 國立臺灣大學醫學院附設醫院北護分院內科部3 國立臺灣大學醫學院臨床醫學研究所4 國立臺灣大學醫學院附設醫院癌醫中心分院5 國立臺灣大學醫學院附設醫院整合醫學科6

Background: Metabolic associated fatty liver disease (MAFLD) is a new disease entity, which represents the hepatic manifestation of a systemic metabolic disorder, without excluding alcohol consumption or other concomitant liver diseases, such as hepatitis B or C. The impact of MAFLD on the outcome of hepatocellular carcinoma (HCC) remained unclear. Aims: To investigate the impact of concurrent MAFLD on the outcomes of patients with HCC receiving radiofrequency ablation (RFA). Methods: We retrospectively included patients with HCC receiving RFA with curative intent at the National Taiwan University Hospital from the electric medical records from 2005 to 2015. Clinical information including age, sex, severity of liver disease, liver biochemistry, tumor size, number, stage of HCC and co-medication (antiviral therapy, aspirin, statin, and metformin) were collected, and those with incomplete medical information were excluded. MAFLD was defined by presence of obesity, diabetes, or two concurrent metabolic factors. The clinical outcomes, including HCC recurrence and overall survival, were analyzed by Cox proportional hazard regression analyses. Results: A total of 649 consecutive patients of HCC received RFA were retrospectively included. Among them, 127 had MAFLD, while 522 did not. Patients with MAFLD group had significantly younger age, greater BMI, male sex, and better liver reserve. The HCC characteristics including size, number, BCLC staging, and ECOG were comparable between MAFLD and non-MAFLD groups. After a median follow-up of 45 months, there were significantly less HCC recurrence, and death in the MAFLD group. After adjusted for age, male sex, alpha-fetoprotein, Fib-4 index, HCC size and number, and BCLC staging, MAFLD independently predicted a low risk of HCC recurrence after RFA (hazard ratio [HR]: 0.47, 95% confidence interval [CI]: 0.29-0.76, P=0.002). Similarly, multivariable analysis demonstrated that MAFLD independently predicted a low risk of allcause mortality after RFA (HR: 0.66, 95%CI: 0.44-0.98, P=0.041). Conclusions: Patients of HCC with concurrent MAFLD were associated with a lower risk of HCC recurrence and mortality after RFA. Further validation of our finding is needed.

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病毒病因決定晚期肝癌免疫治療效果：真實 世界研究 VIRAL ETIOLOGY DETERMINATE OUTCOMES OF IMMUNOTHERAPY IN UNRESECTABLE HEPATOCELLULAR CARCINOMA: A REAL-WORLD STUDY

吳啟榮1,2,3 李懿宬1,3 李沛璋1,3,4 洪雅文1 李杰如1 齊振達1,2,3 侯明志1,3 黃怡翔1,2,3 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學醫學院臨床醫學研究所2 國立陽明交通大學醫學院醫學系3 國立陽明交通大學醫學院藥理學研究所4

Background: As a result of successful IMbrave150 study, Atezolizumab- Bevacizumab has become the 1st -line systemic treatment currently for unresectable HCC (uHCC) with promising treatment responses and survival outcomes. However, one recent study showed non-viral hepatitis related HCC have worse survival outcomes than viral hepatitis related HCC in immunotherapy treated patients. Immunotherapy combination with target therapy has showed higher treatment response rates and better survival than immunotherapy monotherapy. Aims: This study aim to evaluate whether viral etiology effect on outcomes of immunotherapy monotherapy or combination therapy in uHCC. Methods: One hundred Seventy-Four consecutive patients who received immunotherapy for uHCC were prospectively enrolled. Effect of immunotherapy and factors, including etiology of uHCC, associated with progression-free survival (PFS) and overall survival (OS) were analyzed. Results: There was no significant different response rates and survival outcomes between viral and non-viral related uHCC in 174 patients received immunotherapy. However, in 85 patients subgroup who received immunotherapy combination with target therapy, significantly better objective response rate (42.4% vs. 19.2%, p=0.040), median PFS (11.6 vs. 5.3 months) and median OS (19.3 vs. 11.6 months). For the subgroup of patients, viral etiology (HR=0.416, p=0.002) and target therapy experience (HR=1.977, p=0.018) were independent factors for PFS in multivariate analysis. And viral etiology was the only significant factor associated with better PFS (HR=0.402, p=0.004). Conclusions: For patients received immunotherapy combination with target therapy for uHCC, viral hepatitis related patients has significant better response rate and survival outcomes.

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無法手術切除的肝內膽管癌患者接受化學治 療的預後因子分析 OUTCOME PREDICTORS OF GEMCITABINE-BASED OR FLUOROPYRIMIDINEBASED CHEMOTHERAPY FOR UNRESECTABLE INTRAHEPATIC CHOLANGIOCARCINOMA

齊振達1,2 李懿宬1 陳明晃3 李沛璋1 洪逸平3 侯明志1 趙毅3 黃怡翔1,2 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學臨床醫學研究所2 臺北榮民總醫院腫瘤醫學部3

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy, and the resectability rate for curative surgical resection is low. Gemcitabine-based and fluoropyrimidine-based chemotherapy are the mainstay treatments for Unresectable ICC, even though the survival is still far from satisfaction in real-world experience. Aims: This study aimed to assess outcomes and identify the prognostic factors for patients with unresectable ICC patients receiving gemcitabine-based or fluoropyrimidinebased chemotherapy. Methods: From December 2006 to January 2020, consecutive 309 unresectable ICC patients were enrolled. Of them, 162 ICC patients received chemotherapy as first-line treatment were retrospectively reviewed, and 123 patients had evaluable images for tumour response evaluation. Objective response rate (ORR) and overall survival (OS) were assessed and factors associated with ORR and OS were analysed. Results: Of the 162 ICC patients received chemotherapy as first-line therapy, the mean age was 62 years old. Most patients were within Child–Pugh class A (61.7%) and Albumin-bilirubin (ALBI) grade 2/3 (67.3%). Of them, 106 (65.4%) received gemcitabine-based regimen, while 56 (34.6%) patients received fluoropyrimidine-based regimen. The ORR was 26.0% and disease control rate (DCR) was 48.0% in the whole 123 ICC patients with evaluable images (including 32 partial responses, 27 stable diseases, and 64 progressive disease). HBV infection (OR, 3.223; p = 0.032), gemcitabine-based regimen (OR, 4.714; p = 0.008) were the independent predictors of ORR. In general, the median OS of the 162 ICC patients was 6.1 months. Presence of cirrhosis, Albumin ≤ 3.5 g/dl, Child-Pugh B/ C, ALBI grade 2/3, NLR ≧ 3, and CA 19-9 ≧ 300 U/ml

were independent risk factors associated with OS. A novel ALBI‐based scoring system to predict OS was created, the patients could be classified into 4 groups. Kaplan‐Meier analysis showed that the new ALBI‐based model could significantly discriminate OS between contiguous groups (p < 0.001). Noteworthily, patients without any risk factors had a promising overall survival of 21.3 months. Conclusions: Albumin-bilirubin grade is an important factor associated with survival in unresectable ICC patients receiving chemotherapy. The new ALBI‐based model can be applied to select patients who can get the best benefit from chemotherapy.

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比較門脈和囊微靜脈侵犯對早期肝癌切除預 後的影響 COMPARISON OF PORTAL AND CAPSULAR MICROVASCULAR INVASION IN THE OUTCOMES OF EARLY HCC AFTER CURATIVE RESECTION

盧威廷1 劉婷婷2 王植熙3 劉約維3 蔡明釗4 高雄長庚紀念醫院內科部1 高雄長庚紀念醫院病理科2 高雄長庚紀念醫院一般外科3 高雄長庚紀念醫院胃腸肝膽科4

Background: Microvascular vascular invasion (MVI) has been demonstrated as a strong risk factor associated with tumor recurrence and poor overall survival (OS) among hepatocellular carcinoma (HCC) patients after resection. There are two types of MVI, including portal vein and capsular vein invasion types. However, little is known about the impact of different types of MVI on HCC recurrence. This study aimed to compare the portal and capsular MVI on HCC recurrence and OS. Aims: This study aimed to compare the portal and capsular MVI on HCC recurrence and overall survival. Methods: Patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 at Kaohsiung Chang Gung Memorial Hospital were consecutively selected. The types of MVI (portal vein and capsular vein invasion types) were recorded. Factors that influenced overall survival (OS) and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. Results: Of the 857 eligible patients, 327 (38.2%) had MVI and 530 (61.8%) did not. The cumulative incidence of HCC recurrence was significant higher in the MVI group than the non-MVI group (p <0.001). Of the 327 MVI, 85 (26.0%), 178 (54.4%), and 64 (19.6%) were portal vein, capsular vein, and both-MVI types, respectively. Compared with portal or capsular MVI, patients with both-MVI types had higher proportion of BCLC stage A (p <0.001), capsular invasion (p = 0.002), and satellite nodules (p <0.001). In multivariate analysis, diabetes (hazard ratio [HR]: 1.44; p =0.004), liver cirrhosis (HR: 1.63; p <0.001), BCLC stage (HR:1.59; p =0.004), and both-MVI type (HR: 1.71; p =0.001) were independent risk factors for HCC recurrence. In further stratified analysis, the both-MVI type is associated with extrahepatic recurrence compared with other types. Conclusions: Among HCC patients after curative resection, concurrent portal and capsular MVI is a risk factor for HCC recurrence in comparison with non-MVI or only portal or capsular MVI.

主題：肝硬化及其他肝病（一）

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糞便或腸道菌叢植入可改善肝硬化大鼠之門 脈高壓及肝門系統側枝循環 MICROBIOTA TRANSPLANTS FROM FECES OR GUT CONTENT ATTENUATED PORTAL HYPERTENSION AND PORTOSYSTEMIC COLLATERALS IN CIRRHOTIC RATS

黃惠君1,2,3 許劭榮1,2 潘俊傑1,2 黃怡翔1,2 侯明志1,2 李發耀1,2 國立陽明交通大學醫學系, 臺北, 臺灣1 臺北榮民總醫院內科部胃腸肝膽科, 臺北, 臺灣2 臺北榮民總醫院內科部一般內科, 臺北, 臺灣3

Background: Liver cirrhosis and portal hypertension is the end of chronic liver injury with hepatic, splanchnic and portosystemic collateral systems dysregulation. Liver injury is accompanied by gut dysbiosis whereas dysbiosis induces liver fibrosis, splanchnic angiogenesis and dysregulated vascular tones vice versa, making portal hypertension aggravated. It has been proved that intestinal microbiota transplantation alleviates dysbiosis. Nevertheless, the influences of microbiota transplantation on cirrhosis related portal hypertension are not so clear. Aims: To survey the impacts and underlying mechanism of microbiota transplantation on portal hypertension-related parameters. Methods: Liver cirrhosis with portal hypertension was induced by bile duct ligation in male Sprgue-Dawley rats. Sham rats were surgical controls. Rats randomly received vehicle, fecal or gut (terminal ileum) material transplantation. Results: microbiota transplantation from feces or gut material significantly reduced portal pressure in cirrhotic rats (P = .010, .044). Hepatic resistance, vascular contractility, fibrosis and relevant protein expressions were not significantly different among cirrhotic rats. However, microbiota transplantation ameliorated splanchnic hyperdynamic flow and vasodilatation. Mesenteric angiogenesis, defined by whole mesenteric window vascular density, decreased in both transplantation groups and phosphorylated eNOS was downregulated. Portosystemic shunts determined by splenorenal shunt flow decreased in both transplantation groups (P = .037, .032). Shunting severity assessed by microsphere distribution method showed consistent results. Compared to sham rats, cirrhotic rats lacked Lachnospiraceae. Both microbiota transplants increased Bifidobacterium. Conclusions: microbiota transplantation in cirrhotic rats reduced portal pressure, alleviated splanchnic hyperdynamic circulation and portosystemic shunts. The main beneficial effects may be focused on portosystemic collaterals-related events, such as hepatic encephalopathy and gastroesophageal variceal hemorrhage. Further clinical investigations are mandatory.

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嚴重特殊傳染性肺炎疫苗相關之肝炎 HEPATITIS AFTER COVID-19 VACCINATION

吳心耘1 蘇東弘1,2 劉俊人1,2 楊宏志1 蔡佳惠3 陳介章1 董建志1 高嘉宏1,2 陳培哲1,2 國立臺灣大學醫學院附設醫院內科部肝膽腸胃科1 國立臺灣大學醫學院附設醫院肝炎研究中心2 國立臺灣大學醫學院附設醫院病理部3

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with coronavirus disease 2019 (COVID-19) overwhelmed the world, and universal vaccination program has been implemented in Taiwan since March 2021 for prevention. Here we reported a series of patients who developed hepatitis after COVID-19 vaccination. Aims: To investigate the patterns, clinical courses, and etiologies of post-vaccination hepatitis. Methods: COVID-19 vaccination related hepatitis was defined as alanine aminotransferase (ALT) increased > 2-fold upper limit of normal or baseline value after vaccination and without other identifiable precipitating factors. We recruited these patients in our clinical practice at National Taiwan University Hospital and recorded the demographics, underlying liver diseases, types of vaccination, laboratory data, pathology results, treatment courses and outcomes for analyses. Results: From May 2021 till mid December 2021, a total of 18 clinically eligible cases were identified. There were 12 men and the median age was 53.5. Among them, 15 had underlying liver diseases (8 chronic hepatitis B [CHB], 4 fatty liver, 1 resolved hepatitis B, 1 triptorelin drug induced liver injury [DILI], 1 autoimmune hepatitis with primary biliary cholangitis). Regarding vaccination, 7 received viral-vector vaccines (ChAdOx1 nCoV-19) and 11 received mRNA vaccines (9 mRNA1273 and 2 BNT162b2). The median duration between vaccination to hepatitis was 27 days (ranging from 2-105 days) with a median peak ALT level of 674 U/L. The median time for ALT recovery was 41 days (n=11), while 7 still had liver dysfunction until last follow up. The etiologies of hepatitis were hepatitis B reactivation (n=7, 39%), DILI from COVID-19 vaccination (n=6, 33%), and immune-related (n=5, 28%). In patients of CHB, 3 (38%) progressed to decompensation and 2 (25%) deceased due to liver failure even after nucleos(t) ide therapy. One resolved HBV patient sero-reverted to hepatitis B surface antigen positivity. Three (30%) nonCHB patients developed liver decompensation, but all were recovering. The characteristics of post-vaccination hepatitis were comparable in different vaccines subgroups. The etiology of hepatitis was significantly different among CHB (75% HBV reactivation) and non-CHB (50% DILI, 40% immune-related) patients (p=0.019). The percentage of peak ALT increase from baseline was significantly greater in CHB compared with non-CHB patients (113.9% vs 102%, p=0.042), but the median duration of ALT recovery was significantly shorter in CHB patients (23 vs. 76 days, p=0.033). More serological, virological and histological analyses are ongoing. Conclusions: Post-COVID-19 vaccination hepatitis is a rare but severe complication, especially in CHB subjects. HBV reactivation should be closely monitored.

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VON WILLEBRAND FACTOR 可預測肝硬 化病人肝腦病變與自發性腹膜炎的發生 VON WILLEBRAND FACTOR PREDICTS OCCURRENCE OF HEPATIC ENCEPHALOPATHY AND SPONTANEOUS BACTERIAL PERITONITIS IN PATIENTS WITH CIRRHOSIS

謝昀蓁1 李癸汌1 吳佩珊1 黃怡翔1 侯明志1 林漢傑1 臺北榮民總醫院肝膽胃腸科1

Background: Elevated plasma von Willebrand factor (vWF) has been shown to correlate with portal hypertension and predict hepatic decompensation and mortality in cirrhosis in western population. However, the predictive values of vWF in Asian cirrhotic patients remained unclear. Aims: To assess the association between vWF, bacterial translocation and liver function, and whether vWF predicts complications of cirrhosis in Asian population. Methods: We prospectively enrolled 114 cirrhotic patients and 24 healthy controls from 2018-2021 in Taipei Veterans General Hospital. Plasma vWF levels were determined by ELISA kit. Results: Compared to healthy controls, plasma vWF levels significantly elevated in cirrhotic patients (930.20 ± 1247.38 vs 1940.70±1223.35 U/L, p<0.001). vWF correlated with marker of bacterial translocation (lipopolysaccharide, r=0.224, p=0.021) and liver function (Model of End-Stage Liver Disease (MELD) scores, r=0.632, p<0.001). On multivariate analysis, higher vWF levels (≥ 1580 U/L) predicted the occurrence of hepatic encephalopathy (HR, 4.524; 95% CI 1.499-13.656) and the development of spontaneous bacterial peritonitis (HR, 5.445; 95% CI 1.559-19.015) independently of child classification. Conclusions: The plasma vWF level correlates with bacterial translocation and liver function. Additionally, it may predict the occurrence of portal hypertension-related complications and spontaneous bacterial peritonitis in cirrhotic patients.

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PIOGLITAZONE 減緩肝硬化大鼠內毒素血 症導致之慢性腎損傷急性惡化 PIOGLITAZONE AMELIORATES ACUTE ENDOTOXEMIA-INDUCED ACUTE ON CHRONIC RENAL DYSFUNCTION IN CIRRHOTIC ASCITIC RATS

劉思妤1,2,3 黎子豪3,4 黃加璋1,2,3 廖采苓3,5 郭乃榕1,2,3 楊盈盈1,2,3 劉志偉3 侯明志2,3 林漢傑2,3 臺北榮民總醫院教學部1 臺北榮民總醫院內科部2 國立陽明交通大學醫學系3 新光紀念醫院內科部過敏免疫風濕科4 臺中榮民總醫院醫學研究部5

Background: Endotoxemia-activated TNFα/NFκB signals result in acute on chronic inflammation-driven renal dysfunction in advanced cirrhosis. Systemic activation of peroxisome proliferator-activated receptor gamma (PPARγ, with pioglitazone can suppress inflammation-related splanchnic and pulmonary dysfunction in cirrhosis. Aims: To explore the mechanism and effects of pioglitazone treatment on abovementioned renal dysfunction in cirrhotic rats. Methods: Cirrhotic ascitic rats were induced with renal dysfunction by bile duct ligation (BDL). Then, 2 weeks of pioglitazone treatment was administered from the 6th weeks after BDL. Additionally, acute lipopolysaccharide was used to induce acute renal dysfunction. Subsequently, various circulating, renal arterial and renal tissue pathogenic markers were measured. Results: Cirrhotic BDL rats are characterized by decreased mean arterial pressure, increased cardiac output and portal venous pressure, reduced renal arterial blood flow, increased renal vascular resistance, increased relative renal weight/hydroxyproline, downregulated renal PPARγ expression, upregulated renal inflammatory markers, increased adhesion molecules, increased renal macrophages, and progressive renal dysfunction. In particular, acute LPS administration induces acute on chronic renal dysfunction (increasing serum BUN/ creatinine, increasing RVR and decreasing RABF) by increased TNFα-NFκB-mediated renal inflammatory markers as well as renal M1 macrophages infiltration. Activation of systemic, renal vessels and renal tissue levels of PPARγ by chronic pioglitazone treatment has beneficial effects on the endotoxemia-related TNFα/NFκB-mediated acute and chronic renal inflammation in cirrhosis. Conclusions: Normalization of renal and renal arterial levels of PPARγ effectively ameliorated LPS-induced acute and chronic renal dysfunction in cirrhotic ascitic rats.

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低血液淋巴球 - 單核球比、CALCITRIOL 與 CD206 濃度能預測肝硬化病人急性肝衰 竭之發生 LOW LYMPHOCYTE-TO-MONOCYTE RATIO, CALCITRIOL, AND CD206 PREDICT OCCURRENCE OF ACUTE ON CHRONIC LIVER FAILURE IN PATIENTS WITH CIRRHOSIS

郭乃榕1,2,3 黎子豪3,4,5 楊盈盈1,2,3,5 黃加璋1,2,3 朱威奇5 劉志偉1,2,3 侯明志2,3 林漢傑2,3 臺北榮民總醫院教學部1 臺北榮民總醫院內科部2 國立陽明交通大學醫學系3 新光紀念醫院內科部過敏免疫風濕科4 國立陽明交通大學臨床醫學研究所5

Background: Acute on chronic liver failure (ACLF) has been notoriously accompanied by high morbidity and mortality in cirrhotic patients. Several models for prognosis and mortality of ACLF have been reported, but limited literature focused on the occurrence of ACLF. In addition, accumulating evidence has revealed various novel markers including calcitriol, CD206 and Mincle may play some roles in cirrhotic patients. Aims: We aimed to identify the risk factors along with calcitriol, CD206 and Mincle, for occurrence of ACLF in cirrhotic patients. Moreover we managed to derive a model for occurrence of ACLF based on the novel serum markers. Methods: We enrolled patients with cirrhosis without listed exclusion criteria, and measured the serum levels of calcitriol, CD206, and Mincle. We carefully reviewed the medical records of the following 6-month, and applied generalized estimating equation (GEE) to assess the association of the relevant factors with occurrence of ACLF. Accordingly, we derived a model of occurrence of ACLF in the 6-month period; receiver operating characteristic (ROC) analysis with area under curve (AUC) was adopted to evaluate the accuracy. Results: After screening 325 cirrhotic patients, 65 subjects were eligible. By GEE model, low serum level of calcitriol (<3.45 pg/ml, odds ratio [OR] 3.259, 95 % confidence interval [CI] 1.118 – 8.929), low serum level of CD206 (<127.12 ng/ml, OR 2.666, 95 % CI 1.082 - 6.567) were associated with higher OR of ACLF, and lymphocyte-tomonocyte ratio level was a protective factor (OR 0.356, 95 % CI 0.147 – 0.861). We derived the model on the basis of low LMR (<2.014), low calcitriol level, and low CD206; each of these 3 items was allotted as 1 point, and the sum was used to discriminate the occurrence of ACLF in the following 6 months, of which the AUC was 0.734 (95% CI = 0.598 - 0.869). Conclusions: Lower LMR, low calcitriol, and low CD206 are associated with ACLF incidence in cirrhotic patients; the model based on these markers could identify the occurrence of ACLF in the following 6 months.

主題：脂肪肝相關疾病

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有較高程度肝脂肪變性的非酒精性脂肪肝病 人接受肝癌切除手術後有較低的肝癌復發率 HIGHER GRADE OF HEPATIC STEATOSIS WAS ASSOCIATED WITH LOWER RECURRENCE OF RESECTABLE HEPATOCELLULAR CARCINOMA IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE

陳益程1,3 陳聰興1,3 許朝偉1,3 游明晉2,3,4 林口長庚紀念醫院胃腸肝膽科1 林口長庚紀念醫院一般外科2 長庚大學醫學院3 新北市立土城醫院一般外科4

Background: Non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH)-related cirrhosis, is recognized as a critical risk factor for the development of hepatocellular carcinoma (HCC). The HCC recurrence after surgical resection among different grades of hepatis steatosis in NAFLD patients is rarely discussed. Aims: To investigate the associated factors for recurrence of resectable HCC in patients with NAFLD Methods: From 2009 August to 2018 December, patients receiving complete surgical resection of HCC in Chang Gung Memorial Hospital were reviewed retrospectively. The 2017 version of the combined American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) TNM (tumor, node, metastasis) staging system was utilized for HCC staging. Tumors with T1-3N0M0 were selected. Patients with concurrent hepatitis B virus (HBV) infection, history of hepatitis C virus (HCV) infection, autoimmune liver disease, alcoholic liver disease and human immunodeficiency virus (HIV) infection were excluded. HCC recurrence was defined as new appearance of HCC in imaging studies (CT or MRI) during follow-up. Cox proportional hazards regression analysis was performed to find the associated predictor(s) for HCC recurrence. Results: A total of 111 consecutive NAFLD patients who had received complete liver tumor resection, with pathological evidence of hepatic steatosis in non-tumor part and the diagnosis of HCC were included. The median age was 66 years. There were 85 (76.6%) males, 33 (29.7%) cirrhosis and 40 (36%) DM. Recurrence of HCC occurred in 29 (26.1%) patients during a median followup period of 40 (21.1-65.4) months. They were divided in two groups for statistical analysis: (A) low-steatosis (LS, mild, n=45) and (B) high-steatosis (HS, moderate/severe, n=66). The cumulative incidences of HCC recurrence were 11.3%, 33.1% and 42.3% at 1, 2 and 3 years in LS group, respectively and 3%, 9.4% and 14.9% at 1, 2 and 3 years in HS group, respectively (p=0.002 at year 3). Grade of steatosis (moderate/severe vs mild) (HR 0.287, 95% CI 0.125-0.659, p=0.003), AFP (HR 1.000, 95% CI 1.0001.000, p=0.027), single tumor (HR 0.206, 95% CI 0.0760.562, p=0.002) and vascular invasion (HR 3.532, 95% CI 1.469-8.495) were independently factors for HCC recurrence. Conclusions: Higher grade of hepatic steatosis was associated with lower recurrence of resectable HCC in NAFLD patients. Large-scale studies are warranted.

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HSD17B13 基因變異對非酒精性脂肪肝病與 酒精性肝病之保護作用 PROTECTIVE EFFECT OF HSD17B13 GENETIC VARIANT IN NON- ALCOHOLIC FATTY LIVER DISEASE AND ALCOHOLIC LIVER DISEASE

曾少譽1 黃以信1 張天恩1 彭清霖1 黃怡翔1 臺北榮民總醫院內科部胃腸肝膽科; 國立陽明交通大學 醫學院1

Background: Genetic factors play an important role in the development of nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). 17β-hydroxysteroid dehydrogenase (HSD17B) is a group of enzymes catalyzing the conversion between 17-keto- and 17-hydroxysteroids, which involve in the regulation of fatty acid metabolism and cholesterol biosynthesis. A loss-of-function variant in HSD17B13 (rs72613567: TA) introduces an adenine at a splice site, which was found to have a protective effect from NAFLD and ALD in Caucasians. However, little is known about this association in Asians. Aims: To evaluate the association between HSD17B13 rs72613567 genetic variant and the risk of NAFLD and ALD in Taiwanese. Methods: A total of 200 patients with NAFLD, 100 patients with ALD, and 200 healthy controls were enrolled. Their DNA were retrieved for genotype assessment of HSD17B13 rs72613567 genetic variant using the matrixassisted laser desorption ionization-time of flight (MALDITOF). The prevalence of this genotypes and the other risk factors for NAFLD and ALD were evaluated to explicate the association. Results: The control group had highest percentage of HSD17B13 rs72613567 mutant genotype TA/TA (21.0%), followed by ALD group (14.0%) and NAFLD group (9.5%, p = 0.028). Likewise, the controls group had more TA allele (40.0%) than ALD group (34.5%) and NAFLD group (29.8%, p = 0.010). The patients with TA/TA genotype had lower serum ALT and AST levels than those with TA/T and T/T genotypes in NAFLD group, ALD group, controls and whole subjects (p < 0.001). After adjustment with other confounding factors, such as age, sex, body mass index and diabetes mellitus, the HSD17B13 TA genetic variation still possessed the lower risk of NAFLD and ALD (odd ratio: 0.69, 95% CI: 0.51-0.93, p =0.015). Conclusions: The HSD17B13 rs72613567 genetic variant TA has protective effect to NAFLD and ALD in Taiwanese, which can decrease 30% risk of NAFLD or ALD, after adjustment with other risk factors. This genetic polymorphism may be a candidate for further therapeutic target to NAFLD and ALD..

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治療後非酒精性脂肪性肝病纖維化指標可預 測慢性 C 型肝炎患者接受口服抗病毒藥物 治療後的肝臟併發症 POST-THERAPEUTIC NONALCOHOLIC FATTY LIVER DISEASE FIBROSIS SCORE PREDICTS LIVER-RELATED COMPLICATIONS IN CHRONIC HEPATITIS C PATIENTS RECEIVING ORAL AGENTS

許偉帆1,2,3 賴學洲1,3 莊伯恒1 蘇文邦1 陳昇弘1,4 陳浤燿1

王鴻偉1,4 林俊哲1,4 黃冠棠1,4 林肇堂1,4 彭成元1,4 中國醫藥大學附設醫院消化醫學中心1 中國醫藥大學生物醫學研究所2 中國醫藥大學中醫學系3 中國醫藥大學醫學系4

Background: Chronic hepatitis C (CHC) is well known for its extrahepatic manifestations, such as diabetes mellitus. Circulating hepatitis C virus (HCV) virions bind to lipoproteins. Besides, lipids are essential to the HCV life cycle. Therefore, patients with CHC had a higher prevalence of hepatic steatosis and dyslipidemia than health persons and patients with chronic hepatitis B. Aims: We analyzed noninvasive assessments, especially nonalcoholic fatty liver disease (NAFLD)related noninvasive fibrosis test, to predict liver-related complications (LRCs) and hepatocellular carcinoma (HCC) in CHC patients. Methods: This retrospective study enrolled 590 consecutive CHC patients with sustained virologic response (SVR) after direct-acting antiviral agent (DAA) therapy. NAFLD fibrosis score (NFS) with the highest value of area under the receiver operating characteristic curve (AUC) were selected to compare with widely used FIB-4. Results: Of 590 patients, 188 patients had metabolic syndrome (MS). Multivariate Cox regression analysis showed total bilirubin at 3 or 6 months after DAA therapy (PW12), NFS at PW12 (hazard ratio [HR]: 2.125, P = 0.034), and AFP at PW12 (HR: 1.071, P = 0.034) as the independent predictors of LRCs in all patients. In patients with MS, NFS and AFP at PW12 were the independent predictors of LRCs and HCC. Time-dependent AUC values of NFS at PW12 for 1-year, 2-year, 3-year LRCs were higher than those of NFS at baseline in patients with MS. Conclusions: NFS at baseline or PW12 is a better predictor of LRCs compared to FIB-4 in all and patients with MS. NFS at PW12 had higher time-dependent AUC values for the prediction of LRCs compared to those of NFS at baseline. NFS at PW12 could be a useful predictor of LRCs and HCC in CHC patients with SVR after DAA therapy, especially in CHC patients with MS.

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小異二聚體伴侶 (SHP) 在非酒精性脂肪性肝 炎 (NASH) 病人之肝組織入核程度增加與膽 酸累積及肝發炎之相關性 ENHANCED SMALL HETERODIMER PARTNER (SHP) NUCLEAR LOCALIZATION IS ASSOCIATED WITH BILE ACID ACCUMULATION AND HEPATITIS IN NASH PATIENTS

楊凱鈞1 簡世杰1 陳炯瑜1 蔡曜聲4 鄭斌男1 蔡弘文2 林毅志3 謝淑珠5 邱彥程1 邱宏智1 國立成功大學醫學院附設醫院內科部1 國立成功大學醫學院附設醫院病理部2 國立成功大學醫學院附設醫院外科部3 國立成功大學醫學院臨床醫學研究所4 國立成功大學醫學院醫學檢驗生物技術學系5

Background: Non-alcoholic steatohepatitis (NASH) is the coexistence of hepatic steatosis and inflammation, causes chronic hepatitis and cirrhosis. Bile acid (BAs) controls itself homeostasis by BA receptor: SHP. Activation of SHP can reduce BA synthesis and maintain BA homeostasis. Increased serum BA is observed in NASH patients (Figure 1) but mechanism is unknown. In this study, we dissected the role of SHP and related signals in the pathogenesis of increased serum BA level in NASH patients by tissue immunofluorescence staining, and determined the clinical significances of enhanced SHP nuclear localization in NASH patients Aims: To investigate ratio of SHP nuclear localization in hepatic tissues from NASH patients and examine its correlation with related signaling proteins and clinical characteristics of patients Methods: We examined ratio of hepatic SHP nuclear localization and nuclear co-localization with SHP associated proteins by immunofluorescent staining of hepatic tissues from NASH patients and controls. Image data were quantified by TissueQuest software. We correlated its ratio with important clinical parameters, profile of serum BAs, as well as level of tissue mRNAs. Patients with NASH were diagnosed and scored by NASHCRN criteria, and staged according to fibrosis. Statistical comparison between NASH patients and controls was performed by Kruskal Wallis test with corresponding posthoc analysis. Results: 1. SHP was enhanced into nucleus in NASH patients. Immunofluorescent staining showed that the ratio of SHP nuclear localization was significantly higher in NASH patients comparing to that of controls (percent and number of analyzed patients in NASH vs. control: 47.04% (n=20) vs. 2.24% (n=5), p < 0.001, Figure 2). By contrast, immunofluorescent staining revealed that there was a low ratio of FXR nuclear localization and a high ratio of LRH1 nuclear localization both in NASH patients and controls, without statistically significant differences between NASH and controls. 2. Enhanced SHP nuclear localization in NASH patients is associated with higher degree of hepatic steatosis and higher serum hepatitis markers, as well as higher serum BA. Correlation analysis showed that ratio of SHP nuclear localization was significantly and positively correlated with degree of tissue steatosis (Rho=0.73, p <0.0001), and serum hepatitis markers, including ALT (Rho = 0.67, p = 0.0002), AST (Rho = 0.55, p = 0.004), γ-GT (GGT, Rho = 0.52, p = 0.01) and alkaline-P (Alk-P, Rho = 0.53, p=0.009, data not shown). Moreover, patients’ BMI (Rho = 0.60, p = 0.002), fasting serum glucose (Rho = 0.58, p = 0.003), and serum triglyceride (Rho = 0.44, p = 0.02) levels were also positively and significantly correlated with ratio of SHP nuclear localization. On the other hands, ratio of SHP nuclear localization was positive and significant correlations with serum GCA, TCA and total CA levels. More importantly, the ratio of SHP nuclear localization was also positively associated with tissue mRNA level of CYP7A1 (Figure 3). Conclusions: Enhanced SHP nuclear localization is a hallmark of NASH patients, which is associated with hepatitis, metabolic dysfunction, as well as BA accumulation

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身體質量指數對非酒精性脂肪肝病臨床病理 表現的影響 THE IMPACT OF BODY MASS INDEX ON CLINICOPATHOLOGICAL FEATURES OF NONALCOHOLIC FATTY LIVER DISEASE IN TAIWAN

林志陵1 戴啟明2 黃志富3 劉俊人4 鄭斌男5 陳啟益6 彭成元7 王嘉齊8 翁詩涵9 曾岱宗10 高嘉宏10 臺北市立聯合醫院仁愛院區消化內科1 義大醫院內科部胃腸肝膽科2 高雄醫學大學附設醫院肝膽胰內科3 國立臺灣大學醫學院附設醫院肝炎研究中心4 國立成功大學醫學院附設醫院內科部5 嘉義基督教醫院內科部胃腸肝膽科6 中國醫藥大學附設醫院內科部消化系7 臺北慈濟醫院內科部8 臺北市立聯合醫院仁愛院區教學研究部9 國立臺灣大學醫學院設醫院內科部腸胃科10

Background: Non-alcoholic fatty liver disease (NAFLD) has become one of the most prevalent chronic liver diseases in the world, with an incidence of about 15 to 30% in the general population. Aims: The aim of this study was to assess the impact of body mass index (BMI) on the clinical and histological characteristics of patients with NAFLD in Taiwan. Methods: Patients with clinically diagnosed NAFLD who received liver biopsy were retrospectively enrolled from 2007 to 2019. All of the patients were divided into lean body mass (<23 kg/m2), overweight (23–24.9 kg/m2) and obesity (BMI ≧ 25 kg/m2). The clinical manifestations and histological characteristics were compared between 3 groups. Histopathological evaluation was based on the Nonalcoholic Steatohepatitis Clinical Research Network (NAS-CRN) scoring system. Three non-invasive serological markers, including NAFLD fibrosis score, fibrosis index based on four factors (FIB-4) score and aspartate aminotransferase to platelet ratio index (APRI) were used to evaluate the severity of liver fibrosis. Receiver operating characteristic (ROC) curves were constructed and the optimal cut-off values of non-invasive biomarkers were estimated to evaluate the discriminatory ability for severity of fibrosis. Results: A total of 572 patients with histologically confirmed NAFLD, including 40 (6.99%) lean body mass, 54 (9.44%) overweight and 478 (83.57%) obese patients were recruited. Obese NAFLD patients had significantly higher grade of steatosis (grade 3: 29.92% vs. 22.22% vs. 12.5%, P<0.0001) and hepatocyte ballooning (grade 2: 14.85% vs. 12.96% vs. 12.5%, P<0.0001) than lean and overweight NAFLD patients. The prevalence of nonalcoholic steatohepatitis (NASH) were 22.5%, 25.93% and 36.19% in lean, overweight and obese NAFLD patients. In all patients with NAFLD, the fibrosis stage tends to increase in patients with definite NASH. Patients with definite NASH had a higher proportion of significant fibrosis (F2-F4) than non-NASH and borderline patients [95/196 (48.47%) vs. 34/133 (25.57%) vs. 83/243 (34.16%), P<0.0001). Regardless of BMI value, 15% of patients with non-NASH had liver cirrhosis. The FIB4 score can identify NAFLD patients without significant fibrosis or with cirrhosis. The area under receiver operating characteristic curves of FIB-4 score to identify patients without significant fibrosis or with cirrhosis were 0.79 (95% CI:0.69-0.89) and 0.84 (95% CI:0.72-0.96) in lean and overweight NAFLD patients; and were 0.77 (95% CI:0.720.82) and 0.89 (95% CI:0.85-0.92) in obese NAFLD patients. Conclusions: The majority of patients with NAFLD are obese, as defined by BMI. Obesity was significantly associated with NASH and the liver fibrosis severity in patients with NAFLD. FIB-4 may serve as a useful marker for monitoring liver fibrosis progression in NAFLD patients.

主題：上消化道疾病（一）

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探討不同亞型胃食道逆流症病患睡眠障礙與 身心共病之關聯性 INTERACTION BETWEEN SLEEP DISTURBANCES AND PSYCHOLOGICAL DISTRESS IN GERD PATIENT WITH DIFFERENT PHENOTYPES

雷尉毅1 梁書瑋1 王仁宏2 洪睿勝1 翁銘彣1 易志勳1 劉作財1 林霖1 陳健麟1

佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃

科1 佛教慈濟醫療財團法人花蓮慈濟醫院研究醫學部2

Background: Although sleep disturbances and gastroesophageal reflux disease (GERD) are known to be bi-directionally associated, interrelationships between sleep disturbances, reflux parameters, psychological factors, and esophageal hypervigilance are yet unknown. Aims: This study aimed to investigate associations between objective sleep quality, subjective and objective reflux metrics, affective disorders and esophageal hypervigilance in the various GERD phenotypes. Methods: Consecutive adult patients with reflux symptoms were prospectively evaluated with endoscopy and ambulatory pH-impedance monitoring to phenotype GERD into non-erosive reflux disease (NERD), reflux hypersensitivity (RH), and functional heartburn (FH). All patients completed validated questionnaires: gastroesophageal reflux disease questionnaire (GERDQ), reflux symptoms index (RSI), Pittsburgh Sleep Quality Index (PSQI), esophageal hypervigilance and anxiety scale (EHAS), Taiwanese Depression Questionnaire (TDQ), and State-Trait Anxiety Inventory (STAI) score. Acid exposure time (AET) and mean nocturnal baseline impedance (MNBI) were calculated. PSQI>5 defined sleep disturbance. Correlations between PSQI, GERDQ, RSI, EHAS, TDQ, STAI, and reflux parameters were assessed using Pearson’s correlation. Clinical, psychological, and reflux profiles were compared between patients with each GERD phenotype. Results: Of 243 reflux patients with sleep disturbances (48.0±13.6 years, 60.9% female), 43 (18%) had NERD, 96 (39%) had RH, and 104 (43%) had FH. Compared to RH or FH, NERD patients had higher body mass index (p<0.001), higher GERDQ score (p=0.033), and a lower MNBI (p<0.001). There were no differences in sex, RSI, PSQI, EHAS, TDQ and STAI between GERD phenotypes. There was no correlation between PSQI and AET. While PSQI correlated significantly with depression (p=0.001) and anxiety (p=0.047) in NERD, correlation were seen with TDQ (p<0.001), EHAS (p=0.009) and EHAS subscales (hypervigilance, p=0.037; anxiety, p=0.011) in RH and FH. After multivariable analysis, TDQ (p<0.001) and STAI (p=0.047) were the only independent risk factors for sleep disturbances in NERD, while TDQ (p<0.001), EHAS subscales (hypervigilance, p=0.026; anxiety, p=0.011), and EHAS (p=0.007) remained significantly associated with sleep disturbances in RH or FH. Conclusions: Esophageal hypervigilance and anxiety measured using EHAS directly associate with sleep disturbances in RH and FH, but not in NERD. Despite sleep disturbances frequently reported in GERD, acid burden is not a predictor; instead, interrelationships exist between sleep disturbances and psychological distress in all GERD phenotypes. Our findings highlight the role of esophageal hypervigilance and anxiety not only in mediating perception of GERD severity but also in impacting refluxrelated sleep disturbances.

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利用芝加哥診斷標準 3.0 版與 4.0 版在食道 高解析度動力學檢查之判讀 UTILIZATION CHICAGO CLASSIFICATION VERSION 3.0 AND 4.0 ON INTERPRETATION OF ESOPHAGEAL HIGH RESOLUTION MANOMETRY

葉勇呈1,2 王彥博1,2,3,4 宋寬益1,2,4 林弘恩1,2,4 侯明志1,2,4 盧俊良1,2,3,4 臺北榮民總醫院內視鏡診斷暨治療中心1 臺北榮民總醫院胃腸肝膽科2 國立陽明交通大學腦科學研究所3 國立陽明交通大學醫學院醫學系4

Background: High resolution manometry (HRM) with topography plots had facilitated detailed observation of the contractile characteristics of the esophagus and the relaxation of its sphincters. HRM provided a comprehensive descriptions of esophageal peristalsis after wet swallowing that improved both diagnosis and management of esophageal motility disease, especially achalasia. Chicago’s classification had been updated in recent decades from version 1.0 (year 2008), 2.0(year 2012) to 3.0(2015) which categorized esophageal motility disease from disorders with esophagogastric junction obstruction, major disorders of peristalsis, minor disorders of peristalsis and normal. This classification helped clinicians easily identify patients with characterized esophageal motility disease. However, the clinical presentations and severity of patients may not correspond to their manometric findings. Other than achalasia, the management based on the classification was also unclear. Recently, a newly proposed Chicago’s classification version 4.0 was launched in the end 2021 which included both supine and sitting swallowing tests, provocation tests and had new classification in esophageal peristalsis. The influences of this new version of classification on the diagnosis and management of esophageal motility disorders is still unknown. Aims: We aimed to compare the high resoluation mamonetry examination interpretations between using Chicago’s criteria version 4.0 versus Chicago’s criteria version 3.0 to find out the clinical impact of its changes. Methods: e retrospectively reviewed the consecutive HRM records from Oct, 2019 to May, 2021 in Endoscopy center for Diagnosis and Treatment in Taipei Veterans General Hospital. From Oct, 2019, all the HRM were performed under the standardized protocol including supine resting pressure, 10 times of supine wet swallowing 5ml water, 3 times of supine multiple rapid swallowing 10ml water, sitting resting pressure, 10 times of sitting wet swallowing 5ml water, and 3 times of sitting multiple rapid swallowing 10ml water. In patients with EGJ outflow obstruction and absent contractility in both supine and sitting position, bolus transit status was evaluated by impedance analysis first. Timed barium esophagography or 200ml water massive drinking test was performed if incomplete bolus transit was noted. All the HRM examinations were performed using the performed with 32 circumferential pressure channels with 16 impedance channels solidstate catheter (Laborie, Medical Measurement Systems, The Netherlands). Patients receiving peroral endoscopic myotomy, surgical intervention or balloon dilatation within two years before the HRM examination were excluded from this study. Demographic data, clinical symptoms, indications for manometry and previous intervention history were obtained. We manually reviewed the records and analyzed the records by using Chicago’s classification version 3.0 and 4.0. The manometric parameters and diagnosis were recorded and analyzed. Results: 105 patients received HRM in the study period. Total 102 patients completed both supine and sitting tests, while 3 patients didn’t complete sitting examination due to intolerance. 56 patients (54.9%) were male while the mean age were 53.88 years old (Standard deviation 14.65 years old ). 65 patients(63.7%) received HRM due to refractory gastroesophageal reflux disease (GERD) symptoms while 37 patients(36.3%) due to dysphagia. 18 patients (17.6%) had new diagnosis using Chicago’s criteria version 4.0. The chance of having new diagnosis was comparable between refractory GERD symptoms and dysphagia group. (15.3% v.s.21.6%, p=0.43). All 7 patients classified as esophageal gastric junction outflow obstruction (EGJOO) by version 3.0 had new classification by version 4.0, including 3 normal and 4 Ineffective esophageal motility(IEM). In 18 patients classified as (IEM) by Chicago’s criteria version 3.0, 6 (33.3%) were classified as normal by version 4.0. In 11 patients classified as absent contractility by version 3.0, 3(27.3%) were newly classified as Type I achalasia by version 4.0. 2(3.8%) patients who were classified was normal in version 3.0 had new diagnosis according to sitting test data, including 1 hypercontractile esophagus and 1 IEM. No patients initially diagnosed with achalasia had new diagnosis in version 4.0. Conclusions: Chicago’s criteria Version 4.0 caused substantial changes in the diagnosis of esophageal motility disease, especially EGJOO, IEM and absent contractility irrespective of examination indication. Application of Chicago’s criteria ver. 4.0 may save the unnecessary medical resources used for diagnosis.

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台灣巴瑞特氏食道醫療診斷現況及臨床指引 遵從性之探討 QUESTIONNAIRE SURVEYS AND A COMPREHENSIVE UPDATE COURSE TO EXPLORE THE REAL-WORLD MANAGEMENT OF BARRETT’S ESOPHAGUS IN TAIWAN

林霖1 翁銘彣1 梁書瑋1 洪睿勝1 雷尉毅1 劉作財1 易志勳1 李青泰2 王文 2 陳健麟1

佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃

科1 義大醫院內科部肝膽腸胃科2

Background: The current status in guidance and standards on management of Barrett’s esophagus (BE) in clinical practice is less well known in Taiwan. Aims: We aimed to evaluate the preferred diagnosis and management of BE among domestic endoscopists by questionnaire-based surveys before and after comprehensive review and update course (CRUC). Methods: This study invited 60 endoscopists from across Taiwan to participate and respond to the questionnaire including diagnosis, surveillance and treatment of BE. All participants have to complete the same questionnaire before and after CRUC by real-time voting system. We analyzed all the results from questionnaires and compare the results before and after CRUC. Results: After CRUC, the agreement for requiring intestinal metaplasia for the diagnosis of BE was decreased (71% vs. 54.5%, p<0.05), and more endoscopists will adhere to Seattle protocol (3% vs. 20.8%, p<0.05) for biopsy. Preferring the top of gastric fold as esophagogastric junction were similar (70% vs. 60%, p=NS). More attendees agreed to adhere to Prague C&M criteria (42.5% vs. 73%, p<0.05) for endoscopic reporting. Most of the attendees would apply image-enhanced endoscopy (including Magnifying endoscopy, Acetic acid) to detect dysplastic BE during daily practice (100% vs. 97%, p=NS). The agreement to do surveillance in BE patient without dysplasia every 3-5 years was increased (10% vs. 57%, p<0.05). More attendees preferred no ablation therapy in BE patient with low grade dysplasia (39% vs. 61%, p<0.05). All the attendees agreed ablation or resection for BE with high grade dysplasia regardless of the course. The agreement for apply ablation therapy for residual Barrett’s epithelium after endoscopic resection of high-grade dysplasia/adenocarcinoma was significantly increased (33% vs. 92%, p<0.05) after CRUC. Conclusions: This study not only explores the real-world data of BE management, but also highlights the importance of further nationwide education as well as standardization for improving the quality in the management of BE in Taiwan.

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內視鏡抗逆流黏膜介入術於難治型胃食道逆 流的治療——系統回顧與統合分析 ANTI-REFLUX MUCOSAL INTERVENTION (ARMI) PROCEDURES FOR REFRACTORY GASTROESOPHAGEAL REFLUX DISEASE - A SYSTEMATIC REVIEW AND META-ANALYSIS

葉人豪1 李青泰1 林志文1 蕭博仁1 王文 1 義大醫院胃腸肝膽科1

Background: Endoscopic treatments have become increasingly considered for refractory gastroesophageal reflux disease (GERD). Three procedures share the same concept and similar techniques: anti-reflux mucosectomy (ARMS), anti-reflux mucosal ablation (ARMA), and antireflux band ligation (ARBL) are systematically reviewed and collectively named anti-reflux mucosal intervention (ARMI). Aims: To explore the efficacy and safety of ARMI procedures. Methods: PubMed, Embase, and Cochrane Library databases were searched through October 2021. The primary outcome was the clinical success rate. Secondary outcomes included changes of acid exposure time and DeMeester score, need of proton pump inhibitors (PPI), and adverse events. Results: Sixteen studies were included. Pooled clinical success rate was 73.8% (95% confidence interval, CI = 69%-78%) among all studies. For respective technique, pooled clinical success was 68.6% (95% CI = 62.2% - 74.4%) with ARMS, 86.7% (95% CI = 78.7% - 91.9%) with ARMA, and 76.5% (95% CI = 65% - 85.1%) with ARBL. Symptom improvement based on clinical questionnaires appeared lasting at least 12 months. ARMI also result in significantly improved acid exposure time, DeMeester score, and degree of hiatal hernia. 10% patients had dysphagia required endoscopic dilatation after ARMS or ARMA, and ARMS had 2.2% perforation rate. In contrast, no bleeding, perforation, or severe dysphagia was noted with ARBL. Severe hiatal hernia (Hill grade III) may predict treatment failure of ARMA. Conclusions: The ARMI procedures are efficacious and safe for PPI-refractory or PPI-dependent GERD. ARMA and ARBL might be preferrable given the lower adverse events and similar efficacy to ARMS. Further studies are necessary to determine the optimal technique and clinical candidates.

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MOSAPRIDE 對口咽吞嚥生理功能之影響 EFFECTS OF MOSAPRIDE ON OROPHARYNGEAL SWALLOWING PHYSIOLOGY

梁書瑋1 洪睿勝1 翁銘彣1 雷尉毅1 劉作財1 易志勳1 林霖1 陳健麟1

佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃

科1

Background: The 5-Hydroxytryptamine receptor 4 agonist, mosapride modulates esophageal peristalsis and attenuates lower esophageal sphincter compliance. The impact of mosapride on oropharyngeal swallowing physiology has not been well elucidated. Aims: We aimed to investigate whether mosapride influences oropharyngeal swallowing physiology. Methods: Twenty four healthy volunteers (13 man, mean 33 years, 24-56 years) were recruited. Studies were performed one hour after either 40mg mosapride or placebo administration. High resolution impedance manometry studies with a solid-state catheter (Laborie, Solar GI acquisition unit, MMS) were performed to record oropharyngeal segment pressure and impedance. At least three swallows of 5, 10 and 20mL standardized thin and thick liquid (SBMkit, Trisco Foods) were delivered by a syringe. Oropharyngeal swallowing metrics included pharyngeal contractile integral, upper esophageal sphincter (UES) maximum opening admittance, UES integrated relaxation pressure, UES relaxation time, mean hypopharyngeal peak pressure, bolus presence time, distention contraction latency, hypopharyngeal intra-bolus pressure and the global swallow-risk-index. Results: All participants completed the protocol. Mosapride increased UES maximal opening admittance than the placebo during thick swallows (5mL: p=0.017; 10mL: p=0.008). Mosapride decreased UES integrated relaxation pressure (10mL: p=0.018; 20mL: p=0.017) during thick swallows than the placebo. Mosapride had no effect on oropharyngeal swallows during thin swallows. Other pharyngeal metrics were not affected by mosapride. Conclusions: Oral mosapride enhances relaxation diameter and reduces the resistance of UES. These findings may suggest novel physiological evidence that mosapride can modulate neuroregulatory mechanisms mediating UES relaxation.

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以人工智慧加速胃食道逆流症患者酸鹼阻抗 檢查之逆流事件及逆流後吞嚥蠕動波判讀 ARTIFICIAL INTELLIGENCE ASSISTS EFFICIENT MEASUREMENT OF REFLUX EPISODES AND POSTREFLUX SWALLOW-INDUCED PERISTALTIC WAVE INDEX FROM PH-IMPEDANCE STUDIES IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE

翁銘彣1 劉民翔2 雷尉毅1 洪睿勝1 梁書瑋1 林霖1 劉作財1 易志勳1 吳彬安2 陳健麟1

佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃

科1

佛教慈濟醫療財團法人花蓮慈濟醫院人工智慧創新研

發中心2

Background: Reflux episodes and postreflux swallowinduced peristaltic wave (PSPW) index are useful impedance parameters that can augment the diagnosis of gastroesophageal reflux disease. However, original commercialized analysis of pH-impedance monitoring is known to overestimate reflux episodes, which causes time consuming from manually checking individual reflux episodes and PSPW. Aims: This study aims to evaluate whether a supervised learning artificial Intelligence (AI) model is feasible and useful to identify reflux episodes and PSPW. Methods: Consecutive patients with chronic (at least 3 months) reflux symptoms and negative endoscopy underwent 24-hour impedance-pH monitoring were enrolled for analysis. Multiple AI and machine learning with convolutional neural network were explored based on manual interpretation of reflux episodes and PSPW. Data were reported as median and interquartile range (IQR) and were compared using the Wilcoxon signed-rank test, with Bonferroni correction for multiple comparisons among automated analysis, manual interpretation, and AI identification. Results: We retrospectively analyzed 59 eligible patients with 2380 impedance events, of whom 11 patients with pathological acid exposure time (AET) and 48 patients with physiological AET. On the manual interpretation, patients with pathological AET had more reflux episodes and lower PSPW index than those with physiological AET (median reflux episode: 38.5 vs. 27.5, P=0.019; median PSPW index: 37.5% vs. 60%, P=0.008). In patients with chronic reflux symptoms, the number of reflux episodes identified from originally commercialized automated analysis was more than from manual correction (median, 46.5 vs. 31, P<0.001), while the number of reflux episodes identified from AI was similar to manual correction (median, 29 vs. 31, P=0.509). Overall accuracy of AI model for detecting reflux episodes and PSPW were 83% and 75% respectively. Conclusions: Our study indicates that AI has the potential to accurately and efficiently measure these novel impedance metrics in the near future.

主題：其他消化道疾病

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使用雷尼替丁藥品導致暴露在 N- 亞硝基二 甲胺成分之中會增加罹癌風險：一個以全國 人口為對象之縱向世代研究 EXPOSURE TO N-NITROSODIMETHYLAMINE DUE TO RANITIDINE USE MAY INCREASE CANCER RISK: A POPULATION-BASED LONGITUDINAL COHORT STUDY

鍾鎮宇1 牟聯瑞1 張國寬1 林瑞昌1 王俊雄1

臺南市立醫院（委託秀傳醫療社團法人經營）胃腸肝

膽科1

Background: N-nitrosodimethylamine (NDMA), a carcinogenic chemical, was recently identified in ranitidine which was globally recalled from retail drug stores. Many studies have investigated ranitidine use and cancer development. However, there is a lack of sufficient data in the literature on ranitidine use and long-term specific cancer risks. Aims: We aimed to use a large-scale follow-up cohort study to explore ranitidine use and the emergence of cancer over time. Methods: We conducted an observational population-based cohort study using the Taiwan National Health Insurance (NHI) Research Database, which is a universal health insurance program that is compulsory by law, has operated since 1995 and provides comprehensive medical coverage to the 23 million residents of Taiwan. After excluding those who met any of the following criteria: (1) diagnosed with cancer before the index date; (2) ranitidine use for less than three months; (3) follow-up period for less than one year; (4) aged under 40 years old, a total of 75,715 eligible patients (mean age=66.8±14.1 years; median follow-up time: 8.3 years) who had received ranitidine between January 2000 and December 2018 were enrolled in the treated cohort. By propensity score matching (PSM), they were matched 1:1 with 1,022,2170 untreated controls, who were sampled from 2,000,000 insureds of the NHI program, to observe longitudinally for assessing ranitidine exposure and its outcome relationships with various cancer presentations. Results: The covariates, such as age, sex, co-medications, comorbidities, and the Charlson Comorbidity Index, have been well-balanced between ranitidine-treated and ranitidine-untreated groups. After PSM, 55,110 participants were classified as unexposed to NDMA (non-ranitidine users), and 55,110 participants were classified as exposed to NDMA (ranitidine users). Univariable and multivariable Cox regression analyses to compare the hazard for cancer diagnosis between the two groups show that cancer outcomes with risk increases were observed for hepatocellular carcinoma (HCC) (hazard ratio: 1.22, 95% confidence interval: 1.09 to 1.36, p < 0.001), lung cancer (hazard ratio: 1.17, 95% confidence interval: 1.05 to 1.31, p = 0.005), gastric cancer (hazard ratio: 1.26, 95% confidence interval: 1.05 to 1.52, p = 0.012), and pancreatic cancer (hazard ratio 1.35, 95% confidence interval:1.03 to 1.77, p = 0.030). The crude incidence rates of the above four cancers diagnoses in the ranitidine use group were HCC 1.35 cases per 1000 person-years (95% confidence interval 1.251.45); lung cancer 1.23 cases per 1000 person-years (95% confidence interval 1.14-1.33); gastric cancer 0.48 cases per 1000 person-years (95% confidence interval 0.43-0.55); pancreatic cancer 0.23 cases per 1000 person-years (95% confidence interval 0.19-0.27). Being estimated by the modified Kaplan–Meier method, the cumulative incidences of HCC, lung cancer, gastric cancer, and pancreatic cancer in the ranitidine-treated group were significantly higher than that in the untreated group over the span of 18 years. Conclusions: In this large population-based study, the long-term use of NDMA-contaminated ranitidine was associated with an increased risk of HCC, lung, pancreatic, and gastric cancers.

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發炎性腸道疾病接受生物製劑治療後腸道菌 叢的變化 CHANGES IN GUT MICROBIOTA OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE RECEIVING BIOLOGIC THERAPY

蔡雨潔1 姚志謙1 蔡明釗1 戴維震1 蔡成枝1 高雄長庚紀念醫院胃腸肝膽科1

Background: Inflammatory bowel disease (IBD), comprising the predominant forms Crohn’s disease (CD) and ulcerative colitis (UC), is a complex disease, and a general consensus exists that IBD is associated with compositional and metabolic changes in the intestinal dysbiosis. Aims: The aim of this study is to evaluate the composition in the microbiota of IBD patients who received biologic therapy, and determined these changes are produced towards the recovery of healthy-like microbiota. Methods: This is a prospective study at Kaohsiung Chung Gung memorial hospital, Taiwan, from December 2019 and March 2021. In total, we recruited 14 patients with IBD received biologic therapy and 13 IBD controls who received conventional treatment . The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples. The stool samples at baseline, weeks 6 and 48 after biologic therapy initiation were assessed (The samples in control group were collected at baseline and week 48). We also evaluated the level of inflammation and treatment response of biologics by blood inflammatory markers and IBD activity score (CD patient by Crohn’s disease activity index [CDAI] and in UC patient by Mayo score). Results: In CD group, we recruited 7 CD patients receiving biologic therapy (Anti-tumor Necrosis Factor for 4 and anti-integrin for 3) and 6 controls. Patients receiving biologics had significantly higher CDAI score (329.0 and 107.5, p =0.001) and higher ESR at week 0 (22 and 5, p=0.014). CDAI was significant decreasing at week 6 and week 48 after biologic therapy (154.9 and 115.5, respectively) . Community α-diversity was lower in patients receiving biologics at baseline compare to controls but increase abundance after achieving week 48 remission in trend. At the family level, the Clostridiales was more abundant in control group compare to biologic group. By contrast, Enterobacteriaceae and Pseudomonadaceae were significantly more abundant in patients receiving biologics at baseline .Relative Enterobacteriaceae and Pseudomonadaceae loads in patients after biologic therapy but showed no statistically difference. In UC group, we recruited 7 UC patient receiving biological therapy (Anti-tumor Necrosis Factor for 2 and anti-integrin for 5) and 7 controls . Patients receiving biologics had significantly higher mayo score (11.1 and 4.4, p=0.003) and higher ESR at week 0 (14.1 and 3.3, p=0.008). The Mayo score was significant decreasing at week 6 and week 48 after biologic therapy (3.3 and 3.6, respectively) . Community α-diversity showed no significantly changes before and after biologics in UC patients. At the family level, the Enterobacteriaceae and Bacteroidaceae were more abundant in patients who received biologics. Conclusions: Treatment with biologic therapy induced improvement of community diversity in IBD patients which seemed correlate the level of clinical inflammation. The dysbiosis-representative bacteria, such as Enterobacteriaceae, could induce colonic inflammation ,were more abundant in patients who had higher activity of IBD.Further larger prospective studies are needed to determine whether the biologic therapy could induce shortterm or long-term changes of intestinal microbiome.

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透析病人腸道微生態的變化 GUT MICROBIOTA IN PATIENTS WITH LONG-TERM HEMODIALYSIS

王崧維1 謝孟書1 余珮華2 沈群勝1,3 吳登強1,4 吳政毅1,4 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學附設中和紀念醫院腎臟內科2 高雄巿立小港醫院內科3 高雄醫學大學醫學系4

Background: Serum phosphate imbalance is important issue in patients with long-term hemodialysis due to ESRD(end-stage renal disease). Inorganic phosphate is essential element in living cells as well as gut microbiota. Gut microbiota has great impact on human health and nutrition. However, the relationship between electrolytes imbalance and the change of gut microbiota is unclear. Aims: This study aimed to explore the relationship between the blood phosphate level and the gut microbiota in patients with long-term hemodialysis. Methods: To reduce the effects of diet on serum phosphate level, we enrolled the bedridden dialysis patients in the nursing home. Most were fed via nasogastric tube and few were fed with ground diet. The patients who have antibiotics or probiotics in one month, malignancy, diarrhea are excluded. The 16S rRNA gene are sequenced for bacterial analysis, and the microbiome analysis was performed by FLASH(fast length adjustment of short reads). Results: 20 patients were analyzed in this study. The top three dominant bacterial species in those people are Enterobacteriacea, Lachnospiraceae and Lactobacillaceae. Enterobacteriacae are dominant in six of 20 patients, while Lachnospiracea are dmoniant in three of them. P3(Patient 3) had high alpha diversity, while P4 has low alpha diversity. Conclusions: In bed-ridden patients with long-term hemodialysis, nutrition is always insufficient and the phosaphate level is relatively low. Gut microbiota still varies a lot among patients in spite of diet control. Enterobacteriaceae and Lachnospiraceae are the dominant flora in those patients. In some studies, Lachnospiraceae is also related to the mechanism of CKD(chronic kidney disease). However, whether it is related to the metabolism and absorption of phosphate is unknown.

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糖尿病、高血脂及高血壓在胰臟神經內分泌 腫瘤與胃腸神經內分泌腫瘤之間的差異 THE COMPARISON OF DIABETES, DYSLIPIDEMIA, AND HYPERTENSION BETWEEN PANCREATIC AND GASTROINTESTINAL NEUROENDOCRINE TUMORS

李騏宇1 曾逸宏2 王蒼恩1,3,4 陳銘仁1,3,4 劉家源1,3,4 王鴻源1,3,4 張經緯1,3,4

臺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1

臺灣基督長老教會馬偕醫療財團法人馬偕紀念醫院內

分泌暨新陳代謝科2 馬偕學校財團法人- 馬偕醫護管理專科學校3 馬偕學校財團法人- 馬偕醫學院4

Background: The incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) [pancreatic neuroendocrine tumors (PNETs) and gastrointestinal neuroendocrine tumors (GI-NETs)] has been increasing in recent years. Nowadays, GEP-NETs represent the second most common gastrointestinal neoplasm after colorectal adenocarcinoma. An increasing rate in the prevalence of diabetes mellitus (DM) globally is also observed over time. From 2005 to 2014 in Taiwan, the total population with DM increased by 66%, and age-standardized prevalence in patients aged 20–79 years increased by 41%. Due to the increasing prevalence of GEP-NETs and DM, the association between two diseases is an important issue. As an endocrine gland, pancreas functions mostly to regulate blood sugar levels, secreting the hormones insulin, glucagon, somatostatin, and pancreatic polypeptide. Hence, PNETs may represent the stronger risk factor for the development of DM compared with GI-NETs. Aims: In the present study, we performed the retrospective study to observe whether PNETs increase the risk for the development of DM, dyslipidemia, and hypertension compared with GI-NETs. Methods: We enrolled patients who were pathologically diagnosed with GEP-NETs in Taipei and Tamsui MacKay Memorial Hospital from 2013 Jan. to 2018 Dec. The demographic data and data of blood biochemical tests were recorded. DM was considered if there was evidence of a fasting plasma glucose level of ≥ 126 mg/dL or HbA1c ≥ 6.5% or a history of DM at the time of GEPNETs diagnosis. Dyslipidemia was considered if plasma total cholesterol ≥ 200 mg/dL or plasma low-density

lipoprotein ≥ 130 mg/dL or plasma triglyceride ≥ 150 mg/dL or a history of dyslipidemia at the time of GEPNETs diagnosis. Hypertension was considered a history of hypertension at the time of GEP-NETs diagnosis. We grouped patients into the PNETs group and the GI-NETs group (including rectum, colon, small bowel, duodenum, stomach and esophagus). We described the percentage of DM, dyslipidemia and hypertension in two groups. Finally, age and sex adjusted logistic regression was performed to ascertain whether PNETs increase the risk of development of DM, dyslipidemia and hypertension compared with GINETs. For the analysis, statistical significance was set at p<0.05. Results: A total 170 patients were included in this study. Thirty patients were in the PNETs group and 140 patients were GI-NETs group. Among the 170 patients with GEPNETs, the average age was 58.7-year-old (standard deviation: 14.72-year-old) and 57.6% were male (98/170). In GEP-NETs, the percentage of DM, dyslipidemia and hypertension were 27.1% (46/170), 40.6% (69/170) and 16.5% (28/170), respectively. The characteristics of patients are listed in table 1. On age and sex adjusted logistic regression model, PNETs significantly increased the risk of development of DM compared with GI-NETs (OR: 3.69, 95%CI: 1.53-8.9, p: 0.004). However, the risk of development of dyslipidemia (OR: 0.65, 95%CI: 0.27-1.51, p: 0.318) and hypertension (OR: 0.73, 95%CI: 0.24-2.26, p: 0.586) is not statistically significant difference between PNETs and GI-NET. Conclusions: Compared with GI-NETs, PNETs increase the risk of development of DM but has no statistically significant effect on the risk of development of dyslipidemia and hypertension. Our results raised our concern that PNETs may be associated with metabolic disease and cardiovascular disease compared with GI-NETs. Future studies are needed to clarify their relationship.

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轉移性小腸腫瘤 - 一台灣多中心研究 METASTATIC SMALL BOWEL TUMORS: A TAIWAN MULTICENTER STUDY

章振旺1,8 顏旭亨2,8 黃天祐3,8 林偉彬4,8 許文鴻5,8 鍾承軒6,8 戴啟明7,8 林煒晟1 蘇銘堯4,8 陳銘仁1 馬偕紀念醫院1 彰化基督教醫院2 三軍總醫院3 林口長庚紀念醫院4 高醫附設醫院5 亞東紀念醫院6 義大醫院7 臺灣小腸醫學會8

Background: Small bowel accounts for the majority of gastrointestinal tract but its tumors are rare and always overlooked. Intraluminal small bowel neoplasms such as carcinoid, small bowel carcinoma, and lymphoma can cause small bowel obstruction due to luminal narrowing or intussusception. Small bowel tumors, predominantly metastatic malignant tumors, are the second most common cause of small bowel obstruction, accounting for approximately 20 % of cases. However, the reports of metastatic small bowel tumors were rare. Aims: To evaluate the metastatic small bowel tumors in Taiwan. Methods: We conducted a retrospective analysis of 7 medical centers in Taiwan. The data for this study were obtained from electronic medical record of enteroscopy from 2007/11 to 2021/10. All patients were diagnosed with metastatic small bowel tumors based on endoscopic, radiological and pathological examination. Baseline demographic characteristics, clinical, radiologic and endoscopic findings were collected and analyzed to compare between each histological subtype of metastatic small bowel tumors. This multicenter retrospective study were approved by the ethics committee of each participating tertiary center (Mackay Memorial Hospital, Changhua Christian Hospital , Tri-Service General Hospital, Linkou Chang Gung Memorial Hospital, Kaohsiung Medical University Hospital, Far Eastern Memorial Hospital and E-Da Hospital) and informed consent from individual patients was not required because of observational study design. Results: Totally 23 (17male, 6 female) patients with metastatic SB tumors were enrolled from 7 medical centers. Multiple organ metastasis was found in 11(47.8%)

patients In this multicenter retrospective study, we found most of the metastatic small bowel tumors were from lung cancer (26%). The diagnosed interval in multiorgan involving were 184.8±312.1 weeks, and single small bowl metastasis 34.7±39.7 weeks. It implies that some tumors may migrate first to small bowel, and then involving other organ. In the presentation, 3/ 4 patients were GI bleeding, and only 1/ 4 SBO. In the radiologic findings, 1/3 cases cannot be diagnosed from CT. In the endoscopic findings, more than half of cases with ulceration and stricture. Conclusions: Metastatic small bowel tumors are rare, but still need to be pay attention in patient with previous malignant disease.

主題：下消化道疾病（一）

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新冠肺炎全球大流行對發炎性腸道疾病患者 認知及照顧之影響：一個台灣多中心研究 THE IMPACTS OF COVID-19 PANDEMIC ON PATIENT PERCEPTIONS AND INFLAMMATORY BOWEL DISEASE CARE: A MULTICENTER STUDY IN TAIWAN

鍾承軒1,2,3,4 張崇信3,5 魏淑鉁3,4,6 黃天祐3,4,7 戴維震3,4,8 許文鴻3,4,9,10 吳登強3,4,9,10 顏旭亨3,4,11 戴啟明3,4,12 章振旺3,4,13,14 林煒晟3,4,13,14 王鴻源3,4,13,14 林春吉3,15 郭家榮3,4,16 邱正堂3,4,16 林敬斌3,4,17 李熹昌3,4,18 吳嘉峰3,4,19 亞東紀念醫院肝膽胃腸科1 輔仁大學附設醫學院2 臺灣發炎性腸道疾病學會3 臺灣小腸醫學會4 臺中榮民總醫院胃腸肝膽科及發炎性腸道疾病中心5 臺大醫學院附設醫院內科部6 臺北內湖三軍總醫院腸胃內科7 高雄長庚紀念醫院胃腸肝膽科8 高雄醫學院附設醫院內科部9 高雄市立小港醫院內科部10 彰化基督教醫院腸胃科11 義守大學附設醫院內科部12 臺北馬偕紀念醫院胃腸肝膽科13 臺北馬偕醫護管理專科學校14 臺北榮民總醫院外科部15 林口長庚紀念醫院胃腸肝膽科16 中山醫學院附設醫院內科部17 臺北仁愛醫院消化內科18 臺大兒童醫院小兒腸胃科19

Background: The coronavirus disease 2019 (COVID-19) pandemic has enormous impacts on medical system. Aims: This study aimed to evaluate the influences of pandemic on patient perceptions and medical care for inflammatory bowel disease (IBD). Methods: Between July and December 2021, a questionnaire survey on COVID-19 infection status, clinical activity of IBD, patient concerns about the infection risk, the safety of vaccination and telemedicine, was conducted at 14 tertiary centers in Taiwan. A visual analogue scale (VAS) was used to determine the level of anxiety before and after providing educational statements. Results: Totally 472 IBD patients [225 (47.67%) Crohn’s disease (CD), 244 (51.69%) ulcerative colitis (UC) and 3 (0.64%) indeterminate colitis patients] were enrolled. The gender (female/male), mean (±SD) age, body mass

index and IBD disease duration were 37%/63%, 42.69 (±0.67) years old, 23.07 (±0.19) kg/m2, 7.96 (±0.29) years, respectively. The most common concerns were higher adverse event from vaccines (20.34%), higher rate for severe COVID-19 disease (19.28%) and higher risk for COVID-19 infection (16.31%). The most concerned medication were immunomodulators (16.10%), followed by anti-TNFꭤ (9.96%) and steroid (9.32%). 35 (7.42%) patients self-discontinued IBD medication and 12 (34.28%) of them had worse symptoms. Elderly patients (> 50 yearold) (OR 1.10, 95% CI 1.01~1.19, p=0.03) and those with IBD-related complications (OR 1.16, 95% CI 1.04~1.28, p=0.01) were more anxious, while those with higher education level (OR 0.82, 95% CI 0.73~0.93, p<0.01) and residents in areas other than northern-middle Taiwan (OR 0.82, 95% CI 0.75~0.91, p<0.001) were less anxious about COVID-19 pandemic. 293 (62.08%%) patients received COVID-19 vaccination while none of enrolled patients with COVID-19 infection. Only 21 (4.45%) patients had used telemedicine for IBD care. VAS score of anxiety about COVID-19 improved after providing educational statements (3.84 ± 2.33 vs. 2.81 ± 1.96, p<0.0001). Conclusions: The medical behaviors of IBD patients were influenced by COVID-19 pandemic. After conveying correct information, patient concerns could be ameliorated.

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針對下午時段大腸鏡清腸的乾淨程度，同日 使用保可淨並不輸給分兩日使用保可淨。 SAME-DAY PREPARATION WITH SODIUM PICOSULFATE/MAGNESIUM CITRATE (SPMC) IS NOT INFERIOR TO SPLIT-DOSE PREPARATION FOR AFTERNOON COLONOSCOPY

楊承達1 楊佳偉1 黃玄遠1 陳洋源1 黃秀萍1 顏旭亨1 彰化基督教醫院1

Background: Sodium picosulfate/magnesium citrate (SPMC) is a small-volume bowel cleansing agent with similar efficacy and better tolerability than polyethylene glycol. However, there was limited data about the bowel cleansing efficacy of SPMC in comparing the same-day and split-dose preparation for afternoon colonoscopy. Aims: To compare the efficacy of same-day and split-dose preparation of SPMC for afternoon colonoscopy Methods: This randomized, single-center, endoscopistblinded, non-inferior study compared same-day (101 subjects) and split-dose (96 subjects) preparation with SPMC for afternoon colonoscopy. One additional prospective observation group of 100 subjects receiving colonoscopy in the morning was included as an observation group to compare bowel preparation in morning and afternoon colonoscopy. Efficacy of bowel cleansing was evaluated by the Aronchick Scale, Ottawa Bowel Preparation Scale (OBPS), and Boston Bowel Preparation Scale (BBPS). Results: Same-day preparation revealed no inferior to split-dose trial in all four scales. The success rate (excellent and good cleanliness) of the Aronchick Scale was 100% in same-day preparation and 92.7% in split-dose preparation. OBPS was better in the same-day preparation group (1.4 vs. 2.1). BBPS did not differ between groups (7.7 vs. 7.4). Conclusions: Our data suggest same-day preparation with SPMC is non-inferior to split-dose preparation for afternoon colonoscopy.

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USTEKINUMAB 對於中重度克隆氏症患者 誘導緩解的有效性及安全性 THE EFFICACY AND SAFETY OF USTEKINUMAB INDUCTION THERAPY IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE CROHN’S DISEASE: A REAL-WORLD STUDY IN A TERTIARY MEDICAL CENTER

李柏賢1 郭家榮1 蘇銘堯2 邱正堂1 林口長庚紀念醫院胃腸肝膽科1 新北市立土城醫院2

Background: Ustekinumab (UST), a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, has been approved for treatment of Crohn’s Disease (CD). Aims: There was no study showed its efficacy and safety in the induction therapy of Chron’s disease in Taiwan. Methods: We retrospectively collected the patients of moderate to severe Crohn’s disease who received UST treatment during December 2019 and November 2021 in Linkou Chang Gung Memorial Hospital. Patients’ characteristics, laboratory data, clinical response and clinical remission were analyzed. The results were shown as number (percentage) and median (range). Results: A total of 41 patients of moderate to severe Crohn’s disease were selected for analysis. Male (78%) was predominant with median age 36 (23-85) years old. Fortynine percent of them were biological experienced, and the median diagnostic duration was 3 (1-49) years. The median Crohn’s Disease Activity Index (CDAI) and HarveyBradshaw Index (HBI) were 279, 174, 146, 148 and 6, 3, 3, 3 at 0, 4th, 8th and 12th week. Clinical response and remission rates were 71%, 83%, 77% and 22%, 49%, 44% at 4th, 8th and 12th week. The fistula closure rate was 60% at twelfth week. The significant adverse event was noted. Conclusions: UST is an effective and safe biological induction therapy in moderate to severe Crohn’s disease with or without complications.

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糞便微菌移植治療發炎性腸道疾病患者合併 難治性或反覆性困難梭菌感染 FECAL MICROBIAL TRANSPLANTATION IN INFLAMMATORY BOWEL DISEASE PATIENTS WITH REFRACTORY OR RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION

李柏賢1 郭家榮1 邱正堂1 邱政洵2 林口長庚紀念醫院胃腸肝膽科1 林口長庚紀念醫院兒童胃腸科2

Background: The incidence of Clostridioides difficile infection (CDI) is 2-8 times higher in inflammatory bowel disease (IBD) patients than non-IBD patients. It increases the risk of surgery and mortality in IBD patients with CDI. After antibiotics treatment, IBD patients are 33% more likely to develop recurrent CDI, compared to general population. Aims: Fecal microbial transplantation (FMT) is highly effective in treating CDI, but few studies showed its efficacy and safety in refractory or recurrent CDI in IBD patients. Methods: We prospective enrolled IBD patients with acute flares who had recurrent or antibiotics refractory CDI between September 2019 and July 2021. All patients received FMT through colonoscopy, and the transplant material was prepared by Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan. Baseline characteristics, clinical response and follow-up culture/toxin results were analyzed. Results: Twenty-two times FMT (ulcerative colitis: 19 patient-times, Crohn’s disease: 3 patient-times) were performed. The median of disease duration was 27 months (range 1-108 months), and the median of age was 45-yearold (range 24- to 70-year-old). Thirteen patients were men, and five patient combined cytomegalovirus infections according to Immunohistochemical staining results. In patients with ulcerative colitis, 2, 4 and 13 patients had endoscopic Mayo sub-scores 1,2,3 points, respectively. Eighteen patients (82%) patients received FMT due to antibiotics refractory CDI, and others due to recurrent CDI. As far as medication was concerned, 55%, 14% and 41% patients received steroid, azathioprine, and biological treatment, respectively. Eight-two percent patients had significantly clinical improvement, and 86% cases had negative culture/toxin result during follow-up. The median duration of clinical response was 5 days (range 1-21 days) after FMT. The recurrent rate was 27% during follow-up. No obvious adverse events were noted in this study. Conclusions: FMT is effective and safe in treating refractory or recurrent CDI in IBD patients.

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電腦輔助偵測系統分析來自隨機對照試驗大 腸鏡回拉過程的錄影以充氣或換水大腸鏡檢 查之比較 COMPARING POLYP DETECTION RATE OF RIGHT COLON BETWEEN WATER EXCHANGE AND AIR INSUFFLATION BY A COMPUTER-AIDED DETECTION ALGORITHM: AN ANALYSIS OF WITHDRAWAL PHASE VIDEOS FROM A RANDOMIZED CONTROLLED TRIAL

唐家沛1,2 謝毓錫1,2 林土量3 曾志偉1,2 梁菲力4 大林慈濟醫院腸胃內科1 慈濟大學醫學院2 嘉義大學資訊管理學系3 美國加州大學醫學系4

Background: Water exchange (WE) improves polyp (PDR) and adenoma detection rate (ADR) compared with air insufflation, but still misses polyps due to human limitations. Paradoxically in colonoscopy, computer-aided detection (CADe) is negatively impacted by false positives (FPs) which hinders its adoption. A CADe algorithm can overcome human omissions, but is limited by FPs, which might be reduced by salvage-cleaning effect provided by insertion WE. Aims: We hypothesized that the strengths of CADe and WE can complement the weaknesses of each other. Their combination can enhance PDR and ADR and reduce false positive per colonoscopy (FPPC). Methods: We used a locally developed convolutional neural network with YOLOv4 to build a CADe model. Images of polyps were divided in 80% and 20% for training and testing. The model achieved a mean average precision of 94.0% and the area under receiver operating characteristic curve of 0.98. The sensitivity and specificity were set to 0.96 and 0.97, respectively. The positive predictive value was 0.98 and negative predictive value was 0.93. Prior to real-time application, we validated the model in detecting polyps, using edited and coded withdrawal phase videos of the right colon from a RCT comparing right colon adenoma detection between WE and air insufflation. The polyps detected by the CADe were confirmed by the consensus of 2 blinded experienced endoscopists. We also developed a computer-aided diagnosis (CADx) model based on YOLOv4 to characterize the detected polyps as adenomas or not. The primary and secondary outcomes were PDR and the FPPC, respectively. Results: A total of 245 coded videos of colonoscopies inserted with WE (n=123) or air insufflation (n=122) were analyzed. CADe achieved significantly higher PDR in the WE group (53.7%) than in the air insufflation group (38.5%), P=0.021. CADe also had significantly higher additional PDR in the WE group (30.1% vs. 12.3%, P=0.001). The CADx assessed ADR was significantly higher in the WE group than that in the air insufflation group (41.5% vs. 24.6%, P=0.006), after the detected polyps were characterized by the CADx. The mean number of FPPC due to feces (2.13 [1.85] vs. 2.90 [2.36], P = 0.007) and bubbles (0.53 [0.89] vs. 1.25 [2.45], P = 0.001) were significantly lower in the WE group than the air insufflation group. Most of FPs was ≤ 0.5 sec (1602/1678 [95.4%]). Conclusions: The data confirmed the hypothesis that the strengths of CADe and WE complemented the weaknesses of each other, enhanced PDR, ADR and reduced FPPC. The locally developed CADe and CADx are validated for polyp detection and adenoma assignment for real-time application. Furthermore, WE provides an optimal platform for the computer-assisted models.

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使用 U-NET 卷積神經網絡來自動區隔糞便 物質以客觀評估大腸鏡檢查腸道準備品質 USE OF U-NET CONVOLUTIONAL NEURAL NETWORKS FOR AUTOMATED SEGMENTATION OF FECAL MATERIAL TO OBJECTIVE EVALUATION OF BOWEL PREPARATION QUALITY IN COLONOSCOPY

王彥博1,2,4,5 鄭穎淳3,5 宋寬益1,2,5 林弘恩1,2,5 侯明志1,2,5 盧俊良1,2,4,5 臺北榮民總醫院內科部內視鏡診斷與治療中心1 臺北榮民總醫院內科部胃腸肝膽科2 臺北榮民總醫院醫學研究部3 國立陽明交通大學醫學院腦科學研究所4 國立陽明交通大學醫學院醫學系5

Background: Adequate bowel cleansing is important for a complete examination of the colon mucosa during colonoscopy. Current bowel cleansing evaluation scales are subjective with a wide variation in consistency among physicians and low reported rate. Artificial intelligence (AI) has been increasingly used in endoscopy. Aims: We aim to use machine learning to develop a fully automatic segmentation method to mark the fecal residuecoated mucosa for objective evaluation of the adequacy of colon preparation. Methods: Colonoscopy videos were retrieved from a video data cohort and transferred to qualified images, which were randomly divided into training, validation, and verification datasets. The fecal residue was manually segmented by skilled technicians. Deep learning model based on the U-Net convolutional network architecture was developed to perform automatic segmentation. The performance of the automatic segmentation was evaluated on the overlap area with the manual segmentation. Results: A total of 10,118 qualified images from 119 videos were captured, and labelled manually. The model averaged 0.3634 seconds to segmentate one image automatically. The models produced a strong high-overlap area with manual segmentation to 94.7% ± 0.67% with an intersection over union (IOU) of 0.607 ± 0.17. The area predicted by our AI model correlated well with the area measured manually (r=0.915, p<0.001). The AI system can be applied realtime to qualitatively and quantitatively display the mucosa covered by fecal residue. Conclusions: We used machine learning to establish a fully automatic segmentation method to rapidly and accurately mark the fecal residue-coated mucosa for objective evaluation of colon preparation.

主題：膽胰疾病

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針對胰臟癌合併阻塞性黃疸經引流後於術中 進行膽汁細菌培養的研究 THE STUDY OF BACTERIAL COLONIZATION BY INTRA-OPERATIVE BILE CULTURE FOR PATIENTS WITH OBSTRUCTIVE JAUNDICE DUE TO PANCREATIC CANCER TREATED BY BILIARY DRAINAGE

羅翌寧1 黃千睿1 王堯生1 吳忠翰1 康瑞文1 陳炯瑜1 國立成功大學醫學院附設醫院胃腸肝膽科1

Background: Curative surgery is still the key treatment of pancreatic cancer. Pre-operative chemotherapy, biliary drainage for patient with obstructive jaundice may be needed in selective patient. The way for biliary drainage can be performed by endoscopic retrograde biliary drainage (ERBD) with plastic stent (PS), with self-expandable metal stent (MS) or external drainage with percutaneous transhepatic biliary drainage (PTBD). However, bile duct drainage may increase the risk of bile duct bacterial colonization by ascending route from gut or by cutaneous route because of invasive intervention. Aims: To study the intra-operative bile culture for patient with pancreatic cancer with obstructive jaundice after biliary drainage Methods: Patients received biliary drainage for obstructive jaundice due to pancreatic cancer and later conversion surgery with or without pre-operative chemotherapy were enrolled in National Cheng Kung University Hospital from 2015 to 2021 retrospectively. Electric medical records were reviewed. Patients without intra-operative bile culture performed by surgery were excluded. Characteristic of patients, stage of cancer, type of drainage (PTBD, ERBD + PS, ERBD + MS), pre-operative chemotherapy, recurrent biliary obstruction, the results of bile culture including pathogens and antibiotic sensitivity test were analyzed. Results: Total fifty-eight patients with 31 men and 27 women (age: 62.1+/- 10.1 years old) were enrolled finally. All the patients were performed biliary drainage for obstructive jaundice by PTBD (22.4%, n=13), ERBD with PS (44.8%, n=26), or ERBD with MS (32.8%, n =19) respectively. Patients who treated with pre-operative chemotherapy followed by conversion surgery and upfront operation were 69% (n=40) and 31% (n=18) decided by multidisciplinary team conference. Among those patient, 77.6% (45/58) patients had positive results of bacterial colonization from bile culture. 97.8% (44/45) were

mixed florae. The distribution of bacteria was as follows: Enterococcus spp. (80%, n=36); Streptococcus spp. (20%, n=9), Escherichia coli (75.6%, n=34); Klebsiella spp. (46.7%, n=21); Citrobacter spp. (22.2%, n=10); Enterbacter spp. (13.3%, n=6); Pseudomonas spp. (13.3%, n=6); and Yeast (11.1%, n =5). As to antibiotic sensitivity, Gram’s stain positive coccus (GPC) was present 16.7% (n=7) oxacillin resistance, and Gram’s stain negative (GNB) showed 48.9% (n=22) 2nd cephalosporin resistance; 33.3% (n=15) 3rd cephalosporin resistance, and 22.2% (n=10) 4th cephalosporin resistance. By univariate analysis, the risk factors of positive biliary bacterial culture were ERBD (PS: 88.5%, MS: 94.7%, PTBD: 30.8%, p<0.01), and pre-operative chemotherapy (77.0%, n=35, p=0.01). By multivariate analysis, ERBD was the only risk factor rather than age, sex, recurrent biliary obstruction, or chemotherapy. ERBD with PS still had significant higher resistant GPC (31.8%) vs. 0% in PTBD and 0% in MS (p=0.02). Besides, ERBD group also revealed higher E coli colonization (MS: 84.2%; PS: 61.5%; PTBD: 15.4%, p=0.02), and Enterococcus colonization (MS: 78.9%; PS: 69.2%; PTBD: 8.3%, p=0.03) by multivariate analysis. Conclusions: Although drainage of obstructive jaundice in pancreatic cancer before curative surgery varies, endoscopic retrograde biliary drainage with self-expandable metal stent is by far the first recommended option. However, ascending biliary bacterial colonization may occur. Enterococcus, E coli, and Klebsiella were the most common microflorae. Among those Gram’s stain negative bacteria, by far the probability antibiotic resistance to 2nd cephalosporin , 3rd cephalosporin, and 4th cephalosporin were 1/2, 1/3, and around 1/4. Thus, empirical antibiotics for suspected postoperative intra-abdominal infection may start with 3rd cephalosporin with pseudomonas coverage.

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胰臟腫瘤特徵與內視鏡超音波切片診斷率下 降的關聯性之回溯性研究 FEATURES ASSOCIATED WITH LOWER DIAGNOSTIC RATE IN ENDOSCOPIC ULTRASOUND FINE NEEDLE BIOPSY OF PANCREATIC MASS – A RETROSPECTIVE COHORT STUDY

姜學謙1 王堯生1 黃千睿1 張維倫1 林孟穎1 成大醫院內科部1

Background: Pre-treatment pathological diagnosis of a pancreatic mass is important in guiding the following treatment. Endoscopic ultrasound fine needle biopsy (EUS-FNB) is safe and efficient in tissue acquisition for pathological diagnosis. However, 10% to 20% of patients still have an inadequate diagnosis and need extra procedures which would delay their treatment course. Aims: We aimed to investigate the tumor characteristics that are associated with an inadequate diagnosis. Methods: Patients with histological proven solid pancreatic lesions who received EUS-FNB between January 2019 and May 2021 in National Cheng-Kung University Hospital were analyzed retrospectively. The patient’s baseline characteristics, pre-EUS procedures, and image features were recorded. Features that are regarded as difficult in tissue sampling by 2 experienced endosonographic specialists were analyzed for their correlation with inadequate diagnosis, including tumor presented as isoenhancement on CT image, ill-defined tumor border on EUS, tumor size less than 20 mm, previous biliary stenting, tumor encasing celiac or superior mesentery artery, presented with features chronic pancreatitis, and tumor with cystic portion inside. Results: A total of 160 patients were enrolled. Nine patients without a definite diagnosis were excluded. EUSFNB had an overall diagnostic rate of 82.8% (125/151). In the analyzed features, tumor presented as iso-enhancement on CT image (69.7% vs 86.4%, p = 0.024), ill-defined tumor border on EUS (60% vs 89.7%, p < 0.001), and tumor size less than 20 mm (57.1% vs 86.9%, p = 0.001) had lower diagnostic rate compared to tumors without. Previous biliary stenting tends to have a lower diagnostic rate (75% vs 84.9%, p = 0.189). Tumor encasing celiac or superior mesentery artery, presented with features chronic pancreatitis, and the cystic portion inside the tumor didn’t influence the diagnostic rate. Conclusions: In this study, a pancreatic mass with features of size less than 20 mm, with an ill-defined tumor border on EUS, or presence as iso-enhancement on CT had a lower diagnostic rate in EUS-FNB compared to masses without. For patients who had pancreatic mass with these features, a multidisciplinary approach may be needed to ensure adequate diagnostic accuracy.

51 一個以多專科團隊為基礎的治療流程可有效 改善胰臟癌病患的存活率 A MULTIDISCIPLINARY TEAM-BASED COMPREHENSIVE TREATMENT ALGORITHM CAN IMPROVE THE SURVIVAL OF PANCREATIC CANCER PATIENTS

黃千睿1 王堯生1 陳炯瑜1 沈延盛2 國立成功大學醫學院附設醫院內科部1 國立成功大學醫學院附設醫院外科部2

Background: Pancreatic cancer is a disease which was difficult to diagnosed in early stage, which cause that most of the patients had advanced or metastatic disease upon diagnosis. The 5-year survival was still poor compared with other malignant disease. Many systemic treatment or surgical interventional methods were developed in the past decades, but the results were still unsatisfactory. Aims: The study aimed to analyze the improvement of the survival of the pancreatic cancer patients who received the whole treatment course in a tertiary center under a multidisciplinary team (MDT) based comprehensive treatment algorithm in Southern Taiwan. Methods: The study retrospectively collected the patients with pancreatic adenocarcinoma cancer who were diagnosed cytologically and pathologically from 2012 to 2017. The study eligible criteria were those who had complete treatment course in the tertiary center and with a detail medical cancer record in the hospital. The exclusion criteria included those who did not receive the entire treatment course in the tertiary center. Basic characteristics, primary tumor site, clinical cancer staging, lympho-vascular invasion, perineural invasion, and surgical margin were all analyzed. The treatment plan of all the patients were discussed in a multidisciplinary pancreatic cancer team meeting. All patients were treated under the comprehensive algorithm. Results: Total four hundred nighty patients were enrolled in this study, and all the data were collected from the electronical cancer medical record system. In all patients who were diagnosed in 2012-2017 and received complete treatment course, the 1-year survival rate was 51.54% and the median survival was 12.29 months (P< 0.001) regardless of the diagnosed year and disease stage. The 5-year survival were 4.72% in patients who were diagnosed in 2012, 7.77% in 2013, 5.96% in 2013, 11.46% in 2015, and the patients who were diagnosed in 2016 and 2017 not reach the 5-year survival at the data cut-off day (P< 0.001). In locally advanced patients who received treatment (n=69), those who received surgical intervention after neoadjuvant treatment, the median survival increased to 32.32 months in those who had no pathological lymph node metastasis, and only 9.79 in those with pathological lymph node metastasis (P=0.01). In multivariate analysis, pathological lymph node metastasis was also a borderline independent factor to prolong the overall survival in locally advanced patients who received curative surgical resection. Conclusions: Under a multidisciplinary team based (MDTbased) comprehensive treatment algorithm, the 5-year survival rate of pancreatic adenocarcinoma could increase year by year, even greater than 10%, which was in the top of the world. Conversion and salvage surgery after systemic treatment also improved the overall survival in patients with locally advanced or metastatic disease, but the criteria of the resectability still need more investigations. Besides, peri-operative treatment will probably become the gold standard for the treatment of pancreatic cancer in the future.

52 急性胰臟炎之營養治療與死亡率之探討：系 統性回顧與網絡統合分析隨機對照試驗 MORTALITY AMONG NUTRITIONAL THERAPIES FOR ACUTE PANCREATITIS: A SYSTEMATIC REVIEW WITH NETWORK METAANALYSIS OF RANDOMIZED CONTROLLED TRIALS

謝秉翰1 侯明志1 黃怡翔1 楊宗杰1 康以諾2 臺北榮民總醫院內科部胃腸肝膽科1 臺北醫學大學考科藍臺灣2

Background: Mortality of acute pancreatitis (AP) is associated with nutritional therapies including feeding through oral, naso-gastric (NG), nasojejunal (NJ), and total parenteral nutrition (TPN). However, previous systematic reviews of enteral nutrition typically refer to the NJ feeding. Later, network metaanalysis showed NG may be the preferred nutritional route to prevent infections. There was still no evidence which synthesized oral, NG, NJ, TPN, and no nutritional support (NNS) in consistency model with mortality. Aims: This study aimed to test the most critical issue (mortality) of nutrition management in AP via synthesizing randomized controlled trials (RCTs) with comparison of mortality between oral, NG, NJ, TPN, and NNS in treating patients with AP. Methods: The investigators completed comprehensive search in four biomedical databases without restriction on language and publication date until December 8, 2021. We also searched the reference lists of relevant studies for potential RCTs comparing oral, NG, NJ, TPN, and NNS among patients with AP. Quantitative synthesis was conducted in consistency models with frequentist approach. Pooled results of mortality were presented as risk ratio (RR) with 95% confidence interval (CI). P-score was further calculated for showing potentially optimal management of AP. Results: The network meta-analysis of 23 RCTs (a total of 1374 patients) showed that with NNS as reference group, NG (RR=0.34; 95% CI: 0.15 to 0.74) and NJ (RR=0.48; 95% CI: 0.26 to 0.88) had significantly lower mortality rates. Similarly, NG (RR=0.43; 95% CI: 0.22 to 0.82) and NJ also exhibited significantly lower mortality rates (RR=0.61; 95% CI: 0.41 to 0.91) when TPN was reference group. Moreover, based on analysis of ranking probabilities, NG (P-score=0.92) had a better trend in lowering mortality rate among variety of nutritional therapies. Conclusions: Although both NG and NJ exhibit significant findings on lowering the risk of mortality in patients with AP, NG appears to be the most preferred therapy for this population.

53 胰管支架上導線導引插管與雙導線技術於困 難膽道插管的比較 COMPARISON OF WIRE-GUIDED CANNULATION OVER A PANCREATIC STENT AND DOUBLE GUIDEWIRE TECHNIQUE FOR DIFFICULT BILIARY CANNULATION

顏廷宇1 孫煒智1 呂家名1 李昀達1 蔡騌圳1,2 陳文誌1,2 高雄榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學2

Background: In cases of difficult bile duct cannulation with unintentional passage of a guidewire into the pancreatic duct (PD), wire-guided cannulation over a pancreatic stent (WGC-PS) or double-guidewire technique (DGWT) have been used to facilitate biliary cannulation. Previous limited studies reported that WGC-PS technique significantly increased the need for precut sphincterotomy techniques compared with DGWT. Aims: The aim of this study was to compare the efficacy of WGC-PS and DGWT in patients with difficult biliary cannulation. Methods: We conducted a retrospective review of patients who received endoscopic retrograde cholangiopancreatography (ERCP) and encountered difficult bile duct cannulation with inadvertent guidewire insertion into PD while attempting the standard WGC technique between March 2017 to December 2021. Consecutive patients who underwent WGC-PS or DGWT with the aim of selective biliary cannulation were enrolled. Comparison was made between two groups with regard to baseline characteristics, the rate of successful biliary cannulation, the frequency of needle-knife (NKP) or transpancreatic (TPS) precut sphicterotomy techniques, and incidence of specific adverse events including post-ERCP pancreatitis (PEP), bleeding, and perforation. Results: A total of 137 patients including 48 WGC-PS and 89 DGWT were enrolled. The baseline characteristics were comparable with respect to gender, age, cholecystectomy status, periampullary diverticulum, percutaneous biliary drainage, and ERCP indication, and rectal NSAIDs between two groups. The only significant difference was a higher percentage of PD enhancement and PD stent placement in the WGC-PS group compared with the DGWT group (41.7% vs. 10.1% and 100% vs. 83.1%, P < 0.01). The rate of initial successful cannulation was 77.1% (37/48) in the WGC-PS group and 69.1 % (62/89) in the

DGWT group (P = 0.43). Of the patients with initial failed cannulation, 7 (87.5%) NKP and 1 (12.5%) TPS were sequentially performed for further biliary access in the WGC-PS group; 23 (88.5%) WGC-PS and 3 (11.5%) TPS in the DGWT group. In overall, 8 (16.7%) patients in the WGC-PS group and 8 (9.0%) in the DGWT group needed precut sphincterotomy techniques for biliary access (P = 0.26). The rate of overall successful cannulation was 87.5% (42/48) for WGC-PS and 89.9% (80/89) for DGWT (P = 0.78). The incidence of PEP was 6.3% (3/48) in the WGCPS group and 6.7% (6/89) in the DGWT group (P = 1.00). Two patients (2.2%) in the DGWT group had post-ERCP bleeding requiring endoscopic hemostasis and there was no perforation in both groups. Conclusions: In difficult biliary cannulation with unintended achievement of PD guidewire passage during the standard WGC technique, WGC-PS technique had similar effectiveness without increase of need for precut techniques compared with DGWT.

主題：幽門螺旋桿菌

54 探討使用高劑量氫離子幫浦抑制劑的抗生素 敏感試驗療法和經驗療法在第三線幽門螺旋 桿菌的殺菌治療效果 HIGH-DOSE PROTON PUMP INHIBITOR PLUS CULTURE-GUIDED THERAPY AND EMPIRICAL THERAPY IN THE THIRD-LINE TREATMENT OF H. PYLORI INFECTION

王俊偉1,2,3 許秉毅4 林明宏5 蔡峯偉6 吳奕霆4 施長碧4

吳登強1,2 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學醫學院醫學系2 高雄醫學大學醫學院臨床醫學研究所3 臺南市立安南醫院消化內科4 高雄醫學大學醫學院微生物學與免疫學科5 高雄榮民總醫院胃腸肝膽科6

Background: The Maastricht V/Florence Consensus Report recommends culture-guided therapy in the third-line treatment of H. pylori infection. Recent studies indicate that high-dose proton pump inhibitor (PPI) can improve cure rate of anti-H. pylori regimen. Aims: To assess the efficacies of high-dose PPI plus culture-guided or empirical therapy in the third-line treatment of H. pylori infection. Methods: Consecutive H. pylori-infected patients with at least two previous failed eradication attempts received anti-H. pylori therapy according to the results of antimicrobial sensitivity tests plus high-dose PPI and/ or bismuth. They are categorized into three groups: (1) patients who had positive result of culture with equal to or more than three susceptible antibiotics were treated by culture-guided non-bismuth therapy (rabeprazole and three effective antibiotics), (2) patients who had positive result of culture with one or two susceptible antibiotics were treated by culture-guided bismuth-containing therapy (rabeprazole and tripotassium dicitrato bismuthate plus effective antibiotics), and (3) patients who had negative result of culture or whose culture data were unavailable were treated by empirical therapy (rabeprazole plus amoxicillin, tetracycline and levofloxacin) for 14 days. Post-treatment assessment was conducted at the end of week 8. Results: A total of 126 patients participated in the study. Intention-to-treat analysis showed that the eradication rates of culture-guided non-bismuth therapy (n = 50), culture-guided bismuth-containing therapy (n = 46) and empirical therapy (n = 30) were 86.0%, 87.0% and 66.7%,

respectively. Overall, culture-guided therapy achieved a higher eradication rate than empirical therapy (86.5% vs. 66.7%, P = 0.021). Better drug adherence was noted in culture-guided therapy than empirical therapy (95.8% vs. 83.3%, P = 0.035). Besides, culture-guided bismuthcontaining therapy had fewer adverse events than cultureguided non-bismuth-containing therapy (19.6% vs. 42.0%, P = 0.018) and empirical therapy (19.6% vs. 42.9%, P = 0.012). Conclusions: High-dose PPI plus culture-guided therapy achieves a higher eradication rate than empirical therapy in the third-line treatment of H. pylori infection. Thirteen percent of infected subjects fail to eradicate H. pylori infection though the antibiotics in their rescue regimens are effective to treat the bacteria in vitro.

55 運用深度神經網絡偵測幽門桿菌感染的內視 鏡影像 DETECTION OF ENDOSCOPIC IMAGES OF HELICOBACTER PYLORI INFECTION WITH DEEP NEURAL NETWORKS

顏聖烈1 簡國樟2 林國祥2 彰濱秀傳紀念醫院肝膽腸胃科1 國立勤益科技大學資訊工程學系2

Background: Helicobacter Pylori (H. Pylori) infection is a major risk factor of gastric cancer. Endoscopic diagnosis of H. Pylori infection remains nonconclusive, although image-enhanced endoscopy (narrowing band imaging or blue laser imaging) may be helpful. Aims: To evaluate the usefulness of deep learning algorithms on the detection of gastroscopic images from patients with H. Pylori infection. Methods: From July 2020 to June 2021, patients who underwent upper endoscopy examination due to dyspeptic symptoms were included. All patient received endoscopic biopsy and rapid urease test for diagnosis of H. Pylori infection. A diagnosis of H. pylori infection was made if H. pylori were seen on histopathological examination and/ or the rapid urease test was positive. Patients with negative results in both examinations were considered to be H. pylori-negative. All patients underwent magnified blue laser imaging examination. Obtained endoscopic images were analyzed based on deep neural networks, including Inception v3, ResNet-50 and VGGNet-16. Results: A total of 160 patients who underwent upper endoscopy examination were included. There were 80 patients with positive H. Pylori infection group and 80 patients with H. Pylori-negative group. Sixty endoscopic images in each group were used for training and validation and the remaining 20 images in each group were used for testing. By using VGGNet-16, the specificity, sensitivity, positive predictive value, negative predictive value and accuracy of detecting endoscopic images of H. Pylori infection were 95%, 85%, 86.4%, 94% and 90%, respectively. Conclusions: Our study showed that deep neural network using VGGNet-16 is useful in detecting endoscopic images from patients with H. Pylori infection.

56 「混合療法」與「鉍劑四合療法」在第一線 治療具不同抗藥性之幽門螺旋桿菌的比較 COMPARISON OF THE EFFICACIES OF HYBRID THERAPY AND BISMUTH QUADRUPLE THERAPY IN THE FIRST-LINE TREATMENT FOR H PYLORI STRAINS WITH DIFFERENT ANTIBIOTIC RESISTANCES

吳弈霆1,11 陳冠仰2,11 蔡峯偉3,11 蔡成枝4,11 楊智欽5,11 李嘉龍6,11 劉玉華7,11 雷尉毅8,11 陳健麟8,11 許斯淵9,11 李熹昌2,11 許秉毅1,11 吳登強10,11 臺南市立安南醫院暨中國醫藥大學內科部消化內科1 臺北市立聯合醫院仁愛院區內科部胃腸肝膽科2 高雄榮民總醫院內科部胃腸肝膽科3 高雄長庚紀念醫院胃內科部胃腸肝膽科4 國立臺灣大學附設醫院內科部胃腸科5 國泰綜合醫院內科部胃腸肝膽科6 新光吳火獅紀念醫院內科部胃腸科7 花蓮慈濟醫院8 臺中榮民總醫院胃腸肝膽科9 高雄醫學大學附設醫院內科部胃腸科10 臺灣胃酸相關疾病暨微菌叢聯盟11

Background: Both hybrid therapy and bismuth quadruple therapy are recommended as a first-line treatment for Helicobacter pylori (H pylori) infection in several national and international guidelines. Antibiotic resistance is a crucial determinant of the treatment outcome in bacterial eradication. Currently, whether bismuth quadruple therapy can achieve a higher eradication rate than hybrid therapy in areas with high prevalence of clarithromycin-resistant H pylori strains remains unclear. Aims: To investigate the efficacies of hybrid therapy and bismuth quadruple therapy in the first-line treatment for H pylori strains with different antibiotic resistances. Methods: From September 2018 to November 2021, 475 patients with a positive result of H pylori culture in a prospective were randomly assigned to receive hybrid therapy (rabeprazole plus amoxicillin for 14 days, and clarithromycin plus metronidazole for the initial 7 days) or bismuth quadruple therapy (rabeprazole, bismuth, tetracycline and metronidazole for 10 days). Post-treatment H pylori status was assessed by 13C-urea breath test at week 6. The efficacies of the two eradication regimens for H pylori strains with non-resistance, single clarithromycin resistance, single metronidazole resistance and dual resistances were compared. Results: H pylori infection was eradicated in 94.2% of patients who hybrid therapy and 94.4% of patients who received bismuth quadruple therapy—this difference was not significant in the intention-to-treat analysis (P = 0.918). In the 475 H pylori strains isolated from the eligible patients, the proportions of those with non-resistance, single clarithromycin resistance, single metronidazole resistance and dual resistances were 55.2%, 11.2%, 26.1% and 7.2%, respectively. There were no significant differences in eradication rates between hybrid and bismuth quadruple therapies for H pylori strains with non-resistance (94.7% vs 98.5%; P = 0.172), single clarithromycin resistance (96.1% vs 93.8%; P = 0.561), single metronidazole resistance (92.0% vs 90.0%; P = 1.000) and dual resistance (82.4% vs 82.4%; P = 1.000). Conclusions: Hybrid therapy and bismuth quadruple therapy have comparable eradication efficacies for H pylori strains with single clarithromycin resistance, single metronidazole resistance or dual resistance.

57 在糖尿病患者中幽門螺旋桿菌根除與阿茲海 默症的相關性研究 . ERADICATION OF HELICOBACTER PYLORI MAY BE ASSOCIATED WITH THE INCIDENCE OF ALZHEIMER’S DISEASE IN DIABETES MELLITUS PATIENTS

林志豪1 蔡旻軒1 歐昱侖2 郭富珍3 林昆德2,4 吳登強1,4 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學附設中和紀念醫院內分泌新陳代謝內科2 義守大學義大醫院學士後醫學系3 高雄醫學大學醫學系4

Background: Alzheimer’s disease (AD) is the most common form of dementia. Eradication of Helicobacter pylori (H. pylori) could affect the incidence and progression of many diseases; however, there are limited studies of the association between H. pylori eradication and AD outcome. Aims: We utilized the National Health Insurance Research Database (NHIRD) of Taiwan to determine the relationship between H. pylori eradication and AD in a diabetes mellitus (DM) population. Methods: We collected data from the NHIRD and the Diabetes Mellitus Health Database in Taiwan of patients without a prior diagnosis of AD. We specified three cohorts: patients with (1) peptic ulcer disease (PUD) but no H. pylori treatment, without DM (PUD-HPRx in GP); (2) PUD and DM, but no H. pylori eradication therapy (PUDHPRx in DM); (3) PUD and DM, with H. pylori eradication therapy (PUD+HPRx in DM). All cohorts were matched according to age, sex, Charlson Comorbidity Index score, and comorbidities. Results: Data were collected from 2000 to 2010, and 157,231 patients were enrolled in total. We compared the effects of treatment for H. pylori infection on the incidence and mortality of AD. The patients with DM who received H. pylori eradication therapy had a higher incidence of AD than the general population (adjusted hazard ratio of incidence [aHR], 1.088). Subgroup analysis showed that the risk of AD was higher in the younger patients who received H. pylori eradication therapy as compared with those who did not (aHR for younger than 45 years, 1.071; aHR of age 45-54 years, 1.089; aHR of age 55-64 years, 1.079) However, a lower mortality rate was observed in the PUD+HPRx in DM group (aHR, 0.945, compared with PUD-HPRx in DM; P < 0.001). Conclusions: In this study, we demonstrated that DM patients who underwent treatment for eradication of H. pylori had a higher incidence of AD, especially younger patients. Nevertheless, there was a lower mortality rate in patients who received H. pylori treatment. Further study is needed to clarify the interrelated roles of AD and eradication therapy for H. pylori.

58 比較以混合療法及高劑量二合一療法作為幽 門螺旋桿菌第一線治療之效益：一前瞻性隨 機研究 COMPARISON BETWEEN HYBRID THERAPY AND HIGH DOSE DUAL THERAPY FOR FIRSTLINE HELICOBACTER PYLORI ERADICATION: A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL

劉安哲1,2 梁志明1,2 戴維震1,2 胡琮輝1,2 蔡成枝1,2 高雄長庚紀念醫院內科部1 高雄長庚紀念醫院內科部胃腸肝膽系2

Background: The application of hybrid therapy can achieve a high success rate for Helicobacter pylori (H. pylori) eradication, even in patients who are resistant to clarithromycin. On the other hand, high dose dual therapy (HDDT) is able to lengthen the duration of high intra-gastric pH and was reported to achieve a high eradication rate too. Aims: This randomized controlled study compares the real world success rate of naïve H.pylori eradication between hybrid therapy and HDDT and to investigate the factors that affect the eradication rates. Methods: We recruited 163 eligible H. pylori-infected patients after exclusion. They were randomly assigned to 14 days of hybrid therapy (RACM-14, rabeprazole 20 mg and amoxicillin 1 g b.i.d. for 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg b.i.d. for 7 days) or a 14 days of HDDT (RA-14, rabeprazole 20 mg and amoxicillin 750 mg q.i.d for 14 days). Three patients were lost during follow-up (2 in RACM-14 and 1 in RA-14 group, resulting in 80 for RACM-14 group and 80 for RA-14 group in the per protocol (PP) study. The participants were asked to performed urea breath tests eight weeks later. Results: The eradication rates for RACM-14 and RA-14 groups were 92.7% (95% confidence interval [CI] = 84.8%97.3%) and 85.2% (95% CI = 75.6%-92.1%) (p=0.127) in intention-to-treat analysis; 95.0% (95% CI: 87.7%–98.6%) and 86.3% [95% CI: 72.8%–93.0%] (p = 0.058) in per protocol analysis. The adverse event rates were 8.8% in the RA-14 group and 16.5% in the RACM-14 group (p = 0.143). Samples from 79 patients were cultured for H. pylori, and the positive culture rate was 92.4% (73/79). Hence, the antibiotic resistance rates were amoxicillin (1.3%), clarithromycin (10.1%), metronidazole (40.5%), and dual resistance to clarithromycin and metronidazole (5.1%). Conclusions: Hybrid therapy attained > 90% of successful eradication rate, compared to > 85% in HDDT for first line H.pylori eradication.

59 胃類器官在幽門螺旋桿菌感染導致胃癌的研 究 APPLICATION TO GASTRIC CANCER RESEARCH OF HUMAN STOMACH ORGANOIDS INDUCED BY HELICOBACTER PYLORI INFECTION

張景翔1 古家禎2 劉益昌3 戴明泓4 橫山一成3 吳登強1,5 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學醫學研究所2 高雄醫學大學附設中和紀念醫院細胞治療暨研究中心3 國立中山大學生物醫學研究所4 高雄醫學大學醫學系5

Background: The human gastric cancer- and normalorganoids from cancer tissues and iPS cells were established. Owing to the cellular diversity observed in the human stomachs, we attracted significant interest as a novel model system for precision medicine. Aims: However, many questions remain about the extent to which these cultures recapitulate gastro development and mechanism of Helicobacter pylori infected cancer progression. Methods: To clarify the recapitulation of human organoid models, we found several key points for in vitro culturing and differences between normal and cancerous organoids. 1. Effect of ROCK inhibitor; 2. Effect of GSK inhibitor CHIR-99021; 3. Dose of niche factors Results: (1) Effect of ROCK inhibitor; Rho kinase inhibitor was added to the primary cultures to inhibit anoikis and apoptosis were previously observed in purified colonic epithelial cells. (2) Effect of GSK inhibitor CHIR-99021; Treatment with CHIR-99021 ubiquitously and strongly activated beta-catenin-mediated transcription, induced discordant phenotypic alterations in intestinal organoids. Of note, CHIR treatment, in combination with histone deacetylase inactivation via valproic acid, comprised an effective procedure for the enrichment of Lgr5+ cells in intestinal organoids. Thus, we used only for 3 days and removed. (3) Dose of niche factors; R-SPONDIN 1 concentration of normal and cancer organoids are the same as 10 %, but WNT3A in cancer case is 10% and normal organoids required 20%. Conclusions: Here, we demonstrate not only the precise culture conditions of the human gastric organoids in vitro to improve the accuracy of generation of organoid models for apply the therapeutic and medical use, but also the effect of the growth factors such as HDGF/TNFalpha and the antioxidation reagents/ROS controls, and for cancer progression by Helicobacter pylori on stomach organoids.

主題：C 型肝炎（二）

60 慢性 HBV/HCV 合併感染患者以干擾素的治 療和直接作用抗病毒藥物治療對臨床預後的 影響：單一醫學中心的經驗 IMPACT OF INTERFERON-BASED THERAPY AND DIRECT-ACTING ANTIVIRAL AGENT THERAPY ON CLINICAL OUTCOMES OF PATIENTS WITH CHRONIC HBV/HCV COINFECTION: A SINGLE CENTER EXPERIENCE

黃弘睿1 藍耿欣2 黃怡翔2 臺北榮民總醫院內科部1 臺北榮民總醫院內科部胃腸肝膽科2

Background: HBV/HCV coinfection has a faster progression of fibrosis, liver decompensation, and developing hepatocellular carcinoma (HCC). Both interferon (IFN) based therapy and direct-acting antiviral agent (DAA) therapy are used for the treatment of HBV/ HCV coinfection. Whether the incidence of HBsAg loss and clinical outcome improvement among HBV/HCV co-infected patients increases over time after IFN- based therapy or DAA therapy has not been well established. Aims: We conducted a retrospective study to explore the clinical impact in HBV/HCV co-infected patients after IFN-based or DAA therapy. Methods: The retrospective study was conducted at Taipei Veterans General Hospital (VGH). We included the patients with HCV-HBV coinfection and received HCV therapy (n=195). We identified those treated with IFN based therapy (n=78) or DAA therapy (n=73) after excluding those without achieving HCV sustained viral response (SVR) (n=44). Results: HBsAg loss rate within 3 years after starting IFN based therapy was 1.28%, 2.56%, and 7.69% from the first year to the third year, respectively. Among those treated with DAA therapy, the HBsAg loss rate was 1.37% within 3 years. Patients with baseline (BL) FIB-4 score > 3.25 had significant improvement at end of follow up (EOF) compared with baseline in both IFN (BL FIB-4 score 5.5, and 3.52 at EOF, p-value = 0.001) and DAA group (BL FIB-4 score 6.64, and 4.31 at EOF, p-value = 0.011). Significant reduction of AFP was also noted in IFN (BL AFP: 14.29 ng/ml, and 6.37 ng/ml at EOF, p value=0.001) and DAA group (BL AFP: 4.79 ng/ml, and 3.13 ng/ml at EOF, p value=0.001). Conclusions: Higher HBsAg loss rates were noted in the IFN group. Both therapies had significant improvement on FIB-4 score among those with baseline FIB-4 score > 3.25.

61 慢性 C 型肝炎肝硬化病患在接受長效型干 擾素治療後長期肝細胞癌發生率之追蹤研究 以及使用全口服抗病毒藥物作為拯救治療之 影響 LONG-TERM RISK OF HEPATOCELLULAR CARCINOMA DEVELOPMENT FOR CHRONIC HEPATITIS C PATIENTS WITH LIVER CIRRHOSIS TREATED BY PEGYLATED INTERFERON-BASED THERAPY AND THE IMPACT OF RESCUE THERAPY BY DIRECT-ACTING ANTIVIRALS

朱啟仁1,3 蘇品碩1 欒志軒1 林崇棋2,3 蘇建維1,3 李發耀1,3

黃怡翔1,3 侯明志1,3 臺北榮民總醫院內科部胃腸肝膽科1 臺北榮民總醫院健康管理中心2 國立陽明交通大學醫學院醫學系內科3

Background: Multiple longitudinal follow-up studies confirmed that advanced fibrotic chronic hepatitis C (CHC) patients who failed to interferon-based therapy had significantly higher rate of all-cause mortality, liver-related mortality, liver failure and hepatocellular carcinoma (HCC) as compared to CHC patients who achieved sustained virological response (SVR). Fortunately, the therapeutic landscape of CHC evolved dramatically after the invention of all oral direct-acting antivirals (DAAs). As compared with pegylated interferon (Peg-IFN), all oral DAAs provided shorter treatment period, highly efficacy and excellent tolerability. To date, DAAs became a valuable option for patients who are ineligible or failure to Peg-IFNbased therapy. Aims: At present, real-world data evaluating the longterm risk to develop HCC for CHC patients with liver cirrhosis after treating with Peg-IFN plus ribavirin (RBV) with or without SVR are scarce in Taiwan. In addition, current study investigated the impact of rescue therapy by DAAs for patients failed to Peg-IFN on long-term outcome and baseline characteristics associated with future HCC occurrence. Methods: Between January 2011 to June 2018, a total of 79 consecutive CHC patients with liver cirrhosis who treated with Peg-IFN plus RBV by the investigators were enrolled. History of HCC before the initiation of Peg-IFN, liver transplantation and early terminate antiviral therapy with short follow-up period (< 1 year) were excluded. Liver cirrhosis was defined either by pathological report

of biopsy, presence of typically endoscopic/radiological manifestations of cirrhosis, or reliable transient elastography (FibroScan) result with fibrosis degree > 14.0 kPa. SVR was defined by undetectable HCV RNA (< 15 IU/mL) at the end-of-treatment and 24 weeks after the completion of Peg-IFN therapy. For patients who failed to Peg-IFN plus RBV, DAAs were provided for rescue therapy and treatment responses were recorded. Occurrence of HCC was included as the primary outcome and the cumulative incidence of HCC development was measured by Kaplan-Meier statistical method. Results: Mean age of enrolled patients starting Peg-IFN was 59.8 ± 9.3 years, 60.8% of them was female, and mean pre-treatment HCV RNA was 5.98 ± 0.91 log10 IU/mL. Genotype distribution was as follows: 1a: 2.5%; 1b: 64.6%; 2: 26.6%; and mixed 1 and 2: 6.3%. After therapy with PegIFN plus RBV, responses were as follows: SVR: 50.6%; relapser: 25.3%, partial or null-responder: 10.1%, intolerant and early terminate: 13.9%. The median follow-up period post first dose Peg-IFN was 98 months (mean value: 87.0 ± 32.1, range: 15 to 131 months). 31 of 39 (79.5%) patients who failed Peg-IFN plus RBV received all oral DAAs as rescue and 30 of them (96.8%) achieve SVR. A total of 27 (34.2%) patients developed HCC during study period, 13 in SVR and 14 in Peg-IFN failure group. For cirrhotic patients achieved SVR by Peg-IFN + RBV (n=40), incidence to develop HCC at 2, 5, 8, and 10 years was 11.1%, 22.7%, 34.2% and 44.4%, respectively. For Peg-IFN failure (n=39) but majority of them successfully rescued by alloral DAAs, comparable incidence of HCC development was found as compared to SVR group. The incidence of HCC occurrence at 2, 5, 8, and 10 years was 7.7%, 16.2%, 39.4% and 45.0%, respectively. Thrombocytopenia is the most important factor associated with HCC occurrence, regardless of antiviral treatment response. Significantly higher chance of HCC development was noted for patients with baseline platelet < 120,000/cumm as compared to patients with baseline platelet > 120,000/cumm (2, 5, 8, and 10 years: 10.7% vs. 6.2%; 24.6% vs. 12.8%; 51.4% vs. 20.7%; 61.1% vs. 26.8%; log rank p value = 0.011). Conclusions: For cirrhotic CHC patients who failed therapy with Peg-IFN plus RBV, future risk of HCC occurrence can be negatively modified, at least in part, by successful DAAs rescue. Despite viral clearance, the residual risk to develop HCC still existed, especially for patients with platelet < 120,000/cumm. Continuing surveillance of HCC should be arranged for patients with risk factors of liver disease progression.

62 C 型肝炎患者經口服抗病毒藥物治療且達到 持續性病毒反應的情況下，後續仍然產生肝 癌的殘存風險因子 RESIDUAL RISK OF HEPATOCELLULAR CARCINOMA DEVELOPMENT FOR CHRONIC HEPATITIS C PATIENTS TREATED BY ALL ORAL DIRECTACTING ANTIVIRALS WITH SUSTAINED VIROLOGICAL RESPONSE

欒志軒1 蘇品碩1 朱啟仁1,2 蘇建維1,2 林崇祺2,3 李發耀1,2

黃怡翔1,2 侯明志1,2 臺北榮民總醫院內科部肝膽腸胃科1 陽明大學醫學系2 臺北榮民總醫院健檢中心3

Background: The therapeutic landscape of chronic hepatitis C (CHC) evolved dramatically after the invention of all oral direct-acting antivirals (DAAs). After successful antiviral therapy, beneficial effects were documented, reflected by preventing disease progression, significantly reduced overall and liver-related mortality. However, residual risk of liver disease still existed in a small proportional of patients after viral clearance, especially for those with advanced fibrosis. Aims: At present, real-world data evaluating the residual risk to develop hepatocellular carcinoma (HCC) for CHC patients after treating with all oral DAAs with sustained virological response (SVR) are scarce in Taiwan. Therefore, we conducted this study to address the above important issue. Methods: Between January 2017 to April 2018, a total of 327 consecutive CHC patients who successfully treated by all oral DAAs at our hospital were enrolled for analyses. History of HCC before the initiation of DAAs, liver transplantation and short follow-up period (< 1 year) post SVR12 were excluded. Advanced (F3-F4) fibrosis was defined either by presence of typically clinical or radiological manifestations of cirrhosis, reliable transient elastography (FibroScan) result with fibrosis degree > 9.6 kPa, or fibrosis-4 (FIB-4) score ≥ 3.25. Occurrence of HCC after successfully treated with DAAs was included as the primary outcome. Evaluation of baseline variables associated with the primary outcome was conducted using multivariate Cox proportional hazards models. Results: Mean age of enrolled patients was 66.6 ± 11.5 years, 37% of them was male, and 32.4% belonged to advanced fibrosis. Genotype distribution was as follows:

1a:5.8%; 1b:72.2%; 2:21.1%; and 6:0.9%. The median follow-up period post SVR12 was 3.68 years (interquartile range, 2.61–4.28 years). The cumulative incidence to develop HCC for CHC patients post SVR12 was 1.8% at 1 year, 4.3 % at 2 years, 4.6 % at 3 years, and 4.9% at 4 years respectively. Baseline variables independently associated with HCC occurrence were advanced liver fibrosis (hazard ratio [HR]=8.22; 95% CI, 1.45–16.52, P=0.017), body mass index (BMI) > 25 (HR=3.82; 95% CI, 1.06-13.80, P=0.041), and hemoglobin less than 11 g/dL (HR=5.63; 95% CI, 1.35-23.44, P=0.017). Conclusions: Despite viral clearance by DAAs, the risk to develop HCC in SVR patients is not nil, especially for those with advanced fibrosis. Baseline characteristics including lower hemoglobin level and metabolic derangement reflected by BMI over 25 were also independent risk factors associated with HCC occurrence. Accurate predictors or scoring system are helpful to improve risk stratification of future HCC development post SVR12 and refine screening strategies in this growing population.

63 同時具 B 型及 C 型肝炎之患者接受核酸類 口服抗病毒藥物後 C 型肝炎病毒之變化 HEPATITIS C VIRAL LOAD EVOLUTIONS FOLLOWING NUCLEOS(T)IDE ANALOG THERAPIES IN PATIENTS WITH CONCURRENT HEPATITIS B VIRUS AND HEPATITIS C VIRUS INFECTION

蘇以哲1,2,3 張明鈴1,2,3 廖運範1,2,3 林口長庚紀念醫院肝膽胃腸系肝臟科1 林口長庚紀念醫院肝臟研究中心2 長庚大學醫學系3

Background: Concurrent hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is common. HBV reactivation might occur during anti-HCV treatment. Aims: Whether hepatitis C virus (HCV) reactivation occurs and how the viral load evolves in anti-HCV antibody-positive chronic hepatitis B (CHB) patients underwent nucleos(t)ide analogue (Nuc) therapies remained uncertain, and we aimed to investigate them. Methods: A cohort study of 66 CHB patients with positive HCV Ab underwent nucleos(t)ide analog (Nuc) therapies was conducted. The viral loads of HBV and HCV were measured at the start of treatment (baseline), the end of treatment (EOT) and 6 months after EOT (6msEOT). Results: A cohort of 66 such patients was studied. At the start of Nuc treatment (baseline), all had detectable hepatitis B virus (HBV) DNA levels (6.05±1.88 log IU/ml), while HCV RNA levels (3.79±1.43 log IU/ml) were detected [ie. chronic hepatitis C (CHC)] in only 13 patients (19.7 %). Following Nuc therapies, HBV DNA levels reached the nadirs at end of therapy (EOT) (6.05±1.88 vs. 0.25±0.99 log IU/ml, p<0.0001) and relapsed at 6 months after EOT (6mEOT) at a level of 3.45±2.64 log IU/ml, compared with EOT (p<0.0001). Among the 13 CHC patients, non-significant decrease of HCV RNA was noted at EOT (3.79±1.43 vs. 2.77±2.63 log IU/ml, p=0.166), but tended to decrease further at 6mEOT (2.77±2.63 vs. 1.89±2.06 log IU/ml, p=0.063). Two of the 13 CHC patients showed an increase in HCV-RNA ≥1 log10 IU/ mL at EOT and 1 of the 53 patients with undetectable HCV RNA at baseline (ie. resolved past HCV infection) showed detectable HCV RNA at year 1 (3200 IU/ml) and year 2 (1240 IU/ml) following entecavir therapy. Conclusions: HCV reactivation did occur during HBV suppression, and the rate was 4.5% (3/66), 15.4% (2/13) and 1.9% (1/53), of all patients, CHC patients, and patients with resolved past HCV infection, respectively. The reverse viral evolutions of HBV and HCV at 6mEOT indicates that HBV relapse may suppress HCV replication again.

64 以 GRAZOPREVIR/ELBASVIR 治療肝臟 或腎臟移植患者的第 1B 型 C 型肝炎病毒感 染 GRAZOPREVIR/ELBASVIR TREATMENT IN LIVER OR KIDNEY TRANSPLANT RECIPIENTS WITH GENOTYPE-1B HEPATITIS CVIRUS INFECTION

李騰裕1 賴彬卿2 陳呈旭3 鄭隆賓4 游棟閔3 蔡尚峰3 吳明儒3 鄭紹彬5 楊勝舜1 臺中榮民總醫院胃腸肝膽科1 中國醫藥大學腎臟科2 臺中榮民總醫院腎臟科3 中國醫藥大學器官移植中心4 臺中榮民總醫院外科部5

Background: More options regarding the choice of directacting antivirals (DAAs) are helpful for avoiding individual limitations in treating hepatitis C virus (HCV) infection. Aims: We aimed to assess the efficacy and tolerability of grazoprevir (GZR)/elbasvir (EBR) treatment in genotype-1b (GT-1b) HCV-infected liver or kidney transplant recipients. Methods: In this phase 4, single-arm, open-label, multicenter trial, patients received GZR 100mg/EBR 50mg daily for 12 weeks. Patients with any HCV infection other than genotype-1b (GT-1b), liver decompensation, human immunodeficiency virus or hepatitis B virus co-infection, a history of NS5A inhibitor exposure, or any severe drug-drug interactions (DDIs) were excluded. The primary endpoint was sustained virologic response at 12 weeks posttreatment (SVR12). Results: Of the 14 patients (10 kidney and 4 liver transplant subjects) enrolled in this study, 9 (64%) were females; the median age was 64.0 (range: 43-73) years. The regularly used immunosuppressants were tacrolimus (93%), everolimus (29%), and sirolimus (7%), with patient blood levels easily managed and generally stable (all p> 0.05 in quantile regression analysis). The rate of SVR12 was 100% in intent-to-treat analysis. Only one patient discontinued GZR/EBR therapy at 6 weeks posttreatment due to a treatment-unrelated adverse event (AE); however, this patient remained achieving SVR12. Most AEs were mild in severity and deemed to be not treatment-related. No organ rejection episodes or deaths occurred during the study period. Conclusions: The single-tablet regimen of GZR/EBR for 12 weeks is highly effective and well tolerated in GT-1b HCVinfected liver or kidney transplant recipients, and its DDIs are generally easy to manage.

主題：肝腫瘤（二）

65 比較血清 WFA+-M2BP, FIB-4 與 APRI 對於 肝癌病人診斷肝硬化之準確度與食道靜脈瘤 之預測 COMPARISON OF SERUM WFA+-M2BP, FIB-4, AND APRI FOR CIRRHOSIS AND ESOPHAGEAL VARICES PREDICTION IN HEPATOMA PATIENTS

林明宗1 張國欽1 楊志權2 黃昭誠3 王植熙2 胡琮輝1 高雄長庚紀念醫院胃腸肝膽科1 高雄長庚紀念醫院一般外科2 高雄長庚紀念醫院病理科3

Background: Wisteria floribunda agglutinin-positive Mac2 binding protein (WFA+-M2BP) is a novel biomarker for evaluating hepatic fibrosis and hepatocellular carcinoma (HCC) development. However, no previous study has compared its diagnostic accuracy with that of FIB-4 or APRI nor explored its clinical application for predicting esophageal varices bleeding in HCC patients Aims: Compared serum WFA+-M2BP, FIB-4, and APRI for cirrhosis and esophageal varices prediction in hepatoma patients. Methods: 459 HCC patients who underwent curative operation were enrolled in this study. WFA+-M2BP level was evaluated using stored blood samples that were collected during surgery, and liver fibrosis was diagnosed based on findings of surgical specimen analysis. Esophageal or gastric varices were evaluated in 207 patients who underwent esophagogastroduodenoscopy. The correlation between the markers was also determined. Results: WFA+-M2BP level, FIB-4, and APRI had a similar high accuracy of approximately 73% for liver cirrhosis diagnosis. Their levels were significantly correlated with the liver fibrosis stage (P < 0.0001). WFA+M2BP level, FIB-4, and APRI also had high diagnostic accuracy for varices formation (accuracy, 76.8%–80.2%) and high predictive accuracy for variceal bleeding (accuracy, 73.9%–76.3%). Conclusions: WFA+-M2BP level, FIB-4, and APRI have all shown to be very useful noninvasive methods for evaluating liver fibrosis and predicting esophageal varices bleeding to avoid risky liver biopsy and esophagogastroduodenoscopy examination.

66 B 型肝炎相關肝癌射頻燒灼術後局部與遠處 復發之預測因子 DISTINCT PREDICTORS OF LOCAL AND DISTANT RECURRENCE IN PATIENTS WITH HBV-RELATED HEPATOCELLULAR CARCINOMA RECEIVING RADIOFREQUENCY ABLATION

胡果正1 李懿宬1,2 齊振達1,2,3 柳建安3,4 侯明志1,2 黃怡翔1,2,3 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學醫學系2 國立陽明交通大學臨床醫學研究所3 臺北榮民總醫院放射線部4

Background: In patients with hepatocellular carcinoma (HCC) receiving radiofrequency ablation (RFA), tumor, viral and host factors may play distinct prognostic roles in local tumor progression (LTP) and distant recurrence. Especially, the role of quantitative HBsAg in predicting recurrence of HBV-related HCC after RFA remains unclear. Aims: We aim to evaluate the tumor, viral and host factors, including HBsAg, in predicting LTP and distant recurrence among patients with HBV-related HCC undergoing RFA. Methods: Consecutive 397 patients with radiologically confirmed complete tumor ablation after RFA for HBVrelated HCC were retrospectively enrolled. Factors associated with LTP and distant recurrence were evaluated. Results: With a median follow-up period of 50.4 months, 146 (36.8%) and 225 (56.7%) patients developed LTP and distant recurrence respectively. By multivariate analysis, tumor size >2 cm (hazard ratio (HR)=1.859, p<0.001) and tumor adjacent to major blood vessel (HR=1.454, p=0.036) were independent predictors of LTP. FIB-4 >3.25 (HR=1.427, p=0.010), multiple tumors (HR=1.829, p=0.001) and AFP>20 ng/mL (HR=1.313, p=0.047) were independently associated with distant recurrence. In patients without advanced fibrosis (FIB-4 ≤3.25, n=181), HBsAg >100 IU/mL (HR=2.131, p=0.021), male sex (HR=2.297, p=0.015), multiple tumors (HR=2.713, p=0.001) and AFP >20 ng/mL (HR=1.638, p=0.044) independently predicted distant recurrence, while in patients with advanced fibrosis (FIB-4 >3.25, n=216), age >70 years (HR=1.538, p=0.015) and FIB-4 >6 (HR=1.812, p=0.001) were independently associated with distant recurrence. Conclusions: In patients with HBV-related HCC receiving RFA, tumor factors are associated with LTP, while both host and tumor factors are accounted for distant recurrence. HBsAg level strongly predicts distant recurrence in patients without advanced hepatic fibrosis.

67 特定器官對免疫檢查點阻斷劑的反應在晚期 肝細胞癌存活中的角色 ROLE OF ORGAN-SPECIFIC RESPONSE TO IMMUNE CHECKPOINT INHIBITOR IN SURVIVAL FOR ADVANCED HEPATOCELLULAR CARCINOMA

黃國維1 李沛璋1,2,4 趙毅4,5 李懿宬1,4 洪逸平2,3,5 陳三奇2,3,5 侯明志1,4 黃怡翔1,3,4 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學醫學院藥理學研究所2 陽明交通大學臨床醫學研究所3 陽明交通大學醫學系4 臺北榮民總醫院內科部胃腸肝膽科腫瘤醫學部5

Background: Immunotherapy by immune checkpoint inhibitors (ICIs) is an encouraging treatment for unresectable hepatocellular carcinoma (HCC). However, it is unclear which organ has the best response to ICIs as well as the role of individual organ response in survival for advanced HCC. Aims: We aimed to delineate tumor response to ICIs in different involved organs and its impact on survival. Methods: From May 2017 to October 2021, 224 patients who received ICIs for unresectable HCC were retrospectively reviewed. Of them, 174 patients who had follow-up images after ICIs treatment, including 91 intrahepatic tumors only, 19 extrahepatic tumors only and 66 concurrent intra- and extrahepatic tumors, were enrolled for analysis. Organspecific responses were evaluated according to RECIST 1.1 and mRECIST criteria. Results: Of the 174 patients, 77 underwent anti-PD-1 monotherapy, the others received ICI combinations. The median overall survival (mOS) was 13.3 months (95% confidence interval [CI]: 11.4 – 15.3 months). Patients with concurrent intra- and extra-hepatic tumors had the lowest ORR and worse overall survival. The objective response rate (ORR) was the highest for metastatic lymph nodes (26%), followed by liver (24.2%), intraabdominal tumors (21.4%), lung (12.1%) and bone (11.8%). Of the 66 patients with concurrent intra- and extrahepatic HCC, intrahepatic tumor response (HR: 0.247, p = 0.002) and ICI combinations (HR:0.403, p=0.041) were significantly associated with a better OS in multivariate analysis. Conclusions: The response rate to ICIs was lower for lung and bone metastasis than liver and lymph nodes in patients with advanced HCC. For patients with concurrent intra- and extrahepatic HCC, intrahepatic tumor response determines overall survival.

68 肝腫瘤影像學的特徵於接受經動脈肝臟栓塞 術的中期肝癌病人的預後分析 RADIOLOGICAL FEATURES AND OUTCOMES IN PATIENTS WITH INTERMEDIATE STAGE HEPATOCELLULAR CARCINOMA UNDERGOING TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION

洪雅文1 李懿宬1,2 齊振達1,2,3 李潤川4 柳建安4 邱乃祈4 黃宣恩4 趙毅5 侯明志1,2 黃怡翔1,2,3 臺北榮民總醫院內科部腸胃肝膽科1 國立陽明交通大學醫學院醫學系2 國立陽明交通大學臨床醫學研究所3 臺北榮民總醫院放射線部4 臺北榮民總醫院腫瘤醫學部5

Background: For patients with intermediate-stage hepatocellular carcinoma (HCC), the definition of TACEunsuitable has been debated. Aims: This study was aimed to compare the outcome and survival of different radiological features in patients with intermediate-stage HCC undergoing transarterial chemoembolization (TACE). Methods: From October 1 2007 to December 31 2020, 633 treatment-naïve patients with intermediate-stage HCC undergoing TACE were retrospectively enrolled. The median follow-up period was 20.73 months. We compared different radiological features of tumor in radiologic response and survival, including single/multi nodular type, confluent type, infiltrative type, and simple nodular type with extranodular growth. Results: The patients with radiological features classified to confluent type, infiltrative type, and simple nodular type with extranodular growth tend to respond to TACE poorly and have a worse overall survival (OS) than single/multi nodular type. In patients with single/multi nodular type, confluent type, infiltrative type, and simple nodular type with extranodular growth, the median OS is 49.1, 12.8, 7.9 and 21.0 months, respectively (p<0.001). By multivariate analysis, HCC patients with specific radiologic features are significantly associated with progressive disease (PD) after first session (confluent type, odds ratio=2.681, p=0.001; infiltrative type, odds ratio=4.958, p<0.001; single/multi nodular type HCCs with extranodular growth, odds ratio=1.930, p=0.018) and second session of TACE (confluent type, odds ratio=3.947, p<0.001; infiltrative type, odds ratio=5.000, p=0.002; single/multi nodular type HCCs with extranodular growth, odds ratio=3.437, p<0.001). OS is also significantly worse when having those radiologic features by multivariate analysis (confluent type, hazard ratio=1.714, p=0.001; infiltrative type, hazard ratio=2.029, p=0.001; simple nodular type with extranodular growth, hazard ratio=1.403, p=0.009). Conclusions: Intermediate-stage HCC patients with specific radiological features tend to respond poorly to TACE and have a worse overall survival. Thus, alternative treatments such as target therapy or immunotherapy should be considered for TACE unsuitable patients.

69 手術前較高的γ- 谷氨醯轉肽酶有效預測經 治癒性切除之早期 B 型肝炎相關肝癌術後 復發及死亡 HIGH PRE-OPERATIVE GAMMAGLUTAMYL TRANSFERASE LEVEL PREDICTS RECURRENCE AND MORTALITY IN EARLYSTAGE HEPATITIS B-RELATED HEPATOCELLULAR CARCINOMA UNDER CURATIVE RESECTION

黃上秦1,2 蘇東弘3,4 陳祈玲2 徐士哲3,4 廖思涵5 洪俊銘6

劉振驊3,4 曾岱宗3,4 楊宏志3,4 劉俊人2,3,4 陳培哲2,3,4 高嘉宏2,3,4 國立臺灣大學醫學院附設醫院北護分院醫療部內科1 國立臺灣大學醫學院臨床醫學研究所2 國立臺灣大學醫學院附設醫院內科部胃腸肝膽科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附設醫院癌醫中心分院5 國立臺灣大學醫學院附設醫院內科部整合醫學科6

Background: Hepatitis B virus (HBV) infection is a major cause for hepatocellular carcinoma (HCC) development. HCC recurrence is not uncommon after curative resection, and identifying risk predictors for recurrence helps to better manage the disease. Gamma-glutamyl transferase (GGT) has been reported to be a predictor of HCC development. However, the role of pre-operative GGT to predict HCC recurrence or mortality was less clear. Aims: To explore clinical predictors for long-term outcome of HBV-related HCC after curative resection, especially focusing on GGT. Methods: We retrospectively included patients with HBVrelated HCC receiving curative resection at the National Taiwan University Hospital from the electric medical records. Clinical information including age, sex, severity of liver fibrosis, serum biochemistry, tumor size, number, stage of HCC and prescription of antiviral therapy were collected, and those with incomplete medical information were excluded. Receiver operating characteristic curve were used to define the optimal cut-off level of GGT, and a time-dependent Cox proportional hazard regression analysis were used for HCC recurrence and overall survival. Results: A total of 699 consecutive patients with HBVrelated HCC (BCLC 0/A/B: 65/449/185) received curative resection between 2004-2013 were retrospectively included. The mean age was 55, and 82% were men. After a mean follow-up of 5 years, 268 patients (38.3%) had recurrence of HCC. Multivariable analysis demonstrated that pre-operative GGT level >= 38 U/L (vs. <38 U/L, harzard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.18-2.02, P=0.002) after adjustment of confounding factors such as age, sex, albumin, alfa-fetoprotein, Metavir score, antiviral therapy, tumor size and staging. High GGT is predictive for post-operative HCC recurrence in subgroups of male sex, albumin >= 4.5mg/dL, AFP >=10 ng/mL, BCLC A, presence of steatosis, without vascular invasion, and regardless of antiviral therapy and age. Besides, pre-operation high GGT level >= 38 U/L (vs. <38 U/L, harzard ratio[HR]: 1.64, 95% confidence interval [CI]: 1.003-2.69, P=0.048) also predictive for all-cause mortality after surgery. Conclusions: Pre-operative GGT level >=38 U/L independently predicts high risks of HCC recurrence and all-cause mortality in patients with early-stage HBV-related HCC receiving curative resection.

70 肝炎病因對樂衛瑪作為不可切除肝細胞癌一 線治療的影響 IMPACT OF HEPATITIS ETIOLOGIES ON LENVATINIB AS FIRST-LINE THERAPIES FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA.

郭垣宏1 紀廣明1 洪肇宏1 盧勝男1 胡琮輝1 陳建宏1 王景弘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1

Background: Lenvatinib has been approved as a firstline treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Taiwan; however, the influence of virus etiologies on lenvatinib remains undetermined. Aims: This study was to evaluate the association of virus etiologies and lenvatinib treatment in clinical real-world practice. Methods: We retrospectively evaluated patients with unresectable HCC who had undergone lenvatinib treatment between January 2018 and Dec 2020. Patients Patients were excluded if they had previously received other systemic therapy or had become lost to follow-up during treatment. Treatment response was assessed by radiologic imaging according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) Results: A total of 122 patients (Male/Female: 84/38, mean age: 66.2 years) were recruited including 58 (47.5%) patients with hepatitis B virus (HBV) infection, 31 (25.4%) hepatitis C virus (HCV) patients, 2 (1.6%) B+C patients and 31 (25.4%) non-B, non-C (NBNC) patients. The Kaplan-Meier estimate of overall survival (OS) was 18.6 months, and the median time to tumor progression (TTP) survival was 6.5 months. The overall objective response rate (ORR) and disease control rate (DCR) was 18.3% and 71%, respectively. Based on virus etiologies, the TTP of HBV, HCV and NBNC was 5.2, 9.9 and 8.4 months, respectively. The ORR of HBV, HCV and NBNC was 16.7%, 26.1% and 13.6%, respectively. In multivariate analysis, HBV infection was independent factor of tumor progression (Hazard ratio (HR):1.79, 95% Confidence Interval (CI): 1.09-2.94), P=0.022) after adjusting with albumin-bilirubin (ALBI) grade and alpha-fetoprotein (AFP). Furthermore, HCV infection was associated with mortality (HR: 0.47, 95% CI: 0.23-0.95, P=0.037) in multivariate analysis in the adjustment with ALBI grade, AFP, combined treatment and post-lenvatinib treatment. Conclusions: As the first-line therapy, lenvatinib therapy showed a favorable efficacy for unresectable HCC in a real-world practice. Based on virus etiology, HBV infection seemed to increase the risk of tumor progression for HCC patients receiving lenvatinib; whereas HCV infection might be beneficial for overall survival.

主題：上消化道疾病（二）

71 未分化早期胃癌患者接受內鏡鏡黏膜下剝離 術的預後：台灣多中心經驗 PROGNOSIS OF POORLY DIFFERENTIATED EARLY GASTRIC CANCER PATIENTS AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION: A MULTICENTER EXPERIENCE IN TAIWAN

張琮承1 顏旭亨2 戴維震3 李青泰4 鍾承軒1,5 亞東紀念醫院肝膽胃腸科1 彰化基督教醫院胃腸科2 高雄長庚紀念醫院肝膽胃腸科3 義大醫院內視鏡中心與義守大學4 天主教輔仁大學5

Background: Gastric cancer is ranked in the top ten malignancies worldwide, including Taiwan. Endoscopic submucosal dissection (ESD) is one of the first line options for management of early gastric cancer (EGC). Currently, there is no long-term data on ESD for poorly differentiated (PD) subtype of EGC in Taiwan. Aims: We aimed to investigate the outcome after ESD for PD-EGC. Methods: Between January 2010 and December 2020, we retrospectively collected the demographic, endoscopic and pathological data of patients with PD-EGC treated by ESD in four tertiary centers. The inclusion criteria were as followings: 1) adults aged over 20-year-old, 2) PD-EGC with clinical stage T1N0M0 (AJCC 8th edition) treated by ESD. Well-differentiated adenocarcinoma or malignant tumors other than adenocarcinoma were excluded. Enrolled patients were divided into two groups, extended indication (EI) and beyond extended indication (BI) according to the gastric cancer treatment guidelines of the Japanese Gastric Cancer Association. Statistical data were analyzed by Student’s t-test, chi-square test to analyze the outcomes. Results: Totally 21 patients with 22 lesions [ten (45.45%) in EI group and twelve (54.55%) in BI group] were enrolled. The mean (±SD) of age was 62.30 (±8.80) year-old, the gender was female/male of 10 (47.62%)/11 (52.38%) patients. Median procedure time was 93.40 (±72.60) minutes. Rate of postoperative bleeding and perforation during the procedure were 0 % and 8.52 %, respectively. The lesion size, procedure time and complication rate between EI and BI were 8.10 (±3.73) and 89.42 (±252.21) mm (p=0.06), 90.10 (±80.35) and 95.58 (±68.98) min (p=0.49), and 20% vs. 8.33% (p=0.43). Additional surgery was performed in 8 (38.10%) patients while 3 (37.50%, one in EI, two in BI) of them were due to horizontal margin involved by cancer and 5 (62.50%) of them were in BI with margin free. Of the 8 (1 in EI group, 7 in BI group) patients who underwent surgery, 0 (0%) and 3 (42.86%) of those in EI and BI group with residual cancer and all of them were pN0. None had local recurrence, lymph node and distant metastasis during a median followup of 40.61 (±36.42) months. One (4.76%) patient in EI group had metachronous recurrence 8 months later and he was cancer free after subtotal gastrectomy at the end of study period. No patient died of gastric cancer and there was no significant difference in the recurrence-free survival between the two groups. (Fig.1) Conclusions: ESD is effective and safe for the management of PD-EGC with excellent outcome.

72 惡性十二指腸阻塞患者接受金屬支架後的預 後：一個單中心的臨床經驗 OUTCOMES OF PATIENTS WITH MALIGNANT DUODENAL OBSTRUCTION AFTER RECEIVING SELF-EXPANDABLE METALLIC STENTS: A SINGLE CENTER EXPERIENCE

吳佩珊1,2,5 魏天心3,5 李重賓4,5 黃怡翔1,5 李癸汌1,5 侯明志1,2,5 臺北榮民總醫院內科部胃腸肝膽科1 臺北榮民總醫院內視鏡診斷暨治療中心2 臺北市立關渡醫院胃腸肝膽科3 臺北榮民總醫院教學部臨床技術訓練科4 國立陽明交通大學內科學科5

Background: Self-expandable metallic stent (SEMS) placement is a safe and effective palliative treatment for malignant gastric outlet obstruction; however, the clinical outcomes of gastric and duodenal stenoses may differ. Aims: This study aimed to investigate the clinical efficacy of SEMS placement and the predictors of clinical outcome, specifically in malignant duodenal obstruction (MDO). Methods: Between September 2009 and March 2021, 79 patients with MDO who received SEMS placement in our hospital were retrospectively enrolled. Patients were divided into three groups according to the obstruction levels: above-papilla group (type 1), papilla involved group (type 2), and below-papilla group (type 3). The clinical outcomes and predictors of survival were analyzed. Results: The technical and clinical success rates were 97.5% and 80.5%, respectively. Among patients who had successful stent placement, stent restenosis occurred in 17 patients (22.1%). The overall median stent patency time was 103 days. The overall median survival time after stent placement was 116 days. There was no difference in the stent patency, survival, or stent dysfunction. and procedurerelated adverse events among the three groups. A longer length of duodenal stenosis ≥ 4 cm was associated with poor prognosis (hazard ratio [HR] = 1.92, 95% confidence interval [CI] = 1.06–3.49, p = 0.032) and post-stent chemotherapy was associated with lower mortality (HR = 0.33; 95% CI = 0.17–0.63, p = 0.001). Conclusions: SEMS is a safe and effective treatment for MDO. Chemotherapy after SEMS implantation improve the survival for these patients and a longer length of stenosis predicts higher mortality.

73 利用同步化學放射治療前後的身體組成改變 來預測食道癌預後的回溯性研究 BODY COMPOSITIONAL CHANGE DURING CONCURRENT CHEMORADIATION THERAPY PREDICTS PROGNOSIS OF ESOPHAGEAL CANCER PATIENTS: A COHORT STUDY

姜學謙1 張維倫1 成大醫院內科部1

Background: Nutritional status is an important prognostic factor for cancer patients. Body compositions such as skeletal muscle and adipose tissue mass are key indicators of nutritional status. Aims: This study aimed to evaluate whether body compositional change during concurrent chemoradiation therapy (CCRT) could be a predictor of prognosis in esophageal cancer patients. Methods: From January 2006 to March 2018, esophageal cancer patients who received CCRT and had serial chest computed tomography (CT) scans before and after CCRT in National Cheng-Kung University Hospital were included. We assessed body compositions, including subcutaneous fat mass (SCF), intramuscular fat mass (IMF), and skeletal muscle (SM) mass by measuring the crosssectional area (CSA) of the fourth vertebral body. The body compositional change was assessed by comparing baseline and post-CCRT CSA on CT scans. The patients’ baseline characteristics, cancer stage, and treatment modality were recorded and assessed for their association with prognosis. Results: A total of 178 patients were enrolled with a mean baseline BMI of 22.03, and median overall survival of 18.7 months. Baseline BMI and body compositions were not associated with patient prognosis. After CCRT, 32.3% and 37.3% of the patients had increased SCF and SM, respectively. Patients with increased SCF had longer overall survival (median, 21.6 months vs 15.4 months, p = 0.011) than patients with decreased SCF. Interestingly, patients with decreased SM had longer overall survival (median, 21.6 months vs 13.2 months, p = 0.001) than patients with increased SM. In contrast, body weight change did not correlate with survival. Combining the two body compositional changes best predict survival (p <0.001). In multivariate Cox regression analysis, SCF gain (HR: 0.61, 95% CI: 0.42 – 0.89) and SM loss (HR: 0.54, 95% CI: 0.38 – 0.78) during CCRT were two independent

prognostic factors after adjusting age, gender, cancer stage, treatment and BMI. Conclusions: In this study, SCF gain and SM loss during CCRT are associated with better overall survival in esophageal cancer patients. Change in body composition is more sensitive than weight in predicting the overall survival of esophageal cancer patients, which can be easily accessed by CT scan during treatment response evaluation.

74 SAA 在胃癌及肝癌細胞以促炎細胞因子刺 激後的表現 THE PERFORMANCE OF SAA IN GASTRIC CANCER CELLS AND HEPATOCELLULAR CARCINOMA CELLS AFTER PRO-INFLAMMATORY CYTOKINE STIMULATION

蔡旻軒1 劉忠榮1 王耀廣1,2 吳宜珍1,2 郭昭宏1,3 盧建宇1,2 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學醫學系2 高雄巿立小港醫院內科3

Background: Gastric cancer and Liver cancer are some of the most prevalent cancers worldwide. The prognosis of these cancers, especially in patients with advancedstage, is generally poor, thus causing high cancer-related mortality around the world. Serum Amyloid A (SAA) is secreted during the acute phase of inflammation. In the tumor microenvironment, SAA possesses various abilities such as promoting the progression of cancer by stimulating proliferation, migration, invasion in the tumor cells. SAA is secreted during the acute phase of inflammation and its expression is regulated in liver cells by the proinflammatory cytokines IL-1, IL-6, and TNF-α. In healthy donors, the expression levels of SAA are low. Aims: We want to investigate the link between acute phase biology and cancer with a focus on SAA and its involvement in the regulation of cancer immunobiology. Methods: Gastric cancer cells and hepatocellular carcinoma cells are treated with interleukin-1 beta, interleukin-6, and TNF alpha in the experiments. SAA expression in treated cells was detected by ELISA assay, western blot, and real-time PCR. Results: In the present study, human hepatocellular carcinoma hepG2 cells stimulated with IL-1, IL-6, and TNF-α showed a higher expression of SAA. Similarly, IL1, IL-6, and TNF-α treatments in human AGS and N87 gastric cancer cells also increased the expression of SAA, especially in cell lysates. Conclusions: These findings suggest that SAA might play a critical role in gastric and liver cancer progression through stimulation of proinflammatory cytokines

75 IGFBP2 與胃癌惡性度的關係 ROLE OF IGFBP2 IN PARTICIPATING THE PROGRESSION OF GASTRIC CANCER

張哲墉1 劉忠榮1 許文鴻1,2,3 吳宜珍1,2 吳登強1,2 郭昭宏1,2,3 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學醫學系2 高雄巿立小港醫院內科3

Background: Gastric cancer is one of the most common cancers worldwide, and is also the third leading cause of cancer-related mortality. The poor prognosis of gastric cancer may be partly attributed to the complicated molecular networks operating the aggressiveness of gastric cancer. Although a large body of studies has revealed the deregulation of certain genes in gastric carcinogenesis, Aims: To figure out the molecular mechanisms behind gastric tumor development. Methods: We explored the role of IGFBP2 in HOXA9overexpressing human gastric cancer AGS cells. We further co-cultured human gastric cancer cells and human mesenchymal stem cells (HBMMSCs), and then observed these cells interaction by measuring the motility of human gastric cancer cells and HBMMSCs in the co-culture system. Results: In the present study, we found that IGFBP2 is upregulated in HOXA9-overexpressing human gastric cancer cells. Human gastric cancer cells recruited more HBMMSCs through HOXA9-IGFBP2 axis pathway. Recruited HBMMSCs then enhanced cell motility in human gastric cancer cells. Conclusions: Human gastric cancer cells with high activity of HOXA9-IGFBP2 axis pathway recruited more HBMMSCs. HBMMSCs then enhanced the motility of human gastric cancer cells.

76 在懷疑巴瑞特氏食道的病人接受內視鏡的切 片數與腸上皮化生的產出率 THE BIOPSY NUMBERS AND YIELD RATES OF INTESTINAL METAPLASIA IN PATIENTS WITH SUSPECTED BARRETT’S ESOPHAGUS

蔡英楠1,2 徐銘宏2,3 曾政豪1,2 李青泰2,4 王文 2,4 義大癌治療醫院胃腸肝膽科1 義守大學2 義大醫院一般醫學科3 義大醫院胃腸肝膽科4

Background: Detections of Goblet cells and dysplasia are crucial for diagnosis and determining the surveillance program of Barrett’s esophagus (BE). However, the optimal biopsy numbers and their yield rates of intestinal metaplasia (IM) and dysplasia are still uncertain, especially in Asia. Aims: We aimed to assess the biopsy numbers and yield rates of IM in patients with suspected BE to determine the optimal biopsy protocol. Methods: We retrospectively reviewed the upper gastrointestinal endoscopic reports from the database of outpatient setting from January 2008 to December 2020 at E-Da hospital. The numbers of biopsy, length of columnarlined esophagus (CLE) and the corresponding histology were analyzed to assess the yield rates of IM and dysplasia per-biopsy in patients with CLE and without visible cancerous lesions. Results: A total of 120,362 endoscopies were reviewed, and 5,963 (5.0%) cases in 3,135 patients were diagnosed as endoscopic CLE (Length, mean:1.28±0.73 cm; range, 1-10). Among them, 4,675 (78.4%) cases received a total of 8887 biopsies (number, median: 1; range, 1-9). The histology from biopsies revealed that 1,642 (35.1%) cases and 217 (4.6%) cases per-endoscopy yielded the IM and dysplasia, respectively. Among the 913 patients with IMconfirmed BE, the mean age was 53.2 (53.2±15.1) years old and short-segment (<3cm) Barrett’s esophagus (SSBE) were predominated (91%). Overall, the yields of IM (75% vs. 33%) and dysplasia (18.7% vs. 3.5%) were both higher in the long-segment than those in short-segment CLE. Taking one biopsy only revealed a 26% yield of IM and 3.5% yield of dysplasia, respectively. The yield rates were positively correlated with the numbers of biopsy for both IM (3-6 Biopsies reach a plateau: ~50%; 7 biopsies: 100%) and dysplasia (3 Biopsies: 5.7%) in short-segment CLE. On

the contrary, one biopsy could get a 53% yield of IM and 14% yield of dysplasia in long-segment CLE. Conclusions: Sampling bias is a major concern in current clinical practice for diagnosis and management of Barrett’s esophagus. The yield rates of IM and dysplasia were insufficient by taking one biopsy, especially for short-segment CLE. A randomized study is required to determinate the optimal biopsy number for SSBE.

主題：下消化道疾病（二）

77 大腸癌預測模式 A USER-FRIENDLY OBJECTIVE PREDICTION MODEL IN PREDICTING COLORECTAL CANCER BASED ON 234 044 ASIAN ADULTS IN A PROSPECTIVE COHORT

陳建華1, 2 楊基滐2 葉永祥1 陳奎閔2 顏聖烈1 牟聯瑞3 黃明和2 彰濱秀傳紀念醫院1 彰化秀傳紀念醫院2 臺南市立醫院3

Background: Prediction models of colorectal cancer (CRC) had limited application for not being user-friendly. Whether fecal immunochemical tests (FITs) can help predict CRC has been overlooked. Aims: The objective of the study is to assess the value of applying quantitative FIT in improving the model. Methods: With 1972 CRCs identified, 234 044 adults aged ≧ 40 years were successively enrolled between 1994 and 2008. Prediction models were developed by questionnaire/medical screening and quantitative FIT. NNS (number needed to scope to find one cancer) is time dependent, spanning entire study period. Significant ‘risk factors’ were family history, body mass index, smoking, drinking, inactivity, hypertension, diabetes, carcinoembryonic antigen, and C-reactive protein. Results: Positive FIT ( ≧ 20 mg/g hemoglobin/feces) had cancer risk 10-fold larger than negative FIT, and within each age group, another 10-fold difference. The C statistic of FIT (0.81) with age and sex alone was superior to the ‘common risk- factors’ model (0.73). NNS, stratified by age and by FIT values, demonstrated a scorecard of cancer risks, like 1/15 or 1/ 25, in 5 years. When FIT was negative, cancer risk was small (1/750-1/3000 annually). The larger the FIT, the sooner the appearance of CRC. For every 80-mg/g increase of FIT, there were 1.5-year earlier development of CRC incidence and 1- year earlier development of CRC mortality, respectively. Given the same FIT value, CRC events appeared in the proximal colon sooner than the distal colon. Conclusions: A simple user-friendly model based on a single FIT value to predict CRC risk was developed. When positive, NNS offered a simple quantitative value, with a better precision than most risk factors, even combined. When FIT is negative, risk is very small, but requiring a repeat every other year to rule out false negative. FIT values correlated well with CRC prognosis, with worst for proximal CRC.

78 大腸鏡切除小型腺瘤與微型腺瘤後發生後續 進展性大腸腫瘤的風險：一項多中心觀察性 研究報告 THE PREDICTIVE VALUE OF SMALL VERSUS DIMINUTIVE NONADVANCED ADENOMAS FOR METACHRONOUS ADVANCED COLORECTAL NEOPLASIA: A MULTICENTER OBSERVATIONAL STUDY

鄭吉良1 陳碩為2 唐瑞祥3 吳季桓4 郭彥麟1 簡佐軒2 蘇怡佳3 李沐憲4 劉乃仁4 中壢長榮醫院胃腸科1 基隆長庚紀念醫院胃腸肝膽科2 臺北醫學大學附設醫院胃腸肝膽科3 林口長庚紀念醫院胃腸肝膽科系4

Background: Current guidelines for postpolypectomy surveillance intervals treat all 1-9 mm nonadvanced adenomas (NAAs) as carrying the same level of risk for metachronous advanced colorectal neoplasia (ACRN). Aims: To evaluate whether small (6-9 mm) NAAs detected at colonoscopy are associated with greater risk of metachronous ACRN compared with baseline diminutive (1-5 mm) NAAs. Methods: We retrospectively evaluated 10,060 index colonoscopies performed from July 2011 to July 2019 at four hospitals in Taiwan. Patients with advanced adenomas (adenoma ≥10 mm, or with villous histology, or with highgrade dysplasia) or >10 NAAs at index examination were excluded. A total of 1,369 patients with index 1-9 mm NAAs and had follow-up colonoscopies performed at least 1 year apart were included for analysis. Patients were categorized into 5 groups based on size and number of index NAAs: group 1, 1 to 2 adenomas both ≤5 mm (n = 655); group 2, 1 to 2 adenomas with one at least 6-9 mm (n = 529); group 3, 3 to 4 adenomas all ≤5 mm (n = 78); group 4, 3 to 4 adenomas with one at least 6-9 mm (n = 65); and group 5, 5 to 10 adenomas (n = 42). Metachronous ACRN was defined as finding an advanced adenoma or colorectal cancer at follow-up. Results: The mean age of study population was 56.2 ± 10.1 years, and the proportion of men was 53.5%. The mean interval between the index and follow-up examination was 37.5 ± 19.4 months. The absolute risk of metachronous ACRN increased from 7.2% (54/747) in patients with all diminutive NAAs to 12.2% (76/622) in patients with at least 1 small NAA (P = 0.002). After adjusting for the covariates, we observed that group 2 (adjusted odds ratio [AOR], 1.89; 95% confidence interval [CI], 1.21-2.95), group 3 (AOR, 2.40; 95% CI, 1.78-4.90), group 4 (AOR, 2.77; 95% CI, 1.35-5.66), and group 5 (AOR, 3.71; 95% CI, 1.65-8.37) were associated with an increased risk for metachronous ACRN compared with group 1. Conclusions: Patients with baseline small NAAs have an increased risk of metachronous ACRN compared to patients with only diminutive NAAs. Postpolypectomy guidelines should therefore consider including risk stratification between small and diminutive adenomas.

79 大腸直腸內視鏡黏膜下剝離術的有效性和安 全性 - 台灣醫學中心的經驗 EFFICACY AND SAFETY OF COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION: A SINGLE CENTER EXPERIENCE IN TAIWAN

洪宣任1 楊志偉1 黃天祐1 謝財源1 張維國1 陳鵬仁1 三軍總醫院1

Background: Endoscopic submucosal dissection (ESD) achieves higher en bloc resection rates of early colorectal neoplasms as compared to endoscopic mucosal resection. However, complications, such as perforation and bleeding, occur more frequently during ESD Aims: We aimed to evaluate clinical outcomes and complications of colorectal ESD procedures. Methods: 161 patients treated with colorectal ESD in a tertiary center from January 2015 to December 2019 were analyzed in this retrospective study. The degree of submucosal fibrosis was classified into three types (F0–2). Outcomes were en bloc resection rates, perforation rates, bleeding rates, emergency surgery, recurrence, long-term overall and disease-specific survival rates. Results: The mean size of the ESD specimen was 39 ± 18 mm. The overall en bloc resection rate was 98.1 %. Perforation or muscle holes caused by ESD knives occurred in 29 out of 161 patients (18 %). All perforations were successfully treated with endoscopic closure of hemoclips and nonsurgical management. Emergency surgery was not required in any of the cases. Submucosal fibrosis was associated with higher frequency of perforation (P = 0.008). There was no recurrence or disease-related death. Conclusions: Submucosal fibrosis was a risk factor related to perforation during colorectal ESD. Complications of colorectal ESD can be successfully managed nonsurgically.

80 大腸鏡光學診斷之即時通知對患者焦慮和抑 鬱的影響：一項隨機對照試驗的初步研究。 IMPACT OF REAL-TIME NOTIFICATION OF COLONOSCOPIC OPTICAL DIAGNOSIS ON PATIENTS’ ANXIETY AND DEPRESSION: A PILOT STUDY OF A RANDOMIZED CONTROL TRIAL.

郭震亞1 李輔仁1 張吉仰1 邱瀚模2 新北市天主教輔仁大學附設醫院胃腸肝膽內科1 臺北市國立臺灣大學附設醫院內科部2

Background: The accuracy of endoscopic optical diagnosis for colorectal polyps has been approaching histological diagnosis after implementation of image enhancement endoscopic technologies. Before histological diagnosis is available, patients who received colonoscopy often experienced anxiety, depression, and even a decline in quality of life. Aims: The real-time notification of possible nature of resected polyp after colonoscopy is expected to reduce the anxiety and depression level of the patients before the availability of histological diagnosis and improve their quality of life. We designed and conducted a proof-ofconcept pilot study prior to the randomized control trial to confirm this hypothesis. Methods: This pilot study enrolled outpatients from the age of 40 to 80 who are scheduled to undergo sedated colonoscopy. The participants were randomized into “ordinary care group (informed optical and histological diagnosis at next scheduled clinic)” and “real-time notification group (informed optical diagnosis immediately after colonoscopy)”. The level of anxiety, depression and quality of life of the two groups were measured by using Taiwan version questionnaire of Hospital Anxiety and Depression Scale (HADS) and World Health Organization Quality of Life (WHOQOL-BREF) right before the next scheduled clinic for histological diagnosis and compared the difference of outcomes between the two groups. Results: Until Dec 2021, seventy two patients were enrolled. Thirty eight subjects were assigned to the ordinary care group and 34 subjects to the real-time notification group. The baseline characteristics were similar between the two groups. The WHOQOL-BREF score of every domain of the two groups were similar before knowing the histological diagnosis at the next clinic visit. The real-time notification group had a trend with a higher depression score before the next clinic visits (6.912 vs.

5.868, p=0.218) and this trend was further augmented in subjects with colorectal polyps (7.429 vs. 5.828, p=0.181). The anxiety score was similar between the two groups. Conclusions: In this pilot study, real-time notification of optical diagnosis after colonoscopy had a trend of increased degree of depression before knowing the histological diagnosis, especially in subjects with colon polyps.

81 應用組合式及集中化的模式優化小兒大腸鏡 的品質：單一醫學中心回顧 QUALITY OPTIMIZATION OF PEDIATRIC COLONOSCOPY BY APPLICATION OF BUNDLE AND CENTRALIZATION: A SINGLE-CENTER REVIEW

劉語涵1 李宏昌1 楊俊仁1 陳偉燾1 江椿彬1 張思玟1 翁書釗1 馬偕兒童醫院兒童胃腸肝膽暨營養科1

Background: Colonoscopy is largely performed for diagnostic and therapeutic reasons in both adults and children. Intraprocedural quality indicators for pediatric colonoscopy measured in including total procedure time, cecal and ileal intubation rates, and bowel preparation quality.To date, little was mentioned on the practice to optimize the quality of pediatric colonoscopy based on the previously set indicators. Aims: To assess the quality change of our single-center pediatric colonoscopy after applying bundle for bowel preparation and general anesthesia, and centralize the procedure using terminal ileum (TI) intubation rate as the main indicator. Methods: All elective colonoscopies performed for patients younger than 18 years old in MacKay Memorial Hospital from July 2015 through June 2020 (assigned to group 1), and from August 2020 through July 2021 (assigned to group 2) was retrospectively reviewed for demographic characteristics, indications, bowel prepare agent and cleansing level, biopsy, maximum intestinal level reached, and reach cecum and total procedure time. Statistical analysis was done using P value <0.05 considered to be significant. Results: Analysis included 45 and 32 colonoscopies in group 1 and 2, respectively. Bloody stool was the most frequent indication in both groups. Both TI intubation rate (42.2% v.s. 75.0%, P = 0.004) and biopsy rate (45.0% v.s. 72.4%, P = 0.014) increased significantly from group 1 to group 2. The narrower standard deviation of bowel prepare score (1.93 v.s. 1.13) and total colonoscopy duration (37.29 v.s. 21.93) in group 2 indicated a more stable quality, although the mean had no difference. There was no statistical difference in age, gender, body weight, reach cecum rate, and reach cecum time. Conclusions: The quality of pediatric colonoscopy was optimized after applying bundle including bowel preparation and general anesthesia, with additional centralization.

82 大腸鏡拉回時間對人工智慧輔助系統對病灶 偵測數量之影響 WITHDRAWAL TIME FOR DOCTOR AND ARTIFICIAL INTELLIGENCE IN COLONOSCOPY

周宗平1 洪志聖1,2,3 李嘉龍1,2 陳信佑1,2 黃鼎鈞1,2 江技坤1,2 涂天健1,3 國泰綜合醫院消化內科1 輔仁大學醫學院2 臺北醫學大學醫學院3

Background: Computer-assisted diagnosis with the use of artificial intelligence (AI) for colonoscopy is developing rapidly in recent years, significantly increasing the lesion detection rate. In addition, lesion detection by AI is hardly affected by factors such as size, location, and shape, and decreases the loading of the gastroenterologist during the procedure. On the other hand, in a recent meta-analysis, longer colonoscopy withdrawal time was associated with a higher adenoma detection rate. Some studies recommend >9 minutes for colonoscopy withdrawal time. Aims: To our knowledge, there is no study on the relationship between withdrawal time and computerassisted diagnosis with the use of an AI system. Methods: We used a developing deep neural network learning AI system (aetherAI Endo) that helps physicians to identify lesions during colonoscopic examination. Thirty videos of colonoscopies performed by Endoscopist were played by PotPlayer and underwent aetherAI Endo. We compared the number of annotated lesions between the normalplaying speed (Group A) and half-playing speed (Group B). ‘Annotated lesions’ were defined as any lesion framed by the system and ‘highly suspicious lesions’ were defined as lesions framed at least three times or continuously by the system. Both types were counted manually. Results: Based on the Aronchick scale, 26 cases were excellent, 3 were good, and only 1 case was poor. Nineteen cases underwent biopsy, polypectomy, or endoscopic mucosal resection. The average time of the videos was 4:57 (3:09 in the non-procedure group, 5:59 in the procedure group). The mean number of annotated lesions in Group A was 14.1 and 20.8 in Group B. The mean number of highly suspicious lesions was 2.733 in Group A and 4.367 in Group B. The mean difference in annotated lesions was 6.7 (95% CI [4.6497-8.7502], p<0.001) and 1.63 (95% CI [0.83382.4329 ], p<0.001) in highly suspicious lesions. Conclusions: In this study, we used the playing speed to imitate the withdrawal time and evaluate the effect of withdrawal time on the computer-assisted diagnosis with the use of AI for lesion detection. We found that as the withdrawal time doubled, both annotated lesions and highly suspicious lesions increased. Computer-assisted systems are now maturing and can help physicians identify lesions during colonoscopy examination. The effect of withdrawal time on lesion detection must considered.

主題：肝硬化及其他肝病（二）

83 血清天門冬胺酸胺基轉移酶濃度預測新型冠 狀病毒肺炎重症預後 HIGH ASPARTATE AMINOTRANSFERASE LEVEL IS PREDICTIVE OF DISEASE PROGRESSION OF CORONAVIRUS DISEASE 2019

張浩哲1 蘇東弘1,2 黃昱璁3 洪俊銘4 盛望徽5 高嘉宏1,2 臺灣大學醫學院附設醫院內科部肝膽腸胃科1 臺灣大學醫學院附設醫院肝炎研究中心2 臺灣大學醫學院附設醫院檢驗醫學部3 臺灣大學醫學院附設醫院內科部整合醫學科4 臺灣大學醫學院附設醫院內科部5

Background: The coronavirus disease 2019 (COVID-19) has spread throughout the world. By the end of 2021 in Taiwan, there has been more than 17050 confirmed COVID-19 cases, and 850 died. Liver dysfunction is a manifestation of COVID-19, while its impact on the course of COVID-19 remains controversial. Aims: We aimed to investigate liver dysfunction in patients with COVID-19 and its clinical impact in those with or without chronic hepatitis B. Methods: Patients with COVID-19-confirmed cases in National Taiwan University Hospital (NTUH) were retrospectively reviewed from the electrical medical records. The clinical information including demographic data, liver function, and course of COVID-19 hospitalization were reviewed and categorized according to their hepatitis B surface antigen (HBsAg) seropositivity. Statistical analyses were performed between two groups. Results: A total of 109 confirmed COVID-19 cases hospitalized in NTUH between Mar 5, 2020 and Aug 22, 2021 were included in the current study. The median age was 59, and 46% was male. HBsAg-positive group (n=34) has significantly higher alanine aminotransferase (ALT, 26 vs. 16 U/L, P=0.034), platelet counts (224 vs. 183 k/uL, P=0.010) and longer hospitalization days (17 vs. 13 days, P=0.012) compared with HBsAg-negative (n=75) patients. However, the percentage of hepatitis (2fold ALT elevation), usage of oxygen, steroid, remdesivir, tocilizumab, ventilator, transferal to intensive care unit (ICU), or mortality were comparable between two groups. Multivariable analyses showed older age (odds ratio [OR]: 1.04, 95% confidence interval [CI]: 1.00-1.08, P=0.032), and greater aspartate aminotransferase (AST) level (OR: 1.08, 95%CI: 1.004-1.16, P=0.038) were associated with oxygen supplement (severe COVID-19). Higher AST was predictive of ICU admission (OR: 1.11, 95%CI: 1.031.19, P=0.008). Oxygen use (OR: 5.64, 95%CI: 1.6719.09, P=0.005) and development of shock (OR: 5.12, 95%CI: 1.14-22.91, P=0.033) were associated with liver dysfunction at or during hospitalization. Conclusions: Patients of chronic hepatitis B had higher ALT level and longer hospitalization days if infected with COVID-19. High AST level is predictive of severe COVID-19 and ICU admission.

84 COVID-19 疫苗接種後急性發作的自體免疫 性肝炎 EXACERBATION OF AUTOIMMUNE HEPATITIS (AIH) FOLLOWING COVID-19 VACCINATION

林政衡1 李佩倫1 董宏達1 陳志州1 鄭俊達1 莊棠惟1 柳營奇美醫院胃腸肝膽科1

Background: Coronavirus disease 2019 (COVID-19) is continuing to spread around the world. And Vaccines to prevent COVID-19 are perhaps the best hope for ending the pandemic.. Although the efficacy of the vaccines is certified, safety still remains a concern. Since we recommend all of our patients undergo COVID-19 vaccination, we had carefully noticed that some adverse effect exacerbated include acute hepatitis. Aims: To clarify the patient who had acute hepatitis is exacerbation of autoimmune hepatitis and may possible related to mRNA vaccination. Methods: During admission course, we had evaluated the patient’s physical examination and upper abdominal ultrasound. Testing for hepatitis A, B, and C; Epstein-Barr virus; dengue virus; cytomegalovirus; and HIV infections were also examined. Immune titer include Antinuclearantibodies testing, antimitochondrial, anti-smooth muscle and liver-kidney-microsome type-1 antibodies were also checked. And we had also checked anti-Platelet Factor 4 antibody. Results: All 10 patient who had acute hepatitis with physical examination and upper abdominal ultrasound were normal. Testing for hepatitis A, B, and C; Epstein-Barr virus; dengue virus; cytomegalovirus; and HIV infections was negative. Antinuclear-antibodies testing was positive in 2 patients; testing for antimitochondrial, anti-smooth muscle and liver-kidney-microsome type-1 antibody was also negative. Anti-Platelet Factor 4 antibody was positive in 4 patients. Conclusions: These results suggest that some patients with AIH-like syndrome may be a possible complication of Covid-19 vaccination. Coincidence of a medical problem after COVID-19 vaccination and differential diagnosis is hard. Thus, we should be considered this problem in cases of post-vaccination persistent hepatitis without obvious cause.

85 大量飲酒合併有 ALDH2 多型態性會增加 B 型肝炎引起的肝硬化病人的肝癌發生率和死 亡率 HEAVY ALCOHOL INTAKE WITH ALDH2 POLYMORPHISM INCREASES HEPATOCELLULAR CARCINOMA AND MORTALITY IN HEPATITIS B VIRUSRELATED CIRRHOSIS

林志文1,2 蔡明釗3 楊賢馨5 王文 2 許耀峻2 胡瑞庭5 林志哲4 義大大昌醫院胃腸肝膽科／義守大學1 義大醫院胃腸肝膽科／義守大學2 高雄長庚紀念醫院胃腸肝膽科／長庚大學3 高雄長庚紀念醫院外科部／長庚大學4 臺北國泰綜合醫院肝臟中心5

Background: Hepatocellular carcinoma (HCC) is the fifth most commonly occurring cancer and the second most common cause of cancer-related death worldwide. In Western countries, daily alcohol intake of more than 80 g for at least 5 years enhances the progression to cirrhosis, HCC and mortality. Hepatitis B virus (HBV) infection with elevated serum HBV DNA levels has been defined as an important risk factor for cirrhosis, HCC, and mortality. Antiviral nucleos(t)ide analogs (NUCs) have been widely used to reduce the development of HCC and mortality in chronic hepatitis B (CHB) patients with fibrosis or cirrhosis. The synergistic effect of alcohol intake and HBV infection on clinical prognosis has been reported. Furthermore, our previous study demonstrated that heavy alcohol consumption promoted the incidence of HCC in HBV-related cirrhosis and that antiviral therapy reduced the risk of HCC in cirrhotic patients with HBV infection and alcoholism[8]. In addition, the aldehyde dehydrogenase 2 (ALDH2) polymorphism is an effect of the development of HCC in alcoholic liver disease[18-20]. However, the role of heavy alcohol intake and HBV infection in the development of HCC and mortality remains uncertain and needs to be explored. Therefore, we investigated the impact of heavy alcohol intake, ALDH2 polymorphism and HBV infection on the clinical prognosis of cirrhotic patients. Aims: We investigated the effect of heavy alcohol intake, ALDH2 polymorphism, and HBV infection on clinical outcomes and risk factors in cirrhotic patients. Methods: We enrolled 1515 cirrhotic patients (342 patients with HBV infection and alcoholism, 796 patients with HBV infection, and 373 patients with alcoholism) from

three tertiary hospitals in Taiwan between 2005 and 2020. Results: Of patients with concomitant HBV infection and alcoholism, HBV infection alone, and alcoholism alone, 81 (23.7%), 134 (16.8%), and 55 (14.6%) patients developed HCC and 151 (45.3%), 322 (40.5%), and 150 (39.8%) patients experienced mortality, respectively. The 15-year cumulative incidences of HCC (66.4% vs. 46.8% vs. 54.8%, P<0.001) and mortality (88.9% vs. 81.9% vs. 90%, P<0.001) were significantly higher in cirrhotic patients with HBV infection and alcoholism than in those with HBV infection alone or alcoholism alone before and after propensity score matching. The ALDH2 polymorphism (allele GA/AA) with heavy alcohol intake significantly increased HCC and mortality in HBV-related cirrhotic patients. Risk factors for HCC were baseline serum HBV DNA (HR=4.08), antiviral nucleos(t)ide analog (NUC) therapy (HR=0.13), alcohol intake (HR=1.77 and 1.49), abstinence (HR=0.41), and ALDH2 polymorphism (HR=5.09). Risk factors for mortality were abstinence (HR=0.22), ALDH2 polymorphism (HR=1.49), Child-Pugh class (HR= 1.43 and 1.98), serum albumin (HR=0.62), and HCC development (HR=1.57) in cirrhotic patients with HBV infection and alcoholism. Conclusions: Heavy alcohol intake along with the ALDH2 polymorphism significantly increased the risk of HCC and mortality in HBV-related cirrhotic patients.

86 腸道菌胺基酸合成功能下降與肝硬化病患產 生肌少症之相關性 DECLINED BIOSYNTHETIC FUNCTIONS OF GUT MICROBIOTA ASSOCIATE WITH DECREASED SERUM AMINO ACIDS IN CIRRHOTIC PATIENTS WITH SARCOPENIA

李沛璋1 李癸汌1 楊宗杰1 陳宥任1 鄭琮譯1 黃怡翔1 侯明志1 臺北榮民總醫院胃腸肝膽科1

Background: Sarcopenia and the associated gut dysbiosis are poor prognostic factors to cirrhotic patients. Although gut-muscle axis is involved in the pathophysiology of sarcopenia, the association between microbial functional alteration and cirrhotic muscle status is still unclear. Aims: The aim of this study is to investigate the predicted function of gut microbiota and its association with serum amino acids (AAs) in cirrhotic patients with sarcopenia. Methods: From September 2018 to December 2020, patients with liver cirrhosis in Taipei Veterans General Hospital were prospectively enrolled. Of them, 21 cirrhotic patients with both normal muscle mass and muscle strength as well as 29 patients with sarcopenia were taken into analysis for the composition and the predicted functions of gut microbiota. Besides, serum levels of AAs and the correlation with microbiota were also investigated. Results: Significant decreased serum levels of AAs, including alanine (p = 0.021), valine (p = 0.026), isoleucine (p = 0.030), proline (p = 0.008), tryptophan (p = 0.028) and ornithine (p = 0.040) were noted in sarcopenic cirrhotic patients compared with the measurements in the counterpart. A significant gut microbial distinction was observed between cirrhotic patients with different muscle status. Besides, a strong positive correlation between AAs and microbiota enriched in normal-muscle cirrhotics as well as negative correlation between AAs and sarcopenic microbiome were also noticed. According to the PICRUSt2 analysis, predicted microbial functions associated with biosynthesis of AAs, including branched-chain amino acids, were significantly reduced in sarcopenic cirrhotic patients. Conclusions: Gut dysbiosis and the associated functional declines of microbiota in biosynthesis of amino acids were correlated with the decreased serum levels of amino acids in cirrhotic patients with sarcopenia.

87 台中榮總使用顯影劑內視鏡超音波指引細針 切片評估肝臟病變成果 THE USEFULNESS OF EUS-GUIDED FINE-NEEDLE LIVER BIOPSY COMPARED WITH PERCUTANEOUS ROUTE: A SINGLE-CENTERED RETROSPECTIVE STUDY

吳彥穎1 廖思嘉1 廖苡君1 葉宏仁1,2,3 李騰裕1,5 楊勝舜1,4,5 臺中榮民總醫院肝膽腸胃科1 國立陽明交通大學2 童綜合醫療社團法人童綜合醫院沙鹿院區3 國立中興大學生物醫學研究所4 中山醫學大學5

Background: Percutaneous liver biopsy (PC-LB) is the standard procedure of tissue sampling for liver lesions. EUS-guided fine needle biopsy (EUS-FNB) is an alternative method of liver sampling, considered as a rescue method of PCLB, with promising diagnostic accuracy and procedural safety. There were few studies to discuss about the diagnostic accuracy and tissue adequacy for liver sampling between PC-LB and EUS-FNB Aims: The objective of this study was to evaluate the diagnostic accuracy and tissue adequacy between PC-B and EUS-FNB for liver lesions. Methods: Data was obtained from November 2019 to December 2021 in Taichung Veterans General Hospital. PC-LB using a 18-gauge Trucut needle for left lobe of liver was identified retrospectively. Patients receiving liver biopsy due to infiltrative liver diseases (with randomized biopsy), masses greater than 10 cm in diameter or tumors involving both lobes were excluded. EUS-FNB for liver sampling was done due to concurrent EUS-FNB for pancreatic tumor in every patient. The samples that were considered positive or suspicious were categorized as positive for malignancy. The samples that were considered benign or atypical were categorized as negative for malignancy from the pathological report and documented no evidence of malignant cells after more than 6 months follow-up period. A real malignant tumor was defined as confirmation by EUS guided FNB or surgical pathology. The outcomes were the diagnostic accuracy for the liver lesions and the adequacy of the specimen to establish the diagnosis, and the comparison of PC-LB and EUS-FNB were analyzed by nonparametric statistics. Results: Twenty-two patients (11 women; median age, 62. 5 years [range, 12-89]) and ten patients (2 women; median age, 63 years [range, 39-70]) underwent PC-LB and EUSFNB for liver lesions respectively during the study period. The median size of the liver lesions was 2.8cm (range, 10.1-100) and 2.6cm (range, 0.6-4.9) for PC-LB and EUSFNB, respectively. The diagnostic accuracy of EUS-FNB was not inferior to PC-LB (100% and 81.8% for EUS-FNB and PC-LB, respectively) ( p = 0.283). No complication was seen for both groups. Conclusions: EUS-FNB for the tissue acquisition of hepatic masses may be helpful and safe procedure with better diagnostic accuracy compared with PC-LB. It could be performed simultaneously during EUS-FNB for pancreatic masses. Further study with larger sample size may be needed in the future.

壁報展示

第一部分：肝

P.001

高敏感度之 B 型肝炎 DNA 檢測對臨床治療 之影響 THE IMPACT OF HIGHLY SENSITIVE DETECTION FOR THE QUANTIFICATION OF HEPATITIS B VIRUS DNA IN THE CLINICAL PRACTICE

林煒晟1 章振旺1 張經緯1 王蒼恩1 王鴻源1 陳銘仁1 臺北馬偕紀念醫院胃腸肝膽科1

Background: Quantification of the viral burden is an important laboratory tool in the management of hepatitis B virus (HBV)-infected patients. The undetectable HBV DNA with anti-HBe seroconversion, HBsAg loss or antiHBs seroconversion are indications to discontinue HBV treatment. The reimbursement of Taiwanese national health insurance system for withdrawal of anti-HBV agent is one year after undetectable HBV DNA. Previously, the result of “<10 IU/mL “ indicates that HBV DNA was undetected in our hospital. Since Nov 2020, a more sensitive HBV DNA detection of Roche COBAS® with the lower limit of quantification of 4.4 IU/mL was available. Aims: To evaluate the impact of the highly sensitive detection of HBV DNA test in the clinical practice. Methods: We retrospectively collected the chronic HBV patients under anti-HBV agent and received ultra-sensitive HBV DNA in MacKay Memorial Hospital, Taipei. A total of 482 chronic hepatitis B patients used anti-HBV agents in the outpatient department between Aug 2015 to May 2021 were included. Results: One hundred forty patients had regular laboratory testing and received ultra-sensitive HBV DNA, and 11 patients (7.9%) had elevated HBV DNA level during antiHBV agent therapy. Among these patients, the median age was 44 year-old and they had HBV DNA 1.12 log increase after a median follow-up duration of 10.5 ± 5.6 months from last lower sensitive HBV DNA test. The higher rate of HBe antigen positive (72.7% vs 27.1%, P=0.004) in the increased HBV DNA group. There were no difference of age, gender, initial HBV DNA level, ALT, anti-HBV agents and follow-up duration between these two groups. In the clinical management, one patient switched from entecavir to tenofovir alafenamide due to two times of HBV DNA increasing. The other patients filled the same prescription and HBV DNA level decreased after 3 months of higher sensitive test follow-up. Conclusions: The improved sensitivity of HBV DNA tests was of critical importance for the management of chronic HBV infection undergoing anti-viral therapy. The test may have future applications in improving assessment of efficacy of antiviral treatment and guiding therapeutic interventions. P.002

病患接受 B 型肝炎預防性治療於健保擴大 給付後的臨床特徵 CLINICAL CHARACTERISTICS OF PATIENTS RECEIVING HEPATITIS B VIRAL CHEMOPROPHYLAXIS AFTER THE IMPLEMENTATION OF EXPANDED REIMBURSEMENT CRITERIA

黃秉淳1 許偉帆1,2,3 賴學洲1,3 莊伯恒1 陳昇弘1,4 蘇文邦1 陳浤燿1 王鴻偉1,4 林俊哲1,4 黃冠棠1,4 林肇堂1,4 彭成元1,4 中國醫藥大學附設醫院內科部消化系1 中國醫藥大學生物醫學醫學研究所2 中國醫藥大學中醫系3 中國醫藥大學醫學系4

Background: Patients with chronic hepatitis B who receive chemotherapy or immunosuppressive therapy have a higher risk of hepatitis B virus (HBV) reactivation. Patients with past HBV infection (HBsAg-negative & antiHBc-positive) also have a risk of HBV reactivation. Thus, patients receiving therapies which pose a moderate or high risk of HBV reactivation, such as anti-CD20, hematopoietic cell transplantation, and high-dose steroid, should receive nucleos(t)ide analogue (NA) for chemoprophylaxis. The National Health Insurance in Taiwan expanded the reimbursement criteria for patients with current or past HBV infection receiving chemotherapy, rituximab and high-dose steroid for more than one month in March 2021. Aims: We retrospectively investigated the clinical characteristics of patients and the indications of HBV chemoprophylaxis after the implementation of the expanded reimbursement criteria in March 2021. Methods: This retrospective study enrolled 356 patients who received HBV chemoprophylaxis at China Medical University Hospital from March 2021 to July 2021. Exclusion criteria included patients receiving NA therapy other than HBV chemoprophylaxis. Demographic and biochemical data, virological features, indications of NA therapy, and comorbidities recorded at baseline were collected. Results: Of 356 patients, 198 (55.6%) patients were male, and 120 (33.7%) and 236 (66.3%) patients had current (HBsAg positive) and past HBV infection, respectively. The median age was 62.7 (53.4–69.7) years (first quartile–third quartile). The platelet count, aspartate aminotransferase, alanine aminotransferase, total bilirubin levels, and α-fetoprotein level at baseline were 215 (141–284) × 109/L, 22 (17–34) U/L, 21 (13–38) U/

L, 0.6 (0.4–0.8) mg/dL, and 2.95 (2.24–4.55) ng/mL, respectively. In HBsAg (+) patients, only 3 of 94 (3.2%) patients were HBeAg (+). The median anti-HBs (n = 59) and HBV DNA (n = 94) levels were 0.77 (0.36–2.99) mIU/mL and 2.76 (0–4.00) log10 IU/mL, respectively. In patients with past HBV infection, all patients with available HBeAg data (71/71) were HBeAg-negative. The median anti-HBs level (n = 115) was 93.3 (17.53–343.43) mIU/mL with 57 (49.6%) patients >100 mIU/mL, and 2 of 96 (2.1%) patients had detectable HBV DNA. The indications of HBV chemoprophylaxis included chemotherapy in HBsAg(+) patients (n = 101, 28.4%), HBsAg(+) patients receiving rituximab (n = 4, 1.1%), HBsAg(+) patients receiving high-dose steroid (n = 15, 4.2%), and chemotherapy in patients with past HBV infection (n = 236, 66.3%). In patients with past HBV infection, 2.1% (5/236), 6.4% (15/236), 9.7% (23/236), and 9.3% (22/236) patients received regimens including high-dose steroid, rituximab, anthracycline, and combined rituximab and anthracycline, repsectively. The top six diseases of HBV chemoprophyalxis included hematologic malignancy (n = 96, 27.0%), breast cancer (n = 50, 14.0%), colorectal cancer (n = 34, 9.6%), lung cancer (n = 33, 9.3%), head and neck cancer (n = 26, 7.3%), and esophageal cancer (n = 24, 6.7%). HBV prophylaxis for immunosuppressive therapy in non-malignant conditions only accounted for 5.1% (18/356) of all prescriptions. Conclusions: Patients was past HBV infection is the predominant subgroup of patients receiving HBV prophylaxis. Chemotherapy in malignant diseases is the major indication of HBV prophylaxis. Further largescale, prospective study is warranted to elucidate the costeffectiveness of the expanded reimbursement criteria. P.003

屏東地區慢性 B 型肝炎患者以口服核苷酸 類似物貝樂克治療之長期預後探討 LONG-TERM OUTCOME OF ENTECAVIR TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS B IN PINGTUNG COUNTY

文士祺1 賴欣汶1 王潔瑜2 沈欣怡3 屏東寶建醫院內科部胃腸科1 屏東寶建醫院護理部個管師2 屏東寶建醫院護理部內視鏡室3

Background: Hepatitis B virus is a major cause of chronic liver disease associated with an increased risk of hepatocecullar carcinoma (HCC), progressive fibrosis and end-stage liver disease. Suppression of HBV replication is recognized as primary on-treatment goal of antiviral therapy. Entecavir (ETV) is an oral nucleoside analogue (NUC) that effectively inhibits HBV polymerase, resulting in rapid viral suppression. Aims: We determined the antiviral potency, incidence of hepatocecullar carcinoma, viral breakthrough rates, and retreatment rates in patients with chronic hepatitis B (CHB) in Ping-Tung County. We aimed to ascertain predictive factors for HCC development. Methods: We conducted a retrospective study. A total of 123 consecutive CHB patients with chronic hepatitis 80 (65%), cirrhosis 43 (35% ) who received ETV treatment for 2.9±1.6 years were followed up for 7.6±4.3 years. Baseline characteristics were examined to identify factors associated with HCC. Results: The rates of undetectable HBV DNA were 67.9%, 90.2%, 95.2% and 96.7% in 0.5, 1, 2 and 3 years, respectively. The rates of ALT normalization were 82.1%, 88.8% and 91.5% in 1, 2, and 3 years, respectively. Ninetyseven (78.9%) and 26 (21.1%) patients were negative and positive for HBeAg, respectively. HBeAg loss occurred in 15 of 26 (57.7%) subjects. The cumulative probabilities of HBeAg loss after 1, 3, and 5 years of treatment were 23.1%, 50% and 57.7%, respectively. The cumulative probabilities of HCC development exhibited 2.4%, 6.5%, 8.1%, and 8.9% after 1, 3, 5, and 7 years of follow-up period. Virus breakthrough occurred in 6 of 123 (4.9%) subjects. The cumulative probabilities of achieving viral breakthrough after 1, 3, and 7 years of treatment were 1.6%, 4.1%, 4.9%, respectively. Retreatment rates occurred in 31 of 123 (25.2%) subjects with clinical relapse after cessation of NUC. PT (INR) Prothrombin time (international

normalized ratio), and presence of liver cirrhosis were predictive of HCC development in the univariate analysis. Multivariate analysis showed that PT (INR) was predictive of a greater incidence of HCC development (HR: 19.7, p=0.032). Conclusions: Long-term data on patients receiving ETV for CHB have demonstrated high potency, a lower incidence of antiviral resistance and good tolerability. However, in CHB patient with cirrhosis particular liver decompensation was a tread for a greater incidence of HCC. P.004

B 型肝炎之肥胖患者於減重手術後導致 B 型 肝炎活化 HBV REACTIVATION AFTER BARIATRIC SURGERY FOR HBVINFECTED OBESE PATIENTS

戴啟明1 杜鴻賓2 葉明倫3 黃釧鋒3 余明隆3 義大醫院胃腸肝膽科1 高雄醫學大學醫學系公共衛生學科2 高雄醫學大學附設中和紀念醫院肝膽胰內科3

Background: The association between non-alcoholic fatty liver disease and hepatitis B virus (HBV) infection is inconclusive. Aims: The aim of this study was to investigate the viral dynamic of HBV and its association with change of body mass index (BMI), aspartate transaminase (AST) and alanine transaminase (ALT) levels after bariatric surgery. Methods: Patients who underwent bariatric surgery between June 2011, and May 2014, were selected in this retrospective study. BMI, AST, ALT, and HBV DNA levels were calculated pre-operatively and at 1st, 3rd and 6th postoperative months. Results: Two hundred and seventy-nine patients including 34 (12.2%) HBsAg-positive and 245 (87.8%) HBsAgnegative patients were enrolled. Eighteen HBsAg-positive, HBeAg-negative patients were matched with 36 HBsAgnegative patients. A significant decrease in BMI was found since 1st postoperative month in both groups. AST and ALT increased at 1st postoperative month, but decreased at 3rd and 6th postoperative months in both groups. However, a significant increase in HBV DNA level was observed in HBeAg-negative patients since 1st postoperative month with the highest peak at 3rd postoperative month. HBV reactivation occurred in 4 out of 17 (23.5%) patients, 8 out of 16 (50.0%) patients, and 4 out of 12 (33.3%) patients at 1st, 3rd and 6th postoperative months, respectively. The change of HBV DNA was not associated with change of BMI, AST, or ALT after bariatric surgery. Conclusions: Bariatric surgery can achieve significant weight loss and improvement of liver function tests. However, there existed significant risk of HBV reactivation after bariatric surgery for patients with obesity.

P.005

嚴重急性 B 型肝炎活化之預測因子 VALIDATION OF SCORING SYSTEMS FOR PREDICTING SHORT-TERM MORTALITY IN SEVERE ACUTE FLARES UP OF CHRONIC HEPATITIS B

陳文誌1 余冠璋1 高雄榮民總醫院胃腸科1

Background: Chronic hepatitis B(CHB) infection remains endemic in Asia. For patient with hepatitis B infection (HBV) chronically, acute flare up of HBV (AFUOHBV) can be severely, even fatal. The nucleoside/nucleotide analogs and transplant were suggested as early as possible at severe AFUOHBV, but no predicting item or formula of AFUOHBV mortality was found currently. Aims: This study aimed to find a formula or item for predicting short-term mortality of severe AFUOHBV. Methods: The patients, from 2005 to 2020, meeting inclusion criteria of severe AFUOHBV were enrolled, including evidence of acute flare of CHB, HBsAg positive > 6months, ALT ≥ 400U/L, Bilirubin ≥ 2mg/dL or INR ≥ 1.5. All included patients’ laboratory data were pooled together, from admission to discharge, mortality or liver transplant. The contents of MELD Score, King’s College Criteria – non-APAP, age, ALT and PLT were compared with morality rate under statistical analyses. The AFOHBV severity statistical analyses were checked under 2-fold cross-validation. All the data was equaled to 2 parts of training data and validation data. Using new MELD Score, age, ALT and PLT for verifying results. Results: The MELD Score, age, ALT and PLT can accurately predict the short-term mortality. Conclusions: According the score formula or item, the severe AFUOHBV can be recognized predictably. In this group, the transplant need to be considered. P.006

使用SOFOSBUVIR-VELPATASVIR治療慢 性 C 型肝炎病人其腎功能之變化 CHANGES IN RENAL FUNCTION IN PATIENTS WITH CHRONIC HEPATITIS C TREATED WITH SOFOSBUVIRVELPATASVIR

呂詠昕1 張德生1,2 董水義1,2 魏國良1,2 陳慰明1,2 沈建亨1 謝詠諭1 陳奕行1 陳俊憲1 許晃維1 顏志維1 童威霖1 張國基1 嘉義長庚紀念醫院1 長庚大學醫學院2

Background: Direct-acting antivirals (DAAs) have become an effective first-line treatment for chronic hepatitis C (CHC), and the fixed-dose combination of sofosbuvir (SOF) and velpatasvir (VEL) is one of the most important pangenotypic DAA regimen according to present treatment guideline. Aims: This study is aimed to survey the association between SOF-based regimens and renal toxicity. Methods: A total of 953 patients including 130 with estimated glomerular filtration rate (eGFR) ≤ 60 mL/ min/1.73 m² and 823 with eGFR > 60 mL/min/1.73 m² receiving SOF/VEL therapy for 12 weeks, were enrolled in this study. The eGFR was assessed at baseline, end of treatment (EOT), and 12 weeks after completion of the therapy (end of follow-up, EOF) Results: The eGFR in patients with eGFR ≤ 60 mL/ min/1.73 m² increased from baseline (47.89 ± 10.25 mL/ min/1.73 m²) to EOT (51.65 ± 15.92; P < 0.001) and EOF (51.51 ± 14.46 mL/min/1.73 m²; P < 0.05). The eGFR in patients with eGFR > 60 mL/min/1.73 m² at baseline (91.52 ± 22.06 mL/min/1.73 m²) was similar to that at EOT (92.1 ± 49.19; P = 0.82), but was lower at EOF (89 ± 23.64 mL/ min/1.73 m²; P < 0.001). Multivariable analysis showed that a higher serum albumin level was associated with a lower risk of eGFR decrease at EOT, and the patients with baseline eGFR > 60 mL/min/1.73 m² was associated with a higher risk of eGFR decrease at EOF. The rates of sustained virologic response 12 weeks after treatment cessation (SVR12) were 99.2% in per-protocol analysis, and the most common adverse events were fatigue (4.7%), abdominal discomfort (4.5%), and skin itching (3.7%). Conclusions: In conclusion, renal function improved after the SOF/VEL treatment in patients with CHC and chronic kidney disease. Thus, SOF/VEL was safe, effective, and tolerable in these patients.

P.007

兩週一次的 ROPEGINTERFERON ALFA2B 為有效及安全之基因型二型慢性 C 型肝 炎的治療選擇 ROPEGINTERFERON ALFA-2B EVERY TWO WEEKS IS AN EFFECTIVE AND SAFE TREATMENT OPTION FOR GENOTYPE 2 CHRONIC HEPATITIS C

陳啟益1 莊萬龍2 Wen-Hua Zhang3 Li-Ying Zhu4 Guo-Qiang Zhang5 陳志州6 羅清池7 Xinmin Zhou8 Xiaorong Mao9 Ping An10 Jia Shang11 郭行道12 陳建宏13 羅錦河14 Dae Won Jun15 蔡崇偉16 曾冠喬16 Albert Qin16 黃奕文17 陳培哲18 嘉義基督教醫院1 高雄醫學大學2 Gansu Wuwei Tumor Hospital3 Fourth Hospital of Harbin Medical University4 Luoyang Central Hospital5 柳營奇美醫院6 嘉義聖馬爾定醫院7 Xijing Hospital8 First Clinical Medical College, Lanzhou University9 Shenyang Sixth People’s Hospital10 Henan Provincial People’s Hospital, Zhengzhou11 永康奇美醫院12 高雄長庚紀念醫院13 義大醫院14 Hanyang University Hospital15 藥華醫藥股份有限公司16 臺北醫學大學暨附設醫院17 臺大醫學院暨附設醫院18

Background: Ropeginterferon alfa-2b is a novel longacting mono-pegylated recombinant proline-interferon alfa-2b with a 40kD branched polyethylene glycol chain conjugated predominantly at its N-terminus. Aims: We aimed to demonstrate the non-inferiority in sustained virologic response at 12-week post treatment (SVR12) of ropeginterferon to peginterferon alfa-2b (pegIntron®) for patients with genotype 2 chronic hepatitis C (CHC). Methods: This was a phase 3, open-label, randomized study in interferon treatment-naïve adult genotype 2 CHC patients in Taiwan, Korea, and China. The patients were randomized to receive subcutaneous injection of either 400 mcg ropeginterferon alfa-2b every two weeks or 1.5 mcg/ kg peg-Intron weekly for 24 weeks plus ribavirin of 800 mg to 1,400 mg daily. Patients were stratified by IL28B SNP 12979860 genotype (CC or non-CC) and baseline serum HCV RNA (< 800,000 IU/mL or ≥ 800,000 IU/mL). The primary endpoint of non-inferiority in SVR12 was evaluated in both intent-to-treat (ITT) and per protocol (PP) population. Results: A total of 215 patients were randomized, 125 in ropeginterferon group and 90 in peg-Intron group. The SVR12 was 79.8% and 86.7% in ropeginterferon group versus 71.9% and 82.1% in peg-Intron group in ITT and PP population, respectively. The stratified factorsadjusted treatment difference between peg-Intron and ropeginterferon was -7.8% (2-sided 95% CI: -19.52%, 3.99%). Thus, the primary endpoint of non-inferiority of ropeginterferon was met because the upper bound of the one-sided 97.5% CI of the treatment difference was less than the pre-defined non-inferiority margin of 15%. Safety population included 222 patients (additional 7 patients in the initial stage of this study which randomized to 360 mcg ropeginterferon). One (0.8%) patient in ropeginterferon group and three (3.2%) patients in peg-Intron group experienced treatment-related serious TEAEs. Two deaths were reported and was assessed as not or unlikely related to the study treatment. Ten (7.9%) patients experienced ropeginterferon-related dose discontinuation versus 13 (13.7%) patients experienced peg-Intron-related dose discontinuation. Ropeginterferon has less flu-like symptoms (37.8% vs. 54.7%), administration site reaction (1.6% vs. 7.4%), alopecia (9.4% vs. 18.9%), dizziness (7.1% vs. 16.8%), decreased appetite (4.7% vs. 21.1%), and nausea (7.9% vs. 15.8%) than peg-Intron. Conclusions: Ropeginterferon plus ribavirin for 24 weeks is non-inferior in SVR12 to peg-Intron plus ribavirin for patients with genotype 2 CHC. Ropeginterferon is a treatment option with superior safety and tolerability as compared to peg-Intron.

P.008

C 型肝炎患者於抗病毒藥物治療後腎絲球過 濾率之長期變化 LONG-TERM EVOLUTION OF ESTIMATED GLOMERULAR FILTRATION RATE IN PATIENTS WITH ANTIVIRAL TREATMENT FOR HEPATITIS C VIRUS INFECTION

林弘堯1 劉振驊1,2,3 林昭維3 劉俊人1,2,4 蘇東弘1,2 吳若玄5

曾岱宗1,2,6 陳培哲1,2,4 高嘉宏1,2,4,6 國立臺灣大學醫學院附設醫院內科部1 國立臺灣大學醫學院附設醫院肝炎研究中心2 國立臺灣大學醫學院附設醫院雲林分院內科部3 國立臺灣大學醫學院臨床醫學研究所4 美國加州大學聖地牙哥分校漢彌爾頓青光眼中心5 國立臺灣大學醫學院附設醫院醫學研究部6

Background: Data regarding the long-term evolution of estimated glomerular filtration rate (eGFR) in patients receiving antiviral treatment for hepatitis C virus (HCV) are limited. Aims: We aimed to evaluate the trends of eGFR and the risk of ESRD development in patients with chronic HCV infection who received IFN-based or DAA treatment, and to elucidate the effects of antiviral treatment, antiviral responses, and various factors of interest on the long-term renal outcomes in a prospective cohort. Methods: A total of 1987 patients with eGFR ≥ 15 mL/ min/1.73m2 who received interferon (IFN) or directacting antiviral (DAA) treatment were prospectively enrolled in this cohort study. The eGFR was assessed biannually by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation from the time point of sustained virologic response (SVR12). Multivariate generalized estimated equation (GEE) was used to assess the association between the factors of interest and evolution of eGFR following antiviral treatment. Multivariate Cox regression analysis was used to assess the relative risk of end-stage renal disease (ESRD), defined as an eGFR < 15 mL/min/1.73m2 . Results: Patients who achieved SVR12 (adjusted slope coefficient difference: 2.36 mL/min/1.73m2/year, 95% confidence interval [CI]: 1.50 to 3.32; p < 0.001) were associated with eGFR improvement, compared to those who did not achieve SVR12. Among patients who achieved SVR12, the eGFR evolution was comparable (adjusted slope coefficient difference: 0.31 mL/min/1.73m2/year, 95% CI: -0.34 to 0.96; p = 0.35) in those treated with IFN or DAA. The incidence rates of ESRD in patients who achieved and did not achieve SVR12 were 0.06 per 100 person-years (PYs) and 0.37 per 100 PYs. Patients who achieved SVR12 were associated with a lower risk of ESRD (adjusted hazard ratio [aHR]: 0.24, 95% CI: 0.05 to 0.68; p = 0.021). Conclusions: The long-term eGFR evolution and risk of ESRD are significantly improved in patients who achieve SVR12 with anti-HCV treatment.

P.009

整合治療策略用於使用直接作用抗病毒藥物 治療合併美沙冬療法之丙型肝炎病人 INTEGRATED TREATMENT STRATEGY WITH THE USE OF DIRECT-ACTING ANTIVIRALS FOR PATIENTS UNDER METHADONE MAINTENANCE TREATMENT WITH HEPATITIS C VIRUS INFECTION

吳佩叡1 楊畯棋1 郭行道1 許銘仁1 奇美醫療財團法人奇美醫院胃腸肝膽科1

Background: In developed countries, substance use and addiction is an emerging problem. People with illicit drug use demonstrated higher prevalence of chronic hepatitis C virus (HCV) infection. Previous study in Taiwan presented that the anti-HCV seropositive rate of injection drug users was 91.3%. In recent years, direct-acting antivirals (DAA) were developed for treatment of chronic HCV infection and achieved approximately 98% sustained virological response at 12 weeks (SVR 12) in Taiwan. In consequence, it is essential not only for prevention of HCV propagation but public health concerns in virtue of DAA treatment for the group of patients who injected drugs (PWID). Methadone maintenance treatment (MMT) has been used to treat opioid dependence, especially heroin (diacetylmorphine) by a daily dose of methadone as a liquid or pill and provide HCV-treatment within existing structures. As a result, we analyzed the real-world data of a medical center in southern Taiwan of DAA treatment for patients under methadone maintenance therapy with HCV infection. Aims: This retrospective analysis provides real-life data about the patient characters, outcome, and efficacy of DAA treatments within people under methadone maintenance treatment. Methods: Integrated hepatitis C treatment program was started since June 2020. We set up the special viral hepatitis clinic just next to the MMT clinic at the same time period. The patients followed up at MMT clinics would be checked anti-HCV ab first. When anti-HCV ab were seropositive, they should be transferred to special viral hepatitis clinic spontaneously if patient agreed with further survey for hepatitis C. Totally, 156 patients were under MMT with antiHCV ab positive in our hospital from June 2020 to May 2021. Among all patients, we excluded patients (1) Treatment completely in other hospital or department, (2) HCV RNA negative (Resolved), (3) Patient refused treatment. After excluded by above criteria, finally 54 patients treated with DAA in our hospital were included in this observational analysis. They were treated with pan-genotype DAA with predominantly Glecaprevir/Pibrentasvir (Maviret) for 8 weeks (50 patients) and 12 weeks (1 patient) and Sofosbuvir/Velpatasvir (Epclusa) for 12 weeks (3 patients). SVR 12 was defined as sustained virological response at 12 weeks after DAA treatment. Primary outcome was set as their SVR 12 status after complete DAA treatment. Results: In our analysis, 54 patients were included. Among these patients, 5 of them had cirrhosis, 24 patients had normal ALT level and 6 patients had abnormal ALT level (Greater than 2x Upper limit of normal). Ultimately, 47 of 54 patients accomplished DAA treatment with sustained virological response at 12 weeks (SVR 12). One patient lost follow up after 4 weeks glecaprevir plus pibrentasvir and was defined as incomplete treatment. Furthermore, 5 patients lost follow-up after accomplished DAA treatment at the time of 12 weeks after end of treatment. But all of them had viral response at end of treatment. One patient expired during the following period because of HCC deterioration. Moreover, one patient re-infected after being treated with 8 weeks with glecaprevir plus pibrentasvir and achieved SVR 12. Overall, our results showed intent to treat (ITT) population was 47/54 (= 87%) and per-protocol (PP) population was 47/48 (= 97.9%). Conclusions: Integrated hepatitis C treatment program with DAA treatment provided an excellent adherence and efficacy to patients under MMT combined with chronic HCV infection. This turned out to be a successful modelof-care for this highly affected population.

P.010

在口服戒毒療程中治療慢性Ｃ型肝炎病患的 外展門診 - 區域醫院的經驗 HIGH EFFECTIVENESS OF PWID ON OPIOID SUBSTITUTION THERAPY WITH HCV INFECTION IN EXTENDED OUTPATIENT TREATMENT- A REGIONAL HOSPITAL EXPERIENCE

陳冠儒1 蔡青陽1 王嗣仁1 陳錫榮1 陳孟如1 黃文翔2 高雄市阮綜合醫院消化內科1 屏東市屏安精神專科醫院2

Background: In taiwan, like most developing or developed countries, people who inject drugs (PWID) are high population of chronic HCV infection. Due to concerns regarding adherence there have been barriers to treating this patient population in daily practice In the clinical study, ANCHOR Study, 8 week treatment, has proven high efficacy in treating chronic HCV infection in PWID on opioid substitution therapy (OST), even with ongoing drug use. In Taiwan, some people who inject drugs (PWID) received opioid substitution therapy (OST) in psychiatric hospital. Aims: We aimed to evaluate the performance of Directacting antivirals(DAAs) for HCV-infected patients in PWID on opioid substitution therapy (OST). Methods: From June 2021 until October 2021, 73 patients (pts) under opioid substitution therapy(OST) were tested for HCV antibody in Pingtung Ping-An Psychiatric Hospital. The primary analysis was Per Protocol sustained virologic response (SVR) defined as all pts who had an available assessment for SVR 12 post therapy. SVR was defined as HCV RNA ≤25 IU/mL. Results: A total of 73 participants were included in the study: 28(38.3%) patients had anti-HCV antibody positive. In this 28 patients, 11 pts refuse screen HCV RNA, one pts virus was < 12, and 16 pts still virus remain. So, in total, 16 patients received direct-acting antiviral agent (DAA) treatment. Of these patients, the median age was 51 years (range, 43~68 ) and 15 (93%) were men. 4 pts were genotype type 1a (25%), one pts was genotype type Ib (6%), 3 pts were genotype type 2 (18%), 2 pts were genotype type 3 (13%), 4 pts were genotype type 6 (25%), one pts was genotype type Ia+6 (6%) and one pts was Indeterminate genotype (6%). All patients received 8 weeks glecaprevir/ pibrentasvir for the treatment of Chronic Hepatitis C. All 16 patients complete oral direct-acting antiviral agent (DAA) treatment. 16 pts (100%) achieved end of treatment (EOT), 15 pts (93%) without virus remain and 1 pts (6%) had very low virus remain (30 IU/mL). But, only 13 patients had SVR 12 data by now (2021/12). Among 13 patients who had the sustained virologic response at off-treatment week 12 (SVR12), the SVR12 rates by per-protocol populations analyses were 100% (13 of 13 patients). The result of our treatment was very good. Conclusions: 8 weeks treatment of Direct-acting antivirals(DAAs), glecaprevir/pibrentasvir, is high adherence and efficacious for chronic HCV infection. 8 weeks Direct-acting antivirals(DAAs) for all Genotypes (GT 1-6) should be suitable for chronic HCV infection in PWID on opioid substitution therapy (OST).

P.011

C 型肝炎傳染因子在中台灣一間醫學中心的 分析 ANALYSIS OF HEPATITIS C VIRUS TRANSMISSION RISK FACTORS IN A MEDICAL CENTER OF CENTRAL TAIWAN

楊芳琦1 蘇培元1 曾雅慧1 黃秀萍1 顏旭亨1 彰化基督教醫院胃腸肝膽科1

Background: The major risk factors of hepatitis C infection are blood-born transmission. However, the prevalence of the risk factors may be variant in different age groups or gender. Aims: The aim of the study is to analyze the prevalence of each transmission risk factor by age and gender. Methods: Three hundred and nine patients with chronic hepatitis C who received DAA therapy were enrolled. The data were collected by using a structured questionnaire included risk factors for HCV acquisition. Results: 240 (77.7%) patients had risk factors (previous history of operation, nondisposable needle injection, previous history of blood transfusion, injection drug use, and sexual exposure (marital relationship). 113 (47.1%) had one, 102 (42.5%) had two, and 25 (10.4%) had more than two risk factors. The operation and blood transfusion were more common in older (≥ 60 years) than young (< 60 years) HCV patients (p<0.05). Injection drug use was common in young than older HCV patients (74.2% vs 25.8%, p<0.001). Nondisposable needle injection and sexual exposure (marital relationship) showed no significant difference between two groups. Men were more likely to have injection drug use, but women were more likely to have blood transfusion. Conclusions: Young and male HCV patients tend to have HCV acquisition via Injection drug use in a medical center of central Taiwan. However, previous history of operation or blood transfusion are major risk factors in older or female patients. P.012

產前高脂肪與微塑料暴露在後代脂肪肝中的 編程 PROGRAMMING OF MATERNAL HIGH FAT WITH MICROPLASTICS EXPOSURE IN OFFSPRING FATTY LIVER

刁茂盟1 盧怡庭1 于鴻仁1 江凱倫1 高雄長庚紀念醫院小兒科，長庚大學1

Background: Prenatal nutrition and toxic exposure will affect the health and disease of offspring. Prenatal high-fat diet or exposure of microplastics can cause the accumulation of liver fat after delivery, which can cause liver fibrosis and cirrhosis. Aims: To study the offspring fatty liver injury through maternal high-fat diet (1st hit) and microplastics exposure (2nd hit) was with inflammation and apoptosis pathway. Methods: After confirmation of pregnancy on the 14th day after mating, pregnant females Sprague-Dawley rats are randomly divided for the prenatal high--fat diet exposure paradigm (HFD) or left undisturbed (NC) until delivery. The other NC and HFD were fed with microplastics [NCMP1; NC+microplastics (5um, 100ug/ L), NCMP2: NC+microplastics (5um, 1000ug/L), HFDMP1: HFD+microplastics (5um, 100ug/L), HFDMP2: HFD+microplastics (5um, 1000ug/L)]. The offspring was sacrificed 7 days after delivery (PD7). Results: The PD7 offspring increased more hepatic lipid accumulation in the HFDMP1,2 than HFD and NCMP1,2 studied via liver histology. The pregnant maternal liver weight increased in HFD and HFDMP1. The offspring body weight, increase in HFDMP1,2 than NCMP1,2 and HFD. The offspring liver weight, increased in HFDMP1 than HFD but not HFDMP2. The western blot of cleaved caspase 3 expression increased in NCMP1,2, HFD, HFDMP2 (P<0.05) but not HFDMP1. The IL-6 expression increased in more in HFDMP2 than NCMP1,2, HFD, HFDMP1 (P<0.05). Conclusions: Prenatal microplastics with HFD increased more hepatic lipid accumulation in the offspring. The offspring liver apoptosis and inflammation increased more in prenatal high concentration microplastics with HFD.

P.013

聲輻射力脈衝在非酒精性肝炎的臨床應用 CLINICAL APPLICATION OF ACOUSTIC RADIATION FORCE IMPULSE IN NAFLD

林揚笙1,2 李騏宇2 林煒晟2 張經緯2 陳銘仁2 臺北醫學大學臨床醫學研究所1 馬偕紀念醫院胃腸肝膽內科2

Background: Non-alcoholic fatty liver disease (NAFLD) is rapidly emerging in the world and fibrosis representing the strongest prognostic indicator. Shear wave velocity (SWV) measured with acoustic radiation force impulse (ARFI) has been applied for determination of liver fibrosis in NAFLD. However, body mass index is known to interfere with the reliability of the ARFI. Aims: Our aim is to evaluate the impact of associated factors might also interfere with the measure of ARFI. Methods: Ultrasound identified NAFLD with grading of hepatic steatosis and chronic liver disease was enrolled. All the patients had anthropometric and metabolic profiling. Significant liver fibrosis, advanced fibrosis and cirrhosis were determined using ARFI with a cut-off value of 1.33 m/s, 1.78 m/s, and 2.16 m/s, respectively. Results: There were 95 patients with 63% of male, 16% of diabetes, 28% of hypertension, 48% of dyslipidemia. In comparison hepatic fibrosis, BMI (26.4 vs 31.5, P <0.001), waist circumference (90.5 vs 100.3, P <0.001), HOMIIR (3.1 vs 4.7, P=0.007), and fatty liver index (43.1 vs 64.6, P <0.001) were significantly higher in significant to severe fibrosis ( ≧ F2). Measurement of SWV is significant interfered by waist circumference (OR = 1.11, P < 0.001), weight (OR = 1.04, P =0.01), BMI (OR = 1.34, P < 0.001), HOMA-IR (OR = 1.23, P =0.018), FLI (OR = 1.04, P <0.001); but not interfered by visceral fat index (OR = 1.00, P = 0.73), GOT (OR = 1.01, P = 0.26), GPT (OR = 1.01, P = 0.12), GGT (OR = 1.00, P = 0.84). Conclusions: ARFI is quick and easy to perform and provides reproducible results in NAFLD. However, factors as weight, waist circumference, BMI, and insulin resistance significantly influence the measurements. Judge the clinical data with causation and tailored the technique to get reliable results are suggested. P.014

探討運動及飲食調控對肥胖合併肝臟代謝疾 病其脂肪肝參數之影響 EFFECTS OF EXERCISE AND DIET MODIFICATION ON CONTROLLED ATTENUATED PARAMETER VALUES IN OBESE PATIENTS WITH METABOLIC ASSOCIATED FATTY LIVER DISEASE

劉作財1 易志勳1 林霖1 翁銘彣1 梁書瑋1 洪睿勝1 雷尉毅1 陳健麟1

佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃

科1

Background: Metabolic associated (Non-alcoholic) fatty liver disease (MAFLD) represents a growing problem in the world in parallel with the increasing incidence of obesity. Exercise and diet modification is a recommended therapy for MAFLD. Fibroscan device/transient elastography can be used to estimate the degree of liver scarring and steatosis through controlled attenuated parameter (CAP) value. Aims: The aim of this study is to evaluate the effect of exercise and diet modification on values of transient elastography in an obese population with MAFLD. Methods: Thirty-two (32) patients (38.7±8.9 years, 10 male) with MAFLD diagnosed by ultrasonography were included in this prospective follow-up study. All subjects participated in a 3-month exercise and diet modification program. The physical parameters, biochemical testing, and transient elastography values were collected and compared before and after the 3-month program. Results: The body weight, body mass index, waist circumference, hip circumference, waist-to-hip ratio, and blood pressure were significantly reduced after intervention. AST, ALT, creatinine, cholesterol, GGT, and LDL cholesterol also showed improvement after 3-month program intervention. Average CAP was significantly decreased after intervention (297.5 dB/m vs 255.0 dB/ m, P < 0.001). There was no significant difference in liver stiffness values between pre- and post-intervention (5.24kPa versus 4.82kPa, P = 0.09). Conclusions: This study demonstrates that exercise and diet modification can have beneficial effects in reducing weight, body fat, metabolic profile, and liver steatosis among patients with MAFLD. Our study supports the notion that transient elastography could therefore serve as monitoring tools for therapeutic intervention in obese patients with MAFLD.

P.015

代謝異常之脂肪肝於台灣一醫學中心職員之 盛行率 THE PREVALENCE OF METABOLIC ASSOCIATED FATTY LIVER DISEASE AMONG STAFFS IN A MEDICAL CENTER IN TAIWAN

邱宏智1 簡世杰1 邱彥程1 鄭斌男1 國立成功大學附設醫院胃腸肝膽科1

Background: Non-alcoholic liver disease (NAFLD), the most common liver disease worldwide, includes pure hepatic steatosis and non-alcoholic steatohepatitis (NASH). A new nomenclature “metabolic dysfunction associated fatty liver disease (MAFLD)” was proposed in an international expert consensus recently. Aims: The study is aimed to evaluate the prevalence of NAFLD and MAFLD among staffs in a medical center in Taiwan. Methods: We retrospectively review the medical records of employee physical checkup for the staffs in 2020. MAFLD was defined as subjects with fatty liver plus one of the following: obesity, type 2 diabetes mellitus, or at least two of metabolic abnormalities. NAFLD was defined as subjects with fatty liver after excluding viral hepatitis and alcohol abuse. FIB-4 ≧ 2.67 was defined as advanced fibrosis. Results: In total 5745 subjects receiving checkup, 817 subjects also received abdominal ultrasound. All subjects receiving abdominal ultrasound were more than 40-yearold. Fatty liver was detected by ultrasound in 354 subjects (43.3%). Among subjects with fatty liver, 307 (86.7%) subjects were categorized as MAFLD, 323 (91.2%) subjects as NAFLD. Forty-two (11.9%) subjects had non-MAFLD NAFLD, 26 (7.3%) subjects had non-NAFLD MAFLD, and 281 (79.4%) had NAFLD-MAFLD. Compared with subjects with non-MAFLD NAFLD, those with MAFLD had younger age, higher ALT, BMI, triglyceride, glucose, and lower HDL. The rate of advanced fibrosis was similar between different groups because only 0.4% of subjects had FIB-4 ≧ 2.67. Conclusions: A significant portion of staffs in this medical center had MAFLD, although the ratio of advanced fibrosis was low. The long-term and longitudinal follow-up for MAFLD if worthy of further evaluation. P.016

代謝功能障礙相關性脂肪性肝病（MAFLD） 併慢性Ｂ型肝炎病毒感染與否的患者臨床表 現差異 - 多中心研究 THE DIFFERENCES IN CLINICAL MANIFESTATIONS BETWEEN PATIENTS HAVING METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE (MAFLD) WITH VERSUS WITHOUT CHRONIC HEPATITIS B INFECTION-A MULTICENTER STUDY

陳蕙芬1 林志陵1,5 黃奕文2,5 楊勝舜3,5 劉俊人4,5 高嘉宏4,5 臺北市立聯合醫院仁愛院區消化內科肝病中心1 國泰綜合醫院肝臟中心2 臺中榮民總醫院內科部胃腸肝膽科3 國立臺灣大學附設醫院肝炎研究中心4 臺灣肝臟疾病臨床試驗合作聯盟5

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) as the hepatic manifestation of metabolic syndrome, formerly named “NAFLD (non-alcoholic fatty liver disease)”, has become the most common liver disease worldwide. The new definition of MAFLD expands disease spectra and includes chronic viral hepatitis. Mounting studies tend to support there is an inverse association between chronic viral hepatitis B (CHB) and metabolic syndrome. But hepatosteatosis elevates the risk of progression to cirrhosis in CHB patients and increases cardiovascular disease risk. The difference in the clinical presentation of MAFLD with and without CHB infection should be investigated for long-term care. Aims: This study aims to compare the anthropometric parameters, laboratory parameters, and the severity of hepatic fibrosis and steatosis by non-invasive examination, including Transient elastography, between patients having MAFLD with and without chronic viral hepatitis B infection. Methods: This multi-center descriptive study recruited subjects with fatty liver detected by sonographic findings from the Ren-Ai branch, Taipei City Hospital (TPECHRA), National Taiwan University Hospital (NTUH), Cathay General Hospital (CGH), and Taichung Veterans General Hospital (VGHTC). Cases with chronic viral hepatitis C, incomplete data of insulin resistance and HBV infectious status, and who failed to be diagnosed as fatty liver via Transient elastography FibroScan® Controlled Attenuation Parameter (CAP) were excluded.

The data of anthropometric parameters, laboratory tests, liver fibrosis severity by non-invasive methods, and liver stiffness/ hepatosteatosis by FibroScan® were collected. The differences in clinical manifestations between MAFLD with and without CHB infection were compared. Results: There were 253 cases (88 females and 165 males) in MAFLD and 149 cases (32 females and 117 males) in MAFLD with CHB group. No significant difference in terms of age, BMI, waistline, the proportion of hypertension and diabetes mellitus, cholesterol level, total triglyceride level, insulin resistance, or liver stiffness was found between the two groups. Compared with the MAFLD subjects, the MAFLD with CHB patients had more male proportion (78.52% vs. 65.22%, p 0.005), more height (168.98±8.39 vs. 166.00±9.00cm, p 0.001), higher diastolic blood pressure (87.53±12.28 mmHg vs. 84.70±11.12 mmHg, p 0.019), longer Prothrombin time (10.56±1.00 sec vs. 10.30±0.55 sec, p 0.009), lower AST level (32.2±23.07 IU/L vs 39.96±26.61 IU/L, p=0.003), lower ALT level (43.84±37.43 IU/L vs 58.92±45.92 IU/L, p=0.001) and lower CAP level (296.66±43.38 dB/m vs. 316.44±46 dB/ m, p=0.007). Correlation between Chronic viral hepatitis B infection status (HBsAg), insulin resistance (HOMA-IR), fatty severity (CAP), and stiffness via Fibroscan showed a negative correlation between HBsAg and CAP (-0.16, p = 0.041) and a positive correlation between insulin resistance and liver stiffness (0.21, p = 0.008). Conclusions: Compared to the MAFLD patients, the MAFLD with CHB patients had a lower CAP score. Cases of both groups in our study had no advanced fibrosis. Chronic hepatitis B infection had a negative correlation with fatty severity in our study. Insulin resistance had a positive correlation with liver stiffness. P.017

微球經動脈栓塞術合併超音波導引燒灼術治 療肝癌 TRANSARTERIAL EMBOLIZATION USING MICROSPHERES COMBINED WITH ULTRASOUND-GUIDED ABLATION FOR HEPATOCELLULAR CARCINOMA

高偉育1,2 林俊宇3,5 李欣倫4,5 蘇建維7,8 張君照1,2 李冠德2,6 邱仲峯4,5 臺北醫學大學附設醫院內科部胃腸科1 臺北醫學大學醫學院內科學科2 臺北醫學大學附設醫院影像醫學部3 臺北醫學大學附設醫院放射腫瘤部4 臺北醫學大學醫學院放射學科5 臺北醫學大學附設醫院內科部血液腫瘤科6 臺北榮民總醫院內科部胃腸科7 陽明大學醫學院醫學系8

Background: Transcatheter arterial embolization (TAE), radiofrequency ablation (RFA), and microwave ablation (MWA) are effective therapies for unresectable hepatocellular carcinoma (HCC). Aims: This study aimed to evaluated the feasibility, efficacy, and safety of TAE using Microspheres combined with ultrasound-guided ablation in a single session for the treatment of HCC. Methods: We enrolled 15 treatment-naïve and 17 recurrent HCC patients who underwent TAE and RFA or MWA at Taipei Medical University Hospital from November 2015 to March 2021. Ultrasound-guided RFA or MWA was performed one day after TAE with Embozene microspheres. Complete response was defined as complete devascularization at computed tomography or magnetic resonance imaging one month after treatment. Local tumor responses and procedure-related complications were evaluated. Results: Completion of both procedures was obtained in 32 patients for all 43 lesions. The median tumor size was 3.7 cm (interquartile range, 3.2‒4.5 cm). Complete response rates were 90.5% (19/21), 80% (4/5) and 90.6% (29/32) in patients with tumor size 3-5cm, more than 5cm and all patients, respectively. After a median follow-up of 9.5±22.4 months, 4 treatment-naïve HCC patients died and 11 were still alive on their last visit. Four treatment-naïve HCC patients had tumor recurrence, with a median time of development of 8.8 ± 19.4 months. No major treatmentrelated complication was observed.

Conclusions: Single-session combined TAE with Embozene microspheres and ultrasound-guided RFA or MWA is an effective and safe treatment for unresectable HCC and helps the localization of target tumors with the creation of large ablation zone. Further large cohort with long-term follow-up studies are warranted to assess the outcome of TAE using Embozene microspheres combined with ultrasound-guided ablation. P.018

肝癌合併巨觀下血管侵犯：比較東西方病患 的臨床表現差異 THE CHARACTERISTICS OF PATIENT WITH MACROVASCULAR INVASION IN HEPATOCELLULAR CARCINOMA: WHEN EAST MEETS WEST

顏毅豪1 李偉鋒2 紀廣明1 王植熙2 鄭汝汾3 盧勝男1 高雄長庚紀念醫院胃腸肝膽1 高雄長庚紀念醫院一般外科2 高雄長庚紀念醫院放射診斷3

Background: A significant proportion of patients with HCC present with tumor-related macrovascular invasion (MaVI), which results in progression to an advanced disease stage Aims: To evaluate the prevalence and extension of macrovascular invasion (MaVI) in a large cohort of hepatocellular carcinoma (HCC) patients and analyze the association between MaVI and overall survival (OS). Methods: From 2011–2018, 2,540 patients with newly diagnosed HCC who were managed in our institution were enrolled in this retrospective study. Tumor invasion of the intrahepatic branches of the portal or hepatic veins was defined as peripheral MaVI. Tumor invasion of the main portal vein or inferior vena cava was defined as central MaVI. Results: MaVI prevalence was 16.2% (n = 411). Among patients with Barcelona-Clinic Liver Cancer (BCLC) Stage C and Child–Pugh Class A, 165 patients presented with peripheral MaVI and 89 patients with central MaVI. The median OS was 13.2 months (95% confidence interval [CI]: 11.4–15.4) in the peripheral MaVI group and 6.6 months (95% CI: 3.6–9.5) in the central MaVI group (p < 0.001). In patients with BCLC Stage C and Child–Pugh Class B or BCLC Stage D, 68 patients presented with peripheral MaVI and 89 patients with central MaVI. The median OS was 3.6 months (95% CI: 3.1–4.2) in the peripheral MaVI group and 2.8 months (95% CI: 2.1–3.4) in the central MaVI group (p = 0.674). Conclusions: Conclusion: The extension of MaVI significantly affected patient survival only in those with BCLC Stage C and Child-Pugh Class A. In patients with BCLC Stage C and Child-Pugh Class B or BCLC Stage D, survival was poor irrespective of MaVI status.

P.019

單用標靶藥物 SOREFENIB 與多重模式治 療（SORAFENIB/RT/TACE) 在大血管侵犯 肝細胞癌上的治療結果比較 OUTCOME COMPARISON OF SORAFENIB ALONE VERSUS MULTIMODALITY THERAPY (SORAFENIB/ RT/TACE) FOR HEPATOCELLULAR CARCINOMA WITH MACROVASCULAR INVASION

呂孟銓1 黃文彥2 黃瑋琛1 三軍總醫院內科部腸胃科1 三軍總醫院放射腫瘤部2

Background: Hepatocellular carcinoma (HCC), which accounts for about 90% of primary liver cancers, is one of the most lethal malignant tumors in the world. Unfortunately, around 10~40% of HCC patients who present with definite vascular invasion at the time of diagnosis, defined as Barcelona Clinic Liver Cancer (BCLC) stage C disease, have very limited treatment options. Unsuitable for curable surgical resection, liver transplantation, or radiofrequency ablation, these patients have a particularly poor prognosis and the median survival is only prolonged a few months by systemic treatment with tyrosine kinase inhibitors. Therefore, combining multiple therapeutic modalities to enhance treatment responses is urgently needed for selected HCC patients with macrovascular invasion (MVI). Aims: This study compares outcomes of sorafenib alone versus sorafenib/RT/TACE multi-modality therapy for HCC patients with MVI. Methods: From March 2009 to October 2017, 78 HCC patients with MVI who underwent either sorafenib alone (n = 49) or sorafenib/RT/TACE (n = 29) were retrospectively included. We analyzed overall survival (OS) between two groups with Cox regression hazard model using SPSS version 17. We adjusted for imbalances in treatment assignment using propensity score matching (PSM). Results: At the last follow up, 76 patients died and 2 patients were alive, with the median follow-up time of 4.8 months. There were 49 (62.8%) patients with CTP class A and 29 (37.2%) patients were CTP class B. Patients treated with sorafenib/RT/TACE had superior OS than sorafenib alone, with median survival of 9.3 vs 2.7 months and 1-year survival of 37.1 % vs 6.1 % (p < 0.001). In univariable analysis, Eastern Cooperative Oncology Group performance status (HR = 0.48, p = 0.005), new diagnosis/recurrence (HR = 0.32, p < 0.001), and treatment modalities (sorafenib alone vs sorafenib/RT/TACE) (HR = 0.70, p < 0.001) were associated with OS. Multivariable analysis demonstrates new diagnosis/recurrence (HR = 0.52, p = 0.031) and treatment modalities (sorafenib alone vs sorafenib/RT/TACE) (HR = 0.80, p = 0.037) were independent prognostic factors for OS. After propensity score-matching, sorafenib/TACE/RT) still showed superior OS than sorafenib alone (p = 0.002). Conclusions: HCC patients with MVI receiving sorafenib/ RT/TACE resulted in better OS than sorafenib alone in this retrospectively study. Further prospective clinical trial to compare sorafenib/RT/TACE with sorafenib alone is warranted.

P.020

肝細胞癌病人經肝動脈栓塞化學療法後之 ALBI 分級變化分析以及預測肝功能衰退之 指標 THE CHANGE OF ALBI GRADE AND PREDICTOR OF LIVER DYSFUNCTION AFTER TRANSHEPATIC ARTERIAL CHEMO-EMBOLIZATION FOR HEPATOCELLULAR CARCINOMA PATIENTS

鄭坤霖1 鄭煜明2 王嘉齊1 佛教慈濟醫療財團法人臺北慈濟醫院1 童綜合醫療社團法人童綜合醫院2

Background: Although transhepatic arterial chemoembolization (TACE) has been known to be beneficial for intermediate stage hepatocellular carcinoma (HCC) patients, its cost is the damage of liver reserve. Liver dysfunction is one of factors associated with refractory TACE and poor prognosis. Aims: The study aims to determine the prevalence and predictors of liver dysfunction in HCC patients after TACE. Methods: Using the ASUS EMR search 3.0 system, the patients with dischage codes “HCC (C22.0)” plus “TACE” were collected since 2016 till 2021 in Taipei Tzu Chi Hospital. Albi grade inclued grade 1, 2a, 2b, and 3. The liver dysfunction was defined as Albi grade increase at 1-3 month after TACE. Results: A total of 220 HCC patients with 314 TACE were found in 5-year duration. Of them, 91 HCC patients (62 male; mean age 65.86±11.61 year-old) with availabe data of Albi score at month 1-3 after TACE treatment were recruited for final analysis. There were 10 (11%) patients with baseline Albi grade 3. The change of Albi grade between baseline and at Month 1-3 after TACE was shown in Table 1. After excluding those with baseline Albi grade 3, the percentage of Albi grade increase was 27.2% (22/81) after TACE. Tumor size larger than 5 cm was associated with Albi grade increase after TACE using univariate analysis (Table 3) Conclusions: In this retrospective study using EMR search, 11% HCC patients had poor liver reserve of Albi grade 3 before TACE treatment in our study population. Liver dysfunction, which was defined as the increase of Albi grade occurred in 27.2% of HCC patients after TACE. Tumor size larger than 5 cm was the only factor predicting liver dysfunction after TACE, suggesting early shift to systemic therapy or using drug-eluting bead to reduce the risk of liver damage after TACE. P.021

腫瘤負擔指數於肝癌患者接受經動脈化療栓 塞術之預後標記探討 TUMOR BURDEN SCORE AS A NEW PROGNOSTIC MARKER FOR PATIENTS WITH HEPATOCELLULAR CARCINOMA UNDERGOING TRANSARTERIAL CHEMOEMBOLIZATION

廖家毅1 何樹仁2 黃怡翔1 侯明志1 霍德義1 臺北榮民總醫院內科部胃腸肝膽科1 敏盛綜合醫院胃腸肝膽科2

Background: Size and number are major determinants of tumor burden in hepatocellular carcinoma (HCC). Patients with HCC undergoing transarterial chemoembolization (TACE) have variable outcomes due to heterogeneity of tumor burden. Recently, tumor burden score (TBS) was proposed to evaluate the extent of tumor involvement. However, the prognostic accuracy of TBS has not been well evaluated in HCC. Aims: This study aimed to assess the prognostic role of tumor burden score (TBS) in HCC patients undergoing TACE. Methods: A total of 935 treatment-naïve HCC patients receiving TACE were retrospectively analyzed. Multivariate Cox proportional hazards model was used to determine independent prognostic predictors. Results: Tumor burden score tended to increase with increasing size and number of tumors in study patients. The Cox model showed that serum creatinine ≥ 1.2 mg/ dL (hazard ratio[HR]: 1.296, 95% confidence interval [CI]: 1.077–1.559, P = 0.006), serum α-fetoprotein ≥ 400 ng/ dL (HR: 2.245, 95% CI: 1.905–2.645, P < 0.001), vascular invasion (HR: 1.870, 95% CI: 1.520–2.301, P < 0.001), medium TBS (HR: 1.489, 95% CI: 1.206–1.839, P < 0.001) and high TBS (HR: 2.563, 95% CI: 1.823–3.602, P < 0.001), albumin–bilirubin (ALBI) grade 2–3 (HR: 1.521, 95% CI: 1.291–1.792, P < 0.001), and performance status 1 (HR: 1.362, 95% CI: 1.127–1.647, P < 0.001) and status 2 (HR: 1.553, 95% CI: 1.237–1.948, P < 0.001) were associated with increased mortality. Patients with high TBS had poor overall survival in Barcelona Clinic Liver Cancer stage B/C and different ALBI grades. Conclusions: Tumor burden score is a feasible new prognostic surrogate marker of tumor burden in HCC and can well discriminate survival in patients undergoing TACE across different baseline characteristics.

P.022

以 INTERLEUKIN ENHANCER BINDING FACTOR 2 為標靶的 MICRORNAS 調控肝 細胞癌生長的研究 THE STUDY OF INTERLEUKIN ENHANCER BINDING FACTOR 2-TARGETING MICRORNAS IN THE REGULATION OF HEPATOCELLULAR CARCINOMA GROWTH

徐祖岳1 林煊淮1 林榮鈞1 黃信閎2 陳鵬仁1 施宇隆1 張維國1 謝財源1 三軍總醫院內科部胃腸科1 振興醫療財團法人振興醫院內科部胃腸科2

Background: Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte. Interleukin enhancer binding factor 2 (ILF2) plays a role in the development of HCC. Aberrant expressions of microRNAs (miRNAs) are associated with HCC development and progression. Aims: The aim of this study is to investigate the effect of aberrant miRNA expression on ILF2 regulation in HCC. Methods: The potential ILF2-targeting miRNAs are predicted using miRanda (http://www.microrna.org/ microrna/home.do). Quantitative real-time PCR, luciferase reporter assay, Western blotting, and BrdU incorporation assay were performed. Results: ILF2 plays a role in HCC cell proliferation. Of predicted miRNA candidates (miR-122-5p, miR-425-5p, miR-136-5p, miR-7-5p, miR-421 and miR-543), a negative correlation between ILF2 and miR-136-5p expressions was observed in HCC. ILF2 is directly down-regulated by miR-136-5p in HCC cells. In addition, miR-136-5p inhibits HCC cell proliferation. Conclusions: This study indicates that down-regulated miR-136-5p plays a significant regulatory role in ILF2induced HCC cell proliferation. P.023

根治性之早期肝細胞癌的長期預後 - 外科及 非外科處置的比較 LONG TERN OUTCOMES OF EARLY HCC AFTER CURATIVE TREATMENT- COMPARISON BETWEEN SURGICAL AND NON-SURGICAL METHODS

邱瀚緯1 郭明正1 牟聯瑞1 陳祈玲1,2 臺南市立醫院（委託秀傳醫療社團法人經營）1 國立臺灣大學臨床醫學研究所2

Background: We quantified the elusive effects of putative factors on the clinical course of early hepatocellular carcinoma (HCC) after primary surgical or nonsurgical curative treatment. Aims: The aim of our study is to determine if the initial treatment modalities or other clinical factors that could predict recurrence and overall survival rates of early HCC after primary curative treatment. A simple scoring system is also established for HCC outcome predictions. Methods: Patients with newly diagnosed early HCC who received surgical resection (SR) or percutaneous radiofrequency ablation (RFA) with or without transcatheter arterial chemoembolization (TACE) from January 2003 to December 2016 were enrolled. The cumulative overall survival (OS) and disease-free survival (DFS) rates were compared. A polytomous logistic regression was used to estimate factors for early and late recurrence. Independent predictors of OS were identified using Cox proportional hazard regression. Results: One hundred twenty-five patients underwent SR, and 176 patients underwent RFA, of whom 72 were treated with TACE followed by RFA. Neither match analysis based on propensity score nor multiple adjustment regression yielded a significant difference in DFS and OS between the two groups. Multivariate analysis showed high AFP (> 20 ng/mL), and multinodularity significantly increased risk of early recurrence (< 1 year). In contrast, hepatitis B virus, hepatitis C virus and multinodularity were significantly associated with late recurrence (> 1 year). Multivariate Cox regression with recurrent events as time-varying covariates identified older age (HR = 1.55, 95% CI: 1.01–2.36), clinically significant portal hypertension (CSPH) (HR = 1.97, 95% CI:1.26–3.08), early recurrence (HR = 6.62, 95% CI:3.79–11.6) and late recurrence (HR = 3.75, 95% CI:1.99–7.08) as independent risk factors of mortality. A simple risk score showed fair calibration and discrimination in early HCC patients after primary curative treatment.

In the Barcelona Clinic Liver Cancer (BCLC) stage A subgroup, SR significantly improved DFS compared to RFA with or without TACE. Conclusions: Host and tumor factors rather than the initial treatment modalities determine the outcomes of early HCC after primary curative treatment. Statistical models based on recurrence types can predict early HCC prognosis but further external validation is necessary. P.024

利用白蛋白 - 膽紅素等級及簡易白蛋白 - 膽 紅素等級用於預測隱源性肝癌的預後 CRYPTOGENIC HEPATOCELLULAR CARCINOMA: THE PROGNOSTIC ROLE OF ALBUMIN-BILIRUBIN (ALBI) GRADE AND EASY ALBI GRADE

何樹仁1 廖家毅2 蘇建維2 侯明志2 黃怡翔2 霍德義3 敏盛綜合醫院胃腸肝膽科1 臺北榮民總醫院內科部胃腸肝膽科2 臺北榮民總醫院醫學研究部3

Background: The characteristics and prognosis of cryptogenic hepatocellular carcinoma (HCC) remain unclear. The albumin-bilirubin (ALBI) grade and its updated version, easy ALBI (EZ-ALBI) grade, are important prognostic predictors for HCC. Aims: We aimed to investigate long-term survival of patients with cryptogenic HCC and the prognostic role of ALBI and EZ-ALBI grade in these patients. Methods: A prospective cohort of 2,937 HCC patients with viral or cryptogenic etiology were retrospectively analyzed. Multivariate Cox model was used to determine prognostic predictors. Results: Cryptogenic HCC patients were often older and diabetic, had lower serum ɑ-fetoprotein (AFP) level, larger tumor burden, poor performance status, advanced cancer stage, and received non-curative treatments compared with hepatitis B or C-related HCC. Multivariate analysis revealed that age > 65 years (HR: 1.488, 95% CI: 1.1711.893, p<0.001), prolonged INR (HR: 1.502 95% CI: 1.192-1.892, p=0.001), AFP > 20 ng/mL (HR: 1.406, 95% CI: 1.153-1.716, p<0.001), multiple nodules (HR: 1.269, 95% CI: 1.030-1.564, p<0.001), TTV >100 cm3 (HR: 1.443, 95% CI: 1.156-1.802, p<0.001), vascular invasion or distant metastasis (HR: 2.073, 95% CI: 1.650-2.604, p<0.001), performance status 2-4 (HR:1.392, 95% CI: 1.697-1.726, p=0.003), ALBI grade 2 (HR: 1.697, 95% CI: 1.370-2.103, p<0.001) and grade 3 (HR: 2.150, 95% CI: 1.459-3.168 p<0.001), EZ-ALBI grade 2 (HR: 1.709, 95% CI: 1.373-2.129, p<0.001), grade 3 (HR: 2.022, 95% CI: 1.609-2.541, p<0.001), curative treatments (HR: 2.039, 95% CI:1.626-2.588, p<0.001). Significant survival differences were found across ALBI grade and EZ-ALBI grade in cryptogenic HCC and subgroup patients receiving curative or non-curative treatments. The Cancer of Liver Italian Program was the best staging system for cryptogenic HCC.

Conclusions: Patients with cryptogenic HCC have larger tumor burden and advanced cancer stage, associated with decreased survival compared with viral HCC. The ALBI and EZ-ALBI score are robust models to evaluate liver functional reserve for these patients independent of treatment modality. P.025

正常血清胎兒蛋白值的肝細胞癌患者之預後 及其影響因子 THE OUTCOMES AND PROGNOSTIC FACTORS OF PATIENTS WITH HEPATOCELLULAR CARCINOMA AND WITH NORMAL SERUM ALPHA FETOPROTEIN LEVELS

傅家駒1 魏正一1 蘇建維1,2 黃怡翔1,2,3 趙毅2,4 吳肇卿3 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學醫學院醫學系內科部2 國立陽明交通大學醫學院臨床醫學研究所3 臺北榮民總醫院腫瘤醫學部4

Background: Alpha fetoprotein (AFP) is the most widely used tumor marker for hepatocellular carcinoma (HCC). Serum AFP level higher than 20ng/ml is considered abnormal according to the current guidelines. However, more and more patients are diagnosed of HCC with normal serum AFP levels due to the advance of image modalities and the prevalence of health check-up. Nevertheless, few studies investigated the prognostic factors of HCC patients with normal serum AFP levels. Aims: This study aimed to investigate the outcomes and the prognostic factors in patients with HCC and with normal serum AFP levels (AFP ≤20 ng/mL). Methods: We retrospectively enrolled in 2,198 patients with HCC and normal serum AFP levels from 2008 to 2020. We divided the patients into 2 groups, low-normal group (AFP < 7 ng/mL) and high-normal group (AFP between 7 and 20 ng/mL). Overall survival rates were calculated by the Kaplan-Meier method and analysis of the prognostic factors were performed by the Cox proportional hazard model. Results: Among the enrolled patients, 1,385 (63%) patients were in the low-normal group and 813 (37%) patients were within the high-normal group, respectively. Female patients and chronic hepatitis C virus (HCV) infection were more prevalent in the high-normal group. Besides, patients in the high-normal group had low rate of albumin-bilirubin (ALBI) grade 1, higher serum alanine aminotransferase levels, lower platelet counts, multiple tumors compared to those in the low-normal group. After a median follow-up for 32.4 (interquartile range 13.8-62.1) months, 942 patients died, with a 5-year overall survival rate of 54.4%. The 5-year overall survival rates were 57.4% and 49.8% in the low-normal group and in the highnormal group, respectively (p=0.001). In the multivariate

analysis, the independent prognostic factors of poor overall survival were ALBI grade 2 (hazard ratio HR: 1.614, 95% confidence interval CI: 1.242-2.097, HR: 2.261, 95% CI: 1.661-3.076), ALBI grade 3 (HR: 3.875, 95% CI: 2.9875.025, HR: 2.746, 95% CI: 1.713-4.403), presence of vascular invasion (HR: 2.579, 95% CI: 1.913-3.476, HR: 2.728, 95% CI: 1.873-3.972), tumor size≧5cm (HR: 1.552, 95% CI: 1.214-1.984, HR: 1.895, 95% CI: 1.418-2.531) and non-curative treatment modalities (HR: 3.875, 95% CI: 2.957-5.025, HR: 2.315, 95% CI: 1.731-3.097). Serum AFP levels were not associated with overall survival by the multivariate analysis. Conclusions: Liver functional reserve, tumor size, vascular invasion, and treatment modalities, but not serum AFP levels, determined the outcomes of patients with normal serum AFP levels. P.026

以射頻燒灼術合併 NIVOLUMAB 治療肝癌 之免疫監測 IMMUNE PROFILE FOR HEPATOCELLULAR CARCINOMA AFTER SEQUENTIAL TREATMENT OF RADIOFREQUENCY ABLATION WITH NIVOLUMAB

方華珍1 鄭勝偉1 薛聖潔1 吳明順1 張智翔1 粟發滿1 連吉時1 臺北市立萬芳醫院- 委託財團法人臺北醫學大學消化內

科1

Background: Hepatocellular carcinoma (HCC) is currently estimated to be the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide, accounting for 841,000 new cases and 782,000 deaths annually.The treatment with radiofrequency ablation (RFA) has been established as the standard ablative therapy for early HCC, and is currently recognized as the main ablative tool for HCC tumors < 5 cm in size; however, progression and local recurrence remain the main disadvantages of this approach. Nivolumab, an antiPD 1 agent, combined with RFA can induce synergistic anticancer effect in pre-clinical studies, which seems promising through the abscopal effect. Aims: We aimed to evaluate the immune profile for HCC after sequential treatment of RFA with nivolumab. Methods: Supported by the Immune Monitoring Core at Taipei Medical University, a high-parameter flow cytometric analysis is used to assay the immunophenotypes in purified peripheral mononuclear cells. The cells were immunoblocked (Human BD Fc Block™) and immunohybridized with multiple fluorochrome-labeled specific antibodies against cell surface immune markers. Then the cells were analyzed by three-color flow cytometry (Attune™ Nxt, Life Technologies, Carlsbad, CA). Results: RFA monotherapy decreases Th1 and most of Tc and NKT.RFA/Nivolumab sequential therapy increases Th lineage, Tc, and NK/NKT cells Conclusions: Immune panel has a potential value to predict the therapeutic outcome of RFA with Immunotherapy.NKT cells may play a role to evaluate the abscopal effect of combination therapy.

P.027

肺腫瘤併肝轉移之病患接受經皮燒灼術：醫 學中心的五年經驗分析 PERCUTANEOUS ABLATION FOR PATIENTS WITH LUNG CANCER LIVER METASTASES: FIVE-YEAR EXPERIENCE AT A MEDICAL CENTER

康家健1 王蒼恩1, 2, 3 王勝永1, 2, 3 陳彥伯1, 2, 3 陳席軒1, 2, 3 黃詩婷1 劉家源1, 2, 3 陳銘仁1, 2, 3 王鴻源1, 2, 3 張經緯1, 2, 3 馬偕紀念醫院胃腸肝膽內科1 馬偕醫護管理專科學校2 馬偕醫學院3

Background: Radiofrequency thermal ablation (RFA) is widely used for hepatocellular carcinoma (HCC) and is gradually used for local control of liver metastasis. Previous studies had found the benefits of RFA for the survival advantages for colon cancer liver metastasis. However, the benefit of RFA for lung cancer liver metastasis remains unclear. Aims: The purpose of this study was to evaluate the effectiveness and safety of RFA for patients with lung cancer liver metastasis. Methods: The medical records of patients with non-HCC who underwent ablation from 2017 to 2021 in the MacKay Memorial Hospital were reviewed retrospectively. Patients with liver metastasis were enrolled respectively. The treatment outcomes and safety of RFA for patients with lung cancer liver metastasis were evaluated. Results: A total of 40 patients who underwent RFA for liver metastasis were enrolled. The mean age of the patients at the time of diagnosis was 60.59±11.5 years. The sex ratio (male to female) was 1:1.17. The proportion of patients positive for HCV Ab and HBsAg were 0% and 12.5%, respectively. The major primary cancer sites of liver metastasis were breast (7.5%, n=3), esophagus (10%, n=4), colon (32.5%, n=13), and lung (30%, n=12). The major cancer types were adenocarcinoma (55%, n=22) and squamous cell carcinoma (15%, n=6). The total tumor number, total tumor size and maximal tumor size per patient for ablation were 1.82±1.17, 39.65±26.54 mm, and 26.68±15.78 mm, respectively. Furthermore, the survival time during follow-up was 14.78±11 (1-40) months. The ablationrelated major complication rate of tumor seeding and liver abscess were 2.5% (n=1) and 2.5% (n=1), respectively. A total of 12 and 12 patients with colon cancer and lung cancer liver metastasis underwent RFA. The mean age of the patient was 59.41±8.4 and 66.33±9.83, respectively. The total size of liver metastasis was 46.5±34.27mm and 36.12±24.34mm. The 1st local recurrence time was 3.75±1.71 and 8.57±8.94 months. Furthermore, the survival time after ablation during follow-up was 12.58±7.22 months and 16.83±13.45 months. The overall survival after ablation between colon cancer and lung cancer with liver metastasis showed no statistical significance. No ablationrelated major complication nor RFA-related mortality was found in these two groups. Conclusions: Like colon cancer liver metastasis, RFA is safe and successful for patients with lung cancer liver metastasis. The survival benefit after ablation needs more patient data collection for further analysis.

P.028

非 B,C 型肝炎早期肝癌患者代謝性疾病風 險之增加 METABOLIC RISKS ARE INCREASING IN NON-B NON-C EARLY-STAGE HEPATOCELLULAR CARCINOMA: A 10YEAR FOLLOW-UP STUDY

黃國烜1 王植熙2 劉約維2 楊志權2 蔡明釗1 高雄長庚紀念醫院肝膽腸胃科1 高雄長庚紀念醫院一般外科2

Background: Non-B, non-C hepatocellular carcinoma (NBNC-HCC) may be related to metabolic syndrome, and the incidence of this tumor type is increasing annually. The definition of metabolic-associated fatty liver disease (MAFLD) proposed in 2020 may help to more accurately assess the association between metabolic syndrome and NBNC-HCC. However, this new concept has not yet been applied in NBNC-HCC research. Aims: This study aimed to compare the clinicopathological characteristics of patients with NBNC-HCC and CHBHCC diagnosed between 2009-13 and 2014-18, focusing on metabolic risk factors and the new concept of MAFLD. Methods: Patients with BCLC-0/A-HCC who received curative hepatectomy between January 2009 and December 2018 were retrospectively assessed; the associations between clinicopathological characteristics and clinical outcomes of NBNC-HCC and CHB-HCC were analyzed by multivariate analysis. Results: Compared to patients diagnosed in 2009-13, the frequency of metabolic disorders in NBNC-HCC was significantly higher in 2014-18 [DM (p=0.049), HTN (p=0.004), BMI (p=0.017) and MAFLD (p=0.003)]; there was no significant change in patients with CHB-HCC. Moreover, CHB-HCC was an independent risk factor for HCC recurrence (HR, 1.339; 95% CI, 1.010-1.775, p=0.043) and death (HR, 1.700; 95% CI, 1.017-2.842, p=0.043) compared to NBNC-HCC. Conclusions: The risk of MAFLD, obesity, DM, and hypertension in patients with NBNC early-stage HCC have significantly increased in recent years, thus metabolic syndrome should be monitored in this special population. Moreover, NBNC-HCC tend to had a better prognosis than CHB-HCC, probably due to their distinct clinicopathological features. P.029

合併肝動脈化療及碘油栓塞治療肝癌合併主 門脈侵犯之新方法的療效 A NEW REGIMEN OF COMBINING HEPATIC ARTERIAL INFUSION CHEMOTHERAPY AND LIPIODOL EMBOLIZATION IN THE TREATMENT OF HEPATOCELLULAR CARCINOMA WITH MAIN PORTAL VEIN INVASION

陳順益1 蔡維倫1 李明峰1 江佳陵1 陳文誌1 梁慧隆1 高雄榮民總醫院1

Background: The prognosis of hepatocellular carcinoma (HCC) patients with vascular invasion is poor, especially of patients with main portal vein invasion (Vp4). Hepatic artery infusion chemotherapy (HAIC) has been found to be more effective than sorafenib for advanced HCC. In this retrospective study, Aims: To investigate t the therapeutic outcomes by adopting our new HAIC regimen in treating Vp4 HCC patients. Methods: 71 patients (60 male vs 11 female, 34 - 81 years old) received a new regimen of combining HAIC with cisplatin, 5-FU and mitomycin followed by lipiodol embolization therapy between 2002 and 2018. Twenty-two patients (31.0%) also received oral sorafenib. 47 patients (66.2%) had had hepatitis B infection. 56 patients (78.9%) had Child-Pugh A liver function. The mean maximal tumor size was 10.3 cm. 21 patients (29.6%) had extra-hepatic metastasis at their initial diagnosis. Results: The mean follow-up time was 22.9±29.2 months. The objective response rate (ORR) and median overall survival (OS) were 64.8% and 13 months of the 71 Vp4 patients. Median OS was 17 months for responders and 6 months for non-responders, 14 months for Child-Pugh A patients and 6 months for Child-Pugh B patients. The 1-, 2- and 3-year survival rates were 53.1%, 21.5% and 18.7% respectively. In the sub-group analysis, the ORR and median OS were 67.3%/13 months and 59.1%/13 months for patients with HAIC only and HAIC plus sorafenib. Conclusions: Our HAIC new regimen is effective in treating Vp4 HCC patients and may be adopted as the firstline therapy, especially in HBV-predominant regions of the world, where sorafenib has been shown to be less effective.

P.030

肝動脈化療對肝動栓塞治療無反應之肝癌病 患的療效 HEPATIC ARTERIAL INFUSION CHEMOTHERAPY FOR HEPATOCELLULAR CARCINOMA NONRESPONSIVE TO TRANSARTERIAL EMBOLIZATION

熊健亞1 蔡維倫2 陳文誌3 孫煒智3 江佳陵4 梁慧隆4 高雄榮民總醫院內科部1 高雄榮民總醫院一般內科2 高雄榮民總醫院腸胃科3 高雄榮民總醫院放射科4

Background: Hepatocellular carcinoma (HCC) ranks the 2nd cause of cancer death in Taiwan. TACE/TAE is usually suggested as a treatment option in patients with unresectable HCC. However, the response rate of TAE is not high and the effective treatment for HCC patients nonresponsive to TAE is controversial. Aims: To investigate the efficacy of Hepatic arterial infusion chemotherapy (HAIC) for HCC non-responsive to TAE. Methods: From 2004 to 2020, we retrospectively reviewed the data of patients with HCC non-responsive to TAE and treated with HAIC. The baseline characteristics and clinical outcomes were evaluated. Results: Total 90 patients including 68 males and 22 females were enrolled in this study. Forty-one (45.6%) patients had HBV infection and forty (44.4%) patients had HCV infection. Eighty-two (91.1%) patients had cirrhosis. 69 (76.7%) patients had Child ‘A and 12 (13.3%) patients had Child’s B liver reserve. The ALBI grade was 13.5 / 82.0 / 4.5% for grade I/II/III respectively. Twenty-four (26.7%) patients had portal vein invasion and 8 (8.9%) patients had extrahepatic metastasis. The mean numbers of TAE sessions prior to HAIC were 3.5. All patients received mean 2.3 courses of HAIC, and none of them had immediate major complications. The overall 3-, 6-, 9-, 12-month survival rates were78.9%, 58.9%, 36.7%, and 28.9%. The median overall survival time was 10.2 months. The response rate was 8.9% and patients who had response had better survival (borderline significance, P=0.079). Coxregression multi-variate analysis identified PV invasion as an independent factor associated with mortality (P=0.067). Conclusions: HAIC may be an effective treatment option in HCC non-responsive to TAE. P.031

在接受二線全身性化學治療的肝癌病患，合 併局部治療可以提供病人較好的生存表現 COMBINING LOCOREGIONAL THERAPY PROVIDES BETTER SURVIVAL IN HEPATOCELLULAR CARCINOMA PATIENTS RECEIVING 2ND LINE SYSTEMIC REGIMEN

徐毓均1,3 高毓婷1,3 林伯庭2,3 滕威2,3 謝彝中2,3 陳威廷2,3 林成俊2,3 林俊彥2,3 林錫銘2,3 林口長庚紀念醫院內科部1 林口長庚紀念醫院肝膽腸胃科2 長庚大學醫學系3

Background: Locoregional therapy (LRT) has been widely used not in intermediate but also in advanced stage HCC patients. It can not only directly destroy tumor cells but also can alter the tumor microenvironment which might augment the systemic treatment effect. Aims: This study aims to investigate the beneficial effect combing LRT with 2nd line systemic treatment. Methods: From 2015 to 2020, HCC patients receiving regorafenib or immune checkpoint inhibitors (ICI) after sorafenib in Chang Gung Memorial Hospital were recruited. Combing treatment with LRT (including radiofrequency or transarterial chemoembolization) or not was documented. The predictors of survival and outcome were analyzed between groups. Results: A total of 89 patients receiving 2nd line systemic treatment was recruited (regorafenib (n=58) and ICI (n=31). The median age was 63 years old, and 80.9% were male. There were 19 patients combing LRT during the systemic treatment (regorafenib=14 and ICI=5). In multivariate Cox regression analysis, combing LRT (adjusted HR 0.33, P=0.02), and patients with macrovascular invasion (adjusted HR 2.12, P=0.04) were independent predictive factors for mortality. On the other hand, different treatment regimen with regorafenib or ICI after sorafenib showed no significant difference for mortality (adjusted HR 0.61, P=0.17) with comparable treatment response (Disease control rate: regorafenib 72.4 % vs. ICI 67.7 %, P=0.828) and survival outcome (Progression-free survival: regorafenib 3.0 months vs. ICI 2.6 months, P= 0.64). Moreover, combining LRT with 2nd systemic treatment showed better survival outcome (OS not reach vs. 9.8 months P=0.011, and PFS 7.0 vs. 2.5 months, P=0.065) than patients without combining LRT. Conclusions: The treatment efficacy and survival outcome were comparable between regorafenib and ICI after sorafenib treatment. Furthermore, combining LRT with systemic treatment provides better survival outcome in patients with 2nd line systemic treatment.

P.032

DELTA- 新冠病毒屏東報告 THE CLINICAL CHARACTERISTICS AND THERAPEUTIC EFFICACY OF THE DELTA CORONAVIRUS VARIANT IN PINGTUNG, TAIWAN

張庭遠1 余明隆1 高雄醫學大學附設醫院肝膽胰內科1

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first found in China in December 2019, has caused the coronavirus disease 2019 (COVID-19) pandemic. In recent months, the Delta variant of SARS-CoV-2 was globally rampant and was transmitted to Southern Taiwan in June 2021. Aims: In this study, we aimed to elucidate the clinical characteristics of the Delta-variant SARS-CoV-2 infection and the treatment efficacy of antiviral agents in patients from Pingtung County in Southern Taiwan. Methods: A total of 11 patients with Delta-variant COVID-19 were consecutively admitted to a governmental hospital in June 2021. Baseline characteristics and therapeutic efficacy were evaluated. Results: In total, 54.5% patients were asymptomatic. Among symptomatic patients, the most common symptoms were fever and cough (36.4%), followed by headache (9.1%). Two patients developed pneumonia without mechanical ventilation requirement. Compared to patients without pneumonia, those with pneumonia had higher aspartate aminotransferase (AST) (21.0 vs. 126.0 IU/L, P = 0.03), lactate dehydrogenase (LDH) (143.1 vs. 409.0 IU/ mL, P = 0.03), and ferritin (0.2 vs. 2.0 mg/L, P = 0.046) levels and fibrosis index 4 (FIB-4) ≥3.25 (0% vs. 100%, P = 0.02). Pneumonia improved after 2-week treatment, and no mortality occurred after 30 days of diagnosis. Conclusions: We demonstrated the clinical characteristics of Delta-variant COVID-19 and therapeutic efficacy of antiviral agents. The risk factors attributed to pneumonia were higher serum AST, ferritin, and LDH levels and FIB-4 values. P.033

介入性對比劑諧波內視鏡超音波在肝臟疾病 的應用 APPLICATION OF INTERVENTIONAL CONTRAST ENHANCED HARMONIC ENDOSCOPIC ULTRASONOGRAPHY FOR LIVER LESIONS

蔡佩姍1 陳建華1,2 蘇偉志1 蕭宗賢1 徐榮源1,2 趙有誠1,2 臺北慈濟醫院, 佛教慈濟醫療財團法人1 慈濟大學醫學院2

Background: Ultrasound contrast agent is used in the clinic practice for a period of time. Sonazoid® is a secondgeneration ultrasound contrast agent that has excellent stability and resistance to ultrasound destruction and can stably exert a good contrast effect for a prolonged period. Contrast enhanced hormonic endoscopic ultrasonography (CEH-EUS) is useful for the evaluation of liver disease because it permits the observation of the hemodynamics of masses in real time and the subsequent interventional purpose. Aims: To investigate the safety and effectiveness of CEHEUS for histological differentiation of liver tumors and the subsequent appropriate treatment. Methods: A total of 22 consecutive patients are enrolled from 2019-07-01 to 2021-11-30. CEH-EUS was performed for these patients having hepatic lesions. The used echoendoscope is the linear array puncture scope UCT-260, product of Olympus Co., Tokyo, Japan. Sonazoid agent is given according to the patient’s body weight with dosage of 0.015 ml/kg. Contrast enhanced character was classified into two phases, the vascular phase and perfusion phase. The former includes two enhancement patterns (hypo- or iso-enhancement & hyper-enhancement) and the latter is divided into two patterns, homogeneous and heterogeneous. Correlation between vascular patterns and histopathology of biopsy or clinical course was ascertained. Results: The final diagnoses of 22 examined tumors/ lesions were hepatocellular carcinoma (HCC) (n = 7), cholangiocellular carcinoma (CCC) (n =1), dysplastic nodule (n =1), steatosis and large cell change (n =1), lung cancer with liver metastasis (n = 2), pancreatic cancer with liver metastasis (n = 2), ethanol injection at left lobe and caudate lobe of HCC (n = 4) and aspiration of left lobe / caudate lobe abscess (n = 4). In early phase images, all malignancies reveal early enhancement. In late-phase images, 7 of 8 suspected HCCs had the late washout and heterogeneous perfusion pattern; however, the four hepatic metastatic lesions reveal early enhancement and early washout pattern. The liver abscess showed no enhancement at all. Conclusions: CEH-EUS could be useful for targeting tumor biopsy and for distinguishing tumor from other lesions.

P.034

雞肝水解物藉由減少肝纖維化改善肝硬化大 鼠門脈高壓 CHICKEN LIVER HYDROLYSATES AMELIORATED PORTAL HYPERTENSION VIA SUPPRESSION OF LIVER FIBROSIS IN CIRRHOTIC RATS

許劭榮1, 2 黃惠君1, 2, 3 李發耀1, 2 黃怡翔1, 2 侯明志1, 2 國立陽明交通大學醫學院1 臺北榮民總醫院胃腸肝膽科2 臺北榮民總醫院一般內科3

Background: Liver cirrhosis induces portal hypertension and lethal complications. Chicken liver hydrolysates (CLHs) have abundant of hydrophobic amino acids, taurine and carnosine/anserine. Previous reports showed CLHs effectively alleviated oxidative stress in the liver. However, the effects of CLHs in liver cirrhosis were never surveyed. Aims: This study aimed to evaluate the impact of CLHs on liver cirrhosis and portal hypertension. Methods: Male Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as control. The rats then randomly allocated into CLHs or vehicle treated groups. Experiments were performed four weeks after operation. Results: CLHs significantly attenuated portal pressure in cirrhotic rats (14.5% reduction, P=.004). Further analysis showed that hepatic vascular resistance decreased in CLHs group (P=.013). There was no significant change in systemic circulation or splanchnic inflow. Liver fibrosis severity and collagen1αI protein expression in the liver significantly decreased consistently (P=.001; .013, respectively). The antioxidants superoxide dismutase and catalase increased markedly in the liver of CLHs group while there were trends toward increase in glutathione, glutathione peroxidase and trolox equivalent antioxidant capacity. Plasma IL-1β and TNFα decreased in CLHs treated cirrhotic rats. Conclusions: CLHs significantly attenuated portal hypertension though inhibiting liver fibrosis. This was due to amelioration of hepatic oxidative stress and systemic inflammation. P.035

急性環境溫度變化通過 α- 接受器路徑在肝 硬化或門脈高壓大鼠上引發短暫門脈壓力增 加 ACUTE REDUCTION OF ENVIRONMENTAL TEMPERATURE INDUCED TRANSIENT PORTAL PRESSURE SURGE VIA Α-RECEPTORMEDIATED PATHWAY IN CIRRHOTIC OR PORTAL HYPERTENSIVE RATS

潘俊傑1 ,2 許劭榮1 ,2 黃惠君1 ,2 ,3 李發耀1 ,2 黃怡翔1 ,2 侯明志1 ,2 臺北榮民總醫院肝膽胃腸科1 國立陽明交通大學醫學系2 臺北榮民總醫院一般內科3

Background: Portal hypertension leads to lethal complications such as gastroesophageal varices bleeding. The complications correlate significantly with portal pressure and it had been noticed that the incidence rate of variceal bleeding is higher in cold days. Aims: This study aimed to evaluate the impact of temperature change on portal hypertension. Furthermore, to find out a possible prevention strategy through mechanism survey. Methods: Liver cirrhosis was induced in male SpraqueDawley rats, 4 weeks after bile duct ligation (BDL). Portal hypertension was induced by partial portal vein ligation (PVL). The direct effects of temperature change on vasoresponsiveness were evaluated by in situ perfusion for hepatic, splanchnic or collateral system. In acute series, half of the body surface area of the anesthetized rats immersed in the temperature-controlled water and allowed the environmental temperature to be changed within 30 seconds. In chronic series, rats were subjected to temperature-controlled room for 30 minutes, twice a day for 4 weeks. Results: Acute cooling from 25 ℃ to 15 ℃ or 5 ℃ increased the portal pressure by 10.6 or 15.5%, respectively. The transient portal pressure surge started 30 seconds after temperature change and normalized within 5 minutes (figure 1). The heart rate, mean arterial pressure, systemic vascular resistance and splanchnic flow increased significantly at the same time. Acute heating to 37 ℃ did not affect hemodynamics. Chronic temperature change did not affect hemodynamics, either. Phentolamine (α blocker) but not propranolol (non-selective β-blocker) dose dependently inhibited transient portal pressure

surge related to environmental temperature reduction. Experiments in PVL rats showed consistent results. Protein kinase C activity of femoral artery increased in temperature reduction group, which was reduced by phentolamine. Conclusions: Acute temperature reduction induced peripheral vasoconstriction via activation of α adrenergic receptors. The redistribution of blood flow to splanchnic system led to transient portal hypertension surge. It is worth noting that β receptor blocker exerted no obvious effect. The α adrenergic receptor may play a role in the mechanism and can be considered the therapeutic target in cirrhotic patients with gastroesophageal variceal hemorrhage subjected to acute environmental temperature reduction. P.036

肝內微型核糖核酸在活體肝移植後急性黃膽 的肝臟病理調控 HEPATIC MICRO-RNAS REGULATION IN ACUTE JAUNDICE ASSOCIATED WITH LIVER GRAFT PATHOLOGY AFTER LIVING DONOR LIVER TRANSPLANTATION

林淑賢1,2 王植熙2,3 陳肇隆2,3 林志哲2,3 趙景華1,2 高雄長庚紀念醫院胃腸肝膽科1 高雄長庚紀念醫院肝臟移植中心2 高雄長庚紀念醫院一般外科3

Background: Acute jaundice remains critical problems following liver transplantation (LT). MicroRNAs (miRNAs) play a role in regulating the genes related to allograft rejection and immune tolerance. Aims: We aimed to distinguish conditions which might lead to post-LT graft injury and cholestasis and identified hepatic miRNAs expression levels in correlation with liver graft pathology. Methods: A total of 80 recipients undergoing post-LT graft biopsy for the evaluation of acute jaundice were enrolled in this one-year prospective study. By microarray analysis and quantitative real-time RT-PCR confirmation, we identified hepatic miRNAs (miRNA-122, miRNA-301, miRNA-133a, and miRNA-21) differently expressed in variants allograft pathology and the correlation between these expression levels and clinical serum parameters. Results: Pathologic findings of total 80 recipients with acute jaundice after LT were acute cholangitis (AC) in 37 (46%), acute rejection (AR) in 20 (25%), recurrent hepatitis (RH) in 12 (15%), no specific pathological change (NSPC) in 6 (8%) and fatty change (FC) in 5 (6%). In our study, of all these tested hepatic miRNAs expression had no statistical correlation with serum parameters, including neutrophil-lymphocyte ratio (NLR). In AC, hepatic miRNA-122, miRNA-301, miRNA-133a and miRNA-21 were all significantly low expressed (p < 0.05). In contrast, miRNA-122 was highly expressed in cases of AR and RH (p < 0.05). At the meanwhile, miRNA-301 and miRNA-21 were significantly higher expressed in case of RH than those of AC (p < 0.05). Finally, miRNA-133a was significantly higher expressed in case of FC than those of AR (p < 0.05). Conclusions: Our study indicated that specific hepatic miRNAs regulation were related to pathogenesis of allograft injury. The variant expression levels of different hepatic miRNAs as a check list could help to discriminate the diagnosis of acute jaundice following liver transplantation.

P.037

冬凌草素減輕小鼠酒精性肝臟損傷 ORIDONIN ATTENUATES ALCOHOLINDUCED LIVER INJURY IN MICE

顏聖烈1 殷媚晶2, 3 彰濱秀傳紀念醫院肝膽腸胃科1 亞洲大學食品營養與保健生技學系2 中國醫藥大學附設醫院醫學研究部3

Background: Oridonin (Ori) is a diterpenoid naturally present in medicinal plants with a potential as an antioxidant agent. Aims: This study aimed to evaluate the hepatic antioxidative, anti-glycative and anti-inflammatory properties of Ori at 0.125 and 0.25% against chronic ethanol intake in mice. Methods: Mice were divided into five groups: i) normal diet group, ii) Ori group, iii) ethanol diet (Lieber- DeCarli liquid diet with ethanol) group, iv) ethanol diet plus 0.125% Ori and v) ethanol diet plus 0.25% Ori. After 8 weeks of Ori supplementation, blood and liver tissue were used for analyses. Results: Ethanol increased the production of reactive oxygen species and nitric oxide, decreased glutathione content, and lowered the activity of glutathione peroxide, glutathione reductase and catalase. Ethanol suppressed the hepatic mRNA expression of nuclear factor E2-related factor 2. Ori supplements reversed these changes. Ethanol increased hepatic Ne-(carboxyethymethyl)-lysine (CML) and pentosidine levels, and enhanced aldose reductase (AR) activity and mRNA expression. Ori supplements at only 0.25% decreased CML and pentosidine levels, and lowered the AR activity as well as its mRNA expression. Ethanol increased the hepatic release of tumor necrosis factor-alpha, transforming growth factor-beta1, interleukin (IL)-1beta and IL-6. Histological data showed that ethanol induced necrosis and inflammatory cell infiltration, while Ori supplements alleviated these inflammatory responses. Ethanol up-regulated the hepatic mRNA expression of nuclear factor kappa B, myeloperoxidase and p38. Ori supplements reversed these changes. Conclusions: These novel findings suggest that Ori could be used as a potent agent against alcohol-induced hepatotoxicity. P.038

內視鏡超音波指引下細針穿刺抽吸術與細針 穿刺切片術針對肝臟局部病灶組織取樣之比 較 COMPARISON OF ENDOSCOPIC ULTRASOUND-GUIDED FINE-NEEDLE BIOPSY VERSUS FINE-NEEDLE ASPIRATION FOR FOCAL LIVER LESIONS

林榮鈞1 林煊淮1 陳鵬仁1 黃天祐1 張維國1 謝財源1 國防醫學院三軍總醫院內科部胃腸科1

Background: Endoscopic ultrasound (EUS)-guided tissue acquisition is increasingly being performed to diagnose focal liver lesions. Both EUS-guided fine-needle aspiration (EUS-FNA) and EUS-guided fine needle biopsy (EUSFNB) have been widely performed. However, no studies have compared these two tissue acquisition methods. Aims: The aim of this study was to compare the specimen adequacy and diagnostic yield rate between EUS-FNA and EUS-FNB. Methods: A retrospective study was conducted using medical records for patients who underwent a EUS-guided tissue acquisition for liver tumor(s) from 2019 to 2021. The cases were classified into two groups for comparison: a EUS-FNA group and a EUS-FNB group. Results: The mean age was 65.25 years in the EUS-FNA group and 67.83 years in the EUS-FNB group with most patients being female. Diagnostic adequacy was 100% in EUS-FNA and 100% in the EUS-FNB group, whereas diagnostic accuracy was 88.9% in the EUS-FNA group and 100% in the EUS-FNB group (p = 1.000). No evidence of adverse events was observed in any of the study groups. Conclusions: Both EUS-FNA and EUS-FNB of focal liver lesions are safe, provide a very high diagnostic accuracy, and could be considered as an alternative method for liver biopsy.

P.039

腹腔透析液對下腔靜脈直徑和塌陷度測量的 影響 INFLUENCE OF INTRA-ABDOMINAL DIALYSATE ON THE MEASUREMENT OF INFERIOR VENA CAVA DIAMETER AND COLLAPSIBILITY

陳鄭弘堯1 高銘聰2 賴建賓2 高清添2 陳虹如3 楊雅蕙3 高玉貞3 澄清醫院中港分院胃腸科1 澄清醫院中港分院腎臟科2 澄清醫院中港分院腹膜透析室3

Background: The influence of intra-abdominal fluid on inferior vena cava (IVC) size is not well studied. Aims: To study the effect of intra-abdominal fluid on IVC diameter, we assessed the IVC size measured by ultrasound before and after draining out dialysate during one exchange of dialysate in day time. Methods: Seventeen patients undergoing continuous ambulatory peritoneal dialysis (CAPD) aged from 31 to 81 years were enrolled in the study. The anteroposterior IVC diameter was measured 2.0 cm below the diaphragm in the hepatic segment in supine position during normal respiration. Collapsibility index (CI) was calculated by (IVCe [expiration] diameter − IVCi [inspiration] diameter)/ IVCe diameter × 100 %. Three phases of US scanning were performed during one exchange in daytime. Phase I, before dialysate drain out, Phase II, after dialysate drain out, Phase III after dialysate refill in abdomen. The measurement of IVC diameter with B-mode & M-mode using a 4-Mhz curvilinear ultrasound probe. Results: Seventeen CAPD patients (mean age 59.5±11.7 years, male 11, female 6) were evaluated in an outpatient dialysis unit. The mean drained-out volume was 1921±377 ml; the mean filled-in dialysate volume was 1712±359 ml. The net drained-out volume was 209 ± 106 ml. Following dialysate drain, mean IVCe increased from 1.21±0.59 cm to 1.62±0.53 cm (p<0.005), mean ICVi increased from 0.95±0.58 to 1.04±0.55 cm(P 0.241). The mean CI increased from 28.9 ± 16.9% to 41.6 ± 20.4% (p<0.05). Following dialysate refill in mean IVCe decreased from 1.62±0.53 cm to 1.25±0.53 cm (p<0.005), mean IVCi decreased from 0.99±0.57 cm to 0.90±0.57 cm (p 0.272). The mean CI decreased from 41.6±20.4 % to 30.5±24.6 % (p<0.05). Conclusions: Drained-out and refill-in intra-abdominal dialysate did significantly alter IVCe or CI measurements, no significantly alter in IVCi. Performing ultrasound measurements of the IVCe and CI with intra-abdominal fluid is likely to produce clinically meaningful changes. This may be due to decreased intra-abdominal pressure and decompression of the IVC by relief of intra-abdominal fluid.

P.040

肌少症在肝硬化患者的相關因素及其對生活 質量的影響：一個南台灣前瞻性研究 THE ASSOCIATION FACTORS OF SARCOPENIA AND ITS IMPACT ON THE QUALITY OF LIFE IN PATIENTS WITH LIVER CIRRHOSIS: A PROSPECTIVE STUDY IN SOUTHERN TAIWAN

葉文碩1 陳怡莉2 紀廣明1 盧勝男1 陳建宏1 胡琮輝1 洪肇宏1 張國欽1 顏毅豪1 郭垣宏1 王景弘1 高雄長庚紀念醫院內科部胃腸肝膽科系1 高雄長庚紀念醫院內科部2

Background: Sarcopenia is a geriatric syndrome that is associated with the decline of skeletal muscle mass and muscle strength. Sarcopenia might have an impact on the outcome of patients with chronic liver disease, liver cirrhosis Aims: We aimed to explore the association factors of sarcopenia and its impact on patients with liver cirrhosis in southern Taiwan. Methods: Patients with liver cirrhosis, age> 50 years old were enrolled in this study. Patients with unconsciousness, can not do dual-energy x-ray absorptiometry (DXA), can not walk, decompensated liver cirrhosis, HCC history were excluded. DXA, 6-meter gait speed, handgrip strength exams were measured at the beginning of the study. WHO Quality of Life-BREF Questionnaire was evaluated to measure the score of quality of life. Associated laboratory data (Child-Pugh score, FIB-4, ALBI, Vit. D level) were evaluated at the clinics. The definition of possible sarcopenia was decreased gait speed or handgrip strength. The definition of sarcopenia was low appendicular skeletal muscle mass index plus decreased gait speed and/or handgrip strength. Results: A total of 185 patients(male/female: 87/98, age: 63.9±7.5 years) were enrolled in this study. During the primary screening, 140 patients (75.7%) had possible sarcopenia. Female (52.9% vs 28.9%, p=0.005), elder (64.9±7.4 vs 60.8±7.2, p=0.002), higher level of Liver stiffness by FibroScan (21.90±12.13 vs 16.91±8.76, p-=0.016), poor renal function (CKD stage≥ 3, 25% vs 11.1%, p=0.049) and poor quality of life (WHOQOL-BREF score: 53.54±6.20 vs 55.89±5.07, p=0.022) were found in possible sarcopenia group when comparing with non-possible sarcopenia group. After the DXA exam, 51 patients (27.6%) were diagnosed with sarcopenia. Elder (67.0.7±7.0 vs 62.7±7.4, p<0.001), lower BMI (22.84±2.36 vs 27.57±4.08, p<0.001), higher ratio of hypertension (54.9% vs 38.1%, p=0.039), poor renal function (CKD stage≥ 3, 33.3% vs 17.2%, p=0.017), lower ratio of central obesity (47.1% vs 79.1%) and lower platelet level (115.5±51.6 vs 135.1±50.2, p=0.020) were found in sarcopenia group than non-sarcopenia group. The quality of life and vitamin D level did not relate to sarcopenia in patients with cirrhosis. Conclusions: The association factors of possible sarcopenia and sarcopenia on patients with liver cirrhosis were demonstrated in this study. Further clinical outcomes would be followed up in the future.

第二部分：消化道及膽胰疾病

P.041

內視鏡超音波細針穿刺於類肉瘤病的應用 ENDOSCOPIC ULTRASOUND FINE NEEDLE ASPIRATION (EUS-FNA) IN SARCOIDOSIS

林連福1 黃彼得1 葉宏仁1 肝膽腸胃科, 內科部, 童綜合醫院1

Background: The diagnosis of sarcoidosis relies on clinical and radiological presentation, evidence of non-caseating granulomas in histopathology and exclusion of alternative causes of granulomatous inflammation. [J. Clin. Med. 2019, 8, 1327] Sarcoidosis may involve virtually every organ, it affects the lungs and intrathoracic lymph nodes (LN) in 90% of cases. [Rev Port Pneumol. 2014;20(5):235---236] Endoscopic ultrasound guided fine needle aspiration (EUSFNA) of mediastinal LN provides a minimally invasive alternative method for obtaining noncaseating granulomas. [American Journal of Gastroenterology 2010;105:S536] The diagnostic yield of EUS-FNA for sarcoidosis varies between 77% and 94% [Eur Respir J 2005;25:405–409. Respiration 2013;85:]137–143. Aims: The aim of this study is to report our clinical experience on diagnostic yield of EUS-FNA of mediastinal lymph nodes, spleen, the Endoscopic ultrasound (EUS) features, and complications in sarcoidosis. Methods: From July 2009 to Oct 2021, a total number of 8 cases of EUS-FNA in sarcoidosis were analyzed. The inclusion criterion was suspected sarcoidosis in clinical presentation and radiological pictures. The exclusion criterion was metastatic mediastinal lymph nodes in known primary cancer, proven lymphoma. The location of mediastinal LN classification was according to the international association for the study of lung cancer (IASLC) Lymph Node Map [J Thorac Oncol 2009;4(5):568–577.] The EUS features were reviewed. EUS-FNA of mediastinal LNs were performed at station 7,8. EUS-FNA was done on spleen in one of the cases. EUS-FNA was sent for cytology, cell block, and histology for non-caseating granuloma, immunochemical staining of CD56 for histiocytes, tuberculosis (TB) culture, TB polymerase chain reaction (PCR), and fungus culture. Olympus UCT 2000 (Olympus Optical Co., Ltd., Tokyo, Japan) linear echoendoscope, Wilson Cook medical needles 22 G were used, Boston Scientific Acquire 22, Wilson Cook procore 22 G needles were used in the last case. Color Doppler was applied to avoid puncturing vessels, and the initial pass was performed with no negative pressure, and if no tissue was obtained, syringe negative pressure of 10cc was used. Pethidine and midazolam sedation were used in 7 cases, and IV propofol in the last case. Results: There were 8 cases (5 male patients), with the mean age of 43.3 years (29-67 years). The locations of mediastinal LN were station 7 in 5 cases and station 8 in 3 patients. The mean size of mediastinal LN was 2.6cm (1.2-3.5cm), and 1.2cm for spleen in EUSFNA. The EUS pattern were; 7 heterogenous, 1 isoechoic, 6 cluster pattern, no typical granular pattern, and 6 hypervascular pattern on Doppler scanning. The mean number of passes was 5 (46). Sarcoidosis was consistent in 5 cases (62.5%) with noncaseating granuloma, positive immunochemical staining of CD56 for histocytes, negative Langhan giant cell, negative tuberculosis (TB), culture, negative TB polymerase chain reaction (PCR), and negative fungus culture. Negative cases of EUSFNA underwent mediastinoscopy. There was one mild hemopericardium and mild right hemothorax complication. (the condition was stable with conservative treatment, and underwent thoracoscopy for pericardial window). Conclusions: EUS-FNA of mediastinal LN achieved a diagnostic yield of 62.5% for sarcoidosis, and heterogenous echo, cluster, hypervascular patterns are commonly seen.

P.042

一個 WNT 信號通路及癌幹源性之標記具備 促進口腔及食道區域癌化之潛能 A POTENTIAL WNT- AND STEMNESS MARKER CAN PROMOTE ORAL AND ESOPHAGEAL FIELD CANCERIZATION

黃柏瑞1,2 張智翔1,3 林珮均2 蔡坤志1,2 臺北市立萬芳醫院消化內科1 臺北醫學大學臨床醫學研究所2 臺北醫學大學醫學系內科學科3

Background: Stem-like cancer cells or cancer stem cells (CSCs) critically contribute to the malignant progression and metastasis in field cancerization, including esophageal and oral squamous cell carcinoma. The use of surrogate markers combined with xenotransplantation assays has led to the identification of various populations of CSCs in esophageal cancer (EC) and head and neck squamous cell carcinoma (HNSCC), whereas the molecular pathways controlling them remain elusive. Aims: To investigate if ASPM plays a critical role in promoting tumor progression by sustaining cancer stemness in EC and HNSC Methods: The expression patterns of ASPM isoforms were profiled in normal epithelial and EC/HNSC tissues. The functional roles of ASPM in Wnt activity, cancer stemness, and tumor progression, and the underlying signaling processes were investigated. Results: ASPM isoform 1 (ASPMiI) represented higher in expression in cancer cytoplasm of EC and HNSC. Mechanically, ASPMiI interplays DVL1&3 in the cytosol and stabilizes the β-catenin protein, to control the Wnt activity and the stemness properties in EC and HNSC cells. Conclusions: ASPM is a canonical Wnt pathway regulatory module that promotes β-catenin-dependent Wnt pathway activation, cancer stemness, and aggressiveness in EC and HNSCC P.043

改善後的成人腐蝕性傷害流程圖 MODIFIED PRACTICAL FLOWCHART FOR ADULT CAUSTIC INGESTION

鄭浩材1,2,3,4 黃書偉1 黃欣智1 蘇銘堯1 謝森永2

新北市立土城醫院（委託長庚醫療財團法人興建經營）

胃腸肝膽科1 林口長庚紀念醫院胃腸肝膽科系2 長庚大學臨床醫學院3 長庚大學臨床醫學研究所4

Background: Caustic ingestion has gained increasing attention worldwide. However, the insight into whether to use esophagogastroduodenoscopy (EGD) or computed tomography (CT) for first-line investigation remains controversial. Aims: This study aimed to propose a simple yet effective algorithm that combines EGD and CT for rapid triage. Methods: We established an algorithm for our hospital in 2013, aiming to simultaneously maximize the benefits and minimize the limitations of EGD and CT. Then retrospectively analyzed enrolled 163 patients treated between 2014 and 2019 and categorized them into four groups (A = 3, 1.8%; B = 10, 6.1%; C = 91, 55.8%; D = 59, 36.2%) according to initial signs/symptoms and EGD/ CT grading. The morbidity and mortality of each group were analyzed. The predictive values of EGD and CT were examined by univariate/multivariate logistic regression analyses and receiver operating characteristic (ROC) curves. Results: The outcomes under such algorithm were reported. CT was imperative for patients with toxic signs and suspected perforation. For nonemergent operations, additional EGD was safe and helpful in identifying surgical necessity. For patients with initially low perforation risk, EGD alone sufficiently determined admission necessity. Among inpatients, EGD provided excellent discrimination for predicting the risk for signs/symptoms deterioration. Routine additional CT was only beneficial for those with deteriorating signs/symptoms. Conclusions: According to the retrospective analyses, initial signs/symptoms help choose EGD or CT as the firstline investigative tool in caustic patients. Furthermore, CT is necessary for seriously injured patients, but it cannot replace EGD for moderate/mild injuries. The severity stratification and patient categorization help simplify complex scenarios, accelerate decision-making, and prevent unnecessary intervention/therapy.

P.044

利用內視鏡執行口咽吞嚥障礙檢查：老年病 患吸入性肺炎風險評估 ENDOSCOPIC EVALUATION OF OROPHARYNGEAL DYSPHAGIA IN OLDER PATIENTS FOR RISK STRATIFICATION OF PNEUMONIA

林泰瀚1 楊志偉2 黃天祐2 陳鵬仁2 施宇隆2 謝財源2 張維國2 三軍總醫院病理科1 三軍總醫院腸胃科2

Background: Nasogastric tube (NGT) and percutaneous endoscopic gastrostomy (PEG) are widely used techniques to feed older patients with oropharyngeal dysphagia. Aspiration pneumonia is the most common cause of death in these patients. Aims: This study aimed to evaluate the role of oropharyngeal dysphagia in older patients on longterm enteral feeding for risk stratification of pneumonia requiring hospitalization. Methods: We performed modified flexible endoscopic evaluation of swallowing to evaluate oropharyngeal dysphagia in older patients and conducted prospective follow-up for pneumonia requiring hospitalization. A total of 664 oral-feeding patients and 155 tube-feeding patients were enrolled. Multivariate Cox analysis was performed to identify risk factors of pneumonia requiring hospitalization. Results: Multivariate analyses showed that the risk of pneumonia requiring hospitalization was significantly increased in patients with older ages (Adjusted HR 1.03, 95% CI 1.01–1.06, P = 0.004), neurological disorders (Adjusted HR 2.39, 95% CI: 1.49–3.84, P < 0.001), tube feeding (Adjusted HR 2.57, 95% CI: 1.61–4.12, P < 0.001), and oropharyngeal dysphagia (Adjusted HR 1.59, 95% CI: 1.02–2.47, P = 0.006). Subgroup analysis revealed that the risk of pneumonia requiring hospitalization was significantly lower in patients with PEG than in those with NGT among the patients with oropharyngeal dysphagia (Adjusted hazard ratio 0.26, 95% CI: 0.11–0.63, P = 0.003). Conclusions: For older patients with oropharyngeal dysphagia requiring long-term enteral tube feeding, PEG is a better choice than NGT. Further research is needed to elucidate the role of oropharyngeal dysphagia in enteral feeding in older patients. P.045

在難治型胃食道逆流患者發現有較高比 例的 STREPTOCOCCUS, ROSEBURIA, CLOSTRIDIUM_XIVA HIGHER PROPORTION OF STREPTOCOCCUS, ROSEBURIA, CLOSTRIDIUM_XIVA FROM ESOPHAGEAL MICROBIOME AMONG REFRACTORY GASTROESOPHAGEAL REFLUX DISEASE (GERD) PATIENTS.

謝名宗1 張維倫1 許博翔1 陳芃潔2 成功大學附設醫院內科部肝膽胃腸科1 成功大學臨床醫學研究所2

Background: Fusobacterium, Neisseria, Veillonella was shown higher proportion in the esophageal disease, including GERD, Barrett esophagus and esophageal cancer. Those gram-negative bacteria secrets lipopolysaccharides and induced the inflammation. Refractory GERD is a challenge for clinician and related esophageal hypersensitivity and functional heartburn. Gut microbiome secrets neuro-modulator and induces the nocireceptor activation. New therapy for refractory GERD might be related to the gut microbiome. Aims: To investigate the esophageal microbiome between refractory GERD and health control Methods: We enrolled the patients who were willing for esophagogastroduodenoscopy and completed the GERDQ for symptoms evaluation. If GERDQ ≧ 8, patients was assigned for 2 month PPI treatment and devided into refractory GERD group and typical GERD group. Refractory GERD indicated partial or null response to PPI treatment. Otherwise, patients matched GERDQ <8 were assigned to the control group. All patient received biopsy at the site 1cm above esophagogastric junction. The speimens were proceded DNA extraction and genomic sequences. The final data was analysed by Mothur. Results: During 2019/1~2019/12, 18 patients came for endoscopic exam and recieved GERDQ questionnaire. 6 patients were typical GERD presented with GERDQ ≧ 8 and good PPI response. 6 patients presented with GERDQ ≧ 8 and partial/null response to PPI treatment who were assigned to refractory group. Control group had 6 patients. Among 3 groups, Streptococcus, Roseburia, Clostridium_XIVa were abundant in refractory GERD through Metastat analysis. No difference was noted in Shannon diversity index, POCA and NMDS.

Conclusions: Refractory GERD is a challenge for clinician. In our study, refractory GERD patients had abundant Streptococcus, Roseburia, Clostridium_XIVa compared with GERD patients and healthy control in esophageal microbiome. Neuromodulator, like serotonin and chemical molecular, like butyrate secreted by these bacteria should be further investigated to reveal the mechanism between refractory GERD and microbiome. P.046

於腎上腺素注射術後，比較併用氬氣電漿凝 固術或併用止血夾兩者對於消化性潰瘍出血 的止血療效 RANDOMIZED CONTROLLED TRIAL OF ARGON PLASMA COAGULATION PLUS DILUTED ADRENALIN INJECTION VERSUS HEMOCLIPPING PLUS DILUTED ADRENALIN INJECTION FOR TREATMENT OF HIGH–RISK PEPTIC ULCER BLEEDING: AN INTERIM REPORT

王惠民1 蔡峯偉1 高崧碩1 蔡維倫1 陳文誌1 高雄榮民總醫院胃腸肝膽科1

Background: Endoscopic treatment is recommended for initial hemostasis in nonvariceal upper gastrointestinal bleeding. Many endoscopic devices have been demonstrated to be effective in the hemostasis of bleeding ulcers. However, the additional hemostatic efficacy of argon plasma coagulation (APC) after endoscopic injection therapy has not been widely investigated. Aims: The study aim is to compare APC plus diluted adrenalin injection (APC group) with clipping plus diluted adrenalin injection (Clip group) in treating high-risk peptic ulcer bleeding. Methods: From Jan. 2019 to Nov. 2021, consecutive patients with high-risk bleeding ulcers, characterized by active bleeding, non-bleeding visible vessels and adherent clots, were admitted to our hospital. They prospectively randomly underwent either APC therapy plus diluted adrenalin injection or hemoclipping plus diluted adrenalin injection. Pantoprazole infusion was conducted during the fasting period after endoscopy and orally for 8 weeks to encourage ulcer healing. Episodes of rebleeding were retreated with endoscopic combination therapy. Patients who did not benefit from retreatment underwent emergency surgery or arterial embolization. The data were expressed as mean+SD. Quantitative variables were compared according to Student t-test, and qualitative variables were compared using the Chi-square test and Fisher’s exact test when appropriate to compare the location of the bleeding lesions, initial hemostasis, rebleeding, emergency surgery and mortality of both treatment groups. All hypothesis tests were performed against a two-sided alternative, where appropriate. A p < 0.05 was viewed as statistically significant. Analyses were undertaken using SPSS software (SAS, SPSS Inc., Chicago, Ill., USA).

Results: In all, 85 eligible patients were analyzed. Hemostatic efficacy in 41 patients treated with APC plus diluted adrenalin injection (APC group) was prospectively compared with 44 patients treated with hemoclipping plus diluted adrenalin injection (Hemoclip group). The two treatment groups were similar with respect to all baseline characteristics. Initial hemostasis was accomplished in 51 patients treated with APC combined with diluted adrenalin injection therapy, and 57 patients with hemoclipping plus diluted adrenalin injection therapy (98.1% vs. 98.3%, P = 1.000). Bleeding recurred in 4 patients in the APC group, and in 6 patients in the Clip group (7.7% vs. 10.3%, P = 0.746). The transfusion requirements is lesser in APC group than Clip group (2.4+2.2 vs. 3.6+3.2 units, P =0.026). No significant differences were observed between the 2 groups in hospital stay, surgery/arterial embolization and mortality. Conclusions: Endoscopic therapy with APC plus diluted adrenalin injection is similarly effective as hemoclipping plus diluted adrenalin injection for preventing rebleeding in the treatment of high-risk bleeding ulcers. Both treatment methods also have similar safety during therapeutic endoscopy. Nevertheless, APC group requires less blood transfusion requirements, compared with Clip group. P.047

系統性回顧和統合分析：針對胃竇血管擴張 症的治療來比較內視鏡結紮術、射頻灼燒術 和氬氣電漿凝固術三者間的成效 SYSTEMIC REVIEW AND METAANALYSIS: THE COMPARISONS AMONG ENDOSCOPIC BAND LIGATION, RADIOFREQUENCY ABLATION, AND ENDOSCOPIC THERMAL THERAPY FOR GASTRIC ANTRAL VASCULAR ECTASIA

許斯淵1 柯忠旺1 張崇信1 臺中榮民總醫院1

Background: Gastric antral vascular ectasia (GAVE) accounts for up to 4% of nonvariceal upper gastrointestinal bleeding and is frequently associated with iron deficiency and transfusion-dependent anemia. Endoscopic band ligation (EBL), and radiofrequency ablation (RFA) have emerged as alternative therapies in addition to endoscopic thermal therapy (ETT), but the optimum choice among the three endoscopic modalities remains inconclusive. Aims: We conducted a meta-analysis to compare the three treatments for GAVE. Methods: Three major bibliographic databases were reviewed for enrollment of comparative trials prior to December 08, 2021. We included adults with GAVE and focused on the mortality, bleeding cessation, endoscopic improvement, complication, hospitalization, hemoglobin improvement, Number of sessions, and transfusion requirement. Results: Twelve studies involved a total of 571 participants for analysis. When compared with ETT, EBL achieved better bleeding cessation, higher hemoglobin improvement, and lower number of sessions with a pooled OR of 4.48 (95% CI, 1.36~14.77, p=0.01), and pooled mean difference of 1.19 (95% CI, 0.20~2.19, p=0.02), and -0.94 (95% CI, -1.88~-0.01, p=0.05) respectively while RFA showed no difference in these outcomes. Besides, EBL was superior to ETT in endoscopic improvement, hospitalization, and transfusion requirement with statistical significance except for mortality and complication rate. Conclusions: For GAVE, we suggest that EBL be initially recommended, and APC and RFA as alternative treatment choices based on a very low quality of evidence.

P.048

內視鏡真空吸引治療應用於食道術後穿孔或 滲漏之單中心回顧 ENDOSCOPIC VACUUM THERAPY FOR POST-OPERATIVE ESOPHAGEAL PERFORATIONS AND LEAKAGES: A SINGLE CENTER RETROSPECTIVE STUDY

吳季桓1 林政輝1 鄒永寬1 林口長庚紀念醫院胃腸肝膽科系1

Background: Post-operative esophageal wall injury, such as perforations and anastomotic leaks, is nightmare after surgical and endoscopic interventions. Recently, in the form of endoscopically placed vacuum therapy had widely used in such clinical situation Aims: To evaluate whether endoscopic vacuum therapy is effective for post-operative esophageal leak or perforation Methods: We retrospectively collected data from September 2019 to December 2021. 6 patients (5 men and one women) were treated at our institution using endoscopic vacuum therapy (EVT) for post-operative esophageal wall injury Results: The defect in the esophageal wall was successfully closed in four of the six patients (66.7 %) Conclusions: Endoscopic vacuum therapy is a useful tool for management of defects in the esophageal wall and should be considered as a treatment option for patients with post-operative esophageal perforation or leak. P.049

台灣同時合併胃食道逆流及功能性食道疾患 病人之臨床及精神特徵 CLINICAL AND PSYCHOLOGICAL CHARACTERISTICS OF PATIENTS WITH OVERLAPPING GASTROESOPHAGEAL REFLUX DISEASE AND FUNCTIONAL ESOPHAGEAL DISORDERS IN TAIWAN

葉秉威1 陳建全2 吳嘉峯3 李慧娟3 李宜家2 王秀伯2 吳明賢2 曾屏輝2 臺安醫院內科部胃腸肝膽科1 臺灣大學醫學院附設醫院內科部2 臺灣大學醫學院附設醫院小兒部3

Background: Since ROME IV introduced the concept of overlapping gastroesophageal reflux disease (GERD) and functional esophageal disorders, little is known about the clinical and psychological characteristics of these patients. Aims: We aimed to investigate the clinical and psychological characteristics of patients with overlapping GERD and functional esophageal disorders in Taiwan. Methods: From 2010 to 2019, consecutive patients with proven GERD and refractory symptoms despite the use of proton pump inhibitors (PPIs) for ≥ 8 weeks were prospectively enrolled in this study. All patients were assessed using validated symptom questionnaires, including Reflux Disease Questionnaire (RDQ), Patient Assessment of Gastrointestinal Symptom Severity Index (PAGI-SYM), Brief Symptom Rating Scale-5 (BSRS-5), and Pittsburgh Sleep Quality Index (PSQI), as well as manometry and 24-h multichannel intraluminal impedance-pH testing on PPI therapy. Patients were further categorized based on the Lyon consensus and Rome IV criteria. Results: Of the 100 patients analysed, 5 patients were found to have major motility disorders while 66 were diagnosed with overlap functional heartburn (FH), 12 with overlap reflux hypersensitivity (RH), and 17 with residual reflux disease. Patients with overlap FH had higher female predominance (68.2%, p=0.023) and trends toward lower body mass index (p=0.085), and waist (p=0.05) than patients with residual reflux disease. There were no significant differences among these three groups in terms of the reflux symptoms, psychological profile, and sleep quality,. Subgroup analysis showed that patients with overlap FH and psychological comorbidity (BSRS5 total score ≥6) reported higher median symptoms scores on RSI (21 vs. 10.5, p=0.001) and PAGI-SYM (40 vs. 25,

p=0.035), respectively. Conclusions: The prevalence of overlap functional esophageal disorders in Taiwanese patients with refractory GERD is high (78%). The symptom profiles are similar among patients with overlap FH, RH, and residual reflux disease. Patients with overlap FH and psychological comorbidity report more reflux and gastrointestinal symptoms. P.050

大學生地中海飲食習慣與胃食道逆流的相關 性 MEDITERRANEAN DIET ASSOCIATED WITH GASTROESOPHAGEAL REFLUX DISEASE IN COLLEGE STUDENTS, A CROSS-SECTIONAL STUDY

林穎正1 郭馥瑜1 鍾佳凌1 郎惠芬1 王文宏1 連漢仲1,2,3 臺中榮民總醫院胃腸肝膽科1 臺中榮民總醫院營養部2 東海大學3 國立陽明交通大學4

Background: Studies focusing on the relationship between healthy dietary pattern and gastroesophageal reflux disease (GERD) are scarce, especially in young generation. Aims: The aim of the study was to evaluate the association of Mediterranean dietary pattern and GERD among college students in Taiwan. In a cross-sectional study, a total of 821 of 1051 (78.1%) college students completed the survey (551 female, mean age: 20.4 ± 2.7 years). Adherence to the Mediterranean diet was assessed using the 14-item Mediterranean Diet Adherence Screener (MEDAS). GERD was defined as GerdQ score ≥ 8 points. Sex and ageadjusted Logistic regression was conducted to evaluate the association of GERD with Mediterranean dietary pattern. Methods: In a cross-sectional study, a total of 821 of 1051 (78.1%) college students completed the survey (551 female, mean age: 20.4 ± 2.7 years). Adherence to the Mediterranean diet was assessed using the 14-item Mediterranean Diet Adherence Screener (MEDAS). GERD was defined as GerdQ score ≥ 8 points. Sex and ageadjusted Logistic regression was conducted to evaluate the association of GERD with Mediterranean dietary pattern. Results: The prevalence of GERD was 14.4% (17.6% in female; 7.5% in male). After adjustment for age, gender, physical activity, the presence of irritable bowel syndrome, anxiety or depression, adherent to Mediterranean dietary pattern remained inversely associated with risk of GERD (adjusted odds ratio for each 1 point increase in Mediterranean dietary score = 0.859, 95% confidence interval = 0.738–1.00; p = 0.05). Conclusions: Our finding suggested a beneficial effect of Mediterranean dietary pattern in regards to GERD in Taiwanese college students. These findings warrant further prospective studies to confirm the roles of healthy dietary pattern in the management of GERD.

P.051

以海博刀執行之內視鏡黏膜下剝離術治療早 期食道腫瘤的臨床療效：南台灣單一醫學中 心回溯性研究 CLINICAL OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION WITH HYBRIDKNIFE® FOR EARLY ESOPHAGEAL NEOPLASMS: A SINGLE-CENTER EXPERIENCE IN SOUTH TAIWAN

葛振瑜1 姚志謙1 李育騏1 盧龍生1 周業彬1 胡銘倫1 邱逸群1 戴維震1 高雄長庚紀念醫院胃腸肝膽科系1

Background: Endoscopic submucosal dissection (ESD) is accepted as the major treatment modality for early gastrointestinal neoplasm including the esophagus. It is an advanced and risky endoscopic procedure with highly technically demand. Hybridknife® emerged as a new endoscopic knife with high pressure needle-free injection, which can decrease ESD procedure time. Aims: We aimed to analyze the clinical outcomes of ESD with Hybridknife® for early esophageal neoplasms in our hospital, retrospectively. Methods: From January 2019 to December 2021, 69 patients with diagnosis of esophageal neoplasms and received ESD procedure with Hybridknife® are enrolled in this study. All patients underwent chromoendoscopy with narrow-band imaging and Lugol staining before ESD for peripheral margin detection. Endoscopic ultrasound was also performed for invasion depth evaluation before ESD. Results: A total of 97 lesions in 69 patients were enrolled. There were 1 patient with loss follow-up and 7 patients haven’t received surveillance endoscopy yet. 64 patients were men (92.7%). The mean age was 57.97±7.74 years. The mean size of tumors was 12.96±8.88 cm2. En bloc resection rate was 99% (96/97). R0 resection rate was 84.5%. The mean operation time was 53.45±38.6 minutes. There were 21 ESD-related complications, including 18 with post-ESD stricture, 2 with post ESD wound bleeding and 1 with intra-procedure perforation. 5 patients received additional esophagectomy. During a mean of 7.79 months of follow-up, there was no local recurrence and 5 metachronous recurrence (7%) were noted. There was no procedure-related mortality. Tumor size and circumference of the lumen were associated with longer procedure time. Otherwise, tumor size (≥ 10 cm2) and circumference of the lumen (≥ 3/4) were associated with post-ESD stricture. Conclusions: ESD with Hybridknife® is a effective and relatively safe treatment for early esophageal neoplasms. Larger tumor size and circumference of the lumen were associated with longer procedure time and should be aware of post-ESD stricture. P.052

早期食道病變內視鏡黏膜下切除後的食道蠕 動機能變化 ESOPHAGEAL MOTILITY ALTERNATION AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY ESOPHAGEAL NEOPLASM

謝易倫1 王俊偉2 許文鴻2 蘇育正2 吳登強2 高雄醫學大學附設醫院內科部1 高雄醫學大學附設醫院胃腸科2

Background: Esophageal motility impaired by endoscopic submucosal dissection (ESD)might be related to dysphagia. The association between esophageal motility and ESD lesion size was not clear. Aims: The goal of this study is to evaluate changes in esophageal motility after ESD using high-resolution manometry (HRM). This is a before-and-after trial of the effect of ESD on the esophageal motility Methods: Eight patients who underwent ESD for early esophageal neoplasm were enrolled in this study. All lesion sizes of ESD are less than 75% circumferential. No esophageal stricture was noted after the procedure and no patients need subsequent procedures such as endoscopic triamcinolone injection and endoscopic balloon dilatation. Results: The distal contractile integral (DCI) before and after ESD were not significantly different . Association between esophageal motility changes and ESD lesion size were not significantly different (P= 0.3). However, the trend of esophageal motility impairment is associated with larger ESD lesion sizes. Conclusions: The impairment of esophageal motility was possible , especially in patients with large ESD lesion sizes.

P.053

探討 CODEINE 對食道無效性收縮病人蠕 動功能之影響 EFFECTS OF CODEINE ON ESOPHAGEAL PERISTALSIS IN PATIENTS WITH INEFFECTIVE ESOPHAGEAL MOTILITY

梁書瑋1 易志勳1 劉作財1 雷尉毅1 林霖1 洪睿勝1 翁銘彣1 陳健麟1

佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃

科1

Background: Acute administration of codeine impairs lower esophageal sphincter (LES) relaxation and alters primary and secondary peristalsis in health adults. However, acute effects of codeine on esophageal peristalsis in patients with ineffective esophageal motility (IEM) is unclear. Aims: Our study aimed to evaluate the hypothesis whether esophageal peristalsis can be influenced by acute administration of codeine in IEM patients. Methods: We enrolled twelve IEM patients (8 men, mean 36.7 years, aged 23-56 years) undergoing high resolution manometry with a catheter containing a mid-esophageal injection port for inducing secondary peristalsis. All participants had ten wet swallows and ten 20 mL rapid air injections for generating secondary peristalsis. All participants completed the protocol including 2 separate sessions including codeine (60 mg) or the placebo on a randomized order. Results: Codeine significantly increased peristaltic frequency (52% vs. 17%, p = 0.002) and shortened distal latency (DL) (5.6 ± 0.3 vs. 6.6 ± 0.2 seconds, p = 0.005) for primary peristalsis. The distal contractile integral of primary peristalsis was also significantly higher after codeine than the placebo (539 ± 96 vs. 273 ± 50 mmHg/s/cm, p = 0.007). Codeine significantly shortened peristaltic break of primary peristalsis (5.6± 1.4 vs. 7.9 ± 1.1 cm, p = 0.01). Codeine didn’t change 4-s integrated relaxation pressure (IRP-4s) (p = 0.73) or EGJ-CI (p = 0.17) of primary peristalsis. None of secondary peristaltic parameters were changed by codeine. Conclusions: Although there was no effects on LES relaxation or secondary peristaltic activities, our study has demonstrated that codeine increases effectiveness and vigor of primary peristalsis in IEM patients. This work supports the notion that the influence of codeine on esophageal peristaltic physiology may differ between primary and secondary peristalsis in patients with IEM, and also suggests that activation of opioids receptors in controlling esophageal peristalsis appears to be different between IEM patients and healthy adults. P.054

食道二度收縮對酸灌注前後之反應可預測胃 食道逆流症患者其食道黏膜完整性及酸敏感 度 ESOPHAGEAL SECONDARY PERISTALSIS TO ACID INFUSION PREDICTS MUCOSA INTEGRITY AND ACID SENSITIVITY IN PATIENTS WITH GERD

洪睿勝1 翁銘彣1 雷尉毅1 梁書瑋1 劉作財1 易志勳1 林霖1 陳健麟1

佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃

科1

Background: Acid sensitivity can altered in patients with gastroesophageal reflux disease (GERD). Secondary helps clear refluxate from the stomach or residual food bolus after swallowing. Aims: This study aimed to evaluate the interaction among acid sensitivity, secondary peristalsis, and esophageal mucosa integrity before and after esophageal acid infusion. Methods: Adult patients with chronic reflux symptoms and negative endoscopy underwent high resolution manometry (HRM) and 24-h impedance-pH monitoring off acid suppression. The phenotypes of GERD including non-erosive reflux disease (NERD), reflux hypersensitivity (RH) and functional heartburn (FH) were further defined based on data from acid exposure time and symptom association. Primary peristalsis was evaluated using ten supine water swallows, while secondary peristalsis was assessed using five rapid 20 mL air injections into the esophageal lumen. Following HRM with air injection, all subjects underwent infusion of hydrochloric acid (0.1 N) into the mid-esophagus via the injection port of the HRM catheter to assess acid sensitivity, and secondary peristalsis was assessed again by five air injections. Conventional acid infusion parameters were documented including lag time, intensity rating, and sensitivity score. Mucosal integrity was evaluated using distal mean nocturnal baseline impedance (MNBI) from impedance-pH monitoring. Results: 52 patients (age 21-64 years, 66% women) completed all study components, and included 9 patients with NERD, 28 with RH, and 15 with FH. There was no significant difference in acid infusion parameters between patients with NERD, RH and FH or those with and without symptom association. The proportion of patents in whom secondary peristalsis could be elicited was similar at baseline and after acid infusion [39 (75%) vs. 37 (71%), P

= 0.65]. At baseline, acid infusion parameters and MNBI were similar between patients with and without secondary peristalsis. After acid infusion, patients without secondary peristalsis had shorter lag time and lower MNBI than those with secondary peristalsis (lag time: 43.7 vs. 81.8 sec, P = 0.018; MNBI: 2347.3 vs. 2824.1 ohms, P = 0.028). Conclusions: Patient with intact secondary peristalsis have better mucosal integrity and less acid sensitivity following esophageal acid infusion. Our work demonstrates that intact mucosal integrity is important for maintaining esophageal acid sensitization, and both of these physiological features appear to be associated with distension-induced secondary peristalsis. P.055

人類間質幹細胞在胃癌細胞粒線體能量代謝 與進展 ROLE OF HUMAN MESENCHYMAL STEM CELLS IN REGULATING MITOCHONDRIAL ENERGY METABOLISM AND PROGRESS OF GASTRIC CANCER CELLS

蔡一民1 劉忠榮1 余方榮1,2 胡晃鳴1,2,3 吳登強1,2 郭昭宏1,2,4 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學醫學系2 高雄巿立大同醫院內科3 高雄巿立小港醫院內科4

Background: Gastric cancer is one of the most prevalent cancers worldwide, and is also the second leading cause of cancer-related mortality. Altered mitochondrial energy metabolism contributes to more ATP source, and the growth and metastasis of cancer through up-regulating the uptake of energy-rich metabolites such as lactate, ketone bodies and glutamate et al. Adipose-derived mesenchymal stem cells (ADSCs) are reported to promote growth of cancer. Aims: To figure out the the impact and mechanism of ADSCs contribute to the progression of gastric cancer. Methods: We explored the role of ADSCs in the progression of human gastric cancer by co-culturing human gastric cancer cells and ADSCs. We then observed these cells interaction by measuring the levels of lactate, ketone bodies, glutamate and ATP, the effects on growth and motility of human gastric cancer cells in the co-culture system. Results: In the present study, we demonstrated that human AGS gastric cancer cells recruit ADSCs. ADSCs then promote the capacity of growth and invasive motility in human AGS gastric cancer cells. ADSCs increased the levels of lactate, ketone bodies and glutamate through upregulating MCT1 and SLC6A14 transporters in human AGS gastric cancer cells. ADSCs increased ATP level through upregulating the expression of mitochondrial energy metabolism-associated factors including OXCT1/2, ACAT1 and LDH1. ADSCs reverse K604 (ACAT-1 specific inhibitor)-induced mitochondrial damage and K604inhibited invasion in human AGS gastric cancer cells. ADSCs upregulate AGS tumor growth, companied with Ki67 and CD31 overexpression. Conclusions: These results suggest that ADSCs might play the critical role in gastric cancer progress through regulating mitochondrial energy metabolism profiles.

P.056

上消化道內視鏡發現的十二指腸惡性腫瘤： 嘉義長庚醫院的十年經驗 DUODENAL MALIGNANT TUMOR FROM ESOPHAGOGASTRODUODENOSCOPY: TEN YEARS EXPERIENCES IN CHIAYI CGMH

鄭喻夫1 張德生1 董水義1 魏國良1 沈建亨1 謝詠諭1 顏志維1 張國基1 陳奕行1 陳俊憲1 童威霖1 許晃維1 吳正雄1 陳慰明1 嘉義長庚紀念醫院1

Background: Duodenal malignant tumor was rare in gastrointestinal disease. It could be primary or direct invaded by pancreatic or hepato-biliary cancer. Advanced stage because of delay diagnosis and difficult surgical approach caused poor prognosis. However, there was little study to discuss about the difference between primary and invaded duodenal cancer. Aims: Find out the difference between primary and invaded duodenal cancer from real world experience to improve diagnosis accuracy and prognosis. Methods: We reviewed the esophagogastroduodenoscopy(EGD) chart in these ten years. Document with duodenal tumor or mass cases were included. Sub-epithelial tumor(SET) or lacked of tissue proof cases were excluded. Results: About 100,000 EGD was done in these ten years. Only 70 cases (0.07%) were documented with duodenal tumor or mass. We excluded 8 cases, 5 SET and 3 cases without pathology data. In these 62 cases, 19 were benign and 43 were malignant duodenal tumor. There were only 11 duodenal primary cancer, 4 ampulla cancer, 14 pancreatic invaded cancer, and 14 hepato-biliary invaded cancer. Between primary and invaded duodenal malignant tumor, there was no significant differences in age, gender, comorbidity and cancer stage. There was no significant factor can predict the prognosis. Most pancreatic invaded cancer located at 2nd portion with ulcerations. Conclusions: Duodenal malignant tumor was rare in real world experience. There was no significant factor can predict the prognosis between primary and invaded duodenal malignant tumor. Tumor location and ulceration usually found at pancreatic invaded cancer. P.057

「質子幫浦抑制劑」在預防具消化性潰瘍出 血病史之「血小板ADP受體抑制劑使用者」 發生上消化道臨床事件上之效果優於「第二 型抗組織胺受體抑制劑」 PROTON PUMP INHIBITOR IS SUPERIOR TO HISTAMINE-2 RECEPTOR ANTAGONIST IN THE PREVENTION OF UPPER GASTROINTESTINAL EVENTS AMONG ADP RECEPTOR ANTAGONIST USERS WITH A HISTORY OF PEPTIC ULCER BLEEDING

吳弈霆1 蔡峯偉2 石志安3 施長碧1 許秉毅1 臺南市立安南醫院暨中國醫藥大學內科部消化內科1 高雄榮民總醫院內科部胃腸肝膽科2 安泰醫療社團法人安泰醫院內科部胃腸肝膽科3

Background: Proton pump inhibitor (PPI) can prevent recurrent peptic ulcer in clopidogrel users. However, both the US Food and Drug Administration and the European Medicines Agency have posted safety warnings reminding the drug interaction between PPIs and clopidogrel. Aims: To compare the efficacies PPI and histamine-2 receptor antagonist (H2RA) in the prevention of clinically significant upper gastrointestinal (GI) events in ADP receptor antagonist users with a history of peptic ulcer bleeding. Additionally, the incidences of adverse events of the two prophylactic therapies were compared. Methods: Long-term ADP receptor antagonist users with a history of peptic ulcer bleeding who did not have peptic ulcers at an initial endoscopy were randomly received either a pantoprazole (40 mg daily) or a famotidine (40 mg daily) therapy for 48 weeks. Follow-up endoscopy was carried out whenever severe epigastric discomfort, hematemesis or melena occurred. The incidences of clinically significant upper GI event (dyspeptic ulcer and/or peptic ulcer bleeding) and frequencies of adverse events (diarrhea, pneumonia, facture and cardiovascular events) between groups were compared. Additionally, the sequential changes in serum magnesium levels and mineral bony densities were examined according to a standard protocol. Results: The incidences of clinically significant upper GI events in the pantoprazole group (n = 60) and famotidine group (n = 60) were 1.7% and 13.3%, respectively. The former had less upper GI events than the latter (difference: 11.6%; 95% confidence interval, 2.4-20.8%, P = 0.017).

The two study groups had comparable incidences of diarrhea (1.7% vs 1.7%), pneumonia (0% vs 1.7%), fracture (1.7% vs 0%), acute myocardial infarct (1.5% vs 4.5%), and cerebral vascular accident (0% vs 3.4%). Additionally, there were no differences in sequential changes of serum magnesium levels and mineral bony densities between groups. Conclusions: Among patients with atherosclerosis and a history of peptic ulcer bleeding, PPI is superior to H2RA in the prevention of clinically significant upper GI events. The two prophylactic therapies have comparable adverse events and impacts on mineral bony densities. P.058

困難梭菌感染對於住院發炎性腸道疾病患者 的影響 CLOSTRIDIODES DIFFICILE INFECTION IN HOSPITALIZED INFLAMMATORY BOWEL DISEASE PATIENTS

李柏賢1 郭家榮1 邱正堂1 蘇銘堯2 林口長庚紀念醫院胃腸肝膽科1 新北市立土城醫院2

Background: Clostridiodes difficile (C. difficile) infection (CDI) increases the risks of hospitalization, colectomy, and mortality in inflammatory bowel disease (IBD). Aims: There has been no study comprehensively evaluating the risk factors, clinical characteristics, and outcomes of CDI in IBD. We aimed to clarify this important issue. Methods: In this retrospective case-control study, we enrolled hospitalized IBD patients with the culture or toxin A/B results for C. difficile in a medical center between April 2007 and April 2021. They were divided into CDI group and control groups. The risk factors, clinical presentations and outcomes were analyzed. Results: A total of 144 IBD inpatients (45 CDI group and 99 control group) were enrolled for analysis. The median follow-up duration was 15.5 months. The incidence of CDI in IBD inpatients was 31%. The risk factors of CDI included longer IBD duration, biological failure, and biological user. More patients presented as abdominal pain in CDI group (77.8% vs 55.6%, P=0.011). After antibiotics treatment and fecal microbiota transplantation (FMT), 83.3% patients had negative result, and 61.9% had improved clinical symptoms. Regarding clinical outcomes, CDI led to more hospitalizations (median 2 times (range 0-12 times) vs median 1 time (range 0-19 times), P=0.008), lower steroid free remission rate (46.7% vs 67.7%, P=0.017) and higher Mayo score (median 5 points (range 2-12 points) vs median 3 points (range 0-12 points). Compared to antibiotics treatment, the patients receiving FMT had less times of hospitalization and less IBD related complications during follow-up. Conclusions: CDI led to more hospitalizations, lower steroid free remission rate and higher Mayo score in IBD inpatients. FMT should be considered in refractory or recurrent CDI in IBD to improve the clinical outcomes.

P.059

BUDESONIDE MMX 對潰瘍性結腸炎的療 效－一真實世界的經驗 THE EFFICACY OF BUDESONIDE MMX IN ULCERATIVE COLITIS- A REAL WORLD EXPERIENCE

吳冠緯1,3 章振旺1,2,3 林煒晟1,3 張經緯1,3 王鴻源1,3 陳銘仁1,2,3 馬偕紀念醫院肝膽腸胃科1 馬偕醫護管理專科學校2 馬偕醫學系3

Background: Corticosteroid is superior to 5-aminosalicylic acid (5-ASA) in induction of remission in ulcerative colitis (UC), but with significant side effects. It is reserved for patients failed to respond or intolerant to 5-ASA. Budesonide is a locally acting corticosteroid with high first pass metabolism and minimal systemic side effects. And budesonide MMX is a formulation using a novel colonic delivery technology that permits a controlled dose releasing rate throughout the colon. Several RCTs studies confirmed its effect of induction of remission in patients with mild to moderate UC who failed to respond to 5-ASA. Therefore it is recommended as first line oral corticosteroid in IBD clinical guidelines of Britain, Europe and America. However, the experience with Budesonide MMX is relatively limited in Taiwan. Aims: To evaluate the efficacy of budesonide MMX in a real-life setting of patients treated for UC Methods: We conducted a retrospective analysis of patients treated for UC who ever received budesonide MMX in Mackay Memorial Hospital. The data for this study were obtained from electronic medical record from 2005/11 to 2021/12. All patients were diagnosed with UC based on endoscopic, radiologic and pathologic examination. The primary outcome was patient reported outcome and improvement in partial Mayo score Results: There were 16 patients with ulcerative colitis had been treated with budesonide MMX in Mackay Memorial Hospital. In the study subjects, 11 patients (68.8%) reported with response of the treatment. Among these patients with response, 5 were Montreal classification E1, 4 were E2, and 2 were E3. Their partial Mayo score decreased from 5±1.6 to 3.9±1.5. While 5 patients (31.2%) reported nonresponsive, all of them were Montreal classification E3, and their partial Mayo score increased from 5.6±1.5 to 6. The Montreal classification before treatment (p=0.012) and the partial Mayo score improvement (p=0.029) are significantly different between responsive and nonresponsive groups. In the comparison of the laboratory findings before and after the budesonide MMX treatment, the changes of these blood test items before and after the treatment are similar between the two groups (p>0.05). Conclusions: Budesonide MMX is more likely to induce patient reported response in UC patients whose Montreal classification are E1 or E2 before treatment. And among patients who reported responsive, their partial Mayo score is more likely to improve.

P.060

非鎮靜止痛大腸鏡之可行性 DOES NON-SEDATIVE COLONOSCOPY POSSIBLE? EVALUATION OF PAINFUL SENSATION, CECAL INTUBATION AND ADENOMA DETECTION RATE

蘇銘堯1,2,3 何秉竑1 許振銘4 邱正堂3,4 新北市立土城醫院1 長庚大學醫學院2 臺灣小腸醫學會3 林口長庚紀念醫院4

Background: Colon is a long and tortuous tube, so colonoscopy is more invasive and painful procedure then esophagogastroduodenoscopy. Aims: To identify factors that predict painful colonoscopy, cecal intubation rate (CIR) and adenoma detection rate (ADR) in non-sedative colonoscopy. Methods: From January to Aug 2015, A total of 1260 consecutive patients underwent non-sedative colonoscopy were enrolled. This was a prospective, observational study. Prospective data’s collection including patients’ characteristics, previous medical and surgical history, and indications for colonoscopy, bowel preparation status, insertion time and length of colonoscopy. Patients’ anxiety levels were recorded before the procedure and painful sensation were recorded after the procedure by Likert scale from one study nurse blinded to the procedure. Endoscopists’ experiences were recorded also. These factors were analyzed for the correlations of painful sensation, cecal intubation rate (CIR) and adenoma detection rate (ADR). Results: There were no significant differences for the painful sensation of colonoscopy and the factors mentioned above by univariate analysis except gender and patient’s anxiety level. While, patient’s anxiety level, endoscopist’s experience were correlate with painful sensation of colonoscopy by multivariate analysis. Male and older than 50 years patients had higher ADR. While operator’s experience increased both CIR and ADR. Conclusions: In our study, high anxiety level of patients, female gender and unexperienced endoscopists may correlate with painful feeling under non-sedative colonoscopy, while experienced endoscopists and male gender had higher ADR. P.061

結腸炎相關大腸直腸癌的臨床特徵：單一醫 學中心的經驗 CLINICAL FEATURES OF COLITISASSOCIATED COLORECTAL CANCER: A SINGLE MEDICAL CENTER EXPERIENCE

柯孟佑1,2 范泉山1 陳洋源1 顏旭亨1 彰化基督教醫院胃腸肝膽科1 中山醫學大學醫學研究所2

Background: There is increased risk of colorectal cancer (CRC) among patients with inflammatory bowel disease. Recent data suggested the risk of colorectal cancer in Asian patients with ulcerative colitis (UC) was similar to recent estimates in Europe and North America. Colonoscopy surveillance is recommended for these high-risk patients. However, there is scarce data regarding clinical features of colitis in Taiwan. Aims: In this study, we describe the clinical features of colitis-associated cancer in our hospital. Methods: We retrospective reviewed patient data with UC who were diagnosed with colorectal cancer in our hospital. A total of 154 patients with UC were reviewed. Results: Six cases (four men and two women) of CRC were identified. The overall incidence of CRC was 3.9% (6/154) at follow-up. In this group, the mean age of UC diagnosis was 39.8 years and CRC diagnosis were 50.8 years. The median duration of developed CRC after UC diagnosis was 11 years. There were five patients with extensive colitis and one patient with left-side colitis. The presence of primary sclerosing cholangitis was in one patient. All of these six patients had been treated with 5-aminosalicylic acid (5ASA) and steroids before. The location of CRC was 16.7% (1/6) at ascending colon, 33.3% (2/6) at sigmoid colon and 50% (3/6) at rectum. The CRC clinical stage was 33.3% (2/6) for stage I, 16.7% (1/6) for stage IIA, 16.7% (1/6) for stage IIIB and 33.3% (2/6) for stage IIIC. Conclusions: We describe our experience of patients with colitis-associated cancer. The majority of patient developed colitis-associated cancer after long disease duration. Most of the patients were diagnosed at advanced stage and more intensive colonoscopy surveillance is required.

P.062

運用深度學習偵測結腸息肉的內視鏡影像 DETECTION OF ENDOSCOPIC IMAGES OF COLONIC POLYPS WITH DEEP LEARNING

顏聖烈1 賴冠廷2 林國祥2 彰濱秀傳紀念醫院肝膽腸胃科1 國立勤益科技大學資訊工程學系2

Background: Adenomatous polyps are considered the precursor lesions for colon cancer, and adenoma detection rate has been considered as an important quality indicator of colonoscopy. However, histology of small polyp cannot be reliably differentiated with white light colonoscopy, although image-enhanced endoscopy (narrowing band imaging or blue laser imaging) may be helpful. Aims: To evaluate the usefulness of deep learning algorithms on the classification of endoscopic images of small colonic polyps. Methods: From October 2019 to December 2020, patients who underwent colonoscopy examination due to lower gastrointestinal symptoms and screening for colorectal cancer were included. All included patients were found to have small colonic polyp (≤ 5mm) and underwent magnified blue laser imaging (BLI) examination before polyp removal. Obtained magnified BLI images were analyzed based on deep learning using MobileNetV3. Results: A total of 185 colonic polyps were included in the study. There were 94 tubular adenoma and 91 hyperplastic polyps. Fifty eight endoscopic images in tubular adenoma group and 55 images in hyperplastic polyp group were used for training and 18 endoscopic images in each group were used for validation. The remaining 18 images in each group were used for testing. By using MobileNetV3, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of detecting endoscopic images of tubular adenoma were 94.1%, 89.5%, 88.9%, 94.4% and 91.7%, respectively. Conclusions: Our study showed that deep neural network using MobileNetV3 is useful in detecting endoscopic images from patients with small colonic polyps. P.063

結腸直腸癌肝轉移小鼠模型的建立 DEVELOPMENT OF A LIVER METASTATIC MOUSE MODEL OF COLORECTAL CANCER

陳席軒1,2 張經緯1 劉家源1 陳銘仁1 許益超2 陳裕仁3,4 馬偕紀念醫院胃腸肝膽內科1 馬偕醫學院生物醫學研究所2 馬偕紀念醫院放射腫瘤科3 馬偕醫護管理專科學校4

Background: Colorectal cancer is the 3rd most diagnosed cancer worldwide. About half of the patients with colorectal cancer will have a synchrous or metachronous metastatic liver lesion in the course of the disease. Aims: To develop a liver metastatic mouse model of colorectal cancer for further basic research and possible clinical application. Methods: We use immunocompetent BALB/c male mice as the experimental animal, with a mouse colorectal cancer cell line CT-26 and a laparotomy technique of portal vein injection, to develop a liver metastatic mouse model of colorectal cancer. Results: We found that 1x10˄5 cells per injection is an optimal dose for portal vein injection in this model. After a series of practices and modifications, the mouse mortality rate after operation could be decreased from 42.3% to 19.4%, and the successful inoculation rate could be increased from 30.1% to 75.0%. Conclusions: Therefore, we established a stable mouse model for study of liver metastasis in colorectal cancer.

P.064

無害梭菌在發炎性腸道疾病患者扮演的角色 CLOSTRIDIUM INNOCUUM INFECTION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

李柏賢1 郭家榮1 邱正堂1 邱政洵2 蘇銘堯3 林口長庚紀念醫院胃腸肝膽科1 林口長庚紀念醫院兒童胃腸科2 新北市立土城醫院胃腸肝膽科3

Background: Clostridium innocuum (CI) is an anaerobic, gram-positive, spore-forming bacterium. It can lead to extraintestinal infection and C. difficile infection-like antibiotic-associated diarrheal illness. Aims: At present, no clinical study has evaluated the role of CI infection in inflammatory bowel disease (IBD). Methods: In this retrospective cohort study, we enrolled hospitalized IBD patients with culture results for both CI and Clostridioides difficile (CD) in a 3700-bed medical center between October 2019 and April 2021. We analyzed the risk factors, clinical presentations, and outcomes by comparing the CI (CI+/CD−) and control (CI−/CD−) groups. Results: We enrolled a total of 90 patients, including 22, 39, 13, and 16 patients in the CI, control, coinfection, and CD groups. The incidence rates of CI (CI+) and CD (CD+) were 39% (35/90) and 32% (29/90), respectively. We analyzed the differences between CI and control groups. We then identified the use of steroid (77.3% vs. 46.2%, P = 0.018) and 5-aminosalicylic acid (90.9% vs. 64.1%, P = 0.022) as risk factors of CI infection. Results showed that more patients in the CI group presented with bloody stool (77.3% vs. 51.3%, P = 0.046). Although CI group had significantly lower overall occurrence of intraabdominal abscess (0% vs. 17.9%, P = 0.042), it showed a lower clinical remission rate (50% vs. 87.5%, P = 0.044) and higher Mayo score at the end of follow-up (10 points vs. 3 points, P = 0.008) in ulcerative colitis. Conclusions: CI infection may lead to a poorer clinical remission in ulcerative colitis. We should take it into consideration in IBD patents with active inflammation or vancomycin-refractory CD infection. Precise identification of CI is imperative to guide appropriate antimicrobial therapy because of its intrinsic vancomycin resistance nature. P.065

晚期結直腸癌患者 ”核酸錯配修復蛋白” 免疫組織化學染色分析 IMMUNOHISTOCHEMISTRY ANALYSIS OF DNA MISMATCH REPAIR PROTEINS IN PATIENTS OF ADVANCED COLORECTAL CANCER

林世俊1 洪宗義1 張麗文1 劉玉華1 孫灼基1 楊國卿1 林裕民1 新光吳火獅紀念醫院胃腸肝膽科1

Background: Telling colorectal cancer (CRC) of highfrequency microsatellite instability (MSI-high) from microsatellite stable neoplasm (MSS) are important in understanding the tumorigenesis, identifying hereditary Lynch syndrome, selecting efficient treatment and predicting prognosis. The report of MSI status in CRC remained limited in Taiwan. Aims: We aim to understand the presentation of DNA mismatch repair proteins (MMR) to judge the MSI status in advanced CRC. Methods: We acquired data from “Oncology Case Management System” in a single hospital to evaluate key characteristics of MSI-high and MSS CRCs. Immunohistochemistry (IHC) staining for MMR proteins including MLH1, MSH2, MSH6 and PMS2 were applied in advanced CRC (Stage II to Stage IV). Tumors with any deficient staining of these 4 proteins were recorded as MSIhigh neoplasms. The differences of features between MSIhigh and MSS are determined by Chi-squared test. A p value <0.05 is considered as significant. Lynch syndrome was suspected in patients if they met the revised Bethesda criteria. Results: A total of 407 advanced CRCs were enrolled for analysis. MSI-high was detected in 40 patients (9.8%). The staining of MLH1, MSH2, MSH6 and PMS2 were deficient in 70%, 5%, 10% and 85% of these 40 MSI-high patients. The distributions of age and gender revealed no significant differences between MSI-high and MSS individuals. Comparing to those of MSS; patients of MSI-high were associated with higher proportion of proximal location of CRC (Proximal CRC of MSI-high : MSS = 80.0% : 31.3%; p<0.01). There were 5 patients (12.5%) met the revised Bethesda criteria that were highly suspicious for Lynch syndrome among MSI-high CRCs. Conclusions: MSI-high colorectal cancer is not uncommon in Taiwan. Our results suggest routine IHC tests of the MMR on all newly diagnosed CRC should be implemented clinically, thus may improve our abilities to appropriately manage these unique patients.

P.066

妙利散對於大腸瘜肉的臨床效果 THE CLINICAL APPLICATION OF CLOSTRIDIUM BUTYRICUM MIYAIRI FOR PEOPLE WITH COLORECTAL POLYPS

吳秉儒1 許文鴻1,2,3 余方榮1,2 吳孟杰1,4 吳登強1,2 王俊偉1,2 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學醫學系2 高雄巿立小港醫院內科3 高雄巿立大同醫院內科4

Background: Among so many different types of colorectal polyps, adenomatous polyp plays an important role of developing colorectal cancer. Lately more and more researches have revealed the association between the colon cancer and gut microbiota. And gut microbiota is influenced remarkably by dietary behavior. However, there’s no conclusive evidence that whether probiotics can modify gut microbiota flora. Aims: The aim of this study is to access the effect of probiotic on preventing adenoma recurrence and in advance to reduce colorectal cancer risk. Methods: Total we enrolled 381 patients who was diagnosed with colon polyps at the initial colonoscopy and randomly divided into two groups (group A : first year to receive Miyarisan and second year with observation; group B: first year with observation and second year to receive Miyarisan, both group patients should receive colonoscopy at the end of year one and year two.) Results: Finally group A had 44 patients and group B had 33 patients completed the study protocol. In the first year following up, group A showed lower rate of adenoma recurrence than goup B. At the second year, group B who received Miyarisan regimen showed lower rate of adenoma than the same group in year one who kept observation.(fail to reach statistic significantly but p-value is 0.056). Conclusions: Therefore, Miyarisan consumption perhaps can lower the risk of adenoma recurrence rate. But more prospective studies are required to confirmed these connection. P.067

水果酵素應用於黑腸症病人的菌相表現 - 研 究初報 FRUIT ENZYME AFFECTS THE SPECTRUM OF GUT MICROBIOTA IN PATIENTS WITH MELANOSIS COLI- A PRELIMINARY REPORT

何東翰1 薛聖潔1 卓庭毅1 張智翔1,2 吳明順1,2 粟發滿1,2 臺北市立萬芳醫院消化內科1 臺北醫學大學醫學院內科學科2

Background: Melanosis coli is a disorder of pigmentation which the lining of the colon turns a shade of black or brown. The mechanism may be explained by the cells in the colon are destroyed and an excess of the pigment lipofuscin is produced. Generally speaking, melanosis coli is a benign condition and may have no significant correlation with other disease. However, those patients with melanosis coli usually represent chronic constipation in clinical with longterm laxative use. Since fruit enzyme could help digestion and may change distribution of gut microbiota theoretically, we would like to know if the spectrum of gut microbiota in patients with melanosis coli changes and if constipation improves after taking fruit enzyme. Aims: 1)To analyze the differences of the spectrum of gut microbiota between three groups (health, pre-treatment, post treatment). 2)To monitor if constipation improves after taking fruit enzyme. Methods: Between January 2021 and July 2021, a total of 10 patients between 20 to 75 years old with melanosis coli, chronic constipation and long-term laxative use for more than 5 years was included in this study. Each of them took comprehensive digestive enzyme supplements liquid, which fermented from fruits and vegetables, 30ml twice daily for 1 month. No antibiotics or probiotics/prebiotics was taken during study. Stool samples and questionnaire of clinical symptoms were collected before and after taking supplements liquid. Gut microbiotas were analyzed with NGS (Next generation sequencing). Statistical analyses to relative abundance, alpha and beta diversity of spectrum of gut microbiota between three groups were performed. Results: Comparison of relative abundance of gut microbiota between three groups showed no significant difference. Alpha diversity of gut microbiota in Shannon index showed no significant difference between three groups, but showed lesser diversity in pre-treatment group in Simpson index. Beta diversity was analyzed by PCoA (Principal Co-ordinates Analysis), which showed more

similar between health and post-treatment group, however, it was no significant difference in statistic. Change of individual gut microbes between pre-treatment and posttreatment groups showed increased Anaerostipes hadrus and decreased Roseburia intestinalis. Conclusions: In this study, we found the trend that Alpha diversity of gut microbiota seemed increasing after taking fruit enzyme and also Beta diversity became more similar to health group. Even though most of the data showed no significant difference in statistic, most of the participants announced that constipation improved after taking fruit enzyme. The number of Anaerostipes hadrus, which may protect against colon cancer by producing butyric acid, increased in post-treatment group. On the other hand, the number of Roseburia intestinalis, which may be associated with several diseases (irritable bowel syndrome, obesity, Type 2 diabetes mellitus, allergies etc.), decreased after taking fruit enzyme. The limitations of this study are less numbers of participants, short duration of fruit enzyme usage and less times of stool collection. Further large study of spectrum of gut microbiota after fruit enzyme usage may provide more promising data. P.068

經電腦斷層診斷之急性憩室炎，是否需要常 規安排大腸鏡檢查？ SHOULD WE PERFORM COLONOSCOPY ROUTINELY AFTER COMPUTED TOMOGRAPHY- DIAGNOSED ACUTE DIVERTICULITIS?

李庚頷1 李騏宇1 黃詩婷1 林揚笙1,2 陳銘仁1 馬偕紀念醫院胃腸肝膽科1 臺北醫學大學臨床醫學研究所2

Background: Colonoscopy after resolution of acute diverticulitis (AD) is recommended concerning misdiagnosis of colorectal cancer (CRC). With the enhanced accuracy of radiology exam in the recent decade, computed tomography (CT) diagnosed most of the AD correctively. Aims: We aim to evaluate the need for colonoscopy after CT-diagnosed AD in current circumstance. Methods: Patients with CT-diagnosed AD were enrolled in the study. We recorded the location of AD based on CT, location of polyp/adenoma/carcinoma on colonoscopy if available. Results: 81 patients with CT-diagnosed AD and had received colonoscopy from Jan-01-2018 Jan. to Dec-312020 were retrospectively collected in this study. Average age was 56.5-year-old, and 38.2% were male (31/81). Incidence of CRC and adenoma are 2.47% (2/81) and 19.75% (16/81), respectively. Age(P=0.029) was a risk factor for CRC and adenoma. Conclusions: In CT-diagnosed AD, routine colonoscopy for detecting misdiagnosed CRC is unnecessary in most cases. However, advanced age is at risk of CRC.

P.069

THIOPURINE-METHYLTRANSFERASE (TPMT) 和 NUDIX HYDROLASE-15 (NUTD -15) 的基因多態性在潰瘍性結腸炎 的盛行率：台灣中部的一間醫學中心的研究 統計 THE PREVALENCE OF THIOPURINEMETHYLTRANSFERASE AND NUTD15 IN PATIENT WITH ULCERATIVE COLITIS: A HOSPITAL-BASED STUDY IN CENTRAL TAIWAN

吳宜樺1 黃柏儒1 鄭庚申1 周仁偉1 林俊哲1 中國醫藥大學附設醫院1

Background: Thiopurine S-methyltransferase (TPMT) is a cytosolic enzyme involved in the metabolism of these thiopurine drugs. Methylation of thiopurine drugs by TPMT competes with the formation of their active 6-thioguanine nucleotide metabolite, thereby potentially modulating the therapeutic and toxic effects of these drugs. Polymorphisms in TPMT and Nudix hydrolase-15 (NUDT15) have been implicated as the predominant cause of thiopurine induced leukopenia in the Western countries and East Asia respectively., but the frequency of the risk alleles is low in Asians. Recently, a variant in the NUDT15 was reported to be associated with early severe leukopenia in Asians. Exact role of these polymorphisms in Taiwan population with ulcerative colitis (UC) is uncertain. Aims: The aim of this study was to investigate the prevalence of TPMT and NUDT 15 variants and other characteristics in patients with UC in central Taiwan. Methods: A total of 172 consecutive patients with UC, regularly seen at the outpatient unit of the Division of Gastroenterology at the China Medical University Hospital, a tertiary referral center in central Taiwan, were enrolled in this study from January 1980 to December 2021. Clinical characteristics of patients with UC including gender, age at diagnosis, disease phenotype and behavior were collected. We used polymerase chain reaction-restriction fragment length polymorphism method to determine the allelic frequencies of TPMT and NUD15 variants in UC patients. Results: A total of 172 patients with UC were enrolled into our current study. The mean diagnostic age of these enrolled patients was 46.1 years (ranging from 21 years to 75 years old). Male accounted for the majority of all patients in our present study (64.5%). Among these 172 patients with UC, TPMT variants were tested in 138 patients, which showed the allelic frequencies of TPMT*1 were 98.5% (136/138) for patients with UC. The allelic frequencies of TPMT*3C were 1.5% (2/138) for patients with UC. No TPMT*2, 3A, 3B, 3D and 4-8 were found in these populations. In addition, NUD15 was tested in 123 patients, which showed normal metabolizer in 109 patients (88.6%, 109/123), intermediate metabolizer in 14 patients (11.4%, 14/123), and poor metabolizer in 0 patient (0%, 0/123). Conclusions: NUDT15 polymorphism was more frequent than TPMT polymorphisms and was associated with thiopurine induced leukopenia. The measurement of NUDT15 can increase the safety of thiopurine dramatically and is a successful example of personalized medicine in the field of UC. Phenotypic TPMT and NUDT15 analysis could be useful to better manage UC therapy with thiopurines.

P.070

使用 INDOMETHACIN 塞劑下造成逆行性 膽胰管攝影術後之急性胰臟炎及其併發症之 危險因子分析 THE RISK FACTORS OF POST-ERCP PANCREATITIS AND COMPLICATIONS UNDER RECTAL INDOMETHACIN ADMINISTRATION

李騏宇1 林慶忠1 朱正心1 陳志仁1 洪建源1 賴建翰1 林相宏1 臺北馬偕紀念醫院1

Background: Rectal indomethacin administration were the standard method to prevent post-ERCP pancreatitis(PEP), but there were some risk factors exist. Aims: We designed this retrospective study to detect the risk factors of PEP and complications under rectal indomethacin administration and compare the side-effects between singledose and double-dose rectal indomethacin treatment. Methods: We enrolled patients who underwent the ERCP with indomethacin administration in Taipei Mackay Memorial Hospital from 2016 Jun. to 2017 Dec. The patient related baseline parameters, ERCP indication and findings, ERCP related procedures, outcome and complications were included. The primary endpoint was the risk factors of PEP under indomethacin treatment. Results: A total 168 patients were included in this study, and there were 90 patients were assigned to the single-dose group, and 78 patients were assigned to the double-dose group. Concerning the PEP risk factors, there were no difference in sex, age, weight, benign biliary stricture, sphincter of Oddi dysfunction and periampullary diverticulum. There was significant difference in some of the ERCP related procedure to induce PEP including difficult cannulation(p=0.020), precut procedure(p=0.026), show pancreatic duct image(0.020) and mean procedure time(p=0.011, Table 2). About the outcome and complications, there was no difference between single-dose and double-dose rectal indomethacin treatment. The Odds ratio of these risk factors reveals that show p duct image and difficult cannulation is 4.17, pre-cut procedure is 5.35 and the procedure time more than 30 minutes is 7.07. Conclusions: Although rectal indomethacin administration decrease ERCP related PEP down to 6.5% in this study, but there are some procedure related risk factors such as difficult cannulation, pre-cut procedure, show p duct and long procedure time, so early to use pancreatic sphincterotomy and avoid showing p duct and no do more than 30 minutes maybe can reduce the PEP evens. P.071

預防內視鏡逆行性膽胰管攝影後的胰臟炎： 從實證指引到臨床應用 PROPHYLAXIS OF POST-ERCP PANCREATITIS: FROM EVIDENCEBASED GUIDELINES TO CLINICAL PRACTICE IN REAL WORLD

曾子寧1 梁志明1 邱逸群1 盧龍生1 吳鎮琨1 蘇輝明1 郭仲煌1 蔡成枝1 郭仲謀1 高雄長庚紀念醫院腸胃科1

Background: Endoscopic retrograde cholangiopancreatography (ERCP) remains one of the most risky endoscopic techniques. Pancreatitis is the most common serious complication of ERCP. Post-ERCP pancreatitis (PEP) occurs in 6-16% of unselected patients. Even for experienced endoscopists, PEP is an unpredictable event. The European Society of Gastrointestinal Endoscopy (ESGE) and American Society of Gastrointestinal Endoscopy (ASGE) published guidelines on PEP prevention in 2014 and 2017, respectively, where both patient- and procedure-associated risk factors are identified, and prophylaxis methods are evidence-based and recommended. In 2018, we start to apply the high quality strategies for decline the PEP rate. Aims: In this study, we aim to analyze the discrepancy of ERCP complications after the conducting intensive evidence-based guidelines Methods: We retrospectively enrolled 424 endoscopic retrograde cholangiopancreatography (ERCP) patients diagnosed with acute cholangitis and choledocholithiasis between Jan, 2010 and February 2020 at a single hospital. The intervention group was adopted with prevention strategies to reduce adverse effects of ERCP, such as guidewire-based selective cannulation, long-term dilatation (at least 3 minutes) during papilla balloon dilatation, pancreas duct stenting if pancreas cannulation for more than 2 times, the use of rectal indometacin 100mg, and Lactate Ringer aggressive hydration. They were then divided into control group (enrolled from January 2010 to Dec 2013, N=286) and interventional group (enrolled from September 2018 and February 2020, N=138). We excluded the difficult CBD stones larger than 1.5cm. The enrolled patients were randomly matched at a 2:1 ratio using propensity score together with age and sex with the Number Cruncher Statistical System statistical software. After propensity score matching, there were 224 and 117 patients in the control and interventional groups,

respectively Results: The baseline characteristics and endoscopic findings were comparable between control and interventional groups. The rate of pancreas duct stent in place was higher in interventional group than control group (12.0% vs 0.9%, P <0.001 ). The rate of rectal indometacin 100mg was used in 67.5% (79/117) in the patients of interventinal group. The success rate of complete stone extraction was similar between the groups (93.3% vs 94.0%, P = .807). Additionally, the complication rates were comparable between the control group and interventional group (bleeding, 1.8% vs 0.9%, P = .479; pneumonia, 2.2% vs 0.9%, P = .358; perforation, 0.4% vs 1.7%, P = .639; and mortality in 30 days, 1.8% vs 0%, P = .146). There was significantly lower post-ERCP pancreatitis rate in the interventional group comparing with control group (4.3% vs 11.6%, P = .025). Conclusions: Conducting intensive strategies for prophylatic PEP was evidently helpful for the patients with ERCP in real warld practice, and enhance patients safety and quality of health care. P.072

年邁急性膽囊炎病患接受經皮膽囊引流術後 之手術預後 SURGICAL OUTCOME OF ELDER PATIENTS LARGER THAN EIGHTY YEARS OLD WITH ACUTE CHOLECYSTITIS AFTER PERCUTANEOUSLY CHOLECYSTOSTOMY

潘鈺聆1 吳佩珊1,2 李癸汌1,2 黃怡翔1,2 侯明志1,2 臺北榮民總醫院內科部肝膽腸胃科1 國立陽明交通大學醫學院醫學系2

Background: In Tokyo guideline 2018 for acute cholecystitis, it recommended that the patients with acute cholecystitis need immediate cholecystectomy according to disease severity and preoperative factors. Those inoperable patients could receive medical antibiotics treatment or percutaneous cholecystostomy (percutaneous transhepatic gallbladder drainage, PTGBD) first, then arrange surgical intervention after clinical conditions stabilized. In previous studies, PTGBD has been known as a safe and alternative treatment in severe septic patients or patients with serious comorbidities not responding to conservative treatment and/or unfit to undergo surgery. However, there is unclear when the subsequent cholecystectomy is better and the clinical predictors of outcomes for patients elder than 80 years old with acute cholecystitis treated with PTGBD. Aims: The purpose of this study aimed to investigate the outcomes of patients larger than 80 years old who underwent PTGBD for acute cholecystitis. Methods: One hundred and fifty-six consecutive elder patients with acute cholecystitis receiving PTGBD followed by cholecystectomy in Taipei Veterans General Hospital from January 2008 to February 2021 were enrolled and analyzed retrospectively. The outcomes, complications and durations of PTGBD insertion and surgery were analyzed. Results: Among these cases, the mean of ages was 84.3 (+/- SD 3.4) years old. There were 139 patients with ASA grade III and 17 patients with ASA grade IV. One hundred and twelve patients were grade II and 44 patients were grade III by severity grading of Tokyo guideline. The most common comorbidities were hypertension (65.4%), diabetes mellitus (38.5%), and history of malignancy (17.3%). All of the patients received successfully performance of PTGBD. Among the elder patients, most of the laboratory data after PTGBD have significantly improvement in comparison of that before PTGBD. Seventy of them (44.9

%) received laparoscopic cholecystectomy (LC) and 86 patients (55.1%) received open cholecystectomy (OC) after resolution of acute cholecystitis. Twenty-three patients (14.7%) received conversion surgery from LC to OC. In patients receiving subsequent cholecystectomy within four weeks after PTGBD, significantly higher rate of concurrent cholangitis was noted (23.8% vs 10.5%, p = 0.034) and higher proportion of the patients received OC (73.8% vs. 48.2%, p=0.004). The severity, operation time, conversion rates, operative complications were not different between the patients receiving cholecystectomy early than 4 weeks or later than 4 weeks. However, the occurrence rates of recurrent acute cholecystitis or other biliary events were significantly higher in patients receiving cholecystectomy 4 weeks after the PTGBD insertion (9.5% vs 41.2%, p <0.001). Conclusions: In patients elder than 80 years old with acute cholecystitis and PTGBD, high conversion rate of LC to OC was noted. Early surgery had a higher rate of OC and later cholecystectomy had a higher rate of recurrent biliary tract events. P.073

台灣新型冠狀病毒爆發期間之三級警戒暨醫 療降載對內視鏡逆行性膽胰管攝影術檢查治 療之影響：單一醫學中心之回溯性研究 THE IMPACT OF COVID-19 ON ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY DURING THE OUTBREAK IN TAIWAN: A SINGLE CENTER RETROSPECTIVE STUDY

李佳儒1 陳宥任1 張天恩1,2,3 張乃文4 侯明志1,2 黃怡翔1,2

李沛璋1,2 臺北榮民總醫院內科部肝膽胃腸科1 國立陽明交通大學醫學院2 臺北榮民總醫院內視鏡診斷暨治療中心3 臺北榮民總醫院放射線部4

Background: The COVID-19 outbreak began 2019 has already significant influenced the clinical practice of endoscopic procedure worldwide. Due to meticulous management and policy, Taiwan had relatively regular clinical endoscopic procedure practice until the COVID-19 outbreak in May 2021. The Level 3 epidemic alert was announced since 16th, May 2021. The elective medical services including endoscopic procedures were reduced simultaneously. Whether urgent endoscopic procedure affected by the pandemic seems to be controversial. Aims: This study, is aimed to study the influence of commanded medical service scaling-back on the ERCP, including time interval to ERCP and clinical outcomes during the outbreak of COVID-19 in Taiwan. Methods: This retrospective cohort study included patients underwent ERCP during the period of 16th May to 26th July, the Level 3 epidemic alert announced period, at a tertiary center in Taiwan. Hospitalization days, clinical presentations, and outcomes were compared with those who from the same period in 2019. Results: This retrospective cohort study included patients underwent ERCP during the period of 16th May to 26th July, the Level 3 epidemic alert announced period, at a tertiary center in Taiwan. Hospitalization days, clinical presentations, and outcomes were compared with those who from the same period in 2019. Results No significant reduction of case numbers of ERCP during the period between 16th May 26th July. Initial laboratory tests revealed total bilirubin (4.12mg/dL in 2021 versus 3.08 mg/dL in 2019, p=0.014), GGT (378U/L in 2021

versus 261U/L in 2019, p=0.009), and ALKP (254 U/ L in 2021 versus 174 U/L in 2019, p=0.002) were higher in 2021 compared to 2019. Also, hospitalization days showed statistically significant longer in 2021 (11days, [7.00,22.00]) than in 2019 (8days, [6.00,12.00]), p value = 0.002. Furthermore, multivariate analysis revealed patients who had longer hospitalization days in 2021 tended to have hepatobiliary malignancy (31.6% versus 5.1%, p=0.043) or biliary tract stone history (44.7% versus 33.3%, p=0.009). Increased patient referral was also showed during the outbreak. (9.8% in 2019 versus 26.0% in 2021, p=0.022). Patients referred from other local hospitals tend to have higher inflammatory markers than patients from ER or outpatient-department, including WBC(11100 / cumm versus 10500/cumm versus 5900/cumm, p=0.015) and CRP(9.42 mg/dL versus 7.15 mg/dL versus 1.76 mg/dL, p=0.006). Procedure related complications and post treatment laboratory tests before discharge showed no statistical difference between 2019 and 2021. Conclusions: In this study, patients from 2021 16th May to 26th July had longer hospitalization days and higher biliary tract enzyme level, which indicating more severe disease. Nevertheless, post ERCP lab data also reported improved biliary tract enzymes and inflammation markers without increasing complication rate during the COVID-19 outbreak. P.074

新冠肺炎疫情對於轉移性胰臟癌病人之影響 THE COVID-19 PANDEMIC EFFECTS ON PATIENTS WITH METASTATIC PANCREATIC CANCER

李君陽1 李重賓1 臺北榮民總醫院1

Background: The outbreak of COVID-19 pandemic has significant impact in medical resource allocation in many countries. Recent studies implied that COVID-19 pandemic affects the diagnosis and prognosis in many cancers. Aims: We aimed to assess the influence on patients with metastatic pancreatic cancer with COVID-19 pandemic. Methods: This retrospective cohort study included patients who were newly diagnosed with metastatic pancreatic cancer during January 1, 2018 to December 31, 2020 at Taipei Veterans General Hospital. All patients were followed up until death or December 31, 2021. Patients without histologic proof and with neuroendocrine tumors were excluded. We enrolled 251 patients with metastatic pancreatic cancer and divided those patients into two groups: 2018-2019 (pre-COVID) and 2020 (COVID). Overall survival (OS) was estimated using the KaplanMeier method and compared by the log-rank test. Results: In this study, there were 167 patients in the preCOVID cohort and 84 patients in the COVID cohort. The OS was borderlinely longer in the -COVID period. (median 6.0 months in the COVID cohort vs 6.1 months in the preCOVID cohort). The baseline demographics showed a significantly higher proportion of gemcitabine plus nabpaclitaxel(88.2% in the COVID cohort and 43.2% in the pre-COVID cohort, p < 0.001) and lower proportions of FOLFIRINOX (1.5% in the COVID cohort and 20.5% in the pre-COVID cohort, p < 0.001) and gemcitabine (4.4% in the COVID cohort and 22.0% in the pre-COVID cohort, p = 0.001) as 1st line chemotherapy for patients with metastatic pancreatic cancer in the COVID cohort. Conclusions: Patients with pancreatic cancer in Taiwan where COVID-19 is relatively well controlled did not showed a poor OS after the COVID-19 pandemic breakout. In contrary, it disclosed a tendency of a better survival outcome as so far. The use of a newer 1st line of palliative chemotherapy due to National Health Insurance coverage of the nab-paclitaxel from November 1, 2019 in Taiwan may be the major reason.

P.075

膽道塑膠支架置入術或鼻膽管引流術前施行 內視鏡括約肌切開術的效益：一個統合分析 EFFICACY OF ENDOSCOPIC SPHINCTEROTOMY BEFORE BILIARY PLASTIC STENTING OR NASOBILIARY DRAINAGE: A META-ANALYSIS

楊宗杰1,2 吳怡慧2,3 謝秉翰1,2 黃怡翔1,2 侯明志1,2 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學醫學系2 臺北榮民總醫院高齡醫學中心3

Background: It is unclear whether endoscopic sphincterotomy (EST) before endoscopic biliary drainage (EBD) prevents post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). Aims: We conducted a meta-analysis to clarify the efficacy of EST in prevention of PEP following a biliary plastic stent (PS) or nasobiliary drainage (NBD) tube placement. Methods: We searched several electronic databases for studies that compared the effects of EST versus (vs) nonEST in prevention of PEP following a biliary PS or NBD tube placement. Pooled odds ratio (OR) was determined using a fixed or random effects model. The pooled ORs of adverse events (AEs) in the EST group compared with the non-EST group comprised the outcomes. Subgroup analyses based on stent size, indication and location of biliary stricture were performed. Results: Seventeen studies with a total of 3080 patients were extracted. EST reduced the risk of PEP compared with non-EST (4.7% vs 7.8%, OR: 0.460, 95% confidence interval [CI]: 0.319-0.662, p<0.001) following EBD. In subgroup analyses, EST reduced PEP in patients with a small-bore stent (2.6% vs 8.9%, p=0.001), but not of them with a large-bore stent or multiple tubes (p=0.311). EST reduced PEP in patients with bile leak (p=0.047) or biliary stricture (p<0.001), but not of them with acute cholangitis (p=0.674). Except for bleeding (4.1% vs 0.1%, p<0.001), other AEs were not significantly different between the two groups. Conclusions: EST reduces the risk of PEP following EBD in patients with a small-bore stent, bile leak or biliary stricture, but it increases the risk of postprocedural bleeding. P.076

預防性或先發性給予 GABEXATE 滴注是否 能預防 ERCP 術後 PANCREATITIS ？一項 回顧性病例對照研究 PROPHYLACTIC OR PREEMPTIVE GABEXATE INFUSION IN THE PREVENTION OF POST-ERCP PANCREATITIS? A RETROSPECTIVE CASE-CONTROLLED STUDY.

鍾鳳英1 鄭照霖1 張智翔1 吳明順1 粟發滿1 連吉時1 臺北醫學大學臺北市立萬芳醫院消化內科1

Background: Endoscopic retrograde cholangiopancreaticography (ERCP) is a useful diagnostic and therapeutic tool in pancreatico-biliary disease. PostERCP pancreatitis (PEP) is the most common complication and the incidence is as high as 3.47%. Rectal-administered non-steroid anti-inflammatory drug (NSAID) and pancreatic stent placement are two effective methods in prevention of PEP that were strongly recommended in ESGE guideline. Although Gabexate is one of protease inhibitors and is considered as a potential choice to prevent PEP, it is not recommended in ESGE guideline. Recently, new evidence of Gabexate showed that starting infusion of Gabexate more than 30 minutes before ERCP can reduce the incidence of PEP. Hence, the administering timing seems to be an important factor to the effectiveness of Gabexate in prevention of PEP. Aims: In this study, we observe the effect of prophylactic (30 minutes before ERCP) or preemptive (120 minutes after ERCP) Gabexate infusion and development of PEP in a single medical center. Methods: We retrospectively reviewed 1439 patients who received ERCP in Wan Fang Hospital between January 1, 2016 and December 31, 2021. The treatment group included patients who received Gabexate for preventive purpose of PEP. The patients who received Gabexate after developing PEP were excluded. The control group included patients who did not receive gabexate anytime in same admission. Propensity score was applied to matching both groups in Age, gender, Diclofenac suppository and pancreatic stent placement. The incidences of PEP of both groups were calculated. In the subgroup analysis, we further divided the treatment group into two groups who received Gabexate before ERCP or after ERCP. The differences between groups were compared. Results: The baseline characteristics of these patients were as followed, mean age: 68.9±15.5 (17-101) year-

old; M/F: 52.2% to 47.8%; PEP: 75 (5.2%); Diclofenac suppository: 619 (43%), pancreatic stent placement: 155 (10.8%); Gabexate infusion: 128 (8.9 %). The statistics of subgroup analysis with prophylactic and preemptive Gabexate infusion are similar in age (p=0.512), gender (p=0.452), diclofenac suppository (p=0.117) and pancreatic stent placement (p=0.794), however, the development of pancreatitis is significantly lower (p=0.011) in the prophylactic group (1/23, 4.3%) compared with preemptive group (35/105, 33.3%). Conclusions: In comparison with preemptive Gabexate infusion, prophylactic application has significantly lower PEP in this retrospective study. More large-scaled randomized-controlled trial should be conducted for stronger evidence and cost-effective issue. P.077

病例系列報告：膽囊和膽總管結石術中內視 鏡逆行性膽胰管攝影 CASE SERIES REPORT: INTRA-OPERATIVE ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN PATIENTS WITH GALLBLADDER AND COMMON BILE DUCT STONES

張雋威1 唐瑞祥1 黃宏昌2 臺北醫學大學附設醫院內科部消化系1 臺北醫學大學附設醫院消化系外科2

Background: Cholecystocholedocholithiasis is usually managed with laparoscopic cholecystectomy (LC) and pre or postoperative endoscopic retrograde cholangiopancreatography (ERCP). However, patient is either at risk of complications from the common bile duct (CBD) stone while awaiting ERCP, or at the risk of ERCP, and the need of two anesthesia. Single stage LC and intraoperative ERCP (SSLCE) in hybrid operating room offers reduced rates of postoperative pancreatitis, reduced length of hospital stay and reduced cost compared with the two-stage approach. Aims: To evaluate the safety and effectiveness of SSLCE performed in 36 patients, of 28 patients had intraoperative pre-ERCP. Methods: This retrospective study was collected from November 2020 through December 2021, 36 consecutive patients with gallbladder and CBD stone (21 men, 15 women; mean age, 57 years) underwent SSLCE. Results: Technical success rates, complications, and postoperative hospital stay were evaluated. Technical success was achieved in 35 of 36 (97.2%) patients. One patient with delayed postoperative bleeding that need endoscopic hemostasis. No post ERCP pancreatitis was seen. The mean length hospital stay and postoperative length hospital stay were 9 days (2 to 105 days) and 3.4 days (range from 1 to 8 days). Conclusions: Single stage LC and intraoperative ERCP for cholecystocholedocholithiasis removal seems to be a safe and effective method with low complication, reduced length of hospital stay and cost.

P.078

膽胰管鏡輔助下碎石治療困難膽胰管結石： 一醫學中心的經驗 CHOLANGIOPANCREATOSCOPYASSISTED LITHOTRIPSY FOR DIFFICULT BILIARY AND PANCREATIC STONES: EXPERIENCE OF A MEDICAL CENTER

林群凱1 黃文信1 楊其穎1 彭成元1 林俊哲1 林肇堂1 中國醫藥大學附設醫院消化醫學中心1

Background: Difficult biliary and pancreatic stones, including large and/or impacted bile duct and pancreatic duct stones, cystic duct stones, and intrahepatic duct stones cannot usually be treated by conventional endoscopic retrograde cholangiopancreatography (ERCP). Recently, cholangiopancreatoscopy-assisted lithotripsy using electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) provides an alternative modality for ductal clearance. Aims: We aimed to evaluate the clinical outcomes of cholangiopancreatoscopy-assisted lithotripsy in patients with difficult biliary and pancreatic stones. Methods: From April, 2016 to December, 2021, a total of 25 consecutive patients with large and/or impacted common bile/hepatic duct stones (n=10; 40%), cystic duct stones (n=9; 36%), pancreatic duct stones (n=4; 16%), and intrahepatic duct stones (n=2; 8%) undergoing singleoperator cholangiopancreatoscopy-assisted lithotripsy using EHL and/or LL in a medical center were retrospectively analyzed. Stone location, lithotripsy procedure, ductal clearance, and procedural complications were evaluated. Results: Twenty-three (23/25; 92%) patients were successfully treated in 28 (medium 1.2; range 1-3) sessions including LL (n=20) and EHL (n=8) to achieve ductal clearance. Two patients with cystic duct stone and intrahepatic duct were unable to undergo lithotripsy due to difficult anatomy. Adverse events after the procedure occurred in 10 (43%) patients, including fever (n=8) and mild pancreatitis (n=2) without hemodynamic instability, bacteremia or other severe complications. Conclusions: Cholangiopancreatoscopy-assisted lithotripsy is an effective and safe modality for difficult biliary and pancreatic stones. P.079

經胰管壺腹切開術應用於困難膽管插入病人 的胰臟炎預防及臨床結果：一醫學中心經驗 PANCREATITIS PREVENTION AND CLINICAL OUTCOME IN PATIENTS UNDERGOING TRANSPANCREATIC SPHINCTEROTOMY FOR DIFFICULT BILIARY CANNULATION: EXPERIENCE IN A MEDICAL CENTER

吳高明1 莊世杰1 黃文信1 楊其穎1 鄭幸弘1 林群凱1 中國醫藥大學附設醫院消化醫學中心1

Background: Transpancreatic precut sphincterotomy (TPS) is an efficacious option for difficult common bile duct (CBD) access with acceptable post-ERCP pancreatitis (PEP) rate. The effectiveness of rectal NSAID and pancreatic-duct stent as prophylaxis for postERCP pancreatitis (PEP) after transpancreatic precut sphincterotomy (TPS) were uncertain. Aims: We aimed to identify the efficacy of posttranspancreatic precut sphincterotomy (TPS) in difficult bile duct cannulation and the ideal method for preventing post-ERCP pancreatitis (PEP) in a real-world cohort in Taiwan. Methods: Ninety-three patients who met the criteria of difficult cannulation of common bile duct (CBD) and then received TPS in a medical center from January 2018 to November 2021 were retrospectively reviewed. To predict the risk factors and analyze the preventing method for postTPS PEP, their gender, age, ERCP indication, cannulation result and the occurrence of post-ERCP pancreatitis (PEP), and with/without rectal NSAID and pancreatic duct stent placement were assessed. Results: Among total 93 patients, overall cannulation successful rate was 82.8% (77 of 93 patients) and the PEP rate was 16.1% (15 of 93 patients), and the PEP rate in different preventing method showed Group A (with rectal NSAID and pancreatic duct stent; 23.8%, 5 of 21 patients), group B (with rectal NSAID and without pancreatic duct stent; 11.8%, 2 of 17 patients), group C (without rectal NSAID but with pancreatic duct stent; 10%, 4 of 40 patients), group D (without both rectal NSAID and pancreatic duct stent; 26.7%, 4 of 15 patients). The above p-value was 0.321. In the subgroup of post-TPS PEP or not, there is no statistically significant in gender, age, and ERCP indication Conclusions: TPS is efficacious but with higher PEP rate compared with the ordinary cannulation method.

The outcome of using prophylaxis (rectal NSAID and pancreatic-duct stent) for PEP prevention showed no statistically significant difference in our study. There are still no ideal way for preventing post-TPS PEP, and therefore further prospective study is needed to solve this issue. P.080

胰臟癌早期診斷的困難 - 單一醫學中心回溯 性研究 DIFFICULTY IN EARLY DIAGNOSIS OF PANCREATIC CANCER – RETROSPECTIVE STUDY OF A SINGLE MEDICAL CENTER

劉佩嘉1 吳明順1,2 粟發滿1,2 連吉時1,2 張智翔1,2 臺北市立萬芳醫院消化內科1 臺北醫學大學醫學院醫學系內科學科2

Background: The prognosis of pancreatic cancer is poor because of its rapidly growing characteristic and early metastatic potential. Transabdominal ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) are commonly used for detection of pancreatic lesion. However, despite rigorous screening interval and increased physician’s alertness, pancreatic cancer is still frequently missed. Aims: To assess the diagnostic and miss rates of transabdominal US, CT, and MRI for pancreatic cancer, as well as their influences on cancer survival. Methods: We performed a retrospective cohort study in our institution. We searched diagnostic codes via international classification of disease version 10 (ICD-10) system. Patients having related imaging studies before pancreatic cancer diagnosis were included. Electronic charts and images were reviewed. Series treatment modalities, progression free surival (PFS), and overall survival (OS) were collected and analyzed. Results: From 1998/11/1 to 2021/11/30, total 310 patients were diagnosed with pancreatic cancer, either by typical image findings or by definite pathological proof. Patients without related imaging studies (US, CT, MRI) before diagnosis were excluded. After data extraction, total 179 patients were eligible. The miss rates within one year before diagnosis were 45.6% (68/149) for transabdominal US, 6.7% (11/164) for CT, and 25.7% (9/35) for MRI. High miss rate of MRI is due to that MRI was mostly used for examination for equivocal lesion. For patients diagnosed firstly by transabdominal US, the PFS and OS were poorer compared to CT or MRI because of more advanced stages at diagnosis. Conclusions: Successful early detection of pancreatic cancer is still challenging. Regular screening transabdominal US has no benefit on overall survival. One year miss rate of abdominal CT or MRI are still meaningful and couldn’t be ignored. Currently, periodic CT or MRI examinations for high risk patients might be needed.

P.081

單人操作經口膽道內視鏡對於不明原因膽道 狹窄：一醫學中心之經驗 SINGLE-OPERATOR PERORAL CHOLANGIOSCOPY FOR INDETERMINATE BILIARY LESIONS: EXPERIENCE OF A SINGLE MEDICAL CENTER

鄭幸弘1 黃文信1 楊其穎1 莊世杰1 彭成元1 林肇堂1 中國醫藥大學附設醫院消化醫學中心1

Background: Despite advances in pancreaticobiliary imaging and EUS-guided assessment, the characterization of intraductal biliary lesions remains a challenge. Indeterminate biliary lesion is a significant clinical issue in present. In recent years, cholangioscopy has evolved and the availability has increased. Cholangioscopy which facilitates direct visual observation and visually guided tissue sampling, plays an important role in such cases. Aims: The aims of this study is to assess the accuracy of single-operator peroral cholangioscopy to differentiate malignant from benign disease in patients with indeterminate biliary lesions. Methods: A retrospective analysis was performed between 2016 and 2021 at our hospital. Forty-nine patients with indeterminate biliary lesions received cholangioscopy. We reviewed the clinical data of these patients. Results: Forty-nine patients (16 women, 33 men, mean age of 61.8 years, range 39-90 years ) with indeterminate lesions (28 patients with biliary stricture and 21 patients with biliary tumors) underwent cholangioscopy. Indeterminate lesions were located mostly in the hilum. Of 32 patients with a final malignant diagnosis, cholangioscopic impression was malignant in 29 patients (90%) and benign in 3 patient (10%). Of 17 patients with a final benign diagnosis, cholangioscopic impression was malignant in 2 patients (12%) and benign in 15 patients (88%). The overall accuracy of visual impression for differentiating malignant from benign ductal lesions was 89% (44/49). Conclusions: In our experience, cholangioscopy is safe, allows both direct visualization and visually guided tissue sampling, and has better predictive value for excluding or confirming malignancy in patients with indeterminate stricture. P.082

探討老年人之腸胃道及後腹腔腫瘤使用內視 鏡超音波併細針切片術之安全性與有效性 SAFETY AND EFFECTIVENESS OF ENDOSCOPIC ULTRASOUNDGUIDED FINE NEEDLE BIOPSY FOR RETROPERITONEAL AND GASTROINTESTINAL TUMORS IN ELDERLY PATIENTS

賴建翰1 林相宏1 陳銘仁1 林慶忠1 臺北馬偕紀念醫院1

Background: Endoscopic ultrasound with fine needle biopsy (EUS-FNB) is the most useful procedure to obtain tissue samples for confirmation of pancreaticobiliary disease. It was a relative mini-invasive procedure had low complication rate in overall patients. However, there was no study to observe the safety and effectiveness of EUSFNB in elderly patients. Aims: In this study, we aim to evaluate the safety and effectiveness of EUS-FNB in elderly patients, particularly those with comorbidities or who use antithrombotic agents. Methods: We compared the clinical which including the Charlson comorbidity index (CCI) and antithrombotic agents using in elderly patients, tumor factors and EUS characteristics between elderly and younger patients who underwent EUS-FNB in our hospital. Results: Total we enrolled 41 elderly patients > 70 years old who underwent EUS-FNB between April 2019 to January 2021. Most of the elderly patients had high Charlson comorbidity index, and there were 29.3% patients using antithrombotic agents. There were no significant differences in adverse events or cytopathological diagnostic rate between younger and elderly patients. Conclusions: EUS-FNB is a safe and effective diagnostic procedure for elderly patients, even for those with comorbidities or who use antithrombotic agents.

P.083

區域醫院對於惡性腸胃道阻塞置放金屬支架 的經驗 THE CLINICAL EXPERIENCE OF ENTERAL METALLIC STENT FOR MALIGNANT GASTRIC OUTLET OBSTRUCTION IN DISTRICT HOSPITAL

鄭詠霖1 黃彼得1 許政雄2 俞瑞庭3 童綜合醫療社團法人童綜合醫院肝膽胰內科1 童綜合醫療社團法人童綜合醫院腸胃外科2 童綜合醫療社團法人童綜合醫院血液腫瘤科3

Background: Gastric outlet obstruction (GOO) is a frequent feature of advanced gastric and pancreatic carcinoma. Self-expandable metal stents (SEMS) have been utilized for patients who are no candidates for surgical management to bypass the stricture or obstruction site. Aims: The aim of this study is to report our clinical experience with SEMS in the management of gastric and pancreatic carcinoma related GOO. Methods: All patients admitted for management of GOO secondary to gastric or pancreatic adenocarcinoma between August 2019 and June 2020 were collected. Post-stent survival duration, procedure time, technical and clinical success rate were recorded. Results: A total of 4 gastric outlet obstruction patients recieved SEMS management with 3 males and 1 female, and a mean age of 76.5 (range: 73-80 years). There were 2 gastric and 2 pancreatic adenocarcinomas, all with distant metastasis. One gastric antrum adenocarcinoma patient underwent Roux-en-Y jejunostomy that was complicated with recurrent tumor and obstruction. Three patients received chemotherapy with disease progression, while one patient refused further therapy. The median survival of post stenting was 56.2 days (range: 27 – 110 days). The median procedure time were 1 hour 45 minutes (range: 30 minutes to 4 hour). Technical success rate was 100%. Clinical success rate was 100%, with GOO score: 1-2 (clinical success rate were ranking by gastric outlet obstruction scoring system). None of patients suffered any complication or stent dislocation. Conclusions: SEMS are effective in the management of patient with GOO secondary to gastric and pancreatic adenocarcinomas who are not suitable candidates for surgery. Although we had small case number with limited experience as compared to medical centers, our results were not inferior to them. P.084

胃腸道巨細胞病毒感染 CYTOMEGALOVIRUS DISEASES OF THE GASTROINTESTINAL TRACT

李柏賢1 葉柏睿2 吳仁欽3 邱正堂1 蘇銘堯4 林口長庚紀念醫院胃腸肝膽科1 林口長庚紀念醫院兒童胃腸科2 林口長庚紀念醫院病理科3 新北市立土城醫院4

Background: Cytomegalovirus (CMV) infection of the gastrointestinal (GI) tract is fatal in immunocompromised patients. However, very few studies have provided comprehensive analyses and specified the differences in symptoms observed in different parts of the body. Aims: To analyse patient characteristics, clinical manifestations, endoscopic features, treatments, outcomes, and prognostic factors influencing in-hospital mortality of GI CMV disease in a comprehensive manner. Methods: This retrospective cohort study enrolled patients with CMV diseases of the GI tract, confirmed by CMV immunohistochemistry staining, retrieved from the pathology database of a 4000-bed tertiary medical centre between January 2000 and May 2021. Patient characteristics, clinical manifestations, endoscopic features, treatments, outcomes, and prognostic factors were analysed. Results: A total of 356 patients were enrolled, including 46 infected in the oesophagus, 76 in the stomach, 30 in the small intestine, and 204 in the colon. 49.4% patients were immunocompromised, and 24.7% required intensive care unit care. The overall in-hospital mortality rate was 20.8%: CMV enteritis had the highest rate (23.3%). Sixty percent of patients received antiviral treatment, and 16% were administered both intravenous and oral anti-viral drugs (Combo therapy) during the therapeutic course. In patients receiving Combo therapy, the minimal treatment duration was 14 days, the mean durations of intravenous (IV) treatment and overall treatment course were 14.9±7.9 and 39.9±25 days, respectively. Prognostic factors of in-hospital mortality included age (odds ratio [OR] 1.042, 95% confidence interval [CI] 1.005–1.081; p = 0.026), immunocompromised status (OR 9.927, 95% CI 1.575–62.545; p = 0.015), albumin (OR 0.346, 95% CI 0.119–1.001; p = 0.050), platelet (OR 0.993, 95% CI 0.986–0.999; p = 0.027), GI bleeding (OR 6.067, 95% CI 1.611–22.84; p = 0.008), time-to-diagnosis (OR 1.023, 95% CI 1.003–1.044; p = 0.025), and Combo therapy

(OR 0.031, 95% CI 0.002–0.589; p = 0.021). In Kaplan–Meier survival analysis, immunocompetent patients receiving Combo therapy had the best survival curve, and immunocompromised patients receiving non-Combo therapy had the worst survival curve. Furthermore, antiviral therapy (exclusive PO or IV) could not improve the in-hospital mortality, but Combo therapy ≥ 14 days resulted in a better outcome not only in immunocompromised patients but also in immunocompetent patients. Conclusions: CMV GI diseases are not rare in immunocompetent hosts, but have higher mortality rates in immunocompromised hosts. A complete treatment course should be considered for patients with poor prognostic factors. P.085

蘇木素 - 伊紅染色在診斷消化道巨細胞病毒 感染的角色 HEMATOXYLIN AND EOSIN STAINING IN THE DIAGNOSIS OF CYTOMEGALOVIRUS DISEASE OF THE GASTROINTESTINAL TRACT

李柏賢1 葉柏睿2 吳仁欽3 邱正堂1 蘇銘堯4 林口長庚紀念醫院胃腸肝膽科1 林口長庚紀念醫院兒童胃腸科2 林口長庚紀念醫院病理科3 新北市立土城醫院4

Background: Cytomegalovirus (CMV) disease is common and fatal in immunocompromised patients. Accurate diagnosis is crucial for further treatment. However, there is no study evaluating the diagnostic accuracy of Hematoxylin and eosin (H&E) stain and the necessity of immunohistochemistry (IHC) stain in different CMV diseases of the gastrointestinal (GI) tract. Aims: To evaluate the diagnostic accuracy of H&E stain in GI CMV diseases. Methods: In this retrospective study, we enrolled the pathological specimens of GI tract with both H&E and IHC staining results from the pathology database of a 4000bed medical center during January, 2000 and May, 2021. IHC stains were performed duet to clinical physicians or pathologists’ requests. According to H&E staining results, they were divided into suspected CMV infection (HEs) and no clue of CMV infection (HEn) groups. We used IHC staining result as gold standard, and then analyzed the diagnostic accuracy (Sensitivity [SE], specificity [SP], positive predictive value [PPV], negative predictive value [NPV]) of H&E stain. Results: We enrolled 1448 specimens in this study with 467 and 981 in HEs and HEn groups. The SE/SP (%) of H&E stain for the entire tract, esophagus, stomach, small intestine, and colon were 76.1/82.1, 76.1/70, 85.5/71.7, 60/94.2, and 75/87, respectively. The PPV/NPV (%) of the H&E stain in the same order were 58/91.3, 39.3/92, 51.2/93.5, 69.2/91.5, and 68/90.4, respectively. Conclusions: In the patients with high suspicion of CMV GI tract diseases, IHC stain was critical for accurate diagnosis and treatment.

P.086

食道巨細胞病毒感染 RISK FACTORS, CLINICAL AND ENDOSCOPIC FEATURES, AND CLINICAL OUTCOMES IN PATIENTS WITH CYTOMEGALOVIRUS ESOPHAGITIS

李柏賢1 葉柏睿2 吳仁欽3 邱正堂1 蘇銘堯4 林口長庚紀念醫院胃腸肝膽科1 林口長庚紀念醫院兒童胃腸科2 林口長庚紀念醫院病理科3 新北市立土城醫院4

Background: Cytomegalovirus (CMV) esophagitis is the second most common CMV disease of the gastrointestinal tract, and the third leading cause of infectious esophagitis. It is usually diagnosed in immunocompromised patients, but is also seen in immunocompetent patients. Aims: This study aimed to comprehensively analyze risk factors, clinical characteristics, endoscopic features, outcomes, and prognostic factors of cytomegalovirus (CMV) esophagitis. Methods: In this retrospective cohort study, we collected data of patients who underwent esophageal CMV immunohistochemistry (IHC) staining between January 2003 and April 2021 from the pathology database at the Linkou Chang Gung Memorial Hospital. Patients were divided into the CMV and non-CMV groups according to the IHC staining results. Results: We enrolled 148 patients (44 CMV and 104 nonCMV patients). The risk factors for CMV esophagitis were male sex, immunocompromised status, and critical illness. The major clinical presentations of CMV esophagitis included epigastric pain (40.9%), fever (36.4%), odynophagia (31.8%), dysphagia (29.5%), and gastrointestinal bleeding (29.5%). Multiple diffuse variable esophageal ulcers were the most common endoscopic feature of CMV esophagitis. In terms of clinical outcomes, the CMV group had a significantly higher in-hospital mortality rate (18.2% vs. 0%; p<0.001), higher overall mortality rate (52.3% vs. 14.4%; p<0.001), and longer admission duration (median, 24 days [interquartile range (IQR), 11–47 days] vs. 14 days [IQR, 7–24 days]; P=0.015) than the non-CMV group. Acute kidney injury (odds ratio [OR], 174.15; 95% confidence interval [CI], 1.27–23836.21; P=0.040) and intensive care unit admission (OR, 26.53; 95% CI 1.06–665.08; P=0.046) were predictors of in-hospital mortality in patients with CMV esophagitis. Conclusions: The mortality rate of patients with CMV esophagitis was high. Physicians should be aware of the clinical and endoscopic characteristics of CMV esophagitis in high-risk patients for early diagnosis and treatment. P.087

探討以短期糞便微生物移植治療反覆性困難 梭狀桿菌感染之腸道菌叢變化 SHORT-TERM IMPACTS OF RECURRENT CLOSTRIDIUM DIFFICILE INFECTION WITH FECAL MICROBIOTA TRANSPLANTATION THERAPY ON THE GUT MICROBIOTA

蔡佳憲1 翁雅為2 陳文誌1 蔡峯偉1 李昀達1 李沅融3 高雄榮民總醫院胃腸肝膽科1 高雄榮民總醫院感染科2 臺北榮民總醫院玉里分院胃腸肝膽科3

Background: Fecal microbiota transplantation (FMT) has been shown to highly effective in the treatment of recurrent Clostridium difficile infection (CDI). Interest in FMT now expands to other processes with known association to the microbiota, such as antibiotic resistant infections, inflammatory bowel disease, neuropsychiatric disorders and hepatic encephalopathy. Aims: Our study aimed the microbiota change after FMT in patient’s colonization with recurrent CDI. Methods: Patients with recurrent CDI or failure to first line CDI treatment received FMT treatment. Stool samples were collected before FMT treatment and at the end of week 1, week 4 and week 12. We used polymerase chain reaction to amplify the V3-V4 region of the bacterial 16S rRNA gene in stool specimens, and the gene sequenced on Illumina MiSeq platform. Results: Seven patients received FMT treatment for recurrent CDI, and six patients (6/7 = 86%) treated successfully without recurrent after 12 weeks. Three patients who cured CDI after FMT received complete follow-up. FMT therapy resulted in increased relative abundances of Bacteroidetes (P< .001). In contrast, the relative abundance of decreased form Actinobacteria (P <.001). These microbiota changing did not last a long time. There were no significantly different from the relative abundance of all phyla at week 12 and those at baseline. Conclusions: FMT for recurrent CDI had 86% successful rate after a single treatment. Fecal microbiota transplantation therapy can lead to short-term gut microbiota changing. The low recurrent CDI rate after FMT treatment may not be related to microbiota changing.

P.088

雙氣囊小腸內視鏡診斷梅克爾憩室：單一醫 學中心之經驗 MECKEL’S DIVERTICULUM DIAGNOSED BY DOUBLE-BALLOON ENTEROSCOPY: A SINGLE CENTER EXPERIENCE IN TAIWAN

張凱智1 吳宜樺1 黃柏儒1 鄭庚申1,2 周仁偉1,2 中國醫藥大學附設醫院消化醫學中心1 臺灣小腸醫學會2

Background: Patients with Meckel’s diverticulum (MD) are usually asymptomatic; however, some patients present with symptoms, including gastrointestinal bleeding, abdominal pain, intestinal obstruction, and diverticulitis. In the past, MD is difficult to diagnose preoperatively because of the endoscopic inaccessibility. Double-balloon enteroscopy (DBE) is a useful modality in detecting small intestinal disorders Aims: The aim of our present study was to investigate the clinical characteristics, endoscopic features, histopathological findings, treatment methods and outcomes of patients with MD diagnosed by DBE at a single medical center. Methods: From July 2008 to October 2020, we retrospectively collected patients with MD diagnosed by DBE at China Medical University Hospital, a medical center in middle Taiwan. The age, sex, clinical presentations, endoscopic features, histopathological findings, treatment methods, and outcomes of patients were analyzed. Results: A total of 14 patients with MD diagnosed by DBE were enrolled. There were all male patients. The mean age of all patients was 32.3 ± 10.8 years (range: 18-54 years). Gastrointestinal bleeding (78.6%, 11/14) accounted for the major indication of DBE, followed by abdominal pain (28.6%, 4/14), and Crohn’s disease follow-up (7.1%, 1/14). All patients with MD were diagnosed via the retrograde approach of DBE. The diagnostic yield of modalities other than DBE was as follows: capsule endoscopy, 50.0% (1/2); technetium-99 m pertechnetate scintigraphy, 11.1% (1/9); computed tomography, 16.7% (2/12); small bowel series, 0% (0/8); and angiography, 33.3% (1/3). The endoscopic features of MD showed a large ostium in 13 patients (92.9%, 13/14), a small ostium in 1 patient (7.1%, 1/14), and ulcerative lesion in 10 patients (71.4%, 10/14). Surgical treatment was performed in 11 patients (11/14, 78.6%) and conservative treatment was performed in 3 patients (21.4%, 3/14). As for the heterotopic tissue of MD, heterotopic gastric tissue was identified in 3 patients (21.4%, 3/14). Conclusions: Our study showed DBE is a very powerful modality in detecting MD than other conventional modalities. Although symptomatic MD is rare in adults, it should be considered in adult patients presenting with obscure gastrointestinal bleeding in Taiwan.

P.089

在 COVID-19 流行期間使用分類策略延後 低風險靜脈曲張病人接受內視鏡是安全的 TRIAGE POLICY ENGAGED TO POSTPONE ENDOSCOPY FOR PATIENTS WITH LOW-RISK VARICES IS SAFE DURING THE LOCKDOWN PERIOD OF COVID-19 PANDEMIC

陳宥任1 侯明志1,2 楊宗杰1,2 李沛璋1,2 黃怡翔1,2 李發耀1,2 臺北榮民總醫院胃腸肝膽科1 國立陽明交通大學醫學院2

Background: During the COVID-19 pandemic, most of the endoscopic services were electively postponed or suspended. Aims: We aimed to assess the safety of a triage policy in patients receiving esophageal variceal ligation during the COVID-19 pandemic. Methods: Triage policy of endoscopic variceal ligation (EVL) was implemented in our hospital during the lockdown period from 15th May 2021 to 26th July 2021. One experienced gastroenterologist reviewed the priorscheduled list of patients for the EVL prophylaxis program. We compared the clinical characteristics and outcomes with those receiving endoscopy due to esophageal varices from 17th May 2020 to 28th July 2020. Results: Of the 124 patients receiving EVL, a higher percentage of esophageal variceal bleeding (EVB) was noted (9/32, 28.1% vs. 8/92, 8.7%, p=0.006) during the lockdown period in comparison to the normal period. It is due to a higher percentage of EVB in the referrals during the lockdown period (7/9, 77.8% vs. 2/14, 14.2%, p=0.007). Among patients who received prophylactic EVL, 6 of 78 (7.7%) experienced EVB during the normal period, which is no different to 2 of 23 (8.7%) during the lockdown period. Twenty-three patients whose endoscopies were postponed by triage policy due to low-risk or eradicated varices did not experience EVB during the lockdown period. Child-Pughs class C was independent factor predictive of EVB (relative risk 7.674, P=0.004), entering the program of prophylactic EVL was the protective factor of EVB (relative risk 0.158, P=0.004). Conclusions: Entrance into the prophylaxis program does not only decreases risk of EVB but also fosters comprehensive triage to postpone endoscopy during the lockdown period. P.090

黏膜相關淋巴組織淋巴瘤的內視鏡特徵：單 一醫學中心回溯性研究 ENDOSCOPY FEATURES OF GASTRIC MUCOSA-ASSOCIATED LYMPHOID TISSUE LYMPHOMA : A SINGLE CENTER RETROSPECTIVE STUDY

王威翔1 張智翔1 吳明順1 粟發滿1 連吉時1 陳俊男1 臺北醫學大學- 北醫‧萬芳醫院- 內科部- 消化內科1

Background: Primary gastric lymphoma is the most common extranodal site of non-Hodgkin lymphoma, accounting for 5% of gastric malignancies. Mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 38% of the gastric lymphoma, which was the second common etiology followed by diffuse large B cell lymphoma. 90% of the gastric MALT lymphoma is associated with Helicobacter pylori (H.P.) infection and eradication therapy can induce complete remission of low-grade gastric MALT lymphoma in 80% of patients with favorable long-term prognosis. However, the endoscopic features of gastric MALT lymphoma are variable and nonspecific, making it difficult to diagnosis timely. Thus, we performed a retrospective survey of our hospital from 2002 to 2021 to evaluate the endoscopic features of gastric MALT lymphoma. Aims: To evaluate the endoscopic features of gastric MALT lymphoma. Methods: Clinical and endoscopic records of 22 patients with gastric MALT lymphoma were analyzed retrospectively at a single medical center from 2002 to 2021. For endoscopic assessment, the features, locations, Helicobacter pylori infection status and initial endoscopic impression of each subject were retrieved. The endoscopic features were classified as (1) Ulcerative type (2) Superficial type (3) Polypoid type after carefully evaluated the image. Results: Ulcerative type was the predominant feature in patient with MALT lymphoma (59%), followed by superficial type (32%) and polypoid type (9%). Distal stomach was the most common location. Most patients were asymptomatic (41%) and only 32% lesions were suspected malignancy by endoscopy initially. For patients with or without Helicobacter pylori infection, there were no significant difference of endoscopic features between two groups Conclusions: MALT lymphoma should be considered if ulcerative, superficial, polypoid features observed during EGD and multiple biopsies should be performed in order to diagnosis timely.

P.091

對於不明原因消化道出血的病患，使用膠囊 內視鏡與氣囊小腸內視鏡的結果分析比較： 單一醫學中心之回顧性研究 COMPARING VIDEO CAPSULE ENDOSCOPY WITH DEVICE-ASSISTED ENTEROSCOPY IN PATIENTS WITH OBSCURE GASTROINTESTINAL BLEEDING: A SINGLE-CENTER RETROSPECTIVE STUDY

楊世正1 梁志明1 盧龍生1 胡銘倫1 戴維震1 邱逸群1 高雄長庚紀念醫院胃腸肝膽科1

Background: The debate about using video capsule endoscopy (VCE) or device-assisted enteroscopy (DAE) first in patients with obscure gastrointestinal bleeding (OGIB) is not yet closed. Aims: This retrospective study aimed to compare diagnostic yields of OGIB and clinical outcomes of the two approaches. Methods: 117 consecutive adult patients with OGIB that underwent VCE or DAE as the initial examination from January 2017 to December 2020 were enrolled. Electronic records were reviewed. Demographics, indication, findings, completion rates and prognosis were compared. A lesion that was believed to be the source of the bleeding (ulceration, mass/polyp, vascular lesion, visible blood, or others) was considered to be a positive finding. We analyzed the diagnostic yield of VCE and DAE and the etiologies, prognosis of OGIB. Results: VCE and DAE have similar diagnostic yields, at 76.5% (39/51) and 71.2% (47/66), respectively (P=0.652). The most frequent positive findings at VCE were erosions/ulceration (17 patients, 33.3 %) followed by angiodysplastic/vascular lesions (11, 21.6%). The most frequent findings at DAE were erosions/ulceration (20 patients, 30.3 %) followed by angiodysplastic/vascular lesions (16, 24.2%). Of the 99 patients presenting with overt OGIB, 35 had rebleeding during follow-up, the majority (27/35) in the first year. The rebleeding rate at 1 and 3 years was 25.9% and 42.9%, and was significantly different from 11.1% in patients presenting with occult OGIB (P=0.042). 12 patients had a negative study by VCE, and no further bleeding was reported during a median (range) follow-up period of 30 (12-58) months. However, 3 patients (15.8%, 3/19) in case with negative finding on DAE had experienced rebleeding during a median (range) follow-up period of 18 (12-46) months. Conclusions: In this study, we found that VCE and DAE have similar diagnostic yields and erosions/ulceration was the most common reason for OGIB, followed by angiodysplastic/vascular lesions. The likelihood of rebleeding after negative VCE was low, however, most rebleeding episodes occurred within the first 12 months of follow-up.

P.092

運動訓練與益生菌對於腸躁症患者之效益 THE EFFECT OF EXERCISE TRAINING AND PROBIOTICS INTAKE FOR IRRITABLE BOWEL SYNDROME

朝建銘1 趙偉丞2 黃仁杰1 何士奇1 辛政憲1 臺中澄清綜合醫院中港分院腸胃科1 國立中興大學組織工程與再生醫學博士學位學程2

Background: Irritable bowel syndrome is a disease of abnormal intestinal function, and its prevalence rate is as high as about 20%; It’s characterized by abdominal pain or cramps with alternating bowel habit, including bloating, diarrhea or constipation. Because patients with irritable bowel syndrome are often accompanied by a depressed and manic mental state, irritable bowel syndrome has long been regarded as a mental illness rather than a purely physical disease. Recently, probiotics have been proven to have preventive and improved effects on many gastrointestinal diseases, and exercise has also become a feasible and economical treatment for irritable bowel syndrome. Long-term and short-term exercise are also related to the improvement of various psychological indicators. Aims: That is to develop probiotics and exercise patterns that can improve the symptoms of irritable bowel syndrome. Methods: Thirty patients with irritable bowel disease between 20 and 65 years old who have been confirmed by two senior gastroenterology clinicians will be recruited to participate in this year’s study. The subjects will be divided into three groups, each with 10 persons, namely the sports training group, the sports training + probiotics group, and the probiotics group. They will be trained for eight weeks, training twice a week. And twice a day for a total of eight weeks probiotic supplement (Lactobacillus et al, 1.4x1010CFU/pack). Before and after the experiment, the Irritable Bowel Disease Life Scale (IBS-QOL), the Simple Physiological Health Scale (BSRS-5), the Taiwan Activity Amount Questionnaire (IPAQ) and physical fitness test will be performed. This study agreed by institutional review board. Results: Currently, a total of 19 subjects with irritable bowel disease were collected (including 12 women, 7 men, 5 in the exercise training group, 9 in the exercise training + probiotics group, and 5 in the probiotics group, with an average age of 37 years). The questionnaire survey before the study found that the scores of the Irritable Bowel Disease Life Scale were poor (72-83), women had a high tendency to depression (9), and most of the subjects had no exercise habits, normal cardiorespiratory function (54-60), and abdominal muscle weakness (16/minute). After eight weeks of research, the exercise training + probiotics group has all improved in life scale scores (47-51), depression tendency (4), and abdominal muscles (28/minute). Conclusions: Preliminary results show that the combination of exercise training and probiotics can reduce the symptoms of patients with irritable bowel disease, improve the quality of daily life and the strength of the abdominal muscles. In the future, we will continue to collect more subjects to confirm whether there are statistical differences.

P.093

機械流體力對於消化道癌細胞惡性度之影響 MECHANICAL SHEAR FORCE AFFECTS THE MALIGNANCE OF DIGESTIVE TRACT CANCER CELLS

羅寧1 劉忠榮1 施翔耀1 吳宗勳1,2 黃斌3 吳登強1,4 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄巿立大同醫院2 高雄醫學大學生物醫學暨環境生物學系3 高雄醫學大學醫學系4

Background: The mechanical force is a physical signal been known important in regulating cellular physiological responses through changing ion channels and membrane proteins. The metastatic cancer cells encounter shear force, stretch and pressure force during blood shear flow. Aims: To understand how the cancer cells response to the shear flow is interesting. Methods: The high metastatic digestive tract cancer cells, including gastric cancer cell line, MKN45 and AGS, colon cancer cell line SW620 were subjected to the shear flow 20 dyne/cm2 for 0, 5, 60 and 120 min. The cell size, mitochondrial membrane potential, ATP level, and the epithelial-mesenchymal transition (EMT) proteins were investigated. Results: Under shear flow, the cell size of MKN45 and AGS were decrease in contrast to the increased size observed in the SW620. The mitochondrial membrane potential and ATP levels of sheared MKN45 and AGS were not affected, while in SW620 were elevated. In MKN45 and AGS, the western blot revealed that proteins involved in epithelial form, such as Claudin-1, Zonula occludens-1 (ZO-1) and E-cadherin were decreased. As for ß-Catenin, Vimentin, Snail and Twist1, the proteins implicated in mesenchymal transformation were enhanced. In SW620, E-cadherin and ZO-1 were increased. The N-cadherin and Snail were decreased. Conclusions: The present results indicate that shear flow can possibly reduce the malignance of colon cancer cell, while increase the malignance of gastric cancer cells. The more parameters including type of shear flow, treating time and force intensity on cancer malignance can be further investigated. P.094

胃腸道基質細胞瘤：中台灣一醫學中心之經 驗 CLINICOPATHOLOGICAL STUDY OF PRIMARY SMALL BOWEL GASTROINTESTINAL STROMAL TUMORS: A SINGLE INSTITUTE EXPERIENCE IN TAIWAN

黃柏儒1 鄭庚申1,2 吳宜樺1,2 周仁偉1,2,3 中國醫藥大學附設醫院消化醫學中心1 中國醫藥大學2 臺灣小腸醫學會3

Background: Gastrointestinal stromal tumors are common mesenchymal tumors, usually occurring in the gastrointestinal tract. Primary small bowel gastrointestinal stromal tumors are difficult to diagnose preoperatively because of endoscopic inaccessibility. Aims: The aim of the study was to investigate the clinicopathological features of primary small bowel gastrointestinal stromal tumors in Taiwan. Methods: From January 1999 to July 2021, we retrospectively reviewed the medical charts at China Medical University Hospital. Patients who were diagnosed as primary small bowel GISTs via double balloon enteroscopy(DBE) were included into this study. Patients who were diagnosed as primary small bowel GISTs with method of DBE were included into this study. The diagnostic criteria of GISTs were based on the pathological and morphological features as defined by Fletcher et al. Clinical data were obtained from the medical records and from the physicians responsible for patient care. Clinical data abstracted included age, gender, symptoms, tumor size, tumor location, co-mobidity, treatment methods, and outcomes. Results: A total of 37 patients with GIST were enrolled into this study. There were 20 females and 17 males, with a female-to-male ratio of 1.17:1. The mean age was 63.8 years (range, 34-83years). In our present study, as regards clinical symptoms, 33 patients (89%) were symptomatic. They most commonly presented with GI bleeding (28 patients, 78%). Followed by abdominal pain in twenty-one, fever in five, and diarrhea in two, nausea/vomiting in three, and weight loss in one patient. In terms of co-morbidities, 12 of 37 patients (32%) had hypertensive disease, 11 (31%) had chronic kidney disease with or without hemodialysis, 8 (21.6%) had chronic liver disease with or without liver cirrhosis, and three (8%) had diabetes mellitus. Primary

small bowel GISTs involved the duodenum in 15 (40.5%) of 37 patient, the jejunum in 18 (48.6%) of 37 patients, and the ileum 4 in 10.8%. The prognostic grouping of primary tumors, based on tumor size and mitotic activity, immunohistochemical findings . The tumors ranged in size from 3.5 to 34 cm (mean, 9.1 cm). The mitotic activity was variable, ranging from less than 1 to 395 mitotic figures per 50 HPFs (mean, 28; median, 10). CD117 positivity was detected in most of the small bowel GISTs (94.5%, 35/37). CD117 was observed both in the spindle and epithelioid subtypes of GIST in all locations. CD34 was positive in all of the CD117-negative cases. CD34 positivity was documented in 24 (64.8%) of 37 cases. Conclusions: In conclusion, the results of our present study showed primary small bowel GISTs are rare in Taiwan and their diagnosis are usually needs operation. The immunohistochemical staining for different markers has no clear tendency to any particular histologic type or topography. Compared with those reported in other countries, primary small bowel GISTs in Taiwan have the same clinicopathologic and immunohistochemical features. P.095

小腸膠囊內視鏡用聚乙二醇腸道準備時機之 比較效度：一項隨機對照試驗的薈萃分析 COMPARATIVE VALIDITY OF THE TIMING OF BOWEL PREPARATION WITH POLYETHYLENE GLYCOL BEFORE SMALL BOWEL VIDEO CAPSULE ENDOSCOPY: A METAANALYSIS OF RANDOMIZED CONTROLLED TRIALS

陳保中1 陳鵬仁1 林榮鈞1 陳宣位1 楊志偉1 林煊淮1 黃瑋琛1 張肇丰1 施宇隆1 張維國1 謝財源1 黃天祐1 三軍總醫院1

Background: Small bowel capsule endoscopy (SBCE) was introduced into clinical practice in 2001, which played an important role in investigating small bowel illness. Many attempts have been made to augment the clarity of SBCE. Bowel purgatives prior to SBCE is recommended to improve the visibility and diagnostic yield. Aims: The aim of our research is to determine the optimal timing of bowel preparation with polyethylene glycol (PEG) before SBCE. Methods: A systematic search of studies on PEG in bowel preparation for SBCE was conducted mainly in PubMed, Embase, Web of Science and Cochrane Library (up to December, 2021). Our investigations were limited to randomized controlled trials. The odds ratio (OR) of small bowel cleansing quality (SBCQ) of the group ingested PEG >8 hrs versus the group ingested PEG ≦ 4 hrs before SBCE was treated as the primary outcome, whereas the OR of diagnostic yield of the group ingested PEG >8 hrs versus the group ingested PEG ≦ 4 hrs after SBCE comprised the secondary outcome. Results: The meta-analysis included three randomized controlled trials comprising 286 participants in total. The pooled OR of SBCQ in the PEG ≦ 4 hrs arm compared with the PEG >8 hrs arm was 2.649 (95% confidence level [CI]: 1.609 to 4.362, p=0), indicating a improvement in the visibility of small bowel. The pooled OR of diagnostic yield in the PEG ≦ 4 hrs arm compared with the PEG >8 hrs arm showed a significant enhancement (OR: 1.617; 95% CI: 1.012 to 2.586, p=0.045). Conclusions: Bowel purgatives ingestion ≦ 4 hrs prior to SBCE remarkably give a rise to the advancement of SBCQ and DY.

P.096

新診斷口腔癌病人例行性內視鏡檢查：台灣 一個較有效率的篩檢策略 ROUTINE ENDOSCOPIC EXAM AMONG NEWLY DIAGNOSED ORAL CANCER PATIENTS: A COMPARATIVE EFFECTIVENESS STRATEGY IN TAIWAN

陳以勳1 許文鴻2,3 謝慧敏4 吳宜珍1,3 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄巿立小港醫院內科2 高雄醫學大學醫學系3 高雄醫學大學公共衛生學系4

Background: Oral and esophageal cancer are the leading causes of cancer deaths and carry greater economic disease burdens in Taiwan. Both cancers exhibit the highest regional incidence rates in Eastern Asia. Patients with oral cancer are at higher risk of developing second primary esophageal cancer (SPEC) than the general population. However, the consensus on guidelines for screening strategies remains unclear. Aims: This study aimed to examine comparative effectiveness and the stage-shift effect of endoscopic exam among patients with oral cancer. Methods: We identified 45,457 newly diagnosed patients with oral cancer, 2004-2013, and categorized them as screened with endoscopic examination within 180 days or non-screened. Propensity score matching was used to match comparable groups. The study followed each matched patient for at least 5 years and compared detection of incident SPEC and the stage-shift effect of endoscopic exam between screened and non-screened incident oral cancer patients. Cox proportional hazard and competing risk models were analyzed. Statistical analyses were conducted in 2020-2021. Results: Detection of incident SPEC in the screened group was significantly higher than in the non-screened group (hazard ratio: 2.92, 95% confidence interval [CI]=2.293.72). The stage-shift effect from endoscopic exam was found overall in oral cancer patients (odds ratio [OR]: 0.39, 95%CI=0.21-0.70), in particular in advanced-stage patients (OR: 0.25, 95%CI=0.11-0.61), but not in early-stage patients (OR: 0.60, 95%CI=0.26-1.40). Conclusions: This study confirmed that endoscopic exam achieved early detection of SPEC among oral cancer patients. To improve the exam stage-shift effect, patients with oral cancer are encouraged to undergo routine endoscopic screening. P.097

以序列療法治療幽門螺旋桿菌後發生困難梭 菌感染的治療經驗：一個台灣地區醫院之研 究 EXPERIENCE IN THE TREATMENT OF CLOSTRIDIUM DIFFICILE INFECTION AFTER THE TREATMENT OF HELICOBACTER PYLORI WITH SEQUENCE THERAPY: ONE TAIWAN DISTRICT HOSPITAL STUDY

葉欣榮1 方冠傑2,3 高偉育1 唐瑞祥1 張君照1 蘇宜輝2 臺北醫學大學附設醫院內科部消化內科1 屏東枋寮醫院2 明義診所3

Background: There is higher prevalence rate of Helicobacter pylori in South of Pingtung. Sequential therapy has good results for Helicobacter pylori. However, after the treatment is over, a small number of patients will develop a Clostridium difficile infection and diarrhea. They require further antibiotic treatment. Aims: Our goal is to evaluate the proportion of hospitalizations with Clostridium difficile enteritis after antibiotic treatment for Helicobacter pylori by sequential therapy. Methods: After statistics, we found that 720 patients were diagnosed with Helicobacter pylori infection after esophagogastroduodenoscopy receiving sequential therapy ( PPI + Amoxicillin in first week, PPI + Metronidazole + clarimycin in second week ) in Pingtung Fangliao Hospital since January 1, 2019 to September 30, 2021. The ratio of male to female patients is 34% to 66%. Among them, 30 patients are diabetic patients. Finally, total 45 patient had clostridium difficile infection and diarrhea. They are usually admitted to the hospital because of diarrhea, bloody stools, abdominal pain and fever. Diagnosis is mainly based on positive GDH and toxicity tests in stool, or pseudomembranous colitis found in colonoscopy and capsule endoscopy images. They all received treatment in hospital. Among them, 20 had history of receiving Helicobacter pylori treatment within one week to three months before hospitalization. Then these 20 patients are enrolled in this statistics. Results: According to the results of the health insurance C-13 urea breath test after helicobacter pylori eradication by sequential therapy, the success rate in Pingtung Fangliao hospital was 82.3%. But we found that about 2.78% patient had clostridium difficile colitis after helicobacter pylori

eradication. The most common symptoms are diarrhea, abdominal pain, bloody stools and fever. After admission, they often received Metronidazole 500mg tid for ten day. Four patients failed to treat with Metronidazole and were switched to vancomycin for further management. One of these four patients still had Clostridium difficile enteritis after treatment, and was finally successfully treated with Fidaxomicin. Because these patients recovered after treatment with antibiotics, so we did not use (FMT) fecal microbiota transplants. Conclusions: The treatment of gastric ulcer combined with Helicobacter pylori infection is a common treatment in the outpatient department of gastroenterology. However, after treatment, if the patient develops enteritis symptoms such as fever, diarrhea, blood in the stool, etc., Clostridium difficile infection should be considered as one of the main differential diagnosis. If the diagnosis is confirmed, the relevant patients should be treated closely. P.098

包含 VONOPRAZAN 及高劑量 AMOXICILLIN 的七天三合一處方作為治 療幽門螺旋桿菌的一線殺菌藥物，對比目前 標準二週系列性治療 SEVEN-DAY VONOPRAZAN-BASED TRIPLE THERAPY WITH HIGHDOSE AMOXICILLIN AS FIRST-LINE HELICOBACTER PYLORI TREATMENT IN COMPARISON WITH 14-DAY PROTON PUMP INHIBITOR BASED SEQUENTIAL THERAPY

邱毓澤1, 2 李輔仁1, 2 郭震亞1, 2 林暘朝1, 2 梁凱舜1, 2 曾亮瑋1, 2 陳昱宗1, 2 張吉仰1, 2 輔大醫院胃腸肝膽科1 輔大醫學院2

Background: Helicobacter pylori infection is a wellestablished risk factor for peptic ulcer disease and gastric cancer. It’s now a consensus of experts that H.pylori infection should be treated once it is recognized. Extended proton pump inhibitor (PPI)-based sequential therapy as one of the most commonly used first-line regimens provides a satisfactory eradication rate of 90.7% (95% CI, 87.4% - 94.0%). Nevertheless, its complexity of the “sequential” usage is sometimes confusing to the patients and may lead to treatment failure. The emerging new regimen - vonoprazan-based triple therapy, on the other hand, is another appealing choice with simplicity, short treatment duration, and low pill burden. However, there’s still no evidence regarding the use of vonoprazan-based triple therapy with high-dose amoxicillin (1000mg twice daily) as the first-line regimen. Aims: This study aimed to compare the efficacy of the current standard first-line regimen, sequential therapy, with that of vonoprazan-based triple therapy with high-dose Amoxicillin. Methods: Through retrospective analysis of the data from the 13C-urea breath report from the endoscopy room of Fu Jen Catholic University Hospital, patients with H.pylori infection who had received vonoprazan-based triple therapy with high-dose amoxicillin (vonoprazan 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg twice daily for seven days) or extended sequential therapy (lansoprazole 30mg/rabeprazole 20mg/pantoprazole 40mg + amoxicillin 1000mg twice daily for 7 days, followed by lansoprazole 30mg/rabeprazole 20mg/pantoprazole + clarithromycin 500mg + metronidazole 500mg twice

daily for 7 days) since April 2021 to December 2021 were recruited. Patients who received regimen other than vonoprazan triple therapy or extended sequential therapy, were diagnosed with H.pylori infection solely through serology test or unknown method, or took the UBT test not for confirmation of the success of eradication were all excluded. The eradication rates according to the 13C-urea breath report in the two groups were compared with StataSE 14 by Chi-squared test. Major adverse events mentioned in the medical record were also recorded. Results: Total 545 patients were identified in the database of 13C-urea breath report from the endoscopy room of Fu Jen Catholic University Hospital during the time period. After excluding cases according to the above criteria, total 372 patients were recruited, with 76 in the vonoprazan triple therapy group and 296 in extended sequential group. The eradication rate in each group was 79.0% versus 89.2%, respectively (p = 0.018). Four patients in the vonoprazan triple therapy group had received anti-H. pylori treatment before, while only one achieved H.pylori eradication. After excluding non-first line usage, the eradication rate became 81.9% versus 89.2%, respectively (p = 0.092). Major adverse events occurred in none of the vonoprazan triple therapy group but in 11 cases using extended sequential therapy, causing 5 earlier returns to the clinic and 4 treatment failures. Conclusions: The eradiation rate of vonoprazan triple therapy was not as high as reported in the literature and tended to be lower than that of extended sequential therapy, although there were fewer major adverse events in this group. We speculated that it might be due to endemic strains resistant to clarithromycin. A large-scale randomized control trial is still needed for further validation of the result. P.099

「鉀離子競爭性酸阻斷劑高劑量二合療法」 與「質子幫浦抑制劑高劑量二合療法」在治 療幽門螺旋桿菌感染上之比較 POTASSIUM-COMPETITIVE ACID BLOCKER-BASED HIGH-DOSE DUAL THERAPY VERSUS PROTON PUMP INHIBITOR-BASED HIGH-DOSE DUAL THERAPY IN THE FIRST-LINE TREATMENT OF HELICOBACTER PYLORI INFECTION

施長碧1,11 雷尉毅2,11 吳登強3,11 蔡成枝4,11 楊智欽5,11 陳冠仰6,11 蔡峯偉7,11 李嘉龍8,11 陳健麟2,11 劉玉華9,11 許斯淵10,11 李熹昌6,11 許秉毅1,11 臺南市立安南醫院暨中國醫藥大學內科部消化內科1 花蓮慈濟醫院內科部胃腸科2 高雄醫學大學附設醫院內科部胃腸科3 高雄長庚紀念醫院胃內科部胃腸肝膽科4 國立臺灣大學附設醫院內科部胃腸科5 臺北市立聯合醫院仁愛院區內科部胃腸肝膽科6 高雄榮民總醫院內科部胃腸肝膽科7 國泰綜合醫院內科部胃腸肝膽科8 新光吳火獅紀念醫院內科部胃腸科9 臺中榮民總醫院內科部胃腸肝膽科10 臺灣胃酸相關疾病暨微菌叢聯盟11

Background: The minimal inhibitory concentrations of most antibiotics against H. pylori are dependent on the pH of the environment. Vonoprazan is a new gastric acid suppression agent, classified as potassium-competitive acid blocker (PCAB). Its acid inhibition efficacy is superior to that of proton pump inhibitor (PPI). Currently, whether PCAB-based high-dose dual therapy can achieve a higher eradication rate than PPI-based high-dose dual therapy remains unanswered. Aims: To compare the efficacies of PCAB-based high-dose dual therapy and PPI-based high-dose dual therapy in the first-line treatment of Helicobacter pylori infection Methods: From October 2018 to November 2021, 19 patients receiving 14-day vonoprazan-based high-dose dual therapy (vonoprazan 20 mg b.i.d. and amoxicillin 750 mg q.i.d. for 14 days) and 304 H. pylori-infected patients receiving 14-day rabeprazole-based high-dose dual therapy (rabeprazole 20 mg and amoxicillin 750 mg q.i.d. for 14 days) were included in this study. Patients were followed up according to a standard protocol. They were asked to return at the second week to assess drug adherence and adverse events. Post-treatment H pylori status was assessed

by 13C-urea breath test at week 6. Results: Intention-to-treat analysis demonstrated that the eradication rates of vonoprazan-based and rabeprazolebased high-dose dual therapy were 100.0% and 85.5%, respectively. Vonoprazan-based high-dose dual therapy had a borderline significance of increased eradication rate than rabeprazole-based high-dose dual therapy (P = 0.088). The two therapeutic groups had similar frequencies of adverse events (15.8% vs 17.9%, P = 1.000) and drug adherence (100.0% vs 97.7%, P = 1.000). Conclusions: 14-day PCAB-based high-dose dual therapy achieves a borderline higher eradication rate than 14-day PPI-based high-dose dual therapy in the first-line treatment of H. pylori infection. P.100

病患期待高除菌率之一線幽門螺旋桿菌配 方（幽門螺旋桿菌之希望研究 _HOPE_HP SURVEY） HIGH OUTCOME EXPECTED FROM PATIENTS’ PREFERENCE AND EXPECTATION IN THE ERADICATION OF HELICOBACTER PYLORI (HOPE_HP SURVEY)

蔡元榮1 許秉毅2,3 阮盛豪1 郭志榮1 詹益群1 林群峰1 張琳遂1 林連豐1 屏東基督教醫院1 臺南市立安南醫院消化內科暨中國醫藥大學2 臺灣胃酸相關疾病暨微菌叢聯盟3

Background: With the rising prevalence of antimicrobial resistance, the treatment success of standard triple therapy has declined to 66.5% in Japan and less than 80% in most other Asia-Pacific countries. Several novel first-line anti-H pylori regimens including sequential therapy, concomitant quadruple therapy, hybrid therapy, high-dose dual therapy and bismuth-containing quadruple therapy have emerged to cure H pylori infection recently. REAP-HP study was the pioneer study investigating the expectation and preference of physicians across Asia-Pacific in H pylori eradication in 2015. HOPE_HP study was follow-up study of REAPHP focusing on the expectation and preference of patients when being prescribed with anti-H.P regimens in our hospital. Aims: (1) To investigate the preference in regimens for the first-line anti-H pylori therapy among patients in our hospital with the information of eradication rate, side effect and medical cost provided. (2) To survey the minimal eradication rate of a first-line regimen accepted by patients in our hospital, and (3) To further investigate the most concerned factors of patients when receiving anti-H pylori regimens in clinical practice. Methods: A questionnaire for H pylori eradication survey of patients was distributed to the patients who had ever received anti-H pylori therapy before or being diagnosed of H.P. infection was prescribed with relevant regimens. The key questions included the most commonly used therapy, minimal accepted eradication rate of a first-line anti-H pylori regimen in clinical practice, and the most concerned factors during anti-H pylori therapy. Results: A total of 123 patients from Ping Tung Christian Hospital participated in the post HOPE_HP Survey. The top three most anticipated anti-H pylori regimens by patients

in our hospital were 14-day hybrid (including reverse hybrid) therapy (81.3%; n = 100), 7-day standard triple therapy (10.6%; n = 13) and 14-day Bismuth quadruple therapy (5.7%; n =7) respectively. The average minimal accepted eradication rate for first line regimen anticipated by patients is 85.6%. A total of 66.7% of patients chose the combination of eradication rate, side effect and medical costs as their top three most concerned factors when receiving anti-H pylori therapy. Conclusions: Fourteen day hybrid (including reverse hybrid) therapy is the most anticipated first-line anti-H pylori therapy among patients in our hospital because of its high eradication rate. Therefore, patients expect regimen with high outcome in eradication for their first line regimen. P.101

揭露在幽門桿菌感染之胃癌細胞中細胞自噬 是否調控 HDGF 之生成與分泌 TO REVEAL THE ROLE OF AUTOPHAGY IN HDGF SYNTHESIS AND SECRETION IN HELICOBACTER PYLORI-RELATED GASTRIC CANCER CELLS

許峻麒1 林姵妏2 朱曼菱2 劉校生2 吳政毅1,3 吳登強1,3 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學熱帶醫學碩士學位學程2 高雄醫學大學醫學系3

Background: Gastric cancer is the third leading cause of cancer death globally, and hepatoma-derived growth factor (HDGF) is overexpressed and plays an oncogenic role in gastric cancer tumorigenesis. Aims: This study aims to clarify whether HDGF is regulated by secretory autophagy during gastric cancer tumorigenesis in the presence of Helicobacter pylori (H. pylori). Methods: The effect of autophagy on HDGF synthesis and secretion in AGS gastric cancer cells under H. pylori infection was determined using autophagy inducers (rapamycin and amiodarone) and inhibition by genetic knockout of Atg5 gene. Autophagic activity in AGS cells was determined by Western blotting and IFA. HDGF synthesis and secretion from gastric cancer cells was measured by immunoblotting and ELISA, respectively. Results: When regulating autophagy activity by either induction or inhibition, the content of HDGF in gastric cancer cells under H. pylori infection remains unchanged. Moreover, HDGF secretion from H. pylori infected gastric cancer cells was also not affected by autophagic activity. Conclusions: We reveal that autophagy did not participate in either synthesis or secretion of HDGF in H. pylori infected gastric cancer cells.