Abstractboek 2018

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ABSTRACT BOEK 2018

Wetenschappelijke publicaties van AZ Groeninge

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CENTRA 04 ABDOMINALE CHIRURGIE

35 MEDISCHE BEELDVORMING

18 ANESTHESIE / INTENSIEVE ZORG

43 NEUROLOGIE

19 APOTHEEK

49 NUCLEAIRE GENEESKUNDE

20 CARDIOLOGIE

60 ONCOLOGIE

21 GYNAECOLOGIE / VERLOSKUNDE

64 ORTHOPEDIE / HANDGROEP

22 INWENDIGE ZIEKTEN GASTRO-ENTEROLOGIE

69 PLASTISCHE CHIRURGIE 58 RADIOTHERAPIE

28 KINDERGENEESKUNDE 70 UROLOGIE 29 KLINISCH LABORATORIUM 34 LONGZIEKTEN

VU Inge Buyse, Pres. Kennedylaan 4 | 8500 Kortrijk Uitgegeven in opdracht van het wetenschappelijk comité van AZ Groeninge Eindredactie Laurence Beels, Eline Lamaire

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Dit abstractboek is ook te raadplegen via www.azgroeninge.be /azgpublicaties


VOORWOORD

Geachte lezer

V

oor u ligt het abstractboek met de wetenschappelijke publicaties van het jaar 2018, waaraan naar traditie de laatste hand gelegd wordt rond de aanvang van het nieuwe academiejaar. Het is altijd een goede gelegenheid om eens terug te blikken op de evolutie van de wetenschappelijke activiteit in het ziekenhuis. Toen we recent een lijst opstelden van het aantal stafleden met een doctoraat, is gebleken dat hun aantal op enkele jaren verdubbeld was. Het aantal en het niveau van de publicaties gaan er op vooruit. Ook het aantal klinische studies dat in az groeninge wordt opgezet, is de laatste jaren gestegen maar belangrijker nog, het aantal geĂŻncludeerde patiĂŤnten is toegenomen en dat geldt zowel voor wat wij de academische studies noemen (klinische studies zonder enige tussenkomst van farmaceutische bedrijven) als voor gesponsorde klinische studies (studies waarbij doorgaans geneesmiddelen of therapeutische regimes het voorwerp van de studie uitmaken). Intussen lijkt de farmaceutische industrie zich steeds meer te interesseren voor de schat aan klinische data die in de ziekenhuizen aanwezig is en die een heel nieuwe manier om aan geneesmiddelenonderzoek te doen mogelijk maakt. Ook voor eigen wetenschappelijk onderzoek is er een schat aan informatie in de ziekenhuizen aanwezig. Dit wordt zeker een domein om verder te exploreren, waarbij we continu rekening zullen moeten houden met de beperkingen die de GDPR ons oplegt. Intussen zien we dat ook de activiteit in ons ziekenhuis het voorbije jaar is toegenomen. De pathologiezwaarte neemt eveneens toe; de steeds betere samenwerking met onze partners in het E17 ziekenhuisnetwerk zit daar wellicht voor iets tussen. Het dwingt dan ook respect af dat onze artsen en hun verpleegkundige, wetenschappelijke en paramedische medewerkers, steeds weer de energie vinden om in hun schaarse vrije tijd data te registreren en te publiceren. DR. SERGE VANDERSCHUEREN MEDISCH DIRECTEUR

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CENTRUM

ABDOMINALE CHIRURGIE ARTIKELS ABSTRACT 1 Ruminococcus gnavus bacteremia associated with fecal peritonitis secondary to small bowel perforation Struyve M, De Vloo C, Lefever S, et al. Acta Gastro-enterologica Belgica, 2018, 81(3), 451-452

ABSTRACT 3 Conversion for unfavorable intraoperative events results in significantly worse outcomes during laparoscopic liver resection: lessons learned from a multicenter review of 2861 cases Halls MC, Cipriani F, Berardi G, et al. Annals of Surgery, 2018, 268(6), 1051-1057

INTRODUCTION/BACKGROUND Er is geen abstract beschikbaar.

ABSTRACT 2 Chronic refractory constipation due to neurogenic bowel dysfunction can be successfully treated by sacral neurostimulation Nuytens F, D'Hondt M, et al. Acta Chirurgica Belgica, 2018, 118(4), 246-249

INTRODUCTION/BACKGROUND In the last few decades, sacral neurostimulation (SNS) has proven to be an effective treatment option for functional bowel disorders. Experience concerning the role of SNS in the treatment of chronic constipation due to neurogenic bowel dysfunction (NBD) however is limited.

Multiple previous studies demonstrate that laparoscopic liver surgery reduces intraoperative blood loss, hospital stay, and morbidity while maintaining comparable oncological and survival outcomes when compared with open liver resections. However, limited information is available regarding the possible sequelae of conversion to open surgery, especially with regards to cause of conversion.

OBJECTIVE To investigate the risk factors for conversion during laparoscopic liver resection and its effect on patient outcome in a large cohort of patients. Additional analysis of outcomes in patients who required conversion for unfavorable intraoperative findings and conversion for unfavorable intraoperative events will be performed to establish if the cause of conversion effects outcome.

MATERIALS/METHODS MATERIALS/METHODS In this report, we present the case of a 44-year old patient, with chronic refractory neurogenic constipation after a spontaneous cerebral hemorrhage, who was treated with SNS.

RESULTS Prior to treatment with SNS, the Constipation Scoring System showed a score of 22/30. Three months after SNS implantation, this score was reduced to 5/30. Patient had successful evacuation of stool every one to two days. Medication could be reduced to 15 drops of picosulphate per day. Patient experienced a significant improvement in quality of life.

CONCLUSION We believe that SNS could offer a safe, effective and relatively cost-effective treatment for patients with NBD refractory to conservative treatment.

A retrospective analysis of 2861 cases from prospectively maintained databases of 7 tertiary liver centers across Europe was performed.

RESULTS Neo-adjuvant chemotherapy, previous liver resection(s), resections for malignant lesions, postero-superior location, and the extent of the resection are associated with an increased risk of conversion. Patients who require conversion have longer operations with higher blood loss; a longer HDU and total hospital stay, increased frequency and severity of complications and higher 30- and 90-day mortality. Patients who had an elective conversion for an unfavorable intraoperative finding had better outcomes than patients who had an emergency conversion secondary to an unfavorable intraoperative event in terms of HDU and total hospital stay, severity of complication, and 90-day mortality.

CONCLUSION Our study highlights the risk factors for conversion and suggests that conversion for unfavorable intraoperative events is associated with worse outcomes.

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ABSTRACT 4 Laparoscopic versus open parenchymal preserving liver resections in the posterosuperior segments: a casematched study D'Hondt M, Tamby E, Boscart I, et al. Surgical Endoscopy, 2018, 32(3), 1478-1485

INTRODUCTION/BACKGROUND Patients with lesions in the posterosuperior (PS) segments of the liver have been considered poor candidates for laparoscopic liver resection (LLR).

with comparable short-term outcomes as similar OLR. The shorter interval to chemotherapy might provide long-term oncologic benefits in patients who underwent LLR.

ABSTRACT 5 Are the current difficulty scores for laparoscopic liver surgery telling the whole story? An international survey and recommendations for the future Halls MC, Cherqui D, D’Hondt M, et al. HPB (Oxford): the official journal of the international hepato pancreato biliary association, 2018, 20(3), 231-236

OBJECTIVE This study aims to compare short-term outcomes of LLR and open liver resections (OLR) in the PS segments.

MATERIALS/METHODS This multicenter study consisted of all patients who underwent LLR in the PS segments and all patients who underwent OLR in the PS segments between October 2011 and July 2016. Laparoscopic cases were case-matched with those who had an identical open procedure during the same period based on tumor location (same segment) and the Brisbane classification of the resection. Demographics, comorbid factors, perioperative outcomes, short-term outcomes, necessity of adjuvant chemotherapy, and the interval between surgery and initiation of adjuvant chemotherapy were compared between the two groups. Data were retrieved from a prospectively maintained electronic database.

INTRODUCTION/BACKGROUND Recent studies have suggested that the difficulty of laparoscopic liver resections are related to both patient and tumour factors, however the available difficulty scoring systems only incorporate tumour factors.

OBJECTIVE The aim of this study was to assess the opinion of laparoscopic liver surgeons regarding the factors that affect the perceived difficulty of laparoscopic liver resections.

MATERIALS/METHODS Using a Visual Analogue Scale an international survey of laparoscopic liver surgeons was undertaken to assess the perceived difficulty of 26 factors previously demonstrated to affect the difficulty of a laparoscopic liver resection.

RESULTS RESULTS Both groups were comparable for age, sex, ASA score, maximum tumor diameter, and number of patients with additional liver resections outside the posterior segments. Operative time was similar in both groups (median 140 min; p = 0.92). Blood loss was less in the LLR-group (median: 150 vs. 300 ml in OLR-group). Median hospital stay was 6 days in both groups. There was no significant difference in postoperative complications (OLR-group: 31.4% vs. LLR-group: 25.7%; p = 0.60). There was no significant difference in R0 resections (LLR: 97.2 vs. 100% in OLR; p = 1.00). Tumor-free margins were less in the LLR group (LLR: 5 vs. 9.5 mm in OLR; p = 0.012). Patients undergoing LLR were treated with chemotherapy sooner compared to those undergoing OLR (41 vs. 56 days, p = 0.02).

80 surgeons with a combined experience of over 7000 laparoscopic liver resections responded to the survey. The difficulty of laparoscopic liver surgery was suggested to be increased by a BMI > 35 by 89% of respondents; neo-adjuvant chemotherapy by 79%; repeated liver resection by 99% and concurrent procedures by 59% however these factors have not been included in the previous difficulty scoring systems.

CONCLUSION The results suggests that the difficulty of laparoscopic liver surgery is not fully assessed by the available difficulty scoring systems and prompts the development of a new difficulty score that incorporates all factors believed to increase difficulty.

CONCLUSION This study suggests that laparoscopic parenchymal preserving liver resections in the PS segments can be performed

ABDOMINALE CHIRURGIE

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ABSTRACT 6

ABSTRACT 7

The Southampton consensus guidelines for laparoscopic liver surgery: from indication to implementation

Laparoscopic right posterior sectionectomy (LRPS): surgical techniques and clinical outcomes

Abu Hilal M, Aldrighetti L, D’Hondt M, et al. Annals of Surgery, 2018, 268(1), 11-18

Siddigi NN, Abuawwad M, D’Hondt M, et al. Surgical Endoscopy, 2018, 32(5), 2525-2532

INTRODUCTION/BACKGROUND

INTRODUCTION/BACKGROUND

The exponential growth of laparoscopic liver surgery in recent years mandates the development of clinical practice guidelines to direct the speciality's continued safe progression and dissemination.

Right posterior sectionectomy is one of the most technically challenging laparoscopic liver resections. Currently, there is limited published data regarding the technique and results required to better understand its safety and feasibility.

OBJECTIVE

OBJECTIVE

The European Guidelines Meeting on Laparoscopic Liver Surgery was held in Southampton on February 10 and 11, 2017 with the aim of presenting and validating clinical practice guidelines for laparoscopic liver surgery.

To report our experience, results and techniques, highlighting a variety of tips and tricks to facilitate this resection. A video is attached for technical demonstration.

MATERIALS/METHODS

Retrospective review of prospectively maintained databases from June 2006 to June 2016. Three different techniques were used: resection following hilar inflow control, inflow control at Rouviere's sulcus and resection with intra parenchymal control.

MATERIALS/METHODS A unique approach to the development of clinical guidelines was adopted. Three well-validated methods were integrated: the Scottish Intercollegiate Guidelines Network methodology for the assessment of evidence and development of guideline statements; the Delphi method of establishing expert consensus, and the AGREE II-GRS Instrument for the assessment of the methodological quality and external validation of the final statements.

CONCLUSION The European Guidelines Meeting for Laparoscopic Liver Surgery has produced a set of clinical practice guidelines that have been independently validated for the safe development and progression of laparoscopic liver surgery. The Southampton Guidelines have amalgamated the available evidence and a wealth of experts' knowledge taking in consideration the relevant stakeholders' opinions and complying with the international methodology standards.

LRPS is feasible, efficient and safe. However, it is a technically challenging procedure and requires advance skills in liver and laparoscopic surgery. Surgeons should be familiar with a variety of approaches as each offers different advantages depending on the location and nature of the lesion, surgical preference and intraoperative findings.

RESULTS Along with the committee chairman, 22 European experts; 7 junior experts and an independent validation committee of 11 international surgeons produced 67 guideline statements for the safe progression and dissemination of laparoscopic liver surgery. Each of the statements reached at least a 95% consensus among the experts and were endorsed by the independent validation committee.

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RESULTS 29 LRPS were performed over a 10-year period. Median operative time was 240 min (150-480). Pringle's manoeuvre was performed in 19 (65.5%) with a median total duration of 35 (20-75) min. Median perioperative blood loss was 600 (100-2500) ml. Additional liver resections were performed in 16 (55.1%). There were two(6.9%) laparoscopic to open conversions. Median postoperative hospital stay was 5 (2-30) days. The median size of the tumour resected was 25 (10-54) mm with median number of resected lesions were 2 (1-4), median free resection margin was 9.5 (1-45) mm, margins were infiltrated (R1) in two (6.7%) cases. There was one death within 30-days (3.4%).

CONCLUSION


ABSTRACT 8

ABSTRACT 10

The effectiveness of a clinical pathway in liver surgery: a case-control study

Achieving high quality standards in laparoscopic colon resection for cancer: A Delphi consensus-based position paper

Ovaere S, Boscart I, Parmentier I, et al. Journal of Gastrointestinal Surgery, 2018, 22(4), 684-694

INTRODUCTION/BACKGROUND In the field of liver surgery, evidence on the effectiveness of clinical pathways based on ERAS principles is limited.

MATERIALS/METHODS This is a single-center observational study from a prospectively maintained database. Two cohorts were formed of all patients undergoing liver surgery during a defined period before (traditional management) and after introduction of a clinical pathway. Additionally, a case-match analysis-based on approach, tumor location, and Brisbane classification of resection-was performed. A cost analysis and patient satisfaction questionnaire were carried out.

RESULTS In both the overall analysis (n = 229) as well as the case-match analysis (n = 100), hospital stay was significantly reduced from 8 to 4 days and from 6.5 to 4 days, respectively (p < 0.05). Postoperative morbidity (traditional management 11/50 vs clinical pathway 5/50; p = 1.00) and readmission rate did not increase. Cost analysis showed a significant decrease in postoperative costs in favor of the clinical pathway (traditional management €3666.7 vs clinical pathway €1912.2; p < 0.001). Overall, 92.3% of the survey questions were answered with satisfied (86.0%) or very satisfied (6.3%).

CONCLUSION Implementation of clinical pathway for liver surgery is feasible and safe. A clinical pathway significantly reduces hospital stay without increasing postoperative morbidity and readmission rates. Postoperative costs are significantly reduced. Patient satisfaction is high.

ABSTRACT 9 Response: "Conversion during resections: a step forward"

Lorenzon L, Biondi A, D’Hondt M, et al. European Journal of Surgical Oncology, 2018, 44(4), 469483

OBJECTIVE To investigate the rate of laparoscopic colectomies for colon cancer using registries and population-based studies. To provide a position paper on mini-invasive (MIS) colon cancer surgery based on the opinion of experts leader in this field.

MATERIALS/METHODS A systematic review of the literature was conducted using PRISMA guidelines for the rate of laparoscopy in colon cancer. Moreover, Delphi methodology was used to reach consensus among 35 international experts in four study rounds. Consensus was defined as an agreement ≥75.0%. Domains of interest included nosology, essential technical/ oncological requirements, outcomes and MIS training.

RESULTS Forty-four studies from 42 articles were reviewed. Although it is still sub-optimal, the rate of MIS for colon cancer increased over the years and it is currently >50% in Korea, Netherlands, UK and Australia. The remaining European countries are un-investigated and presented lower rates with highest variations, ranging 7-35%. Using Delphi methodology, a laparoscopic colectomy was defined as a "colon resection performed using key-hole surgery independently from the type of anastomosis". The panel defined also the oncological requirements recognized essential for the procedure and agreed that when performed by experienced surgeons, it should be marked as best practice in guidelines, given the principles of oncologic surgery be respected (R0 procedure, vessel ligation and mesocolon integrity).

CONCLUSION laparoscopic

Halls MC, Cipriani F, D’Hondt M, et al. Annals of Surgery, 2018, 268(6), 81-82

liver

The rate of MIS colectomies for cancer in Europe should be further investigated. A panel of leaders in this field defined laparoscopic colectomy as a best practice procedure when performed by an experienced surgeon respecting the standards of surgical oncology.

Er is geen abstract beschikbaar.

ABDOMINALE CHIRURGIE

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ABSTRACT 11

ABSTRACT 12

Perioperative radiotherapy is an independent risk factor for major LARS: a cross-sectional observational study

Development and validation of a difficulty score to predict intraoperative complications during laparoscopic liver resection

D’Hondt M, Develtere D, Sergeant G, et al. International Journal of Colorectal Disease, 2018, 33(8), 1063-1069

INTRODUCTION/BACKGROUND

INTRODUCTION/BACKGROUND

Sphincter-preserving surgery for rectal cancer is often associated with low anterior resection syndrome (LARS).

OBJECTIVE

Previous studies have demonstrated that patient, surgical, tumour and operative variables affect the complexity of laparoscopic liver resections. However, current difficulty scoring systems address only tumour factors.

The aim of our study was to determine the prevalence of LARS in our institution and identify possible risk factors for LARS. Furthermore, we evaluated which of the LARS symptoms was considered most disabling by patients and whether or not there is an adaptation of the LARS score over time.

The aim of this study was to develop and validate a predictive model for the risk of intraoperative complications during laparoscopic liver resections.

MATERIALS/METHODS

MATERIALS/METHODS The prospectively maintained databases of seven European tertiary referral liver centres were compiled. Data from two-thirds of the patients were used for development and one-third for validation of the model. Intraoperative complications were based on a modified Satava classification. Using the methodology of the Framingham Heart Study, developed to identify risk factors that contribute to the development of cardiovascular disease, factors found to predict intraoperative complications independently were assigned points, and grouped into low-, moderate-, highand extremely high-risk groups based on the likelihood of intraoperative complications.

RESULTS

CONCLUSION Perioperative radiotherapy is an independent risk factor for major LARS. Fragmentation is considered the most disabling complaint in the majority of patients with major LARS. There is no significant adaptation of the LARS score over time.

ABSTRACTBOEK | 2018

OBJECTIVE

This study includes a prospective database of 100 patients who underwent total or partial mesorectal excision between January 2009 and September 2014. Patients were contacted after a median postoperative time of 38 (5-45) months to determine the LARS score and to identify LARS symptoms that were considered most disabling. Uni- and multivariate regression analysis was performed to identify risk factors for LARS and major LARS. Finally, the LARS score was evaluated over time after restoration of bowel continuity.

Out of the 100 patients, 16 had minor LARS (score 21-29) and 51 patients had major LARS (score 30-42). Radiotherapy was an independent risk factor for major LARS (p = 0.04). For the majority of patients with major LARS (22%), fragmentation was considered the most disabling complaint. There was no correlation between interval after restoration of bowel continuity and the severity of the LARS score.

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Halls MC, Berardi G, D’Hondt M, et al. The British Journal of Surgery, 2018, 105(9), 1182-1191

RESULTS A total of 2856 patients were included. Neoadjuvant chemotherapy, lesion type and size, classification of resection and previous open liver resection were found to be independent predictors of intraoperative complications. Patients with intraoperative complications had a longer duration of hospital stay (5 versus 4 days; P < 0·001), higher complication rates (32·5 versus 15·5 per cent; P < 0·001), and higher 30-day (3·0 versus 0·3 per cent; P < 0·001) and 90-day (3·8 versus 0·8 per cent; P < 0·001) mortality rates than those who did not. The model was able to predict intraoperative complications (area under the receiver operating characteristic (ROC) curve (AUC) 0·677, 95 per cent c.i. 0·647 to 0·706) as well as postoperative 90-day mortality (AUC 0·769, 0·681 to 0·858).


CONCLUSION This comprehensive scoring system, based on patient, surgical and tumour factors, and developed and validated using a large multicentre European database, helped estimate the risk of intraoperative complications.

ABSTRACT 13 Outcomes after minimally-invasive versus open pancreatoduodenectomy: A Pan-European propensity score matched study

(24% vs 19% vs 25%), and mortality (2.9% vs 5.2% vs 5.4%), with a fewer conversions in robot-assisted- versus laparoscopic MIPD (5% vs 26%, P < 0.001).

CONCLUSION In the early experience of 14 European centers performing ≥10 MIPDs annually, no differences were found in major morbidity, mortality, and hospital stay between MIPD and OPD. The high rates of POPF and conversion, and the lack of superior outcomes (ie, hospital stay, morbidity) could indicate that more experience and higher annual MIPD volumes are needed.

Klompmaker S, van Hilst J, D’Hondt M, et al. Annals of Surgery, 2018

ABSTRACT 14 INTRODUCTION/BACKGROUND Current evidence on MIPD is based on national registries or single expert centers. International, matched studies comparing outcomes for MIPD and OPD are lacking.

Foreign body granuloma reaction following SIRT mimicking peritoneal metastases: a word of caution Willems E, D’Hondt M, Dedeurwaerdere F, et al. Acta Chirurgica Belgica, 2018, 9, 1-3

OBJECTIVE To assess short-term outcomes after minimally invasive (laparoscopic, robot-assisted, and hybrid) pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) among European centers.

MATERIALS/METHODS Retrospective propensity score matched study comparing MIPD in 14 centers (7 countries) performing ≥10 MIPDs annually (2012-2017) versus OPD in 53 German/Dutch surgical registry centers performing ≥10 OPDs annually (2014-2017). Primary outcome was 30-day major morbidity (Clavien-Dindo ≥3).

INTRODUCTION/BACKGROUND Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy with poor survival rates. Surgical resection is the only curative treatment option, yet only a small portion of cases are resectable. In unresectable situations, suggested therapy consists of a systemic chemotherapy regimen with cisplatinum and gemcitabine. Selective internal radiation therapy (SIRT) has been proposed as an alternative treatment option and may lead to downstaging of unresectable iCCA to surgery.

MATERIALS/METHODS RESULTS Of 4220 patients, 729/730 MIPDs (412 laparoscopic, 184 robot-assisted, and 130 hybrid) were matched to 729 OPDs. Median annual case-volume was 19 MIPDs (interquartile range, IQR 13-22), including the first MIPDs performed in 10/14 centers, and 31 OPDs (IQR 21-38). Major morbidity (28% vs 30%, P = 0.526), mortality (4.0% vs 3.3%, P = 0.576), percutaneous drainage (12% vs 12%, P = 0.809), reoperation (11% vs 13%, P = 0.329), and hospital stay (mean 17 vs 17 days, P > 0.99) were comparable between MIPD and OPD. Grade-B/C postoperative pancreatic fistula (POPF) (23% vs 13%, P < 0.001) occurred more frequently after MIPD. Single-row pancreatojejunostomy was associated with POPF in MIPD (odds ratio, OR 2.95, P < 0.001), but not in OPD. Laparoscopic, robot-assisted, and hybrid MIPD had comparable major morbidity (27% vs 27% vs 35%), POPF

We present a case of a female patient diagnosed with an unresectable iCCA treated with SIRT in order to obtain downstaging.

RESULTS Explorative laparoscopy three months later showed multiple peritoneal lesions in the left upper quadrant, mimicking peritoneal metastases. Anatomopathological investigation showed a foreign body granuloma surrounding the SIRT resin particles. These findings have important consequences, as the presence of peritoneal metastases implies a palliative situation.

CONCLUSION Anatomopathological confirmation of any intraabdominal lesion mimicking peritoneal metastases should be carried out.

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ABSTRACT 15 Are the current difficulty scores for laparoscopic liver surgery telling the whole story? An international survey and recommendations for the future

PRESENTATIES/ CONGRESSEN ABSTRACT 1

Halls MC, Cherqui D, D’Hondt M, et al. The Official Journal of the International Hepato-Pancreato-Biliary Association, 2018, 20 (3), 231-236

Simultaneous laparoscopic colorectal and hepatic resection for patients with colorectal cancer and synchronous liver metastases: a multicenter, retrospective study

INTRODUCTION/BACKGROUND Recent studies have suggested that the difficulty of laparoscopic liver resections are related to both patient and tumour factors, however the available difficulty scoring systems only incorporate tumour factors.

First World Congress of the International Laparoscopic Liver Society van der Poel MJ, D’Hondt M, Gobardhan PD, et al. July 2018, Paris, France

OBJECTIVE

INTRODUCTION/BACKGROUND

The aim of this study was to assess the opinion of laparoscopic liver surgeons regarding the factors that affect the perceived difficulty of laparoscopic liver resections.

Laparoscopic resection is considered a viable treatment option for both colorectal cancer and colorectal liver metastases. Simultaneous laparoscopic resections have been described in preliminary studies with promising overall results.

MATERIALS/METHODS Using a Visual Analogue Scale an international survey of laparoscopic liver surgeons was undertaken to assess the perceived difficulty of 26 factors previously demonstrated to affect the difficulty of a laparoscopic liver resection.

OBJECTIVE The aim of this study was to present the results of a combined, multicenter experience with totally laparoscopic simultaneous colorectal and liver resection.

RESULTS

MATERIALS/METHODS

80 surgeons with a combined experience of over 7000 laparoscopic liver resections responded to the survey. The difficulty of laparoscopic liver surgery was suggested to be increased by a BMI > 35 by 89% of respondents; neo-adjuvant chemotherapy by 79%; repeated liver resection by 99% and concurrent procedures by 59% however these factors have not been included in the previous difficulty scoring systems.

All associated centers retrospectively reviewed databases containing their complete experience with laparoscopic liver resection (LLR) until January 2017 and selected all patients with colorectal liver metastases that underwent simultaneous resection of c olorectal primary and liver metastases. Patient, tumor and procedure characteristics, operative variables and postoperative outcomes were reported.

CONCLUSION

A total of 63 patients, 35 (55%) males with a mean age of 64 (range 35-91), met the inclusion criteria. Patients most frequently presented with a primary tumor located in the sigmoid (n=27, 42%) and a solitary or multiple small liver metastases. In most cases (n=54, 86%) single stage minor liver resection sufficed for a curative resection. Hand-assistance was used in 6 (9%) and robot-assistance was used in 2 (3%) cases. Overall median operative time was 206 minutes (IQR 170-310) and median blood loss was 200 ml (IQR 100-700). A conversion was necessary in 3 patients (5%). Major postoperative morbidity and 30 day mortality were 18% (n=11) and 0%, respectively.

RESULTS The results suggests that the difficulty of laparoscopic liver surgery is not fully assessed by the available difficulty scoring systems and prompts the development of a new difficulty score that incorporates all factors believed to increase difficulty.

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CONCLUSION Laparoscopic simultaneous colorectal and liver resection seems a safe and a feasible treatment strategy in patients with synchronous colorectal liver metastasis. Especially during early experience, patients with solitary or multiple small liver metastasis that require minor liver resection only should be considered ideal candidates for this approach.

World Congress of the International Laparoscopic Liver Society D’Hondt M, Ververken F, Vansteenkiste F July 2018, Paris, France

INTRODUCTION/BACKGROUND

ABSTRACT 2

Glucagonoma is a rare neuroendocrine tumor. Delays in diagnosis are common for this slow growing tumor and half of patients will have metastatic disease when diagnosed. Complete resection of the primary tumor and all metastases is the only chance of cure.

Laparoscopic right anterior and right posterior sectionectomy – a standardized approach. Video presentation

Video presentation

World Congress of the International Laparoscopic Liver Society Ovaere S, Ververken F, D’Hondt M July 2018, Paris, France

INTRODUCTION/BACKGROUND Both laparoscopic right posterior (RP) and right anterior (RA) sectionectomies are technically demanding procedures. A recently published systematic review of more than 9000 laparoscopic liver resections showed that only 1.2% of all published laparoscopic liver resections are RP sectionectomies and 0.15% are RA sectionectomies.

OBJECTIVE Video presentation

OBJECTIVE

MATERIALS/METHODS This video shows a case of a 79 year old female diagnosed with a large symptomatic glucagonoma of the distal pancreas, a large liver metastasis in segment V and a smaller one in segment VIII. She suffered from anorexia, cheilitis, glossitis, weight loss and necrolytic migratory erythema.

RESULTS A laparoscopic distal pancreatectomy, splenectomy, wedge resection of the colon and laparoscopic hepatectomy (anatomical segment V resection and metastasectomy in segment VIII) was perfomed. Operative time was 325 minutes and the estimated blood loss was 200 mL. The patient had a short hospital stay with quick recovery and good outcome at 10 months follow-up.

MATERIALS/METHODS This video illustrates a step-by-step approach for both RA and RP sectionectomies.

RESULTS In our center, both procedures are standardized. RA sectionectomies are installed in supine position, whereas semiprone position for RP sectionectomies is used. This semiprone position achieves maximal working space between the right subphrenic region. The sulcus of Rouvière, present in 82% of patients, is an important anatomical landmark in both procedures. A Glissonian approach is used to allow for safe and masse control of portal structures. Emphasis is put on the importance of patient positioning, anatomical landmarks, adequate mobilization of the liver and assessment of liver viability after pedicle clamping.

ABSTRACT 3 Laparoscopic hepato-pancreatectomy for metastatic glucagonoma. Video presentation.

ABSTRACT 4 Combined laparoscopic transdiaphragmatic resections of right sided colorectal lung metastases in patients undergoing laparoscopic liver resection in the posterosuperior segments World Congress of the International Laparoscopic Liver Society D’Hondt M, Willems E, Lerut P July 2018, Paris, France

INTRODUCTION/BACKGROUND A recently published analysis based on the LiverMetSurvey demonstrated that patients with simultaneously diagnosed colorectal liver and lung metastases (SLLM) suitable for resection of all metastases have a survival similar to that of patients who undergo removal of isolated liver metastases. We recently reported our first experience with combined minimally invasive liver resections in the anterolateral segments and transdiaphragmatic resections of peripheral lung metastases in the left lung.

ABDOMINALE CHIRURGIE

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OBJECTIVE

OBJECTIVE

This video aims to demonstrate our first experience of a combined minimally invasive transdiaphragmatic resection of right sided colorectal lung metastases in a patient undergoing a laparoscopic liver resection of a liver metastasis in the posterosuperior segments.

The aim of this manuscript was to share our experience in LRPS in semiprone position and to highlight technical aspects of the surgical technique.

MATERIALS/METHODS The patient was positioned in semiprone position in order to get better exposure during laparoscopic liver and lung resection. A laparoscopic resection of a large metastasis in segment VII was performed. The right lung was deflated and the right diaphragm was opened. Using intra-operative ultrasound, the two metastasis in the right lung were localized and resected using endoscopic 60-mm vascular staplers. A thoracic tube was inserted and the diaphragm was closed with a non-absorbable running suture. Operative time was 215 min and blood loss was 300ml.

RESULTS The postoperative course was uneventful and the patient was discharged on postoperative day 4. Tumorfree margins of 6mm for the liver and 12mm for the lung were achieved.

MATERIALS/METHODS This is a single-center retrospective descriptive analysis of all patients who underwent a LRPS between September 2011 and October 2017. Pre-, peri- and postoperative data were retrieved from a prospectively maintained electronic database.

RESULTS In total 18 patients underwent a LRPS in semiprone position. In 17 cases indication for surgery was malignancy (colorectal liver metastases in 6 cases, hepatocellular carcinoma in 6 cases and non colorectal liver metastases in 5 cases). Median operative time was 162 (IQR:140-190) minutes and median blood loss was 375 (OQR:150-450) ml. Pringle manoeuver was never used. In 15 cases the Glisonean approach was used. In 3 cases Rouvières´ sulcus was absent. One conversion was required. There were 2 minor complications, and one major complication. Median hospital stay was 6 days (range 5-8 days). All patients had an R0 resection. There was no 90-day mortality.

ABSTRACT 5 Beclomethasone dipropionaat is effective for microscopic colitis: results of an open label multicenter study (COLCO). 13th Congress of the European Crohn's and Colitis Organisation, Inflammatory Bowel Diseases De Corte T, Janssens E, Dejaegher K, et al. Februari 2018, Vienna, Austria

CONCLUSION LRPS in semiprone position is feasible and safe. Semiprone position offers a maximum amount of working space.The Glissonean approach allows safe and masse control of the portal structures of the posterior sector without prolonged dissection prior to parenchymal transection and resulting in less blood loss during transection.

Er is geen abstract beschikbaar.

ABSTRACT 7 ABSTRACT 6 Laparoscopic right posterior sectionectomy in semiprone position and using the glissonean approach: technical aspects and single-center results 13th International Hepato-Pancreato Biliary Association World Congres D'Hondt M, Vandeputte M, Parmentier I, Ovaere S September 2018, Genève, Switzerland

INTRODUCTION/BACKGROUND Laparoscopic right posterior sectionectomy (LRPS) is a technically demanding procedure. The Glissonean approach is our technique of choice.

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ABSTRACTBOEK | 2018

Short term and oncologic outcomes of the first 250 laparoscopic liver resections performed by a laparoscopically trained liver surgeon 13th International Hepato-Pancreato Biliary Association World Congress D'hondt M, Willems E, Parmentier I, et al. September 2018,Genève, Switzerland

OBJECTIVE To evaluate the results of the first 250 laparoscopic liver resections(LLR) performed by a single surgeon trained in laparoscopic surgery and hepatobiliary surgery, and to investigate whether a learning curve is present.


MATERIALS/METHODS

MATERIALS/METHODS

Retrospective review of a prospectively set up database of all patients who underwent LLR between October 2011 and November 2017.

Retrospective review of a prospectively collected database of all patients who underwent a laparoscopic liver resection for lesions in the PS segments between September 2011 and December 2017.

RESULTS During 73 months,379 liver resections were performed, of which 251 procedures were performed by a pure laparoscopic approach (66%). From the first year to the most recent year, the percentage of LLRs increased from 45% to 69.2%.One hundred and eleven patients were installed in semiprone position for resections in the posterosuperior segments.Malignancy was present in 217 (86.8%) of patients (colorectal liver metastases(CRLM) in 136 cases (54%)).Thirty-two patients (12.8%) underwent a repeat hepatectomy.Median blood loss was 100ml (IQR:50-250ml). Median operative time was 135 minutes (IQR:90-180min). Conversion rate was 2.4% (6 patients).Peri-operative blood transfusion was needed in 5 patients.Major complication rate (Clavien-Dindo ≥ grade III) was 3.2% (8 patients).R0 resection rate was 94.8%(238 cases).There was no 30-day mortality.In patients with CRLM, 5-year survival rate was 65%. Five consecutive groups were evaluated to investigate the presence of a learning curve.There were no significant differences, apart from a shorter hospital stay (p< 0.001) caused by the implementation of a clinical pathway.

CONCLUSION Trained laparoscopic surgeons with an additional hepatobilairy fellowship may enter practice directly from training and perform LLR with short term and oncologic outcomes in line with early adopters and most experienced laparoscopic liver surgeons.

RESULTS One hundred and eleven patients underwent a laparoscopic liver resection in the PS segments. Multiple resections were performed in 36 patients. Median age was 68 years (IQR:60-75). Indication for resection was colorectal metastases in 70 patients (63.0%) and hepatocellular carcinoma in 20 patients (18.0%). Conversion occurred in 3 patients (2.7%). Median operative time was 150 minutes (IQR:120180min). Median operative blood loss was 150ml (IQR:100350ml). Transfusion was necessary in 3 patients (2.7%). Six patients (5.4%) presented with severe postoperative complications (Clavien-Dindo ≥ grade III). Median hospital stay was 5 days (IQR:4-7). R0 resection rate was 96.4%. There was no 90-day mortality. Analysis of two consecutive groups showed no significant differences in operative time (140min (IQR:120-180) VS 165min (IQR:130-190), p=0.092) or blood loss (150ml (IQR:50-300) VS 150ml (IQR:100-375), p=0.72), indicating the absence of a steep learning curve.

CONCLUSION Pure laparoscopic liver resections in the PS segments in semiprone position are safe and feasible. Using the semiprone position enables this approach through improved visualisation, and avoids a steep learning curve.

ABSTRACT 9 Laparoscopic liver resection for liver tumors in proximity to major vasculature: a comparative study

ABSTRACT 8 Pure laparoscopic liver resections in the posterosuperior segments in semiprone Position: a single surgeon experience of 111 consecutive cases 13th International Hepato-Pancreato Biliary Association Congress D'Hondt M, Willems E, Parmentier I, et al. September 2018, Genève, Switzerland

13th International Hepato-Pancreato Biliary Association World Congress Willems E, D'Hondt M, Parmentier I, et al. September 2018,Genève, Switzerland

INTRODUCTION/BACKGROUND Only small case series have been published regarding laparoscopic liver resection (LLR) for tumors in proximity to major vessels(MVs).

INTRODUCTION/BACKGROUND Pure laparoscopic liver resections in the posterosuperior (PS) segments remain technically challenging. Exposure is limited. Installation of the patient in semiprone position may lead to a better exposure and may limit blood loss.

OBJECTIVE The aim of this study is to compare peri-operative outcomes of these resections and LLRs for tumors ≥2cm from the MVs.

ABDOMINALE CHIRURGIE

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MATERIALS/METHODS Retrospective analysis of a prospectively collected database of all LLRs(October 2011-August 2017)performed by a single surgeon. Proximity to MVs was defined as a distance of 20mm or less to the vena cava,hepatic veins and portal vein (main trunk and first branches).

RESULTS Two hundred and thirty-five LLRs were performed, of which 60 patients had lesions in proximity to major vasculature. Median distance to MVs was 10mm (range 0-17). Significantly more patients in the Major Vessels Group (MVG) received neo-adjuvant chemotherapy (36.7% vs 24.2%, p= 0.0094). In the MVG, the median Difficulty Score for LLR was significantly higher (8.5 (IQR: 6.0- 9.0) vs 5.0(IQR: 3.06.0), p< 0.001). The use of CUSA was significantly higher (p< 0.001). Pringle manoeuver was used more frequently in the MVG (15% vs 5.1%; p< 0.001). Operative time was significantly longer (180.0min (IQR: 140.0- 210.0) vs 120.0min (IQR: 75.0-150.0), p< 0.001) and blood loss was significantly higher (190.0ml (IQR: 100.0-325.0) vs 75.0ml (IQR:50.0220.0), p< 0.001) in the MVG. This did not result in a difference in perioperative blood transfusion (5.0% vs 2.8%, p= 0.42) or in postoperative morbidity (15.0% vs 14.3%, p= 0.89). There was no mortality in both groups. There was no significant correlation between the distance to MVs and blood loss (p= 0.80);operative time(p= 0.95).Correlation between central venous pressure drop and blood loss was borderline significant (p= 0.06).

CONCLUSION In selected patients, LLRs of lesions in proximity to MVs is safe and feasible when performed by experienced surgeons working in an experienced team.

cally demanding. Therefore, recently a novel technique, i.e. the laparoscopic long sleeve gastrostomy (LPG), has been described. This video demonstrates all aspects of this pioneering procedure.

MATERIALS/METHODS To perform the LPG mobilization of the distal pancreatic stump for only 1 cm is needed and the main pancreatic duct is stented. The stomach is brought down to decide the location of the sleeve. At least 3 cm away from the lesser curvature a linear stapler is applied to create a vertical 6 cm gastric sleeve tube. A single layer running suture with Vicryl 3-0 is used to create the end-to-end anastomosis. An absorbable fibrin sealant patch is applied to the proximal pancreatic stump. Two Jackson-Pratt drains are placed for drainage.

RESULTS Operative time was 164 minutes and estimated blood loss was < 50 ml. Hospital stay was prolonged due to a grade B postoperative pancreatic fistula which was managed conservatively. Final pathology confirmed the diagnosis of a main duct intraductal papillary mucinous neoplasm. No other events occurred during 6 months of follow-up.

CONCLUSION The LPG is an innovative method to drain the pancreatic stump after laparoscopic CP. In addition, pancreatic tissue is maximally spared and minimal morbidity is observed. Further research is required to gain evidence and establish this practice.

ABSTRACT 11 Laparoscopic radical resection for type II perihilar cholangiocarcinoma

ABSTRACT 10 Laparoscopic long sleeve pancreaticogastrostomy: a pancreas sparing alternative for distal pancreatectomy 13th International Hepato-Pancreato Biliary Association World Congress Capelle M, Willems E, Vansteenkiste F, D'Hondt M September 2018,Genève, Switzerland

INTRODUCTION/BACKGROUND Central pancreatectomy (CP) is considered as a safe surgical approach in the treatment of benign and low-grade malignant tumors of the pancreatic body. However, pancreatic leakage is associated with significant morbidity and performing a laparoscopic pancreaticojejunostomy is techni-

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ABSTRACTBOEK | 2018

13th International Hepato-Pancreato Biliary Association World Congress Capelle M, D'Hondt M September 2018, Genève, Switzerland

INTRODUCTION/BACKGROUND The only curative treatment for perihilar cholangiocarcinoma is radical surgical resection. Recently more extensive approaches have been advocated to obtain tumor free resection margins increasing postoperative morbidity, certainly in patients with pre-existing comorbidities. Moreover, comorbid conditions themselves act as an independent factor of unfavorable prognosis in patients diagnosed with extrahepatic cholangiocarcinoma.


RESULTS

RESULTS

A 75-year-old male with multiple comorbidities (ASA IV) presented with painless obstructive jaundice. A type II perihilar cholangiocarcinoma without evidence for distant metastases was diagnosed on CT and MR. CA19.9 was 720 IU/L at the time of diagnosis. Laparoscopy was negative for peritoneal metastases. Operative time was 240 minutes and estimated blood loss was 50 ml. A postoperative biliary leakage was observed which resolved spontaneously. Final pathology revealed a moderately differentiated cholangioadenocarcinoma with negative lymph nodes and perineural invasion (pT2N0M0G2Lv0Pn1R0). The patient completed adjuvant gemcitabine and cisplatin combination chemotherapy. At 9 months postoperative there is no evidence of disease.

CVP drop was used to select patients for a laparoscopic approach when the tumor was located in segment 1 or in proximity to the hepatocaval confluence.The use of a laparoscopic Pringle manoeuver and a hanging manoeuver of the right hepatic vein to control the hepatocaval confluence are shown. Advantages of placing the patient in semiprone position during LLRs in the posterosuperior segments are explained.In total 60 patients underwent a LLR for lesions in proximity of the major vessels. Median distance to major vessels was 10 mm (range 0-17). Operative time was 180.0min (IQR: 140.0 - 210.0),median blood loss was 190.0ml (IQR:100.0-325.0).Transfusion rate was 5.0%.Postoperative complication rate was 15.0%.There was no mortality. There was no significant correlation between the distance to major vasculature and blood loss (p=0.80) or operative time (p=0.95). Correlation between CVP drop and blood loss was borderline significant (p=0.06).

CONCLUSION This report demonstrates the technical feasibility, safety and minimal postoperative morbidity associated with minimal invasive biliary surgery in patients with perihilar cholangiocarcinoma. This less extensive resection, avoiding a hepatectomy, should be considered in patients with multiple pre-existing comorbid conditions.

CONCLUSION When using a range of techniques to prevent blood loss LLRs for lesions in proximity to major vessels are feasible and safe.

ABSTRACT 12

ABSTRACT 13

Technical aspects for laparoscopic liver resections of tumors in proximity to major vessels

Laparoscopic liver resection for tumors in proximity to major vasculature and the impact of neo-adjuvant systemic therapy

13th International Hepato-Pancreato Biliary Association World Congress D'Hondt M, Willems E September 2018,Genève, Switzerland

ESMO 20th World Congress on Gastro-Intestinal cancer Willems E, D’Hondt M, Parmentier I, et al. June 2018, Barcelona, Spain

INTRODUCTION/BACKGROUND

INTRODUCTION/BACKGROUND

Bleeding during parenchymal division of the liver still remains a major complication of hepatectomy leading to 20% of perioperative deaths.

Only small case series have been published regarding laparoscopic liver resection (LLR) for tumors in proximity to major vessels (MVs).

MATERIALS/METHODS

OBJECTIVE

The development of several transection devices, laparoscopic techniques for inflow and outflow control and the positive pressure of the CO2-pneumoperitoneum are the main reasons for less blood loss during laparoscopic resections(LLRs).However, tumors in proximity to major vasculature are often resected by open liver surgery. We describe several techniques which were helpful to prevent blood loss during LLRs with tumors in proximity to major vessels.

The aim of this study is to compare peri-operative outcomes of LLR for tumors < 20 and ≥ 20mm from MVs.

MATERIALS/METHODS Retrospective analysis of a prospectively collected database of consecutive LLR (October 2011 – August 2017) performed by a single surgeon. Proximity to MVs was defined as a distance of 20 mm or less to the caval vein, hepatic veins and portal vein (main trunk and first branches).

ABDOMINALE CHIRURGIE

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RESULTS

MATERIALS/METHODS

A total of 235 LLR were performed, of which 60 patients (24%) had lesions in proximity to major vasculature, median distance to MV 10 mm (range 0-17 mm). Significantly more patients in the close-to-major-vessels group (CTMV) received neo-adjuvant chemotherapy (36.7% vs 24.2%, p = 0.0094). In the CTMV group, the median Difficulty Score for LLR was significantly higher (8.5 (IQR: 6.0-9.0) vs 5.0 (IQR: 3.0-6.0), p < 0.001) as was the use of CUSA (p < 0.001) and Pringle manoeuver (8.3% vs 1.7%; p = 0.028). Operative time was significantly longer (180min (IQR: 140-210) vs 120min (IQR: 75-150), p < 0.001) and blood loss was significantly higher (190ml (IQR: 100-325) vs 75ml (IQR: 50-220), p < 0.001) in the CTMV group. This did not result in a difference in perioperative blood transfusion (3.3% vs 1.7%, p = 0.60) or in postoperative morbidity (15.0% vs 14.3%, p = 0.89). There was no mortality in both groups. There was no significant correlation between the distance to MVs and blood loss (p = 0.80) or operative time (p = 0.95). Correlation between central venous pressure drop and blood loss was borderline significant (p = 0.06). There was a significantly higher R1 resection rate in the CMTV group (10% vs 1.7%, p = 0.0098). On long-term follow-up, there were no significant differences in 5-year overall survival (41% vs 69%, p = 0.12) and 5-year disease-free survival (31% vs 20%, p = 0.98) between the CTMV group and the other group.

Retrospective analysis of a prospectively collected database of consecutive LLR (October 2011 – August 2017) performed by a single surgeon. Proximity to MVs was defined as a distance of 20 mm or less to the caval vein, hepatic veins and portal vein (main trunk and first branches).

CONCLUSION In selected patients, LLRs of lesions in proximity to MVs is safe and feasible with acceptable long-term and oncological results. These patients received more neo-adjuvant systemic therapy.

RESULTS A total of 235 LLR were performed, of which 60 patients (24%) had lesions in proximity to major vasculature, median distance to MV 10 mm (range 0-17 mm). Significantly more patients in the close-to-major-vessels group (CTMV) received neo-adjuvant chemotherapy (36.7% vs 24.2%, p = 0.0094). In the CTMV group, the median Difficulty Score for LLR was significantly higher (8.5 (IQR: 6.0-9.0) vs 5.0 (IQR: 3.0-6.0), p < 0.001) as was the use of CUSA (p < 0.001) and Pringle manoeuver (8.3% vs 1.7%; p = 0.028). Operative time was significantly longer (180min (IQR: 140-210) vs 120min (IQR: 75-150), p < 0.001) and blood loss was significantly higher (190ml (IQR: 100-325) vs 75ml (IQR: 50220), p < 0.001) in the CTMV group. This did not result in a difference in perioperative blood transfusion (3.3% vs 1.7%, p = 0.60) or in postoperative morbidity (15.0% vs 14.3%, p = 0.89). There was no mortality in both groups. There was no significant correlation between the distance to MVs and blood loss (p = 0.80) or operative time (p = 0.95). Correlation between central venous pressure drop and blood loss was borderline significant (p = 0.06). There was a significantly higher R1 resection rate in the CMTV group (10% vs 1.7%, p = 0.0098). On long-term follow-up, there were no significant differences in 5-year overall survival (41% VS 69%, p = 0.12) and 5-year disease-free survival (31% VS 20%, p = 0.98) between the CTMV group and the other group.

ABSTRACT 14 Laparoscopic liver resection for liver tumors in proximity to major vasculature: a single-center comparative study Belgian Surgical Week Willems E, D'Hondt M, Parmentier I, et al. May 2018, Oostende, Belgium

INTRODUCTION/BACKGROUND

ABSTRACT 15

Only small case series have been published regarding laparoscopic liver resection (LLR) for tumors in proximity to major vessels(MVs).

Laparoscopic versus open parenchymal preserving liver resections in the posterosuperior segments: a casematched study

OBJECTIVE

Belgian Group for Endoscopic Surgery Ovaere S, Vansteenkiste F, D'Hondt M. March 2018, Belgium

The aim of this study is to compare peri-operative outcomes of LLR for tumors < 20 and ≼ 20mm from MVs.

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CONCLUSION In selected patients, LLRs of lesions in proximity to MVs is safe and feasible when performed by experienced surgeons working in an experienced team. Long-term and oncological results are acceptable.


INTRODUCTION/BACKGROUND Patients with lesions in the posterosuperior (PS) segments of the liver have been considered poor candidates for laparoscopic liver resection (LLR).

OBJECTIVE This study aims to compare short-term outcomes of LLR and open liver resections (OLR) in the PS segments.

MATERIALS/METHODS This multicenter study consisted of all patients who underwent LLR in the PS segments and all patients who underwent OLR in the PS segments between October 2011 and July 2016. Laparoscopic cases were case-matched with those who had an identical open procedure during the same period based on tumor location (same segment) and the Brisbane classification of the resection. Demographics, comorbid factors, perioperative outcomes, short-term outcomes, necessity of adjuvant chemotherapy, and the interval between surgery and initiation of adjuvant chemotherapy were compared between the two groups. Data were retrieved from a prospectively maintained electronic database.

RESULTS Both groups were comparable for age, sex, ASA score, maximum tumor diameter, and number of patients with additional liver resections outside the posterior segments. Operative time was similar in both groups (median 140 min; p = 0.92). Blood loss was less in the LLR-group (median: 150 vs. 300 ml in OLR-group). Median hospital stay was 6 days in both groups. There was no significant difference in postoperative complications (OLR-group: 31.4% vs. LLR-group: 25.7%; p = 0.60). There was no significant difference in R0 resections (LLR: 97.2 vs. 100% in OLR; p = 1.00). Tumor-free margins were less in the LLR group (LLR: 5 vs. 9.5 mm in OLR; p = 0.012). Patients undergoing LLR were treated with chemotherapy sooner compared to those undergoing OLR (41 vs. 56 days, p = 0.02).

CONCLUSION This study suggests that laparoscopic parenchymal preserving liver resections in the PS segments can be performed with comparable short-term outcomes as similar OLR. The shorter interval to chemotherapy might provide long-term oncologic benefits in patients who underwent LLR.

ABDOMINALE CHIRURGIE

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CENTRUM

ANESTHESIE/ INTENSIEVE ZORG ARTIKELS ABSTRACT 1 Ruminococcus gnavus bacteremia associated with fecal peritonitis secondary to small bowel perforation Struyve M, De Vloo C, Lefever S, et al. Acta Gastro-enterologica Belgica, 2018, 81 (3), 451-452 Er is geen abstract beschikbaar.

PRESENTATIES / CONGRESSEN ABSTRACT 1 Peripheral nerve blocks: Do we still need the big five? The European Society of Regional Anaeshesia & Pain Therapy Annual Congress Van Herreweghe I, Desmet M, Coppens S, et al. September 2018, Dublin, Ireland

INTRODUCTION/BACKGROUND Interscalene, axillary, transversus abdominis plane, femoral, and popliteal blocks, sometimes referred to as the “big five”, have been the golden standard for decades. Ultrasound guidance led to the development of new regional approaches. A survey was conducted to unveil shifts of “golden standard” techniques to other peripheral nerve blocks.

MATERIALS/METHODS Together with the Belgian Association of Regional Anesthesia (BARA), two surveys were conducted (February to August 2017). One was sent to members of the BARA mailing list and questioned regional techniques for surgery. Another was sent to responders of the first survey to identify their postoperative pain management 5-10 years ago. Both surveys consisted out of a web-based questionnaire.

RESULTS We received 220 and 136 answers, representing a 9,6% and 61,8% response rate. Among responders, the interscalene block remains the golden standard for shoulder surgery. The supraclavicular block gains interest for elbow and distal upper limb surgery, while there is a decrease in use of the axillary nerve block. Transversus abdominis plane blocks are considerably more used in laparoscopic abdominal

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ABSTRACTBOEK | 2018

surgery than 5-10 years ago. For hip surgery, the fascia iliaca compartment block is more frequently used than the femoral nerve block. Beside the frequently used femoral nerve block, the adductor canal block and local infiltration analgesia are remarkable new methods for knee surgery. The popliteal nerve block is the ultimate golden standard for foot surgery.

CONCLUSION The aim of this survey was to determine the most up-todate peripheral nerve block technique in correlation with the surgical procedure. Prominent trends cannot be neglected.


CENTRUM

APOTHEEK PRESENTATIES / CONGRESSEN ABSTRACT 1 Implementation of check of appropriateness (COA) in the back office validation of electronic prescriptions in AZ Groeninge

CONCLUSION The COA has been successfully implemented which plays a role in the medication reconciliation of patients during hospitalization. Pharmacist interventions are important to intercept discrepancies of prescriptions at an early stage so the quality of care, drug therapy and patient safety is improved in AZ Groeninge.

European Society of Clinical Pharmacy Annual Congress Wittezaele, J October 2018, Belfast, Ireland

INTRODUCTION/BACKGROUND Previous studies concluded pharmacists, within a multidisciplinary team, can influence the identification and prevention of medication errors. The aim of this study is to expand and standardize the clinical back office validation and implementation of the COA in the pharmacy back office (BO) activities of AZ Groeninge in order to further reduce medication errors.

MATERIALS/METHODS Prospective monocentric study; Before implementation of COA, a baseline measurement was executed. A second and third measurement were done after implementation, respectively the BO validation of ordered medication in 1st line (before dispensing) and validation of prescriptions generated in a query in 2nd line (after dispensing). Four queries were implemented in this research: posology of inhalers, IV/PO switch, overrules of very serious interactions and crushing medication. Tools for validation in BO 1st and 2nd line were made to improve the COA. Registration of the interventions was done by a pharmacist. These were recorded in an intervention form consisting of the following elements: the drug, intervention phase, reason, given advice, way of communication and acceptance degree.

RESULTS In this research a total of 18558 electronic prescription lines were validated by a pharmacist of which 452 interventions were recorded. An error rate of 0.4% was intercepted during the baseline measurement, which increased significantly to a percentage of 1.1% during the BO 1st line. During the BO 2nd line, the error rate was even higher (7.2%; significant) which shows that the implementation of the tools used in BO 1st and 2nd line ensure that even more prescribing errors can be intercepted. The acceptance rate was significantly lower in BO 2nd (54.7%) compared to the BO 1st line (81.0%). Which indicates that uni-directional communication of electronic notes, significantly more used in the BO 2nd line, isn’t effective enough.

APOTHEEK

19


CENTRUM

CARDIOLOGIE ARTIKELS ABSTRACT 1 A preliminary study of pulmonary vein implant applicability and safety as a potential ablation platform in a follow-up study in pigs Vandecasteele T, Schauvliege S, Boussy T, et al. Pacing and Clinical Electrophysiology, 2018, 41(2), 167-171

INTRODUCTION/BACKGROUND Recurrence of atrial fibrillation after an ablation procedure remains a major problem which emphasizes the need for improved pulmonary vein isolation techniques.

OBJECTIVE The aim of this study was to describe an implantation procedure of a pulmonary vein-stent which may possibly serve as an ablation technique in the future and to examine stent safety in a follow-up study in pigs.

MATERIALS/METHODS Eight pigs were catheterized and nine self-expanding nitinol stents were implanted through a transfemoral or transatrial approach into the antra of the pulmonary veins. After 3 months' follow-up, the animals were euthanized for further examination.

RESULTS During the follow-up phase, no complications were observed. Absence of thrombus formation or pulmonary vein wall dissection was noticed during anatomical and histological evaluation of the heart-lung packages. All implants were almost completely covered by neo-intima, of which thickness varied between 0.2 and 3.9 mm.

CONCLUSION Stents can safely be positioned and deployed into the antra of the pulmonary veins without any acute or long-term (3 months) adverse effects. In the future, these implants could function as a permanently implanted ablation device and provide new therapeutic strategies for pulmonary vein isolation in patients with atrial fibrillation

20 ABSTRACTBOEK | 2018


CENTRUM

GYNAECOLOGIE / VERLOSKUNDE

ARTIKELS ABSTRACT 1 Sonographic development of the pericallosal vascularization in the first and early second trimester of pregnancy De Keersmaecker B, Pottel H, Naulaers G, De Catte L American Journal of Neuroradiology, 2018, 39(3), 589-596

INTRODUCTION/BACKGROUND Anomalies of the corpus callosum are rare. Routine scanning in midtrimester of the pregnancy often fails to identify defective development. The purpose of the study was to identify the pericallosal artery and all its main branching arteries during early gestation from the first trimester onward, to measure the length of the pericallosal artery during its development, and to establish a normal vascular map for each week of development.

MATERIALS/METHODS We performed a single-center prospective, longitudinal clinical study in 15 patients between 11 and 22 weeks of gestation. The origin and course of the different blood vessels were identified.

RESULTS There was a linear association among gestational age, the biparietal diameter, and the length of the pericallosal artery. The curvature of the developing pericallosal artery increases linearly with the gestational age and biparietal diameter, and 4 variations of branching of the callosomarginal artery were observed.

CONCLUSION The pericallosal artery and its branches can be identified and measured from 11 weeks on, and the pericallosal artery takes its characteristic course. A defective course or an abnormal biometry of the pericallosal artery could be an early sonographic marker of abnormal development of the corpus callosum.

GYNAECOLOGIE / VERLOSKUNDE

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CENTRUM

INWENDIGE ZIEKTEN / GASTRO-ENTEROLOGIE ARTIKELS ABSTRACT 1 Ruminococcus gnavus bacteremia associated with fecal peritonitis secondary to small bowel perforation Struyve M, De Vloo C, Van Moerkercke W., et al. Acta Gastro-enterologica Belgica, 2018, 81 (3), 451-452

RESULTS Short-term clinical benefit was achieved in 101 patients (44%) and was less frequent in infliximab failures [37% vs 50%, Odds ratio 0.57 (95% CI 0.34-0.97), P = 0.038]. After a median of 2.8 (1.7-5.1) months, 164 patients (71%) needed ADM discontinuation (n = 35, 15%) or dose escalation (n = 129, 56%). Dose escalation was successful in 77/129 (60%). Dose de-escalation was attempted in 71% (55/77) after a median of 4.3 (2.9-7.2) months and was successful in 80% (43/54).

Er is geen abstract beschikbaar

CONCLUSION ABSTRACT 2 A severe case of ulcerative esophagitis in an immunocompetent host Callens R, Persyn D, Van Moerkercke W Acta Gastroenterology Belgica, 2018, 81(1), 115 Er is geen abstract beschikbaar

ABSTRACT 3 Incidence and predictors of success of adalimumab dose escalation and de-escalation in ulcerative colitis: a real-world Belgian cohort study

In this cohort, 56% of patients with UC required ADM dose escalation with a 60% success rate. Of note, most patients could be successfully de-escalated later on.

ABSTRACT 4 Golimumab Dried Blood Spot Analysis (GOUDA): a Prospective Trial Showing Excellent Correlation with Venepuncture Samples and More Detailed Pharmacokinetic Information Van Moerkercke W,Detrez I, Schops G, et al. AAPS Journal, 2018 Dec 18;, 21(1), 10. doi: 10.1208/s12248018-0282-x.

INTRODUCTION Van de Vondel S, Baert F, Van Moerkercke W, et al. Inflammatory Bowel Diseases, 24(5), 1099-1105

INTRODUCTION/BACKGROUND Adalimumab (ADM) has been shown efficacious in ulcerative colitis (UC). In randomized controlled trials, dose escalation from 40 mg ADM every other week to 40 mg every week was required in 20%-25% of patients within 1 year. Real-life data suggest higher escalation rates. Attempts for dose de-escalation have not been studied yet. We assessed the need for, outcome of, and predictors of dose escalation and de-escalation in a large retrospective cohort of UC patients treated with ADM.

MATERIALS/METHODS We included 231 consecutive patients from 10 Belgian centers initiating ADM treatment for active UC before September 1, 2015 (follow-up ≥1 year in each patient). We performed detailed chart review to identify variables associated with short-term clinical benefit (based on physician global assessment and absence of rectal bleeding at week 10), success of dose escalation, and dose de-escalation. Backward Cox regression and Wald Logistic regression were used to identify predictive variables.

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ABSTRACTBOEK | 2018

Development of a dried blood spot (DBS) method for golimumab will facilitate sample collection in a study setting and will give a more complete insight in the total drug exposure (area under the curve, AUC). We established a DBS method and assessed its robustness, user-friendliness and clinical usefulness in 10 patients with ulcerative colitis during golimumab induction and maintenance regimens. DBS was obtained through spotting of golimumab spiked in whole citrated blood to a filter paper. Several extraction conditions were evaluated and the selected extraction condition analytically validated. In a clinical setting, DBS and serum samples were taken simultaneously through intensive sampling regimens and a conversion factor was determined. Golimumab concentrations were measured using an in-house-developed ELISA and a CE-marked ELISA kit. User-friendliness was evaluated using a questionnaire. Mucosal healing was evaluated at week 14. A total of 79 matched pairs of serum and DBS sample golimumab concentrations revealed an overall conversion factor of 3.9. DBS golimumab concentrations after conversion correlated strongly with serum golimumab concentrations (ICC = 0.984). During induction, no linear correlation was found between golimumab trough concentration (TC) and AUC (R2 = 0.29). Multiple peaks emerged during


drug absorption. Patients who achieved mucosal healing appeared to have less fluctuating TC and a constant AUC over time. Nine out of 10 patients reported DBS sampling as user-friendly. The GOUDA study showed that DBS sampling is a robust and patient-friendly alternative to venous blood collection. DBS sampling may provide better insights into golimumab absorption and exposure. (ClinicalTrials.gov NCT02910375).

ABSTRACT 5 An atypical presentation of an acute gastric Helicobacter felis infection Van Moerkercke W, Ghysen K, Smet A, et al. Acta Gastroenterol Belgica, 2018, Jul-Sep, 81(3), 436-438.

transmitted diseases (STD) in all patients presenting with rectal symptoms. A history of anal sexual intercourse should be made, especially in men having sex with men (MSM). Moreover, the possibility of a primary syphilis infection of the rectum should be considered. Endoscopic findings might be diverse, whereas a typical chancre can present as an anorectal ulcer associated with regional lymphadenopathy. It is important to consider other causes of anorectal ulcers, like other STD, inflammatory bowel disease (IBD) or even malignant causes. The diagnosis of anorectal syphilis is based on the combination of the clinical presentation, serology tests, endoscopic findings and biopsies. The cornerstone of the treatment is based on an intramuscularly administration of a long-acting preparation of penicillin (benzathine penicillin G).

INTRODUCTION

ABSTRACT 7

Helicobacter pylori is a Gram negative bacterium that has been associated with a wide variety of gastric pathologies in humans. Besides this well studied gastric pathogen, other Helicobacter spp. have been detected in a minority of patients with gastric disease. These species, also referred to as "H. heilmanii sensu lato" or "non Helicobacter pylori Helicobacter spp. (NHPH)", have a very fastidious nature which makes their in vitro isolation difficult. This group compromises several different Helicobacter species which naturally colonize the stomach of animals. In this article we present a case of a patient with severe gastritis in which H. felis was identified. The necrotic lesions observed at gastroscopy differ from the less active and less severe lesions generally associated with NHPH infections in human patients. The patient was successfully treated with a combination of amoxicillin, clarithromycin and pantoprazole. Infections with NHPH should be included in the differential diagnosis of gastritis when anatomopathological findings show an atypically shaped helicobacter.

Outcome of Pregnancies in Female Patients With Inflammatory Bowel Diseases Treated With Vedolizumab

ABSTRACT 6 Primary syphilitic proctitis : case report and literature review Struyve M, Meersseman W, Van Moerkercke W Acta Gastroenterol Belgica, 2018, Jul-Sep, 81(3), 430-432.

INTRODUCTION Rectal ulcerations are an uncommon presentation of a primary syphilis infection. Anorectal syphilis is difficult to diagnose because of its often asymptomatic or atypical clinical presentation. It is important to consider sexually

Van Moerkercke W, Moens A, van Hoeve K, et al. Belgian IBD Research and Development group (BIRD), Journal Crohns Colitis, 2019 Jan 1, 13(1), 12-18, doi: 10.1093/ecco-jcc/ jjy142. Het abstract is terug te vinden op pagina 24.

ABSTRACT 8 Acute non-cirrhotic portal vein thrombosis : review Salembier A, Verhamme M, Verhamme P, Van Moerkercke W. Acta Gastroenterol Belg, 2018, Apr-Jun, 81(2), 318-322

INTRODUCTION A 35-year-old man with a medical history of myocardial infarction, presenting with fever, general malaise and vague abdominal discomfort, was diagnosed with a portomesenteric venous thrombosis and acute cytomegalovirus (CMV) infection. Thrombophilia screening resulted in detection of heterozygosity for factor II G20210A gene mutation. Low molecular weight heparin in therapeutic dose was started, followed by disappearance of thrombus on imaging CT two months after diagnosis. The multifactorial origin of portal thrombosis and the importance of awareness of the link between CMV infection and an increased risk of thrombosis is emphasized with this case and review of the literature. Identifying CMV infection as a trigger for thrombosis can help to avoid extended anticoagulation. Acute non-cirrhotic PVT is a rare but probably underestimated condition as symp-

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toms may be discrete or non-specific. The origin of portal thrombosis is frequently multifactorial. Recent literature has emphasized the increasing prevalence of CMV-induced PVT in immunocompetent patients. The multifactorial origin of portal thrombosis and the importance of awareness of the link between CMV infection and an increased risk of thrombosis is emphasized with this review of the literature and included case. Identifying CMV infection as a trigger for thrombosis can help to avoid extended anticoagulation.

PRESENTATIES / CONGRESSEN

(n = 2, hip dysplasia and pulmonary valve stenosis). Of the five patients with active disease at conception, three pregnancies were unaffected, one female lost her foetus due to chorioamnionitis at week 22 and one had an active termination due to relational problems. One patient flared during pregnancy and delivered a child with Hirschsprung’s disease. VDZ was continued throughout pregnancy in two females and was stopped in the first, second and third trimester in 4, 11, and 1 patient, respectively. The median (IQR) gestational age, Apgar score at birth and birth weight were respectively 39 (37–39.4) weeks, 9 (9–9) and 3305 (2823–3698) grams. Eight children were breastfed for a median (IQR) of 10 (4–26) weeks. All newborns were vaccinated according to the standard Belgian regimen with 44% receiving Rotavirus vaccination. No serious infections or malignancies were reported during the first year of life.

ABSTRACT 1 Outcome of pregnancies in female IBD patients treated with Vedolizumab European Crohn’s and Colitis Organisation Annual Meeting Moens A, van Hoeve K, Van Moerkercke W, et al. Februari 2018, Vienna, Austria

INTRODUCTION/BACKGROUND Vedolizumab (VDZ) is a gut-targeted IgG1 anti-α4β7 integrin approved for treatment of inflammatory bowel disease (IBD). As IBD typically affects women at childbearing age, studies on pregnancy outcomes in patients under VDZ are important. Animal studies showed that MAdCAM-1, the ligand for α4β7-integrin, is expressed by maternal vessels during placental development and α4β7-expressing cells of the macrophage/monocyte lineage are therefore considered important in maternal/foetal tolerance. Blocking this interaction by VDZ might affect this process.

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ABSTRACTBOEK | 2018

CONCLUSION This is the largest cohort study on pregnancy outcomes in patients treated with VDZ. Despite the still low number of pregnancies, we observed a number of prenatal complications and congenital malformations, which urges more studies on the function of α4β7-MAdCAM1 interaction in the placenta. In the meanwhile, vigilance and strict follow-up of pregnant IBD patients treated with VDZ is necessary.

ABSTRACT 2 Effectiveness and persistence of Vedolizumab in patients with inflammatory bowel disease: results from the belgian REal-Life Study with VEdolizumab (Be-RELIVE) BIRD Meeting at Belgian week of gastroenterology Reenaers C, Cremer A, Van Moerkercke W, et al. Februari 2018, Antwerpen, Belgium

MATERIALS/METHODS

INTRODUCTION/BACKGROUND

This retrospective, national observational study evaluated the outcome of pregnancies in IBD patients under VDZ. Details on disease activity, prenatal complications, delivery and neonatal outcome were collected.

RESULTS

Vedolizumab (VDZ) was efficacious in inducing and maintaining remission in Crohn’s disease (CD) and ulcerative colitis (UC) in the Phase III GEMINI studies. This retrospective study assessed effectiveness and treatment persistence of VDZ in a Belgian real-world cohort of patients with CD or UC, including more than 25% of biologic-naïve patients.

A total of 23 pregnancies were reported. All but five women had disease remission at conception. There were 18 live births (72% female, incl. two twins), two interrupted pregnancies and five pregnancies are still ongoing. Maternal characteristics are displayed. Patients, who remained in remission (n =12), reported the following complications: intra-uterine growth retardation (n = 1), eclampsia (n = 1), premature rupture of the membranes (n = 2) and congenital malformation

CD and UC patients who started VDZ between 01/09/2015 and 31/07/2016 and who attended at least 1 visit after first infusion were included from 15 Belgian centres. Data were collected at baseline (before first infusion), week (W)10, W14 (CD patients only), and month (M)6. Last data were collected in January 2017. Treatment response and remission rates were assessed

MATERIALS/METHODS


based on the changes in disease activity scores. Data analyses were performed according to disease type (UC/CD), and further stratified by treatment history (biologic-naïve/ failure patients). Treatment persistence was assessed using Kaplan–Meier analysis. Adverse events (AEs) recorded in patients’ files were collected.

RESULTS Of the 418 patients who started VDZ (safety population), 325 (202 CD and 123 UC) eligible patients were included in data analyses (effectiveness population). 22.2% of UC and 34.2% of CD patients were biologic-naïve. About three-quarters of the patients achieved clinical response at W10/W14 (CD: 71.4%; UC: 77.2%) that persisted up to M6 (CD: 75.6%; UC: 83.9%). At M6, 66.7% of CD patients were in remission; the response and remission rates were numerically higher among biologic-naïve patients (UC, respectively, additional 9% and 24%; CD, additional 22% and 35.8%) (Table 2) .At M6, 87.6% of CD and 86.1% of UC patients were still on VDZ treatment. For 7.7% of patients, VDZ dose was escalated to every 4W. The most common AEs (n = 418) were arthralgia (3.8%), fatigue (3.6%), skin eruption (3.1%), headache (2.9%) and gastroenteritis (2.6%).

CONCLUSION After 6 months of treatment with VDZ, about 85% of patients were still on treatment, of whom more than 40% achieved remission. Treatment effectiveness appeared higher in biologic-naïve compared with biologic-failure patients. No new safety signals were raised. These results are consistent with findings from the Phase III and real-world evidence studies with VDZ.

ABSTRACT 3 Ustekinumab induces clinical and biological remission in biologic refractory Crohn’s disease patients: A realworld belgian cohort study European Crohn’s and Colitis Organisation Annual Meeting Liefferinckx C, Verstockt B, Van Moerkercke W, et al. Februari 2018, Vienna, Austria

MATERIALS/METHODS Prospectively collected data were retrospectively analyzed according intention-to-treat. Patients received IV UST (induction) and 90 mg SC q8 weeks from week 8. Primary endpoints were clinical response/remission at week 8 and 16. Clinical response/remission were defined as a reduction in Harvey Bradshaw Index (HBI) of ≥3 and HBI≤4, respectively. Biological response/remission were defined as 50% drop of C-reactive protein (CRP) and CRP <5 mg/l respectively if CRP ≥ 5 mg/l at baseline. Serum UST samples were available in 94 patients at week 8 and were measured with an ELISA developed by KU Leuven. Paired analysis was performed for faecal calprotectin (fCal) at baseline and week 8(=60) and week 16 (n = 33).

RESULTS Demographic and baseline data of the study population of 157 (142 reached week 16) patients are presented. Clinical response and remission, clinical and biological response and remission, and steroid-free remission at week 8 and week 16 are presented in Figure 1. CRP significantly decreased from baseline (14.7 mg/l, IQR [8.8–27.7]) to 6.2 mg/l at week 8 (IQR [2.85–11.85], p < 0.0001) and 6.6 mg/l (IQR [2.2–14.9] at week 16, p < 0.0001). In subset with available paired samples, a 50% drop in fCal was observed in 33% (20/60) and in 39.4% (13/33) of patients at week 8 and 16. Week 8 UST levels were not significantly associated with (short-term) clinical response (p = 0.15). However, a significant inverse correlation was seen between UST levels and CRP at week 8 (p = 0.002). At induction, 33.3% of patients (47/141) experienced arthralgia (excluding patients with ankylosing spondylitis, n = 16), disappearing in 25.5% and 34% of them at week 8 and 16 respectively. By week 16 only 3.2% of patients (5/157) had reported side effects and 5.7% of patients (9/157) required CD surgery. Clinical response and remission, clinical and biological response and remission, and steroid-free remission at week 8 and week 16.

CONCLUSION UST is effective in inducing short-term clinical response and remission in this highly refractory CD cohort, including a significant reduction in CRP levels and fCal UST levels at week 8 inversely correlate with CRP but not with short-term outcome.

INTRODUCTION/BACKGROUND

ABSTRACT 4

Ustekinumab (UST), a fully humanized IgG1 monoclonal antibody targeting IL12/23p40, was recently approved for moderate to severe Crohn’s disease (CD). We report real-world short-term efficacy data in a Belgian cohort with prior exposure to both anti-TNF and vedolizumab and correlate outcome with week eight UST serum levels.

Beclomethasone dipropionaat is effective for microscopic colitis: results of an open-label multicentre study (COLCO). European Crohn’s and Colitis Organisation Annual Meeting De Corte T, Janssens E, Van Moerkercke W, et al. Februari 2018, Vienna, Austria

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INTRODUCTION/BACKGROUND

ABSTRACT 5

Microscopic colitis (MC: collagenous (CC) or lymphocytic colitis (LC)) is characterised by chronic watery diarrhoea and possibly fecal incontinence. Budesonide has proven effective for MC: the two commercially available preparations are released in the ileum. Beclomethasone dipropionaat (Clipper) is a synthetic corticosteroid with topical colonic release. We hereby report the first series of MC patients treated with open label beclomethasone.

La guérison précoce de la muqueuse chez les patients atteints de colite ulcéreuse modérée à sévère sous traitement par golimumab prédit des résultats favorables : l’étude BE-SMART Les Journées Francophones d’Hépato-gastroentérologie en d’Oncologie Digestive D’Heygere F, Bossuyt P, Baert F, et al. Maart 2018, Paris, France

MATERIALS/METHODS Prospectively collected data of 23 patients with CC or LC from six centres were retrospectively analysed. Inclusion criteria were: confirmed diagnosis of MC and symptomatic disease (DAI ≥ 21, i.e. ≥21 loose stools over 7 days). Treatment consisted of beclomethasone 10 mg/day for 4 weeks, followed by 5 mg/day for 4 weeks. Patients filled out a Bristol stool scale diary at baseline, Week 4 and Week 8. At Week 12, patients were contacted again by telephone for follow-up. The primary endpoint is the proportion of patients in remission (DAI≤11) after 8 weeks. Secondary endpoints are the proportion of patients responding to therapy (defined as subjective improvement by physician global assessment) at Week 4 and Week 8, remission at Week 4 and Week 12, and relapse at Week 12. Reported adverse events were collected.

RESULTS Baseline characteristics are presented. At Week 8, two patients had prematurely stopped treatment due to constipation. At Week 8, 16 patients (70%, LC 63%, CC 83%) were in remission, 18 (78%, LC75%, CC83%) responded to treatment. The mean number of stools a day decreased from 7 (range 3–30) at baseline to 1.72 (0–5) with 0.73 (0–5) diarrhoea (Figure 1). After 4 weeks of treatment, 22 patients (95%, LC94%, CC100%) were responsive, 18 patients (78%, LC75%, CC83%) were in remission. At week 12, 15 patients (65%, LC63%, CC67%) were still in remission, four initial responders (3LC, 1CC) relapsed. Of the seven patients who received budesonide during another flare, four reported better/faster response with beclomethasone, three similar response. Eleven patients reported 14AE: constipation (n = 4) flushing (n = 2), muscle cramps (n = 2), hyperglycaemia (n = 1), hyperactivity (n =1), vaginal discharge (n = 1), headache (n = 1), and hoarseness (n = 1). All AE were graded as mild and transient, except for one case of muscle cramps and one of hyperglycaemia.

CONCLUSION This open-label study suggests that an 8-week course of beclomethasone is a promising and relatively safe treatment for MC. A controlled study is warranted.

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ABSTRACTBOEK | 2018

INTRODUCTION/BACKGROUND Golimumab (GOL) est enregistré pour le traitement de la colite ulcéreuse (CU) modérée à sévère. Les données sur l'utilisation de GOL dans la pratique clinique quotidienne sont limitées. Actuellement, les facteurs prédictifs de résultat favorable ne sont pas clairement établis. Le but principal, est a évaluer les résultats à moyen terme de GOL chez les patients atteints d'CU modérée à sévère et déterminer les prédicteurs de résultat favorable.

MATERIALS/METHODS Évaluation des résultats à moyen terme des patients inclus dans l'étude SMART (NCT02155335). Enregistrement rétrospectif des données démographiques, des caractéristiques de la maladie et des antécédents médicaux. Collecte des données sur l'activité de la maladie (basée sur le score MAYO total), les médicaments antérieurs et concomitants, le dosage de GOL, la guérison de la muqueuse (Mayo 0 ou 1), les effets indésirables (colectomie, hospitalisation) et les biomarqueurs (protéine C réactive, calprotectine fécale, hémoglobine et albumine) à l’inclusion et aux semaines 2, 6, 14, 26 et 52. Le critère d'évaluation primaire était la poursuite du GOL sans stéroïdes à la semaine 26.

RESULTS Huit patients de l'étude SMART sur 100 ont dû être exclus (faible activité de la maladie à l’inclusion, diagnostic erroné, perte de suivi). Sur les 92 patients (42 % de femmes, âge médian de 41 ans, durée médiane de la maladie de 5 ans), 4 % étaient des fumeurs actifs, 25 % présentaient une colite extensive et 38 % avaient un score endoscopique Mayo de 3 à l’inclusion. Le score Mayo médian à l’inclusion (IIQ) était de 9 (8-10). Alors que 76 % des patients avaient déjà échoué au traitement par immunomodulateurs (IMiDs), la majorité d’entre eux (87 %) n’avaient jamais reçu de traitement par facteur de nécrose tumorale (TNF). Un traitement par GOL combiné à des IMiDs et à des stéroïdes a été initié chez respectivement 38 % et 64 %. Le suivi médian (IIQ) de la thérapie par GOL était de 36 (12-106) semaines. Vingt-six semaines après l’induction de GOL,


38 patients (41 %) étaient toujours sous traitement par GOL sans stéroïdes. Six d’entre eux ont nécessité une optimisation du dosage de GOL. La guérison à court terme de la muqueuse à la semaine 14 a pu être évaluée chez 52 % des patients et a été atteinte chez la moitié d'entre eux. Dans l'analyse multivariée, seuls les stéroïdes systémiques concomitants (p = 0,044) permettaient de prédire une guérison à court terme de la muqueuse. Les patients qui présentaient une guérison à court terme de la muqueuse ont plus fréquemment atteint le critère d'évaluation primaire [67 % contre 29 %, OR 4,86 (95 %CI 1,43-16,50), p = 0,011]. Au cours d'un suivi médian (IIQ) de 26 (23-30) mois, 78 % ont eu besoin d'une intervention thérapeutique et 63 % ont arrêté de prendre le GOL. La guérison à court terme de la muqueuse était significativement associée à la survie sans intervention (p = 0,030) et au traitement prolongé par GOL (p = 0,002).

patients participating in the vedolizumab PASS study (a new user cohort study). At recruitment, collected parameters included demographics, IBD characteristics and medical history, disease activity (Harvey-Bradshaw Index (HBI; remission <5)/ partial Mayo Score (pMS; remission <3 with no sub score >1) and quality of life (SIBDQ). Patients have a follow-up visit every 6 months for 3 years with reassessment of the above parameters, adverse events, hospitalisations, surgery and medical resource use. This interim analysis focuses on a subset of registry participants who were on vedolizumab maintenance therapy (beyond the 14 weeks of induction period) at the time of recruitment, representing a prospective maintenance cohort. The results are reported as observed.

RESULTS

MATERIALS/METHODS

Of the 200 patients in the registry 196 had data available for analysis. Among them, 167 were under vedolizumab maintenance therapy at recruitment, these patients form the maintenance cohort. Ninety seven patients in the maintenance cohort have reached at least the first 6-monthly follow-up visits (medium follow-up = 6 months, range =4-13 months) and no patients have dropped out of the registry. Thirteen patients (7.8%) have discontinued therapy (0 in UC and 13 in CD) for intolerance (4), insufficient response (8), patient choice (2) or malignancy (2). The proportion of patients in remission at recruitment, 6 months and 12 months follow-up was 63%, 90%, 89% for UC and 57%, 57%, 67% for CD respectively. The proportion of UC patients with normal stool frequency increased from 50% at recruitment to 89% at 12 months. The proportion of UC patients with no rectal bleeding was 83% at recruitment and reached 89% after 12 months. Among CD patients, the mean number of liquid stools per day decreased from 2.3 at recruitment to 1.5 at 12 months follow-up. C-reactive protein levels remained low during follow-up with median values of 2.9, 3.0 and 1.8 mg/dL at recruitment, 6 months and 12 months follow-up respectively. SIBDQ overall score and SIBDQ fatigue score at recruitment, 6 months and 12 months follow-up were relatively constant at 51, 50, 50 (overall) and 4.2, 4.0 4.3 (fatigue), although no PRO measurement was available prior to recruitment. No drug-related SAEs occurred during follow-up.

Two hundred UC and CD patients treated with vedolizumab were prospectively enrolled during 2016/17 from 19 Belgian centres into the Belgium Prevalent Vedolizumab Users Registry. Inclusion criteria included ongoing vedolizumab therapy started at least 15 days prior to recruitment, age 18 or older, and patient not participating in a clinical trial. Patients enrolled in this registry were non-overlapping with

These real life data from UC and CD patients under maintenance therapy with vedolizumab confirm in everyday practice over one year the sustained clinical beneficial effects reported in clinical trials. No safety signals were observed.

CONCLUSION Bien que des interventions thérapeutiques soient fréquemment nécessaires, les données de la vie réelle confirment l'efficacité à moyen terme de GOL dans le traitement de la CU modérée à sévère. La guérison à court terme de la muqueuse prédit un résultat favorable.

ABSTRACT 6 Vedolizumab maintenance in everyday practice is associated with a sustained benefit measured by clinical scores and patient reported outcomes United European Gastroenterology Week D’Heygere F, De Vos M, Colard A, et al. October 2018, Vienna, Austria

INTRODUCTION/BACKGROUND Pivotal clinical trials have demonstrated clinical efficacy of vedolizumab as maintenance therapy for Crohn’s disease (CD) and ulcerative colitis (UC). The aim of this prospective cohort study is to assess maintenance clinical benefit, safety and Patients Reported Outcomes (PROs) in real life practice in Belgium.

CONCLUSION

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CENTRUM

KINDERGENEESKUNDE ARTIKELS

ABSTRACT 2

ABSTRACT 1

Renal progression factors in young patients with tuberous sclerosis complex: a retrospective cohort study

Prospective and longitudinal natural history study of patients with Type 2 and 3 spinal muscular atrophy: baseline data NatHis-SMA study

Janssens P, Van Hoeve K, De Waele L, et al. Pediatric Nephrology, 2018, 33(11), 2085-2093

Chabanon A, Seferian AM, De Waele L, et al. Plos One, 2018, 13(7), e0201004

INTRODUCTION/BACKGROUND Spinal muscular atrophy (SMA) is a monogenic disorder caused by loss of function mutations in the survival motor neuron 1 gene, which results in a broad range of disease severity, from neonatal to adult onset. There is currently a concerted effort to define the natural history of the disease and develop outcome measures that accurately capture its complexity. As several therapeutic strategies are currently under investigation and both the FDA and EMA have recently approved the first medical treatment for SMA, there is a critical need to identify the right association of responsive outcome measures and biomarkers for individual patient follow-up. As an approved treatment becomes available, untreated patients will soon become rare, further intensifying the need for a rapid, prospective and longitudinal study of the natural history of SMA Type 2 and 3. Here we present the baseline assessments of 81 patients aged 2 to 30 years of which 19 are non-sitter SMA Type 2, 34 are sitter SMA Type 2, 9 non-ambulant SMA Type 3 and 19 ambulant SMA Type 3. Collecting these data at nine sites in France, Germany and Belgium established the feasibility of gathering consistent data from numerous and demanding assessments in a multicenter SMA study. Most assessments discriminated between the four groups well. This included the Motor Function Measure (MFM), pulmonary function testing, strength, electroneuromyography, muscle imaging and workspace volume. Additionally, all of the assessments showed good correlation with the MFM score. As the untreated patient population decreases, having reliable and valid multi-site data will be imperative for recruitment in clinical trials. The pending two-year study results will evaluate the sensitivity of the studied outcomes and biomarkers to disease progression.

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ABSTRACTBOEK | 2018

BACKGROUND/INTRODUCTION Renal pathology in tuberous sclerosis complex (TSC) is characterized by the growth of angiomyolipoma and renal cysts, and in rare cases renal cell carcinoma. Other consequences of renal involvement in TSC, including hypertension, proteinuria, and hyperfiltration, are not well studied. We aimed to analyze the early manifestations of the renal TSC phenotype in a young TSC cohort and to explore common, modifiable risk factors.

MATERIALS/METHODS In this retrospective cohort study, TSC patients attending the TSC clinics of two tertiary hospitals were included. Data on demographics, history, genotype, kidney function, hematuria, proteinuria, blood pressure, and renal imaging were collected.

RESULTS Eighty patients were included, with a median age of 0.8 years (0.0-63.0) at first presentation, and a median follow-up time of 10.2 (0.4-41.0) years. Mutation analysis was available in 64 patients (80%). Renal lesions (cysts or angiomyolipoma) were observed in 55/73 (75%). Thirty-two percent (19/60) were hypertensive, 8/51 (16%) had proteinuria, and 18/71 (25%) had hyperfiltration (median eGFR 154 ml/min/m2). Six (7.5%) patients had developed end stage renal disease at the last follow-up. No association was found between hyperfiltration, hypertension, or proteinuria and CKD ≥ 3. Cox regression showed a significant positive association between the presence of a renal intervention and CKD ≥ 3 (HazardRatio 3.91, P < 0.05).

CONCLUSION Besides renal cysts and angiomyolipoma, the modifiable progression factors hypertension, proteinuria, and hyperfiltration occur frequently and early in TSC patients. This represents a preventive treatment target.


CENTRUM

KLINISCH LABORATORIUM ARTIKELS

ABSTRACT 3 Ruminococcus gnavus bacteremia associated with fecal peritonitis secondary to small bowel perforation

ABSTRACT 1 Circulating microRNA biomarkers for metastatic disease in neuroblastoma patients

Struyve M, De Vloo C, Lefever S, et al. Acta Gastro-enterologica Belgica, 2018, 81 (3), 451-452

Zeka F, Van Maerken T, Van Goethem A, et al. JCI Insight, 2018, 3(23), e97021

Er is geen abstract beschikbaar.

OBJECTIVE

ABSTRACT 4

In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease.

Cellulitis bij een immuungecompromitteerde patiĂŤnt De Bel A, Boudewijns M, Vankeirsbilck C, et al. Tijdschrift voor Geneeskunde, 2018, 74 (2), 138-141

MATERIALS/METHODS

INTRODUCTION/BACKGROUND

After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in 2 independent cohorts of 131 and 54 patients.

The case of a 77-year-old, immunocompromised male patient with Campylobacter fetus bacteremia complicated by cellulitis, is reported. The infection was characterized by a protracted course with one recurrence, responding to a prolonged course of amoxicillin-clavulanic acid treatment. Campylobacter are very motile, curved, microaerophilic Gramnegative bacteria. Among the species of Campylobacter, C. fetus usually presents as an extra-intestinal infection, mainly bacteremia, but rarely induces digestive symptoms. In humans, C. fetus infection is observed in patients with severe underlying disease, such as immunodeficiency.

RESULTS Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis, and overall survival revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential abundance analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume. These findings were validated in longitudinal serum samples from metastatic neuroblastoma patients, where the 9 miRNAs were associated with disease burden and treatment response.

ABSTRACT 5 A pragmatic bottom-up approach to harmonize the units of clinical chemistry tests among Belgian clinical laboratories, focusing on immunoassays Demarteau M, Cammaert P, Vandevelde NM, et al. Clinical Chemistry and Laboratory Medicine, 2018, 57(1), 12-19

INTRODUCTION/BACKGROUND ABSTRACT 2 Performance of the preanalytical check module of the Stago STA R Max2 mechanical endpoint detection analyzer for assessing the impact of hemolysis, lipemia, and icterus on aPTT and PT

Harmonization of units is an important step to improve the comparability of clinical chemistry results, but few examples exist of successful harmonization efforts. We present the results of a pragmatic approach that was implemented in Belgium from 2012.

MATERIALS/METHODS Florin L, Oyaert M, Van Maerken T, et al. International Journal of Laboratory Hematology, 2018, 40(6), e109-e112 Er is geen abstract beschikbaar.

After a large consultation and information of stakeholders, preferred units were proposed for 140 assays, including the 23 immunoassays discussed in more detail here. The change occurred in two phases, first involving assays for which there was no change in the numerical result, then

KLINISCH LABORATORIUM

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changes involving a change in numerical results. Laboratories were invited to participate in this harmonization on a voluntary basis. The project was based on a bottom-up approach, large consultation and the pragmatic choice of the proposed units, including conventional and SI units.

RESULTS The large heterogeneity of units was drastically reduced; adoption of the preferred units increased from 3% (insulin) 45% (HCG) to 70% (insulin) - 96% (LH and FSH). Adoption of the preferred units was higher if it involved no change in numerical values (90%) than when there was a change (76%).

over 40 hours was observed in the BAM model in contrast to 2D cell culture, showing the capacity of the BAM model to function as a drug depot. We also determined compound toxicity on the BAMs by measuring creatine kinase release in the medium, which increased with increasing toxic insult. Taken together, we show that the BAM is an injectable human 3D cell culture model that can be used to measure release and metabolism of injected compounds in vitro.

PRESENTATIES / CONGRESSEN

CONCLUSION We believe that the harmonization effort has reached its goals. Without aiming at implementing SI units for all parameters, our strategy was successful with a large majority of the laboratories switching to the proposed units. Moreover, the harmonization program is still progressing, with additional laboratories converting to the consensus units

ABSTRACT 6 Human tissue-engineered skeletal muscle: a novel 3D in vitro model for drug disposition and toxicity after intramuscular injection Gholobova D, Gerard M, Callewaert N, Thorrez L, et al. Scientific Reports, 2018, 8, 12206

INTRODUCTION/BACKGROUND The development of laboratory-grown tissues, referred to as organoids, bio-artificial tissue or tissue-engineered constructs, is clearly expanding. We describe for the first time how engineered human muscles can be applied as a preor non-clinical model for intramuscular drug injection to further decrease and complement the use of in vivo animal studies. The human bio-artificial muscle (BAM) is formed in a seven day tissue engineering procedure during which human myoblasts fuse and differentiate to aligned myofibers in an extracellular matrix. The dimensions of the BAM constructs allow for injection and follow-up during several days after injection. A stereotactic setup allows controllable injection at multiple sites in the BAM. We injected several compounds; a dye, a hydrolysable compound, a reducible substrate and a wasp venom toxin. Afterwards, direct reflux, release and metabolism were assessed in the BAM constructs in comparison to 2D cell culture and isolated human muscle strips. Spectrophotometry and luminescence allowed to measure the release of the injected compounds and their metabolites over time. A release profile

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ABSTRACT 1 Biotin and anti-streptavidin antibodies interference on Roche thyroid function tests: validation of the new Elecsys FT4 III Royal Belgian Society of Laboratory Medicine Annual Meeting Verougstraete N, Callewaert N November 2018, Brussel, Belgium

INTRODUCTION/BACKGROUND In several immunoassay platforms the biotin-streptavidin interaction is used for separation of the formed immune complexes. The Roche thyroid function tests (TFTs) are vulnerable to analytical interference due to biotin or streptavidin antibodies, leading to falsely increased results with competitive assays (FT3 and FT4) and falsely decreased results with sandwich assays (TSH). The combination of interferences mimics a biochemical hyperthyroidism, with a risk of misdiagnosis and mistreatment of the patient. Recently, Roche has launched a 3th generation FT4 assay in which blocking proteins are added in order to improve robustness against these interferences. We validated this new assay and checked the influence of the blocking proteins on real patient samples with high concentrations of biotin or streptavidin antibodies.

MATERIALS/METHODS Precision was evaluated according to the CLSI EP15-A3 protocol: 2 QC levels (PC Universal; L1 14.2 and L2 39.1 pmol/L) were analysed 5 times per day for 5 days. The repeatability and intermediate precision variation coefficients (CV%) were calculated using a one-way nested ANOVA. Total error (TE) was calculated from the reproducibility data. For method comparison 40 routine serum samples were measured simultaneously with the 2nd and 3th generation FT4 assays. All measurements were performed on a Cobas e602 analyzer.


Three samples from a patient with streptavidin antibodies were analyzed with both assays, before and after a neutralization protocol with streptavidin coated microparticles. FT4 levels were also determined in a sample before and 1h after the intake of 20mg biotin. These samples were also analyzed on a biotin-streptavidin independent platform (Architect, Abbott).

RESULTS Within- and between-day precision ranged from 1.7% to 1.9% and from 2.4% to 3.2%, respectively. TE for the low and high QC were 5.5% and 4.9%, respectively. Results from patients samples on both assays showed a linear correlation (Spearman ρ= 0.993) and the Passing-Bablok regression equation was y=0.10+0.98x, which means comparable results were obtained.

of his hemodynamic function despite early aggressive fluid resuscitation, he was transferred to ICU. Abdominal cramps worsened and a fulminant diarrhea developed, resulting in hypovolemic shock and cardiorespiratory collapse. Despite full supportive therapy, the patient died approximately 10 hours after injection due to multiple organ failure. Ricinine was quantified by LC–MS/MS after LLE with diethyl ether using ricinine-D3 as internal standard. Six hours after injection, ricinine concentrations in serum and blood were 16.5 and 12.9 ng/mL, respectively, which decreased to 12.4 and 10.6 ng/mL, 4 hours later. The urinary concentration was 81.1 ng/mL 7 hours after injection, which amply exceeded the levels previously reported in similar cases with lethal outcome. Concentrations of ricinine, compatible with a lethal exposure to castor beans, were detected in serum, blood and urine. Ricinine was also found in bile and liver tissue.

CONCLUSION The Elecsys FT4 III has overall good assay performance. Results from non-interfering samples are comparable with the previous generation, but the new assay is indeed more robust against biotin and streptavidin interference by addition of blocking proteins. In order to cope with these interferences, the other TFTs should similarly be optimized.

ABSTRACT 3 Room decontamination with no-toch technology: comparison between hydrogen peroxide and QUAT's European Society of Clinical Microbiology and Infectious Diseases De Bel A, Boudewijns M, Leroux-Roels I April 2018, Madrid, Spain

ABSTRACT 2 Lethal injection of a castor bean extract: quantification of ricinine as a marker for ricin exposure using a simple fully validated LC-MS/MS method The International Association of Forensic Toxicologists Annual Meeting Verougstraete N, Deprez C, Casier I, et al. August 2018, Gent, Belgium

INTRODUCTION/BACKGROUND Ricin is a highly toxic agent derived from the castor bean plant (Ricinus communis). Poisoning occurs commonly by oral ingestion of the beans. Injection of ricin is believed to be more lethal. Ricin is a large glycosylated protein difficult to detect in clinical samples. Instead, ricinine, a small alkaloid found in the same beans, is used as surrogate marker for ricin exposure. We describe a simple LC–MS/MS method for the detection of ricinine in serum, blood and urine, validated according to EMA guidelines and successfully applied to patient samples of a suicidal death after injection of a castor bean extract. A 26-year-old man self-presented to the emergency department with severe abdominal cramps and nausea after injection of a castor bean extract. Due to rapid deterioration

INTRODUCTION/BACKGROUND Environmental contamination plays an important role in the transmission of health careassociated pathogens. No-touch technologies for room disinfection are an attractive option and a modern response to labour-intensive disinfection as they remove much of the variance inherent in human cleaning activity via a high degree of automation, creating a sustained cleaning quality with possible feedback loops for verification that contact times were adequate. In this study we evaluated the efficacy and user-friendliness of three nebulizing systems in intentionally contaminated rooms.

MATERIALS/METHODS The tested systems were (1) NDP Air Total® 50 and 300 ml (Vesismin), a single use nebulizer based on quaternary ammonium compounds (QUAT’s), (2) Nocospray® combined with 12% hydrogen peroxide solution (Nocolyse®, Oxypharm) at 5 and 3 ml/m3 , and (3) Aerosept compact 250® with Aseptanios AD® (Laboratories Anios), which is a stabilised solution of 0.12% peracetic acid and 2.5% hydrogen peroxide. If applicable, H2O2 concentrations were measured during processes with BIOXX1® (Oxypharm) or X-am 5100® (Dräger) device. Dried dilution series of four clinical isolates

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(Acinetobacter baumannii OXA-23 like, Klebsiella pneumoniae OXA-48, Enterococcus faecalis vanA and MRSA) were exposed to the three technologies in real life furnished patient rooms. Afterwards viable germs were recuperated with Rodac contact plates. Each experiment was performed in duplicate at least. A 5 log10 reduction of the inoculum, as stated in NF-T-72-281, was aimed.

methods (Umic® (Biocentric) and SensiTest® (ELITech)). Microdilution by Sensititre® (Thermo Fisher) was used as reference method, in line with EUCAST recommendations. All susceptibility methods were performed according to manufacturers’ instructions. MIC results were interpreted using the breakpoints by the joint CLSI-EUCAST working group. Real-time PCR for detection of mcr genes (mcr-1 to mcr-4) was performed on colistin resistant isolates.

RESULTS The obtained results are presented in Table 1. Only Nocospray® with 12% Nocolyse® yielded the desired results in all tested settings. However, H2O2 concentrations above 1 ppm were measured in the neighbouring hallway. On the other hand, the results of NDP Air Total® were unsatisfactory. As Aerosept®/Aseptanios® is a NF-T-72-281 labelled technology, local implementation cannot be excluded as the cause of suboptimal results, since a minimal concentration target to obtain for the active compound for successful process control is lacking.

RESULTS Twenty isolates exhibited susceptibility to colistin and 20 isolates acquired resistance from which 7 were mcr-1 positive E. coli isolates. The essential and categorical agreements are shown in table 1. With Vitek 2®, Phoenix® and Umic® false susceptible results were found. These isolates had a MIC of 2 mg/L on Vitek 2® and Umic®, but a MIC of 4 mg/L on Sensititre®. Both isolates were mcr1 positive. The false sensitive result on Phoenix® also had a MIC of 2 mg/L, but a MIC of >8 mg/L on Sensititre®.

CONCLUSION

CONCLUSION

The three systems were convenient to use but efficacy of NDP Air Total® is insufficient. There is a clear need for a validated target concentration for the active compound to balance potential toxicity and disinfection efficacy.

All test methods showed good essential and categorical agreements. With exception of the Sensitest® method, MIC results within one-dilution step below the S breakpoint however may indicate false susceptibility, especially in mcr1 positive isolates, leading to very major errors. Such results need confirmation by another well-validated method.

ABSTRACT 4 Evaluation of four commercial methods for colistin susceptibility testing European Congress of Clinical Microbiology and Infectious Diseases De Bont E, De BeL A, Van den Abeele A, Boudewijns M April 2018, Madrid, Spain

INTRODUCTION/BACKGROUND Acquired resistance to colistin in enterobacterial isolates is rising. There is however no optimal method for susceptibility testing. The joint CLSI-EUCAST Polymyxin Breakpoints working group recommends broth microdilution like Sensititre®, but studies on other commercial testing methods are limited. The aim of this study is the evaluation of four different commercial methods to help selection.

ABSTRACT 5 Epidemiology of plasmid-mediated colistin resistance among Enterobacteriaceae in a Belgian regional hospital: a prospective study European Congress of Clinical Microbiology and Infectious Diseases Boudewijns M, De Bel A April 2018, Madrid, Spain

INTRODUCTION/BACKGROUND There is concern about spread of colistin resistance, especially in multidrug-resistant (MDR) strains. However, the endemicity of acquired colistin-resistance due to mcr-genes among enterobacterial clinical isolates from hospitalized patients in Western Europe is largely unknown.

MATERIALS/METHODS Susceptibility testing was performed on a collection of 40 clinical isolates of Enterobacteriaceae from AZ Groeninge hospital, Belgium. Colistin MIC was determined in parallel by four methods: two automated methods (Vitek2® (Biomérieux) and Phoenix® (BD)) and two microdilution

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MATERIALS/METHODS This prospective observational study was conducted in a Belgian regional hospital with 1066 beds during a oneyear period (September 2016 – August 2017). Antimicrobial susceptibility testing including colistin was performed


on enterobacterial isolates from clinical samples by Vitek 2 (bioMérieux). This method was used as screening method (colistin MIC cut-off value > 0,5 mg/L). Confirmation of colistin MIC was performed by broth microdilution (Sensititre®, Thermo Fisher Scientific), in line with EUCAST recommendations. Presence of mcr genes (mcr-1 to mcr-4) was detected by in house PCR. Determination of clonality was performed by enterobacterial repetitive intergenic consensus (ERIC) PCR. MDR Enterobacteriaceae were defined according to ECDC/CDC definition.

RESULTS In total 4788 clinical isolates of Enterobacteriaceae were tested. Colistin resistance was detected in 30 isolates (0,6%) from 18 patients. Seven out of 18 strains tested positive for mcr genes (38,9%). They were all mcr-1 gene positive Escherichia coli. There were no other types of mcr genes detected. Most of the mcr-1 gene positive isolates (85,7%) were MDR, confined to penicillins (+/betalactamase inhibitor), fluoroquinolones and folate pathway inhibitors. Extended spectrum betalactamase-production and carbapenemase-production was not found among the mcr-1 gene positive isolates. ERIC typing of these seven isolates did not reveal clonality and the seven patients were not epidemiologically related in place and time.

CONCLUSION Acquired mcr-mediated colistin resistance in clinical isolates from hospitalized patients is still rare in Belgium. It is most prevalent in MDR isolates of E. coli, although not being highly drug-resistant, and is confined to the presence of mcr-1 gene. The absence of clonality among the clinical isolates indicates sporadic but repeated introduction in the hospital with potential risk of transmission.

Two commercial MALDI-TOF MS IVD systems are widely used in clinical laboratories: Vitek MS® (bioMérieux) and MALDI Biotyper® (Bruker Daltonics). Several comparative studies of these systems have already been published. Recently the Vitek MS® database has been extended and updated however.

MATERIALS/METHODS A prospective comparative study was conducted in two routine hospital laboratories (AZ Groeninge, Kortijk, Belgium and Sint-Andries, Tielt, Belgium). Isolates were collected from clinical samples during a 5 week period, with a maximum of 25 consecutive isolates per site and day. Isolates were subcultured on the same medium type from where they were initially recovered. After incubation isolates were tested in parallel on the Vitek MS® system with Vitek MS® v3.0 database and on the MALDI Biotyper ® system with v4.2.3 software and MBT Lib-5989 database. Interpretation was according to manufacturers’ instructions. In case of discordant results isolates were further identified by molecular testing.

RESULTS A total of 1003 isolates were tested representing 129 different bacterial species (53 genera) and 11 different yeast species (2 genera). Overall concordance between both methods was 92,5%, with 73 discrepant identification results. Vitek MS® and MALDI Biotyper® provided 94,6% and 97,9% correct identifications to the species level and an additional 2,9% and 0,1% to the genus level, respectively. Conversely, 1,1% and 0,1% of isolates were unidentified whereas 1,4% and 1,9% were misidentified by Vitek MS® and MALDI Biotyper®, respectively. Misidentifications were similarly distributed between Gram-positive and Gram-negative bacteria for both Vitek MS® and MALDI Biotyper®.

CONCLUSION ABSTRACT 6 Comparison of updated Vitek MS v3.0 with MALDI Biotyper MALDI-TOF MS for routine identification in the clinical microbiology laboratory European Congress of Clinical Microbiology and Infectious Diseases De Bont E, Van Hoecke F, De Bel A, Boudewijns M April 2018, Madrid, Spain

Under routine testing conditions the percentage of correctly identified clinical isolates was similar for both systems. Despite extension of the database, Vitek MS® resulted more often in no identification, whereas MALDI Biotyper® resulted slightly more often in misidentification in case of absence of an organism in the database. Overall, the observed differences were small.

INTRODUCTION/BACKGROUND Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDITOF MS) has revolutionized bacterial and fungal identification in the routine laboratory.

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CENTRUM

LONGZIEKTEN ARTIKELS ABSTRACT 1 A 64-year-old woman with interstitial lung disease and positive antibodies against aminoacyl-transfer RNA synthetases in the absence of myositis: presentation of an anti-PL-12 positive antisynthetase syndrome Ghysen K, Leys M Acta Clinica Belgica, 2018, 73(5), 389-392

INTRODUCTION/BACKGROUND The antisynthetase syndrome is a rare autoimmune disease described by the presence of inflammatory myositis, interstitial lung disease and antibodies against aminoacyltransfer RNA synthetases. Interstitial lung disease can be the only manifestation in the absence of an inflammatory myositis. Other clinical signs are Raynaud phenomenon, hyperkeratotic skin lesions, fever and inflammatory polyarthritis. We report the case of a 64-year old woman who complained of a dry cough, progressive dyspnea and arthralgia since 2 years, with no other systemic symptoms. High resolution computed tomography (HRCT) of the thorax showed the presence of bilateral ground glass opacities, reticular opacities and some traction bronchiectasis. Further biochemical testing revealed the presence of anti-PL12 antibodies.

OBJECTIVE With this case, we would like to point out the importance of a thorough clinical, biochemical, radiological and functional evaluation in patients presenting with an interstitial lung disease. Awareness of the antisynthetase syndrome is important since an early diagnosis is associated with a better response to therapy and less evolution to pulmonary fibrosis.

RESULTS The diagnosis of antisynthetase syndrome was made and the patient was treated with steroids and azathioprine with a good response.

CONCLUSION The search for antisynthetase antibodies should always be considered in patients with an interstitial lung disease without any other clinical symptoms or signs of an underlying connective tissue disease.

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CENTRUM

MEDISCHE BEELDVORMING ARTIKELS

ABSTRACT 3 The Spinnaker-Sail Sign: neonatal pneumomediastinum

ABSTRACT 1 Pulmonale reumanoduli en reumatoïde artritis ontrafeld: een case report met review

Vanden Berghe S, Devlies F, Seynaeve P, et al. Journal of the Belgian Society of Radiology, 2018, 102 (1), 51

INTRODUCTION/BACKGROUND Debrouwere T, Ghysen K, Herpels V, et al. Tijdschrift voor geneeskunde, 2018, 74 (21), 1454-1462

INTRODUCTION/BACKGROUND Reumatoïde artritis (RA) is het meest gekend vanwege zijn articulaire aantasting. In deze casus gaat het om een patiënte met pulmonale noduli die zelfs met correcte RA-therapie aan een gestaag tempo blijven doorgroeien. Zonder een gedegen achtergrondkennis van deze noduli zou men een foutieve diagnose kunnen plakken op deze longnodules bij een initieel klinisch en radiologisch onderzoek. In sommige gevallen werden patiënten al onterecht geopereerd waarbij aan een tumorale oorzaak gedacht werd. De hemoptyse en de nodulose, samen met het caviterende voorkomen op röntgenfoto en CT-onderzoek, bemoeilijken de zaak alleen nog maar. Daarnaast kan deze entiteit ook nog in combinatie met pneumoconiose voorkomen en veroorzaakt dan het weinig gekende en zeldzame caplansyndroom.

A 34-year-old woman has a vaginal partus after 38 weeks and one day of pregnancy. The delivery is induced because of pregnancy diabetes. There are no complications during delivery with epidural anesthesia. The neonate is a boy with a weight of 3150 g and a length of 50 cm. APGAR scores are 8 and 9 after one and five minutes. Twenty-five minutes after delivery the neonate begins to grunt and shows tachypnea. Saturation levels remain good at 96% without the need of extra oxygenation. There are no signs of cardiocirculatory distress. A chest X-ray (Figures 1 and 2) shows a pneumothorax at the left lung apex and the Spinnaker-Sail sign, a sign of pneumomediastinum. Because of the favorable cardiocirculatory condition of the neonate and the minor need for oxygenation, the clinicians opt for a conservative approach. The patient is admitted in the neonatal care unit and receives extra oxygenation in an incubator. Oxygenation is decreased during the following days and is ceased on day three. There is a favorable clinical evolution, with minor tachypnea and desaturation during breastfeeding. On day eight the respiratory function is back to normal.

ABSTRACT 2 Anatomically based classification of medial clavicle fractures Van Tongel A, Toussaint A, Herregods S, et al. Acta Orthopaedica Belgica, 2018, 84 (1), 62-67

INTRODUCTION/BACKGROUND Medial clavicle fractures represent less than 5% of all clavicle injuries. The purpose of this study was to evaluate reliability of a new anatomically based (AB) classification system compared to other classification systems and to evaluate the clinical outcome of nonoperative treated fractures. 55 acute medial clavicle fractures (55 patients) were 3D reconstructed and evaluated using the Edinburgh (ED), Throckmorton (TR) and new AB classification. The AB classification classified the fracture as medial (Type 1) or lateral (Type 2) to the costoclavicular ligament and no or minimal displaced (Type A) or displaced (Type B). Next, a consecutive retrospective clinical evaluation of 38 of these patients was performed using the Oxford Shoulder and Constant Score. An anatomically based classification shows the highest inter- and intra-observer reliability. In case the fracture line originate medial to the costoclavicular ligament and is displaced the Constant and Oxford scores are significantly less.

RESULTS The Spinnaker-Sail sign can be seen on a frontal plain radiograph of the chest and is characteristic for a pneumomediastinum in neonates. Both lobes of the thymus are lifted and displaced laterally due to the air in the mediastinum. This creates a wedge-shaped opacity extending into the superior mediastinum that has a sharp delineation inferiorly by the translucent mediastinal air. The Spinnaker-Sail sign is named after the headsail of a boat, which has a similar shape when it is stretched by the wind. Another name for this sign is the ‘Angel Wing’ sign. Pneumomediastinum occurs in approximately 1 per 1000 births. Sometimes the pneumomediastinum can occur due to positive pressure ventilation, birth trauma or meconium aspiration, although it is often idiopathic. In idiopathic pneumomediastinum, a difference in pressure between the alveoli and the surrounding tissues causes alveolar rupture. This allows air to escape alongside the peribronchial and perivascular structures to the mediastinum. In most cases the infant is asympomatic and not every case is detected. When the neonate remains stable, a conservative approach is the treatment of choice and a control chest radiograph can be used for follow-up.

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ABSTRACT 4 Trapeziometacarpal stabilization through dorsoradial ligament reconstruction: an early post-surgery in vivo biomechanical analyses

secondary to large-vessel occlusions. Here, we evaluated EmboTrap's safety and efficacy compared with established stent retrievers.

MATERIALS/METHODS Kerkhof FD, Vereecke EE, Vanovermeire O, et al. Journal of orthopaedic research, 2018, 36(11), 2851-2864

INTRODUCTION/BACKGROUND Ligament reconstruction can provide pain relief in patients with a painful, unstable, pre-arthritic trapeziometacarpal (TMC) joint. Imbrication of the dorsoradial ligament (DRL) has been proposed as a minimal invasive stabilization technique. It requires less invasive surgery than an Eaton-Littler technique and shows promising long-term clinical outcome. We used dynamic CT to objectively review the effects of the imbrication. Four patients with pain and laxity at the TMC joint, but without radiographic signs of osteoarthritis, were recruited. Dynamic CT scans were made during active thumb abduction-adduction, flexion-extension, and two functional grip tasks using a radiolucent jig. Scans of the patients were acquired before and 3 to 6 months after DRL reconstruction. Motion of each bone in the articular chain of the thumb was quantified. In addition, we mapped changes in the contact patterns between the articular facets during the entire thumb motion. After DRL imbrication, we found no overall decrease in MC1 movement in three out of four patients. Furthermore, no increase in TMC joint congruency, defined as proximity area size, was found for three out of four patients. Pre- and post-operative differences in congruency across different tasks were patient-dependent and relatively small. We demonstrated that, from a biomechanical perspective, there is high variability in post-operative outcome between patients that undergo identical surgical procedures performed by the same surgeon. A post-operative decrease in range of motion, increase in joint congruency or decrease in proximity area shift during thumb motion is not omnipresent.

ABSTRACT 5 Primary results of the multicenter ARISE II study (analysis of revascularization in ischemic stroke with embotrap)

ARISE II (Analysis of Revascularization in Ischemic Stroke With EmboTrap) was a single-arm, prospective, multicenter study, comparing the EmboTrap device to a composite performance goal criterion derived using a Bayesian meta-analysis from the pivotal SWIFT (Solitaire device) and TREVO 2 (Trevo device) trials. Patients at 11 US and 8 European sites were eligible for inclusion if they had large-vessel occlusions and moderate-to-severe neurological deficits within 8 hours of symptom onset. The primary efficacy end point was achievement of modified Thrombolysis in Cerebral Ischemia (mTICI) reperfusion scores of ≥2b within 3 EmboTrap passes as adjudicated by the core laboratory. The primary safety end point was a composite of symptomatic intracerebral hemorrhage and serious adverse device effects. Secondary end points included functional independence (modified Rankin Scale, 0-2) and all-cause mortality at 90 days.

RESULTS Between October 2015 and February 2017, 227 patients were enrolled and treated with the EmboTrap device. The primary efficacy end point (mTICI ≥2b within 3 passes) was achieved in 80.2% (95% confidence interval, 74%-85% versus 56% performance goal criterion; P value, <0.0001), and mTICI 2c/3 was 65%. After all interventions, mTICI 2c/3 was achieved in 76%, and mTICI ≥2b was 92.5%. The rate of first pass (mTICI ≥2b following a single pass) was 51.5%. The primary safety end point composite rate of symptomatic intracerebral hemorrhage or serious adverse device effects was 5.3%. Functional independence and all-cause mortality at 90 days were 67% and 9%, respectively.

CONCLUSION The EmboTrap stent-retriever mechanical thrombectomy device demonstrated high rates of substantial reperfusion and functional independence in patients with acute ischemic stroke secondary to large-vessel occlusions;

ABSTRACT 6 Zaidat O, Bozorgchami H, Andersson T, et al. Stroke, 2018, 49(5), 1107-1115

The LUNA aneurysm embolization system for intracranial aneurysm treatment: short-term, mid-term and long-term clinical and angiographic results

INTRODUCTION/BACKGROUND EmboTrap is a novel stent retriever designed to achieve rapid and substantial flow restoration in acute ischemic stroke

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Pioton M, Biondi A, Sourour N, et al. Journal of Neurointerventional Surgery, 2018, 10(12), 1-8


INTRODUCTION/BACKGROUND

INTRODUCTION/BACKGROUND

Intrasaccular aneurysm flow disruption represents an emerging endovascular approach to treat intracranial aneurysms. The purpose of this study was to determine the clinical and angiographic outcomes of using the LUNA aneurysm embolization system (AES) for treatment of intracranial aneurysms.

The recent success of endovascular stroke treatment has heralded a new era in the management of acute ischemic stroke (AIS) with significantly improved outcome for patients. A large number of patients may be amenable to this new treatment and as the evidence expands the number of patients eligible for mechanical thrombectomy continues to increase. Recent evidence suggests that the time window for treatment can be extended up to 24 h after symptom onset for patients with anterior circulation strokes; however, many clinicians and medical professionals may not be aware of these recent changes and it is important that they are kept up-to-date with this rapidly evolving treatment. This review provides an overview of the recent successful trials and highlights important steps that should be instituted in order to achieve rapid reperfusion and optimize the outcome for ischemic stroke patients. It also looks at the remaining controversies facing the field of thrombectomy. A short summary of each of these contentious areas is provided and the current state of the art.

MATERIALS/METHODS The LUNA AES Post-Market Clinical Follow-Up study is a prospective, multicenter, single-arm study that was designed to evaluate device safety and efficacy. Bifurcation and sidewall aneurysms were included. Aneurysm occlusion was assessed using the Raymond-Roy classification scale. Disability was assessed using the Modified Rankin Scale (mRS). Morbidity was defined as mRS >2 if baseline mRS ≤2, increase in mRS of 1 or more if baseline mRS >2, or mRS >2 if aneurysm was ruptured at baseline. Clinical and angiographic follow-up was conducted at 6, 12 and 36 months.

RESULTS Sixty-three subjects with 64 aneurysms were enrolled. Most aneurysms were unruptured (60/63 (95.2%)); 49 were bifurcation or terminal (49/64 (76.6%)). Mean aneurysm size was 5.6±1.8 mm (range, 3.6–14.9 mm), and mean neck size was 3.8±1.0 mm (range, 1.9–8.7 mm). Though immediate postoperative adequate occlusion was low (11/63, 18%), adequate occlusion was achieved in 78.0% (46/59) and 79.2% (42/53) of the aneurysms at 12 months and 36 months, respectively. Four patients were retreated by the 12-month follow-up (4/63 (6.3%)) and three patients were retreated by the 36-month follow-up (3/63 (4.8%)). There were two major strokes (2/63 (3.2%)), one minor stroke (1/63 (1.6%)) and three incidents of intracranial hemorrhage in two subjects (2/63 (3.2%)) prior to the 12-month follow-up. There was one instance of mortality (1/63, 1.6%). Morbidity was 0% (0/63) and 1.8% (1/63) at the 12-month and 36-month follow-ups, respectively.

ABSTRACT 8 Intracranial stenting after failure of thrombectomy with the EmboTrap® device Cornelissen SA, Andersson T, Holmberg A, et al. Clinical Neuroradiology, 2018, 1-7

INTRODUCTION/BACKGROUND Approved alternatives in the guidelines for acute ischemic stroke patients who have failed intracranial thrombectomy are lacking. Primary permanent intracranial stenting was initially used in the era before thrombectomy and might still be a useful rescue treatment in acute stroke patients suffering from ongoing large vessel occlusion refractory to thrombectomy.

MATERIALS/METHODS CONCLUSION LUNA AES is safe and effective for the treatment of bifurcation and sidewall aneurysms.

ABSTRACT 7 Mechanical thrombectomy - a brief review of a revolutionary new treatment for thromboembolic stroke

The prospectively collected registry of patients with acute stroke caused by large vessel occlusions and treated with the emboTrap® device in Karolinska Hospital from October 2013 through March 2017 were retrospectively reviewed. Clinical outcome of non-recanalized patients with a thrombolysis in cerebral infarction (TICI) score of 0-1 after failed thrombectomy were compared with those who were treated with permanent intracranial stenting as rescue therapy. Favorable outcome was defined as modified Rankin scale 0-2.

Bhogal P, Andersson T, Maus V, et al. Clinical Neuroradiology, 2018, 28(3), 313-326

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RESULTS

RESULTS

The emboTrap® device was used in 201 patients. Persistent re-occlusions on withdrawal of the thrombectomy device were seen in 26 patients (13%) and of those, 12 individuals (46%) were treated with intracranial stenting. Baseline National Institutes of Health stroke scale (NIHSS), occlusion site, and onset-to-puncture time did not differ between the stenting group and the non-recanalized group. During the procedure half dose (5/12 patients) or full dose abciximab (6/12 patients), or aspirin (1/12 patient) was given intravenously immediately after stent placement. In 2 patients (17%) multiple stents were implanted. The stenting group had better functional outcomes at 3 months compared to the non-stenting group with 8/12 (66%) vs. 3/14 (21.4%, p < 0.05). Of the patients 5 (36%) in the non-stented group had died at 3 months follow-up, whereas mortality in the stenting cohort was 0% (p < 0.05) and no symptomatic intracranial hemorrhage (ICH) occurred in either group.

Finally, a thoracoscopic right bilobectomy was performed. Histopathology of the specimens revealed an amyloid tumor with maximal diameter of 35 mm. Extensive diagnostic work-up for systemic amyloidosis remained negative. The diagnosis of pulmonary amyloidosis was confirmed.

CONCLUSION Intracranial stenting after failure of recanalization with thrombectomy led to a better rate of clinical outcome than leaving the patient non-recanalized. The required antiplatelet therapy, predominantly abciximab, did not lead to additional ICH.

ABSTRACT 9 A solitary pulmonary nodule: pulmonary amyloidosis Standaert C, Herpels V, Seynaeve P, et al. Journal of the Belgian Society of Radiology, 2018, 102(1), 20

INTRODUCTION/BACKGROUND A 67-year-old male and former smoker was admitted to the hospital because of abdominal pain. An abdominal CT scan revealed not only acute biliary pancreatitis, but also a pulmonary nodule in the right lower lobe.

MATERIALS/METHODS On 18-Fluoro-deoxyglucose (18F-FDG) PET-CT scan the solitary pulmonary nodule posterior in the right lower lobe revealed a high 18F-FDG-uptake. No enlarged or high uptake lymph nodes nor distant metastasis were seen. So far, a malignant tumor was suspected. By CT-guided biopsy of the nodule, a specimen was obtained and revealed necrotic tissue without evidence of malignancy. Mediastinoscopy for mediastinal mapping was performed. All biopsies showed normal lymph node tissue and no malignancy.

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COMMENTS Amyloidosis refers to a variety of disorders associated with extracellular deposition of protein, caused by the aggregation of misfolded proteins. Localized amyloidosis refers to amyloid deposition in a single organ, usually amyloid light chain type, while in systemic amyloidosis concurrent involvement in other organs is described. Most cases of pulmonary amyloidosis are part of systemic amyloidosis and the diagnosis of localized pulmonary amyloidosis requires the absence of systemic amyloidosis. Three main forms and CT patterns of pulmonary amyloidosis have been described: tracheobronchial amyloidosis, diffuse interstitial amyloidosis and nodular pulmonary amyloidosis [1]. Tracheobronchial amyloidosis is characterized by mural nodules and calcification of the thickened tracheobronchial wall, localized or multifocal. Patients present with stridor, dyspnea, recurrent pneumonia, or atelectasis. The differential diagnosis includes diffuse tracheal diseases such as relapsing polychondritis, granulomatosis with polyangitis, sarcoidosis, and inflammatory bowel disease. Diffuse interstitial amyloidosis is the least common form and has the worst prognosis. It is characterized by ground-glass infiltrates, reticular opacities, interlobular septal thickening, nodules of 2–4 mm in size and consolidation in the subpleural region. It should be differentiated from other interstitial lung diseases, such as lymphangitic carcinomatosis. In nodular pulmonary amyloidosis, single or multiple nodules appear radiologically with sharp and lobulated margins. Amyloid nodules in the lung parenchyma are usually incidental findings on chest radiographs. They are more often found in the lower lobes, in the subpleural or peripheral regions and should be considered in the differential diagnosis of pulmonary primary or metastatic neoplasms. Over time, the nodules may grow and cavitate, calcify, or resolve spontaneously.

CONCLUSION Amyloidosis refers to a variety of disorders associated with extracellular deposition of protein, caused by the aggregation of misfolded proteins. Localized amyloidosis refers to amyloid deposition in a single organ, usually amyloid light chain type, while in systemic amyloidosis concurrent involvement in other organs is described. Most cases of pulmonary amyloidosis are part of systemic amyloidosis


and the diagnosis of localized pulmonary amyloidosis requires the absence of systemic amyloidosis. Three main forms and CT patterns of pulmonary amyloidosis have been described: tracheobronchial amyloidosis, diffuse interstitial amyloidosis and nodular pulmonary amyloidosis [1]. Tracheobronchial amyloidosis is characterized by mural nodules and calcification of the thickened tracheobronchial wall, localized or multifocal. Patients present with stridor, dyspnea, recurrent pneumonia, or atelectasis. The differential diagnosis includes diffuse tracheal diseases such as relapsing polychondritis, granulomatosis with polyangitis, sarcoidosis, and inflammatory bowel disease. Diffuse interstitial amyloidosis is the least common form and has the worst prognosis. It is characterized by ground-glass infiltrates, reticular opacities, interlobular septal thickening, nodules of 2–4 mm in size and consolidation in the subpleural region. It should be differentiated from other interstitial lung diseases, such as lymphangitic carcinomatosis. In nodular pulmonary amyloidosis, single or multiple nodules appear radiologically with sharp and lobulated margins. Amyloid nodules in the lung parenchyma are usually incidental findings on chest radiographs. They are more often found in the lower lobes, in the subpleural or peripheral regions and should be considered in the differential diagnosis of pulmonary primary or metastatic neoplasms. Over time, the nodules may grow and cavitate, calcify, or resolve spontaneously.

RESULTS BME had SN of 68.9%, SP of 74.0% and LR+ of 2.6 for diagnosis of spondyloarthritis. BME in absence of intra-articular signal changes had a lower SN and LR+ for spondyloarthritis (SN = 20.5%, LR+ 1.4). Concomitant BME and high T1 signal (SP = 97.2%, LR + = 10.5), BME and fluid signal (SP = 98.6%, LR + = 10.3) or BME and ankylosis (SP = 100%) had higher SP and LR+ for spondyloarthritis. Concomitant BME and VP had low LR+ for spondyloarthritis (SP = 91%, LR + =0.9). When BME was absent, intra-articular signal changes were less prevalent, but remained highly specific for spondyloarthritis.

CONCLUSION Our results suggest that both periarticular and intra-articular MR signal of the sacroiliac joint should be examined to determine whether an MRI is ‘positive’ or ‘not positive’ for sacroiliitis associated with spondyloarthritis.

ABSTRACT 11 Thrombectomy using the EmboTrap device: core laboratory-assessed results in 201 consecutive patients in a real-world setting Brouwer PA, Yeo LLL, Andersson T, et al. Journal of NeuroInterventional Surgery, 2018, 10(10), 964-968

INTRODUCTION/BACKGROUND ABSTRACT 10 MRI of the sacroiliac joints in spondyloarthritis: the added value of intra-articular signal changes for a 'positive MRI' Laloo F, Herregods N, Verstraete K, et al. Skeletal Radiology, 2018, 46, 1-11

INTRODUCTION/BACKGROUND To determine if intra-articular signal changes at the sacroiliac joint space on MRI have added diagnostic value for spondyloarthritis, when compared to bone marrow edema (BME).

MATERIALS/METHODS A retrospective study was performed on the MRIs of sacroiliac joints of 363 patients, aged 16–45 years, clinically suspected of sacroiliitis. BME of the sacroiliac joints was correlated to intra-articular sacroiliac joint MR signal changes: high T1 signal, fluid signal, ankylosis and vacuum phenomenon (VP). These MRI findings were correlated with final clinical diagnosis. Sensitivity (SN), specificity (SP), likelihood ratios (LR), predictive values and post-test probabilities were calculated.

We studied patients treated with the EmboTrap revascularization device in a prospective registry which is core laboratory evaluated by physicians from external centers. The goal was to determine how the EmboTrap would perform under the everyday conditions of a high-volume stroke center.

MATERIALS/METHODS We examined all patients with acute stroke treated with the Embotrap device from October 2013 to March 2017 in our center. Imaging parameters and times were adjudicated by core laboratory personnel blinded to clinical information, treating physician, and clinical outcomes. Clinical evaluation was performed by independent neurologists and entered in a national registry. Evaluated endpoints were: successful revascularization (modified Thrombolysis in Cerebral Infarction (mTICI) 2b-3) and good clinical outcomes at 3 months (modified Rankin Scale (mRS) 0-2).

RESULTS 201 consecutive patients with a median NIH Stroke Scale (NIHSS) score of 15 (range 2-30) were included. 170 patients (84.6%) achieved mTICI 2b-3 reperfusion. The median number of attempts was 2 (range 1-10) with 52.8% of

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the population achieving good functional outcomes (mRS 0-2) at 3 months. On univariate analysis, good functional outcome was associated with the number of attempts, puncture-to-reperfusion time, anterior circulation occlusion, and NIHSS score. On multivariate analysis, pre-treatment NIHSS (OR 0.845 per point, 95% CI 0.793 to 0.908, P<0.001) and puncture-to-reperfusion time (OR 0.9952 per min, 95% CI 0.9914 to 0.9975, P=0.023) were associated with good functional outcomes at 3 months.

Jans L, De Kock I, Verstraete K, et al. Annals of the rheumatic diseases, 2018, pii Er is geen abstract beschikbaar.

ABSTRACT 14 Posterior circulation occlusions may be associated with distal emboli during thrombectomy: factors for distal embolization and a review of the literature.

CONCLUSION The Embotrap device has a high rate of successful reperfusion. Our core laboratory-audited single-center experience suggests the technical feasibility and safety of the Embotrap for first-line use in a real-world setting.

Yeo LLL, Holmberg A, Andersson T, et al. Clinical Neuroradiology, 2018, https://doi.org/10.1007/ s00062-018-0679-z

INTRODUCTION/BACKGROUND ABSTRACT 12 De toekomst van forensische leeftijdsschatting bij levende adolescenten en jongvolwassenen: magnetische resonantie beeldvorming en automatisering De Tobel J, de Haas M, Verstraete K, et al. Het tandheelkundig jaar, 2018, 1-19

INTRODUCTION/BACKGROUND De huidige praktijk van leeftijdsschatting bij levende adolescenten en jongvolwassenen vindt zijn grootste toepassing in asielprocedures en in de sport. Deze procedure verloopt in België anders dan in Nederland, respectievelijk met en zonder inbreng van de forensisch tandarts. Om de leeftijd te schatten worden röntgenfoto’s van verschillende zich ontwikkelende structuren beoordeeld. De huidige praktijk kent verschillende nadelen en ethische bezwaren. Daarom wordt onderzoek gedaan naar een alternatieve aanpak. Magnetische resonantie beeldvorming wordt door verschillende onderzoeksgroepen naar voren geschoven als een volwaardig alternatief, dat bovendien extra mogelijkheden biedt. De onderzoekers zijn het erover eens dat een combinatie van structuren moet worden onderzocht om een accurate leeftijdsschatting mogelijk te maken. De reproduceerbaarheid van de leeftijdsschatting kan daarnaast verbeterd worden door geautomatiseerde methoden te gebruiken voor het beoordelen van de zich ontwikkelende structuren.

ABSTRACT 13 Response to: 'The use of dual-energy CT to detect and depict bone marrow oedema in rheumatoid arthritis: is it ready to substitute MRI?' by Wu et al.

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Distal embolization or movement of the thrombus to previously uninvolved vasculature are feared complications during stroke thrombectomy. We looked at associated factors in a consecutive series of patients who underwent thrombectomy with the same endovascular device.

MATERIALS/METHODS We included all patients with acute ischemic stroke in the anterior or posterior circulation, who underwent thrombectomy with the same thrombectomy device for acute stroke from 2013 to 2016. Distal embolization was defined as any movement of the thrombus into a previously uninvolved portion of the cerebral vasculature or the presence of thrombotic material further downstream in the affected vessel, which occurred after the initial angiogram. We studied patient-related as well as technical factors to determine their association with distal emboli.

RESULTS In this study 167 consecutive acute stroke patients treated with the emboTrap® device Cerenovus, Irvine, CA,USA) were included with a median National Institutes of Health Stroke Scale (NIHSS) of 15 (range 2-30) and mean age of 67 years (SD 13.1 years). Of the patients in our cohort 20 (11.9%) experienced distal emboli, with 2.3% into a new territory and 9.6% into a territory distal to the primary occlusion. On univariate analysis, age, intravenous tissue plasminogen activator (tPA), posterior circulation occlusions, and general anesthesia were associated with distal emboli. On multivariate analysis, only posterior circulation occlusions (odds ratio OR 4.506 95% confidence interval CI 1.483-13.692, p = 0.008) were significantly associated with distal emboli. Distal embolization was not significantly associated with worse functional outcomes at 3 months, increased mortality or increased bleeding risk.


CONCLUSION

ABSTRACT 4

Posterior circulation occlusions were significantly associated with distal emboli during thrombectomy, possibly due to the lack of flow arrest during such procedures. New techniques and devices should be developed to protect against embolic complications during posterior circulation stroke thrombectomy.

Accuracy of estimating PET activity depends on medical display color characteristics

PRESENTATIES / CONGRESSEN ABSTRACT 1 The use of magnetic resonance imaging (MRI) in forensic age estimation of living children, adolescents, and subadults: protocol for a systematic review and preliminary results American Academy of Forensic Sciences Annual Scientific Meeting De Tobel J, Parmentier G, Verstraete K, et al. Februari 2018, Seattle, USA Er is geen abstract beschikbaar.

Society for Imaging Informatics in Medicine Annual Meeting Avanaki A, Espig K, Vanovermeire O, et al. June 2018, National Harbour, USA

INTRODUCTION/BACKGROUND Estimation of uptake value in a PET/CT image is a clinically common task. We suspect the color characteristics of the display affect radiologists’ performance in this task. Three commonly used display color calibration methods are compared. DICOM grayscale standard display function (GFSD) is the standard for greyscale radiology visualization, ensuring a perceptually uniform behavior for gray. sRGB is a de facto color standard for internet almost ubiquitous in nonmedical imaging. CSDF is a color calibration method proposed by Barco ensuring the display behaves perceptually uniform with respect to color as well as gray.

OBJECTIVE Accuracy in estimation of uptake values in PET/CT images shown on a display depends on color characteristics of the display. A display calibrated to CSDF results in a higher accuracy than one calibrated to sRGB or GSDF.

MATERIALS/METHODS ABSTRACT 2 Magnetic resonance imaging (MRI) of third molars in forensic age estimation: validation of the Gent and Graz protocols American Academy of Forensic Sciences 70th Annual Scientific Meeting De Tobel J, Parmentier G, Verstraete K, et al. Februari 2018, Seattle, USA Er is geen abstract beschikbaar.

ABSTRACT 3 Magnetic resonance imaging of third molars in forensic age estimation: comparison of the Ghent and Graz protocols focusing on apical closure Meeting of the Study Group on Forensic Age Diagnostics De Tobel J, Parmentier G, Verstraete K, et al. March 2018, Berlin, Germany Er is geen abstract beschikbaar.

An experiment was conducted to gauge radiologists’ performance in estimation of uptake values in PET/CT images on a Barco Coronis Uniti (MDMC-12133) display calibrated to sRGB, GSDF, and CSDF. PET/CT composites were rendered using a rainbow color scale, with a randomly chosen region of the image marked by easily visible black margins. The task was to estimate the uptake amount by clicking the area on a color scale with the same color as the marked image region. This was repeated for several regions of the image, once per calibration, taking 10-15 minutes to complete. Prior to the experiment, each participant was given a short description and went through a training to ensure familiarity with the task. The clinical relevance of the experiment was confirmed by a non-participating radiologist. A total of 28 radiologists participated in the experiment conducted at RSNA 2017 Medical Image Perception Lab, funded by National Cancer Institute.

RESULTS We define the estimation performance based on the slope of estimated vs actual PET value. Let xi show the actual PET value at the ith randomly chosen region of the image. Let cij, gij, and rij show the estimated PET value by the jth par-

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ticipant for the ith region, using display calibrations CSDF, GSDF, and sRGB respectively. Thus, the slope of estimated vs actual PET value xi for GSDF calibration averaged over 26 participants (removed two participants that did not follow the instructions and clicked on a constant value) is given by:

denoting such slopes under sRGB and CSDF calibrations, are calculated similarly. Ideally, such slopes should be constant. That means it is desirable that a change in actual PET value, xi, causes the same change in estimated PET value independent of i. Therefore, a smaller variation of the slope under a certain calibration indicates a better estimation performance. Slope variation for the three color calibrations is calculated. The results are reported in Table 1.

Slope variation

CSDF

sRGB

GSDF

74.9

172.9

286.3

CONCLUSION Accuracy in estimation of uptake values in PET/CT images depends on color characteristics of the display. A display calibrated to CSDF results in a higher accuracy than one calibrated to sRGB or GSDF.

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CENTRUM

NEUROLOGIE ARTIKELS ABSTRACT 1 PCSK9-inhibitoren in secundaire preventie voor ischemisch CVA : praktische implementatie in Belgische praktijk

CONCLUSION The new class of PCSK9-inibitors is available in Belgium since one year and has already established its large potential in lipid lowering. Despite this potential there still are large gaps in the knowledge about the long term effects and their role in secondary prevention to reduce the stroke risk. Therefore more and larger studies are needed in the future with an additional focus on cost-effectiveness.

Serrien A, Pinson H, Vanacker P, et al. Neuron, 2018, 23(7), 13-17

ABSTRACT 2 INTRODUCTION/BACKGROUND Since 2003 we know that a gain of function mutation in proprotein convertase subtilisin/kexin type 9 (PCSK9) can be one of the causes in familial hypercholesterolemia. [1] PCSK9 induces degradation of the LDL-receptor in the endosome in the lever and therefore causes LDL-cholesterol to stay in the blood circulation. [2] The PCSK9-inhibitors that we use nowadays are three monoclonals antibodies (Evolocumab, a IgG2-antibody; Alirocumab, a IgG1-antibody; Bococizumab). A recent study shows that the majority of (young) patients suffering from familial hypercholesterolemia does not take any lipid-lowering medication. Now that a new class is available, more efforts should be made for screening and treatment in these patients.

MRI-guided thrombolysis for stroke with unknown time of onset Thomalla G, Simonsen CZ, Boutitie F, et al. The New England Journal of Medicine, 2018, 379, 611-622

INTRODUCTION/BACKGROUND Under current guidelines, intravenous thrombolysis is used to treat acute stroke only if it can be ascertained that the time since the onset of symptoms was less than 4.5 hours. We sought to determine whether patients with stroke with an unknown time of onset and features suggesting recent cerebral infarction on magnetic resonance imaging (MRI) would benefit from thrombolysis with the use of intravenous alteplase.

RESULTS

MATERIALS/METHODS

The independent relation between the LDL-cholesterol level and the stroke risk has been established clearly in the past. In addition we know that several PCSK9-polymorphisms are linked with a higher stroke risk. This raises the question whether the new PCSK9-inhibitors could play a role in the secondary prevention after ischemic stroke. Recent phase II and II trials (OSLER en ODYSSEY LONG-TERM) show the effect on the LDL-cholesterol level and show a trend towards less cerebrovascular events. Nevertheless, the superiority and cost-effectiveness of PCSK9-inhibitors to the much cheaper statins has not yet been established. Possibly the studies were too small and larger studies will have to be performed to prove this better effect. Yet there is a large trust in this new class of medication due to their good safety profile. In addition, the large group with hypercholesterolemia and intolerance to statins now have a valuable alternative option. The PCSK9-inhibitors are used subcutaneously with one injection every two weeks. The major reported adverse events are cutaneous reactions and upper respiratory tract infections. The long term side effects are not yet known. The criteria for refund are complicated and significantly different for the different molecules. Moreover, only cardiologists and specialists in internal medicine can do the request for the refund, which makes the procedure even more complex.

In a multicenter trial, we randomly assigned patients who had an unknown time of onset of stroke to receive either intravenous alteplase or placebo. All the patients had an ischemic lesion that was visible on MRI diffusion-weighted imaging but no parenchymal hyperintensity on fluid-attenuated inversion recovery (FLAIR), which indicated that the stroke had occurred approximately within the previous 4.5 hours. We excluded patients for whom thrombectomy was planned. The primary end point was favorable outcome, as defined by a score of 0 or 1 on the modified Rankin scale of neurologic disability (which ranges from 0 [no symptoms] to 6 [death]) at 90 days. A secondary outcome was the likelihood that alteplase would lead to lower ordinal scores on the modified Rankin scale than would placebo (shift analysis).

RESULTS The trial was stopped early owing to cessation of funding after the enrollment of 503 of an anticipated 800 patients. Of these patients, 254 were randomly assigned to receive alteplase and 249 to receive placebo. A favorable outcome at 90 days was reported in 131 of 246 patients (53.3%) in the alteplase group and in 102 of 244 patients (41.8%) in the placebo group (adjusted odds ratio, 1.61; 95% confidence interval [CI], 1.09 to 2.36; P=0.02).

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The median score on the modified Rankin scale at 90 days was 1 in the alteplase group and 2 in the placebo group (adjusted common odds ratio, 1.62; 95% CI, 1.17 to 2.23; P=0.003). There were 10 deaths (4.1%) in the alteplase group and 3 (1.2%) in the placebo group (odds ratio, 3.38; 95% CI, 0.92 to 12.52; P=0.07). The rate of symptomatic intracranial hemorrhage was 2.0% in the alteplase group and 0.4% in the placebo group (odds ratio, 4.95; 95% CI, 0.57 to 42.87; P=0.15).

CONCLUSION In patients with acute stroke with an unknown time of onset, intravenous alteplase guided by a mismatch between diffusion-weighted imaging and FLAIR in the region of ischemia resulted in a significantly better functional outcome and numerically more intracranial hemorrhages than placebo at 90 days. (Funded by the European Union Seventh Framework Program; WAKE-UP ClinicalTrials.gov number, NCT01525290; and EudraCT number, 2011-005906-32 .)

for a median of 11 months when the trial was terminated early because of a lack of benefit with regard to stroke risk and because of bleeding associated with rivaroxaban. The primary efficacy outcome occurred in 172 patients in the rivaroxaban group (annualized rate, 5.1%) and in 160 in the aspirin group (annualized rate, 4.8%) (hazard ratio, 1.07; 95% confidence interval [CI], 0.87 to 1.33; P=0.52). Recurrent ischemic stroke occurred in 158 patients in the rivaroxaban group (annualized rate, 4.7%) and in 156 in the aspirin group (annualized rate, 4.7%). Major bleeding occurred in 62 patients in the rivaroxaban group (annualized rate, 1.8%) and in 23 in the aspirin group (annualized rate, 0.7%) (hazard ratio, 2.72; 95% CI, 1.68 to 4.39; P<0.001).

CONCLUSION Rivaroxaban was not superior to aspirin with regard to the prevention of recurrent stroke after an initial embolic stroke of undetermined source and was associated with a higher risk of bleeding. (Funded by Bayer and Janssen Research and Development; NAVIGATE ESUS ClinicalTrials.gov number, NCT02313909 .)

ABSTRACT 3 Rivaroxaban for stroke prevention after embolic stroke of undetermined source Hart R, Sharma M, Mundl H, et al. The New England Journal of Medicine, 2018, 378, 21912201

INTRODUCTION/BACKGROUND Embolic strokes of undetermined source represent 20% of ischemic strokes and are associated with a high rate of recurrence. Anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, may result in a lower risk of recurrent stroke than aspirin.

MATERIALS/METHODS We compared the efficacy and safety of rivaroxaban (at a daily dose of 15 mg) with aspirin (at a daily dose of 100 mg) for the prevention of recurrent stroke in patients with recent ischemic stroke that was presumed to be from cerebral embolism but without arterial stenosis, lacune, or an identified cardioembolic source. The primary efficacy outcome was the first recurrence of ischemic or hemorrhagic stroke or systemic embolism in a time-to-event analysis; the primary safety outcome was the rate of major bleeding.

RESULTS A total of 7213 participants were enrolled at 459 sites; 3609 patients were randomly assigned to receive rivaroxaban and 3604 to receive aspirin. Patients had been followed

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ABSTRACT 4 Hemorrhagic transformation in patients with acute ischemic stroke and atrial fibrillation: time to initiation of oral anticoagulant therapy and outcomes. Paciaroni M, Bandini F, Agnelli G, et al. Journal of the American Heart Association, 2018, 7(22), e010133

INTRODUCTION/BACKGROUND In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation ( HT ). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT , (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days.

RESULTS HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT . Pa-


tients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT ; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT . On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). In patients with HT , anticoagulation was initiated about 12 days later than patients without HT . This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability.

ABSTRACT 5 Thrombectomy using the EmboTrap device: core laboratory-assessed results in 201 consecutive patients in a real-world setting Brouwer PA, Yeo LLL, Andersson T, et al. Journal of NeuroInterventional Surgery, 2018, 10(10), 964-968 Het abstract is terug te vinden op pagina 39.

PRESENTATIES / CONGRESSEN ABSTRACT 1 Acute ischemic stroke due to tandem occlusions of the internal carotid artery: results of endovascular recanalization and clinical outcome European Society of Radiology Voormolen M, Van der Zijden T, Vanacker P, et al. March 2018, Vienna, Austria Er is geen abstract beschikbaar.

INTRODUCTION/BACKGROUND With increasing age of acute stroke patients being admitted to hospitals, more data are needed on indications, complications and outcome of endovascular treatment (EVT) in the very elderly.

MATERIALS/METHODS All patients with acute ischemic stroke hospitalized within 24h were included if they were (A) aged ≼90y, (B) treated with EVT (based on local guidelines) alone or bridged with IV thrombolysis and (C) followed-up with data available at 7 and 90 days. Patients were selected based on intention to treat, i.e. included even if the procedure was unsuccessful. Safety assessment comprised on the presence of peri-procedural complications, hemorrhagic transformation < 24hours (SITS-MOST classification) or other serious adverse event < 7 days. Efficacy and outcome measures were successful recanalization (TICI score 2b-3), 3-months mortality and favorable outcome, defined as Modified Rankin Score (mRS) 0-2.

RESULTS A total of 43 nonagenarians were included (median age 92 years; 77% women; median premorbid mRS=2). Main occlusion sites were carotid -T in 23 %, M1 in 51% and basilar artery in 7%, correlating with high NIHSS scores on admission (median=18; IQR 10-24). Bridging with IV thrombolysis was performed in 72% (n=31). In 76,1% (n=32) patients a successful recanalization was achieved, within median 58 minutes after groin puncture. In 19% (n=8) endovascular treatment was unsuccessful due to vascular anatomy or treatment was aborted due to unfavorable clinical evolution. At 3 months, the mortality rate was 63 % and favorable outcome 15%.

CONCLUSION This study shows a substantially poor outcome of severe strokes in the very elderly patients, even when treated with EVT, indicating the need to be very strict in patient selection. A high pre-stroke mRS probably contributes to the unfavorable outcome and may be a reason to deter from EVT. More data on potential outcome predictors for EVT in this population are needed.

ABSTRACT 2 ABSTRACT 3

Multicenter, retrospective analysis of endovascular treatment in nonagenarians with acute ischemic stroke: eligibility, outcome and safety.

A personalized digital coaching program after stroke (beroertecoach.be): preliminary results

European Stroke Organisation Conference Janssen H, Francois O, Michel P, Vanacker P, et al. May 2018, Gothenburg, Sweden

European Stroke Organisation Conference Kamoen O, Mahieu D, Vanacker P, et al. May 2018, Gothenburg, Sweden

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INTRODUCTION/BACKGROUND

CONCLUSION

Risk of stroke recurrence is prevalent and associated with disability and socio-economic costs. Adequate management of risk factors may reduce its risk. Nurseled interventions in stroke patients show potential to decrease readmissions on short term by focus on the transition between hospital and home and on long term by optimizing cardiovascular risk factor control, patient satisfaction, decline stroke recurrence, enhance therapeutic adherence and reduce readmissions thirty days after discharge. On behalf of the Belgian Stroke Council, a nurse-led self-management and health literacy program was developed, using both a personalized coaching combined with a digital platform.

Our nurse-led self-management, transmural program consisting of a stroke coach and a personal digital platform shows promise in improving stroke recurrence rates, therapeutic adherence and quality of life in patients after stroke in a Belgian healthcare setting. A further health-economic analysis of the project is foreseen in the near future.

MATERIALS/METHODS We carried out a prospective multicenter interventional cohort study (05/2017-12/2017) combined with a historical control group (2011). The project was enrolled in four Belgian hospitals (University Hospital Antwerp, AZ Groeninge Kortrijk, Sint-Lucashospital Bruges, Sint-Janhospital Bruges-Ostend). Their local stroke coach provided at least one educational session during hospitalization. After discharge, the patient received individualized tips and tricks concerning a healthy life style through the customized platform. The stroke nurse overviewed recorded cardiovascular parameters and set up video-appointments through the beroertecoach.be platform at regular intervals (0.5-1-2-6m). Risk factor control, measured by the SCORE risk at 6 months was compared with a historical control group (n=69) who received standard of care. Research was funded with a project grant of the Belgian National Institute for Health and Disability Insurance (NIHDI) for mHealth applications.

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ABSTRACT 4 A personalized, digital coaching program after stroke (beroertecoach.be): patients and caregivers view on usability and applicability. European Stroke Organization Conference Lorrez A, Mahieu D, Vanacker P, et al. May 2018, Gothenburg, Sweden

INTRODUCTION/BACKGROUND A pilot project consisting of a stroke coach and a digital platform (beroertecoach.be) was enrolled in four Belgian hospitals with the aim of improving secondary prevention after stroke. This initiative was launched in 2015 with support of the Belgian Stroke Council.

MATERIALS/METHODS The participating centers recruited 147 patients for a follow- up period of 6 months (May 2017-April 2018). The stroke coach provided at least one educational session during hospitalization. After discharge, the patient received individualized tips and tricks concerning a healthy life style through the individualized platform. The stroke nurse overviewed recorded parameters and set up either a video-appointments or a phone interview through the platform at regular intervals (0,5-1-2-6 months).

RESULTS

RESULTS

A total of 147 patients were included for a follow- up period of 6 months. Our primary endpoint, a significant reduction (-3.2%; 0.94- 4.83, p < 0.001) of the cardiovascular SCORE risk at six months compared to the control group, proved non-significant (p=0.55) if compared to the evolution of the historical cohort. However outcome of the secondary endpoints are promising: patient adherence was 96% and the reported quality of life significantly improved (F = 35.15, p < 0.001). No significant improvement in the modified Rankin scale was seen (F = 1.29, p = 0.278), probably due to an already low mRS score at inclusion. Five percent of patients in the intervention group had an recurrent stroke at six months. Patient and caregiver satisfaction within the program was high.

96% of patients would recommend the stroke coach and digital platform to others. Advantages reported by the patients were the early follow- up, additional support and easy access to the coach through the platform. 64% of patients used the ability to contact the coach through a special link in the platform. 84% of patients felt they had enough information about stroke. 55% still prefer regular appointments with his/ her neurologist instead of an online- based follow- up. 100% of the involved neurologists agree that use of the stroke coach and the platform after discharge leads to a more thorough follow- up of the patient 90% of neurologists feel that the platform increases patient compliance. 90% wants to have immediate access to the patientdata on cardiovascular riskfactors. There was no perceived time gain with follow- up through the platform.


CONCLUSION Both patients and caregivers believe the stroke coach and the digital platform provide added value to patient followup after stroke. Based on the remarks some important adaptations were made.

ABSTRACT 5 Catheter thrombo-aspiration as first pass procedure in endovascular recanalization of acute ischemic stroke patients

tomy procedure was performed at AZ Groeninge hospital (in Kortrijk, Belgium). Fresh Tthrombi were immediately fixed in 4 % paraformaldehyde, embedded in paraffin and cut into 5 µm sections. Histological analysis was performed using hematoxylin and eosin, martius scarlet blue staining, Feulgen staining, and both immunohistochemical and immunofluorescence analysis of Von Willebrand factor (VWF), platelets (GPIb), fibrin, DNA and white blood cells (CD45). Multicolor immunofluorescent analysis was performed on a subset of thrombi (n = 8).

RESULTS European Society of Neuroradiology Annual Meeting Voormolen M, Vanacker P, et al. September 2018, Rotterdam, The Netherlands Er is geen abstract beschikbaar.

ABSTRACT 6 Structural features of acute ischemic stroke thrombi European Congress on Thrombosis and Haemostasis Staessens S, Denorme F, François O, Dewaele T, Vanacker P , Andersson T, et al. October 2018, Marseille, France

Stroke thrombi are heterogenous. Nevertheless, histological analysis reveals common structural features. In general, stroke thrombi are composed of red blood cell-rich (RBC-rich) areas, interspersed with platelet-rich areas. On a microstructural level, RBC-rich areas consist of red blood cells that are trapped within a relatively loose fibrin network in a honeycomb structure in which platelets and VWF are absent. In contrast to RBC-rich areas, platelets-rich zones consist of much denser fibrin structures that in addition are lined with VWF. These fibrin-VWF organizations are filled with platelets. White blood cells tend to accumulate on the boundaries between RBC-rich and platelet-rich areas. DNA networks are seen throughout the thrombus in some but not all thrombi, and are particularly present in the platelet-rich areas and in the boundary zones.

INTRODUCTION/BACKGROUND Acute ischemic stroke is still one of the leading causes of death and disability worldwide. Despite the huge clinical, economical and social burden associated with ischemic stroke, only two strategies are currently available to remove the occluding thrombus and restore blood flow to the brain: (i) pharmacological thrombolysis using tissue plasminogen activator (t-PA) and (ii) mechanical removal of the thrombus via endovascular thrombectomy. However, more than half of the patients receiving t-PA do not respond to therapy due to so called 't-PA resistance'. In addition, 20 % of thrombi are also resistant to thrombectomy, leading to thrombectomy failure. The factors contributing to such therapy resistance are not known, but are most likely linked to specific characteristics of the culprit ischemic stroke thrombi.

OBJECTIVE The aim of this study was to analyze ischemic stroke thrombi retrieved from patients treated with thrombectomy to better understand thrombus characteristics and structure.

MATERIALS/METHODS A total of 176 tThrombi (n = 176) were collected from endovascular treated ischemic stroke patients after a thrombec-

CONCLUSION We describe the complex microstructure of patient stroke thrombi. These structural characteristics could be of high relevance to improve current stroke therapy acute revascularization therapies. Alignment of fibrin and VWF in dense platelets-rich structures, together with DNA networks that span through the thrombus can possibly explain t-PA resistance observed in patients. The dense platelet-rich zones that are interspersed within loosely arranged RBC areas might hinder efficient mechanical penetration of thrombectomy devices, contributing to thrombectomy failure.

ABSTRACT 7 Platelet-rich but not RBC-rich areas in stroke thrombi consist of dense fibrin structures, VWF and extracellular DNA Belgian Society on Thrombosis and Haemostasis Annual Meeting Staessens S, Denorme F, François O, Dewaele T, Vanacker P , Andersson T, et al. July 2018, Brussels, Belgium

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INTRODUCTION/BACKGROUND

CONCLUSION

Acute ischemic stroke is one of the leading causes of death and disability worldwide. Despite the huge clinical, economical and social burden associated with ischemic stroke, only two strategies are currently available to remove the occluding thrombus and restore blood flow to the brain: (i) pharmacological thrombolysis using tissue plasminogen activator (t-PA) and (ii) mechanical removal of the thrombus via endovascular thrombectomy. However, more than half of the patients receiving t-PA do not respond to the therapy due to so called 't-PA resistance'. In addition, the thrombectomy procedure is not successful in 10-20 % of patients. The factors contributing to such therapy resistance are not known but are most likely linked to specific characteristics of the thrombus that is occluding the blood vessel in stroke patients.

We describe the complex microstructure of patient stroke thrombi. Fibrin and VWF align in dense platelet-rich structures, together with DNA networks that span through the thrombus. These observations corroborate our previous findings that VWF and DNA can contribute to t-PA resistance. Whether the dense platelet-rich zones that are interspersed within loosely arranged RBC areas influence efficiency of mechanical thrombus retrieval during thrombectomy is currently being investigated. The identification of these defined thrombus characteristics is crucial for further research to improve acute ischemic stroke therapy.

OBJECTIVE The aim of this study was to analyze ischemic stroke thrombi retrieved from patients treated with thrombectomy to better understand thrombus characteristics and structure. Materials/methods A total of 176 thrombi were collected from endovascular treated ischemic stroke patients at Groeninge Hospital (Kortrijk, Belgium). Fresh thrombi were fixed in 4 % paraformaldehyde, embedded in paraffin and cut into 5 Âľm sections. Histological analysis was performed using hematoxylin and eosin, martius scarlet blue staining, Feulgen staining, and both immunohistochemical and immunofluorescence analysis of von Willebrand factor (VWF), platelets (GPIb), fibrin, DNA and white blood cells (CD45). Multicolor immunofluorescent analysis was performed on a randomly selected subset of thrombi (n = 8).

RESULTS Stroke thrombi are heterogenous. Nevertheless, histological analysis reveals common structural features. In general, stroke thrombi are composed of red blood cell (RBC)-rich areas, interspersed with platelet-rich areas. On a microstructural level, RBC-rich areas consist of red blood cells that are trapped within a relatively loose fibrin network in a honeycomb structure in which platelets and VWF are absent. In contrast to RBC-rich areas, platelet-rich zones consist of much denser fibrin structures that in addition are lined with VWF. These fibrin-VWF organizations are filled with platelets. White blood cells tend to accumulate on the boundaries between RBC-rich and platelet-rich areas. DNA networks are seen throughout the thrombus in some but not all thrombi and are particularly present in the platelet-rich areas and in the boundary zones.

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CENTRUM

NUCLEAIRE GENEESKUNDE ARTIKELS ABSTRACT 1 Liver transplantation for very severe hepatopulmonary syndrome due to vitamin A-induced chronic liver disease in a patient with Shwachman-Diamond syndrome Bucciol G, Cassiman D, Gheysens O, et al. Orphanet Journal of Rare Diseases, 2018, 13(1), 69

INTRODUCTION/BACKGROUND Vitamin A intoxication is a rare cause of liver disease, but the risk increases in patients with underlying liver dysfunction. We present a patient with Shwachman-Diamond Syndrome who developed liver fibrosis, portal hypertension and very severe hepatopulmonary syndrome as a consequence of chronic vitamin A intoxication. She underwent successful liver transplantation with complete resolution of the pulmonary shunting.

mation & Infection Committees of the European Association of Nuclear Medicine (EANM), the Cardiovascular Council of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), and the PET Interest Group (PIG), and endorsed by the American Society of Nuclear Cardiology (ASNC). The aim of this joint paper is to provide recommendations and statements, based on the available evidence in the literature and consensus of experts in the field, for patient preparation, and FDG-PET/CT(A) acquisition and interpretation for the diagnosis and follow-up of patients with suspected or diagnosed LVV and/or PMR. This position paper aims to set an internationally accepted standard for FDG-PET/CT(A) imaging and reporting of LVV and PMR.

ABSTRACT 3 Targeting coagulase activity in staphylococcus aureus bacteraemia: a randomized controlled single-centre trial of staphylothrombin inhibition Peeterman M, Liesenborghes L, Gheysens O, et al. Thrombosis and Haemostasis, 2018, 118(5), 818-829

ABSTRACT 2 FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group (PIG), and endorsed by the ASNC Slart R, Members of the EANM Cardivascular Committee, Members of EANM Infection & Inflammation Committee, et al. European Journal of Nuclear Medicine and Molecular Imaging, 2018, 45(7), 1250-1269

INTRODUCTION/BACKGROUND Staphylococcus aureus (S. aureus) bacteraemia is frequent and carries a high morbidity and mortality. Coagulases secreted by S. aureus initiate blood coagulation by directly activating prothrombin. This pathogen-activated coagulation is insensitive to most antithrombotic drugs, with the exception of small molecule direct thrombin inhibitors (DTIs). DTIs inhibit the coagulase-prothrombin complex, or staphylothrombin, and improve outcome in preclinical models of S. aureus infection.

INTRODUCTION/BACKGROUND Large vessel vasculitis (LVV) is defined as a disease mainly affecting the large arteries, with two major variants, Takayasu arteritis (TA) and giant cell arteritis (GCA). GCA often coexists with polymyalgia rheumatica (PMR) in the same patient, since both belong to the same disease spectrum. FDG-PET/ CT is a functional imaging technique which is an established tool in oncology, and has also demonstrated a role in the field of inflammatory diseases. Functional FDG-PET combined with anatomical CT angiography, FDG-PET/CT(A), may be of synergistic value for optimal diagnosis, monitoring of disease activity, and evaluating damage progression in LVV. There are currently no guidelines regarding PET imaging acquisition for LVV and PMR, even though standardization is of the utmost importance in order to facilitate clinical studies and for daily clinical practice. This work constitutes a joint procedural recommendation on FDG-PET/CT(A) imaging in large vessel vasculitis (LVV) and PMR from the Cardiovascular and Inflam-

OBJECTIVE A single-centre, randomized, controlled feasibility and safety trial of staphylothrombin inhibition with DTIs in patients with S. aureus bacteraemia.

MATERIALS/METHODS Consecutive eligible adult patients with S. aureus positive blood cultures in the University Hospitals Leuven (Belgium) were randomized 1:1 to DTI (oral dabigatran 110 mg twice daily or intravenous argatroban according to activated partial thromboplastin time [aPTT]) for 7 to 10 days, or subcutaneous enoxaparin 40 mg once daily. Primary outcomes were feasibility and safety of DTI in patients with S. aureus bacteraemia. Secondary outcomes include D-dimer evolution (day 0-4) as marker of coagulation activation; inflammatory and microbiological parameters; and clinical outcomes including metastatic infections.

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RESULTS Thirty-one percent (94/303) of screened patients were enrolled. Dabigatran plasma levels inhibited staphylothrombin. Clinically relevant bleeding (5/47 vs. 5/47) and thrombotic (7/47 vs. 7/47) complications were similar in both groups. Coagulase inhibition with DTIs was associated with a trend towards faster D-dimer decrease at day 4 (-662 ± 249 ng/mL vs. -40 ± 213 ng/mL for DTI-treated patients vs. control; p = 0.06) and a numerically lower number of persistently positive blood cultures. No differences in inflammatory parameters or other clinical outcomes were observed.

CONCLUSION Targeting staphylothrombin with DTIs is feasible in a subset of S. aureus bacteraemic patients, with comparable safety to standard thromboprophylaxis. In future studies of staphylothrombin inhibition, feasibility can be further improved by rapid diagnostics and by strategies without concomitant anticoagulant effect.

ABSTRACT 4 68Ga-NOTA-functionalized ubiquicidin: cytotoxicity, biodistribution, radiation dosimetry, and first-in-human PET/CT imaging of infections Ebenhan T, Sathekge M, Gheysens O, et al. Journal of Nuclear Medicine, 2018, 59(2), 334-339

INTRODUCTION/BACKGROUND Ubiquicidin is an antimicrobial peptide with great potential for nuclear imaging of infectious diseases, as its cationic-rich fragment TGRAKRRMQYNRR (UBI) has been functionalized with NOTA to allow complexation to 68Ga (68Ga-NOTA-UBI). We herein assess the cytotoxicity and radiation dosimetry for 68Ga-NOTA-UBI and a first-in-human evaluation to diagnose infectious processes.

MATERIALS/METHODS Cytotoxicity was evaluated in green monkey kidney epithelial (Vero) cells and MT-4 leukocytes. Tracer susceptibility was studied in vitro using different bacterial and fungal strains. PET/CT-based biodistribution, pharmacokinetics, and radiation dosimetry were performed on nonhuman primates. Two healthy volunteers and 3 patients with suspected infection underwent 68Ga-NOTA-UBI PET/CT imaging.

min half-life) and predominant renal clearance in nonhuman primates. Human radiation dose estimates indicated the bladder wall as the dose-critical tissue (185 μSv/MBq), followed by the kidneys (23 μSv/MBq). The total absorbed body dose was low (<7 μSv/MBq); the effective dose was estimated at 17 μSv/MBq. 68Ga-NOTA-UBI could diagnose bone- and soft-tissue infection in 3 of 3 patients.

CONCLUSION 68Ga-NOTA-UBI is considered a nontoxic, safe-to-administer radiopharmaceutical unlikely to cause adverse effects in humans. The favorable tracer biodistribution and the first-in-human results will make 68Ga-NOTA-UBI PET/CT an encouraging future diagnostic technique with auxiliary clinical relevance.

ABSTRACT 5 Use of 18F-fluorodeoxyglucose positron emission tomography in the diagnosis of polymyalgia rheumatica-A prospective study of 99 patients Henckaerts L, Gheysens O, Vanderschueren S, et al. Rheumatology, 2018, 57(11), 1908-1916

OBJECTIVE Previous studies have shown that the majority of patients with PMR have increased 18F-fluorodeoxyglucose (FDG) uptake around the shoulders, hips and processes of the cervical and lumbar spine on PET. The specificity of these findings for PMR is, however, not known.

MATERIALS/METHODS We prospectively included 99 consecutive patients with a possible clinical diagnosis of PMR. All patients underwent 18F-FDG-PET scanning before treatment with glucocorticoids was started. The clinical suspicion of PMR was quantified by the treating physician on a scale from 1 to 5. FDG uptake was scored visually in 12 articular regions (scores 0-2) and a total skeletal score was calculated reflecting the FDG uptake in these 12 articular regions. Receiver operating characteristics analysis was performed to determine the optimal clinical and total skeletal score for diagnosing PMR. The gold standard for a diagnosis of PMR was the judgement of an experienced clinician after at least 6 months of follow-up.

RESULTS RESULTS Negligible cytotoxicity was determined for NOTA-UBI. 68Ga-NOTA-UBI showed moderate blood clearance (29-

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Sixty-seven patients were diagnosed with PMR while 32 patients got another diagnosis. A clinical score of 4 or more had a sensitivity of 67.2%, specificity of 87.5%, positive pre-


dictive value (PPV) of 91.8% and a negative predictive value (NPV) of 56.0% for the diagnosis of PMR. A total skeletal score of 16 or more had a sensitivity, specificity, PPV and NPV of, respectively, 85.1, 87.5, 93.4 and 73.7%.

ABSTRACT 6 18F-FDG-PET before starting glucocorticoid therapy improves the diagnostic accuracy compared with a clinical scoring system in patients with clinical suspicion of PMRImaging of bacteria: is there any hope for the future based on past experience? Ebenhan T, Lazzeri E, Gheysens O, et al. Current Pharmaceutical Design, 2018, 24(7), 772-786

INTRODUCTION/BACKGROUND Infectious diseases remain a major health problem and cause of death worldwide. It is expected that the socio-economic impact will further intensify due to escalating resistance to antibiotics, an ageing population and an increase in the number of patients under immunosuppressive therapy and implanted medical devices. Even though radiolabeled probes and leukocytes are routinely used in clinical practice, it might still be difficult to distinguish sterile inflammation from inflammation caused by bacteria. Moreover, the majority of these probes are based on the attraction of leukocytes which may be hampered in neutropenic patients. Novel approaches that can be implemented in clinical practice and allow for swift diagnosis of infection by targeting the microorganism directly, are posing an attractive strategy. Here we review the current strategies to directly image bacteria using radionuclides and we provide an overview of the preclinical efforts to develop and validate new approaches. Indeed, significant progress has been made in the past years, but very few radiopharmaceuticals (that were promising in preclinical studies) have made it into clinical practice. We will discuss the challenges that remain to select good candidates for imaging agents targeting bacteria.

of non-caseating granulomas. The diagnosis of sarcoidosis is based on clinical and imaging presentation, histologic confirmation and the absence of alternative diseases. Radiology and Nuclear Medicine play an essential role in the diagnostic work-up of patients with sarcoidosis to assess disease extent and activity. In addition, imaging modalities have shown their potential in managing these patients in terms of treatment response and prognostic assessment. Sarcoidosis has a predilection for chest involvement, showing typical and atypical manifestations in the lungs, airways and hilar/mediastinal lymph nodes. Chest radiography (X-ray) still plays an important role in suggesting diagnosis for cases with typical presentation of sarcoidosis, while computed tomography (CT) has higher accuracy in detecting early stage disease and in narrowing differential diagnosis, particularly in atypical manifestations. For extrathoracic involvement, both CT and MR (magnetic resonance) have comparable performance even though MR is the modality of choice for assessing neurosarcoidosis and cardiac sarcoidosis. In the last decades positron emission tomography/CT (PET/CT) has demonstrated an increasing and relevant value in assessing disease extent and activity, treatment planning and therapy response, with a crucial role in the management of cardiac sarcoidosis. In this article, an overview of the possible imaging manifestations of thoracic and extrathoracic sarcoidosis and current concepts on staging, response assessment and prognosis is provided. Finally, the potential applications of non-FDG radiotracers is briefly discussed.

ABSTRACT 8 Mixed response on regorafenib treatment for GIST (gastro-intestinal stromal tumor) according to 18F-FDGPET/CT Van Weehaeghe D, Gheysens O, Vandecaveye V, et al. BMC Cancer, 2018, 18(1), 253

INTRODUCTION/BACKGROUND ABSTRACT 7 Radiological and nuclear medicine imaging of sarcoidosis Larici A, Glaudemans A, Gheysens O, et al. The Quarterly Journal of Nuclear Medicine and Molecular Imaging, 2018, 62(1), 14-33

Gastro-intestinal stromal tumors (GISTs) are very rare tumors of the gastro-intestinal tract, originating from the interstitial cells of Cajal or a common cell precursor which both express type III tyrosine kinase receptors. Regorafenib is an oral multi-kinase inhibitor used to treat gastro-intestinal stromal tumors. To our knowledge this is the first case in literature to show the response of regorafenib on PET.

INTRODUCTION/BACKGROUND

RESULTS

Sarcoidosis is a multisystem chronic inflammatory disease of unknown etiology characterized by widespread growth

A 37-year-old male with lower abdominal pain and weight loss was referred to our hospital. Abdominal ultrasound

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and computed tomography (CT) showed diffuse peritoneal implants. Surgical specimen histology showed a GIST with c-KIT exon 11 deletion (c.1708_1728del) and treatment with imatinib 400 mg/day was initiated. Due to disease progression illustrated on baseline versus follow-up 18F-FDG-PET/ CT scans therapy was switched to imatinib 800 mg/day and later to sunitinib 50 mg/day. Upon further disease progression 10 months later, third line treatment with regorafenib 160 mg/day was initiated. 18F-FDG-PET/CT showed the metabolic responses after 4 months regorafenib treatment ranging from complete response to the appearance of a new lesion in the liver. The new hypermetabolic lesion was only seen on the non-attenuation-corrected images because of breathing motion artifact.

and BCR-ABL1 (n = 5) and KMT2A rearrangements (n = 2) in secondary cases. A complex karyotype was seen in 17% of de novo and 39% of secondary cases. Most prevalent treatment was induction chemotherapy followed by consolidation chemotherapy (n = 10) or allogeneic stem cell transplantation (n = 9) for de novo and radiotherapy (n = 11) for secondary cases.

CONCLUSION De novo myeloid sarcoma mostly presented isolated. Lesions were often localized at skin and lymph nodes. Genetic aberrations frequently involved core-binding factor rearrangements in de novo cases and a complex karyotype in secondary cases.

CONCLUSION This case illustrates that metabolic response can occur in GIST lesions without morphological response after third line regorafinib treatment. Furthermore this is the first case in literature to show regorafinib response on PET

ABSTRACT 10 Sheep can be used as animal model of regional myocardial remodelling and controllable work Duchenne J, Claus P, Gheysens O, et al. Cardiology Journal, 2018, doi: 10.5603/CJ.a2018.0007

ABSTRACT 9 Clinicopathological characteristics of de novo and secondary myeloid sarcoma: A monocentric retrospective study Claerhout H, Van Aelst S, Gheysens O, et al. European Journal of Haematology, 2018, 100(6), 603-612

INTRODUCTION/BACKGROUND A-V-sequential pacing has been shown to induce reversible conduction delay and subsequent asymmetric remodelling of the left ventricle (LV) in dogs and pigs. Both species have disadvantages in animal experiments. Therefore aim of this study focusses at developing a more feasible and easy-touse animal model in sheep.

INTRODUCTION/BACKGROUND Diagnosing myeloid sarcoma remains challenging, and we aimed to provide clinicopathological features to facilitate diagnosis.

MATERIALS/METHODS Clinicopathological data from 41 patients with de novo and 31 with secondary myeloid sarcoma were reviewed.

MATERIALS/METHODS Dual-chamber pacing (DDD) pacemakers (right atrium + right ventricular free wall) were surgically implanted in 13 sheep. All animals underwent 8 weeks of chronic rapid pacing at 180 bpm. Reported observations were made at 110 bpm.

RESULTS RESULTS Most de novo cases presented with isolated myeloid sarcoma (n = 19) or myeloid sarcoma with concurrent acute myeloid leukemia (n = 15). Most secondary cases presented after acute myeloid leukemia (n = 11), myeloproliferative neoplasm (n = 9), or myelodysplastic syndrome (n = 8). Most frequent localizations were skin and lymph nodes. Immunohistochemistry showed immature and/or aberrant antigenic expression in 29% of de novo and 39% of secondary cases. Most genetic abnormalities were RUNX1-RUNX1T1 (n = 4), CBFB-MYH11 (n = 2), KMT2A-MLLT3 (n = 2), and JAK2 V617F (n = 2) mutations in de novo myeloid sarcoma,

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DDD pacing acutely induced a left bundle branch block (LBBB) - like pattern with almost doubling in QRS width and septal flash, indicating mechanical dyssynchrony. Atrial pacing (AAI) resulted in normal ventricular conduction and function. During 8 weeks of rapid DDD pacing, animals developed LV remodelling (confirmed with histology) with septal wall thinning (-30%, p < 0.05), lateral wall thickening (+22%, p < 0.05), LV volume increase (+32%, p < 0.05), decrease of LV ejection fraction (-31%, p < 0.05), and functional mitral regurgitation. After 8 weeks, segmental pressure-strain-loops, representing regional myocardial work, were recorded. Switching from AAI to DDD decreased


immediately work in the septum and increased it in the lateral wall (-69 and +41%, respectively, p < 0.05). Global LV stroke work and dP/dtmax decreased (-27% and -25%, respectively, p < 0.05).

CONCLUSION Herein is developed a new sheep model with an asymmetrically remodelled LV. Simple pacemaker programming allows direct modulation of regional myocardial function and work. This model provides a new and valuable alternative for canine or porcine models and has the potential to become instrumental for investigating regional function and loading conditions on regional LV remodelling.

RESULTS Patient baseline characteristics at diagnosis of PTLD differed significantly depending on immunosuppression before diagnosis. Compared with immunosuppression before diagnosis, significantly fewer patients received an antimetabolite or a calcineurin inhibitor (CNI) after diagnosis of PTLD. Relapse risk measured as landmark TTP was significantly higher for patients on corticosteroids compared to all others (P = 0.010) as well as for patients on ciclosporin compared with those on tacrolimus (P = 0.002), but similar for those on antimetabolites compared with all others (P = 0.912). In a Cox regression analysis of landmark TTP, corticosteroid-containing immunosuppression after diagnosis of PTLD (P = 0.002; hazard ratio, 11.195) and age (P = 0.001; hazard ratio, 1.076/year) were identified as independent, significant risk factors for PTLD relapse.

ABSTRACT 11 Immunosuppression is associated with clinical features and relapse risk of B cell posttransplant lymphoproliferative disorder: a retrospective analysis based on the prospective, international, multicenter PTLD-1 trials

CONCLUSION In the prospective PTLD-1 trials, corticosteroid use after diagnosis of PTLD is associated with an increased risk of relapse, whereas the use of antimetabolites is not. These findings require prospective validation

Zimmermann H, Babel N, Gheysens O, et al. Transplantation, 2018, 102(11), 1914-1923

ABSTRACT 12 INTRODUCTION/BACKGROUND Current guideline recommendations for immunosuppression reduction after diagnosis of posttransplant lymphoproliferative disorder (PTLD) include stopping antimetabolites, reducing calcineurin inhibitors, and maintaining corticosteroids. However, the effect of immunosuppression on PTLD relapse risk after up-to-date therapy is unclear.

MATERIALS/METHODS This is a retrospective analysis of immunosuppression, patient baseline characteristics, and relapse risk measured as landmark time to progression (TTP) starting 1 year after start of therapy in 159 patients with B cell PTLD after solid organ transplantation treated in the prospective, international, multicenter PTLD-1 trials with either sequential treatment (rituximab followed by cyclophosphamide (CHOP-21 chemotherapy) 750 mg/m intravenously [IV] day (d) 1, doxorubicin 50 mg/m IV d1, vincristine 1.4 mg/m (maximum, 2 mg) IV d1, and prednisone 50 mg/m PO d1-5, every 21 days) or risk-stratified sequential treatment (rituximab followed by rituximab or rituximab (R-CHOP-21 immunochemotherapy) 375 mg/m IV day (d) 1, cyclophosphamide 750 mg/m IV d1, doxorubicin 50 mg/m IV d1, vincristine 1.4 mg/m (max. 2 mg) IV d1, and prednisone 50 mg/m PO d1-5, every 21 days).

Other immunomodulatory agent-related lymphoproliferative diseases: a single-center series of 72 biopsy-confirmed cases Marcelis L, Berghen C, Gheysens O, et al. Modern Pathology, 2018, 31(9), 1457-1469

INTRODUCTION/BACKGROUND Ongoing development of new drugs, as well as novel indications in the treatment of autoimmune diseases leads to the increasing use of immunomodulatory and immunosuppressive drugs. Immunomodulatory agent-related lymphoproliferative disorders are a known and potentially life threatening complication of chronic administration of these drugs, but are less well characterized compared with post-transplant lymphoproliferative disorders. The heterogeneous drug targets, various underlying disease indications, different drug combinations used and relatively low incidence render data collection and interpretation difficult. In this retrospective paper, we describe the clinicopathological characteristics of a larger single-center series of 72 immunomodulatory agent-related lymphoproliferative disorder cases. We divided the cases according to the therapy, administered in the year preceding diagnosis of a lymphoproliferative disorder, in an immunosuppressive drug, an immunomodulatory drug and a combination of immuno-

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suppressive and immunomodulatory drugs group. We observed differences in "time to lymphoproliferative disorder development" with a shorter time for all the immunomodulatory drug-related cases combined (immunomodulatory and immunomodulatory + immunosuppressive = immunomodulatory-all) vs immunosuppressive-only (p = 0.0031). The proportion of malignant cases in patients receiving immunomodulatory therapy was, however, also significantly lower when compared with the immunosuppressive treated cases (43 vs 88%; p = 0.0184). The immunomodulatory/ suppressive agent-related lymphoproliferative disorders were less often associated with the Epstein-Barr virus (EBV) (31 vs 66%; p = 1.829e-05) and the lymphoproliferative disorders incidence in the first year after immunomodulatory/immunosuppressive therapy initiation was lower (18 vs 41%; p = 0.04151)-compared with a published series of 140 post-transplant lymphoproliferative disorder cases from the same center. However, a similar histopathological spectrum from nondestructive, to polymorphic and monomorphic lesions as in post-transplant lymphoproliferative disorders is observed. With increasing use of immunosuppressive and especially immunomodulatory therapy, a higher incidence of immunomodulatory/suppressive agent-related lymphoproliferative disorders is to be expected. Life-long awareness for development of immunomodulatory/suppressive agent-related lymphoproliferative disorders with clinical follow-up and timely biopsies of suspicious lesions is required since these lymphoproliferative disorders arise both early after therapy initiation and many years later. Histopathological confirmation and correct classification is necessary to guide therapy and EBV ISH should be a part of routine pathological diagnostics

MATERIALS/METHODS Human embryonic stem cells (ESCs) were gene-edited via zinc finger nucleases to express Fluc and either hNIS or hSSTr2 in the safe harbor locus, adeno-associated virus integration site 1. Firstly, these cells were exposed to 4.8 MBq 177Lu-DOTATATE in vitro and cell survival was monitored via bioluminescence imaging (BLI). Afterwards, hNIS+ and hSSTr2+ ESCs were transplanted subcutaneously and teratomas were allowed to form. At day 59, baseline 124I and 68Ga-DOTATATE PET and BLI scans were performed. The day after, animals received either saline or 55 MBq 177Lu-DOTATATE. Weekly BLI scans were performed, accompanied by 124I and 68Ga-DOTATATE PET scans at days 87 and 88, respectively. Finally, hSSTr2+ ESCs were differentiated towards CMs and transplanted intramyocardially in the border zone of an infarct that was induced by left anterior descending coronary artery ligation. After transplantation, the animals were monitored via BLI and PET, while global cardiac function was evaluated using cardiac magnetic resonance imaging.

RESULTS

INTRODUCTION/BACKGROUND

Teratoma growth of both hNIS+ and hSSTr2+ ESCs could be followed noninvasively over time by both PET and BLI. After 177Lu-DOTATATE administration, successful cell killing of the hSSTr2+ ESCs was achieved both in vitro and in vivo, indicated by reductions in total tracer lesion uptake, BLI signal and teratoma volume. As undifferentiated hSSTr2+ ESCs are not therapeutically relevant, they were differentiated towards CMs and injected in immune-deficient mice with a MI. Long-term cell survival could be monitored without uncontrolled cell proliferation. However, no improvement in the left ventricular ejection fraction was observed.

Pluripotent stem cells (PSCs) are being investigated as a cell source for regenerative medicine since they provide an infinitive pool of cells that are able to differentiate towards every cell type of the body. One possible therapeutic application involves the use of these cells to treat myocardial infarction (MI), a condition where billions of cardiomyocytes (CMs) are lost. Although several protocols have been developed to differentiate PSCs towards CMs, none

We developed isogenic hSSTr2-expressing ESCs that allow noninvasive cell monitoring in the context of PSC-derived regenerative therapy. Furthermore, we are the first to use the hSSTr2 not only as an imaging reporter gene, but also as a suicide mechanism for radionuclide therapy in the setting of PSC-derived cell treatment

ABSTRACT 13 The human somatostatin receptor type 2 as an imaging and suicide reporter gene for pluripotent stem cellderived therapy of myocardial infarction Neyrinck K, Breuls N, Gheysens O, et al. Theranostics, 2018, 8(10), 2799-2813

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of these provide a completely pure population, thereby still posing a risk for neoplastic teratoma formation. Therefore, we developed a strategy to (i) monitor cell behavior noninvasively via site-specific integration of firefly luciferase (Fluc) and the human positron emission tomography (PET) imaging reporter genes, sodium iodide symporter (hNIS) and somatostatin receptor type 2 (hSSTr2), and (ii) perform hSSTr2-mediated suicide gene therapy via the clinically used radiopharmacon 177Lu-DOTATATE.

CONCLUSION


ABSTRACT 14 18F-FDG PET/CT and MRI of a mediastinal malignant granular cell tumor with associated recurrent pericarditis D'hulst L, Deroose C, Gheysens O, et al. Clinical Nuclear Medicine, 2018, 43(8), 589-590

fenidone treatment after lung transplantation. Our findings provide further evidence that pirfenidone appears to be safe and may attenuate the rate of decline in lung function in patients with RAS, but the actual clinical benefit cannot be assessed in the context of this study design and requires further investigation in a larger randomized trial.

INTRODUCTION/BACKGROUND

ABSTRACT 16

We report a rare case of a mediastinal malignant granular cell tumor in a 41-year-old man presenting with dyspnea, retrosternal chest pain, and recurrent pericardial effusion under treatment with corticosteroids. Because of recurrent episodes, further investigations with chest MRI and F-FDG PET/CT revealed a large infiltrating and strongly hypermetabolic mass in the mediastinum with pericarditis. Histopathology and immunohistochemical analysis showed large cells with greater pleomorphism and eosinophilic granular cytoplasm with positive staining for S100 protein and CD68 as well as high Ki67 proliferative index (15%) confirming the diagnosis of a malignant granular cell tumor.

A joint procedural position statement on imaging in cardiac sarcoidosis: from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging, and the American Society of Nuclear Cardiology

ABSTRACT 15 Pirfenidone in restrictive allograft syndrome after lung transplantation: A case series Vos R, Wuyts W, Gheysens O, et al. American Journal of Transplantation, 2018, 18(12), 30453059

Slart R, Glaudemans A, Gheysens O, et al. Journal of Nuclear Cardiology, 2018, 25(1), 298-319

INTRODUCTION/BACKGROUND This procedural position paper on the use of imaging in the management of patients with known or suspected cardiac sarcoidosis has been developed under the auspices of the Cardiovascular and the Inflammation and Infection Committee of the European Association of Nuclear Medicine, the European Association of Cardiovascular Imaging of the European Society of Cardiology, and the American Society of Nuclear Cardiology, highlighting the close collaboration between the societies on this topic.

INTRODUCTION/BACKGROUND

ABSTRACT 17

Pirfenidone may attenuate the decline of pulmonary function in restrictive allograft syndrome (RAS) after lung transplantation. We retrospectively assessed all lung transplant recipients with RAS who were treated with pirfenidone for at least 3 months (n = 11) in our lung transplant center and report on their long-term outcomes following initiation of pirfenidone. Main outcome parameters included evolution of pulmonary function and overall survival. Pirfenidone appears to attenuate the decline in forced vital capacity and forced expiratory volume in 1 second. Notably, 3 patients were bridged to redo-transplantation with pirfenidone for 11 (5-12) months and are currently alive, while 3 other patients demonstrate long-term stabilization of pulmonary function after 26.6 (range 18.4-46.6) months of treatment. Median overall 3-year survival after RAS diagnosis was 54.5%. Subjective intolerance, mainly anorexia and nausea, necessitating pirfenidone dose de-escalation in 55% of patients, as well as calcineurin dose increase requirements with about 20% are important complications during pir-

Bone scintigraphy in poststreptococcal periostitis with dysproteinemia Bourgeois S, Peetermans W, Gheysens O, et al. Clinical Nuclear Medicine, 2018, 43(10), e366-e367

INTRODUCTION/BACKGROUND A 39-year-old man presented with severe bone pain in the tibiae and forearms in the wake of a poststreptococcal sepsis complicated with pneumonia and erysipelas 4 months earlier. Bone scintigraphy was indicative of periostitis of the tibia, ulna, and radius bilaterally, and in combination with the increased inflammatory parameters and dysproteinemia, the diagnosis of Goldbloom syndrome was made. Goldbloom syndrome is an idiopathic periosteal hyperostosis associated with dysproteinemia and elevated inflammatory parameters. Although it has only been described in children/adolescents, this case illustrates that, in the specific clinical and biochemical setting, it should also be considered in adults.

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ABSTRACT 18 Unraveling the cause of anuria transplantation by renal scintigraphy

RESULTS post

kidney

Van Keerberghen C, Naesens M, Gheysens O, et al. Clinical Nuclear Medicine, 2018, 43(12), e458-e459

INTRODUCTION/BACKGROUND A dynamic renal scintigraphy is widely used after renal transplantation to evaluate transplant function and possible complications. We report the case of a 27-year-old man with persisting anuria after kidney transplantation. A renal scintigraphy using Tc-ethylenedicysteine followed by SPECT/CT of the abdomen was performed showing tracer accumulation in the colon without any activity in the bladder, as a result of ureter reimplantation onto the sigmoid instead of onto the previously reconstructed bladder. Renal scintigraphy identified the cause and localization of the urinary leak, which led to immediate surgical reimplantation of the ureter onto the augmented bladder with onset of diuresis.

ABSTRACT 19

ABSTRACT 20

Sathekge M, Lengana T, Maes A, et al. European Journal of Nuclear Medicine and Molecular Imaging, 2018, 45(2), 226-234

68Ga-PSMA-HBED-CC PET/CT imaging in Black versus White South African patients with prostate carcinoma presenting with a low volume, androgen-dependent biochemical recurrence: a prospective study

INTRODUCTION/BACKGROUND

MATERIALS/METHODS 68Ga-PSMA-11 PET/CT imaging findings were compared to histological, biochemical and morphological imaging data. Patients were grouped into three Gleason grade groups (GG), GG 1 (scores 3 + 3 and 3 + 4), GG2 (scores 4 + 3 and 4 + 4) and GG3 (scores 9 and 10), and the PSA difference among the groups was determined. Inter-racial difference in SUVmax of the primary tumor as well as its correlation with serum PSA were also determined.

ABSTRACTBOEK | 2018

CONCLUSION SUVmax values proved significantly related to GG and to be significantly higher in BSAs when compared to WSAs. Also, SUVmax significantly correlated with serum PSA values, which was significantly higher in BSAs when compared with WSAs.

68Ga-PSMA-11 PET/CT in primary staging of prostate carcinoma: preliminary results on differences between black and white South-Africans

The incidence of prostate cancer is 60% higher and the mortality rate is two- to three-times greater in black versus white men. We report on differences in 68Ga-PSMA-11 PET/ CT imaging findings in 77 black South-African (BSAs) and 18 white South-African (WSAs) treatment-naïve primary prostate carcinoma (PPC) patients.

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Ninety-three out of 95 PPC where readily identified on 68Ga-PSMA-11 PET/CT imaging. Median PPC SUVmax and serum PSA values proved significantly higher (p = 0.033 and p = 0.003) in GG3 patients (median 16.4 and 180 ng/ml) when compared to GG1 patients (median 9.6 and 25.1 ng/ ml) or GG2 patients (median 8.8 and 46.2 ng/ml). SUVmax significantly correlated with serum PSA-values (r = 0.377 (p = 0.0001)). Age, frequency of lymph node involvement and distant metastases, and GGs (p ≥ 0.153) were similar in BSAs and WSAs, both median serum PSA-values as well as SUVmax values proved significantly higher in BSAs when compared to WSAs, respectively, 81.6 ng/ml versus 14.5 ng/ml (p = 0.0001) and 11.9 versus 4.38 (p = 0.004). Moreover, Gleason-score normalized median SUVmax values proved 2.5 times higher in BSAs when compared to WSAs (p = 0.005).

Lengana T, Van de Wiele C, Lawal I, et al. Nuclear Medicine Communications, 2018, 39(2), 179-185

INTRODUCTION/BACKGROUND To compare the diagnostic accuracy of Ga-prostate-specific membrane antigen (PSMA)-HBED-CC PET/computed tomography (CT) imaging for the detection of androgen-dependent recurrent prostate carcinoma (ADPC) in Black South Africans (BSAs) versus White South Africans (WSAs) with increasing serum prostate-specific antigen (PSA) values below or equal to 10 ng/ml.

MATERIALS/METHODS A total of 61 patients with ADPC were prospectively included in the study (mean age: 66.7 years): 38 WSAs and 23 BSAs. Ga-PSMA-HBED-CC PET/CT imaging results obtained were related to serum PSA levels and to ethnicity.


RESULTS A total of 41 (67%) patients had a positive Ga-PSMA-HBEDCC scan result. Ga-PSMA-HBED-CC PET/CT positivity was significantly higher in patients with PSA values more than 2 ng/ml [32/38 (84%) patients] when compared with patients with PSA values less than 0.5 ng/ml [6/11 (55%) patients] or PSA values of 0.5-2 ng/ml [3/12 (25%) patients] (P=0.0001). Mean PSA values proved not significantly different in patients presenting with extrapelvic involvement when compared with those with intrapelvic involvement or between patients who presented with bone involvement versus those who did not on Ga-PSMA-HBED-CC PET/CT) (P≥0.147). Age, Gleason-scores, median PSA values, the frequency of a positive scan result, the frequency of bone involvement, and extrapelvic involvement proved similar in WSAs and BSAs (P≥0.417).

CONCLUSION Ga-PSMA-HBED-CC PET/CT imaging identified a recurrence in 67% of the patients under study. Higher PSA levels were associated with Ga-PSMA-HBED-CC PET/CT positivity and the detection rate. Imaging results obtained proved similar in BSAs and WSAs, suggesting that the tumor burden and growth rate of ADPC are similar in both races.

ABSTRACT 21 Tuberculosis Ankrah A, Glaudemans A, Maes A, et al. Seminars in Nuclear Medicine, 2018, 48(2), 108-130

INTRODUCTION/BACKGROUND Tuberculosis (TB) is currently the world's leading cause of infectious mortality. Imaging plays an important role in the management of this disease. The complex immune response of the human body to Mycobacterium tuberculosis results in a wide array of clinical manifestations, making clinical and radiological diagnosis challenging. 18F-FDGPET/CT is very sensitive in the early detection of TB in most parts of the body; however, the lack of specificity is a major limitation. 18F-FDG-PET/CT images the whole body and provides a pre-therapeutic metabolic map of the infection, enabling clinicians to accurately assess the burden of disease. It enables the most appropriate site of biopsy to be selected, stages the infection, and detects disease in previously unknown sites. 18F-FDG-PET/CT has recently been shown to be able to identify a subset of patients with latent TB infection who have subclinical disease. Lung inflammation as detected by 18F-FDG-PET/CT has shown promising signs that it may be a useful predictor of progression from

latent to active infection. A number of studies have identified imaging features that might improve the specificity of 18F-FDG-PET/CT at some sites of extrapulmonary TB. Other PET tracers have also been investigated for their use in TB, with some promising results. The potential role and future perspectives of PET/CT in imaging TB is considered. Literature abounds on the very important role of 18F-FDG-PET/ CT in assessing therapy response in TB. The use of 18F-FDG for monitoring response to treatment is addressed in a separate review.

ABSTRACT 22 Patient-specific lean body mass can be estimated from limited-coverage computed tomography images Devriese J, Beels L, Maes A, et al. Nuclear Medicine Communications, 2018, 39(6), 521-526

INTRODUCTION/BACKGROUND In PET/CT, quantitative evaluation of tumour metabolic activity is possible through standardized uptake values, usually normalized for body weight (BW) or lean body mass (LBM). Patient-specific LBM can be estimated from wholebody (WB) CT images. As most clinical indications only warrant PET/CT examinations covering head to midthigh, the aim of this study was to develop a simple and reliable method to estimate LBM from limited-coverage (LC) CT images and test its validity.

MATERIALS/METHODS Head-to-toe PET/CT examinations were retrospectively retrieved and semiautomatically segmented into tissue types based on thresholding of CT Hounsfield units. LC was obtained by omitting image slices. Image segmentation was validated on the WB CT examinations by comparing CT-estimated BW with actual BW, and LBM estimated from LC images were compared with LBM estimated from WB images. A direct method and an indirect method were developed and validated on an independent data set.

RESULTS Comparing LBM estimated from LC examinations with estimates from WB examinations (LBMWB) showed a significant but limited bias of 1.2 kg (direct method) and nonsignificant bias of 0.05 kg (indirect method).

CONCLUSION This study demonstrates that LBM can be estimated from LC CT images with no significant difference from LBMWB.

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ABSTRACT 23

INTRODUCTION/BACKGROUND

Blood-brain barrier transport kinetics of NOTA-modified proteins: the somatropin case

68Ga ligands targeting prostate-specific membrane antigen (PSMA) are rapidly emerging as a significant step forward in the management of prostate cancer. PSMA is a type II transmembrane protein with high expression in prostate carcinoma cells. We prospectively evaluated the use of 68Ga-PSMA positron emission tomography/computed tomography (PET/CT) in patients with prostate cancer and compared the results to those for technetium-99m (99mTc)-10-metacyloyloxydecyl dihydrogen phosphate (MDP) bone scintigraphy (BS).

Bracke N, Janssens Y, Maes A, et al. The Quarterly Journal of Nuclear Medicine and Molecular Imaging, 2018, DOI: 10.23736/S1824-4785.18.03025-X

INTRODUCTION/BACKGROUND Chemical modifications such as PEG, polyamine and radio labeling on proteins can alter their pharmacokinetic behaviour and their blood-brain barrier (BBB) transport characteristics. NOTA, i.e. 1,4,7-triazacyclononane-1,4,7-triacetic acid, is a bifunctional chelating agent that has attracted the interest of the scientific community for its high complexation constant with metals like gallium. Until now, the comparative BBB transport characteristics of NOTA-modified proteins versus unmodified proteins are not yet described.

MATERIALS/METHODS Somatropin (i.e. recombinant human growth hormone), NOTA-conjugated somatropin and gallium-labelled NOTA-conjugated somatropin were investigated for their brain penetration characteristics (multiple time regression and capillary depletion) in an in vivo mice model to determine the blood-brain transfer properties.

RESULTS The three compounds showed comparable initial brain influx, with Kin = 0.38 ± 0.14 μL/(g×min), 0.36 ± 0.16 μL/ (g×min) and 0.28 ± 0.18 μL/(g×min), respectively. Capillary depletion indicated that more than 80% of the influxed compounds reached the brain parenchyma. All three compounds were in vivo stable in serum and brain during the time frame of the experiments.

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MATERIALS/METHODS A total 113 patients with biopsy-proven prostate cancer referred for standard-of-care BS were prospectively enrolled onto this study. 68Ga-PSMA PET/CT was performed after BS. Metastasis diagnosed on each technique was compared against a final diagnosis based on CT, magnetic resonance imaging, skeletal survey, clinical follow-up, and histologic correlation.

RESULTS Ninety-one bone lesions were interpreted as bone metastases in 25 men undergoing 68Ga-PSMA PET/ CT compared to only 61 lesions in 19 men undergoing 99mTc-MDP BS. Of the 7 bone scans that missed skeletal metastases, 54% of these missed lesions were due to either marrow or lytic skeletal metastases. The median standardized uptake value in all malignant bone lesions was 13.84. 68Ga-PSMA PET/CT showed significantly higher sensitivity and accuracy than BS (96.2% vs. 73.1%, and 99.1% vs. 84.1%) for the detection of skeletal lesions. For extraskeletal lesions, 68Ga-PSMA PET/ CT showed an additional 96 unexpected lesions with a median standardized uptake value of 17.6.

CONCLUSION

CONCLUSION

Our results show that modification of NOTA as well as gallium chelation onto proteins, in casu somatropin, does not lead to a significantly changed pharmacokinetic profile at the blood-brain barrier.

68Ga-PSMA PET/CT is superior to and can potentially replace bone scan in the evaluation for skeletal metastases in the clinical and trial setting because of its ability to detect lytic and bone marrow metastases.

ABSTRACT 24

ABSTRACT 25

68Ga-PSMA PET/CT replacing bone scan in the initial staging of skeletal metastasis in prostate cancer: a fait accompli?

Prognostic value of pre-treatment F-18 FDG PET metabolic metrics in patients with locally advanced carcinoma of the anus with and without HIV infection

Lengana T, Lawal I, Maes A, et al. Clinical Genitourinary Cancer, 2018, 16(5), 392-401

Lawal I, Ankrah A, Maes A, et al. Nuklearmedizin, 2018, 57(5), 190-197


INTRODUCTION/BACKGROUND

INTRODUCTION/BACKGROUND

To investigate the prognostic value of F-18 FDG PET metabolic parameters in patients with anal carcinoma with and without human immunodeficiency virus infection (HIV).

The aim of this study was to compare liver and oncologic lesion standardized uptake values (SUV) obtained through two different reconstruction protocols, GE's newest clinical lesion detection protocol (Q.Clear) and the EANM Research Ltd (EARL) harmonization protocol, and to assess the clinical relevance of potential differences and possible implications for daily clinical practice using the PERCIST lesional inclusion criteria.

MATERIALS/METHODS Maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were obtained on F-18 FDG PET/CT images of treatment-naïve patients with locally advanced anal squamous cell carcinoma (ASSC). We compared patients' characteristics and F-18 FDG PET metabolic metrics between the HIV-infected patients and the HIV-uninfected patients. We did a simple Cox regression analysis followed by a multiple Cox regression analysis to determine factors predictive of death.

RESULTS We studied 33 patients including 21 HIV-infected individuals, mean age = 46.06 ± 12.59, female = 16, males = 17. Median CD4 count among HIV-infected patients was 400.50 cells/mm3 (IQR: 304.0 - 642.25). HIV-infected patients were younger than the HIV-uninfected patients at the time of diagnosis; 38.71 ± 7.98 vs. 58.92 ± 7.88 respectively, p < 0.001. No significant difference in the TNM stage and F-18 FDG metabolic parameters between the two groups. In a simple Cox regression analysis, MTV and TLG were significant predictors of death. Following a multiple Cox regression analysis, MTV and SUVmean were significant predictors of death. The median overall survival was 44.63 (95 % CI: 34.12 - 55.14) among HIV-infected patients versus 54.65 (95 % CI: 45.73 - 63.57) among HIV-uninfected patients, p = 0.415.

MATERIALS/METHODS NEMA phantom recovery coefficients (RC) and SUV normalized for lean body mass (LBM), referred to as SUV normalized for LBM (SUL), of liver and lesion volumes of interest were compared between the two reconstruction protocols. Head-to-toe PET/CT examinations and raw data from 64 patients were retrospectively retrieved. PET image reconstruction was carried out twice: once optimized for quantification, complying with EARL accreditation requirements, and once optimized for lesion detection, according to GE's Q.Clear reconstruction settings.

RESULTS The two reconstruction protocols showed different NEMA phantom RC values for different sphere sizes. Q.Clear values were always highest and exceeded the EARL accreditation maximum for smaller spheres. Comparison of liver SULmean showed a statistically significant but clinically irrelevant difference between both protocols. Comparison of lesion SULpeak and SULmax showed a statistically significant, and clinically relevant, difference of 1.64 and 4.57, respectively.

CONCLUSION

CONCLUSION

HIV-infected patients are diagnosed with ASSC at a younger age compared with HIV-uninfected patients. F-18 FDG PET metabolic metrics especially MTV predicts overall survival in patients with ASCC. There is no difference in the overall survival of HIV-infected and HIV-uninfected patients treated similarly for ASSC.

For treatment response assessment using PERCIST criteria, the harmonization reconstruction protocol should be used as the lesion detection reconstruction protocol using resolution recovery systematically overestimates true SUL values.

ABSTRACT 26 Impact of PET reconstruction protocols on quantification of lesions that fulfil the PERCIST lesion inclusion criteria Devriese J, Beels L, Maes A, et al. European Journal of Nuclear Medicine and Molecular Imaging Physics, 2018, 5(1), 35-48

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CENTRUM

ONCOLOGIE ARTIKELS

CONCLUSION

ABSTRACT 1

Despite heterogeneity, majority of reported models for oncological home-hospitalization demonstrated that this is a safe, equivalent and acceptable alternative to ambulatory hospital care. More well-designed trials are needed to evaluate its economic impact.

Screening methods for age-related hearing loss in older patients with cancer: a review of the literature Debruyne P, Van Eygen K, Boterberg T, et al. Geriatrics, 2018, 3(3), 48-60

ABSTRACT 3 Cellulitis bij een immuungecompromitteerde patiënt

INTRODUCTION/BACKGROUND As people grow older, they may experience loss in hearing sensitivity. Age-related hearing loss may negatively affect the patient’s quality of life as it may lead to social isolation. In older patients with cancer, hearing loss can seriously interfere with the patient’s ability to deal properly with all aspects of their disease, and may have a cumulative effect on their already decreased quality of life. Therefore, the proper screening of those conditions is essential in order to optimise the patient’s comfort during and after treatment. This review article aims at providing a concise image of the nature of age-related hearing loss, and provides an overview of the screening methods that could be used in older patients with cancer.

Louwagie A,Boudewijns M,Van Eygen K, Pattyn I, et al. Tijdschrift voor Geneeskunde, 2018, 74 (2), 138-141

ABSTRACT 2

We previously validated uHear™ to screen for hearing loss in older patients with cancer without a known hearing loss, as part of a comprehensive geriatric assessment (CGA). In view of low specificity, we tested a new modified uHear™ scoring system as described by Handzel.

Het abstract is terug te vinden op pagina 29.

ABSTRACT 4 The use of uHear™ to screen for hearing loss in older patients with cancer as part of a comprehensive geriatric assessment Lycke M, Debruyne P, Lefebvre T, et al. Acta Clinica Belgica, 2018, 73(2), 132-138

OBJECTIVE Organization, quality and cost of oncological homehospitalization: a systematic review Desmedt L, De Jonghe P, Foulon V, Van Eygen K, et al. Critical Reviews in Oncology/Hematology, 2018, 126, 145-153

MATERIALS/METHODS INTRODUCTION/BACKGROUND Home-hospitalization might be a patient-centred approach facing the increasing burden of cancer on societies. This systematic review assessed how oncological home-hospitalization has been organized and to what extent its quality and costs were evaluated.

RESULTS Twenty-four papers describing parenteral cancer drug administration to adult patients in their homes were included. Most papers concluded oncological home-hospitalization had no significant effect on patientreported quality of life (7/8=88%), but large majority of patients were satisfied (12/13, 92%) and preferred home treatment (7/8, 88%). No safety risks were associated with home-hospitalization (10/10, 100%). The cost of home-hospitalization was found beneficial in five trials (5/9, 56%); others reported no financial impact (2/9, 22%) or additional costs (2/9, 22%).

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Patients, aged ≥70 years, were evaluated by uHear™ and conventional audiometry, which is considered the gold standard, as part of a CGA. The pass or fail screening cut-off for uHear™ was defined as having ≥2 consecutive hearing grades starting from the moderate-severe threshold zone ranging from 0.5 to 2.0 kHz (modified Handzel-uHear™ scoring system). To accept the modified Handzel-uHear™ as screening tool, it was predefined that the combined sensitivity (S) and specificity (Sp) of the test (S + Sp/2) was at least 80% and that an actual combined (S + Sp)/2 of 90% would be found.

RESULTS Ninety ears (45 subjects) were tested. Of those ears, 24.4% were identified as impaired by conventional audiometry. Modified Handzel-uHear™ identified 26.7% of tested ears as impaired. The combined (S + Sp)/2 of the modified Handzel-uHear™ was calculated as 77.5%, while in previ-


ous cohort, this was retrospectively calculated as 94.6%. A new uHear™ scoring system was proposed and tested in current and previous cohort. A (S + Sp)/2 of 80.2 and 78.8%, respectively, were obtained.

ABSTRACT 6 Incidence of medication-related osteonecrosis of the jaw in patients treated with both bone resorption inhibitors and vascular endothelial growth factor receptor tyrosine kinase inhibitors

CONCLUSION uHear™ is a feasible tool for use within the CGA and shows promising results. However, further research is warranted to optimize the cut-off method before it could be routinely implemented within geriatric oncology.

ABSTRACT 5 Disease and treatment characteristics of polycythaemia vera patients in Belgium: results from a scientific survey Devos T, Beguin Y, Van Eygen K, et al. European Journal of Hematology, 2018, 100(4), 361-366

van Cann T, Loyson T, Debruyne P, et al. Supportive Care in Cancer, 2018, 26(3), 869-878

INTRODUCTION/BACKGROUND Several case reports and small case series have suggested a higher incidence of medication-related osteonecrosis of the jaw (MRONJ) in patients treated concomitantly with bone resorption inhibitors (BRIs) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), as compared to patients treated with BRIs alone. We aimed to assess ONJ-incidence in patients exposed concomitantly to BRIs and VEGFR-TKIs.

OBJECTIVE

MATERIALS/METHODS

The current survey aimed to gather predefined disease parameters and treatment strategies to characterize the polycythemia vera (PV) patient population in Belgium.

We reviewed the records of all patients who received VEGFR-TKIs concomitantly with BRIs. Patients, who were treated with BRIs without VEGFR-TKI, served as a control group. Endpoints of the study were total MRONJ-incidence, MRONJ-incidence during the first and second year of exposure, and time-to-ONJ-incidence.

MATERIALS/METHODS Cross-sectional data from PV patients, seen at least once between May 2014 and May 2015 at 10 sites in Belgium, were collected in aggregated form and analyzed descriptively and quantitatively.

RESULTS Data from 343 PV patients were collected. Of these, 174 (50.7%) were male and 256 (74.6%) were ≥60 years of age. Ninety-two (26.8%) had a prior history of thrombotic events. Considerable proportions of patients had increased hematological parameters (hematocrit > 45% [31.2%], leukocytes > 10 × 109 /L [33.3%], and platelet > 400 × 109 /L [38.2%]). Most patients had non-palpable spleen (284, 87.7%) and no phlebotomies during the past 6 months (197, 57.4%). Low-dose aspirin was given as thrombosis prophylaxis in 249 (72.6%) patients, while 232 (67.6%) received hydroxyurea (HU) as cytoreductive treatment. Forty-one patients (12.0%) were reported as resistant and/or intolerant to HU. Seventeen patients (5.0%) received ruxolitinib in the context of clinical trials.

CONCLUSION

RESULTS Ninety patients were treated concomitantly with BRIs and VEGFR-TKIs with a median BRI-exposure of 5.0 months. Total MRONJ-incidence was 11.1%. During the first year of BRI-exposure (with a median concomitant exposure of 4.0 months), 6 out of 90 patients (6.7%) developed a MRONJ, compared to 1.1% in the control group (odds ratio 5.9; 95%CI 2.0-18.0; p = 0.0035). In Kaplan-Meier estimates, time-to-ONJ-incidence was significantly shorter in patients treated with BRIs and VEGFR-TKIs compared to BRIs alone (hazard ratio 9.5; 95%CI 3.1-29.6; p < 0.0001). MRONJs occurred earlier in patients treated concomitantly compared to patients treated with BRIs only (after a median exposure of 4.5 and 25.0 months, respectively; p = 0.0033).

CONCLUSION With a global MRONJ-incidence of 11%, patients receiving concomitant treatment with VEGFR-TKIs and BRIs have a five to ten times higher risk for development of MRONJ compared to patients treated with BRIs alone.

This survey provides better insight into the characteristics of Belgian PV patients and currently used treatment strategies. It shows that 232 (67.6%) PV patients continue to receive HU despite being potentially HU-resistant.

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PRESENTATIES / CONGRESSEN ABSTRACT 1 An observational pilot study to evaluate the feasibility and quality of (partial) oncological home-hospitalization International Forum on Quality and Safety in Healthcare 2018 Cool L, Missiaen J, Debruyne P, et al. May 2018, Amsterdam, The Netherlands

INTRODUCTION/BACKGROUND The increasing availability of high-effective (systemic) treatment options have led to an encouraging decrease of cancer-related mortality. However, the increasing prevalence of cancer and high costs associated with these innovative therapies, place a major burden for society. Oncological home-hospitalization might be a patient-centred and cost-effective approach facing these challenges. However, empirical evidence regarding the quality and efficiency of this care model is scarce. As such, more accurate and valid data are needed in order to correctly inform all stakeholders on the potential of generalizing this new model into clinical practice. This study was conducted at the oncology day care unit of the general hospital groeninge, Kortrijk, Belgium. A new care model for (partial) home-based cancer treatment was developed, implemented and subsequently evaluated.

OBJECTIVE A pilot study was conducted to evaluate health-related quality of life (QoL) and relevant endpoints among a cohort of adult cancer patients being treated (partially) at home or at the oncology day care unit. A set of validated patient-reported outcome measures (PROM’s) was used in order to select, based on the results of this pilot, those questionnaires that are most sensitive and specific within this setting for a subsequent randomized-controlled trial.

Within this non-randomized prospective pilot study, patients were allocated –based on their preferences- to (partial) home-treatment (n=32; intervention cohort) or standard ambulatory hospital care (n=28; control cohort). Patients were included between 17/01/17 and 14/04/2017. PROM’s for QoL (FACT-G, EQ-5D-3L and MyCaW); anxiety and depression (HADS); distress (Distress Barometer); satisfaction (OUT-PATSAT35 CT) and safety (self-designed questionnaire) were presented at the start of treatment as well as eight weeks later. An additional study-specific questionnaire was presented to the intervention cohort at study-end, questioning their satisfaction with and preferences for the provided homecare. The average difference in scores on each of the abovementioned PROM’s (baseline vs. eight weeks) was evaluated between both cohorts.

RESULTS On average, 4 ±2 home visits and 5 ±2 hospital visits were scheduled for the intervention cohort and 5 ±2 hospital visits for the control cohort during eight weeks of follow-up. None of the PROM’s evaluated revealed significant differences between both cohorts (all p>0.05). 96% of patients who received (partial) home treatment declared to be satisfied with the provided homecare and would like to have it continued. 88% of these patients felt themselves at home as safe as at the hospital. Retrospective analysis of the waiting time for treatment at the oncology day care unit demonstrated that if the assessments prior to therapy were performed at “day -1”, the average waiting time diminished with 1h12’ (i.e. 40%; p<0.001).

CONCLUSION Home-hospitalization is a patient-centred opportunity to deal with the challenges (cancer) healthcare is facing. Well-designed randomized trials should be organized to investigate the quality and economic consequences of oncological home-hospitalization.

MATERIALS/METHODS Adult cancer patients starting an ambulatory treatment (EGOG≤2 and living within a 30-minute drive from the hospital) were visited at home by a clinical nurse specialist to conduct all necessary assessments prior to therapy: nursing review, toxicity scoring, vital signs monitoring, blood sampling, and intravenous line access provision. These assessments were performed one day prior to actual therapy administration at the hospital (“day -1”), enabling the oncologist to prescribe and pharmacy to prepare cancer therapy before arrival of the patient. In addition, subcutaneous cancer therapies (i.e. bortezomib and azacitidine) were administered at the patient’s home.

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ABSTRACT 2 The added value of an assessment of the patient’s hand grip strength to the comprehensive geriatric assessment in g8-abnormal older patients with cancer in routine practice International Society of Geriatric Oncology Annual Congress Lycke M, Ketelaars L, Van Eygen K, Debruyne P, et al. November 2018, Amsterdam, The Netherlands


OBJECTIVE A comprehensive geriatric assessment (CGA) is the key treatment approach to guide decisions in older patients with cancer. In this paper, the added value of an assessment of the patient’s hand grip strength to predict survival in patients with an abnormal G8-questionnaire (G8) score is investigated.

MATERIALS/METHODS Patients were screened by the G8, followed by a CGA in case of an abnormal screening (≤14.0). Hand grip strength was assessed by use of the JAMAR® hydraulic hand dynamometer. Cut-offs were applied according to the Fried frailty criteria. The survival rate was calculated twelve months after the CGA date.

RESULTS We retrospectively reviewed data of 2071 patients who were treated at the Kortrijk Geriatric Oncology Clinic (General Hospital Groeninge, Belgium) between November 2012 and December 2016. Of those, 944 patients with a mean age of 79.6 years were included in the analyses. 64.2% of patients presented an abnormal hand grip strength score. A log rank test revealed a statistical significant result between patients when accounting for the hand grip strength score (p < .01). When added to a Cox regression model, a significant result was found (p < .01). However, this added only 0.4% to the explained variance of the model.

CONCLUSION While the JAMAR® shows a statistically significant result when added to a regression model for survival, our data indicate that such assessment may clinically be less relevant when included in an already extensive test battery and may therefore provide only limited information in terms of patient survival.

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CENTRUM

ORTHOPEDIE / HANDGROEP ARTIKELS

ABSTRACT 2 Synovial fluid fatty acid profiles differ between osteoarthritis and healthy patients

ABSTRACT 1 Three-dimensional displacement after a medializing calcaneal osteotomy in relation to the osteotomy angle and hindfoot alignment

Van de Vyver A, Clockaerts S, van de Lest CHA, et al. Cartilage, 2018, doi: 10.1177/1947603518798891

Peiffer M, Belvedere C, Clockaerts S, et al. Foot Ankle Surgery, 2018, doi: 10.1016/j.fas.2018.11.015

Free fatty acids (FAs) may influence cartilage metabolism and osteoarthritis (OA) disease progression. It is not clearly studied which FAs are present in the synovial fluid of knee joints and whether there are differences in FA content between nonsymptomatic and OA knee joints.

INTRODUCTION/BACKGROUND

INTRODUCTION/BACKGROUND A medializing calcaneal osteotomy is frequently performed to correct adult-acquired flatfoot deformities, but there is lack of data on the associated three-dimensional variables defining the final correction.

OBJECTIVE The aim of this study was to assess the correlation between the pre-operative hindfoot valgus deformity and calcaneal osteotomy angles and the post-operative calcaneal displacement.

MATERIALS/METHODS Weight-bearing CT scans obtained pre- and post-operatively were retrospectively analyzed for sixteen patients. Corresponding three-dimensional bone models were used to measure valgus deformity pre- and post-operatively, inclination of the osteotomy and displacement of the calcaneus. Linear regression was conducted to assess the relationship between these measurements.

OBJECTIVE The aim of this study was to investigate the presence of different types of FAs in synovial fluid of both OA- and nonsymptomatic control joints, and to analyze differences between both groups.

MATERIALS/METHODS A total of 23 synovial fluid samples were collected from patients with end-stage knee OA undergoing total knee replacement, with approval of the medical ethical committee. As controls, 6 synovial fluid samples were obtained from postmortem donors without any history of joint disease or arthritis. Measurement of free FA concentration was done by mass spectrometry for saturated FAs (SFA), monounsaturated FAs (MUFA), and omega-3 and omega-6 polyunsaturated FAs (n-3 PUFAs and n-6 PUFAs).

RESULTS RESULTS On average, the hindfoot valgus changed from 13.1° (±4.6) pre-operatively to 5.7° (±4.3) post-operatively. A mean inferior displacement of 3.2mm (±1.3) was observed along the osteotomy with a mean inclination of 54.6° (±5.6), 80.5° (±10.7), -13.7° (±15.7) in the axial, sagittal and coronal planes, respectively. A statistically significant positive relationship (p<.05, R2=0.6) was found between the pre-operative valgus, the axial osteotomy inclination, and the inferior displacement.

Our measurements demonstrated the presence of SFAs, MUFAs, n-3 and n-6 PUFAs in synovial fluid of both nonsymptomatic and OA knee joints. The n-6/n-3 ratio was significantly lower in the OA group ( P = 0.0005). Arachidonic acid (n-6 PUFA) concentrations were also lower in OA synovial fluid ( P = 0.01), while tetracosadienoic acid ( P = 0.0001) and nervonic acid ( P = 0.001) (MUFAs) were higher in synovial fluid of patients with knee OA.

CONCLUSION CONCLUSION This study shows that the degree of pre-operative hindfoot valgus and the axial osteotomy angle are predictive factors for the amount of post-operative inferior displacement of the calcaneus. These findings demonstrate the added value of a computer-based pre-operative planning in clinical practice.

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Synovial fluid contains a broad spectrum of free FAs. The FAs profile differs between OA and control subjects, including a tendency for less n-6 FAs in OA joints.


ABSTRACT 3

ABSTRACT 4

Weightbearing CT in normal hindfoot alignment – Presence of a constitutional valgus?

Searching for consensus in the approach to patients with chronic lateral ankle instability: ask the expert

Clockaerts S, Burssens A, Van Herzele E, et al. Foot and Ankle Surgery, 2018, 24(3), 213-218

Michels F, Pereira H, Calder J, et al. Knee Surgery, Sports Traumatology, Arthroscopy, 2018, 26(7), 2095-2102

INTRODUCTION/BACKGROUND The normal hindfoot angle is estimated between 2° and 6° of valgus in the general population. These results are solely based on clinical findings and plain radiographs.

OBJECTIVE The purpose of this study is to propose recommendations for the treatment of patients with chronic lateral ankle instability (CAI) based on expert opinions.

OBJECTIVE The purpose of this study is to assess the hindfoot alignment using weightbearing CT.

MATERIALS/METHODS Forty-eight patients, mean age of 39.6±13.2 years, with clinical and radiological absence of hindfoot pathology were included. A weightbear CT was obtained and allowed to measure the anatomical tibia axis (TAx) and the hindfoot alignment (HA). The HA was firstly determined using the inferior point of the calcaneus (HAIC). A density measurement of this area was subsequently performed to analyze if this point concurred with an increased ossification, indicating a higher load exposure. Secondly the HA was determined by dividing the calcaneus in the long axial view (HALA) and compared to the (HAIC) to point out any possible differences attributed to the measurement method. Reliability was assessed using an intra class correlation coefficient (ICC).

MATERIALS/METHODS A questionnaire was sent to 32 orthopaedic surgeons with clinical and scientific experience in the treatment of CAI. The questions were related to preoperative imaging, indications and timing of surgery, technical choices, and the influence of patient-related aspects.

RESULTS Thirty of the 32 invited surgeons (94%) responded. Consensus was found on several aspects of treatment. Preoperative MRI was routinely recommended. Surgery was considered in patients with functional ankle instability after 3-6 months of non-surgical treatment. Ligament repair is still the treatment of choice in patients with mechanical instability; however, in patients with generalized laxity or poor ligament quality, lateral ligament reconstruction (with grafting) of both the ATFL and CFL should be considered.

RESULTS

CONCLUSION

The mean HAIC equaled 0.79° of valgus ±3.2 (ICCHA IC=0.73) with a mean TAx of 2.7° varus ±2.1 (ICCTA=0.76).The HALA equaled 9.1° of valgus ±4.8 (ICCHA LA=0.71) and differed significantly by a P <0.001 from the HAIC, which showed a more neutral alignment. Correlation between both was shown to be good by a Spearman's correlation coefficient of 0.74. The mean density of the inferior calcaneal area equaled 271.3±84.1 and was significantly higher than the regional calcaneal area (P<0.001).

Most surgeons request an MRI during the preoperative planning. There is a trend towards earlier surgical treatment (after failure of non-surgical treatment) in patients with mechanical ligament laxity (compared with functional instability) and in high-level athletes. This study proposes an assessment and a treatment algorithm that may be used as a recommendation in the treatment of patients with CAI.

CONCLUSION These results show a more neutral alignment of the hindfoot in this group of non-symptomatic feet as opposed to the generally accepted constitutional valgus. This could have repercussion on hindfoot position during fusion or in quantifying the correction of a malalignment. The inferior calcaneus point in this can be used during pre-operative planning of a hindfoot correction as an anatomical landmark due to its shown influence on load transfer.

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PRESENTATIES / CONGRESSEN ABSTRACT 1 The anterior tibiotalar fat pad as a source of pain and inflammation in osteoarthritis of the ankle: anatomy, histology and imaging KBVR Clockaerts, S September 2018, Spa, Belgium

INTRODUCTION/BACKGROUND To gain a better insight in the pathophysiology of ankle osteoarthritis (OA), a pathology which is underrepresented in current and past research. The most important etiological factor in ankle OA is trauma (70-80% of cases), which can result in direct joint damage, malalignment, incongruency or instability. Despite successful conservative treatment or surgical intervention, many cases of ankle trauma evolve towards OA. Posttraumatic inflammation is hypothesized to be an important initiator of posttraumatic ankle OA. Pro-inflammatory mediators in the synovial fluid are elevated after injury, which may increase the imbalance between cartilage destruction and repair. In the knee, the infrapatellar fat pad is identified as an important source of inflammatory mediators. To date, the role of fatty tissues in the ankle joint has not been defined, although arthroscopic findings indicate the presence of adipose tissue anterior to the ankle joint.

MATERIALS/METHODS Three Tesla MRI scans (T1 and T2 sequences) were performed on 3 cadaveric human feet, which were obtained from the human body donation of the university. The anterior compartment of the ankle joint was dissected and the exact location of the anterior adipose tissue was documented. Histological analyses of the dissected fat pad were performed with hematoxyline eosine staining and immunohistochemistry for the inflammatory marker CD45 (leucocytes). The obtained histological sections were used to confirm structures seen during dissection and on MRI. To investigate the presence of inflammation in the anterior tibiotalar fat pad (ATTFP) of ankle joints, 30 ankle MRI scans of patients with chronic pain after trauma, OA, bone marrow oedema, persistent Achilles tendinopathy or fasciitis plantaris were scored for the presence of ankle pathology (including bone marrow oedema, effusion, synovitis, cartilage lesions, osteophytes, loose bodies). The presence of signal

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alteration in the adipose tissue on sagittal T2 sequences was scored as the number of slices showing signal alteration. Based on these scores, we categorized ankle pathology and signal alteration into: 0=no pathology, 1-2=mild, 3-5=moderate, >5=severe. Statistical analysis was performed with a Kruskal-Wallis test.

RESULTS We found adipose tissue to be present posterior to the extensor tendon sheaths, at the level of the ankle joint. It attaches to the periosteum of the tibia, 1 cm proximally to the joint line. It is mediolaterally delimited by the deltoid ligament and the anterior talofibular ligament. Anteromedially, it reaches as far as the neck of the talus. We defined it as the anterior tibiotalar fat pad (ATTFP). There is no joint capsule between the adipose tissue and the joint as determined macroscopically and microscopically. CD45+ cells were found in the ATTFP of cadaveric feet. On MRI, higher signal alterations were mainly present in the ATTFP in ankles with radiological presence of joint pathology, in particular in more severe cases (p=0.01).

CONCLUSION We found adipose tissue to be present posterior to the extensor tendon sheaths, at the level of the ankle joint. It attaches to the periosteum of the tibia, 1 cm proximally to the joint line. It is mediolaterally delimited by the deltoid ligament and the anterior talofibular ligament. Anteromedially, it reaches as far as the neck of the talus. We defined it as the anterior tibiotalar fat pad (ATTFP). There is no joint capsule between the adipose tissue and the joint as determined macroscopically and microscopically. CD45+ cells were found in the ATTFP of cadaveric feet. On MRI, higher signal alterations were mainly present in the ATTFP in ankles with radiological presence of joint pathology, in particular in more severe cases (p=0.01).

ABSTRACT 2 Biomechanics and diagnosis of midfoot injuries The Belgian Association of Orthopaedics and Traumatology Annual Congress Clockaerts, S May 2018, Brussels, Belgium Er is geen abstract beschikbaar.


ABSTRACT 3 How to drill the tunnels in ATFL and CFL reconstruction?

in the bone of the calcaneus is lower than in talus, oversizing of the interference screw is allowed.

Japanese Society for Surgery of Foot Annual Meeting Michels F October 2018, Tokyo, Japan

External landmarks are useful for to guide tunnel direction when performing ATFL and CFL reconstruction.

CONCLUSION

INTRODUCTION/BACKGROUND Reconstruction of the anterior talofibular ligament(ATFL) and calcaneofibular ligament(CFL) may be indicated in cases of residual instability of the ankle. Currently, bone tunnels are often used for fixation of the graft. The entry of this tunnel should be at the normal anatomical insertion point. The tunnel can be oriented in different directions with an impact on surrounded bone, fixation strength, risk of damage of joint cartilage and soft tissue structures.

ABSTRACT 4 The lateral malleolus as a landmark to find the calcaneofibular ligament footprint on the calcaneus 18th ESSKA Congress Michels F, Clockaerts S, Baekelandt L, et al. May 2018, Glasgow, Scotland

INTRODUCTION/BACKGROUND OBJECTIVE The purpose is to give an overview of the different tunnel positions for fixation of the ATFL and CFL and the relation with external anatomical landmarks.

The advent of new endoscopic and percutaneous techniques to treat ankle instability increases the need for anatomical landmarks. When performing an anatomical reconstruction of the calcaneofibular ligament(CFL), the footprint on the calcaneus is difficult to indicate.

MATERIALS/METHODS Different directions of 3 tunnels were assessed in talus, fibula and calcaneus. Dissection of cadaveric specimens was performed to assess the risk of soft tissue damage. CT-scans were used to generate 3D bone models to assess the surrounding bone and the distance to joint surface. A tunnel surrounded by a large amount of bone, allows a better fixation strength.

OBJECTIVE The purpose of this study is to evaluate a method to locate the footprint of the CFL related to the palpable landmarks of the lateral malleolus.

MATERIALS/METHODS

Talar tunnel A blind ended tunnel was found to be safest when directed to the posterior point of the medial malleolus. The tunnel should be limited to a diameter of 5 mm and a depth of 20 mm. Alternatively, if a transosseous tunnel is preferred, the tunnel should be directed to the most distal part of the medial malleolus.

1. 10 lower leg cadaveric specimens 2. K wire is drilled at the intersection of 2 lines: 2.1. A line parallel with the fibula passing through the posterior point of the lateral malleolus was determined. 2.2. A second line with an angle of 45 degrees to the first one and passing through the fibular obscure tubercle was marked. A second wire was drilled blinded to the earlier marked landmarks and pin to assess the interobserver reliability. 3. Dissection and measurements

Fibular tunnel As the insertion sites of the ATFL and CFL on the fibula are confluent, it is recommended to create only one common tunnel for fixation of both ligaments. An oblique tunnel increases tunnel length and has less risk to damage the cribriform bone surface in this area.

The mean distance to the centre of the CFL footprint was 1.7 mm (0-11mm). The mean distance between both pins was 3.17 mm. The mean distance to the sural nerve was 1.7 mm. The mean distance to the peroneal tendons was 7.1 mm.

Calcaneal tunnel The calcaneal tunnel should be directed towards the anterior medial edge of the tuber calcanei to avoid damage to the neurovascular bundle. As bone mineral density

The described guidelines are useful to locate the CFL footprint when reconstructing the CFL. In addition, relative positions to local landmarks may be more adapted to the

RESULTS

RESULTS

CONCLUSION

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variation in foot size in patients. The close position of the CFL footprint to the sural nerve and the peroneal tendons increases the risk of damage when using percutaneous techniques. A small percutaneous placed needle at the estimated footprint can be very helpful during endoscopic and even open surgical techniques.

ABSTRACT 5 Midfoot Osteoarthritis, Diagnosis and conservative treatment Orthopaedica Belgica Michels, F May 2018, Brussels, Belgium

INTRODUCTION/BACKGROUND Midfoot osteoarthritis is a common problem in a population of people older 50 with a prevalence of 10%. The most important causes are trauma, idiopathic and inflammatory diseases. The second tarsometatarsal, followed by the talonavicular and the first tarsometatarsal are the most affected joints. The most important diagnostic tools are history taking and physical examination especially when surgical treatment is not yet considered. The most common complaints are chronic midfoot pain, difficulty in walking, localized swelling. Symptoms may be aggravated with activities that require heel rise, such as climbing stairs or walking uphill. During physical examination we often seen localized swelling and bone prominences. Those can cause difficulties in shoe wear. We pay attention to the arch of the foot, which can be fallen, or a deviation of the forefoot. Palpation and mobilisation can be painful. We perform passive pronation and supination. In addition we can squeeze the forefoot to provoke the complaints. Palpation of the TMT joints mostly gives the same pain. Different imaging tools can be used. As usual we use weightbearing radiographs in 3 directions. The radiographic signs to determine osteoarthritis are joint space narrowing, osteophyte formation, sclerosis and cyst formation. Radiographs also allow to visualize other deformities for example a disturbed arch or a lateral deviation of the forefoot. The other technical tools are valuable when surgery is considered. It is important to identify all the symptomatic joints when planning an arthrodesis. MRI can visualise bone edema, cartilage lesions and subchondral cysts. Very often the abnormalities are present on both sides of the joint giving the appearance of kissing lesions. CT is also valuable to assess the involved joints. We try to obtain them with the

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ankle in neutral position. Which is not the case in this image. Neutral position allows a better view in the axial planes. The SPECT-CT combines the images of a bonescan with those of a CT-scan and combines the information about the anatomy with the physiology. It tells us on the one hand which joints are damaged and on the other hand which joints cause inflammation and pain. This diagnostic tool is very valuable when planning surgery. The most important risk factors are female gender, overweight, a short achilles tendon, a long second metatarsal, a hypermobile medial column and an elevated first metatarsal. The conservative treatment possibilities are limited. Physical therapy offers a variety of treatment options for foot OA: specific exercises, achilles tendon stretch, joint mobilization, massage, electrical stimulation, laser and ultrasound. All these treatments are widely used, but research supporting their efficacy and effectiveness is non-existent. Antiflogistics have been shown useful in pain reduction during some weeks. In other joints there is prove that they are more effective at reducing pain compared to placebo. 2 studies have been published about the use of corticosteroid injections. A good pain relief was found in patients with midfoot osteoarthritis up to 3 months after infiltration. Shoe inserts or insoles remain the gold standard and are supported by level 3 and level 4 studies. They have some biomechanical effects and reduce loading of the midfoot. In addition, they improve pain and increase footwear comfort. Full length semi rigid or rigid customised insoles demonstrated to provide the best results.


CENTRUM

PLASTISCHE CHIRURGIE

ARTIKELS ABSTRACT 1 Thread-lift sutures: still in the lift? A systematic review of the literature

statement about thread-lift sutures as made by Villa et al. in 2006 in terms of efficacy or safety. All included literature in the authors' review, except two studies, demonstrated at best a very limited durability of the lifting effect. The two positive studies were sponsored by the companies that manufacture the thread-lift sutures.

GĂźlbitti HA, Colebunders B, Pirayesh A, et al. Plastic and Reconstructive Surgery, 2018, 141(3), 341-347

INTRODUCTION/BACKGROUND In 2006, Villa et al. published a review article concerning the use of thread-lift sutures and concluded that the technique was still in its infancy but had great potential to become a useful and effective procedure for nonsurgical lifting of sagged facial tissues. As 11 years have passed, the authors now performed again a systematic review to determine the real scientific current state of the art on the use of threadlift sutures.

MATERIALS/METHODS A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed database and using the Medical Subject Headings search term "Rhytidoplasty." "Rhytidoplasty" and the following entry terms were included by this Medical Subject Headings term: "facelift," "facelifts," "face Lift," "Face Lifts," "Lift," "Face," "Lifts," "Platysmotomy," "Platysmotomies," "Rhytidectomy," "Rhytidectomies," "Platysmaplasty," "and "Platysmaplasties." The Medical Subject Headings term "Rhytidoplasty" was combined with the following search terms: "Barbed suture," "Thread lift," "APTOS," "Suture suspension," "Percutaneous," and "Silhouette suture." RefWorks was used to filter duplicates. Three of the authors (H.A.G., B.C., and B.L.) performed the search independently.

RESULTS The initial search with all search terms resulted in 188 articles. After filtering the duplicates and the articles about open procedures, a total of 41 articles remained. Of these, the review articles, case reports, and letters to the editor were subsequently excluded, as were reports dealing with nonbarbed sutures, such as Vicryl and Prolene with GoreTex. This resulted in a total of 12 articles, seven additional articles since the five articles reviewed by Villa et al.

CONCLUSION The authors' review demonstrated that, within the past decade, little or no substantial evidence has been added to the peer-reviewed literature to support or sustain the promising

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CENTRUM

UROLOGIE ARTIKELS

CONCLUSION

ABSTRACT 1

ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial Ost P, Reynders D, Billiet I, et al. Journal of clinical oncology, 2018, 36(5), 446-453

ABSTRACT 2 Antitumour activity and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer previously treated with abiraterone acetate plus prednisone for ≥24 weeks in Europe

INTRODUCTION/BACKGROUND Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival.

de Bono J, Chowdhury S, Werbrouck P, et al. European Urology, 2018, 74(1), 37-45

OBJECTIVE

Enzalutamide and abiraterone acetate plus prednisone, which target the androgen receptor axis, have expanded the treatment of advanced prostate cancer. Retrospective analyses suggest some cross-resistance between these two drugs when used sequentially, but robust, prospective studies have not yet been reported.

INTRODUCTION/BACKGROUND We aimed to assess the benefit of MDT in a randomized phase II trial.

MATERIALS/METHODS In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography-computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)-free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases.

RESULTS Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed.

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OBJECTIVE To fulfil a regulatory postregistration commitment by evaluating the efficacy and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed following abiraterone acetate plus prednisone treatment.

MATERIALS/METHODS Multicentre, single-arm, open-label study, enrolled patients with progressing mCRPC after ≥24 wk of abiraterone acetate plus prednisone treatment. All patients maintained castration therapy during the trial. Prior chemotherapy was allowed but not required. Patients received enzalutamide 160mg/d orally. The primary endpoint was radiographic progression-free survival. Secondary endpoints were overall survival, prostate- specific antigen (PSA) response, and time-to-PSA progression. Safety data were also assessed. Kaplan-Meier methods were used to descriptively analyse time-toevent endpoints.

RESULTS Overall, 214 patients received enzalutamide treatment, 145 of whom were chemotherapy-naïve. Median radiographic progression-free survival was 8.1 mo (95% confidence interval: 6.1-8.3); median overall survival had not been reached. Unconfirmed PSA response rate was 27% (48 of 181). Median time-to-PSA progression was 5.7 mo (95% confidence interval: 5.6-5.8). The most common


treatment-emergent adverse events were fatigue (32%), decreased appetite (25%), asthenia (18%), back pain (17%), and arthralgia (16%). No seizures were reported.

CONCLUSION Enzalutamide showed antitumour activity in some patients with mCRPC who had previously progressed following ≥24 wk of abiraterone acetate plus prednisone treatment.

CONCLUSION Enzalutamide anti-tumor activity was maintained in patients with hormone-naïve prostate cancer at 3 years. Overall, bone mineral density, global health status and safety results were similar to those at 2 years.

PRESENTATIES / CONGRESSEN

ABSTRACT 3 Long-term Anti-tumor Activity and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 3-year, Open-label, Follow-up Results Tombal B, Borre M, Werbrouck P, et al. The Journal of Urology, 2018, 199(2), 459-464

INTRODUCTION/BACKGROUND A phase 2 study of enzalutamide monotherapy in patients with hormone-naïve prostate cancer demonstrated high prostate-specific antigen response rates at 25 weeks, 1 year and 2 years, with minimal effects on total body bone mineral density and favorable safety. This follow-up analysis evaluated enzalutamide's anti-tumor activity and safety at 3 years.

MATERIALS/METHODS Sixty-seven patients with hormone-naïve prostate cancer and non-castrate testosterone (≥230 ng/dL) received enzalutamide 160 mg/day orally until disease progression or unacceptable toxicity in a single-arm analysis. The primary end point was prostate-specific antigen response (≥80% decline from baseline).

RESULTS No patients discontinued treatment during year 3. Of 42 patients with prostate-specific antigen assessments at 3 years, 38 (90.5%; 95% confidence interval 77.4, 97.3) maintained a prostate-specific antigen response. Of 26 patients with metastases at baseline, 17 (65.4%) had complete or partial response as the best overall response over 3 years. In patients who completed the 3-year visit, minimal mean changes from baseline were observed in total body bone mineral density or bone mineral density of the femoral neck, trochanter, spine L1-L4 or forearm(range, -2.7% to -0.1%). At 3 years, total body fat increased (mean, 16.5%), total lean body mass decreased (mean, -6.5%) and global health status minimally decreased from baseline. Common adverse events were gynecomastia, fatigue, hot flush and nipple pain.

ABSTRACT 1 Implementatie van Active Surveillance voor laag risico prostaatkanker in België tussen 2010 en 2015 Elautprijs Veys R, Joniau S, Van Bruwaene S January 2018, Leuven, Belgium

INTRODUCTION/BACKGROUND Active surveillance (AS) is de voorbije jaren uitgegroeid tot dé voorkeursbehandeling voor laag risico prostaatkanker (PCa) teneinde patiënten te behoeden voor potentiële schade en complicaties die met radicale behandeling gepaard gaan. Volgens de literatuurgegevens stijgt de toepassing van AS wereldwijd, hoewel er een hoge variabiliteit bestaat tussen verschillende landen onderling. In de huidige studie willen we de implementatie van AS in België tussen 2010 en 2015 nagaan.

MATERIALS/METHODS Als AS frequenter toegepast wordt, dan zouden het aantal AS-kandidaten die heelkunde ondergaan (vb. robot assisted laparoscopic prostatectomy (RALP)) en het aantal laag risico PCa op definitief pathologisch onderzoek (APO) logischerwijze moeten dalen over de jaren. Daarom exploreerden we de prospectief aangelegde database van alle opeenvolgende patiënten die een RALP kregen in België tussen 2000-2015 (Be-RALP database). In deze cohorte werden AS kandidaten gedefinieerd volgens de PRIAS criteria (klinisch T1-T2, PSA ≤10 ng/mL, Gleason score 6 in 20% van de biopsies) en werd laag risico PCa gedefinieerd als Gleason 6 op definitief (APO). De 6 ziekenhuizen met het grootste aantal RALP’s in de Be-RALP database tussen 2010-2015 werden verder geanalyseerd om variabiliteit in implementatie van AS tussen de verschillende ziekenhuizen verder te investigeren. Om onze resultaten te correleren met de evolutie in prostaatkankerincidentie in België werd de nationale prostaatkankerdatabase van het Belgian Cancer Registry (BCR database) gebruikt.

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RESULTS Van de 7760 kandidaten die in aanmerking kwamen voor het huidige studie-opzet, hebben 1396 AS kandidaten (18%) een RALP gekregen tussen 2010-2015. Er is een dalende trend over de 5 jaar in zowel absolute als relatieve aantal AS kandidaten die een RALP krijgen; van 270 patienten (23%) in 2010 tot 145 patienten (10%) in 2015. Bovendien daalde het aantal laag risico PCa op definitief APO in de Be-RALP database van 62% tot 39% (OR 0.81(0.780.86)), terwijl de diagnose van laag risico PCa, resulterend uit de BCR database, lichtjes steeg van 32% tot 35% (OR 1.10 (1.09-1.21)). Hoewel de fractie van AS kandidaten die een RALP ondergingen globaal daalde in België, bemerken we verschillen binnen de ziekenhuizen onderling met een fractie variërend van 9%-35% in 2010 en een variatie tussen 6%-18% in 2015.

CONCLUSION Binnen de chirurgische RALP cohorte stellen we tussen 2010 en 2015 een significante daling vast van zowel de proportie AS kandidaten als van de proportie laag risico PCa op definitief APO, terwijl de incidentie van laag risico PCa in België globaal toeneemt. Dit bevestigt, op indirecte wijze, een toenemende implementatie van AS in België. Hoewel deze trend zichtbaar is in het merendeel van de ziekenhuizen, bestaat er toch nog een grote variabiliteit tussen de verschillende ziekenhuizen onderling.

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NOTITIES

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NOTITIES

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AZ Groeninge is internationaal erkend door jci voor veilige zorg en kwaliteit. www.azgroeninge.be/kwaliteit


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