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Background and Aim: This study aims to evaluate the effect of time to Crohn's disease (CD) diagnosis on perianal fistula (PAF) outcomes in patients with a fistula as first manifesting sign., Methods: In this multicenter, retrospective study, CD patients with a PAF preceding CD diagnosis between November 2015 and June 2022 were included. The primary outcome parameter was the time to CD diagnosis and its correlation with long-term outcomes., Results: In total, 126 patients with a PAF prior to CD diagnosis were identified. Median time to CD diagnosis was 15.0 months (IQR 3.8-47.3). A total of 49 patients (38.9%) had a clinically closed fistula of which 21 patients (42.9%) achieved radiological healing. 25 patients (19.8%) underwent defunctioning, of which 9 patients (36.0%) needed proctectomy. Median time to CD diagnosis was shortest in patients with radiological healing (4.0 months, IQR 2.0-16.5) or clinical closure without radiological healing (11.0 months, IQR 3.0-47.8). In patients without fistula closure (n=51), median time to CD diagnosis was significantly longer compared to patients with fistula closure, 18.0 months vs 8.0 months (p=0.031). In patients who needed defunctioning, median time to diagnosis was more than twice as long compared to patients without defunctioning, 30.0 months vs 12.0 months (p=0.054)., Conclusion: A prolonged time to CD diagnosis in patients with a PAF as a manifesting sign is associated with worse long-term outcomes. Patients in whom radiological healing could be achieved had the shortest time to CD diagnosis, emphasizing the relevance of increased clinical awareness of underlying CD in fistula patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Retrospective research suggests that excision of the affected mesentery can improve outcomes after an ileocoecal resection in Crohn's disease. However, prospective data from randomised controlled trials are scarce. We aimed to compare rates of postoperative recurrence in patients with Crohn's disease who underwent extended mesenteric resection., Methods: This international, randomised controlled trial was done in six hospitals and tertiary care centres in the Netherlands and Italy. Eligible patients were aged 16 years or older and had Crohn's disease that was previously confirmed by endoscopy in the terminal ileum or ileocolic region (L1 or L3 disease), with an imaging update in the past 3 months (ultrasound, MRI, or CT enterography). Eligible patients were scheduled to undergo primary ileocolic resection with ileocolic anastomosis. Enrolled patients were assigned by use of simple random allocation (1:1) to either extended mesenteric resection (intervention) or conventional mesenteric sparing resection (control). The primary endpoint was endoscopic recurrence 6 months after surgery. Analyses were done in all patients with primary endpoint data, excluding those who had no anastomosis, a postoperative diagnosis other than Crohn's disease, or withdrew consent. This trial was registered with ClinicalTrials.gov, NCT04538638., Findings: Between Feb 19, 2020, and April 24, 2023, we assessed 217 patients for eligibility. 78 patients were excluded due to failure to meet the inclusion criteria or refusal to participate. 139 patients were enrolled and randomly assigned to either extended mesenteric resection (n=71) or mesenteric sparing resection (n=68). All 139 patients underwent surgery. Six patients were excluded after random assignment due to withdrawal of consent (n=2), postoperative diagnosis other than Crohn's disease (n=2) and no anastomosis performed (in case of a stoma; n=2). Two patients were lost to follow-up, and two more patients deviated from the protocol by undergoing investigations other than endoscopy 6 months after. 133 patients were included in the baseline analysis (67 in the extended resection group and 66 in the sparing resection group) of whom 57 (43%) were male. Baseline characteristics were similar between the groups, and median patient age was 36 years (IQR 25-54). 131 patients were analysed for the primary outcome. There was no difference between groups in the rate of endoscopic recurrence at 6 months after surgery (28 [42%] of 66 patients in the extended mesenteric resection group vs 28 [43%] of 65 patients in the mesenteric sparing resection group, relative risk 0·985, 95% CI 0·663-1·464; p=1·0). Five (8%) of 66 patients in the extended mesenteric resection group had anastomotic leakage within the 30 days after surgery, as did one (2%) of 65 in the mesenteric sparing group. Postoperative complications of Clavien-Dindo grade IIIa or higher were reported in seven (11%) patients in the mesenteric resection group and five (8%) in the mesenteric sparing group., Interpretation: Extended mesenteric resection was not superior to conventional resection with regard to endoscopic Crohn's disease recurrence. These data support the guideline-recommended mesenteric sparing approach., Funding: Topconsortia voor Kennis en Innovatie-Topsector Life Sciences & Health., Competing Interests: Declaration of interests MD received speaking fees from Bristol Meyers Squibb, Takeda, and Galapagos; served in an advisory board for AbbVie, Bristol Meyers Squibb, Celltrion, Galapagos, Janssen, and Takeda; and received grant or research support from Pfizer, Bristol Meyers Squibb, Galapagos, and Janssen. AS acted as a consultant or speaker for Johnson and Johnson, Striker, and Oasis. FF received consultant fees from AbbVie and MSD and has served for speaker for Janssen and Pfizer. GRD has served as an advisor or speaker for AbbVie, Alimentiv, Amgen, Biora, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Ferring, Eli Lilly, enGene, Galapagos, Glaxo Smith Kline, Immunic, Index Pharmaceuticals, Johnson and Johnson, Landos, Lument, Mitsubishi Pharma, Polpharma, Prometheus Biosciences, Prometheus Laboratories, Procise Diagnostics, Protagonist, Sandoz, Setpoint, Takeda, Tillotts, and Ventyx. SD reports consultancy fees from AbbVie, Alimentiv, Allergan, Amgen, Applied Molecular Transport, AstraZeneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Morphic, MSD, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, Teladoc Health, TiGenix, UCB, Vial, and Vifor and reports lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals, Gilead, Janssen, Mylan, Pfizer, and Takeda. CJB reports an unrestricted research grant from Boehringer Ingelheim, and Roche; received speaker's fees from Takeda, AbbVie, Janssen, MSD, and Tillots Pharma; and is part of the advisory board of Takeda. VB declares to have received support for attending a conference from THD. WAB has received research funding from VIFOR and is a consultant for Braun. The other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background : Incidences of perianal fistulas (PAFs) as a first manifestation of Crohn's disease (CD) vary widely in the literature. Aim: To analyse the percentage of patients with a PAF preceding CD diagnosis and assess the time to diagnosis. Methods : A systematic literature search was conducted. Studies reporting on patients with a PAF preceding CD diagnosis were identified. Primary outcomes were the (weighted) percentage of patients with CD with a PAF preceding CD and their time to CD diagnosis. Secondary outcomes were the (weighted) percentage of patients with CD with a PAF preceding CD diagnosis in predefined patient subgroups, including (1) sex (men vs. women), (2) ethnicity (Asian vs. non-Asian), and (3) age (paediatric (0-18 y) and patients with elderly onset CD (>60 y) vs. adult patients (18-60 y)). Results : Seventeen studies were included (34,030 patients with CD). In the overall CD population, a PAF preceded CD in 8.6% [95%CI; 5.72; 12.71] with a weighted mean time to CD diagnosis of 45.9 (31.3) months. No studies reported details on sex differences in patients with a PAF as a manifesting sign of CD. In Asian populations, a PAF preceded CD in 17.66% [95%CI; 11.45; 26.25], which was significantly higher when compared with non-Asians (4.99% [95%CI; 3.75; 6.60], OR:3.99, p < 0.0001). In adolescents, an incidence of 9.17% [95%CI; 5.92; 13.93] was found with significantly lower incidences in paediatric patients (6.38% [95%CI; 1.84; 19.85], OR:0.53, p < 0.0001), and elderly-onset patients (3.77% [95%CI; 1.68; 8.25], OR:0.44, p = 0.0035). Conclusions : This systematic review shows that in the literature, almost 10% of patients present with a PAF as a first manifestation of CD, with a mean time to diagnosis of almost four years. These results emphasise that increased clinical awareness is needed.

Background: Data on effects of intra-gastric balloon (IGB) on metabolic dysfunction-associated steatotic liver disease (MASLD) are scarce, in part with contradictory results, and mainly obtained in tertiary care patients with diabetes and other comorbidities. We here explore effects of IGB in patients with MASLD referred to a first-line obesity clinic., Methods: In this prospective cohort study, patients with at least significant fibrosis (≥ F2) and/or severe steatosis (S3) according to screening transient elastography (FibroScan®) were offered a second FibroScan® after 6 months lifestyle modification with or without IGB (based on patient preference)., Results: 50 of 100 consecutively screened patients (generally non-diabetic) qualified for repeated evaluation and 29 (58%) of those had a second FibroScan®. At baseline, at least significant fibrosis was present in 28% and severe steatosis in 91%. IGB was placed in 19 patients (59%), whereas 10 patients (41%) preferred only lifestyle modification (no differences in baseline characteristics between both groups). After 6 months, liver stiffness decreased markedly in the IGB group (median: from 6.0 to 4.9 kPa, p = 0.005), but not in the lifestyle modification only group (median: from 5.5 to 6.9 kPa, p = 0.477). Steatosis improved in both groups, (controlled attenuation parameter values; IGB, mean ± SD: from 328 ± 34 to 272 ± 62 dB/m, p = 0.006: lifestyle modification only, mean ± SD: from 344 ± 33 to 305 ± 43 dB/m: p = 0.006)., Conclusion: Both steatosis and fibrosis improve markedly in overweight/obese patients with MASLD after 6 months IGB combined with lifestyle modification. Our results warrant further research into long-term effect of IGB in these patients., (© 2023. The Author(s).)

Background and Aims: Adequate endoscopic scoring in Crohn's disease [CD] is crucial, as it dictates the need for initiating postoperative medical therapy and is utilized as an outcome parameter in clinical trials. Here we aimed to observe anastomotic wound healing in relation to endoscopic scoring of both inverted and everted stapled lines in side-to-side anastomoses., Methods: Two prospective patient cohorts were included: ileocolic resection [ICR] for CD, and right-sided colon resection for colorectal cancer [CRC]. Videos taken during colonoscopy 6 months postoperatively were evaluated. The Simplified Endoscopic Activity Score for Crohn's Disease and modified Rutgeerts score were determined. The primary outcome was the presence of ulcerations in CD patients on both the inverted and the everted stapled lines. Secondary outcomes were the presence of anastomotic ulcerations in CRC patients and the number of cases having ulcerations exclusively at the inverted stapled line., Results: Of the 82 patients included in the CD cohort, ulcerations were present in 63/82 [76.8%] at the inverted- vs 1/71 [1.4%] at the everted stapled line. Likewise in the CRC cohort, ulcerations were present in 4/6 [67.7%] at the inverted vs 0/6 [0%] at the everted stapled line. In total, 27% of the 63 patients in the CD cohort had ulcerations exclusively on the inverted stapled line., Conclusion: Inverted stapled lines heal with ulcerations, whereas everted stapled lines heal without any ulcerations, in both CD and non-CD patients. The abnormalities at the inverted stapled line might interfere with endoscopic scoring of recurrence, with potentially an impact on patients' quality of life and on healthcare costs if postoperative treatment is initiated incorrectly., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: T1 colorectal cancer (CRC) without histological high-risk factors for lymph node metastasis (LNM) can potentially be cured by endoscopic resection, which is associated with significantly lower morbidity, mortality and costs compared to radical surgery. An important prerequisite for endoscopic resection as definite treatment is the histological confirmation of tumour-free resection margins. Incomplete resection with involved (R1) or indeterminate (Rx) margins is considered a strong risk factor for residual disease and local recurrence. Therefore, international guidelines recommend additional surgery in case of R1/Rx resection, even in absence of high-risk factors for LNM. Endoscopic full-thickness resection (eFTR) is a relatively new technique that allows transmural resection of colorectal lesions. Local scar excision after prior R1/Rx resection of low-risk T1 CRC could offer an attractive minimal invasive strategy to achieve confirmation about radicality of the previous resection or a second attempt for radical resection of residual luminal cancer. However, oncologic safety has not been established and long-term data are lacking. Besides, surveillance varies widely and requires standardization., Methods/design: In this nationwide, multicenter, prospective cohort study we aim to assess feasibility and oncological safety of completion eFTR following incomplete resection of low-risk T1 CRC. The primary endpoint is to assess the 2 and 5 year luminal local tumor recurrence rate. Secondary study endpoints are to assess feasibility, percentage of curative eFTR-resections, presence of scar tissue and/or complete scar excision at histopathology, safety of eFTR compared to surgery, 2 and 5 year nodal and/or distant tumor recurrence rate and 5-year disease-specific and overall-survival rate., Discussion: Since the implementation of CRC screening programs, the diagnostic rate of T1 CRC is steadily increasing. A significant proportion is not recognized as cancer before endoscopic resection and is therefore resected through conventional techniques primarily reserved for benign polyps. As such, precise histological assessment is often hampered due to cauterization and fragmentation and frequently leads to treatment dilemmas. This first prospective trial will potentially demonstrate the effectiveness and oncological safety of completion eFTR for patients who have undergone a previous incomplete T1 CRC resection. Hereby, substantial surgical overtreatment may be avoided, leading to treatment optimization and organ preservation. Trial registration Nederlands Trial Register, NL 7879, 16 July 2019 ( https://trialregister.nl/trial/7879 )., (© 2022. The Author(s).)

Background: Guidelines on Crohn's perianal fistulas recommend anti-tumour necrosis factor (TNF) treatment and suggest considering surgical closure for patients with surgically amenable disease. However, long-term outcomes following these two strategies have not been directly compared. The aim of this study was to assess radiological healing in patients who received short-term anti-TNF treatment and surgical closure compared with those who received anti-TNF treatment alone., Methods: The PISA-II trial was a multicentre, patient preference study done in nine hospitals in the Netherlands and one hospital in Italy. Adult patients with Crohn's disease and an active high perianal fistula with a single internal opening were eligible for inclusion. After counselling, patients with no treatment preference were randomly assigned (1:1) using random block randomisation (block sizes of six without statification), to 4-month anti-TNF therapy and surgical closure or anti-TNF therapy for 1 year, after seton insertion. Patients with a treatment preference received their preferred therapy. The primary outcome was radiological healing assessed by MRI at 18 months, defined as a complete fibrotic tract or a MAGNIFI-CD (Magnetic Resonance Index for Fistula Imaging in Crohn's Disease) score of 0, assessed according to the intention-to-treat principle. Secondary outcomes included clinical closure, number of patients undergoing surgical reintervention and number of reinterventions, recurrences, and impact on quality of life measured by the Perianal Disease Activity Index (PDAI). Analyses were performed on an intention-to-treat basis and additionally an as-treated analysis for radiological healing and clinical closure. This study was registered at the Dutch Trial Registry, NL7625, and with EudraCT, 2018-002064-15, and is closed to accrual due to completion., Findings: Between Sept 14, 2013, and Dec 7, 2019, 94 patients were enrolled onto the trial, of whom 32 (34%) were randomly assigned and 62 (66%) chose a specific treatment. 38 (40%) patients were assigned to the surgical closure group and 56 (60%) patients to the anti-TNF group. At 18 months, radiological healing was significantly more common in the surgical closure group (12 [32%] patients) than in the anti-TNF group (five [9%] patients; p=0·005). By contrast, clinical closure was not significantly different between the two treatment groups (26 [68%] patients in the surgical closure group vs 29 [52%] patients in the anti-TNF group; p=0·076). Significantly fewer patients required a reintervention in the surgical closure group than in the anti-TNF therapy group (five [13%] patients in the surgical closure group, median one reintervention [IQR one to three] vs 24 [43%] patients in the anti-TNF group, median two reinterventions [one to two]; p=0·005). Among patients who reached clinical closure during follow-up, four (14%) of 29 in the surgical closure group and five (16%) of 31 in the anti-TNF therapy group had a recurrence, which occurred only in patients without radiological healing. PDAI was significantly lower in the surgical closure group than in the anti-TNF group after 18 months (p=0·031). Adverse events and serious adverse events were similar in both treatment groups and mostly entailed reinterventions. Ten (11%) patients had side-effects associated with anti-TNF treatment. Two serious adverse events unrelated to study treatment occurred (appendicitis and myocardial infarction). One patient died from a tongue base carcinoma, unrelated to study treatment., Interpretation: Short-term anti-TNF treatment combined with surgical closure induces long-term MRI healing more frequently than anti-TNF therapy in patients with Crohn's perianal fistulas. These data suggest that patients with Crohn's perianal fistula amenable for surgical closure should be counselled for this therapeutic approach., Funding: Netherlands Organisation for Health Research and Development and Broad Medical Research Program., Competing Interests: Declaration of interests GRD'H reports grants from Arena Pharmaceuticals, Bristol Myers Squibb, Celltrion, Eli Lilly, Galapagos, Pfizer, Johnson & Johnson, Procise Diagnostics, Prometheus laboratories, Prometheus Biosciences, and Progenity; consulting fees from AbbVie, Agomab, AstraZeneca, AM Pharma, AMT, Arena Pharmaceuticals, Bristol Myers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Exo Biologics, Galapagos, Index Pharmaceuticals, Kaleido, Roche, Gilead, GlaxoSmithKline, Gossamerbio, Pfizer, Immunic, Johnson & Johnson, Origo, Polpharma, Procise Diagnostics, Prometheus Laboratories, Prometheus Biosciences, Progenity, Protagonist; and speaker's honoraria from AbbVie, Merck Sharp & Dohme, Tillotts, Janssen, Takeda, Pfizer, and Bristol Myers Squibb. GRD'H participated on a Data Safety Monitoring Board or Advisory Board for Galapagos, Astrazeneca, and AbbVie. KBG reports grants from Pfizer, Galapagos, and Celltrion; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, ImmunicTherapeutics, Janssen Pharmaceuticals, Novartis, Pfizer, Samsung Bioepis, and Takeda; consulting fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Novartis, Pfizer, Samsung Bioepis, and Takeda; and speaker's honoraria from Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer, Samsung Bioepis, Takeda, and Tillotts. SD reports consulting fees from AbbVie, Alimentiv, Allergan, Amgen, AstraZaneca, Athos Therapeutics, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Dr Falk Pharma, Eli Lilly, Enthera, Ferring Pharmaceuticals, Gilead, Hospira, Inotrem, Janssen, Johnson & Johnson, Mundipharma, Mylan, Pfizer, Roche, Sandoz, Sublimity Therapeutics, Takeda, TiGenix, UCB, and Vifor. WAB has served as speaker for Takeda, Johnson & Johnson, and Braun; and reports research grants from Braun and Vifor. CJB has an unrestricted grant from Boehringer Ingelheim and Roche; reports consultancy fees or speaker's honoraria from AbbVie, Merck Sharp & Dohme, Tillotts, Janssen, and Takeda. All other authors declared no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aim: The aim of this study was to investigate, by comparing clinical and histological outcomes, whether laparoscopic (hybrid) wedge resection (LWR) could be a less invasive and safe alternative to laparoscopic oncological colon resection (OCR) for patients with an endoscopically unresectable, suspected benign, colon polyp., Method: All patients with an endoscopically unresectable colon polyp who were referred for surgery between 2009 and 2018 and without biopsy-proven colon cancer were identified from a prospectively maintained database. Patients with macroscopic features of malignancy during endoscopy were excluded. Clinical and histological results for patients who underwent OCR or LWR were reviewed., Results: One hundred-and-twenty-two patients were included. Ninety-seven patients underwent OCR and 25 LWR. Major complications occurred in 16.7% (n = 16) of the OCR group compared with 4.0% (n = 1) of the LWR group (p = 0.06). In the OCR group the anastomotic leakage rate was 6.3% (n = 6) and the mortality rate 3.1% (n = 3). No anastomotic leakage or deaths occurred in the LWR group. The median length of hospital stay after OCR was 5 days [interquartile range (IQR) 5-9 days)] compared with 2 days (IQR 2-4 days) after LWR (p < 0.0001). Definite pathology showed a malignancy rate of 4.2% (n = 4) in the OCR group and 4.0% (n = 1) (without high-risk features) in the LWR group., Conclusion: This study shows that LWR was associated with significantly lower complication rates and acceptable oncological risks compared with OCR. Therefore we suggest that LWR is a safe alternative treatment, next to other endoscopic options. The treatment that is most suitable for an individual patient should be discussed in a multidisciplinary meeting., (© 2021 The Authors. Colorectal Disease published by John Wiley & Sons Ltd on behalf of Association of Coloproctology of Great Britain and Ireland.)

Background and Aims: Most patients with perianal Crohn's fistula receive medical treatment with anti-tumour necrosis factor [TNF], but the results of anti-TNF treatment have not been directly compared with chronic seton drainage or surgical closure. The aim of this study was to assess if chronic seton drainage for patients with perianal Crohn's disease fistulas would result in less re-interventions, compared with anti-TNF and compared with surgical closure., Methods: This randomised trial was performed in 19 European centres. Patients with high perianal Crohn's fistulas with a single internal opening were randomly assigned to: i] chronic seton drainage for 1 year; ii] anti-TNF therapy for 1 year; and iii] surgical closure after 2 months under a short course anti-TNF. The primary outcome was the cumulative number of patients with fistula-related re-intervention[s] at 1.5 years. Patients declining randomisation due to a specific treatment preference were included in a parallel prospective PISA registry cohort., Results: Between September 14, 2013 and November 20, 2017, 44 of the 126 planned patients were randomised. The study was stopped by the data safety monitoring board because of futility. Seton treatment was associated with the highest re-intervention rate [10/15, versus 6/15 anti-TNF and 3/14 surgical closure patients, p = 0.02]. No substantial differences in perianal disease activity and quality of life between the three treatment groups were observed. Interestingly, in the PISA prospective registry, inferiority of chronic seton treatment was not observed for any outcome measure., Conclusions: The results imply that chronic seton treatment should not be recommended as the sole treatment for perianal Crohn's fistulas., (© European Crohn’s and Colitis Organisation (ECCO) 2020.)

Background and Aims: In contrast to the adverse event (AE) risk of endoscopic resection (ER) of adenomas, the intra- and postprocedural AE risks of ER of T1 colorectal cancer (CRC) are scarcely reported in the literature. It is unclear whether ER of early CRCs, which grow into the submucosal layer and sometimes show incomplete lifting, is associated with an increased AE risk. We aimed to identify the AE rate after ER of T1 CRCs and to identify the risk factors associated with these AEs., Methods: Medical records of patients with T1 CRCs diagnosed between 2000 and 2014 in 15 hospitals in the Netherlands were reviewed. Patients who underwent primary ER were selected. The primary outcome was the occurrence of endoscopy-related AEs. The secondary outcome was the identification of risk factors. Multivariate logistic regression was performed., Results: Endoscopic AEs occurred in 59 of 1069 (5.5%) patients, among which 37.3% were classified as mild, 59.3% as moderate, and 3.4% as severe. AEs were postprocedural bleeding (n = 40, 3.7%), perforation (n = 13, 1.2%), and postpolypectomy electrocoagulation syndrome (n = 6, 0.6%). No fatal AEs were observed. Independent predictors for AEs were age >70 years (odds ratio, 2.11; 95% confidence interval, 1.12-3.96) and tumor size >20 mm (odds ratio, 2.22; 95% confidence interval, 1.05-4.69)., Conclusions: In this large multicenter retrospective cohort study, AE rates of ER of T1 CRC (5.5%) are comparable with reported AE rates for adenomas. Larger tumor size and age >70 years are independent predictors for AEs. This study suggests that endoscopic treatment of T1 CRCs is not associated with an increased periprocedural AE risk., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Identifying a hereditary colorectal cancer (CRC) syndrome or familial CRC (FCC) in a CRC patient may enable the patient and relatives to enroll in surveillance protocols. As these individuals are insufficiently recognized, we evaluated an online family history tool, consisting of a patient-administered family history questionnaire and an automated genetic referral recommendation, to facilitate the identification of patients with hereditary CRC or FCC. Between 2015 and 2016, all newly diagnosed CRC patients in five Dutch outpatient clinics, were included in a trial with a stepped-wedge design, when first visiting the clinic. Each hospital continued standard procedures for identifying patients at risk (control strategy) and then, after a predetermined period, switched to offering the family history tool to included patients (intervention strategy). After considering the tool-based recommendation, the health care provider could decide on and arrange the referral. Primary outcome was the relative number of CRC patients who received screening or surveillance recommendations for themselves or relatives because of hereditary CRC or FCC, provided by genetic counseling. The intervention effect was evaluated using a logit-linear model. With the tool, 46/489 (9.4%) patients received a screening or surveillance recommendation, compared to 35/292 (12.0%) in the control group. In the intention-to-treat-analysis, accounting for time trends and hospital effects, this difference was not statistically significant (p = 0.58). A family history tool does not necessarily assist in increasing the number of CRC patients and relatives enrolled in screening or surveillance recommendations for hereditary CRC or FCC. Other interventions should be considered.

Objective: Colorectal cancer screening programmes are implemented worldwide; many are based on faecal immunochemical testing (FIT). The aim of this study was to evaluate two frequently used FITs on participation, usability, positivity rate and diagnostic yield in population-based FIT screening., Design: Comparison of two FITs was performed in a fourth round population-based FIT-screening cohort. Randomly selected individuals aged 50-74 were invited for FIT screening and were randomly allocated to receive an OC -Sensor (Eiken, Japan) or faecal occult blood (FOB)-Gold (Sentinel, Italy) test (March-December 2014). A cut-off of 10 µg haemoglobin (Hb)/g faeces (ie, 50 ng Hb/mL buffer for OC-Sensor and 59 ng Hb for FOB-Gold) was used for both FITs., Results: In total, 19 291 eligible invitees were included (median age 61, IQR 57-67; 48% males): 9669 invitees received OC-Sensor and 9622 FOB-Gold; both tests were returned by 63% of invitees (p=0.96). Tests were non-analysable in 0.7% of participants using OC-Sensor vs 2.0% using FOB-Gold (p<0.001). Positivity rate was 7.9% for OC-Sensor, and 6.5% for FOB-Gold (p=0.002). There was no significant difference in diagnostic yield of advanced neoplasia (1.4% for OC-Sensor vs 1.2% for FOB-Gold; p=0.15) or positive predictive value (PPV; 31% vs 32%; p=0.80). When comparing both tests at the same positivity rate instead of cut-off, they yielded similar PPV and detection rates., Conclusions: The OC-Sensor and FOB-Gold were equally acceptable to a screening population. However, FOB-Gold was prone to more non-analysable tests. Comparison between FIT brands is usually done at the same Hb stool concentration. Our findings imply that for a fair comparison on diagnostic yield between FIT's positivity rate rather than Hb concentration should be used., Trial Registration Number: NTR5385; Results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: In January 2014, a national bowel cancer screening program started in the Netherlands. The program is being implemented in phases until 2019. Due to this program, an increase in patients referred for a colorectal resection for benign, but endoscopically unresectable polyps, is expected. So far, most resections are performed according to oncological principles despite no pre-operative histological diagnosis of malignancy. The aim of this study was to analyze the increase in referred patients during the first year of the screening program and to compare pathological results and clinical outcome of resections of patients undergoing resection for benign polyps before and after implementation of screening., Methods: Patients referred for colorectal resection without biopsy-proven cancer between January 2009 and January December 2014 were identified from a prospectively maintained database. Patients with endoscopically macroscopic features of carcinoma were excluded., Results: Seventy-six patients were included. Forty-seven patients (61.8%) were operated on in the 5 years prior to implementation of the screening program, and 29 patients (38.2%) were operated during the first year of implementation of the screening program. The overall malignancy rate before the introduction of the program was 14.1 and 6.6% after it had started (p = .469). All resections were performed laparoscopically; the conversion rate was 3.9% (n = 3). The overall mortality rate was 2.7% (n = 2), major complications (Clavien-Dindo > 3b) occurred in 11.8% (n = 9) of patients. The anastomotic leakage rate was 3.9% (n = 3)., Conclusions: The number of patients referred for benign polyps tripled after introduction of the screening program. With an overall major morbidity and mortality rate of 11.8%, it seems valid to discuss whether an endoscopic excision with advanced techniques with or without laparoscopic assistance would be preferable in this patient group, accepting a 6.6% reoperation rate for additional oncological resection with lymph node sampling in patients in whom a malignancy is found on histological analysis of the complete polyp.

Background: Reported epidemiology and phenotype distributions vary widely and disease burden of inflammatory bowel disease (IBD) is poorly described. Our aim was to establish these features in a population-based cohort covering 319 976 inhabitants. Furthermore, differences between tertiary referral and peripheral hospital patients were quantified., Methods: IBD patients in the adherence area of three peripheral hospitals (2004-2012) were included. Medical and surgical treatment data were obtained. Quality of life and disease activity were evaluated. An outpatient cohort from a tertiary referral centre was accrued., Results: A total of 1461 patients were included: 761 (52.1%) with ulcerative colitis (UC), 579 (39.5%) with Crohn's disease (CD) and 121 (8.3%) with IBD-unspecified. Point prevalence of IBD was 432.1 per 100 000 inhabitants in 2010, which increased significantly over time, P-value of less than 0.0001. The mean annual incidence was 17.2 for UC, 10.5 for CD and 2.2 for IBD-unspecified. Tertiary referral Crohn's patients used thiopurines and biological therapy and underwent surgery significantly more often than patients in peripheral hospitals (P<0.0001). Disease activity correlated negatively with quality of life (P<0.0001) in UC and CD., Conclusion: The prevalence of IBD is still increasing. Burden of disease was significantly more severe, mainly in Crohn's patients, in the referral centre, highlighting the importance of population-based studies to accurately describe phenotype distribution and disease burden.

Background and Study Aims: Fecal immunochemical tests (FIT) are used to detect blood in feces, which might indicate the presence of colorectal neoplasia. The aim of this study was to investigate whether FIT results vary depending on the characteristics of colonic lesions., Patients and Methods: This was a retrospective analysis of lesions detected in a cohort of asymptomatic individuals (aged 50 - 75 years) who were invited to participate in a FIT-based screening pilot in The Netherlands. The mean FIT result was compared across subgroups of individuals defined by histopathology of the most advanced lesion detected. In addition, the results were compared with data from a primary colonoscopy screening trial, in which participants also completed a FIT., Results: In three rounds of FIT-based screening, a total of 877 FIT-positive individuals underwent colonoscopy. Higher mean FIT results (hemoglobin [Hb]/g feces) were observed in individuals with carcinomas (199 μg Hb/g) and advanced adenomas (87 μg Hb/g) compared with participants with nonadvanced adenomas (50 μg Hb/g) or those with serrated lesions (46 μg Hb/g) (P < 0.001). In the primary colonoscopy trial, 1256 participants completed a FIT test and underwent colonoscopy. The number of participants with nonadvanced adenomas as the most advanced lesion was comparable between this group and the FIT-based screening group (20 % vs. 22 %)., Conclusion: In FIT-based screening, the mean FIT results varied depending on the characteristics of the most advanced colonic lesion. The proportion of participants with a nonadvanced adenoma as the most advanced lesion was similar in the FIT-based screening group and in the primary colonoscopy screening group, suggesting that these lesions are coincidental findings rather than FIT-detected findings., Clinical Trial Registration: www.trialregister.nl number NTR2755., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Specific genes, such as BCAT1 and IKZF1, are methylated with high frequency in colorectal cancer (CRC) tissue compared to normal colon tissue specimens. Such DNA may leak into blood and be present as cell-free circulating DNA. We have evaluated the accuracy of a novel blood test for these two markers across the spectrum of benign and neoplastic conditions encountered in the colon and rectum., Methods: Circulating DNA was extracted from plasma obtained from volunteers scheduled for colonoscopy for any reason, or for colonic surgery, at Australian and Dutch hospitals. The extracted DNA was bisulphite converted and analysed by methylation specific real-time quantitative PCR (qPCR). A specimen was deemed positive if one or more qPCR replicates were positive for either methylated BCAT1 or IKZF1 DNA. Sensitivity and specificity for CRC were estimated as the primary outcome measures., Results: Plasma samples were collected from 2105 enrolled volunteers (mean age 62 years, 54 % male), including 26 additional samples taken after surgical removal of cancers. The two-marker blood test was run successfully on 2127 samples. The test identified 85 of 129 CRC cases (sensitivity of 66 %, 95 % CI: 57-74). For CRC stages I-IV, respective positivity rates were 38 % (95 % CI: 21-58), 69 % (95 % CI: 53-82), 73 % (95 % CI: 56-85) and 94 % (95 % CI: 70-100). A positive trend was observed between positivity rate and degree of invasiveness. The colonic location of cancer did not influence assay positivity rates. Gender, age, smoking and family history were not significant predictors of marker positivity. Twelve methylation-positive cancer cases with paired pre- and post-surgery plasma showed reduction in methylation signal after surgery, with complete disappearance of signal in 10 subjects. Sensitivity for advanced adenoma (n = 338) was 6 % (95 % CI: 4-9). Specificity was 94 % (95 % CI: 92-95) in all 838 non-neoplastic pathology cases and 95 % (95 % CI: 92-97) in those with no colonic pathology detected (n = 450)., Conclusions: The sensitivity for cancer of this two-marker blood test justifies prospective evaluation in a true screening population relative to a proven screening test. Given the high rate of marker disappearance after cancer resection, this blood test might also be useful to monitor tumour recurrence., Trial Registration: ACTRN12611000318987 .

Background: The effectiveness of colorectal cancer screening programs based on the fecal immunochemical test (FIT) is influenced by program adherence during consecutive screening rounds. We aimed to evaluate the participation rate, yield, and interval cancers in a third round of biennial CRC screening using FIT and to compare those with the first and the second screening round., Methods: A total of 3566 average-risk individuals aged 50-75 years were invited to participate in a third round of biennial FIT-based CRC screening. All FIT positives were recommended to undergo colonoscopy. We merged our data with the national cancer registry in the Netherlands to identify all non-screen-detected cancers in our cohort., Results: Of the invitees, 2142 (60%) returned the FIT in this third screening round, compared to 56% in the second round and 57% in the first round. Overall, 153 of the third-round participants (7.1%) had a positive FIT result, versus 7.9% in the second round and 8.1% in the first round (P=0.05). Of all FIT positives, 123 (80%) underwent colonoscopy. Within this group, 33 persons had advanced neoplasia. The predictive value of FIT positivity for advanced neoplasia was 27% (33/123), compared to 42% in the second round and 54% in the first round - a significant decline (P<0.01)., Conclusion: In an FIT-based screening program, participation rates remained stable over consecutive biennial screening rounds, while the FIT positivity rate and positive predictive value for advanced neoplasia gradually declined. Cancers in non-participants are significantly more advanced in staging than cancers in participants in the first round of screening., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Transient elastography is a noninvasive tool to quantify liver fibrosis by liver stiffness measurements (LSMs). Previous studies have extensively evaluated the accuracy of LSMs compared to liver biopsy. In this retrospective study we explore potential impact of LSMs on clinical decisions in chronic viral hepatitis., Material and Methods: LSM-based medical advice whether to start antiviral treatment and/or surveillance for hepatocellular carcinoma (HCC) and clinical follow-up after LSMs were analyzed in 349 patients., Results: In 20% of 184 hepatitis B virus (HBV)-infected patients and 38% of 165 hepatitis C virus (HCV)-infected patients, significant fibrosis (≥F2) was detected. In 5% (n = 7) of the 129 untreated HBV patients and in 12% (n = 19) of the HCV-infected patients, antiviral treatment was recommended solely based on LSMs. Advice for surveillance for HCC was in 40 patients based solely on LSMs (11% of all patients). Furthermore, 95% of 19 non-viremic HCV-patients (after spontaneous clearance or sustained viral response) could be discharged due to favorable LSMs (≤F2). Medical advice was followed by the treating physician in the majority of cases. However, in only 47% of 51 HCV-infected patients with advice to start treatment, this was followed in clinical practice., Conclusions: Transient elastography has a major impact on clinical practice, both as an indication to start or postpone antiviral treatment, to start surveillance for HCC, and to discharge HCV patients from follow-up after viral clearance and favorable LSMs. Medical advice to start antiviral treatment is followed in the large majority of HBV patients, but in only half of HCV patients.

Gastrointestinal motility and the effects on luminal contents that are brought about by it can be studied in several ways. In clinical practice, manometry remains one of the most important investigational techniques, in particular for oesophageal and anorectal disorders. Radiographic examination of bolus transit through the gastrointestinal tract also continues to be a valuable tool. Scintigraphy still is the gold standard for assessment of gastric emptying, but (13)(C) breath tests are an alternative. Many other techniques are used mainly in the context of scientific research but some of these may become incorporated in the diagnostic armamentarium.

Background: Recently, non-invasive techniques such as 3 dimensional ultrasonography (3DUS) have been developed to assess gastric wall characteristics and to investigate their relationship with upper gastrointestinal sensations. To date, no head-to-head comparison has been carried out between the barostat and the 3DUS technique., Aim: To compare barostat and 3DUS and to investigate the relationship between gastric volumes and sensations in patients with functional dyspepsia and in healthy subjects., Patients and Methods: Gastric accommodation was studied in 15 patients with functional dyspepsia and in 15 healthy subjects after ingestion of a liquid nutrient (300 kcal) using barostat and 3DUS in random order for 60 min. Proximal gastric relaxation was measured using barostat and gastric volume using 3DUS. Change in gastric volume, acquired by 3DUS, was expressed as total gastric volume/proximal volume ratio (TGV/PV) and compared with changes in barostat volume (fundal accommodation)., Results: Patients with functional dyspepsia showed a smaller change in proximal gastric volume than healthy subjects using barostat (mean (SD) 82 (61) v 205 (79) ml, p<0.01) and 3DUS (118 (41) v 199 (39) ml, p<0.01). Dysaccommodation of the proximal stomach was observed in 7 of 15 (46%) patients using the barostat technique. 10 of 15 (67%) patients were found to have an abnormal change in proximal gastric volume using TGV/PV ratio. At 5 min postprandially, fullness was related to the change in distal gastric volume (r = 0.51, p = 0.006) in the 3DUS study, whereas no relationship was observed in the barostat study., Conclusion: 3DUS is a feasible non-invasive technique to measure gastric volumes and shows a distinct overlap with barostat data in healthy subjects and patients with functional dyspepsia. Fullness relates to distal gastric volumes when assessed by non-invasive 3DUS.

The origin of postprandial gastrointestinal sensations and their relation to gastric accommodation remain unclear. Our aim was to investigate the relation between antral and fundal accommodation and sensations. (A) In eight healthy volunteers fundus accommodation was measured using a barostat after a 200-ml (300-kcal) liquid nutrient. Antral area (AA) was measured using ultrasound. Data on bag volumes, AA, and sensations were assessed. (B) In another eight healthy volunteers gastric volume was measured after a 500-ml (300-kcal) liquid nutrient using 2-D/3-D ultrasound. Sensations were scored using VAS. Distal and proximal volumes were calculated from 3-D datasets. (A) Fullness was correlated with AA (r = 0.48, P = 0.002). Fullness and bag volume were not correlated. (B) Fullness was correlated with AA (r = 0.77, P < 0.001) and distal volume (r = 0.75, P < 0.001). Proximal volume was not correlated with fullness (r = 0.10, P = NS). We conclude that fullness is related to antral volume and area rather than proximal volume. The gastric antrum may play a key role in normal appetite regulation.

Scintigraphy and the 13C-octanoic acid breath test are both applied to assess gastric emptying. Using the 13C-octanoic acid breath test, excretion curves show 13C excretion immediately after ingestion of a solid egg meal, in contrast with scintigraphy where gastric emptying is observed after a lag phase. The aim of our study was to investigate whether transpyloric flow occurs during and directly after meal ingestion. Therefore, transpyloric flow was measured during and after ingestion of an egg meal labeled with 13C-octanoic acid, using Doppler ultrasonography. The breath test was performed simultaneously, with samples taken at regular intervals. The first emptying episode was observed 6.9 (3.9-16.2) min after start of meal ingestion. A significant relation between recovery of 13C and total duration of gastric emptying during the first 20 min was observed (partial correlation coefficient r = 0.80, p < 0.001). In conclusion, transpyloric flow starts during ingestion of a solid egg meal and results in detectable excretion of 13C.

The barostat is the gold standard for measurement of proximal gastric accommodation. Ultrasonography can be used to measure gastric volume. The aim was to investigate the effects of the barostat bag on gastric accommodation and transpyloric flow. Accommodation after a liquid meal (300 ml, 450 kcal) was measured twice at random in eight healthy volunteers. Proximal accommodation was measured once using barostat and once using ultrasound (US). Antrum accommodation was measured using US. Bag volume (BV), antral area (AA), proximal gastric area, and proximal gastric diameter (PGD) data were assessed before and 1, 5, 15, 30, 40, 50, and 60 min postprandially. Transpyloric flow was measured using Doppler 1-5 min postprandially. Fasted, AA size was not affected by the barostat bag (1 mmHg > minimal distension pressure; 2.7 +/- 0.5 vs. 2.6 +/- 0.3 cm(2)). Postprandially, AAs were larger with the bag present (ANOVA, P < 0.04). Maximum AA was reached with the bag in 5 min, without the bag in 1 min postprandially (15.1 +/- 2.3 vs. 9.4 +/- 1.5 cm(2); P < 0.03). Furthermore, AAs were related to BVs (r = 0.57; P < 0.01). After bag deflation, AA decreased (11.9 +/- 1.8 to 7.0 +/- 0.9 cm(2); P = 0.02) and was comparable with the 60-min AA size without the bag (7.1 +/- 1.2 cm(2); P = 0.76) present. Proximal gastric radius calculated from the BVs and PGDs was larger with the bag present (ANOVA, P < 0.001). No effect on early gastric emptying was observed. Postprandially, the barostat bag causes dilatation of the antrum due to meal displacement without influencing early gastric emptying. This antral dilatation is likely to induce exaggerated proximal gastric relaxation observed in studies using the barostat to evaluate fundic accommodation.