Background Extensive colectomy (subtotal or total colectomy) is often advised for carriers of Lynch syndrome with colorectal cancer. However, the risk of metachronous colorectal cancer might differ... Show moreBackground Extensive colectomy (subtotal or total colectomy) is often advised for carriers of Lynch syndrome with colorectal cancer. However, the risk of metachronous colorectal cancer might differ by Lynch syndrome variant, meaning that partial colectomy, which has better functional outcomes, might be adequate for some patients with lowrisk variants. We aimed to assess the risk of metachronous colorectal cancer after partial colectomy and extensive colectomy in carriers of Lynch syndrome with different pathogenic variants. Methods For this retrospective cohort study, carriers of Lynch syndrome with colorectal cancer in the Netherlands were identified by linkage of the Dutch Foundation for the Detection of Hereditary Tumors (StOET) database and the Dutch Nationwide Network and Registry of Histopathology and Cytopathology (PALGA) database. Data on demographics, Lynch syndrome variants, colorectal cancers, surgery types, mortality, and surveillance colonoscopies were extracted. Data on colorectal cancer and surveillance colonoscopies were updated until Feb 28, 2022. Data on survival status was updated until Feb 7, 2022. MLH1, MSH2, and EPCAM were classified as high-risk variants and MSH6 and PMS2 as low-risk variants. Patients for whom the type of surgery was unknown were excluded. Cox regression time-to-event analyses were done to assess the risk of metachronous colorectal cancer in four subgroups based on pathogenic variant (high-risk vs low-risk variants) and the extent of surgery (extensive colectomy vs partial colectomy). Sex, age at the time of primary colorectal cancer, primary colorectal cancer stage, performance of surveillance colonoscopies, adherence to the surveillance guidelines, and time period of primary colorectal cancer diagnosis were added to the model as possible confounders. Metachronous colorectal cancer was defined as colorectal cancer diagnosed more than 6 months after the primary colorectal cancer. Patients were censored at time of death or assembly of the database. Findings Of 1908 carriers of Lynch syndrome registered in StOET, 532 with a history of colorectal cancer were identified after linkage with PALGA. Five carriers were excluded because of an unknown surgery type, leaving 527 in our sample (mean age at primary colorectal cancer 48·7 years [SD 12·1]; 274 [52%] male and 253 [48%] female). 121 (23%) patients developed metachronous colorectal cancer (median time from primary colorectal cancer to metachronous colorectal cancer 11·0 years [IQR 2·1–17·8]). Metachronous colorectal cancer occurred in 12 (12%) of 97 patients with high-risk variants and extensive colectomy, in 85 (32%) of 267 patients with high-risk variants and partial colectomy, in zero (0%) of 11 patients with low-risk variants and extensive colectomy, and in 24 (16%) of 152 patients with low-risk variants and partial colectomy. Partial colectomy was associated with a higher risk of metachronous colorectal cancer than extensive colectomy in the high-risk variant group (hazard ratio 1·97, 95% CI 1·04–3·73; p=0·039). The risk of metachronous colorectal cancer did not differ between carriers of low-risk variants who had partial colectomy and those of high-risk variants who had extensive colectomy (1·14, 0·55–2·36; p=0·72). Interpretation The risk of metachronous colorectal cancer after partial colectomy in carriers of low-risk variants is similar to the risk after extensive colectomy in carriers of high-risk variants. This finding suggests that partial colectomy followed by endoscopic surveillance is an appropriate management approach to treat colorectal cancer in carriers of low-risk Lynch syndrome variants. Show less
Background: Despite its effectiveness in treating Crohn's disease, adalimumab is associated with an increased risk of infections and high health-care costs. We aimed to assess clinical outcomes of... Show moreBackground: Despite its effectiveness in treating Crohn's disease, adalimumab is associated with an increased risk of infections and high health-care costs. We aimed to assess clinical outcomes of increased adalimumab dose intervals versus conventional dosing in patients with Crohn's disease in stable remission. Methods: The LADI study was a pragmatic, open-label, multicentre, non-inferiority, parallel, randomised controlled trial, done in six academic hospitals and 14 general hospitals in the Netherlands. Adults (aged >= 18 years) diagnosed with luminal Crohn's disease (with or without concomitant perianal disease) were eligible when in steroid-free clinical and biochemical remission (defined as Harvey-Bradshaw Index [HBI] score <5, faecal calprotectin <150 mu g/g, and C-reactive protein <10 mg/L) for at least 9 months on a stable dose of 40 mg subcutaneous adalimumab every 2 weeks. Patients were randomly assigned (2:1) to the intervention group or control group by the coordinating investigator using a secure web-based system with variable block randomisation (block sizes of 6, 9, and 12). Randomisation was stratified on concomitant use of thiopurines and methotrexate. Patients and health-care providers were not masked to group assignment. Patients allocated to the intervention group increased adalimumab dose intervals to 40 mg every 3 weeks at baseline and further to every 4 weeks if they remained in clinical and biochemical remission at week 24. Patients in the control group continued their 2-weekly dose interval. The primary outcome was the cumulative incidence of persistent flares at week 48 defined as the presence of at least two of the following criteria: HBI score of 5 or more, C-reactive protein 10 mg/L or more, and faecal calprotectin more than 250 mu g/g for more than 8 weeks and a concurrent decrease in the adalimumab dose interval or start of escape medication. The non-inferiority margin was 15% on a risk difference scale. All analyses were done in the intention-to-treat and per-protocol populations. This trial was registered at ClinicalTrials.gov, NCT03172377, and is not recruiting. Findings Between May 3, 2017, and July 6, 2020, 174 patients were randomly assigned to the intervention group (n=113) or the control group (n=61). Four patients from the intervention group and one patient from the control group were excluded from the analysis for not meeting inclusion criteria. 85 (50%) of 169 participants were female and 84 (50%) were male. At week 48, the cumulative incidence of persistent flares in the intervention group (three [3%] of 109) was non-inferior compared with the control group (zero; pooled adjusted risk difference 1 center dot 86% [90% CI -0 center dot 35 to 4 center dot 07). Seven serious adverse events occurred, all in the intervention group, of which two (both patients with intestinal obstruction) were possibly related to the intervention. Per 100 person-years, 168 center dot 35 total adverse events, 59 center dot 99 infection-related adverse events, and 42 center dot 57 gastrointestinal adverse events occurred in the intervention group versus 134 center dot 67, 75 center dot 03, and 5 center dot 77 in the control group, respectively. Interpretation The individual benefit of increasing adalimumab dose intervals versus the risk of disease recurrence is a trade-off that should take patient preferences regarding medication and the risk of a flare into account. Show less
Background Adenoma detection rate (ADR) is a well-established quality indicator for colonoscopy and is inversely associated with the incidence of interval post-colonoscopy colorectal cancer.... Show moreBackground Adenoma detection rate (ADR) is a well-established quality indicator for colonoscopy and is inversely associated with the incidence of interval post-colonoscopy colorectal cancer. However, interval post-colonoscopy colorectal cancers frequently develop from serrated polyps, which are not included in the ADR. Therefore, the proximal serrated polyp detection rate (PSPDR) has been proposed as a quality indicator, but its association with interval post-colonoscopy colorectal cancer has not been studied. We aimed to evaluate this potential association based on data collected in the Dutch colorectal cancer screening programme. Methods In this population-based study, using colonoscopy data from the Dutch faecal immunochemical test-based colorectal cancer screening programme and cancer data from the Netherlands Cancer Registry, we evaluated the association between endoscopists' individual PSPDR and their patients' risk of interval post-colonoscopy colorectal cancer with a shared frailty Cox proportional-hazard regression analysis. Participants in the screening programme who were eligible for inclusion were aged 55-76 years, had a positive faecal immunochemical test (cutoff 15 mu g Hb/g faeces at start and changed mid-2014 to 47 mu g Hb/g faeces), were asymptomatic, and underwent a colonoscopy between Jan 1, 2014, and Dec 31, 2020. The PSPDR was defined as the proportion of colonoscopies in which at least one serrated polyp proximal to the descending colon was detected, confirmed by histopathology. The ADR was defined as the proportion of all colonoscopies in which at least one conventional adenoma was detected, confirmed by histopathology. Detection rates were determined for each endoscopist individually. We additionally evaluated the risk of interval post-colonoscopy colorectal cancer for endoscopists with a PSPDR and ADR above the median versus endoscopists with either one or both parameters below the median. This study is registered with the Netherlands Trial Registry, NL8350. Findings During the study period, 329 104 colonoscopies were done, of which 277 555, done by 441 endoscopists, were included in the PSPDR calculations. The median PSPDR was 11.9% (IQR 8.3-15.8) and median ADR was 66.3% (61.4-69.9). The correlation between the PSDPR and ADR was moderate (r=0.59; p < 0middot0001). During a median follow-up of 33 months (IQR 21-42), 305 interval post-colonoscopy colorectal cancers were detected. For each percentage point increase in PSPDR, the adjusted interval post-colonoscopy colorectal cancer hazard was 7% lower (hazard ratio [HR] 0.93, 95% CI 0.90-0.95; p < 0middot0001). Compared with endoscopists with a PSPDR greater than 11middot9% and ADR greater than 66middot3%, the HR of interval post-colonoscopy colorectal cancer for endoscopists with a low PSPDR and high ADR was 1.79 (95% CI 1.22-2.63), for endoscopists with a high PSPDR and low ADR was 1.97 (1.19-3.24), and for endoscopists with a low PSPDR and low ADR was 2.55 (1.89-3.45). Gastroenterology, (Prof Gastroenterology the (Prof Interpretation The PSPDR of an endoscopist is inversely associated with the incidence of interval post-colonoscopy colorectal cancer. Implementation of PSPDR monitoring, in addition to ADR monitoring, could optimise colorectal cancer prevention. Copyright (C) 2022 Elsevier Ltd. All rights reserved. Show less
GASTROSWOT is a strategic analysis of the current and projected states of the different subspecialties in gastroenterology that aims to provide guidance for research, clinical, and financial... Show moreGASTROSWOT is a strategic analysis of the current and projected states of the different subspecialties in gastroenterology that aims to provide guidance for research, clinical, and financial planning in gastroenterology. We executed a consensus-based international strengths, weaknesses, opportunities, and threats (SWOT) analysis. Four general coordinators, six field coordinators, and 12 experts participated in the study. SWOTs were provided for the following fields: neurogastroenterology, functional gastrointestinal disorders, and upper gastrointestinal diseases; inflammatory bowel disease; pancreatology and biliary diseases; endoscopy; gastrointestinal oncology; and hepatology. The GASTROSWOT analysis highlights the following in the current state of the field of gastroenterology: the incidence and complexity of several gastrointestinal diseases, including malignancies, are increasing; the COVID-19 pandemic has affected patient care on several levels; and with the advent of technical innovations in gastroenterology, a well trained workforce and strategic planning are required to optimise health-care utilisation. The analysis calls attention to the following in the future of gastroenterology: artificial intelligence and the use of big data will speed up discovery and smarter health-care provision in the field; the growth and diversification of gastroenterological specialties will improve specialised care for patients, but could promote fragmentation of care and health system inefficiencies; and furthermore, thoughtful planning is needed to reach an effective balance between the need for subspecialists and the value of general gastroenterology services. Show less
Background In 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a... Show moreBackground In 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a cutoff value for positivity of 47 mu g haemoglobin per g faeces. We aimed to assess CRC incidence, mortality, tumour characteristics, and treatment before and after introduction of this screening programme.Methods We did a retrospective, observational, population-based study in the Netherlands and gathered CRC incidence data from the Netherlands Cancer Registry from Jan 1, 2010, to Dec 31, 2019, in people aged 55 years or older. Patients with a CRC diagnosis between Jan 1, 2014, and Dec 31, 2018, in the Netherlands Cancer Registry were linked with the nationwide registry of histopathology and cytopathology (PALGA) to identify mode of detection (ie, screening-detected vs clinically detected). We calculated age-standardised CRC incidence rates and used data from Statistics Netherlands to calculate CRC-related mortality in 2010-19. We compared localisation, stage distribution, and treatment of screening-detected CRCs with clinically detected CRCs diagnosed in 2014-18 in patients aged 55-75 years.Findings Between Jan 1, 2010, and Dec 31, 2019, 125 215 CRCs were diagnosed in individuals aged 55 years or older and were included in the analyses for CRC incidence. Before the introduction of the screening programme, the age-standardised CRC incidence rate was 214.3 per 100 000 population in 2013 in people aged 55 years or older. After the introduction of the screening programme, this rate initially increased to 259.2 per 100 000 population in 2015, and subsequently decreased to 181.5 per 100 000 population in 2019. Age-standardised incidence rates for advanced CRCs (stage III and IV) were 117.0 per 100 000 population in 2013 and increased to 122.8 per 100 000 population in 2015; this rate then decreased to 94.7 per 100 000 population in 2018. Age-standardised CRC mortality decreased from 87.5 deaths per 100 000 population in 2010 to 64.8 per 100 000 population in 2019. Compared with clinically detected CRCs, screening-detected CRCs were more likely to be located in the left side of the colon (48.6% vs 35.2%) and to be detected at an early stage (I or II; 66. 7% vs 46.2%). Screening-detected CRCs were more likely to be treated by local excision compared with clinically detected CRCs, and this fmding persisted when stage I CRCs were analysed separately.Interpretation After introduction of this national screening programme, a decrease in overall and advanced-stage CRC incidence was observed. In view of this observation, together with the observed shift to detection at earlier stages and more screening-detected CRCs being treated by local excision, we might cautiously conclude that, in the long-term, faecal immunochemical testing-based screening could ultimately lead to a decrease in CRC-related morbidity and mortality. Copyright (C) 2021 Elsevier Ltd. All rights reserved. Show less
Background Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop... Show moreBackground Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop symptomatic gallstone disease. This trial assessed the efficacy of ursodeoxycholic acid versus placebo for the prevention of symptomatic gallstone disease after bariatric surgery.Methods This multicentre, double-blind, randomised, placebo-controlled superiority trial enrolled patients with an intact gallbladder scheduled for laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy in three hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module to receive 900 mg ursodeoxycholic acid daily for 6 months or matched placebo. Randomisation was stratified by the presence of asymptomatic gallstones at baseline and type of surgery. Patients, clinicians, and study staff were masked to treatment allocation. The primary endpoint was symptomatic gallstone disease within 24 months, assessed in the modified intention-to-treat population (all randomly assigned eligible patients with any postrandomisation measurement). Prespecified subgroup analyses were done based on the stratification groups. Safety was assessed in all patients who took at least one dose of the study drug. This trial is registered with the Netherlands Trial Register, NL5954.Findings Between Jan 11, 2017, and Oct 22, 2018, 985 patients were randomly assigned to receive either ursodeoxycholic acid (n=492) or placebo (n=493). 967 patients were included in the modified intention-to-treat population, of whom 959 had data available for primary endpoint assessment. 189 (20%) patients had asymptomatic gallstones at baseline and 78 (8%) received a sleeve gastrectomy. Symptomatic gallstone disease occurred in 31 (6.5%) of 475 patients in the ursodeoxycholic acid group and in 47 (9.7%) of 484 patients in the placebo group (relative risk 0.67, 95% CI 0.43-1.04, p=0.071). Logistic regression showed a significant interaction between ursodeoxycholic acid and the presence of asymptomatic gallstones at baseline (p=0.046), with an effect of ursodeoxycholic acid in patients without (0.47, 0.27-0.84, p=0.0081), and no effect in patients with asymptomatic gallstones at baseline (1.22, 0.61-2.47, p=0.57). The effect was stronger in patients without gallstones at baseline undergoing RYGB (0.37, 0.20-0.71, p=0.0016), whereas the subgroup of patients undergoing sleeve gastrectomy was too small to draw clear conclusions. Adverse events were rare. In the ursodeoxycholic acid group, diarrhoea occurred in four (0.9%) of 444 patients and skin rash in two (0.5%) patients. In the placebo group, diarrhoea occurred in two (0.4%) of 453 patients and skin rash in two (0.4%) patients. The total number of serious adverse events did not significantly differ between the trial groups (75 [17%] in 444 patients in the ursodeoxycholic acid group and 102 [23%] in 453 patients in the placebo group). The most common serious adverse events were abdominal pain and internal hernia. No serious adverse event was attributed to the study drug.Interpretation Ursodeoxycholic acid prophylaxis did not significantly reduce the occurrence of symptomatic gallstone disease in all patients after bariatric surgery. In patients without gallstones before RYGB surgery, ursodeoxycholic acid treatment reduced the occurrence of symptomatic gallstone disease compared with placebo. Further research is needed to assess the efficacy of ursodeoxycholic acid after sleeve gastrectomy. Copyright (C) 2021 Elsevier Ltd. All rights reserved. Show less
BackgroundIn 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a... Show moreBackgroundIn 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a cutoff value for positivity of 47 μg haemoglobin per g faeces. We aimed to assess CRC incidence, mortality, tumour characteristics, and treatment before and after introduction of this screening programme.MethodsWe did a retrospective, observational, population-based study in the Netherlands and gathered CRC incidence data from the Netherlands Cancer Registry from Jan 1, 2010, to Dec 31, 2019, in people aged 55 years or older. Patients with a CRC diagnosis between Jan 1, 2014, and Dec 31, 2018, in the Netherlands Cancer Registry were linked with the nationwide registry of histopathology and cytopathology (PALGA) to identify mode of detection (ie, screening-detected vs clinically detected). We calculated age-standardised CRC incidence rates and used data from Statistics Netherlands to calculate CRC-related mortality in 2010–19. We compared localisation, stage distribution, and treatment of screening-detected CRCs with clinically detected CRCs diagnosed in 2014–18 in patients aged 55–75 years.FindingsBetween Jan 1, 2010, and Dec 31, 2019, 125 215 CRCs were diagnosed in individuals aged 55 years or older and were included in the analyses for CRC incidence. Before the introduction of the screening programme, the age-standardised CRC incidence rate was 214·3 per 100 000 population in 2013 in people aged 55 years or older. After the introduction of the screening programme, this rate initially increased to 259·2 per 100 000 population in 2015, and subsequently decreased to 181·5 per 100 000 population in 2019. Age-standardised incidence rates for advanced CRCs (stage III and IV) were 117·0 per 100 000 population in 2013 and increased to 122·8 per 100 000 population in 2015; this rate then decreased to 94·7 per 100 000 population in 2018. Age-standardised CRC mortality decreased from 87·5 deaths per 100 000 population in 2010 to 64·8 per 100 000 population in 2019. Compared with clinically detected CRCs, screening-detected CRCs were more likely to be located in the left side of the colon (48·6% vs 35·2%) and to be detected at an early stage (I or II; 66·7% vs 46·2%). Screening-detected CRCs were more likely to be treated by local excision compared with clinically detected CRCs, and this finding persisted when stage I CRCs were analysed separately.InterpretationAfter introduction of this national screening programme, a decrease in overall and advanced-stage CRC incidence was observed. In view of this observation, together with the observed shift to detection at earlier stages and more screening-detected CRCs being treated by local excision, we might cautiously conclude that, in the long-term, faecal immunochemical testing-based screening could ultimately lead to a decrease in CRC-related morbidity and mortality. Show less
Weiland, C.J.S.; Smeets, X.J.N.M.; Kievit, W.; Verdonk, R.C.; Poen, A.C.; Bhalla, A.; ... ; Dutch Pancreatitis Study G 2021
Background Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs... Show moreBackground Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Prophylactic rectal administration of non-steroidal anti-inflammatory drugs (NSAIDs) is considered as standard of care to reduce the risk of post-ERCP pancreatitis. It has been suggested that aggressive hydration might further reduce this risk. Guidelines already recommend aggressive hydration in patients who are unable to receive rectal NSAIDs, although it is laborious and time consuming. We aimed to evaluate the added value of aggressive hydration in patients receiving prophylactic rectal NSAIDs.Methods FLUYT, a multicentre, open-label, randomised, controlled trial done across 22 Dutch hospitals, included patients aged between 18 and 85 years with moderate to high risk of post-ERCP pancreatitis. Patients were randomly assigned (1:1) by a web-based module with varying block sizes to a combination of aggressive hydration and rectal NSAIDs (100 mg diclofenac or indomethacin; aggressive hydration group) or rectal NSAIDs (100 mg diclofenac or indomethacin) alone (control group). Randomisation was stratified according to treatment centre. Aggressive hydration comprised 20 mL/kg intravenous Ringer's lactate solution within 60 min from the start of ERCP, followed by 3 mL/kg per h for 8 h. The control group received normal intravenous saline with a maximum of 1.5 mL/kg per h and 3 L per 24 h. The primary endpoint was post-ERCP pancreatitis and was analysed on a modified intention-to-treat basis (including all patients who underwent randomisation and an ERCP and for whom data regarding the primary outcome were available). The trial is registered with the ISRCTN registry, ISRCTN13659155.Findings Between June 5, 2015, and June 6, 2019, 826 patients were randomly assigned, of whom 388 in the aggressive hydration group and 425 in the control group were included in the modified intention-to-treat analysis. Post-ERCP pancreatitis occurred in 30 (8%) patients in the aggressive hydration group and in 39 (9%) patients in the control group (relative risk 0.84, 95% CI 0.53-1.33, p=0.53). There were no differences in serious adverse events, including hydration-related complications (relative risk 0.99, 95% CI 0.59-1.64; p=1.00), ERCP-related complications (0.90, 0.62-1.31; p=0.62), intensive care unit admission (0.37, 0.07-1.80; p=0.22), and 30-day mortality (0.95, 0.50-1.83; p=1.00).Interpretation Aggressive periprocedural hydration did not reduce the incidence of post-ERCP pancreatitis in patients with moderate to high risk of developing this complication who routinely received prophylactic rectal NSAIDs. Therefore, the burden of laborious and time-consuming aggressive periprocedural hydration to further reduce the risk of post-ERCP pancreatitis is not justified. Copyright (c) 2021 Elsevier Ltd. All rights reserved. Show less
