Tuft cells act as regenerative stem cells in the human intestine.

In mice, intestinal tuft cells have been described as a long-lived, postmitotic cell type. Two distinct subsets have been identified: tuft-1 and tuft-2 (ref. 1). By combining analysis of primary human intestinal resection material and intestinal organoids, we identify four distinct human tuft cell states, two of which overlap with their murine counterparts. We show that tuft cell development depends on the presence of Wnt ligands, and that tuft cell numbers rapidly increase on interleukin-4 (IL-4) and IL-13 exposure, as reported previously in mice2-4. This occurs through proliferation of pre-existing tuft cells, rather than through increased de novo generation from stem cells. Indeed, proliferative tuft cells occur in vivo both in fetal and in adult human intestine. Single mature proliferating tuft cells can form organoids that contain all intestinal epithelial cell types. Unlike stem and progenitor cells, human tuft cells survive irradiation damage and retain the ability to generate all other epithelial cell types. Accordingly, organoids engineered to lack tuft cells fail to recover from radiation-induced damage. Thus, tuft cells represent a damage-induced reserve intestinal stem cell pool in humans.

Clinical trial: The effectiveness of long-acting somatostatin analogue for output reduction of high-output intestinal fistula or small bowel enterostomy. A randomised controlled trial.

BACKGROUND: High-output intestinal fistulas and small bowel enterostomies are associated with morbidity and mortality. Current standard treatment for output reduction consists of fluid and dietary restrictions and medical therapy. There is conflicting evidence regarding the use of somatostatin analogues for output reduction. AIM: The aim of this study is to investigate whether lanreotide, added to current standard treatment, further reduces intestinal output in patients with high-output fistulas and enterostomies. METHODS: This was an open-label, multicentre, randomised controlled trial. Adult patients with a high-output intestinal fistula (>500 mL/24 h) or small bowel enterostomy (>1500 mL/24 h) more than 4 weeks post-surgery and receiving standard medical treatment (dietary- and fluid restriction, PPI, loperamide and codeine) for at least 2 weeks were eligible for inclusion. We randomised patients 1:1 between continuing standard treatment (control), and subcutaneous lanreotide 120 mg every 4 weeks with standard treatment. The primary outcome was the number of responders, with response defined as an output reduction of ≥25%, 8 weeks after randomisation. We also investigated the proportional change in output. RESULTS: We randomised 40 patients; 17 had a fistula and 23 a small bowel enterostomy. There were 9/20 responders in the intervention group and 2/20 in the control group (p = 0.013). The proportional output reduction was -26% (IQR -4 to -38) in the intervention group, compared to an increase of 4% (IQR 20 to -13) in the control group (p = 0.004). CONCLUSIONS: In patients with a high-output fistula or small bowel enterostomy, addition of lanreotide to current standard treatment can provide a clinically relevant output reduction. TRIAL REGISTRATION: EudraCT: 2013-003998-10.

Effect of mesenteric sparing or extended resection in primary ileocolic resection for Crohn's disease on postoperative endoscopic recurrence (SPICY): an international, randomised controlled trial.

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.

How Reliable Is Endoscopic Scoring of Postoperative Recurrence in Crohn Disease?: A Systematic Review and Meta-Analysis.

Objective: Guidelines advise to perform endoscopic surveillance following ileocolic resection (ICR) in Crohn disease (CD) for timely diagnosis of recurrence. This study aims to assess the variation in endoscopic recurrence (ER) rates in patients after ICR for CD using the most commonly used classification systems, the Rutgeerts score (RS) and modified Rutgeerts score (mRS) classifications. Methods: A systematic literature search using MEDLINE, Embase, and the Cochrane Library was performed. Randomized controlled trials and cohort studies describing ER < 12 months after an ICR for CD were included. Animal studies, reviews, case reports (<30 included patients), pediatric studies, and letters were excluded. The Newcastle-Ottawa Quality Assessment Scale and Cochrane Collaboration's tool were used to assess risk of bias. Main outcome was the range of ER rates within 12 months postoperatively, defined as RS ≥ i2 and/or mRS ≥ i2b. A proportional meta-analysis was performed. The final search was performed on January 4, 2022. The study was registered at PROSPERO, CRD42022363208. Results: Seventy-six studies comprising 7751 patients were included. The weighted mean of ER rates in all included studies was 44.0% (95% confidence interval, 43.56-44.43). The overall range was 5.0% to 93.0% [interquartile range (IQR), 29.2-59.0]. The weighted means for RS and mRS were 44.0% and 41.1%, respectively. The variation in ER rates for RS and mRS were 5.0% to 93.0% (IQR, 29.0-59.5) and 19.8% to 62.9% (IQR, 37.3-46.5), respectively. Within studies reporting both RS and mRS, the weighted means for ER were 61.3% and 40.6%, respectively. Conclusions: This study demonstrates a major variation in ER rates after ICR for CD, suggesting a high likelihood of inadequate diagnosis of disease recurrence, with potentially impact on quality of life and health care consumption. Therefore, there is an important need to improve endoscopic scoring of recurrent disease.

Surgeon Preference and Clinical Outcome of 3D Vision Compared to 2D Vision in Laparoscopic Surgery: Systematic Review and Meta-Analysis of Randomized Trials.

Objective: To assess the added value of 3-dimensional (3D) vision, including high definition (HD) technology, in laparoscopic surgery in terms of surgeon preference and clinical outcome. Background: The use of 3D vision in laparoscopic surgery has been suggested to improve surgical performance. However, the added value of 3D vision remains unclear as a systematic review of randomized controlled trials (RCTs) comparing 3D vision including HD technology in laparoscopic surgery is currently lacking. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines with a literature search up to May 2023 using PubMed and Embase (PROSPERO, CRD42021290426). We included RCTs comparing 3D versus 2-dimensional (2D) vision in laparoscopic surgery. The primary outcome was operative time. Meta-analyses were performed using the random effects model to estimate the pooled effect size expressed in standard mean difference (SMD) with corresponding 95% confidence intervals (CIs). The level of evidence and quality was assessed according to the Cochrane risk of bias tool. Results: Overall, 25 RCTs with 3003 patients were included. Operative time was reduced by 3D vision (-8.0%; SMD, -0.22; 95% CI, -0.37 to -0.06; P = 0.007; n = 3003; 24 studies; I 2 = 75%) compared to 2D vision. This benefit was mostly seen in bariatric surgery (-16.3%; 95% CI, -1.28 to -0.21; P = 0.006; 2 studies; n = 58; I 2 = 0%) and general surgery (-6.7%; 95% CI, -0.34 to -0.01; P = 0.036; 9 studies; n = 1056; I 2 = 41%). Blood loss was nonsignificantly reduced by 3D vision (SMD, -0.33; 95% CI, -0.68 to 0.017; P = 0.060; n = 1830; I 2 = 92%). No differences in the rates of morbidity (14.9% vs 13.5%, P = 0.644), mortality (0% vs 0%), conversion (0.8% vs 0.9%, P = 0.898), and hospital stay (9.6 vs 10.5 days, P = 0.078) were found between 3D and 2D vision. In 15 RCTs that reported on surgeon preference, 13 (87%) reported that the majority of surgeons favored 3D vision. Conclusions: Across 25 RCTs, this systematic review and meta-analysis demonstrated shorter operative time with 3D vision in laparoscopic surgery, without differences in other outcomes. The majority of surgeons participating in the RCTs reported in favor of 3D vision.

The economic impact of anastomotic leakage after colorectal surgery: a systematic review.

BACKGROUND: Anastomotic leakage (AL) remains a burdensome complication following colorectal surgery, with increased morbidity, oncological compromise, and mortality. AL may impose a substantial financial burden on hospitals and society due to extensive resource utilization. Estimated costs associated with AL are important when exploring preventive measures and treatment strategies. The purpose of this study was to systematically review the existing literature on (socio)economic costs associated with AL after colorectal surgery, appraise their quality, compare reported outcomes, and identify knowledge gaps. METHODS: Health economic evaluations reporting costs related to AL after colorectal surgery were identified through searching multiple online databases until June 2023. Pairs of reviewers independently evaluated the quality using an adapted version of the Consensus on Health Economic Criteria list. Extracted costs were converted to 2022 euros (€) and also adjusted for purchasing power disparities among countries. RESULTS: From 1980 unique abstracts, 59 full-text publications were assessed for eligibility, and 17 studies were included in the review. The incremental costs of AL after correcting for purchasing power disparity ranged from €2250 (+39.9%, Romania) to €83,633 (+ 513.1%, Brazil). Incremental costs were mainly driven by hospital (re)admission, intensive care stay, and reinterventions. Only one study estimated the economic societal burden of AL between €1.9 and €6.1 million. CONCLUSIONS: AL imposes a significant financial burden on hospitals and social care systems. The magnitude of costs varies greatly across countries and data on the societal burden and non-medical costs are scarce. Adherence to international reporting standards is essential to understand international disparities and to externally validate reported cost estimates.

Management of Colorectal Neoplasia in IBD Patients: Current Practice and Future Perspectives.

Inflammatory bowel disease [IBD] patients are at increased risk of developing colorectal neoplasia [CRN]. In this review, we aim to provide an up-to-date overview and future perspectives on CRN management in IBD. Advances in endoscopic surveillance and resection techniques have resulted in a shift towards endoscopic management of neoplastic lesions in place of surgery. Endoscopic treatment is recommended for all CRN if complete resection is feasible. Standard [cold snare] polypectomy, endoscopic mucosal resection and endoscopic submucosal dissection should be performed depending on lesion complexity [size, delineation, morphology, surface architecture, submucosal fibrosis/invasion] to maximise the likelihood of complete resection. If complete resection is not feasible, surgical treatment options should be discussed by a multidisciplinary team. Whereas [sub]total and proctocolectomy play an important role in management of endoscopically unresectable CRN, partial colectomy may be considered in a subgroup of patients in endoscopic remission with limited disease extent without other CRN risk factors. High synchronous and metachronous CRN rates warrant careful mucosal visualisation with shortened intervals for at least 5 years after treatment of CRN.

Clinical statistical analysis plan for the ACCURE trial: the effect of appendectomy on the clinical course of ulcerative colitis, a randomised international multicentre trial.

BACKGROUND: The primary treatment of ulcerative colitis (UC) is medical therapy using a standard step-up approach. An appendectomy might modulate the clinical course of UC, decreasing the incidence of relapses and reducing need for medication. The objective of the ACCURE trial is to assess the efficacy of laparoscopic appendectomy in addition to standard medical treatment in maintaining remission in UC patients. This article presents the statistical analysis plan to evaluate the outcomes of the ACCURE trial. DESIGN AND METHODS: The ACCURE trial was designed as a multicentre, randomised controlled trial. UC patients with a new diagnosis or a disease relapse within the past 12 months, treated with 5-ASA, corticosteroids, or immunomodulators until complete clinical and endoscopic remission (defined as total Mayo score < 3 with endoscopic subscore of 0 or 1), were counselled for inclusion. Also, patients previously treated with biologicals who had a washout period of at least 3 months were considered for inclusion. Patients were randomised (1:1) to laparoscopic appendectomy plus maintenance treatment or a control group (maintenance therapy only). The primary outcome is the 1-year UC relapse rate (defined as a total Mayo-score ≥ 5 with endoscopic subscore of 2 or 3, or clinically as an exacerbation of symptoms and rectal bleeding or FCP > 150 or intensified medical therapy other than 5-ASA therapy). Secondary outcomes include number of relapses per patient, time to first relapse, disease activity, number of colectomies, medication usage, and health-related quality of life. DISCUSSION: The ACCURE trial will provide comprehensive evidence whether adding an appendectomy to maintenance treatment is superior to maintenance treatment only in maintaining remission in UC patients. TRIAL REGISTRATION: Dutch Trial Register (NTR) NTR2883 . Registered May 3, 2011. ISRCTN, ISRCTN60945764 . Registered August 12, 2019.

Optimising surgical anastomosis in ileocolic resection for Crohn's disease with respect to recurrence and functionality: two international parallel randomized controlled trials comparing handsewn (END-to-end or Kono-S) to stapled anastomosis (HAND2END and the End2End STUDIES).

BACKGROUND: The most common intestinal operation in Crohn's disease (CD) is an ileocolic resection. Despite optimal surgical and medical management, recurrent disease after surgery is common. Different types of anastomoses with respect to configuration and construction can be made after resection for example, handsewn (end-to-end and Kono-S) and stapled (side-to-side). The various types of anastomoses might affect endoscopic recurrence and its assessment, the functional outcome, and costs. The objective of the present study is to compare the three types of anastomoses with respect to endoscopic recurrence at 6 months, gastrointestinal function, and health care consumption. METHODS: This is a randomized controlled multicentre superiority trial, allocating patients either to side-to-side stapled anastomosis as advised in current guidelines or a handsewn anastomoses (an end-to-end or Kono-S). It is hypothesized that handsewn anastomoses do better than stapled, and end-to-end perform better than the saccular Kono-S. Two international studies with a similar setup will be conducted mainly in the Netherlands (End2End) and Italy (HAND2END). Patients diagnosed with CD, aged over 16 years in the Netherlands and 18 years in Italy requiring (re)resection of the (neo)terminal ileum are eligible. The first part of the study compares the two handsewn anastomoses with the stapled anastomosis. To detect a clinically relevant difference of 25% in endoscopic recurrence, a total of 165 patients will be needed in the Netherlands and 189 patients in Italy. Primary outcome is postoperative endoscopic recurrence (defined as Rutgeerts score ≥ i2b) at 6 months. Secondary outcomes are postoperative morbidity, gastrointestinal function, quality of life (QoL) and costs. DISCUSSION: The research question addresses a knowledge gap within the general practice elucidating which type of anastomosis is superior in terms of endoscopic and clinical recurrence, functionality, QoL and health care consumption. The results of the proposed study might change current practice in contrast to what is advised by the guidelines. TRIAL REGISTRATION: NCT05246917 for HAND2END and NCT05578235 for End2End ( http://www. CLINICALTRIALS: gov/ ).

Better stoma care using the Stoma App: does it help? A first randomized double-blind clinical trial on the effect of mobile healthcare on quality of life in stoma patients.

BACKGROUND: Receiving a stoma significantly impacts patients' quality of life. Coping with this new situation can be difficult, which may result in a variety of physical and psychosocial problems. It is essential to provide adequate guidance to help patients cope with their stoma, as this positively influences self-efficacy in return. Higher self-efficacy reduces psychosocial problems increasing patient's quality of life. This study investigates whether a new mobile application, the Stoma App, improves quality of life. And if personalized guidance, timed support, and peer contact offered as an in-app surplus makes a difference. METHODS: A double-blind, randomized controlled trial was conducted between March 2021 and April 2023. Patients aged > 18 years undergoing ileostomy or colostomy surgery, in possession of a compatible smartphone were included. The intervention group received the full version of the app containing personalized and time guidance, peer support, and generic (non-personalized) stoma-related information. The control group received a restricted version with only generic information. Primary outcome was stoma quality of life. Secondary outcomes included psychological adaption, complications, re-admittance, reoperations, and length of hospital stay. RESULTS: The intervention version of the app was used by 96 patients and the control version by 112 patients. After correction for confounding, the intervention group reported a significant 3.1-point improvement in stoma-related quality of life one month postoperatively (p = 0.038). On secondary outcomes, no significant improvements could be retrieved of the intervention group. CONCLUSION: The Stoma App improves the quality of life of stoma patients. Peer support and personalized guidance are of significant importance in building self-efficacy. It is to be recommended to implement Stoma app-freely available software qualifying as a medical device-in standard stoma care pathways for the benefits of both patients and healthcare providers.

The clinical relevance of an inflamed appendix in Crohn's disease.

BACKGROUND AND AIMS: An appendectomy for appendiceal inflammation has been suggested to ameliorate the clinical course of patients with ulcerative colitis (UC). In contrast, for Crohn's disease (CD) an inverse association has been suggested with a higher incidence of CD and worse prognosis after appendectomy. The aim of this study was to analyse the clinical relevance of an inflamed appendix in CD patients undergoing ileocoecal resection (ICR). METHODS: All consecutive patients undergoing primary ICR between 2007 and 2018 were considered for inclusion. Microscopic data of available appendiceal resection specimens (n=99) were revised by a dedicated IBD-pathologist and scored as inflamed or not inflamed. Eighteen patients had a previous appendectomy. Pathological findings were correlated with disease characteristics and recurrence rates (clinical, endoscopic and intervention-related). RESULTS: In total, 117 patients were included: 77 (65.8%) females with a median age of 30 years [IQR 24 - 43] with a median follow up of 102 months [IQR 76-114]. Of patients without previous appendectomy (n=99), 39% had an inflamed appendix. No significant differences in disease characteristics (e.g. disease location, behaviour, time to surgery) or prognosis could be demonstrated between the two groups. In contrast, previous appendectomy (n=18) was associated with penetrating disease and numerically shorter disease duration at the time of resection. Furthermore, a trend was seen towards a stronger association with postoperative recurrence. CONCLUSION: The current study could not confirm a different prognosis for CD patients with and without an inflamed appendix. In contrast, in patients with a previous appendectomy a trend was seen towards increased postoperative recurrence, which might be related to the higher incidence of penetrating disease.

A personalized app to improve quality of life of patients with a stoma: A protocol for a multicentre randomized controlled trial.

AIM: Proper education, guidance and support is crucial before and following creation of a stoma. Patients with a stoma and their close relatives need to adapt to and cope with this new - and sometimes unforeseen - situation, which may result in insecurities and a variety of psychosocial problems. Self-efficacy is associated both with a reduction in psychosocial problems and with improved quality of life. The main objective of this study was to investigate whether self-reported quality of life of patients with a stoma can be enhanced by offering personalized and timed guidance, as well as peer contact, in a patient-centred mobile application. METHOD: A multicentre, double-blind, randomized controlled trial will be conducted. Consented adults >18 years of age who will receive an ileostomy or colostomy and possess an eligible smartphone will be included. The intervention group will be given the full version of the application (containing personalized and timed guidance, such as operation-specific information and information on the associated care pathway) to install on their smartphone. In addition, the intervention group has access to a protected peer-support platform within the app. The control group will receive a restricted version of the application that contains only generic (non-personalized) stoma-related information. The primary outcome is quality of life, 3 months postoperatively. Secondary outcomes are Patient Reported Outcome Measures (PROMs), such as psychological adaption, as well as number of complications, re-admission and re-operation rates and the length of hospital stay. RESULTS: Patient enrolment began in March 2021. Data collection was not complete when this protocol was submitted. CONCLUSION: We hypothesize that patients with a stoma who are supported by the intervention version of the app will report a significantly higher quality of life than patients with a stoma who are supported by the control version of the app (ie, are not offered personalized and timed guidance and information and do not have access to peer support in the app).

Short-term anti-TNF therapy with surgical closure versus anti-TNF therapy alone for Crohn's perianal fistulas (PISA-II): long-term outcomes of an international, multicentre patient preference, randomised controlled trial.

Background: The PISA-II trial showed that short-term anti-tumour necrosis factor (anti-TNF) therapy followed by surgical closure induces radiological healing of perianal fistulas in patients with Crohn's disease more frequently than anti-TNF therapy alone after 18 months. This study aimed to compare long-term outcomes of both treatment arms. Methods: Follow-up data were collected from patients who participated in the PISA-II trial, an international patient preference randomised controlled trial. This multicentre trial was performed in nine hospitals in the Netherlands and one hospital in Italy. Patients with Crohn's disease above the age of 18 years with an active high perianal fistula and a single internal opening were asked to participate. Patients were allocated to anti-TNF therapy (intravenous infliximab, or subcutaneous adalimumab, at the discretion of the gastroenterologist) for one year, or surgical closure combined with 4-months anti-TNF therapy. Patients without a treatment preference were randomised (1:1) using random block randomisation (block sizes of six without stratification), and patients with a treatment preference were treated according to their preferred treatment arm. For the current follow-up study, data were collected until May 2022. Primary outcome was radiological healing on magnetic resonance imaging (MRI), including all participants with a MRI made less than 6 months ago at the time of data collection. Analysis was based on observed data. Findings: Between September 14, 2013, and December 7, 2019, 94 patients were enrolled in the trial. Long-term follow-up data were available in 91 patients (36/38 (95%) anti-TNF + surgical closure, 55/56 (98%) anti-TNF). A total of 14/36 (39%) patients in the surgical closure arm were randomly assigned, which was not significantly different in the anti-TNF treatment arm (16/55 (29%) randomly assigned). Median follow-up was 5.7 years (interquartile range (IQR) 5-7). Radiological healing occurred significantly more often after anti-TNF + surgical closure (15/36 = 42% versus 10/55 = 18%; P = 0.014). Clinical closure was comparable (26/36 = 72% versus 34/55 = 62%; P = 0.18) in both groups. However, clinical closure in the surgical group was achieved with less re-interventions 4/26 (= 15%) versus 18/34 (= 53%), including (redo-)surgical closure procedures. Recurrences occurred in 0/25 (0%) patients with radiological healing versus 27/76 (36%) patients with clinical closure, sometime during follow-up. Anti-TNF trough levels were higher in patients with long-term clinical closure in both groups (P = 0.031 and P = 0.014). In 6/11 (55%) patients in the anti-TNF group with available trough levels, recurrences were diagnosed within three months of a drop under 3.5ug/ml. 36 patients stopped anti-TNF, after which 0/14 (0%) patients with radiological healing developed a recurrence and 9/22 (41%) with clinical closure. Self-rated (in)continence was comparable between groups, and 79% (60/76) of patients indicated comparable/improved continence after treatment. Decision-regret analysis showed that all (30/30) anti-TNF + surgical closure patients agreed or strongly agreed that surgery was the right decision versus 78% (36/46) in the anti-TNF arm. All surgical closure patients would go for the same treatment again, whereas this was 89% (41/46) in the anti-TNF arm. Interpretation: This study confirmed that surgical closure should be considered in amenable patients with perianal fistulas and Crohn's disease as long-term outcomes were favourable, and that radiological healing should be the aim of treatment as recurrences only occurred in patients without radiological healing. In patients with complete MRI closure, anti-TNF could be safely stopped. Funding: None.

Endoscopic and surgical treatment outcomes of colitis-associated advanced colorectal neoplasia: a multicenter cohort study.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of advanced neoplasia (high-grade dysplasia or colorectal cancer). The authors aimed to (1) assess synchronous and metachronous neoplasia following (sub)total or proctocolectomy, partial colectomy or endoscopic resection for advanced neoplasia in IBD, and (2) identify factors associated with treatment choice. MATERIAL AND METHODS: In this retrospective multicenter cohort study, the authors used the Dutch nationwide pathology databank (PALGA) to identify patients diagnosed with IBD and colonic advanced neoplasia (AN) between 1991 and 2020 in seven hospitals in the Netherlands. Logistic and Fine & Gray's subdistribution hazard models were used to assess adjusted subdistribution hazard ratios for metachronous neoplasia and associations with treatment choice. RESULTS: The authors included 189 patients (high-grade dysplasia n =81; colorectal cancer n =108). Patients were treated with proctocolectomy ( n =33), (sub)total colectomy ( n =45), partial colectomy ( n =56) and endoscopic resection ( n =38). Partial colectomy was more frequently performed in patients with limited disease and older age, with similar patient characteristics between Crohn's disease and ulcerative colitis. Synchronous neoplasia was found in 43 patients (25.0%; (sub)total or proctocolectomy n =22, partial colectomy n =8, endoscopic resection n =13). The authors found a metachronous neoplasia rate of 6.1, 11.5 and 13.7 per 100 patient-years after (sub)total colectomy, partial colectomy and endoscopic resection, respectively. Endoscopic resection, but not partial colectomy, was associated with an increased metachronous neoplasia risk (adjusted subdistribution hazard ratios 4.16, 95% CI 1.64-10.54, P <0.01) compared with (sub)total colectomy. CONCLUSION: After confounder adjustment, partial colectomy yielded a similar metachronous neoplasia risk compared to (sub)total colectomy. High metachronous neoplasia rates after endoscopic resection underline the importance of strict subsequent endoscopic surveillance.

Increased Proportion of Colorectal Cancer in Patients With Ulcerative Colitis Undergoing Surgery in the Netherlands.

INTRODUCTION: The aim of the current study was to assess whether there is an indication shift for surgery in patients with ulcerative colitis (UC) from refractory disease to malignant degeneration over the past 3 decades. METHODS: All patients with histologically confirmed UC who underwent a colorectal resection between 1991 and 2020 were extracted from the nationwide Dutch Pathology Registry. The primary outcome was the proportion of colorectal cancer (CRC) in the colon specimens. Outcomes were compared between 3 periods (P1: 1991-2000, P2: 2001-2010, and P3: 2011-2020). RESULTS: Overall, 6,094 patients with UC were included of which 4,854 underwent a (procto)colectomy and 1,240 a segmental resection. In 1,031 (16.9%) patients, CRC was demonstrated in the pathological resection specimen after a median disease duration of 11 years (IQR 3.0-19.0). The proportion of CRC increased from 11.3% in P1, to 16.1% in P2, and 22.8% in P3 ( P < 0.001). Median disease duration at the time of resection increased from 4 years in P1, to 10 years in P2, and 17 years in P3 ( P < 0.001). The proportion of patients diagnosed with advanced malignancy (pT3/T4) (P1: 61.2% vs P2: 65.2% vs P3: 62.4%, respectively, P = 0.633) and lymph node metastasis (N+) (P1: 33.0% vs P2: 41.9% vs P3: 38.2%, respectively, P = 0.113) did not change over time. DISCUSSION: This nationwide pathology study demonstrated an increased proportion of surgery for CRC over the past 3 decades. We hypothesize that the expanding therapeutic armamentarium for UC leads to exhausting medical options and hence postponed colectomy. This, however, might be at the expense of an increased risk of CRC in the long term.

Detection of colon cancer recurrences during follow-up care by general practitioners vs surgeons.

BACKGROUND: In the I CARE study, colon cancer patients were randomly assigned to receive follow-up care from either a general practitioner (GP) or a surgeon. Here, we address a secondary outcome, namely, detection of recurrences and effect on time to detection of transferring care from surgeon to GP. METHODS: Pattern, stage, and treatment of recurrences were described after 3 years. Time to event was defined as date of surgery, until date of recurrence or last follow-up, with death as competing event. Effects on time to recurrence and death were estimated as hazard ratios (HRs) using Cox regression. Restricted mean survival times were estimated. RESULTS: Of 303 patients, 141 were randomly assigned to the GP and 162 to the surgeon. Patients were male (67%) with a mean age of 68.0 (8.4) years. During follow-up, 46 recurrences were detected; 18 (13%) in the GP vs 28 (17%) in the surgeon group. Most recurrences were detected via abnormal follow-up tests (74%) and treated with curative intent (59%). Hazard ratio for recurrence was 0.75 (95% confidence interval [CI] = 0.41 to 1.36) in GP vs surgeon group. Patients in the GP group remained in the disease-free state slightly longer (2.76 vs 2.71 years). Of the patients, 38 died during follow-up; 15 (11%) in the GP vs 23 (14%) in the surgeon group. Of these, 21 (55%) deaths were related to colon cancer. There were no differences in overall deaths between the groups (HR = 0.76, 95% CI = 0.39 to 1.46). CONCLUSION: Follow-up provided by GPs vs surgeons leads to similar detection of recurrences. Also, no differences in mortality were found.

Short- and Long-term Outcomes After Laparoscopic Emergency Resection of Left-Sided Obstructive Colon Cancer: A Nationwide Propensity Score-Matched Analysis.

BACKGROUND: The role of laparoscopy for emergency resection of left-sided obstructive colon cancer remains unclear, especially regarding impact on survival. OBJECTIVE: This study aimed to determine short- and long-term outcomes after laparoscopic versus open emergency resection of left-sided obstructive colon cancer. DESIGN: This observational cohort study compared patients who underwent laparoscopic emergency resection to those who underwent open emergency resection between 2009 and 2016 by using 1:3 propensity-score matching. Matching variables included sex, age, BMI, ASA score, previous abdominal surgery, tumor location, cT4, cM1, multivisceral resection, small-bowel distention on CT, and subtotal colectomy. SETTING: This was a nationwide, population-based study. PATIENTS: Of 2002 eligible patients with left-sided obstructive colon cancer, 158 patients who underwent laparoscopic emergency resection were matched with 474 patients who underwent open emergency resection. INTERVENTIONS: The intervention was laparoscopic versus open emergency resection. MAIN OUTCOME MEASURES: The main outcome measures were 90-day mortality, 90-day complications, permanent stoma, disease recurrence, overall survival, and disease-free survival. RESULTS: Intentional laparoscopy resulted in significantly fewer 90-day complications (26.6% vs 38.4%; conditional OR, 0.59; 95% CI, 0.39-0.87) and similar 90-day mortality. Laparoscopy resulted in better 3-year overall survival (81.0% vs 69.4%; HR, 0.54; 95% CI, 0.37-0.79) and disease-free survival (68.3% vs 52.3%; HR, 0.64; 95% CI, 0.47-0.87). Multivariable regression analyses of the unmatched 2002 patients confirmed an independent association of laparoscopy with fewer 90-day complications and better 3-year survival. LIMITATIONS: Selection bias was the limitation that cannot be completely ruled out because of the retrospective nature of this study. CONCLUSIONS: This population-based study with propensity score-matched analysis suggests that intentional laparoscopic emergency resection might improve outcomes in patients with left-sided obstructive colon cancer compared to open emergency resection. Management of those patients in the emergency setting requires proper selection for intentional laparoscopic resection if relevant expertise is available, thereby considering other alternatives to avoid open emergency resection (ie, decompressing stoma). See Video Abstract at http://links.lww.com/DCR/B972 . RESULTADOS A CORTO Y LARGO PLAZO DESPUS DE LA RESECCIN LAPAROSCPICA DE EMERGENCIA EN CNCER DE COLON IZQUIERDO OBSTRUCTIVO UN ANLISIS EMPAREJADO POR PUNTAJE DE PROPENSIN A NIVEL NACIONAL: ANTECEDENTES:El papel de la laparoscopia en la resección de emergencia en cáncer de colon izquierdo obstructivo sigue sin estar claro, especialmente con respecto al impacto en la supervivencia.OBJETIVO:El objetivo de este estudio fue determinar los resultados a corto y largo plazo después de la resección de emergencia laparoscópica versus abierta en cáncer de colon izquierdo obstructivo.DISEÑO:Estudio observacional de cohortes comparó pacientes que se sometieron a resección de laparoscópica de emergencia versus resección abierta de emergencia entre 2009 y 2016, mediante el uso de emparejamineto por puntaje de propensión 1: 3. Las variables emparejadas incluyeron sexo, edad, IMC, puntaje ASA, cirugía abdominal previa, ubicación del tumor, cT4, cM1, resección multivisceral, distensión del intestino delgado en la TAC y colectomía subtotal.ENTORNO CLINICO:A nivel nacional, basado en la población.PACIENTES:De 2002 pacientes elegibles con cáncer de colon izquierdo obstructivo, 158 pacientes con resección laparoscópica s de emergencia e emparejaron con 474 pacientes con resección abierta de emergencia.INTERVENCIONES:Resección laparoscópica de emergencia versus abierta.PRINCIPALES MEDIDAS DE RESULTADO:Las medidas primarias fueron la mortalidad a 90 días, complicaciones a 90 días, estoma permanente, recurrencia de la enfermedad, supervivencia general y supervivencia libre de enfermedad.RESULTADOS:La laparoscopia intencional dió como resultado significativamente menos complicaciones a los 90 días (26,6 % vs 38,4 %, cOR 0,59, IC del 95 %: 0,39-0,87) y una mortalidad similar a los 90 días. La laparoscopia resultó en una mejor supervivencia general a los 3 años (81,0 % vs 69,4 %, HR 0,54, IC del 95 % 0,37-0,79) y supervivencia libre de enfermedad (68,3 % vs 52,3 %, HR 0,64, IC del 95 % 0,47-0,87). Los análisis de regresión multivariable de los 2002 pacientes no emparejados confirmaron una asociación independiente de la laparoscopia con menos complicaciones a los 90 días y una mejor supervivencia a los 3 años.LIMITACIONES:El sesgo de selección no se puede descartar por completo debido a la naturaleza retrospectiva de este estudio.CONCLUSIONES:Estudio poblacional con análisis emparejado por puntaje de propensión sugiere que la resección laparoscópica de emergencia intencional podría mejorar los resultados a corto y largo plazo en pacientes con cáncer de colon izquierdo obstructivo en comparación con resección abierta de emergencia, lo que justifica la confirmación en estudios futuros. El manejo de esos pacientes en el entorno de emergencia requiere una selección adecuada para la resección laparoscópica intencional si se dispone de experiencia relevante, considerando así otras alternativas para evitar la resección abierta de emergencia (es decir, ostomia descompresiva). Consulte Video Resumen en http://links.lww.com/DCR/B972 . (Traducción- Dr. Francisco M. Abarca-Rendon & Dr. Fidel Ruiz Healy).

Predicting Mortality Within 90 Days of First Intervention in Patients With Left-Sided Obstructive Colon Cancer.

BACKGROUND: Acute resection for left-sided obstructive colon carcinoma is thought to be associated with a higher mortality risk than a bridge-to-surgery approach using decompressing stoma or self-expandable metal stent, but prediction models are lacking. OBJECTIVE: This study aimed to determine the influence of treatment strategy on mortality within 90 days from the first intervention in patients presenting with left-sided obstructive colon carcinoma. DESIGN: This was a national multicenter cohort study that used data from a prospective national audit. SETTINGS: The study was performed in 75 Dutch hospitals. PATIENTS: Patients were included if they underwent resection with curative intent for left-sided obstructive colon carcinoma between 2009 and 2016. INTERVENTIONS: First intervention was either acute resection, bridge to surgery with self-expandable metallic stent, or bridge to surgery with decompressing stoma. MAIN OUTCOME MEASURES: The main outcome measure was 90-day mortality after the first intervention. Risk factors were identified using multivariable logistic analysis. Subsequently, a risk model was developed. RESULTS: In total, 2395 patients were included, with the first intervention consisting of acute resection in 1848 patients (77%), stoma as bridge to surgery in 332 patients (14%), and stent as bridge to surgery in 215 patients (9%). Overall, 152 patients (6.3%) died within 90 days from the first intervention. A decompressing stoma was independently associated with lower 90-day mortality risk (HR, 0.27; 95% CI, 0.094-0.62). Other independent predictors for mortality were age, ASA classification, tumor location, and index levels of serum creatinine and C-reactive protein. The constructed risk model had an area under the curve of 0.84 (95% CI, 0.81-0.87). LIMITATIONS: Only patients who underwent surgical resection were included. CONCLUSIONS: Treatment strategy had a significant impact on 90-day mortality. A decompressing stoma considerably lowers the risk of mortality, especially in older and frail patients. The developed risk model needs further external validation. See Video Abstract at http://links.lww.com/DCR/B975 .PREDICCIÓN DE LA MORTALIDAD A 90 DÍAS POSTERIORES A LA PRIMERA CIRUGÍA EN PACIENTES CON CÁNCER DE COLON OBSTRUCTIVO DEL LADO IZQUIERDOANTECEDENTES:Se cree que la resección aguda para el carcinoma de colon obstructivo del lado izquierdo está asociada con un mayor riesgo de mortalidad que un enfoque puente a la cirugía que utiliza un estoma de descompresión o un stent metálico autoexpandible, pero faltan modelos de predicción.OBJETIVO:Determinar la influencia de la estrategia de tratamiento sobre la mortalidad dentro de los 90 días desde la primera intervención utilizando un modelo de predicción en pacientes que presentan carcinoma de colon obstructivo del lado izquierdo.DISEÑO:Un estudio de cohorte multicéntrico nacional, utilizando datos de una auditoría nacional prospectiva.ENTORNO CLINICO:El estudio se realizó en 75 hospitales holandeses.PACIENTES:Se incluyeron los pacientes que se sometieron a una resección con intención curativa de un carcinoma de colon obstructivo del lado izquierdo entre 2009 y 2016.INTERVENCIONES:La primera intervención fue resección aguda, puente a cirugía con stent metálico autoexpandible o puente a cirugía con estoma descompresor.PRINCIPALES MEDIDAS DE VALORACIÓN:La principal medida de resultado fue la mortalidad a los 90 días después de la primera intervención. Los factores de riesgo se identificaron mediante análisis logístico multivariable. Posteriormente se desarrolló un modelo de riesgo.RESULTADOS:En total se incluyeron 2395 pacientes, siendo la primera intervención resección aguda en 1848 (77%) pacientes, estoma como puente a la cirugía en 332 (14%) pacientes y stent como puente a la cirugía en 215 (9%) pacientes. En general, 152 pacientes (6,3%) fallecieron dentro de los 90 días posteriores a la primera intervención. Un estoma de descompresión se asoció de forma independiente con un menor riesgo de mortalidad a los 90 días (HR: 0,27, IC: 0,094-0,62). Otros predictores independientes de mortalidad fueron la edad, la clasificación ASA, la ubicación del tumor y los niveles índice de creatinina sérica y proteína C reactiva. El modelo de riesgo construido tuvo un área bajo la curva de 0,84 (IC: 0,81-0,87).LIMITACIONES:Solo se incluyeron pacientes que se sometieron a resección quirúrgica.CONCLUSIONES:La estrategia de tratamiento tuvo un impacto significativo en la mortalidad a los 90 días. Un estoma descompresor reduce considerablemente el riesgo de mortalidad, especialmente en pacientes mayores y frágiles. Se desarrolló un modelo de riesgo, que necesita una mayor validación externa. Consulte Video Resumen en http://links.lww.com/DCR/B975 . (Traducción-Dr. Ingrid Melo ).

Endoscopic Recurrence or Anastomotic Wound Healing Phenomenon after Ileocolic Resection for Crohn's Disease: The Challenges of Accurate Endoscopic Scoring.

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.

Oncological Safety and Potential Cost Savings of Routine vs Selective Histopathological Examination After Appendectomy: Results of the Multicenter, Prospective, Cross-Sectional FANCY Study.

OBJECTIVE: To investigate the oncological safety and potential cost savings of selective histopathological examination after appendectomy. BACKGROUND: The necessity of routine histopathological examination after appendectomy has been questioned, but prospective studies investigating the safety of a selective policy are lacking. METHODS: In this multicenter, prospective, cross-sectional study, inspection and palpation of the (meso)appendix was performed by the surgeon in patients with suspected appendicitis. The surgeon's opinion on additional value of histopathological examination was reported before sending all specimens to the pathologist. Main outcomes were the number of hypothetically missed appendiceal neoplasms with clinical consequences benefiting the patient (upper limit two-sided 95% confidence interval below 3:1000 considered oncologically safe) and potential cost savings after selective histopathological examination. RESULTS: Seven thousand three hundred thirty-nine patients were included. After a selective policy, 4966/7339 (67.7%) specimens would have been refrained from histopathological examination. Appendiceal neoplasms with clinical consequences would have been missed in 22/4966 patients. In 5/22, residual disease was completely resected during additional surgery. Hence, an appendiceal neoplasm with clinical consequences benefiting the patient would have been missed in 1.01:1000 patients (upper limit 95% confidence interval 1.61:1000). In contrast, twice as many patients (10/22) would not have been exposed to potential harm due to re-resections without clear benefit, whereas consequences were neither beneficial nor harmful in the remaining seven. Estimated cost savings established by replacing routine for selective histopathological examination were €725,400 per 10,000 patients. CONCLUSIONS: Selective histopathological examination after appendectomy for suspected appendicitis is oncologically safe and will likely result in a reduction of pathologists' workload, less costs, and fewer re-resections without clear benefit.