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Background: Anal squamous intraepithelial lesions (ASILs) correspond to premalignant changes preceding the development of anal squamous cell carcinoma., Objective: To describe a new endoscopic technique to detect and remove ASILs in non-anesthetized patients and compare it with standard surgical treatment., Methods: For endoscopic treatment, high resolution (HR) flexible endoscopes with a distal attachment were used. Underwater inspection of the anal canal was performed in near-focus mode with white light and narrow-band imaging. Detected lesions were resected with a diathermia snare after local injection of xylocaine/adrenaline. We did a retrospective comparison of all patients who underwent endoscopic or standard surgical treatment for ASILs at Ersta hospital in Stockholm between 2018 and 2020. Patient files were reviewed for number of lesions, treatments until macroscopic radicality, degree of dysplasia, bleeding, pain and other complications., Results: Endoscopic ( n  = 37) and surgical ( n  = 43) treatment displayed comparable number of lesions per patient ( p  = .37). The number of procedures until macroscopic radicality was higher for endoscopy than surgery ( p  = .04). However, in endoscopic follow up of 12 of the surgically treated patients, residual ASIL was found in 10 cases. Post-procedural bleeding requiring healthcare occurred in two endoscopy patients and one surgically treated patient., Conclusions: Underwater resection using a HR flexible endoscope in non-anesthetized is a new, feasible and well tolerated method for ASILs treatment. Its efficacy and risk of complications seem comparable to standard surgical treatment while avoiding general anesthesia. However, minor lesions might be overlooked at surgery.

Purpose: The Swedish National Patient Register (SNPR) is frequently used in studies of colonic diverticular disease (DD). Despite this, the validity of the coding for this specific disease in the register has not been studied., Methods: From SNPR, 650 admissions were randomly identified encoded with ICD 10, K572-K579. From the years 2002 and 2010, 323 and 327 patients respectively were included in the validation study. Patients were excluded prior to, or up to 2 years after a diagnosis with IBD, Celiac disease, IBS, all forms of colorectal cancer (primary and secondary), and anal cancer. Medical records were collected and data on clinical findings with assessments, X-ray examinations, endoscopies and laboratory results were reviewed. The basis of coding was compared with internationally accepted definitions for colonic diverticular disease. Positive predictive values (PPV) were calculated., Results: The overall PPV for all diagnoses and both years was 95% (95% CI: 93-96). The PPV for the year 2010 was slightly higher 98% (95% CI: 95-99) than in the year 2002, 91% (95% CI: (87-94) which may be due to the increasing use of computed tomography (CT)., Conclusion: The validity of DD in SNPR is high, making the SNPR a good source for population-based studies on DD.

Background and Aims: Inflammatory bowel disease may cause long-standing inflammation and fibrosis and may increase the risk of adverse events in colonoscopy. We evaluated whether inflammatory bowel disease and other potential risk factors are associated with bleeding or perforation in a nationwide, population-based, Swedish study., Methods: Data from 969 532 colonoscopies, including 164 012 [17%] on inflammatory bowel disease patients, between 2003 and 2019, were retrieved from the National Patient Registers. ICD-10 codes for bleeding [T810] and perforation [T812] within 30 days of the colonoscopy were recorded. Multivariable logistic regression was used to test if inflammatory bowel disease status, inpatient setting, time period, general anaesthesia, age, sex, endoscopic procedures, and antithrombotic treatment were associated with higher odds for bleeding and perforation., Results: Bleeding and perforation were reported in 0.19% and 0.11% of all colonoscopies, respectively. Bleeding [odds ratio 0.66, p <0.001] and perforation [odds ratio 0.79, p <0.033] were less likely in colonoscopies in individuals with inflammatory bowel disease status. Bleeding and perforation were more common in inpatient than in outpatient inflammatory bowel disease colonoscopies. The odds for bleeding but not perforation increased between 2003 to 2019. General anaesthesia was associated with double the odds for perforation., Conclusions: Individuals with inflammatory bowel disease did not have more adverse events compared with individuals without inflammatory bowel disease status. However, the inpatient setting was associated with more adverse events, particularly in inflammatory bowel disease status. General anaesthesia was associated with a greater risk of perforation., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: The etiopathogenesis of diverticular disease is unknown., Objective: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study., Methods: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/-5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not., Results: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not ( p  = .027)., Conclusions: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas . The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.

Objectives: Long-standing inflammatory bowel disease (IBD) colitis is an indication for endoscopic surveillance. Postcolonoscopy colorectal cancer (PCCRC), cancer detected after a negative colonoscopy, is a quality indicator for colonoscopy. In analogy with PCCRC, we aimed to assess postendoscopy CRC (PECRC) in individuals with IBD who had undergone colectomy., Methods: This register study included Swedish adults with an IBD diagnosis who had undergone colectomy and later were examined by either colonoscopy or sigmoidoscopy during 2001-2012. The final study population had a CRC diagnosis within 36 months of the index examination. Poisson regression was used to assess the relative risks (RR) of PECRC., Results: A total of 33 individuals, 12 with an ileorectal anastomosis and 21 with a rectal remnant, had a CRC diagnosis within 36 months of the index endoscopy. Eleven cancers were detected as CRCs, and 22 (67%) were PECRCs. Compared with individuals aged >70 years, individuals aged <30 years had an RR of 3.1 (P = 0.054) and individuals aged 30-50 years had a RR of 2.6 (P = 0.030). A longer interval between colectomy and index endoscopy (>10 vs. <10 years) was associated with a lower risk of PCCRC (RR = 0.5; P = 0.007). There was no significant difference between the risk for Crohn's disease vs. ulcerative colitis, or between ileorectal anastomosis and rectal remnant risks., Conclusions: Continuous surveillance of IBD patients after colectomy is important. In the postcolectomy context, PECRC may be used as a quality indicator., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Adequate bowel cleansing is essential for high-quality colonoscopy. Recently, a new very low-volume 1 litre (1L) polyethylene glycol (PEG) plus ascorbate solution (ASC) has been introduced. Our aims were to assess the effectiveness and tolerability of this product compared to low-volume 2L PEG-ASC and high-volume 4L PEG solutions, in a real-life setting. In six endoscopy units in Sweden, outpatients undergoing colonoscopy were either prescribed solutions according to local routines, or the very low-volume solution in split dose regimen. Bowel cleansing effectiveness and patient experience was assessed using the Boston Bowel preparation scale (BBPS) and a patient questionnaire. A total of 1098 patients (mean age 58 years, 52% women) were included. All subsegment and the total BBPS scores were significantly greater for 1L PEG-ASC in comparison to other solutions (p < 0.05 for 1L PEG-ASC and 4L PEG for transverse and left colon, otherwise p < 0.001). Nausea was more frequent with 1L PEG-ASC compared to 2L PEG-ASC (p < 0.001) and vomiting were more often reported compared to both other solutions (p < 0.01 and p < 0.05 for 2L PEG-ASC and 4L PEG, respectively). Smell, taste, and total experience was better for 1L PEG-ASC compared to 4L PEG (p < 0.001), and similar compared to the 2L PEG-ASC. In conclusion, 1L PEG-ASC leads to better bowel cleansing compared to 2L PEG-ASC or 4L PEG products, with similar or greater patient satisfaction.

Histologic sections from patients with inflammatory bowel disease (IBD) usually exhibit crypts with architectural distortions and branching crypts. It has been postulated that crypt branching should be assessed only in well-oriented, upright crypts. However, those crypts are mostly found in sections from colectomy specimens and colon mucosectomies. Sections from endoscopic biopsies are fortuitously cut in a horizontal plane, a procedure mostly revealing cross-cut crypt rings. In endoscopic biopsies from UC patients we previously detected cross-cut crypts heralding the crest domain of branching crypts. Recently, the scrutiny of biopsies from IBD patients revealed that branching-crest domains concurred either with crypts in symmetric branching, typified by twin, amalgamating back-to-back isometrics crypt-rings, or with crypts in asymmetric branching, characterized by ≥2 amalgamating anisometric crypt-rings; both symmetric and asymmetric branching-crest domains were encased by a thin muscularis mucosae. Quantitative studies in biopsies from Swedish and German patients with IBD showed that crypts in asymmetric branching outnumbered those in symmetric branching. Because crypt-branching seldom occurs in the normal colon in adults and considering that colon crypts typically divide once or twice during a lifetime, the accruing of asymmetric branching crypts in IBD biopsies emerges as a significant histologic parameter. Although the biological significance of asymmetric crypt-branching in IBD remains at present elusive, their occurrence deserves to be further investigated. The future policy will be to include in our pathologic reports, the number of crypts in asymmetric branching, in order to monitor their frequency in prospective surveillance biopsies in patients with IBD., (© 2021 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: An individual's drive to seek medical help remains a complex behavioural process, incorporating psychological, social and symptom-specific factors. Within irritable bowel syndrome (IBS), gastrointestinal symptoms only predict a small portion of the high healthcare-seeking experienced., Aim: To examine the moderating role of quality of life (QoL) domains on this relationship to help explain the variance observed., Methods: This is an analysis of a Swedish population-based prospective study of healthcare use over a 12-year period. At baseline, gastrointestinal symptoms were measured with the valid Gastrointestinal Symptom Rating Scale, and QoL via the SF-36. 1159 subjects (57% female; mean age 48.6 years) had their health records matched with the initial survey. 164 were classified as IBS by Rome II criteria. Negative binomial or logistic models were fit to evaluate the moderating effect of particular QoL domains on the relationship between gastrointestinal symptoms and prospective healthcare utilisation., Results: Gastrointestinal symptoms were associated with prospective healthcare use, but moderation in this relationship by particular QoL domains was not supported; most models did not reach statistical significance. Furthermore, the impact of IBS status did not alter the moderation hypotheses., Conclusions: Particular QoL domains did not impact the relationship between gastrointestinal symptoms on prospective healthcare seeking. Future research should continue to examine other psychological, social and symptom variables to identify predictors of high healthcare consumers in IBS., (© 2021 John Wiley & Sons Ltd.)

1: ESGE suggests performing segmental biopsies (at least two from each segment), which should be placed in different specimen containers (ileum, cecum, ascending, transverse, descending, and sigmoid colon, and rectum) in patients with clinical and endoscopic signs of colitis.Weak recommendation, low quality of evidence. 2: ESGE recommends taking two biopsies from the right hemicolon (ascending and transverse colon) and, in a separate container, two biopsies from the left hemicolon (descending and sigmoid colon) when microscopic colitis is suspected.Strong recommendation, low quality of evidence. 3: ESGE recommends pancolonic dye-based chromoendoscopy or virtual chromoendoscopy with targeted biopsies of any visible lesions during surveillance endoscopy in patients with inflammatory bowel disease. Strong recommendation, moderate quality of evidence. 4: ESGE suggests that, in high risk patients with a history of colonic neoplasia, tubular-appearing colon, strictures, ongoing therapy-refractory inflammation, or primary sclerosing cholangitis, chromoendoscopy with targeted biopsies can be combined with four-quadrant non-targeted biopsies every 10 cm along the colon. Weak recommendation, low quality of evidence. 5: ESGE recommends that, if pouch surveillance for dysplasia is performed, visible abnormalities should be biopsied, with at least two biopsies systematically taken from each of the afferent ileal loop, the efferent blind loop, the pouch, and the anorectal cuff.Strong recommendation, low quality of evidence. 6: ESGE recommends that, in patients with known ulcerative colitis and endoscopic signs of inflammation, at least two biopsies be obtained from the worst affected areas for the assessment of activity or the presence of cytomegalovirus; for those with no evident endoscopic signs of inflammation, advanced imaging technologies may be useful in identifying areas for targeted biopsies to assess histologic remission if this would have therapeutic consequences. Strong recommendation, low quality of evidence. 7: ESGE suggests not biopsying endoscopically visible inflammation or normal-appearing mucosa to assess disease activity in known Crohn's disease.Weak recommendation, low quality of evidence. 8: ESGE recommends that adequately assessed colorectal polyps that are judged to be premalignant should be fully excised rather than biopsied.Strong recommendation, low quality of evidence. 9: ESGE recommends that, where endoscopically feasible, potentially malignant colorectal polyps should be excised en bloc rather than being biopsied. If the endoscopist cannot confidently perform en bloc excision at that time, careful representative images (rather than biopsies) should be taken of the potential focus of cancer, and the patient should be rescheduled or referred to an expert center.Strong recommendation, low quality of evidence. 10: ESGE recommends that, in malignant lesions not amenable to endoscopic excision owing to deep invasion, six carefully targeted biopsies should be taken from the potential focus of cancer.Strong recommendation, low quality of evidence., Competing Interests: M. Barret has received consultancy fees from Medtronic (2018 to present) and Pentax (2019 to present). R. Bisschops has received consultancy and speaker’s fees from Fujifilm, Pentax, Medtronic (all 2015 to present), and Norgine (2016 to present), consultancy fees from Boston Scientific, Cook (both 2015 to present), CDx Diagnostics (2017 to present), and GI Supply (2018 to present), and speaker’s fees from Medivators (2017 to 2018) and Ipsen (2020 to present); his department has received research grants from Fujifilm, Pentax (both 2015 to present), Cook (2016 to 2019), and Medtronic (2018 to present). M. Dinis Ribeiro is co-editor-in-chief of Endoscopy; his department has received a research grant from Fujifilm (2020 to present) and an educational grant from Olympus (2020 to present). M. Iacucci has received research grant support from Pentax (2016 to present), Olympus (2018 to 2020), and Fujifilm (2019 to present). M.C.W. Spaander has received research support from Boston Scientific (2013 to present) and Cook Medical (2009 to 2013). J.E. van Hooft has received lecture fees from Medtronic (2014, 2015, and 2019) and Cook Medical (2019), and consultancy fees from Boston Scientific (2014 to 2017) and Olympus (2021); her department has received research grants from Abbot (2014 to 2017) and Cook Medical (2014 to 2019). K. Biermann, L. Czakó, K.B. Gecse, G. de Hertogh, T. Hucl, M. Jansen, R.E. Pouw, M. Rutter, E. Savarino, P.T. Schmidt, and M. Vieth declare that they have no conflict of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

Objective: Sessile serrated lesions without dysplasia (SSL-ND) are epitomised by dilated crypts with epithelial serrations and architectural distortions portraying boot-shapes, L-shapes or inverted-T shapes. Recently, crypts in asymmetric fission were detected in SSL-ND. The purpose was to assess the frequency of crypts in asymmetric fission in a cohort of SSL-ND., Methods: The frequency of crypts in fission was assessed in 60 SSL-ND, the distribution of cell proliferation in 48 SSL-ND and the expression of maspin, a tumour-suppressor protein, in 29 SSL-ND., Results: Out of the 60 SSL-ND, 40 (66.7%) showed crypts in fission: 39 (65%) SSL-ND had crypts in asymmetric fission and one SSL-ND (1.7%), in symmetric fission (p<0.05). Of 1495 crypts recorded in the 60 SSL-ND, 73 (4.9%) were in asymmetric fission but only one (0.06%), in symmetric fission (p<0.05). Out of the 48 Ki67-immunostained SSL-ND,15 (31%) showed randomly distributed proliferating cell-domains. All 29 SSL-ND revealed maspin-upregulation (including crypts in asymmetric and symmetric fission). In contrast, the normal colon mucosa showed occasional single crypts in symmetric fission, proliferating cell-domains limited to the lower thirds of the crypts, absence of crypts in asymmetric fission and remained maspin negative., Conclusions: SSL-ND thrive with crypts in asymmetric fission displaying randomly distributed proliferating cell-domains and maspin-upregulation. These histo-biological aberrations disclose pathological cryptogenesis and suggest possibly unfolding somatic mutations in SSL-ND. The present findings may open new vistas on the parameters pertinent to the susceptibility of SSL-ND to develop dysplasia and carcinoma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

1: ESGE recommends that, where there is a suspicion of eosinophilic esophagitis, at least six biopsies should be taken, two to four biopsies from the distal esophagus and two to four biopsies from the proximal esophagus, targeting areas with endoscopic mucosal abnormalities. Distal and proximal biopsies should be placed in separate containers.Strong recommendation, low quality of evidence. 2: ESGE recommends obtaining six biopsies, including from the base and edge of the esophageal ulcers, for histologic analysis in patients with suspected viral esophagitis.Strong recommendation, low quality of evidence. 3: ESGE recommends at least six biopsies are taken in cases of suspected advanced esophageal cancer and suspected advanced gastric cancer.Strong recommendation, moderate quality of evidence. 4: ESGE recommends taking only one to two targeted biopsies for lesions in the esophagus or stomach that are potentially amenable to endoscopic resection (Paris classification 0-I, 0-II) in order to confirm the diagnosis and not compromise subsequent endoscopic resection.Strong recommendation, low quality of evidence. 5: ESGE recommends obtaining two biopsies from the antrum and two from the corpus in patients with suspected Helicobacter pylori infection and for gastritis staging.Strong recommendation, low quality of evidence. 6: ESGE recommends biopsies from or, if endoscopically resectable, resection of gastric adenomas.Strong recommendation, moderate quality of evidence. 7: ESGE recommends fine-needle aspiration (FNA) and fine-needle biopsy (FNB) needles equally for sampling of solid pancreatic masses.Strong recommendation, high quality evidence. 8: ESGE suggests performing peroral cholangioscopy (POC) and/or endoscopic ultrasound (EUS)-guided tissue acquisition in indeterminate biliary strictures. For proximal and intrinsic strictures, POC is preferred. For distal and extrinsic strictures, EUS-guided sampling is preferred, with POC where this is not diagnostic.Weak recommendation, low quality evidence. 9: ESGE suggests obtaining possible non-neoplastic biopsies before sampling suspected malignant lesions to prevent intraluminal spread of malignant disease.Weak recommendation, low quality of evidence. 10: ESGE suggests dividing EUS-FNA material into smears (two per pass) and liquid-based cytology (LBC), or the whole of the EUS-FNA material can be processed as LBC, depending on local experience.Weak recommendation, low quality evidence., Competing Interests: M. Barret has received consultancy fees from Medtronic (2018 to present) and Pentax (2019 to present). R. Bisschops has received consultancy and speaker’s fees from Fujifilm, Pentax, Medtronic (all 2015 to present), and Norgine (2016 to present), consultancy fees from Boston Scientific, Cook (both 2015 to present), CDx Diagnostics (2017 to present), and GI Supply (2018 to present), and speaker’s fees from Medivators (2017 to 2018) and Ipsen (2020 to present); his department has received research grants from Fujifilm, Pentax (both 2015 to present), Cook (2016 to 2019), and Medtronic (2018 to present). M. Dinis Ribeiro is co-editor-in-chief of Endoscopy; his department has received a research grant from Fujifilm (2020 to present) and an educational grant from Olympus (2020 to present). M. Iacucci has received research grant support from Pentax (2016 to present), Olympus (2018 to 2020), and Fujifilm (2019 to present). M.C.W. Spaander has received research support from Boston Scientific (2013 to present) and Cook Medical (2009 to 2013). J.E. van Hooft has received lecture fees from Medtronic (2014, 2015, and 2019) and Cook Medical (2019), and consultancy fees from Boston Scientific (2014 to 2017) and Olympus (2021); her department has received research grants from Abbot (2014 to 2017) and Cook Medical (2014 to 2019). K. Biermann, L. Czakó, K.B. Gecse, G. de Hertogh, T. Hucl, M. Jansen, R.E. Pouw, M. Rutter, E. Savarino, P.T. Schmidt, and M. Vieth declare that they have no conflict of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

Aims: We previously found colonic crypts with asymmetric fission bordering regenerating ulcers in ulcerative colitis (UC). The present objective was to assess the frequency of asymmetric crypt-fission in colectomy specimens from patients with long-lasting UC., Methods: H&E-stained sections from seven colectomies from patients with UC without dysplasia or carcinoma were investigated. Symmetric fission was characterised by branched colon crypts showing ≥2 identical crypts, whereas asymmetric fission exhibited branched colon crypt portraying ≥2 dissimilar crypts, differing in diameter, length and/or shape., Results: The number of crypts in fission in the 89 sections was 3586; of those, 2930 (81.7%) were asymmetric and the remaining 656 (18.3%), symmetric. Out of 927 vertically-cut crypts (in well-oriented sections), 912 (98.4%) were asymmetric, and the remaining 14 (1.6%), symmetric, and out 2660, cross-cut (transected) crypts in fission, 2018 (75.9%) were asymmetric and the remaining 642 (24.1%), symmetric., Conclusion: Crypt fission is rarely found in the normal colon in adults. Symmetric crypt fission found in UC is possibly triggered by a compensatory homeostatic mechanism of crypt production in mucosal areas replaced by chronic inflammation. But asymmetric crypt fission is a pathological aberration that affects crypts in patients with a particular predisposition to develop mucosal dysplasia. It is suggested that this previously unattended histological parameter be included in the pathological descriptions of colectomy specimens from patients with UC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: We previously found crypts in symmetric fission (CSF) and in asymmetric fission (CAF) in colectomy-specimens with ulcerative colitis. We now analyzed CSF and CAF (CSAF) in biopsies from 80 patients with inflammatory bowel disease (IBD) without dysplasia or carcinoma., Patients and Methods: One unselected double-biopsy from affected endoscopic areas was investigated in the 80 cases., Results: A total of 353 crypts in fission were found. The median number of CAF/biopsy was 3.7 and for CSF/biopsy, 0.7 (p<0.00001)., Conclusion: CSAF often occur in unselected biopsies from patients with IBD. Whereas the increased frequency of CSF might mirror a compensatory mechanism of crypt production in areas occupied by inflammation, CAF reflects a pathological aberration of cryptogenesis, probably generated by somatic mutations. The biological significance of CAF in IBD without dysplasia or carcinoma, deserves to be further investigated., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Artificial intelligence (AI) is predicted to have profound effects on the future of video capsule endoscopy (VCE) technology. The potential lies in improving anomaly detection while reducing manual labour. Existing work demonstrates the promising benefits of AI-based computer-assisted diagnosis systems for VCE. They also show great potential for improvements to achieve even better results. Also, medical data is often sparse and unavailable to the research community, and qualified medical personnel rarely have time for the tedious labelling work. We present Kvasir-Capsule, a large VCE dataset collected from examinations at a Norwegian Hospital. Kvasir-Capsule consists of 117 videos which can be used to extract a total of 4,741,504 image frames. We have labelled and medically verified 47,238 frames with a bounding box around findings from 14 different classes. In addition to these labelled images, there are 4,694,266 unlabelled frames included in the dataset. The Kvasir-Capsule dataset can play a valuable role in developing better algorithms in order to reach true potential of VCE technology.

Background/aim: We recently noticed in nonpolypoid adenomas (NPA) and the adjacent normal mucosa, nondysplastic crypts in symmetric and asymmetric fission (NDCSAF)., Patients and Methods: All NDCSAF found in 80 small NPA and in the adjacent mucosa were registered., Results: A total of 178 NDCSAF (mean, 2.2) were found: 12 (6.7%) interspersed between adenomatous glands, 36 (20.2%) partially replaced by dysplastic epithelium, and 130 (73%) underneath the adenomatous tissue. Of the 61 cases with normal mucosa adjacent to NPA, 40 (65.6%) disclosed NDCSAF, and the remaining 21 (34.4%) normal crypts, exclusively., Conclusion: The accruing of NDCSAF within NPA and surrounding mucosa, are outstanding findings. Given that colonic crypts may undergo only one fission every 30-40 years, the accruing of NDCSAF in and about small NPA reveals mucosal hubs with pathological aberrations of cryptogenesis, probably conveyed by somatic mutations. The findings support the existence of field cancerization in the colonic mucosa., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

ESGE recommends the "pull" technique as the standard method for percutaneous endoscopic gastrostomy (PEG) placement.Strong recommendation, low quality evidence.ESGE recommends the direct percutaneous introducer ("push") technique for PEG placement in cases where the "pull" method is contraindicated, for example in severe esophageal stenosis or in patients with head and neck cancer (HNC) or esophageal cancer.Strong recommendation, low quality evidence.ESGE recommends the intravenous administration of a prophylactic single dose of a beta-lactam antibiotic (or appropriate alternative antibiotic, in the case of allergy) to decrease the risk of post-procedural wound infection.Strong recommendation, moderate quality evidence.ESGE recommends that inadvertent insertion of a nasogastric tube (NGT) into the respiratory tract should be considered a serious but avoidable adverse event (AE).Strong recommendation, low quality evidence.ESGE recommends that each institution should have a dedicated protocol to confirm correct positioning of NGTs placed "blindly" at the patient's bedside; this should include: radiography, pH testing of the aspirate, and end-tidal carbon dioxide monitoring, but not auscultation alone.Strong recommendation, low quality evidence.ESGE recommends confirmation of correct NGT placement by radiography in high-risk patients (intensive care unit [ICU] patients or those with altered consciousness or absent gag/cough reflex).Strong recommendation, low quality evidence.ESGE recommends that EN may be started within 3 - 4 hours after uncomplicated placement of a PEG or PEG-J.Strong recommendation, high quality evidence.ESGE recommends that daily tube mobilization (pushing inward) along with a loose position of the external PEG bumper (1 - 2 cm from the abdominal wall) could mitigate the risk of development of buried bumper syndrome.Strong recommendation, low quality evidence., Competing Interests: T. Beyna receives consultancy honoraria and lecture fees from Olympus and Boston Scientific (ongoing), and lecture fees from Medtronic, the Falk Foundation, and Erbe. E.J. Despott has received consultancy fees and speaker’s honoraria from Boston Scientific, Ambu, and Fujifilm (2007 to 2019); his department has received educational grants from Fujifilm, Pentax, Olympus, Boston Scientific, Norgine, Cook, Erbe, Medtronic, Ankon, Diagmed, and US Endoscopy (2017 to 2019). S.M. Schneider has been a board member for Nutricia France (2016 to 2018); he has been or is a consultant for Laboratoires Grand Fontaine (2013), Nestlé Health Sciences (2020), and Baxter (2019). J.E. van Hooft has received lecture fees from Medtronic (2014 to 2015, 2019) and Cook Medical (2019), and consultancy fees from Boston Scientific (2014 to 2017); her department has received research grants from Cook Medical (2014 to 2019), and Abbott (2014 to 2017). M. Arvanitakis, A. Ballarin, K. Boeykens, P. Elbe, I. Gisbertz, P. Gkolfakis, A. Hoyois, O. Mosteanu, D. Sanders, and P. Thelin-Schmidt declare that they have no conflicts of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

ESGE recommends considering the following indications for enteral tube insertion: (i) clinical conditions that make oral intake impossible (neurological conditions, obstructive causes); (ii) acute and/or chronic diseases that result in a catabolic state where oral intake becomes insufficient; and (iii) chronic small-bowel obstruction requiring a decompression gastrostomy.Strong recommendation, low quality evidence.ESGE recommends the use of temporary feeding tubes placed through a natural orifice (either nostril) in patients expected to require enteral nutrition (EN) for less than 4 weeks. If it is anticipated that EN will be required for more than 4 weeks, percutaneous access should be considered, depending on the clinical setting.Strong recommendation, low quality evidence.ESGE recommends the gastric route as the primary option in patients in need of EN support. Only in patients with altered/unfavorable gastric anatomy (e. g. after previous surgery), impaired gastric emptying, intolerance to gastric feeding, or with a high risk of aspiration, should the jejunal route be chosen.Strong recommendation, moderate quality evidence.ESGE suggests that recent gastrointestinal (GI) bleeding due to peptic ulcer disease with risk of rebleeding should be considered to be a relative contraindication to percutaneous enteral access procedures, as should hemodynamic or respiratory instability.Weak recommendation, low quality evidence.ESGE suggests that the presence of ascites and ventriculoperitoneal shunts should be considered to be additional risk factors for infection and, therefore, further preventive precautions must be taken in these cases.Weak recommendation, low quality evidence.ESGE recommends that percutaneous tube placement (percutaneous endoscopic gastrostomy [PEG], percutaneous endoscopic gastrostomy with jejunal extension [PEG-J], or direct percutaneous endoscopic jejunostomy [D-PEJ]) should be considered to be a procedure with high hemorrhagic risk, and that in order to reduce this risk, specific guidelines for antiplatelet or anticoagulant use should be followed strictly.Strong recommendation, low quality evidence.ESGE recommends refraining from PEG placement in patients with advanced dementia.Strong recommendation, low quality evidence.ESGE recommends refraining from PEG placement in patients with a life expectancy shorter than 30 days.Strong recommendation, low quality evidence*., Competing Interests: T. Beyna receives consultancy honoraria and lecture fees from Olympus and Boston Scientific (ongoing), and lecture fees from Medtronic, the Falk Foundation, and Erbe (ongoing). E.J. Despott has received consultancy fees and speaker’s honoraria from Boston Scientific, Ambu, and Fujifilm (2007 to 2019); his department has received educational grants from Fujifilm, Pentax, Olympus, Boston Scientific, Norgine, Cook, Erbe, Medtronic, Ankon, Diagmed, and US Endoscopy (2017 to 2019). S.M. Schneider has been a board member for Nutricia France (2016 to 2018); he has been or is a consultant for Laboratoires Grand Fontaine (2013), Nestlé Health Sciences (2020), and Baxter (2019). J.E. van Hooft has received lecture fees from Medtronic (2014 to 2015, 2019) and Cook Medical (2019), and consultancy fees from Boston Scientific (2014 to 2017); her department has received research grants from Cook Medical (2014 to 2019), and Abbott (2014 to 2017). M. Arvanitakis, A. Ballarin, K. Boeykens, P. Elbe, I. Gisbertz, P. Gkolfakis, A. Hoyois, O. Mosteanu, D. Sanders, and P. Thelin-Schmidt declare that they have no conflicts of interest., (European Society of Gastrointestinal Endoscopy. All rights reserved.)

Background: Recently, we found crypts with asymmetric fission bordering ulcers in colectomy specimens from patients with ulcerative colitis (UC). Here, we report crypts with asymmetric fission found in biopsies from patients with UC., Patients and Methods: Sections from endoscopic biopsies from five patients with UC were reviewed. The number of transected (cut-across) crypts in symmetric and asymmetric fission was assessed in sections from three biopsies in each patient., Results: A total of 89 crypts in fission were recorded in the 15 biopsies; 36 (40.4%) were in symmetric fission and the remaining 53 (59.6%) in asymmetric fission., Conclusion: A high frequency of asymmetric crypts in fission was demonstrated in endoscopic biopsies from patients with UC. It is suggested that this previously unaddressed histological parameter is included in pathological descriptions of endoscopic biopsies from patients with UC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Artificial intelligence is currently a hot topic in medicine. However, medical data is often sparse and hard to obtain due to legal restrictions and lack of medical personnel for the cumbersome and tedious process to manually label training data. These constraints make it difficult to develop systems for automatic analysis, like detecting disease or other lesions. In this respect, this article presents HyperKvasir, the largest image and video dataset of the gastrointestinal tract available today. The data is collected during real gastro- and colonoscopy examinations at Bærum Hospital in Norway and partly labeled by experienced gastrointestinal endoscopists. The dataset contains 110,079 images and 374 videos, and represents anatomical landmarks as well as pathological and normal findings. The total number of images and video frames together is around 1 million. Initial experiments demonstrate the potential benefits of artificial intelligence-based computer-assisted diagnosis systems. The HyperKvasir dataset can play a valuable role in developing better algorithms and computer-assisted examination systems not only for gastro- and colonoscopy, but also for other fields in medicine.

Background & Aims: There is debate over the optimal method for colonoscopic surveillance of patients with inflammatory bowel diseases. Guidelines recommend chromoendoscopy, but the value of chromoendoscopy in high-definition colonoscopy has not been proven. Furthermore, the value of random biopsies is controversial., Methods: We performed a prospective study of 305 patients with ulcerative colitis or Crohn's colitis referred for surveillance colonoscopy at a university hospital in Sweden, from March 2011 through April 2016. Patients randomly assigned to a group that received high-definition chromoendoscopy with indigo carmine (HD-CE; n = 152), collection of 32 random biopsies, and targeted biopsies or polypectomies or to a group that received high-definition white light endoscopy (HD-WLE; n = 153), collection of 32 random biopsies, and targeted biopsies or polypectomies. The primary endpoint was number of patients with dysplastic lesions., Results: Dysplastic lesions were detected in 17 patients with HD-CE and 7 patients with HD-WLE (P = .032). Dysplasias in random biopsies (n = 9760) were detected in 9 patients: 6 (3.9%) in the HD-CE group and 3 (2.0%) in the HD-WLE group (P = .72). Of the 9 patients with dysplasia, 3 patients (33%) had primary sclerosing cholangitis-only 18% of patients (54/305) included in the study had primary sclerosing cholangitis. The number of dysplastic lesions per 10 min of withdrawal time was 0.066 with HD-CE and 0.027 with HD-WLE (P = .056)., Conclusions: In a randomized trial, we found HD-CE with collection of random biopsies to be superior to HD-WLE with random biopsies for detection of dysplasia per colonoscopy. These results support the use of chromoendoscopy for surveillance of patients with inflammatory bowel diseases. ClinicalTrials.gov no: NCT01505842., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: The ethiopathogenesis of irritable bowel syndrome (IBS) is unknown. While a link to the gut microbiome is postulated, the heterogeneity of the healthy gut makes it difficult to draw definitive conclusions. We aimed to describe the faecal and mucosa-associated microbiome (MAM) and health correlates on a community cohort of healthy and IBS individuals with no colonoscopic findings., Design: The PopCol study recruited a random sample of 3556 adults; 745 underwent colonoscopy. IBS was defined by Rome IV criteria and organic disease excluded. 16S rRNA gene sequencing was conducted on sigmoid biopsy samples from 376 representative individuals (63 IBS cases) and faecal samples from 185 individuals (32 IBS cases)., Results: While sigmoid MAM was dominated by Lachnospiraceae, faeces presented a higher relative abundance of Ruminococcaceae. Microbial richness in MAM was linearly correlated to that in faeces from the same individual (R²=0.255, p<3E-11) as was diversity (R²=0.06, p=0.0022). MAM diversity decreased with increasing body mass index (BMI; Pearson's r=-0.1, p=0.08) and poorer self-rated health (r=-0.15, p=0.007), but no other health correlates. Faecal microbiome diversity was correlated to stool consistency (r=-0.16, p=0.043). Several taxonomic groups were correlated to age, BMI, depression and self-reported health, including Coprococcus catus associated with lower levels of depression (r=-0.003, p=0.00017). The degree of heterogeneity observed between IBS patients is higher than that observed between healthy individuals., Conclusions: No distinct microbial signature was observed in IBS. Individuals presenting with low self-rated health or high BMI have lower gut microbiome richness., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: There is controversy about whether psychological factors (anxiety and depression) increase health care seeking by patients with irritable bowel syndrome (IBS). We investigated whether psychological factors increase health care seeking by patients with IBS and the effects of extragastrointestinal (extra-GI) symptoms., Methods: We performed a population-based prospective study of health care use over a 12-year period in Sweden. From 2002 through 2006, 1244 subjects were selected randomly for an examination by a gastroenterologist and to complete questionnaires, including the Rome II modular questionnaire. Psychological factors were measured with the valid Hospital Anxiety and Depression scale and extra-GI symptoms were measured with a symptom checklist. Responses from 1159 subjects (57% female; mean age, 48.65 y) were matched with health records in 2016 (164 were classified as having IBS based on Rome II criteria)., Results: The overall association between depression or anxiety and health care use varied in subjects with and without IBS at baseline. The presence of extra-GI symptoms strengthened the relationship between anxiety and depression and prospective psychiatric visits for subjects with IBS and without IBS (incidence rate ratio, 1.14-1.26). Extra-GI symptoms did not alter the association of anxiety or depression with use of GI or extra-GI health care., Conclusions: In a population-based study in Sweden, we found that individuals with high baseline anxiety or depression were more likely to seek psychiatric health care, but not GI or extra-GI health care, in the presence of extra-GI symptoms at baseline. Patients with IBS might benefit from more thorough assessments that examine extra-GI and psychological symptoms, to reduce health care utilization., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background/aim: Sessile serrated polyps without dysplasia (SSPND) are characterized by crypts with serrated epithelium, albeit with irregular, corrupted shapes (CCS)., Patients and Methods: Cell proliferation was explored in the CCS from 60 SSPND and in the crypts from 12 normal colons. Sections were immuno-stained with the Ki-67 proliferation-cell (PC) marker, and with the p53 tumour-suppressor gene., Results: Three predominant PC-phenotypes were found in the CCS from the 60 SSPND: 44 (73.3%) exhibited ectopic, asymmetric, randomly distributed PC-clusters, 12 (20.0%), continuous PC in one or in both slopes of the crypts, and in the remaining 4 (6.7%), single, randomly distributed PC were recorded. In contrast, the scrutiny of more than 200,000 normal colon crypts (controls) showed symmetrically aligned PC, restricted to the lower third of the crypts. p53-up-regulation in CCS was recorded in 11(18.3%) of the 60 NDSSP, but in none of the normal crypts in the 12 controls., Conclusion: The non-dysplastic epithelium that lines CCS in SSPND coexists with an asymmetric relocation of the PC-domains. In addition, the CCS in nearly one-fifth of the SSPND exhibited p53-up-regulated cells. Taken together, the non-dysplastic CCS epithelium in SSPND thrives with somatic mutations. The accretion of putative mutated non-dysplastic CCS might be a crucial event in the evolution of colonic SSPND towards sessile serrated adenomas., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Obesity is a risk factor for colorectal cancer (CRC)., Objective: The objective of this article is to investigate whether anthropometric measures reflecting visceral obesity are better predictors of CRC than body mass index (BMI)., Methods: Data were analysed from the Malmö Diet and Cancer study in Sweden, comprising 16,669 women and 10,805 men (median age 56.6 and 59.1 years) followed for a median 21.5 years. Diagnoses of CRC were identified using Swedish national registers. Cox regression was used to test the associations of BMI, waist circumference (WC), waist-hip ratio, waist-to-height ratio, waist-to-hip-to-height ratio, A Body Shape Index (ABSI) and percentage body fat with the development of CRC adjusted for age, alcohol consumption, smoking, education and physical activity in men and women., Results: None of the measures were significantly associated with an increased risk for CRC in women. WC was the strongest predictor of colon cancer (CC) in men and the only measure that was independent of BMI. ABSI was the only measure significantly associated with the risk of rectal cancer in men., Conclusions: Visceral obesity, best expressed as WC, is a risk factor for CC in men but a poor predictive marker for CRC in women., (© Author(s) 2019.)

Background/aim: Colonic crypts with normal epithelium albeit with corrupted shapes (CCS) were previously found beneath nonpolypoid adenomas (NPA). This study aimed to analyze the distribution of proliferating cells (PC) and p53-up-regulated cells in CCS., Materials and Methods: Sections from 48 NPA were immunostained with the proliferating-marker Ki67 and against the tumor-suppressor protein p53., Results: Asymmetric-haphazardly distributed PC were found in 87.5% of the NPA, continuous PC-domains in 8.3%, asymmetric-haphazardly distributed single PC in 4.2% and p53-up-regulated cells in 29.2%. In 12 controls, the normal-shaped crypts revealed symmetrically-distributed PC-domains in their lower thirds, and no p53-up-regulated cells., Conclusion: The normal epithelium that lines the CCS below NPA, thrives with relocated PC-domains, and with occasional p53-up-regulated cells. These findings strongly suggest that the normal epithelium of CCS beneath NPA might harbor somatic mutations. The accretion of putative mutated CCS might play an important role in the evolution of nonpolypoid adenomas in the human colon., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and study aims: Barrett's esophagus is a premalignant condition in the distal esophagus associated with esophageal adenocarcinoma. Since gastroesophageal reflux is known to be of etiological importance in both Barrett's esophagus and esophageal adenocarcinoma, we aimed to study which endoscopic alterations at the Z-line can be attributed to a previous history of reflux symptoms. Patients and methods: From 1988, a population cohort in Sweden has been prospectively studied regarding gastrointestinal symptoms, using a validated questionnaire. In 2012, the population was invited to undergo a gastroscopy and participate in the present study. In order to determine which endoscopic alterations that can be attributed to a previous history of gastroesophageal reflux, three different endoscopic definitions of columnar-lined esophagus (CLE) were used: (1) ZAP I, An irregular Z-line with a suspicion of tongue-like protrusions; (2) ZAP II/III, Distinct, obvious tongues of metaplastic columnar epithelium; (3) CLE ≥1 cm, The Prague C/M-classification with a minimum length of 1 cm. Results: A total of 165 community subjects were included in the study. Of these, 40 had CLE  ≥  1 cm, 99 had ZAP I, and 26 had ZAP II/III. ZAP II/III was associated with an over threefold risk of previous GER symptoms (OR: 3.60, CI: 1.49-8.70). No association was found between gastroesophageal reflux and ZAP I (OR: 2.06, CI: 0.85-5.00), or CLE ≥1 cm (OR: 1.64, CI: 0.77-3.49). Conclusions: In a general community, the only endoscopic alteration to the Z-line definitely linked to longstanding GER symptoms was the presence of obvious tongues of metaplastic columnar epithelium (ZAP II/III).

Background/aim: Sessile serrated polyps (SSP) are characterized by crypts with corrupted shapes (CCS)., Materials and Methods: The number of CCS and the lateral size of 60 non-dysplastic SSP (NDSSP) were investigated., Results: Out of 60 NDSSP, 34 were small (≤9 mm) and 26, large (≥10 mm). In total, 1,101 CCS were recorded: 547 CCS were connected to the lumen (CCSL) and 554 CCS were not (CCSNL). The lateral size of NDSSP, the total number of CCS and the number of CCSNL were significantly higher in large NDSSP than in small NDSSP. Conversely, the number of CCS connected to the lumen/mm (CCSL/mm) and of crypts with normal shapes connected to the lumen/mm (CCSNL/mm), were significantly lower in large NDSSP than in small NDSSP., Conclusion: The lateral expansion of large NDSSP ensues via increased numbers of CCS at the expense of a decreased number of both CCSL/mm and CCSNL/mm., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

We previously found colonic crypts with normal epithelial lining but with corrupted shapes (NECS) beneath the adenomatous tissue of conventional adenomas (CoAs). Here we assessed the distribution of proliferating cells (PCs) and explored the possible occurrence of p53-upregulated cells in the NECS in a cohort of CoAs. Sections from 70 CoAs and from 12 normal colon segments were immunostained with the proliferation marker Ki67. In 60 of the 70 CoAs, additional sections were immunostained for the tumor suppressor p53 protein. NECS with asymmetric, haphazardly distributed single PC or PC clusters were recorded in 80% of the CoAs, with a continuous PC domain in one or both slopes of the crypts in 17%, and with haphazardly distributed single PCs in the remaining 3% of the CoAs. In the 12 normal segments (controls), the colon crypts demonstrated normal shapes with symmetric PC domains limited to the lower third portion of the crypts. In 30% of the 60 CoAs immunostained with p53 the NECS revealed haphazardly distributed p53-upregulated cells, singly or in clusters. In sum, the apparently normal epithelium of the NECS beneath the adenomatous tissue of CoAs revealed an unprecedented relocation of the normal PC domains. This unexpected event and the occurrence of p53-upregulated cells strongly suggest that the crypts beneath the neoplastic tissue of CoAs harbor somatic mutations. The accretion of putative mutated NECS beneath the neoplastic canopy of CoA emerges as a previously unaddressed major event, an event that might play an important role in the histogenesis of CoA in the human colon., (© 2019 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Background: Studies on incidence rates of first-time colonic diverticular disease are few, and population-based estimates of lifetime risk are lacking. In this observational study, the incidence, admission rates and lifetime risks of hospitalization and surgery for diverticular disease were investigated., Methods: Considering the entire Swedish population as an open cohort, incidence and admission rates, and lifetime risk estimates (considering death as a competing risk) of hospitalization and surgery for diverticular disease were calculated using data from cross-linked national registers and population statistics from 1987 to 2010., Results: In total, there were 144 107 hospital admissions for diverticular disease in 95 049 individual patients. Of these, 17 599 were admissions with bowel resection or stoma formation in 16 824 patients. The total number of person-years in the population during the study period was 213 949 897. Age-standardized incidence rates were 47·4 (95 per cent c.i. 47·1 to 47·7) for first-time hospitalization with diverticular disease and 8·4 (8·2 to 8·5) per 100 000 person-years for diverticular disease surgery. The corresponding admission rates (including readmissions) were 70·8 (70·4 to 71·2) and 8·7 (8·6 to 8·9) per 100 000 person-years. Following an increase in 1990-1994, rates stabilized. Based on incidence and mortality rates from 2000 to 2010, the estimated remaining lifetime risk of hospitalization from 30 years of age was 3·1 per cent in men and 5·0 per cent in women. The corresponding risk of surgery was 0·5 per cent in men and 0·8 per cent in women., Conclusion: Diverticular disease is a common reason for hospital admission, particularly in women, but rates are stable and the lifetime risk of surgery is low., (© 2019 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Objective: Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease., Design: Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry., Results: We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p<0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3×10 -10 and 0.002 (OR allelic =1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33)., Conclusion: In silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Low-grade chronic inflammation has been suggested to play a role in uncomplicated asymptomatic and symptomatic diverticular disease. However, population-based studies are lacking. We investigated whether community participants with diverticulosis, with or without symptoms, would have colonic inflammation on histology and serology., Methods: In a nested case-control study of 254 participants from the population-based colonoscopy (PopCol) study, colonic histological inflammatory markers and serological C-reactive protein levels were analyzed in cases with diverticulosis and controls without diverticulosis. Statistical methods included logistic and linear regression models., Results: Background variables including age (P = 0.92), sex (P = 1.00), body mass index (P = 0.71), smoking (P = 0.34), and recent antibiotic exposure (P = 0.68) were similar between cases and controls. Cases reported more abdominal pain (P = 0.04) and diarrhea symptoms (mushy and high-frequency stools) than controls (P = 0.01 and P = 0.03, respectively) but were otherwise similar. The median C-reactive protein levels were similar among cases and controls [1.05 mg/L (0.3, 2.7) vs 0.8 (0.4, 2.2), P = 0.53]. There was a trend of increased numbers of cecal lymphoid aggregates in cases vs controls (P = 0.07), but no other associations between diverticulosis and inflammatory markers on histology were found. Similarly, no serological or mucosal inflammation was associated with symptomatic cases of diarrhea or abdominal pain vs asymptomatic controls., Conclusions: In a general community sample, both asymptomatic and symptomatic diverticulosis are not associated with colonic mucosal inflammation. Other explanations for symptomatic colonic diverticulosis need to be identified.

Background: Colonic crypts with normal epithelial lining exhibiting corrupted shapes (NECS) have been previously found beneath the adenomatous tissue of polypoid conventional adenomas, in both rats and humans., Aim: To assess the frequency of NECS in non-polypoid colonic flat adenomas (FAs) and lateral-spreading adenomas (LSAs)., Materials and Methods: Histological hematoxylin and eosin-stained sections from 51 non-polypoid colonic adenomas were scrutinized over a 10-mm field of vision (FOV). FAs were regarded lesions encompassed within the FOV and LSAs as those surpassing that limit. The NECS/mm ratio was calculated in individual lesions as the number of NECS beneath the adenomatous tissue, divided by the length (mm) of the FA and LSA., Results: Out of the 51 non-polypoid adenomas, 27 were FAs and the remaining 24 LSAs. All 51 non-polypoid lesions were tubular adenomas. The mean number of NECS in FAs was 6.29 (range=2-10) and in LSAs was 15.29 (range=7-41) (p<0.05). On the other hand, the mean NECS/mm ratio in FAs was 0.94 (range=0.50-2.00) and in LSAs was 0.92 (range=0.40-2.93). Thus, no essential differences in the number of NECS/mm was found between FA and LSA., Conclusion: The accretion of NECS below the neoplastic canopy of FA and LSA contrasts with the rare occurrence of NECS in normal colonic mucosa. This finding emerges as a previously unaddressed major event, an event that might play an important role in the histogenesis of non-polypoid adenomas of the colon., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Patients with irritable bowel syndrome (IBS) often associate their symptoms to certain foods. In congenital sucrase-isomaltase deficiency (CSID), recessive mutations in the SI gene (coding for the disaccharidase digesting sucrose and 60% of dietary starch) 1 cause clinical features of IBS through colonic accumulation of undigested carbohydrates, triggering bowel symptoms. 2 Hence, in a previous study, 3 we hypothesized that CSID variants reducing SI enzymatic activity may contribute to development of IBS symptoms. We detected association with increased risk of IBS for 4 rare loss-of-function variants typically found in (homozygous) CSID patients, because carriers (heterozygous) of these rare variants were more common in patients than in controls. 1,4 Through a 2-step computational and experimental strategy, the present study aimed to determine whether other (dys-)functional SI variants are associated with risk of IBS in addition to known CSID mutations. We first aimed to identify all SI rare pathogenic variants (SI-RPVs) on the basis of integrated Mendelian Clinically Applicable Pathogenicity (M-CAP) and Combined Annotation Dependent Depletion (CADD) predictive (clinically relevant) scores; next, we inspected genotype data currently available for 2207 IBS patients from a large ongoing project to compare SI-RPV case frequencies with ethnically matched population frequencies from the Exome Aggregation Consortium (ExAC)., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The burden of diverticular disease on society is high and is increasing with an aging population. It is therefore important to identify risk factors for disease development or progression. Many lifestyle behaviors during adolescence affect risk for later disease. We searched for adolescent lifestyle factors that affect risk of diverticular disease later in life., Methods: We performed a retrospective analysis of data from 43,772 men (age, 18-20 y) conscripted to military service in Sweden from 1969 through 1970, with a follow-up period of 39 years. All conscripts underwent an extensive mental and physical health examination and completed questionnaires covering alcohol consumption, smoking, and use of recreational drugs; cardiovascular fitness was assessed using an ergometer cycle at the time of conscription. Outcome data were collected from national registers to identify discharge diagnoses of diverticular disease until the end of 2009. We performed Cox regression analysis to determine whether body mass index, cardiovascular fitness, smoking, use of recreational drugs, alcohol consumption, and risky use of alcohol, at time of conscription are independent risk factors for development of diverticular disease., Results: Overweight and obese men had a 2-fold increased risk of diverticular disease compared to normal-weight men (hazard ratio, 2.00; P < .001). A high level of cardiovascular fitness was associated with a reduced risk of diverticular disease requiring hospitalization (P = .009). Smoking (P = .003), but not use of recreational drugs (P = .11), was associated with an increased risk of diverticular disease requiring hospitalization. Risky use of alcohol, but not alcohol consumption per se, was associated with a 43% increase in risk of diverticular disease requiring hospitalization (P = .007)., Conclusions: In a retrospective analysis of data from 43,772 men in Sweden, we associated being overweight or obese, a smoker, a high-risk user of alcohol, and/or having a low level of cardiovascular fitness in late adolescence with an increased risk of developing diverticular disease requiring hospitalization later in life. Improving lifestyle factors among adolescents might reduce the economic burden of diverticular disease decades later., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Colonic crypts with normal epithelial lining displaying corrupted shapes (called non-dysplastic crypts with corrupted shapes, NDCs) were earlier recorded underneath the adenomatous glands of conventional colon adenomas in rats., Aim: To assess the frequency of NDCs in clinical sporadic conventional (tubular/villous) adenomas., Materials and Methods: NDCs found underneath the adenomatous epithelium in 255 sporadic conventional adenomas removed at endoscopy were classified into four groups: i) With fission distortions, ii) with length distortions, iii) with outline distortions, and iv) with axial polarity distortions. In 22 controls, the colonic mucosa proximal or distal to surgically removed colonic adenocarcinomas was scrutinized for NDCs., Results: Nearly three-quarters of the sporadic conventional adenomas investigated here had three or more NDCs underneath the adenomatous tissue, those with ≥4 NDCs being more frequent (46.3%) than those having 1, 2 or 3 NDCs (p<0.05). Nineteen out of the 22 control colon segments had normal crypts and the remaining three had occasional NDCs (mean=3.7, range=2-5)., Conclusion: NDCs were found underneath the adenomatous glands in all 255 sporadic conventional adenomas. Occasionally, NDCs were present in the mucosa of the stalk of pediculated conventional adenomas. The absence of adenomatous tissue in NDCs of the stalk should rule out the possibility that the adenomatous tissue on top had directly orchestrated the development of NDCs below. Moreover, NDCs rarely occurred in controls. Accordingly, NDCs emerge as a genuine phenomenon of crypt deformation in sporadic conventional adenomas. Considering that human colonic crypts typically divide at most once or twice during a lifetime, with an average crypt cycle length of 36 years, the accumulation of NDCs underneath sporadic conventional adenomas is remarkable. In light of these considerations, it is suggested that these putative mutated NDCs may represent the initial histological recordable event heralding the development of sporadic conventional adenomas in the human colon., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Appendicitis and acute diverticulitis share clinical features and are both influenced by genetic and environmental factors. Appendectomy has been positively associated with diverticular disease in hospital-based case-control studies., Objective: The aim of the present study was to investigate, in a population-based setting, whether appendectomy, with or without appendicitis, is associated with an altered risk of hospitalization with diverticular disease., Design: This was a population-based case-control study., Settings: The study was based on national healthcare and population registers., Patients: We studied 41,988 individuals hospitalized between 2000 and 2010 with a first-time diagnosis of colonic diverticular disease and 413,115 matched control subjects., Main Outcome Measures: The association between appendectomy with or without appendicitis and diverticular disease was investigated by conditional logistic regression, including a model adjusting for hospital use., Results: A total of 2813 cases (6.7%) and 19,037 controls (4.6%) had a previous record of appendectomy (appendectomy with acute appendicitis: adjusted OR = 1.31 (95% CI, 1.24-1.39); without appendicitis: adjusted OR = 1.30 (95% CI, 1.23-1.38)). Appendectomy was most strongly associated with an increased risk of diverticular disease within 1 year (with appendicitis: adjusted OR = 2.26 (95% CI, 1.61-3.16); without appendicitis: adjusted OR = 3.98 (95% CI, 2.71-5.83)), but the association was still present ≥20 years after appendectomy (with appendicitis: adjusted OR = 1.22 (95% CI, 1.12-1.32); without appendicitis: adjusted OR = 1.19 (95% CI, 1.10-1.28))., Limitations: Detailed clinical information on the cases was not available. There were unmeasured potential confounders, such as smoking and dietary factors., Conclusions: The findings are consistent with a hypothesis of appendectomy causing an increased risk of diverticular disease, for example, by affecting the mucosal immune system or the gut microbiome. However, several other mechanisms may contribute to, or account for, the positive association, including a propensity for abdominal pain increasing the risk of both the exposure and the outcome. See Video Abstract at http://links.lww.com/DCR/A604.

The continuity of the subepithelial band of lamina propria-indigenous macrophages (SBLP-M) discourages commensal gut bacteria from invading the host. In this Review we analyzed the impact of a disintegrating SBLP-M in inflammatory bowel disease (IBD), which results in microbiota inflow, inadequate immune responses and IBD-associated colon cancer. In previous work, we analyzed endoscopic biopsies taken from normal-looking descending colon in 247 patients with IBD, and 167 from control patients without IBD. Sections immunostained for cluster of differentiation 68 (CD68) protein showed no inflammatory changes. In IBD, the band of CD68+ SBLP-M was fragmented or minute in 59% (47/80) and absent in 9% (7/80). In contrast, only 31% (51/167) of the biopsies from control patients had a fragmented/minute band of CD68+ SBLP-M and this band was not absent in any (p<0.05). The finding that the band of CD68+ SBLP-M was fragmented to totally lost in IBD suggests a long-lasting defect in the barrier against the gut microbiome in IBD. The lack of ongoing inflammation in colonic biopsies should rule-out the participation of bone marrow-derived inflammation-elicited macrophages in loss of the barrier. Today, it is widely accepted that dysbiosis and inappropriate immune response to microbial flora play a pivotal role in the pathogenesis and development of IBD-associated colon cancer. Based on present knowledge, it is submitted that defects in the SBLP-M barrier in IBD encourage the trespassing of the gut microflora into the host, thereby destabilizing host immunity. These events in concert may play the ultimate pivotal role in the evolution of colon cancer in patients with IBD., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background & Aims: Genetic factors are believed to affect risk for irritable bowel syndrome (IBS), but there have been no sufficiently powered and adequately sized studies. To identify DNA variants associated with IBS risk, we performed a genome-wide association study (GWAS) of the large UK Biobank population-based cohort, which includes genotype and health data from 500,000 participants., Methods: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations., Results: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 × 10 -8 ) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0×10 -6 ). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 × 10 -10 in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKBKAP), which is mutated in patients with familial dysautonomia., Conclusions: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background/aim: In ulcerative colitis (UC) the colonic mucosa shows, in addition to a high number of inflammatory cells, crypts with architectural distortions, called corrupted colonic crypts (CCC). Here we classify the histologic repertoire and assess the frequency of CCC in UC., Patients and Methods: Five-hundred and sixteen histologic sections from 29 colectomy specimens with UC (24 having adenocarcinoma and five, high-grade dysplasia, HGD) were reviewed., Results: The vast majority of the colonic mucosa portrayed countless crypts with normal shapes (CNS) lined with normal epithelium, except for 45 CNS: 28 showed inconclusive-suspected cellular changes (ISCC), and 17, high-grade dysplasia (HGD). CCC were subdivided into four groups: i) Crypts with fission distortions, ii) Crypts with length distortions, iii) Crypts with outline distortions and iv) Crypts with axial polarity distortions. The most frequent CCC group had axial polarity distortions (33.4%), and the less frequent CCC group, outline distortions (21.1%) (p<0.05). No apparent differences in frequency between groups were found in colectomies with HGD/carcinoma, or in colectomies preformed for medically-refractory UC without HGD/carcinoma. Out of the 902 CCC present in the specimens, 343 (38.0%) displayed ISCC, 186 (20.6%) HGD, and the remaining 373 (41.4%) normal epithelium. Hence, of the 203 crypts exhibiting HGD, 186 (91.6%) were CCC and the remaining 17 (8.4%) CNS (p<0.05)., Conclusion: Based on these findings it is suggested that the microscopic search for HGD in UC colectomy-specimens should preferentially be focused on mucosal areas exhibiting CCC. This view is validated by recent findings showing that p53 overexpression (a biomarker of epithelial carcinogenesis) significantly correlated with architectural distortions of the crypts in UC., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aims: The integrity of the band of indigenous macrophages in the subepithelial layer of the lamina propria (SLP) is crucial in preventing the commensal gut microbiota from attacking the host. The breakdown of the SLP macrophage barrier results in microbiota inflow and improper immune responses; this might lead to inflammatory bowel disease (IBD). During inflammation, the SLP macrophage barrier is reinforced by inflammation-elicited macrophages (IEMs), which are derived from blood-circulating monocytes. The aim was to explore the characteristics of the SLP macrophage band in a cohort of biopsies without inflammation, in patients with ulcerative colitis in remission (UCre), and in patients with right-sided Crohn's colitis (RCC)., Methods and Results: Endoscopic biopsies were taken from endoscopically normal descending colon in 247 patients; 80 with IBD (27 UCre and 53 RCC), and 167 without IBD [90 had colonic diarrhoea, 63 were enrolled in a colorectal cancer (CRC) surveillance programme, seven had microscopic colitis in remission, and seven had miscellaneous colonic ailments]. Sections showed no inflammatory changes; they were immunostained with CD68. Among patients with UCre and RCC, the SLP band of CD68+ macrophages was fragmented or minute in 59% (47/80) and negative in 9% (7/80). In contrast, only 31% (51/167) of the biopsies from control patients had a fragmented/minute SLP band of CD68+ macrophages, and none had a negative SLP band of CD68+ macrophages (IBD versus controls, P < 0.05)., Conclusions: The finding that the SLP macrophage barrier was fragmented to totally abrogated in UCre and RCC patients suggests a longlasting defect in the SLP CD68+ macrophage barrier in these patients. The lack of ongoing inflammation in colonic biopsies should rule out the participation of bone marrow-derived IEMs in the abrogation of the SLP macrophage barrier reported here., (© 2017 John Wiley & Sons Ltd.)

Objective: IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase-isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase ( SI ) gene variants for their potential relevance in IBS., Design: We sequenced SI exons in seven familial cases, and screened four CSID mutations (p.Val557Gly, p.Gly1073Asp, p.Arg1124Ter and p.Phe1745Cys) and a common SI coding polymorphism (p.Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p.Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population., Results: CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05)., Conclusions: SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients., Competing Interests: Competing interests: The work was partially financed by an unrestricted grant from Medical Need Europe AB to MDA. MDA and HYN have received unrestricted research grants and lecturing honoraria from QOL Medical, and LC has served on a scientific advisory board for QOL Medical., (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/.)

Aims: The majority of the colorectal carcinomas (CRC) arise in a vast mucosal area built with columnar cells and mucus-producing goblet cells. These carcinomas evolve via the conventional (tubular/villous) adenoma-carcinoma pathway, or the serrated adenoma-carcinoma pathway. Much less frequently CRC arise in the gut-associated lymphoid tissue (GALT) mucosal domain via the third pathway of colorectal carcinogenesis., Methods: All publications on human colorectal GALT carcinomas in the literature were reviewed., Results: Only 23 GALT-carcinomas found in 20 patients are in record. The GALT carcinomas were detected at surveillance colonoscopic biopsy in 11 patients (four had ulcerative colitis, two were members of a Lynch syndrome family, two of a CRC family, one had familial adenomatous polyposis (FAP), one prior colon adenomas and one a submucosal tumour), or at diagnostic colonoscopic biopsy in the remaining nine patients (three had rectal bleedings, two abdominal pains, one diverticular disease and one protracted constipation. In three, no ground disease or symptoms were provided). In six of the 23 GALT carcinomas, the luminal surface showed tumour cells, ulcerations or no descriptions were given. Ten (66.7%) of the remaining 15 GALT carcinomas showed on top, adenomas (n=8) or high-grade dysplasia (n=2)., Conclusions: The low frequency of GALT carcinomas might be explained by the fact that the colorectal mucosal areas occupied by GALT domains are minute. The finding that two-thirds of the 15 remaining GALT carcinomas ( vide supra ) were covered by high-grade dysplasia or by conventional adenomas strongly suggest that conventional non-invasive neoplasias might have preceded the majority of the GALT carcinomas in record., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: To describe the development and implementation of a person-centered endoscopy safety checklist and to evaluate the effects of a "checklist intervention"., Methods: The checklist, based on previously published safety checklists, was developed and locally adapted, taking patient safety aspects into consideration and using a person-centered approach. This novel checklist was introduced to the staff of an endoscopy unit at a Stockholm University Hospital during half-day seminars and team training sessions. Structured observations of the endoscopy team's performance were conducted before and after the introduction of the checklist. In addition, questionnaires focusing on patient participation, collaboration climate, and patient safety issues were collected from patients and staff., Results: A person-centered safety checklist was developed and introduced by a multi-professional group in the endoscopy unit. A statistically significant increase in accurate patient identity verification by the physicians was noted (from 0% at baseline to 87% after 10 mo, P < 0.001), and remained high among nurses (93% at baseline vs 96% after 10 mo, P = nonsignificant). Observations indicated that the professional staff made frequent attempts to use the checklist, but compliance was suboptimal: All items in the observed nurse-led "summaries" were included in 56% of these interactions, and physicians participated by directly facing the patient in 50% of the interactions. On the questionnaires administered to the staff, items regarding collaboration and the importance of patient participation were rated more highly after the introduction of the checklist, but this did not result in statistical significance ( P = 0.07/ P = 0.08). The patients rated almost all items as very high both before and after the introduction of the checklist; hence, no statistical difference was noted., Conclusion: The intervention led to increased patient identity verification by physicians - a patient safety improvement. Clear evidence of enhanced person-centeredness or team work was not found., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report.

Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT 4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT 4 R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT 4 receptor gene HTR4 to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms HTR4b/i and putatively impairs HTR4 expression. Subsequent miRNA-profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms. In vitro assays confirmed expression regulation via three 3'UTR binding sites. The novel isoform HTR4b&#95;2 lacking two of the three miRNA binding sites escapes miR-16/103/107 regulation in SNP carriers. We provide the first evidence that HTR4 expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or by diminished levels of miR-16 and miR-103 suggesting that HTR4 might be involved in the development of IBS-D.