Colonic ulcerations may predict steroid-refractory course in patients with ipilimumab-mediated enterocolitis

To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy

Roadmap on structured light

Structured light refers to the generation and application of custom light fields. As the tools and technology to create and detect structured light have evolved, steadily the applications have begun to emerge. This roadmap touches on the key fields within structured light from the perspective of experts in those areas, providing insight into the current state and the challenges their respective fields face. Collectively the roadmap outlines the venerable nature of structured light research and the exciting prospects for the future that are yet to be realized

Colonic ulcerations may predict steroid-refractory course in patients with ipilimumab-mediated enterocolitis

AIM: To investigate management of patients who develop ipilimumab-mediated enterocolitis, including association of endoscopic findings with steroid-refractory symptoms and utility of infliximab as second-line therapy. METHODS: We retrospectively reviewed all patients at our center with metastatic melanoma who were treated with ipilimumab between March 2011 and May 2014. All patients received a standard regimen of intravenous ipilimumab 3 mg/kg every 3 wk for four doses or until therapy was stopped due to toxicity or disease progression. Basic demographic and clinical data were collected on all patients. For patients who developed grade 2 or worse diarrhea (increase of 4 bowel movements per day), additional data were collected regarding details of gastrointestinal symptoms, endoscopic findings and treatment course. Descriptive statistics were used. RESULTS: A total of 114 patients were treated with ipilimumab during the study period and all were included. Sixteen patients (14%) developed ≥ grade 2 diarrhea. All patients were treated with high-dose corticosteroids (1-2 mg/kg prednisone daily or equivalent). Nine of 16 patients (56%) had ongoing diarrhea despite high-dose steroids. Steroid-refractory patients received one dose of intravenous infliximab at 5 mg/kg, and all but one had brisk resolution of diarrhea. Fourteen of the patients underwent either colonoscopy or sigmoidoscopy with variable endoscopic findings, ranging from mild erythema to colonic ulcers. Among 8 patients with ulcers demonstrated by sigmoidoscopy or colonoscopy, 7 patients (88%) developed steroid-refractory symptoms requiring infliximab. With a median follow-up of 264 d, no major adverse events associated with prednisone or infliximab were reported. CONCLUSION: In patients with ipilimumab-mediated enterocolitis, the presence of colonic ulcers on endoscopy was associated with a steroid-refractory course

Optimizing perioperative Crohn's disease management: Role of coordinated medical and surgical care

AimTo investigate rates of re-establishing gastroenterology care, colonoscopy, and/or initiating medical therapy after Crohn's disease (CD) surgery at a tertiary care referral center.MethodsCD patients having small bowel or ileocolonic resections with a primary anastomosis between 2009-2012 were identified from a tertiary academic referral center. CD-specific features, medications, and surgical outcomes were abstracted from the medical record. The primary outcome measure was compliance rates with medical follow-up within 4 wk of hospital discharge and surveillance colonoscopy within 12 mo of surgery.ResultsEighty-eight patients met study inclusion criteria with 92% (n=81) of patients returning for surgical follow-up compared to only 41% (n=36) of patients with documented gastroenterology follow-up within four-weeks of hospital discharge, P<0.05. Factors associated with more timely postoperative medical follow-up included younger age, longer length of hospitalization, postoperative biologic use and academic center patients. In the study cohort, 75.0% of patients resumed medical therapy within 12 mo, whereas only 53.4% of patients underwent a colonoscopy within 12 mo of surgery.ConclusionOur study highlights the need for coordinated CD multidisciplinary clinics and structured handoffs among providers to improve of quality of care in the postoperative setting

Targeted next-generation sequencing supports serrated epithelial change as an early precursor to inflammatory bowel disease–associated colorectal neoplasia

Serrated epithelial change (SEC) manifests in patients with long-standing inflammatory bowel disease (IBD) and is characterized by disorganized crypt architecture, irregular serrations, and goblet cell–rich epithelium. The serrated nature of SEC is reminiscent of serrated colorectal polyps, which frequently harbor KRAS/BRAF mutations. SEC is, however, not only histologically distinct from sporadic serrated polyps but also associated with colorectal neoplasia. Whether SEC is a precursor to IBD-associated neoplasia remains unclear. To further define the relationship of SEC with serrated colorectal polyps and IBD-associated neoplasia, we performed targeted next-generation sequencing on colorectal specimens to include the following: SEC without dysplasia/neoplasia (n = 10), SEC with separate foci of associated dysplasia/adenocarcinoma from the same patients (n = 17), and uninvolved mucosa (n = 10) from 14 patients. In addition, we molecularly profiled sessile serrated lesion (SSL)–like or serrated lesion, not otherwise specified (SL-NOS), specimens, from 11 patients who also had IBD. This control cohort included SSL-like/SL-NOS without dysplasia/neoplasia (n = 11), SSL-like/SL-NOS with associated low-grade dysplasia (n = 2), and uninvolved mucosa (n = 8). By next-generation sequencing, the most frequently mutated gene in SEC without neoplasia and associated dysplasia/adenocarcinoma from separate foci in the same patients was TP53. Recurrent TP53 mutations were present in 50% of SEC specimens without dysplasia/neoplasia. In addition, alterations in TP53 were detected at a prevalence of 71% in low-grade dysplasia, 83% in high-grade dysplasia, and 100% in adenocarcinoma. Paired sequencing of SEC and associated neoplasia revealed identical TP53 missense mutations for 3 patients. In contrast, 91% of SSL-like/SL-NOS specimens without dysplasia/neoplasia harbored KRAS/BRAF mutations, which were conserved in associated low-grade dysplasia. No genomic alterations were found in uninvolved mucosa from either patients with SEC or patients with SSL-like/SL-NOS. Based on our findings, we conclude SEC is distinct from SSL-like serrated colorectal lesions in patients with IBD and an early precursor to IBD-associated neoplasia that warrants colonoscopic surveillance

Nearly a Third of High-Grade Dysplasia and Colorectal Cancer Is Undetected in Patients with Inflammatory Bowel Disease

It is unclear whether intensive surveillance protocols have resulted in a decreased incidence of colorectal cancer (CRC) in inflammatory bowel disease (IBD). To determine the prevalence and characteristics of IBD associated high-grade dysplasia (HGD) or CRC that was undetected on prior colonoscopy. This is a single-center, retrospective study from 1994 to 2013. All participants had a confirmed IBD diagnosis and underwent a colectomy with either HGD or CRC found in the colectomy specimen.The undetected group had no HGD or CRC on prior colonoscopies. The detected group had HGD or CRC identified on previous biopsies. Of 70 participants, with ulcerative colitis (UC) (n = 47), Crohn's disease (CD) (n = 21), and indeterminate colitis (n = 2), 29% (n = 20) had undetected HGD/CRC at colectomy (15 HGD and 5 CRC). In the undetected group, 75% had prior LGD, 15% had indefinite dysplasia, and 10% had no dysplasia (HGD was found in colonic strictures). Patients in the undetected group were more likely to have pancolitis (55 vs. 20%) and multifocal dysplasia (35 vs. 8%). The undetected group was less likely to have CRC at colectomy (25 vs. 62%). There was a trend toward right-sided HGD/CRC at colectomy (40 vs. 20%; p = 0.08). In addition, 84% of the lesions found in the rectum at colectomy were not seen on prior colonoscopy in the undetected group. The prevalence of previously undetected HGD/CRC in IBD found at colectomy was 29%. The high proportion of undetected rectal and right-sided HGD/CRC suggests that these areas may need greater attention during surveillance

Constrained multiple instance learning for ulcerative colitis prediction using histological images

[EN] Background and Objective: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) affecting the colon and the rectum characterized by a remitting-relapsing course. To detect mucosal inflammation as-sociated with UC, histology is considered the most stringent criteria. In turn, histologic remission (HR) correlates with improved clinical outcomes and has been recently recognized as a desirable treatment target. The leading biomarker for assessing histologic remission is the presence or absence of neutrophils. Therefore, the finding of this cell in specific colon structures indicates that the patient has UC activity. However, no previous studies based on deep learning have been developed to identify UC based on neu-trophils detection using whole-slide images (WSI). Methods: The methodological core of this work is a novel multiple instance learning (MIL) framework with location constraints able to determine the presence of UC activity using WSI. In particular, we put forward an effective way to introduce constraints about positive instances to effectively explore additional weakly supervised information that is easy to obtain and enjoy a significant boost to the learning process. In addition, we propose a new weighted embedding to enlarge the relevance of the positive instances. Results: Extensive experiments on a multi-center dataset of colon and rectum WSIs, PICASSO-MIL, demon-strate that using the location information we can improve considerably the results at WSI-level. In com-parison with prior MIL settings, our method allows for 10% improvements in bag-level accuracy. Conclusion : Our model, which introduces a new form of constraints, surpass the results achieved from current state-of-the-art methods that focus on the MIL paradigm. Our method can be applied to other histological concerns where the morphological features determining a positive WSI are tiny and similar to others in the image.This work has received funding from Horizon 2020, the European Unions Framework Programme for Research and Innovation, under grant agreement No. 860627 (CLARIFY) , the Spanish Ministry of Economy and Competitiveness through project PID2019-105142RB-C21 (AI4SKIN) and GVA through projects PROMETEO/2019/109 and INNEST/2021/321 (SAMUEL) . Roco del Amor and Adrin Colomer work have also been supported by the Spanish Government under FPU Grant (FPU20/05263) and the Universitat Politcnica de Valncia (PAID-10-21-Subprograma 1), respectively. We gratefully acknowledge the support from the Generalitat Valenciana (GVA) with the donation of the DGX A100 used for this work, action co-financed by the European Union through the Operational Program of the European Regional Development Fund of the Comunitat Valenciana 2014¿2020 (IDIFEDER/2020/030).Del Amor, R.; Meseguer, P.; Lorenzo Parigi, T.; Villanacci, V.; Colomer, A.; Launet, L.; Bazarova, A.... (2022). Constrained multiple instance learning for ulcerative colitis prediction using histological images. Computer Methods and Programs in Biomedicine. 224:1-8. https://doi.org/10.1016/j.cmpb.2022.1070121822