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In summer 2011, Shiga toxin producing Escherichia coli (EHEC) serotype O104:H4 caused the most severe EHEC outbreak in Germany to date. The case of a previously recovered patient with symptomatic postinflammatory colonic stenosis following EHEC- infection prompted us to conduct a prospective study to assess the macro- and microscopic intestinal long-term damage in a cohort of patients who had suffered from severe EHEC colitis.Following EHEC infection in 2011, 182 patients were offered to participate in this study between January 2013 and October 2014 as part of the post-inpatient follow-up care at the University Medical Center Hamburg-Eppendorf and to undergo colonoscopy with stepwise biopsies. Prior to colonoscopy, medical history and persistent post-infectious complaints were assessed.Out of 182 patients, 22 (12%) participated in the study, 18 (82%) were female. All patients had been hospitalized due severe EHEC enterocolitis: 20 patients (90%) had subsequently developed hemolytic uremic syndrome (HUS), 16 patients (72%) had additionally required dialysis. On assessment prior to colonoscopy, all patients denied any abdominal complaints before EHEC-infection but 8 (36%) patients reported persistent post-infectious symptoms. According to the ROME IV criteria, 4 (18%) patients met the definition for post-infectious irritable bowel syndrome (PI-IBS). In all patients with persistent symptoms, colonoscopies and histological examination were unremarkable. Only in one symptom-free patient, biopsy revealed a locally limited cryptitis of the caecum, while all patients without complaints had inconspicuous histological and endoscopical findings.Following infection colonic stenosis is a serious but rare long-term complication in patients who had suffered from severe enterocolitis. However, a significant proportion of these patients develop PI-IBS.Im Sommer 2011 verursachten Shiga-Toxin produzierende Escherichia coli (EHEC) -Serotyp O104: H4 den bislang schwersten EHEC-Ausbruch in Deutschland und Europa. Der Fall einer zuvor gesunden Patientin mit symptomatischer, postentzündlicher Kolonstenose nach EHEC-Infektion veranlasste uns, die makro- und mikroskopischen Langzeitschäden des Kolons prospektiv in einer Kohorte von Patienten zu untersuchen, die an einer schweren EHEC-Kolitis gelitten hatten.Zwischen Januar 2013 und Oktober 2014 wurden 182 Patienten mit nachgewiesener EHEC O104:H4-Infektion im Rahmen der poststationären Nachsorge am Universitätsklinikum Hamburg-Eppendorf eine Studienteilnahme einschließlich einer kompletten Ileo-Koloskopie mit Stufenbiopsien angeboten. Der bisherige Krankheitsverlauf sowie postinfektiös anhaltende Beschwerden wurden vor der Koloskopie erfasst.Von 182 Patienten nahmen 22 (12%) an der Studie teil,18 (82%) waren weiblich. Alle Patienten waren aufgrund einer schwerer EHEC-Enterokolitis stationär behandelt worden: 20 Patienten (90%) hatten während der Infektion ein hämolytisch-urämisches Syndrom (HUS) entwickelt, 16 Patienten waren intermittierend dialysepflichtig. Alle Patienten verneinten abdominelle Beschwerden vor der stattgehaben EHEC-Infektion, aber 8 (36%) Patienten berichteten über anhaltende postinfektiöse Symptome. Gemäß den ROME IV-Kriterien erfüllten 4 (18%) Patienten die Definition für das postinfektiöse Reizdarmsyndrom (PI-IBS). Bei allen Patienten mit persistierenden Beschwerden zeigte sich in der folgenden Koloskopie ein unauffälliger makro- und mikroskopischer Befund. Nur bei einem symptomfreien Patienten ergab die Biopsie eine lokal begrenzte Kryptitis des Coecums.Nach einer Infektion ist eine Kolonstenose eine schwerwiegende, aber seltene Langzeitkomplikation bei Patienten mit schwerer Enterokolitis. Ein signifikanter Anteil dieser Patienten entwickelt jedoch PI-IBS.

Objective The aim is to improve morphological diagnostics, including differential, of UC and IBS, identifying morphological features of cellular infiltration in the mucous membrane ofthe large intestine. Patients and methods Material and methods: Autopsy and biopsy material - fragments of the mucous membrane of the large intestine was used in this study. All the material was divided into 5 groups. Group 1 included autopsy material from 6 cases, in which no general pathological processes in the gastrointestinal tract were detected during autopsy and microscopic examination. Group 2 included biopsy material from 34 patients with diagnosed UC of the 1st activity degree. Group 3 included the biopsy material of 27 patients with UC of the 2nd degree of activity. Group 4 included biopsy material from 19 patients, diagnosed with UC of the 3rd degree of activity. Group 5 included biopsy material from 82 patients with clinically diagnosed IBS. Histological, morphometrical, immunohistochemical and statistical methods of investigation were used. Results Results: The mucous membrane of the large intestine in patients with ulcerative colitis of varying degrees of activity, compared with the physiological norm, has pronounced infiltration by plasma cells, T-lymphocytes, B-lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic leukocytes in the superficial parts of the epithelium, crypts,lamina propria. There is also an increase in the number and size of lymphoid follicles in the lamina propria. Predominant cellular elements in the infiltrate are plasma cells, T-lymphocytes, eosinophilic and neutrophilic leukocytes. The growth of ulcerative colitis activity leads to an increase the inflammatory cell infiltration in the mucous membrane of the colon, as evidenced an increase the density of cellular infiltrate; the severity of inflammatory changes in crypts and an increase in the number of crypt abscesses; a decrease the number of cases with focal infiltration in the lamina propria and an increase the number of cases with diffuse infiltration; the spread of inflammatory cell infiltration from the superficial parts of the lamina propria to its deep parts with the subsequent involvement of its entire thickness; an increase the central trends of the indexes of the severity of all cellular infiltration, infiltration by plasma cells, T-lymphocytes, macrophages, neutrophilic leukocytes. The mucous membrane of the large intestine in patients with irritable bowel syndrome has moderately pronounced cellular infiltration in the superficial epithelium andlamina propria, in comparison with the physiological norm. The number and size of lymphoid follicles increase. Inflammatory cell infiltration often spreads to the upper onethird or two thirds of the thickness of the lamina propria, characterized by the presence of plasma cells, T-lymphocytes, B-lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic leukocytes. In this case, plasma cells, T-lymphocytes, mast cells and macrophages dominate. The indexes of the severity of all cellular infiltration, as well as infiltration by plasma cells, T-lymphocytes, B-lymphocytes, macrophages, mast cells, eosinophilic and neutrophilic leukocytes, increases in the mucous membrane of the large intestine in irritable bowel syndrome in comparison with the norm. In the mucous membrane of the large intestine in irritable bowel syndrome compared with ulcerative colitis of varying degrees of activity inflammatory cell infiltration is less pronounced. It often extends to one third or two thirds of the thickness of the lamina propria. There are fewer lymphoid follicles, cryptitis and crypt abscesses are not determined. The indexes of the severity of all cellular infiltration, as well as infiltration by plasma cells, T-lymphocytes, eosinophilic and neutrophilic leukocytes are lower. Conclusion Conclusions: The revealed features of cellular infiltration in the mucous membrane of the large intestine make it possible to improve morphological diagnostics, including differential, of ulcerative colitis of varying degrees of activity and irritable bowel syndrome.

Background and study aim: The term non-specific colitis refers to an inflammatory condition of the colon that microscopically lacks the characteristic features of any specific form of colitis and is commonly seen in pathology reports of colonoscopy biopsies. In fact, it has been questioned whether it is a separate pathological entity or it is merely an intermediate stage in the course of inflammatory bowel disease. This study was conducted to estimate the prevalence of non-specific colitis among patients with colitis and characterize its natural history over a 6 months year period. Patients and methods: Eighty adult patients presented for colonoscopy were enrolled. In the final analysis they were divided into Group A; the non-specific colitis Group and Group B; the inflammatory bowel disease Group. All patients were subjected to: full history taking, full clinical examination, laboratory investigations: which included stool analysis, CRP, ESR, complete colonoscopy and entire random colon biopsies for histopathological examination. Results: Group A included 67 patients (83.75%) while Group B included 13 (16.25%) patients. Patients with IBD had clinical and laboratory features of inflammation significantly higher than patients with non-specific colitis. Six patients (8.95%) of non-specific colitis group developed histologic features of florid inflammatory bowel disease after 6 months. There were no independent predictors of this conversion. Conclusion: Among our 80 patients with colonoscopy and biopsy 67 (83.75%) were diagnosed as non-specific colitis and out of them 6 patients (8.95%) were reexamined after 6 months and proved to have inflammtory bowel disese this change was not linked to predictive factors. Resumo: Introdução e objetivos: O termo colite inespecífica (CI) refere-se a uma condição inflamatória do cólon que microscopicamente não apresenta características de qualquer forma específica de colite; é comumente observada em relatórios patológicos de biópsias de colonoscopia. De fato, tem-se questionado se esta seria uma entidade patológica separada ou apenas um estágio intermediário no curso da DII. Este estudo foi realizado para estimar a prevalência de CI entre pacientes com colite e caracterizar seu curso durante um período de seis meses. Pacientes e métodos: O estudo incluiu 80 pacientes adultos que se apresentaram para colonoscopia. Na análise, os pacientes foram divididos em dois grupos: grupo A (CI) e grupo B (DII) Todos os pacientes foram submetidos a anamnese completa, exame clínico completo e investigações laboratoriais que incluíram análise de fezes, PCR, VHS, colonoscopia completa e biópsias aleatórias de cólon para exame histopatológico. Resultados: Do total de pacientes, 67 foram alocados no grupo A (83,75%) e 13 (16,25%) no grupo B. Os pacientes com DII apresentavam sinais clínicos e laboratoriais de inflamação significativamente maiores do que o observado em pacientes com CI. Seis pacientes (8,95%) do grupo CI desenvolveram características histológicas de DII florida após seis meses. Não foram identificados preditores independentes para essa conversão. Conclusão: Entre os 80 pacientes submetidos a colonoscopia e biópsia, o diagnóstico de CI foi feito em 67 (83,75%); destes, seis pacientes (8,95%) foram reexaminados após seis meses e apresentaram DII, sendo que essa conversão não foi associada a fatores preditivos. Keywords: Nonspecific colitis, Inflammatory bowel disease, Colonoscopy, Cryptitis, Palavras-chave: Colite inespecífica, Doença inflamatória intestinal, Colonoscopia, Criptite

Background The clinical features of amoebic colitis resemble those of inflammatory bowel disease (IBD), and therefore the risk of misdiagnosis is very high. The aim of this study was to analyse the characteristics of the endoscopic and pathological findings of amebic colitis and the lessons from our patients, which were useful for diagnosing the amebic colitis timely and avoiding the serious complication. Methods We retrospectively reviewed data of all amebic colitis admitted to Beijing Friendship Hospital from January 2015 to January 2020. Cases were diagnosed by clinical presentation, laboratory examinations, and colonoscopy with biopsy and histological examination, no ELISA stool antigen or PCR tests were used. Results 16 patients were diagnosed with amebic colitis by the colonoscopy accompanied by biopsy and microscopic examination. At first time, 12 (75%) patients were misdiagnosed as IBD. Cecum was the most common site of amebic colitis (100%), and the caecum and rectum were also involved in many lesions (68.75%). Multiple lesions of erosion and/or ulcer were recognized in all patients (100%).The endoscopic findings included multiple irregular shaped ulcers and erosions with surrounding erythema, and the ulcers and erosions were covered by the white or yellow exudates. The intervening mucosae between the ulcers or erosions were normal. The features of rectums can be divided to 2 types: in 6 patients (54.5%), the irregular ulcer or erosions covered with white or yellow exudates were observed in rectum and cecum, and the bloody exudates in rectum were more severe than those in cecum; in other 5 patients (45.5%), rectal lesions were much less severe than those in cecum, the small superficial erosion or reddened mucosa were observed in the rectal ampulla. All patients were diagnosed as detection of amebic trophozoites from HE-stained biopsy specimens. The number of trophozoites ranged from 1/HPF to > 50/HPF. Among 16 cases, mild architectural alteration of colon crypt were observed in 10 cases (62.5%), and serious architectural alteration of colon crypt was found which had crypt branch in 1 case (16.7%). Cryptitis was observed in 12 cases (75%) and its severity was mild or moderate. No crypts abscess was observed in all cases. Conclusions The colonoscopy with histological examination are very important to diagnose the amebic colitis. Detect the amoebic trophozoites in the exudates by histological examination is the vital. Sometimes a negative biopsy does not rule out amebiasis, repeated biopsies may be needed to make the diagnosis.

Inflammatory bowel diseases are gaining more interest in the past few years. Ulcerative colitis (UC) is a chronic disease that requires accurate follow-up for a good treatment plan. Colonoscopy alone cannot be efficient to detect disease extent and has a high risk of perforation in acute severe UC and toxic megacolon. Computed tomographic enterocolonography (CTE) is widely used now to detect intramural, extra-intestinal involvement and intestinal complications. Hence, this study aimed to evaluate CTE in the assessment of the degree of activity of UC.This cross-sectional study was carried on 50 UC patients, divided into 36 males and 14 females presented at the Gastroenterology Unit, Alexandria Main University, Faculty of Medicine. Assessment of UC activity was done to all patients on three levels; the ulcerative colitis disease activity index for the clinical level, ulcerative colitis endoscopic index of severity by endoscopy and pathologically by degree of neutrophilic invasion, crypt abscess or cryptitis, presence of oedema and mucosal surface ulceration, then CTE was done and the findings were compared with the histopathological findings. Bowel wall thickening in CTE was divided into: normal (3 mm, score 0), mild (3-6 mm, score 1), moderate (6-9 mm, score 2) and severe (9 mm, score 3). Mesenteric hyperaemia, mucosal hyper enhancement and enlarged pericolic lymph nodes were recorded.CTE findings in the form of bowel wall thickening and hyper enhancement were found in 74% of active cases and were correlated with all histopathological findings investigated in this study with high statistical significance except in chronic stages, whereas lymph node enlargement and mesenteric hyperaemia did not show statistical significance with disease activity.CTE is a good tool for diagnosing disease activity in UC.

Tacrolimus is a common immunosuppressant used in solid organ transplant recipients. Although most patients develop diarrheal symptoms, data regarding patterns of injury in patients taking tacrolimus are limited. We performed this study to characterize tacrolimus-related features of colonic injury. We retrospectively identified colonic samples from 20 patients receiving tacrolimus monotherapy. Records were reviewed for symptoms, endoscopic findings, other medications, and infections. None of the patients had gastrointestinal infections or used other drugs known to cause colonic injury; none had received mycophenolate within 6 months of presentation. Cases were evaluated for the nature and distribution of inflammation and crypt abnormalities, including distortion, destruction, and apoptosis. Eighteen (90%) patients were solid organ transplant recipients. Seventeen (85%) had gastrointestinal symptoms, particularly diarrhea (75%). More than 50% had endoscopic colitis and 15% had ulcers and/or erosions. Most (90%) cases showed regenerative epithelial changes; apoptotic crypt cells were present in 55% and numerous in 10% of cases. Neutrophilic cryptitis was present in 60% of cases; 35% showed crypt destruction. Plasma cell-rich lamina propria inflammation and crypt distortion were observed in 40% and 25% of cases, respectively. There was no correlation between therapy duration and features of chronic injury. We conclude that tacrolimus can cause symptomatic colitis. Histologic abnormalities are often mild, featuring regenerative crypts and scattered apoptotic debris. However, 40% of symptomatic patients have chronic colitis, most likely reflecting drug-induced immune dysregulation. Pathologists should be aware of these associations because colitis often resolves with decreasing drug dosage rather than treatment directed toward inflammatory bowel disease.

Gastrointestinal side effects of interferon (IFN) therapy for chronic hepatitis C virus (HCV) infection are non-specific. Rarely, this therapy has been reported to induce ischemic colitis and even ulcerative colitis. However, IFN-induced Crohn’s disease (CD) has previously been reported in only two individuals. We share our own experience of a patient treated for chronic HCV infection who developed CD after IFN therapy for chronic HCV infection. A 28-year-old asymptomatic man with a history only of chronic HCV infection was treated with IFN and ribavirin, which he tolerated for 18 months and achieved sustained viral response (SVR). Halfway through the IFN regimen, he noticed infrequent painful bowel movements and bloody diarrhea. Following treatment, his symptoms resolved. Six months after therapy, colonoscopy showed a normal terminal ileum and colitis with skipped lesions and rectal sparing. Pathology demonstrated spotty chronic active colitis, with diffuse cryptitis, crypt distortion, and abundant abscesses, compatible with CD. The patient declined treatment and remained asymptomatic for two years. Labs including C-​reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin, and celiac panel were normal. Upper GI endoscopy and capsule endoscopy were normal. Repeat colonoscopy showed normal terminal ileum and normal colonic mucosa, and biopsies of the terminal ileum and all segments of the colon were unremarkable. The patient was observed off treatment and has continued to remain asymptomatic, with a resolution of symptoms and disease continuing away from IFN exposure. This is a rare case of CD induced by IFN, exhibiting significant importance regarding the evaluation of new cases of inflammatory bowel disease (IBD). Gastroenterologists need to keep in mind that INF therapy can be an uncommon cause of IBD.

Granulomatous appendicitis is uncommon. It can be caused by infectious or systemic disorders, such as Crohn’s disease (CD) and sarcoidosis. It is therefore essential to investigate systematic causes of granulomatous appendicitis after surgery by appropriate examinations. It is also rare for acute appendiceal inflammation to develop due to active CD. We herein report a case of CD presenting as granulomatous appendicitis. The patient was a 28-year-old man who arrived at the emergency room with right lower abdominal pain. Computed tomography showed a low-density lesion with a clear boundary and a small high-density spot in its center behind the cecum. Acute appendicitis with abscess formation was suspected and conservative treatment was started. After 3 consecutive days of conservative treatment there was no improvement in his condition. We therefore performed open appendectomy. Histopathological examination showed numerous noncaseous epithelioid granulomas in the wall of the appendix. Specific staining revealed no evidence of acid-fast bacilli or fungi. During follow-up after discharge, colonoscopy demonstrated erosion from the cecum to the transverse colon. A colon biopsy showed severe inflammation with cryptitis, Paneth cells, and a granulomatous lesion. The patient was therefore diagnosed with CD and treatment with mesalazine was started. Careful examination is necessary to diagnose and properly treat patients with granulomatous inflammation of the appendix.

In patients with Crohn’s disease (CD) that underwent surgery, predictive factors of surgical recurrence have been only partially identified. The aim of our study was to identify potential factors associated with an increased risk of surgical recurrence. A monocentric retrospective observational study was conducted including patients diagnosed with CD, according to ECCO criteria who received their first ileocolic resection. Overall, 162 patients were enrolled in our study; 54 of them were excluded due to a lack of sufficient data. The median follow-up was 136.5 months, IQR 91.5–176.5, and the surgical recurrence rate after the median follow-up was 21.3%. In the multivariate analysis, an age ≤ 28 years at the first surgical resection (aHR = 16.44, p < 0.001), current smoking (aHR = 15.84, p < 0.001), female sex (aHR = 7.58, p < 0.001), presence of granulomas at local lymph nodes (aHR = 12.19, p < 0.001), and treatment with systemic corticosteroids after the first surgical resection (aHR = 7.52, p = 0.002) were factors significantly associated with a risk of surgical recurrence, while cryptitis resulted in a protective factor (aHR = 0.02, p < 0.001). In conclusion, the heterogeneous spectrum of factors associated to the risk of surgical recurrence in patients with CD that underwent ileocolic resection supports the need of a personalized follow-up taking into account different clinical, surgical, and histologic features.

Background Various molecular-targeted therapeutic agents that inhibit cytokines and immune checkpoints are used in clinical practice. Some of these biologics that control immunity, such as anti-interleukin-17, anti-programmed cell death protein-1, and anti-cytotoxic T-lymphocyte-associated protein antibodies, affect intestinal immune homeostasis and cause intestinal inflammation. Development of enteritis due to dupilumab (an anti-IL-4Ralpha monoclonal antibody) therapy is not yet reported in the literature. Case presentation A 17-year-old man was administered an injection of dupilumab and continued to receive it for refractory atopic dermatitis. After 3 months of initiating dupilumab therapy, he developed intermittent abdominal pain, tenesmus, and had diarrhea. Colonoscopy examination showed decreased vascularity, mild friability, and erythema in the cecum, part of the ascending colon, sigmoid colon, and rectum without any pathogenic bacteria. Histological examination revealed moderate mixed inflammatory cell infiltration, cryptitis, destruction of the crypt, decreased goblet cells, mucosal erosions, and edema. He was diagnosed with UC and was prescribed oral mesalazine (4800 mg/day) treatment. Within a month of the treatment, his diarrhea improved and the frequency of defecation decreased. Conclusions This is a first report that dupilumab mimicked ulcerative colitis. Careful monitoring for adverse effects with the onset of an intestinal inflammation will be recommended after dupilumab administration.

Introduction/Objective A segment of right colon is sometimes included with small intestinal allografts to preserve the ileocecal valve and maintain water reabsorption. We correlated pathological findings of colon allograft biopsies obtained during surveillance colonoscopies with clinical, endoscopic, and microbiologic findings. Methods/Case Report All colon allograft biopsies from surveillance colonoscopies over a 3-year period were reviewed for crypt apoptotic activity, cryptitis, lamina propria inflammation, ulceration, and crypt architectural distortion. Clinical and endoscopic findings, and positive cultures a week before and after the biopsies were recorded. Results (if a Case Study enter NA) There were 129 colon biopsies from 29 patients; 98 were histologically normal, whereas 28 showed rare apoptoses (n=14), focal cryptitis (n=8), increased intraepithelial lymphocytes (n=2), moderate acute rejection (n=1), and crypt architectural distortion (n=2). Of these 29 patients, 8 had abnormal endoscopic findings, 21 were normal. Out of 8 patients with abnormal endoscopic exams, 50% had normal histology on biopsy. Twenty-one biopsies were associated with positive cultures in the blood (n=5), urine (n=16) or wound, peritoneal, stool (n=6); 3 had abnormal endoscopies, and 4, abnormal histology. One patient with C.difficle toxin had normal endoscopy and focal cryptitis, whereas another with CMV DNA in blood showed endoscopically congested mucosa and rare apoptoses on biopsy. Of 12 biopsies (7 patients) with abnormal endoscopic findings, (erythema, congestion, ulceration), 4 biopsies had no pathologic findings, 8 had rare apoptosis, and one each had focal cryptitis and chronic colitis. Paired small intestinal biopsies were present with 59 biopsies; 10 showed rare apoptosis and 2, focal cryptitis. Of 70 without paired small intestinal biopsies, there were 5 with rare apoptotic bodies, 5 with focal cryptitis, and 2 with crypt architectural distortion. Conclusion The correlation of histologic, endoscopic, and microbiologic findings in colonic allograft surveillance biopsies is inconsistent. Colon allograft biopsies have limited utility in the follow-up of patients, particularly in absence of paired small intestinal biopsies.

Background Knowledge about inflammatory bowel disease (IBD) in patients with Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles, could provide insights into IBD in general. Objective To expand the understanding of IBD in patients with HPS. Methods Retrospective review of records from patients with HPS evaluated at the National Institutes of Health Clinical Center from 1995 to 2019 was conducted. Clinical features of IBD, genotyping results and histologic findings of colectomy specimens were analysed. Results IBD affected 37 (14.2%; 12 male, 25 female) of 261 patients with HPS. Median age of onset was 17 years; range was 1 to 52 years. The most common symptoms of HPS IBD were hematochezia, abdominal pain and loose stools. Fistulae or extra-intestinal manifestations developed in 30% or 22%, respectively. Genotyping showed that patients with biallelic variants in HPS1, HPS3, HPS4 or HPS6 were diagnosed with IBD. Six children had very early-onset IBD. Patients with HPS-3 had mild manifestations of IBD. Medical therapy and bowel resection were utilized to treat 73% and 35% of patients with HPS IBD, respectively; 7 of 13 patients receiving anti-tumor necrosis factor alpha therapy had prolonged clinical responses. Active cryptitis, chronic inflammatory changes, granulomas and ceroid lipofuscinosis were histopathologic findings in three colectomy specimens. Conclusions IBD resembling Crohn's disease affects some patients with HPS; genetic heterogeneity is a feature of HPS IBD. HPS3 is a new gene associated with human IBD. Very early-onset IBD can develop in HPS.

Aims and methodsFaecal calprotectin (FCP) measurement is used especially to investigate for inflammatory bowel disease (IBD). To assess the utility of sampling endoscopically normal large bowel among patients first presenting with elevated FCP, this study identified 115 such patients out of 652 patients with elevated FCP from approximately 6000 primary care tests processed over 15 months.Results23 cohort patients showed histologically abnormal large bowel biopsies. Only four cases demonstrated acute inflammation and two such patients only showed scattered cryptitis and did not develop IBD. A third patient demonstrated similar histology but, following repeat colonoscopy, her elevated FCP was attributed to small intestinal inflammation. Only the fourth patient’s large bowel biopsies showed features suggesting Crohn’s disease, but this represented an IBD detection rate out of 115 sets of large bowel biopsies of 0.9%.ConclusionsSampling of endoscopically normal large bowel among patients first presenting with elevated FCP is not clinically justified.

The aim of this study was to investigate the use of a standardized animal model subjected to antibiotic treatment, and the effects of this treatment on the course of dextran sodium sulphate (DSS)-induced colitis in mice. By decontamination with selective antibiotics and observation of pathogenesis of ulcerative colitis (UC) induced chemically by exposure of mice to various concentrations of DSS, we obtained an optimum animal PGF model of acute UC manifested by mucin depletion, epithelial degeneration and necrosis, leading to the disappearance of epithelial cells, infiltration of lamina propria and submucosa with neutrophils, cryptitis, and accompanied by decreased viability of intestinal microbiota, loss of body weight, dehydration, moderate rectal bleeding, and a decrease in the selected markers of cellular proliferation and apoptosis. The obtained PGF model did not exhibit changes that could contribute to inflammation by means of alteration of the metabolic status and the induced dysbiosis did not serve as a bearer of pathogenic microorganisms participating in development of ulcerative colitis. The inflammatory process was induced particularly by exposure to DSS and its toxic action on compactness and integrity of mucosal barrier in the large intestine. This offers new possibilities of the use of this animal model in studies with or without participation of pathogenic microbiota in IBD pathogenesis.

Summary Microscopic colitis (MC) is characterized by chronic watery diarrhea, endoscopically normal findings, and abnormal histology. While mostly encountered in adults, pediatric cases are rare and may show varying presentations. Our pathology data system was searched from 1984 to 2019 for patients ≤18 years of age with a lymphocytic colitis (LC) or collagenous colitis (CC) pattern of injury. Twenty-seven cases (23 LC and 4 CC) were retrieved. LC was more prevalent than CC (85% vs 15%, respectively) and affected slightly younger individuals (mean, 9.8 years versus 12.25 years). Immune dysregulation was documented in 11 (41%) patients. Most patients presented with watery diarrhea (n = 26, 96%) and either abdominal pain (n = 18, 67%), nausea/vomiting (n = 5, 19%), flatulence (n = 6, 22%), and/or weight loss (n = 1, 4%). A subset of patients (n = 10, 37%) demonstrated endoscopic abnormalities. Histologically, some patients with LC and CC displayed focal cryptitis or crypt abscess formation (n = 7, 26%) and focally increased crypt apoptosis (n = 9, 33%) in the absence of chronic injury. Clinical follow-up data were available for 23 (85%) patients with variable clinical responses recorded. Only 8 patients experienced complete symptom resolution. Twelve patients (11 LC and 1 CC) had subsequent biopsy material; of which, one developed histologic features of inflammatory bowel disease and another was found to have a CTLA-4 deficiency. Our study shows that pediatric patients with MC may have atypical clinical, histologic, and endoscopic findings and variable clinical responses. Underlying inflammatory and/or genetic conditions may be eventually unmasked, and genetic testing may be helpful in a small subset of patients.

Introduction Surgical resection is not curative in Crohn’s disease (CD) and, recurrence after surgery is a common situation. The identification of patients at high risk of recurrence remains disappointing in clinical practice. Objective To evaluate the impact of residual microscopic disease on margins on the risk of recurrence after ileocaecal resection in CD. Patients and methods All patients who underwent ileocaecal resection between January 1992 and December 2016 were prospectively identified. Demographic data, clinical, surgical and histological variables were retrospectively collected. Positive histologic margin was assessed prospectively and defined by the presence of acute inflammatory lesions on margins: erosion, ulceration, chorion infiltration by neutrophils, cryptic abscesses or cryptitis. Results One hundred twenty five patients were included, with a median follow-up of 8 years (Interquartile Range (IQR), 4.3–15.2). Half (49.6%, n = 62) were women, and the median age at surgery was 33 years (IQR, 24–42). Fifty-six (44.8%) had positive inflammatory margins. Five years after surgery, respectively 29 (51%) and 23 (34%) patients with positive and negative margins had clinical recurrence (p = 0.034). At the end of the follow-up, respectively 60% (n = 34) and 47% (n = 33) patients had clinical recurrence (p = 0.07). CD-related hospitalizations were observed in respectively 37.5% (n = 21) and 18.8% (n = 13) with positive and negative margins (p = 0.02). Fourteen patients (25%) with positive intestinal margins had surgical recurrence at the end of the follow-up compared to 5 patients (7%) with negative margins (p = 0.04). Multivariate analysis confirmed that positive intestinal margin was independently associated with surgical recurrence (OR, 4.7 (CI95%, 1.4–15.3), p = 0.01). Conclusion Positive histologic margin was associated with an increased risk of clinical and surgical recurrence after ileocaecal resection for Crohn’s disease.

Background Gastro-intestinal manifestations in systemic lupus erythematosus (SLE) can affect up to 40% of patients, including enteritis presenting as mesenteric vasculitis, pseudo-obstruction or protein-losing enteropathy. We present a case of lupus enteritis successfully treated with anti-TNFalpha inhibitor. Methods A 28-year-old woman was evaluated for diarrhea, abdominal pain, fever and rectal bleeding not responsive to antibiotics. She had a thirteen-year history of SLE in remission with Mycophenolate Mofetil and previous muco-cutaneous and haematologic relapses, myocarditis and end-stage renal disease (IV-class glomerulonephritis). She previously underwent multiple immunosuppressants including ciclophosphamide, cyclosporine,anti-CD20, immunoglobulins. One month before the onset of symptoms she discontinued MMF for worsening anemia. Simultaneously we reported signs of lupic flare (low C3, haemolytic anemia, lymphopenia, fever, arthralgias and malar rash). Pulse-steroids and IVIg followed by cyclosporine were initially performed with only temporary benefit. Enteric CT-scan and endoscopy revealed chronic and acute colo–rectal and gastric inflammation (cryptitis, erosions, necrosis, microgranulomas). Anti-TNFalpha inhibitor Infliximab (5 mg/kg) was added to Azathioprine 50 mg/daily. Within a month we observed clinical and serological sustained remission. Results Typically, mesenteric vasculitis involves small arteries or venules. Histological examination reveals submucosal and muscular layers infiltration and necrotizing vasculitis, with panmural predominant eosinophilic, neutrophilic or mixed infiltrate. The distinction of inflammatory bowel disease (IBD) from enteric-SLE can be challenging. In this case, an early anti-flogistic therapy may have led to uncomplete microscopic patterns not fullfilling criteria neither for enteric vasculitis nor IBD. A lupic flare with predominant gastro-enteric presentation is the most plausible hypothesis because of the infrequent association between SLE and IBD and simultaneous extra-intestinal lupic features. Abdominal involvement in a patient previously treated with high dosage cyclophosphamide (10 g) and the lack of response to azathioprine lead to the introduction of anti-TNFalpha inhibitor. Conclusion The role of TNFalpha in SLE is controversial and TNFalpha inhibitors are reported to control SLE-arthritis. Further studies are needed to evaluate their role in the management of gastro-enteric SLE.

Aims In clinical practice, patients of ulcerative colitis showing divergence between the histological findings and endoscopic findings are often encountered. Therefore, we compared histological findings with endoscopic findings, indicating the severity of the inflammation of ulcerative colitis. Methods and results The study group comprised 191 patients (527 biopsy specimens) with ulcerative colitis who underwent lower gastrointestinal endoscopy with biopsy in our hospital from July 2015 to June 2016. Endoscopic findings of the mucosa at the biopsy site were classified into seven levels according to the severity of inflammation: noninflamed mucosa, red signs, loss of visible vascular patterns, granular mucosa, friable mucosa, spontaneous bleeding, and erosions/ulcers (E/U). All biopsy samples were examined for the presence or absence of five histological findings (basal plasmacytosis [BP], neutrophil infiltration, cryptitis, crypt abscess [CAb], and E/U), and the results were contrasted with endoscopic findings. The 191 patients comprised 123 (64.4%) males and 68 (35.6%) females, with a median age of 47 years (range, 8-82). Among the 527 specimens, the detection rates of BP, CAb, and E/U in mucosa with endoscopic E/U were 58.5, 27.4, and 18.3%. The detection rate of BP in mucosa with red signs was 22.4%; in mucosa, with loss of visible vascular patterns, it was 16.9%; in granular mucosa, it was 35.7%, and in mucosa with E/U, it was 58.5%. BP was frequently seen in severely inflamed mucosa associated with E/U on endoscopic examination. Conclusion BP was considered an important finding, suggesting the presence of active and severe inflammation.

AIM To determine the pathological features of colonic ischaemia (CI) and their relationship to symptom duration, disease distribution and clinical outcome in a real-world, clinical setting. METHOD A retrospective, multicentre chart review was performed in patients diagnosed with CI at Montefiore Medical Center (January 2005 to July 2015), and Yale-New Haven Hospital (January 2005 to June 2010). Patients were included if clinical presentation, colonoscopic findings and colonic pathology were all consistent with CI. RESULTS Six hundred and sixteen patients with pathologically proven CI were included. Common pathological findings included inflammation (51.1%), ulceration (38.2%), fibrosis (26.0%) and necrosis (20.4%). Infarction and ghost cells were seen in 1.6% and 0.2% of cases, respectively. There was a significant relationship between symptom duration and hyalinization of the lamina propria (P = 0.05) and cryptitis/crypt abscesses (P = 0.01). Patients with isolated right CI (IRCI) were more likely than patients with isolated left CI (ILCI) to exhibit necrosis (P < 0.01), cryptitis/crypt abscess (P < 0.01) and inflammation (P = 0.03). Patients with poor outcomes were more likely to exhibit necrosis (P < 0.01) and capillary fibrin thrombi (P < 0.01) and less likely to exhibit fibrosis (P < 0.01) and epithelial changes (P < 0.01). CONCLUSION CI is accompanied by a broad spectrum of pathological findings. The traditional pathognomonic findings of CI are rare and cannot be relied upon to exclude the diagnosis. Patients with IRCI and/or poor outcomes were more likely to have pathological findings of necrosis than patients who had ILCI and/or nonpoor outcomes.

We herein report a case of immune-related colitis induced by the long-term use of nivolumab. A 62-year-old Japanese man was treated with nivolumab at 3 mg/kg every 2 weeks for advanced lung adenocarcinoma. The patient was admitted to our hospital due to non-bloody watery diarrhea after the 70th dose of nivolumab. A biopsy specimen of the colon mucosa revealed evidence of colitis with cryptitis and crypt microabscesses. He was diagnosed with immune-related colitis and started on predonisolone 60 mg/day. Subsequently, his symptoms remarkably resolved. Consideration of immune-related adverse events up to several years after the initiation of nivolumab is important.

Background/aims The therapeutic goal for treating ulcerative colitis (UC) patients has shifted to achieving mucosal healing over the past few years. However, at present, limited data is available on the correlation between endoscopic findings and histological remission in patients with endoscopic mucosal healing. Methods This was a prospective observational study conducted over a period of 18 months (January 2014 to June 2015) at Dayanand Medical College and Hospital, Ludhiana, Punjab, India. Patients diagnosed with UC who had been in clinical remission (n=76) for at least 6 months were evaluated for endoscopic remission. Those in endoscopic remission (Mayo score ≤1; 46/76, 60.5%) were subjected to multiple biopsies from the rectosigmoid region and histological remission, which was then defined as grade 0/1 as per the Geboes criteria. Results Of the 46 patients in endoscopic remission (age, 18-73 years; male:female=1.5:1.0), majority had E1 (proctitis) disease (21/46, 45.6%) followed by E2 (left sided colitis) (18/46, 39.1%) and E3 disease (pancolitis) (7/46, 15.2%) at baseline. Histological remission was noted in 67.3% (31/46) of the patients, while 32.7% (15/46) still retained the histologically active disease in the form of infiltration of the lamina propria by eosinophils and neutrophils (13/15, 86.6%), cryptitis (14/15, 93.3%), and crypt abscesses (8/15, 53.3%). On follow-up, after 1 year, 87.1% (27/31) of the patients who had been in histological remission remained clinically asymptomatic, while 12.9% (4/31) had relapsed. Among the 15 histologically active patients, 46.6% (7/15) remained in clinical remission, while 53.3% (8/15) had relapsed. Conclusions Histological remission, rather than endoscopic remission, predicts a sustained clinical remission and allows monitoring of therapy for the subsequent disease course in patients with UC.

Background Chronic intestinal pseudo-obstruction (CIPO) is a rare condition that is not commonly associated with Crohn’s disease (CD). We performed a cohort study aiming at identifying clinical, immunological and genetic features as well as response to conventional CD treatments of patients co-affected with CIPO and CD. Methods We conducted an observational retrospective cohort study in two tertiary CIPO and IBD centers. Patients with parenteral nutrition-dependent CIPO and features of CD including large intestinal or perianal ulcers, strictures, abscesses and fistula with pathology findings compatible with CD, were included. We used flow-cytometry and targeted-next generation sequencing to identify immune defects and monogenic causes in 129 predefined genes responsible for monogenic enteropathies Results Eight unrelated patients were studied. 5 had a myogenic phenotype and 3 had a neurogenic form with histological exam for all patients. CD involved small bowel in all cases whereas one patient had ileocolonic involvement. Two patients had perianal complex fistula. Seven patients had a stricturing form and 1 had an inflammatory-only behavior. No patient had a penetrating form. All patients were diagnosed with CIPO prior to CD. Median age at CIPO diagnosis was 11.5 years old (IQR 0,31.5) while it was 22.5 (IQR 19,29) at CD diagnosis. At CD diagnosis, mean fecal calprotectin level was 551 ug/g (range 390 - 1200) and citrulline averaged 23.6 umol/l (range 15–35 umol/l). Histopathological analyses of intestinal specimens revealed ulcerations for half of the patients, increase in intraepithelial lymphocytes in 3, granuloma and cryptitis in 1 patient. Abnormalities in peripheral lymphocytes’ subsets were found in 2 patients. 5 patients were ultimately diagnosed with monogenic forms of enteropathy: 2 in ACTG2, with an autosomal dominant inheritance, 1 with a STAT1gain of function, (GOF) and two with recessive inheritance: TYMP. All patients received steroids with clinical response in 2. 6 patients received antiTNF, with only one sustained remission. Two patients received vedolizumab and 2 were treated with ustekinumab. Except for antiTNF in 1 patient, common CD treatments did not lead to any improvement. Of note, antiJAK therapy in a patient with STAT1GOF failed to induce remission. Conclusion Herein is described the first cohort of extensively genetically and immunologically explored patients co-affected with CIPO and CD. Immune defects were common and monogenic forms were found with a high prevalence. Rates of response to biologic treatment were very low. Identification of monogenic cause through immunological and genetic explorations is warranted in patient with CIPO-CD association as it could lead to targeted therapy and genetic counseling.

A 44-year-old patient with known ulcerative colitis presented with abdominal pain and an abdominal mass. CT revealed cecal stranding, a mass at the left colonic flexure involving the pancreas and multiple lesions in the lungs, retroperitoneum and liver. The patient had also developed a scalp rash as well as impaired hearing. Biopsies from the abdominal mass and lungs revealed necrotic inflammation, and the clinical suspicion of malignancy could not be ruled out. After further examination, the patient was treated with high-dose steroids, which rapidly reduced the extraintestinal manifestations. Due to a persistent abscess formation at the left colonic flexure and pancreas, the patient was referred to our hospital for a total colectomy. Histology showed acute and chronic inflammation with cryptitis, indicating ulcerative colitis. Our case is a rare presentation of extensive extraintestinal disease in organs such as the lungs and liver, as well as necrotic mass formation at the colon site which mimicked malignancy.

Introduction: Coronavirus Disease 2019 (COVID-19) has been shown to infect gastrointestinal tissues, and a wide variety of gastrointestinal manifestations have been described including alterations in the composition of the intestinal microbiome. Microbiome changes have been implicated in the pathogenesis of inflammatory bowel disease (IBD), but a clear relationship between viral infection and IBD has not been established. Case description/methods: Case 1 A 45-year-old woman presented to clinic with painless hematochezia and fecal urgency 2 weeks after developing anosmia and being diagnosed with COVID-19. She had a history of constipation but no other gastrointestinal problems. Her vital signs were normal and her exam was unremarkable. Her labs showed iron deficiency anemia with hemoglobin 10.2 and ferritin

Introduction: Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare entity, mostly associated with autoimmune conditions such as SLE. It is benign, focal, selflimited, and despite abundant literature, its pathogenesis remains unknown. We report a unique case of KFD in a patient with coexisting Crohn's disease. Case description/methods: A 23-year-old female with no medical history was evaluated for Iron deficiency anemia and anorexia. She underwent a colonoscopy which revealed normal colonic mucosa, however, an ulcerated and congested terminal ileum was seen. Biopsies were significant for acute cryptitis and granuloma. Serology was positive for anti-Saccharomyces cerevisiae antibody and fecal calprotectin was elevated. She was initially started on oral corticosteroids and later transitioned to azathioprine and Adalimumab, with a good response. 7 months later, she was planned for a repeat colonoscopy to check for endoscopic healing, however, at her pre-procedure COVID testing, she was noted to have rubbery painless LAD of the right neck. The procedure was postponed and she was immediately asked to discontinue her medications. She was referred to an oncologist. A CT chest was unremarkable and an excisional biopsy of the largest of the lymph node revealed necrotizing lymphadenitis, favoring KFD. Infectious workup was negative. Over the next 2 months, her LAD spontaneously resolved without the need for medications. A repeat colonoscopy was aborted due to poor prep. A follow-up MRE revealed long segment mid and distal Crohn's ileitis, and fecal calprotectin remained elevated. She was started on oral budesonide with plans to restart biological therapy after repeating a colonoscopy. Discussion: KFD may rarely involve the terminal ileum, potentially masquerading as Crohn's disease. Our patient, however, had histological findings pathognomic for Crohn's and her ileitis did not resolve with the resolution of LAD. Lymphoma remains a feared adverse outcome of both immunomodulators and Anti-TNF medications, thus necessitating their cessation upon signs of LAD. However negative EBV testing, an unrevealing chest CT, and a benign histological diagnosis of KFD may allow our patient to safely resume these medications to treat her Crohn's.

Objective To describe the prevalence, clinical presentation and current treatment regimens of inflammatory bowel disease (IBD) in patients with primary immunodeficiency disorders (PIDs). Methods A systematic review was conducted. The following databases were searched: MEDLINE, Embase, Web of Science, the Cochrane Library and Google Scholar. Results A total of 838 articles were identified, of which 36 were included in this review. The prevalence of IBD in PIDs ranges between 3.4% and 61.2%, depending on the underlying PID. Diarrhea and abdominal pain were reported in 64.3% and 52.4% of the patients, respectively. Colon ulceration was the most frequent finding on endoscopic evaluation, while cryptitis, granulomas, ulcerations and neutrophilic/lymphocytic infiltrates were the most frequently reported histopathological abnormalities. Described treatment regimens included oral corticosteroids and other oral immunosuppressive agents, including mesalazine, azathioprine and cyclosporin, leading to clinical improvement in the majority of patients. In case of treatment failure, biological therapies including TNF- α blocking agents, are considered. Conclusions The overall prevalence of IBD in patients with PID is high, but varies between different PIDs. Physicians should be aware of these complications and focus on characteristic symptoms to reduce diagnostic delay and delay in initiation of treatment. Treatment of IBD in PIDs depends on severity of symptoms and may differ between various PIDs based on distinct underlying pathogenesis. An individualized diagnostic and therapeutic approach is therefore warranted.

We reviewed the records of patients with immune checkpoint inhibitor (ICI)-induced diarrhea during 2015 to 2019. ICI included nivolumab and ipilimumab. There were 11 patients with ICI-induced diarrhea aged 46-81 years (median, 63 years). On colonoscopy, four patients appeared normal, whereas loss of vascularity, erythema, granularity, erosions or ulcerations apparently mimicking ulcerative colitis were found in seven patients. Those seven patients had acute inflammation, cryptitis, crypt abscess and apoptosis, suggestive of ICI-induced colitis. Five of the seven patients were treated with prednisolone, two of whom were resistant to prednisolone and required infliximab. In contrast, none of the four patients without ICI-induced colitis required further treatment. Our observations suggest that diversity exists in the clinical, endoscopic and histological severity of patients with ICI-induced diarrhea. Colonoscopy together with biopsy is inevitable for the diagnosis of ICI-induced colitis, which requires intensive treatment.

Background: Behcet’s disease (BD) is an idiopathic, chronic, inflammatory systemic vasculitis characterized by recurrent oral and genital aphthous ulcers, skin lesions, and ocular involvement. It can also affect multiple visceral organ and system such as heart, lung, blood vessels, gastrointestinal (GI) system, and central nervous system (1). The etiology of the disease is still unknown. New diagnostic criteria for pediatric Behcet’s patients have been established In 2015, and its largely based on clinical findings (2). Although the GI manifestations are not take part in to the diagnostic criteria, it can be emerge in great deal of patients and associated with significant morbidity and mortality. The most common GI symptoms in BD are abdominal pain, nausea, diarrhea and GI bleeding in, respectively. Also, the most common reported site of intestinal involvement was ileocecal. The literature data related to GI involvement of BD are frequently concern adult patients and pediatric studies are limited. Objectives: We analyzed the GI manifestations and its endoscopic findings in children diagnosed with BD. Methods: We retrospectively reviewed the clinical records of 64 patients who fulfilled the international pediatric classification criteria for BD from December 2015 to December 2018. Endoscopic examination results of 13 patients were also collected and analyzed. Results: Of the 64 children with BD, 37 were male and 27 were female, and sex ratio (male/female) was 1.37/1. The mean age of our patients was 9.49±4.10 and 11.52±3.50; at onset of symptoms and at the time of diagnosis, respectively. Assessment of our 64 patients revealed that the prevalence of GI symptoms is 60% (39/64). The most frequent GI symptoms were abdominal pain in 56% (36/64), chronic diarrhea in 18% (12/64), nausea/vomiting in 11% (7/64), chronic constipation in 12% (8/64), and regurgitation or heartburn in 7% (5/64). Upper GI endoscopy was performed in 7 patients and colonoscopy in 6. All of the patients who underwent the endoscopy or colonoscopy, had findings support the GI inflammation. The endoscopic findings shown in the patients are; gastric inflammation in 100% (7/7), oesophageal inflammation in 57% (4/7), duodenal inflammation in 42% (3/7), colonic erythema and inflammation in 83% (5/6), polyps in 50% (3/6), ulceration in 66% (4/6), and hemorrhoids in 16% (1/6). Upper GI ulceration was not observed. Pathology specimens were taken in 7 upper endoscopies and 6 colonoscopies within our patients. The findings of pathology specimens were vascular congestion and inflammation in 100% (7/7) of upper GI biopsies and 83% (5/6) of colonic biopsies, cryptitis in 66% (4/6) of colonic biopsies. Acute colitis in pathology specimens was shown in 83% (5/6) of the patients. Three of the patients with colitis had punch ulcers, and these patients were evaluated as BD-associated colitis. The other two patients were diagnosed and treated as Crohn’s colitis accompanying BD. Conclusion: The GI system is one of the most frequently affected organ by the BD. It may cause the inflammation and ulceration in the GI tract. Inflammatory bowel diseases can also cause GI inflammation similar to BD. In patients with symptoms of GI inflammation, upper and lower GI endoscopic examination and pathological analysis may be helpful in determine the underlying etiology. References [1] - Sakane T, Takeno M, Suzuki N, Inaba G. Behcet’s disease. N Engl J Med1999;341:1284-91 [2] - Kone-Paut I, Shahram F, Darce-Bello M, Cantarini L, Cimaz R, Gattorno Met al, PEDBD group. Consensus classification criteria for paediatric Behcet’s disease from a prospective observational cohort: PEDBD. Ann Rheum Dis. 2016;75:958-64. Acknowledgement: We are grateful to all participating children and their families. Disclosure of Interest: None Declared

Introduction Lewis and Huff briefly described the presence of “microcystic cryptitis” in some of fetal vermiform appendices (VA) at autopsy. We further characterized these crypt changes (CC), their timing of occurrence, and tested their association with infection/inflammatory conditions. Methods Hematoxylin and eosin-stained slides of 345 VA were evaluated for the presence or absence of CC and their different morphologies. Autopsy reports were reviewed for evidence of amniotic fluid or fetal systemic infection and placental inflammatory conditions. Results Crypt dilatation with or without irregularity of the lumen, crypt dilatation with semiattenuated epithelium, intraluminal apoptotic debris and inflammatory cells, especially eosinophils, and foci of swirled spindled cells with calcifications or multinucleated giant cells were observed, either alone or in combination, in at least 58.5% (202/345) of the VA. CC began to appear at 17 weeks, peaked at 20 to 25 weeks (with up to 82% of VA exhibiting CC during this time), and followed by a steady decline beyond 28 weeks gestation. χ2 test of independence showed no significant association ( P = .435; >0.05) between the presence and absence of CC and infection status of the fetus or placenta. Conclusion The underrecognized CC of the developing fetal vermiform appendix (VA) showed distinct temporal pattern of occurrence and did not seem to be affected by the presence or absence of infection, which so far favored their being a part of the normal gut developmental process.

International audience; Background and AimsDifferent types of histologic lesions at the ileal margin, detected by histology, have been associated with increased rates of recurrence after ileocaecal surgery in patients with Crohn’s disease (CD). We aimed to characterize histologic features of the ileal margin and to evaluate their association with disease recurrence.MethodsWe collected histologic data from 211 patients with ileal or ileocolonic CD who underwent ileocolonic resections at hospitals in France from September 2010 through December 2016. Ileal margins were analyzed. Early endoscopic recurrence was defined by a Rutgeerts score of i2 or more, 6 months after surgery. We also collected data from 10 adults with healthy ileum who underwent ileocecal resection for colonic tumors (controls). Clinical relapse was defined by CD-related symptoms confirmed by imaging, endoscopy, therapy intensification, CD-related complication, or subsequent surgery.ResultsSix months after surgery, 49% of patients had endoscopic recurrence; 5 years after surgery, 57% of patients had clinical relapse. Ileal margins were macroscopically affected in 20.9% of patients. CD transmural lesions at the margin (defined by mucosal ulceration or cryptitis, submucosal fibrosis and lymphoplasmacytic infiltrate of the subserosa) were observed in 13.6% of patients. Endoscopic recurrence was observed in 75% of patients with CD transmural lesions vs 46% of patients without (P =.005). In multivariate analysis, CD transmural lesions at the margin were independently associated with early endoscopic recurrence (OR, 3.83; 95% CI, 1.47-11.05; P =.008) and clinical recurrence (OR 2.04; 95% CI, 1.09-3.99; P =.026).ConclusionIn patients with CD, transmural lesions at the ileal margin were associated with an increased risk of post-operative recurrence. Histologic features of the ileal margin should be included in making decisions about post-operative therapy.

Upper gastrointestinal (UGI) tract involvement of inflammatory bowel disease (IBD) is commonly seen in pediatric patients. Upper endoscopy is included in the routine workup of children with suspected IBD to enhance the diagnosis and management of these patients. Currently, childhood IBD is classified into ulcerative colitis (UC), atypical UC, Crohn's disease (CD) and IBD unclassified. Histologic confirmation of UGI tract involvement, in particular the presence of epithelioid (non-caseating) granulomas, is helpful in confirming the diagnosis of IBD and its classification. Herein, we reviewed selected IBD-associated UGI tract manifestations in children. Lymphocytic esophagitis, seen predominantly in CD, is histologically characterized by increased intraepithelial lymphocytes (> 20 in one high-power field) in a background of mucosal injury with absence of granulocytes. Focally enhanced gastritis is a form of gastric inflammation in pediatric IBD marked by a focal lymphohistiocytic pit inflammation with or without granulocytes and plasma cells in a relatively normal background gastric mucosa. Duodenal inflammation seen in children with IBD includes cryptitis, villous flattening, increased intraepithelial lymphocytes, and lamina propria eosinophilia. Finally, epithelioid granulomas not associated with ruptured gland/crypt are a diagnostic feature of CD. The clinicopathologic correlation and differential diagnosis of each microscopic finding are discussed. Clinicians and pathologists should be cognizant of the utility and limitations of these histologic features.

Background Ulcerative Colitis (UC) is characterized by intestinal inflammation with chronic inflammatory features. Along with the typical neutrophil-predominant inflammation, there has been growing understanding of the role of eosinophils in UC and the potential therapeutic benefit of Vedolizumab (VDZ) in those cases. VDZ blocks gastrointestinal homing of T lymphocytes and eosinophil recruitment to the intestinal mucosa via blocking α4β7 which plays a major role in eosinophils localization to the intestinal mucosa. We aimed to assess whether mucosal eosinophilia can predict response to VDZ. Methods A retrospective study in a single IBD center. Active UC patients who were initiated on VDZ were identified. All patients had at least one documented encounter of VDZ infusion, colonoscopy prior to initiation of VDZ and afterwards with mucosal biopsies at both time points. The endoscopic activity was scored using Mayo endoscopic subscore (MES) with remission as MES 0 or 1. Clinical response was assessed using Physician’s Global Assessment (PGA) as no response, partial or complete clinical response and clinical remission. Histology was reported by an expert GI pathologist and the response was assessed as none, partial or complete. Mucosal eosinophilia was graded at initial and follow-up biopsies as not conspicuous vs. conspicuous with predominance of eosinophils (>100 eosinophils in at least 2 hpf). Eosinophil activity defined as presence of at least 1 of the 3 histologic features: eosinophilic microabscesses, eosinophilic cryptitis, or degranulated eosinophils Results 107 UC patients were included in the study with a mean age of 44.9 years, majority were males (N = 61, 55.5%), Caucasians (N = 96, 87.3%) and with pancolonic location (N = 100, 90.9%). Mean disease duration was 11.3 yrs (SD, 8.6). 55.5% of patients had prior aTNF exposure. Clinical remission was observed in (N = 63, 57.3%) and endoscopic remission (N = 73, 66.4%) after initiating VDZ. Complete histological response was observed in (N=50, 46.7%). Baseline characteristics based on endoscopic remission is shown where male sex, disease location and the proportion of patients with conspicuous eosinophils with abnormal activity in mucosal biopsies as well as no improvement in eosinophil activity compared to pre-treatment biopsies is greater among those not in endoscopic remission. In a stepwise backward logistic regression model including sex and disease location, improvement in abnormal eosinophilic activity was independently associated with increased odds of endoscopic remission after initiating vedolizumab (OR 4.3; CI, 1.1 - 16.4, p = 0.03). Conclusion In ulcerative colitis, change in mucosal eosinophilia after initiating VDZ was an independent predictor of endoscopic remission with VDZ.

Crohn’s disease is a chronic, idiopathic autoimmune disorder that primarily targets the gastrointestinal (GI) system. It is characterized by transmural inflammation of the GI tract that can occur anywhere from the mouth to the anus. Not infrequently, the disease may also have extraintestinal manifestations (EIMs) that can affect almost any organ system. It is estimated that EIMs affect up to 36% of patients with Crohn’s disease, but the incidence and prevalence of pulmonary involvement are variable in the literature and may be as low as 0.4%. There are few case reports documenting pulmonary manifestations, as they are often overlooked, especially if respiratory symptoms are present before the diagnosis of GI manifestations, as in the present case. A 44-year-old otherwise healthy woman presented with nonspecific respiratory complaints, recurrent pneumonias, and multiple computed tomography images showing diffuse, migratory, nodular, and consolidative parenchymal lung disease, with a largely unremarkable infectious and rheumatologic evaluation. Lung biopsy revealed necrotizing and nonnecrotizing granulomas, raising concern for sarcoidosis. Subsequent imaging revealed an incidental mass in the cecum. Biopsy of the cecum lesion revealed acute cryptitis, crypt abscess, and a single poorly formed granuloma, suggesting the possibility of Crohn’s disease. In this report, we present a patient whose pulmonary manifestations ultimately led to the diagnosis of Crohn’s disease.

BACKGROUND & AIMS: Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte-associated antigen-4, is a treatment for metastatic melanoma that can induce immune-related adverse effects, such as enterocolitis. We aimed to characterize the clinical, endoscopic, and histologic features of ipilimumab-induced colitis and evaluate the efficacy of therapy for this reaction.METHODS: We performed a retrospective analysis of 27 consecutive patients who developed colitis after treatment with ipilimumab infusion therapy for castration-resistant prostate cancer or metastatic melanoma, from April 2007 through September 2012. Clinical, endoscopic, and histologic information was collected from the database of the VU University Medical Center, Amsterdam, The Netherlands. Selected cases were ascertained by cross-checking with endoscopy reports.RESULTS: All patients had diarrhea (range, 3-20 stools per day); 26% had concurrent rectal blood loss and 30% had abdominal pain. These symptoms usually started after 2 infusions of ipilimumab (range, 1-4) and all patients except for 1 (who received no treatment for colitis) were given corticosteroids. Twelve patients had steroid-refractory colitis, for which they received infliximab (5 mg/kg). Diarrhea resolved in all the patients. Colon erythema was detected by endoscopy in 84% of patients, with an absent vascular pattern in all patients. In histologic analyses, colon biopsy specimens ranged from having normal architecture to severe active inflammation. Intraepithelial neutrophilic leucocytes were detected in 72% of samples, cryptitis in 92%, and crypt abscesses in 60%. Crypt irregularities were found in 40% of colon biopsy specimens, indicating chronic disease.CONCLUSIONS: In a retrospective analysis, we associated ipilimumab-associated colitis diarrhea with a variety of endoscopic and histologic features. Treatment with corticosteroids, followed by infliximab in steroid-refractory patients, was successful for all cases.

Background: Histopathologic evaluation of colonoscopic mucosal biopsy remains one of the earliest modalities of investigation in patients clinically suspected of ulcerative colitis. Pathologists should be aware of classical histomorphological features to avoid misdiagnosis. The aim of the present study was to evaluate histopathologic features as well as to determine possible atypical presentation.Materials and Methods: Forty newly diagnosed cases of ulcerative colitis were included in the study. Colonoscopic biopsies taken from rectum as well as various areas of colon and ileum depending upon clinical extent of involvement were submitted for histopathological evaluation. Diagnosis of ulcerative colitis was made by correlating clinical, endoscopic and histopathologic findings.Results: Out of 47 cases suspected of ulcerative colitis, histopathologic features were consistent with Ulcerative colitis in 40 cases. Almost all cases (97.5%) showed diffuse active colitis. Cryptitis (100%), crypt abscesses (75%) and basal plasmacytosis (85%) along with crypt architectural abnormalities (75%) and goblet cell depletion (70%) were classical histological changes associated with ulcerative colitis in active phase. Atypical presentations noticed were focal active colitis (2.5%), backwash ileitis (2.5%), rectal sparing (2.5%) and skip areas (5%).Conclusion: Accurate diagnosis of ulcerative colitis requires elaborate knowledge of histopathologic features along with awareness of possible atypical presentation.