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

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World Journal of Gastroenterology 2017年第11期23卷 2023-2028页

作者： Animesh Jain Evan J Lipson William H Sharfman Steven R Brant Mark G Lazarev Division of Gastroenterology and Hepatology Department of Internal MedicineUniversity of North Carolina Chapel Hill Department of Oncology Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center Division of Gastroenterology and Hepatology Department of Internal MedicineJohns Hopkins University School of Medicine

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 centerwith 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 highdose 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 steroidrefractory 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.

关键词： Ipilimumab Melanoma Enterocolitis Colitis Infliximab Corticosteroid Colonic ulcer

Altered tryptophan hydroxylase 2 expression in enteric serotonergic nerves in Hirschsprung's-associated Enterocolitis

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World Journal of Gastroenterology 2016年第19期22卷 4662-4672页

作者： David Coyle Justin M Murphy Brian Doyle Anne Marie O’Donnell John Gillick Prem Puri Temple Street Children's University Hospital Dublin 1 Ireland National Children's Research Centre Our Lady's Children's Hospital Dublin 12 Ireland

AIM: To determine if expression of colonic tryptophan hydroxylase-2(TPH2), a surrogate marker of neuronal 5-hydroxytryptamine, is altered in Hirschsprung's-associated Enterocolitis. METHODS: Entire resected colonic specimens were collected at the time of pull-through operation in children with Hirschsprung's disease(HSCR, n = 12). Five of these patients had a history of pre-operative Hirschsprung's-associated Enterocolitis(HAEC). Controls were collected at colostomy closure in children with anorectal malformation(n = 10). The distribution of expression of TPH2 was evaluated using immunofluorescence and confocal microscopy. Protein expression of TPH2 was quantified using western blot analysis in the deep smooth muscle layers. RESULTS: TPH2 was co-expressed in nitrergic and cholinergic ganglia in the myenteric and submucosal plexuses in ganglionic colon in HSCR and healthy controls. Co-expression was also seen in submucosal interstitial cells of Cajal and PDGFRα+ cells. The density of TPH2 immuno-positive fibers decreased incrementally from ganglionic bowel to transition zonebowel to aganglionic bowel in the myenteric plexus. Expression of TPH2 was reduced in ganglionic bowel in those affected by pre-operative HAEC compared to those without HAEC and healthy controls. However, expression of TPH2 was similar or high compared to controls in the colons of children who had undergone diverting colostomy for medically refractory HAEC.CONCLUSION: Altered TPH2 expression in colonic serotonergic nerves of patients with HSCR complicated by HAEC may contribute to intestinal secretory and motor disturbances, including recurrent HAEC.

关键词： Serotonin Tryptophan hydroxylase 2 Hirschsprung Enterocolitis Ganglionic

Efficacy of peritoneal drainage in very-low-birth-weight neonates with Bell’s stage II necrotizing Enterocolitis:A single-center retrospective study

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World Journal of Gastrointestinal Surgery 2023年第7期15卷 1416-1422页

作者： Yong Shen Yu Lin Yi-Fan Fang Dian-Ming Wu Yuan-Bin He Department of Pediatric Surgery Fujian Children’s Hospital(Fujian Branch of Shanghai Children’s Medical Center)College of Clinical Medicine for Obstetrics and Gynecology and PediatricsFujian Medical UniversityFuzhou 350000Fujian ProvinceChina

BACKGROUND Currently,pediatric surgeons are challenged by a lack of consensus on the optimal management strategy(conservative or surgical)for children with Bell’s stage II necrotizing Enterocolitis(NEC).AIM To evaluate the clinical efficacy of peritoneal drainage in very-low-birth-weight(VLBW)neonates with modified Bell’s stage II NEC.METHODS This was a retrospective analysis of 102 NEC(modified Bell’s stage II)neonates born with VLBW who were treated at the Fujian Children’s Hospital(Fujian Branch of Shanghai Children’s Medical Center)between January 2017 and January 2020;these included 24 cases in the peritoneal drainage group,36 cases in the exploratory laparotomy group,and 42 cases in the conservative treatment group.RESULTS The general characteristics were comparable in the three groups(P>0.05).Compared with conservative treatment,peritoneal drainage was associated with significantly shorter fasting time,abdominal distension relief time,fecal occult blood(OB)negative conversion time,and reduced hospital length of stay(HLOS)(P0.05).Compared to exploratory laparotomy,the fecal OB negative conversion time was significantly shorter in the peritoneal drainage group(P0.05).CONCLUSION Peritoneal drainage,an easy-to-operate procedure,can improve the clinical symptoms of VLBW neonates with Bell’s stage II NEC and help reduce the HLOS.

关键词： Stage II necrotizing Enterocolitis Enterocolitis Very-low-birth-weight Peritoneal drainage Hospital length of stay

An ironic case of liver infections:Yersinia Enterocolitis in the setting of thalassemia

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World Journal of Gastroenterology 2013年第37期19卷 6296-6298页

作者： Nathan Selsky Faripour Forouhar George Y Wu Division of Gastroenterology and Hepatology Department of MedicineUniversity of Connecticut Health Center Department of Anatomic Pathology University of Connecticut Health Center

A 49 years old Vietnamese male with a history of thalassemia,presented with gastrointestinal symptoms and signs of hemolysis.He was diagnosed with yersinia Enterocolitis.Yersinia is a gram-negative rod that most frequently occurs in children especially during the winter months.In the current case,the bone marrow biopsy showed hemophagocytosis along with positive cultures for Yersinia.The microorganism likely triggered hemophagocytosis.This syndrome,also known as,hemophagocytic lymphohistiocytosis,is defined by fever for more than 7 d,cytopenia of two or more cell lines,hemophagocytosis,hepatitis,serum ferritin greater than500,jaundice,lymphadenopathy,and hepatosplenomegaly.This disorder can be either familial or secondary to a strong immunologic activation.Both have an overwhelming activation of T-cells and macrophages.

关键词： Yersinia Enterocolitis Bone marrow Liver biopsy Thalassemia Hemophagocytic lymphohistiocytosis

Hirschsprung's disease associated Enterocolitis:A comprehensive review

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World Journal of Clinical Pediatrics 2023年第3期12卷 68-76页

作者： Eric M Gershon Leonel Rodriguez Ricardo A Arbizu Section of Pediatric Gastroenterology Yale University School of MedicineNew HavenCT 06520United States

Hirschsprung’s disease(HSCR)is a congenital disorder characterized by failure of the neural crest cells to migrate and populate the distal bowel during gestation affecting different lengths of intestine leading to a distal functional obstruction.Surgical treatment is needed to correct HSCR once the diagnosis is confirmed by demonstrating the absence of ganglion cells or aganglionosis of the affected bowel segment.Hirschsprung’s disease associated Enterocolitis(HAEC)is an inflammatory complication associated with HSCR that can present either in the pre-or postoperative period and associated with increased morbidity and mortality.The pathogenesis of HAEC remains poorly understood,but intestinal dysmotility,dysbiosis and impaired mucosal defense and intestinal barrier function appear to play a significant role.There is no clear definition for HAEC,but the diagnosis is primarily clinical,and treatment is guided based on severity.Here,we aim to provide a comprehensive review of the clinical presentation,etiology,pathophysiology,and current therapeutic options for HAEC.

关键词： Hirschsprung’s Enterocolitis Pathogenesis Microbiome Dysbiosis Dysmotility Treatment

Research advances on the diagnostic score of Hirschsprung-associated Enterocolitis

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Chinese Journal of Pediatric Surgery 2024年第5期45卷 477-480页

作者： Zhao Z. Hua Z. Children's Hospital of Chongqing Medical University Chongqing 400014 China

As a particularly severe complication of Hirschsprung’s disease（HD），Hirschsprung associated Enterocolitis （HAEC） is characterized by explosive diarrhea （usually bloody），fever and abdominal distension. Currently there is no consensus on diagnostic score of HAEC. Thus it is imperative to construct a more reasonable scoring system for early diagnosis and intervention. Summarizing the latest researches of diagnostic scores for HAEC，this review provides references for an early diagnosis of HAEC and improving the outcomes. © 2024 Chinese Medical Journals Publishing House Co.Ltd. All rights reserved.

关键词： Diagnosis Enterocolitis Hirschsprung disease

Neutropenic Enterocolitis:A clinico-pathological review

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World Journal of Gastrointestinal Pathophysiology 2019年第3期10卷 36-41页

作者： Rong Xia Xuchen Zhang Department of Pathology State University of New YorkDownstate Medical CenterBrooklynNY 11203United States Department of Pathology Yale University School of MedicineNew HavenCT 06520United States

Neutropenic Enterocolitis(NE)is a predominantly cecum-based disease with high mortality seen in patients post chemotherapy.The pathogenesis of NE is poorly understood and probably multifactorial involving mucosal injury,neutropenia,and impaired host defense to intestinal organisms.The clinical presentation is characterized as ileocolonic inflammation and bowel wall thickening in patients with neutropenia,fever,and abdominal pain.The pathological features of NE include patchy necrosis,hemorrhage,ulcer,edema,perforation,infiltrating organisms,and characteristically,depletion of inflammatory cells(neutrophils).NE should always be considered as a possible diagnosis in immunosuppressed patients,especially those receiving chemotherapy.High clinical and histological diagnostic discordance rate exists.High index of clinical suspicion and prompt appropriate personalized management are essential to achieve a lower mortality rate.

关键词： Neutropenic Enterocolitis Typhlitis Chemotherapy Neutropenia

Expression of SIRT1 signaling pathway in intestinal tissues of neonatal necrotizing Enterocolitis

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Journal of Hainan Medical University 2019年第8期25卷 18-23页

作者： Lan Zhang Bo-Liang Wang Li Wang Qiong Gao Zhao-Xia Xi Yan-Hong Gui Hui-Ping Wang The Second Affiliated Hospital of Xi'an JiaoTong University Department of Pediatric NeonatalShaanxi ProvinceXi'an 710004China

Objective:To analyze the expression of sirtuin type 1 (SIRT1) signal pathway in intestinal tissues of neonatal necrotizing Enterocolitis (NEC), and to preliminarily explore the role of SIRT1 in the occurrence of NEC.Methods: From January 2017 to June 2017, the ileal tissues of 35 neonates with NEC underwent one-stage fistula treatment were selected as NEC group, and the ileal tissues of these 35 neonates underwent two-stage fistula treatment were selected as control group. The expression levels of SIRT1, transcription factor-nuclear factor (NF-κB), and SUMO specific protease 1 (SENP1) were detected by qRT-PCR;the expressions of SIRT1, NF-κB, and SENP1 were detected by immunohistochemistry and Western blotting (WB). Results: SIRT1 mRNA, protein positive expression rate, average optical density, and relative protein expression in intestinal tissues of children in NEC group were significantly lower than those in control group (P<0.05), however, the expression of NF-κB, the SENP1 mRNA and protein positive expression rates, the average optical density, and relative protein expression were significantly increased (P<0.05).Conclusion: SIRT1 is low expressed in intestinal tissues of children with NEC, the possible reason is that SIRT1 signaling pathway is suppressed and then NEC occurs.

关键词： Sirtuin type 1 Neonatal necrotizing Enterocolitis Transcription factor-nuclear factor SUMO-specific protease 1

Microscopic colitis in patients with mild duodenal damage:A new clinical and pathological entity(“lymphocytic Enterocolitis”)?

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World Journal of Gastrointestinal Pathophysiology 2016年第4期7卷 307-313页

作者： Gabriele Antonio Bonagura Davide Giuseppe Ribaldone Sharmila Fagoonee Nicoletta Sapone Gian Paolo Caviglia Giorgio Maria Saracco Marco Astegiano Rinaldo Pellicano Unit of Gastroenterology and Hepatology Molinette Hospital Institute for Biostructures and Bioimages-CNR c/o Molecular Biotechnology Center University of Torino Department of Medical Sciences University of Turin Department of Oncology University of Torino

AIM To evaluate the potential association between mild duodenal damage and microscopic colitis(MC).METHODS We retrospectively included 105 consecutive patients with type I Marsh-Oberhuber duodenal damage and negativity for immunoglobulin A anti-endomysium and anti-tissue transglutaminase.The following parameters were analyzed:Sex,age at execution of esophagogastroduodenoscopy,duodenal damage,and number of intraepithelial lymphocytes at biopsies,prevalenceof Helicobacter pylori infection,age at execution of colonoscopy,macroscopic and microscopic features of colonoscopy,family history of gastrointestinal and autoimmune diseases,smoking habits,biochemical parameters of inflammation and autoimmunity,use of proton pump inhibitors or nonsteroidal anti-inflammatory drugs,adverse reactions to drugs or foods,pathologies known to be associated with celiac disease or MC,living on a gluten-free diet or on a gluten-low diet for at least 1 mo.RESULTS Colonoscopy was performed in 59 patients,but only in 48 of them biopsies were taken in the entire colon.Considering the latter cohort,the diagnosis of MC was met in 25(52.1%) patients while in 18 patients other pathologic findings were reported:13(27%) cases of nonspecific inflammatory bowel disease,2(4.2%) cases of Crohn's disease,2(4.2%) cases of eosinophilic gastroenteritis,and 1(2.1%) case of autoimmune enteritis.Five(10.4%) patients had a normal colonoscopic result.Matching the groups by age,and considering only patients who underwent colonoscopy(42.7 ± 15.5 years) vs those who did not undergo colonoscopy(36.9 ± 10.6 years),a statistical difference was found(P = 0.039).Focusing on symptoms,diarrhea was statistically more prevalent in MC group than in patients who did not undergo colonoscopy(P = 0.03).CONCLUSION Mild duodenal damage is associated with MC in more than half of the cases.This association supports the hypothesis of a link between these two entities.

关键词： Autoimmune diseases Celiac disease Helicobacter pylori Intraepithelial lymphocytes Lymphocytic colitis Lymphocytic Enterocolitis Microscopic colitis