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Relationship between pouch microbiota and pouchitis following restorative proctocolectomy for ulcerative colitis

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World Journal of Gastroenterology 2014年第29期20卷 9665-9674页

作者： imerio angriman Marco Scarpa Ignazio Castagliuolo Department of Surgery Gastroenterology and OncologyUniversity of Padova Surgical Oncology Unit Veneto Institute of Oncology (IOV-IRCCS) Department of Molecular Medicine University of Padova

Restorative proctocolectomy with ileal pouch-anal anastomosis(IPAA)has become the surgical treatment of choice for many patients with medically refractory ulcerative colitis(UC)and familial adenomatous polyposis(FAP).UC patients with IPAA(UC-IPAA)are,nevertheless,susceptible to inflammatory and noninflammatory sequelae such as pouchitis,which is only rarely noted in FAP patients with *** is the most frequent long-term complication of UC-IPAA patients,with a cumulative prevalence of up to 50%.Although the aetiology of pouchitis remains unclear,accumulating evidence suggests that a dysbiosis of the pouch microbiota and an abnormal mucosal immune response are implicated in its *** using culture and molecular techniques have detected a dysbiosis of the pouch microbiota in patients with *** factors,genetic associations,and serological markers suggest that interactions between the host immune response and the pouch microbiota underlie the aetiology of this idiopathic inflammatory *** systematic review focuses on the dysbiosis of the microbiota that inhabit the pouch in UC and FAP patients and its interaction with the mucosal immune system.A metaanalysis was not attempted due to the highly heterogeneous microbiota composition and the different detection methods used by the various *** no specific bacterial species,genus,or family has as yet been identified as pathogenic,there is evidence that a dysbiosis characterized by decreased gut microbiota diversity in UC-IPAA patients may,in genetically predisposed subjects,lead to aberrant mucosal immune regulation triggering an inflammatory process.

关键词： Pouchitis Inflammation of the ileal pouch Microbiota Bacteria Microbiome Ileal-pouch-anal anastomosis Ulcerative colitis Crohn's disease Inflammatory bowel disease

Perianal Crohn's disease: Is there something new?

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World Journal of Gastroenterology 2011年第15期17卷 1939-1946页

作者： Cesare Ruffolo Marilisa Citton Marco Scarpa imerio angriman Marco Massani Ezio Caratozzolo Nicolò Bassi Ⅱ Department of Surgery (IV unit) Regional Hospital Ca' Foncello 31100 Treviso Italy Department of Surgicaland Gastroenterological Sciences University of Padova 35122 Padua Padova Italy Department of Oncological Surgery VenetoOncological Institute 35100 Padova Italy Department of Surgicaland Gastroenterological Sciences University of Padova 35122Padua Padova Italy

Perianal lesions are common in patients with Crohn's disease, and display aggressive behavior in some cases. An accurate diagnosis is necessary for the optimal management of perianal lesions. Treatment of perianal Crohn's disease includes medical and/or surgical options. Recent discoveries in the pathogenesis of this disease have led to advances in medical and surgical therapy with good results. Perianal lesions in Crohn's disease remain a challenging aspect for both gastroenterologists and surgeons and lead to a greatly impaired quality of life for all patients affected by this disease. A multidisciplinary approach is mandatory to obtain the best results.

关键词： Crohn disease Diagnosis Biologic therapy Surgery Rectal fistula

Inflammatory colonic carcinogenesis: A review on pathogenesis and immunosurveillance mechanisms in ulcerative colitis

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World Journal of Gastroenterology 2014年第22期20卷 6774-6785页

作者： Marco Scarpa Ignazio Castagliuolo Carlo Castoro Anna Pozza Melania Scarpa Andromachi Kotsafti imerio angriman Surgical Oncology Unit Veneto Institute of Oncology (IOV-IRCCS)35128 PadovaItaly Department of Molecular Medicine University of Padova35128 PadovaItaly Department of Surgery Gastroenterology and OncologyUniversity of Padova35128 PadovaItaly

Ulcerative colitis(UC)is characterized by repeated flare-ups of inflammation that can lead to oncogenic insults to the colonic ***-associated carcinogenesis presents a different sequence of tumorigenic events compared to those that contribute to the development of sporadic colorectal *** fact,in UC,the early events are represented by oxidative DNA damage and DNA methylation that can produce an inhibition of oncosuppressor genes,mutation of p53,aneuploidy,and microsatellite *** of tumor suppressor and DNA mismatch repair gene promoter regions is an epigenetic mechanism of gene silencing that contribute to tumorigenesis and may represent the first step in inflammatory ***,p53 is frequently mutated in the early stages of UC-associated *** is an independentrisk factor for forthcoming carcinogenesis in *** cell-T-cell cross-talk mediated by CD80 is a key factor in controlling the progression from low to high grade dysplasia in UC-associated carcinogenesis.

关键词： Colorectal cancer Ulcerative colitis Carcinogenesis Immune surveillance

B1a lymphocytes in the rectal mucosa of ulcerative colitis patients

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World Journal of Gastroenterology 2012年第2期18卷 144-149页

作者： Lino Polese Riccardo Boetto Giuseppe De Franchis imerio angriman Andrea Porzionato Lorenzo Norberto Giacomo Carlo Sturniolo Veronica Macchi Raffaele De Caro Stefano Merigliano Department of Surgical and Gastroenterological Sciences University of PadovaVia Giustiniani 235128 PadovaItaly Department of Laboratory Medicine Padova University HospitalVia Giustiniani 235128 PadovaItaly Department of Human Anatomy and Physiology University of PadovaVia Gabelli 6535128 PadovaItaly

AIM:To assess B1a cell expression in the rectal mucosa of ulcerative colitis (UC) patients in comparison with healthy ***:Rectal mucosa biopsies were collected from 15 UC patients and 17 healthy ***5 + B cells were analysed by three colour flow cytometry from rectal mucosal samples after mechanical disaggregation by Medimachine.Immunohistochemical analysis of B and T lymphocytes was also *** between,on the one hand,rectal B1a cell concentrations and,on the other,erythrocyte sedimentation rate and C-reactive protein levels and clinical,endoscopic and histological disease activity indices were ***:Rectal B-lymphocyte (CD19 + /CD45 +) rate and concentration were higher in UC patients compared with those in healthy controls (47.85% ± 3.12% vs 26.10% ± 3.40%,P=0.001 and 501 ± 91 cells/mm 2 vs 117 ± 18 cells/mm 2,P < 0.001);Rectal B1a cell density (CD5 + CD19 +) was higher in UC patients than in healthy controls (85 ± 15 cells/mm 2 vs 31 ± 6.7 cells/mm 2,P=0.009).Rectal B1a cell (CD5/CD19 +) rate correlated inversely with endoscopic classification (Rs=-0.637,P < 0.05).CONCLUSION:B1a lymphocytes seem to be involved in the pathogenesis of UC,however,the role they play in its early phases and in disease activity,have yet to be defined.

关键词： B1 cell CD5 Flow cytometry Rectum Ulcerative colitis

Relevance of fecal calprotectin and lactoferrin in the postoperative management of inflammatory bowel diseases

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World Journal of Gastrointestinal Surgery 2016年第3期8卷 193-201页

作者： Roberta Caccaro imerio angriman Renata D'Incà Department of Surgery Oncology and Gastroenterology Gastroenterology Section University Hospital of Padua Department of Surgery Oncology and Gastroenterology Surgery Section University Hospital of Padua

The role of fecal lactoferrin and calprotectin has been extensively studied in many areas of inflammatory bowel disease(IBD) patients' management. The postoperative setting in both Crohn's disease(CD) and ulcerative colitis(UC) patients has been less investigated although few promising results come from small, crosssectional studies. Therefore, the current post-operative management still requires endoscopy 6-12 mo after intestinal resection for CD in order to exclude endoscopic recurrence and plan the therapeutic strategy. In patients who underwent restorative proctocolectomy, endoscopy is required whenever symptoms includes the possibility of pouchitis. There is emerging evidence that fecal calprotectin and lactoferrin are useful surrogate markers of inflammation in the post-operative setting, they correlate with the presence and severity of endoscopic recurrence according to Rutgeerts' score and possibly predict the subsequent clinical recurrence and response to therapy in CD patients. Similarly, fecal markers show a good correlation with the presence of pouchitis, as confirmed by endoscopy in operated UC patients. Fecal calprotectin seems to be able to predict the short-term development of pouchitis in asymptomatic patients and to vary according to response to medical treatment. The possibility of both fecal markers to used in the routine clinical practice for monitoring IBD patients in the postoperative setting should be confirmed in multicentric clinical trial with large sample set. An algorithm that can predict the optimal use and timing of fecal markers testing, the effective need and timing of endoscopy and the cost-effectiveness of these as a strategy of care would be of great interest.

关键词： Calprotectin Lactoferrin Fecal markers Inflammatory bowel disease Post-operative Surgery Crohn’s disease Ulcerative colitis

Persistence of high CD40 and CD40L expression after restorative proctocolectomy for ulcerative colitis

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World Journal of Gastroenterology 2005年第34期11卷 5303-5308页

作者： Lino Polese imerio angriman Giuseppe De Franchis Attilio Cecchetto Giacomo C.Sturniolo Renata D'Incà Marco Scarpa Cesare Ruffolo Lorenzo Norberto Mauro Frego Davide F D'Amico Department of Gastroenterological and Surgical Sciences. Surgical Unit University of Padova Italy Department of Laboratory Medicine University of Padova Italy Department of Pathology University of Padova Italy Department of Gastroenterological and Surgical Sciences Gastroenterological Unit University of Padova Italy

AIM： To focus on the role of CD40 and CD40L in their pathogenesis. METHODS： We analyzed by immunohistochemistry the CD40 and CD40L expression in the pouch mucosa of 28 patients who had undergone RPC for UC, in the terminal ileum of 6 patients with UC and 11 healthy subjects. We also examined by flow cytometry the expression of CEH0 by B lymphoo/tes and monocytes in the peripheral blood of 20 pouch patients, 15 UC patients and 11 healthy controls. RESULTS： Ileal pouch mucosa leukocytes presented a significantly higher expression of CD40 and CD40L as compared to controls. This alteration correlated with pouchitis, but was also present in the healthy pouch and in the terminal ileum of UC patients. CD40 expression of peripheral B lymphocytes was significantly higher in patients with UC and pouch, respect to controls. Increased CD40 levels in blood B cells of pouch patients correlated with the presence of spondyloarthropathy, but not with pouchitis, or inflammatory indices. CONCLUSION： High CD40 expression in the ileal pouch mucosa could be implied in the pathogenesis of pouchitis following proctocolectomy for UC, whereas its increased levels on peripheral blood B lymphocytes are associated with the presence of extraintestinal manifestations.

关键词： Ulcerative colitis Pouchitis Spondyloarthropathy CD40 CD4OL Arthritis

Effects of iron manipulation on trace elements level in a model of colitis in rats

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World Journal of Gastroenterology 2005年第28期11卷 4396-4399页

作者： M Barollo R D'Incà M Scarpa V Medici R Cardin M Bortolami C Ruffolo I angriman GC Sturniolo Department of Surgical and Gastroenterological Sciences University of Padua Italy

AIM: Trace elements (TE) metabolism is altered in inflammatory bowel diseases. TE (zinc and copper) are constituents of antioxidant enzymes. Iron is involved in the pathogenesis of chronic inflammation. The aim was to evaluate zinc and copper status and the effects of iron manipulation in experimental ***: Twenty-four male Sprague-Dawley rats were divided into four groups: standard diet, iron-deprived diet,iron-supplemented diet, and sham-treated *** damage was scored. DNA adducts were measured in the colon. Liver and colonic concentration of TE were ***: Macroscopic damage was reduced in irondeprived groups and increased in iron-supplemented *** to the DNA was reduced in iron-deprived groups and increased in iron-supplemented groups. Liver and colonic iron concentrations were reduced in iron-deprived and increased in iron-supplemented rats. Liver zinc concentration was reduced after supplementation whereas colonic levels were similar in controls and treated rats. Liver copper concentration was reduced in all the colitic groups except in the iron-supplemented group whereas colonic concentration was increased in iron-deprived ***: Iron deprivation diminishes the severity of DNBS colitis while supplementation worsens colitis. Zinc and copper status are modified by iron manipulation.

关键词： Trace elements Colitis

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中毒性巨结肠症的早期手术治疗

世界核心医学期刊文摘（胃肠病学分册） 2006年第2期2卷 8-8页

作者： D' Amico C. Vitale A. angriman I. 尹勇 Department of Surgical and Gastroenterological Sciences University of Padua School of Medicine Via Giustiniani 2 IT-35128 Padova Italy

Background: Toxic megacolon (TM) is a potentially lethal complication of idiopathic inflammatory bowel disease or infectious colitis, characterized by total or segmental non- obstructive colonic dilatation of at least 6cm associated with systemic toxicity. Methods: Overall, 15 patients had surgery for TM at our institutions over a 10- year period (1993- 2003). In contrast to other studies that used medical therapy as the first- line treatment for TM, in our experience all patients underwent surgery as soon as possible after diagnosis of TM (early surgery). Results: 14 patients underwent subtotal colect- omy with terminal ileostomy, while for 1 patient the surgical procedure consisted only in a decompressive cecostomy. Two major complications occurred consisting of 2 cases of multiple organ failure leading to death. No other major complications or deaths were reported. The overall mortality rate was therefore 13% (0% in patients < 65 years). Conclusion: This study shows that early surgery has the potential to represent a valid therapeutic strategy for patients with TM resulting in a small number of TM- related complications and deaths. Elderly patients seem to have a high risk of multiple organ dysfunction syndrome and postsurgical death.

关键词：中毒性巨结肠全结肠切除感染性结肠炎全身中毒症状盲肠造口术炎症性肠病回肠造口术多脏器衰竭

协同刺激分子CD80、CD86以及IFNγ在溃疡性结肠炎发病机制中的意义

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世界核心医学期刊文摘（胃肠病学分册） 2005年第7期1卷 10-10页

作者： Scarpa M. Behboo R. angriman I. 王志宇 Azienda Ospedaliera di Padova Università di Padova Sez. Clinica Chirurgica I Via Giustiniani 2 35128 Padova Italy Dr

Several studies showed that costimulatory signals on antigen presenting cells are up- regulated in inflammatory bowel disease. We quantified the expression of CD80, CD86, and IFNγ in colonie mucosa of patients affected by ulcerative c olitis and correlated it with clinical and biochemical parameters to identify th e context of this up regulation. We enrolled 21 patients affected by ulcerative colitis and 6 healthy subjects. We evaluated for each patient gender, age, durat ion of disease, clinical, endoscopic and histologic disease activity index, medi cal therapy, ESR, serum CRP, WBC, and serum α 1- acid glycoprotein. CD80, CD86 , and IFNγ expression in the colonie mucosa was quantified using reverse trans cription polymerase chain reaction. Statistical analysiswas performed using Mann - Whitney U test and Spearman’ s rank correlation test. Significance was set a t P<0.05. CD80 was detectable in seven patients, while CD86 and IFNγ expressio n was evident in all UC patients. CD80 and CD86 were not detectable in control s pecimens. Colonie CD80 expression was correlated to the age of the patients. CD8 6 expression showed an inverse correlation with duration of disease and a direct correlation with serum CRP levels and histologic grade of disease activity. IFN γ was not correlated with any of the examined parameter. Our study confirms a major role in ulcerative colitis pathogenesis for CD86 which correlates with his tologic grade of disease and with serum CRP levels, and its up- regulation seem s to be higher at the beginning of the disease. In “ in vivo" conditions IFNγ may not be the only factor responsible for CD86 up- regulation in the ulcerati ve colitis colonic mucosa.

关键词： CD80 CD86 IFNγ 协同刺激分子溃疡性结肠炎疾病活动度炎症性肠病肠黏膜酸性糖蛋白疾病活动指数