Medical management of Crohn's disease

The medical approach to Crohn's disease has been modified in recent years thanks to the introduction of new therapies, like biologics. Also, well-designed studies and systematic reviews have allowed better evaluation of the role of old drugs like steroids and immunosuppressors. This review aims to evaluate the recent evidence on the medical approach to Crohn's disease in the different settings of the disease.Randomized controlled trials and meta-analyses were included in the review. The research on all the studies discussed was based on the Cochrane Library, Medline and Embase, using the following medical subject headings: Crohn's disease, clinical trial, therapy, 5-aminosalicylic acid, ste…

Letter: psoriasiform eruption during vedolizumab therapy

IL-23R determines susceptibility in Crohnʼs disease in a mediterranean area

Mycophenolate mofetil is a valid option in patients with inflammatory bowel disease resistant to TNF-α inhibitors and conventional immunosuppressants.

Abstract Background Few studies investigated the role of mycophenolate mofetil in inflammatory bowel disease, and none of them had specifically focused on patients with previous multiple intolerances and/or nonresponses to conventional immunosuppressants and biologics. Aims To evaluate clinical benefit and tolerability profile of mycophenolate mofetil in patients with inflammatory bowel disease and limited treatment options. Methods All consecutive patients with previous multiple intolerances and/or nonresponses to immunosuppressants and biologics who started an off-label treatment with mycophenolate mofetil from January 2014 to February 2016 were entered in a prospectively maintained datab…

Delayed-Onset Superior Mesenteric Artery Syndrome Presenting as Oesophageal Peptic Stricture

Superior mesenteric artery (SMA) syndrome is an infrequent cause of vomiting and weight loss due to compression of the third part of the duodenum by the SMA. We describe the case of a 17-year-old woman, admitted to our department for progressive dysphagia and severe weight loss due to an oesophageal peptic stricture, caused by chronic acid reflux secondary to duodenal compression by the SMA. Symptoms improved after (par)enteral nutrition and repeated oesophageal dilatation, thus supporting the role of intensive medical and endoscopic intervention as an alternative to surgery, at least in some cases.

Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in post-operative Crohn's disease

Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in postoperative Crohn's disease. Renna S, Cammà C, Modesto I, Cabibbo G, Scimeca D, Civitavecchia G, Mocciaro F, Orlando A, Enea M, Cottone M. Dipartimento di Medicina, Pneumologia e Fisiologia della Nutrizione Umana, Università di Palermo, Palermo, Italy. BACKGROUNDS & AIMS: The benefit of therapy for prevention of postoperative recurrence of Crohn's disease (CD) is limited. Clinical relapse and severe endoscopic recurrence are the main outcomes in the evaluation of trials on prevention of recurrence. The aim of this meta-analysis was to focus on knowledge of the placebo rates of relapse and recurr…

Leukocytapheresis in patients with moderate-severe steroid-dependant ulcerative colitis: Clinical Response without Endoscopic Response

Infliximab in the treatment of Crohn's disease: Predictors of response in an Italian multicentric open study

Abstract Background. Almost 20% of patients with active Crohn's disease are refractory to conventional therapy. Infliximab is a treatment of proven efficacy in this group of patients and it is not clear which variables predict a good response. Aims. To evaluate the role of infliximab looking at the predictors of response in a large series of patients with Crohn's disease. Patients and methods. Five hundred and seventy-three patients with luminal refractory Crohn's disease (Crohn's Disease Activity Index (CDAI) > 220–400) (312 patients) or with fistulising disease (190 patients) or both of them (71 patients) were treated with a dose of 5 mg/kg in 12 Italian referral centres. The primary endp…

Comparing medical treatments for Crohn’s disease

The drugs available for inflammatory bowel disease are aminosalicylates, antibiotics, steroids, immunosuppressors and biologics. The effectiveness of these drugs has been evaluated in many randomized clinical trials, mainly versus placebo. Few studies have been conducted comparing the different drugs among themselves, owing to the methodological problems raised by comparative trials, such as sample size and blindness. This review focuses mainly on the randomized clinical trials that have compared different treatments. Of course comparisons are mainly between drugs used in a particular setting (mild, moderate and severe disease). However, on many occasions there is no homogeneity in these cl…

Multifocal Pyoderma Gangrenosum Resistant to Infliximab in Active Ulcerative Colitis: Donʼt Forget the Role of Cyclosporin

Is 5-ASA Still the Treatment of Choice for Ulcerative Colitis?

5-Amino-salacylic acid (5-ASA) is up to now the treatment of choice in the induction and maintenance of remission of mild-to-moderate ulcerative colitis (UC). Sulfasalazine, despite similar efficacy, is hampered by more side effects, but in presence of peripheral arthopaties it remains the treatment of choice. The new delayed release MMX formulation seems to be promising in reducing compliance problems, but further studies are warranted to show the superiority of new MMX formulation compared with the older formulations of 5-ASA. Some trials evaluated also the efficacy and safety of once-daily dosing of older 5-ASA formulations in maintenance of remission, finding a greater adherence to ther…

Combined treatment with adalimumab and surgery in a patient with steroid-dependent Crohn's disease complicated by perianal disease

Use of corticosteroids and immunosuppressive drugs in inflammatory bowel disease: Clinical practice guidelines of the Italian Group for the Study of Inflammatory Bowel Disease

Abstract The two main forms of intestinal bowel disease, namely ulcerative colitis and Crohn’s disease, are not curable but can be controlled by various medical therapies. The Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) has prepared clinical practice guidelines to help physicians prescribe corticosteroids and immunosuppressive drugs for these patients. The guidelines consider therapies that induce remission in patients with active disease as well as treatment regimens that maintain remission. These guidelines complement already existing guidelines from IG-IBD on the use of biological drugs in patients with inflammatory bowel diseases.

Clinical benefit of vedolizumab on articular manifestations in patients with active spondyloarthritis associated with inflammatory bowel disease.

Vedolizumab (VDZ) is a new biological agent which was recently approved for the treatment of inflammatory bowel disease (IBD)1 following the good clinical responses reported by clinical trials for both Crohn's disease2 and ulcerative colitis.3 However, the effects of VDZ on extraintestinal manifestations were not reported in these trials, and the ‘real life’ experience is still limited. On these premises, we read with interest the recent work by Varkas et al 4 reporting a series of five patients with IBD who were treated with VDZ and promptly developed new onset or exacerbation of spondyloarthritis (SpA), irrespective of the response to treatment on intestinal symptoms. Although the hypothe…

Oral lichen planus after certolizumab pegol treatment in a patient with Crohn's disease

Dear Sir , Lichen planus (LP) is a relatively uncommon inflammatory dermatosis of the mucocutaneous surfaces that can present with a variety of clinical manifestations and, most commonly, affecting middle-aged adults. The disease course may be short or chronic, although most cases may resolve after 1 month to 7 years. The real prevalence of LP is unknown, but is estimated to be 1% in the USA.1 The pathogenesis of LP is not entirely understood. In general, activated T lymphocytes are recruited to the dermal–epidermal junction and induce apoptosis in basal keratinocytes. Both CD4+ and CD8+ T lymphocytes are found in the lichenoid infiltrate of LP, with a predominance of the latter cell type b…

Infliximab in severe ulcerative colitis: short-term results of different infusion regimens and long-term follow-up

Background Severe ulcerative colitis is a life-threatening disorder, despite i.v. glucocorticoids treatment. Infliximab has been proposed as a safe rescue therapy. Aim To evaluate short- and long-term effectiveness and safety of infliximab in severe refractory ulcerative colitis. Methods Eighty-three patients with severe ulcerative colitis (i.v. glucocorticoids treatment-refractory) were treated with infliximab in 10 Italian Gastroenterology Units. Patients underwent one or more infusions according to the choice of treating physicians. Short-term outcome was colectomy/death 2 months after the first infusion. Long-term outcome was survival free from colectomy. Safety data were recorded. Resu…

W1113 Efficacy and Safety of Endoscopic Balloon Dilation of Symptomatic Intestinal Crohn's Disease Strictures

Aim: To evaluate prospectively the clinical efficacy and safety of endoscopic hydrostatic balloon dilation in a consecutive cohort of symptomatic intestinal Crohn’s disease strictures. Methods: Between September 2003 and December 2008 we performed endoscopic balloon dilations in 37 Crohn’s disease patients with 39 intestinal symptomatic strictures (4 naive and 35 postoperative). Dilations were performed using a Rigiflex through-the-scope balloon. Clinical success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation, following technical success. Actuarial curves of clinical, endoscopic (redilation) and surgical recurrence were obtaine…

MINIMIZING INFLIXIMAB TOXICITY IN THE TREATMENT OF INFLAMMATORY BOWEL DISEASE

Abstract Background Infliximab is a widely used biological agent for the treatment of inflammatory bowel disease, and has a favorable risk/benefit ratio. Aim It is useful to know that patients treated with infliximab are exposed to developing adverse events that could be reduced with a prudent and a rational clinical approach and by optimizing the treatment protocol. Methods PubMed (including Epub) was searched in October 2006 and again in March 2007. Results The high immunogenic potential of infliximab determines the antibodies that inhibit the effect of infliximab and the appearance of subsequent acute and delayed infusion reactions. Infliximab has an immunomodulatory effect, thus increas…

Cytomegalovirus disappearance after treatment for refractory ulcerative colitis in 2 patients treated with infliximab and 1 patient with leukapheresis

Physicians’ Knowledge and Application of Immunization Strategies in Patients with Inflammatory Bowel Disease: A Survey of the Italian Group for the Study of Inflammatory Bowel Disease

<b><i>Background:</i></b> No data on European countries about knowledge and application of immunization strategies in patients with inflammatory bowel disease (IBD) are available. <b><i>Objectives:</i></b> We designed a questionnaire aimed at exploring these issues among Italian gastroenterologists dealing with adult and paediatric IBD. <b><i>Methods:</i></b> An anonymous, 24-item, questionnaire was sent via e-mail to all members of the Italian Group for the study of Inflammatory Bowel Disease. Three sets of questions were formulated: (1) Characteristics of respondents; (2) General opinions on the role of vaccines in IB…

Advanced age is an independent risk factor for severe infections and mortality in patients given anti-tumor necrosis factor therapy for inflammatory bowel disease.

See related article, Oostlander AE et al, on page 116 in Gastroenterology. BACKGROUND & AIMS: Few data are available on effects of biologic therapies in patients more than 65 years old with inflammatory bowel disease (IBD). We evaluated the risk and benefits of therapy with tumor necrosis factor (TNF) inhibitors in these patients. METHODS: We collected data from patients with IBD treated with infliximab (n 2475) and adalimumab (n 604) from 2000 to 2009 at 16 tertiary centers. Ninety-five patients (3%) were more than 65 years old (52 men; 37 with ulcerative colitis and 58 with Crohn’s disease; 78 treated with infliximab and 17 with adalimumab). The control group comprised 190 patients 65 yea…

Mongersen, an oral SMAD7 antisense oligonucleotide, and crohn's disease

Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor β1 (TGF-β1) due to high levels of SMAD7, an inhibitor of TGF-β1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7.In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activit…

The METEOR Trial: The Burial of Methotrexate in Ulcerative Colitis?

Investigational agents for Crohn's disease.

IMPORTANCE OF THE FIELD: Increased understanding of the biological mechanisms of Crohn's disease has opened the door to a large number of new molecules; some of these are approved for clinical use, while others remain under evaluation. In this review, we examine the clinical efficacy of all the new drugs that have been evaluated in controlled trials in the last 12 years. AREAS COVERED IN THIS REVIEW: Anti-TNF therapy has been reviewed briefly, given the many comprehensive reviews on this topic; attention is focused mainly on the other biological therapies. In assessing the clinical efficacy of these molecules, we consider only the remission rate, as this is considered the most meaningful en…

The role of CARD15 mutations and smoking in the course of Crohn's disease in a Mediterranean area.

To evaluate the role of CARD15 mutations and smoking in the main events of Crohn's disease (CD).A total of 182 patients with CD were included in a prospective study in order to evaluate the role of CARD15 mutations and smoking in the main outcomes of disease course: first operation and surgical recurrence. The following variables were evaluated in a univariable and multivariable analysis: age, sex, site of disease, pattern, smoking habit, extraintestinal manifestations, duration of disease, and CARD15 mutation. The Kaplan-Meier method for survival curves and Cox model for multivariable analysis were, respectively, used.A total of 110 patients were operated on and 32 were reoperated on. The …

Infliximab, azathioprine or combination therapy in the treatment of active Crohn's disease.

The treatment of moderate-to-severe steroid-dependent Crohn's disease has been a challenging issue for the gastroenterologist. Until to 10 years ago, immunosuppressors, mainly azathioprine or 6-mercaptopurine, were the best possible treatments available, and remission rates ranged from 30 to 60% according to the results of open studies and controlled trials. Recently, infliximab has been shown to be effective in steroid-dependent patients and, combined with azathioprine, it has been shown to increase 1-year remission rates. A recent large randomized controlled trial comparing infliximab, azathioprine and infliximab plus azathioprine demonstrated that the combination of infliximab plus azath…

Diagnostic and vaccine strategies to prevent infections in patients with inflammatory bowel disease.

Summary Objectives The treatment of inflammatory bowel disease (IBD) has been revolutionized by the use of immunomodulatory agents. Although these potent drugs are effective in controlling disease activity, they also cause an increased risk of new infections or reactivation of latent infections. On these premises, we aimed to provide guidance on the definitions of immunocompromised patients, opportunistic infections and the risk factors associated with their occurrence in an IBD context, and to suggest the proper screening tests for infectious diseases and the vaccination schedules to perform before and/or during therapy with immunomodulators. Methods All the most recent evidences – filtere…

Fatal necrotising fasciitis associated with intramuscular injection of nonsteroidal anti-inflammatory drugs after uncomplicated endoscopic polypectomy.

Summary Necrotising fasciitis is a life-threatening infection of the superficial muscle fascia and the adjacent deep layer of subcutaneous tissue that is often fatal. A 46-year-old woman was admitted to the intensive care unit (ICU) three days after an uncomplicated endoscopic polypectomy because of necrotising fasciitis of left tight, buttock and retroperitoneal space and septic shock. Six hours after the polypectomy she was given an intramuscular injection of ketorolac in the left tight because of moderate low abdominal pain. Twelve and 24h later she was treated with another two intramuscular injection of diclofenac in the left tight for severe pains in the left hip joint region. The shoc…

A real life comparison of the effectiveness of adalimumab and golimumab in moderate-to-severe ulcerative colitis, supported by propensity score analysis

Abstract Background Adalimumab and golimumab are effective in the treatment of moderate to severe ulcerative colitis. Aims We reported the comparative effectiveness of adalimumab and golimumab in ulcerative colitis. Methods 118 patients treated with adalimumab and 79 treated with golimumab were included and evaluated at 8 weeks and at the end of follow up. Results Overall clinical benefit was 72.6% at 8 weeks and 58.9% at the end of follow up. Patients with longer disease duration and those treated with adalimumab had a better outcome. Clinical benefit was 78.8% in adalimumab patients and 63.3% in golimumab patients (p = 0.026) after 8 weeks; it was 66.9% in adalimumab patients and 46.8% in…

Efficacy and safety of endoscopic balloon dilation of symptomatic intestinal Crohn's disease strictures

Abstract Aim To evaluate prospectively the clinical efficacy and safety of endoscopic hydrostatic balloon dilation in a consecutive cohort of symptomatic intestinal Crohn's disease strictures. Methods Between September 2003 and December 2008 we performed endoscopic balloon dilations in 37 Crohn's disease patients with 39 intestinal symptomatic strictures (4 naive and 35 postoperative). Dilations were performed using a Rigiflex through-the-scope balloon. Clinical success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation, following technical success. Actuarial curves of clinical, endoscopic (redilation) and surgical recurrence were …

Intestinal permeability and genetic determinants in patients, first-degree relatives, and controls in a high-incidence area of Crohn's disease in Southern Italy.

1. Am J Gastroenterol. 2005 Dec;100(12):2730-6. Intestinal permeability and genetic determinants in patients, first-degree relatives, and controls in a high-incidence area of Crohn's disease in Southern Italy. Fries W, Renda MC, Lo Presti MA, Raso A, Orlando A, Oliva L, Giofré MR, Maggio A, Mattaliano A, Macaluso A, Cottone M. Dipartimento di Medicina Interna e Terapia Medica, Università di Messina, Messina, Italy. OBJECTIVE: A defect of gastrointestinal barrier function is considered to represent an important step in the pathogenesis of Crohn's disease (CD) but the mechanisms leading to an increased intestinal permeability (IP) are poorly understood. Since IP is influenced by pro-inflammat…

Persistence on Anti-Tumour Necrosis Factor Therapy in Older Patients with Inflammatory Bowel Disease Compared with Younger Patients: Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD)

BACKGROUND AND OBJECTIVE: Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). METHODS: We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls < 60 years of age at their first course of anti-TNF treatment. Data concerning persistence on therapy over the first year of treatment (primary objective) together …

Course of Crohn’s Disease

Crohn’s disease (CD) is an inflammatory bowel disease with a chronic course and it is characterized by different events within time, which are in relation to the heterogeneity of the disease. The main events during the course of disease are activity, remission, relapse, obstruction, fistulizing, surgical resection, cancer and death. Unselected inception cohort studies are the best ones on which rely in order to avoid the selection bias from referral centers. Data produced using inception-cohort have shown a more benign course of CD than expected, an increased risk of surgery over time, with a trend which has been being reduced in the last decades, together with an increased use of biologics…

Can the serological status of anti-HBc alone be considered a sentinel marker for detection of occult HBV infection?

Some individuals have “occult” infection with hepatitis B virus (HBV), defined as presence of HBV genome in the serum or liver tissue without HBV surface antigen (HBsAg) in the serum. The aim of this study was to investigate whether serum antibodies against HBV core antigen in isolation (“anti-HBc alone”) are a useful marker of “occult” HBV in patients with or without hepatitis C virus (HCV) infection. “Anti-HBc alone” was detected in the sera of 119/6,544 (1.8%) asymptomatic outpatients referred to the diagnostic laboratory for routine testing for viral hepatitis, 62/607 (10.2%) drug users, and 42/195 (21.5%) patients with hepatocellular carcinoma. Using three in-house nested-PCR amplifica…

Familial Occurrence of Inflammatory Bowel Disease in Celiac Disease

BACKGROUND The authors have previously reported a possible increased risk of the familial occurrence of Crohn's disease in patients with celiac disease. AIM The aim of the current study was to evaluate in a case-control study the familial occurrence of inflammatory bowel disease (IBD) in first-degree relatives of patients with celiac disease. METHODS One hundred eleven consecutive patients with biopsy-proven celiac disease were interviewed to ascertain whether IBD was present in first-degree relatives. The number of relatives, their ages, and possible IBD status were collected in a questionnaire. When a diagnosis of familial IBD was reported, the diagnosis was checked in the hospital record…

Safety and potential interaction of immunosuppressive drugs for the treatment of inflammatory bowel disease in elderly patients

Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are chronic diseases associated with increased morbidity and reduced quality of life. Age may represent a risk factor for adverse events, due to the multimorbidity and polypharmacy, common in elderly patients. Elderly are often not included in clinical trials evaluating efficacy and safety of study drugs for the treatment of inflammatory bowel diseases. Several drugs, such as aminosalicylates, systemic corticosteroids, immunosuppressant drugs, biological drugs and Janus Kinase inhibitors, are available for the management of inflammatory bowel diseases. With the increasing spectrum of therapeutic options, it is th…

An Unusual Presentation of Zollinger-Ellison Syndrome

Abstract Zollinger-Ellison syndrome is an often progressive, persistent and frequently life-threatening disease, described for the first time as characterized by ulceration of the upper jejunum, hypersecretion of gastric acid and non-beta islet cell tumors of the pancreas; this syndrome is due to the hypersecretion of gastrin. We report a case of Zollinger-Ellison syndrome presenting as severe esophagitis evolving in stenosis, which demonstrates how a delayed diagnosis may induce risk of disease spreading. In this setting new diagnostic approaches, such as somatostatin receptor scanning and positron emission tomography with 68 Ga-labeled octreotide, could be particularly useful, as well as …

Treatment of small hepatocellular carcinoma with percutaneous ethanol injection: a validated prognostic model.

OBJECTIVE: Percutaneous ethanol injection may prolong the survival of patients with small hepatocellular carcinoma associated with cirrhosis. The aim was to identify prognostic factors of survival and of local recurrence, as well as separate new lesions. METHODS: We performed Cox regression analysis in 115 consecutive patients with hepatocellular carcinoma (81 Child-Pugh class A, 34 Child-Pugh class B) treated by percutaneous ethanol injection. The validity of the model was tested by comparing predicted and observed survival in 105 independent patients from an external series. RESULTS: Overall survival rates were 89%, 63%, and 43% at 1, 2, and 3 yr, respectively. The 1-, 2-, and 3-yr surviv…

Incidence of Crohn's disease and CARD15 mutation in a small township in Sicily.

Background: The incidence of Crohn's disease (CD) has been shown to be lower in Southern than in Northern Europe. Data on the frequency of the NOD2/CARD15 mutations for Mediterranean area are very scant. Aim: To determine the incidence of CD from 1979 to 2002 in a township in Sicily together with the allele frequency of NOD2/CARD15 mutations in patients, family members and controls, and to determine the allele frequency of these mutations in sporadic CD from other areas of Sicily in comparison with a control population. Methods: Casteltermini is a small town close to Agrigento (Sicily) with a population of 9,130 inhabitants. All the diagnoses of inflammatory bowel disease (IBD) made from 19…

Mesalazine for the treatment of inflammatory bowel disease

Ulcerative colitis (UC) and Crohn's disease (CD) represent a chronic inflammatory condition of the bowel that often require lifelong medical therapy for the induction and maintenance of the remission. Mesalazine therapies are available both as oral delayed-release and sustained-release formulation, topical formulations and as prodrug.Available literature regarding mesalazine is extensively reviewed in this article, covering its mechanism of action, pharmaceutics and pharmacokinetics, clinical efficacy, safety and tolerability in different settings.Mesalazine has a well-established role in the management of UC. It is the treatment of choice in active and inactive mild-to-moderate UC combinin…

Suboptimal performance of APRI and FIB-4 in ruling out significant fibrosis and confirming cirrhosis in HIV/HCV co-infected and HCV mono-infected patients

Purpose: We aimed to assess the diagnostic reliability of two indirect biomarkers, APRI and FIB-4, for the staging of liver fibrosis using transient elastography (TE) as reference standard, among HIV/HCV co-infected and HCV mono-infected patients. Methods: This is an observational, retrospective study on subjects who had access to the RESIST HCV from October 2013 to December 2016, a regional network encompassing 22 hospitals and academic centers throughout Sicily. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) < 9.5 kPa (significant fibrosis) and LSM ≥ 12.5 kPa (cirrhosis) were determined by receiver operator characteristics …

Toxic megacolon and human Cytomegalovirus in a series of severe ulcerative colitis patients

Abstract Background Human Cytomegalovirus (HCMV) infection has been reported to be a cause of refractory ulcerative colitis (UC). Toxic megacolon (TM) is a rare but severe complication of an acute attack of UC. Objectives Aim of this study is to evaluate in a case-control study the association between HCMV and TM. Study design All patients who were admitted at Medicine Department of V. Cervello Hospital in Palermo (tertiary referral center) for a severe UC flare-up complicated by the onset of TM (diameter of the transverse colon > 6 cm) between January 1990 and November 2011 were identified through the electronic database. A total of 24 consecutive patients (16 male/8 female) with TM were i…

Effectiveness and safety of biologics in pediatric inflammatory boweldisease: Real-life data from the Sicilian Network

Background: Biological therapies have modified the disease course of pediatric inflammatory bowel disease (IBD) and are routinely used in clinical practice. Our observational study aims to evaluate effectiveness and safety of biologics in IBD. Method: Clinical benefit and safety data of 93 children with IBD, receiving biologics (Infliximab – IFX, Adalimumab – ADA, Golimumab – GOL) from January 2013 to December 2017, were extracted from the cohort of the Sicilian Network of IBD. Results: Among 87 children aged 7–17 years (63 Crohn's disease [CD], 24 Ulcerative colitis [UC]), 101 out of 108 biologic treatments were considered. Evaluation of 74 biologic treatments in CD patients at 26, 52, 104…

AISF position paper on HCV in immunocompromised patients.

Abstract This report summarizes the clinical features and the indications for treating HCV infection in immunocompromised and transplanted patients in the Direct Acting Antiviral drugs era.

Clinical course of ulcerative colitis

. Dig Liver Dis. 2008 Jul;40 Suppl 2:S247-52. Clinical course of ulcerative colitis. Cottone M, Scimeca D, Mocciaro F, Civitavecchia G, Perricone G, Orlando A. Department of Medicine, Pneumology and Nutrition Clinic, V. Cervello Hospital, University of Palermo, Palermo, Italy. AIM: To provide a review of studies on prognosis in ulcerative colitis by reviewing the relevant population-based cohort studies. On the basis of incidence and population studies, ulcerative colitis has a favourable clinical course, with good quality of life, a chronic course characterized by at least one relapse, and a surgery rate of 30% after 10 years from diagnosis. Patients affected by severe ulcerative colitis h…

Methodology for high-quality studies on course and prognosis of inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) are characterized by a chronic course with an alternation of relapses and remissions. Questions about prognosis are important for the patient who wants to know how the disease will affect his/her life and also for clinicians to make management decisions. Correct selection of the patients is the basis for good methodological studies on the course of IBD. A great proportion of data on the course of IBD is derived from a limited number of cohort studies. Studies help to define the endpoints for clinical trials and to identify subsets of patients in whom the prognosis of the disease can be stratified according to clinical features. Specific scientific requirem…

Six year adalimumab efficacy in steroid-dependent Crohn's disease patients: A prospective single-center real life study.

Abstract Background Adalimumab is effective in the treatment of Crohn's disease. We have already reported data on the efficacy of adalimumab in 110 steroid-dependent patients. At the end of the study 90 patients (64.5%) maintained clinical remission. Aims To assess efficacy and safety of adalimumab after 6 years in patients of the original cohort who responded to treatment. Methods The present study is an extension of the published paper on 90/110 patients. We report results on clinical remission and safety of 6 year maintenance therapy with adalimumab. Results Of the original cohort 90 patients completed the study, 17 were lost to follow-up and 3 died. At the end of follow-up (74.16 ± 10.3…

Clinical implications of mucosal healing in the management of patients with inflammatory bowel disease

AbstractThe natural history of Crohn's Disease and ulcerative colitis is characterized by repeated episodes of inflammation and ulceration of the bowel. This results in complications implying a worse quality of life and significant healthcare costs, due to hospitalization, surgery and an escalation of therapy.The main goal of the therapy in inflammatory bowel disease is to achieve and maintain disease remission, with an improved health-related quality of life, less hospitalization, and less surgery. The concept of remission has changed in the recent years. In fact the concept of clinical remission, where only the patients’ symptoms are in remission, has been replaced by the new concept of d…

Adalimumab in steroid-dependent Crohn's disease patients: prognostic factors for clinical benefit.

Background: Corticosteroids are effective in the treatment of Crohn's disease but some patients relapse during tapering or after discontinuation. We report data on efficacy and prognostic factors of response of adalimumab in steroid-dependent patients. Methods: In all, 110 steroid-dependent patients were treated with adalimumab (80/40 or 160/80 mg every other week followed by 40 mg every other week). Clinical remission was defined as steroid discontinuation without symptomatic recurrence and clinical response as the reduction or maintenance of the initial Crohn's Disease Activity Index (CDAI) value reducing steroid dosage but without its discontinuation at week 6 and at the end of follow-up…

Could JC virus provoke metastasis in colon cancer?

AIM: To evaluate the prevalence of John Cunningham virus (JC virus) in a small cohort of patients with colon cancer and to assess its presence in hepatic metastasis. METHODS: Nineteen consecutive patients with histologically diagnosed colon cancer were included in our study, together with ten subjects affected by histologically and serologically diagnosed hepatitis C virus infection. In the patients included in the colon cancer group, JC virus was searched for in the surgical specimen; in the control group, JC virus was searched for in the hepatic biopsy. The difference in the prevalence of JC virus in the hepatic biopsy between the two groups was assessed through the χ2 test. RESULTS: Four…

Improving patients' QoL: how the success of treatment can improve workability

The Selective Use of Combination Therapy in Patients with Inflammatory Bowel Disease Resistant to Anti-TNF: to Whom, How and How Long?

Sir, We read with interest the recent work by Peyrin-Biroulet and colleagues on the long-term outcome for patients starting anti-TNF monotherapy for Crohn’s disease [CD] and for those needing the addition of an immunomodulator [IM].1 We agree with the main finding of the study, i.e. starting with anti-TNF monotherapy does not worsen long-term disease outcomes. This is in line with data from the literature2 and with our recent prospective study on the concomitant use of an IM and infliximab [IFX] in patients with CD or ulcerative colitis who have had a primary or secondary non-response to IFX monotherapy3: …

Treatment of small hepatocellular carcinoma associated with cirrhosis by percutaneous ethanol injection. A trial with a comparison group.

Ethanol injection has been reported to be effective in the treatment of hepatocellular carcinoma, but no controlled randomized trials have been performed. We therefore performed a trial comparing ethanol injection with an untreated, matched historical comparison group in the treatment of hepatocellular carcinoma.From 1992 to 1993, 35 patients (14 Child's A and 21 Child's B cirrhosis) with small (4 cm) hepatocellular carcinoma associated with cirrhosis were treated by ethanol injection. Each patient was matched with an untreated case (followed up during the period 1984-89) for variables known to have independent prognostic value (age, Child's classification, number of lesions, alpha-fetoprot…

Severe acute colitis associated with CMV: a prevalence study.

Abstract Background. Cytomegalovirus has been identified as a pathogen that contributes to flares of colitis when detected in colonic specimens of patients with inflammatory bowel disease. Aim. To determine the overall prevalence and the role of cytomegalovirus infection in a consecutive series of patients with acute severe colitis admitted to our department from 2000 to 2003. Methods. Among 42 patients (38 with ulcerative colitis and 4 with Crohn's disease) admitted to our hospital for acute severe colitis, we performed proctoscopy and biopsy together with blood sample for cytomegalovirus determination at the time of admission, regardless of their steroid resistance. Results. In the 42 pat…

A Propensity Score-matched Comparison of Infliximab and Adalimumab in Tumour Necrosis Factor-α Inhibitor-naïve and Non-naïve Patients with Crohn's Disease: Real-Life Data from the Sicilian Network for Inflammatory Bowel Disease

Background and aims There is an unmet need to better understand the effectiveness of different biologics in inflammatory bowel diseases. We aimed at performing a multicentre, real-life comparison of the effectiveness of infliximab [IFX] and adalimumab [ADA] in Crohn's disease [CD]. Methods Data of consecutive patients with CD treated with IFX and ADA from January 2013 to May 2017 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. We used propensity score-matching accounting for the main baseline characteristics in TNF-α inhibitor-naive and non-naive patients. Results A total of 632 patients [735 total treatments] were included. Among naive patients, a cli…

Is Epstein-Barr virus infection associated with the pathogenesis of microscopic colitis?

Abstract Background Epstein-Barr virus (EBV) has been associated with inflammation in the colon, particularly in patients with inflammatory bowel disease (IBD). Even if a relevant plasmocytosis, similar to IBD, is present in microscopic colitis (MC), the frequency of EBV infection in this setting is unknown. Objectives We aimed to compare the frequency of colonic EBV infection in patients with MC, ulcerative colitis (UC), and irritable bowel syndrome (IBS). Study design The frequency of colonic EBV infection in biopsies of 30 patients with MC, 30 patients with UC, and 30 controls with IBS was retrospectively assessed. PCR was performed to detect viral EBV DNA in colonic biopsies. In situ hy…

Placebo Therapy in Crohn's disease

The knowledge of the outcome among patients receiving placebo is important for evaluating the response to therapy, for evaluating the natural history of a disease and for calculating the sample size for future clinical trials. In Crohn's disease placebo has been used in therapeutic trials in every relevant setting: active disease, prevention of relapse after induced medical remission and after surgery and fistulising disease. The analysis of the placebo response shows that in every setting there is a high heterogeneity demonstrating mainly that the selection of patients is not often homogeneous and that the outcome criteria used in the trials is not highly reliable. Better selection of pati…

COVID-19 Vaccination Willingness and Hesitancy in Patients With Inflammatory Bowel Diseases: Analysis of Determinants in a National Survey of the Italian IBD Patients’ Association

The coronavirus disease 2019 (COVID-19) pandemic has not finished yet, and the most promising option towards its ending is widespread vaccination. Because patients with inflammatory bowel diseases (IBDs), namely Crohn’s disease (CD) and ulcerative colitis (UC), often require immune-modifying treatment, which might increase the risk of opportunistic infection,1 their vaccination history for several infectious diseases is routinely checked, and when inadequate, vaccination is performed at diagnosis or ideally before immune suppressive treatment is started.1 However, IBD patients were not found to be at an increased risk of developing COVID-19 or of experiencing a more severe disease course.2

Cancer in Crohn's Disease patients treated with infliximab: a long-term multicenter matched pair study

Background: The long-term risk of neoplasia in Crohn's disease (CD) patients treated with infliximab is undefined. The aim was to assess, in a multicenter, matched-pair study, whether infliximab use in CD is associated with an increased frequency of neoplasia in the long term. Methods: A multicenter, long-term, matched-pair study was conducted in 12 referral inflammatory bowel disease (IBD) centers. An initial cohort of 808 CD patients, including 404 infliximab-treated (CD-IFX) and 404 matched CD controls never treated with infliximab (CD-C) studied from 1999 to 2004, was followed up for an additional 4 years (2004–2008). Cases and controls were matched for: sex, age (±5 years), CD site, fo…

Blood-based prognostic biomarkers in Crohn’s Disease patients on biologics: a promising tool to predict endoscopic outcomes

There is a growing need for biomarkers to predict therapeutic outcome in Crohn's disease (CD).The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics.Patients with CD who started biologics were enrolled. Multivariate analysis was used to evaluate whether NLR, PLR, ELR and ENLR at baseline and at w12 could predict ER (Simple Endoscopic Score for Crohn's disease [SES-CD] ≤2 or SES-CD≤2 and Rutgeerts i0-i1) after 52 weeks of treatment. Area under the curve (AUC) was calcul…

The Addition of an Immunosuppressant After Loss of Response to Anti-TNFα Monotherapy in Inflammatory Bowel Disease: A 2-Year Study

Background The addition of an immunosuppressant (IM) after loss of response to anti-TNFα monotherapy is an emerging strategy of therapeutic optimization in patients with inflammatory bowel disease (IBD). However, few clinical data have been reported to date. We aimed to evaluate the efficacy and safety of this selective combination therapy in patients with IBD. Methods All consecutive patients with loss of response to anti-TNFα monotherapy despite an intensive dose optimization who added an IM from October 2014 to October 2016 were entered into a prospective database. Results Among 630 patients treated with anti-TNFα agents during the study period, 46 (7.3%) added an IM. A total of 31 patie…

Cyclosporine or infliximab as rescue therapy in severe refractory ulcerative colitis: Early and long-term data from a retrospective observational study

Introduction: About 30-40% of patients with acute severe ulcerative colitis (UC) fail to respond to intensive intravenous (iv) corticosteroid treatment. Iv cyclosporine and infliximab are an effective rescue therapy in steroid-refractory UC patients but up to now it is still unclear which is the best therapeutic choice. Methods: We reviewed our series of severe steroid-refractory colitis admitted consecutively since 1994 comparing two historical cohort treated with iv cyclosporine (2 mg/kg) or iv infliximab (5 mg/kg). The main outcome was the colectomy rate at 3 months, 12 months and at the end of the follow-up. Results: A total of 65 patients were included: 35 in the cyclosporine group and…

The role of portal vein thrombosis in the clinical course of inflammatory bowel diseases: report on three cases and review of the literature.

Inflammatory bowel diseases are associated with an increased risk of vascular complications. The most important are arterial and venous thromboembolisms, which are considered as specific extraintestinal manifestations of inflammatory bowel diseases. Among venous thromboembolism events, portal vein thrombosis has been described in inflammatory bowel diseases. We report three cases of portal vein thrombosis occurring in patients with active inflammatory bowel disease. In two of them, hepatic abscess was present. Furthermore, we performed a systematic review based on the clinical literature published on this topic.

Early postoperative recurrence of severe crohnʼs disease, with colonic involvement and associated human cytomegalovirus infection, treated with oral valganciclovir and adalimumab

Biliary sludge and gallstones in pregnancy: Incidence, risk factors, and natural history

To evaluate the incidence and symptoms of and risk factors for biliary sludge and gallstones during pregnancy and to assess the natural history of these conditions in the first year after delivery.Cohort study.A total of 272 pregnant women recruited in the first trimester.Biliary sludge and gallstones were diagnosed using ultrasonography, both during pregnancy and after delivery. Predictors of the presence or disappearance of sludge and stones were examined.Overall, from the first trimester of pregnancy until the immediate postpartum period, 67 women were newly diagnosed with biliary sludge, and 6 women were newly diagnosed with gallstones. The respective incidence rates were 31% (95% Cl, 2…

P463 COVID-19 vaccination willingness and hesitancy in patients with Inflammatory Bowel Diseases (IBD): analysis of determinants in a national survey of the Italian IBD patients’ association (AMICI Onlus)

Abstract Background Vaccine hesitancy, the delay in acceptance or refusal of vaccination despite its availability, represents a threat to the diffusion and lethality of infectious diseases. COVID-19 vaccination has been recommended by national and international organizations in patients with Inflammatory Bowel Diseases (IBD). The aim of the study was to evaluate COVID-19 vaccine willingness and hesitancy in a population of Italian patients with IBD, and their determinants. Methods In February 2021 an online questionnaire focused on COVID-19 vaccine was proposed to a representative sample of Italian IBD patients. Socio-demographic characteristics, IBD features, lifestyle, perception of COVID…

HLA antigens in ulcerative colitis: a study in the Sicilian population

HLA antigens were investigated in 41 Sicilian patients with ulcerative colitis and in 151 healthy controls. Frequencies of HLA-B5 and DR2 were increased in the group of patients with ulcerative colitis whereas the DR3 antigen frequency was decreased. However the corrected p values were not significant. Thus, present results indicate that in ulcerative colitis HLA linked genetic factors play a marginal role, if any.

Infliximab three-dose induction regimen in severe corticosteroid-refractory ulcerative colitis: Early and late outcome and predictors of colectomy

Abstract Background Infliximab is effective as rescue therapy in severe corticosteroid-refractory ulcerative colitis. The optimal dose regimen and the long term benefits are not well defined. The aim of the present study was to evaluate short- and long-term colectomy rate in a cohort of patients with severe corticosteroid-refractory ulcerative colitis who received a three-dose infliximab induction regimen. Methods One hundred and thirteen patients admitted to 11 Italian IBD referral centres and treated with infliximab according to an intention to treat three-dose regimen were included. The co-primary endpoints were 3- and 12-month colectomy rate. The secondary end-points were the overall co…

JC Virus, Helicobacter pylori, and Oesophageal Achalasia: Preliminary Results from a Retrospective Case-Control Study.

Occult Hepatitis B and Infliximab-induced HBV Reactivation

Risk of Pneumonia Caused by Pneumocystis jiroveci in Inflammatory Bowel Disease: The Role of Concomitant Pulmonary Comorbidities

Radiofrequency thermal ablation vs. percutaneous ethanol injection for small hepatocellular carcinoma in cirrhosis: meta-analysis of randomized controlled trials.

Radiofrequency thermal ablation (RF) and percutaneous ethanol injection (PEI) have been employed in the treatment of small hepatocellular carcinoma (HCC) as curative treatments. The aim of the study was to review the available evidence comparing RF to PEI for small HCC.Cochrane, MEDLINE, CANCERLIT, and ENBASE databases were used.randomized clinical trials evaluating RF vs. PEI. Data were extracted from each randomized controlled trial (RCT). Primary outcomes were overall survival and local recurrence. Meta-analysis software was used and risk differences (RDs) and their 95% confidence intervals and Q-test for heterogeneity were calculated.Five RCTs were identified including 701 patients. The…

Tolerability profile of thiopurines in inflammatory bowel disease: a prospective experience

The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting.All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported.Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2-75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurren…

Postoperative maintenance therapy for inflammatory bowel disease.

. Curr Opin Gastroenterol. 2006 Jul;22(4):377-81. Postoperative maintenance therapy for inflammatory bowel disease. Cottone M, Orlando A, Modesto I. Department of General Medicine, Pneumology and Nutrition Clinic, Palermo University, Palermo, Italy. PURPOSE OF REVIEW: This review will highlight the knowledge gained from studies published in the year 2005 on maintenance treatment after surgery for inflammatory bowel diseases. RECENT FINDINGS: In Crohn's disease the role of smoking in increasing the risk of relapse and recurrence after surgery is confirmed. Ornidazole seems effective in reducing endoscopic recurrence and clinical relapse after surgery. Probiotics do not appear to be effective…

An update on medical management on Crohn's disease.

The management of Crohn's disease (CD) is continuously evolving. New issues emerging from more recent studies could influence the decision-making process in clinical practice.The aim of this review article is to highlight critical issues on the management of CD, new evidence from clinical trials, long-term prospective studies and real life experience, beyond the current guidelines.The role of mucosal healing in clinical practice is uncertain, clinical remission remains the primary end point. The timing for the definition of steroid-resistant CD should be considered between 2 and 4 weeks. Early treatment strategy with immunomodulators is effective for inducing remission but no controlled dat…

Blood-based prognostic biomarkers in Crohn’s Disease patients on biologics: a promising tool to predict endoscopic outcomes

There is a growing need for biomarkers to predict therapeutic outcome in Crohn’s disease (CD). The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics. Patients with CD who started biologics were enrolled. Multivariate analysis was used to evaluate whether NLR, PLR, ELR and ENLR at baseline and at w12 could predict ER (Simple Endoscopic Score for Crohn’s disease [SES-CD] ≤2 or SES-CD≤2 and Rutgeerts i0-i1) after 52 weeks of treatment. Area under the curve (AUC) was calc…