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BACKGROUND Disease phenotype and outcome of late-onset Crohn's disease are still poorly defined. METHODS In this Italian nationwide multicentre retrospective study, patients diagnosed ≥65 years (late-onset) were compared with young adult-onset with 16-39 years and adult-onset Crohn's disease 40-64 years. Data were collected for 3 years following diagnosis. RESULTS A total of 631 patients (late-onset 153, adult-onset 161, young adult-onset 317) were included. Colonic disease was more frequent in late-onset (P < 0005), stenosing behaviour was more frequent than in adult-onset (P < 0003), but fistulising disease was uncommon. Surgery rates were not different between the three age groups. Systemic steroids were prescribed more frequently in young adult-onset in the first year, but low bioavailability steroids were used more frequently in late-onset in the first 2 years after diagnosis (P < 0.036, P < 0.041, respectively). The use of immunomodulators and anti-TNF's even in patients with more complicated disease, that is, B2 or B3 behaviour (Montreal classification), remained significantly inferior (P < 0.0001) in late-onset compared to young adult-onset. Age at diagnosis, Charlson comorbidity index, and steroid used in the first year were negatively associated with the use of immunomodulators and biologics. Comorbidities, related medications and hospitalizations were more frequent in late-onset. Polypharmacy was present in 56% of elderly Crohn's disease patients. CONCLUSION Thirty-two percent of late-onset Crohn's disease presented with complicated disease behaviour. Despite a comparable use of steroids and surgery, immunomodulators and biologics were used in a small number of patients.

Inflammatory bowel diseases are chronic conditions of unknown etiology, showing a growing incidence and prevalence in several countries, including Italy. Although the etiology of Crohn's disease and ulcerative colitis is unknown, due to the current knowledge regarding their pathogenesis, effective treatment strategies have been developed. Several guidelines are available regarding the efficacy and safety of available drug treatments for inflammatory bowel diseases. Nevertheless, national guidelines provide additional information adapted to local feasibility, costs and legal issues related to the use of the same drugs. These observations prompted the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) to establish Italian guidelines on the safety of currently available treatments for Crohn's disease and ulcerative colitis. These guidelines discuss the use of aminosalicylates, systemic and low bioavailability corticosteroids, antibiotics (metronidazole, ciprofloxacin, rifaximin), thiopurines, methotrexate, cyclosporine A, TNFα antagonists, vedolizumab, and combination therapies. These guidelines are based on current knowledge derived from evidence-based medicine coupled with clinical experience of a national working group.

Background and Aims. Thiopurines are commonly used for treating ulcerative colitis (UC), despite the fact that controlled evidence supporting their efficacy is limited. The aim of this study was to evaluate the long-term outcome of thiopurines as maintenance therapy in a large cohort of UC patients. Methods. All UC patients receiving thiopurine monotherapy at three tertiary IBD centers from 1995 to 2015 were identified. The primary endpoint was steroid-free clinical remission. Secondary endpoints were mucosal healing (MH), defined as Mayo endoscopic subscore 0, long-term safety, and predictors of sustained clinical remission. Results. We identified 192 patients, contributing a total of 747 person-years of follow-up (median follow-up 36 months, range 1–210 months). Steroid dependency was the most common indication for thiopurine treatment (58%). Steroid-free remission occurred in 45.3% of patients; 36.3% stopped thiopurines because of treatment failure and 18.2% for adverse events or intolerance. The cumulative probability of maintaining steroid-free remission while on thiopurine treatment was 87%, 76%, 67.6%, and 53.4% at 12, 24, 36, and 60 months, respectively. MH occurred in 57.9% of patients after a median of 18 months (range 5–96). No independent predictors of sustained clinical remission could be identified. Conclusions. Thiopurines represent an effective and safe long-term maintenance therapy for UC patients.

Background Ustekinumab (UST) is increasingly used in Italy for the treatment of refractory Crohn’s disease (CD), however very few data concerning real-life experience has been reported. Therefore, the aim of this study was to assess the long-term effectiveness of UST in refractory CD patients treated in a large Italian cohort. Methods A retrospective study was conducted in 5 Italian tertiary centers. All adult CD patients who started UST because of anti-tumor necrosis factor (TNF) failure were included. The co-primary outcomes were steroid-free clinical remission (defined as Harvey Bradshaw Index, HBI ≤4) at weeks 26 and 52. Secondary outcomes were changes in HBI score, changes in C-reactive protein (CRP) values, normalization of CRP (≤0.5 mg/dl) at weeks 8, 26, and 52, and adverse events. Categorical variables were expressed as frequency and percentage. Unpaired t-test was used to compare variables. A p-value Results Between Nov 2018 and Feb 2020,140 patients (51.4% male; median age 45.0 years, IQR 36.3-54.0; median disease duration 16.0 years, IQR 8.0-22.0) were included. The majority of patients had ileocolonic disease (L1, 38.6%; L2, 11.4%; L3, 50.0%) and an inflammatory phenotype (B1, 50.7%; B2, 31.0%; B3, 18.3%). All patients had previously been exposed to at least one anti-TNF agent, 27.1% to 2 anti-TNF agents, and 20.0% to vedolizumab . At inclusion 15.7% of patients received corticosteroids and 8.6% immunomodulators. All patients received an intravenous dose of 6 mg/kg, followed by subcutaneous administration of 90 mg every 8 (90%) or 12 weeks (10%) according to clinical judgment. The proportion of patients achieving steroid-free clinical remission was 61.0% and 64.2% at weeks 26 and 52 respectively. A significant decrease in the mean HBI was reported from baseline to week 8 (6.8 ± 3.6 vs 4.5 ± 3.1; p Conclusion To our knowledge this is one of the largest Italian cohort followed up to 1 year, and the results confirm that UST is an effective and safe treatment in refractory CD patients.

Background Prevention of postoperative recurrence is a critical goal in Crohn’s disease (CD) management. Currently, postsurgical CD management and treatment are based on endoscopic monitoring performed within the first year after surgery. However, colonoscopy (CS) is an invasive and expensive procedure, unpleasant to patients. A non-invasive and patient friendly approach is required. Methods Consecutive CD patients who underwent ileo-cecal resection from July 2017 to January 2020 were prospectively enrolled in three Italian Centers and performed CS and bowel ultrasound (US) after six months from the surgery, in a blinded fashion. The patients also underwent complete clinical assessment and blood and stool samples were obtained for C-reactive protein (CRP), and fecal calprotectin (FC) measurements. The disease was considered clinically active if the Harvey–Bradshaw Index (HBI) was higher than 4. Uni- and multivariable analyses were used to assess the correlation between non-invasive parameters, including bowel US findings and FC values and endoscopic recurrence, defined by a Rutgeerts’s score (RS) > 2. Sensitivity, specificity, accuracy, PPV and NPV of bowel US parameters alone and in combination with FC in assessing endoscopic recurrence were calculated. Results Seventy patients were enrolled, 45 patients (64%) had an endoscopic recurrence (RS > 2) at 6 months. Thirteen out of 45 (29%) were symptomatic (HBI > 4). Bowel wall thickness (BWT), bowel wall flow (BWF, presence of vascular signals at color Doppler), the presence of mesenteric hypertrophy, the presence of limph-nodes and FC values significantly correlated with the endoscopic recurrence (p < 0.005). Independent predictors for endoscopic recurrence were BWT (for 1-mm increase: OR 2.63; 95% CI 1.136.12; p= 0.024), presence of lymph-nodes (OR 23.24; 95% CI 1.85291.15; p= 0.014) and FC > 50 µg/g (OR 11.86; 95% CI 2.60–54.09; p= 0.001). Sensitivity, specificity, accuracy, PPV and NPV of bowel US and/or FC are showed in Table 1. Table 1: Diagnostic accuracy of Bowel US and/or FC compared to CS in assessing endoscopic activity (CI 95%): per-patient analysis Conclusion Combined use of bowel US and FC is accurate in assessing endoscopic recurrence at 6 months in CD patients and represent a valid alternative to endoscopic assessment after surgery

Background Neuroendocrine Neoplasms (NENs) are a heterogeneous group of tumours deriving from the diffuse endocrine system. NENs may occur almost everywhere in the body but are most common in the gastrointestinal tract, the pancreas, and the lungs, with gastroenteropancreatic (GEP) tumours representing 70% of all NENs. GEP-NENs have rarely been reported in association with inflammatory bowel diseases (IBDs) but no definitive relationship between these tumours and IBD has been established Methods This was an ECCO COllaborative Network For Exceptionally Rare case reports project (ECCO-CONFER). We included cases of GEP-NENs diagnosed in patients with IBD that met the diagnostic criteria for NEN according to the European Neuroendocrine Tumour Society. Data were retrospectively collected in a standardized case report form and analysed for event association with patient’s and IBD-related factors Results GEP-NEN was diagnosed in 100 patients with IBD [61% female, 55% Crohn’s disease, median age 48 years (IQR 37–59)]. Overall the most common location was the appendix (39/100) followed by the colon (22/100). Complete IBD-related data was available for 50 individuals with a median follow-up of 30.5 months (IQR 11.2–70) following NEN diagnosis. At the last follow-up data, 47/50 patients were alive. Three deaths occurred, of which 2 were related to NEN. Median duration of IBD at NEN diagnosis was 84 months (IQR 10–151), and in 18% of cases NEN and IBD were diagnosed concomitantly. 20/50 of NENs were at stage I (T1N0M0) and 28/50 graded G1 (ki 67 ≤2 %) at diagnosis. Incidental diagnosis of NEN either during follow-up or during surgery as well as receiving diagnosis of NEN concomitantly with IBD was significantly associated with an earlier NEN stage (p< 0.01 and p Conclusion In the largest case series to date, prognosis of patients with concomitant GEP-NEN and IBD seems favorable. Incidental NEN diagnosis correlates with an earlier NEN stage and IBD-related therapies are independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis

Background The appropriate maintenance treatment for patients with acute severe ulcerative colitis (ASUC) responsive to intravenous steroids (IVS) is still a matter of debate. Although major Guidelines consider thiopurine maintenance an option in this setting, the long-term benefit of early immunomodulator (IMMs) initiation is not well established. The aim of our study was to explore the long-term outcome of patients with ASUC responsive to IVS who received different maintenance strategies Methods In a multicenter retrospective study, all patients with ASUC hospitalized between January 2005 and December 2017 in 14 Italian IBD referral centres were reviewed. Thiopurine and biologic-naïve patients experiencing their first acute severe attack and who responded to IVS were included in the study. Maintenance treatment was prescribed by attending physicians according to their clinical judgment. The main outcomes were recurrent flares requiring escalation of therapy, new hospitalization, and long-term colectomy rate. The Kaplan-Meier survival method was used to estimate the cumulative probability of a course without the main outcomes. Differences between curves were tested using the log-rank test. A propensity score matching analysis was performed to establish comparable groups of patients who received different maintenance treatment Results Overall 372 patients were reviewed. Of these, 141 met the inclusion criteria (males 61.7%, median age 34.5 (IQR 23–50). After response to IVS, 82 patients (58.1%) received maintenance treatment with aminosalicylates, 42 (29.8%) received IMMs and 17 (12.1%) were maintained with scheduled infliximab (IFX) + thiopurines. After a median follow-up of 48 (IQR 25–90) months, 94 patients (68.8%) experienced a flare requiring escalation of therapy, 51 (36.1%) required new hospitalization and 18 (12.8%) underwent colectomy. After 12, 36 and 60 months after the acute attack, the cumulative probability of a course without escalation of therapy was 59.6%, 33.3% and 23.1%; the cumulative probability of a hospitalization-free course was 83.9%, 67.4% and 59.5%; the cumulative probability of a colectomy-free course was 96.3%, 90.2%, and 88.9%. No differences were observed between patients receiving aminosalicylates, IMMs or IFX as maintenance treatment (log-rank test: p= 0.39; p = 0.41; p = 0.11 respectively). After a propensity score matching analysis, no significant difference in main outcomes was observed between patients maintained with aminosalicylates or IMMs/IFX Conclusion IMM-naïve ASUC patients responsive IVS remain at risk of relapse requiring escalation of therapy. Early IMMs introduction after the acute attack did not reduce the risk of escalation of therapy, hospitalization or colectomy

Background: Late-onset UC represents an important issue for the near future, but its outcomes and relative therapeutic strategies are yet poorly studied. Aim: To better define the natural history of late-onset ulcerative colitis. Methods: In a multicenter retrospective study, we investigated the disease presentation and course in the first 3 years in 1091 UC patients divided into 3 age-groups: diagnosis >65 years, 40-64 years, and

Background Inflammatory bowel disease (IBD) patient’s knowledge is a key factor for shared treatment decision making. Some studies have already investigated IBD knowledge but never focused on patient’s awareness about the major disease outcomes nor clinical course nor therapeutic aspects. The aim of the present study is to assess disease knowledge in IBD patients using a novel 11 items questionnaire. Methods An 11 items questionnaire was developed. The questionnaire explored different aspects of IBD course and prognosis: pattern of symptoms, disease complications, need for surgery, risk and prevention of colon-rectal cancer (CRC), extra-intestinal manifestations (EIMs), predictors of poor prognosis, benefit/risk of immunosuppressive and biological therapy and IBD in pregnancy. The questionnaire was handed out to consecutive Crohn’s disease (CD) and ulcerative colitis (UC) patients in regular follow-up at a referral centre. Clinical and socio-demographic characteristics were collected in a dedicate database. Descriptive analysis of quantitative variables was presented as mean or median. Fisher test and Student’s t-test were used for categorical and continuous variables. A p < 0.05 was considered statistically significant. Results Three hundred and four patients were enrolled and 290 completed the questionnaire (95%). Of these 53% UC and 47% CD. The mean age was 51 years (range 18–83); 56% were male. Most of the patients were in clinical remission (85%). The mean number of appropriate answer was 4 upon 11. Overall only 26% answered successfully more than half of the items. Looking at the single items, two third of patients were aware of current strategies of CRC prevention, chance of EIMs and woman capability to become pregnant. The questions about immunosuppression and biologic therapy were more correctly answered by those patients who had experienced them (p = 0.000001), whereas those about the risk of surgery were not influenced by the patient’s previous clinical history (UC p = 1; CD p = 0.067). Only about one third of women were aware of the most relevant risk factor of worst pregnancy outcome. Age Conclusion These results suggest that the overall disease knowledge in IBD patients is low and should be improved. Young age, education and biologic exposure are associated with an adequate awareness of disease course. This questionnaire should be validated and correlated to other patient-related measures such as health engagement and health literacy in prospective studies.

Background Saphenous vein conduits are still used in a large proportion of coronary artery bypass graft (CABG) operations. A recently commercialized nitinol mesh seems to improve venous graft patency. The aim of this study was to control nitinol mesh vein graft patency in a series of isolated CABG patients by computed tomographic (CT) scan. Methods In 25 patients (mean age: 61.0 ± 9.65 years), operated for isolated CABG, the eSVS nitinol mesh (Kips Bay Medical Inc., Minneapolis, Minnesota, United States) was used to wrap one vein graft in each patient. Nitinol mesh vein graft was used to revascularize the right coronary (4 patients; 16%), the posterior descending (18 patients; 72%), and the obtuse marginal (3 patients; 12%) arteries. CT scans were performed at 1, 6, and 12 months postoperatively. Results The procedure was uneventful in all patients. CT controls showed an overall patency rate of 86.9, 42.7, and 34.1% at 1, 6, and 12 months, respectively. The 4 mm mesh had a significantly higher patency rate at 12 months (83.33%) than the 3.5 mm one which showed quite unsatisfactory results (20%) (p = 0.02). Patients with graft occlusion underwent stress testing which was mildly positive in two cases. One of them underwent a percutaneous revascularization. Conclusion Despite promising early results, use of nitinol mesh for saphenous veins was disappointing in our experience. Further refinements are probably needed.

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 colectomy-free survival and the identification of predictors of colectomy. Results The 3- and 12-month colectomy rates were 18.6% (95%CI 11.8%–26.9%) and 25.6% (95%CI 17.9%–34.7%) respectively. High CRP values and severe endoscopic lesions were associated with the risk of colectomy: Risk Ratio (RR) = 2.15 (95%CI 1.05–4.36), and RR = 5.13 (95%CI 1.55–16.96), respectively. In patients escaping early colectomy, the probability of a colectomy-free course at 12, 24, 36 and 60 months was 91%, 85%, 81% and 73%, respectively. Endoscopic severity was the only predictor of long term colectomy (RR = 7.0; 95%CI 1.09–44.7). Adverse events occurred in 16 patients (14%); there was one death (0.88%) due to pulmonary abscess. Conclusions Infliximab is an effective and safe rescue therapy for severe corticosteroid-refractory ulcerative colitis. A three-dose induction regimen seems to be the treatment of choice for preventing early colectomy. Severe endoscopic lesions appear to be predictor of short- and long-term colectomy.

Introduction : The incidence of endoscopic recurrence (ER) in Crohn's disease following curative resection is up to 75% at 1 year. Endoscopy is the most sensitive method to detect the earliest mucosal changes and the severe ER at 1 year seems to predict a clinical relapse. Methods : The aim of this prospective study was to evaluate the incidence of early ER 6 months after curative resection. Secondary outcome was to evaluate the role of 5-aminosalicylic acid (5-ASA) in the prevention of ER at 6 months. A total of 170 patients were included in the study. They were carried-out from the evaluation of the appearance of ER during a trial performed to assess the role of azathioprine vs. 5-ASA as early treatment of severe ER. All the patients started 5-ASA treatment 2 weeks after surgery. Results : Six months after surgery ER was observed in 105 patients (62%). The endoscopic score was reported as severe in 78.1% of them (82 out of 105). At univariable analysis only ileo-colonic disease influenced the final outcome associating to a lower risk of severe ER (p = 0.04; OR 0.52, 95% CI 0.277–0.974). Conclusion: In this prospective Italian multicenter IG-IBD study a great proportion of ER occur within 6 months from ileo-colonic resection, with a significant rate of severe ER. Furthermore this study confirms the marginal role of 5-ASA in the prevention of ER. This suggests that post-surgical endoscopic evaluation should be performed at 6 months instead of 1 year to allow an adequate early treatment.

Background and aims The effectiveness of adalimumab in the treatment of ulcerative colitis is under debate. Although controlled trials have shown that adalimumab is significantly better than placebo, the absolute clinical benefit is modest. We report data on the effectiveness of adalimumab in a cohort of ulcerative colitis patients treated in 22 Italian centres. Methods All patients with active disease treated with adalimumab were retrospectively reviewed. Co-primary endpoints were clinical remission at weeks 4, 12, 24 and 54. Secondary endpoints were sustained clinical remission, steroid discontinuation, endoscopic remission and need for colectomy. Results Eighty-eight patients were included. Most patients had received previous infliximab treatment. Clinical remission rates were 17%, 28.4%, 36.4% and 43.2% at 4, 12, 24 and 54 weeks respectively. Twenty-two patients required colectomy. Clinical remission and low C-reactive protein at week 12 predicted clinical remission at week 54 (OR 4.17, 95% CI 2.36–19.44; OR 2.63, 95% CI 2.32–14.94, respectively). Previous immunosuppressant use was associated with a lower probability of clinical remission at week 54 (OR 0.67, 95% CI 0.08–0.66) and with a higher rate of colectomy (HR 9.7, 95% CI 1.46–9.07). Conclusion In this large “real-life” experience adalimumab appears effective in patients with otherwise medically refractory ulcerative colitis. Patients achieving early remission can expect a better long-term outcome.

Most patients with Crohn's disease will require surgery during the course of their disease. However, surgery is not curative and post-operative recurrence is quite inexorable. One year after resection up to 80% of patients have new lesions at the neo-terminal ileum and after 10 years approximately 50% of patients will experience recurrence of symptoms and 35% will need further surgery. Prevention of post-operative recurrence has, therefore, a central role in the management of Crohn's Disease. Several drugs have been evaluated to decrease the risk of both endoscopic and clinical recurrence but the overall results are largely not impressive. Among the different drugs evaluated, mesalazine, antibiotics (metronidazole and ornidazole), thiopurines and anti-TNFα antibodies have been shown to be effective whereas budesonide, probiotics and interleukin 10 are not effective. This review focuses on the actual evidence on the prevention of postoperative recurrence: randomised controlled trials and meta-analyses are critically reviewed and discussed with particular attention to the methodological aspects.

Objectives Carbon dioxide (CO(2)) insufflation was used by some devices for endoscopic vein harvest to create a subcutaneous tunnel and facilitate the vein harvest. In the literature, some cases of CO(2) micro- and macro-embolisms or hypercarbia during this procedure are described. The purpose of this study was to evaluate if the use of an open CO(2) system rather than a sealed system might be associated with different CO(2) absorption during the procedure. Methods Patients were randomized into two groups: those patients in the first group were submitted to endoscopic vein harvest using a sealed CO(2) insufflation; in the second group, the harvest was undertaken with an open CO(2) insufflation. Partial pressure of CO(2) in the arterial blood (PaCO(2)) and end-tidal CO(2) (ETCO(2)) was recorded following anaesthesia induction and before the endoscopic procedure (T0), every 10 min during the endoscopic step (T1) and end after 10 min from the CO(2) insufflation termination (T2). Results A total of 60 patients were enrolled. PaCO(2) increased significantly between T0, T1 and T2 in both groups (P = 0.0001) during the endoscopic harvest, but the PaCO(2) level was significantly higher in the group that used the sealed system (44.5 ± 7.9 vs 39.7 ± 7.9 mmHg) at the end of the procedure (P = 0.01). No significant differences between end-tidal CO(2) measured at the same intervals between groups were detected. Conclusions There was a constant increase in the blood gas concentration compared with the basal pre-procedure values. Sealed systems were associated with a significantly higher CO(2) concentration at the end of the procedure compared with the open ones.

Crohn's disease and ulcerative colitis are inflammatory bowel diseases characterised by a chronic relapsing course. Corticosteroids represent the mainstay of medical treatment of inflammatory bowel disease for the induction of remission. Despite the high efficacy of systemic steroids, their use is limited by the high incidence of potentially serious adverse effects. The topically acting steroids are synthetic compounds characterised by high anti-inflammatory activity and low systemic effects by virtue of efficient first-pass hepatic inactivation. Budesonide and Beclomethasone Dipropionate are the two most studied topically acting steroids in inflammatory bowel disease. Oral Budesonide has been extensively studied in the treatment of mild to moderate ileo-caecal Crohn's disease but few data are available concerning oral Beclomethasone Dipropionate. This review focuses on the available evidence of efficacy and safety of oral Beclomethasone Dipropionate in the management of ulcerative colitis and Crohn's disease and a possible role of this steroid in clinical practice is suggested.

Cardiac involvement has been studied quite extensively in patients affected by inflammatory bowel disease but, as of now, there is no data regarding QT alterations which are well known to be linked to the risk of dangerous arrhythmias. In this study, QT parameters were digitally measured on standard 12-lead ECG in a population of 20 patients affected by inflammatory bowel disease (IBD), with no prior (recent or old) history of cardiac disease and no evidence of electrolyte imbalance. Eighteen healthy subjects formed the control group. The results obtained using non-parametric statistics (Wilcoxon-Mann-Whitney test) showed that heart rate corrected QT interval (QTc) and QTc dispersion (QTc d) values were both significantly higher in IBD patients than in the control group. QTc rank sum values in patients affected by inflammatory bowel disease were 469 versus 311 in healthy subjects (Z = 1.939, p = 0.0263). QTc d rank sum values were 460 in IBD patients versus 320 in controls (Z = 1.686 with p = 0.0459). Regardless of the cause of these QT alterations, it appears evident that accurate monitoring of QT parameters is required in these patients who often experience electrolyte disturbances and who may, in some cases, be undergoing treatment with potentially cardiotoxic drugs such as infliximab.

Aims To compare early endoscopic retrograde cholangiopancreatography with conservative management for the treatment of acute biliary pancreatitis: a meta-analysis of prospective randomized trials. Method Pertinent studies were selected from the Medline, Embase, and the Cochrane Library Databases, references from published articles and reviews. Conventional meta-analysis according to DerSimonian and Laird method was used for the pooling of the results. The rate difference (95% CI) and the number needed to treat were used as a measure of the therapeutic effect. Results Five prospective randomized trials including 702 patients were selected. Overall complications and mortality rates were 31% and 6%, respectively. In predicted severe pancreatitis the pooled rate difference for complications in early endoscopic retrograde cholangiopancreatography was 38.5% (95% CI −53% to −23.9%); p Conclusions Early endoscopic retrograde cholangiopancreatography reduces pancreatits-related complications in patients with predicted severe pancreatitis although mortality rate is not affected. In predicted mild pancreatitis early endoscopic retrograde cholangiopancreatography has no advantage compared to conservative management.

Background About 20% of ulcerative colitis patients will experience a severe attack during the course of the disease. Intensive treatment, early surgery and, more recently, “rescue therapies” improved prognosis. Aims To evaluate in-hospital colectomy and mortality rates for severe ulcerative colitis over 40 years in two referral centres. Methods All in-patients with severe ulcerative colitis from 1976 to 2010 were considered. 159 patients were assigned to 4 cohorts: cohort 1 n = 34 (1976–1980); cohort 2 n = 29 (1986–1990); cohort 3 n = 45 (1996–2000); cohort 4 n = 51 (2006–2010). Results The colectomy rate was 64.7%, 62.0%, 44.4% and 9.8%, respectively, in the four cohorts ( p p = 0.04). Infliximab was used only in cohort 4 (17 patients). Conclusions A significant reduction of colectomy and mortality rates in severe ulcerative colitis was observed in the last 40 years. Better management of patients, reduced attitude to operate severe ulcerative colitis, as well as the use of Infliximab in the last cohort, all could have contributed to the improved outcome.

Summary Background Surgical resection is almost inevitable in Crohn’s disease. Surgery is usually performed for refractory or complicated disease: no studies appear to have been carried out, so far, to evaluate the potential benefits of performing surgery early in the course of the disease. Aim To compare the long-term course of Crohn’s disease following ileo-caecal resection performed at the time of diagnosis (early surgery) or during the course of the disease (late surgery). Patients and methods Overall 207 patients with ileo-caecal Crohn’s disease at their first resection were reviewed: 83 patients underwent surgery at the time of diagnosis (early surgery), while 124 underwent surgery 54.2 months (range 1–438) after diagnosis (late surgery). The mean follow-up after surgery was 147 months (range 12–534). The primary endpoint was clinical recurrence, defined as need for corticosteroids for symptomatic disease in the presence of endoscopic and/or radiologic recurrence. Secondary endpoints were need for immunosuppressants and surgical recurrence. Statistical analysis: Kaplan–Meier survival method and Cox proportional hazards regression model. Results Within 10 years after surgery, the cumulative probability of clinical recurrence was significantly lower in the early surgery group (Log Rank test P = 0.01). A trend was observed regarding the need for immunosuppressants (P = 0.05). No difference was observed regarding surgical recurrence. At multivariate analysis, early surgery was the only independent variable associated with a reduced risk of clinical recurrence (Hazard ratio, HR = 0.57; 95% CI 0.35 to 0.92, P = 0.02), but not with need for immunosuppressants and surgical recurrence (HR = 0.51; 95% CI 0.20 to 1.30, P = 0.15; HR = 0.66; 95% CI 0.33 to 1.35, P = 0.25, respectively). Conclusion Early surgery prolongs clinical remission compared to surgery performed during the course of the disease, but the natural history of disease is not modified.

Background. Seasonal variations in onset of symptoms have been reported in ulcerative colitis but not in Crohn’s disease. Aim. To investigate whether our inflammatory bowel diseases patients presented seasonal variations in onset of symptoms. Patients and methods. Patients with a diagnosis of inflammatory bowel diseases established between 1995 and May 2004, and consecutively observed from June 2003 to May 2004, were included in the study. Onset of symptoms (year, season and month) was recorded. Expected onsets with a uniform distribution during the year were calculated and compared to observed onsets. Statistical analysis: chi-square test, odds ratio (95% confidence interval). Results. Overall 425 inflammatory bowel diseases patients were enrolled. Onset of symptoms (year and season) was established in 353/425 patients (83%; 150 Crohn’s disease; 203 ulcerative colitis). Onset of symptoms in inflammatory bowel diseases patients as a whole occurred more frequently in spring–summer compared to autumn–winter (odds ratio 1.39; 95% confidence interval 1.03–1.87; p < 0.03). This variation was observed in Crohn’s disease (odds ratio 1.59; 95% confidence interval 1.00–2.51; p < 0.05) and a similar trend, although not significant, was observed in ulcerative colitis (odds ratio 1.27; 95% confidence interval 0.86–1.88; p = 0.27). Conclusions. These data indicate that onset of Crohn’s disease symptoms occurred more frequently during spring-summer. A similar trend was observed in ulcerative colitis. Environmental factors, such as associated infections, smoking, use of drugs and seasonal changes in immune function may be responsible for triggering the clinical onset of inflammatory bowel diseases. © 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Leukocytes are thought to play an important role in the pathogenesis of inflammatory bowel diseases; granulocyte monocyte adsorptive (GMA) apheresis, an extracorporeal technique aimed at removing activated circulating leukocytes from the blood, may represent a safe and effective therapeutic tool in these patients. The Italian Registry of Therapeutic Apheresis performed an observational, multicentric study involving 24 Gastroenterology Units. In this study, laboratory data and clinical outcomes of 230 patients (148 males, mean age 43.5 years) affected with ulcerative colitis (UC, n 5 194) or Crohn’s disease (CD, n 5 36) who underwent one or more cycles of GMA were analyzed. Each cycle consisted of five GMA treatments. The patients were followed up for a mean of 8.7 (min. 3 to max. 12) months. At 3 months, positive outcome was achieved in 77.7% of UC patients (72.0% remission, 5.7% clinical response) and 61.3% of CD patients (54.8% remission, 6.5% clinical response). The cumulative proportion of positive outcome at 12 months was 87.1% for UC patients (83.7% remission, 3.4% clinical response) and 77.4% for CD patients (74.2% remission, 3.2% clinical response). No single clinical or laboratory parameter among those analyzed (age, sex, disease characteristics, history of smoking, medication history, baseline values of clinical activity index (CAI)/Crohn’s disease activity index (CDAI), hemoglobin, white blood cells count, and erythrocyte sedimentation rate) was independently associated with clinical outcome. The procedure was well tolerated with no significant adverse effects registered. J. Clin. Apheresis 26:332–337, 2011.

Pulmonary pseudoaneurysms are an uncommon but life-threatening condition of congenital or acquired cause, most commonly involving the branch pulmonary arteries and generally requiring emergent intervention. We describe a case of postoperative main pulmonary artery pseudoaneurysm after a complex aortic arch procedure, in which thoracic computed tomography provided full information for its definition before surgical correction.

AIMS Transcatheter aortic valve implantation (TAVI) is increasingly considered as a viable alternative to conventional aortic valve replacement (AVR) in high-risk patients. Long-term results, however, are still scarce and medical community hesitates in enlarging indications to lower-risk patients. Moreover, available devices are expensive and a strict potential candidate selection is necessary. METHODS From April 2008 to August 2012, a total of 212 patients, originally referred for percutaneous treatment, were thoroughly evaluated by the aortic team of our department in order to choose the optimal procedure. Of them, 55 patients (35 women; 20 men) were considered as still acceptable candidates for conventional AVR. RESULTS Mean age was 80.7 ± 4.7 years; mean additive and logistic Euroscore I were 9.7 ± 1.8 and 17.8 ± 9.5%, respectively. Mean Euroscore II was 7.9 ± 5.5%. Mean New York Heart Association class was 2.9 ± 0.5. The majority of patients (87.2%) presented a geriatric frailty score of 0-1. Four patients showed a heavily calcified ascending aorta, and five patients (9%) underwent reoperations. Hospital mortality was 10.9% (six patients). Mean follow-up was 535.9 ± 407.4 days (range: 6-1365 days). Six other patients died during this period for a mean survival of 74.4 ± 6.9% at 2 years. Mean New York Heart Association class at 1 year was 1.25 ± 0.5 (P

Sternal marrow haemostasis is often obtained with the application of bone wax, with potential side effects pertaining to sternal wound healing. We illustrate an alternative technique which also offers some protection to sternal edges. Two lengths of tubing from the discarded cardiopulmonary bypass (CPB) circuit are cut longitudinally on one side. After sternotomy they are placed across each sternal edge and kept in position by two stitches and the spreader blades. They are removed just before sternal closure.

Background: Postoperative sternal wound complications are infrequent events that negatively affect recovery and may have serious consequences. Sternal wrapping, a technique of sternal care, has hemostatic properties without bone wax, and offers mechanical and microbiologic protection. Methods: From February 1998 to December 2011, 258 patients in 2 Italian institutions underwent various cardiac surgery procedures with sternal wrapping in place, and were followed up for no less then 6 months. Results: Two (0.8%) extremely compromised patients with ischemic sternal osteonecrosis and deep sternal wound infection required a sternal stabilizing procedure. Four (2%) other patients developed sternal wound complications that were treated entirely medically; 3 of them were very trivial, and 1 was an atypical mediastinitis without sternal involvement. Overall, 46.1% of patients (45.3% of isolated coronary artery bypass, 49.3% of isolated on-pump coronary artery bypass, and 18.2% of off-pump coronary artery bypass patients) were transfused. None of the complications was related to sternal wrapping, bleeding from the sternal edge, or sternal wound problems. Conclusions: Sternal wrapping showed a very low incidence and severity of sternal wound complications, with good prevention of sternal osteomyelitis. Hemostatic properties were satisfactory, with transfusion rates within an acceptable range.

Background Transcatheter aortic valve implantation (TAVI) is increasingly considered as a viable alternative to conventional aortic valve replacement (AVR) in high-risk patients. However, long term results are still scarce and medical community hesitates in enlarging indications to lower risk subjects. Moreover, available devices are expensive and a strict potential candidate selection is necessary.

To assess the diagnostic accuracy of the platelet count/spleen diameter ratio for identification of oesophageal varices and/or hypertensive gastropathy in patients with compensated cirrhosis.Platelet count/spleen diameter ratio was calculated in 87 consecutive patients with compensated cirrhosis. A new cut-off with the highest sensitivity and specificity for the presence/absence of oesophageal varices and/or hypertensive gastropathy was identified. Performance of the platelet count/spleen diameter ratio considering previously reported cut-off values were then tested in our population.A platelet count/spleen diameter ratio936.4 had the best sensitivity and specificity for the diagnosis of oesophageal varices and for all endoscopic findings of portal hypertension. A value lower than 936.4 allowed identification of 64.5% of patients with oesophageal varices and 66.7% of patients with any sign of portal hypertension; a value higher than 936.4 excluded oesophageal varices in 64.3% of patients and any sign of portal hypertension in 68.6% of patients.In patients with compensated cirrhosis, the platelet count/spleen diameter ratio is not a useful parameter to avoid unnecessary upper endoscopy, independently of the cut-off.

Methotrexate (MTX) is a folate-antagonist used in several neoplastic and inflammatory diseases. Reports of pulmonary complications in patients given low-dose MTX therapy are increasing. Pulmonary toxicity from MTX has a variable fre- quency and can present with different forms. Most often MTX-induced pneumonia in patients affected by rheumatoid arthritis (RA) is reported. In this paper we describe a case of MTX-related pneumonitis in a relatively young woman affected by Crohn's disease who presented non-productive cough, fever and dyspnea on exer- cise. Chest X-ray demonstrated bilateral interstitial infil- trates and at computed tomography (CT) ground-glass opac- ities appeared in both lungs. At spirometry an obstructive defect was demonstrated. A rapid improvement of symptoms and the regression of radiographic and spirometric alter- ations was achieved through MTX withdrawal and the intro- duction of corticosteroid therapy.

Pulmonary toxicity is a well recognised but infrequent adverse event of treatment with methotrexate. The vast majority of cases have occurred in patients with rheumatoid arthritis; here we present the case of a 44-year old woman with ileo-colonic Crohn's disease who developed methotrexate pneumonitis. The patient had a 10 year history of Crohn's disease and, in the last 18 months, she was treated with oral methotrexate because of steroid-dependency and intolerance to thiopurines. She was admitted to the hospital because of acute dyspnoea, non-productive cough and fever. High-resolution CT scan showed diffuse bilateral areas of ground-glass opacity, and pulmonary function tests disclosed a mild obstructive pattern with a decrease in carbon monoxide diffusing capacity. Blood cultures for pathogenic bacteria or fungi were negative as well as serologic tests against major pneumotropic agents. Methotrexate-induced lung injury was considered: the drug was discontinued and the patient received a steroid course with rapid symptomatic improvement. After 4 weeks pulmonary function tests and high-resolution chest CT scan were normal. To our knowledge this is the second reported case of methotrexate-induced pneumonitis occurring in a patient with Crohn's disease. A definite diagnosis has been made not invasively according to clinical, laboratory and radiological criteria and excluding any infectious aetiology of the pulmonary findings.

Aminosalicylates (5-ASA) are first-line treatment for mild-moderate ulcerative colitis (UC). Systemic corticosteroids (CS) are considered for patients in whom 5-ASA has been unsuccessful, but their use is limited by adverse effects. Beclomethasone dipropionate (BDP), a topically acting steroid with low systemic bioavailability, has a more favorable safety profile, but its role in clinical practice is not yet well established.The aim of the present study is to assess whether oral BDP can be an alternative treatment to systemic CS for patients with mild-moderate UC not responding to first-line therapy with 5-ASA.From 2003 to 2006, all consecutive patients with mild-moderate UC unresponsive to oral and topical 5-ASA (+/-topical CS) administered for at least 3 weeks received an 8-week course of oral BDP (10 mg/day for 4 weeks and 5 mg/day for an additional 4 weeks). Co-primary end-points were: (1) clinical remission within 8 weeks, without need of systemic CS; (2) steroid-free remission for 12 months.Sixty-four patients were included. In this study, within 8 weeks, 48/64 patients (75%) entered remission without systemic CS, while 16/64 (25%) failed to enter remission. Within 12 months, 37/64 patients (58%) had prolonged steroid-free remission, while 11/64 (17%) relapsed. During 1 year, 75% of patients receiving oral BDP could avoid systemic CS.Oral BDP can avoid the use of systemic CS in the vast majority of patients with mild-moderate UC not responding to 5-ASA and could be considered as a second-line treatment for these patients.

Background Prevention of post-operative recurrence has a central role in the management of Crohn's Disease (CD). Many drugs have been evaluated in prospective randomised controlled trials (RCTs) but the results are disappointing. Mesalazine, the drug more extensively investigated, has been shown to be effective for preventing recurrence in the short-term; however, the overall benefit is small and no data are available on the long-term effectiveness. Aim To compare the long-term occurrence of post-operative recurrence in patients who received regular prophylactic treatment with mesalazine with patients who did not receive prophylaxis after the first radical resection for ileo-caecal CD. Patients and methods The records of 216 patients with ileo-caecal CD at their first resection were reviewed: 146 patients (67.6%) received post-operative prophylaxis with mesalazine while 70 patients (32.4%) received no prophylaxis. Allocation of patients in the two groups was determined by patients' preferences and by different policies in the post-operative prophylactic approach. The mean follow-up after surgery was 153.7 months (range 12–544). The co-primary endpoints were post-operative clinical and surgical recurrence. Statistical analysis: Kaplan–Meier survival method, Chi-square, Student t -test. Results The two groups were comparable with regard to gender, age at surgery, smoking habits, pattern of CD (perforating/not perforating), and disease duration before surgery. One year after surgery, a small, not statistically significant, risk reduction in clinical recurrence was observed in mesalazine treated group (−7.6%; 95% CI −18.0% to 2.8%). Within 10 years after surgery, the cumulative probability of clinical recurrence and surgical recurrence were similar in the two groups (Log Rank test p =0.9 and p =0.1 respectively). Conclusion Mesalazine prophylaxis is not effective for preventing the long-term post-operative recurrence in ileo-caecal Crohn's disease.

Dear Sir , We read with great interest the paper of Leuven group which appeared on JCC.1 The authors described the long term clinical outcome in a consecutive cohort of 121 outpatients retrospectively studied who received Infliximab for refractory moderate-to-severe ulcerative colitis (UC). They found that over a median follow-up period of 33 months, 17% of patients needed colectomy. As 67% …

Severe ulcerative colitis is a potentially life-threatening condition. Due to advances in medical therapy, the mortality rate has dropped to2% over the past 30 years, but the colectomy rate reaches 30%. Recently, infliximab has been shown to be effective as rescue therapy but little is known about long-term benefits.To evaluate short-and long-term colectomy rates for severe ulcerative colitis in the era of biological treatment and to identify predictive factors of long-term colectomy.From 2001 to 2006 all in-patients with severe ulcerative colitis, according to Truelove and Witts criteria, were retrospectively reviewed. All patients had received intravenous steroid treatment; infliximab (5 mg/kg at 0, 2 and 6 weeks) was used as rescue therapy in steroid-refractory patients; colectomy was performed in patients who deteriorated whilst on steroid treatment or failed to respond to infliximab.Of the 314 ulcerative colitis patients hospitalized during the study period, 52 (16.5%) met the criteria of severe ulcerative colitis. After median 7 days (range 4-15) on intravenous steroids, 37/52 (71%) patients showed a clinical response, while 15/52 (29%) were steroid-refractory. Of these, four underwent urgent colectomy and 11 received infliximab. A clinical response was observed in all infliximab-treated patients. In the long-term, another six patients underwent elective colectomy. The overall colectomy rate, following the acute attack, was 19%; the cumulative probability of a course without colectomy was 90%, 86%, 84%, 81%, after 6, 12, 18 and 24 months, respectively. No deaths occurred. The long-term colectomy risk was comparable in patients treated with infliximab and in steroid-responsive patients (18% vs. 11% respectively; OR 1.9; 95% CI 0.26-14.5). No predictive factors of colectomy, in the long-term, were identified.Surgery continues to play an important role in acute severe ulcerative colitis. Infliximab can avoid urgent colectomy in steroid-refractory patients but the risk of elective colectomy, in the long-term, is not modified.

Lung transplantation represents the only therapeutic option for patients affected by end-stage cystic fibrosis (CF). We performed 76 lung transplantations in 73 patients from 1996-2007. The mean time on the waiting list was 10+/-6 months. The median follow-up after the transplantation was 69.3 months. Twenty-one transplants (27.6%) were performed under cardiopulmonary bypass. Perioperative mortality, excluding retransplants, was 16.4% (12 patients) and the causes of death were sepsis, primary graft failure, and myocardial infarction. The overall survival was 74.5%+/-5%, 62.9%+/-5%, 54.1%+/-6%, and 43.4%+/-6% at 1, 3, 5, and 10 years, respectively. The accurate selection of potential recipients and the correct timing of referral and transplantation are factors that play crucial roles to obtain satisfactory results in term of improvement of quality of life and long-term survival.

The two-dimensional model introduced by Marrucci and Maffettone is explored in the limit of small shear rate. A tumbling motion for the director n of the nematic phase has been found. Explicit expressions for the shear and normal stresses have been derived for both the elastic and viscous contributions. The present results indicate that the model is able to describe the experimentally observed positive to negative to positive normal stresses transitions with increasing shear rate

During the last 2 decades, long-term survival after lung transplantation has significantly improved. However, among the complications related to the continuous administration of immunosuppressive drugs, malignancy plays an important role. We retrospectively revisited our series of patients to report our experience. From January 1991 we performed 134 lung transplantations in 128 recipients (mean age, 33.4 +/- 13.5 years). In all patients the first-line immunosuppressive regimen was based on a calcineurin inhibitor (cyclosporine or tacrolimus), an antimetabolic agent (azathioprine), and steroids. Five patients (4.2%) developed malignancy and the mean time of occurrence after the transplantation was 46.4+/-23 months. The mean age was 41 +/- 16 years (P = not significant [ns]). The tumors were as follows: laryngeal cancer (radiotherapy), colon cancer (surgery plus adjuvant chemotherapy), gastric cancer (surgery plus adjuvant chemotherapy), endobronchial non-Hodgkin lymphoma (NHL) (endoscopic resection plus chemoradiotherapy), and cutaneous and visceral Kaposi's sarcoma (KS) (chemotherapy). All patients have reduced the dose of immunosuppressive drugs; in 1 of them, tacrolimus was changed to rapamycin. Two patients died because of neoplastic dissemination, another 1 due to obliterans bronchiolitis. The 2 patients with NHL and KS are alive at 6 and 9 months, respectively, without signs of recurrence. Malignancies after lung transplantation represent an important problem. A multidisciplinary approach is mandatory to obtain satisfactory results in terms of improved quality of life and long-term survival.