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Background In cirrhotics with low circulating platelets (PLT), restoration of normal cell counts has been traditionally recommended before invasive procedures. However, there is neither consensus on the PLT transfusion threshold nor evidence of its clinical efficacy. Patients In order to fill this gap of knowledge, we prospectively collected and analyzed data on circulating PLT counts [and International Normalized Ratio (INR)] values in a case series of 363 cirrhotics scheduled to undergo invasive investigations. PLT and/or fresh-frozen plasma (FFP) units were infused at the discretion of the attending physician, and the occurrence of post-procedural bleeding was related to pre-and post-infusion results. Results 852 Procedures were carried out in 363 cirrhotics sub-grouped according to the Child-Pugh-Turcotte (CPT) classification (class A/B/C: 124/154/85). The infusion of PLT and/or FFP improved only marginally circulating PLT counts and INR values. Ten post-procedural bleeds occurred in the whole case series, i.e. 1 episode every 85 procedures or every 36 patients. Post-procedural bleeding was unrelated to the PLT counts, to the degree of INR abnormalities, nor to the CPT classes, but was more frequent in patients who underwent repeated investigations. In the 10 patients with the most profound alterations in PLT and/or INR values, no post-procedural bleeding occurred. Conclusions In cirrhotic patients with low PLT and/or abnormal INR values undergoing invasive investigations, post-procedural bleeding was rare and unpredicted by PLT counts or abnormal INR values. In particular, the recommendation to infuse platelets when counts are 3 /L is not substantiated by this case series of cirrhotic patients.

OBJECTIVES: To provide health-care providers, patients, and physicians with an exhaustive assessment of prospective studies on rates of complications and fatalities associated with endoscopic retrograde cholangiopancreatography (ERCP). METHODS: We searched MEDLINE (1977-2006) for prospective surveys on adult patients undergoing ERCP. "Grey literature" was sought by looking at cited references to identify further relevant studies. Data on postprocedural pancreatitis, bleeding, infections, perforations, and miscellaneous events as well as their associated fatalities were extracted independently by two reviewers. Sensitivity analysis was performed to test for data consistency between multicenter versus single center studies, and old (1977-1996) versus recent (1997-2005) reports. RESULTS: In 21 selected surveys, involving 16,855 patients, ERCP-attributable complications totaled 1,154 (6.85%, Cl 6.46-7.24%), with 55 fatalities (0.33%, Cl 0.24-0.42%). Mild-to-moderate events occurred in 872 patients (5.17%, Cl 4.83-5.51%), and severe events in 282 (1.67%, Cl 1.47-1.87%). Pancreatitis occurred in 585 subjects (3.47%, Cl 3.19-3.75%), infections in 242 (1.44%, Cl 1.26-1.62%), bleeding in 226 (1.34%, Cl 1.16-1.52%), and perforations in 101 (0.60%, Cl 0.48-0.72%). Cardiovascular and/or analgesia-related complications amounted to 173 (1.33%, Cl 1.13-1.53%), with 9 fatalities (0.07%, Cl 0.02-0.12%). As compared with old reports, morbidity rates increased significantly in most recent studies: 6.27% versus 7.51% (P c = 0.029). CONCLUSIONS: ERCP remains the endoscopic procedure that carries a high risk for morbidity and mortality. Complications continue to occur at a relatively consistent rate. The majority of events are of mild-to-moderate severity.

Methods: The efficacy of pancreatic stenting in the prevention of pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) was evaluated by a meta-analysis of 6 controlled studies; 12 additional uncontrolled studies were analyzed for rates of associated risk. Results: Post-ERCP pancreatitis (PEP) developed in 16.5% of controls, and in 5.1 or 9.6% of the stent group at the per-protocol (PP) or intention-to-treat (ITT) analyses. By analyzing only the 4 randomized trials, PEP developed in 24.1% of controls, and in 6.1 or 12.0% of the stented patients at the PP or ITT analyses. Risk was significantly lower in the stent group when compared with controls: OR 0.44 (95% CI 0.24–0.81). The absolute risk reduction is 12.0 (95% CI 3.0–21.0), the number needed to treat 8 (95% CI 5–34), and the publication bias 2. ORs for mild to moderate PEP were reduced in the stent group (OR = 0.537, 95% CI 0.283–1.021), as were those for severe PEP (OR = 0.123, 95% CI 0.021–0.726). Non-pancreatic complications were 4.2%, and included early stent migration (1.4%), perforations (0.4%), bleeding (1.4%), and infections (1.0%). Conclusion: Available trials show benefit for pancreatic stenting in the prophylaxis of PEP, but more randomized studies are needed before endorsing a routine use of this endoscopic procedure.

Summary Background : Anti-Saccharomyces cerevisiae mannan antibodies have been proposed as a new serological marker associated with Crohn's disease. However, their clinical value is still unclear; furthermore, a standardization of anti-S. cerevisiae mannan measurements is lacking. Aim : In this study, we aimed to assess the correlation between anti-S. cerevisiae mannan detection and specific clinical features in Crohn's disease and ulcerative colitis. Moreover, we tested the concordance of four different anti-S. cerevisiae mannan assays. Materials and methods : Serum samples from 196 patients with Crohn's disease, 197 patients with ulcerative colitis and 100 unrelated healthy controls were tested for anti-S. cerevisiae mannan with a standard enzyme-linked immunosorbent assay method (Lille) by one of the authors (VP). Subsequently, 60 randomly selected serum samples (27 Crohn's disease, 28 ulcerative colitis and five healthy controls) were tested for anti-S. cerevisiae mannan with three different commercial kits. Results : With the Lille assay, anti-S. cerevisiae mannan were detected in 100 of 196 patients with Crohn's disease (51%; P

Objective: To assess the prevalence of pancreatic exocrine insufficiency (PEI) inpatients with diabetes mellitus (DM). Design: Meta-analysis of prospective, observational studies that used fecal elastase-1 estimation to determine PEI in patients with DM. Data extraction: A total of 11 studies out of 1156 retrieved references, published between 2000 and 2013, fulfilled the inclusion criteria. The primary outcome measure was proportions of patients with DM and PEI. Results: Of the 2891 patients enrolled, 921 (31.8%) showed abnormal (i.e, 100 but

OBJECTIVE Previous studies have reported genetic anticipation, genomic imprinting, and phenotypic concordance of some clinical features in familial cases of Crohn's disease (CD) and ulcerative colitis (UC). The aim of our study was to investigate the phenotypic features of affected members in a large sample of CD and UC Italian families. METHODS In a multicenter study, CD and UC families were recruited. Affected members were questioned about date of birth, gender, age at onset of symptoms and at diagnosis, location and extension of disease, occurrence of extraintestinal manifestations, use of steroids and/or of immunosuppressive drugs, need for resective surgery, and number of relapses per year ( or = 1 yr). Statistical analysis was performed with chi2, Fisher's, Mann-Whitney U, and binomial probability tests, when appropriate. RESULTS A total of 128 families with 270 affected members were studied: 35 were CD, 64 UC, and 29 mixed families (when UC and CD affected different members). In 99 of 128 families (77%), the diagnosis was concordant. In CD families, a high concordance for localization (46%), extraintestinal manifestations (67%), need for steroids (77%), need for immunosuppressive drugs (100%), need for surgery (29%), and relapse rate (36%) was found. In UC families, a high concordance for disease extension (33%), need for steroids (47%), and relapse rate (34%) was disclosed. A higher than expected concordance for ileal localization (p < 0.4) in CD families and extensive colitis (p < 0.05) in UC families was demonstrated. A generation difference of 15-20 yr in mean ages at onset of symptoms and at diagnosis was recorded. No features of more aggressive disease in subsequent generations and no differences in gender of transmitting parents and relatives were found. CONCLUSIONS Our study shows a high rate of concordance for diagnosis and clinical features in UC and, especially, CD families. The disease occurred 15-20 yr earlier than in previous generations without features of increased severity.

OBJECTIVE: Previous studies have reported genetic anticipation, genomic imprinting, and phenotypic concordance of some clinical features in familial cases of Crohn’s disease (CD) and ulcerative colitis (UC). The aim of our study was to investigate the phenotypic features of affected members in a large sample of CD and UC Italian families. METHODS: In a multicenter study, CD and UC families were recruited. Affected members were questioned about date of birth, gender, age at onset of symptoms and at diagnosis, location and extension of disease, occurrence of extraintestinal manifestations, use of steroids and/or of immunosuppressive drugs, need for resective surgery, and number of relapses per year ( RESULTS: A total of 128 families with 270 affected members were studied: 35 were CD, 64 UC, and 29 mixed families (when UC and CD affected different members). In 99 of 128 families (77%), the diagnosis was concordant. In CD families, a high concordance for localization (46%), extraintestinal manifestations (67%), need for steroids (77%), need for immunosuppressive drugs (100%), need for surgery (29%), and relapse rate (36%) was found. In UC families, a high concordance for disease extension (33%), need for steroids (47%), and relapse rate (34%) was disclosed. A higher than expected concordance for ileal localization (p CONCLUSIONS: Our study shows a high rate of concordance for diagnosis and clinical features in UC and, especially, CD families. The disease occurred 15–20 yr earlier than in previous generations without features of increased severity.

An increasing body of evidence supports theconcept of genetic heterogeneity within inflammatorybowel disease (IBD). In this study, a polymorphism ofthe motilin gene, which determines an amino acidsubstitution in the motilin protein, has been investigatedin IBD patients. Fifty patients with ulcerative colitis(UC), and 52 with Crohn's disease (CD) were investigatedfor anti-neutrophil cytoplasmatic antibodies (ANCA) and the polymorphism in the second exonof the motilin gene. Sixty unrelated blood donors servedas controls. ANCA were found in 30% of UC and 13% of CD.In controls the DNA polymorphism identified two alleles (1 and 2) at a frequency of 42% and58%, respectively. Patients with either UC or CD showeda slight increase in the frequency of allele 2 (69% and60%, respectively; P > 0.05 vs controls). This allele was predominant in ANCA-positive CDpatients (86%; P < 0.04) while in UC it did notdiffer. All ANCA-positive CD patients had the diseaseconfined to the colon. A polymorphism of second exon of the motilin gene, leading to a proteinvariant, is significantly more frequent in the subset ofANCA-positive CD patients. This subgroup of patientsappears to share peculiar genetic and clinical features.

In patients with severe attacks of ulcerative colitis (UC), IV steroids represent the first-line treatment, leading to clinical improvement in approximately 50-60% of patients.The aim of this study was to prospectively compare the efficacy and safety of different modalities of steroid administration, and to evaluate predictors of failure to therapy.In a single-center, double-blind trial, consecutive patients with a severe attack of UC received 1 mg/kg/day of 6-methyl-prednisolone administered randomly by either a bolus injection (group A) or continuous infusion (group B).Sixty-six patients were enrolled (35 men, mean age 38 +/- 15, range 18-75 yr), 15 of them at their first attack of UC; in the remaining cases, the mean duration of disease was 4.5 +/- 5 yr. At inclusion, forty patients (60%) had pancolitis and the remainder had left-sided colitis. Overall, thirty-three patients (50%) underwent clinical remission after 7 days of treatment: 16 of 32 in group A and 17 of 34 in group B. Thirty-one patients eventually underwent total colectomy (12 in group A and 9 in group B), which was carried out by the first month in 10 patients (5 in each group). Twenty-eight patients (15 in group A and 13 in group B) experienced steroid-related adverse reactions. All differences between groups were not statistically significant. Previous use of steroids (OR 13.6, CI 2-86) and active smoking (OR 11.6, CI 1.4-107) were independent predictors of nonresponse.In severe attacks of UC, methyl-prednisolone given as a continuous infusion was no better than bolus administration in terms of efficacy and safety.

PURPOSE: Perinuclear antineutrophil cytoplasmic antibodies have been found consistently in patients with ulcerative colitis; however, their pathogenetic and clinical role is still uncertain. In this study we tested the prevalence of perinuclear antineutrophil cytoplasmic antibodies in a large population of patients with ulcerative colitis and Crohn's disease, with particular attention to the possible correlation with clinical features. METHODS: Perinuclear antineutrophil cytoplasmic antibody reactivity was investigated with indirect immunofluorescence in 279 patients with ulcerative colitis, 110 patients with Crohn's disease, and 252 unrelated healthy subjects. RESULTS: Perinuclear antineutrophil cytoplasmic antibodies were found in 84 of 279 patients with ulcerative colitis (30 percent), 10 of 110 patients with Crohn's disease (9 percent), and 2 of 252 healthy subjects (

To date, only a few studies of gastric emptying in Crohn's disease have been published in the literature. This might be clinically important because slow-release drug formulations are increasingly available for treatment. Studies in children with gastric involvement suggest that gastric emptying may be delayed in this condition. We studied the scintigraphic gastric emptying of 21 adult patients with nonobstructive Crohn's disease and without gastric or duodenal involvement by the disease, compared with that of 20 healthy volunteers. Overall, no significant differences were found, but subgroup analysis showed that symptomatic patients [half-time (t1/2) 133 +/- 75.9] and those with colonic involvement (t1/2 127.2 +/- 64) had a significantly (p0.01) delayed gastric emptying over controls (t1/2 85.5 +/- 15.4). Such a difference was also observed between symptomatic and asymptomatic patients (p0.05). We conclude that gastric emptying is slowed in symptomatic patients with nonobstructive Crohn's disease and in those with colonic involvement. This may have therapeutic implications.