Grazia Napolitano

Incidence rates of post-ERCP complications: A systematic survey of prospective studies

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%, CI 6.46–7.24%), with 55 fatalities (0.33%, CI 0.24–0.42%). Mild-to-moderate events occurred in 872 patients (5.17%, CI 4.83–5.51%), and severe events in 282 (1.67%, CI 1.47–1.87%). Pancreatitis occurred in 585 subjects (3.47%, CI 3.19–3.75%), infections in 242 (1.44%, CI 1.26–1.62%), bleeding in 226 (1.34%, CI 1.16–1.52%), and perforations in 101 (0.60%, CI 0.48–0.72%). Cardiovascular and/or analgesia-related complications amounted to 173 (1.33%, CI 1.13–1.53%), with 9 fatalities (0.07%, CI 0.02–0.12%). As compared with old reports, morbidity rates increased significantly in most recent studies: 6.27% versus 7.51% (Pc = 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.

Gastrointestinal Motility Disorders in Patients with Inactive Crohn's Disease

BACKGROUND Although some symptoms of Crohns disease may be related to gastrointestinal motility disorders, studies on gastrointestinal motility in inactive Crohns disease are lacking. METHODS Fasting and postprandial motor activity (1 h) was recorded in the gastric antrum and upper small intestine of 35 patients with inactive Crohns disease and 18 controls, using conventional manometry. RESULTS Motor disorders were observed in 26 of 35 patients. The number of phase-II contractions was reduced (1.3 +/- 0.7/min versus 1.8 +/- 0.6/min in controls; P < 0.02) (mean +/- standard deviation), whereas the incidence of propagated single (2.2 +/- 3.2/h versus 0.5 +/- 0.6/h; P < 0.03) and clustered contractions (3.8 +/- 7/h versus 1.1 +/- 1.4, P < 0.04) was markedly increased. Motor abnormalities were more frequent and severe in patients with Crohns ileitis than in controls, and in patients with gastrointestinal symptoms than in asymptomatic patients. CONCLUSION Most patients with inactive, uncomplicated Crohns disease show marked gastrointestinal motor disorders, characterized either by reduced incidence of small-bowel contractions and increased incidence of single or clustered propagated contractions.

Continuous infusion versus bolus administration of steroids in severe attacks of ulcerative colitis: a randomized, double-blind trial.

BACKGROUND: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.AIM: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.MATERIALS AND METHODS: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).RESULTS: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.CONCLUSIONS:In severe attacks of UC, methyl-prednisolone given as a continuous infusion was no better than bolus administration in terms of efficacy and safety.

Pancreatic Duct Stents in the Prophylaxis of Pancreatic Damage after Endoscopic Retrograde Cholangiopancreatography: A Systematic Analysis of Benefits and Associated Risks

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.

Gastric emptying of solids in patients with nonobstructive Crohn's disease is sometimes delayed.

To date, only a few studies of gastric emptying in Crohns 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 Crohns 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 (p < 0.01) delayed gastric emptying over controls (t1/2 85.5 +/- 15.4). Such a difference was also observed between symptomatic and asymptomatic patients (p < 0.05). We conclude that gastric emptying is slowed in symptomatic patients with nonobstructive Crohns disease and in those with colonic involvement. This may have therapeutic implications.

HLA-DRB1 Alleles May Influence Disease Phenotype in Patients With Inflammatory Bowel Disease: A Critical Reappraisal With Review of the Literature

PURPOSEThe HLA region has been implicated in determining the disease susceptibility or the clinical phenotype of inflammatory bowel disease. The aim of this study was to assess the relation between HLA-DRB1 alleles with the clinical features of Crohn’s disease and ulcerative colitis and the presence of anti-neutrophil cytoplasmic and anti-Saccharomyces cerevisiae antibodies.METHODSBlood samples were obtained from 102 Crohn’s disease patients, 114 ulcerative colitis patients, and 264 unrelated healthy controls. Anti-neutrophil cytoplasmics were detected by a standard immunofluorescence method, and anti-Saccharomyces cerevisiaes were examined by an enzyme-linked immunosorbent assay immunoglobulin G/immunoglobulin A commercial assay. HLA-DRB1 typing of 26 alleles was performed by polymerase chain reaction sequence-specific primes. Patients were phenotyped according to gender, disease location, extent, and behavior, surgical resection, need of steroid, and anti-neutrophil cytoplasmic/anti-Saccharomyces cerevisiae status.RESULTSAs a whole, after applying Bonferroni’s correction for multiple comparisons, no significant association of HLA-DRB1 alleles with Crohn’s disease or ulcerative colitis was found. After stratifying HLA-DRB1 alleles by clinical phenotypes of patients with ulcerative colitis, an excess of DRB1*1309*1320*1325*1329 allele (DR13) was found in conjunction with pancolitis (P < 0.0001), surgical resection (P < 0.0003), and extraintestinal manifestations (P < 0.0001). In Crohn’s disease patients, an excess of DRB1*0304*0305*0307*0309 allele (DR3) was found in those with colonic disease (P < 0.0001) and patients with extraintestinal manifestations (P = 0.0003). This statistical association, however, emerged in only 3 of 114 patients with ulcerative colitis and in 3 of 102 patients with Crohn’s disease. We found no association with the presence of anti-Saccharomyces cerevisiae or anti-neutrophil cytoplasmic.CONCLUSIONSSome clinical features of Crohn’s disease and ulcerative colitis may be influenced by specific HLA-DR alleles; in particular, in ulcerative colitis some alleles appear to segregate with more aggressive disease, whereas in Crohn’s disease different alleles cosegregate in patients with colonic disease and extraintestinal manifestations.

Antineutrophil cytoplasmic antibodies in inflammatory bowel disease: clinical role and review of the literature.

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 Crohns 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 Crohns 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 Crohns disease (9 percent), and 2 of 252 healthy subjects (<1 percent;P<0.001), respectively. Perinuclear antineutrophil cytoplasmic antibodies were significantly more frequent in patients with ulcerative colitis with higher relapse rate (43vs. 27 percent;P<0.002), and patients with Crohns disease with colitis (27vs. 2.5 percent;P<0.0003). Perinuclear antineutrophil cytoplasmic antibodies were also significantly less frequent in patients with ulcerative colitis in remission (18vs. 34 percent;P<0.0025). CONCLUSIONS: In this study we confirm the relative specific of perinuclear antineutrophil cytoplasmic antibodies, either for ulcerative colitis or for Crohns disease involving the colon. Perinuclear antineutrophil cytoplasmic antibodies were more frequently found in patients with ulcerative colitis with a more aggressive clinical behavior; however, their presence had a limited value in identifying homogeneous subgroups of patients in our population.

Bleeding after invasive procedures is rare and unpredicted by platelet counts in cirrhotic patients with thrombocytopenia

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 <50×103/L is not substantiated by this case series of cirrhotic patients.

Polymorphism of motilin gene in patients with Crohn's disease.

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 Crohns 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.

Exocrine Pancreatic Insufficiency, as Assessed by Fecal Elastase-1 Levels, in Diabetic Patients: An Estimate of Prevalence in Prospective Studies

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 <200 μg/g) in elastase-1 excretion. In 921 patients with type-1 DM, the weighted rate of PEI was 37.7% (CI 27.2-49.5), and 26.2% (CI 19.4-34.3) in 1970 type-2 diabetic patients, a difference of 11.5% (p=0.09). Of patients with abnormal (<200 μg/g) fecal elastase-1 concentrations, severe PEI was present in 53.4% (CI 45.2-61.4) of type-1, and in 50.3% (CI 40.7-59.9) of type-2 diabetic patients. Limitation: Some variables, which may influence fecal elastase-1 excretion, could not be controlled due to missing data. Conclusions: When explored by fecal elastase-1 testing, one in three patients with DM showed signs of impaired exocrine function. The results suggest that testing for PEI should be part of the diagnostic work-up of patients with DM.