Angelo Andriulli

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.

Genome-wide association identifies multiple ulcerative colitis susceptibility loci

Ulcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation underlying ulcerative colitis risk, we present two distinct genome-wide association studies of ulcerative colitis and their joint analysis with a previously published scan, comprising, in aggregate, 2,693 individuals with ulcerative colitis and 6,791 control subjects. Fifty-nine SNPs from 14 independent loci attained an association significance of P < 10−5. Seven of these loci exceeded genome-wide significance (P < 5 × 10−8). After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were significantly associated with ulcerative colitis (P < 5 × 10−8), including the immunoglobulin receptor gene FCGR2A, 5p15, 2p16 and ORMDL3 (orosomucoid1-like 3). We confirmed association with 14 previously identified ulcerative colitis susceptibility loci, and an analysis of acknowledged Crohns disease loci showed that roughly half of the known Crohns disease associations are shared with ulcerative colitis. These data implicate approximately 30 loci in ulcerative colitis, thereby providing insight into disease pathogenesis.

Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10−11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10−10, OR = 1.63) and 17q12-21 (P = 1.7 × 10−10, OR = 1.38).

Individualized treatment duration for hepatitis C genotype 1 patients: A randomized controlled trial

It was hypothesized that in hepatitis C virus (HCV) genotype 1 patients, variable treatment duration individualized by first undetectable HCV RNA is as effective as standard 48‐week treatment. Patients (n = 696) received peginterferon alfa‐2a, 180 mg/week, or peginterferon alfa‐2b, 1.5 mg/kg/week, plus ribavirin, 1000‐1200 mg/day, for 48 weeks (standard, n = 237) or for 24, 48, or 72 weeks if HCV‐RNA–negative at weeks 4, 8, or 12, respectively (variable, n = 459). Sustained virologic response (SVR) was achieved in 45.1% [95% confidence interval (CI) 38.8‐51.4] of the patients in the standard group and in 48.8% (CI 44.2‐53.3) of the patients in the variable group (P = 0.37). The percentages of patients who first achieved undetectable HCV RNA at weeks 4, 8, or 12 were 26.7%, 27.8%, and 11.3%, respectively. In the standard treatment group, 87.1%, 70.3%, and 38.1% of patients who first achieved undetectable HCV RNA at 4, 8, or 12 weeks attained SVRs, respectively. In the variable group, corresponding SVR rates were 77.2%, 71.9%, and 63.5%. Low viremia levels and young age were independent predictors of response at week 4 [rapid virologic response (RVR)]. RVR patients with baseline viremia ≥400,000 IU/mL achieved higher SVR rates when treated for 48 weeks rather than 24 weeks (86.8% versus 73.1%, P = 0.14). The only predictive factor of SVR in RVR patients was advanced fibrosis. Conclusion: Variable treatment duration ensures SVR rates similar to those of standard treatment duration, sparing unnecessary side effects and costs. (HEPATOLOGY 2007.)

European Society of Gastrointestinal Endoscopy (ESGE) Guideline: Prophylaxis of post-ERCP pancreatitis

Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). Risk factors for post-ERCP pancreatitis (PEP) are both patient-related and procedure-related. Identification of patients at high risk for PEP is important in order to target prophylactic measures. Prevention of PEP includes administration of nonsteroidal inflammatory drugs (NSAIDs), use of specific cannulation techniques, and placement of temporary pancreatic stents. The aim of this guideline commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to provide practical, graded, recommendations for the prevention of PEP.

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

OBJECTIVES: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.METHODS:Search strategy: Cochrane, MEDLINE, CANCERLIT, and ENBASE databases were used. Selection criteria: 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.RESULTS:Five RCTs were identified including 701 patients. The overall survival was significantly higher in patients treated with RF than in those treated with PEI (RD 0.116, 95% CI 0.173/0.060; heterogeneity not present). Local recurrence rate is significantly higher in patients treated with PEI than in those treated with RF. In the RF group the 1, 2, and 3 years cancer-free survival rates were significantly better than in the PEI-treated patients (respectively: RD 0.098—95% CI 0.006/0.189; heterogeneity P=0.57; RD 0.187, 95% CI 0.082/0.293; heterogeneity P=0.98; RD 0.210, 95% CI 0.095/0.325; heterogeneity P = 0.78). A small number of adverse events were reported in the two treatments.CONCLUSIONS:RF ablation is superior to PEI in the treatment of small HCC with respect to overall survival, 1, 2, and 3 years survival rates, 1, 2, and 3 cancer-free survival rates, and tumor response. RF shows a significantly smaller risk of local recurrence.

Randomized controlled trial of botulinum toxin versus laparoscopic heller myotomy for esophageal achalasia

Objective:To compare laparoscopic cardia myotomy and fundoplication with botulinum toxin (BoTx) injection in patients with esophageal achalasia. Summary Background Data:Although myotomy is thought to offer better results, recent studies have reported 80% success rates after 2 BoTx injections a month apart. No randomized controlled trials comparing the 2 treatments have been published so far. Materials and Methods:Newly diagnosed achalasia patients were randomly assigned to BoTx injection or laparoscopic myotomy. Symptoms were scored; lower esophageal sphincter resting and nadir pressures were measured by manometry; barium swallow was used to assess esophageal diameter pre- and post-treatment. Eight to one hundred units of BoTx were injected twice, a month apart, at the esophagogastric junction. Myotomy included anterior partial (Dor) or Nissen fundoplication. Results:Eighty patients were involved in the study: 40 received BoTx and 40 underwent myotomy. Mortality was nil. One surgical patient bled from the trocar site. Median hospital stay was 6 days for surgery; BoTox patients were treated as day-hospital admissions. All patients completed the follow-up. After 6 months, the results in the 2 groups were comparable, although symptom scores improved more in surgical patients (82% confidence interval [CI] 76–89 vs. 66% CI 57–75, P < 0.05). The drop in lower esophageal sphincter pressure was similar in the 2 groups; the reduction in esophageal diameter was greater after surgery (19% CI 13–26 vs. 5% CI 2–11, P < 0.05). Later on, symptoms recurred in 65% of the BoTx-treated patients and the probability of being symptom-free at 2 years was 87.5% after surgery and 34% after BoTx (P < 0.05). Conclusion:Laparoscopic myotomy is as safe as BoTx treatment and is a 1-shot treatment that cures achalasia in most patients. BoTx should be reserved for patients who are unfit for surgery or as a bridge to more effective therapies, such as surgery or endoscopic dilation.

Pharmacologic treatment can prevent pancreatic injury after ERCP: a meta-analysis

BACKGROUND The identification of therapeutic agents that can prevent the pancreatic injury after endoscopic retrograde cholangiopancreatography (ERCP) is of considerable importance. METHODS We performed a meta-analysis including 28 clinical trials on the use of somatostatin (12 studies), octreotide (10 studies), and gabexate mesilate (6 studies) after ERCP. Outcome measures evaluated were the incidence of acute pancreatitis, hyperamylasemia, and pancreatic pain. Three analyses were run separately: for all available studies, for randomized trials only, and for only those studies published as complete reports. RESULTS When all available studies were analyzed, somatostatin and gabexate mesilate were significantly associated with improvements in all three outcomes. Odds ratios (OR) for gabexate mesilate were 0.27 (95% CI [0.13, 0. 57], p = 0.001) for acute pancreatitis, 0.66 (95% CI [0.48, -0.89], p = 0.007) for hyperamylasemia, and 0.33 (95% CI [0.18, 0.58], p = 0. 0005) for post-procedural pain. Somatostatin reduced acute pancreatitis (OR 0.38: 95% CI [0.22, 0.65], p < 0.001), pain (OR 0. 24: 95% CI [0.14, 0.42], p < 0.001), and hyperamylasemia (OR 0.65: 95% CI [0.48, 0.90], p = 0.008). Octreotide was associated only with a reduced risk of post-ERCP hyperamylasemia (OR 0.51: 95% CI [0.31, 0.83], p = 0.007) but had no effect on acute pancreatitis and pain. The statistical significance of data did not change after analyzing randomized trials only or studies published as complete reports. For each considered outcome, the publication bias assessment and the number of patients that need to be treated to prevent one adverse effect were, respectively, higher and lower for somatostatin than for gabexate mesilate. CONCLUSIONS The pancreatic injury after ERCP can be prevented with the administration of either somatostatin or gabexate mesilate, but the former agent is more cost-effective. Additional studies comparing the efficacy of short-term infusion of somatostatin versus gabexate mesilate in patients at high risk for post-ERCP complications seem warranted.

A multicentre randomised study of intrasphincteric botulinum toxin in patients with oesophageal achalasia

BACKGROUND Intrasphincteric injection of botulinum toxin (Botx) has been proposed as treatment for oesophageal achalasia. However, the predictors of response and optimal dose remain unclear. AIMS To compare the effect of different doses of Botx and to identify predictors of response. PATIENTS/METHODS A total of 118 achalasic patients were randomised to receive one of three doses of Botx in a single injection: 50 U (n=40), 100 U (n=38), and 200 U (n=40). Of those who received 100 U, responsive patients were reinjected with an identical dose after 30 days. Clinical and manometric assessments were performed at baseline, 30 days after the initial injection of botulinum toxin, and at the end of follow up (mean 12 months; range 7–24 months). RESULTS Thirty days after the initial injection, 82% of patients were considered responders without a clear dose related effect. At the end of follow up however, relapse of symptoms was evident in 19% of patients who received two injections of 100 U compared with 47% and 43% in the 50 U and 200 U groups, respectively. Using Kaplan-Meier analysis, patients in the 100×2 U group were more likely to remain in remission at any time (p<0.04), with 68% (95% CI 59–83) still in remission at 24 months. In a multiple adjusted model, response to Botx was independently predicted by the occurrence of vigorous achalasia (odds ratio 3.3) and the 100×2 U regimen (odds ratio 3.2). CONCLUSIONS Two injections of 100 U of Botx 30 days apart appeared to be the most effective therapeutic schedule. The presence of vigorous achalasia was the principal determinant of the response to Botx.

Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis: a multicenter, placebo-controlled, randomized clinical trial.

BACKGROUND ERCP is frequently complicated by pancreatitis. The aims of this study were to assess the efficacy of somatostatin and gabexate for prevention of post-ERCP pancreatitis in high-risk patients and to determine predisposing factors for post-ERCP pancreatitis. A meta-analysis was conducted of all published studies on the use of somatostatin or gabexate for prevention of post-ERCP pancreatitis. METHODS A double blind, multicenter, placebo-controlled trial was conducted in patients at high risk for post-ERCP pancreatitis. Patients were randomized to receive an intravenous infusion of somatostatin (750 mg), gabexate (500 mg), or placebo that was started 30 minutes before endoscopy and continued for 2 hours afterward. Patients were evaluated clinically and serum amylase levels determined at 4 and 24 hours after endoscopy. RESULTS No significant difference in the occurrence of pancreatitis, hyperamylasemia, or abdominal pain was observed among placebo-, gabexate-, and somatostatin-treated patients. A sphincterotomy longer than 2 cm (p = 0.0001), more than 3 pancreatic injections (p = 0.0001), and unsuccessful cannulation (p = 0.008) were predictive of post-ERCP pancreatitis. Hyperamylasemia was predicted by more than 3 pancreatic injections (p = 0.0001) and sphincterotomy (p = 0.02). The meta-analysis of trials of short-term infusion of gabexate or somatostatin did not show efficacy for either drug. CONCLUSIONS Short-term administration of gabexate or somatostatin in patients at high risk for pancreatitis is ineffective for prevention of ERCP-induced pancreatitis. Pancreatic injury is related to maneuvers used to obtain biliary access rather than to any patient characteristic or endoscopist experience.