Incidence of Primary Biliary Cholangitis in a Rural Midwestern Population.

BACKGROUND: Primary biliary cholangitis (PBC) is a rare disease with incidence that varies with time and geography. Only two studies have assessed PBC incidence in the United States, with the most recent appearing over a decade ago. The objective of the present study was to assess PBC incidence in the United States in a more recent era. METHODS: The incidence of PBC was assessed in a population-based cohort in rural, Midwestern Wisconsin over two decades spanning from June 1992 through June 2011. Cases were initially identified in the electronic medical record and then manually verified for inclusion according to the American Association for the Study of Liver Disease criteria for PBC. Additional data were abstracted for verified cases. RESULTS: A total of 79 cases of PBC were identified over the 20-year period for an overall age- and sex-standardized incidence of 4.9 cases per 100,000 person-years. Incidence was higher in females, but changes over time were not significant. After a mean 7.3 years follow-up, all-cause mortality of those with PBC was 29%, and estimated 10-year survival was 76%. CONCLUSIONS: The overall incidence of PBC in a Midwestern population of the United States has remained relatively stable over the last two decades. Patients have better prognosis, and the survival of PBC cases has improved.

Outcomes in Dieulafoy's Lesion: A 10-Year Clinical Review.

BACKGROUND: Dieulafoy's lesion (DL) is a rare, but serious cause of gastrointestinal bleeding, most frequently treated with endoscopic therapy. We examined 10 years of data to assess clinical outcomes in DL. METHODS: Data were captured by retrospective chart review to assess 109 patients treated endoscopically for bleeding DL from 2003 to 2013. Data collected included demographics, comorbidities, presenting symptoms, risk factors, laboratory values, treatment, rebleeding, surgical intervention, and mortality. Treatment success, rebleeding rates, and mortality were the main outcomes measured. RESULTS: Of 109 patients with bleeding DL, 54 % were male and 46 % were female. Mean age was 79.4 years; mean follow-up duration was 40.4 ± 35.8 months. Clinical presentation for most patients included melena, hematemesis, hematochezia, and/or anemia with approximately one-third of patients also experiencing anemia-related symptoms. Most lesions were located in stomach (53 %) followed by duodenum/jejunum (33 %) and large intestine (13 %). Thermal endoscopic therapy (70 %) was the most frequently performed procedure followed by injection (46 %) and mechanical (46 %) endoscopy therapy at equal frequency. Combined therapy (51 %) was common, with over half of patients undergoing two or more endoscopic modalities simultaneously. The finding that only 11 (10 %) patients had rebleeding from DL suggests that endoscopic therapy resulted in successful hemostasis in the remaining 98 patients (90 %) during follow-up. Mortality related to DL was low. CONCLUSIONS: Most patients with bleeding DL presented with symptoms of acute bleeding, but many had symptoms suggesting subacute or chronic bleeding. Endoscopic therapy resulted in successful hemostasis in approximately 90 % of patients during follow-up. Rebleeding was rare and particularly uncommon in those treated with combined endoscopic therapy.

Endotherapy in symptomatic pancreas divisum: a systematic review.

Pancreas divisum (PD) is the most common congenital variant of the pancreas and has been implicated as a cause of pancreatitis; however, endoscopic treatment is controversial. Our objective was to examine patient response to endotherapy for treatment of symptomatic PD in adult patients in a systematic review of the literature. A systematic review of all case series and case-control studies with ten or more patients undergoing endotherapy for treatment of symptomatic PD indicated by acute recurrent pancreatitis (ARP), chronic pancreatitis (CP), or chronic abdominal pain (CAP) was performed. PubMed, Embase, and Web of Science databases were searched from inception through February 2013 using [pancreas divisum] AND [endoscopic retrograde cholangiopancreatography (ERCP)] OR [endotherapy] OR [endoscopy] as search terms. Importantly, the majority of studies were retrospective in nature, significantly limiting analysis capacity. Main outcomes measures included endotherapy response rate in patients with PD and ARP, CP, or CAP. Twenty-two studies were included in the review, with a total of 838 patients. Response to endoscopy was seen in 528 patients, but response rate varied by clinical presentation. Patients with ARP had a response rate ranging from 43% to 100% (median 76%). Reported response rates were lower in the other two groups, ranging from 21% to 80% (median 42%) for patients with CP and 11%-55% (median 33%) for patients with CAP. Complications reported included perforation, post-endoscopic retrograde cholangiopancreatography pancreatitis, bleeding, and clogged stents. Endotherapy appears to offer an effective treatment option for patients with symptomatic PD, with the best results in patients presenting with ARP.

Urosdeoxycholic acid in primary sclerosing cholangitis: a meta-analysis and systematic review.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease with no proven effective medical therapy. Ursodeoxycholic acid (UDCA) was proposed as a potential treatment for this disorder. However, several randomised controlled trials reported conflicting results regarding the usefulness of UDCA. The aim of this meta-analysis and systematic review is to investigate the efficacy of UDCA in PSC. PATIENTS AND METHODS: Literature review was performed to include randomised controlled trials and non-randomised studies comparing UDCA to a placebo in PSC. The included controlled trials were assigned a quality score. Random effects model was used. Outcomes were measured with Weight Mean Difference, Risk Ratio or Risk Difference. Heterogeneity was measured by I(2) measure of inconsistency. RESULTS: Seven RCTs satisfied the inclusion criteria with a total number of 553 patients. Low dose UDCA was used in 4 studies, high dose UDCA (17-30mg/kg) was used in three studies. UDCA did not decrease the risk of mortality compared to placebo (RR=1.04, 95% CI 0.46-2.35) or the need for liver transplant (RR=1.22, 95% CI 0.7-2.12). UDCA also had no effect on the clinical symptoms. Liver Function Tests (LFTs) were significantly improved in the UDCA treated patients. UDCA did not decrease the incidence of cholangiocarcinoma. CONCLUSION: UDCA had no beneficial effect on the patients' survival, liver histology, prevention of cholangiocarcinoma, or improvement of clinical symptoms. High dose UDCA was associated with increased mortality in one of the large randomised trial included in this analysis.

Pancreatic stents for prophylaxis against post-ERCP pancreatitis: a meta-analysis and systematic review.

BACKGROUND: Acute pancreatitis is a common complication of ERCP. Several randomized, controlled trials (RCTs) have evaluated the use of pancreatic stents in the prevention of post-ERCP pancreatitis with varying results. OBJECTIVE: We conducted a meta-analysis and systematic review to assess the role of prophylactic pancreatic stents for prevention of post-ERCP pancreatitis. DESIGN: MEDLINE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, PubMed, and recent abstracts from major conference proceedings were searched. RCTs and retrospective or prospective, nonrandomized studies comparing prophylactic stent with placebo or no stent for post-ERCP pancreatitis were included for the meta-analysis and systematic review. Standard forms were used to extract data by 2 independent reviewers. The effect of stents (for RCTs) was analyzed by calculating pooled estimates of post-ERCP pancreatitis, hyperamylasemia, and grade of pancreatitis. Separate analyses were performed for each outcome by using the odds ratio (OR) or weighted mean difference. Random- or fixed-effects models were used. Publication bias was assessed by funnel plots. Heterogeneity among studies was assessed by calculating I(2) measure of inconsistency. SETTING: Systematic review and meta-analysis of patients undergoing pancreatic stent placement for prophylaxis against post-ERCP pancreatitis. PATIENTS: Adult patients undergoing ERCP. INTERVENTIONS: Pancreatic stent placement for the prevention of post-ERCP pancreatitis. MAIN OUTCOME MEASUREMENTS: Post-ERCP pancreatitis, hyperamylasemia, and complications after pancreatic stent placement. RESULTS: Eight RCTs (656 subjects) and 10 nonrandomized studies met the inclusion criteria (4904 subjects). Meta-analysis of the RCTs showed that prophylactic pancreatic stents decreased the odds of post-ERCP pancreatitis (odds ratio, 0.22; 95% CI, 0.12-0.38; P<.01). The absolute risk difference was 13.3% (95% CI, 8.8%-17.8%). The number needed to treat was 8 (95% CI, 6-11). Stents also decreased the level of hyperamylasemia (WMD, -309.22; 95% CI, -350.95 to -267.49; P≤.01). Similar findings were also noted from the nonrandomized studies. LIMITATIONS: Small sample size of some trials, different types of stents used, inclusion of low-risk patients in some studies, and lack of adequate study of long-term complications of pancreatic stent placement. CONCLUSIONS: Pancreatic stent placement decreases the risk of post-ERCP pancreatitis and hyperamylasemia in high-risk patients.

Statin use does not prevent recurrent adenomatous polyp formation in a VA population.

PURPOSE: To evaluate whether statin use was associated with recurrent adenomatous polyps. METHODS: We conducted a retrospective cohort study. We used electronic health records to evaluate veterans who underwent polypectomy between January 1, 1999 and December 31, 2001 and surveillance colonoscopy by December 2006. We obtained data on pathology, demographics, body mass index, comorbidity, habits, family history, and medications. We used multivariate proportional hazards regression models to analyze data. RESULTS: We evaluated 197 eligible patients from among 821 who underwent colonoscopy during this period; their mean (SD) age was 63.1 (8.8) years, 192 (98%) were men, and 80 (41%) non-Hispanic white. Surveillance colonoscopy was performed after a mean (SD) 1207 (452) days and 108 (55%) patients had recurrent adenomas. During follow-up, 88 (47%) of patients received statins, but use was not protective against recurrent adenomas (hazard ratio = 1.36, 95% CI 0.35-8.27). Only number of polyps at initial colonoscopy predicted recurrent adenomas (1.98, 95% CI 1.27-3.08). CONCLUSIONS: The use of statins was not protective against the recurrence of adenomatous polyps.

Mechanism of interferon-gamma-induced increase in T84 intestinal epithelial tight junction.

Interferon-gamma (IFN-gamma) is an important proinflammatory cytokine that plays a central role in the intestinal inflammatory process of inflammatory bowel disease. IFN-gamma induced disturbance of the intestinal epithelial tight junction (TJ) barrier has been postulated to be an important mechanism contributing to intestinal inflammation. The intracellular mechanisms that mediate the IFN-gamma induced increase in intestinal TJ permeability remain unclear. The aim of this study was to examine the role of the phosphatidylinositol 3-kinase (PI3-K) pathway in the regulation of the IFN-gamma induced increase in intestinal TJ permeability using the T84 intestinal epithelial cell line. IFN-gamma caused an increase in T84 intestinal epithelial TJ permeability and depletion of TJ protein, occludin. The IFN-gamma induced increase in TJ permeability and alteration in occludin protein was associated with rapid activation of PI3-K; and inhibition of PI3-K activation prevented the IFN-gamma induced effects. IFN-gamma also caused a delayed but more prolonged activation of nuclear factor-kappaB (NF-kappaB); inhibition of NF-kappaB also prevented the increase in T84 TJ permeability and alteration in occludin expression. The IFN-gamma induced activation of NF-kappaB was mediated by a cross-talk with PI3-K pathway. In conclusion, the IFN-gamma induced increase in T84 TJ permeability and alteration in occludin protein expression were mediated by the PI3-K pathway. These results show for the first time that the IFN-gamma modulation of TJ protein and TJ barrier function is regulated by a cross-talk between PI3-K and NF-kappaB pathways.

Effect of music on patients undergoing colonoscopy: a meta-analysis of randomized controlled trials.

PURPOSE: Music has been utilized as a therapeutic tool during colonoscopy, but various randomized controlled trials (RCTs) have been inconsistent. We conducted a meta-analysis to analyze the effect of music on patients undergoing colonoscopy. PATIENTS AND METHODS: Multiple medical databases were searched (12/06). Only RCTs on adult subjects that compared music versus no music during colonoscopy were included. Meta-analysis was analyzed for total procedure time, dose of sedative medications (midazolam and mepiridine), and patients' pain scores, experience, and willingness to repeat the same procedure in the future. RESULTS: Eight studies (N = 712) met the inclusion criteria. Patients' overall experience scores (P < 0.01) were significantly improved with music. No significant differences were noted for patients' pain scores (P = 0.09), mean doses of midazolam (P = 0.10), mean doses of meperidine (P = 0.23), procedure times (P = 0.06), and willingness to repeat the same procedure in future (P = 0.10). CONCLUSIONS: Music improves patients' overall experience with colonoscopy.

Prophylactic antibiotics in necrotizing pancreatitis: a meta-analysis.

PURPOSE: Prophylactic antibiotics have been used in acute necrotizing pancreatitis with mixed results. This meta-analysis analyzes the effects of prophylactic antibiotics in necrotizing pancreatitis. METHODS: Multiple databases and abstracts were searched for randomized trials comparing treatment with prophylactic antibiotics to treatment without prophylactic antibiotics in necrotizing pancreatitis. Prophylactic antibiotics' effects were analyzed by calculating pooled estimates of mortality, infected pancreatic necrosis, length of hospital stay, nonpancreatic infections, and surgical intervention. RESULTS: Seven studies (n = 429) met the inclusion criteria. Prophylactic antibiotics for acute necrotizing pancreatitis significantly decreased the length of hospital stay (P = 0.04) and the rate of nonpancreatic infections (P < 0.01). No significant differences were noted for mortality (P = 0.22), infected necrosis (P = 0.18), and surgical intervention (P = 0.40). CONCLUSIONS: Prophylactic antibiotics in necrotizing pancreatitis reduced the length of hospital stay and rate of nonpancreatic infections but did not decrease mortality, infected necrosis, or surgical intervention.

Role of prophylactic antibiotics in laparoscopic cholecystectomy: a meta-analysis.

BACKGROUND: The role of prophylactic antibiotics in laparoscopic cholecystectomy in low-risk patients is controversial. We conducted a meta-analysis to evaluate the efficacy of prophylactic antibiotics in low-risk patients (those without cholelithiasis or cholangitis) undergoing laparoscopic cholecystectomy. METHODS: Multiple databases and abstracts were searched. Randomized controlled trials (RCTs) comparing prophylactic antibiotics to placebo or no antibiotics in low-risk laparoscopic cholecystectomy were included. The effects of prophylactic antibiotics were analyzed by calculating pooled estimates of overall infections, superficial wound infections, major infections, distant infections, and length of hospital stay. Separate analyses were performed for each outcome by using odds ratio or weighted mean difference. Both random and fixed effects models were used. Publication bias was assessed by funnel plot. Heterogeneity among studies was assessed by calculating I (2) measure of inconsistency. RESULTS: Nine RCTs (N = 1,437) met the inclusion criteria. No statistically significant reduction was noted for those receiving prophylactic antibiotics and those who did not for overall infectious complications (p = 0.20), superficial wound infections (p = 0.36), major infections (p = 0.97), distant infections (p = 0.28), or length of hospital stay (p = 0.77). No statistically significant publication bias or heterogeneity were noted. CONCLUSIONS: Prophylactic antibiotics do not prevent infections in low-risk patients undergoing laparoscopic cholecystectomy.

Early versus delayed feeding after placement of a percutaneous endoscopic gastrostomy: a meta-analysis.

BACKGROUND: Traditionally, tube feedings have been delayed after percutaneous endoscopic gastrostomy (PEG) placement to the next day and up to 24 h postprocedure. However, results from various randomized controlled trials (RCTs) indicate earlier feeding may be an option. We conducted a meta-analysis to analyze the effect of early feedings (< or = 4 h) after PEG placement. METHODS: Multiple databases were searched (November 2007). Only RCTs on adult subjects that compared early (< or = 4 h) versus delayed or next-day feedings after PEG placement were included. Meta-analyses for the effect of early and delayed feedings were analyzed by calculating pooled estimates of complications, death < or = 72 h, and significant increases in postprocedural gastric residual volume during day 1. RESULTS: Six studies (N = 467) met the inclusion criteria. No statistically significant differences were noted between early (< or = 4 h) and delayed or next-day feedings for patient complications (OR 0.86, 95% CI 0.47-1.58, P = 0.63) or death in < or = 72 h (OR 0.56, 95% CI 0.18-1.74, P = 0.31). A statistically significant increase in gastric residual volumes during day 1 was noted (OR 1.80, 95% CI 1.02-3.19, P = 0.04). CONCLUSIONS: Early feeding < or = 4 h after PEG placement may represent a safe alternative to delayed or next-day feedings. Although an increase in significant gastric residual volumes at day 1 was noted, overall complications were not affected.

Role of the JNK signal transduction pathway in inflammatory bowel disease.

The c-Jun NH2-terminal Kinase (JNK) pathway represents one sub-group of the mitogen-activated protein (MAP) kinases which plays an important role in various inflammatory diseases states, including inflammatory bowel disease (IBD). Significant progress towards understanding the function of the JNK signaling pathway has been achieved during the past few years. Blockade of the JNK pathway with JNK inhibitors in animal models of IBD lead to resolution of intestinal inflammation. Current data suggest specific JNK inhibitors hold promise as novel therapies in IBD.