A meta-analysis on the role of rectal diclofenac and indomethacin in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis.

Clinical trials evaluating the protective effect of nonsteroidal anti-inflammatory drugs (NSAIDs) for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) have yielded inconclusive results. Our objective was to conduct a meta-analysis of the data to date to evaluate the efficacy and safety of rectal NSAIDs for PEP prophylaxis. We did a systematic search of PubMed/MEDLINE, Embase, and Web of Science databases and the Cochrane Central Register of Controlled Trials. The meta-analysis was performed using a fixed-effect method because of the absence of significant heterogeneity in the included trials. Seven randomized, controlled trials involving 2133 patients were included. The meta-analysis showed that rectal NSAIDs decreased the overall incidence of PEP (risk ratio, 0.44; 95% confidence interval, 0.34-0.57; P < 0.01). The number needed to treat was 11. The NSAID prophylaxis also decreased the incidence of moderate to severe PEP (risk ratio, 0.37; 95% confidence interval, 0.27-0.63; P < 0.01). The number needed to treat was 34. No differences of the adverse events attributable to NSAIDs were observed. In conclusion, prophylactic use of rectal NSAIDs reduces the incidence and severity of PEP. There is neither a difference in efficacy between rectal indomethacin and diclofenac nor a difference in efficacy between the timing of administration of rectal NSAIDs, that is, immediate pre-ERCP and post-ERCP.

Defining the accuracy of secretin pancreatic function testing in patients with suspected early chronic pancreatitis.

OBJECTIVES: The diagnosis of chronic pancreatitis in patients with characteristic symptoms but normal pancreatic imaging is challenging. Assessment of pancreatic function through secretin pancreatic function testing (SPFT) has been advocated in this setting, but its diagnostic accuracy is not fully known. METHODS: This was a retrospective review of patients who received SPFT at our tertiary care institution between January 1995 and December 2008 for suspected chronic pancreatitis. For all patients, medical records were reviewed for evidence of subsequent development of chronic pancreatitis by imaging and/or pathology. Patients were then categorized as "true positive" or "true negative" for chronic pancreatitis based on follow-up imaging or histologic evidence. RESULTS: In all, 116 patients underwent SPFT. Of the 27 patients who tested positive, 7 were lost to follow-up. Of the remaining 20 SPFT-positive patients, 9 (45%) developed radiologic or histologic evidence of chronic pancreatitis after a median of 4 years (1-11 years). Of the 89 patients who had negative SPFT testing, 19 were lost to follow-up. Of the remaining 70 patients, 2 were eventually diagnosed with chronic pancreatitis based on subsequent imaging/histology after a median follow-up period of 7 years (3-11 years). The sensitivity of the SPFT in diagnosing chronic pancreatitis was 82% with a specificity of 86%. The positive predictive value (PPV) of chronic pancreatitis was 45% with a negative predictive value (NPV) of 97%. CONCLUSIONS: In patients with suspected early chronic pancreatitis and normal pancreatic imaging, SPFT is highly accurate at ruling out early chronic pancreatitis with a NPV of 97%.

An unusual variant of anomalous pancreaticobiliary junction in a patient with pancreas divisum diagnosed with secretin-magnetic resonance cholangiopancreatography.

Anomalous pancreaticobiliary junction is an unusual variant of pancreaticobiliary anatomy of clinical importance because it is associated with increased risk of pancreatitis and, also, for the development of cholangiocarcinoma. We report an unusual variant of anomalous pancreaticobiliary junction, occurring in a patient with pancreas divisum, with an anomalous communication between the dorsal pancreatic and the common bile duct. The patient presented with a distal biliary stricture. This variant anatomy was occult on magnetic resonance cholangiopancreatography but was diagnosed on magnetic resonance cholangiopancreatography that was performed with intravenous secretin administration and further delineated by endoscopic retrograde cholangiopancreatography. The features that allowed the diagnosis to be made and the implications of this diagnosis are described in this report.

International consensus guidelines for surgical resection of mucinous neoplasms cannot be applied to all cystic lesions of the pancreas.

BACKGROUND & AIMS: International consensus guidelines, aimed at predicting malignancy, are available for surgical resection of mucinous cysts but not for other cystic lesions of the pancreas. We sought to determine whether the consensus guidelines can be applied to all cystic lesions of the pancreas. METHODS: We identified all patients who underwent surgical resection of pancreatic cysts from 2001-2007. Pathology analyses of surgical specimens served as the reference standard. Surgical resection criteria proposed by the Sendai Guidelines and 5 modifications of these criteria were tested to determine their accuracy for diagnosis of malignant cysts. RESULTS: Patients with cystic lesions of the pancreas (n = 154; mean age, 59.8 years; 64% women) underwent resection and met prespecified study criteria. Twenty-one patients had a malignancy. The classification cyst size > or = 3 cm had an accuracy of 56%, negative predictive value of 84%, and identified only 57% of the malignant cysts. The classification cyst size > or = 3 cm or cyst with main pancreatic duct > or = 10 mm had an accuracy of 55%, negative predictive value of 86%, and identified 66% of malignant cysts. The modified criterion of cyst size > or = 3 cm or cyst with main pancreatic duct > 3 mm had an accuracy of 48%, negative predictive value of 94%, and identified 91% (19/21) of the malignancies. Cyst size (odds ratio, 1.05) and pancreatic duct dilation > 3 mm (odds ratio, 10.5) were strong and independent predictors of malignancy. CONCLUSIONS: When applied to all cystic lesions of the pancreas, the international consensus criteria cause some malignant cysts to be missed. Modified criteria could identify most malignant cysts, although overall accuracy remains low.

Comparison of carcinoembryonic antigen and molecular analysis in pancreatic cyst fluid.

BACKGROUND: Pancreatic-cyst fluid carcinoembryonic antigen (CEA) levels and molecular analysis are useful diagnostic tests in differentiating mucinous from nonmucinous cysts. OBJECTIVE: To assess agreement between CEA and molecular analysis for differentiating mucinous from nonmucinous cysts. DESIGN: Retrospective analysis. SETTING: Academic medical center. METHODS: Patients who underwent EUS-guided FNA for evaluation of pancreatic cysts were identified. The following information was used to designate a cyst mucinous: the CEA criterion was CEA level >or=192 ng/mL and the molecular analysis criteria were DNA quantity >or=40 ng/microL and/or k-ras 2-point mutation and/or >or=2 allelic imbalance mutations. Pathologic analysis of cysts served as the criterion standard. RESULTS: From 2006 to 2007, 100 patients met the study criteria. The average age of the patients was 63 years, 65% were women, and 30% were symptomatic. The mean diameter of pancreatic cysts was 2.5 cm. The median CEA value was 83 ng/mL (range 1-50,000 ng/mL), the mean DNA content was 16 ng/microL (range 1-212 ng/microL), 11% had K-ras mutations, and 43% had >or=2 allelic imbalance mutations. When using prespecified criteria, there was poor agreement between CEA and molecular analysis for the classification of mucinous cysts (kappa = 0.2). Poor agreement existed between CEA and DNA quantity (Spearman correlation = 0.2; P = .1), K-ras mutation (kappa = 0.3), and >or=2 allelic imbalance mutations (kappa = 0.1). Of the 19 patients for whom a final pathologic diagnosis was available, CEA had a sensitivity of 82% compared with 77% for molecular analysis. When CEA and molecular analysis were combined, 100% sensitivity was achieved. LIMITATIONS: Retrospective analysis and small sample size. CONCLUSION: There was poor agreement between CEA levels and molecular analysis for diagnosis of mucinous cysts. Diagnostic sensitivity was improved when results of CEA levels and molecular analysis were combined.

Are health related outcomes in acute pancreatitis improving? An analysis of national trends in the U.S. from 1997 to 2003.

CONTEXT: Acute pancreatitis is a common inflammatory disorder of the pancreas. Within the past decade our ability to diagnose and treat complications of acute pancreatitis has improved. Despite advances in diagnostic and therapeutic technology it is unclear whether we have been able to impact health related outcomes of acute pancreatitis such as incidence and mortality. OBJECTIVE: The aim of this study was to use a national database of U.S. hospitals to evaluate the trends in the incidence and mortality associated with acute pancreatitis. We also examined the impact that patient demographic and hospital characteristics have on health related outcomes in acute pancreatitis. METHODS: We analyzed the National Inpatient Sample Database (NIS) for all subjects in which acute pancreatitis (ICD-9 code: 577.0) was the principal discharge diagnosis during the period from 1997-2003. All identified subjects were analyzed for demographic characteristics as well as hospital characteristics. MAIN OUTCOME MEASURES: The mean frequency of discharges for acute pancreatitis, percentage mortality and mean length of stay for acute pancreatitis were determined for all identified cases. STATISTICS: The statistical significance of the difference in the discharge frequency, mortality and length of stay over the study period was determined by utilization of the chi-square test for trend and the linear regression. RESULTS: During the study period there were 1,476,498 admissions with a principal discharge diagnosis of acute pancreatitis. The frequency of discharges with acute pancreatitis increased by 30.2% (P<0.001) during the period from 1997-2003. The average mortality associated with acute pancreatitis decreased by 35.2% (P<0.001) and the median length of stay decreased by 9.4% (P=0.002). Most discharges with acute pancreatitis were in the Southern U.S. and were at large non-teaching hospitals located in urban areas. DISCUSSION: Possible explanations for the results of our study are the improvements in our ability to diagnose acute pancreatitis, an increase in the availability of medical ICU's and an increase in hospital admissions for gallstones and alcohol use during the study period.

Meta-analysis of the placebo response in ulcerative colitis.

PURPOSE: The placebo response rate in randomized controlled trials (RCTs) in ulcerative colitis (UC) varies from 0 to 76%. The aims of this study were to quantify the pooled placebo response rate and identify the factors affecting it. METHODS: We performed a meta-analysis of 110 RCTs carried out between 1955 and 2005 and published in English. Regression analysis was used to identify factors significantly modifying placebo response. RESULTS: The pooled placebo remission rate was 23% (95%CI: 18.4-28%) and the pooled placebo improvement rate was 32.1% (95%CI: 28.1-36.3%). Multivariate analysis showed that the country where the study was performed (P = 0.025 for placebo remission and P = 0.0083 for placebo response rates) significantly influenced the placebo remission and response rates. CONCLUSION: Placebo remission and response rates in RCTs of UC are highly variable and are significantly influenced by the country in which the RCT is performed.

The panc 3 score: a rapid and accurate test for predicting severity on presentation in acute pancreatitis.

GOAL: The goal of our study was to develop a simple rule that could rapidly identify those at risk for severe acute pancreatitis (SAP) in the ER. METHODS: We identified all published studies reporting risk factors for SAP. We identified 3 risk factors which had been shown to predict SAP. The risk factors we identified were a serum hematocrit greater than 44 mg/dL, a body mass index (BMI) greater than 30 mg/kg, and a chest x-ray which reveals a pleural effusion (Panc 3 criteria). We computed the test-operating characteristics and likelihood ratios for each risk factor using the patients originally sampled in each of the studies (n=393). For validation, we examined Panc 3's ability to predict SAP in patients seen at our medical center [University of North Carolina at Chapel Hill (UNC) hospitals n=238]. RESULTS: The likelihood ratios positive and negative for HCT, BMI>30 kg/M, and a chest x-ray with a pleural effusion were 14, 9.8, and 8.7, respectively, for the original data and 178, 2.4, and 1.3 for the UNC data. Sensitivity analysis revealed satisfaction of the HCT, BMI, and pleural effusion criteria had a posttest likelihood of disease 99% when the pretest probability of disease varied from 12-25%. These values were true for the original and UNC data. CONCLUSIONS: The Panc 3 score is easy to use and accurate for the prediction of SAP. The serum HCT was the strongest predictor of SAP. The combination of the Panc 3 variables was highly predictive of SAP.

Association of industry sponsorship to published outcomes in gastrointestinal clinical research.

BACKGROUND & AIMS: Recent years have seen an increase in industry sponsorship of clinical trials throughout medicine. We conducted a study to evaluate the association of industry sponsorship to published outcomes in gastrointestinal (GI) clinical research. Our aims were (1) to evaluate the trends in the source of funding for GI clinical research during the period from 1992 to 2002-2003, (2) to determine whether the source of study funding predicted the likelihood that a study would publish results that favor the drug or device being tested, and (3) to determine whether differences exist in the methodologic quality of the investigational study methods used in studies funded by private industry versus other sources. METHODS: We selected all clinical studies evaluating a drug or device from 4 prominent GI journals (Gastroenterology, The American Journal of Gastroenterology, Hepatology, and Gastrointestinal Endoscopy). All studies were abstracted by using a standardized data abstraction form. We evaluated the trends in funding source for studies published during the years 1992, 2002, and 2003. All selected studies were scored for methodologic quality by using a previously validated scoring system. The percentage of studies that reported outcomes that favored the device or drug being tested against the standard therapy or placebo was determined for each funding source. A funnel plot was constructed to assess for the presence of negative publication bias. RESULTS: A total of 6326 studies were reviewed. For the 1992 trend data, 1860 studies were reviewed, and 135 were selected for inclusion in the study. Ninety-five studies were studies involving the investigation of drugs, and 40 studies involved the testing of a device. For the 2002-2003 data 4466 studies were reviewed, and 315 were selected for inclusion in the study. Two hundred twenty-two studies were clinical trials involving the investigation of drugs, and 93 were clinical trials involving devices. In comparing 1992 to 2002, the percentage of studies funded by industry sources more than doubled from 10% to greater than 28% of the total studies assessed. There was an associated decline in the proportion of studies with funding from non-industry sources during this period (62% to less than 48%). The percentage of studies that did not disclose a funding source fell modestly from 28% to 24%. We found that 86% of studies funded by private industry reported a result favorable to the study drug or device, and 83% of studies funded by academic sources reported a result favorable to the study drug or device (P=.572). On average, studies funded by private industry had a higher methodology score than studies funded by traditional academic sources (75 of 100 vs 65 of 100; P=.005). Analysis of the funnel plot did not reveal evidence of bias against the publication of small studies with insignificant results. CONCLUSIONS: The proportion of research funded by industry has more than doubled during the last decade and currently comprises almost half of the funding for GI clinical research. Industry-sponsored studies are, on average, of superior methodologic quality to studies funded by other sources. Industry-sponsored studies in leading GI journals were no more likely than other studies to publish results that favored the study sponsor, although an extremely high percentage of all studies in these journals reported positive results. There has been only a modest decline in studies not acknowledging a funding source.

The risk of retention of the capsule endoscope in patients with known or suspected Crohn's disease.

OBJECTIVES: Capsule endoscopy (CE) allows visualization of the mucosa of the entire small bowel and is therefore a potentially important tool in the evaluation of patients with known or suspected Crohn's disease (CD). However, small bowel strictures, which are not uncommon in Crohn's, are considered to be a contraindication to CE for fear of capsule retention. Our goal was to determine the risk of capsule retention in patients with suspected or known CD. METHODS: We retrospectively reviewed the records of 983 CE cases performed at three private gastroenterology practices between December 2000 and December 2003, and selected those with suspected or proven Crohn's. RESULTS: A total of 102 cases were identified in which CE was used in patients with suspected (N = 64) or known (N = 38) CD. Only one of 64 patients (1.6%) with suspected CD had a retained capsule. However, in five of 38 (13%) patients with known Crohn's, the capsule was retained proximal to a stricture. Of the five cases of retained capsules, three strictures were previously unknown. In four cases, the obstructing lesions were resected without complications, leading to complete resolution of the patient's underlying symptoms. One patient chose not to undergo surgery and has remained without an episode of small bowel obstruction for over 38 months. CONCLUSIONS: Capsule retention occurred in 13% (95% CI 5.6%-28%) of patients with known CD, but only in 1.6% (95% CI 0.2%-10%) with suspected Crohn's. A retained capsule may indicate unsuspected strictures in Crohn's that may require an unexpected, but therapeutic, surgical intervention. Patients and physicians should be aware of these potential risks when using CE in CD.

Endoscopic sphincterotomy permits interval laparoscopic cholecystectomy in patients with moderately severe gallstone pancreatitis.

Patients with moderately severe gallstone pancreatitis with substantial pancreatic and peripancreatic inflammation, but without organ failure, frequently have an open cholecystectomy to prevent recurrent pancreatitis. In these patients, prophylactic endoscopic retrograde cholangiography (ERC) with endoscopic sphincterotomy (ES) may prevent recurrent pancreatitis, permit laparoscopic cholecystectomy, and decrease risks. The medical records of all patients with pancreatitis undergoing cholecystectomy from 1999-2004 at the University of North Carolina Memorial Hospital were reviewed. Data regarding demographics, clinical course, etiology of pancreatitis, operative and endoscopic interventions, and outcome were extracted. Moderately severe gallstone-induced pancreatitis was defined as pancreatitis without organ failure but with extensive local inflammation. Thirty patients with moderately severe gallstone pancreatitis underwent ERC and ES and were discharged before cholecystectomy. Mean interval between ES and cholecystectomy was 102 +/- 17 days. Cholecystectomy was performed laparoscopically in 27 (90%) patients, open in three (10%) patients, and converted to open in two (7%) patients, with a morbidity rate of 7% (two patients). No patient required drainage of a pseudocyst or developed recurrent pancreatitis. Interval complications resulted in hospital readmission in seven (23%) patients. In conclusion, recurrent biliary pancreatitis in patients with moderately severe gallstone pancreatitis is nil after ERC and ES. Hospital discharge of these patients permits interval laparoscopic cholecystectomy, but close follow-up is necessary in these potentially ill patients.

The perception of cancer risk in patients with prevalent Barrett's esophagus enrolled in an endoscopic surveillance program.

BACKGROUND & AIMS: Patients with Barrett's esophagus (BE) have a risk of esophageal adenocarcinoma of approximately 0.5% per year. Patients may have difficulty understanding this risk. This study assessed the perceived risk of cancer in patients with BE, and correlated their risk estimates with their health care use behaviors. METHODS: We performed a survey of patients with BE participating in an endoscopic surveillance program at 2 sites: a university teaching hospital and a Veterans' Administration hospital. A questionnaire also elicited their demographics as well as their sources of health information. Health care behaviors, including physician visits and endoscopic surveillance behaviors, were assessed. Patients were classified as either overestimators or nonoverestimators of risk. Characteristics of overestimators, as well as health care use patterns, were assessed. RESULTS: One hundred eighteen patients met entry criteria, and 92 (78%) completed all the questionnaires. Sixty-eight percent of patients overestimated their 1-year risk of cancer, with a mean estimated 1-year cancer risk being 13.6%. The lifetime risk also was overestimated by 38% of patients. Patients who overestimated risk were more likely to be Veterans' Administration medical center patients, have more symptomatic reflux, and were more likely to use the Internet to get health care information. There was no significant difference in physician visits between overestimators and nonestimators (1.2 visits per year vs 1.0, P = .20), nor in endoscopy use (5.7 endoscopies per 5-year period vs 5.0, P = .42). CONCLUSIONS: The majority of patients with prevalent BE participating in an endoscopic surveillance program overestimated their chances of developing adenocarcinoma of the esophagus. Efforts to improve education of such patients with BE are warranted.

A national comparison of surgical versus percutaneous drainage of pancreatic pseudocysts: 1997-2001.

Case series results indicate that a surgical approach is superior to percutaneous drainage of pancreatic pseudocysts. To determine if this surgical advantage is persistent, national outcomes for both approaches were compared from 1997 through 2001. The National Inpatient Sample, a 20% sample of all nonfederal hospital discharges, was searched for patients who had a pancreatic pseudocyst diagnosis, an ICD-9 diagnosis code 577.2, and an ICD-9 procedure code of 52.01 for percutaneous drainage (PD) or 52.4 and 52.96 for the surgical approaches. Variables were compared by using either t test or chi2 analysis. Confounding variables were controlled for by linear or logistic regression models. No clinically significant demographic, comorbidity, and disease-specific severity-of-illness differences existed between the two groups. Significant differences in complications, length of stay (15+/-15 versus 21+/-22 days, P<0.0001), and inpatient mortality (5.9% versus 2.8%, P<0.0001) favored the surgical approach. In addition, endoscopic retrograde cholangiopancreatography use had a protective effect on mortality (odds ratio, 0.7), whereas percutaneous drainage had an increased risk of mortality (odds ratio, 1.4). This population-based study suggests that surgical drainage of pancreatic pseudocysts, particularly when coupled with use of endoscopic retrograde cholangiopancreatography, leads to decreased complications, length of stay, and mortality in comparison with percutaneous drainage.

Screening for upper gastrointestinal tract malignancies.

The screening for malignancies involving the upper gastrointestinal (GI) tract has taken on new importance as the incidence of cancers such as adenocarcinoma of the esophagus has risen. The availability of new screening technology and molecular biological techniques has dramatically improved our ability to detect early lesions. We have also developed a detailed understanding of the natural history of many upper GI malignancies. This new knowledge has led to significant improvement in population-based screening programs. In this review we will detail the evidence supporting our current screening methods and provide a concise overview of current screening recommendations for select upper GI malignancies.

Digestive and liver diseases statistics, 2004.

BACKGROUND & AIMS: Digestive and liver diseases are associated with substantial morbidity and mortality in the United States. Statistics about the incidence, prevalence, mortality, and resource utilization of digestive and liver diseases in the United States may be cumbersome to obtain because they are scattered in multiple sources. These data may be useful for policy makers, grant applicants, and authors. METHODS: Data on the most common gastrointestinal and liver diseases were collected from large publicly available national databases. Information was collected on inpatient and outpatient gastrointestinal complaints and diagnoses, gastrointestinal cancers, and deaths from common liver diseases. RESULTS: The leading gastrointestinal complaint prompting an outpatient visit is abdominal pain, with 12.2 million annual visits, followed by diarrhea, nausea, and vomiting. Abdominal pain is the leading outpatient gastrointestinal diagnosis, accounting for 5.2 million visits annually, followed by gastroesophageal reflux disease, with 4.5 million visits. Gallstone disease is the most common inpatient diagnosis, with 262,411 hospitalizations and a median inpatient charge of USD$11,584. Colorectal cancer is the most common gastrointestinal cause of death and is the most common gastrointestinal cancer, with an incidence of 54 per 100,000. Among gastrointestinal cancers, primary liver cancer had the highest increase in incidence from 1992 to 2000. CONCLUSIONS: Gastrointestinal and liver diseases are associated with significant outpatient and inpatient healthcare utilization. Following trends in utilization is important for determining allocation of resources for health care and research.

Urinary trypsinogen activation peptide is more accurate than hematocrit in determining severity in patients with acute pancreatitis: a prospective study.

OBJECTIVE: The management of patients with acute pancreatitis is complicated by the inability to distinguish mild from severe disease during the early stages. It has been previously shown that urinary trypsinogen activation peptide (TAP) and hematocrit (Hct) may serve as early predictors of severity in patients with acute pancreatitis. To establish which marker is more accurate in the determination of severity in patients with acute pancreatitis, a prospective study was performed. METHODS: A consecutive series of patients admitted with pain consistent with acute pancreatitis and an amylase of three times the upper limit of normal were included. The admission and 24-h Hct was obtained. A urine sample was obtained within 12 h of admission. Urinary TAP was determined using a modified solid phase ELISA. Severity was defined by the Atlanta Symposium, as the presence of organ failure and/or pancreatic necrosis. RESULTS: Fifty-eight consecutive patients with acute pancreatitis participated. There were 33 men and 25 women with a mean age of 60 +/- 19. Thirty-nine patients had mild disease; 19 had severe disease. Urinary TAP was elevated in 26 patients. All patients with severe pancreatitis were correctly identified as having severe disease by an elevated urinary TAP (sensitivity 100%, specificity 77%). The admission Hct was higher than 47 in only three patients, all with mild disease. Of the patients with a rise in Hct, eight had mild disease, and only one had severe disease. Using a Hct of 44 as a cutoff did not affect the accuracy. There was no association between a rise in Hct and failure of Hct to decrease in the determination of severity. CONCLUSIONS: In comparison to admission Hct, urinary TAP was more accurate in determining severity in patients with acute pancreatitis by Atlanta, APACHE II, and Ranson criteria. We conclude that urinary TAP is a more accurate predictor of severity in patients with acute pancreatitis compared with Hct. Urinary TAP should be used to determine severity in patients early in the course of acute pancreatitis.