American Society for Gastrointestinal Endoscopy guideline on management of post-liver transplant biliary strictures: methodology and review of evidence.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach for strategies to manage biliary strictures in liver transplant recipients. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline addresses the role of ERCP versus percutaneous transhepatic biliary drainage and covered self-expandable metal stents (cSEMSs) versus multiple plastic stents for therapy of strictures, use of MRCP for diagnosing post-transplant biliary strictures, and administration of antibiotics versus no antibiotics during ERCP. In patients with post-transplant biliary strictures, we suggest ERCP as the initial intervention and cSEMSs as the preferred stent. In patients with unclear diagnosis or intermediate probability of a stricture, we suggest MRCP as the diagnostic modality. We suggest that antibiotics should be administered during ERCP when biliary drainage cannot be assured.

American Society for Gastrointestinal Endoscopy guideline on management of post-liver transplant biliary strictures: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy provides an evidence-based approach for strategies to manage biliary strictures in liver transplant recipients. This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline addresses the role of ERCP versus percutaneous transhepatic biliary drainage and covered self-expandable metal stents (cSEMSs) versus multiple plastic stents for therapy of post-transplant strictures, use of MRCP for diagnosing post-transplant biliary strictures, and administration of antibiotics versus no antibiotics during ERCP. In patients with post-transplant biliary strictures, we suggest ERCP as the initial intervention and cSEMSs as the preferred stent for extrahepatic strictures. In patients with unclear diagnoses or intermediate probability of a stricture, we suggest MRCP as the diagnostic modality. We suggest that antibiotics should be administered during ERCP when biliary drainage cannot be ensured.

Interobserver Agreement for Classifying Post-liver Transplant Biliary Strictures in Donation After Circulatory Death Donors.

INTRODUCTION: Biliary strictures are a common complication of donation after circulatory death (DCD) liver transplantation (LT) and require multiple endoscopic retrograde cholangiopancreatography (ERCP) procedures. Three classification systems, based on cholangiograms, have been proposed for categorizing post-LT biliary strictures. We examined the interobserver agreement for each of the three classifications. METHODS: DCD LT recipients from 2012 through March 2017 undergoing ERCP for biliary strictures were included in the study. Initial cholangiograms delineating the entire biliary tree prior to endoscopic intervention were selected. One representative cholangiogram was selected from each ERCP. Five interventional endoscopists independently viewed each anonymized cholangiogram and classified the post-LT stricture according to each of the three classification systems. The Ling classification proposes four types of post-LT strictures based on their location. The Lee classification proposes four classes based on location and number of intrahepatic strictures. The binary system classifies strictures into anastomotic or non-anastomotic types. The Krippendorff's alpha reliability estimate was used to grade the strength of agreement as "poor," "fair," "moderate," "good," or "excellent" for values between 0-0.20, 0.21-0.4, 0.41-0.6, 0.61-0.08, and 0.81-1, respectively. RESULTS: One hundred DCD LT recipients (age 57.07 ± 8.8 years; 71 males) were initially evaluated. Of these, 49 patients who underwent 206 ERCP procedures for biliary strictures were included in the analysis. One hundred thirty-nine cholangiograms were selected and subsequently classified by five endoscopists. Interobserver agreement for post-LT biliary strictures was 0.354 for Ling classification (fair agreement), 0.405 for Lee classification (fair agreement), and 0.421 for the binary classification (moderate agreement). The binary classification provided the least amount of detail regarding the location and number of biliary strictures. DISCUSSION: The currently available classification systems for assessing post-LT biliary strictures have sub-optimal interobserver agreement. A better-designed classification system is needed for categorizing post-LT biliary strictures.

Predictors of Biliary Strictures After Liver Transplantation Among Recipients of DCD (Donation After Cardiac Death) Grafts.

INTRODUCTION: Biliary strictures are a common complication among donation after cardiac death (DCD) liver transplantation (LT) recipients and may require multiple endoscopic retrograde cholangiopancreatography (ERCP) procedures. We evaluated the risk factors associated with development of biliary strictures in DCD LT recipients. METHODS: DCD LT recipients who underwent transplantation from 2012 to 2017 were divided into 2 groups: (a) those with anastomotic or non-anastomotic biliary strictures who required ERCP ("stricture group") and (b) those who did not require ERCP or had cholangiograms without evidence of biliary strictures ("non-stricture group"). Clinical data, cholangiograms and laboratory values at day 0 and day 7 after LT were compared between the two groups. RESULTS: Forty-nine of the 100 DCD LT recipients underwent ERCP. Thirty-four of these 49 LT recipients had evidence of anastomotic or non-anastomotic biliary strictures (stricture group), while the remaining 66 LT recipients comprised the non-stricture group. Donor age was significantly higher in stricture group compared to non-stricture group (49.2 ± 1.8 vs 42.8 ± 1.57 years, respectively; p = 0.01). The stricture group had a significantly higher total bilirubin at day 0 (3.5 ± 0.37 vs 2.6 ± 0.21 mg/dL; p = 0.02) and INR at day 7 (1.24 ± 0.06 vs 1.13 ± 0.01; p = 0.048) compared to the non-stricture group. Multi-variate analysis demonstrated significant association between biliary strictures and total bilirubin at day 0 of LT and age of donor. CONCLUSION: Biliary strictures occur frequently in DCD LT recipients and may be associated with older age of donor. Hyperbilirubinemia immediately after transplant and higher INR in the first 7 days after transplant may predict subsequent development of biliary strictures.

Outcomes in Adults With Acute Liver Failure Between 1998 and 2013: An Observational Cohort Study.

BACKGROUND: Acute liver failure (ALF) is a rare syndrome of severe, rapid-onset hepatic dysfunction-without prior advanced liver disease-that is associated with high morbidity and mortality. Intensive care and liver transplantation provide support and rescue, respectively. OBJECTIVE: To determine whether changes in causes, disease severity, treatment, or 21-day outcomes have occurred in recent years among adult patients with ALF referred to U.S. tertiary care centers. DESIGN: Prospective observational cohort study. (ClinicalTrials .gov: NCT00518440). SETTING: 31 liver disease and transplant centers in the United States. PATIENTS: Consecutively enrolled patients-without prior advanced liver disease-with ALF (n = 2070). MEASUREMENTS: Clinical features, treatment, and 21-day outcomes were compared over time annually for trends and were also stratified into two 8-year periods (1998 to 2005 and 2006 to 2013). RESULTS: Overall clinical characteristics, disease severity, and distribution of causes remained similar throughout the study period. The 21-day survival rates increased between the two 8-year periods (overall, 67.1% vs. 75.3%; transplant-free survival [TFS], 45.1% vs. 56.2%; posttransplantation survival, 88.3% vs. 96.3% [P < 0.010 for each]). Reductions in red blood cell infusions (44.3% vs. 27.6%), plasma infusions (65.2% vs. 47.1%), mechanical ventilation (65.7% vs. 56.1%), and vasopressors (34.9% vs. 27.8%) were observed, as well as increased use of N-acetylcysteine (48.9% vs. 69.3% overall; 15.8% vs. 49.4% [P < 0.001] in patients with ALF not due to acetaminophen toxicity). When examined longitudinally, overall survival and TFS increased throughout the 16-year period. LIMITATIONS: The duration of enrollment, the number of patients enrolled, and possibly the approaches to care varied among participating sites. The results may not be generalizable beyond such specialized centers. CONCLUSION: Although characteristics and severity of ALF changed little over 16 years, overall survival and TFS improved significantly. The effects of specific changes in intensive care practice on survival warrant further study. PRIMARY FUNDING SOURCE: National Institutes of Health.

ACG Clinical Guideline: Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis is a chronic cholestatic liver disease that can shorten life and may require liver transplantation. The cause is unknown, although it is commonly associated with colitis. There is no approved or proven therapy, although ursodeoxycholic acid is used by many on an empiric basis. Complications including portal hypertension, fat-soluble vitamin deficiency, metabolic bone diseases, and development of cancers of the bile duct or colon can occur.

Vitamin D deficiency, parathyroid hormone levels, and bone disease among patients with end-stage liver disease and normal serum creatinine awaiting liver transplantation.

UNLABELLED: Vitamin D deficiency is common among patients with end-stage liver disease (ESLD). The primary aim of our study was to assess the prevalence of vitamin D deficiency, secondary hyperparathyroidism, and bone disease in patients with ESLD awaiting LT. METHODS: We retrospectively studied 190 patients at our center. Serum total 25-hydroxyvitamin D (25-OH D), parathyroid hormone (PTH), calcium, and bone mineral analysis (BMA) were recorded. Standard World Health Organization (WHO) criteria were used to diagnose osteopenia/osteoporosis. Only patients with normal serum creatinine were analyzed. RESULTS: Thirty-two of 190 patients were excluded from the final analysis (missing serum total 25-OH D levels in three patients and elevated serum creatinine, 29 patients). 105 of 158 (66.4%) evaluable patients had 25-OH D levels <25 ng/mL. Patients included in the analysis (n = 158) were divided according to serum total 25-OH D levels: 0-10 ng/mL (n = 23), 11-20 ng/mL (n = 64), and >20 ng/mL (n = 71). There were no significant differences in mean serum PTH and corrected calcium levels among the three subgroups. Only three patients had elevated serum PTH. Patients with total 25-OH D ≤ 10 ng/mL had higher model for end-stage liver disease (MELD) scores vs. those with 25-OH D > 20 ng/mL (13.3 ± 3, range 8-21, vs. 11.9 ± 3.4, range 6-29, p = 0.004). Irrespective of vitamin D status, bone disease was present in 64.6% of patients. CONCLUSION: Low vitamin D levels and bone disease are common among patients with ESLD awaiting LT. Despite a high prevalence of low serum total 25-OH D, our cohort maintained normal corrected calcium levels and did not develop secondary hyperparathyroidism. We propose that free serum 25-OH D and vitamin D-binding protein may be necessary to accurately establish the diagnosis of vitamin D deficiency in the setting of ESLD. Additional studies are needed to further define mechanisms of bone disease in patients with ESLD.

Pancreatitis before pancreatic cancer: clinical features and influence on outcome.

OBJECTIVES: Pancreatitis is considered a possible risk factor for and a presentation of pancreatic adenocarcinoma (PA). We aimed to evaluate a large PA patient registry to determine whether prior history of pancreatitis influenced survival. METHODS: We retrospectively analyzed the Mayo Clinic Biospecimen Resource for Pancreas Research database from January 1992 to September 2011. Data collected included demographic characteristics, history of tobacco or alcohol use, diabetes mellitus (DM), cholelithiasis, pseudocyst, and details regarding PA. Clinical characteristics and outcomes of PA patients with pancreatitis were compared with PA patients without pancreatitis history. RESULTS: We analyzed 2573 patients with PA diagnosis. Among these patients, 195 (8%) were identified who had pancreatitis diagnosis ≥ 10 days before PA diagnosis. The cohort with pancreatitis history included more patients with DM (30% vs. 18%; P<0.001) and more smokers (68% vs. 58%; P=0.02). Compared with patients without pancreatitis history, these patients received diagnoses of PA at a younger age (63 vs. 65 y; P=0.005) and earlier stage (stages I and II; 52% vs. 37%; P<0.001). A greater percentage had history of surgery with curative intent (50% vs. 43%; P=0.001) and significantly better survival [median (range), 387 d (314 to 460 d) vs. 325 d (306 to 344 d); P=0.003]. CONCLUSIONS: Patients with PA and pancreatitis had more weight loss and DM, but had PA diagnosis at an earlier stage, were more likely to have pancreatic surgery, and therefore better survival than PA patients without pancreatitis, likely due to the earlier diagnosis. Further studies are needed to evaluate whether screening for PA in patients with pancreatitis history would provide survival benefit.

Impact of fentanyl in lieu of meperidine on endoscopy unit efficiency: a prospective comparative study in patients undergoing EGD.

BACKGROUND: Turnaround time is an important component of endoscopy unit efficiency. Any reduction in the total time from patient arrival in the endoscopy room to departure from the recovery area may translate into better endoscopy unit efficiency. OBJECTIVE: To evaluate the effects on endoscopy unit efficiency of a change in narcotic choice for moderate sedation in patients undergoing EGD at an ambulatory surgery center. DESIGN: Prospective, comparative, quality-improvement project. SETTING: Endoscopy unit of a tertiary-care academic medical center. PATIENTS: We enrolled consecutive patients (n = 1963) who underwent outpatient EGD by 1 of 5 endoscopists between November 2008 and November 2010. INTERVENTION: Moderate sedation with midazolam plus fentanyl versus meperidine. MAIN OUTCOME MEASUREMENTS: Sedation-dependent endoscopy unit efficiency and total procedure time (induction-to-intubation, intubation-to-extubation, and extubation-to-discharge). RESULTS: Fentanyl was associated with reduced total procedure time by 10.1 minutes resulting from both shorter induction-to-intubation time and extubation-to-discharge time (P < .001). The mean (± SD) sedation-dependent endoscopy unit efficiency was 3.2 (± 1.9) procedures per hour for the meperidine group and 3.9 (± 2.7) procedures per hour for the fentanyl group (P = .012); this would translate into possibly increasing the endoscopy suite efficiency by 22%. Based on dosage equivalency conversion, equal doses of fentanyl and meperidine were used. No sedation-related complications or need for reversal agents were recorded. LIMITATIONS: No randomization was performed. CONCLUSION: Compared with meperidine, fentanyl in combination with midazolam was associated with significantly shorter total procedure time. By improving the turnaround time, sedation-dependent endoscopy unit efficiency may be improved by 22%.

Endoscopic treatment of anastomotic biliary strictures after living donor liver transplantation: outcomes after maximal stent therapy.

BACKGROUND: Living-donor liver transplantation (LDLT) has emerged as a viable strategy in an era of organ shortage. However, biliary strictures are a common complication of LDLT, and these strictures frequently require surgical revision after unsuccessful endoscopic therapy. The optimal endoscopic treatment for anastomotic biliary strictures (ABSs) after LDLT is undefined. OBJECTIVE: To determine the outcome of an aggressive endoscopic approach to ABSs after LDLT that uses endoscopic dilation followed by maximal stent placement. DESIGN: A retrospective study. SETTING: A tertiary-care academic medical center. PATIENTS: Forty-one patients with a diagnosis of ABS. INTERVENTIONS: Endoscopic retrograde cholangiography with balloon dilation and maximal stenting. MAIN OUTCOME MEASUREMENTS: Stricture resolution, stricture recurrence, and complication rates. RESULTS: Of 110 LDLTs completed, a biliary stricture developed after transplantation in 41 (37.3%), which included 38 patients with duct-to-duct anastomosis. The median (interquartile range [IQR]) follow-up time is 74.2 (2.5-120.8) months. Among them, 23 (60.5%) were male, and 20 (52.6%) had bile leakage associated with ABSs. The median time (IQR) to the development of an ABS after LDLT was 2.1 (1.2-4.1) months. Endoscopic retrograde cholangiography was attempted as initial therapy in all patients: 32 were managed entirely by endoscopic therapy, and 6 required initial percutaneous transhepatic cholangiography (PTC) to cross the biliary stricture, with endoscopic therapy performed thereafter. A median (IQR) of 4.0 (3.0-5.3) endoscopic interventions and 7.0 (4.0-10.3) stents were required to resolve the stricture. The time from the first intervention to stricture resolution was 5.3 (range 3.8-8.9) months. Biochemical markers including aspartate transaminase (76 vs 39 U/L, P = .001), alanine transaminase (127.5 vs 45.5 U/L, P < .001), alkaline phosphatase (590 vs 260 IU/L, P < .001), and total bilirubin (2.57 vs 1.73 mg/dL, P = .017) significantly improved after intervention. Recurrent stricture was observed after initial treatment in 8 (21%) patients. All recurrences were successfully re-treated endoscopically. All patients have been managed without surgical revision or retransplantation, resulting in 100% success by an intention-to-treat analysis. LIMITATIONS: Retrospective study, small sample size. CONCLUSIONS: In this series, aggressive endoscopy-based treatment with maximal stent placement strategy allows 100% resolution of all duct-to-duct ABSs after LDLT without the need for surgical intervention or retransplantation.

Outcomes of endoscopic retrograde cholangiography and percutaneous transhepatic biliary drainage in liver transplant recipients with a Roux-en-Y biliary-enteric anastomosis.

Backgrounds/Aims: Data regarding outcomes of endoscopic retrograde cholangiography (ERC) in liver transplant (LT) recipients with biliary-enteric (BE) anastomosis are limited. We report outcomes of ERC and percutaneous transhepatic biliary drainage (PTBD) as first-line therapies in LT recipients with BE anastomosis. Methods: All LT recipients with Roux-BE anastomosis from 2001 to 2020 were divided into ERC and PTBD subgroups. Technical success was defined as the ability to cannulate the bile duct. Clinical success was defined as the ability to perform cholangiography and therapeutic interventions. Results: A total of 36 LT recipients (25 males, age 53.5 ± 13 years) with Roux-BE anastomosis who underwent biliary intervention were identified. The most common indications for a BE anastomosis were primary sclerosing cholangitis (n = 14) and duct size mismatch (n = 10). Among the 29 patients who initially underwent ERC, technical success and clinical success were achieved in 24 (82.8%) and 22 (75.9%) patients, respectively. The initial endoscope used for the ERC was a single balloon enteroscope in 16 patients, a double balloon enteroscope in 7 patients, a pediatric colonoscope in 5 patients, and a conventional reusable duodenoscope in 1 patient. Among the 7 patients who underwent PTBD as the initial therapy, six (85.7%) achieved technical and clinical success (p = 0.57). Conclusions: In LT patients with Roux-BE anastomosis requiring biliary intervention, ERC with a balloon-assisted enteroscope is safe with a success rate comparable to PTBD. Both ERC and PTBD can be considered as first-line therapies for LT recipients with a BE anastomosis.

Comparison of the yield and miss rate of narrow band imaging and white light endoscopy in patients undergoing screening or surveillance colonoscopy: a meta-analysis.

OBJECTIVES: Colonoscopy has an appreciable miss rate for adenomas and colorectal cancer. The goal of advanced endoscopic imaging is to improve lesion detection. Compared with standard definition, high-definition (HD) colonoscopes have the advantage of increased field of visualization and higher resolution; narrow band imaging (NBI) utilizes narrow band filters for enhanced visualization of surface architecture and capillary pattern. The objective of this study was to compare the yield and miss rates of HD-NBI and HD-WLE (white light endoscopy) for the detection of colon polyps using meta-analysis. METHODS: A recursive literature search of randomized controlled trials (RCTs) comparing the yield of HD-NBI and HD-WLE for detection of colon polyps in patients undergoing screening/surveillance colonoscopy. Authors were contacted for missing data. In RCT with tandem colonoscopy (RCT-t), findings from the first-pass examinations were used in the yield analysis and from the tandem pass for the miss rate analysis. Data on the yield of polyps were extracted, pooled, and analyzed using RevMan 4.2.9 software. Odds ratio (OR) and 95% confidence intervals (CIs) for the pooled data for the yield and miss rates of NBI and WLE were calculated. A fixed effect model (FEM) was used for analyses without, and a random effect model (REM) for analyses with heterogeneity. RESULTS: The yield analysis revealed no significant difference between HD-NBI and HD-WLE for the detection of adenomas (six studies; n=2,284; OR: 1.01; CI: 0.74-1.37; REM); patients with polyps (six studies; n=2,275; OR: 1.15; CI: 0.8-1.64; REM); patients with adenomas (four studies; n=2,177; OR: 1.0; CI: 0.83-1.20; FEM); detection of adenomas <10 mm (five studies; n=1,618; OR: 1.32; CI: 0.92-1.88; FEM); flat adenomas (five studies; n=1,675; OR: 1.26; CI: 0.62-2.57; REM); and flat adenomas per patient (five studies; n=2,200; OR: 1.63; CI: 0.71-3.74; REM). The miss rate analysis revealed no difference in polyp miss rate (three studies; n=524; OR: 1.17; CI: 0.8-1.71; FEM) or adenoma miss rate (three studies; n=524; OR: 0.65; CI: 0.4-1.06; FEM) between the two techniques. CONCLUSIONS: Compared with HD-WLE, HD-NBI does not increase the yield of colon polyps, adenomas, or flat adenomas, nor does it decrease the miss rate of colon polyps or adenomas in patients undergoing screening/surveillance colonoscopy.

Increased adenoma detection rate with system-wide implementation of a split-dose preparation for colonoscopy.

BACKGROUND: Recent studies using split-dose preparations (SDPs) suggest a significant improvement in the quality of preparation and patient compliance. However, the effects of SDP on other quality indicators of colonoscopy, such as cecal intubation and adenoma detection rates, have not been previously reported, to our knowledge. OBJECTIVE: The primary objective of this study was to compare polyp detection rates (PDRs) and adenoma detection rates (ADRs) before and after the implementation of an SDP as the preferred bowel preparation. The secondary objectives were to compare the quality of the preparation and colonoscopy completion rates before and after implementation of the SDP. DESIGN: Retrospective study. SETTING: Tertiary care medical center. PATIENTS: Patients undergoing colonoscopy for screening and surveillance of colon polyps and cancer. INTERVENTIONS: System-wide implementation of SDP. RESULTS: A total of 3560 patients in the pre-SDP group and 1615 patients in the post-SDP group were included in the study. SDP use increased significantly from 9% to 74% after implementation. In comparison with the pre-SDP group, both PDRs (44.1%-49.5%; P < .001) and ADRs (26.7%-31.8%; P < .001) significantly improved in the post-SDP group. The colonoscopy completion rate significantly increased from 93.6% to 95.5% in the post-SDP group (P = .008). Bowel preparation quality also improved significantly (P < .001) in the post-SDP group. LIMITATIONS: Retrospective design; not all endoscopists were the same in both periods. CONCLUSIONS: System-wide implementation of an SDP as the primary choice for colonoscopy significantly improved both PDRs and ADRs, overall quality of the preparation, and colonoscopy completion rates.

Comparison of single- versus double-balloon assisted-colonoscopy for colon examination after previous incomplete standard colonoscopy.

BACKGROUND: Colonoscopy fails to achieve cecal intubation in 5-10 % of cases. Many of these cases can be completed using balloon-assisted colonoscopy, either with the single-balloon colonoscopy (SBC) or the double-balloon colonoscopy (DBC) techniques. AIM: To compare the completion rates of SBC and DBC in patients with previous incomplete conventional colonoscopy. METHODS: Between August 2009 and July 2011 either SBC or DBC was performed in 53 patients in whom previous conventional colonoscopy did not achieve cecal intubation. The medical records of these 53 patients were reviewed retrospectively for details regarding (1) indication for the initial colonoscopy, (2) patient characteristics, (3) data from the initial colonoscopy, and (4) details on both SBC and DBC. RESULTS: SBC was successful in intubating the cecum in 100 % (26/26) of patients and DBC was successful in 93 % (25/27) of patients. The median (range) time to reach the cecum was 17 (9-43) min in the SBC group and 20 (7-58) min in the DBC group (P = 0.37). The presence of polyps was an entirely new finding in 35 % (9/26) of patients in the SBC group and 30 % (8/27) of patients in DBC group. Therapeutics were performed in 73 % (19/26) of patients in SBC group and 67 % (18/27) of patients in DBC group. CONCLUSION: For patients with incomplete conventional colonoscopy, SBC and DBC offer high cecal intubation rates as well as detection of additional polyps and therapeutic capability. Either SBC or DBC can be considered after incomplete conventional colonoscopy.

High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis.

OBJECTIVES: Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28-30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS: Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS: Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30-20.10, P=0.02). CONCLUSIONS: Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC.

The predictors of the presence of varices in patients with primary sclerosing cholangitis.

UNLABELLED: The predictors for developing varices in patients with primary sclerosing cholangitis (PSC) have not been well studied prospectively. We sought to define the predictors for the presence of varices at baseline and for newly developing varices in patients with PSC. We used prospectively collected data from a multicenter randomized trial of high dose ursodeoxycholic acid for PSC. All 150 patients enrolled were reviewed for predictors of varices and we excluded 26 patients who had esophageal varices at baseline so that predictors of newly developing varices could be determined. Clinical examination, blood tests, and upper endoscopy were done before randomization, at 2 years and after 5 years. Liver biopsy was performed at entry and at 5 years. The median age (interquartile range) of patients was 45.9 years (35.8, 54.9). In a multivariable logistic regression, a higher Mayo risk score (> or =0.87) or a higher aspartate/alanine aminotransferase (AST/ALT) ratio (> or =1.12) were significantly associated with the presence of varices at initial endoscopy (odds ratio = 1.9 and 3.9). By the end of the study, 25 patients had new varices (20.2%). In a Cox model, after adjustment for baseline variables lower platelet count and higher total bilirubin at 2 years were significantly associated with the presence of new varices. The platelet count of 205 (x 10(9)/L) and the total bilirubin level of 1.7 mg/dL were the best cutoff values for the detection of new varices. CONCLUSION: A higher Mayo risk score and higher AST/ALT ratio were significantly associated with the presence of varices at initial endoscopy. Lower platelet count and higher total bilirubin at 2 years were significantly associated with an increased risk of developing new varices in patients with PSC.

High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis.

UNLABELLED: Previous controlled trials are inconclusive regarding the efficacy of ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC). One hundred fifty adult patients with PSC were enrolled in a long-term, randomized, double-blind controlled trial of high-dose UDCA (28-30 mg/kg/day) versus placebo. Liver biopsy and cholangiography were performed before randomization and after 5 years. The primary outcome measures were development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The study was terminated after 6 years due to futility. At enrollment, the UDCA (n = 76) and placebo (n = 74) groups were similar with respect to sex, age, duration of disease, serum aspartate aminotransferase and alkaline phosphatase levels, liver histology, and Mayo risk score. During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group (P < 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre-established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo (P < 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria (P = 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [P < 0.01]). CONCLUSION: Long-term, high-dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events.

The role of endoscopy in the management of obscure GI bleeding.

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy (ASGE) prepared this text. In preparing this guideline, we performed a search of the medical literature by using PubMed. Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time the guidelines were drafted. Further controlled clinical studies may be needed to clarify aspects of this guideline. This guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. The recommendations are based on reviewed studies and are graded on the strength of the supporting evidence (Table 1).(1) The strength of individual recommendations is based both upon the aggregate evidence quality and an assessment of the anticipated benefits and harms. Weaker recommendations are indicated by phrases such as "we suggest," whereas stronger recommendations are typically stated as "we recommend." This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions in any particular case involve a complex analysis of the patient's condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from these guidelines.

Increased prevalence of reduced estimated glomerular filtration rate in chronic hepatitis C patients.

BACKGROUND: To investigate the prevalence and severity of reduced estimated glomerular filtration rate (eGFR) in patients with chronic hepatitis C (CHC). METHODS: Medical record review of 831 consecutive CHC patients seen in our clinic between July 2000 and August 2003; eGFR was estimated using the abbreviated Modification of Diet in Renal Disease (aMDRD) equation. The stage of kidney disease was determined based on eGFR expressed in milliliters per minute per 1.73 m(2): stage 1 (signs of kidney damage but normal or elevated (eGFR >or= 90), stage 2 (eGFR 60-89), stage 3 (30-59), stage 4 (eGFR 15-29), stage 5 (eGFR < 15 or dialysis-dependent). RESULTS: A total of 522 patients had available data with using the aMDRD equation, 51% had abnormal eGFR (stage 1, 4.6%; stage 2, 36.4%; stage 3 or 4, 6.1%; stage 5, 3.8%). Of 190 patients with stage 2 kidney disease, 189 patients (99.5%) had normal serum creatinine and only one patient (0.5%) had elevated creatinine concentrations (>1.4 mg/dl). Of the 32 patients with stage 3 or 4 disease, 20 (62.5%) had a normal serum creatinine concentration. Of 349 patients without diseases known to cause renal insufficiency, 38% had stage 2-4 renal disease. In a subset of these patients, 95/522 (18%) the measured creatinine clearance showed good correlation with their aMDRD (R = 0.47, (p < 0.0001). CONCLUSIONS: In CHC patients, a normal serum creatinine concentration does not assure normal kidney function. Estimation of eGFR with the aMDRD equation is a more accurate method of identifying patients with chronic kidney disease and reduced eGFR. Therefore, CHC patients should be screened more rigorously for chronic kidney disease because of the high prevalence of reduced eGFR. Lastly, in all CHC patients, the aMDRD eGFR should be used in each encounter with these patients when assessing their renal function irrespective of their serum creatinine.

The natural history of a branch duct intraductal papillary mucinous neoplasm in a patient with Lady Windermere syndrome: a case report.

CONTEXT: "Low-risk" branch duct intraductal papillary mucinous neoplasm (IPMN) is defined as pancreatic epithelial cellular proliferation of small branch ducts that lack malignant characteristics. At present, our understanding of the natural history of "low-risk" branch duct IPMN is still evolving. Lady Windermere syndrome is a disorder seen in non-smoking women with no pre-existing pulmonary disease affecting the lingula and/or right middle lobe with Mycobacterium avium-intracellulare complex. We present a case with pancreatic adenocarcinoma after a six-year surveillance of "low-risk" branch duct IPMN in an asymptomatic elderly white woman with Lady Windermere syndrome. CASE REPORT: A 79-year-old woman was referred to our institution because of pancreatic cystic abnormalities and elevated carbohydrate antigen 19-9 (CA 19-9). While at our institution, she was also diagnosed with Lady Windermere syndrome. Multiple abdominal imaging studies, endoscopic retrograde cholangiopancreatography, computer tomography, and magnetic resonance cholangiopancreatography (MRCP) were performed in the ensuing 6 years, all consistent with "low-risk" branch duct IPMN. No progression was seen until year 6 when MRCP showed a 2 cm pancreatic cancer. Because of multiple comorbidities, the patient chose chemotherapy over a pancreaticoduodenectomy. She developed respiratory failure and died after one cycle of gemcitabine. CONCLUSIONS: "Low-risk" branch duct IPMN may be a heterogeneous disease in which some cases can transform into malignant pancreatic neoplasms despite the absence of the so-called "high risk" features on imaging studies. Clinical management, therefore, requires individualized flexibility. In addition, when there is coexistence of Lady Windermere syndrome and pancreatic cancer, prompt diagnosis and treatment of Lady Windermere syndrome should be considered prior to chemoradiotherapy or surgery.