Prognostic Factors for Non-anastomotic Biliary Strictures Following Adult Liver Transplantation: A Systematic Review and Meta-Analysis.

INTRODUCTION: The development of non-anastomotic biliary strictures (NAS) following orthotopic adult liver transplantation (OLT) is associated with significant morbidity. We performed a systematic review and meta-analysis to identify all prognostic factors for the development of NAS. METHODS: A systematic review was conducted following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. We used the Newcastle-Ottawa scale to assess the quality of the included studies. Using the random-effects model, we calculated the weighted pooled odds ratios (OR), mean differences (MD), hazard ratios (HR), and 95% confidence intervals (CI) of the risk factors. RESULTS: Based on 19 international studies that included a total of 8269 adult LT patients, we calculated an 8% overall incidence of NAS. In this study, 7 potential prognostic factors were associated with a statistically significant hazard ratio for NAS in pooled analyses including (1) DCD donors compared to DBD donors (2) PSC as an indication for a liver transplant (3) Roux-en-Y bile duct reconstruction compared to duct-to-duct reconstruction (4) hepatic artery thrombosis (5) longer cold ischemia time (6) longer warm ischemia time (7) and total operative times. CONCLUSION: In this systematic review and meta-analysis, we identified 7 prognostic factors for the development of NAS following OLT. These findings might lay the groundwork for development of diagnostic algorithms to better risk stratify patients at risk for development of NAS.

Diagnostic Accuracy of Laboratory Tests and Diagnostic Imaging in Detecting Biliary Strictures After Liver Transplantation.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is often required to diagnose post-liver transplant (LT) biliary strictures. We evaluated the diagnostic accuracy of noninvasive laboratory and imaging tests in detecting post-LT biliary strictures. METHODS: Adult LT recipients who underwent ERCP between 2008 and 2015 were evaluated. Biliary strictures were diagnosed after blinded review of cholangiograms by three interventional endoscopists. The accuracy of liver enzymes, ultrasound, and MRI was determined using cholangiography as the reference standard. To evaluate the accuracy of change in liver enzymes, the difference between baseline and liver enzymes prior to ERCP (Δlab) was utilized. RESULTS: Biliary strictures were present on cholangiogram in 48 (58%) of 82 LT recipients meeting inclusion criteria. Baseline liver enzyme values did not differ significantly between patients with and without strictures. The optimal cutoffs for ΔALT, ΔAST, Δbilirubin, and Δalkaline phosphatase (AP) were determined to be 174 IU/L, 75 IU/L, 3.1 mg/dL, and 225 IU/L, respectively. ΔALT had a sensitivity of 100%, specificity 43%, and negative predictive value 100%. ΔAP had the highest specificity (53%) but modest sensitivity (69%) with a positive predictive value of 67%. Ultrasound had sensitivity of 29% and specificity of 69%, while MRI had sensitivity of 78% and specificity of 56%. DISCUSSION: The diagnostic accuracy of liver enzymes and imaging modalities is modest in detecting post-LT biliary strictures and cannot be used solely to identify patients needing further workup.

Requirement of a single high-risk feature as an indication for EUS for the diagnosis of asymptomatic pancreatic cysts.

BACKGROUND AND AIMS: Endoscopic ultrasound (EUS) is widely used to evaluate pancreatic cysts. Recent American Gastroenterological Association (AGA) guideline limits EUS for evaluation of cysts with at-least two high-risk features (size ≥ 3 cm, dilated main pancreatic duct or presence of a solid component). We have investigated the impact of this guideline on sensitivity of EUS for pancreatic cancer and the reduction of EUS procedures for pancreas cysts. METHODS: EUS procedures performed between 2004 and 2015 and related patient records were retrospectively reviewed to determine the presence or absence of high-risk features, and for the results of fine needle aspiration cytology. RESULTS: Two hundred ten patients (108 males) underwent EUS for diagnostic evaluation of pancreatic cysts. Four patients (1.9%), all with at-least one high-risk feature, were diagnosed with cytologically-proven pancreatic cancer. Only 2 patients with cancer had at-least two high-risk features that would have warranted EUS examination based on the new AGA guideline. The requirement for at-least two high-risk features would have decreased the number of EUS procedures by 91%, but reduced the sensitivity for pancreatic malignancy to 50%. If only one high-risk feature was required, EUS procedures would have been decreased by 67%, with a sensitivity of 100%. CONCLUSION: Limiting EUS to patients with pancreatic cysts with 2 or more high-risk features may substantially reduce the sensitivity for pancreatic malignancy. Performing EUS in patients with at least one high-risk feature may substantially decrease the need of invasive procedures without reducing sensitivity for detecting malignancy.

Colon Adenocarcinoma Metastasis Through Ileocolic Fistula to Small Bowel in the Setting of Crohn's Disease.

Patients with Crohn's disease are at higher risk of developing colorectal cancer and gastrointestinal fistula. Few cases in the past described colorectal cancer metastasized within the gastrointestinal tract through a fistula. We report a case of sigmoid colon adenocarcinoma in a patient with Crohn's disease that metastasized to the ileum through an ileocolic fistula tract. In addition to presenting a unique pathological phenomenon in these patients, this case raises awareness of the importance of regular follow-up and early initiation of inflammatory bowel disease therapies.

Early laboratory values after liver transplantation are associated with anastomotic biliary strictures.

BACKGROUNDS/AIMS: The aim of this study was to evaluate longitudinal changes of post-liver transplantation (LT) biliary anatomy and to assess the association of increased laboratory values after LT with the development of post-LT anastomotic biliary stricture (ABS). METHODS: Adult deceased donor LT recipients from 2008 and 2019 were evaluated. ABS was defined after blinded review of endoscopic cholangiograms. Controls were patients who underwent LT for hepatocellular carcinoma who did not have any clinical or biochemical concerns for ABS. RESULTS: Of 534 patients who underwent LT, 57 patients had ABS and 57 patients served as controls. On MRI, ABS patients had a narrower anastomosis (2.47 ± 1.32 mm vs. 3.38 ± 1.05 mm; p < 0.01) and wider bile duct at 1-cm proximal to the anastomosis (6.73 ± 2.45 mm vs. 5.66 ± 1.95 mm; p = 0.01) than controls. Association between labs at day 7 and ABS formation was as follows: aspartate aminotransferase hazard ratio (HR): 1.014; 95% confidence interval (CI): 1.008-1.020, p = 0.001; total bilirubin HR: 1.292, 95% CI: 1.100-1.517, p = 0.002; and conjugated bilirubin HR: 1.467, 95% CI: 1.216-1.768, p = 0.001. Corresponding analysis results for day 28 were alanine aminotransferase HR: 1.004, 95% CI: 1.002-1.006, p = 0.001; alkaline phosphatase HR: 1.005, 95% CI: 1.003-1.007, p = 0.001; total bilirubin HR: 1.233, 95% CI: 1.110-1.369, p = 0.001; and conjugated bilirubin HR: 1.272, 95% CI: 1.126-1.437, p = 0.001. CONCLUSIONS: Elevation of laboratory values early after LT is associated with ABS formation.

Presence of SPINK-1 variant alters the course of chronic pancreatitis.

BACKGROUND AND AIMS: There is growing evidence that genetic mutations/variants increase susceptibility to the development and progression of chronic pancreatitis (CP). Several mutations have been identified that have a direct and indirect role in events leading to CP. Mutations in the serine protease inhibitor, Kazal type-1 (SPINK-1) gene have been reported to lower the threshold for pancreatitis in the presence of other genetic or environmental factors. The prevalence and impact of SPINK-1 mutations on the clinical course and outcomes of CP remains unclear. This study was conducted to assess the prevalence of the SPINK-1/N34S variant in patients with CP, and to understand the impact of the SPINK-1 mutation on the natural history of CP. METHODS: A retrospective-prospective analysis of 239 patients with CP was performed. A detailed history, including duration of symptoms, type of pain (intermittent flares or chronic continuous pain), number of flares requiring hospital admission, alcohol and smoking history, and family history was obtained. The baseline morphological stage of CP was categorized by Cambridge classification. Clinical outcome variables included frequency and severity of pain episodes, presence of exocrine failure (defined by presence of steatorrhea and/or fecal elastase < 200 ug/g), and diabetes. The genetic tests included the cationic trypsinogen gene-1 mutation, cystic fibrosis gene mutations (Genzyme assay), and the SPINK-1/N34S mutation. RESULTS: Of the 239 patients with CP, 13 (5.4%) were positive for the SPINK-1/N34S mutation. There were 35 (14.6%) patients with idiopathic pancreatitis (IP) in this cohort. Most of the patients who were positive for the SPINK-1/N34S mutation had IP and were Caucasian (69.2%). The patients with the SPINK-1/N34S mutation had a younger age of onset (32.9 ± 10.2 vs 40.1 ± 13.6 years; P = 0.108) than those with IP and no mutation. Over a median follow up of 9.6 years, the patients with the SPINK-1/N34S mutation had a significantly greater number of acute flares each year, as compared to those without the mutation (11.8 ± 1.5 vs 4 ± 0.98; P = 0.0001). CONCLUSIONS: The prevalence of the SPINK-1/N34S mutation in patients with CP is 5.4%, and is approximately 37.1% in patients with IP. These mutations are more prevalent in Caucasian patients with CP. The SPINK-1/N34S mutation predisposes to early onset IP and more frequent acute flares of pancreatitis that might ultimately lead to pancreatic insufficiency. The patients with IP and borderline alcohol history should be considered for testing for genetic analysis, including SPINK-1 mutations, initially restricted to clinical trials.

Significant infections in liver transplant recipients undergoing endoscopic retrograde cholangiography are few and unaffected by prophylactic antibiotics.

INTRODUCTION: Current practice guidelines recommend prophylactic antibiotics prior to endoscopic retrograde cholangiopancreatography (ERCP) in liver transplant recipients (LTR). This study evaluated the risk of clinically significant infections after ERCP in LTR who received antibiotic prophylaxis compared to those who did not. METHODS: This retrospective case-cohort study evaluated all LTR who underwent elective, outpatient ERCP from 2008 to 2015. Hospitalized patients, pediatric allograft recipients and patients with cholangitis or incomplete biliary drainage were excluded. The primary outcome was unanticipated hospitalization from procedure-related clinically significant infection occurring within 3 days of ERCP. RESULTS: Sixty-nine patients (48 males; mean age 60.5 ±â€¯7.4 years) underwent 191 ERCPs after liver transplantation. Prophylactic antibiotics were administered during 82 ERCPs and not administered for 109 ERCPs. Unscheduled admissions for fever within 3 days occurred in 4 patients. Only 2 patients had documented bacteremia, of which only 1 patient received prophylactic antibiotics and also met primary outcome. Interventions during ERCP, patient demographics, and time from transplantation were not associated with increased risk of hospitalization from infections or bacteremia. CONCLUSIONS: The risk of infectious complications after ERCP in LTR is low and not affected by administration of prophylactic antibiotics. A tailored approach to antibiotic prophylaxis may be more appropriate than universal prophylaxis in selected LTR at low risk of infections.

Critical appraisal of a fixed combination of esomeprazole and low dose aspirin in risk reduction.

Low dose aspirin (

Esomeprazole: a proton pump inhibitor.

Proton pump inhibitors (PPIs) are the most potent inhibitors of gastric acid secretion available, and they are effective for treating all acid-related disorders. Esomeprazole is one of several most recent PPIs that became available to the market in 2001. Esomeprazole is indicated for the treatment of gastroesophageal reflux disease in adults and children, risk reduction of NSAIDs-associated gastric ulcer, Helicobacter pylori eradication and control of pathological hypersecretory conditions associated with Zollinger-Ellison syndrome. Esomeprazole is available in both oral and intravenous formulations. A number of studies have compared esomeprazole with other PPIs. While differences supporting esomeprazole have been reported, the magnitude of differences has been variable and of uncertain clinical importance. Cost plays a major role in prescribing patterns of PPIs.

The utility of head computed tomography in the emergency department evaluation of syncope.

OBJECTIVE: Current guidelines for evaluation of syncope recommend that in the absence of objective focal neurologic findings, head computed tomography (HCT) may not be necessary. Compliance with this recommendation is highly variable, which may be due in part to the lack of currently available evidence. We undertook the following investigation to determine whether HCT aids in the diagnostic investigation of syncope. METHODS: This study was a retrospective chart review of all adult patients who presented to an urban emergency department, and who had a HCT ordered for syncope, during a 6-month period in 2001. Patients with competing indications for HCT, or those with a presentation consistent with seizures were excluded. Charts were assigned to the "positive" or "negative" HCT group depending on whether the treating physician considered HCT findings relevant to the syncopal event. RESULTS: A total of 202 patients had a HCT performed for syncope. Eighty-five patients met one or more of the exclusion criteria. HCT of the remaining 117 patients were analyzed. None of the 117 patients had a HCT finding that was clinically related to the syncopal event. CONCLUSIONS: HCT yielded no relevant clinical findings in our entire sample of patients with syncope. Our findings combined with previous studies add to the growing body of evidence that HCT for syncope in the absence of focal neurologic findings may not be necessary.