Comparison of the diagnostic performance of 2 core biopsy needles for EUS-guided tissue acquisition from solid pancreatic lesions.

BACKGROUND AND AIMS: A new core biopsy needle with a novel tip, opposing bevel, and sheath design has recently been introduced for EUS-guided fine-needle biopsy (FNB). The diagnostic utility of this needle for differentiating solid pancreatic masses is currently unknown. The aim of this study was to compare the diagnostic performance and yield for tissue acquisition from solid pancreatic lesions of the opposing bevel needle with those of a reverse bevel EUS-FNB needle. METHODS: Consecutive patients with solid pancreatic masses undergoing EUS-FNB using the opposing bevel (n = 101) and the reverse bevel (n = 100) core biopsy needles were included in the study. Final diagnosis was based on positive histology or at least 12 months of follow-up in cases with a negative biopsy. The primary outcome was the diagnostic performance of the 2 needles for malignant pancreatic masses. A secondary outcome was the diagnostic yield. RESULTS: Compared with the reverse bevel needle, using strict criteria the opposing bevel needle provided significantly higher sensitivity (71.1% vs 90.1%; P = .0006) and overall accuracy (74% vs 92%; I = 0.0006) for discriminating malignant from benign solid pancreatic masses. The proportion of samples classified as adequate for histologic analysis was 87% for the reverse bevel needle versus 99% for the opposing bevel needle (p = 0.002) Multivariate analysis controlling the needle gauge and site did not show any significant difference in accuracy and sensitivity between the 2 groups. There were no adverse events in either group. CONCLUSIONS: In this first, large, single-center preliminary cohort study, an EUS core biopsy needle with a novel tip, opposing bevel, and sheath design afforded substantially superior tissue yield and diagnostic performance compared with a reverse-bevel needle. If replicated by randomized controlled trials, our findings suggest that similarly designed needles could become the standard of care for EUS-guided tissue acquisition from solid pancreatic masses.

Prevalence and risk factors for liver involvement in individuals with PiZZ-related lung disease.

RATIONALE: α1-Antitrypsin deficiency is one of the most common heritable human diseases, predisposing to liver and lung injury. Significant heterogeneity in phenotypic expression is well documented, but less is known of the prevalence, severity, and correlates of chronic liver disease among individuals presenting with lung disease. OBJECTIVES: To determine the frequency of and risk factors for severe liver fibrosis and cirrhosis among individuals with PiZZ-related lung disease. METHODS: A well-characterized cohort of 57 PiZZ adults attending a tertiary referral respiratory clinic was screened prospectively for clinical, laboratory, radiologic, and (when appropriate) histologic evidence of chronic liver disease. MEASUREMENTS AND MAIN RESULTS: Thirty-six (63.2%) of 57 had a history or clinical findings suggestive of liver disease; or had one or more abnormalities of liver function, or liver ultrasound, and 24 of these underwent liver biopsy. Ten (17.5%) had evidence of severe fibrosis or cirrhosis and were more likely to have higher body mass index (P = 0.04), alanine transaminase (P = 0.0001), alkaline phosphatase (P = 0.0009), prothrombin time (P = 0.0005), and maximal vital capacity (VCmax) (P = 0.04); lower platelet count (P = 0.007); abnormal liver echogenicity (P < 0.001); and splenomegaly (P = 0.001) at ultrasound. Screening with liver ultrasound provided a sensitivity and negative predictive value for severe fibrosis or cirrhosis of 100%, as were the specificity and positive predictive value for platelet count less than or equal to 174,000 per mm(3) and splenomegaly. Among individuals undergoing liver biopsy, fibrosis stage correlated with increasing VCmax (P = 0.02) and % predicted VCmax (P = 0.05), and decreasing residual volume/total lung capacity (TLC) (P = 0.02) and % predicted residual volume/TLC (P = 0.05). CONCLUSIONS: Significant chronic liver disease is common in PiZZ individuals with lung disease and can be screened effectively by a combination of conventional tests of liver function, platelet count, and liver ultrasound.

Sex and age are determinants of the clinical phenotype of primary biliary cirrhosis and response to ursodeoxycholic acid.

UNLABELLED: BACKGROUND, & AIMS: Studies of primary biliary cirrhosis (PBC) phenotypes largely have been performed using small and selected populations. Study size has precluded investigation of important disease subgroups, such as men and young patients. We used a national patient cohort to obtain a better picture of PBC phenotypes. METHODS: We performed a cross-sectional study using the United Kingdom-PBC, patient cohort. Comprehensive data were collected for 2353 patients on diagnosis reports, response to therapy with ursodeoxycholic acid (UDCA), laboratory results, and symptom impact (assessed using the PBC-40 and other related measures). RESULTS: Seventy-nine percent of the patients reported current UDCA, therapy, with 80% meeting Paris response criteria. Men were significantly less likely to have responded to UDCA than women (72% vs 80% response rate; P < .05); male sex was an independent predictor of nonresponse on multivariate analysis. Age at diagnosis was associated strongly and independently with response to UDCA; response rates ranged from 90% among patients who presented with PBC when they were older than age 70, to less than 50% for those younger than age 30 (P < .0001). Patients who presented at younger ages also were significantly more likely not to respond to UDCA therapy, based on alanine aminotransferase and aspartate aminotransferase response criteria, and more likely to report fatigue and pruritus. Women had mean fatigue scores 32% higher than men's (P < .0001). The increase in fatigue severity in women was related strongly (r = 0.58; P < .0001) to higher levels of autonomic symptoms (P < .0001). CONCLUSIONS: Among patients with PBC, response to UDCA, treatment and symptoms are related to sex and age at presentation, with the lowest response rates and highest levels of symptoms in women presenting at younger than age 50. Increased severity of fatigue in women is related to increased autonomic symptoms, making dysautonomia a plausible therapeutic target.

Diagnostic accuracy of quantitative EUS elastography for discriminating malignant from benign solid pancreatic masses: a prospective, single-center study.

BACKGROUND: Recent data suggest that quantitative EUS elastography, a novel technique that allows real-time quantification of tissue stiffness, can accurately differentiate malignant from benign solid pancreatic masses. OBJECTIVE: To externally validate the diagnostic utility of this technique in an independent cohort. DESIGN AND SETTING: Prospective, single-center study. PATIENTS, INTERVENTIONS, AND METHODS: A total of 104 patients with evidence of a solid pancreatic mass on cross-sectional imaging and/or endosonography underwent 111 quantitative EUS elastography procedures. Multiple elastographic measurements of the mass lesion and soft-tissue reference areas were undertaken, and the corresponding strain ratios (SRs) were calculated. The final diagnosis was based on pancreatic cytology or histology. MAIN OUTCOME MEASUREMENTS: The area under the receiver-operating characteristic curve, sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of quantitative EUS elastography for discriminating malignant from benign pancreatic masses. RESULTS: The final diagnoses were primary pancreatic carcinoma (71.2%), neuroendocrine tumor (10.6%), metastatic cancer (1.9%), and pancreatitis (16.3%). Malignant masses had a higher SR (P = .01) and lower mass elasticity (P = .003) than inflammatory ones. The areas under the receiver-operating characteristic curve for the detection of pancreatic malignancy of both SR and mass elasticity (0.69 and 0.72, respectively) were less favorable than reported recently. At the cut points providing the highest accuracy in this cohort (4.65 for SR and 0.27% for mass elasticity), quantitative EUS elastography had a sensitivity of 100.0% and 95.7%, specificity of 16.7% and 22.2%, positive predictive value of 86.1% and 86.4%, negative predictive value of 100.0% and 50.0%, and overall accuracy of 86.5% and 83.8%, respectively. LIMITATIONS: Relatively small number of patients with benign disease. CONCLUSION: In the largest single-center study to date, the diagnostic utility of quantitative EUS elastography for discriminating pancreatic masses was modest, suggesting that it may only supplement rather than supplant the role of pancreatic tissue sampling in the future.

Diagnostic and therapeutic utility of single-operator peroral cholangioscopy for indeterminate biliary lesions and bile duct stones.

BACKGROUND AND AIM: We aimed to evaluate the diagnostic utility of single-operator peroral cholangioscopy (SOC) for indeterminate biliary lesions and its usefulness in electrohydraulic lithotripsy (EHL) of biliary stones not amenable to conventional endoscopic therapy. PATIENTS AND METHODS: All patients undergoing SpyGlass SOC in four UK tertiary centres between 2008 and 2010 were retrospectively enrolled. Patients were followed up until death or the last clinic visit until May 2011. The operating characteristics of SOC for detecting malignant lesions and the stone clearance rate after SOC-guided EHL were calculated. RESULTS: A total of 165 patients underwent 179 SOC procedures. Sixty-six percent were referred for indeterminate biliary strictures, 13% for filling defects and 21% for SOC-guided EHL. Cannulation with the SOC system was successful in 95% but visualization was inadequate in 13%. Primary sclerosing cholangitis was a risk factor for failed cannulation and conscious sedation (vs. general anaesthesia) for inadequate visualization (P<0.05). The accuracy of SOC for diagnosing malignant lesions was 87%. SOC-guided biopsies were adequate in 72%. Obtaining at least four versus less than four biopsy specimens resulted more often in adequate samples (90 vs. 64%, P=0.037). Complete stone clearance could be achieved in 73% of patients. The adverse event rate was 9.6%. Cholangitis was the most common event (56%, one fatal). CONCLUSION: SOC is useful for the differential diagnosis of indeterminate biliary lesions and the treatment of 'difficult' biliary stones. The adequacy of SOC-guided biopsies is related to the number of specimens obtained. Primary sclerosing cholangitis is related to failed cannulation with the SOC system, whereas general anaesthesia is related to adequate visualization.

Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis.

In addition to the HLA locus, six genetic risk factors for primary biliary cirrhosis (PBC) have been identified in recent genome-wide association studies (GWAS). To identify additional loci, we carried out a GWAS using 1,840 cases from the UK PBC Consortium and 5,163 UK population controls as part of the Wellcome Trust Case Control Consortium 3 (WTCCC3). We followed up 28 loci in an additional UK cohort of 620 PBC cases and 2,514 population controls. We identified 12 new susceptibility loci (at a genome-wide significance level of P < 5 × 10⁻8) and replicated all previously associated loci. We identified three further new loci in a meta-analysis of data from our study and previously published GWAS results. New candidate genes include STAT4, DENND1B, CD80, IL7R, CXCR5, TNFRSF1A, CLEC16A and NFKB1. This study has considerably expanded our knowledge of the genetic architecture of PBC.

The impact of serum potassium concentration on mortality after liver transplantation: a cohort multicenter study.

BACKGROUND: Potassium plays a key role in human metabolism in both health and disease. The impact of recipient serum potassium concentration [K] on mortality after liver transplantation has not been described previously. METHODS: We assessed the effect of recipient [K] on the survival of adult first single-organ liver transplant recipients in the United Kingdom and Ireland between March 1, 1994, and February 28, 2007 (n=5942), adjusting for recipient, donor, and graft characteristics. RESULTS: The overall risk-adjusted mortality significantly varied by [K], being higher among hyperkalemic ([K]>5.0 mmol/L) recipients (n=424, hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.01-1.88) and those with [K] of 4.5-5.0 mmol/L (n=1154, HR 1.47, 95% CI 1.13-1.91), compared with hypokalemic ([K]<3.5 mmol/L) recipients (n=360). However, the excess mortality was confined to the first posttransplant year among hyperkalemic recipients (HR 1.61, 95% CI 1.10-2.35) with no significant difference thereafter (HR 1.03, 95% CI 0.62-1.73). This was also true for recipients with [K] of 4.5 to 5.0 mmol/L (< or =1 year: HR 1.70, 95% CI 1.22-2.38; >1 year: HR 1.09, 95% CI 0.71-1.66). In contrast, those with [K] of 3.5 to 3.9 mmol/L (n=1518) and [K] of 4.0-4.4 mmol/L (n=2091) had similar risk-adjusted mortality at the above time points. When [K] was used as a continuous variable in the multivariable analysis, a mmol increase in [K] was associated with an increased adjusted risk of mortality of 27% (95% CI 12%-44%) at 1 year and 19% (95% CI 7%-31%) at 5 years. CONCLUSION: Recipient [K] is an independent predictor of death after liver transplantation. This finding could be of clinical utility in the management, risk stratification, selection, and prioritization of appropriate candidates for transplantation among patients with end-stage liver disease.

Candidate selection and organ allocation in liver transplantation.

Optimal candidate selection and organ allocation should offer liver transplantation to those who are sufficiently sick to justify the procedure but not too sick to benefit from it, in an order determined by patients' projected survival benefit, matching organs of sufficiently good quality to the appropriate recipients. Significant steps have been made in recent years toward devising selection and allocation criteria based on more objective and evidence-based definitions of candidate disease severity, transplant futility, organ quality, and appropriate donor-recipient matching. However, much work remains to be done in the future.