Subepithelial tumors: How does endoscopic full-thickness resection & submucosal tunneling with endoscopic resection compare with laparoscopic endoscopic cooperative surgery?

Background and study aims Endoscopic techniques are rapidly emerging for resection of subepithelial tumors (SETs). Submucosal tunneling for endoscopic resection (STER), endoscopic full-thickness resection (EFTR) and laparoscopic endoscopic cooperative surgery (LECS) are current alternatives to open surgery. In this study, we aimed to compare the three endoscopic techniques. Patients and methods Consecutive patients who underwent resection of a submucosal esophageal or gastric lesion at several tertiary care centers were included in a dedicated registry over 3 years. Demographics, size and location of resected lesion, histology of specimen, length of procedure, adverse events (AEs), duration of hospital stay, and follow-up data were collected. Results Ninety-six patients were included (47.7 % male, mean age 62): STER n = 34, EFTR n = 34, LECS n = 280. The lesions included leiomyoma, gastrointestinal stromal tumors (GISTs) and other. The mean lesion size was 28 mm (STD 16, range 20-72 mm). The majority of lesions in the EFTR and laparoscopic-assisted resection group were GISTs. There was no significant difference in clear resection margins, post-procedure complication rates, recurrence rate and total follow-up duration between the groups. However, the LECS group had a procedure time at least 30 minutes longer than STER or EFTR ( P  < 0.01). Total hospital stay for the laparoscopic-assisted resection group was also longer when compared to STER (1.5) and EFTR (1.8) ( P  < 0.01). Conclusions STER, EFTR, and laparoscopic-assisted resection are efficacious approaches for resection of SETs with similar R0 resection rates, complication rates, and AE rates. Laparoscopic assisted resection appears more time-consuming and is associated with a longer hospital stay.

Endoscopic ultrasound-guided biliary drainage in benign biliary pathology with normal foregut anatomy: a multicenter study.

BACKGROUND AND AIMS: Biliary drainage using endoscopic ultrasound (EUS-BD) has been developed as a novel technique to obtain biliary access and drainage when ERCP fails. Numerous studies have demonstrated its safety and efficacy specifically pertaining to those with malignant distal biliary obstruction or altered foregut anatomy. The aim of this study is to evaluate the safety and efficacy of EUS-BD in benign indications in patients with normal foregut anatomy. METHODS: We performed a retrospective comparative study from 5 academic medical centers (2008-2018) involving patients with benign biliary obstruction and native foregut anatomy who had an initial failed ERCP with subsequent attempt at biliary decompression via EUS-BD or by repeating ERCP. RESULTS: 36 patients (mean age 61.6 ± 2.2, 38.9% female) who underwent attempted EUS-BD following initial failed ERCP were compared to 50 patients (mean age 62.7 ± 2.3, 73.5% female) who underwent repeat ERCP following an initial failed cannulation. EUS-BD was technically successful in 28 (77.8%) patients with rendezvous being the most common approach (86.1%). A higher level of pre-procedural bilirubin was found to be associated with technical success of EUS-BD (3.65 ± 0.63 versus 1.1 ± 0.4, p value 0.04). Success of repeat ERCP following failed cannulation was 86%. Adverse events were significantly more frequent in the EUS-BD cohort when compared to the repeat ERCP (10 (27.8%) versus 4 (8.0%), p = 0.02, OR 4.32. CONCLUSIONS: EUS-BD remains a viable therapeutic option in the setting of benign biliary disease, with success rates of 77.8%. Adverse events were significantly more common with EUS-BD vs. repeat ERCP, emphasizing the need to perform in expert centers with appropriate multidisciplinary support and to strongly consider the urgency of biliary decompression before considering same session EUS-BD after failed initial biliary access.

Incidence, Mortality and Predictors of Acute Kidney Injury in Patients with Cirrhosis: A Systematic Review and Meta-analysis.

Background and Aims: Acute kidney injury (AKI) is common in patients with cirrhosis but the incidence is heterogeneous among studies. We performed a meta-analysis to describe the incidence of AKI and its impact on patient mortality in patients with cirrhosis. We also evaluated the admission variables predicting development of AKI. Methods: A systematic search of various databases was performed up to November 2018. Meta-analyses were performed using random effects models. Results: Of 18,474 patients with cirrhosis from 30 selected studies, 5,648 developed AKI, with a pooled incidence of 29% (95% confidence interval [CI]: 28-30%, I 2 of 99%). In-hospital mortality assessed in eight studies was six-fold higher among AKI patients, as compared to those without AKI (odds ratio [OR] 6.72, 95% CI: 3.47-13, p<0.0001, I 2 of 70%). Three studies on patients admitted to intensive care showed about six-fold higher mortality among AKI patients (OR 5.90, 95% CI: 3.21-10.85, p>0.0001). Mortality remained significantly high, at days 30 and 90 and even at 1-year follow up after development of AKI. Of 12 admission variables analyzed, model for end-stage liver disease score, Child-Pugh-Turcotte stage C, presence of ascites, and presence of sepsis/septic shock were statistically significant risk factors for AKI. Conclusions: AKI occurred in about 29% of patients with cirrhosis and is associated with a six-fold increased risk of in-hospital mortality. Mortality remained high even in long-term follow-up of 1 year. Patients at risk for AKI development can be recognized at admission. Prospective studies are needed to develop strategies for improving outcome of these patients.

Primary EUS-guided biliary drainage versus ERCP drainage for the management of malignant biliary obstruction: A systematic review and meta-analysis.

EUS-guided biliary drainage (EUS-BD) has been used as a salvage modality for relief of malignant biliary obstruction (MBO) after a failed ERCP. Multiple recent randomized controlled trials (RCTs) and observational studies have been published to assess the suitability of EUS-BD as a first-line modality for achieving palliative BD. We aimed to perform a systematic review and meta-analysis comparing primary EUS-BD versus ERCP for MBO. We searched PubMed, Medline, and Embase up to January 1, 2019, to identify RCTs and observational studies evaluating the efficacy and safety of primary EUS-BD (without a prior attempted ERCP) versus ERCP. Quality of RCTs and observational studies was assessed using Jadad and Newcastle-Ottawa scores, respectively. The outcomes of interest were technical success, clinical success, odds of requiring a repeat intervention, and procedure-related adverse events. Odds ratios (ORs) and standard mean difference were calculated for categorical and continuous variables, respectively. Meta-analysis was performed using the random effects model in RevMan 5.3 (the Cochrane Collaboration, the Nordic Cochrane Centre, Copenhagen, Denmark). Five studies (three RCTs and two observational studies) with 361 patients were included. Both procedures achieved comparable technical success (OR: 1.20 [0.44-3.24], I2 = 0%) and clinical success (OR: 1.44, confidence interval [CI]: 0.63-3.29, I2 = 0%). The overall adverse outcomes (OR: 1.59 [0.89-2.84]) did not differ between the two groups. In the ERCP group, 9.5% of patients developed procedure-related pancreatitis versus zero in the EUS group (risk difference = 0.08%, P = 0.02). There was no statistically significant difference in nonpancreatitis-related adverse events. The odds of requiring reintervention for BD (1.68 [0.76-3.73], I2 = 42%) did not differ significantly. The ERCP group had significantly higher odds of requiring reintervention due to tumor overgrowth (5.35 [1.64-17.50], I2 = 0%). EUS-BD has comparable technical and clinical success to ERCP and can potentially be used as a first-line palliative modality for MBO where expertise is available. ERCP-related pancreatitis which can cause significant morbidity can be completely avoided with EUS.

Model for End-Stage Liver Disease Score Predicts Development of First Episode of Spontaneous Bacterial Peritonitis in Patients With Cirrhosis.

OBJECTIVE: To examine whether baseline model for end-stage liver disease (MELD) score in patients with cirrhosis and ascites predicts the future development of first spontaneous bacterial peritonitis (SBP) episode. METHODS: A retrospective case-control study was performed at three academic centers to select patients admitted with first SBP episode (cases) and those with ascites admitted for decompensation without SBP (controls). Medical records from these centers were reviewed between January 1, 2008, and December 31, 2013. Cases and controls were matched (1:2) for age, sex, and race. Conditional logistic recession models were built to determine whether baseline MELD score (within a month before hospitalization) predicts first SBP episode. RESULTS: Of 697 patients (308, 230, and 159 from centers A, B, and C, respectively), cases and controls were matched in 94%, 89%, and 100% at three respective centers. In the pooled sample, probability of SBP was 11%, 31%, 71%, and 93% at baseline MELD scores less than or equal to 10, from 11 to 20, from 21 to 30, and greater than 30, respectively. Compared with MELD score less than or equal to 10, patients with MELD scores from 11 to 20, 21 to 30, and greater than 30 had six- (3- to 11-), 29- (12- to 69-), and 115- (22- to 598-) folds (95% CI) risk of SBP, respectively. Based on different MELD score cutoff points, MELD score greater than 17 was most accurate in predicting SBP occurrence. Analyzing 315 patients (152 cases) with available data on ascitic fluid protein level controlling for age, sex, and center, MELD score but not ascitic fluid protein associated with first SBP episode with respective odds ratios of 1.20 (1.14 to 1.26) and 0.88 (0.70 to 1.11). CONCLUSION: Baseline MELD score predicts first SBP episode in patients with cirrhosis and ascites.

Association between cannabis laws and opioid prescriptions among privately insured adults in the US.

We examine the association between opioid prescription patterns in privately insured adults and changes in state cannabis laws among five age groups (18-25, 26-35 36-45, 46-55 and 56-64 years). Using the 2016 Clinformatics Data Mart, a nationwide commercial health insurance database, we performed a cross-sectional analysis of two types of opioid prescribing (>30-day and >90-day prescriptions) among all adults aged 18-64 based on the stringency of cannabis laws. We found a significant interaction between age and cannabis law on opioid prescriptions. Age-stratified multilevel multivariable analyses showed lower opioid prescription rates in the four younger age groups only in states with medical cannabis laws, when considering both >30 day and >90 day opioid use [>30 day adjusted odds ratio (aOR) = 0.56, in 18-25, aOR = 0.67 in 26-35, aOR = 0.67 in 36-45, and aOR = 0.76 in 46-54 years; >90 day aOR = 0.56, in 18-25, aOR = 0.68 in 26-35, aOR = 0.69 in 36-45, and aOR = 0.77 in 46-54 years, P < 0.0001 for all]. This association was not significant in the oldest age group of 55-64 years. There was no significant association between opioid prescriptions and other categories of cannabis laws (recreational use and decriminalization) in any of the age groups studied.

Endoscopic Retrograde Cholangiopancreatography and Endoscopic Ultrasound-Guided Gallbladder Drainage.

"Gallbladder disease is one of the most common gastrointestinal diseases encountered in clinical practice. Surgical removal and percutaneous drainage are both widely available and effective in the management of acute cholecystitis. Several endoscopic approaches exist as an alternative to these interventions. These include transpapillary approaches via endoscopic retrograde cholangiopancreatography (ERCP), transmural drainage and access approaches via endoscopic ultrasound (EUS), and endoscopic surgical approaches using natural orifice transluminal endoscopic surgery (NOTES) techniques. This article reviews the epidemiology and pathophysiology of gallbladder diseases and discusses the various percutaneous, surgical, and endoscopic approaches to managing gallbladder disease."

Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome.

BACKGROUND: More effective treatments are needed for patients with postinfectious, diarrhoea-predominant, irritable bowel syndrome (IBS-D). Accordingly, we conducted a randomised, double-blind, placebo-controlled, 8-week-long trial to assess the efficacy and safety of oral glutamine therapy in patients who developed IBS-D with increased intestinal permeability following an enteric infection. METHODS: Eligible adults were randomised to glutamine (5 g/t.i.d.) or placebo for 8 weeks. The primary end point was a reduction of ≥50 points on the Irritable Bowel Syndrome Severity Scoring System (IBS-SS). Secondary endpoints included: raw IBS-SS scores, changes in daily bowel movement frequency, stool form (Bristol Stool Scale) and intestinal permeability. RESULTS: Fifty-four glutamine and 52 placebo subjects completed the 8-week study. The primary endpoint occurred in 43 (79.6%) in the glutamine group and 3 (5.8%) in the placebo group (a 14-fold difference). Glutamine also reduced all secondary endpoint means: IBS-SS score at 8 weeks (301 vs 181, p<0.0001), daily bowel movement frequency (5.4 vs 2.9±1.0, p<0.0001), Bristol Stool Scale (6.5 vs 3.9, p<0.0001) and intestinal permeability (0.11 vs 0.05; p<0.0001). 'Intestinal hyperpermeability' (elevated urinary lactulose/mannitol ratios) was normalised in the glutamine but not the control group. Adverse events and rates of study-drug discontinuation were low and similar in the two groups. No serious adverse events were observed. CONCLUSIONS: In patients with IBS-D with intestinal hyperpermeability following an enteric infection, oral dietary glutamine supplements dramatically and safely reduced all major IBS-related endpoints. Large randomised clinical trials (RCTs) should now be done to validate these findings, assess quality of life benefits and explore pharmacological mechanisms. TRIAL REGISTRATION NUMBER: NCT01414244; Results.

Association of Hospitalist Years of Experience With Mortality in the Hospitalized Medicare Population.

Importance: Substantial numbers of hospitalists are fresh graduates of residency training programs. Current data about the effect of hospitalist years of experience on patient outcomes are lacking. Objective: To describe the association of hospitalist years of experience with 30-day mortality and hospital mortality of their patients. Design, Setting, and Participants: We used a 5% sample of national Medicare data of patient and hospital characteristics to build a multilevel logistic regression model to predict mortality as a function of years of experience of the hospitalists. We created 2 cohorts. The first was a cross-sectional cohort of 21 612 hospitalists working between July 1, 2013, and June 30, 2014, with a 5-year look-back period to assess their years of prior experience as a hospitalist, and the second was a longitudinal cohort of 3860 hospitalists in their first year of practice between July 1, 2008, and June 30, 2011, who continued practicing hospital medicine for at least 4 years. Main Outcomes and Measures: Thirty-day postadmission mortality adjusted for patient and hospital characteristics in a 3-level logistic regression model. Hospital mortality was a secondary outcome. Results: Among 21 612 hospitalists caring for Medicare inpatients from July 1, 2013, to June 30, 2014, 5445 (25%) had 1 year of experience or less, while 11 596 (54%) had 4 years of experience or more. We then identified 3860 physicians in their first year as hospitalists who continued to practice as hospitalists for 4 years. There was a significant association between hospitalist experience and mortality. Observed 30-day mortality was 10.50% for patients of first-year hospitalists vs 9.97% for patients of hospitalists in their second year. The mortality odds for patients of second-year hospitalists were 0.90 (95% CI, 0.84-0.96) compared with patients of first-year hospitalists. Observed hospital mortality was 3.33% for patients cared for by first-year hospitalists vs 2.96% for second-year hospitalists. (odds ratio, 0.84; 95% CI, 0.75-0.95). For both 30-day and hospital mortality, there was little change in odds of mortality between the second year and subsequent years of experience. Conclusions and Relevance: Patients cared for by hospitalists in their first year of practice experience higher mortality. Early-career hospitalists may require additional support to ensure optimal outcomes for their patients.

Pharmacological Therapies for Hepatorenal Syndrome: A Systematic Review and Meta-Analysis.

BACKGROUND: Hepatorenal syndrome (HRS) is a serious complication of advanced chronic liver disease. Different pharmacological therapies have variable efficacy. We performed a systematic review and meta-analysis to compare the efficacy of various drugs in the treatment of HRS. STUDY: Randomized controlled trials comparing active drug with placebo or comparing 2 different drugs were included in this analysis. Primary study outcome was reversal of HRS. Secondary outcomes were HRS relapse and patient survival. Subgroup analysis was performed on patients with type 1 HRS. RESULTS: Thirteen randomized controlled trial were eligible for analysis. Terlipressin plus albumin was more efficacious than placebo plus albumin (odds ratio=4.72; 95% confidence interval, 1.72-12.93; P=0.003) or midodrine plus albumin and octreotide (odds ratio=5.94; 95% confidence interval, 1.69-20.85; P=0.005), for HRS reversal. However, no significant difference was noted comparing terlipressin plus albumin versus noradrenaline plus albumin, octreotide plus albumin versus placebo plus albumin or noradrenaline plus albumin versus midodrine plus albumin and octreotide. None of the comparisons showed difference on HRS relapse or patient survival. Subgroup analysis revealed that terlipressin was more effective than placebo for type 1 HRS reversal, but no significant differences were noted between any other comparisons, and none of the comparisons showed difference on HRS relapse or patient survival. CONCLUSIONS: Intravenous infusion of terlipressin is the most effective medical therapy for reversing HRS. Intravenous infusion of noradrenaline is an acceptable alternative. Studies are needed as basis for developing pharmacological strategies to reduce relapse of HRS and improve patient survival.

PNPLA3 as a Genetic Determinant of Risk for and Severity of Non-alcoholic Fatty Liver Disease Spectrum.

Background and Aims:Patatin-like phospholipase domain protein 3 (PNPLA3) polymorphisms (rs738409 C>G) are associated with non-alcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to examine the association of PNPLA3 polymorphisms with the spectrum and severity of this disease. Methods: Studies evaluating the association between the PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) and NAFLD were included. Pooled data are reported as odds ratios (ORs) with 95% confidence intervals. Results: Of 393 potentially relevant studies, 35 on NAFLD were included in the analysis. Compared to healthy controls, the pooled ORs for rs738409 CG and GG compared to CC among patients with non-alcoholic fatty liver (NAFL) were 1.46 (1.16-1.85) and 2.76 (2.30-3.13), and were 1.75 (1.24-2.46) and 4.44 (2.92-6.76) among patients with non-alcoholic steatohepatitis respectively. The respective ORs for CG and GG compared to the CC genotype were 2.35 (0.90-6.13) and 5.05 (1.47-17.29) when comparing non-alcoholic hepatocellular carcinoma to NAFL patients. Among the NAFLD patients, the ORs for G allele frequency when comparing steatosis grade 2-3 to grade 0-1 NAFL, when comparing the NAFLD activity score of ≥ 4 to score ≤ 3, when comparing NASH to NAFLD, when comparing the presence of lobular inflammation to absence, and when comparing the presence of hepatocyte ballooning to absence were 2.33 (1.43-3.80), 1.80 (1.36-2.37), 1.66 (1.42-1.94), 1.58 (1.19-2.10), and 2.63 (1.87-3.69) respectively. Subgroup analysis based on ethnicity showed similar results. Conclusions:PNPLA3 polymorphisms have strong association with the risk for and severity of NAFLDs. PNPLA3 polymorphism plays an evolving role in diagnosis and treatment decisions in patients with NAFLD.

PNPLA3 polymorphism increases risk for and severity of chronic hepatitis C liver disease.

AIM: To examine the association of PNPLA3 polymorphisms in chronic hepatitis C patients and development of liver disease spectrum. METHODS: Literature was searched systematically from PubMed/MEDLINE, EMBASE, and Cochrane search engines for full-length articles written in English that examined PNPLA3 polymorphism in chronic hepatitis C (CHC) patients. Studies evaluating the association of PNPLA3 polymorphism spectrum (fatty liver, steatohepatitis, cirrhosis, and hepatocellular carcinoma) of CHC were included. Pooled data are reported as OR with 95%CI. Our study endpoint was the risk of the entire liver disease spectrum including: Steatosis/fatty liver, cirrhosis, and hepatocellular carcinoma in CHC patients with PNPLA3 polymorphisms. RESULTS: Of 380 studies identified, a total of 53 studies were included for full-text review. Nineteen on chronic hepatitis C were eligible for analysis. Pooled ORs for rs738409 GG compared to CC and CG among patients with fatty liver was 2.214 (95%CI: 1.719-2.853). ORs among advanced fibrosis/cirrhosis were 1.762 (95%CI: 1.258-2.468). Similar odds ratios among hepatocellular carcinoma patients were 2.002 (95%CI: 1.519-2.639). Pooled ORs for rs738409 GG and CG compared to CC among patients with fatty liver were 1.750 (95%CI: 1.542-1.986). Pooled ORs for advanced fibrosis/cirrhosis patients were 1.613 (95%CI: 1.211-2.147). All analyses were homogenous and without publication bias except one. The associations were maintained after adjusting for publication bias and heterogeneity. CONCLUSION: PNPLA3 polymorphisms have strong association with increased risk and severity of the liver disease spectrum in CHC patients.

PNPLA3 Gene Polymorphism Is Associated With Predisposition to and Severity of Alcoholic Liver Disease.

OBJECTIVES: The genetic polymorphism with an isoleucine-to-methionine substitution at position 148 (rs738409 C>G) in the patatin-like phospholipase domain protein 3 (PNPLA3) gene confers risk of steatosis. PNPLA3 polymorphism is shown to be associated with alcoholic liver disease (ALD). We performed a systematic review and meta-analysis to examine association of this genetic polymorphism with ALD spectrum and its severity. METHODS: Medline, Embase, and Cochrane Library were searched for studies on association of PNPLA3 polymorphism and ALD spectrum: alcoholic fatty liver (AFL), alcoholic liver injury (ALI), alcoholic cirrhosis (AC), and hepatocellular carcinoma (HCC). Pooled data are reported as odds ratio (OR) with 95% confidence interval. Heterogeneity was assessed using the I(2) statistics and publication bias using Egger's test and Begg and Mazumdar's test. Individual participant data obtained from five studies were used for subgroup analyses. RESULTS: Among 10 studies included in this pooled analysis, compared with controls, OR for rs738409 CG and GG among ALI patients was 1.45 (1.24-1.69) and 2.22 (1.50-3.28), respectively, compared with CC. Respective OR among AC patients was 2.09 (1.79-2.44) and 3.37 (2.49-4.58) and among AC patients with HCC was 2.87 (1.61-5.10) and 12.41 (6.99-22.03). Data for AFL were inconsistent. Among ALD patients, OR of CG and GG genotypes was 2.62 (1.73-3.97) and 8.45 (2.52-28.37), respectively, for AC compared with fatty liver (FL) patients. Similar OR for AC compared with ALI was 1.98 (1.24-3.17) and 3.86 (1.18-12.60). The OR for CG and GG genotypes among AC patients for HCC occurrence was 1.43 (0.76-2.72) and 2.81 (1.57-5.01), respectively. Individual participant data analysis showed age to predispose to AC among ALI patients. CONCLUSIONS: PNPLA3 genetic polymorphism (rs738409 C>G) is associated with increased risk for the entire spectrum of ALD among drinkers including ALI, AC, and HCC. Studies are needed to clarify association of PNPLA3 polymorphism and steatosis in alcoholics. PNPLA3 gene may potentially be a therapeutic target in ALD.

Evolving frequency and outcomes of simultaneous liver kidney transplants based on liver disease etiology.

BACKGROUND: The frequency of simultaneous liver kidney (SLK) transplantation is increasing. Data are scanty on outcomes of SLK transplants for liver disease etiology. METHODS: Outcomes for liver and kidney grafts and patients survival at 5 years were compared for liver disease etiology among adults receiving SLK during 2002 and 2011 in the United States. Cox regression analysis models were built to determine the independent impact of liver disease etiology on outcomes. RESULTS: A total of 2,606 patients (mean age 53 years, 69% males, 55% Caucasians) received SLK for primary biliary cirrhosis (PBC, n=76), primary sclerosing cholangitis (n=81), hepatitis C virus (HCV) (n=945), alcoholic liver disease (n=495), alcohol and HCV (n=152), cryptogenic cirrhosis (CC, n=289), nonalcoholic steatohepatitis (NASH) (n=221), hepatitis B virus (HBV) (n=98), and hepatocellular carcinoma (HCC) (n=249). HCV and NASH+CC contributed to about 44% and 9%, respectively, of all SLK transplants in 2002. Corresponding figures in 2011 were 34% and 22%, respectively. Compared to PBC, 5-year outcomes were worse for NASH, HCV, and HCC for liver graft (72%, 66%, and 72% vs. 82%; hazard ratio, HR: 2.5-3.1), kidney graft (71%, 65%, and 71% vs. 80%; HR: 2.3-2.8), and patient survival (74%, 69%, and 69% vs. 82%; HR: 2.4-2.7). Follow-up renal function assessed at 1, 3, and 5 years showed poor renal function among patients receiving SLK for HCV, NASH, CC, and HBV. CONCLUSIONS: Frequency of SLK transplants is increasing among NASH patients. Overall graft and patient outcomes are good. However, SLK for NASH, HCV, and HCC do worse. Strategies are needed to improve outcomes for SLK in HCV and NASH patients.

Histo-biological comparative analysis of bilateral breast cancer.

Bilateral breast cancer occurs in approximately 7% of surviving breast cancer patients. However, a dilemma exists concerning the notion of whether this represents a de novo second primary tumor versus a breast metastasis. We analyzed 81 patients with bilateral breast cancer, 47 (58%) synchronous tumors and 34 (42%) metachronous tumors. Additionally, charts were reviewed for age, family history, full histology data and biological receptors. We found there were no significant differences in concordance between the first and second primary tumors (in both synchronous and metachronous bilateral breast cancer) with respect to histology; grade; T-category; N-category; ER, PR and HER-2 status. In addition, there was no significant difference in the strength of correlation between ER and PR in the first and secondary primary tumors. Our findings suggest that the differentiation of the origin of contralateral breast cancer based on routine histological and biological concordance is inconclusive. Furthermore, the dilemma will continue to exist until additional molecular approaches are applied routinely for research purposes to resolve the debate.

Management practices of hepatitis C virus infected alcoholic hepatitis patients: A survey of physicians.

AIM: To survey gastroenterologists and hepatologists regarding their current views on treating hepatitis C virus (HCV) infected alcoholic hepatitis (AH) patients. METHODS: A sixteen item questionnaire was electronically mailed to gastroenterologists and hepatologists. A reminder was sent after 2 mo to increase the response rate. Participation of respondents was confidential. Accessing secured web site to respond to the questionnaire was considered as informed consent. Responses received on the secured website were downloaded in an excel sheet for data analysis. RESULTS: Analyzing 416 responses to 1556 (27% response rate) emails, 57% respondents (56% gastroenterologists) reported HCV prevalence > 20% amongst AH patients. Sixty nine percent often treated AH and 46% preferred corticosteroids (CS). Proportion of respondents with consensus (75% or more respondents agreeing on question) on specific management of HCV infected AH were: routine HCV testing (94%), HCV not changing response to CS (80%) or pentoxifylline (91%), no change in approach to treating HCV infected AH (75%). None of respondent variables: age, specialty, annual number of patients seen, and HCV prevalence could predict respondent to be in consensus on any of or all 4 questions. Further, only 4% would choose CS for treating HCV infected AH as opposed to 47% while treating HCV negative AH. CONCLUSION: Gastroenterologists and hepatologists believe that AH patients be routinely checked for HCV. However, there is lack of consensus on choice of drug for treatment and outcome of HCV positive AH patients. Studies are needed to develop guidelines for management of HCV infected AH patients.

Evolving frequency and outcomes of liver transplantation based on etiology of liver disease.

BACKGROUND: In the background of availability of better treatments for specific liver diseases and listing of nonalcoholic steatohepatitis (NASH) as an etiology for liver transplantation (LT), data are unclear on the impact of disease etiology on the frequency of LT and liver posttransplantation outcomes. METHODS: The United Network for Organ Sharing database (1994-2009) was queried for adults receiving first LT for primary biliary cirrhosis (PBC; n=3052), primary sclerosing cholangitis (PSC; n=3854), hepatitis C virus (HCV; n=15,147), alcoholic cirrhosis (AC; n=8940), HCV+alcohol (n=6066), NASH (n=1368), cryptogenic cirrhosis (CC; n=5856), hepatitis B virus (HBV; n=1816), and hepatocellular carcinoma (HCC; n=8588). Graft and patient survival were compared and Cox models were built to determine independent prediction of outcomes by disease etiology. RESULTS: The frequency of LT increased for NASH, HCC, and HCV+alcohol, remained stable for AC, and decreased for PBC, PSC, HCV, CC, and HBV. The proportion of simultaneous liver-kidney transplants increased from approximately 3% in 2001 to 10% in 2009. Compared with PBC, 5-year graft and patient survival were (a) similar for PSC, NASH, and HBV (80-85%), (b) poorer for AC and CC (hazard ratio, 1-1.5), and (c) worst for HCV, HCV+alcohol, and HCC (hazard ratio, 1.5-2.4). Five-year outcomes for HCV-associated HCC were poorer compared with HCC due to other etiologies. CONCLUSIONS: LT performed for NASH and HCC are increasing. Potent treatment options resulted in a decrease in number of transplants for HBV, HCV, and PBC. Better treatment modalities for HCV are expected to further reduce the number of LT for HCV. Excellent posttransplantation outcomes for NASH and AC are encouraging, resulting in wider acceptance of transplants for these etiologies.

How does preoperative radiotherapy affect the rate of sphincter-sparing surgery in rectal cancer?

The use of preoperative radiotherapy has resulted in significant downstaging and downsizing of tumor, this in turn facilitated resections permitting sphincter preservation and coloanal anastomosis for patients who would otherwise have not been candidates for this type of surgery as concluded by some small studies. On the other hand, other clinical trials have shown that the effect of radiotherapy on the rate of sphincter preservation is still not clear. Moreover, different modes of radiotherapy have been tested on the rate of sphincter preservation such as pelvic irradiation with or without combination of chemotherapy, short or conventional course radiotherapy, and preoperative or postoperative radiotherapy with different timing intervals of surgery. Unfortunately, these trials didn't clearly answer the question of radiotherapy benefit for the sake of sphincter preserving of rectal cancer patients and the question remained hotly debated.