Ditah, Ivo

Goals: A systematic review and meta-analysis of published clinical validity studies was conducted to evaluate the predictive performance of the TSP-9 test. Background: Identifying patients with Barrett’s esophagus (BE) who will progress to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) is challenging. The tissue systems pathology (TSP-9) test can predict risk of progression to HGD/EAC in BE patients. Study: Databases were searched for studies that assessed the clinical validity of TSP-9, and data describing progressors, non-progressors, TSP-9 results, and hazard ratios (HR) with 95% confidence intervals (CIs) were extracted. Odds ratios (OR), sensitivity, specificity, and prevalence-adjusted positive and negative predictive values (PPV adj /NPV adj ) were calculated and used for meta-analysis. Results: Six studies met eligibility criteria, comprising 699 patients. ORs and HRs for TSP-9 had mean common effect size estimates of 6.52 (95% CI: 4.40-9.66, P <0.0001, I 2 =33%) and 6.66 (95% CI: 4.59-9.66, P <0.0001, I 2 =0%), respectively, for predicting progression to HGD/EAC. Mean common effect size estimates were 61% (95% CI: 54%-68%) for sensitivity, 81% (95% CI: 78%-84%) for specificity, 28% (95% CI: 17%-42%) for PPV adj (high risk), 14% (95% CI: 9%-21%) for PPV adj (high/int risk), and 97% (95% CI: 96%-98%) for NPV adj with minimal inter-study heterogeneity ( I 2 =79%, 21%, 0%, 0%, and 0%, respectively). Conclusions: Effect estimates of TSP-9 performance demonstrate that the test provides risk stratification for BE patients. The TSP-9 test can provide clinically impactful results to enable escalation of care for high-risk patients or to identify low-risk patients who can be safely managed with routine surveillance.

Background. Liver arteriovenous malformations (AVM) in hereditary hemorrhagic telangiectasia (HHT) can necessitate liver transplantation. There is limited data on HHT patients undergoing liver transplantation (LT) in the United States. Methods. Two sources of data were used: (1) Scientific Registry of Transplant Recipients (SRTR) database (1998-2016) (2) Single center liver transplant database (Mayo Clinic Rochester, MN). The aims of this study were (1) to determine trends in LT for HHT-related liver involvement in the United States using the SRTR database; (2) to identify clinical characteristics, indications, and outcomes for LT in HHT. Results. Thirty-nine HHT patients were listed for LT in the SRTR database from 1998-2016 to 1998-2001 (n = 1); 2002-2005 (n = 4); 2006-2010 (n = 10), and 2011-2016 (n = 24). Twenty-four underwent LT at a median age of 47.5 years (interquartile range, 37.0-58.5 years). Median calculated MELD score at time of LT was 8.0 (interquartile range, 7.0-9.5), and 75% received an exception MELD score. Two status-1 patients died during transplant surgery. Nineteen (86%) patients were alive after a median post-LT follow-up of 48 months, whereas 2 patients were lost to follow-up. Five of the aforementioned HHT patients underwent LT at Mayo Clinic, 4 with high output cardiac failure, and 1 with biliary ischemia. All 5 were alive at the time of last follow-up with good graft function and resolution of heart failure. Conclusions. Outcomes after LT for HHT patients are excellent with 86% survival after a median follow-up of 48 months and resolution of heart failure. LT listing for HHT has increased in substantially in more recent eras.

228 Background: Even though gemcitabine monotherapy is commonly used as first-line treatment for metastatic pancreatic cancer, many novel treatment approaches have focused on combination chemotherapy. FOLFIRINOX, a combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin, has recently been shown to improve survival compared to gemcitabine. However, it is unclear whether survival benefits are counterbalanced by a poor quality of life due to the adverse effects. The aim of this study was to review emerging strategies that enhance treatment of patients with metastatic pancreatic cancer. Methods: Two authors independently conducted a comprehensive search of the Cochrane library PUBMED, and published proceedings from major oncologic and gastrointestinal cancer meetings from January 1980 to July 2012. Only published randomized controlled trials were eligible for inclusion. Our primary outcome measures were: progression-free survival (PFS), overall survival (OS) and serious adverse events (grade 3 or 4). Results: Thirty-one studies involving 7,957 patients were included in the analysis. There was an overall statistically significant increase in OS (RR 1.10, 95% CI 1.03-1.30) and PFS (RR 1.27, 95% CI 1.14-1.46) for the gemcitabine-based combination therapy group versus the gemcitabine monotherapy group. Subgroup analysis showed that only patients with fluoropyrimidine and platinum containing regimens showed prolonged survival: RR 1.33, 95% CI 1.04-1.76 and RR 1.38, 95% CI 1.08-1.76, respectively. The most common severe adverse event (neutropenia) was found in 45% of patients treated with FOLFIRINOX. Conclusions: Overall, gemcitabine in combination with fluoropyrimidine or platinum containing regimens can improve overall survival in patients with metastatic pancreatic cancer compared to gemcitabine alone. Even though, FOLFIRINOX therapy is associated with better survival outcomes than gemcitabine, the prolonged survival comes at the cost of poorer quality of life due to a higher incidence of adverse events. More data is needed from studies involving novel combination therapy such as hedgehog pathway inhibitors and radio-immunotherapy.

AbstractBackground & AimsAntiviral drugs are safe and effective in the third trimester to prevent intrauterine transmission of hepatitis B virus, and are recommended for hepatitis B virus (HBV) infected gravid mothers (between weeks 28 and 32) with high viral load, followed by postnatal hepatitis B immunization in the newborn. We estimated the comparative efficacy of antiviral drugs for prevention of vertical transmission of HBV, through a network meta‐analysis of clinical trials.MethodsWe conducted a comprehensive search of MEDLINE, EMBASE and published proceedings from major liver meetings from January 1980 to November 2014. We conducted pair‐wise meta‐analyses and Bayesian framework using Markov chain Monte Carlo methods, combining direct and indirect evidence for any given pair of treatments.ResultsSeventeen clinical trials involving 2764 newborns of hepatitis B surface antigen seropositive mothers were eligible for analysis. There were no clinical trials involving tenofovir or entecavir. On pair‐wise meta‐analyses, telbivudine (hazard ratio, HR 0.12, 95% confidence interval (CI) 0.04–0.37; I2 = 0%), and Lamivudine (HR 0.40, 95% CI 0.24–0.65; I2 = 0%), were more effective than placebo in reducing vertical transmission of HBV in high viremic hepatitis B e antigen (HBeAg)‐positive chronic Hepatitis B Chinese patients. Sensitivity analyses limited to studies with HBeAg seropositive mothers revealed similar results.ConclusionsBased on a Bayesian network meta‐analysis of clinical trials, combining direct and indirect treatment comparisons, telbivudine appears to be more effective than Lamivudine for preventing vertical transmission of HBV infection. Trials assessing the efficacy of tenofovir or entecavir compared to placebo or other antiviral drugs are lacking.

The rise in incidence of hepatocellular carcinoma (HCC) in the United States has been well documented. The purpose of this analysis was to examine temporal trends in HCC incidence, mortality, and survival within the U.S. population. The Surveillance, Epidemiology, and End Results data were used to examine incidence and incidence‐based (IB) mortality in HCC from 1973 to 2011. Secular trends in age‐adjusted incidence and IB mortality by sex and cancer stage were characterized using the Joinpoint Regression program. In 1973, HCC incidence was 1.51 cases per 100,000, whereas in 2011, HCC incidence was 6.20 cases per 100,000. Although HCC incidence continues to increase, a slowing of the rate of increase occurs around 2006. In a sensitivity analysis, there was no significant increase in incidence and IB mortality from 2009 to 2011. There was a significant increase in overall median survival from the 1970s to 2000s (2 vs. 8 months; P < 0.001). On multivariable Cox's regression analysis, age, sex, race, tumor grade, stage at diagnosis, lymph/vascular invasion, number of primary tumors, tumor size, and liver transplant were independently associated with mortality. Conclusion: Our results indicate a deceleration in the incidence of HCC around 2006. Since 2009 and for the first time in four decades, there is no increase in IB mortality and incidence rates for HCC in the U.S. population. The nonsignificant increase in incidence and IB mortality in recent years suggest that the peak of the HCC epidemic may be near. A significant survival improvement in HCC was also noted from 1973 to 2010, which seems to be driven by earlier detection of HCC at a curative stage and greater utilization of curative modalities (especially transplant). (Hepatology 2015;61:191–199)

BACKGROUNDSince 2002, priority Model for End‐stage Liver Disease (MELD) exception status has been given to patients with hepatocellular carcinoma (HCC) who meet the Milan criteria. Since then, the number of liver transplantations performed in patients with HCC has increased, but to the authors' knowledge, few studies to date have examined the effect of MELD exception recommendations on therapy use and survival rates in a nationwide sample. The current study examines therapy use and long‐term survival rates among patients with HCC tumors meeting the Milan criteria in the post‐MELD exception era.METHODSThe current study is a retrospective cohort study of 2179 patients with localized HCC meeting the Milan criteria who were registered between 2004 and 2007 in the Surveillance, Epidemiology, and End Results database.RESULTSA total of 43% of patients did not receive any specific therapy. Overall, the 5‐year relative survival rate for patients receiving only supportive care was dismal at 24% (95% confidence interval [95% CI], 21%‐27%), whereas that for patients undergoing liver transplantation was 77% (95% CI, 71%‐82%). Long‐term survival was found to be dependent on age, race/ethnicity, and type of therapy received. A multivariate Cox proportional hazards model adjusted for age, race/ethnicity, and type of therapy received demonstrated that, compared with white patients, black patients had significantly poorer survival outcomes (hazards ratio, 1.23; 95% CI, 1.03‐1.47 [P = .02]), whereas Asian/Pacific Islander patients had significantly better survival rates when compared with white patients (HR, 0.66; 95% CI, 0.57‐0.77 [P < .001]).CONCLUSIONSDespite having localized disease that met transplantation criteria, nearly 50% of the large nationwide cohort of patients with HCC in the current study received only supportive care and had dismal 5‐year relative survival rates, especially among black patients. Cancer 2014;120:1725–1732. © 2014 American Cancer Society.