HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK

\ua9 The Author 2016. Background: Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings. Objectives: We examined darunavir DRMs emerging in clinical practice in the UK. Patients and methods: Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PInaive controls. Results: Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group. Conclusions: Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility

Time-Related Changes in the Prognostic Significance of the Total Number of Examined Lymph Nodes in Node-Negative Pancreatic Head Cancer

Background and ObjectivesThe aim of study was to assess time trends in the association between the total number of lymph nodes examined (TNLE) and survival in patients operated for adenocarcinoma of the head of pancreas. MethodsPatients operated for node-negative adenocarcinoma of the head of pancreas between 1988 and 2007 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Patients diagnosed between 1988 and 2002 were compared to those diagnosed between 2003 and 2007. ResultsA total of 3,406 patients were included. Although TNLE was associated with survival, the effect was not uniform. Compared to patients with >12 TNLE, survival decreased with lower TNLE (4-12 TNLE: hazard ratio [HR] 1.27, 95% CI 1.10-1.46; <4 TNLE: HR 1.39, 95% CI 1.20-1.60) among patients diagnosed between 1988 and 2002. In contrast, for those diagnosed between 2003 and 2007, while there was decreased survival for those with <4 nodes (HR 1.44, 95% CI 1.22-1.71), no effect was seen for patients with TNLE 4-12 (HR 0.98, 95% CI 0.85-1.14). ConclusionThe prognostic significance of the TNLE in patients operated for adenocarcinoma of the head of the pancreas is not constant over time. J. Surg. Oncol. 2014 110:858-863. (c) 2014 Wiley Periodicals, Inc

Comparing neoadjuvant chemotherapy with or without radiation therapy for pancreatic ductal adenocarcinoma: National Cancer Database cohort analysis

Background: Neoadjuvant treatment is important for improving the rate of R0 surgical resection and overall survival outcome in treating patients with pancreatic ductal adenocarcinoma (PDAC). However, the true efficacy of radiotherapy (RT) for neoadjuvant treatment of PDAC is uncertain. This retrospective study evaluated the treatment outcome of neoadjuvant RT in the treatment of PDAC. Methods: Collected from the National Cancer Database, information on patients with PDAC who underwent neoadjuvant chemotherapy (NAC) and pancreatectomy between 2010 to 2016 was used in this study. Short- and long-term outcomes were compared between patients who received neoadjuvant chemoradiotherapy (NACRT) and NAC. Results: The study included 6936 patients, of whom 3185 received NACRT and 3751 NAC. The groups showed no difference in overall survival (NACRT 16.1 months versus NAC 17.4 months; P = 0.054). NACRT is associated with more frequent margin negative resection (86.1 versus 80.0 per cent; P < 0.001) but a more unfavourable 90-day mortality than NAC (6.4 versus 3.6 per cent; P < 0.001). The odds of 90-day mortality were higher in the radiotherapy group (odds ratio 1.81; P < 0.001), even after adjusting for significant covariates. Patients who received NACRT received single-agent chemotherapy more often than those who received NAC (31.5 versus 10.7 per cent; P < 0.001). Conclusion: This study failed to show a survival benefit for NACRT over NAC alone, despite its association with negative margin resection. The significantly higher mortality in NACRT warrants further investigation into its efficacy in the treatment of pancreatic cancer