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

Evaluating surgical treatment options for small nonfunctional pancreatic neuroendocrine tumors in the NCDB.

645 Background: The role of surgery for small (≤2 cm), nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) remains controversial due to the wide range of tumor aggressiveness. Consensus guidelines of the US, Europe, and Japan offer different recommendations for treatment of small NF-PNETs. The objective of this study is to evaluate the survival benefit of surgical resection for small NF-PNETs. Methods: Patients with NF-PNETs were identified in the National Cancer Database from 2004 to 2018. Small NF-PNETs were divided into two groups: group 1a (tumor ≤1 cm) and group 1b (tumor 1.1 – 2.0 cm). Cox regression models were used to compare the overall survival between resected and unresected small NF-PNETs patients. Interactions between preoperative factors and surgery were estimated using subgroup analyses. Results: We identified 1,278 patients in group 1a and 3,363 patients in group 1b. After adjusting for preoperative factors, surgery was associated with longer survival for patients in group 1b (HR, 0.58; 95% CI, 0.42–0.80; P &lt;0.001), but not for patients in group 1a (HR, 0.68; 95% CI, 0.41–1.11; P = 0.122). Interaction analysis found that age younger than 65 years, fewer comorbidities, treatment at academic institutions, distal pancreatic tumors, and clinical lymph node metastasis were factors associated with longer survival in group 1b by surgery. Conclusions: Findings from this large study support surgical resection for some patients with NF-PNETs (1.1 – 2.0 cm). This, of course, must be taken in context with the patient’s clinical situation. Based on data available for analysis in this study, resection for subcentimeter NF-PNETs does not appear to be of general benefit, but should also be investigated in the context of Ki-67 index.[Table: see text] </jats:p

Evaluation of Survival Following Surgical Resection for Small Nonfunctional Pancreatic Neuroendocrine Tumors

ImportanceThe number of patients with small nonfunctional pancreatic neuroendocrine tumors (NF-PanNETs) is increasing. However, the role of surgery for small NF-PanNETs remains unclear.ObjectiveTo evaluate the association between surgical resection for NF-PanNETs measuring 2 cm or smaller and survival.Design, Setting, and ParticipantsThis cohort study used data from the National Cancer Database and included patients with NF-pancreatic neuroendocrine neoplasms who were diagnosed between January 1, 2004, and December 31, 2017. Patients with small NF-PanNETs were divided into 2 groups: group 1a (tumor size, ≤1 cm) and group 1b (tumor size, 1.1-2.0 cm). Patients without information on tumor size, overall survival, and surgical resection were excluded. Data analysis was performed in June 2022.ExposuresPatients with vs without surgical resection.Main Outcomes and MeasuresThe primary outcome was overall survival of patients in group 1a or group 1b who underwent surgical resection compared with those who did not, which was evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Interactions between preoperative factors and surgical resection were analyzed with a multivariable Cox proportional hazards regression model.ResultsOf the 10 504 patients with localized NF-PanNETs identified, 4641 were analyzed. These patients had a mean (SD) age of 60.5 (12.7) years and included 2338 males (50.4%). The median (IQR) follow-up time was 47.1 (28.2-71.6) months. In total, 1278 patients were in group 1a and 3363 patients were in group 1b. The surgical resection rates were 82.0% in group 1a and 87.0% in group 1b. After adjustment for preoperative factors, surgical resection was associated with longer survival for patients in group 1b (hazard ratio [HR], 0.58; 95% CI, 0.42-0.80; P &amp;amp;lt; .001) but not for patients in group 1a (HR, 0.68; 95% CI, 0.41-1.11; P = .12). In group 1b, interaction analysis found that age of 64 years or younger, absence of comorbidities, treatment at academic institutions, and distal pancreatic tumors were factors associated with increased survival after surgical resection.Conclusions and RelevanceFindings of this study support an association between surgical resection and increased survival in select patients with NF-PanNETs measuring 1.1 to 2.0 cm who were younger than 65 years, had no comorbidities, received treatment at academic institutions, and had tumors of the distal pancreas. Future investigations of surgical resection for small NF-PanNETs that include the Ki-67 index are warranted to validate these findings.</jats:sec