Nationwide questionnaire survey of the contemporary surgical management of pancreatic cancer in the United Kingdom & Ireland

AbstractThis paper reports the results of a questionnaire-based survey of pancreatic surgical specialists in the United Kingdom addressing aspects of staging, resection volume and outcome.A postal survey was undertaken of the 517 members of the Association of upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS). 57 surgeons undertook pancreatic resection from 162 overall respondents. Cross-checking with the list of members of the Pancreatic Society of Great Britain and Ireland yielded 64 pancreatic surgeons. 734 pancreaticoduodenectomy (PD) were reported by respondents compared with 822 procedures according to Government maintained Hospital Episode Statistics.The modal resection volume performed per annum was 6–10. There were 24 in-hospital deaths in 732 resections (3%) mortality. For individual respondents the modal percentage mortality was 5% (0 to 16%). All clinicians with mortality rates in excess of 10% did less than 10 resections per annum. Respondents favoured “amylase rich discharge beyond 7th post-operative day” as optimal for definition of post-resection pancreatic fistula.Accepting the limitations of questionnaire surveys, the results provide an important overview of pancreatic surgical practice: pancreaticoduodenectomy is carried out by a range of specialists, lower volume resectionists appear to have poorer outcomes and this study shows widespread agreement on optimum terminology for post-operative pancreatic fistula

Assessing the impact of AGS-004, a dendritic cell-based immunotherapy, and vorinostat on persistent HIV-1 Infection

Approaches to deplete persistent HIV infection are needed. We investigated the combined impact of the latency reversing agent vorinostat (VOR) and AGS-004, an autologous dendritic cell immunotherapeutic, on the HIV reservoir. HIV+, stably treated participants in whom resting CD4+ T cell-associated HIV RNA (rca-RNA) increased after VOR exposure ex vivo and in vivo received 4 doses of AGS-004 every 3 weeks, followed by VOR every 72 hours for 30 days, and then the cycle repeated. Change in VOR-responsive host gene expression, HIV-specific T cell responses, low-level HIV viremia, rca-RNA, and the frequency of resting CD4+ T-cell infection (RCI) was measured at baseline and after each cycle. No serious treatment-related adverse events were observed among five participants. As predicted, VOR-responsive host genes responded uniformly to VOR dosing. Following cycles of AGS-004 and VOR, rca-RNA decreased significantly in only two participants, with a significant decrease in SCA observed in one of these participants. However, unlike other cohorts dosed with AGS-004, no uniform increase in HIV-specific immune responses following vaccination was observed. Finally, no reproducible decline of RCI, defined as a decrease of >50%, was observed. AGS-004 and VOR were safe and well-tolerated, but no substantial impact on RCI was measured. In contrast to previous clinical data, AGS-004 did not induce HIV-specific immune responses greater than those measured at baseline. More efficacious antiviral immune interventions, perhaps paired with more effective latency reversal, must be developed to clear persistent HIV infection

Diagnostic and prognostic value of plasma tumor M2 pyruvate kinase in periampullary cancer: evidence for a novel biological marker of adverse prognosis

Objective: This prospective study examines the diagnostic and prognostic use of tumor-M2-pyruvate kinase (Tu-M2-PK) used in conjunction with carbohydrate antigen (CA) 19-9 in patients with subsequently histologically confirmed periampullary malignancy. Methods: Plasma Tu-M2-PK and serum CA 19-9 levels were measured at admission in a cohort of patients with suspected pancreatic cancer. Values for Tu-M2-PK and serum CA 19-9 were compared with a control group comprising jaundiced patients in whom malignancy was excluded by endoscopic retrograde cholangiopancreatography and nonjaundiced individuals undergoing laparoscopic cholecystectomy. Results: The mean (SD) plasma Tu-M2-PK level for patients with histologically proven malignancy was 40.5 (26.4) U/mL and for noncancer patients, 29.9 (20.9) U/mL (Mann-Whitney U = 1163, P = 0.006). Tumor-M2-pyruvate kinase had an area under the curve of 0.623 on receiver operating characteristic curve analysis, and at optimal cutoff of 27 U/mL, sensitivity is 66%, and specificity is 58%.However, on multivariate Cox regression modeling, elevated Tu-M2-PK (>27 U/mL) was strongly correlated with the subsequent finding of poorly differentiated cancer and/or metastatic disease and strongly predicted survival on Kaplan-Meier analysis. Conclusion: An elevated Tu-M2-PK more than 27 U/mL measured on admission in suspected periampullary cancer is a predictor of adverse prognosis in periampullary cancer