Management and surveillance of non-functional pancreatic neuroendocrine tumours: Retrospective review.

BACKGROUND: /Objective. To determine the outcomes of a non-operative management approach for sporadic, small, non-functional pancreatic neuroendocrine tumours. METHODS: A retrospective chart review of patients with non-functional pancreatic neuroendocrine tumours initially managed non-operatively at a single institution was performed. Patients were identified through a search of radiologic reports, and individuals with ≥2 cross-sectional imaging studies performed >6 months apart from Jan. 1, 2000 to Dec. 31, 2013 were included. Data on tumour size, radiologic characteristics at diagnosis, interval radiologic growth, and surgical outcomes were recorded. RESULTS: Over the thirteen-year study period, 95 patients met inclusion criteria and were followed radiologically for a median of 36 months (18-69 months). Median initial tumour size on first imaging was 14.0 mm (IQR 10-19 mm). Median overall tumour growth rate was 0.03 mm/month (IQR: 0.00-0.14 mm/month). There was no significant relationship between initial tumour size and growth rate for tumours ≤ 2 cm or for lesions between 2 and 4 cm. Thirteen (14%) patients initially managed non-operatively underwent resection during the follow-up period. Reasons for surgery included interval tumour growth, patient anxiety or preference, or diagnostic uncertainty. Median time to surgery was 14 months (IQR 8-19 months). No patients progressed beyond resectability or developed metastatic disease during the observation period. CONCLUSION: For patients with sporadic, small, non-functional pancreatic neuroendocrine tumours, radiologic surveillance appears to be a safe initial approach to management.

How Do Different Indices of Hepatic Enhancement With Gadoxetic Acid Compare in Predicting Liver Failure and Other Major Complications After Hepatectomy?

OBJECTIVE: The objective of this study was to assess the accuracy of gadoxetic acid hepatic enhancement indices in predicting posthepatectomy liver failure (PHLF) and other major complications (OMCs). METHODS: Sixty-five patients underwent prehepatectomy gadoxetic acid-enhanced magnetic resonance imaging. Enhancement indices were calculated by obtaining regions of interest on magnetic resonance images and segmented volumes of the liver and spleen. Multivariate regression analysis was performed to predict PHLF and OMC as a function of the indices, and areas under the receiver operator characteristic (AUROC) curves were calculated. RESULTS: Areas under the receiver operator characteristic values varied from 0.412 to 0.681 and 0.462 to 0.738 in predicting PHLF and OMC, respectively. The most accurate indices in predicting PHLF were the region of interest-based, fat-normalized relative liver enhancement and liver enhancement index (AUROC, 0.681). The most accurate index in predicting OMC was the volumetric least-squares regression slope of a pharmacokinetic model (Khep_V, AUROC, 0.738). CONCLUSIONS: Indices of gadoxetic acid liver enhancement demonstrate variable performance in predicting PHLF and OMC.

The economics of recovery after pancreatic surgery: detailed cost minimization analysis of an enhanced recovery program.

BACKGROUND: Clinical pathways (CPW) are considered safe and effective at decreasing postoperative length of stay (LoS), but the effect on economic costs is uncertain. This study sought to elucidate the effect of a CPW on direct hospitalization costs for patients undergoing pancreaticoduodenectomy (PD). METHODS: A CPW for PD patients at a single Canadian institution was implemented. Outcomes included LoS, 30-day readmissions, and direct costs of hospital care. A retrospective cost minimization analysis compared patients undergoing PD prior to and following CPW implementation, using a bootstrapped t test and deviation-based cost modeling. RESULTS: 121 patients undergoing PD after CPW implementation were compared to 74 controls. Index LoS was decreased following CPW implementation (9 vs. 11 days, p = 0.005), as was total LoS (10 vs. 11 days, p = 0.003). The mean total cost of postoperative hospitalization per patient decreased in the CPW group ($15,678.45 CAD vs. $25,732.85 CAD, p = 0.024), as was the mean 30-day cost including readmissions ($16,627.15 CAD vs. $29,872.72 CAD, p = 0.016). Areas of significant cost savings included laboratory tests and imaging investigations. CONCLUSIONS: CPWs may generate cost savings by reducing unnecessary investigations, and improve quality of care through process standardization and decreasing practice variation.

The impact of a clinical pathway on patient postoperative recovery following pancreaticoduodenectomy.

BACKGROUND: Pancreaticoduodenectomies (PD) are complex surgical procedures. Clinical pathways (CPW) are surgical process improvement tools that guide postoperative recovery and are associated with high quality care. Our objective was to report the quality of surgical care following implementation of a CPW. METHODS: We developed and implemented a CPW for patients undergoing PD at a single high volume hepato-pancreato-biliary (HPB) centre. Patient outcomes were collected prospectively during the implementation period. A comparator cohort was selected by identifying patients that underwent a PD prior to CPW development. RESULTS: 122 patients underwent a PD during the CPW implementation period; 83 patients were initiated on the CPW. 74 patients underwent PD during the 12-month period prior to the CPW. The median hospital stay decreased after the implementation of the CPW (11 vs 8 days, p < 0.01) with no significant changes to mortality, morbidity, reoperation, or readmission rates. In-hospital complications were significantly higher in patients that were not initiated on the CPW (54% vs 74%, p = 0.03). CONCLUSION: Results suggest the CPW reduced variability and allowed a greater proportion of patients to receive all elements of care, resulting in improved quality and efficiency of care based on current best evidence recommendations.

Type I Interferon Impairs Specific Antibody Responses Early during Establishment of LCMV Infection.

Elicitation of type I interferon (IFN-I) has been shown to both enhance and impair cell-mediated immune responses in acute and persistent viral infections, respectively. Here, we show that, in addition to its effect on T cells, IFN-I drives impairment of specific antibody responses through interaction with B cells in the acute phase of lymphocytic choriomeningitis virus (LCMV) infection. This impairment was limited to the T cell-dependent B cell response and was associated with disruption of B cell follicles, development of hypergammaglobulinemia (HGG), and expansion of the T follicular helper cell population. Antigen-specific antibody responses were restored by ablation of IFN-I signaling through antibody-mediated IFN-I receptor blockade and B cell-specific IFN-I receptor knockout. Importantly, IFN-I receptor deficiency in B cells also accelerated the development of LCMV neutralizing antibodies and alleviated HGG. These results provide a potential therapeutic target toward efficient treatment measures that limit immunopathology in persistent viral infections.

Comparison of Clinical Outcomes following Glue versus Polyvinyl Alcohol Portal Vein Embolization for Hypertrophy of the Future Liver Remnant prior to Right Hepatectomy.

PURPOSE: To report outcomes after portal vein embolization (PVE) and right hepatectomy in patients receiving embolization with N-butyl cyanoacrylate (NBCA) glue + central AMPLATZER Vascular Plug (AVP; glue group) or polyvinyl alcohol (PVA) particles ± coils (PVA group). MATERIALS AND METHODS: Between March 2008 and August 2013, all patients having PVE with NBCA + AVP or PVA ± coils before right hepatectomy were retrospectively reviewed; 85 patients underwent PVE with NBCA + AVP (n = 45) or PVA ± coils (n = 40). The groups were compared using Mann-Whitney U and χ2 tests. RESULTS: Technical success of embolization was 100%. Degree of hypertrophy (16.2% ± 7.8 vs 12.3% ± 7.62, P = .009) and kinetic growth rate (3.5%/wk ± 2.0 vs 2.6%/wk ± 1.9, P = .016) were greater in the glue group versus the PVA group. Contrast volume (66.1 mL ± 44.8 vs 189.87 mL ± 62.6, P < .001) and fluoroscopy time (11.2 min ± 7.8 vs 23.49 min ± 11.7, P < .001) were significantly less during the PVE procedure in the glue group. Surgical outcomes were comparable between groups, including the number of patients unable to go onto surgery (P = 1.0), surgical complications (P = .30), length of hospital stay (P = .68), and intensive care unit admissions (P = .71). There was 1 major complication (hepatic abscess) in each group after PVE. CONCLUSIONS: PVE performed with NBCA + AVP compared with PVA ± coils resulted in greater degree of hypertrophy of the future liver remnant, less fluoroscopic time and contrast volume, and similar complication rates.

GGCX and VKORC1 inhibit osteocalcin endocrine functions.

Osteocalcin (OCN) is an osteoblast-derived hormone favoring glucose homeostasis, energy expenditure, male fertility, brain development, and cognition. Before being secreted by osteoblasts in the bone extracellular matrix, OCN is γ-carboxylated by the γ-carboxylase (GGCX) on three glutamic acid residues, a cellular process requiring reduction of vitamin K (VK) by a second enzyme, a reductase called VKORC1. Although circumstantial evidence suggests that γ-carboxylation may inhibit OCN endocrine functions, genetic evidence that it is the case is still lacking. Here we show using cell-specific gene inactivation models that γ-carboxylation of OCN by GGCX inhibits its endocrine function. We further show that VKORC1 is required for OCN γ-carboxylation in osteoblasts, whereas its paralogue, VKORC1L1, is dispensable for this function and cannot compensate for the absence of VKORC1 in osteoblasts. This study genetically and biochemically delineates the functions of the enzymes required for OCN modification and demonstrates that it is the uncarboxylated form of OCN that acts as a hormone.