Indications and outcomes of enucleation versus formal pancreatectomy for pancreatic neuroendocrine tumors

Background: Pancreatoduodenectomy (PD) or distal pancreatectomy (DP) are common procedures for patients with a pancreatic neuroendocrine tumor (pNET). Nevertheless, certain patients may benefit from a pancreas-preserving resection such as enucleation (EN). The aim of this study was to define the indications and differences in long-term outcomes among patients undergoing EN and PD/DP. Methods: Patients undergoing resection of a pNET between 1992 and 2016 were identified. Indications and outcomes were evaluated, and propensity score matching (PSM) analysis was performed to compare long-term outcomes between patients who underwent EN versus PD/DP. Results: Among 1034 patients, 143 (13.8%) underwent EN, 304 (29.4%) PD, and 587 (56.8%) DP. Indications for EN were small size (1.5 cm, IQR:1.0–1.9), functional tumors (58.0%) that were mainly insulinomas (51.7%). After PSM (n = 109 per group), incidence of postoperative pancreatic fistula (POPF) grade B/C was higher after EN (24.5%) compared with PD/DP (14.0%) (p = 0.049). Median recurrence-free survival (RFS) was comparable among patients who underwent EN (47 months, 95% CI:23–71) versus PD/DP (37 months, 95% CI: 33–47, p = 0.480). Conclusion: Comparable long-term outcomes were noted among patients who underwent EN versus PD/DP for pNET. The incidence of clinically significant POPF was higher after EN

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Patterns of readmission among the elderly after hepatopancreatobiliary surgery

Background: The objective of this study was to examine risk factors and outcomes of hospital readmission following complex hepatopancreatobiliary (HPB) surgery among the elderly. Methods: The Nationwide Readmissions Database was queried for patients 65 60 years who underwent HPB surgery during 2010\u20132015. Results: The incidence of 30- and 90-day readmission was similar among patients 60\u201374 vs. 6575 (P &gt; 0.05). Patients age 60\u201374 years with 652 comorbidities had an increased odds of 30-day (OR 1.13, p = 0.021) and 90-day (OR 1.13, p = 0.005) readmission. Patients 6575 years with 652 comorbidities had the highest in-hospital mortality (5%) whereas patients 60\u201374 years with 0 or 1 comorbidity had the lowest in-hospital mortality on readmission (3%). Conclusion: Following an HPB procedure, roughly 1 in 7 elderly patients were readmitted within 30 days and 1 in 4 patients within 90 days. Elderly patients with multiple comorbidities were more likely to be readmitted at non-index hospitals

Index versus Non-index Readmission After Hepato-Pancreato-Biliary Surgery: Where Do Patients Go to Be Readmitted?

Introduction: The Center for Medicare and Medicaid Services (CMS) has identified readmission as an important quality metric. With an increased emphasis on regionalization of complex hepato-pancreato-biliary (HPB) surgery to high-volume centers, care of readmitted HPB patients may be fragmented if readmission occurs at a non-index hospital. We sought to define the proportion of HPB readmissions, as well as evaluate outcomes, that occur at an index versus non-index hospitals and to identify factors associated with non-index hospital readmission. Methods: The National Readmissions Database (NRD) was used to identify patients who underwent major HPB surgery between 2010 and 2015. Factors associated with readmission at 30 and 90&nbsp;days at index versus non-index hospitals were analyzed. Differences in mortality and complications were analyzed among patients readmitted to index versus non-index hospitals. Results: A total of 49,080 patients underwent HPB surgery (liver n = 27,081, 55%; pancreas n = 14,787, 30%; biliary n = 7212, 15%). Overall, 6643 (14%) and 11,709 (24%) patients were readmitted within 30 and 90&nbsp;days, respectively. Among all first readmissions, 18 and 21% were to a non-index hospital within the first 30 and 90&nbsp;days, respectively. On multivariable analysis, factors associated with readmission to a non-index hospital included age (OR 1.19, 95% CI 1.05, 1.34), pancreatic cancer (OR 1.40, 95% CI 1.14, 1.34) and 65 3 comorbidities (OR 1.34, 95% CI 1.10, 1.63), while procedures on the pancreas (OR 0.69, 95% CI 0.61, 0.80), private insurance (OR 0.77, 95% CI 0.68, 0.87), initial admission at a large hospital (OR 0.77, 95% CI 0.65, 0.91), and initial admission length of stay &gt; 7&nbsp;days (OR 0.77, 95% CI 0.69, 0.86) were associated with decreased odds of a non-index hospital readmission (all p &lt; 0.05). Patients readmitted to a non-index hospital had higher inpatient mortality (3.7 vs. 2.7%, p = 0.010). Conclusions: Roughly 1 in 5 patients were readmitted to a non-index hospital where the initial HPB operation had not taken place. Readmission to a non-index hospital was associated with higher overall in-hospital mortality. The impact of regionalization of HPB care relative to site of subsequent readmission may have important implications for patients

Identification of circulating plasma ceramides as a potential sexually dimorphic biomarker of pancreatic cancer‐induced cachexia

Abstract Background Cancer patients who exhibit cachexia lose weight and have low treatment tolerance and poor outcomes compared with cancer patients without weight loss. Despite the clear increased risk for patients, diagnosing cachexia still often relies on self‐reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes. Methods Targeted metabolomics, which included panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia and control patients without cancer (n = 10/group, equally divided by sex). Additional patient samples were analysed (total n = 95), and receiver operating characteristic (ROC) analyses were performed to establish if any metabolite could effectively serve as a biomarker of cachexia. Results Targeted profiling revealed that cachectic patients had decreased circulating levels of three sphingolipids compared with either non‐cachectic PDAC patients or patients without cancer. The ratio of C18‐ceramide to C24‐ceramide (C18:C24) outperformed a number of other previously proposed biomarkers of cachexia (area under ROC = 0.810). It was notable that some biomarkers, including C18:C24, were only altered in cachectic males. Conclusions Our findings identify C18:C24 as a potentially new biomarker of PDAC‐induced cachexia that also highlight a previously unappreciated sexual dimorphism in cancer cachexia

Perioperative use of blood products is associated with risk of morbidity and mortality after surgery

Background: Administration of blood products may be associated with increased morbidity and perioperative mortality in surgical patients. Methods: Patients aged 18 + who underwent gastrointestinal surgery at the Ohio State University Wexner Medical Center 9/10/2015-5/9/2018 were identified. Multivariable logistic regression models were used to evaluate impact of blood product use on survival and complications, as well as to identify factors associated with receipt of transfusions. Results: Among 10,756 patients, 35,517 units of blood products were transfused. Preoperative nadir hemoglobin was associated with receipt of blood product transfusion (OR 0.55, 95% CI 0.53, 0.68). After adjusting for patient and procedural characteristics, patients undergoing transfusion of blood products had an increased risk of perioperative mortality (OR 7.80, 95% CI 6.02, 10.10). Conclusions: The use of blood products was associated with increased risk of complication and death. Patient blood management programs should be implemented to provide rational criteria and guidance for the transfusion of blood products

The Cost of Failure: Assessing the Cost-Effectiveness of Rescuing Patients from Major Complications After Liver Resection Using the National Inpatient Sample

Objective: To estimate the cost of rescue and cost of failure and determine cost-effectiveness of rescue from major complications at high-volume (HV) and low-volume (LV) centers Methods: Ninety-six thousand one hundred seven patients undergoing liver resection were identified from the Nationwide Inpatient Sample (NIS) between 2002 and 2011. The incremental cost of rescue and cost of FTR were calculated. Using propensity-matched cohorts, a cost-effectiveness analysis was performed to determine the incremental cost-effectiveness ratio (ICER) between HV and LV hospitals. Results: Ninety-six thousand one hundred seven patients were identified in NIS. The overall mortality was 2.3% and was lowest in HV centers (HV 1.4% vs. MV 2.1% vs. LV 2.6%; p &lt; 0.001). Major complications occurred in 14.9% of hepatectomies and were comparable regardless of volume (HV 14.2% vs. MV 14.3% vs. LV 15.4%; p &lt; 0.001). The FTR rate was substantially lower among HV centers (HV 7.7%, MV 11%, LV 12%; p &lt; 0.001). At a willingness to pay benchmark of $50,000 per year of life saved, both HV (ICER =$3296) and MV (ICER = $4182) centers were cost-effective at rescuing patients from a major complication compared to LV hospitals. Conclusion: Not only was FTR less common at HV hospitals, but the management of most major complications was cost-effective at higher volume centers