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

Current Landscape of Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma

The liver maintains a balance between immune tolerance and activation in its role as a filtration system. Chronic inflammation disrupts this immune microenvironment, thereby allowing for the rise and progression of cancer. Hepatocellular carcinoma (HCC) is a liver tumor generally diagnosed in the setting of chronic liver disease. When diagnosed early, the primary treatment is surgical resection, liver transplantation, or liver directed therapies. Unfortunately, patients with HCC often present at an advanced stage or with poor liver function, thereby limiting options. To further complicate matters, most systemic therapies are relatively limited and ineffective among patients with advanced disease. Recently, the IMbrave150 trial demonstrated that the combination of atezolizumab and bevacizumab was associated with better survival compared to sorafenib among patients with advanced HCC. As such, atezolizumab and bevacizumab is now recommended first-line therapy for these patients. Tumor cells work to create an immunotolerant environment by preventing the activation of stimulatory immunoreceptors and upregulating expression of proteins that bind inhibitory immunoreceptors. ICIs work to block these interactions and bolster the anti-tumor function of the immune system. We herein provide an overview of the use of ICIs in the treatment of HCC

A Comparison of Open and Minimally Invasive Surgery for Hepatic and Pancreatic Resections Among the Medicare Population

Introduction: Minimally invasive surgery (MIS) has become standard of care for many gastrointestinal surgical procedures. Despite possible clinical benefits, MIS may be underutilized in some populations. The aim of this study was to access the utilization of MIS among Medicare patients undergoing hepatopancreatic procedures and define clinical outcomes, as well as costs, of minimally invasive techniques compared with the conventional open approach. Methods: The Medicare Provider Analysis and Review (MEDPAR) Inpatient Files were reviewed to identify Medicare patients who underwent pancreatic and liver procedures between 2013 and 2015. Primary outcomes of the analysis included perioperative clinical outcomes such as rates of complications, index hospitalization length-of-stay (LOS), failure-to-rescue, rates, and causes of 90-day readmission, as well as 90-day mortality. Secondary outcomes were Medicare payments for index hospitalization and readmission. Multivariable logistic regression was used to investigate the impact of MIS on clinical outcomes and health expenditures. Results: A total of 13,716 (90.6%) patients underwent open resection, while MIS was performed in 1424 (9.4%) patients. LOS was shorter among patients undergoing MIS (mean 7.3 \ub1 SD 7.3) versus open (mean 9.3 \ub1 SD 9.1) surgery (p 0.05). Mean total payments for open pancreatic surgery were on average $1421 higher in the open versus MIS pancreatic group (p = 0.01); in contrast, there was no difference in the overall payment for hepatic resection (p > 0.05). Conclusion: The MIS approach was underutilized among patients undergoing liver and pancreatic procedures. MIS was associated with lower complication and readmission and shorter LOS, as well as comparable/slightly lower Medicare payments, compared with the open approach. The MIS approach should strongly be considered among older patients undergoing liver and pancreatic procedures

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

Synergistic Effects of Perioperative Complications on 30-Day Mortality Following Hepatopancreatic Surgery

Background: Data on the interaction effect of multiple concurrent postoperative complications relative to the risk of short-term mortality following hepatopancreatic surgery have not been reported. The objective of the current study was to define the interaction effect of postoperative complications among patients undergoing HP surgery on 30-day mortality. Methods: Using the ACS-NSQIP Procedure Targeted Participant Use Data File, patients who underwent HP surgery between 2014 and 2016 were identified. Hazard ratios (HRs) for 30-day mortality were estimated using Cox proportional hazard models. Two-way interaction effects assessing combinations of complications relative to 30-day mortality were calculated using the relative excess risk due to interaction (RERI) in separate adjusted Cox models. Results: Among 26,824 patients, 10,886 (40.5%) experienced at least one complication. Mortality was higher among patients who experienced at least one complication versus patients who did not experience a complication (3.0 vs 0.1%, p&nbsp;&lt; 0.001). The most common complications were blood transfusion (16.9%, n = 4519), organ space infection (12.2%, n = 3273), and sepsis/septic shock (8.2%, n = 2205). Combinations associated with additive effect on mortality included transfusion + renal dysfunction (RERI 12.3, 95% CI 5.2\u201319.4), pulmonary dysfunction + renal dysfunction (RERI 60.9, 95% CI 38.6\u201383.3), pulmonary dysfunction + cardiovascular complication (RERI 144.1, 95% CI 89.3\u2013199.0), and sepsis/septic shock + renal dysfunction (RERI 11.5, 95% CI 4.4\u201318.7). Conclusion: Both the number and specific type of complication impacted the incidence of postoperative mortality among patients undergoing HP surgery. Certain complications interacted in a synergistic manner, leading to a greater than expected increase in the risk of short-term mortality

Prognosis and Adherence with the National Comprehensive Cancer Network Guidelines of Patients with Biliary Tract Cancers: an Analysis of the National Cancer Database

Background: The National Comprehensive Cancer Network (NCCN) guidelines recommend chemotherapy for patients with inoperable biliary tract cancers (BTC), as well as patients following resection of BTC with lymph node metastasis (N1)/positive margins (R1). We sought to define overall adherence, as well as long-term outcomes, with the NCCN guidelines for BTC using the National Cancer Database (NCDB). Methods: A total of 176,536 patients diagnosed with BTC at a hospital participating in the NCDB between 2004 and 2015 were identified. Results: Among all patients, 63% of patients received medical therapy (chemotherapy or best supportive care), 11% underwent surgical palliation, and 26% underwent curative-intent surgery. According to the NCCN guidelines, 86% (n = 152,245) of patients were eligible for chemotherapy, yet, only 42.2% (n = 64,615) received chemotherapy. Factors associated with a lower adherence with NCCN guidelines included patient age (&gt; 65&nbsp;years: OR = 1.02), ethnicity (Black: OR = 1.14, Hispanic: OR = 1.21, Asian: OR = 1.24), and insurance status (non-private: OR = 1.45, all p &lt; 0.001). A smaller subset of patients was either recommended chemotherapy but refused (n = 9269, 10.6%) or had medical factors that contraindicated chemotherapy (n = 8275, 9.4%). On multivariable analysis, adjusting for clinical and tumor-specific factors, adherence with NCCN guidelines was associated with a survival benefit for patients receiving medical therapies (HR = 0.74) or undergoing curative-intent surgery (HR = 0.73, both p &lt; 0.001). Conclusion: Less than half of patients with BTC received systemic chemotherapy in adherence with NCCN guidelines. While a subset of patients had contraindications or refused chemotherapy, other factors such as insurance status and ethnicity were associated with adherence. Adherence with chemotherapy guidelines may influence long-term outcomes

The implications of fragmented practice in hepatopancreatic surgery

Background: Familiarity with the surgical work environment has been demonstrated to improve out-comes. We sought to investigate the impact of the rate of fragmented practice on textbook outcomes, a validated composite outcome representing an "optimal" postoperative course.Methods: Patients who underwent a hepatic or pancreatic surgical procedure between 2013 and 2017 were identified from the Medicare Standard Analytic Files. The rate of fragmented practice was defined as the surgeon's volume over the study period relative to the number of facilities practiced at. The as-sociation between the rate of fragmented practice and textbook outcomes was assessed using multi -variable logistic regression.Results: A total of 37,599 patients were included (pancreatic: n = 23,701, 63.0%; hepatic: n = 13,898, 37.0%). After controlling for relevant characteristics, patients who underwent surgery by surgeons in higher rate of fragmented practice categories had lower odds of achieving a textbook outcome (refer-ence: low rate of fragmented practice; intermediate rate of fragmented practice: odds ratio = 0.88 [95% confidence interval 0.84-0.93]; high rate of fragmented practice: odds ratio = 0.58 [95% confidence interval 0.54-0.61]) (both P &lt; .001). Of note, the adverse effect of a high rate of fragmented practice on the achievement of textbook outcomes remained substantial, regardless of the county-level social vulnerability index [high rate of fragmented practice; low social vulnerability index: odds ratio = 0.58 (95% confidence interval 0.52-0.66); intermediate social vulnerability index: odds ratio = 0.56 (95% confidence interval 0.52-0.61); high social vulnerability index: odds ratio = 0.60 (95% confidence in-terval 0.54-0.68)] (all P &lt; .001). Patients in intermediate and high social vulnerability index counties had 19% and 37% greater odds of undergoing surgery by a high rate of fragmented practice surgeon (refer-ence: low social vulnerability index; intermediate social vulnerability index: odds ratio = 1.19 [95% confidence interval 1.12-1.26]; high social vulnerability index: odds ratio = 1.37 [95% confidence interval 1.28-1.46]).Conclusion: Owing to the impact of the rate of fragmented practice on postoperative outcomes, decreasing fragmentation of care may be an important target for quality initiatives and a means to alleviate social disparities in surgical care.(c) 2023 Elsevier Inc. All rights reserved

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