No survival benefit with suboptimal CA19-9 response: defining effective neoadjuvant chemotherapy in resectable or borderline resectable pancreatic cancer.

BACKGROUND/PURPOSE: Neoadjuvant chemotherapy (NAC) is gaining popularity over a surgery-first (SF) approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, what constitutes effective neoadjuvant chemotherapy is unknown. METHODS: We retrospectively analyzed resectable and borderline resectable PDAC patients who underwent pancreaticoduodenectomy (2010-2019) at a single institution. Optimal CA19-9 response was defined as normalization AND >50% reduction. We utilized Kaplan-Meier and multivariable-adjusted Cox models and competing risk subdistribution methods for statistical analysis. RESULTS: 586 patients were included in this study. The multivariable-adjusted analysis demonstrated OS benefit in the NAC group only when OS was calculated from diagnosis (HR = 0.72, p = 0.02), but not from surgery (HR = 0.81, p = 0.1). However, in 59 patients who achieved optimal CA19-9 response, OS is significantly longer than the 134 patients with suboptimal CA19-9 response (39.3 m vs. 21.5 m, p = 0.005) or the 117 SF patients (39.3 m vs. 19.5 m, p < 0.001). Notably, a suboptimal CA19-9 response conferred no OS advantage compared to SF patients. The accumulative incidence of liver metastases (but not other metastases) was significantly reduced only in patients with optimal CA19-9 response to NAC (multivariable-adjusted subdistribution HR = 0.26, p = 0.03). CONCLUSION: CA19-9 response to NAC may serve as the marker for effective NAC. These findings warrant validation in a multi-institutional study.

The use of angiotensin system inhibitors correlates with longer survival in resected pancreatic adenocarcinoma patients.

BACKGROUND: Activities and inhibition of the Renin-Angiotensin-Aldosterone System (RAAS) may affect the survival of resected pancreatic ductal adenocarcinoma (PDAC) patients METHOD: A single-institution retrospective analysis of resected PDAC patients between 2010 and 2019. To estimate the effect of angiotensin system inhibitors (ASIs) on patient survival, we performed Kaplan Meier analysis, Cox Proportional Hazards model, Propensity Score Matching (PSM), and inverse probability weighting (IPW) analysis. RESULTS: 742 patients were included in the analysis. The average age was 67.0 years, with a median follow-up of 24.1 months. The use of ASI was associated with significantly longer overall survival in univariate (p = 0.004) and multivariable (HR = 0.70 [0.56-0.88],p = 0.003) adjusted analysis. In a propensity score-matched cohort of 400 patients, ASI use was again associated with longer overall survival (p = 0.039). Lastly, inverse probability weighting (IPW) analysis suggested that the use of ASI was associated with an average treatment effect on the treated (ATT) of HR = 0.68 [0.53-0.86],p = 0.002) for overall survival. CONCLUSION: In this single-institution retrospective study focusing on resected PDAC patients, the use of ASI was associated with longer overall survival in multiple statistical models. Prospective clinical trials are needed before routine clinical implementation of ASI as an adjuvant to existing therapy can be recommended.

Nutrition during extracorporeal life support: A review of pathophysiological bases and application of guidelines.

BACKGROUND: Patients on extracorporeal life support (ECLS), either for respiratory or cardiac support, are at high risk of malnutrition; guidelines on nutrition in critical care have not incorporated solid evidence regarding these settings. The aim of this narrative review is to gather the available evidence in the existing literature and transpose general principles to the ECLS population. METHODS: A literature review of observational and interventional studies on nutrition during ECLS, and evaluation of nutrition guidelines in this perspective. RESULTS: Nutrition is paramount for improving outcomes in ECLS, as well as in critically ill patients. The caloric needs during ECLS can vary according to the severity of the clinical state, sedation, paralysis, and temperature stability. Precise evaluation of energy expenditure by indirect calorimetry is difficult because ECLS is a system dedicated to removing carbon dioxide; however, modified equations composed of carbon dioxide values taken from the membrane lung are available. Guidelines suggest starting early enteral nutrition (EN) with a hypocaloric (70%-80% of the needs) strategy, also in acute states such as septic or cardiogenic shock. Moreover, EN, despite previous concerns, is feasible in prone position, an increasingly adopted strategy during mechanical ventilation. The catabolic state is maximal in these patients, causing a protein and muscular reduction. Therefore, adequate protein delivery should be guaranteed by administering a high protein intake of up to 2 g/kg/day. CONCLUSIONS: Studies on nutrition tailored to ECLS patients are warranted. Early hypocaloric EN with high protein intake, tailored on indirect calorimetry, may be the most appropriate option.

Pancreatic-Portal Vein Fistula: a Rare Diagnosis with Wide-Ranging Complications-13-Year Experience of a Pancreas Center of Excellence.

PURPOSE: To determine factors affecting mortality, and long-term patency of portal vein, in patients with pancreatic-portal vein fistula (PPVF). METHODS: Consecutive cases of PPVF at the University of Pittsburgh Medical Center from 2008 to 2020 were retrospectively identified. Clinical history, imaging studies, management strategies, complications, and long-term outcomes were analyzed. RESULTS: Fourteen patients, representing the largest PPVF cohort reported to date (mean age 58.6 years, 64.3% women, median follow-up 10 months [1-98 months]) were identified. Underlying chronic pancreatitis was seen in 9 (64.3%) patients, while 5 (35.7%) developed PPVF with first attack of acute pancreatitis. PPVF involved proximal main portal vein (MPV) in 10 (78.6%) patients. Of the 5 patients (35.7%) who died, all had occlusive (n=4) or near-occlusive (n=1) PPVF-associated filling defect (FD) in the MPV. Conversely, 7 of 9 survivors (87.5%) had subocclusive FD and patent MPV. In patients with sepsis (n=5), 1 underwent surgical necrosectomy and survived, while 3 of 4 (75%) patients without debridement died. CONCLUSION: Occlusive/near-occlusive PPVF-associated MPV FD, and sepsis, are associated with high mortality rates, while subocclusive MPV FD is associated with survival and long-term MPV patency. PPVF is a potentially life-threatening, and possibly under-diagnosed, entity that warrants early clinical suspicion for timely diagnosis, to facilitate optimal management.