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BackgroundOverall survival (OS) for operable pancreatic cancer (PC) is optimized when 4–6 months of nonsurgical therapy is combined with pancreatectomy. Because surgery renders the delivery of postoperative therapy uncertain, total neoadjuvant therapy (TNT) is gaining popularity.MethodsWe performed a retrospective cohort study of patients with operable PC and compared TNT with shorter course neoadjuvant therapy (SNT). Primary outcomes of interest included completion of neoadjuvant therapy (NT) and resection of the primary tumor, receipt of 5 months of nonsurgical therapy, and median OS.ResultsWe reviewed 541 consecutive patients from 2009 to 2019 including 226 (42%) with resectable PC and 315 (58%) with borderline resectable (BLR) PC. The median age was 66 years (IQR [59, 72]), and 260 (48%) patients were female. TNT was administered to 89 (16%) patients and SNT was administered to 452 (84%). Both groups were equally likely to complete intended NT and surgery (p = 0.90). Patients who received TNT and surgical resection were more likely to have a complete pathologic response (8% vs 4%, p < 0.01) and were more likely to receive at least 5 months of nonsurgical therapy (67% vs 45%, p < 0.01). The median OS was 26 months [IQR (15, 57)]; not reached among patients treated with TNT, and 25 months [IQR (15, 56)] among patients treated with SNT (p = 0.19).ConclusionsTNT ensures the delivery of intended systemic therapy prior to a complicated operation without decreasing the chance of successful surgery; a window of operability was not lost. Patients who can tolerate SNT will likely benefit from TNT.

Background The benefit of chemotherapy for surgically resected intrahepatic cholangiocarcinoma (ICC) remains poorly defined. The present study sought to determine the survival impact of chemotherapy for surgically resected ICC. Methods Patients with non-metastatic ICC who underwent surgery were identified from the National Cancer Database (1998–2011) and stratified by receipt of chemotherapy. Survival outcomes were analyzed following propensity score modeling using the greedy matching algorithm. Results A total of 2751 patients were identified (median age 64 years); 985 (35.8 %) received chemotherapy. Younger age, advanced tumor stage, R1/R2 surgical margins, and lymph node metastasis were all independently associated with receipt of chemotherapy ( p  < 0.05). Following propensity score matching, advanced tumor stage, lymph node metastasis, poorly differentiated tumors, and R1/R2 surgical margins were associated with poorer overall survival (OS) ( p  < 0.05). Median OS comparing patients who received chemotherapy compared with surgery alone was 23 versus 20 months ( p  = 0.09). However, when stratified by lymph node status, chemotherapy demonstrated a significant improvement in median OS among N1 patients (19.8 vs. 10.7 months; p  < 0.001). In contrast, patients with N0 disease derived no benefit from chemotherapy (29.4 vs. 29 months; p  = 0.33). Additional tumor characteristics associated with improved survival with chemotherapy included T3/T4 tumors (21.3 vs. 15.6 months; p  < 0.001) and R1/R2 surgical margins (19.5 vs. 11.6 months; p  = 0.006). Conclusion The use of chemotherapy was associated with a survival benefit only for ICC patients with nodal metastasis, advanced tumor stage, or an inadequate surgical resection. Chemotherapy for resected ICC should be strongly considered for tumors harboring high-risk features.

Early postoperative mortality risk prediction is crucial for clinical management of gastric cancer. This study aims to predict 90-day mortality in gastric cancer patients undergoing gastrectomy using automated machine learning (AutoML), optimize models for preoperative prediction, and identify factors influential in prediction. National Cancer Database was used to identify stage I–III gastric cancer patients undergoing gastrectomy between 2004 and 2016. 26 features were used to train predictive models using H2O.ai AutoML. Performance on validation cohort was measured. In 39,108 patients, 90-day mortality rate was 8.8%. The highest performing model was an ensemble (AUC = 0.77); older age, nodal ratio, and length of inpatient stay (LOS) following surgery were most influential for prediction. Removing the latter two parameters decreased model performance (AUC 0.71). For optimizing models for preoperative use, models were developed to first predict node ratio or LOS, and these predicted values were inputted for 90-day mortality prediction (AUC of 0.73–0.74). AutoML performed well in predicting 90-day mortality in a larger cohort of gastric cancer patients that underwent gastrectomy. These models can be implemented preoperatively to inform prognostication and patient selection for surgery. Our study supports broader evaluation and application of AutoML to guide surgical oncologic care.

Background Resection of the superior mesenteric vein (SMV)-portal vein (PV)-splenic vein (SV) confluence during pancreatectomy for pancreatic cancer requires management of the SV. Discussion Simple SV ligation can result in sinistral portal hypertension if the inferior mesenteric vein (IMV) enters the confluence and is thereby resected, or if the IMV is insufficient to drain the SV. We describe herein three patients whose clinical course confirms the importance of the IMV decompressing the SV to avoid sinistral hypertension.

Neighborhood adversity’s impact on postoperative/adjuvant therapy delivery and overall survival (OS) is poorly described in patients with localized pancreatic cancer (PC). Area Deprivation Index (ADI) is a validated measure classifying neighborhood adversity. Higher ADI signifies increasing adversity. The 2013 national ADI scores were obtained from patients who completed preoperative/neoadjuvant therapy and surgery. Patients were categorized as having high (>50%) or low (≤50%) ADI. Of the 224 patients, 163 (73%) had low ADI and 61 (27%) had high ADI. Adjuvant therapy was delivered to 129 (58%) patients, including 62% (101/163) with low ADI and 46% (28/61) with high ADI (p = 0.03). Patients with high ADI had 55% (95%CI 0.23–0.86; p = 0.02) decreased odds of receiving adjuvant therapy, independent of other factors. The median OS was 45 months for 129 patients who received adjuvant therapy and 31 months for 94 patients who did not receive adjuvant therapy (p = 0.03). Patients with high ADI are less likely to receive adjuvant therapy for localized PC. Future studies should address impediments to care in patients from higher ADI neighborhoods. [Display omitted] •Area Deprivation Index (ADI) is validated to stratify patients by ZIP code adversity.•Patients with localized pancreatic cancer were stratified as having high or low ADI.•Patients with higher/disadvantaged ADI were less likely to receive adjuvant therapy.•Patients with lower/advantaged ADI had a survival benefit from adjuvant therapy.

Purpose/Objectives Most patients with pancreatic adenocarcinoma (PDAC) will present with distant metastatic disease at diagnosis. We sought to identify clinical characteristics associated with prolonged overall survival (OS) in patients presenting with metastatic PDAC. Materials/Methods Patients presenting with metastatic PDAC that received treatment at our institution with FOLFIRINOX or gemcitabine‐based chemotherapies between August 1, 2011 and September 1, 2017 were included in the study. Metastatic disease burden was comprehensively characterized radiologically via individual diagnostic imaging segmentation. Landmark analysis was performed at 18 months, and survival curves were estimated using the Kaplan–Meier method and compared between groups via the log‐rank test. ECOG and Charlson Comorbidity Index (CCI) were calculated for all patients. Results 121 patients were included with a median age of 62 years (37–86), 40% were female, 25% had ECOG 0 at presentation. Of the 121 patients included, 33% (n = 41) were alive at 12 months and 25% (n = 31) were alive at 18 months. Landmark analysis demonstrated a significant difference between patients surviving <18 months and ≥18 months regarding the presence of lung only metastases (36% vs. 16%, p = 0.04), number of organs with metastases (≥2 vs. 1, p = 0.04), and disease volume (mean of 19.1 cc vs. 1.4 cc, p = 0.04). At Year 1, predictors for improved OS included ECOG status at diagnosis (ECOG 0 vs. ECOG 1, p = 0.04), metastatic disease volume at diagnosis (≤0.1 cc vs. >60 cc, p = 0.004), metastasis only in the liver (p = 0.04), and normalization of CA 19‐9 (p < 0.001). At Year 2, the only predictor of improved OS was normalization of the CA 19‐9 (p = 0.03). In those patients that normalized their CA 19‐9, median overall survival was 16 months. Conclusions In this exploratory analysis normalization of CA‐19‐9 or volumetric metastatic disease burden less than 0.2 cc demonstrated a remarkable OS, similar to that of patients with non‐metastatic disease. These metrics are useful for counseling patients and identifying cohorts that may be optimal for trials exploring metastatic and/or local tumor‐directed interventions. In this study, we sought to identify clinical characteristics associated with prolonged overall survival (OS) in patients presenting with metastatic pancreatic ductal adenocarcinoma. In this exploratory analysis, normalization of CA‐19‐9 or volumetric metastatic disease burden less than 0.2 cc demonstrated a remarkable OS, similar to that of patients with non‐metastatic disease. At Year 1, predictors for improved OS included ECOG status at diagnosis, metastatic disease volume at diagnosis, metastasis only in the liver, and normalization of CA 19‐9.

BackgroundResponse to second-line (2L) neoadjuvant therapy for operable pancreatic cancer (PC) is understudied. This study examined carbohydrate antigen 19-9 (CA19-9) response to first-line (1L) and 2L chemotherapy.MethodsThe study identified patients with operable PC and elevated CA19-9 (≥ 35 U/mL with total bilirubin < 2 mg/dL) who received 1L FOLFIRINOX (FFX). The patients were restaged after 2 months and based on response, received additional FFX or gemcitabine/nab-paclitaxel (GnP) as part of total neoadjuvant therapy. Response was defined as a decrease in tumor size on computed tomography (CT) imaging or a decline in CA19-9 of 50% or more and preserved performance status.ResultsFor operable PC with an elevated CA19-9, 108 patients received 1L FFX. After 2 months of chemotherapy, the decision was made to continue FFX (FFX ≥ FFX) for 76 (70%) of the 108 patients and switch to GnP (FFX ≥ GnP)) for 32 (30%) of the patients. Of the 32 FFX ≥ GnP patients, 27 had no evidence of radiographic or biochemical (CA19-9) response to 1L FFX. Of these 27 patients, 26 (96%) demonstrated a response to 2L GnP. After 4 months of chemotherapy, 62 (82%) of the 76 FFX ≥ FFX patients had a CA19-9 response compared with 31 (97%) of the 32 FFX ≥ GnP patients (p = 0.04).ConclusionsLack of biochemical response to 2 months of 1L FFX may identify a subgroup of patients with a very high rate of response to 2L GnP, emphasizing the importance of assessing treatment response at 2-month intervals.

BackgroundTwo-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management, and outcomes of patients completing TSH in major hepatobiliary centers in the United States (US).MethodsA retrospective review from five liver centers in the US identified patients who completed a TSH procedure for bilateral CRLM.ResultsFrom December 2000 to March 2016, a total of 196 patients were identified. The majority of procedures were performed using an open technique (n = 194, 99.5%). The median number of tumors was 7 (range 2–33). One-hundred and twenty-eight (65.3%) patients underwent portal vein embolization. More patients received chemotherapy prior to the first stage than chemotherapy administration preceding the second stage (92% vs. 60%, p = 0.308). Median overall survival (OS) was 50 months, with a median follow-up of 28 months (range 2–143). Hepatic artery infusion chemotherapy was administered to 64 (32.7%) patients with similar OS as those managed without an infusion pump (p = 0.848). Postoperative morbidity following the second-stage resection was 47.4%. Chemotherapy prior to the second stage did not demonstrate an increased complication rate (p = 0.202). Readmission following the second stage was 10.3% and was associated with a decrease in disease-free survival (p = 0.003). OS was significantly decreased by positive resection margins and increased estimated blood loss (EBL; p = 0.036 and p = 0.05, respectively).ConclusionThis is the largest TSH series in the US and demonstrates evidence of safety and feasibility in the management of bilateral CRLM. Outcomes are influenced by margin status and operative EBL.

Introduction. Gallbladder volvulus is a rare, potentially fatal condition unless diagnosed and treated early. Choledochal cysts are rare congenital malformations of the biliary tree predisposing to different pathologies and posing the risk of degradation into cholangiocarcinoma and gallbladder cancer. Dealing with both diseases at once has not been published yet in the literature. Presentation of Case. We report a case of gallbladder volvulus in an elderly female who happened to have a concomitant type I choledochal cyst. Treatment was achieved with a cholecystectomy and observation and follow-up of the choledochal cyst. Discussion. Prompt diagnosis and surgical management of gallbladder volvulus is important to avoid the morbidity and mortality of gangrenous cholecystitis and biliary peritonitis in a frail old population of patients. Precise clinical diagnosis, supplemented with specific imaging clues, helps in the diagnosis. Management of choledochal cysts is also surgical; however the timing of surgery is still a matter of debate. Conclusion. We describe in this report the first case of gallbladder volvulus in a patient with a choledochal cyst and propose a management algorithm of a very rare biliary tree pathology combination.