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BACKGROUND: The role of postoperative chemotherapy in patients with resected pancreatic cancer who receive neoadjuvant treatment is unknown. Clinicians use changes in CA19-9 and histopathologic scores to assess treatment response. We sought to investigate if CA19-9 normalization in response to NAT can help guide the need for postoperative treatment. METHODS: Patients with elevated baseline CA19-9 (CA19-9 > 37U/mL) who received NAT followed by surgery between 2011 and 2019 were retrospectively reviewed. Treatment response was determined by CA19-9 normalization following NAT and histopathologic scoring. The role of postoperative chemotherapy was analyzed in light of CA19-9 normalization and histopathologic response. RESULTS: We identified and included 345 patients. Following NAT, CA19-9 normalization was observed in 125 patients (36.2%). CA19-9 normalization was associated with a favorable histopathologic response (41.6% vs 23.2%, p < 0.001) and a lower ypT (p < 0.001) and ypN stage (p = 0.003). Receipt of adjuvant chemotherapy was associated with improved overall survival in patients in whom CA19-9 did not normalize following NAT (26.8 vs 16.4 months, p = 0.008). In patients who received 5FU-based NAT and in whom CA19-9 did not normalize, receipt of 5FU-based adjuvant chemotherapy was associated with improved OS (p = 0.014). CONCLUSION: CA19-9 normalization in response to NAT was associated with favorable outcomes and can serve as a biomarker for treatment response. In patients where CA19-9 did not normalize, receipt of postoperative chemotherapy was associated with improved OS. These patients also benefited from additional 5FU-based postoperative chemotherapy following 5FU-based NAT.

Purpose:Patient-derived organoids (PDO) are a promising technology to support precision medicine initiatives for patients with pancreatic ductal adenocarcinoma (PDAC). PDOs may improve clinical next-generation sequencing (NGS) and enable rapid ex vivo chemotherapeutic screening (pharmacotyping).Experimental Design:PDOs were derived from tissues obtained during surgical resection and endoscopic biopsies and studied with NGS and pharmacotyping. PDO-specific pharmacotype is assessed prospectively as a predictive biomarker of clinical therapeutic response by leveraging data from a randomized controlled clinical trial.Results:Clinical sequencing pipelines often fail to detect PDAC-associated somatic mutations in surgical specimens that demonstrate a good pathologic response to previously administered chemotherapy. Sequencing the PDOs derived from these surgical specimens, after biomass expansion, improves the detection of somatic mutations and enables quantification of copy number variants. The detection of clinically relevant mutations and structural variants is improved following PDO biomass expansion. On clinical trial, PDOs were derived from biopsies of treatment-naïve patients prior to treatment with FOLFIRINOX (FFX). Ex vivo PDO pharmacotyping with FFX components predicted clinical therapeutic response in these patients with borderline resectable or locally advanced PDAC treated in a neoadjuvant or induction paradigm. PDO pharmacotypes suggesting sensitivity to FFX components were associated with longitudinal declines of tumor marker, carbohydrate-antigen 19–9 (CA-19–9), and favorable RECIST imaging response.Conclusions:PDOs established from tissues obtained from patients previously receiving cytotoxic chemotherapies can be accomplished in a clinically certified laboratory. Sequencing PDOs following biomass expansion improves clinical sequencing quality. High in vitro sensitivity to standard-of-care chemotherapeutics predicts good clinical response to systemic chemotherapy in PDAC.See related commentary by Zhang et al., p. 3176

Supplementary Figure from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response

Supplementary Table from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response

Supplementary Data from Precision Medicine in Pancreatic Cancer: Patient-Derived Organoid Pharmacotyping Is a Predictive Biomarker of Clinical Treatment Response

Purpose: Patient-derived organoids (PDO) are a promising technology to support precision medicine initiatives for patients with pancreatic ductal adenocarcinoma (PDAC). PDOs may improve clinical next-generation sequencing (NGS) and enable rapid ex vivo chemotherapeutic screening (pharmacotyping). Experimental Design: PDOs were derived from tissues obtained during surgical resection and endoscopic biopsies and studied with NGS and pharmacotyping. PDO-specific pharmacotype is assessed prospectively as a predictive biomarker of clinical therapeutic response by leveraging data from a randomized controlled clinical trial. Results: Clinical sequencing pipelines often fail to detect PDAC-associated somatic mutations in surgical specimens that demonstrate a good pathologic response to previously administered chemotherapy. Sequencing the PDOs derived from these surgical specimens, after biomass expansion, improves the detection of somatic mutations and enables quantification of copy number variants. The detection of clinically relevant mutations and structural variants is improved following PDO biomass expansion. On clinical trial, PDOs were derived from biopsies of treatment-naïve patients prior to treatment with FOLFIRINOX (FFX). Ex vivo PDO pharmacotyping with FFX components predicted clinical therapeutic response in these patients with borderline resectable or locally advanced PDAC treated in a neoadjuvant or induction paradigm. PDO pharmacotypes suggesting sensitivity to FFX components were associated with longitudinal declines of tumor marker, carbohydrate-antigen 19–9 (CA-19–9), and favorable RECIST imaging response. Conclusions: PDOs established from tissues obtained from patients previously receiving cytotoxic chemotherapies can be accomplished in a clinically certified laboratory. Sequencing PDOs following biomass expansion improves clinical sequencing quality. High in vitro sensitivity to standard-of-care chemotherapeutics predicts good clinical response to systemic chemotherapy in PDAC. See related commentary by Zhang et al., p. 3176

Background: Intraoperative blood cell salvage and autotransfusion (IBSA) during liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial for concern regarding adversely impacting oncologic outcomes. Objective: We aimed to evaluate the long-term oncologic outcomes of patients who underwent LT with incidentally discovered HCC who received IBSA compared with those who did not receive IBSA. Methods: Patients undergoing LT (January 2001–October 2018) with incidental HCC on explant pathology were retrospectively identified. A 1:1 propensity score matching (PSM) was performed. HCC recurrence and patient survival were compared. Kaplan–Meier survival analyses were performed, and univariable Cox proportional hazard analyses were performed for risks of recurrence and death. Results: Overall, 110 patients were identified (IBSA, n = 76 [69.1%]; non-IBSA, n = 34 [30.9%]). Before matching, the groups were similar in terms of demographics, transplant, and tumor characteristics. Overall survival was similar for IBSA and non-IBSA at 1, 3, and 5 years (96.0%, 88.4%, 83.0% vs. 97.1%, 91.1%, 87.8%, respectively; p = 0.79). Similarly, the recurrence rate at 1, 3, and 5 years was not statistically different (IBSA 0%, 1.8%, 1.8% vs. non-IBSA 0%, 3.2%, 3.2%, respectively; p = 0.55). After 1:1 matching (26 IBSA, 26 non-IBSA), Cox proportional hazard analysis demonstrated similar risk of death and recurrence between the groups (IBSA hazard ratio [HR] of death 1.26, 95% confidence interval [CI] 0.52–3.05, p = 0.61; and HR of recurrence 2.64, 95% CI 0.28–25.30, p = 0.40). Conclusions: IBSA does not appear to adversely impact oncologic outcomes in patients undergoing LT with incidental HCC. This evidence further supports the need for randomized trials evaluating the impact of IBSA use in LT for HCC.

The unprecedented impact of the Sars-CoV-2 pandemic (COVID-19) has strained the healthcare system worldwide. The impact is even more profound on diseases requiring timely complex multidisciplinary care such as pancreatic cancer. Multidisciplinary care teams have been affected significantly in multiple ways as healthcare teams collectively acclimate to significant space limitations and shortages of personnel and supplies. As a result, many patients are now receiving suboptimal remote imaging for diagnosis, staging, and surgical planning for pancreatic cancer. In addition, the lack of face-to-face interactions between the physician and patient and between multidisciplinary teams has challenged patient safety, research investigations, and house staff education. In this study, we discuss how the COVID-19 pandemic has transformed our high-volume pancreatic multidisciplinary clinic, the unique challenges faced, as well as the potential benefits that have arisen out of this situation. We also reflect on its implications for the future during and beyond the pandemic as we anticipate a hybrid model that includes a component of virtual multidisciplinary clinics as a means to provide accessible world-class healthcare for patients who require complex oncologic management.

Intraoperative blood cell salvage and autotransfusion (IBSA) during liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial for concern regarding adversely impacting oncologic outcomes.We aimed to evaluate the long-term oncologic outcomes of patients who underwent LT with incidentally discovered HCC who received IBSA compared with those who did not receive IBSA.Patients undergoing LT (January 2001-October 2018) with incidental HCC on explant pathology were retrospectively identified. A 1:1 propensity score matching (PSM) was performed. HCC recurrence and patient survival were compared. Kaplan-Meier survival analyses were performed, and univariable Cox proportional hazard analyses were performed for risks of recurrence and death.Overall, 110 patients were identified (IBSA, n = 76 [69.1%]; non-IBSA, n = 34 [30.9%]). Before matching, the groups were similar in terms of demographics, transplant, and tumor characteristics. Overall survival was similar for IBSA and non-IBSA at 1, 3, and 5 years (96.0%, 88.4%, 83.0% vs. 97.1%, 91.1%, 87.8%, respectively; p = 0.79). Similarly, the recurrence rate at 1, 3, and 5 years was not statistically different (IBSA 0%, 1.8%, 1.8% vs. non-IBSA 0%, 3.2%, 3.2%, respectively; p = 0.55). After 1:1 matching (26 IBSA, 26 non-IBSA), Cox proportional hazard analysis demonstrated similar risk of death and recurrence between the groups (IBSA hazard ratio [HR] of death 1.26, 95% confidence interval [CI] 0.52-3.05, p = 0.61; and HR of recurrence 2.64, 95% CI 0.28-25.30, p = 0.40).IBSA does not appear to adversely impact oncologic outcomes in patients undergoing LT with incidental HCC. This evidence further supports the need for randomized trials evaluating the impact of IBSA use in LT for HCC.

Colorectal cancer is the third most common cancer diagnosis in the world, and the second most common cause of cancer-related deaths. Despite significant progress in management strategies for colorectal cancer over the last several decades, metastatic disease remains difficult to treat and is often considered incurable. However, for patients with colorectal liver metastases (CRLM), surgical resection offers the best opportunity for survival, can be curative, and remains the gold standard. Unfortunately, surgical treatment options are underutilized. Misperceptions regarding resectable and unresectable CRLM likely play a role in this. The assessment of factors that impact resectability status like medical fitness, technical considerations, and disease biology can be difficult, necessitating careful multidisciplinary input and discussion. The identification of ideal operative time windows that align with the multimodal management of these patients can also be perplexing. For all patients with CRLM it may therefore be advantageous to obtain surgical evaluation at the time of discovering liver metastases to mitigate these challenges and minimize the risk of undertreatment. In this review we summarize current surgical management strategies for CRLM and discuss factors to be considered when determining resectability.

Introduction Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. Methods A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. Results Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. Conclusions Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma.

BACKGROUND Morbidity and costs after pancreatoduodenectomy remain increased, driven by postoperative pancreatic fistula (POPF). A risk-based pathway for pancreatoduodenectomy (RBP-PD) was implemented and the clinical and cost outcomes compared with that of our historic practice. METHODS Prospective clinical and cost outcomes for our RBP-PD cohort treated from September 2014 to September 2015 were compared with a previously published cohort of pancreatoduodenectomies from January 2007 to February 2014. RESULTS A total of 128 RBP-PD cases were compared with 808 historic controls. Apart from less blood loss, there were no significant clinical differences between the 2 groups. Overall POPF rate did not change. Average duration of stay decreased to 10 days from 12 (P

Intrahepatic lesions of mixed hepatocellular (HCC) and intrahepatic cholangiocellular carcinoma (ICC) histology are rare. The aim was to describe the natural history of these tumors relative to monomorphic ICC or HCC utilizing the National Cancer Data Base (NCDB).Patients with ICC, HCC, and mixed histology (cHCC-CCA) were identified in the NCDB (2004-2012). Inter-group comparisons were made. Kaplan-Meier and multivariable Cox Proportional Hazards analyzed overall survival.The query identified 90,499 patients with HCC; 14,463 with ICC; and 1141 with cHCC-CCA histology. Patients with cHCC-CCA histology were relatively young (61 vs. 62 (HCC, p = 0.877) and 67 (ICC, p 0.001) years) and more likely to have poorly differentiated tumor (29.2% vs. 10.3% (HCC) and 17.2% (ICC) p 0.001). Median overall survival for cHCC-CCA was 7.9 months vs. 10.8 (HCC) and 8.2 (ICC, all p 0.001). Stage-specific survival for mixed histology tumors was most similar to that of HCC for all stages. cHCC-CCA were transplanted at a relatively high rate, and transplant outcomes for mixed tumors were substantially worse than for HCC lesions.cHCC-CCA demonstrate stage-specific survival similar to HCC, but post-surgical survival more consistent with ICC. Patients with a pre-operative diagnosis of cHCC-CCA should undergo resection when appropriate.

Patient triage in anatomically resectable, early stage pancreatic ductal adenocarcinoma (PDAC) with elevated carbohydrate antigen 19-9 (CA 19-9) remains unclear. We hypothesized that any CA 19-9 elevation indicates biologically borderline resectability.The National Cancer Data Base (NCDB 2010 to 2012) was reviewed for PDAC patients with reported CA 19-9. Nonsecretors were analyzed separately. Early stage (I/II) patients were stratified by CA 19-9 above or below normal (37 U/mL). Unadjusted Kaplan-Meier and adjusted Cox proportional hazards survival modeling were performed.Of 113,145 patients, only 28,074 (24.8%) had CA 19-9 measured and reported, and this proportion was stage independent. Among early stage patients (n = 10,806), there were 957 (8.8%) nonsecretors, 2,708 (25.1%) with normal levels, and 7,141 (66.1%) with elevated levels. Demographics and perioperative outcomes were similar between these groups. Survival was worse in all stages in patients with CA 19-9 elevation. Nonsecretors had survival similar to that of patients with normal levels. Early stage patients with elevated CA 19-9 had decreased survival at 1, 2, and 3 years (56% vs 68%, 30% vs 42%, 15% vs 25%, all p0.001) relative to patients with normal levels. Adjusted modeling confirmed this finding (hazard ratio [HR] 1.26, p0.001). Repeat modeling in the neoadjuvant cohort demonstrated this to be the only treatment sequence to completely abrogate increased mortality due to CA 19-9 elevation (p = 0.11).The minority of PDAC patients have CA 19-9 measured and reported in NCDB. The CA 19-9 nonsecretors and normal-level patients achieve equivalent survival. Elevation of CA 19-9 is associated with decreased stage-specific survival, with the greatest difference in early stages. Neoadjuvant systemic therapy followed by curative intent surgery best mitigates the increased mortality hazard. Patients with PDAC who have elevated CA 19-9 levels at diagnosis are biologically borderline resectable regardless of anatomic resectability, and neoadjuvant systemic therapy is suggested.

Current National Comprehensive Cancer Network guidelines for Stages II and III rectal cancer recommend neoadjuvant chemoradiation followed by curative intent surgery and adjuvant chemotherapy. It is unclear whether therapies in addition to surgery are truly beneficial in elderly patients. Our aim was to compare the survival of patients over 80 with Stages II and III rectal cancer undergoing curative intent surgery with or without additional therapy. The National Cancer Data Base (NCDB 2006–2011) was queried for patients over 80 with Stages II and III rectal cancer. The primary outcome was overall survival. Patients were stratified based upon therapy group. Univariate group comparisons were made. Unadjusted Kaplan–Meier and multivariable Cox proportional hazards modeling survival analyses were performed. The query yielded 3098 patients over 80 with Stage II (N = 1566) or Stage III (N = 1532) disease. Approximately, half of the patients received surgery only. Kaplan–Meier analysis showed improved survival for patients receiving neoadjuvant and/or adjuvant therapy in addition to surgery, but there was no significant difference between those that received guideline concordant care (GCC), neoadjuvant chemoradiation only, or post-operative chemotherapy only. Cox proportional hazard modeling identified age >90 and margin positivity as independent risk factors for decreased overall survival. Analysis of NCDB data for Stages II and III rectal cancer in patients over 80 shows a survival benefit of adjuvant and/or neoadjuvant therapy over surgery alone. There does not appear to be a difference in survival between patients who received neoadjuvant chemoradiation, post-resection adjuvant chemotherapy, or GCC.

BackgroundElderly patients undergoing open pancreatoduodenectomy (OPD) are at increased risk for surgical morbidity and mortality. Whether totally laparoscopic pancreatoduodenectomy (TLPD) mitigates these risks has not been evaluated.MethodsA retrospective review of outcomes in patients submitted to pancreatoduodenectomy during 2007–2014 was conducted (n = 860). Outcomes in elderly patients (aged ≥70 years) were compared with those in non elderly patients with respect to risk adjusted postoperative morbidity and mortality. Differences in outcomes between patients submitted to OPD and TLPD, respectively, were evaluated in the elderly subgroup.ResultsIn elderly patients, the incidences of cardiac events (odds ratio [OR] 3.21, P

Safety of synchronous hepatectomy and colorectal resection (CRR) for metastatic colorectal cancer remains controversial. We hypothesized that both the extent of hepatectomy and CRR influences postoperative outcomes. Prospective 2005–2013 ACS-NSQIP data were retrospectively reviewed for mortality and major morbidity (MM) after (1) isolated hepatectomy, (2) isolated CRR, and (3) synchronous resection for colorectal cancer. Hepatectomy and CRR risk categories were created based on mortality and MM of respective isolated resections. The synchronous cohort was then stratified based on risk categories. Cumulative asynchronous mortality and MM were estimated compared to that observed in the synchronous cohort via unadjusted relative risk and risk difference. There were 43,408 patients identified. Among isolated hepatectomy patients (N = 6,661), trisectionectomy and right hepatectomy experienced the greatest mortality and were defined as “major” hepatectomy. Among isolated CRR patients (N = 35,825), diverted left colectomy, abdominoperineal resection, total abdominal colectomy, and total abdominal proctocolectomy experienced the greatest MM and were defined as “high risk” CRR. Synchronous patients (N = 922) were stratified by hepatectomy and CRR risk categories; mortality and MM varied from 0.9 to 5.0 % and 25.5 to 55.0 %, respectively. Mortality and MM were greatest for patients undergoing “high risk” CRR and “major” hepatectomy and lowest for synchronous CRR and “minor” hepatectomy. As both CRR and hepatectomy risk categories increased, there was a significant trend in increasing mortality and MM in synchronous patients. Additionally, comparison of the synchronous resections versus the estimated cumulative asynchronous outcomes showed that (1) mortality was significantly less after synchronous minor hepatectomy and either low or high risk CRR, and (2) neither mortality nor major morbidity differed significantly after major hepatectomy with either high or low risk CRR. Major morbidity after synchronous hepatic and colorectal resections vary incrementally and are related to both the risk of hepatectomy and CRR. Stratification of outcomes by the hepatectomy and CRR components may reflect a more accurate description of risks. Comparison of synchronous and combined outcomes of individual operations supports a potential benefit for synchronous resections with minor hepatectomy.

BACKGROUND Clinical trials demonstrate that postresection chemotherapy conveys survival benefit to patients with stage III colon cancer. It is unclear whether this benefit can be extrapolated to the elderly, who are underenrolled in clinical trials. OBJECTIVE The purpose of this study was to determine outcomes of selected octogenarians with stage III colon cancer with/without postresection adjuvant therapy. DESIGN This was a retrospective cohort study (2006-2011) using unadjusted Kaplan-Meier and adjusted Cox proportional hazards analyses of overall survival. SETTING The study was conducted with the National Cancer Database. PATIENTS We included patients 80 to 89 years of age who were undergoing curative-intent surgery for stage III colon cancer and excluded patients who received neoadjuvant therapy, died within 6 weeks of surgery, or had high comorbidity. MAIN OUTCOME MEASURES Overall survival was the main measure. RESULTS A total of 8141 octogenarians were included; 3483 (42.8%) received postresection chemotherapy, and 4658 (57.2%) underwent surgery alone. Patients receiving chemotherapy were younger (82.0 vs 84.0 years; p < 0.001), healthier (73.1% vs 70.4% with no comorbidities; p = 0.009), and more likely to have N2 disease (40.4% vs 32.8%; p < 0.001). Overall survival was improved in patients receiving adjuvant chemotherapy (median = 61.7 vs 35.0 months; p < 0.001). Subgroup analysis of patients offered chemotherapy but refusing (n = 1315) demonstrated overall survival worse than those receiving adjuvant chemotherapy (median = 42.7 vs 61.7 months; p < 0.001). Multivariable analysis adjusting for potential confounders showed therapy with surgery alone to be independently associated with increased mortality hazard (HR = 1.83; p < 0.001), and the mortality hazard remained elevated in patients who voluntarily refused adjuvant therapy (HR = 1.45; p < 0.001). LIMITATIONS The study was limited by its retrospective, nonrandomized design. CONCLUSIONS In selected octogenarians with stage III colon cancer, postresection adjuvant chemotherapy was associated with superior overall survival. However, less than half of the octogenarians with stage III colon cancer in the National Cancer Database received it. The remaining majority, who were all fit and survived ≥6 weeks postsurgery, could have derived benefit from adjuvant chemotherapy. This represents a substantial opportunity for quality improvement in treating octogenarians with stage III colon cancer.

Primary pancreatic small cell carcinomas (PSCCs) are rare, and benefits of surgery are unknown. Utilizing the National Cancer Data Base, surgical outcomes of PSCC were determined and compared with pancreatic ductal adenocarcinoma (PDAC).Patients with histologically confirmed PSCC (n = 541) and PDAC (n = 156,733) were identified from the National Cancer Data Base (1998-2011). Parametric comparisons of patient and outcomes data were made. Unadjusted Kaplan-Meier and Cox proportional hazards analyses were performed.Primary pancreatic small cell carcinomas accounted for 0.2% of all pancreatic tumors. Demographics were similar to PDAC. A higher proportion of PSCC were metastatic at diagnosis (75.6% vs 53.6%, P0.001). In stage I/II, 45.6% of PDAC versus 21.8% of PSCC underwent surgery. Node status, lymphovascular invasion, margin negativity rates, and perioperative outcomes were similar. Median unadjusted overall survival was similar for resected PDAC and PSCC (16.9 vs 20.7 months; P = 0.337). On multivariable analysis within resectable PSCC (stages I-II), the greatest independent predictors of mortality were age 65 years or older (hazards ratio, 2.78; 95% confidence interval, 1.56-4.97; P = 0.00055) and nonreceipt of surgery (hazards ratio, 2.66; 95% confidence interval, 1.24-5.71; P = 0.01).Although PSCC commonly presents with distant disease, patients with anatomically resectable tumors derive similar benefit from aggressive surgical intervention as PDAC and should be counseled accordingly.

Adjuvant chemotherapy improves survival after curative intent resection for localized pancreatic adenocarcinoma (PDAC). Given the differences in perioperative morbidity, we hypothesized that patients undergoing distal partial pancreatectomy (DPP) would receive adjuvant therapy more often those undergoing pancreatoduodenectomy (PD). The National Cancer Data Base (2004–2012) identified patients with localized PDAC undergoing DPP and PD, excluding neoadjuvant cases, and factors associated with receipt of adjuvant therapy were identified. Overall survival (OS) was analyzed using multivariable Cox proportional hazards regression. Overall, 13,501 patients were included (DPP, n = 1933; PD, n = 11,568). Prognostic characteristics were similar, except DPP patients had fewer N1 lesions, less often positive margins, more minimally invasive resections, and shorter hospital stay. The proportion of patients not receiving adjuvant chemotherapy was equivalent (DPP 33.7%, PD 32.0%; p = 0.148). The type of procedure was not independently associated with adjuvant chemotherapy (hazard ratio 0.96, 95% confidence interval 0.90–1.02; p = 0.150), and patients receiving adjuvant chemotherapy had improved unadjusted and adjusted OS compared with surgery alone. The type of resection did not predict adjusted mortality (p = 0.870). Receipt of adjuvant chemotherapy did not vary by type of resection but improved survival independent of procedure performed. Factors other than type of resection appear to be driving the nationwide rates of post-resection adjuvant chemotherapy in localized PDAC.

Expected mortality after elective pancreaticoduodenectomy (PD) in contemporary series is less than 5% in elderly patients; however, to our knowledge, mortality rate has not been correlated with indication for PD. We hypothesized that perioperative risk following PD would correlate with diagnostic indication in older patients.The American College of Surgeons NSQIP database was reviewed to identify patients (80 and ≥80 years) who underwent PD from January 1, 2005, through December 31, 2012. High- and low-risk diagnoses were determined by using 30-day, major-morbidity data. Univariate and multivariable analyses were used to compare outcomes.Pancreatic cancer and chronic pancreatitis were found to be low-risk diagnoses in elderly patients, whereas bile duct and ampullary neoplasm, duodenal neoplasm, and neuroendocrine tumors were high-risk diagnoses. The risk of 30-day mortality for older patients (≥80 y) undergoing PD was 6.1% for those with high-risk diagnoses vs 4.5% for those with low-risk diagnoses (P = .27). On multivariable analysis (controlling for confounders), a high-risk diagnosis was shown to be an independent predictor of prolonged length of stay, superficial surgical-site infection (SSI), and organ-space SSI. There was no increased risk of complications in patients ≥80 years with low-risk diagnoses.In patients 80 or older undergoing PD, perioperative risk varies by diagnostic indication. Patients should receive preoperative counseling about their risk.

Background Pancreatic leak is common after distal pancreatectomy. This trial sought to compare TissueLink closure of the pancreatic stump to that of SEAMGUARD. Methods A multicenter, prospective, trial of patients undergoing distal pancreatectomy randomized to either TissueLink or SEAMGUARD. Results Enrollment was closed early due to poor accrual. Overall, 67 patients were enrolled, 35 TissueLink and 32 SEAMGUARD. The two groups differed in American Society of Anesthesiologist class and diagnosis at baseline and were relatively balanced otherwise. Overall, 37 of 67 patients (55%) experienced a leak of any grade, 15 (46.9%) in the SEAMGUARD arm and 22 (62.9%) in the TissueLink arm ( P = 0.19). The clinically significant leak rate was 17.9%; 22.9% for TissueLink and 12.5% for SEAMGUARD ( P = 0.35). There were no statistically significant differences in major or any pancreatic fistula–related morbidity between the two groups. Conclusions This is the first multicentered randomized trial evaluating leak rate after distal pancreatectomy between two common transection methods. Although a difference in leak rates was observed, it was not statistically significant and therefore does not provide evidence of the superiority of one technique over the other. Choice should remain based on surgeon comfort, experience, and pancreas characteristics.

Outcomes of neoadjuvant systemic therapy versus an upfront operation for clinical, stage III pancreatic adenocarcinoma remain poorly defined. Our aim was to compare survival among patients receiving neoadjuvant chemotherapy versus surgery-first with an intention-to-treat analysis.The National Cancer Data Base was reviewed from 2002-2011 for patients with clinical, stage III adenocarcinoma of the head or body of the pancreas. Patients were categorized as neoadjuvant or surgery-first. The intention-to-treat analysis included all neoadjuvant therapy patients in whom a potentially curative operation was planned and all surgery-first patients for whom adjuvant therapy was recommended. Intention-to-treat overall survival was compared by Kaplan-Meier and Cox proportional hazards multivariable regression.A total of 593 patients were identified: 377 (63.6%) in the neoadjuvant cohort, wherein 104 (27.6%) experienced preoperative attrition, and 216 (36.4%) in the surgery-first cohort, of whom 30 (13.9%) failed to receive intended adjuvant chemotherapy. Intention-to-treat Kaplan-Meier analysis demonstrated superior survival for neoadjuvant compared to surgery-first (median overall survival 20.7 months vs 13.7 months, log rank P .001). Intention-to-treat multivariable regression analysis revealed a decreased mortality hazard (hazard ratio = 0.68, 95% confidence interval 0.53-0.86, P = .0012) for neoadjuvant compared to surgery-first.Despite preoperative attrition, neoadjuvant therapy in clinical, stage III pancreatic cancer patients is associated with improved overall survival when compared to patients receiving surgery-first.

Background A clinical risk score for pancreatic fistula (CRS-PF) was recently reported to predict postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). An independent external validation has not been performed. Our hypothesis was that CRS-PF predicts POPF after both laparoscopic and open PD. Study Design The CRS-PF was calculated from a retrospective review of patients undergoing PD from January 2007 to February 2014. Postoperative pancreatic fistula was graded using International Study Group of Pancreatic Fistula criteria. Grade B and C leaks were defined as clinically significant. Performance was measured based on sensitivity, specificity, positive and negative predictive value, accuracy, and R 2 . Results There were 808 patients who met inclusion criteria; 539 (66.7%) had open and 269 (33.3%) had laparoscopic PD. The CRS-PF was high risk in 134 patients, intermediate in 492, low in 135, and negligible in 47. Postoperative pancreatic fistula occurred in 191 (23.6%) patients (grade A, 3.8%; B, 14.2%; and C, 5.6%), and it increased with risk category (R 2 = 0.935 all, 0.898 open, and 0.968 laparoscopic). High and intermediate risk categories were combined and classified as "test positive," and negligible and low risk categories were combined and classified "test negative," resulting in a CRS-PF with a sensitivity of 95% and a negative predictive value of 96% for predicting POPF. Contrary to previous studies, grade A POPF increased with increasing CRS-PF and POPF did not correlate with estimated blood loss (R 2 = 0.04). Conclusions The CRS-PF was validated independently by predicting POPF for both laparoscopic and open PD. Predictive performance was at least as good for laparoscopic PD as for open PD. Lack of correlation with estimated blood loss suggests CRS-PF might be tailored for improved performance. The CRS-PF is a clinically useful tool for POPF risk stratification after PD and allows for targeted intra- and postoperative measures to address patients at increased risk.

In patients undergoing elective hepatectomy, we aimed to evaluate the effect of preoperative anemia on postoperative mortality, morbidity, readmission, risk of blood transfusion, and duration of hospital stay.A total of 4,170 patients who underwent elective hepatectomy from 2010 to 2012 were identified in the American College of Surgeons National Surgical Quality Improvement Program. Univariate and multivariate analyses were performed by examination of the association of preoperative anemia (defined as hematocrit5) and the risk of any perioperative blood transfusion (defined as ≥1 unit of blood within 72 hours of operation), mean duration of stay, prolonged duration of stay (defined as ≥9 days, which represented the 75th percentile of this cohort), 30-day readmission, major morbidity, and mortality.A total of 948 patients had preoperative anemia (22.7%). Preoperative anemia was associated with increased risk of any perioperative blood transfusion, prolonged duration of stay, major postoperative complication, and 30-day mortality (P.05 for all analyses). After controlling for potentially confounding covariates, there was nearly a 3-fold greater risk of blood transfusion (adjusted OR = 2.79, P.001) and 2-fold greater risk of prolonged duration of stay in anemic versus nonanemic patients (adjusted OR = 1.66, P.001). Mean duration of stay was 10.0 days and 7.4 days for anemic and nonanemic patients, respectively (P.001).Anemia is associated with an almost 3-fold increased risk of blood transfusion, 2-fold increased risk of prolonged duration of hospitalization, and hospital stays were 2.6 days greater in anemic patients. Anemia may significantly impact resource utilization for elective hepatectomy.

e15797 Background: Duodenal adenocarcinoma is a rare tumor representing approximately 0.3% of all gastrointestinal tract cancers. Prognostic factors in relation to survival outcomes for these patients are sporadically reported in the medical literature. We aimed to evaluate outcomes of patients with duodenal adenocarcinoma who underwent pancreaticojejunostomy treated at Mayo Clinic Rochester from January 1, 2006 to December 31, 2016. Methods: Clinicopathological data of 52 duodenal cancer patients were collected. JMP software was used for statistical analysis. Kaplan-Meier method and log-rank tests were used for survival analysis, and multivariate cox proportional hazards model was used to evaluate the prognostic effect of pertinent clinical variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 65.9 years (range 39-81). The median overall survival was 51 months (95% CI 31.3-105.4) and the median progression free survival was 30.4 months with median follow up of 73.4 months. There were 3, 9, 21, and 19 patients with stage I, II, III, and IV disease, respectively. Depth of tumor invasion (p = 0.0156) and lymph node metastasis (p = 0.0441) were associated with overall survival on multivariate analysis. Advanced clinical staging influenced overall survival in univariate analysis, but lost prognostic significance in multivariate analysis. Age, gender, surgical technique, presence of metastases, tumor size, number of lymph nodes removed, location of duodenal segment involvement, and adjuvant treatment had no significant impact on overall survival. Laparoscopic approach did not influence survival but was associated with less hospital days (p = 0.0437). Conclusions: Depth of tumor invasion and lymph node status were associated with improved overall survival in patients with duodenal adenocarcinoma. Laparoscopic procedure decreased the hospital stay without affecting outcomes.

e15703 Background: The aim of this study is to identify prognostic factors and effects of adjuvant therapy for patients with ampullary adenocarcinoma who had pancreatoduodenectomy. Methods: A cohort of 123 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from January 1, 2006, through August 31, 2016 at Mayo Clinic in Rochester, MN. Only patients with ampullary carcinoma by pathology review were included and were histologically classified as pancreaticobiliary or intestinal subtypes. Median follow-up duration was 41.0 months. Patient survival and its correlation with patient and tumor variables were tested by univariate and multivariate analysis. Results: Pancreatoduodenectomy was curative-intent in 120 out of 123 patients. All 123 patients underwent radical surgery, 32 patients (26.0%) had laparoscopic pancreatoduodenectomy. Among 123 patients, there were 76 men (61.8%).Median age at diagnosis was 67.2 years. 54 patients (45%) without metastatic disease upon surgery had adjuvant therapy (35 patients had chemotherapy only while 19 patient also had radiation). Median overall survival (OS) was 91.8 months. Poor performance status at disease diagnosis (ECOG > = 1), old age ( > = 70 years), primary tumor infiltration (T), lymph node metastasis (N), and advanced disease stage (TNM) had a significant negative impact on survival (p < 0.05 by univariate analysis). Gender, diabetes at disease diagnosis, laparoscopic surgery approach, number of lymph nodes removed, number of positive lymph nodes, and tumor size did not influence survival. In multivariate analysis, ECOG score > = 1, adjuvant treatment, primary tumor infiltration (T) and lymph node metastasis (N) remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (P = 0.0388) and overall survival (p = 0.030) for patients with advanced disease (stage IIB and above). Conclusions: Poor performance status and advanced disease stage are associated with decreased survival in patients with ampullary adenocarcinoma. Patients with advanced disease should be considered for adjuvant chemotherapy.

Outcomes after hepatectomy have been assessed incompletely and have not been stratified by both extent of resection and diagnosis. We hypothesized that operative risk is better assessed by stratifying diagnoses into low- and high-risk categories and extent of resection into major and minor resection categories to more accurately evaluate the outcomes after hepatectomy. ACS-NSQIP was reviewed for 30-day operative mortality and major morbidity after partial hepatectomy (PH), left hepatectomy (LH), right hepatectomy (RH), and trisectionectomy (TS). Mortality was reviewed per diagnosis. “High Risk” was defined as the diagnoses associated with the greatest mortality. Major and minor resections were defined by comparison of outcomes for extent of resection by univariate analysis. Chi-square tests, t tests, Fisher’s exact tests, and multivariable logistic regression were utilized to compare the outcomes across groups. Among the 7,043 patients, the greatest mortality was observed with hepatocellular carcinoma (5.2 %) and cholangiocarcinoma (8.2 %), either intra- or extrahepatic, which were classified “High Risk”. Metastatic disease, benign neoplasms, and gallbladder cancer had a mortality rate of 1.3, 0.5, and 1.0 %, respectively, and were classified “Low Risk”. PH and LH were similar statistically for operative mortality and major morbidity within respective diagnosis risk groups (Low Risk: PH vs. LH and High Risk: PH vs. LH; all p > 0.05) and were defined as “Minor Resections”. Similarly, RH and TS had similar operative mortality and major morbidity within respective diagnosis risk groups (Low Risk: RH vs. TS and High Risk: RH vs. TS; all p > 0.05) and were defined as “Major Resections”. Risks of major morbidity and mortality increased for both diagnoses and the extent of resection. With minor resections, mortality and major morbidity were 5 and 1.6 times greater respectively for high-risk diagnosis than for low-risk diagnosis. With major resections, mortality and major morbidity were 4 and 1.6 times greater, respectively, for high-risk diagnoses than low-risk diagnoses. With low-risk diagnoses, mortality and major morbidity were 2.9 and 1.7 times greater, respectively, for major resections than minor resections (p

Congenital agenesis of the gallbladder and cystic duct represents a rare anomaly of the biliary system. It likely results from an embryologic mishap in the development of the hepatobiliary bud and can occur with other associated malformations. We report the case of congenital absence of the gallbladder and cystic duct incidentally found during laparoscopy in a 44-year-old Caucasian female. Based on the clinical presentation and ultrasonography findings, the patient was presumed to have symptomatic cholelithiasis and chronic cholecystitis. A laparoscopic cholecystectomy was planned. After introducing the laparoscope, the gallbladder and cystic duct were absent and the procedure aborted. Gallbladder and cystic duct agenesis was confirmed by magnetic resonance cholangiopancreatography. We describe here the difficulties with diagnosis and pain management, and review the literature of this rare pathology.

BackgroundStudies of pancreaticoduodenectomy (PD) frequently overlook diagnosis as a variable when evaluating postoperative outcomes or generically group patients according to whether they have ‘benign’ or ‘malignant’ disease. Large multicentre studies comparing postoperative outcomes in PD stratified by diagnosis are lacking. The present study was conducted to verify the hypothesis that postoperative morbidity and length of stay (LoS) following PD vary by diagnosis and that patients may be grouped into low- and high-risk categories.MethodsThe database of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) was reviewed for all PDs performed during 2005–2011. Diagnoses were identified using ICD-9 codes and grouped based on the incidence of major morbidity. Univariate and multivariate analyses were utilized to assess the impact of diagnosis on PD outcomes.ResultsOf 5537 patients, those with pancreas cancer (n = 3173) and chronic pancreatitis (n = 485) experienced similar incidences of major morbidity (P = 0.95) and were grouped as having low-risk diagnoses. Patients with bile duct and ampullary (n = 1181), duodenal (n = 558) and neuroendocrine (n = 140) disease experienced similar levels of major morbidity (P = 0.78) and were grouped as having high-risk diagnoses. A high-risk diagnosis was identified as an independent risk factor for a prolonged LoS [odds ratio (OR) 1.67], organ space infection (OR 2.57), sepsis or septic shock (OR 1.83), and major morbidity (OR 1.70). Diagnosis did not predict readmission.ConclusionsThe high-risk diagnosis is independently associated with postoperative morbidity and prolonged LoS. Patients with PD should be stratified by diagnosis to more accurately reflect their risk for postoperative complications and the complexity of care they will require.