Clinical Relevance of Cancerization of Ducts in Resected Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Although prevalent in 50%-90% of pancreatic ductal adenocarcinomas, the clinical relevance of "cancerization of ducts" (COD) remains unknown. METHODS: Pathologists retrospectively reviewed slides classifying prevalence of COD. Histopathological parameters, location of first recurrence, recurrence-free survival (RFS), and overall survival (OS) were collected from the institutional pancreatectomy registry. RESULTS: Among 311 pancreatic ductal adenocarcinomas, COD was present in 216 (69.5%) and more prevalent in the cohort that underwent upfront surgery (75.3% vs 63.1%, P = 0.019). Furthermore, COD was associated with female gender (P = 0.040), advanced T stage (P = 0.007), perineural invasion (P = 0.014), lymphovascular invasion (P = 0.025), and R1 margin (P = 0.009), but not N stage (P = 0.401) or tumor differentiation (P = 0.717). In multivariable regression, COD was associated with less liver recurrence (odds ratio, 0.44; P < 0.005). This association was driven by the cohort of patients who had received preoperative treatment (odds ratio, 0.18; P < 0.001). COD was not predictive for RFS or OS. CONCLUSIONS: Cancerization of ducts was not associated with RFS or OS. Currently underrecognized, standardized implementation into histopathological reports may have merit, and further mechanistic scientific experiments need to illuminate its clinical and biologic impact.

Distinctive Pathology Associated With Focal Stenosis of the Main Pancreatic Duct Secondary to Remote Trauma: A Long-term Complication of Seat Belt Pancreatitis.

The radiologic finding of focal stenosis of the main pancreatic duct is highly suggestive of pancreatic cancer. Even in the absence of a mass lesion, focal duct stenosis can lead to surgical resection of the affected portion of the pancreas. We present four patients with distinctive pathology associated with non-neoplastic focal stenosis of the main pancreatic duct. The pathology included stenosis of the pancreatic duct accompanied by wavy, acellular, serpentine-like fibrosis, chronic inflammation with foreign body-type giant cell reaction, and calcifications. In all cases, the pancreas toward the tail of the gland had obstructive changes including acinar drop-out and interlobular and intralobular fibrosis. Three of the four patients had a remote history of major motor vehicle accidents associated with severe abdominal trauma. These results emphasize that blunt trauma can injure the pancreas and that this injury can result in long-term complications, including focal stenosis of the main pancreatic duct. Pathologists should be aware of the distinct pathology associated with remote trauma and, when the pathology is present, should elicit the appropriate clinical history.

Exploring the Clinical Use of Molecular Profiling of Intrahepatic Cholangiocarcinoma in a Comprehensive Multidisciplinary Clinic.

BACKGROUND: Molecular profiling of intrahepatic cholangiocarcinoma (ICC) can detect actionable molecular alterations and guide targeted therapies. We explore the clinical use of molecular profiling of ICC in our comprehensive multidisciplinary clinic. STUDY DESIGN: Patients with a tissue diagnosis of ICC seen between 2019 and 2023 were identified. A retrospective review was performed to identify their molecular profiles and targeted therapy. The association between the detection of actionable molecular alterations and overall survival (OS) from the first clinic visit date was studied. Patients with an OS of less than 2 months were excluded. RESULTS: Among 194 patients with ICC, 125 had molecular profiling. Actionable molecular alterations were detected in 56 (45%) patients, including microsatellite instability (n = 3), high tumor mutational burden (>10 muts/mb; n = 5), isocitrate dehydrogenase 1 and 2 mutations (n = 22 and 6, respectively), BRAF V600E mutations (n = 2), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha mutations (n = 7), breast cancer 1 and breast cancer 2 mutations (n = 5), mesenchymal epithelial transition amplification (n = 2), fibroblast growth factor receptor 2 and 3 fusions (n = 13), erb-b2 receptor tyrosine kinase 2 overexpression (n = 6), and receptor tyrosine kinase 1 fusion (n = 1). Twenty-one patients received targeted therapies during their treatment course. Survival analysis revealed that for 120 patients with molecular profiling, the detection of an actionable molecular alteration was associated with improved mean OS (34.1 vs 23.6 months, p = 0.008). Among 70 patients with nonmetastatic ICC, the detection of an actionable molecular alteration was associated with improved mean OS (32.1 vs 27.5 months, p = 0.02). CONCLUSIONS: Actionable molecular alterations were frequently observed in patients with ICC. Detection of actionable alterations was associated with improved OS. The role of targeted therapy needs further exploration in prospective multicenter studies.

Cancer-cell-derived sialylated IgG as a novel biomarker for predicting poor pathological response to neoadjuvant therapy and prognosis in pancreatic cancer.

BACKGROUND: Neoadjuvant therapy (NAT) is increasingly applied in pancreatic ductal adenocarcinoma (PDAC); however, accurate prediction of therapeutic response to NAT remains a pressing clinical challenge. Cancer-cell-derived sialylated immunoglobulin G (SIA-IgG) was previously identified as a prognostic biomarker in PDAC. This study aims to explore whether SIA-IgG expression in treatment-naïve fine needle aspirate (FNA) biopsy specimens could predict the pathological response (PR) to NAT for PDAC. METHODS: Endoscopic ultrasonography-guided FNA biopsy specimens prior to NAT were prospectively obtained from 72 patients with PDAC at the Johns Hopkins Hospital. SIA-IgG expression of PDAC specimens was assessed by immunohistochemistry. Associations between SIA-IgG expression and PR, as well as patient prognosis, were analyzed. A second cohort enrolling surgically resected primary tumor specimens from 79 patients with PDAC was used to validate the prognostic value of SIA-IgG expression. RESULTS: SIA-IgG was expressed in 58.3% of treatment-naïve FNA biopsies. Positive SIA-IgG expression at diagnosis was associated with unfavorable PR and can serve as an independent predictor of PR. The sensitivity and specificity of SIA-IgG expression in FNA specimens in predicting an unfavorable PR were 63.9% and 80.6%, respectively. Both positive SIA-IgG expression in treatment-naïve FNA specimens and high SIA-IgG expression in surgically resected primary tumor specimens were significantly associated with shorter survival. CONCLUSIONS: Assessment of SIA-IgG on FNA specimens prior to NAT may help predict PR for PDAC. Additionally, SIA-IgG expression in treatment-naïve FNA specimens and surgically resected primary tumor specimens were predictive of the prognosis for PDAC.

Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer.

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.

Postoperative Chemotherapy is Associated with Improved Survival in Patients with Node-Positive Pancreatic Ductal Adenocarcinoma After Neoadjuvant Therapy.

BACKGROUND: Postoperative chemotherapy following pancreatic cancer resection is the standard of care. The utility of postoperative chemotherapy for patients who receive neoadjuvant therapy (NAT) is unclear. METHODS: Patients who underwent pancreatectomy after NAT with FOLFIRINOX or gemcitabine-based chemotherapy for non-metastatic pancreatic adenocarcinoma (2015-2019) were identified. Patients who received less than 2 months of neoadjuvant chemotherapy or died within 90 days from surgery were excluded. RESULTS: A total of 427 patients (resectable, 22.2%; borderline resectable, 37.9%; locally advanced, 39.8%) were identified with the majority (69.3%) receiving neoadjuvant FOLFIRINOX. Median duration of NAT was 4.1 months. Following resection, postoperative chemotherapy was associated with an improved median overall survival (OS) (28.7 vs. 20.4 months, P = 0.006). Risk-adjusted multivariable modeling showed negative nodal status (N0), favorable pathologic response (College of American Pathologists score 0 & 1), and receipt of postoperative chemotherapy to be independent predictors of improved OS. Regimen, duration, and number of cycles of NAT were not significant predictors. Thirty-four percent (60/176) of node-positive and 50.1% (126/251) of node-negative patients did not receive postoperative chemotherapy due to poor functional status, postoperative complications, and patient preference. Among patients with node-positive disease, postoperative chemotherapy was associated with improved median OS (27.2 vs. 10.5 months, P < 0.001). Among node-negative patients, postoperative chemotherapy was not associated with a survival benefit (median OS, 30.9 vs. 36.9 months; P = 0.406). CONCLUSION: Although there is no standard NAT regimen for patients with pancreatic cancer, postoperative chemotherapy following NAT and resection appears to be associated with improved OS for patients with node-positive disease.

The Impact of the COVID-19 Pandemic on Multidisciplinary Clinics: A High-Volume Pancreatic Cancer Center Experience.

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.

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.

Current Surgical Management Strategies for Colorectal Cancer Liver Metastases.

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.

Perception versus reality: A National Cohort Analysis of the surgery-first approach for resectable pancreatic cancer.

INTRODUCTION: Although surgical resection is necessary, it is not sufficient for long-term survival in pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate survival after up-front surgery (UFS) in anatomically resectable PDAC in the context of three critical factors: (A) margin status; (B) CA19-9; and (C) receipt of adjuvant chemotherapy. METHODS: The National Cancer Data Base (2010-2015) was reviewed for clinically resectable (stage 0/I/II) PDAC patients. Surgical margins, pre-operative CA19-9, and receipt of adjuvant chemotherapy were evaluated. Patient overall survival was stratified based on these factors and their respective combinations. Outcomes after UFS were compared to equivalently staged patients after neoadjuvant chemotherapy on an intention-to-treat (ITT) basis. RESULTS: Twelve thousand and eighty-nine patients were included (n = 9197 UFS, n = 2892 ITT neoadjuvant). In the UFS cohort, only 20.4% had all three factors (median OS = 31.2 months). Nearly 1/3rd (32.7%) of UFS patients had none or only one factor with concomitant worst survival (median OS = 14.7 months). Survival after UFS decreased with each failing factor (two factors: 23 months, one factor: 15.5 months, no factors: 7.9 months) and this persisted after adjustment. Overall survival was superior in the ITT-neoadjuvant cohort (27.9 vs. 22 months) to UFS. CONCLUSION: Despite the perceived benefit of UFS, only 1-in-5 UFS patients actually realize maximal survival when known factors highly associated with outcomes are assessed. Patients are proportionally more likely to do worst, rather than best after UFS treatment. Similarly staged patients undergoing ITT-neoadjuvant therapy achieve survival superior to the majority of UFS patients. Patients and providers should be aware of the false perception of 'optimal' survival benefit with UFS in anatomically resectable PDAC.

Blood Cell Salvage and Autotransfusion Does Not Worsen Oncologic Outcomes Following Liver Transplantation with Incidental Hepatocellular Carcinoma: A Propensity Score-Matched Analysis.

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.

Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.

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.

Implementation of prospective, surgeon-driven, risk-based pathway for pancreatoduodenectomy results in improved clinical outcomes and first year cost savings of $1 million.

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 < .001) despite similar readmission rates. Postsurgical interventional radiology procedures decreased to 18.0% from 26.4% (P = .048). Utilization of and duration of stay in monitored care decreased to 23.4% from 35.6% (P < .01) and to 1 day from 3 (P < .01). On multivariable analysis RBP-PD was independently associated with decreased odds of higher postoperative pancreatic fistula grade, monitored care, and prolonged duration of stay. Inpatient cost of care decreased $6,387 per patient (-11.1%, P = .016), and total 30-day costs decreased $8,565 per patient (-13.7%, P = .01), representing a total 30-day cost savings of $1.1 million. CONCLUSION: RBP-PD significantly improved patient outcomes, decreased costs of care, and likely has applicability for surgical care beyond pancreatoduodenectomy.

Type of Resection (Whipple vs. Distal) Does Not Affect the National Failure to Provide Post-resection Adjuvant Chemotherapy in Localized Pancreatic Cancer.

INTRODUCTION: 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). METHODS: 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. RESULTS: 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). CONCLUSION: 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.

A multicenter randomized controlled trial comparing pancreatic leaks after TissueLink versus SEAMGUARD after distal pancreatectomy (PLATS) NCT01051856.

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.

Benefit of Postresection Adjuvant Chemotherapy for Stage III Colon Cancer in Octogenarians: Analysis of the National Cancer Database.

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.

Risk by indication for pancreaticoduodenectomy in patients 80 years and older: a study from the American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: In patients 80 or older undergoing PD, perioperative risk varies by diagnostic indication. Patients should receive preoperative counseling about their risk.

Overall survival is increased among stage III pancreatic adenocarcinoma patients receiving neoadjuvant chemotherapy compared to surgery first and adjuvant chemotherapy: An intention to treat analysis of the National Cancer Database.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Mixed hepatocellular and cholangiocarcinoma: a rare tumor with a mix of parent phenotypic characteristics.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. DISCUSSION: 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.