Faculty Bibliography

OBJECTIVE:Neoadjuvant therapy increases rates of margin-negative resection of borderline resectable pancreatic ductal adenocarcinoma (BL-PDAC). Criteria for BL-PDAC resection following neoadjuvant chemotherapy and radiation therapy (NCRT) have not been clearly defined. METHODS:Fifty consecutive patients with BL-PDAC who received NCRT from 2007 to 2012 were identified. Computed tomography (CT) scans pre- and post-treatment were centrally reviewed. RESULTS:< 0.001). Of patients undergoing resection, 93 % were margin-negative, 72 % were node-negative, and 54 % demonstrated moderate pathologic response to NCRT. CONCLUSION/CONCLUSIONS:Apparent radiographic extent of vascular involvement does not change significantly after NCRT. Patients without metastatic disease should be chosen for surgical exploration based on adequate performance status and lack of disease progression.

BACKGROUND: The purpose of this study was to evaluate preoperative treatment with full-dose gemcitabine, oxaliplatin, and radiation therapy (RT) in patients with localized pancreatic cancer. METHODS: Eligibility included confirmation of adenocarcinoma, resectable or borderline resectable disease, a performance status /=3 adverse events during preoperative therapy included neutropenia (32%), thrombocytopenia (25%), and biliary obstruction/cholangitis (14%). Forty-three patients underwent resection (63%), and complete (R0) resection was achieved in 36 of those 43 patients (84%). The median overall survival was 18.2 months (95% confidence interval, 13-26.9 months) for all patients, 27.1 months (95% confidence interval, 21.2-47.1 months) for those who underwent resection, and 10.9 months (95% confidence interval, 6.1-12.6 months) for those who did not undergo resection. A decrease in CA 19-9 level after neoadjuvant therapy was associated with R0 resection (P = .02), which resulted in a median survival of 34.6 months (95% confidence interval, 20.3-47.1 months). Fourteen patients (21%) are alive and disease free at a median follow-up of 31.4 months (range, 24-47.6 months). CONCLUSIONS: Preoperative therapy with full-dose gemcitabine, oxaliplatin, and RT was feasible and resulted in a high percentage of R0 resections. The current results are particularly encouraging, because the majority of patients had borderline resectable disease.

BACKGROUND:Malignant melanoma only rarely metastasizes to the pancreas. As such, there is limited medical literature on the clinical course and outcomes for patients who have undergone surgical management of these tumors. The aim of our study was to review our experience with the surgical resection of melanoma metastatic to the pancreas. METHODS:The records of five patients (four females, one male) with surgically resected melanoma metastatic to the pancreas were retrospectively reviewed. Tumor characteristics, patient presentation, operative details, and follow-up data were evaluated. RESULTS:The primary site of melanoma was known in three cases and unknown in two cases. Four patients were symptomatic at presentation, including abdominal pain (n = 3), jaundice (n = 2), abdominal distension (n = 1), bleeding metastases (n = 1), and fatigue (n = 1). In one patient, the metastasis was an incidental discovery. Surgical resection was accomplished by pylorus-preserving pancreaticoduodenectomy in four patients and distal pancreatectomy in one patient. Single-site resection was done in two patients while the other three underwent synchronous multiple-site resections. Complications developed post-operatively in three patients. Two patients had progression of disease in the form of new metastatic lesions and received subsequent chemotherapy. The median survival was 11.4 months (range, 3-26 months). CONCLUSIONS:Aggressive surgical management of pancreatic metastases provides palliative relief of symptoms and may be considered in appropriately selected candidates.

BACKGROUND:Prognosis after surgery for pancreatic ductal adenocarcinoma (PDAC) is typically reported from the date of surgery. Survival estimates, however, are dynamic and may change based on the time already survived. The authors sought to assess conditional survival among a large cohort of patients who underwent resection of PDAC. METHODS:Between 1970 and 2008, 1822 patients who underwent resection for PDAC with curative intent were identified. Kaplan-Meier and Cox regression analyses were performed to validate established predictors of survival, and results were compared with 2-year conditional survival. RESULTS:Actuarial survival was 18% at 5 years, with a median survival of 18 months. Multivariate analysis revealed that tumor size, lymph node ratio, and positive margins were associated with worse survival (all P < .001). Differences in actuarial versus conditional survival estimates were greater the more years already survived by the patient. The 2-year conditional survival at 3 years-the probability of surviving to postoperative year 5 given that the patient had already survived 3 years-was 66% versus a 5-year actuarial survival calculated from the time of surgery of 18%. Stratification of 2-year conditional survival by lymph node ratio and margin status revealed that patients with high lymph node ratio or positive margins saw the greatest increase in 2-year conditional survival as more time elapsed (both P ≤ .01). CONCLUSIONS:Differences in actuarial versus conditional survival estimates were more pronounced based on the additional years already survived by the patient. Conditional survival may be a helpful tool in counseling patients with PDAC, as it is a more accurate assessment of future survival for those patients who have already survived a certain amount of time.

A better molecular characterization of intraductal papillary mucinous neoplasm (IPMN), the most frequent cystic precursor lesion of pancreatic adenocarcinoma, may have a pivotal role in its early detection and in the development of effective therapeutic strategies. BRG1, a central component of the chromatin remodeling complex SWI/SNF regulating transcription, is inactive in several malignancies. In this study, we evaluate the Brg1 expression in intraductal papillary mucinous neoplasm to better understand its role in the pancreatic carcinogenesis. Tissue microarrays of 66 surgically resected IPMNs were immunolabeled for the Brg1 protein. Expression patterns were then correlated with clinicopathologic parameters. Normal pancreatic epithelium strongly immunolabeled for Brg1. Reduced Brg1 expression was observed in 32 (53.3%) of the 60 evaluable IPMN lesions and occurred more frequently in high-grade IPMNs (13 of 17 showed loss; 76%) compared to intermediate-grade (15 of 29 showed loss; 52%) and low-grade IPMNs (4 of 14 showed loss; 28%) (P = .03). A complete loss of Brg1 expression was observed in 5 (8.3%) of the 60 lesions. Finally, a decrease in Brg1 protein expression was furthermore found in a low-passage noninvasive IPMN cell line by Western blot analysis. We did not observe correlation between Brg1 expression and IPMN subtype or with location of the cyst. We provide first evidence that Brg1 expression is lost in noninvasive cystic precursor lesions of pancreatic adenocarcinoma.

BACKGROUND:The incidence of hepatocellular carcinoma (HCC) is rising, and the options for surgical therapy of HCC have evolved recently, but use of surgical therapy has not been characterized on a representative, nationwide basis. We quantified trends in use, mortality, and patient and hospital characteristics for 3 surgical therapies for HCC (resection, ablation, and transplantation) in the United States from 1998 to 2008. METHODS:Hospital discharge data from the Nationwide Inpatient Sample were used to quantify procedure-related data for each year. Trends over time were summarized as the average annual percent change (AAPC) and corresponding 95% confidence interval (CI). RESULTS:The number of surgical procedures for HCC increased from 1416 to 6769 (AAPC, 13.5%; 95% CI, 10.2%-16.8%). Volumes increased for all surgical procedures, most notably for ablation (AAPC, 17.3%; 95% CI, 6.6%-29.2%) and transplantation (AAPC, 20.9%; 95% CI, 14.1%-28.1%). When analyzed as a proportion of total procedures, there were declines in the relative use of major hepatectomy (35% to 16%; AAPC, -7.2%, 95% CI, -8.8% to -5.6%) and wedge resection (37% to 22%; AAPC, -4.8%; 95% CI, -6.2% to -3.4%), while the proportion accounted for by transplantation increased (16% to 35%; AAPC, 4.4%; 95% CI, 0.2%-8.9%). Inpatient mortality decreased for each procedure individually and overall from 7.3% to 4.6% (AAPC, -7.7%; 95% CI, -10.8% to -4.5%), despite increasing age and comorbidity burden. CONCLUSIONS:The use of surgical therapy for HCC has increased dramatically over the last decade, with a relative shift away from liver resection and toward liver transplantation. These therapeutic modalities must be better targeted to make the most appropriate use of limited health care resources.