Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades.
ABSTRACT Randomized trials have demonstrated a benefit associated with adjuvant therapy for pancreatic cancer, and retrospective studies have demonstrated improvements in postoperative mortality. The purpose of this study was to evaluate whether these improvements could be identified in a cohort of patients who underwent resection for pancreatic cancer at a single institution over three decades.
Short- (30 days), intermediate- (1 year), and long-term survival were compared between decades. Long-term survival focused on patients who survived at least 1 year to minimize the effects of perioperative mortality and patient selection.
Between 1983 and 2009, 1147 pancreatic resections were performed for ductal adenocarcinoma, including 123 resections in the 1980s, 399 in the 1990s, and 625 in the 2000s. The 30-day mortality rates were 4.9%, 1.5% (P = 0.03 vs. 1980s), and 1.3% (P = 0.007 vs. 1980s). The 1-year mortality rates were 42%, 31% (P < 0.001 vs. 1980s), and 24% (P < 0.001 vs. 1980s and 1990s). In the group of patients who survived 1 year, the overall survivals were 23.2 months, 25.6 months (P = 0.6 vs. 1980s), and 24.5 months (P = 0.2 vs. 1980s). In a multivariate analysis adjusted for pathologic features, the decade of resection was not a significant predictor of long-term survival (hazard ratio = 1.1, P = 0.3).
Patients who underwent resection for pancreatic cancer between 2000 and 2009 experienced improved operative mortality and 1-year survival compared to those who underwent resection in the 1980s, while the long-term survival was similar over all three decades. These results underscore the need for early detection strategies and more effective adjuvant therapies for patients with pancreatic cancer.
Article: A novel survival-based tissue microarray of pancreatic cancer validates MUC1 and mesothelin as biomarkers.[show abstract] [hide abstract]
ABSTRACT: One-fifth of patients with seemingly 'curable' pancreatic ductal adenocarcinoma (PDA) experience an early recurrence and death, receiving no definable benefit from a major operation. Some patients with advanced stage tumors are deemed 'unresectable' by conventional staging criteria (e.g. liver metastasis), yet progress slowly. Effective biomarkers that stratify PDA based on biologic behavior are needed. To help researchers sort through the maze of biomarker data, a compendium of ∼2500 published candidate biomarkers in PDA was compiled (PLoS Med, 2009. 6(4) p. e1000046). Building on this compendium, we constructed a survival tissue microarray (termed s-TMA) comprised of short-term (cancer-specific death <12 months, n = 58) and long-term survivors (>30 months, n = 79) who underwent resection for PDA (total, n = 137). The s-TMA functions as a biological filter to identify bona fide prognostic markers associated with survival group extremes (at least 18 months separate survival groups). Based on a stringent selection process, 13 putative PDA biomarkers were identified from the public biomarker repository. Candidates were tested against the s-TMA by immunohistochemistry to identify the best markers of tumor biology. In a multivariate model, MUC1 (odds ratio, OR = 28.95, 3+ vs. negative expression, p = 0.004) and MSLN (OR = 12.47, 3+ vs. negative expression, p = 0.01) were highly predictive of early cancer-specific death. By comparison, pathologic factors (size, lymph node metastases, resection margin status, and grade) had ORs below three, and none reached statistical significance. ROC curves were used to compare the four pathologic prognostic features (ROC area = 0.70) to three univariate molecular predictors (MUC1, MSLN, MUC2) of survival group (ROC area = 0.80, p = 0.07). MUC1 and MSLN were superior to pathologic features and other putative biomarkers as predicting survival group. Molecular assays comparing cancers from short and long survivors are an effective strategy to screen biomarkers and prioritize candidate cancer genes for diagnostic and therapeutic studies.PLoS ONE 01/2012; 7(7):e40157. · 4.09 Impact Factor
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ABSTRACT: Our understanding of pancreatic ductal adenocarcinoma (PDAC) is shifting away from a disease of malignant ductal cells-only, toward a complex system where tumor evolution is a result of interaction of cancer cells with their microenvironment. This change has led to intensification of research focusing on the fibrotic stroma of PDAC. Pancreatic stellate cells (PSCs) are the main fibroblastic cells of the pancreas which are responsible for producing the desmoplasia in chronic pancreatitis (CP) and PDAC. Clinically, the effect of desmoplasia is two-sided; on the negative side it is a hurdle in the diagnosis of PDAC because the fibrosis in cancer resembles that of CP. It is also believed that PSCs and pancreatic fibrosis are partially responsible for the therapy resistance in pancreatic cancer. On the positive side, a fibrotic pancreas is safer to operate on compared to a fatty and soft pancreas which is prone for postoperative pancreatic fistula. In this review the impact of pancreatic fibrosis on diagnosis of pancreatic cancer and surgical decisions are discussed from a clinical point of view.Frontiers in physiology. 01/2012; 3:389.