Surgical resection of malignant melanoma metastatic to the pancreas: case series and review of literature.

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.

Pancreatic cancer.

Substantial progress has been made in our understanding of the biology of pancreatic cancer, and advances in patients' management have also taken place. Evidence is beginning to show that screening first-degree relatives of individuals with several family members affected by pancreatic cancer can identify non-invasive precursors of this malignant disease. The incidence of and number of deaths caused by pancreatic tumours have been gradually rising, even as incidence and mortality of other common cancers have been declining. Despite developments in detection and management of pancreatic cancer, only about 4% of patients will live 5 years after diagnosis. Survival is better for those with malignant disease localised to the pancreas, because surgical resection at present offers the only chance of cure. Unfortunately, 80-85% of patients present with advanced unresectable disease. Furthermore, pancreatic cancer responds poorly to most chemotherapeutic agents. Hence, we need to understand the biological mechanisms that contribute to development and progression of pancreatic tumours. In this Seminar we will discuss the most common and deadly form of pancreatic cancer, pancreatic ductal adenocarcinoma.

Genetic and epigenetic alterations of familial pancreatic cancers.

BACKGROUND: Little is known about the genetic and epigenetic changes that contribute to familial pancreatic cancers. The aim of this study was to compare the prevalence of common genetic and epigenetic alterations in sporadic and familial pancreatic ductal adenocarcinomas. METHODS: DNA was isolated from the microdissected cancers of 39 patients with familial and 36 patients with sporadic pancreatic adenocarcinoma. KRAS2 mutations were detected by BstN1 digestion and/or cycle sequencing. TP53 and SMAD4 status were determined by immunohistochemistry on tissue microarrays of 23 archival familial pancreatic adenocarcinomas and in selected cases by cycle sequencing to identify TP53 gene mutations. Methylation-specific PCR analysis of seven genes (FoxE1, NPTX2, CLDN5, P16, TFPI-2, SPARC, ppENK) was done on a subset of fresh-frozen familial pancreatic adenocarcinomas. RESULTS: KRAS2 mutations were identified in 31 of 39 (80%) of the familial versus 28 of 36 (78%) of the sporadic pancreatic cancers. Positive immunolabeling for p53 was observed in 57% of the familial pancreatic cancers and loss of SMAD4 labeling was observed in 61% of the familial pancreatic cancers, rates similar to those observed in sporadic pancreatic cancers. The mean prevalence of aberrant methylation in the familial pancreatic cancers was 68.4%, which was not significantly different from that observed in sporadic pancreatic cancers. CONCLUSION: The prevalence of mutant KRAS2, inactivation of TP53 and SMAD4, and aberrant DNA methylation of a seven-gene panel is similar in familial pancreatic adenocarcinomas as in sporadic pancreatic adenocarcinomas. These findings support the use of markers of sporadic pancreatic adenocarcinomas to detect familial pancreatic adenocarcinomas.