Our data support an important role for BRCA2 germline mutations in a subpopulation of families with familial pancreatic cancer. BRCA2 mutation analysis should be included in molecular genetic testing and counseling strategies in families with at least two first-degree relatives affected with ductal adenocarcinoma of the pancreas.

CDKN2A germline mutations are rare in FPC families. However, these data provide further evidence for a pancreatic cancer-melanoma syndrome associated with CDKN2A germline mutations affecting p16. Thus, all members of families with combined occurrence of pancreatic cancer and melanoma should be counseled and offered screening for p16 mutations to identify high-risk family members who should be enrolled in a clinical screening program.

See "Notes" following "References." See "Appendix" for the names of the members of the German Familial Pancreatic Cancer (FaPaCa) study group of the Deutsche Krebshilfe and the EUROPAC study group.

The presence of p16INK4a alterations in resected tumors of patients with PC is connected with a worse prognosis, indicating patients that might benefit from adjuvant therapy regimens. p53 alterations, MDM2 overexpression, and loss of Rb expression could not be identified as prognostic markers from this study, but a larger study with greater statistical power might show a different result with regard to p53.

Based on several case-control studies, it has been estimated that familial aggregation and genetic susceptibility play a role in up to 10% of patients with pancreatic cancer, although conclusive epidemiologic data are still lacking. Therefore, we evaluated the prevalence of familial pancreatic cancer and differences to its sporadic form in a prospective multicenter trial. A total of 479 consecutive patients with newly diagnosed, histologically confirmed adenocarcinoma of the pancreas were prospectively evaluated regarding medical and family history, treatment and pathology of the tumour. A family history for pancreatic cancer was confirmed whenever possible by reviewing the tumour specimens and medical reports. Statistical analysis was performed by calculating odds ratios, regression analysis with a logit-model and the Kaplan-Meier method. Twenty-three of 479 (prevalence 4.8%, 95% CI 3.1-7.1) patients reported at least 1 first-degree relative with pancreatic cancer. The familial aggregation could be confirmed by histology in 5 of 23 patients (1.1%, 95% CI 0.3-2.4), by medical records in 9 of 23 patients (1.9%, 95% CI 0.9 -3.5) and by standardized interviews of first-degree relatives in 17 of 23 patients (3.5%, 95% CI 2.1-5.6), respectively. There were no statistical significant differences between familial and sporadic pancreatic cancer cases regarding sex ratio, age of onset, presence of diabetes mellitus and pancreatitis, tumour histology and stage, prognosis after palliative or curative treatment as well as associated tumours in index patients and families, respectively. The prevalence of familial pancreatic cancer in Germany is at most 3.5% (range 1.1-3.5%) depending on the mode of confirmation of the pancreatic carcinoma in relatives. This prevalence is lower than so far postulated in the literature. There were no significant clinical differences between the familial and sporadic form of pancreatic cancer.

Ineffective stress-coping strategies correlate with poor virtual laparoscopic performance. The need for effective intraoperative stress-coping strategies is evident.

Background/Aims: The molecular mechanisms contributing to the tumorigenesis of insulinomas are poorly understood. Disruption of the cell cycle due to inactivation of the p16^INK4a tumor-suppressor gene was identified in a variety of human tumors, including gastrinomas and nonfunctioning endocrine pancreatic carcinomas. In this study the role of p16^INK4a in the tumorigenesis of insulinomas was evaluated. Methods: Seventeen insulinomas (14 benign, 3 malignant) were analyzed for genetic alterations in the p16^INK4a tumor-suppressor gene by SSCP, PCR-based deletion and methylation-specific assays. p16 expression was determined by immunohistochemistry. Results: One malignant insulinoma showed a homozygous deletion of p16^INK4a and another two benign insulinomas revealed aberrant methylation of the p16^INK4a promoter region. All three tumors lacked p16 expression according to immunohistochemistry. None of the insulinomas carried intragenic p16^INK4a mutations. In total, 17% of insulinomas had p16^INK4a alterations. Conclusions: The p16^INK4a tumor-suppressor gene contributes to tumorigenesis in only a small subset of insulinomas.

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