New aspects of genetics and surgical management in pancreatic cancer: The Johns Hopkins experience

Pancreatic cancer remains a leading cause of cancer death in the USA. Recent progress provides hope for a better understanding of the molecular biology of pancreatic cancer. Structural chromosomal studies have identified recurrent chromosome abnormalities. Allelotype work has helped identify the loci of tumour suppressor genes (p53, DPC4, p16 and BRCA2), all of which appear to play a role in pancreatic carcinogenesis. K-ras oncogene activation has been linked to cigarette smoking, may be an early event in carcinogenesis and appears promising as a tool for early detection. Additionally, molecular genetics has enabled the accumulation of information in cases of familial pancreatic cancer, supporting the National Familial Pancreas Tumor Registry at Johns Hopkins. The recent surgical experience at Johns Hopkins is encouraging. In a cohort of 149 consecutive patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, the postoperative in-hospital mortality rate was 0.7%. The data for 201 resected patients from 1970 to 1994 indicated a 21% actuarial five-year survival rate, with 11 five-year survivors. Multivariate analysis indicated that the factors favouring long-term survival following pancreaticoduodenectomy include a tumour diameter less than 3 cm, negative resected lymph nodes, negative resection margins and surgery in the decade of the 1990s. The use of postoperative combined modality chemoradiation therapy also favoured long-term survival.