Adenocarcinoma of the pancreas: recent controversies, current management, and future therapies

Pancreatic cancer is the fourth leading cause of adult cancer mortality. The etiology of cancer of the pancreas remains a mystery despite the implication of various agents such as coffee, alcohol and cigarettes. Adenocarcinoma of the pancreas most commonly occurs in the pancreatic head where symptomatic jaudice or gastric outlet obstruction may cause the patient to seek medical care when the tumor is localized to the pancreas. In contrast, adenocarcinoma of the pancreatic body or tail is characterized by clinically silent growth, resulting in an advanced clinical stage at the time of diagnosis. Rational anticancer therapy for patients with adenocarcinoma of the pancreatic head is based upon an accurate knowledge, of the natural history and patterns of treatment failure. Patients who undergo surgical resection for adenocarcinoma of the pancreatic head have a long-term survival rate of only 13-25%'-and a median survival of 12-24 months.^7-10 Disease recurrence is common: local recurrence occurs in up to 90% of patients, ^11-15 liver métastases in 50-70% of patients, 8-9-12-16 and peritoneal recurrence (abdominal carcinomatosis) in approximately 50% of patients.17 Such modest survivals in patients with localized, early stage disease, combined with the potential morbidity and lengthy recovery period associated with pancreaticoduodenectomy, have resulted in confusion on the part of physicians regarding the appropriate use of surgery, both for curative resection and palliation. The current management of patients with pancreatic cancer at our institution involves: 1) a selective approach to the use of laparotomy based on the use of accurate radiographie imaging techniques, ajid the availability of reliable minimally invasive techniques for biliary decompression, 2) the use of multimodality therapy in all patients with localized, potentially resectable disease, and 3) a standardized approach to surgery and perioperative patient management. The goals of this approach are to maximize length and quality of patient survival while minimizing treatment-related toxicity and limiting the social and economic impact of complicated, multimodality therapy. The data in support of such an approach will be reviewed along with recent developments in the ongoing quest for effective systemic therapy.