Al B. Benson III, MD, FACP

This management guide covers the risk factors, symptoms, diagnosis, staging, and treatment of pancreatic cancer, pancreatic cystic neoplasms, pancreatic endocrine tumors (PETs), carcinoid tumors of the GI tract, adrenocortical carcinoma, and pheochromocytoma.

Treatment for patients with locally advanced, resectable rectal cancer has clearly evolved, with significant refinements in preoperative assessment, surgical technique, and use of preoperative chemoradiation.

Pancreatic cancer is the fifth leading cause of cancer death in the United States. In the year 2009, an estimated 42,470 new cases are expected to be diagnosed, and 35,240 deaths are expected to occur.

Localized pancreatic cancer, whether resectable or unresectable, is a separate entity from metastatic pancreatic cancer. Multiple studies have demonstrated that even in the setting of unresectable disease, the progression-free and overall survival of patients with localized pancreatic cancer exceeds that associated with metastatic pancreatic cancer.

Inoperable pancreatic adenocarcinoma is a dilemma that oncologists frequently encounter. Only 15% to 20% of patients are diagnosed when cancer of the pancreas is still surgically resectable. However, pancreaticoduodenectomy is the only curative option for this disease and should be offered to all patients who meet resection criteria and do not have significant comorbidities. For inoperable pancreatic cancer, the goals of treatment are to palliate symptoms and prolong life. Improved survival in locally advanced disease has been demonstrated with chemoradiation plus fluorouracil or with gemcitabine (Gemzar) alone. In metastatic disease, single-agent gemcitabine has been associated with improvement in symptoms and survival. Trials combining various chemotherapeutic agents with gemcitabine have not had a significant impact on overall survival, although meta-analyses suggest a small benefit. The targeted agent erlotinib (Tarceva) has shown a modest improvement in overall survival in combination with gemcitabine. This combination is another option for first-line therapy in patients with locally advanced or metastatic disease. Despite these recent advances, survival for patients with inoperable pancreatic cancer continues to be poor. Future investigations need to focus on understanding the molecular nature of this malignancy, with the goal of developing interventions based on this knowledge.

Pancreatic cancer is the fifth leading cause of cancer death in the United States.In the year 2005, an estimated 32,180 new cases will be diagnosed, and 31,800deaths will be ascribed to this cancer.

Cancers of the gallbladder andbile ducts are uncommon, aggressivemalignancies thatpresent both a diagnostic and therapeuticchallenge. With an annual incidenceof 7,200 cases in the UnitedStates, and the difficulty in diagnosingbiliary tract tumors, there is a paucityof data supporting therapeuticoptions. This comprehensive updateby Daines et al demonstrates the advancesin diagnostic and staging techniques,which have led to appropriatesurgical resection. Despite these advances,the prognosis of gallbladderand cholangiocarcinoma remains bleak,without significant improvement in survival,contrary to the author's optimisticintroduction. There is a lack of activechemotherapy and clinical trials exploringadjuvant and palliative therapy.Guidelines such as those advocated bythe National Comprehensive CancerNetwork (NCCN) help to establish standardsfor the evaluation and treatmentof these uncommon tumors and providea framework for the developmentof clinical trials.[1]

In the “Current Status of AdjuvantTherapy for Colorectal Cancer,”Dr. O’Connell provides importanthighlights of historical and recent developmentsin adjuvant treatment forcolon and rectal cancer. In addition,he provides insight into the future directionsof research for adjuvant therapyof cancer of the colon and rectum.As the review is thorough, wewould like to expand upon a coupleof areas including lymph node evaluation,changes to the staging system,and the use of molecular prognosticand predictive markers in futurestudies.

Both irinotecan (CPT-11, Camptosar) and paclitaxel have beenshown to have single-agent activity in adenocarcinomas of the esophagusand gastric cardia. A phase I trial of the combination at UCLAestablished the dose as irinotecan at 225 mg/m2 and paclitaxel at100 mg/m2 every 3 weeks. Preliminary data from a phase II trial of thisregimen in adenocarcinomas of the gastroesophageal junction showgood tolerability and promising activity (response rate of 27%), even inA previously treated patients.

The US National Cancer Institute Gastrointestinal Intergroup has contributed to the development of chemotherapy and radiation regimens for the treatment of stage II and III rectal cancer. The first Intergroup trial demonstrated improvement in relapse-free and overall survival for patients who received protracted venous infusion fluorouracil (5-FU) with radiation compared to those treated with bolus 5-FU.

The treatment of advanced colorectal cancer has been evaluated in a series of randomized trials, including infusional and modulated 5-fluorouracil (5-FU), and three meta-analyses encompassing trials of 5-FU plus