Gastrointestinal Cancer

Adenocarcinoma of the pancreas remains a lethal malignancy: The majority of patients with pancreatic cancer continue to present with advanced disease and die within a year of diagnosis. Despite this grim fact, some progress has been made over the past decade, particularly in the surgical management of patients with resectable and advanced disease. This well-constructed review by Drs. Ahrendt and Pitt succinctly details the advances that have been made and highlights many of the unresolved issues.

It is with great pleasure that I comment on the excellent article authored by Drs. Ahrendt and Pitt, who have provided a well-written, succinct, up-to-date review focusing on adenocarcinoma of the pancreas. The authors introduce the topic, discuss preoperative staging and assessment of resectability, cover the critical issues regarding resectional therapy and palliative surgery, and provide data on the results of such therapy, including mortality, morbidity, and quality-of-life outcomes. Emphasizing the importance of this topic, the authors note that pancreatic cancer is the fifth leading cause of cancer death in the United States.

Pancreatic cancer is the fifth leading cause of cancer death in the United States, with an overall survival rate of 3%. Unfortunately, only a minority of patients present with localized disease amenable to surgical resection.

Drs. Ahrendt and Pitt should be congratulated on a comprehensive and well-presented review of the surgical management of pancreatic cancer. Unfortunately, pancreatic cancer continues to be a major cause of cancer-related death. The majority (80%) of patients still present with unresectable locally advanced or metastatic disease.

Preoperative or postoperative pelvic radiation plus concurrent fluorouracil-based chemotherapy is standard adjuvant treatment for patients with T3 and/or N1/2 rectal cancer. Newer chemotherapeutic regimens have been developed for the treatment of patients with metastatic disease.

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.

Over the past decade, patients with locally advanced rectal cancer at The University of Texas M. D. Anderson Cancer Center have been managed with preoperative chemoradiation. Patients achieving a complete clinical response to preoperative chemoradiation have had better pelvic tumor control, sphincter preservation, and overall survival than those with gross residual disease. Some patients achieving a complete clinical response have even had rectal-preserving surgery (full-thickness local excision).

EAST MELBOURNE, Australia-A new prospective study has confirmed the usefulness of 18F-FDG PET in treatment planning for patients with confirmed or suspected colorectal cancer recurrence. In this study, 60% of planned surgeries were found to be unnecessary as the result of PET.

The combination of irinotecan (CPT-11, Camptosar) and gemcitabine (Gemzar) produced a 1-year survival rate of 27%, which is greater than that reported for gemcitabine alone in previous studies in patients with advanced pancreatic cancer (15% and 18% 1-year survival rates, respectively). These study results were published in a recent issue of the Journal of Clinical Oncology (20:1182-1191, 2002).

Studies of a new treatment strategy for colorectal cancer using a therapeutic cancer vaccine technology have begun enrolling patients at several trial sites around the United States and Canada.

The multistep process of carcinogenesis, which can take many years, provides many opportunities for intervention to inhibit disease progression. Effective chemoprevention agents may reduce the risk of cancer by inhibiting the initiation stage of carcinoma through induction of apoptosis or DNA repair in cells harboring mutations, or they may act to prevent promotion of tumor growth. Similarly, chemoprevention may entail blocking cancer progression to an invasive phenotype.

Recent combinations of chemotherapy have significantly improved the response rate and survival time for patients with metastatic colorectal cancer.

Tumor angiogenesis is a complicated process that is regulated by numerous factors simultaneously and in a coordinated fashion.

Cyclooxygenase-2 (COX-2) is the enzyme that normally synthesizes prostaglandins during an inflammatory response.

The prognosis for patients with metastatic colorectal cancer is poor. Use of irinotecan (CPT-11, Camptosar) results in modest response rates of approximately 20% in refractory patients diagnosed with this advanced stage of disease and offers a side-effect profile that improves on that of previous standard treatments.

Capecitabine (Xeloda) and irinotecan (CPT-11, Camptosar) both have demonstrated single-agent activity in patients with colorectal cancer.

Lorus Therapeutics announced recently that it has initiated a phase III trial to evaluate the macrophage activator Virulizin for the treatment of advanced pancreatic cancer. The company will present the results of this trial to the US Food and Drug Administration (FDA) in a new drug application at the completion of the study.

Solomon et al have written a valuable primer to guide clinicians in identifying, diagnosing, and treating familial colon cancer syndromes. The authors succinctly describe the essential features of each of the well-defined hereditary colon cancer syndromes, including those associated with colonic adenomas (hereditary nonpolyposis colorectal cancer [HNPCC] and familial adenomatous polyposis [FAP]) and colonic hamartomas (Peutz-Jeghers syndrome, juvenile polyposis, and Cowden syndrome). In addition to the specific features that might trigger recognition of one of these syndromes, we advise health-care providers to consider the possibility of hereditary cancer in cases with the following features:

This article is a comprehensive review of genetic testing for hereditary colorectal cancer detection. There is no longer any doubt that hereditary factors contribute to an increased risk of colon cancer. It remains to be seen how great their contribution is, how best to identify high-risk groups, and how best to care for carriers of the mutated genes. Approximately 25% of colorectal cancers occur in younger individuals or those with a family history of the disease, suggesting a heritable susceptibility.[1]

Surgery is still the most important treatment for solid tumors, regardless of the age of the patient. In this article, we discuss the physiology of aging as it relates to risk assessment in the elderly surgical oncology patient. A brief review of the role of surgery in the treatment of breast, colorectal, pancreatic, and gastric cancer is provided, because these solid tumors primarily affect elderly patients.

Over 130,000 new cases of colon cancer are diagnosed annually. Approximately 20% to 30% of these are attributable to familial risk, and 3% to 5% belong to a hereditary colorectal cancer predisposition syndrome.

LISBON, Portugal-The combination of capecitabine (Xeloda) and oxaliplatin (investigational in the United States) produced a 55% response rate in a phase II study of patients with advanced or metastatic colorectal cancer, Chris Twelves, MD, of Beatson Oncology Centre, Glasgow, Scotland, said at the 11th European Cancer Conference (abstract 1005). In addition, he said, 32% of patients in the study had stable disease.

The results of a 10-year study of a three-pronged treatment (surgical resection followed by chemotherapy and radiotherapy) for adenocarcinoma of the stomach showed that patients who underwent both surgical resection and postoperative

LISBON, Portugal-Short-term preoperative radiotherapy significantly lowers the risk of local recurrence in patients with rectal cancer who undergo standardized total mesorectal excision (TME), Cornelis J.H. van de Velde, MD, PhD, reported at

The article by Drs. Levy and Wiersema is an excellent overview of the indications, technical nuances, and efficacy of endoscopic ultrasound in the diagnosis and staging of pancreatic neoplasms. Endoscopic ultrasonography was introduced into the diagnostic armamentarium for gastroenterology approximately 15 years ago. Although the literature suggests a general increase in the utility and experience with endoscopic ultrasound, the technique remains most effective in the hands of experienced experts like Drs. Levy and Wiersema. Their article is a complete and thorough review of the indications and expected accuracy of the technique when evaluating a variety of different pancreatic lesions.