Cancer Control

Pancreatic cancer is an aggressive disease with a poor prognosis. Hereditary factors have been reported in up to 10% of cases of pancreatic cancer. The clinical characteristics and genetic abnormalities have been identified for a proportion of this high-risk group, and the development of preventive strategies for these individuals is now a primary goal of cancer clinicians.

A review of the current literature regarding the genetics, screening, and prevention of pancreatic cancer and its precursor lesions was undertaken.

Risk factors for pancreatic cancer include smoking, chronic pancreatitis, and a genetic predisposition. The role of diabetes or a diet high in fat or meat remains unclear. The genetic mutations that accompany pancreatic cancer appear to occur in a temporal sequence, beginning in the earliest of precursor lesions. These mutations are detectable in pancreatic juice and, in conjunction with imaging, form the basis of screening programs for high-risk individuals. Not all precursor lesions will undergo malignant transformation, and testing is currently limited in its ability to determine which lesions will undergo transformation.

Avoiding tobacco smoking and minimizing risk factors associated with chronic pancreatitis are recommended to reduce the risk of pancreatic cancer. Individuals with a high-risk genetic background require counseling, genetic testing if appropriate (BRCA2 mutation or p16^INK4A inactivity) and secondary screening for pancreatic cancer in specialist centers. Risk stratification will improve as more genetic abnormalities causing pancreatic cancer are defined.

Accurate staging of pancreatic cancer is essential for surgical planning and for identification of locally advanced and metastatic disease that is incurable by surgery. Advances in endoscopic sonography (EUS), computed tomography (CT), and positron emission tomography have improved the accuracy of staging and reduced the number of incomplete surgical resections. Tissue acquisition is necessary in nonsurgical cases when chemoradiotherapy is considered. The complex regional anatomy of the pancreas makes cytologic diagnosis of malignancy at this region difficult without exploratory surgery. Although CT-guided fine-needle aspiration (FNA) is used for this purpose, reports of an increased risk of peritoneal dissemination of cancer cells and a false-negative rate of nearly 20% make this a poor choice. The ability to position the EUS-transducer in direct proximity to the pancreas by means of the stomach and duodenum, combined with the use of FNA, increases the specificity of EUS in detecting pancreatic malignancies.

The current literature regarding the accuracy of EUS with FNA in the evaluation of pancreatic cancer is reviewed.

EUS accuracy ranges from 78% to 94% for tumor staging and from 64% to 82% for nodal staging. EUS also enables FNA of lesions that are too small to be identified by CT or MRI or too well encased by surrounding vascular structures to safely allow percutaneous biopsy. The accuracy for detecting invasion into the superior mesenteric artery and vein is lower than that for detecting portal or splenic vein invasion, especially for large tumors. EUS permits delivery of localized therapy such as celiac plexus neurolysis for pain control and direct intra-lesional injection of antitumor therapy.

EUS in combination with FNA is a highly accurate method of preoperative staging of pancreatic cancer, especially those too small to be characterized by CT or MRI, and it has the ability to obtain cytological confirmation of pancreatic cancer.

Pancreatic cancer remains a difficult disease to treat. Diagnosis at an early stage may allow curative treatment with resection. In the past, the mortality associated with surgical treatment of pancreatic carcinoma was prohibitive but mortality associated with resection is now commensurate with all other major oncologic resections. Thus, the focus of surgical management has shifted to address several issues: the diagnosis and evaluation of patients with suspected pancreatic cancer, the role of preoperative endobiliary stenting, the role of laparoscopy, the extent of resection, the role of adjuvant and neoadjuvant treatment, and the role of specialized centers in treating the disease.

The current literature is reviewed to address these issues and help guide physicians who first encounter patients with suspected pancreatic cancer as well as surgeons who ultimately resect them. Practical evidence-based information to guide the decision-making process is provided.

Surgical morbidity and mortality have achieved parity with other types of major oncologic resection, and a distinct survival advantage is possible when such therapy is applied early in the disease stage. Issues regarding the use of stents, extent of resection, and pre- vs post-operative chemoradiation therapy are becoming clearer as our collective experience broadens.

Surgical treatment of pancreatic cancer should be aggressively pursued given the clearly established survival advantage and relief of symptoms achieved when it is applied appropriately.

Despite the acceptance of gemcitabine as the standard first-line agent for the treatment of advanced pancreatic cancer as well as the improved response rates seen with gemcitabine combinations, novel therapies are needed for this disease, which has one of the lowest survival rates. The growing understanding of the molecular basis of pancreatic cancer and the recent introduction of targeted therapeutic agents have initiated novel studies that have the potential to improve on existing treatments.

We review the rationale and the clinical studies of therapeutic agents that target some of the molecular abnormalities commonly found in pancreatic cancer.

Matrix metalloproteinase inhibitors (MMPIs), farnesyltransferase inhibitors (FTIs), and tyrosine-kinase inhibitors and monoclonal antibodies against growth factors or their receptors are novel agents that have undergone phase II or III trials. Phase III studies of MMPIs, alone or in combination with gemcitabine, and phase III studies of FTIs have produced disappointing results. Other agents in earlier phases of clinical development remain promising.

Despite the negative studies of MMPIs and FTIs, the results of phase II trials of other drugs are encouraging. Targeted agents may improve the prognosis of pancreatic cancer.

Pancreatic cancer is a formidable health problem, representing the 10th most common malignancy in the United States and the 4th most common cause of all cancer deaths. The overall 5-year survival rate is 4%, making this disease a model tumor in which to address the specialized care issues of palliative medicine.

General considerations in both medical decision-making and symptom management are reviewed. Treatment of patients with locally unresectable, recurrent, or metastatic disease is individualized, based on considerations that include patient age, patient wishes, family influence, insurance constraints, and geographic practice variations.

Success in managing progressive symptoms is needed to palliate patients with advanced pancreatic cancer. Common problems include biliary obstruction, depression, pain, intestinal obstruction, and fatigue.

Relief of pain and suffering associated with critical illness is required in managing patients with cancer. Pancreatic cancer is a model illness that mandates this need.

Cardiotoxicity is a rare but well-documented adverse effect of 5-fluorouracil (5-FU). The underlying cause of this side effect of 5-FU is uncertain.

We present a case report of a 63-year-old man treated for metastatic colon cancer who experienced chest pain while being treated with the FOLFIRI regimen. This case report documents coronary artery spasm on catheterization observed with the continuous infusion of 5-FU.

Cardiac catheterization obtained within 36 hours of the onset of chest pain revealed marked coronary vasospasm in the obtuse marginal coronary artery and a right coronary artery with a critical obstructive atherosclerotic plaque. Electrocardiogram revealed the myocardium area associated with the event was diffuse rather than localized to the right coronary artery.

This observation supports the vasospastic hypothesis for 5-FU–induced angina. Although rare, this type of cardiotoxicity with 5-FU is a potentially lethal side effect. Therapy with 5-FU should be discontinued and patients should be promptly treated.