PANCREATIC CANCER
Pancreatic cancer is the fifth leading cause of cancer death in the United States. In the year 2007, an estimated 37,170 new cases are expected to be diagnosed and 33,370 deaths are expected to occur.
Incidence and epidemiology
Gender The incidence of pancreatic cancer is slightly higher in males than in females. These gender differences are most prominent among younger individuals.
Age The peak incidence of pancreatic carcinoma occurs in the seventh decade of life. Two-thirds of new cases occur in people > 65 years old.
Race The incidence of pancreatic cancer is higher in the black population, with an excess risk of 40%-50% over that in whites. Perhaps more importantly, black males probably have the highest risk of pancreatic cancer worldwide.
Survival Cancer of the pancreas is a highly lethal disease historically, with few reports of 5-year survivors. However, more recent series have shown a decrease in both operative mortality and overall morbidity. There has also been a significant increase in 5-year survival after curative resection (21%–25%). Factors that appear to be important in predicting long-term survival after resection include clear surgical margins, negative lymph nodes, and reduced perioperative mortality.
Adenocarcinoma of the pancreas, the most common histologic type, has a median survival of 9–12 months and an overall 5-year survival rate of 3% for all stages. At the time of diagnosis, over 50% of patients with pancreatic adenocarcinoma have clinically apparent metastatic disease. Among patients whose disease is considered to be resectable, 50% will die of recurrent tumor within 2 years.
Etiology and risk factors
The specific risk factors for pancreatic cancer are not as striking as those for other GI malignancies, such as esophageal and gastric carcinomas. There does, however, appear to be a significant relationship between pancreatic cancer and environmental carcinogens.
Cigarette smoking Cigarette smoke is one of the carcinogens directly linked to the causation of pancreatic malignancies. Heavy cigarette smokers have at least a twofold greater risk of developing pancreatic carcinoma than nonsmokers. In Japan, cigarette smoking carries an even greater risk, which can be as much as 10-fold in men smoking one to two packs of cigarettes daily.
N-nitroso compounds, found particularly in processed meat products, reliably induce pancreatic cancer in a variety of laboratory animals. No study has directly linked dietary carcinogens to pancreatic cancers in humans.
Caffeine The contribution of caffeine consumption to the development of pancreatic carcinoma is controversial. A case-controlled study showed a correlation between caffeine consumption and pancreatic cancer. However, other studies have been unable to confirm this relationship.
Alcohol A clear-cut relationship between alcohol use and pancreatic carcinoma has not been shown.
Diabetes does not seem to be a risk factor for pancreatic cancer. However, 10% of all patients with pancreatic carcinoma present with new-onset diabetes.
Genetic factors Cancer of the pancreas is a genetic disease. To date, more than 80% of resected pancreatic cancers have been found to harbor activating point mutations in K-ras. In addition, the tumor-suppressor genes p16, p53, and DPC4 are all frequently inactivated in this cancer.
Familial pancreatic carcinoma has been associated with the following genetic syndromes: hereditary pancreatitis, ataxia-telangiectasia, hereditary nonpolyposis colorectal cancer (HNPCC), familial atypical mole melanoma (FAMM) syndrome, Peutz-Jeghers syndrome, and familial breast cancer. Families with p16 germline mutations may be at higher risk of developing pancreatic cancer than those without these mutations.
Signs and symptoms
The initial clinical features of pancreatic carcinoma include anorexia, weight loss, abdominal discomfort or pain, and new-onset diabetes mellitus or thrombophlebitis. The vague nature of these complaints may delay diagnosis for several months.
Pain Specific symptoms usually relate to localized invasion of peripancreatic structures. The most common symptom is back pain, which stems from tumor invasion of the splanchnic plexus and retroperitoneum or pancreatitis. This pain is described as severe, gnawing, and radiating to the middle of the back. Pain can also be epigastric or in the right upper quadrant if bile duct obstruction is present.
Jaundice In a majority of cases, patients with pancreatic cancer present with epigastric or back pain and/or jaundice. Painless or sometimes painful jaundice occurs with early lesions near the intrapancreatic bile duct.
GI symptoms Tumor invasion of the duodenum or gastric outlet may give rise to nausea or vomiting as a presenting symptom. This symptom is rare early in the course of the disease. Changes in bowel habits related to pancreatic insufficiency may also be present, along with associated steatorrhea.
Glucose intolerance Recent onset of glucose intolerance in an elderly patient associated with GI symptoms should alert physicians to the possibility of pancreatic carcinoma.
A palpable gallbladder occurring in the absence of cholecystitis or cholangitis suggests malignant obstruction of the common bile duct until proven otherwise. This so-called Courvoisier’s sign is present in about 25% of all patients with pancreatic cancer.
Other physical findings include Trousseau’s syndrome (migratory superficial phlebitis), ascites, Virchow’s node (left supraclavicular lymph node), or a periumbilical mass (Sister Mary Joseph’s node).
Screening and diagnosis
Early diagnosis of pancreatic carcinoma is difficult but essential if surgical resection and cure are to be improved. Defining early lesions at a resectable stage remains a diagnostic challenge. To date, leading medical organizations have not recommended routine screening of asymptomatic individuals for pancreatic cancer.
Serum markers The use of serologic tumor markers for pancreatic carcinoma, such as CA19-9, was originally thought to be appropriate as a screening tool. However, since the prevalence of pancreatic carcinoma in the general population is extremely low (0.01%), many false-positive screening results are generated. Also, the sensitivity of CA19-9 is not high (20%) in stage I cancers. Nevertheless, CA19-9 may be a useful marker for diagnosing patients at high risk with the appropriate symptoms, such as smokers, recent-onset diabetics, those with familial pancreatic cancer, or those with unexplained weight loss or diarrhea. This marker also is useful in following disease and in assessing the adequacy of resection or therapy.
No currently available serum marker is sufficiently accurate to be considered reliable for screening asymptomatic patients.
Laparoscopy is useful for staging patients with pancreatic carcinoma and for formulating treatment plans. Approximately 10%–15% of patients thought to have resectable disease are found to have distant metastases at laparoscopy. The false-negative rate of laparoscopy is < 10%. The strongest indications for laparoscopy are locally advanced disease and tumors of the body and tail of the pancreas.
Peritoneal cytology also is being explored for the diagnosis of pancreatic carcinoma. Cytology is positive in 5%-10% of patients who are thought to have localized disease. There are anecdotal cases of long-term survival after resection where positive cytology of peritoneal washings was noted. However, the clinical/prognostic value of this test is not yet known.
Imaging techniques
Imaging for pancreatic carcinoma is best performed with conventional ultrasonography and CT.
Ultrasonography The limit of sonographic resolution for early pancreatic carcinoma is a diameter of 1.0–1.5 cm. A mass located in the pancreatic head will produce dilatation of the common bile duct and pancreatic duct. The actual sensitivity of ultrasonography in the diagnosis of pancreatic carcinoma is ~70%.
CT provides better definition of the tumor and surrounding structures than does ultrasonography and is operator-independent. CT correctly predicts unresectable tumors in 85% of patients and resectable tumors in 70% of patients. Findings of tumor unresectability on CT scanning include distant lymphadenopathy, encasement or occlusion of the superior mesenteric artery (SMA) or celiac artery, occlusion of the portal vein or superior mesenteric vein (SMV), and distant metastases. Spiral CT increases the accuracy of detecting pancreatic carcinoma in general and vessel encasement in particular. This technique permits rapid data acquisition and computer-generated three-dimensional (3D) images of the mesenteric arterial and venous tributaries in any plane. Spiral CT is quicker and less expensive and uses less contrast medium than angiography.
PET The use of positron emission tomography with 18fluorodeoxyglucose (FDG-PET) in the evaluation of patients with pancreatic cancer is expanding. A recent study of 126 patients with focal, malignant, or benign pancreatic lesions showed high sensitivity of FDG-PET for detection of small pancreatic neoplasms. Lack of focal glucose uptake excludes pancreatic neoplasms (sensitivity 85.4%, specificity 60.9%).
MRI At present, MRI is not as accurate as CT in diagnosing and staging pancreatic carcinoma. MRI may be as useful as CT in staging and can provide magnetic resonance angiography and magnetic resonance cholangiopancreatography (MRC) images if needed. As yet, MRC is not a standard test for the diagnosis of pancreatic carcinoma, but it may become helpful in the future.
Endoscopic ultrasonography (EUS) is a newer modality for the diagnosis of pancreatic carcinoma, with an overall diagnostic accuracy rate of approximately 85%–90%. For the assessment of regional lymph node metastases, the accuracy of EUS is 50%–70%. This technique is also important in the evaluation of portal vein/SMV involvement by tumor. In addition, EUS-guided fine-needle cytology of periampullary tumors may yield new information with respect to the diagnosis of pancreatic cancer and may be less risky in spreading cells by needle tracking than by percutaneous biopsies.
In a comparison of EUS and spiral CT, both techniques showed comparable efficacy in detecting tumor involvement of lymph nodes and the SMVs and portal veins. However, EUS is less helpful in the evaluation of the SMA.
Endoscopic retrograde cholangiopancreatography (ERCP) may someday be supplanted as a diagnostic tool by EUS, although, at present, ERCP is used in many clinics. Also, if a patient presents with jaundice and the CT scan reveals dilatation of the common bile duct without an obvious mass, ERCP may be complementary to spiral CT. ERCP findings of pancreatic cancer include an abrupt or tapered cutoff of either or both the main pancreatic and common bile ducts.
