Pancreatic, Neuroendocrine GI, and Adrenal Cancers

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, such as CA19-9, for pancreatic carcinoma 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 who have appropriate symptoms; such individuals include smokers, recent-onset diabetics, those with familial pancreatic cancer, or those with unexplained weight loss or diarrhea. This marker correlates with tumor burden and is useful in following disease and in assessing the adequacy of resection or therapy. CA19-9 should be interpreted with caution in patients who have biliary obstruction or jaundice, because it is falsely elevated in such patients. Furthermore, 5% to 15% of the population are unable to synthesize CA19-9; in such patients, levels of this marker would be falsely low, even in the presence of extensive tumor burden.

Laparoscopy

This diagnostic tool is useful for staging patients with pancreatic carcinoma and for formulating treatment plans. Approximately 10% to 15% of patients considered 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.

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 to 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 about 70%.

CT. This diagnostic tool provides better definition of the tumor and surrounding structures than does ultrasonography. CT scan is also 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 (with thin "cuts" of the pancreas) increases the accuracy of detecting pancreatic carcinoma in general and vessel encasement in particular. This technique permits rapid data acquisition and computer-generated 3D images of the mesenteric arterial and venous tributaries on many planes. Spiral CT is quicker and less expensive than angiography and uses less contrast medium.

PET. The use of positron emission tomography (PET) with ¹⁸fluorodeoxyglucose (FDG) in the evaluation of patients with pancreatic cancer has been proposed for evaluation of the primary tumor and detection of distant metastases. A 2001 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%). Although potentially useful in selected clinical scenarios, routine application of FDG-PET for pancreatic cancer staging is not recommended by consensus groups, including the National Comprehensive Cancer Network (NCCN).

MRI. MRI is considered equivalent to pancreatic protocol CT imaging for the initial evaluation of pancreatic cancer by consensus groups, including the NCCN. Although MRI techniques have improved, endoscopic retrograde cholangiopancreatography (ERCP) is mandatory for the workup of many patients, in particular those who require therapeutic intervention such as stent placement.

Endoscopic ultrasonography (EUS). 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. EUS is also valuable in obtaining tissue confirmation of the pancreatic mass before starting treatment for unresectable or borderline resectable lesions.

Recently, some investigators have expressed interest in using EUS to screen high-risk patients, individuals with defined genetic syndromes, and those with a strong family history of pancreatic cancer for evidence of the disease. In a recent study of 78 high-risk patients, screening showed neoplastic changes in 10% of the subjects. However, the challenge of EUS is the current inability to detect malignant precursor lesions, known as PanIN (pancreatic intraepithelial neoplasia).

Endoscopic retrograde cholangiopancreatography (ERCP). This technique may some day be supplanted as a diagnostic tool by EUS and magnetic resonance cholangiopancreatography (MRCP), although ERCP is now 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. Complications of bile and pancreatic duct manipulation include infection and pancreatitis. These risks must be carefully weighed against the added value of ERCP in a completely imaged patient.

Pathology

Adenocarcinoma

This type of tumor, arising from the exocrine gland ductal system, is the most common type of pancreatic cancer, accounting for 95% of all cases. Two-thirds of these cancers originate in the pancreatic head; the remainder arise in the body or tail. Most ductal carcinomas are mucin-producing tumors and usually are associated with a dense desmoplastic reaction.

Although most pancreatic adenocarcinomas arise from the ductal epithelium, pancreatic acinar carcinomas and cancers arising from mucinous cystic neoplasms are also found.

Multicentricity. Multicentricity, which is usually microscopic, is not unusual.

TABLE 1TNM staging of pancreatic tumors

FIGURE 1Actuarial survival as a function of regional lymph node status in patients with pancreatic cancer.

Metastatic spread. Perineural invasion occurs in the majority of patients with pancreatic carcinoma. In addition, pancreatitis distal to and surrounding the tumor is usually present. Most patients present with lymph node metastases in the region of the pancreaticoduodenal drainage basins. The subpyloric and inferior pancreatic head, SMA, and para-aortic lymph node groups also may be involved. Distant metastatic spread most commonly involves the liver and peritoneal surfaces.

Staging and Prognosis

Pancreatic adenocarcinoma is staged according to local spread of disease, nodal status, and distant metastatic involvement using the American Joint Committee on Cancer (AJCC) TNM system (Table 1). The tumor (T) staging of the primary tumor includes an analysis of direct extension of disease to the duodenum, bile duct, or peripancreatic tissues. A T4 advanced cancer may extend directly to the SMA or celiac axis, meaning that the cancer is unresectable.

Independent prognostic factors

Lymph node metastases and tumor size and differentiation have independent prognostic values in patients with pancreatic carcinoma. Significantly improved survival is seen in patients with smaller lesions, lymph node-negative tumors, and tumors in which the surgical margins are not involved.

Lymph node and margin status

Prior to the era of adjuvant therapy, lymph node status was the most dominant prognostic factor (Figure 1). It is now rivaled by surgical margin status in series where surgical margins have been meticulously examined.