Clinical Review

Early Identification of Pancreatic Cancer

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Differential Diagnosis

It is critical to explore the many differential diagnoses for abdominal pain; the history and physical examination should guide the evaluation. Characterizing the pain according to location, chronology, severity, aggravating and alleviating factors, and associated symptoms can be most helpful. Pregnancy should be excluded in all women of childbearing age who present with abdominal pain.30,31

When pancreatic cancer is suspected, the differential diagnosis should include a malignant obstruction of the common bile duct, gastric cancer, cholangitis, cholelithiasis, choledolithiasis, cholecystitis, a choledochal cyst, duodenal or gastric ulcers, and acute or chronic pancreatitis.3 Additionally, conditions whose symptoms can mimic those of pancreatic cancer include abdominal aortic aneurysm, intestinal ischemia, and stricture of the bile duct. Symptoms associated with pancreatic ductal adenocarcinoma may also occur in patients with tumors of the bile duct, pancreatic lymphoma, gastric lymphoma, ampullary carcinoma, or hepatocellular carcinoma.3


Testing should include a complete metabolic panel, lipase, amylase, and a complete blood count with differential. These will reveal abnormalities in the total bilirubin and/or liver enzymes, and possible elevation of lipase and/or amylase, which could indicate acute, chronic, or hereditary pancreatitis—all of which are implicated in pancreatic cancer.2,35-37

No distinct tumor markers for pancreatic cancer have yet been identified. Though low in specificity for pancreatic cancer, the serum marker cancer antigen 19-9 (CA 19-9) is elevated in most patients when pancreatic cancer is diagnosed.38 Also, postsurgical levels of CA 19-9 are effective in evaluating patients’ response to neoadjuvant therapy and determining patient prognosis.39


Because it is noninvasive and relatively inexpensive, abdominal ultrasound (US) is often used first to investigate abdominal pain or jaundice; results suggestive of pancreatic cancer might include low echoic mass or dilatation of the pancreatic duct or of the common bile duct.40 However, conventional US is only 50% to 70% accurate for a diagnosis of pancreatic tumor.40,41

In many trials of imaging options for early detection and staging of pancreatic cancer, endoscopic US (EUS) has been deemed an effective modality for defining local T and N staging and for evaluating the potential for vascular involvement; CT has been pronounced effective for defining distant metastasis.23 For an algorithm detailing evaluation of the patient with a suspected pancreatic tumor, see Figure 2.23

All patients with suspected pancreatic cancer should be evaluated initially using CT or MRI.5Multidetector row CT (MDR-CT) is the most commonly used imaging modality for the detection and staging of pancreatic carcinoma.23 On contrast-enhanced CT, pancreatic adenocarcinoma commonly appears as a low-density area. EUS-guided fine-needle aspiration is an appropriate option for making a diagnosis with tissue samples.3,23,40 Triphasic pancreatic protocol CT provides about 90% accuracy for predicting resectability of a pancreatic tumor; EUS is comparably effective.3,5

MR ­cholangiopancreatography (MRCP) is a useful tool for visualizing the pancreas and the bile duct, while endoscopic retrograde cholangiopancreatography (ERCP) combines endoscopy and x-ray to visualize the pancreas and biliary tree.18,42 In one prospective, controlled study comparing these two modalities, MRCP and ERCP had 84% and 70% sensitivity, respectively, and 97% and 94% specificity, respectively, for diagnosis of pancreatic cancer (in cases actually diagnosed by histologic findings following surgical or fine-needle biopsy).42 Although ERCP makes it possible to obtain cytology and histology samples and to perform biliary stenting in patients with obstructive jaundice, it can miss tumors in the uncinate process, the accessory duct, and the tail of the pancreas.23,40

Tumor Staging for Pancreatic Cancer

Pancreatic tumors can develop from various pancreatic cell lines; they are defined by appearance, hormonal function, and origin cell type.43 The staging system for pancreatic exocrine cancer continues to evolve.44,45 In the seventh edition of the American Joint Committee on Cancer’s AJCC Staging Manual (2011),44 the AJCC bases the preoperative clinical staging of pancreatic cancer on the results of high-quality cross-sectional imaging, through which local resectability and the absence or presence of distant disease are determined44,45 (see Table 3,44,45).

Clinical staging categories for the pancreatic tumor are:

  • Resectable
  • Borderline resectable
  • Locally advanced, and
  • Metastatic disease.8

The significance of tumor staging extending past resectable versus unresectable is currently unknown, as treatment has had little effect on survival. Cancers involving the pancreas are typically described according to the location of involvement within the organ: the head, the body, the tail, or the uncinate process.8

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