Ductal adenocarcinoma – diagnosis and staging
The most widespread and available imaging modality is transabdominal ultrasonography, which is able to identify pancreatic masses. However, ultrasound is poorly accurate in depicting the characteristics of the tumor, because the pancreas is located deep in the abdomen. On ultrasonography, pancreatic ductal adenocarcinoma appears as an hypoechoic mass (darker than the surrounding pancreas). The associated dilation of the common bile duct, when present, is well detectable.
In jaundiced patients, it may be necessary to place a stent (a small tube made of plastic or of metal) to relieving a blocked common bile duct and resolve jaundice. This is usually done through an endoscopic procedure called ERCP (endoscopic retrograde cholangiopancreatography). The procedure consists of two distinct phases:
- Diagnostic phase: a very small catheter is endoscopically guided through the ampulla of Vater into the common bile duct. A small amount of contrast material is then injected, and x-rays are taken. This dye outlines the bile duct and the pancreatic duct, and shows the site and the morphology of biliary blockage that might be due to pancreatic cancer.
- Operative phase: a small cut is made on the ampullary orifice (papillotomy), then the stent is passed through the endoscope and is placed into the bile duct. The stent helps keep the common bile duct open and resists compression from the surrounding cancer.
In the course of an ERCP it is possible to perform a brushing biopsy of the common bile duct to check for neoplastic cells, especially if the pancreatic duct has been extensively infiltrated by the pancreatic neoplasms. This type of biopsy is however poorly accurate. ERCP is an invasive procedure which is associated with a specific complication profile, including severe acute pancreatitis. Furthermore, ampullary cannulation may be difficult, and guidewire and stent placement may fail if the bile duct is small or tortuous. In such cases, jaundice can be resolved placing a percutaneous transhepatic biliary drainage (PTBD). A thin catheter is placed percutaneously within the intrahepatic bile ducts until the common bile duct.
The finding of a pancreatic mass suspicious for ductal adenocarcinoma requires high-quality cross-sectional imaging to confirm the radiologic diagnosis and to stage the neoplasm. A staging system is a standardized way in which the cancer care team describes the extent that a cancer has spread, and contains different pieces of information, including:
- The size of the primary tumor
- Whether the tumor has spread to nearby organs or vessels
- Whether the tumor has spread to nearby lymph nodes
- Whether the tumor has spread (metastasized) to distant organs
Here are described the imaging tests to diagnose and stage pancreatic ductal adenocarcinoma.
- Contrast-enhanced computed tomography (CT). The CT scan is an x-ray test (it uses ionizing radiations) that produces detailed cross-sectional images of the body. 3D reconstruction softwares allow detailed tumor characterization. CT scans show the pancreas fairly clearly and often can confirm the location of the tumor, which appears hypodense and poorly enhanced. CT scans can also show the organs near the pancreas, as well as lymph nodes and distant organs where the cancer might have spread.
- Magnetic resonance imaging (MRI). MRI scan use radio waves and strong magnets instead of x-rays. It is a multiplanar imaging modality. MRI is less employed than CT-scan for the staging of pancreatic ductal adenocarcinoma, but it may be very useful when the tumor has a complex morphology (mixed lesion with solid and cystic areas), or when the differential diagnosis with other pancreatic neoplasms is unclear.
- Contrast-enhanced ultrasonography (CEUS). This is an new imaging technique that involves the use of microbubble contrast agents to show real-time tissue perfusion information. In CEUS examination, ductal adenocarcinoma typically shows poor enhancement during all the dynamic phases. Loco-regional CEUS staging of ductal adenocarcinoma in expert hands is accurate. Both margins and size of the lesion are more visible, improving the detection of vascular infiltration. In addition, CEUS improves hepatic staging.
- Ecoendoscopic ultrasound (EUS). Endoscopic ultrasound is performed using an ultrasound probe that is attached on the tip of an endoscope. This allows direct vision of the duodenum and of the papillary region as well as a very detailed ultrasonography of the pancreas, which sits next to the duodenum. It is probably better than CT scan for spotting small tumors. If a tumor is seen, a trans-gastric or a trans-duodenal biopsy can be performed during this procedure.
- Positron-emission tomography (PET). PET-scan involves the use of a very small dose of a intravenous radiotracer (known as 18-fluorodeoxyglucose or FDG). Neoplastic cells absorb large amount of FDG, which is detected by the scanner. These functional images have however insufficient spatial resolution; hence PET-scan is combined with CT-scan (PET-CT) to provide detailed images of the primary tumor. PET-CT may be especially useful for spotting cancer that has spread beyond the pancreas.
In the diagnostic work-up of pancreatic ductal adenocarcinoma, Ca 19.9 serum levels are often measured. Ca 19.9 is a simple blood test that measures the level of antigens released by pancreatic tumor cells. Ca 19.9 levels are elevated in the blood of many patients with pancreatic ductal adenocarcinoma. However, there are also some non-cancerous conditions that cause a high level of Ca 19.9, such as gallstones, pancreatitis, cystic fibrosis, liver disease, pulmonary and thyroid diseases. Furhermore, Ca 19.9 can be elevated in people with obstruction of the bile ducts, that is the case of many patients with pancreatic ductal adenocarcinoma. On the contrary, in patients who lack the Lewis antigen (a blood type protein on red blood cells), which is about 10% of the Caucasian population, Ca19.9 is not expressed, even in those with large tumors. That’s why Ca 19.9 is not particularly useful as a diagnostic test for pancreatic cancer. After the diagnosis of pancreatic cancer is confirmed and if the individual’s Ca 19.9 level was elevated before treatment, the Ca 19.9 test can be used as a prognostic factor.
Once the radiologic characterization has been obtained (tumor size, relation with peripancreatic vessels, lymph node status, presence of metastases), this information is combined to assign a stage. The current staging is based on the TNM system (tumor/node/metastasis), according to the American Joint Commitee on Cancer (AJCC, www.cancerstaging.org). Tumor stage is expressed in Roman numerals I through IV. Here are the AJCC stage groups of pancreatic ductal adenocarcinoma (seventh edition, 2010):
- Stage IA: The tumor is confined to the pancreas and is less than 2 cm in size. It has not spread to nearby lymph nodes or distant sites.
- Stage IB: The tumor is confined to the pancreas and is larger than 2 cm in size. It has not spread to nearby lymph nodes or distant sites.
- Stage IIA: The tumor is growing outside the pancreas but not into superior mesenteric artery or celiac trunk. It has not spread to nearby lymph nodes or distant sites.
- Stage IIB: The tumor is either confined to the pancreas or growing outside the pancreas but not superior mesenteric artery or celiac trunk. It has spread to nearby lymph nodes but not distant sites.
- Stage III: The tumor is growing outside the pancreas into superior mesenteric artery or celiac trunk. It may or may not have spread to nearby lymph nodes. It has not spread to distant sites.
- Stage IV: The cancer has spread to distant sites.
Radiologic staging divides pancreatic ductal adenocarcinoma into groups based on whether or not it is likely it can be removed surgically:
- Resectable disease (stage IA, IB, IIA, IIB)
- Locally advanced unresectable disease (stage III)
- Metastatic disease (stage IV)
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