Detection and Diagnosis of Pancreatic Cancer
Detecting and diagnosing pancreatic cancer can be difficult, especially because the symptoms are not always obvious, often develop gradually, and can be mistaken for other conditions. At times, pancreatic tumors are found incidentally when a patient is exploring another medical condition. If pancreatic cancer is suspected, there are a variety of tests your doctor may perform. After assessing your situation, your doctor may then perform blood tests, order imaging studies, and/or biopsy the mass. These tests will help your doctor arrive at the most accurate diagnosis and help to direct your treatment plan.
Your evaluation will begin with a thorough medical history and physical examination focusing on signs and symptoms associated with pancreatic cancer. Questions will focus on your symptoms, any unintentional weight loss, smoking history and family history. The physical examination will begin with your eyes and skin, looking for signs of jaundice and then focus on your abdomen. Your doctor will check for masses or fluid buildup in the areas near your pancreas, stomach, liver, and gallbladder. Your doctor will search for signs of (lymph nodes at the belly button or above the left collar bone).
After a history and physical, your doctor will order tests to secure the diagnosis. Tests commonly used in the workup and management of patients with pancreatic cancer are outlined below.
There is no currently available blood test that can be used to definitively diagnose pancreatic cancer. Despite this, several blood tests are helpful in the workup and management of patients with the disease, including liver function tests and certain tumor markers.
The liver function panel includes a measurement of the protein level (albumin), the bilirubin, the transaminases (AST and ALT), and the alkaline phosphatase. This panel is obtained early in the workup of patients with pancreatic cancer. Obstruction of the bile will cause an elevation in the bilirubin level and the alkaline phosphatase level, and may cause an elevation in the transaminases. Because many patients with pancreatic cancer have lost considerable weight, the protein level and albumin level are often low.
Tumor markers are molecules produced by a cancer that are released into the blood stream and can be measured. The two tumor markers that are commonly used in the management of patients with pancreatic cancer are CA 19-9 and CEA.
CA 19-9 is a carbohydrate commonly released into the blood by pancreatic cancer, and can be used as a barometer reflecting response to therapy. In patients with a known diagnosis of pancreatic cancer, if an elevated CA 19-9 that falls with therapy, this is a good indication that the therapy is working. However, some benign conditions, like pancreatitis and jaundice, will elevate the CA 19-9 level in the absence of cancer. For this reason, CA 19-9 cannot and should not be used as a screening tool for pancreatic cancer. Furthermore, not every person or tumor is capable of making CA 19-9, so it is only useful in a subset of patients with pancreatic cancer. The normal range of CA 19-9 in the blood of a healthy individual is 0-37 U/mL (units/milliliter).
CEA (carcinoembryonic antigen) is a protein that is released into the blood by several gastrointestinal cancers. Initially described in colon cancer, CEA is also released by many pancreatic cancers, making it a useful tool in the management of many patients with pancreatic cancer. However, the CEA can be elevated by several other factors in the absence of cancer (most notably smoking), so it is not a useful screening tool. Like CA19-9, CEA is most useful as a tool to measure the effectiveness of therapy. A falling CEA suggests that the therapy is working, while a rising CEA suggests that the treatment strategy may need to be revised. The normal range of CEA is less than 2.5 ng/mL (nanograms per milliliter).
The CEA is also useful in the workup and diagnosis of pancreatic cysts. There are several different types of pancreatic cysts. When fluid is aspirated from a cyst and sent for biochemical analysis, the CEA can be measured. Mucin producing cysts, most of which are benign at presentation, have malignant potential. An elevation of the cyst fluid CEA (typically above 192 ng/mL) is helps making the diagnosis of a mucin producing cyst. The absolute level of CEA within the cyst fluid has not, however, been correlated with the presence or risk of developing a cancer in that cyst.
Imaging studies provide vital information about the location of a pancreatic mass, its relationship to the surrounding structures, and whether there is any evidence that the tumor has spread beyond the pancreas. Many of the commonly used imaging modalities used in the evaluation and management of patients with pancreatic cancer are outlined below.
Abdominal Ultrasound (Transabdominal)
A transabdominal ultrasound is a non-invasive test using sound waves, in which a probe is place on the patient’s abdomen and back to scan the abdominal organs. The technician uses a gel to interface between the probe and the patient’s body, because sound waves travelling through air are not captured by the machine. Using this technology, the radiologist can assess the liver, kidneys, spleen, and gallbladder. It is often used to diagnose gallstones. Certain portions of the pancreas can also be visualized. However, because there is often air in the stomach, which lies over the pancreas, many parts of the pancreas cannot be well visualized using a transabdominal ultrasound. Secondary signs of pancreatic cancer, such as dilated bile ducts, can e well seen. Ultrasound does not involve ionizing radiation.
Computed Tomography (CT, CAT) Scan
CT scanning is almost always used in the evaluation and management of patients with pancreatic cancer. The computer reconstructs images in three different planes allowing your physicians to determine the location of the tumor and its relationship to the surrounding structure. It is important that patients have both oral and intravenous contrast during the exam for accurate evaluation. The best quality images are obtained when the scan is timed properly to assess the arteries and veins around the pancreas and within the liver. During the exam, the patient lies on a table than moves through a ring shaped imager. CT scans do involve the use of ionizing radiation.
Alert: Some patients are sensitive to the intravenous contrast dye that is used for CT scans. CT scanning without the IV contrast has little utility for patients with pancreatic cancer. Many patients with a contrast sensitivity can safely receive the dye after being pre-medicated. Patients with a severe allergy to the dye, will need to be evaluated using another imaging modality.
Also, the dye used for CT scans can affect kidney function. Many patients with mild renal insufficiency can safely undergo CT scanning with intravenous contrast, but some will require an alternative imaging modality.
Magnetic Resonance Imaging (MRI)
MRI scans use radio waves and powerful magnets to produce images of the body and is often used in the evaluation of patients with pancreatic cancer. An MRI produces detailed cross-sectional images of the body in three different planes. In many respects, CT and MRI provide similar images, but the MRI gives the radiologist more options for altering the sequences to obtain images for specific purposes
An MRI exam can take up to an hour and a half and requires the patient to lie on a bed within a narrow tube. The machine often also makes a loud banging noise during the scan. Image quality is highly dependent upon the patient’s ability to lie still for the test and to breath hold for short periods of time. Also, some patients feel claustrophobic within the machine and may require a mild sedative to tolerate the exam. Finally, many types of metal (including pacemakers) cannot be taken into the MRI machine. Certain medical devices that are made out of metal are specially designed to be MRI compatible (such as the metal stents used in bile ducts). Finally, an open MRI is generally not powerful enough to produce useful images of the abdomen. An MRI does not use ionizing radiation.
Magnetic Resonance Cholangiopancreatography (MRCP)
MRCP is a just one of the alternative sequences that can be obtained during an MRI of the abdomen. (This type of image cannot be produced by a CT scan.) The MRCP is a detailed image of the pancreatic and bile ducts and can be very helpful in the evaluation and management of patients with pancreatic disease. It is especially useful in patients being followed for cystic tumors of the pancreas, because these are especially well seen on a quality MRCP. The same restrictions and expectations related to MRI apply to MRCP.
Positron Emission Tomography (PET) Scan
A PET scans produces images based on the amount of sugar being used as a fuel source by different organs in the body. To generate the images, the patient receives an injection of a radio-labeled glucose analogue. The machine then measures the minute amounts of radioactivity that are emitted from the body. The differences between the radioactivity in each part of the body allows the computer to reconstruct the images. Areas of the body that use a lot of energy, like the brain and the heart, will be very bright. There will be a low level of background (energy use) in the remaining organs in the body at rest. Cancers often have an increased metabolic rate due to their natural tendency to continually divide and grow. So, many (but not all) cancers will appear “bright’ on a PET scan. While the PET scan is useful to observe the metabolic or functional activity of the tumor, it does not provide anatomic the anatomic detail of a CT scan or MRI. For this reason, a PET scan is often combined with a CT scan and the images are fused on the viewer.
EUS combines the use of endoscopy and ultrasound technology to obtain very detailed information about the pancreas and any potential tumor within it. Typically performed in an outpatient setting under sedation, an endoscope is inserted through the mouth and advanced into the stomach and first part of the small intestine called the duodenum which lie adjacent to the pancreas. EUS provides information about the pancreas itself (good for evaluating for signs of chronic pancreatitis) and about any potential tumors in the pancreas, both benign and malignant. It also provides information about the relationship of the tumor to surrounding vital structures such as the blood vessels to the liver and small bowel that are commonly involved by cancers of the pancreas. It can also provide information about the relationship of a cyst of benign tumor to the main pancreatic duct which is helpful when planning as operation. The exam can also provide valuable information about the left lobe of the live which is adjacent to the stomach. Finally, EUS gives the endosocpist the opportunity to perform a needle biopsy of any lesions seen (both solid and cystic) on the exam in both the left lobe of the liver and throughout the entire pancreas. An EUS is a minimally invasive procedure, but does have small risks associated with it that your doctor will discuss with you before the procedure.
Endoscopic Retrograde Cholangiopancreatography (ERCP)
ERCP is a procedure that allows your doctor to produce a detailed image of the bile duct and pancreatic duct. (Similar, in many ways, to the image that can be produced non-invasively by an MRCP.) However, ERCP also provides the opportunity for tissue sampling (biopsy) and for therapeutic intervention, such as placing a stent in the bile duct to relieve jaundice. Like an EUS, the procedure is typically performed in an outpatient setting under sedation and requires advancing an endoscope from your mouth though your stomach and into your duodenum. The endoscopist then cannulates the bile duct and or pancreatic duct at the ampulla of Vater and obtains an xray. This is a minimally invasive procedure that does come with risk. The most frequent complication is pancreatitis which will be discussed with you by your doctor before the exam.
Fine Needle Aspiration (FNA)
When a tumor is identified in the pancreas, it may be necessary to obtain tissue to secure the diagnosis. This tissue is most commonly obtained using a fine needle to aspirate cells from the tumor. Access to the tumor is often best achieved using endoscopic ultrasound (EUS) for image guidance. The needle is passed from the endoscope, through the back of the stomach and into the tumor in the pancreas. Any shed cells are digested by your stomach acid, so ‘needle tract’ seeding of tumor cells is generally not a concern with this approach. An alternative approach would be a needle passed directly through the abdominal wall under CT guidance. This approach has been associated with ‘needle tract’ seeding and is therefore not a first line approach. While FNA is a very valuable tool, the false negative rate (chances that a person with an actual cancer will have a negative or non-diagnostic result) is as high as 30%. So, unfortunately, a negative biopsy never rules out the presence of cancer. But a positive result is almost always (>99%) diagnostic of cancer.
Laparoscopy is a minimally invasive surgical procedure done under general anesthesia in which the surgeon introduces a camera through a small hole in the abdomen usually created just above or just below the belly button. This allows the surgeon to directly visualize the abdominal organs and the lining of the abdominal cavity called the peritoneum. This short procedure is often done before a pancreas operation that is planned for cancer, or prior to starting chemotherapy in patients with a locally advanced tumor, to rule out the presence of metastatic disease that was not seen on preoperative imaging. Disease spread will be seen at laparoscopy in about 5% of patients who appeared to have localized disease on CT or MRI. The recovery is quick and the procedure is often done as an outpatient.