History. The early symptoms of pancreatic cancer are vague and nonspecific. The most common symptoms are abdominal pain, back pain, weight loss, anorexia, nausea, jaundice, diarrhea, malabsorption, depression, and abdominal mass.
An insidious weight loss with anorexia and nausea, accompanied by upper abdominal pain radiating to the back, is the most common presentation. Greater than 90% of the patients initially have jaundice. Common bile duct obstruction by a tumor in the head of the pancreas may result in jaundice while the mass is still small. Tumors located in the body and tail of the organ may result in jaundice in later stages either by extension or due to metastasis to the porta hepatis or the liver parenchyma.
Up to 70% of the patients may present with diabetes mellitus or glucose intolerance. The decreased or delayed insulin secretion is thought to arise from loss of ОІcells due to the desmoplastic reaction of the tumor.
Migratory thrombophlebitis (Trousseau’s sign) may be a mode of presentation. However, this entity is not specific for pancreatic cancer. It may occur with other malignancies such as carcinomas of the stomach, colon, ovary, and lung.
A minority of the patients may also present with a picture of acute pancreatitis, cholangitis, gastrointestinal bleeding, polyarthritis, and skin nodules due to fat necrosis.
The physical examination in most instances is not helpful. The major findings in a subpopulation of patients are jaundice, palpable gallbladder, epigastric mass, and nodular liver if metastases are present.
Warning signs for early diagnosis. The initial symptoms of pancreatic cancer are usually ignored by the patient (patient delay) and the physician (physician delay). The mean duration of symptoms before diagnosis in most series is 3 to 4 months. Most of the tumors are unresectable and, therefore, the disease is fatal. The following warning signs may facilitate an early diagnosis of this malignancy:
- Recent upper abdominal or back pain consistent with retroperitoneal lesion.
- Recent upper abdominal pain or discomfort with negative gastrointestinal investigations.
- Jaundice with or without pruritus.
- Weight loss greater than 5% of normal body weight.
- Unexplained acute pancreatitis.
- Unexplained onset of diabetes mellitus.
A variety of malignant and benign disorders of other organs may present with features similar to pancreatic cancer. Also it is important to remember that pancreatic cancer may coexist in a patient with a common benign disorder such as gallstones or peptic or diverticular disease, and normal contrast studies of the gastrointestinal tract, serum chemistries, and hemogram do not rule out the presence of pancreatic cancer, especially if the tumor is small.
- Laboratory tests. There are no specific laboratory tests for the early detection of pancreatic cancer. If there is involvement of the liver or the biliary tract, this will be reflected in the serum chemistries. The serum amylase and lipase in most instances are normal. A subgroup of patients has elevated blood glucose levels.
- Tumor markers. Various serologic tumor markers including tumor associated antigens, enzymes, and hormones have been investigated for early detection of pancreatic cancer. These are carcinoembryonic antigen, CA 19-9, alpha-fetoprotein, pancreatic oncofetal antigens, pancreatic ribonuclease, and galactosyl transferase isoenzyme II. The sensitivity and specificity of these assays have not been adequate for early diagnosis of this disease.
Because levels of CA 19-9 are frequently normal in the early stages of pancreatic cancer, the test is not reliable for use in screening. The presence of high levels may help to differentiate between benign diseases of the pancreas and pancreatic cancer. When the pancreatic cancer is completely resected, the CA 19-9 levels fall, suggesting that it is a useful marker for follow-up surveillance.
The ratio of testosterone to dihydrotestosterone is below 5 (normal is 10) in more than 70% of men with pancreatic cancer, presumably because of increased conversion of testosterone by the pancreatic tumor. This ratio may be more sensitive than CA 19-9 in detecting smaller pancreatic cancers and more specific than the other markers.
- Ultrasound and computed tomography. Ultrasonography usually is the first examination for suspected pancreatic cancer. Computed tomography is used when satisfactory imaging is not obtained with ultrasound (Ultrasound). These two techniques are by far the most sensitive and specific for pancreatic disease. They both demonstrate enlargement of the gland, alteration in contour or consistency of the gland, the presence of masses, and biliary or pancreatic duct dilatation. Computed tomography scans may also delineate peripancreatic nodal enlargement as well as invasion of other organs and vessels. Metastasis to the liver and porta hepatis may be detected.Ultrasound and computed tomography are complementary in imaging the pancreas. The lesions in the head of the pancreas are seen well by Ultrasound, whereas those in the body and tail are detected better by computed tomography scan. However, small lesions, especially in the body or tail, may be missed by both techniques.
- Endoscopic retrograde cholangiopancreatography. The diagnosis of pancreatic cancer by endoscopic retrograde cholangiopancreatography depends on radiographic demonstration of pancreatic duct stenosis or obstruction caused by the tumor. An accompanying cholangiogram may further delineate abnormalities along the course of the common bile duct. It can also visualize and differentiate ampullary and duodenal carcinomas. In experienced hands, it has greater than 90% sensitivity and specificity in providing a definitive diagnosis of pancreatic cancer.
In addition, biopsies of periampullary tissue and cytologic examination of aspirated pancreatic juice may increase the diagnostic yield further. Endoscopic retrograde cholangiopancreatography is usually performed if an abnormality is noted on the Ultrasound or computed tomography scan or if an abnormality is suspected but cannot be demonstrated by these methods.
In addition to diagnosis, endoscopic retrograde cholangiopancreatography may be used to place stents in the obstructed biliary and pancreatic ducts to relieve obstruction and palliate patients with unresectable tumors.
Percutaneous transhepatic cholangiogram. In patients with obstructive jaundice with dilated bile ducts, percutaneous transhepatic cholangiogram (percutaneous transhepatic cholangiography) may visualize the common bile duct and the site of its obstruction. A drainage catheter may then be introduced percutaneously for biliary decompression.
- Angiography. Celiac and superior mesenteric angiography with selective cannulation of the pancreatic vessels may provide a sensitive diagnostic tool. However, this invasive technique is best used to determine resectability of the tumor before surgery. Arterial encasement, venous occlusion, and tumor vascularity can be visualized, and angiography may save the patient an unnecessary abdominal exploration. If a tumor is resectable, the arterial blood supply and anatomic variations of the foregut vasculature can be delineated by angiography to help in the planning of surgery.
- Cytologic diagnosis. Direct percutaneous fine-needle aspiration can be performed with Ultrasound, computed tomography, or angiographic guidance. The aspirated material is used for cytologic examination. This technique may provide the tissue diagnosis and allow differentiation of lymphoma or endocrine tumors from adenocarcinoma without surgery; it is especially useful in elderly patients in whom the morbidity and mortality of laparotomy are high.
The drawbacks of this procedure are that a negative result cannot exclude the presence of a malignant tumor, especially if the tumor is small, and that tumor seeding may occur along the needle tract with possible peritoneal spread of the tumor.
- Endoscopic ultrasonography. The pancreas may be visualized clearly with this method from the lumina of the duodenum, antrum, and gastric fundus to localize pancreatic cancers that are too small to be seen by computed tomography or transabdominal Ultrasound. Associated lymph nodes and vascular involvement are accurately demonstrated. The sensitivity of endoscopic ultrasonography compares favorably with that of computed tomography and angiography. Staging of pancreatic cancer with endoscopic ultrasonography may become routine before selection of therapy.
- Laparoscopy. The most common sites of distant metastasis from pancreatic cancer are the liver, the peritoneum, and the omentum. These lesions, which may be too small to be detected by computed tomography, may be directly visualized by laparoscopy. Because the presence of these metastases contraindicates surgery, laparoscopy may help to increase the accuracy of staging.
Magnetic resonance imaging, especially fat-saturation magnetic resonance imaging, improves the examination of the pancreas for tumor. Fat-saturation Magnetic resonance imaging is especially valuable in looking for suspected tumors in a pancreas that is not enlarged.