eMedicine Specialties > Radiology > Gastrointestinal

Pancreas, Adenocarcinoma

Author: Mahesh Kumar Neelala Anand, MBBS, DNB, FRCR,, Consultant Radiologist, Department of Radiology, Pennine Acute Hospitals NHS Trust, Manchester, UK
Coauthor(s): Colm Boylan, MB, BCh, MRCP, FRCR, Assistant Professor of Radiology, McMaster University; Staff Radiologist, St Joseph's Hospital, Canada; Narainder Gupta, MBBS, MSc, FRCR, MD, Assistant Professor of Cardiothoracic Radiology, Division Director, Division of Cardiothoracic Radiology, Thomas Jefferson University Hospital
Contributor Information and Disclosures

Updated: Mar 5, 2010

Introduction

Background

Of all the GI malignancies, pancreatic adenocarcinoma, as shown in the images below, is the second most common cause of death from cancer. In clinical practice, pancreatic cancer is synonymous with pancreatic ductal adenocarcinoma, which constitutes 90% of all primary malignant tumors arising from the pancreatic gland.

Tumors may arise from pancreatic ducts (99%) or from acinar cells (1%). More than 90% of pancreatic cancers appear in the late stage of disease; this observation emphasizes the role of radiology in early detection and determination of resectability of the tumor. The role of diagnostic imaging is to demonstrate the tumor and its relationship to surrounding vasculature, and the results determine the possibility of curative resection.

The diagnosis of pancreatic cancer is rarely made at an early stage. This is one of the main reasons for failing to achieve a cure in most patients.

For excellent patient education resources, visit eMedicine's Cancer and Tumors Center. Also, see eMedicine's patient education article Pancreatic Cancer.

Epidemiology and etiology

The definitive causative factors that indicate an increased incidence of pancreatic cancer are unknown. High-protein and high-fat diets, cigarette smoking, and exposure to industrial carcinogens are implicated as causative factors. An increased incidence has been reported in chemists, workers in metal industries, and coke- and gas-plant employees.

Hereditary pancreatitis is present in 40% of patients with pancreatic carcinoma. Cigarette smoking increases the risk by 2 times and diabetes by 2 times more than the general population. Alcohol abuse is seen in 4% of patients. Asbestos exposure is not associated with pancreatic carcinoma.

Undoubtedly, an association exists between pancreatic cancer and diabetes mellitus. Association of alcohol and pancreatic cancer is indirectly related to the development of alcohol-induced pancreatitis. The acquired variety of chronic pancreatitis does not seem to be strongly related to pancreatic cancer. Individuals with the hereditary type of chronic pancreatitis seem to have a predisposition for pancreatic cancer stronger than that of the general population.

Recent studies

Macari et al determined that at portal venous phase dual-source dual-energy CT, pancreatic malignant-tumor conspicuity is greater at 80 kVp than with 120-kVp acquisition simulated with a weighted-average acquisition. The mean difference in attenuation for pancreatic tumors and adjacent normal pancreas was 83.27 +/- 29.56 (SD) HU at 80 kVp and 49.40 +/- 23.00 HU at weighted-average 120 kVp. At 80 kVp, contrast-to-noise ratio was significantly higher, as was duct visualization.¹

In a Johns Hopkins/Mayo Clinic collaborative study of adjuvant chemoradiation therapy (CRT) versus surgery alone for pancreatic adenocarcinoma, Hsu et al found that the use of CRT was associated with improved survival after pancreaticoduodenectomy. Median survival was 18.8 months. Survival rates for CRT versus surgery alone were as follows: median survival, 21.1 vs 15.5 months; 2-year overall survival, 44.7 vs 34.6%; and 5-year overall survival, 22.3 vs. 16.1%.²

Jing et al evaluated the diagnostic yields for pancreatic ductal adenocarcinomas when fine-needle aspiration (FNA) was combined with brushing cytology (BC). The authors found that there were more true diagnoses with FNA than BC, but in 10 cases, BC but not FNA detected neoplasms. The authors found that when used in combination, the 2 modalities complemented each other and achieved better diagnostic yields than either modality used alone. The findings were as follows³ :

• Diagnostic sensitivities for FNA alone, BC alone, and BC/FNA were 69.2, 50.8, and 84.6.
• Diagnostic specificities for FNA alone, BC alone, and BC/FNA were 93.8, 100, and 100.
• Diagnostic positive predictive values for FNA alone, BC alone, and BC/FNA were 95.7, 100, and 100.
• Diagnostic negative predictive values for FNA alone, BC alone, and BC/FNA were 60, 50, and 76.2.
• Diagnostic accuracy rates for FNA alone, BC alone, and BC/FNA were 77.3, 67, and 89.7.

Pathophysiology

Pathologically, the adenocarcinomas may be classified as follows:

• Duct cell origin
  • Duct cell adenocarcinoma
  • Giant cell carcinoma
  • Giant cell carcinoma (epulis-osteoid)
  • Adenosquamous carcinoma
  • Microadenocarcinoma
  • Mucinous (colloid) carcinoma
  • Cystadenocarcinoma (mucinous)
• Acinar cell origin
  • Acinar cell carcinoma
  • Cystadenocarcinoma (acinar cell)

Most of the tumors produce mucin (75%) and are located in the head of the pancreas.

Frequency

United States

Pancreatic cancer is the fifth leading cause of cancer deaths in the United States. Approximately 28,000 new pancreatic cancers are diagnosed in the United States each year. Of the affected patients, 60% have liver metastasis, malignant ascites, or other evidence of tumor spread at the time of diagnosis.

International

The incidence of cancer has tripled over the past 40 years throughout the Western world. It is highly fatal and has one of the lowest survival rates. In England and Wales, pancreatic cancer accounts for approximately 6000 deaths each year.

Mortality/Morbidity

In the United States, pancreatic cancer accounts for an estimated 8.4 deaths per 100,000 persons. Adenocarcinoma of the pancreatic head has a 3-year survival rate of only 2%, and the 5-year survival rate after resection is about 20%. The overall survival rate is 0.5%. Approximately 80-90% of patients have regional and distant metastases by the time the disease is diagnosed and are not suitable for curative resection. Only 4-16% of the tumors are resectable at diagnosis.

Currently, as many as 30% of patients who are referred for surgery on the basis of their CT findings are discovered to be unsuitable candidates. In most patients, even palliation cannot be achieved because of advanced disease at presentation. Overall, fewer than 5% of patients undergo resection, but among these, as many as 20% survive 5 years. The median survival is less than 18 months after surgery.

Sex

Pancreatic cancer is more common in men than in women. The male-to-female ratio has been decreasing recently, suggesting that more women are developing the malignancy.

Age

Those aged 60-80 years are most affected. Pancreatic adenocarcinoma is uncommon but not rare in those younger than 55 years. It is uncommon in those younger than 40 years.

Anatomy

The pancreas is divided into head, neck, body, and tail segments for descriptive purposes, and it lies in the retroperitoneum within the anterior pararenal space. The head is the portion of the gland lying within the C-loop curve of the duodenum. The head is prolonged inferiorly and medially to extend behind the superior mesenteric vein. The uncinate process usually stops short at the level of the right renal hilum inferiorly.

The neck of the gland is the constricted segment of the gland lying anterior to the superior mesenteric vessels. The body is a horizontal segment of the gland lying behind the lesser sac and stomach. Dorsal to the body runs the splenic vein. The tail of pancreas may be slightly cephalic to the level of the head. It follows the splenic vessels into the splenic hilum.

The main pancreatic duct (duct of Wirsung) opens at the major duodenal papilla, measuring 3-4 mm in diameter in adults. It enlarges slightly with advancing age. The diameter of the duct tapers to 1-2 mm toward the tail. A slight narrowing at the head and body of the pancreas is a normal variation. The accessory pancreatic duct (duct of Santorini) opens at the minor duodenal papilla, proximal to the major duodenal papilla. The 2 ducts join in the head of pancreas in 90-95% of patients.

In 20-30% of patients, the accessory duct retains a patent orifice at the minor papilla. Small side branches that are delicate, tapering, and gracile originate at approximately right angles to the main duct throughout the length of the gland. A prominent side branch seen as common normal variations include one from the midbody and another from the uncinate process.

On cross-sectional images, the measurements of normal pancreas diameters generally are as follows: head of the pancreas, 3 cm; neck and body of the pancreas, 2.5 cm; and tail, as long as 2 cm.

The position, size, and shape of the pancreas vary among patients. The pancreas gradually diminishes with advancing age, sometimes becoming more marked beyond the seventh decade. The surface of the pancreas is smooth in 80% of patients and lobulated in approximately 20%.

Presentation

Clinical symptoms and signs develop late and depend on the site of the tumor. Tumors in the body and tail produce late symptoms. Pain is the most consistent symptom. Painless jaundice alone is uncommon and is seen in 13% of patients. Approximately 34% present with pain alone, and about 46% with pain and jaundice. Severe pain invariably indicates spread of tumor to perineural lymphatics.

Weight loss and anorexia are observed in 7% of patients. Hematemesis and melena occasionally occur in late cases, and these may be caused by direct invasion of the adjacent duodenum or stomach or as a result of portal hypertension from splenic and portal vein obstruction.

Physical examination

A palpable gall bladder (Courvoisier sign) is observed in approximately 25% of patients with operable tumors. Tumors in the body and tail appear late, as they do not cause any immediate pressure effects on ducts. They present with pain when large. Hepatomegaly is seen in 65% of patients and may indicate liver metastasis, although the sign is nonspecific.

Positive clinical signs indicate incurable disease, and a palpable abdominal mass is observed in 10% and ascites in 5%, which suggests advanced disease. Obstructive jaundice is seen in 75% of patients. Other signs include new onset of diabetes in 25-50% of patients, thrombophlebitis, and fatigue. More than 90% of patients present at a late stage in the disease process.

Laboratory tests reveal elevated bilirubin concentrations. The total bilirubin level tends to be greater with malignant obstruction, as compared with the increase in bilirubin levels due to ductal obstruction caused by choledocholithiasis (mean levels of 15 vs 5 mg/dL). Conjugated bilirubin and alkaline phosphatase levels are higher in patients with obstructive jaundice than in those with liver parenchymal disease. Elevation of serum amylase values is less common and seen in about 5% of patients with pancreatic cancer.

Staging

American Joint Committee for Cancer (AJCC) staging of carcinoma of the pancreas is as follows:

• T stages
  • T1 - No direct extension of the primary tumor beyond the pancreas
  • T2 - Limited direct extension to duodenum, bile duct, or stomach
  • T3 - Advanced direct extension, incompatible with surgical resection
  • TX - Direct extension not assessed
• N stages
  • N0 - Regional lymph nodes not involved
  • N1 - Regional lymph nodes involved
  • NX - Regional lymph nodes not assessed
• M stages
  • M0 - No distant metastases
  • M1 - Distant metastases present
  • MX - Distant metastases not assessed

Preferred Examination

There is much debate concerning the sensitivity and specificity of imaging investigations in the diagnosis and staging of pancreatic carcinoma.

Multisection CT is generally accepted to be the first line of investigation in a patient with suspected pancreatic cancer. The best imaging technique is determined by local availability and expertise, but this will nearly always be spiral CT (ideally multisection CT). The reasons for this preference include its wide availability, speed, thin sections, optimal enhancement, high spatial resolution, and consistently good images.

The importance of good CT technique cannot be overemphasized, and the key elements are the following: oral water as negative intraluminal contrast, 120-150 mL of iodinated contrast material intravenously administered at a rate of 3-4 mL/s, and scanning with thin (2- to 3-mm) collimation during pancreatic parenchymal phase (at 25-35 s) with the liver phase obtained at 60-70 s.

If the patient is clinically jaundiced and when biliary ductal dilatation is demonstrated on ultrasonographic (US) examination, endoscopic retrograde cholangiopancreatography (ERCP) is the next investigation of choice with a view to a drainage procedure. ERCP reliably demonstrates the point of obstruction.

US is often the initial test in symptomatic patients. US is used for diagnosis rather than staging, although liver metastasis and ascites may be seen. Significant technical improvements in US have occurred. It may be used for problem solving in thin patients. Portal venous involvement may be more apparent on sonograms than on CT and/or MRI images, and liver lesions can be characterized as cystic or solid.

MRI has improved considerably in recent years, and it continues to evolve. Studies comparing CT and MRI found that detection and assessment of resectability to be similar with both modalities. MRI takes longer, it costs more, it is more complex, and it is limited by artifacts. The current role of MRI is probably problem solving. That is if the mass is not demonstrable with CT and US, MRI could be used to evaluate the pancreas in obstructive jaundice. MRI is also helpful in evaluating and characterizing liver lesions in patients with pancreatic cancer.

In the detection and staging of small tumors, endoscopic US (EUS) can be reliable when it is performed by experienced imagers. Previous studies have demonstrated a higher sensitivity and specificity with EUS than with other modalities, but these results probably reflect the use of suboptimal CT and MR techniques. Recent evidence suggests that EUS is similar to CT in diagnosis and staging of pancreatic cancer. EUS requires special endoscopic skills and expertise, and it is less readily available worldwide.

EUS-guided fine-needle aspiration (FNA) is safe and effective, especially for pancreatic head masses. EUS-guided FNA has sensitivity and specificity similar to that of CT-guided FNA cytology (FNAC).

Limitations of Techniques

The detection of a mass on imaging is nonspecific and 5-15% of pancreatic resections show benign pathology.

Transabdominal US (TAUS) has a relatively poor sensitivity, and its results are not satisfactory for assessment in approximately 20% of patients because of a poor acoustic window due to bowel gas.

MRI is sensitive in the detection and staging of pancreatic cancer with sensitivity and specificity similar to that of multisection CT. MRI involves expensive equipment and meticulous attention to the image technique. Other technical limitations are movement artifacts due to bowel peristalsis and breathing. Because the high sensitivity and specificity of MRI in detection and staging small tumors has not been achieved consistently and universally, debate continues about the superiority of MRI over CT.

Multisection CT should be used first in the detection of pancreatic adenocarcinoma. When CT findings are negative, MRI or EUS should be applied for detection and for the assessment of resectability. Although conventional angiography is obsolete in primary staging, it is occasionally required to assess peripancreatic vessels before surgery. Modern multislice CT scanners are capable of excellent depiction of arterial and venous branches. The role of MR angiography (MRA) in the assessment of mesenteric vessels prior to surgery is not firmly established, though some encouraging study results are reported.

Differential Diagnoses

Pancreas, Islet Cell Tumors
Pancreas, Mucinous Cystic Neoplasm
Pancreas, Serous Cystadenoma
Pancreatitis, Chronic

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