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Cancer of the Pancreas

Pancreatic cancer accounts for approximately 27,000 deaths per year in the United States and 50,000 deaths per year in Europe (excluding the former USSR). Only 1% to 4% of patients with adenocarcinoma of the pancreas will be alive 5 years after diagnosis. Thus, incidence rates are virtually identical.

EPIDEMIOLOGY

The incidence of pancreatic cancer declined slightly from 1973 to 1991, with 26,300 new cases (2% of all cancer diagnoses) estimated in 2006. Studies evaluating this trend suggest that the decreased incidence is due to a steady decline in the rate for white men, which peaked during the period 1970 to 1974. By contrast, rates for white women, black men, and black women have not fallen. In Japan, the incidence of cancer of the pancreas has increased sharply from 1.8/100,000 in 1960 to 5.3 in 100,000 in 1985. Overall, incidence in mortality statistics are very similar.

The risk of developing pancreatic cancer is low in the first three to four decades of life but increases sharply after age 50, with most patients between ages 65 and 80 at cancer of the pancreas. The male to female ratio has ranged from 1.7:1.0 in older series to 1.3:1.0 in a more contemporary series. Historically, the male to female ratio was reported. Racial differences in mortality rates for pancreatic cancer have also been observed.

ETIOLOGIC FACTORS

Recent investigations have identified a number of factors that may contribute to the pathogenesis.

ENVIRONMENTAL FACTORS

A number of important environmental risk factors have been investigated for their role in the etiology of pancreatic cancer.

Cigarette Smoking

Cigarette smoking is the most firmly established risk factor associated with pancreatic cancer. Pancreatic malignancies can be induced in animals through long-term administration of tobacco-specific agents.

Over the past 10 years, numerous dietary factors have been implicated in pancreatic cancer development. Generally, high intakes of fat or meat increase risk, and diets high in fruits and vegetables reduce risk. When the available studies are analyzed in greater detail.

Chronic Pancreatitis

An association between pancreatitis and an increased risk of pancreatic cancer has long been suspected, although the magnitude of the risk remains uncertain. Older clinical studies suggested that chronic forms of pancreatitis, particularly those accompanied by pancreatic calcifications, were most closely associated with the subsequent development of pancreatic cancer. A series of recent reports have validated the epidemiologic association between chronic pancreatitis and pancreatic cancer.

FAMILIAL PANCREATIC CANCER

The recent emergence of the importance of inherited genetic abnormalities in gastrointestinal tract neoplasia has led to closer investigation of the potential role for heritable factors in pancreatic cancer. Several rare hereditary disorders predispose persons to both endocrine and exocrine pancreatic.

TREATMENT OF POTENTIALLY RESECTABLE DISEASE

PREOPERATIVE AND POSTOPERATIVE CHEMORADIATION

External-beam radiation therapy (EBRT) and concomitant 5-FU chemotherapy (chemoradiation) were shown to prolong survival in patients with locally advanced adenocarcinoma of the pancreas. Those data

PANCREATICODUODENECTOMY

Current surgical treatment is based on the procedure of pancreaticoduodenectomy as described in 1935 by Whipple and coworkers. Their two-stage pancreaticoduodenectomy consisted of biliary diversion

ADJUVANT ELECTRON-BEAM INTRAOPERATIVE RADIATION THERAPY

EB-IORT is a means of delivering a higher dose of radiation to the pancreatic bed and high-risk nodal groups to decrease the risk of local tumor recurrence. The effectiveness of EB-IORT in controlling the

TREATMENT DECISIONS: POTENTIALLY RESECTABLE DISEASE

The use of contrast-enhanced, helical CT allows accurate assessment of local tumor resectability. Objective CT criteria for resectability have replaced exploratory laparotomy as a means of assessing

TREATMENT OF LOCALLY ADVANCED DISEASE

CHEMORADIATION

A pilot trial of 5-FU and supervoltage radiation therapy in patients with locally advanced adenocarcinoma of the pancreas served as the foundation for a subsequent study of 5-FU-based chemoradiation by the GITSG. All patients were surgically staged; only patients with disease confined to

EXTERNAL-BEAM RADIATION THERAPY

Treatment planning using high-quality CT allows precise definition of the volume to be treated, enabling the delivery of high-dose EBRT to restricted tumor volumes. The EBRT treatment field encompasses the primary tumor and regional lymph nodes including the celiac axis and the SMA origin. Although

INTRAOPERATIVE RADIATION THERAPY

Additional boost irradiation can be given to an unresectable pancreatic cancer during surgery with EB-IORT. The use of EB-IORT with or without EBRT in patients with locally advanced pancreatic cancer has been extensively studied. The use of both EB-IORT and EBRT has been reported to result in improved survival rates compared with surgical bypass alone or EB-IORT alone. This combined

TREATMENT DECISIONS: LOCALLY ADVANCED, NONMETASTATIC DISEASE

Patients with clear evidence of encasement of the celiac axis or SMA or occlusion of the SMPV confluence on contrast-enhanced, helical CT do not require laparotomy to confirm that the tumor is unresectable; cytologic confirmation of malignancy can be achieved with CT-guided FNA. This

TREATMENT DECISIONS: METASTATIC DISEASE

The complex pathophysiologic abnormalities accompanying metastatic pancreatic cancer often make specific treatment decisions extremely difficult. Many patients present to the medical oncologist or