SCREENING FOR EARLY PANCREATIC DUCTAL ADENOCARCINOMA IN HEREDITARY PANCREATITIS - 06/09/11
Résumé |
The risk of ductal adenocarcinoma is greatly increased in patients with hereditary pancreatitis (HP). Analysis of the biggest series of HP patients studied to date resulted in an estimated lifetime risk for the development of ductal adenocarcinoma of 40%. Only patients in whom the disease was transmitted paternally contracted cancer, giving a lifetime risk for this subset of individuals of 70%.44 Lerch et al42 established that the risk of pancreatic cancer is also increased with maternal transmission of HP.
Patients with sporadic chronic pancreatitis also have an increased risk of developing pancreatic cancer, which has been shown to be six times greater than that of unaffected individuals.43 Lowenfels et al44 showed that patients had chronic pancreatitis for at least 20 years before the development of pancreatic cancer. Patients who developed pancreatic cancer had more severe disease, manifested by increased complications of pancreatitis and increased calcification of the pancreas gland, compared with age-matched controls. This finding suggests that the relationship between the development of pancreatic cancer in patients with HP may be due to the duration and severity of the disease as a precursor to malignant pathogenesis, rather than the genetic predisposition of developing pancreatitis.
Secondary screening for pancreatic ductal adenocarcinoma in patients with HP is desirable and feasible, given the high risk of cancer and the long lead time between the development of pancreatitis and pancreatic cancer. Conventional methods of diagnosis of pancreatic ductal adenocarcinoma are limited. Tumor markers are falsely elevated in 10% of patients with chronic pancreatitis,47 in cigarette smokers, and in the presence of jaundice.68 They are of little use in the diagnosis of lesions suitable for curative surgery because the sensitivity for detection in early tumors is less than 50%.29, 48 The sensitivity of CA19-9 for the detection of early pancreatic cancer (< 20 mm and confined to the pancreas) is only 43% in pure pancreatic juice and 0% in the serum.50 Other tumor markers, such as CEA, SPAN-1, and CA50, used alone or in combination, have been assessed and have a lower sensitivity than CA19-9.59
The accuracy of imaging early pancreatic lesions is disappointing. The sensitivity of detecting pancreatic ductal adenocarcinoma using computed tomography (CT) scan alone is approximately 33% for tumors less than 2 cm and 50% for tumors less than 3 cm.27 Muller et al56 found similar rates of detection in early pancreatic lesions, with 4 of 10 (40%) lesions less than 2 cm and 8 of 15 (67%) lesions less than 3 cm being visible on dynamic helical CT scan. Midwinter et al51 performed spiral CT scan on 24 patients with histologically proven ductal adenocarcinoma of the pancreas, who were being assessed for surgical resection. Mass lesions were detected in 23 of 26 pancreatic tumors of all stages; the remaining 3 tumors, which were missed, had a mean size of 22 mm. In another study, Phoa et al61 used spiral CT scan for the preoperative staging of potentially resectable pancreatic cancer. CT scan showed a mass lesion in 54 of 56 cases, with a mean diameter of 28 mm. Only half of these patients, however, were suitable for resection because of undiagnosed metastatic disease or understaged local invasion. In five of the patients with pancreatic cancer, distinction from chronic pancreatitis by CT scan criteria alone was not possible, suggesting that the sensitivity for the detection of pancreatic cancer in a background of chronic pancreatitis is likely to be even less. Johnson and Outwater37 used dynamic magnetic resonance (MR) imaging with gadolinium to differentiate chronic pancreatitis from ductal adenocarcinoma of the pancreas. Both groups showed abnormal pancreatic enhancement indicative of disease; however, there was considerable overlap between the two groups, precluding distinction of the two entities. The similar appearance of chronic pancreatitis and pancreatic cancer on imaging may be explained, in part, by the abundant fibrosis that occurs in both conditions.
Endoscopic techniques for the diagnosis of pancreatic cancer are well established. Endoluminal ultrasound for the detection of malignancy on a background of chronic pancreatitis may be more sensitive than CT scan and MR imaging51 but because of poor specificity gives a positive predictive value of only 60%.1, 5, 65 Endoscopic retrograde cholangiopancreatography (ERCP) used in isolation is not sufficiently sensitive to detect subtle pancreatic ductal changes associated with early neoplastic lesions. Bakkevold et al4 prospectively examined stage I ductal adenocarcinomas and ampullary lesions and found that ERCP was 78% sensitive for diagnosing these lesions.
Diagnosis of pancreatic cancer by using cytology alone on pancreatic juice obtained at ERCP has a sensitivity of 30% to 70% for the diagnosis of pancreatic cancer at all stages.21, 74 Studies that have correlated the stage of the pancreatic cancer have found that the sensitivity for detecting stage I and II pancreatic cancers using this method is only 56%.50
The sensitivity of conventional methods for diagnosing early pancreatic cancer, particularly in the presence of chronic pancreatitis, is disappointing. Advances in understanding of the molecular biology of chronic pancreatitis and pancreatic cancer have enabled the development of new strategies for the early diagnosis of pancreatic cancer, which are potentially more sensitive and specific than existing conventional modalities.
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| Address reprint requests to John Neoptolemos, MA, MBChB, FRCS, MD, Department of Surgery, Royal Liverpool University Hospital, Daulby Street, Liverpool L69 3GA UK, e-mail: J.P.Neoptolemos@liv.ac.uk |
Vol 84 - N° 3
P. 719-738 - mai 2000 Retour au numéro
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