Pancreatic Cancer - Early Detection

2/21/01 (Dhruva)

RE: a  60 y/o male with dark urine, nausea vomiting, yellow eyes

Question:  What is an effective way to diagnose pancreatic cancer early?

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Unique Identifier: 99365860

Authors: DiMagno EP.

Institution: Division of Gastroenterology, Mayo Clinic, Mayo Medical School, Rochester, MN, USA.

Abstract: The diagnosis of pancreatic cancer usually depends upon symptoms; consequently it is late when there is no chance for cure. At this point, pain, anorexia, early satiety, sleep problems and weight loss are present. Back pain also may be prominent, which predicts unresectability and shortened survival after resection. However, earlier recognition of symptoms of pancreatic cancer might improve early detection of the cancer. For example, 25% of patients have symptoms compatible with upper abdominal disease up to 6 months prior to diagnosis and 15% of patients may seek medical attention more than 6 months prior to diagnosis. These symptoms erroneously may be attributed to problems such as irritable syndrome. Symptoms, however, may be less common. For example a quarter of patients with pancreatic cancer may have no pain at diagnosis, and half, particularly those with pancreatic head tumors, may have little pain compared with patients with body-tail tumors. However, if the tumor is suspected because of predisposing conditions, earlier diagnosis may be possible. These conditions include diseases such as chronic pancreatitis, intraductal papillary mucinous tumor (IPMT), and recent onset of diabetes mellitus, particularly if the diabetes occurs during or beyond the sixth decade. In addition inherited syndromes also are associated with an increased risk of pancreatic cancer including familial pancreatic cancer, hereditary pancreatitis, familial adenomatous polyposis syndrome (FAP) and familial atypical multiple mole melanoma (FAMMM) syndrome (hereditary dysplastic nevus syndrome). Of these conditions, recent onset of diabetes may be the best clue and should be included in a clinical profile of patients prior to the onset of symptoms to identify a high-risk group to apply screening strategies for detection of early disease. Contrary to a clinical aphorism that pancreatic cancer patients are elderly, lean and recently may have developed diabetes, we found that patients who develop pancreatic cancer are overweight prior to onset of symptoms compared to controls (body mass index, 28 vs 25). Forty percent had the diagnosis of diabetes made at the time of diagnosis of pancreatic cancer and more patients with a resectable tumor had diabetes (58%) compared to patients with locally unresectable or metastatic disease (37%). Perhaps, screening overweight persons who have new-onset diabetes may lead to a diagnosis of asymptomatic, early, resectable pancreatic cancer. [References: 44]

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Unique Identifier: 99365851

Authors: Tascilar M. Caspers E. Sturm PD. Goggins M. Hruban RH. Offerhaus GJ.

Institution: Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.

Abstract: BACKGROUND: Unresectability at the time of presentation is the most important reason for the poor survival rate of pancreatic carcinoma. Molecular-based tests might improve the early detection of pancreatic cancer at a time when surgical resection is still an option for cure. METHODS: The literature was reviewed concerning the role of molecular-based tests applied to sources other than pancreatic tissue itself, including ERCP-samples, blood and stool, with emphasis on the detection of K-ras mutations and mutant p53 gene product. RESULTS: K-ras mutations have been successfully detected in ERCP brush samples, leading to an increase of the sensitivity and improvement of the diagnostic yield. When pancreatic juice and duodenal fluid are tested for K-ras mutations, the yield is less. K-ras mutations can also be detected in the blood, especially in patients with larger tumors. The presence of K-ras mutations proved also to be useful in discriminating benign and malignant liver nodules, i.e. when during surgery there is suspicion of liver metastases of pancreatic cancer. The accumulation of p53 gene product to immunochemically detectable levels in ERCP brush samples also increases the sensitivity of conventional light microscopy. Other molecular markers such as telomerase and TIMP-1 may prove to be useful too, but await more extensive evaluation. CONCLUSION: Molecular-based tests may be of value in the early detection of pancreatic cancer and might therefore contribute to a better patient survival rate. [References: 70]

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Unique Identifier: 99245445

Authors: Nakaizumi A. Uehara H. Takenaka A. Uedo N. Sakai N. Yano H. Ohigashi H. Ishikawa O. Ishiguro S. Sugano K. Tatsuta M.

Institution: Department of Gastroenterology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.

Abstract: BACKGROUND/AIMS: Cytological examination of pancreatic juice is useful in the diagnosis of an occult cancer of the pancreas. The early diagnosis of pancreatic carcinoma using traditional radiographic or ultrasonographic methods is extremely difficult. METHODOLOGY: In order to detect an early pancreatic cancer, cytological examination, measurement of tumor marker, and detection of K-ras point mutation were performed using the samples of pure pancreatic juice aspirated endoscopically in patients who had symptoms or findings that suggested pancreatic disease. RESULTS: By routine ERP-cytology, positive cytologic results were obtained in 15 (4%) out of 359 patients without a mass. With the aid of intra-operative cytodiagnosis, all 15 occult neoplasms of the pancreas were successfully resected. One patient died from another disease without evidence of recurrence. However, the other patients were alive with no evidence of recurrence for an average of 5.5 years following surgery. The patients who had negative ERP-cytology results were observed, but no further cases of pancreatic cancer were found. The CEA levels in the pure pancreatic juice were significantly higher in patients with pancreatic cancer than in those with pancreatitis. K-ras point mutation at codon 12 was detected not only in cases of pancreatic cancer, but also in cases of chronic pancreatitis as well as control subjects. CONCLUSIONS: Cytological examination of pancreatic juice is useful in the diagnosis of an early and potentially curable in situ cancer of the pancreas. The CEA levels in the pure pancreatic juice provided useful information for differentiating the pancreatic cancer from chronic pancreatitis. K-ras point mutation at codon 12 in pancreatic juice was considered to be useful in identifying patients at high risk for the development of pancreatic cancer.