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Published in: Journal of Gastrointestinal Surgery 12/2007

01-12-2007

Detection of Micrometastases in Peritoneal Washings of Pancreatic Cancer Patients by the Reverse Transcriptase Polymerase Chain Reaction

Authors: Kimberly Moore Dalal, Yanghee Woo, Charles Galanis, Mithat Gonen, Laura Tang, Peter Allen, Ronald DeMatteo, Yuman Fong, Daniel G. Coit

Published in: Journal of Gastrointestinal Surgery | Issue 12/2007

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Abstract

Objective

Pancreatic cancer patients with positive (+) peritoneal cytology have a prognosis similar to stage IV patients. We studied the ability of quantitative real time-polymerase chain reaction (RT-PCR) to detect micrometastases in patients undergoing staging laparoscopy.

Methods

Peritoneal washes were obtained prospectively from 35 consecutive patients with pancreatic adenocarcinoma undergoing staging laparoscopy and 16 patients undergoing laparoscopy for benign disease. Each sample was assessed by cytologic examination and RT-PCR analysis for tumor markers: CEA, CK7, Kras2, and MUC1. Markers and their combinations were evaluated on the basis of their deviance from the ideal marker.

Results

Pathologic stages for pancreatic cancer patients were: 1A-1 (3%), IB-1 (3%), IIA-5 (15%), IIB-13 (38%), III-5 (15%), IV-9 (26%). Eight patients were cytology (+) and stages IIA-1, IIB-2, IV-5. Twenty-five patients were RT-PCR (+). The optimal threshold for cycle amplification was 35 based on a receiver operating characteristic curve. CEA had the best profile of sensitivity, specificity, PPV, NPV, and the smallest deviance.

Conclusion

RT-PCR using a panel of tumor markers, including CEA, was comparable in sensitivity, specificity, PPV, and NPV to cytology. RT-PCR could represent a more sensitive method for detection of subclinical peritoneal tumor dissemination; this may be useful in patient selection for operative management and clinical trials.
Literature
1.
go back to reference Conlon KC, Klimstra D, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg 1996;223:273–279.PubMedCrossRef Conlon KC, Klimstra D, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg 1996;223:273–279.PubMedCrossRef
2.
go back to reference Henne-Bruns D, Vogel I, Luttges J, Kloppel G, Kremer B. Ductal adenocarcinoma of the pancreas head: survival after regional versus extended lymphadenectomy. Hepatogastroenterology 1998;45:855–866.PubMed Henne-Bruns D, Vogel I, Luttges J, Kloppel G, Kremer B. Ductal adenocarcinoma of the pancreas head: survival after regional versus extended lymphadenectomy. Hepatogastroenterology 1998;45:855–866.PubMed
3.
go back to reference Warshaw AL. Implications of malignant-cell DNA content for treatment of patients with pancreatic cancer. Ann Surg 1991;214:645–647.PubMedCrossRef Warshaw AL. Implications of malignant-cell DNA content for treatment of patients with pancreatic cancer. Ann Surg 1991;214:645–647.PubMedCrossRef
4.
go back to reference Merchant NB, Conlon K, Saigo P, Dougherty E, Brennan MF. Positive peritoneal cytology predicts unresectability of pancreatic adenocarcinoma. J Am Coll Surg 1999;188:421–426.PubMedCrossRef Merchant NB, Conlon K, Saigo P, Dougherty E, Brennan MF. Positive peritoneal cytology predicts unresectability of pancreatic adenocarcinoma. J Am Coll Surg 1999;188:421–426.PubMedCrossRef
5.
go back to reference Ferrone CR, Haas B, Tang L, Coit DG, Fong Y, Brennan MF, Allen PJ. The influence of positive peritoneal cytology on survival in patients with pancreatic adenocarcinoma. J Gastrointest Surg 2006;10:1347–53.PubMedCrossRef Ferrone CR, Haas B, Tang L, Coit DG, Fong Y, Brennan MF, Allen PJ. The influence of positive peritoneal cytology on survival in patients with pancreatic adenocarcinoma. J Gastrointest Surg 2006;10:1347–53.PubMedCrossRef
6.
go back to reference Vogel I, Kruger U, Marxsen J, Soeth E, Kalthoff H, Henne-Bruns D, Kremer B, Juhl H. Disseminated tumor cells in pancreatic cancer patients detected by immunocytology: a new prognostic factor. Clin Cancer Res 1991;5:593–599. Vogel I, Kruger U, Marxsen J, Soeth E, Kalthoff H, Henne-Bruns D, Kremer B, Juhl H. Disseminated tumor cells in pancreatic cancer patients detected by immunocytology: a new prognostic factor. Clin Cancer Res 1991;5:593–599.
7.
go back to reference Kodera Y, Nakanishi H, Yamamura Y, Shimizu Y, Torii A, Hirai T, Yasui K, Morimoto T, Kato T, Kito T, Tatematsu M. Prognostic value and clinical implications of disseminated cancer cells in the peritoneal cavity detected by reverse transcriptase-polymerase chain reaction and cytology. Int J Cancer 1998;79:429–433.PubMedCrossRef Kodera Y, Nakanishi H, Yamamura Y, Shimizu Y, Torii A, Hirai T, Yasui K, Morimoto T, Kato T, Kito T, Tatematsu M. Prognostic value and clinical implications of disseminated cancer cells in the peritoneal cavity detected by reverse transcriptase-polymerase chain reaction and cytology. Int J Cancer 1998;79:429–433.PubMedCrossRef
8.
go back to reference Kodera Y, Nakanishi H, Ito S, Yamamura Y, Kanemitsu Y, Shimizu Y, Hirai T, Yasui K, Kato T, Tatematsu M. Quantitative detection of disseminated free cancer cells in peritoneal washes with real-time reverse transcriptase-polymerase chain reaction: a sensitive predictor of outcome for patients with gastric carcinoma. Ann Surg 2002;235:499–506.PubMedCrossRef Kodera Y, Nakanishi H, Ito S, Yamamura Y, Kanemitsu Y, Shimizu Y, Hirai T, Yasui K, Kato T, Tatematsu M. Quantitative detection of disseminated free cancer cells in peritoneal washes with real-time reverse transcriptase-polymerase chain reaction: a sensitive predictor of outcome for patients with gastric carcinoma. Ann Surg 2002;235:499–506.PubMedCrossRef
9.
go back to reference Kodera Y, Nakanishi H, Ito S, Yamamura Y, Fujiwara M, Koike M, Hibi K, Ito K, Tatematsu M, Nakao A. Prognostic significance of intraperitoneal cancer cells in gastric carcinoma: detection of cytokeratin 20 mRNA in peritoneal washes, in addition to detection of carcinoembryonic antigen. Gastric Cancer 2005;8:142–148.PubMedCrossRef Kodera Y, Nakanishi H, Ito S, Yamamura Y, Fujiwara M, Koike M, Hibi K, Ito K, Tatematsu M, Nakao A. Prognostic significance of intraperitoneal cancer cells in gastric carcinoma: detection of cytokeratin 20 mRNA in peritoneal washes, in addition to detection of carcinoembryonic antigen. Gastric Cancer 2005;8:142–148.PubMedCrossRef
10.
go back to reference Kodera Y, Yamamura Y, Shimizu Y, Torii A, Hirai T, Yasui K, Morimoto T, Kato T. Peritoneal washing cytology: prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection. J Surg Oncol 1999;72:60–64.PubMedCrossRef Kodera Y, Yamamura Y, Shimizu Y, Torii A, Hirai T, Yasui K, Morimoto T, Kato T. Peritoneal washing cytology: prognostic value of positive findings in patients with gastric carcinoma undergoing a potentially curative resection. J Surg Oncol 1999;72:60–64.PubMedCrossRef
11.
go back to reference Yamashita K, KidaY, Shinoda H, Kida M, Okayasu I. K-ras point mutations in the supernatants of pancreatic juice and bile are reliable for diagnosis of pancreas and biliary tract carcinomas complementary to cytologic examination. Jpn J Cancer Res 1999;90:240–248.PubMed Yamashita K, KidaY, Shinoda H, Kida M, Okayasu I. K-ras point mutations in the supernatants of pancreatic juice and bile are reliable for diagnosis of pancreas and biliary tract carcinomas complementary to cytologic examination. Jpn J Cancer Res 1999;90:240–248.PubMed
12.
go back to reference Hornick JL, Lauwers G, Odze RD. Immunohistochemistry can help distinguish metastatic pancreatic adenocarcinomas from bile duct adenomas and hamartomas of the liver. Am J Surg Pathol 2005;29:381–389.PubMedCrossRef Hornick JL, Lauwers G, Odze RD. Immunohistochemistry can help distinguish metastatic pancreatic adenocarcinomas from bile duct adenomas and hamartomas of the liver. Am J Surg Pathol 2005;29:381–389.PubMedCrossRef
13.
go back to reference Chu PG, Schwarz R, Lau SK, Yen Y, Weiss LM. Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Am J Surg Pathol 2005;29:359–367.PubMedCrossRef Chu PG, Schwarz R, Lau SK, Yen Y, Weiss LM. Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Am J Surg Pathol 2005;29:359–367.PubMedCrossRef
14.
go back to reference Goldstein NS, Bassi D. Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of Vater adenocarcinomas. Percentage of positivity and distribution is affected by the cut-point threshold. Am J Clin Pathol 2001;115:695–702.PubMedCrossRef Goldstein NS, Bassi D. Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of Vater adenocarcinomas. Percentage of positivity and distribution is affected by the cut-point threshold. Am J Clin Pathol 2001;115:695–702.PubMedCrossRef
15.
go back to reference Sipos B, Moser S, Kalthoff H, Torok V, Lohr M, Kloppel G. A comprehensive characterization of pancreatic ductal carcinoma cell lines: towards the establishment of an in vitro research platform. Virchows Arch 2003;442(5):444–445.PubMed Sipos B, Moser S, Kalthoff H, Torok V, Lohr M, Kloppel G. A comprehensive characterization of pancreatic ductal carcinoma cell lines: towards the establishment of an in vitro research platform. Virchows Arch 2003;442(5):444–445.PubMed
16.
go back to reference Zweigh MH, Campbell G. Receiver-operating characteristics (ROC) plots, a fundamental evaluation tool in clinical medicine. Clin Chem 1993;39:561–577. Zweigh MH, Campbell G. Receiver-operating characteristics (ROC) plots, a fundamental evaluation tool in clinical medicine. Clin Chem 1993;39:561–577.
Metadata
Title
Detection of Micrometastases in Peritoneal Washings of Pancreatic Cancer Patients by the Reverse Transcriptase Polymerase Chain Reaction
Authors
Kimberly Moore Dalal
Yanghee Woo
Charles Galanis
Mithat Gonen
Laura Tang
Peter Allen
Ronald DeMatteo
Yuman Fong
Daniel G. Coit
Publication date
01-12-2007
Publisher
Springer-Verlag
Published in
Journal of Gastrointestinal Surgery / Issue 12/2007
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-007-0283-z

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