Abstract
Surgeons wish to know of any correlation between an operation and the incidence of metastasis. In perioperative periods, pancreatic cancer cells were identified by detecting mutant K‐ras gene by two‐step PCR and RFLP analysis in blood samples taken from peripheral blood. In no case was K‐ras point mutation detected in blood before operation, although the mutant band was observed in all cases at the time the lesion was resected. Surprisingly, in five of ten cases, positive bands were identified just after laparotomy, before we had reached the primary lesion. In almost all cases, mutant K‐ras was detected until the fourteenth postoperative day. These findings suggest that cancer cells exist in the circulation, and have a potential for hematogenous metastasis during the perioperative period. In conclusion, surgical stress causes hematogenous dissemination of pancreatic cancer cells, and surgeons should employ the appropriate anti‐metastasis therapy in the perioperative period.
Keywords: Pancreatic cancer, Blood, Metastasis, K‐ras, PCR
Full Text
The Full Text of this article is available as a PDF (286.3 KB).
REFERENCE
- 1.Nakao , A. and Takagi , H.Isolated pancreatectomy for pancreatic head carcinoma using catheter bypass of the portal vein . Hepato-Gastroenterology , 40 , 426 – 429 ( 1993. ). [PubMed] [Google Scholar]
- 2.Nakao , A. , Harada , A. , Nonami , T. , Kaneko , T. , Inoue , S. and Takagi , H.Clinical significance of portal invasion by pancreatic head carcinoma . Surgery , 117 , 50 – 55 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 3.Tada , M. , Omata , M. , Kawai , S. , Saisho , H. , Ohto , M. , Saiki , K. and Sninsky , J. J.Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma . Cancer Res ., 53 , 2472 – 2474 ( 1993. ). [PubMed] [Google Scholar]
- 4.Gustincich , S. , Manfioletti , G. , Del Sal , G. , Schneider , C. and Carninci , P.A first method for high‐quality genomic DNA extraction from whole human blood . BioTechniques , 11 , 298 – 302 ( 1991. ). [PubMed] [Google Scholar]
- 5.Kahn , S. M. , Jiang , W. , Culbertson , T. A. , Weinstein , I. B. , Williams , G. M. , Tomita , N. and Ronai , Z.Rapid and sensitive nonradioactive detection of mutant K‐ras genes via ‘enriched’ PCR amplification . Oncogene , 6 , 1079 – 1083 ( 1991. ). [PubMed] [Google Scholar]
- 6.Poste , G. and Fidler , I. J.The pathogenesis of cancer metastasis . Nature , 28 , 139 – 146 ( 1980. ). [DOI] [PubMed] [Google Scholar]
- 7.Glaves , D. , Huben , R. P. and Weiss , L.Haematogenous dissemination of cells from human renal adenocarcinomas . Br. J. Cancer , 57 , 32 – 35 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Almoguera , C. , Shibata , D. , Forrester , K. , Martin , J. , Arnheim , N. and Perucho , M.Most human carcinomas of the exocrine pancreas contain mutant c‐K‐ras genes . Cell , 53 , 549 – 554 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 9.Yanagisawa , A. , Ohtake , K. , Ohashi , K. , Hori , M. , Kitagawa , T. , Sugano , H. and Kato , Y.Frequent c‐Ki‐ras oncogene activation in mucous cell hyperplasias of pancreas suffering from chronic inflammation . Cancer Res ., 53 , 953 – 956 ( 1993. ). [PubMed] [Google Scholar]
- 10.Caldas , C. , Hahn , S. A. , Hruban , R. H. , Redston , M. S. , Yeo , C. J. and Kern , S. E.Detection of K‐ras mutation and pancreatic ductal hyperplasia . Cancer Res ., 54 , 3568 – 3573 ( 1994. ). [PubMed] [Google Scholar]
- 11.Inoue , S. , Nakao , A. , Kasai , Y. , Harada , A. , Nonami , T. and Takagi , H.Detection of hepatic micrometastasis in pancreatic adenocarcinoma patients by two‐stage polymerase chain reaction / restriction fragment length polymorphism analysis . Jpn. J. Cancer Res ., 86 , 626 – 630 ( 1995. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Smith , B. , Selby , P. , Southgate , J. , Pittman , K. , Bradley , C. and Blair , G. E.Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction . Lancet , 338 , 1227 – 1229 ( 1991. ). [DOI] [PubMed] [Google Scholar]
- 13.Moreno , J. G. , Croce , C. M. , Fischer , R. , Monne , M. , Vihko , P. , Mulholland , S. G. and Gomella , L. G.Detection of hematogenous micrometastasis in patients with prostate cancer . Cancer Res ., 52 , 6110 – 6112 ( 1992. ). [PubMed] [Google Scholar]
- 14.Shapiro , J. , Jersky , J. , Katzav , S. , Feldman , M. and Segal , S.Anesthetic drugs accelerate the progression of postoperative metastases of mouse tumors . J. Clin. Invest ., 68 , 678 – 685 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Azuma , K. , Mike , N. , Fujiwara , Y. , Shimada , Y. and Watanabe , T.Effect of halothane on intracellular adhesion molecule‐1(ICAM‐1) in melanoma cells . J. Anesth ., 7 , 442 – 446 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 16.Fidler , I. J.Metastasis: quantitative analysis of distribution and fate of tumor emboli labeled with 125I‐5‐iodo‐2′‐deoxyuridine . J. Natl. Cancer Inst ., 45 , 773 – 782 ( 1970. ). [PubMed] [Google Scholar]
- 17.Glaves , D.Metastasis: reticuloendothelial system and organ retention of disseminated malignant cells . Int. J. Cancer , 26 , 115 – 122 ( 1980. ). [DOI] [PubMed] [Google Scholar]