{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T15:07:35Z","timestamp":1770822455257,"version":"3.50.1"},"reference-count":26,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1995,5]]},"abstract":"<jats:p>Differential diagnosis of pancreatic cancer and chronic pancreatitis is sometimes difficult and cytological examination of brushings or aspirated material collected during endoscopic retrograde cholangiopancreatography (ERCP) remains disappointing. As point mutations in codon 12 of the c-Ki-ras 2 gene are found in most pancreatic adenocarcinoma and not in chronic pancreatitis, this study analysed prospectively the presence of these mutations in brushing samples collected during ERCP in 45 patients (26 males, 19 females) showing a dominant stricture of the main pancreatic duct at pancreatography: 24 with pancreatic adenocarcinoma, 16 with chronic pancreatitis, and five intraductal mucin hypersecreting neoplasms. Twenty of 45 patients presented equivocal ERCP findings that did not permit a definite diagnosis. Ki-ras mutations at codon 12 were detected using a rapid and sensitive method based on polymerase chain reaction mediated restriction fragment length polymorphism analysis and confirmed by direct sequencing of polymerase chain reaction products. Results were compared with those provided by routine brush cytology. A definitive diagnosis was established for each patient. Mutations were detected in 20 of 24 patients with pancreatic adenocarcinoma (83%), but in none of the chronic pancreatitis patients and intraductal mucin hypersecreting neoplasms, irrespective of their location. By contrast, only 13 of 24 pancreatic adenocarcinoma (54%) were detected by conventional cytological examination, which yielded four false negative and seven non-contributive results. Sensitivity, specificity, and accuracy of molecular biological and cytological methods were 83%-76%, 100-83%, and 90%-58%, respectively. Notably the mutations could be detected in six patients with small tumour size (&lt; or = 2 cm). In conclusion, Ki-ras analysis performed on pancreatic brushing samples is an efficient procedure, more accurate than cytology in the diagnosis of pancreatic adenocarcinoma, and highly specific in the differentiation between neoplastic and chronic inflammatory ductal changes, especially in patients showing inconclusive ERCP findings.<\/jats:p>","DOI":"10.1136\/gut.36.5.781","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"781-787","source":"Crossref","is-referenced-by-count":72,"title":["Detection of c-Ki-ras gene codon 12 mutations from pancreatic duct brushings in the diagnosis of pancreatic tumours."],"prefix":"10.1136","volume":"36","author":[{"given":"J L","family":"Van Laethem","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Vertongen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Deviere","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J","family":"Van Rampelbergh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Rickaert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Cremer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Robberecht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1995,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1002\/1097-0142(19871101)60:9<2284::AID-CNCR2820600930>3.0.CO;2-V","article-title":"Cancer of the pancreas. 50 years of surgery","volume":"60","author":"Gudjonsson, B.","year":"1987","unstructured":"Gudjonsson B. Cancer of the pancreas. 50 years of surgery. Cancer 1987; 60: 2284-303.","journal-title":"Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1056\/NEJM199305203282001","article-title":"et al and the Intemational Pancreatitis study group. Pancreatitis and the risk of pancreatic cancer","volume":"328","author":"Lowenfels, A.B.; Maisonneuve, P.; Cavallini, G.; Amman, R.W.; Lankisch, P.G.; Andersen, JR","year":"1993","unstructured":"Lowenfels AB, Maisonneuve P, Cavallini G, Amman RW, Lankisch PG, Andersen JR, et al and the Intemational Pancreatitis study group. Pancreatitis and the risk of pancreatic cancer. N EnglJ, Med 1993; 328: 1433-7.","journal-title":"N EnglJ, Med"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1097\/00006676-199201000-00011","article-title":"Diagnosis of pancreatic carcinoma. Imaging techniques and tumors markers","volume":"7","author":"Niederau, C.; Grendell, J.H.","year":"1992","unstructured":"Niederau C, Grendell JH. Diagnosis of pancreatic carcinoma. Imaging techniques and tumors markers. Pancreas 1992; 7: 66-86.","journal-title":"Pancreas"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1002\/1097-0142(19900215)65:4<893::AID-CNCR2820650412>3.0.CO;2-G","article-title":"Role of endoscopic retrograde cholangiopancreatography in differentiating pancreatic cancer coexisting with chronic pancreatitis","volume":"65","author":"Shemesh, E.; Czemiak, A.; Nass, S.; Klein, E.","year":"1990","unstructured":"Shemesh E, Czemiak A, Nass S, Klein E. Role of endoscopic retrograde cholangiopancreatography in differentiating pancreatic cancer coexisting with chronic pancreatitis. Cancer 1990; 65: 893-6.","journal-title":"Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1055\/s-2007-1010273","article-title":"Endoscopic ultrasonography in the diagnosis and staging of pancreatic adenocarcinoma: results of a prospective study with comparison to ultrasonography and CT scan","volume":"25","author":"Palazzo, L.; Roseau, G.; Gayet, B.; Vilgrain, V.; Belghiti, J.; Fekete, F.","year":"1993","unstructured":"Palazzo L, Roseau G, Gayet B, Vilgrain V, Belghiti J, Fekete F, et al. Endoscopic ultrasonography in the diagnosis and staging of pancreatic adenocarcinoma: results of a prospective study with comparison to ultrasonography and CT scan. Endoscopy 1993; 25: 143-50.","journal-title":"Endoscopy"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/0016-5085(92)91800-J","article-title":"Staging of pancreatic and ampullary carcinoma by endoscopic ultrasonography. Comparison with conventional sonography, computed tomography and angiography","volume":"102","author":"true","year":"1992","unstructured":"Rosch Th, Brais C, Gain Th, Feurbach S, Siewert JR, Schusdziarra V, et al. Staging of pancreatic and ampullary carcinoma by endoscopic ultrasonography. Comparison with conventional sonography, computed tomography and angiography. Gastroenterology 1992; 102: 188-99.","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/0016-5085(90)91178-9","article-title":"Endoscopic retrograde brush cytology: a new technique","volume":"99","author":"Venu, R.P.; Geenen, J.E.; Kini, M.; Hogan, W.J.; Payne, M.; Johnson, K.","year":"1990","unstructured":"Venu RP, Geenen JE, Kini M, Hogan WJ, Payne M, Johnson K, et al. Endoscopic retrograde brush cytology: a new technique. Gastroenterology 1990; 99: 1475-9.","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1002\/1097-0142(19810315)47:6+<1652::AID-CNCR2820471432>3.0.CO;2-F","article-title":"Cytologic studies for the diagnosis of pancreatic cancer","volume":"47","author":"Goodale, R.L.; Gajl-Peczalaka, K.; Dressel, T.; Samuelson, J.","year":"1981","unstructured":"Goodale RL, Gajl-Peczalaka K, Dressel T, Samuelson J. Cytologic studies for the diagnosis of pancreatic cancer. Cancer 1981; 47: 1652-5.","journal-title":"Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1002\/1097-0142(19921201)70:11<2610::AID-CNCR2820701107>3.0.CO;2-Y","article-title":"Cytologic examination of pure pancreatic juice in the diagnosis of pancreatic carcinoma","volume":"70","author":"Nakaizumi, A.; Tatsuta, M.; Vehara, H.; Yamamoto, R.; Takenaka, A.","year":"1992","unstructured":"Nakaizumi A, Tatsuta M, Vehara H, Yamamoto R, Takenaka A, et al. Cytologic examination of pure pancreatic juice in the diagnosis of pancreatic carcinoma. Cancer 1992; 70: 2610-4.","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/304501a0","article-title":"Structure and organisation of the human Ki-Ras oncogene and a related pseudogene","volume":"304","author":"McGrath, J.P.; Capon, D.J.; Smith, D.H.; Chen, E.Y.; Seeburg, P.H.; Soeddel, D.V.","year":"1983","unstructured":"McGrath JP, Capon DJ, Smith DH, Chen EY, Seeburg PH, Soeddel DV, et al. Structure and organisation of the human Ki-Ras oncogene and a related pseudogene. Nature 1983; 304: 501-6.","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/0092-8674(88)90571-5","article-title":"Most human carcinomas of the exocrine pancreas contain mutant c-Ki-ras genes","volume":"53","author":"Almoguera, C.; Shibata, D.; Forrester, K.; Martin, J.; Arnheim, N.; Perucho, M.","year":"1988","unstructured":"Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-Ki-ras genes. Cell 1988; 53: 549-54.","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0016-5085(91)90606-L","article-title":"Clinical application of ras gene mutation for diagnosis of pancreatic adenocarcinoma","volume":"100","author":"Tada, M.; Omata, M.; Ohto, M.","year":"1991","unstructured":"Tada M, Omata M, Ohto M. Clinical application of ras gene mutation for diagnosis of pancreatic adenocarcinoma. Gastroenterology 1991; 100: 233-8.","journal-title":"Gastroenterology"},{"key":"ref_13","first-page":"230","article-title":"Ki-ras oncogene activation","volume-title":"preinvasive pancreatic cancer. Gastroenterology 1992; 102","author":"Lemoine, N.R.; Jain, S.; Hughes, C.M.; Staddon, S.L.; Maillet, B.; Hall, P.A.","unstructured":"Lemoine NR, Jain S, Hughes CM, Staddon SL, Maillet B, Hall PA, et al. Ki-ras oncogene activation in preinvasive pancreatic cancer. Gastroenterology 1992; 102: 230-6."},{"key":"ref_14","first-page":"4507","article-title":"Ki-ras mutation is an early event in pancreatic duct carcinogenesis in the Syrian golden hamster","volume":"52","author":"Cerny, W.L.; Mangold, K.A.; Scarpelli, D.G.","year":"1992","unstructured":"Cerny WL, Mangold KA, Scarpelli DG. Ki-ras mutation is an early event in pancreatic duct carcinogenesis in the Syrian golden hamster. Cancer Res 1992; 52: 4507-13.","journal-title":"Cancer Res"},{"key":"ref_15","first-page":"953","article-title":"Frequent c-Ki-ras oncogene activation in mucous cell hyperplasias of pancreas suffering from chronic inflammation","volume":"53","author":"Yanagisawa, A.; Ohtake, K.; Ohashi, K.; Hori, M.; Kitasawa, T.; Sugano, H.","year":"1993","unstructured":"Yanagisawa A, Ohtake K, Ohashi K, Hori M, Kitasawa T, Sugano H, et al. Frequent c-Ki-ras oncogene activation in mucous cell hyperplasias of pancreas suffering from chronic inflammation. Cancer Res 1993; 53: 953-6.","journal-title":"Cancer Res"},{"key":"ref_16","first-page":"1279","article-title":"Detection of c-K-ras mutations in fine needle aspirates from human pancreatic adenocarcinomas","volume":"50","author":"Shibata, D.; Almoguera, C.; Forrester, K.; Dunitz, J.; Martin, S.E.; Cosgrove, M.M.","year":"1990","unstructured":"Shibata D, Almoguera C, Forrester K, Dunitz J, Martin SE, Cosgrove MM, et al. Detection of c-K-ras mutations in fine needle aspirates from human pancreatic adenocarcinomas. Cancer Res 1990; 50: 1279-83.","journal-title":"Cancer Res"},{"key":"ref_17","first-page":"2472","article-title":"Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma","volume":"53","author":"Tada, M.; Omata, M.; Kawai, S.; Saisho, H.; Ohto, M.; Saiki, R.K.","year":"1993","unstructured":"Tada M, Omata M, Kawai S, Saisho H, Ohto M, Saiki RK, et al. Detection of ras gene mutations in pancreatic juice and peripheral blood of patients with pancreatic adenocarcinoma. Cancer Res 1993; 53: 2472-4.","journal-title":"Cancer Res"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/0016-5085(91)90032-G","article-title":"Intraductal mucin-hypersecreting neoplasms of the pancreas. A clinicopathologic study of eight patients","volume":"101","author":"Rickaert, F.; Cremer, M.; Deviere, J.; Tavares, L.; Lambillotte, J.P.; Schroder, S.","year":"1991","unstructured":"Rickaert F, Cremer M, Deviere J, Tavares L, Lambillotte JP, Schroder S, et al. Intraductal mucin-hypersecreting neoplasms of the pancreas. A clinicopathologic study of eight patients. Gastroenterology 1991; 101: 512-9.","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8093","DOI":"10.1093\/nar\/17.20.8093","article-title":"Detection of minority point mutations by modified PCR technique: a new approach for a sensitive diagnosis of tumor-progression markers","volume":"17","author":"Haliassos, A.; Chomel, J.C.; Grandjouan, S.; Kruh, J.; Kaplan, J.C.; Kitzis, A.","year":"1989","unstructured":"Haliassos A, Chomel JC, Grandjouan S, Kruh J, Kaplan JC, Kitzis A. Detection of minority point mutations by modified PCR technique: a new approach for a sensitive diagnosis of tumor-progression markers. Nucleic Acids Res 1989; 17: 8093-9.","journal-title":"Nucleic Acids Res"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1016\/0016-5085(92)91427-6","article-title":"Mutations in c-K-ras 2 gene codon 12 during colorectal tumorigenesis in familial adenomatous polyposis","volume":"103","author":"Ando, M.; Takemura, K.; Maruyama, M.; Endo, M.; Iwama, T.; Yuasa, Y.","year":"1992","unstructured":"Ando M, Takemura K, Maruyama M, Endo M, Iwama T, Yuasa Y. Mutations in c-K-ras 2 gene codon 12 during colorectal tumorigenesis in familial adenomatous polyposis. Gastroenterology 1992; 103: 1725-31.","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5463","DOI":"10.1073\/pnas.74.12.5463","article-title":"DNA sequencing with chain-terminating inhibitors","volume":"74","author":"Sanger, F.; Niklen, S.; Coulson, A.R.","year":"1977","unstructured":"Sanger F, Niklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 1977; 74: 5463-7.","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref_22","first-page":"844","article-title":"Liver and pancreas","author":"Tao, L.C.","unstructured":"Tao LC. Liver and pancreas. In: Bibbo M, ed. Comprehensive cytopathology. Philadelphia: W B Saunders, 1991:844."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1002\/1097-0142(19910201)67:3<634::AID-CNCR2820670318>3.0.CO;2-7","article-title":"Ras gene mutations in intraductal papillary neoplasms of the pancreas: analysis in five cases","volume":"67","author":"Tada, M.; Omata, M.; Ohto, M.","year":"1991","unstructured":"Tada M, Omata M, Ohto M. Ras gene mutations in intraductal papillary neoplasms of the pancreas: analysis in five cases. Cancer 1991; 67: 634-7.","journal-title":"Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1111\/j.1349-7006.1991.tb01756.x","article-title":"c-Ki-ras point mutations in ductectatic-type mucinous cystic neoplasms of the pancreas","volume":"82","author":"Yanagisawa, A.; Kato, Y.; Ohtake, K.; Kitagawa, T.; Ohashi, K.; Hori, M.","year":"1991","unstructured":"Yanagisawa A, Kato Y, Ohtake K, Kitagawa T, Ohashi K, Hori M, et al. c-Ki-ras point mutations in ductectatic-type mucinous cystic neoplasms of the pancreas. Jpn J Cancer Res 1991; 82: 1057-60.","journal-title":"Jpn J Cancer Res"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1002\/1097-0142(19890915)64:6<1329::AID-CNCR2820640627>3.0.CO;2-S","article-title":"Intraductal papillary neoplasms of the pancreas: a clinicopathologic study of six patients","volume":"64","author":"Morohoshi, T.; Kanda, M.; Asanuma, K.; Kloppel, G.","year":"1989","unstructured":"Morohoshi T, Kanda M, Asanuma K, Kloppel G. Intraductal papillary neoplasms of the pancreas: a clinicopathologic study of six patients. Cancer 1989; 64: 1329-35.","journal-title":"Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1148\/radiology.170.3.2916036","article-title":"Mucinous pancreatic duct ectasia in the body of the pancreas","volume":"170","author":"Agostini, S.; Choux, R.; Payan, M.J.; Sastre, B.; Sahel, J.; Clement, J.P.","year":"1989","unstructured":"Agostini S, Choux R, Payan MJ, Sastre B, Sahel J, Clement JP. Mucinous pancreatic duct ectasia in the body of the pancreas. Radiology 1989; 170: 815-6.","journal-title":"Radiology"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.36.5.781","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T19:59:45Z","timestamp":1765655985000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.36.5.781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,5]]},"references-count":26,"journal-issue":{"issue":"5","published-online":{"date-parts":[[1995,5,1]]},"published-print":{"date-parts":[[1995,5]]}},"alternative-id":["10.1136\/gut.36.5.781"],"URL":"https:\/\/doi.org\/10.1136\/gut.36.5.781","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"value":"0017-5749","type":"print"},{"value":"1468-3288","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,5]]}}}