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Erschienen in: Journal of Gastrointestinal Surgery 5/2016

08.03.2016 | Original Article

Intra-pancreatic Distal Bile Duct Carcinoma is Morphologically, Genetically, and Clinically Distinct from Pancreatic Ductal Adenocarcinoma

verfasst von: Vikram Deshpande, Ioannis T. Konstantinidis, Carlos Fernandez-del Castillo, Aram F. Hezel, Kevin M. Haigis, David T. Ting, Nabeel Bardeesy, Lipika Goyal, Andrew X. Zhu, Andrew L. Warshaw, Keith D. Lillemoe, Cristina R. Ferrone

Erschienen in: Journal of Gastrointestinal Surgery | Ausgabe 5/2016

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Abstract

Purpose

Differentiating intra-pancreatic distal bile duct carcinoma invading the pancreas from pancreatic ductal adenocarcinomas (PDAC) surrounding the distal common bile duct (CBD) can be challenging. Our aim is to identify clinical, morphological, and genetic features characteristic of intra-pancreatic distal bile duct carcinoma.

Methods

Clinicopathologic data of 550 patients undergoing a pancreaticoduodenectomy between September 1990 and May 2008 were reviewed. KRAS status was assessed with mass-spectrometric genotyping.

Results

Ninety-seven patients with intra-pancreatic adenocarcinomas surrounding the CBD were identified; slides were available for 80. Two relationships with the CBD were recognized as follows: type I (n = 42): cancer grew concentrically around the CBD and type II (n = 38): cancer grew asymmetrically around the CBD. Type I adenocarcinomas were associated with high-grade biliary dysplasia (45 vs. 13 %; p = 0.003); type II were associated with high-grade pancreatic intra-epithelial neoplasia (PanIN-2 or -3) (39 vs. 9 %; p = 0.003). Type I tumors had a better median survival (46 months) compared to type II (23 months) or other PDAC (20 months) (p < 0.001). Mutated KRAS was identified in 3/26 (11 %) type I and 20/21 (95 %) type II cancers (p < 0.001). There may be poorer survival in the presence of a KRAS mutation than wild-type KRAS (22.9 vs. 41.6 months; p = 0.3).

Conclusions

Distal periductal adenocarcinomas fall into two distinct groups with biologic, morphologic and genetic differences. Those growing symmetrically around the CBD are more likely to be intra-pancreatic distal bile duct carcinomas and are associated with improved survival whereas cancers with asymmetric growth are more likely to have KRAS mutations and to be PDACs. These findings facilitate a more accurate histopathological diagnosis, which could improve patient selection for therapeutic trials.
Literatur
1.
Zurück zum Zitat Ferrone CR, Brennan MF, Gonen M, et al.: Pancreatic adenocarcinoma: the actual 5-year survivors. J Gastrointest Surg 12:701–6, 2008CrossRefPubMed Ferrone CR, Brennan MF, Gonen M, et al.: Pancreatic adenocarcinoma: the actual 5-year survivors. J Gastrointest Surg 12:701–6, 2008CrossRefPubMed
2.
Zurück zum Zitat Winter JM, Cameron JL, Campbell KA, et al.: 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg 10:1199–210. discussion 1210–1, 2006CrossRefPubMed Winter JM, Cameron JL, Campbell KA, et al.: 1423 pancreaticoduodenectomies for pancreatic cancer: A single-institution experience. J Gastrointest Surg 10:1199–210. discussion 1210–1, 2006CrossRefPubMed
3.
Zurück zum Zitat Schnelldorfer T, Ware AL, Sarr MG, et al.: Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg 247:456–62, 2008CrossRefPubMed Schnelldorfer T, Ware AL, Sarr MG, et al.: Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? Ann Surg 247:456–62, 2008CrossRefPubMed
4.
Zurück zum Zitat Riall TS, Cameron JL, Lillemoe KD, et al.: Resected periampullary adenocarcinoma: 5-year survivors and their 6- to 10-year follow-up. Surgery 140:764–72, 2006CrossRefPubMed Riall TS, Cameron JL, Lillemoe KD, et al.: Resected periampullary adenocarcinoma: 5-year survivors and their 6- to 10-year follow-up. Surgery 140:764–72, 2006CrossRefPubMed
5.
Zurück zum Zitat DeOliveira ML, Cunningham SC, Cameron JL, et al.: Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 245:755–62, 2007CrossRefPubMedPubMedCentral DeOliveira ML, Cunningham SC, Cameron JL, et al.: Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution. Ann Surg 245:755–62, 2007CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Allen PJ, Reiner AS, Gonen M, et al.: Extrahepatic cholangiocarcinoma: a comparison of patients with resected proximal and distal lesions. HPB (Oxford) 10:341–6, 2008CrossRef Allen PJ, Reiner AS, Gonen M, et al.: Extrahepatic cholangiocarcinoma: a comparison of patients with resected proximal and distal lesions. HPB (Oxford) 10:341–6, 2008CrossRef
7.
Zurück zum Zitat Valle J, Wasan H, Palmer DH, et al.: Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362:1273–81, 2010CrossRefPubMed Valle J, Wasan H, Palmer DH, et al.: Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 362:1273–81, 2010CrossRefPubMed
8.
Zurück zum Zitat Kulke MH, Tempero MA, Niedzwiecki D, et al.: Randomized phase II study of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in patients with metastatic pancreatic cancer: CALGB 89904. J Clin Oncol 27:5506–12, 2009CrossRefPubMedPubMedCentral Kulke MH, Tempero MA, Niedzwiecki D, et al.: Randomized phase II study of gemcitabine administered at a fixed dose rate or in combination with cisplatin, docetaxel, or irinotecan in patients with metastatic pancreatic cancer: CALGB 89904. J Clin Oncol 27:5506–12, 2009CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Wilkowski R, Boeck S, Ostermaier S, et al.: Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer--a multi-centre randomised phase II study. Br J Cancer 101:1853–9, 2009CrossRefPubMedPubMedCentral Wilkowski R, Boeck S, Ostermaier S, et al.: Chemoradiotherapy with concurrent gemcitabine and cisplatin with or without sequential chemotherapy with gemcitabine/cisplatin vs chemoradiotherapy with concurrent 5-fluorouracil in patients with locally advanced pancreatic cancer--a multi-centre randomised phase II study. Br J Cancer 101:1853–9, 2009CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Rijken AM, Hu J, Perlman EJ, et al.: Genomic alterations in distal bile duct carcinoma by comparative genomic hybridization and karyotype analysis. Genes Chromosomes Cancer 26:185–91, 1999CrossRefPubMed Rijken AM, Hu J, Perlman EJ, et al.: Genomic alterations in distal bile duct carcinoma by comparative genomic hybridization and karyotype analysis. Genes Chromosomes Cancer 26:185–91, 1999CrossRefPubMed
11.
Zurück zum Zitat Fong Y, Blumgart LH, Lin E, et al.: Outcome of treatment for distal bile duct cancer. Br J Surg 83:1712–5, 1996CrossRefPubMed Fong Y, Blumgart LH, Lin E, et al.: Outcome of treatment for distal bile duct cancer. Br J Surg 83:1712–5, 1996CrossRefPubMed
12.
Zurück zum Zitat Nakeeb A, Pitt HA, Sohn TA, et al.: Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg 224:463–73; discussion 473–5, 1996CrossRefPubMedPubMedCentral Nakeeb A, Pitt HA, Sohn TA, et al.: Cholangiocarcinoma. A spectrum of intrahepatic, perihilar, and distal tumors. Ann Surg 224:463–73; discussion 473–5, 1996CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Argani P, Shaukat A, Kaushal M, et al.: Differing rates of loss of DPC4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts. Cancer 91:1332–41, 2001CrossRefPubMed Argani P, Shaukat A, Kaushal M, et al.: Differing rates of loss of DPC4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts. Cancer 91:1332–41, 2001CrossRefPubMed
14.
Zurück zum Zitat Edge SB, Byrd DR, Compton CC, et al. (eds): AJCC Cancer Staging Handbook (ed 7). New York, NY, Springer 2010. Edge SB, Byrd DR, Compton CC, et al. (eds): AJCC Cancer Staging Handbook (ed 7). New York, NY, Springer 2010.
15.
16.
Zurück zum Zitat Thomas RK, Baker AC, Debiasi RM, et al.: High-throughput oncogene mutation profiling in human cancer. Nat Genet 39:347–51, 2007CrossRefPubMed Thomas RK, Baker AC, Debiasi RM, et al.: High-throughput oncogene mutation profiling in human cancer. Nat Genet 39:347–51, 2007CrossRefPubMed
17.
Zurück zum Zitat Almoguera C, Shibata D, Forrester K, et al.: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549–54, 1988CrossRefPubMed Almoguera C, Shibata D, Forrester K, et al.: Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53:549–54, 1988CrossRefPubMed
18.
Zurück zum Zitat Motojima K, Tsunoda T, Kanematsu T, et al.: Distinguishing pancreatic carcinoma from other periampullary carcinomas by analysis of mutations in the Kirsten-ras oncogene. Ann Surg 214:657–62, 1991CrossRefPubMedPubMedCentral Motojima K, Tsunoda T, Kanematsu T, et al.: Distinguishing pancreatic carcinoma from other periampullary carcinomas by analysis of mutations in the Kirsten-ras oncogene. Ann Surg 214:657–62, 1991CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Hidaka E, Yanagisawa A, Seki M, et al.: High frequency of K-ras mutations in biliary duct carcinomas of cases with a long common channel in the papilla of Vater. Cancer Res 60:522–4, 2000PubMed Hidaka E, Yanagisawa A, Seki M, et al.: High frequency of K-ras mutations in biliary duct carcinomas of cases with a long common channel in the papilla of Vater. Cancer Res 60:522–4, 2000PubMed
20.
Zurück zum Zitat Ohashi K, Tstsumi M, Nakajima Y, et al.: Ki-ras point mutations and proliferation activity in biliary tract carcinomas. Br J Cancer 74:930–5, 1996CrossRefPubMedPubMedCentral Ohashi K, Tstsumi M, Nakajima Y, et al.: Ki-ras point mutations and proliferation activity in biliary tract carcinomas. Br J Cancer 74:930–5, 1996CrossRefPubMedPubMedCentral
Metadaten
Titel
Intra-pancreatic Distal Bile Duct Carcinoma is Morphologically, Genetically, and Clinically Distinct from Pancreatic Ductal Adenocarcinoma
verfasst von
Vikram Deshpande
Ioannis T. Konstantinidis
Carlos Fernandez-del Castillo
Aram F. Hezel
Kevin M. Haigis
David T. Ting
Nabeel Bardeesy
Lipika Goyal
Andrew X. Zhu
Andrew L. Warshaw
Keith D. Lillemoe
Cristina R. Ferrone
Publikationsdatum
08.03.2016
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Surgery / Ausgabe 5/2016
Print ISSN: 1091-255X
Elektronische ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-016-3108-0

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