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01-11-2008 | 2008 ssat plenary presentation

Nodal Microinvolvement in Patients with Carcinoma of the Papilla of Vater Receiving No Adjuvant Chemotherapy

Authors: Dean Bogoevski, Hassan Chayeb, Guell Cataldegirmen, Paulus G. Schurr, Jussuf T. Kaifi, Oliver Mann, Emre F. Yekebas, Jakob R. Izbicki

Published in: Journal of Gastrointestinal Surgery | Issue 11/2008

Abstract

Background

To assess the prognostic significance of nodal microinvolvement in patients with carcinoma of the papilla of Vater.

Methods

From 1993 to 2003 at the University Clinic Hamburg, 777 patients were operated upon pancreatic and periampullary carcinomas. The vast majority of patients were operated upon pancreatic ductal adenocarcinoma (n = 566, 73%), followed by carcinomas of the papilla of Vater (n = 112, 14%), pancreatic neuroendocrine carcinomas (n = 39, 5%), intraductal papillary mucinous neoplasms (n = 33, 4%), and distal bile duct carcinomas (n = 27, 3%). Fresh-frozen tissue sections from 169 lymph nodes (LNs) classified as tumor free by routine histopathology from 57 patients with R0 resected carcinoma of the papilla of Vater who had been spared from adjuvant chemotherapy were immunohistochemically (IHC) examined, using a sensitive IHC assay with the anti-epithelial monoclonal antibody Ber-EP4 for tumor cell detection. With regard to histopathology, 39 (63%) of the patients were staged as pT1/pT2, 21 (37%) as pT3/pT4, 30 (53%) as pN0, while 38 (67%) as G1/G2.

Results

Of the 169 “tumor-free” LNs, 91 LNs (53.8%) contained Ber-EP4-positive tumor cells. These 91 LNs were from 40 (70%) patients. The mean overall survival in patients without nodal microinvolvement of 35.8 months (median—not yet reached) was significantly longer than that in patients with nodal microinvolvement (mean 16.6; median 13; p = 0.019). Multivariate Cox regression analysis for overall survival revealed that grading was the most significant independent prognostic factor (p = 0.001), followed by nodal microinvolvement (p = 0.013).

Conclusions

The influence of occult tumor cell dissemination in LNs of patients with histologically proven carcinoma of the papilla of Vater supports the need for further tumor staging through immunohistochemistry.

Iwama T, Mishima Y, Utsunomiya J. The impact of familial adenomatous polyposis on the tumorigenesis and mortality at the several organs. Its rational treatment. Ann Surg 1993;217(2):101–108. doi:10.1097/00000658-199302000-00002.PubMedCrossRef

Galle TS, Juel K, Bulow S. Causes of death in familial adenomatous polyposis. Scand J Gastroenterol 1999;34(8):808–812. doi:10.1080/003655299750025741.PubMedCrossRef

Tonelli F, Nardi F, Bechi P, et al. Extracolonic polyps in familial polyposis coli and Gardner’s syndrome. Dis Colon Rectum 1985;28(9):664–668. doi:10.1007/BF02553447.PubMedCrossRef

Fischer HP, Zhou H. Pathogenesis and histomorphology of ampullary carcinomas and their precursor lesions review and individual findings. Pathologe 2003;24(3):196–203.PubMed

Abrams RA, Grochow LB, Chakravarthy A, et al. Intensified adjuvant therapy for pancreatic and periampullary adenocarcinoma: survival results and observations regarding patterns of failure, radiotherapy dose and CA19-9 levels. Int J Radiat Oncol Biol Phys 1999;44(5):1039–1046. doi:10.1016/S0360-3016(99)00107-8.PubMed

Albores-Saavedra J, Henson DE, Sobin LH. The WHO histological classification of tumors of the gallbladder and extrahepatic bile ducts. A commentary on the second edition. Cancer 1992;70(2):410–414. doi:10.1002/1097-0142(19920715)70:2<410::AID-CNCR2820700207>3.0.CO;2-R.PubMedCrossRef

Alstrup N, Burcharth F, Hauge C, Horn T. Transduodenal excision of tumours of the ampulla of Vater. Eur J Surg 1996;162(12):961–967.PubMed

Pantel K, Brakenhoff RH. Dissecting the metastatic cascade. Nat Rev Cancer 2004;4(6):448–456. doi:10.1038/nrc1370.PubMedCrossRef

Byrne J, Waldron R, McAvinchey D, Dervan P. The use of monoclonal antibodies for the histopathological detection of mammary axillary micrometastases. Eur J Surg Oncol 1987;13(5):409–411.PubMed

10.

Passlick B, Izbicki JR, Kubuschok B, et al. Immunohistochemical assessment of individual tumor cells in lymph nodes of patients with non-small-cell lung cancer. J Clin Oncol 1994;12(9):1827–1832.PubMed

11.

Latza U, Niedobitek G, Schwarting R, et al. Ber-EP4: new monoclonal antibody which distinguishes epithelia from mesothelial. J Clin Pathol 1990;43(3):213–219. doi:10.1136/jcp.43.3.213.PubMedCrossRef

12.

Raymond WA, Leong AS. Immunoperoxidase staining in the detection of lymph node metastases in stage I breast cancer. Pathology 1989;21(1):11–15. doi:10.3109/00313028909059522.PubMedCrossRef

13.

Pantel K, Izbicki JR, Angstwurm M, et al. Immunocytological detection of bone marrow micrometastasis in operable non-small cell lung cancer. Cancer Res 1993;53(5):1027–1031.PubMed

14.

Bussolati G, Gugliotta P, Morra I, et al. The immunohistochemical detection of lymph node metastases from infiltrating lobular carcinoma of the breast. Br J Cancer. 1986;54(4):631–636.PubMed

15.

Chen ZL, Perez S, Holmes EC, et al. Frequency and distribution of occult micrometastases in lymph nodes of patients with non-small-cell lung carcinoma. J Natl Cancer Inst 1993;85(6):493–498. doi:10.1093/jnci/85.6.493.PubMedCrossRef

16.

Casson AG, Rusch VW, Ginsberg RJ, et al. Lymph node mapping of esophageal cancer. Ann Thorac Surg 1994;58(5):1569–1570.PubMedCrossRef

17.

de Mascarel I, Bonichon F, Coindre JM, Trojani M. Prognostic significance of breast cancer axillary lymph node micrometastases assessed by two special techniques: reevaluation with longer follow-up. Br J Cancer 1992;66(3):523–527.PubMed

18.

Martini N, Flehinger BJ, Zaman MB, Beattie EJ Jr. Results of resection in non-oat cell carcinoma of the lung with mediastinal lymph node metastases. Ann Surg 1983;198(3):386–397. doi:10.1097/00000658-198309000-00015.PubMedCrossRef

19.

Momburg F, Moldenhauer G, Hammerling GJ, Moller P. Immunohistochemical study of the expression of a Mr 34,000 human epithelium-specific surface glycoprotein in normal and malignant tissues. Cancer Res 1987;47(11):2883–2891.PubMed

20.

Pantel K, Schlimok G, Angstwurm M, et al. Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow. J Hematother 1994;3(3):165–173.PubMed

21.

Bogoevski D, Yekebas EF, Schurr P, et al. Mode of spread in the early phase of lymphatic metastasis in pancreatic ductal adenocarcinoma: prognostic significance of nodal microinvolvement. Ann Surg 2004;240(6):993–1000. discussion 1000–1. doi:10.1097/01.sla.0000145922.25106.e3.PubMedCrossRef

22.

Izbicki JR, Hosch SB, Pichlmeier U, et al. Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with completely resected esophageal cancer. N Engl J Med 1997;337(17):1188–1194. doi:10.1056/NEJM199710233371702.PubMedCrossRef

23.

Kasper M, Stosiek P, Typlt H, Karsten U. Histological evaluation of three new monoclonal anti-cytokeratin antibodies. 1. Normal tissues. Eur J Cancer Clin Oncol 1987;23(2):137–147. doi:10.1016/0277-5379(87)90007-1.PubMedCrossRef

24.

Z’Graggen K, Centeno BA, Fernandez-del Castillo C, et al. Biological implications of tumor cells in blood and bone marrow of pancreatic cancer patients. Surgery 2001;129(5):537–546. doi:10.1067/msy.2001.113819.PubMedCrossRef

25.

Scheunemann P, Stoecklein NH, Rehders A, et al. Frequency and prognostic significance of occult tumor cells in lymph nodes in patients with adenocarcinoma of the papilla of Vater. HPB Oxf 2007;9(2):135–139. doi:10.1080/13651820601090646.CrossRef

26.

Yekebas EF, Bogoevski D, Bubenheim M, et al. Strong prognostic value of nodal and bone marrow micro-involvement in patients with pancreatic ductal carcinoma receiving no adjuvant chemotherapy. World J Gastroenterol 2006;12(40):6515–6221.PubMed

27.

Pedrazzoli S, DiCarlo V, Dionigi R, et al. Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann Surg 1998;228(4):508–517. doi:10.1097/00000658-199810000-00007.PubMedCrossRef

28.

UICC. TNM classification of malignant tumors. 4th ed. New York: Springer, 1987.

29.

Moeschberger ML, Klein JP. Statistical methods for dependent competing risks. Lifetime Data Anal 1995;1(2):195–204. doi:10.1007/BF00985770.PubMedCrossRef

30.

Cox D. Regression models and life tables with discussion. J R Stat Soc [Ser A] 1972;34:187–220.

31.

Ouaissi M, Sielezneff I, Alves A, et al. Long term outcome following 26 surgical ampullectomies. Ann Chir 2006;131(5):322–327. doi:10.1016/j.anchir.2006.03.004.PubMedCrossRef

32.

Group ILBCS. Prognostic importance of occult axillary lymph node micrometastases from breast cancers. Lancet 1990;335(8705):1565–1568.

33.

Nakano K, Chijiiwa K, Toyonaga T, et al. Combination therapy of resection and intraoperative radiation for patients with carcinomas of extrahepatic bile duct and ampulla of Vater: prognostic advantage over resection alone? Hepatogastroenterology 2003;50(52):928–933.PubMed

34.

Lee JH, Whittington R, Williams NN, et al. Outcome of pancreaticoduodenectomy and impact of adjuvant therapy for ampullary carcinomas. Int J Radiat Oncol Biol Phys 2000;47(4):945–953. doi:10.1016/S0360-3016(00)00537-X.PubMed

35.

Hosch S, Kraus J, Scheunemann P, et al. Malignant potential and cytogenetic characteristics of occult disseminated tumor cells in esophageal cancer. Cancer Res 2000;60(24):6836–6840.PubMed

36.

Witzigmann H, Mobius C, Uhlmann D, et al. Treatment concept of adenomas of Vater’s ampulla. Chirurg 2000;71(2):196–201.PubMed

37.

Demetriades H, Zacharakis E, Kirou I, et al. Local excision as a treatment for tumors of ampulla of Vater. World J Surg Oncol 2006;4:14. doi:10.1186/1477-7819-4-14.PubMedCrossRef

38.

Beger HG, Treitschke F, Gansauge F, et al. Tumor of the ampulla of Vater: experience with local or radical resection in 171 consecutively treated patients. Arch Surg 1999;134(5):526–532. doi:10.1001/archsurg.134.5.526.PubMedCrossRef

39.

Yoon YS, Kim SW, Park SJ, et al. Clinicopathologic analysis of early ampullary cancers with a focus on the feasibility of ampullectomy. Ann Surg 2005;242(1):92–100. doi:10.1097/01.sla.0000167853.04171.bb.PubMedCrossRef

40.

Fidler IJ, Kripke ML. Metastasis results from preexisting variant cells within a malignant tumor. Science 1977;197(4306):893–895. doi:10.1126/science.887927.PubMedCrossRef

41.

Muhlhofer A, Kronawitter U, Zoller WG. Prognostic value of immunohistochemically identifiable tumor cells in lymph nodes of patients with RO-resected esophageal carcinoma. Z Gastroenterol 1998;36(5):479–481.PubMed

42.

Garrido F, Ruiz-Cabello F, Cabrera T, et al. Implications for immunosurveillance of altered HLA class I phenotypes in human tumours. Immunol Today 1997;18(2):89–95. doi:10.1016/S0167-5699(96)10075-X.PubMedCrossRef

43.

Delcore R, Rodriguez FJ, Forster J, et al. Significance of lymph node metastases in patients with pancreatic cancer undergoing curative resection. Am J Surg 1996;172(5):463–468. discussion 468–9. doi:10.1016/S0002-9610(96)00237-1.PubMedCrossRef

44.

Bodmer WF, Browning MJ, Krausa P, et al. Tumor escape from immune response by variation in HLA expression and other mechanisms. Ann N Y Acad Sci 1993;690:42–49. doi:10.1111/j.1749-6632.1993.tb43994.x.PubMedCrossRef

45.

Fleming KA, McMichael A, Morton JA, et al. Distribution of HLA class 1 antigens in normal human tissue and in mammary cancer. J Clin Pathol. 1981;34(7):779–784. doi:10.1136/jcp.34.7.779.PubMedCrossRef

Title: Nodal Microinvolvement in Patients with Carcinoma of the Papilla of Vater Receiving No Adjuvant Chemotherapy
Authors: Dean Bogoevski
Hassan Chayeb
Guell Cataldegirmen
Paulus G. Schurr
Jussuf T. Kaifi
Oliver Mann
Emre F. Yekebas
Jakob R. Izbicki
Publication date: 01-11-2008
Publisher: Springer-Verlag
Published in: Journal of Gastrointestinal Surgery / Issue 11/2008
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-008-0683-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Nodal Microinvolvement in Patients with Carcinoma of the Papilla of Vater Receiving No Adjuvant Chemotherapy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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