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Annals of Surgical Oncology

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01-11-2009 | Pancreatic Tumors

Prognostic Relevance of Extracapsular Lymph Node Involvement in Pancreatic Ductal Adenocarcinoma

Authors: Gregory Sergeant, MD, Nadine Ectors, MD, PhD, Steffen Fieuws, PhD, Raymond Aerts, MD, Baki Topal, MD, PhD

Published in: Annals of Surgical Oncology | Issue 11/2009

Abstract

Background

In several malignancies extracapsular lymph node involvement (ECLNI) identifies a subgroup of patients with worse prognosis but no data are available on its significance in pancreatic ductal adenocarcinoma (PDAC). The aim of our study was to assess the prognostic relevance of ECLNI in resectable PDAC.

Methods

A retrospective analysis was performed of 137 consecutive pancreatic resections for PDAC. Two investigators blinded for survival data systematically reviewed all pathological data. Survival curves were estimated using the Kaplan-Meier method. Multivariable Cox regression models were used to identify predictors of disease-free survival (DFS) and overall survival (OS). The median follow-up after surgery was 19 months.

Results

ECLNI was identified in 59 of 99 node-positive patients. The median DFS in patients with ECLNI vs. intracapsular LNI (ICLNI) was 6.8 vs. 12.0 months, respectively (P = .027). The median OS in patients with ECLNI vs. ICLNI was 16.1 and 21.8 months, respectively (P = .098). On multivariable analysis extracapsular lymph node ratio (ECLNR) was identified as an independent predictor of OS (P = .003). In patients with ECLNI, both OS and DFS were improved after adjuvant chemoradiation compared with those who did not receive adjuvant treatment (P = .01).

Conclusions

Extracapsular lymph node ratio is an independent predictor of survival in patients with PDAC. Patients with ECLNI from pancreatic cancer seem to benefit from adjuvant chemoradiation but not from chemotherapy alone.

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.CrossRefPubMed

Luttges J, Schemm S, Vogel I, Hedderich J, Kremer B, Klöppel G. The grade of pancreatic ductal carcinoma is an independent prognostic factor and is superior to the immunohistochemical assessment of proliferation. J Pathol. 2000;191:154–61.CrossRefPubMed

Cleary SP, Gryfe R, Guindi M, Greig P, Smith L, Mackenzie R, et al. Prognostic factors in resected pancreatic adenocarcinoma: analysis of actual 5-year survivors. J Am Coll Surg. 2004;198:722–31.CrossRefPubMed

Lim JE, Chien MW, Earle CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg. 2003;237:74–85.CrossRefPubMed

Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4:567–79.CrossRefPubMed

House M, Gönen M, Jarnagin,W, D’Angelica M, DeMatteo RP, Fong Y, et al. Prognostic significance of pathologic nodal status in patients with resected pancreatic cancer. J Gastrointest Surg. 2007;11:1549–55.CrossRefPubMed

Slidell MB, Chang DC, Cameron JL, Wolfgang C, Herman JM, Schulick RD, et al. Impact of total lymph node count and lymph node ratio on staging and survival after pancreatectomy for pancreatic adenocarcinoma: A large, population-based analysis. Ann Surg Oncol. 2008;15:165–74.CrossRefPubMed

Sierzega M, Popiela T, Kulig J, Nowak K. The ratio of metastatic/resected lymph nodes is an independent prognostic factor in patients with node-positive pancreatic head cancer. Pancreas. 2006;33:240–5.CrossRefPubMed

Berger AC, Watson JC, Ross EA, Hoffman JP. The metastatic/examined lymph node ratio is an important prognostic factor after pancreaticoduodenectomy for pancreatic adenocarcinoma. Am Surg. 2004;70:235–40; discussion 240.PubMed

10.

Pawlik TM, Gleisner AL, Cameron JL, Winter JM, Assumpcao L, Lillemoe KD, et al. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery. 2007;141:610–8.CrossRefPubMed

11.

Wind J, Lagarde SM, Ten Kate FJ, Ubbink DT, Bemelman WA, van Lanschot JJ. A systematic review on the significance of extracapsular lymph node involvement in gastrointestinal malignancies. Eur J Surg Oncol. 2007;33:401–8.CrossRefPubMed

12.

Cubila A, Fitzgerald P. Tumors of the exocrine pancreas. In: Atlas of tumor pathology. 2nd ed. Washington: Armed Forces Institute of Pathology; 1984.

13.

Solcia E, Capella C, Klöppel G. Tumors of the pancreas. In: Atlas of tumor pathology. 3rd ed. Washington: Armed Forces Institute of Pathology; 1997.

14.

Peters K, Klöppel G. Undifferenzierte Pankreaskarzinome. Der Sprung ins Chaos. Pathologe. 2005;26:18–21.CrossRefPubMed

15.

Exocrine pancreas. In: American joint committee on cancer: AJCC cancer staging manual. 6th ed. New York: Springer, 2002. p. 157–64.

16.

Lagarde SM, ten Kate FJ, de Boer DJ, Busch OR, Obertop H, van Lanschot JJ. Extracapsular lymph node involvement in node-positive patients with adenocarcinoma of the distal esophagus or gastroesophageal junction. Am J Surg Pathol. 2006;30:171–6.CrossRefPubMed

17.

Bland JM AD. Survival probabilities. The Kaplan-Meier method. BMJ. 1998;317:1572.PubMed

18.

Klein J, Moeschberger M. Survival analysis: techniques for censored and truncated data. New York: Springer, 1992. p. 187–228.

19.

Klein J, Moeschberger M. Survival analysis: techniques for censored and truncated data. New York: Springer, 1992. p. 229–68.

20.

Austin PC, Tu JV. Automated variable selection methods for logistic regression produced unstable models for predicting acute myocardial infarction mortality. J Clin Epidemiol. 2004;57:1138–46.CrossRefPubMed

21.

Heagerty PJ, Zheng Y. Survival model predictive accuracy and ROC curves. Biometrics. 2005;61:92–105.CrossRefPubMed

22.

Pencina MJ, D’Agostino RB, Sr., D’Agostino RB, Jr., Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157–72; discussion 207–12.CrossRefPubMed

23.

van der Gaag NA, ten Kate FJ, Lagarde SM, Busch OR, van Gulik TM, Gouma DJ. Prognostic significance of extracapsular lymph node involvement in patients with adenocarcinoma of the ampulla of Vater. Br J Surg. 2008;95:735–43.CrossRefPubMed

24.

Lerut T, Coosemans W, Decker G, De Leyn P, Ectors N, Fieuws S, et al. Extracapsular lymph node involvement is a negative prognostic factor in T3 adenocarcinoma of the distal esophagus and gastroesophageal junction. J Thorac Cardiovasc Surg. 2003;126:1121–8.CrossRefPubMed

25.

Garcea G, Dennison AR, Ong SL, Pattenden CJ, Neal CP, Sutton CD, et al. Tumour characteristics predictive of survival following resection for ductal adenocarcinoma of the head of pancreas. Eur J Surg Oncol. 2007;33:892–7.PubMed

26.

Zhou X, Temam S, Oh M, Pungpravat N, Huang BL, Mao L, et al. Global expression-based classification of lymph node metastasis and extracapsular spread of oral tongue squamous cell carcinoma. Neoplasia. 2006;8:925–32.CrossRefPubMed

27.

Yamagata K, Kumagai K. Experimental study of lymphogenous peritoneal cancer dissemination: migration of fluorescent-labelled tumor cells in a rat model of mesenteric lymph vessel obstruction. J Exp Clin Cancer Res. 2000;19:211–7.PubMed

28.

Goyal A, Douglas-Jones AG, Newcombe RG, Mansel RE. Effect of lymphatic tumor burden on sentinel lymph node biopsy in breast cancer. Breast J. 2005;11:188–94.CrossRefPubMed

29.

Tomlinson JS, Jain S, Bentrem DJ, Sekeris EG, Maggard MA, Hines OJ, et al. Accuracy of staging node-negative pancreas cancer: a potential quality measure. Arch Surg. 2007;142:767–73; discussion 773–74.CrossRefPubMed

30.

Schwarz RE, Smith DD. Extent of lymph node retrieval and pancreatic cancer survival: information from a large US population database. Ann Surg Oncol. 2006;13:1189–200.CrossRefPubMed

31.

Gutierrez JC, Franceschi D, Koniaris LG. How many lymph nodes properly stage a periampullary malignancy? J Gastrointest Surg. 2008;12:77–85.CrossRefPubMed

32.

Cserni G. Axillary sentinel lymph node micrometastases with extracapsular extension: a distinct pattern of breast cancer metastasis? J Clin Pathol. 2008;61:115–8.CrossRefPubMed

33.

Horn LC, Hentschel B, Galle D, Bilek K. Extracapsular extension of pelvic lymph node metastases is of prognostic value in carcinoma of the cervix uteri. Gynecol Oncol. 2008;108:63–7.CrossRefPubMed

34.

Carter RL, Barr LC, O’Brien CJ, Soo KC, Shaw HJ. Transcapsular spread of metastatic squamous cell carcinoma from cervical lymph nodes. Am J Surg. 1985;150:495–9.CrossRefPubMed

35.

Smeenk HG, Erdmann J, van Dekken H, van Marion R, Hop WC, Jeekel J, et al. Long-term survival after radical resection for pancreatic head and ampullary cancer: a potential role for the EGF-R. Dig Surg. 2007;24:38–45.CrossRefPubMed

36.

Van den Broeck A, Sergeant G, Ectors N, Van Steenbergen W, Aerts R, Topal B. Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma. Eur J Surg Oncol. 2009;35:600–4.PubMed

37.

Shimada K, Sakamoto Y, Sano T, Kosuge T. The role of paraarotic lymph node involvement on early recurrence and survival after macroscopic curative resection with extended lymphadenectomy for pancreatic carcinoma. J Am Coll Surg. 2006;203:345–52.CrossRefPubMed

38.

Ozaki H, Hiraoka T, Mizumoto R, Matsuno S, Matsumoto Y, Nakayama T, et al. The prognostic significance of lymph node metastasis and intrapancreatic perineural invasion in pancreatic cancer after curative resection. Surg Today. 1999;29:16–22.CrossRefPubMed

39.

Mitsunaga S, Hasebe T, Kinoshita T, Konishi M, Takahashi S, Gotohda N, et al. Detail histologic analysis of nerve plexus invasion in invasive ductal carcinoma of the pancreas and its prognostic impact. Am J Surg Pathol. 2007;31:1636–44.CrossRefPubMed

40.

Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Büchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91:586–94.CrossRefPubMed

41.

van Roest MH, Gouw AS, Peeters PM, Porte RJ, Slooff MJ, Fidler V, et al. Results of pancreaticoduodenectomy in patients with periampullary adenocarcinoma: perineural growth more important prognostic factor than tumor localization. Ann Surg. 2008;248:97–103.CrossRefPubMed

42.

Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine vs. observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–77.CrossRefPubMed

43.

Sakai M, Nakao A, Kaneko T, Takeda S, Inoue S, Kodera Y, et al. Para-aortic lymph node metastasis in carcinoma of the head of the pancreas. Surgery. 2005;137:606–11.CrossRefPubMed

44.

Kayahara M, Nagakawa T, Ohta T, Kitagawa H, Ueno K, Tajima H, et al. Analysis of paraaortic lymph node involvement in pancreatic carcinoma: a significant indication for surgery? Cancer. 1999;85:583–90.CrossRefPubMed

45.

Ferrone CR, Finkelstein DM, Thayer SP, Muzikansky A, Fernandez-delCastillo C, Warshaw AL. Perioperative CA19-9 levels can predict stage and survival in patients with resectable pancreatic adenocarcinoma. J Clin Oncol. 2006;24:2897–902.CrossRefPubMed

46.

Safi F, Schlosser W, Falkenreck S, Beger HG. Prognostic value of CA 19-9 serum course in pancreatic cancer. Hepatogastroenterology. 1998;45:253–9.PubMed

47.

Dominguez I, Crippa S, Thayer SP, Hung YP, Ferrone CR, Warshaw AL, et al. Preoperative platelet count and survival prognosis in resected pancreatic ductal adenocarcinoma. World J Surg. 2008;32:1051–6.CrossRefPubMed

48.

Kang CM, Kim JY, Choi GH, Kim KS, Choi JS, Lee WJ, et al. The use of adjusted preoperative CA 19-9 to predict the recurrence of resectable pancreatic cancer. J Surg Res. 2007;140:31–5.CrossRefPubMed

49.

Sergeant G, Ectors N, Topal B. Prognostic significance of extracapsular lymph node involvement in patients with adenocarcinoma of the ampulla of Vater (Br J Surg 2008; 95: 735–743). Br J Surg. 2008;95:1188; author reply 1188–9.CrossRefPubMed

Title: Prognostic Relevance of Extracapsular Lymph Node Involvement in Pancreatic Ductal Adenocarcinoma
Authors: Gregory Sergeant, MD
Nadine Ectors, MD, PhD
Steffen Fieuws, PhD
Raymond Aerts, MD
Baki Topal, MD, PhD
Publication date: 01-11-2009
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 11/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-009-0627-x

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Springer Medicine

Prognostic Relevance of Extracapsular Lymph Node Involvement in Pancreatic Ductal Adenocarcinoma

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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