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Journal of Gastrointestinal Surgery

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01-01-2015 | 2014 SSAT Plenary Presentation

Importance of Lymph Node Involvement in Pancreatic Neuroendocrine Tumors: Impact on Survival and Implications for Surgical Resection

Authors: Thomas Curran, Barbara A. Pockaj, Richard J. Gray, Thorvardur R. Halfdanarson, Nabil Wasif

Published in: Journal of Gastrointestinal Surgery | Issue 1/2015

Abstract

Background

Conflicting data exist on predictors of nodal metastases and their impact on survival in patients with pancreatic neuroendocrine tumors (PNETs). We aim to identify factors associated with lymph node involvement and evaluate the effect of nodal metastases on survival.

Methods

All patients undergoing surgery for PNETs in the Surveillance, Epidemiology, and End Results (SEER) tumor registry from 1988 to 2010 were included. Predictors of lymph node involvement and disease-specific survival (DSS) were evaluated using logistic regression and Cox regression, respectively.

Results

Patients (1,915) underwent surgery for a PNET (62 % nonfunctional). Nodal positivity was associated with increasing tumor size (p < 0.001) and grade (p < 0.001). Unadjusted DSS at 5 years was 81 % for N0, 74 % for Nx, and 69 % for N1, respectively, (p < 0.001). After adjustment for tumor size and grade, DSS was significantly decreased in N1 patients (HR 1.57; 95 % CI 1.23–1.95). For patients who had at least one node examined and had low-grade PNETs <1 cm, no nodal metastases were found.

Conclusions

High tumor grade and increasing size predict nodal metastases in patients with PNETs. N1 status is independently associated with decreased DSS. Low-grade tumors <1 cm may be observed or enucleated.

Yao, J.C., M. Hassan, A. Phan, C. Dagohoy, C. Leary, J.E. Mares, E.K. Abdalla, J.B. Fleming, J.N. Vauthey, A. Rashid and D.B. Evans, One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol, 2008. 26(18): p. 3063–72.PubMedCrossRef

de Herder, W.W., Biochemistry of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab, 2007. 21(1): p. 33–41.PubMedCrossRef

Modlin, I.M., K. Oberg, D.C. Chung, R.T. Jensen, W.W. de Herder, R.V. Thakker, M. Caplin, G. Delle Fave, G.A. Kaltsas, E.P. Krenning, S.F. Moss, O. Nilsson, G. Rindi, R. Salazar, P. Ruszniewski and A. Sundin, Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol, 2008. 9(1): p. 61–72.PubMedCrossRef

Kloppel, G., A. Perren and P.U. Heitz, The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci, 2004. 1014: p. 13–27.PubMedCrossRef

Bosman, F.T., World Health Organization and International Agency for Research on Cancer, WHO classification of tumours of the digestive system. 4th ed. World Health Organization classification of tumours. 2010, Lyon: International Agency for Research on Cancer. 417 p.

Rindi, G., G. Kloppel, H. Alhman, M. Caplin, A. Couvelard, W.W. de Herder, B. Erikssson, A. Falchetti, M. Falconi, P. Komminoth, M. Korner, J.M. Lopes, A.M. McNicol, O. Nilsson, A. Perren, A. Scarpa, J.Y. Scoazec and B. Wiedenmann, TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch, 2006. 449(4): p. 395–401.PubMedCentralPubMedCrossRef

Boyar Cetinkaya, R., M. Vatn, L. Aabakken, D.S. Bergestuen and E. Thiis-Evensen, Survival and prognostic factors in well-differentiated pancreatic neuroendocrine tumors. Scand J Gastroenterol, 2014. 49(6): p. 734–41.

Cherenfant, J., S.J. Stocker, M.K. Gage, H. Du, T.A. Thurow, M. Odeleye, S.W. Schimpke, K.L. Kaul, C.R. Hall, I. Lamzabi, P. Gattuso, D.J. Winchester, R.W. Marsh, K.K. Roggin, D.J. Bentrem, M.S. Baker, R.A. Prinz and M.S. Talamonti, Predicting aggressive behavior in nonfunctioning pancreatic neuroendocrine tumors. Surgery, 2013. 154(4): p. 785–91; discussion 791–3.PubMedCrossRef

Bilimoria, K.Y., D.J. Bentrem, R.P. Merkow, J.S. Tomlinson, A.K. Stewart, C.Y. Ko and M.S. Talamonti, Application of the pancreatic adenocarcinoma staging system to pancreatic neuroendocrine tumors. J Am Coll Surg, 2007. 205(4): p. 558–63.PubMedCrossRef

10.

Ito, H., M. Abramson, K. Ito, E. Swanson, N. Cho, D.T. Ruan, R.S. Swanson and E.E. Whang, Surgery and staging of pancreatic neuroendocrine tumors: a 14-year experience. J Gastrointest Surg, 2010. 14(5): p. 891–8.PubMedCrossRef

11.

Han, X., X. Xu, D. Jin, D. Wang, Y. Ji and W. Lou, Clinicopathological characteristics and prognosis-related factors of resectable pancreatic neuroendocrine tumors: a retrospective study of 104 cases in a single Chinese center. Pancreas, 2014. 43(4): p. 526–31.PubMedCentralPubMedCrossRef

12.

Partelli, S., S. Gaujoux, L. Boninsegna, R. Cherif, S. Crippa, A. Couvelard, A. Scarpa, P. Ruszniewski, A. Sauvanet and M. Falconi, Pattern and clinical predictors of lymph node involvement in nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). JAMA Surg, 2013. 148(10): p. 932–9.PubMedCrossRef

13.

Sarmiento, J.M., M.B. Farnell, F.G. Que and D.M. Nagorney, Pancreaticoduodenectomy for islet cell tumors of the head of the pancreas: long-term survival analysis. World J Surg, 2002. 26(10): p. 1267–71.PubMedCrossRef

14.

Scarpa, A., W. Mantovani, P. Capelli, S. Beghelli, L. Boninsegna, R. Bettini, F. Panzuto, P. Pederzoli, G. delle Fave and M. Falconi, Pancreatic endocrine tumors: improved TNM staging and histopathological grading permit a clinically efficient prognostic stratification of patients. Mod Pathol, 2010. 23(6): p. 824–33.PubMedCrossRef

15.

Tomassetti, P., D. Campana, L. Piscitelli, R. Casadei, D. Santini, F. Nori, A.M. Morselli-Labate, R. Pezzilli and R. Corinaldesi, Endocrine pancreatic tumors: factors correlated with survival. Ann Oncol, 2005. 16(11): p. 1806–10.PubMedCrossRef

16.

Toste, P.A., B.E. Kadera, S.F. Tatishchev, D.W. Dawson, B.M. Clerkin, R. Muthusamy, R. Watson, J.S. Tomlinson, O.J. Hines, H.A. Reber and T.R. Donahue, Nonfunctional pancreatic neuroendocrine tumors <2 cm on preoperative imaging are associated with a low incidence of nodal metastasis and an excellent overall survival. J Gastrointest Surg, 2013. 17(12): p. 2105–13.PubMedCrossRef

17.

Bettini, R., L. Boninsegna, W. Mantovani, P. Capelli, C. Bassi, P. Pederzoli, G.F. Delle Fave, F. Panzuto, A. Scarpa and M. Falconi, Prognostic factors at diagnosis and value of WHO classification in a mono-institutional series of 180 non-functioning pancreatic endocrine tumours. Ann Oncol, 2008. 19(5): p. 903–8.PubMedCrossRef

18.

Haynes, A.B., V. Deshpande, T. Ingkakul, P.A. Vagefi, J. Szymonifka, S.P. Thayer, C.R. Ferrone, J.A. Wargo, A.L. Warshaw and C. Fernandez-del Castillo, Implications of incidentally discovered, nonfunctioning pancreatic endocrine tumors: short-term and long-term patient outcomes. Arch Surg, 2011. 146(5): p. 534–8.PubMedCentralPubMedCrossRef

19.

Rindi, G., M. Falconi, C. Klersy, L. Albarello, L. Boninsegna, M.W. Buchler, C. Capella, M. Caplin, A. Couvelard, C. Doglioni, G. Delle Fave, L. Fischer, G. Fusai, W.W. de Herder, H. Jann, P. Komminoth, R.R. de Krijger, S. La Rosa, T.V. Luong, U. Pape, A. Perren, P. Ruszniewski, A. Scarpa, A. Schmitt, E. Solcia and B. Wiedenmann, TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. J Natl Cancer Inst, 2012. 104(10): p. 764–77.PubMedCrossRef

20.

Kaplan, E.L. and P. Meier, Nonparametric Estimation from Incomplete Observations Journal of the American Statistical Association, 1958. 53(282): p. 457–481.CrossRef

21.

Hashim, Y.M., K.M. Trinkaus, D.C. Linehan, S.S. Strasberg, R.C. Fields, D. Cao and W.G. Hawkins, Regional lymphadenectomy is indicated in the surgical treatment of pancreatic neuroendocrine tumors (PNETs). Ann Surg, 2014. 259(2): p. 197–203.PubMedCentralPubMedCrossRef

22.

Hasegawa, T., K. Yamao, S. Hijioka, V. Bhatia, N. Mizuno, K. Hara, H. Imaoka, Y. Niwa, M. Tajika, S. Kondo, T. Tanaka, Y. Shimizu, T. Kinoshita, T. Kohsaki, I. Nishimori, S. Iwasaki, T. Saibara, W. Hosoda and Y. Yatabe, Evaluation of Ki-67 index in EUS-FNA specimens for the assessment of malignancy risk in pancreatic neuroendocrine tumors. Endoscopy, 2014. 46(1): p. 32–8.PubMed

23.

Weynand, B., I. Borbath, V. Bernard, C. Sempoux, J.F. Gigot, C. Hubert, V. Lannoy, P.H. Deprez and A. Jouret-Mourin, Pancreatic neuroendocrine tumour grading on endoscopic ultrasound-guided fine needle aspiration: high reproducibility and inter-observer agreement of the Ki-67 labelling index. Cytopathology, 2013. doi: 10.1111/cyt.12111

24.

Katanuma, A., H. Maguchi, K. Yane, S. Hashigo, T. Kin, M. Kaneko, S. Kato, R. Kato, R. Harada, M. Osanai, K. Takahashi and M. Nojima, Factors predictive of adverse events associated with endoscopic ultrasound-guided fine needle aspiration of pancreatic solid lesions. Dig Dis Sci, 2013. 58(7): p. 2093–9.PubMedCentralPubMedCrossRef

25.

Kishi, Y., K. Shimada, S. Nara, M. Esaki, N. Hiraoka and T. Kosuge, Basing Treatment Strategy for Non-functional Pancreatic Neuroendocrine Tumors on Tumor Size. Ann Surg Oncol, 2014. p 28882–8

26.

Manasanch, E.E., J.K. Smith, A. Bodnari, J. McKinney, C. Gray, T.P. McDade and J.F. Tseng, Tumor registry versus physician medical record review: a direct comparison of patients with pancreatic neuroendocrine tumors. J Oncol Pract, 2011. 7(2): p. 111–6.PubMedCentralPubMedCrossRef

Title: Importance of Lymph Node Involvement in Pancreatic Neuroendocrine Tumors: Impact on Survival and Implications for Surgical Resection
Authors: Thomas Curran
Barbara A. Pockaj
Richard J. Gray
Thorvardur R. Halfdanarson
Nabil Wasif
Publication date: 01-01-2015
Publisher: Springer US
Published in: Journal of Gastrointestinal Surgery / Issue 1/2015
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI: https://doi.org/10.1007/s11605-014-2624-z

At a glance: The STEP trials

Springer Medicine

Importance of Lymph Node Involvement in Pancreatic Neuroendocrine Tumors: Impact on Survival and Implications for Surgical Resection

Abstract

Background

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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