Outcomes after Surgery for Malignant Pancreatic Neuroendocrine Tumors
https://doi.org/10.24017/science.2019.ICHMS.4
Abstract views: 1422 / PDF downloads: 0 / PDF downloads: 0 / PDF downloads: 965Abstract
The aim of the study is to declare the role of surgery in potentially curative malignant pancreatic neuroendocrine tumors, in term of prognosis, survival and complications after the surgical procedures. Does the surgery play a significant role in the best patient’s interest even in metastatic pancreatic neuroendocrine tumors? Clinical and pathological factors that changed the outcomes were also analyzed. It is retrospective, case series study. All patients who were undergoing surgery for malignant pancreatic neuroendocrine tumors from 2013 to 2018. Results show that, sixteen patients were recruited with a mean age at diagnosis of 49.31 years, (ranging from 19-80 years). There were 8 male and 8 female patients. Common symptoms were abdominal pain 12 (75%) of them three cases had clinical jaundice 3 (18.8%) and one case had acute pancreatitis and pancreatic necrosis. One (6.3%) patient had functional tumor, and the rest 15 (93.8%) were nonfunctional tumors; all of the patients were sporadic pancreatic neuroendocrine tumors. Overall morbidity was (43.8%) with no perioperative mortality. The median follow-up period was 23 months, ranging from 5-68 months. Recurrence occurred in four cases with a median disease-free interval of 9.5 moths with grade of differentiation (P-value 0.027), lymph node metastases (P-value 0.027) and tumor stage (P-value 0.017) were associated with recurrent disease. The overall 5 year survival was 81.2% and the disease free survival was (75%) at 5 year, with grade of tumor (P-value 0.001), lymph node metastases (P-value 0.001), invasion of other visceral organs(P-value 0.018) and recurrence (P-value 0.001)were associated with decreased survival. In conclusion, pancreatic neuroendocrine tumors have favorable long-term survival after surgical resections even in the presence of liver metastases depending on the grade of differentiation of tumor and lymph node metastases rather than liver metastases and other factors
Keywords:
Pancreatic, Malignant neuroendocrine tumors, Outcomes, Survival, Recurrence.
References
[1] J. C. Yao, M. Hassan, A. Phan, C. Dagohoy, C. Leary, J. E. Mares, et al., "One hundred years after"carcinoid":epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States," Journal of clinical oncology, vol. 26, pp. 3063-3072, 2008.
https://doi.org/10.1200/JCO.2007.15.4377
[2] H. Dai, X. Hong, X. Wang, C. Lin, W. Wu, and Y. Zhao, "Pancreatic neuroendocrine tumor cancer stem cells: potential novel therapeutic targets?," Translational Cancer Research, vol. 5, pp. 860-870, 2016.
https://doi.org/10.21037/tcr.2016.12.07
[3] F. Ehehalt, H. D. Saeger, C. M. Schmidt, and R. Grützmann, "Neuroendocrine tumors of the pancreas," The oncologist, vol. 14, pp. 456-467, 2009.
https://doi.org/10.1634/theoncologist.2008-0259
[4] J. Franko, W. Feng, L. Yip, E. Genovese, and A. J. Moser, "Non-functional neuroendocrine carcinoma of the pancreas:incidence, tumor biology, and outcomes in 2,158 patients,"Journal of Gastrointestinal Surgery, vol. 14, pp. 541-548, 2010.
https://doi.org/10.1007/s11605-009-1115-0
[5] T. R. Halfdanarson, K. Rabe, J. Rubin, and G. M. Petersen, "Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival," Annals of oncology, vol. 19, pp. 1727-1733, 2008.
https://doi.org/10.1093/annonc/mdn351
[6] M. Modlin, K. Oberg, D. C. Chung, R. T. Jensen, W. W. de Herder, R. V. Thakker, et al., "Gastroenteropancreatic neuroendocrine tumours," The lancet oncology, vol. 9, pp. 61-72, 2008.
https://doi.org/10.1016/S1470-2045(07)70410-2
[7] R. S. Chamberlain, D. Canes, K. T. Brown, L. Saltz, W. Jarnagin, Y. Fong, et al., "Hepatic neuroendocrine metastases:does intervention alter outcomes?,"Journal of the American College of Surgeons, vol. 190, pp. 432-445, 2000.
https://doi.org/10.1016/S1072-7515(00)00222-2
[8] M. Modlin, K. D. Lye, and M. Kidd, "A 5?decade analysis of 13,715 carcinoid tumors," Cancer: Interdisciplinary International Journal of the American Cancer Society, vol. 97, pp. 934-959, 2003.
https://doi.org/10.1002/cncr.11105
[9] K. Öberg and B. Eriksson, "Endocrine tumours of the pancreas," Best practice & research Clinical gastroenterology, vol. 19, pp. 753-781, 2005.
https://doi.org/10.1016/j.bpg.2005.06.002
[10] G. Klöppel, A. Perren, and P. U. Heitz, "The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification," Annals of the New York academy of sciences, vol. 1014, pp. 13-27, 2004.
https://doi.org/10.1196/annals.1294.002
[11] D. C. Metz and R. T. Jensen, "Gastrointestinal neuroendocrine tumors:pancreatic endocrine tumors," Gastroenterology, vol. 135, pp. 1469-1492, 2008.
https://doi.org/10.1053/j.gastro.2008.05.047
[12] J. C. Yao, M. P. Eisner, C. Leary, C. Dagohoy, A. Phan, A. Rashid, et al., "Population-based study of islet cell carcinoma," Annals of surgical oncology, vol. 14, pp. 3492-3500, 2007.
https://doi.org/10.1245/s10434-007-9566-6
[13] J. Sun, "Pancreatic neuroendocrine tumors," Intractable & rare diseases research, vol. 6, pp. 21-28, 2017.
https://doi.org/10.5582/irdr.2017.01007
[14] M. H. Kulke, M. H. Shah, A. B. Benson, E. Bergsland, J. D. Berlin, L. S. Blaszkowsky, et al., "Neuroendocrine tumors, version 1.2015," Journal of the National Comprehensive Cancer Network, vol. 13, pp. 78-108, 2015.
https://doi.org/10.6004/jnccn.2015.0011
[15] H. Nave, E. Mössinger, H. Feist, H. Lang, and H.-R. Raab, "Surgery as primary treatment in patients with liver metastases from carcinoid tumors: a retrospective, unicentric study over 13 years," Surgery, vol. 129, pp. 170-175, 2001.
https://doi.org/10.1067/msy.2001.110426
[16] G. Capurso, R. Bettini, M. Rinzivillo, L. Boninsegna, G. Delle Fave, and M. Falconi, "Role of resection of the primary pancreatic neuroendocrine tumour only in patients with unresectable metastatic liver disease: a systematic review," Neuroendocrinology, vol. 93, pp. 223-229, 2011.
https://doi.org/10.1159/000324770
[17] E. Dixon and J. L. Pasieka, "Functioningand nonfunctioning neuroendocrine tumors of the pancreas," Current opinion in oncology, vol. 19, pp. 30-35, 2007.
https://doi.org/10.1097/CCO.0b013e328011a236
[18] S. N. Hochwald, S. Zee, K. C. Conlon, R. Colleoni, O. Louie, M. F. Brennan, et al., "Prognostic factors in pancreatic endocrine neoplasms: an analysis of 136 cases with a proposal for low-grade andintermediate-grade groups,"Journal of Clinical Oncology, vol. 20, pp. 2633-2642, 2002.
https://doi.org/10.1200/JCO.2002.10.030
[19] H. L. O'Grady and K. C. Conlon, "Pancreatic neuroendocrine tumours," Eur J Surg Oncol, vol. 34, pp. 324-32, Mar 2008.
https://doi.org/10.1016/j.ejso.2007.07.209
[20] M. Lombardi, N. De Lio, N. Funel, C. Sardella, D. Russo, C. Urbani, et al., "Prognostic factors for pancreatic neuroendocrine neoplasms (pNET) and the risk of small non-functioning pNET," Journal of endocrinological investigation, vol. 38, pp. 605-613, 2015.
https://doi.org/10.1007/s40618-014-0219-x
[21] J. S. Hill, J. T. McPhee, T. P. McDade, Z. Zhou, M. E. Sullivan, G. F. Whalen, et al., "Pancreatic neuroendocrine tumors:the impact of surgical resection on survival," Cancer: Interdisciplinary International Journal of the American Cancer Society, vol. 115, pp. 741-751, 2009.
https://doi.org/10.1002/cncr.24065
[22] R. Doi, "Determinants of surgical resection for pancreatic neuroendocrine tumors," Journal of Hepato?Biliary?Pancreatic Sciences, vol. 22, pp. 610-617, 2015.
https://doi.org/10.1002/jhbp.224
[23] V. Fendrich, P. Langer, I. Celik, D. K. Bartsch, A. Zielke, A. Ramaswamy, et al., "An aggressive surgical approach leads to long-term survival in patients with pancreatic endocrine tumors," Annals of surgery, vol. 244, p. 845, 2006.
https://doi.org/10.1097/01.sla.0000246951.21252.60
[24] J. M. Sarmiento, F. G. Que, C. S. Grant, G. B. Thompson, M. B. Farnell, and D. M. Nagorney, "Concurrent resections of pancreatic islet cell cancers with synchronous hepatic metastases: outcomesof an aggressive approach," Surgery, vol. 132, pp. 976-983, 2002.
https://doi.org/10.1067/msy.2002.128615
[25] G. K. Bonney, D. Gomez, S. H. Rahman, C. S. Verbeke, K. R. Prasad, G. J. Toogood, et al., "Results following surgical resection for malignant pancreatic neuroendocrine tumours. A single institutional experience," JOP, vol. 9, pp. 19-25, 2008.
[26] M. S. Janot, S. Kersting, T. Herzog, A. M. Chromik, and W. Uhl, "Prognosis and long-term survival after operation in patients with pancreatic and peripancreatic neuroendocrine tumors of a single center," JOURNAL OF THE PANCREAS, vol. 17, pp. 182-188, 2016.
[27] T. Ito, H. Sasano, M. Tanaka, R. Y. Osamura, I. Sasaki, W. Kimura, et al., "Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan," Journal of gastroenterology, vol. 45, pp. 234-243, 2010.
https://doi.org/10.1007/s00535-009-0194-8
[28] P. Tomassetti, D. Campana, L. Piscitelli, R. Casadei, D. Santini, F. Nori, et al., "Endocrine pancreatic tumors:factors correlated with survival,"Annals of Oncology, vol. 16, pp. 1806-1810, 2005.
https://doi.org/10.1093/annonc/mdi358
[29] F. Yu, D. J. Venzon, J. Serrano, S. U. Goebel, J. L. Doppman, F. Gibril, et al., "Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing Zollinger-Ellison syndrome," Journal of Clinical Oncology, vol. 17, pp. 615-615, 1999.
https://doi.org/10.1200/JCO.1999.17.2.615
[30] J. A. Norton and R. T. Jensen, "Resolved and unresolved controversies in the surgical management of patients with Zollinger-Ellison syndrome," Annals of surgery, vol. 240, p. 757, 2004.
https://doi.org/10.1097/01.sla.0000143252.02142.3e
[31] R. Kanthan, J.-L. Senger, S. Ahmed, and S. C. Kanthan, "Pancreatic Neuroendocrine Tumors in the 21st Century-An Update," Journal of Cancer Therapy, vol. 8, p. 1194, 2017.
https://doi.org/10.4236/jct.2017.813103
[32] B. Zhou, J. Duan, S. Yan, J. Zhou, and S. Zheng, "Prognostic factors of long?term outcome in surgically resectable pancreatic neuroendocrine tumors: A 12?year experience from a single center," Oncology letters, vol. 13, pp. 1157-1164, 2017.
https://doi.org/10.3892/ol.2017.5561
[33] H. Yamaguchi, Y. Kimura, M. Imamura, M. Nagayama, T. Ito, T. Nobuoka, et al., "Oncological Features and Outcomes of Curatively Resected Non-Functional Pancreatic Neuroendocrine Tumor: Single Institute Experiences," JOP. J Pancreas (Online), vol. 18, pp. 380-386, 2017.
https://doi.org/10.1200/JCO.2007.15.4377
[2] H. Dai, X. Hong, X. Wang, C. Lin, W. Wu, and Y. Zhao, "Pancreatic neuroendocrine tumor cancer stem cells: potential novel therapeutic targets?," Translational Cancer Research, vol. 5, pp. 860-870, 2016.
https://doi.org/10.21037/tcr.2016.12.07
[3] F. Ehehalt, H. D. Saeger, C. M. Schmidt, and R. Grützmann, "Neuroendocrine tumors of the pancreas," The oncologist, vol. 14, pp. 456-467, 2009.
https://doi.org/10.1634/theoncologist.2008-0259
[4] J. Franko, W. Feng, L. Yip, E. Genovese, and A. J. Moser, "Non-functional neuroendocrine carcinoma of the pancreas:incidence, tumor biology, and outcomes in 2,158 patients,"Journal of Gastrointestinal Surgery, vol. 14, pp. 541-548, 2010.
https://doi.org/10.1007/s11605-009-1115-0
[5] T. R. Halfdanarson, K. Rabe, J. Rubin, and G. M. Petersen, "Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival," Annals of oncology, vol. 19, pp. 1727-1733, 2008.
https://doi.org/10.1093/annonc/mdn351
[6] M. Modlin, K. Oberg, D. C. Chung, R. T. Jensen, W. W. de Herder, R. V. Thakker, et al., "Gastroenteropancreatic neuroendocrine tumours," The lancet oncology, vol. 9, pp. 61-72, 2008.
https://doi.org/10.1016/S1470-2045(07)70410-2
[7] R. S. Chamberlain, D. Canes, K. T. Brown, L. Saltz, W. Jarnagin, Y. Fong, et al., "Hepatic neuroendocrine metastases:does intervention alter outcomes?,"Journal of the American College of Surgeons, vol. 190, pp. 432-445, 2000.
https://doi.org/10.1016/S1072-7515(00)00222-2
[8] M. Modlin, K. D. Lye, and M. Kidd, "A 5?decade analysis of 13,715 carcinoid tumors," Cancer: Interdisciplinary International Journal of the American Cancer Society, vol. 97, pp. 934-959, 2003.
https://doi.org/10.1002/cncr.11105
[9] K. Öberg and B. Eriksson, "Endocrine tumours of the pancreas," Best practice & research Clinical gastroenterology, vol. 19, pp. 753-781, 2005.
https://doi.org/10.1016/j.bpg.2005.06.002
[10] G. Klöppel, A. Perren, and P. U. Heitz, "The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification," Annals of the New York academy of sciences, vol. 1014, pp. 13-27, 2004.
https://doi.org/10.1196/annals.1294.002
[11] D. C. Metz and R. T. Jensen, "Gastrointestinal neuroendocrine tumors:pancreatic endocrine tumors," Gastroenterology, vol. 135, pp. 1469-1492, 2008.
https://doi.org/10.1053/j.gastro.2008.05.047
[12] J. C. Yao, M. P. Eisner, C. Leary, C. Dagohoy, A. Phan, A. Rashid, et al., "Population-based study of islet cell carcinoma," Annals of surgical oncology, vol. 14, pp. 3492-3500, 2007.
https://doi.org/10.1245/s10434-007-9566-6
[13] J. Sun, "Pancreatic neuroendocrine tumors," Intractable & rare diseases research, vol. 6, pp. 21-28, 2017.
https://doi.org/10.5582/irdr.2017.01007
[14] M. H. Kulke, M. H. Shah, A. B. Benson, E. Bergsland, J. D. Berlin, L. S. Blaszkowsky, et al., "Neuroendocrine tumors, version 1.2015," Journal of the National Comprehensive Cancer Network, vol. 13, pp. 78-108, 2015.
https://doi.org/10.6004/jnccn.2015.0011
[15] H. Nave, E. Mössinger, H. Feist, H. Lang, and H.-R. Raab, "Surgery as primary treatment in patients with liver metastases from carcinoid tumors: a retrospective, unicentric study over 13 years," Surgery, vol. 129, pp. 170-175, 2001.
https://doi.org/10.1067/msy.2001.110426
[16] G. Capurso, R. Bettini, M. Rinzivillo, L. Boninsegna, G. Delle Fave, and M. Falconi, "Role of resection of the primary pancreatic neuroendocrine tumour only in patients with unresectable metastatic liver disease: a systematic review," Neuroendocrinology, vol. 93, pp. 223-229, 2011.
https://doi.org/10.1159/000324770
[17] E. Dixon and J. L. Pasieka, "Functioningand nonfunctioning neuroendocrine tumors of the pancreas," Current opinion in oncology, vol. 19, pp. 30-35, 2007.
https://doi.org/10.1097/CCO.0b013e328011a236
[18] S. N. Hochwald, S. Zee, K. C. Conlon, R. Colleoni, O. Louie, M. F. Brennan, et al., "Prognostic factors in pancreatic endocrine neoplasms: an analysis of 136 cases with a proposal for low-grade andintermediate-grade groups,"Journal of Clinical Oncology, vol. 20, pp. 2633-2642, 2002.
https://doi.org/10.1200/JCO.2002.10.030
[19] H. L. O'Grady and K. C. Conlon, "Pancreatic neuroendocrine tumours," Eur J Surg Oncol, vol. 34, pp. 324-32, Mar 2008.
https://doi.org/10.1016/j.ejso.2007.07.209
[20] M. Lombardi, N. De Lio, N. Funel, C. Sardella, D. Russo, C. Urbani, et al., "Prognostic factors for pancreatic neuroendocrine neoplasms (pNET) and the risk of small non-functioning pNET," Journal of endocrinological investigation, vol. 38, pp. 605-613, 2015.
https://doi.org/10.1007/s40618-014-0219-x
[21] J. S. Hill, J. T. McPhee, T. P. McDade, Z. Zhou, M. E. Sullivan, G. F. Whalen, et al., "Pancreatic neuroendocrine tumors:the impact of surgical resection on survival," Cancer: Interdisciplinary International Journal of the American Cancer Society, vol. 115, pp. 741-751, 2009.
https://doi.org/10.1002/cncr.24065
[22] R. Doi, "Determinants of surgical resection for pancreatic neuroendocrine tumors," Journal of Hepato?Biliary?Pancreatic Sciences, vol. 22, pp. 610-617, 2015.
https://doi.org/10.1002/jhbp.224
[23] V. Fendrich, P. Langer, I. Celik, D. K. Bartsch, A. Zielke, A. Ramaswamy, et al., "An aggressive surgical approach leads to long-term survival in patients with pancreatic endocrine tumors," Annals of surgery, vol. 244, p. 845, 2006.
https://doi.org/10.1097/01.sla.0000246951.21252.60
[24] J. M. Sarmiento, F. G. Que, C. S. Grant, G. B. Thompson, M. B. Farnell, and D. M. Nagorney, "Concurrent resections of pancreatic islet cell cancers with synchronous hepatic metastases: outcomesof an aggressive approach," Surgery, vol. 132, pp. 976-983, 2002.
https://doi.org/10.1067/msy.2002.128615
[25] G. K. Bonney, D. Gomez, S. H. Rahman, C. S. Verbeke, K. R. Prasad, G. J. Toogood, et al., "Results following surgical resection for malignant pancreatic neuroendocrine tumours. A single institutional experience," JOP, vol. 9, pp. 19-25, 2008.
[26] M. S. Janot, S. Kersting, T. Herzog, A. M. Chromik, and W. Uhl, "Prognosis and long-term survival after operation in patients with pancreatic and peripancreatic neuroendocrine tumors of a single center," JOURNAL OF THE PANCREAS, vol. 17, pp. 182-188, 2016.
[27] T. Ito, H. Sasano, M. Tanaka, R. Y. Osamura, I. Sasaki, W. Kimura, et al., "Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan," Journal of gastroenterology, vol. 45, pp. 234-243, 2010.
https://doi.org/10.1007/s00535-009-0194-8
[28] P. Tomassetti, D. Campana, L. Piscitelli, R. Casadei, D. Santini, F. Nori, et al., "Endocrine pancreatic tumors:factors correlated with survival,"Annals of Oncology, vol. 16, pp. 1806-1810, 2005.
https://doi.org/10.1093/annonc/mdi358
[29] F. Yu, D. J. Venzon, J. Serrano, S. U. Goebel, J. L. Doppman, F. Gibril, et al., "Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long-standing Zollinger-Ellison syndrome," Journal of Clinical Oncology, vol. 17, pp. 615-615, 1999.
https://doi.org/10.1200/JCO.1999.17.2.615
[30] J. A. Norton and R. T. Jensen, "Resolved and unresolved controversies in the surgical management of patients with Zollinger-Ellison syndrome," Annals of surgery, vol. 240, p. 757, 2004.
https://doi.org/10.1097/01.sla.0000143252.02142.3e
[31] R. Kanthan, J.-L. Senger, S. Ahmed, and S. C. Kanthan, "Pancreatic Neuroendocrine Tumors in the 21st Century-An Update," Journal of Cancer Therapy, vol. 8, p. 1194, 2017.
https://doi.org/10.4236/jct.2017.813103
[32] B. Zhou, J. Duan, S. Yan, J. Zhou, and S. Zheng, "Prognostic factors of long?term outcome in surgically resectable pancreatic neuroendocrine tumors: A 12?year experience from a single center," Oncology letters, vol. 13, pp. 1157-1164, 2017.
https://doi.org/10.3892/ol.2017.5561
[33] H. Yamaguchi, Y. Kimura, M. Imamura, M. Nagayama, T. Ito, T. Nobuoka, et al., "Oncological Features and Outcomes of Curatively Resected Non-Functional Pancreatic Neuroendocrine Tumor: Single Institute Experiences," JOP. J Pancreas (Online), vol. 18, pp. 380-386, 2017.
Downloads
How to Cite
[1]
O. H. Ghalib Azeez Hawramy, K. Seerwan Abdullah, B. M.M. Salih, Q. Hussein A. Kasnazani, D. Taib Gharib, and D. Ahmed Mohammed, “Outcomes after Surgery for Malignant Pancreatic Neuroendocrine Tumors”, KJAR, vol. 4, no. 3, pp. 37–49, Aug. 2019, doi: 10.24017/science.2019.ICHMS.4.
Article Metrics
Published
22-08-2019
Issue
Section
Pure and Applied Science
