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Published in: BMC Surgery 1/2021

Open Access 01-12-2021 | Metastasis | Research article

Increased neutrophil–lymphocyte ratio predicts recurrence in patients with well-differentiated pancreatic neuroendocrine neoplasm based on the 2017 World Health Organization classification

Authors: Takayuki Miura, Hideo Ohtsuka, Takeshi Aoki, Shuichi Aoki, Tatsuo Hata, Tatsuyuki Takadate, Shimpei Maeda, Kyohei Ariake, Kei Kawaguchi, Kunihiro Masuda, Masaharu Ishida, Masamichi Mizuma, Kei Nakagawa, Takanori Morikawa, Fumiyoshi Fujishima, Takashi Kamei, Hironobu Sasano, Michiaki Unno

Published in: BMC Surgery | Issue 1/2021

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Abstract

Background

The prognostic values of inflammation-based markers in well-differentiated pancreatic neuroendocrine neoplasms, diagnosed according to the new 2017 World Health Organization classification, have remained unclear. Therefore, we assessed the ability to predict the recurrence of such markers after curative resection in patients with these neoplasms.

Methods

Circulating/systemic neutrophil–lymphocyte, monocyte–lymphocyte, platelet–lymphocyte, and platelet–white cell ratios were evaluated in 120 patients who underwent curative resection for well-differentiated pancreatic neuroendocrine neoplasms without synchronous distant metastasis between 2001 and 2018. Recurrence-free-survival and overall survival were compared using Kaplan–Meier analysis and log-rank tests. Univariate or multivariate analyses, using a Cox proportional hazards model, were used to calculate hazard ratios with 95% confidence intervals.

Results

Univariate analysis demonstrated that preoperative neutrophil–lymphocyte ratio, tumor size, European Neuroendocrine Tumor Society TMN classification, 2017 World Health Organization classification, and venous invasion were associated with recurrence. The optimal preoperative neutrophil–lymphocyte ratio cut-off value was 2.62, based on receiver operating characteristic curve analysis. In multivariate analysis, a higher preoperative neutrophil–lymphocyte ratio (HR = 3.49 95% CI 1.05–11.7; P = 0.042) and 2017 World Health Organization classification (HR = 8.81, 95% CI 1.46–168.2; P = 0.015) were independent recurrence predictors.

Conclusions

The circulating/systemic neutrophil–lymphocyte ratio is a useful and convenient preoperative prognostic marker of recurrence in patients with well-differentiated pancreatic neuroendocrine neoplasm based on the 2017 World Health Organization classification.
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Literature
1.
go back to reference Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 2005;19(5):753–81.CrossRef Oberg K, Eriksson B. Endocrine tumours of the pancreas. Best Pract Res Clin Gastroenterol. 2005;19(5):753–81.CrossRef
2.
go back to reference Cives M, Strosberg J. An update on gastroenteropancreatic neuroendocrine tumors. Oncology (Williston Park). 2014;28(9):749–56. Cives M, Strosberg J. An update on gastroenteropancreatic neuroendocrine tumors. Oncology (Williston Park). 2014;28(9):749–56.
3.
go back to reference Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008;135(5):1469–92.CrossRef Metz DC, Jensen RT. Gastrointestinal neuroendocrine tumors: pancreatic endocrine tumors. Gastroenterology. 2008;135(5):1469–92.CrossRef
4.
go back to reference Doi R. Determinants of surgical resection for pancreatic neuroendocrine tumors. J Hepatobiliary Pancreat Sci. 2015;22(8):610–7.CrossRef Doi R. Determinants of surgical resection for pancreatic neuroendocrine tumors. J Hepatobiliary Pancreat Sci. 2015;22(8):610–7.CrossRef
5.
go back to reference Fendrich V, Langer P, Celik I, Bartsch DK, Zielke A, Ramaswamy A, et al. An aggressive surgical approach leads to long-term survival in patients with pancreatic endocrine tumors. Ann Surg. 2006;244(6):845–51; discussion 852–43.CrossRef Fendrich V, Langer P, Celik I, Bartsch DK, Zielke A, Ramaswamy A, et al. An aggressive surgical approach leads to long-term survival in patients with pancreatic endocrine tumors. Ann Surg. 2006;244(6):845–51; discussion 852–43.CrossRef
6.
go back to reference Shah MH, Goldner WS, Halfdanarson TR, Bergsland E, Berlin JD, Halperin D, et al. NCCN Guidelines insights: neuroendocrine and adrenal tumors, Version 2.2018. J Natl Compr Canc Netw. 2018;16(6):693–702.CrossRef Shah MH, Goldner WS, Halfdanarson TR, Bergsland E, Berlin JD, Halperin D, et al. NCCN Guidelines insights: neuroendocrine and adrenal tumors, Version 2.2018. J Natl Compr Canc Netw. 2018;16(6):693–702.CrossRef
7.
go back to reference Frilling A, Modlin IM, Kidd M, Russell C, Breitenstein S, Salem R, et al. Recommendations for management of patients with neuroendocrine liver metastases. Lancet Oncol. 2014;15(1):e8-21.CrossRef Frilling A, Modlin IM, Kidd M, Russell C, Breitenstein S, Salem R, et al. Recommendations for management of patients with neuroendocrine liver metastases. Lancet Oncol. 2014;15(1):e8-21.CrossRef
8.
go back to reference Hijioka S, Hosoda W, Matsuo K, Ueno M, Furukawa M, Yoshitomi H, et al. Rb loss and KRAS mutation are predictors of the response to platinum-based chemotherapy in pancreatic neuroendocrine neoplasm with Grade 3: a Japanese multicenter pancreatic NEN-G3 study. Clin Cancer Res. 2017;23(16):4625–32.CrossRef Hijioka S, Hosoda W, Matsuo K, Ueno M, Furukawa M, Yoshitomi H, et al. Rb loss and KRAS mutation are predictors of the response to platinum-based chemotherapy in pancreatic neuroendocrine neoplasm with Grade 3: a Japanese multicenter pancreatic NEN-G3 study. Clin Cancer Res. 2017;23(16):4625–32.CrossRef
9.
go back to reference Singhi AD, Klimstra DS. Well-differentiated pancreatic neuroendocrine tumours (PanNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs): concepts, issues and a practical diagnostic approach to high-grade (G3) cases. Histopathology. 2018;72(1):168–77.CrossRef Singhi AD, Klimstra DS. Well-differentiated pancreatic neuroendocrine tumours (PanNETs) and poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs): concepts, issues and a practical diagnostic approach to high-grade (G3) cases. Histopathology. 2018;72(1):168–77.CrossRef
10.
go back to reference Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol. 2013;24(1):152–60.CrossRef Sorbye H, Welin S, Langer SW, Vestermark LW, Holt N, Osterlund P, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study. Ann Oncol. 2013;24(1):152–60.CrossRef
11.
go back to reference Lloyd ROR, Kloppel G, et al. WHO classification of tumours of endocrine organs. 4th ed. Lyon: International Agency for Research on Cancer Press; 2017. Lloyd ROR, Kloppel G, et al. WHO classification of tumours of endocrine organs. 4th ed. Lyon: International Agency for Research on Cancer Press; 2017.
12.
go back to reference Scoazec JY, Couvelard A. Classification of pancreatic neuroendocrine tumours: changes made in the 2017 WHO classification of tumours of endocrine organs and perspectives for the future. Ann Pathol. 2017;37(6):444–56.CrossRef Scoazec JY, Couvelard A. Classification of pancreatic neuroendocrine tumours: changes made in the 2017 WHO classification of tumours of endocrine organs and perspectives for the future. Ann Pathol. 2017;37(6):444–56.CrossRef
13.
go back to reference Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7.CrossRef Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7.CrossRef
14.
go back to reference Ohira M, Yoshizumi T, Yugawa K, Kosai-Fujimoto Y, Inokuchi S, Motomura T, et al. Association of inflammatory biomarkers with long-term outcomes after curative surgery for mass-forming intrahepatic cholangiocarcinoma. Surg Today. 2020;50(4):379–88.CrossRef Ohira M, Yoshizumi T, Yugawa K, Kosai-Fujimoto Y, Inokuchi S, Motomura T, et al. Association of inflammatory biomarkers with long-term outcomes after curative surgery for mass-forming intrahepatic cholangiocarcinoma. Surg Today. 2020;50(4):379–88.CrossRef
15.
go back to reference Migita K, Matsumoto S, Wakatsuki K, Ito M, Kunishige T, Nakade H, et al. The prognostic significance of inflammation-based markers in patients with recurrent gastric cancer. Surg Today. 2018;48(3):282–91.CrossRef Migita K, Matsumoto S, Wakatsuki K, Ito M, Kunishige T, Nakade H, et al. The prognostic significance of inflammation-based markers in patients with recurrent gastric cancer. Surg Today. 2018;48(3):282–91.CrossRef
16.
go back to reference Cananzi FCM, Ruspi L, Quagliuolo VL. Preoperative monocyte-to-lymphocyte ratio predicts recurrence in gastrointestinal stromal tumors. J Surg Oncol. 2019;119(7):1026.CrossRef Cananzi FCM, Ruspi L, Quagliuolo VL. Preoperative monocyte-to-lymphocyte ratio predicts recurrence in gastrointestinal stromal tumors. J Surg Oncol. 2019;119(7):1026.CrossRef
17.
go back to reference Kawai M, Hirono S, Okada KI, Miyazawa M, Shimizu A, Kitahata Y, et al. Low lymphocyte monocyte ratio after neoadjuvant therapy predicts poor survival after pancreatectomy in patients with borderline resectable pancreatic cancer. Surgery. 2019;165(6):1151–60.CrossRef Kawai M, Hirono S, Okada KI, Miyazawa M, Shimizu A, Kitahata Y, et al. Low lymphocyte monocyte ratio after neoadjuvant therapy predicts poor survival after pancreatectomy in patients with borderline resectable pancreatic cancer. Surgery. 2019;165(6):1151–60.CrossRef
18.
go back to reference Chen F, Lin L, Yan L, Qiu Y, Cai L, He B. Preoperative neutrophil-to-lymphocyte ratio predicts the prognosis of oral squamous cell carcinoma: a large-sample prospective study. J Oral Maxillofac Surg. 2017;75(6):1275–82.CrossRef Chen F, Lin L, Yan L, Qiu Y, Cai L, He B. Preoperative neutrophil-to-lymphocyte ratio predicts the prognosis of oral squamous cell carcinoma: a large-sample prospective study. J Oral Maxillofac Surg. 2017;75(6):1275–82.CrossRef
19.
go back to reference Rindi G, Kloppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006;449(4):395–401.CrossRef Rindi G, Kloppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Arch. 2006;449(4):395–401.CrossRef
20.
go back to reference Genc CG, Falconi M, Partelli S, Muffatti F, van Eeden S, Doglioni C, et al. Recurrence of pancreatic neuroendocrine tumors and survival predicted by Ki67. Ann Surg Oncol. 2018;25(8):2467–74.CrossRef Genc CG, Falconi M, Partelli S, Muffatti F, van Eeden S, Doglioni C, et al. Recurrence of pancreatic neuroendocrine tumors and survival predicted by Ki67. Ann Surg Oncol. 2018;25(8):2467–74.CrossRef
21.
go back to reference Song KB, Kim SC, Kim JH, Hong SM, Park KM, Hwang DW, et al. Prognostic factors in 151 patients with surgically resected non-functioning pancreatic neuroendocrine tumours. ANZ J Surg. 2016;86(7–8):563–7.CrossRef Song KB, Kim SC, Kim JH, Hong SM, Park KM, Hwang DW, et al. Prognostic factors in 151 patients with surgically resected non-functioning pancreatic neuroendocrine tumours. ANZ J Surg. 2016;86(7–8):563–7.CrossRef
22.
go back to reference Rindi G, Falconi M, Klersy C, Albarello L, Boninsegna L, Buchler MW, et al. TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. J Natl Cancer Inst. 2012;104(10):764–77.CrossRef Rindi G, Falconi M, Klersy C, Albarello L, Boninsegna L, Buchler MW, et al. TNM staging of neoplasms of the endocrine pancreas: results from a large international cohort study. J Natl Cancer Inst. 2012;104(10):764–77.CrossRef
23.
go back to reference Rebours V, Cordova J, Couvelard A, Fabre M, Palazzo L, Vullierme MP, et al. Can pancreatic neuroendocrine tumour biopsy accurately determine pathological characteristics? Dig Liver Dis. 2015;47(11):973–7.CrossRef Rebours V, Cordova J, Couvelard A, Fabre M, Palazzo L, Vullierme MP, et al. Can pancreatic neuroendocrine tumour biopsy accurately determine pathological characteristics? Dig Liver Dis. 2015;47(11):973–7.CrossRef
24.
go back to reference Zou J, Li Q, Kou F, Zhu Y, Lu M, Li J, et al. Prognostic value of inflammation-based markers in advanced or metastatic neuroendocrine tumours. Curr Oncol. 2019;26(1):e30–8.CrossRef Zou J, Li Q, Kou F, Zhu Y, Lu M, Li J, et al. Prognostic value of inflammation-based markers in advanced or metastatic neuroendocrine tumours. Curr Oncol. 2019;26(1):e30–8.CrossRef
25.
go back to reference Zhou B, Zhan C, Wu J, Liu J, Zhou J, Zheng S. Prognostic significance of preoperative neutrophil-to-lymphocyte ratio in surgically resectable pancreatic neuroendocrine tumors. Med Sci Monit. 2017;23:5574–88.CrossRef Zhou B, Zhan C, Wu J, Liu J, Zhou J, Zheng S. Prognostic significance of preoperative neutrophil-to-lymphocyte ratio in surgically resectable pancreatic neuroendocrine tumors. Med Sci Monit. 2017;23:5574–88.CrossRef
26.
go back to reference Tong Z, Liu L, Zheng Y, Jiang W, Zhao P, Fang W, et al. Predictive value of preoperative peripheral blood neutrophil/lymphocyte ratio for lymph node metastasis in patients of resectable pancreatic neuroendocrine tumors: a nomogram-based study. World J Surg Oncol. 2017;15(1):108.CrossRef Tong Z, Liu L, Zheng Y, Jiang W, Zhao P, Fang W, et al. Predictive value of preoperative peripheral blood neutrophil/lymphocyte ratio for lymph node metastasis in patients of resectable pancreatic neuroendocrine tumors: a nomogram-based study. World J Surg Oncol. 2017;15(1):108.CrossRef
27.
go back to reference Salman T, Kazaz SN, Varol U, Oflazoglu U, Unek IT, Kucukzeybek Y, et al. Prognostic value of the pretreatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for patients with neuroendocrine tumors: an Izmir oncology group study. Chemotherapy. 2016;61(6):281–6.CrossRef Salman T, Kazaz SN, Varol U, Oflazoglu U, Unek IT, Kucukzeybek Y, et al. Prognostic value of the pretreatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for patients with neuroendocrine tumors: an Izmir oncology group study. Chemotherapy. 2016;61(6):281–6.CrossRef
28.
go back to reference Harimoto N, Hoshino K, Muranushi R, Hagiwara K, Yamanaka T, Ishii N, et al. Prognostic significance of neutrophil-lymphocyte ratio in resectable pancreatic neuroendocrine tumors with special reference to tumor-associated macrophages. Pancreatology. 2019;19(6):897–902.CrossRef Harimoto N, Hoshino K, Muranushi R, Hagiwara K, Yamanaka T, Ishii N, et al. Prognostic significance of neutrophil-lymphocyte ratio in resectable pancreatic neuroendocrine tumors with special reference to tumor-associated macrophages. Pancreatology. 2019;19(6):897–902.CrossRef
29.
go back to reference Strosberg JR, Coppola D, Klimstra DS, Phan AT, Kulke MH, Wiseman GA, et al. The NANETS consensus guidelines for the diagnosis and management of poorly differentiated (high-grade) extrapulmonary neuroendocrine carcinomas. Pancreas. 2010;39(6):799–800.CrossRef Strosberg JR, Coppola D, Klimstra DS, Phan AT, Kulke MH, Wiseman GA, et al. The NANETS consensus guidelines for the diagnosis and management of poorly differentiated (high-grade) extrapulmonary neuroendocrine carcinomas. Pancreas. 2010;39(6):799–800.CrossRef
30.
go back to reference Basturk O, Yang Z, Tang LH, Hruban RH, Adsay V, McCall CM, et al. The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms. Am J Surg Pathol. 2015;39(5):683–90.CrossRef Basturk O, Yang Z, Tang LH, Hruban RH, Adsay V, McCall CM, et al. The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms. Am J Surg Pathol. 2015;39(5):683–90.CrossRef
31.
go back to reference Hata T, Mizuma M, Motoi F, Ishida M, Morikawa T, Takadate T, et al. Diagnostic and prognostic impact of neutrophil-to-lymphocyte ratio for intraductal papillary mucinous neoplasms of the pancreas with high-grade dysplasia and associated invasive carcinoma. Pancreas. 2019;48(1):99–106.CrossRef Hata T, Mizuma M, Motoi F, Ishida M, Morikawa T, Takadate T, et al. Diagnostic and prognostic impact of neutrophil-to-lymphocyte ratio for intraductal papillary mucinous neoplasms of the pancreas with high-grade dysplasia and associated invasive carcinoma. Pancreas. 2019;48(1):99–106.CrossRef
32.
go back to reference Takakura K, Ito Z, Suka M, Kanai T, Matsumoto Y, Odahara S, et al. Comprehensive assessment of the prognosis of pancreatic cancer: peripheral blood neutrophil–lymphocyte ratio and immunohistochemical analyses of the tumour site. Scand J Gastroenterol. 2016;51(5):610–7.CrossRef Takakura K, Ito Z, Suka M, Kanai T, Matsumoto Y, Odahara S, et al. Comprehensive assessment of the prognosis of pancreatic cancer: peripheral blood neutrophil–lymphocyte ratio and immunohistochemical analyses of the tumour site. Scand J Gastroenterol. 2016;51(5):610–7.CrossRef
33.
go back to reference Gregory AD, Houghton AM. Tumor-associated neutrophils: new targets for cancer therapy. Cancer Res. 2011;71(7):2411–6.CrossRef Gregory AD, Houghton AM. Tumor-associated neutrophils: new targets for cancer therapy. Cancer Res. 2011;71(7):2411–6.CrossRef
34.
go back to reference Barnes TA, Amir E. HYPE or HOPE: the prognostic value of infiltrating immune cells in cancer. Br J Cancer. 2017;117(4):451–60.CrossRef Barnes TA, Amir E. HYPE or HOPE: the prognostic value of infiltrating immune cells in cancer. Br J Cancer. 2017;117(4):451–60.CrossRef
35.
go back to reference Halazun KJ, Hardy MA, Rana AA, Woodland DCT, Luyten EJ, Mahadev S, et al. Negative impact of neutrophil–lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma. Ann Surg. 2009;250(1):141–51.CrossRef Halazun KJ, Hardy MA, Rana AA, Woodland DCT, Luyten EJ, Mahadev S, et al. Negative impact of neutrophil–lymphocyte ratio on outcome after liver transplantation for hepatocellular carcinoma. Ann Surg. 2009;250(1):141–51.CrossRef
36.
go back to reference Ito T, Lee L, Hijioka M, Kawabe K, Kato M, Nakamura K, et al. The up-to-date review of epidemiological pancreatic neuroendocrine tumors in Japan. J Hepatobiliary Pancreat Sci. 2015;22(8):574–7.CrossRef Ito T, Lee L, Hijioka M, Kawabe K, Kato M, Nakamura K, et al. The up-to-date review of epidemiological pancreatic neuroendocrine tumors in Japan. J Hepatobiliary Pancreat Sci. 2015;22(8):574–7.CrossRef
37.
go back to reference Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. 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):3063–72.CrossRef Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. 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):3063–72.CrossRef
38.
go back to reference Treglia G, Castaldi P, Rindi G, Giordano A, Rufini V. Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis. Endocrine. 2012;42(1):80–7.CrossRef Treglia G, Castaldi P, Rindi G, Giordano A, Rufini V. Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis. Endocrine. 2012;42(1):80–7.CrossRef
39.
go back to reference Sadowski SM, Neychev V, Millo C, Shih J, Nilubol N, Herscovitch P, et al. Prospective study of 68Ga-DOTATATE positron emission tomography/computed tomography for detecting gastro-entero-pancreatic neuroendocrine tumors and unknown primary sites. J Clin Oncol. 2016;34(6):588–96.CrossRef Sadowski SM, Neychev V, Millo C, Shih J, Nilubol N, Herscovitch P, et al. Prospective study of 68Ga-DOTATATE positron emission tomography/computed tomography for detecting gastro-entero-pancreatic neuroendocrine tumors and unknown primary sites. J Clin Oncol. 2016;34(6):588–96.CrossRef
40.
go back to reference Matsumoto T, Okabe H, Yamashita YI, Yusa T, Itoyama R, Nakao Y, et al. Clinical role of fludeoxyglucose (18F) positron emission tomography/computed tomography ((18)F-FDG PET/CT) in patients with pancreatic neuroendocrine tumors. Surg Today. 2019;49(1):21–6.CrossRef Matsumoto T, Okabe H, Yamashita YI, Yusa T, Itoyama R, Nakao Y, et al. Clinical role of fludeoxyglucose (18F) positron emission tomography/computed tomography ((18)F-FDG PET/CT) in patients with pancreatic neuroendocrine tumors. Surg Today. 2019;49(1):21–6.CrossRef
Metadata
Title
Increased neutrophil–lymphocyte ratio predicts recurrence in patients with well-differentiated pancreatic neuroendocrine neoplasm based on the 2017 World Health Organization classification
Authors
Takayuki Miura
Hideo Ohtsuka
Takeshi Aoki
Shuichi Aoki
Tatsuo Hata
Tatsuyuki Takadate
Shimpei Maeda
Kyohei Ariake
Kei Kawaguchi
Kunihiro Masuda
Masaharu Ishida
Masamichi Mizuma
Kei Nakagawa
Takanori Morikawa
Fumiyoshi Fujishima
Takashi Kamei
Hironobu Sasano
Michiaki Unno
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Metastasis
Published in
BMC Surgery / Issue 1/2021
Electronic ISSN: 1471-2482
DOI
https://doi.org/10.1186/s12893-021-01178-3

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