Skip to main content
Top
Published in: Surgery Today 8/2021

01-08-2021 | Colon Cancer | Original Article

The updated five-year overall survival and long-term oxaliplatin-related neurotoxicity assessment of the FACOS study

Authors: Emiko Takeshita, Keiichiro Ishibashi, Keiji Koda, Noritaka Oda, Kazuhiko Yoshimatsu, Yu Sato, Masatoshi Oya, Satoru Yamaguchi, Hideo Nakajima, Tomoyuki Momma, Hiroshi Maekawa, Masahiro Tsubaki, Takeshi Yamada, Michiya Kobayashi, Kohji Tanakaya, Hideyuki Ishida

Published in: Surgery Today | Issue 8/2021

Login to get access

Abstract

Purpose

We previously reported the first evidence of oncological benefits from a Japanese phase II trial of oxaliplatin-based adjuvant chemotherapy in patients with stage III colon cancer (the FACOS study). We herein report the long-term survival and persistent oxaliplatin-related peripheral sensory neuropathy (PSN) for patients enrolled in this trial.

Methods

Patients were scheduled to receive the mFOLFOX6 or CAPOX regimen in the adjuvant setting. The five-year overall survival (OS) rate and persistent PSN were evaluated.

Results

A total of 130 patients (mFOLFOX6, n = 73; CAPOX, n = 57) were eligible. The 5-year OS rate was 91.4%. No significant difference in the OS rate was observed between regimens (mFOLFOX6, 94.4%; CAPOX, 87.4%; P = 0.25). The incidence of PSN during adjuvant treatment was 55.4% in grade 1 (G1), 30.0% in G2, and 4.6% in G3. No patients showed G3 PSN at 12 months, but G1 or G2 residual PSN after 5 years was observed in 21.8% (G1, 20%; G2, 1.8%).

Conclusions

Updated results from the FACOS study support the benefits of oxaliplatin-based adjuvant chemotherapy in terms of the long-term survival among Japanese patients with stage III colon cancer. However, long-term persistent PSN occurs in about 20% of survivors, counterbalancing the favorable OS.
Literature
1.
go back to reference André T, de GramontVernerey AD, Chibaudel B, Bonnetain F, Tijeras-Raballand A, et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015;33:4176–87.CrossRef André T, de GramontVernerey AD, Chibaudel B, Bonnetain F, Tijeras-Raballand A, et al. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015;33:4176–87.CrossRef
2.
go back to reference Kuebler JP, Wieand HS, O’Connell MJ, Smith RE, Colangelo LH, Yothers G, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25:2198–204.CrossRef Kuebler JP, Wieand HS, O’Connell MJ, Smith RE, Colangelo LH, Yothers G, et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007;25:2198–204.CrossRef
3.
go back to reference Schmoll HJ, Tabernero J, Maroun J, de BraudPrice FT, Van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results of the NO16968 randomized controlled phase III trial. J Clin Oncol. 2015;33:3733–40.CrossRef Schmoll HJ, Tabernero J, Maroun J, de BraudPrice FT, Van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results of the NO16968 randomized controlled phase III trial. J Clin Oncol. 2015;33:3733–40.CrossRef
4.
go back to reference Ishibashi K, Kumamoto K, Koda K, Kato H, Nishimura G, Yoshimatsu K, et al. A phase II clinical study of mFOLFOX6/XELOX as adjuvant chemotherapy after curative resection of stage III colon cancer: the FACOS study. Ann Cancer Res Ther. 2016;24:17–22.CrossRef Ishibashi K, Kumamoto K, Koda K, Kato H, Nishimura G, Yoshimatsu K, et al. A phase II clinical study of mFOLFOX6/XELOX as adjuvant chemotherapy after curative resection of stage III colon cancer: the FACOS study. Ann Cancer Res Ther. 2016;24:17–22.CrossRef
5.
go back to reference Yoshimatsu K, Ishibashi K, Koda K, Yokomizo H, Oda N, Oshiro M, et al. A Japanese multicenter phase II study of adjuvant chemotherapy with mFOLFOX6/CAPOX for stage III colon cancer treatment after D2/D3 lymphadenectomy. Surg Today. 2019;49:498–506.CrossRef Yoshimatsu K, Ishibashi K, Koda K, Yokomizo H, Oda N, Oshiro M, et al. A Japanese multicenter phase II study of adjuvant chemotherapy with mFOLFOX6/CAPOX for stage III colon cancer treatment after D2/D3 lymphadenectomy. Surg Today. 2019;49:498–506.CrossRef
6.
go back to reference Kosugi C, Koda K, Ishibashi K, Yoshimatsu K, Tanaka S, Kato R, et al. Safety of FOLFOX6/XELOX as adjuvant chemotherapy after curative resection of stage III colon cancer: phase II clinical study (the FACOS study). Int J Colorectal Dis. 2018;33:809–17.CrossRef Kosugi C, Koda K, Ishibashi K, Yoshimatsu K, Tanaka S, Kato R, et al. Safety of FOLFOX6/XELOX as adjuvant chemotherapy after curative resection of stage III colon cancer: phase II clinical study (the FACOS study). Int J Colorectal Dis. 2018;33:809–17.CrossRef
7.
go back to reference Brungs D, Aghmesheh M, de Souza P, et al. Safety and efficacy of oxaliplatin doublet adjuvant chemotherapy in elderly patients with stage III colon cancer. Clin Colorectal Cancer. 2018;17(3):e549–55.CrossRef Brungs D, Aghmesheh M, de Souza P, et al. Safety and efficacy of oxaliplatin doublet adjuvant chemotherapy in elderly patients with stage III colon cancer. Clin Colorectal Cancer. 2018;17(3):e549–55.CrossRef
8.
go back to reference Pietrangeli A, Leandri M, Terzoli E, Jandolo B, Garufi C. Persistence of high-dose oxaliplatin-induced neuropathy at long-term follow-up. Eur Neurol. 2006;56:13–6.CrossRef Pietrangeli A, Leandri M, Terzoli E, Jandolo B, Garufi C. Persistence of high-dose oxaliplatin-induced neuropathy at long-term follow-up. Eur Neurol. 2006;56:13–6.CrossRef
9.
go back to reference Land SR, Kopec JA, Cecchini RS, Ganz PA, Wieand HS, Colangelo LH, et al. Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07. J Clin Oncol. 2007;25:2205–11.CrossRef Land SR, Kopec JA, Cecchini RS, Ganz PA, Wieand HS, Colangelo LH, et al. Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07. J Clin Oncol. 2007;25:2205–11.CrossRef
10.
go back to reference Yoshino T, Yamanaka T, Oki E, Kotaka M, Manaka D, Eto T, et al. Efficacy and long-term peripheral sensory neuropathy of 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy for colon cancer the ACHIEVE phase 3 randomized clinical trial. JAMA Oncol. 2019;5:1574–81.CrossRef Yoshino T, Yamanaka T, Oki E, Kotaka M, Manaka D, Eto T, et al. Efficacy and long-term peripheral sensory neuropathy of 3 vs 6 months of oxaliplatin-based adjuvant chemotherapy for colon cancer the ACHIEVE phase 3 randomized clinical trial. JAMA Oncol. 2019;5:1574–81.CrossRef
11.
go back to reference Yoshino T, Kotaka M, Shinozaki K, Touyama T, Manaka D, Matsui T, et al. JOIN trial: treatment outcome and recovery status of peripheral sensory neuropathy during a 3-year follow-up in patients receiving modified FOLFOX6 as adjuvant treatment for stage II/III colon cancer. Cancer Chemother Pharmacol. 2019;84:1269–77.CrossRef Yoshino T, Kotaka M, Shinozaki K, Touyama T, Manaka D, Matsui T, et al. JOIN trial: treatment outcome and recovery status of peripheral sensory neuropathy during a 3-year follow-up in patients receiving modified FOLFOX6 as adjuvant treatment for stage II/III colon cancer. Cancer Chemother Pharmacol. 2019;84:1269–77.CrossRef
12.
go back to reference Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27:3109–16.CrossRef Andre T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27:3109–16.CrossRef
13.
go back to reference Haller DG, Tabernero J, Maroun J, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011;29(11):1465–71.CrossRef Haller DG, Tabernero J, Maroun J, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011;29(11):1465–71.CrossRef
14.
go back to reference Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito Y, Japanese Society for Cancer of the Colon and Rectum, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol. 2018;23:1–34.CrossRef Watanabe T, Muro K, Ajioka Y, Hashiguchi Y, Ito Y, Saito Y, Japanese Society for Cancer of the Colon and Rectum, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol. 2018;23:1–34.CrossRef
15.
go back to reference Japanese Society for Cancer of the Colon and Rectum. Japanese classification of colorectal carcinoma. 2nd ed. Tokyo: Kanehara; 2009. Japanese Society for Cancer of the Colon and Rectum. Japanese classification of colorectal carcinoma. 2nd ed. Tokyo: Kanehara; 2009.
17.
go back to reference Brierley JD, Gospodarowicz MK, Wittekind C. The TNM classification of malignant tumours. 8th ed. Hoboken: Wiley; 2016. Brierley JD, Gospodarowicz MK, Wittekind C. The TNM classification of malignant tumours. 8th ed. Hoboken: Wiley; 2016.
18.
go back to reference Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018;378:1177–88.CrossRef Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, et al. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018;378:1177–88.CrossRef
19.
go back to reference Kotaka M, Yoshino T, Oba K, Shinozaki K, Touyama T, Manaka D, et al. Initial safety report on the tolerability of modified FOLFOX6 as adjuvant therapy in patients with curatively resected stage II or III colon cancer (JFMC41-1001-C2: JOIN trial). Cancer Chemother Pharmacol. 2015;76:75–84.CrossRef Kotaka M, Yoshino T, Oba K, Shinozaki K, Touyama T, Manaka D, et al. Initial safety report on the tolerability of modified FOLFOX6 as adjuvant therapy in patients with curatively resected stage II or III colon cancer (JFMC41-1001-C2: JOIN trial). Cancer Chemother Pharmacol. 2015;76:75–84.CrossRef
20.
go back to reference Pectasides D, Karavasilis V, Papaxoinis G, Gourgioti G, Makatsoris T, Raptou G, et al. Randomized phase III clinical trial comparing the combination of capecitabine and oxaliplatin (CAPOX) with the combination of 5-fluorouracil, leucovorin and oxaliplatin (modified FOLFOX6) as adjuvant therapy in patients with operated high-risk stage II or stage III colorectal cancer. BMC Cancer. 2015;15:384.CrossRef Pectasides D, Karavasilis V, Papaxoinis G, Gourgioti G, Makatsoris T, Raptou G, et al. Randomized phase III clinical trial comparing the combination of capecitabine and oxaliplatin (CAPOX) with the combination of 5-fluorouracil, leucovorin and oxaliplatin (modified FOLFOX6) as adjuvant therapy in patients with operated high-risk stage II or stage III colorectal cancer. BMC Cancer. 2015;15:384.CrossRef
21.
go back to reference Beijers AJ, Mols F, Tjan-Heijnen VC, Faber CG, van de Poll-Franse LV, Vreugdenhil G. Peripheral neuropathy in colorectal cancer survivors: the influence of oxaliplatin administration. Results from the population-based PROFILES registry. Acta Oncol. 2015;54(4):463–9.CrossRef Beijers AJ, Mols F, Tjan-Heijnen VC, Faber CG, van de Poll-Franse LV, Vreugdenhil G. Peripheral neuropathy in colorectal cancer survivors: the influence of oxaliplatin administration. Results from the population-based PROFILES registry. Acta Oncol. 2015;54(4):463–9.CrossRef
22.
go back to reference Gill S, Sargent D. End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival? Oncologist. 2006;11(6):624–9.CrossRef Gill S, Sargent D. End points for adjuvant therapy trials: has the time come to accept disease-free survival as a surrogate end point for overall survival? Oncologist. 2006;11(6):624–9.CrossRef
23.
go back to reference Loree JM, Sha A, Soleimani M, Kennecke HF, Ho MY, Cheung WY, et al. Survival impact of CAPOX versus FOLFOX in the adjuvant treatment of stage III colon cancer. Clin Colorectal Cancer. 2018;17(2):156–63.CrossRef Loree JM, Sha A, Soleimani M, Kennecke HF, Ho MY, Cheung WY, et al. Survival impact of CAPOX versus FOLFOX in the adjuvant treatment of stage III colon cancer. Clin Colorectal Cancer. 2018;17(2):156–63.CrossRef
24.
go back to reference Chau I, Norman AR, Cunningham D, Tait D, Ross PJ, Iveson T, et al. A randomised comparison between 6 months of bolus fluorouracil/leucovorin and 12 weeks of protracted venous infusion fluorouracil as adjuvant treatment in colorectal cancer. Ann Oncol. 2005;16:549–57.CrossRef Chau I, Norman AR, Cunningham D, Tait D, Ross PJ, Iveson T, et al. A randomised comparison between 6 months of bolus fluorouracil/leucovorin and 12 weeks of protracted venous infusion fluorouracil as adjuvant treatment in colorectal cancer. Ann Oncol. 2005;16:549–57.CrossRef
25.
go back to reference Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005;352:2696–704.CrossRef Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005;352:2696–704.CrossRef
26.
go back to reference Ishibashi K, Okada N, Miyazaki T, Sano M, Ishida H. Effect of calcium and magnesium on neurotoxicity and blood platinum concentrations in patients receiving mFOLFOX6 therapy: a prospective randomized study. Int J Clin Oncol. 2010;15(1):82–7.CrossRef Ishibashi K, Okada N, Miyazaki T, Sano M, Ishida H. Effect of calcium and magnesium on neurotoxicity and blood platinum concentrations in patients receiving mFOLFOX6 therapy: a prospective randomized study. Int J Clin Oncol. 2010;15(1):82–7.CrossRef
27.
go back to reference Gamelin L, Boisdron-Celle M, Delva R, et al. Prevention of oxaliplatin-related neurotoxicity by calcium and magnesium infusions: a retrospective study of 161 patients receiving oxaliplatin combined with 5-fluorouracil and leucovorin for advanced colorectal cancer. Clin Cancer Res. 2004;10:4055–61.CrossRef Gamelin L, Boisdron-Celle M, Delva R, et al. Prevention of oxaliplatin-related neurotoxicity by calcium and magnesium infusions: a retrospective study of 161 patients receiving oxaliplatin combined with 5-fluorouracil and leucovorin for advanced colorectal cancer. Clin Cancer Res. 2004;10:4055–61.CrossRef
28.
go back to reference Lersch C, Schmelz R, Eckel F, Erdmann J, Mayr M, Schulte-Frohlinde E, et al. Prevention of oxaliplatin-induced peripheral sensory neuropathy by carbamazepine in patients with advanced colorectal cancer. Clin Colorectal Cancer. 2002;2(1):54–8.CrossRef Lersch C, Schmelz R, Eckel F, Erdmann J, Mayr M, Schulte-Frohlinde E, et al. Prevention of oxaliplatin-induced peripheral sensory neuropathy by carbamazepine in patients with advanced colorectal cancer. Clin Colorectal Cancer. 2002;2(1):54–8.CrossRef
29.
go back to reference Penz M, Kornek GV, Raderer M, Ulrich-Pur H, Fiebiger W, Scheithauer W. Subcutaneous administration of amifostine: a promising therapeutic option in patients with oxaliplatin-related peripheral sensitive neuropathy. Ann Oncol. 2001;12(3):421–2.CrossRef Penz M, Kornek GV, Raderer M, Ulrich-Pur H, Fiebiger W, Scheithauer W. Subcutaneous administration of amifostine: a promising therapeutic option in patients with oxaliplatin-related peripheral sensitive neuropathy. Ann Oncol. 2001;12(3):421–2.CrossRef
30.
go back to reference Guo Y, Jones D, Palmer JL, Forman A, Dakhil SR, Velasco MR, et al. Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial. Support Care Cancer. 2014;22(5):1223–31.CrossRef Guo Y, Jones D, Palmer JL, Forman A, Dakhil SR, Velasco MR, et al. Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial. Support Care Cancer. 2014;22(5):1223–31.CrossRef
31.
go back to reference Gedlicka C, Scheithauer W, Schüll B, Kornek GV. Effective treatment of oxaliplatin-induced cumulative polyneuropathy with alpha-lipoic acid. J Clin Oncol. 2002;20(15):3359–61.CrossRef Gedlicka C, Scheithauer W, Schüll B, Kornek GV. Effective treatment of oxaliplatin-induced cumulative polyneuropathy with alpha-lipoic acid. J Clin Oncol. 2002;20(15):3359–61.CrossRef
32.
go back to reference Takimoto N, Sugawara S, Iida A, Sakakibara T, Mori K, Sugiura M, et al. Prevention of oxaliplatin-related neurotoxicity by glutathione infusions. Gan To Kagaku Ryoho. 2008;35(13):2373–6 (in Japanese).PubMed Takimoto N, Sugawara S, Iida A, Sakakibara T, Mori K, Sugiura M, et al. Prevention of oxaliplatin-related neurotoxicity by glutathione infusions. Gan To Kagaku Ryoho. 2008;35(13):2373–6 (in Japanese).PubMed
33.
go back to reference Cascinu S, Catalano V, Cordella L, Labiance R, Giordani P, Baldelli AM, et al. Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2002;20(16):3478–83.CrossRef Cascinu S, Catalano V, Cordella L, Labiance R, Giordani P, Baldelli AM, et al. Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2002;20(16):3478–83.CrossRef
34.
go back to reference Kawashiri T, Shimizu S, Shigematsu N, Kobayashi D, Shimazoe T. Donepezil ameliorates oxaliplatin-induced peripheral neuropathy via a neuroprotective effect. J Pharmacol Sci. 2019;140(3):291–4.CrossRef Kawashiri T, Shimizu S, Shigematsu N, Kobayashi D, Shimazoe T. Donepezil ameliorates oxaliplatin-induced peripheral neuropathy via a neuroprotective effect. J Pharmacol Sci. 2019;140(3):291–4.CrossRef
35.
go back to reference Nakagawa T, Kaneko S. Roles of transient receptor potential ankyrin 1 in oxaliplatin-induced peripheral neuropathy. Biol Pharm Bull. 2017;40(7):947–53.CrossRef Nakagawa T, Kaneko S. Roles of transient receptor potential ankyrin 1 in oxaliplatin-induced peripheral neuropathy. Biol Pharm Bull. 2017;40(7):947–53.CrossRef
36.
go back to reference Nishida K, Takeuchi K, Hosoda A, Sugano S, Morisaki E, Ohishi A, et al. Ergothioneine ameliorates oxaliplatin-induced peripheral neuropathy in rats. Life Sci. 2018;207:516–24.CrossRef Nishida K, Takeuchi K, Hosoda A, Sugano S, Morisaki E, Ohishi A, et al. Ergothioneine ameliorates oxaliplatin-induced peripheral neuropathy in rats. Life Sci. 2018;207:516–24.CrossRef
37.
go back to reference Guillaumot MA, Cerles O, Bertrand HC, Benoit E, Nicco C, Chouzenoux S, et al. Oxaliplatin-induced neuropathy: the preventive effect of a new super-oxide dismutase modulator. Oncotarget. 2019;10(60):6418–31.CrossRef Guillaumot MA, Cerles O, Bertrand HC, Benoit E, Nicco C, Chouzenoux S, et al. Oxaliplatin-induced neuropathy: the preventive effect of a new super-oxide dismutase modulator. Oncotarget. 2019;10(60):6418–31.CrossRef
38.
go back to reference Park SB, Kiernan MC. Oxaliplatin and neuropathy: a role for sodium channels. Clin Neurophysiol. 2018;129(3):670–1.CrossRef Park SB, Kiernan MC. Oxaliplatin and neuropathy: a role for sodium channels. Clin Neurophysiol. 2018;129(3):670–1.CrossRef
39.
go back to reference Starobova H, Vetter I. Pathophysiology of chemotherapy-induced peripheral neuropathy. Front Mol Neurosci. 2017;10:174.CrossRef Starobova H, Vetter I. Pathophysiology of chemotherapy-induced peripheral neuropathy. Front Mol Neurosci. 2017;10:174.CrossRef
Metadata
Title
The updated five-year overall survival and long-term oxaliplatin-related neurotoxicity assessment of the FACOS study
Authors
Emiko Takeshita
Keiichiro Ishibashi
Keiji Koda
Noritaka Oda
Kazuhiko Yoshimatsu
Yu Sato
Masatoshi Oya
Satoru Yamaguchi
Hideo Nakajima
Tomoyuki Momma
Hiroshi Maekawa
Masahiro Tsubaki
Takeshi Yamada
Michiya Kobayashi
Kohji Tanakaya
Hideyuki Ishida
Publication date
01-08-2021
Publisher
Springer Singapore
Published in
Surgery Today / Issue 8/2021
Print ISSN: 0941-1291
Electronic ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-021-02230-8

Other articles of this Issue 8/2021

Surgery Today 8/2021 Go to the issue