Skip to main content
Top
Published in: Journal of Gastrointestinal Surgery 11/2023

22-09-2023 | Original Article

Delayed-Onset Organ/Space Surgical Site Infection Worsens Prognosis in High-Risk Stage II and III Colorectal Cancer

Authors: Jun Okui, Kohei Shigeta, Yujin Kato, Shodai Mizuno, Kiyoaki Sugiura, Yuki Seo, Jumpei Nakadai, Hideo Baba, Hiroto Kikuchi, Akira Hirata, Akitsugu Makino, Takayuki Kondo, Shimpei Matsui, Ryo Seishima, Koji Okabayashi, Hideaki Obara, Yasunori Sato, Yuko Kitagawa

Published in: Journal of Gastrointestinal Surgery | Issue 11/2023

Login to get access

Abstract

Background

It is unclear how early- and delayed-onset organ/space surgical site infections (SSIs) affect the long-term prognosis of patients with colorectal cancer, who are potential candidates for adjuvant chemotherapy. This study aimed to investigate the association between the timing of SSI onset and clinical outcome.

Methods

This retrospective, multicenter cohort study evaluated patients who were diagnosed with high-risk stage II or III colorectal cancer and underwent elective surgery between 2010 and 2020. Five-year recurrence-free survival (RFS) was the primary endpoint and was compared between early SSI, delayed SSI (divided based on the median date of SSI onset), and non-SSI groups.

Results

A total of 2,065 patients were included. Organ/space SSI was diagnosed in 91 patients (4.4%), with a median onset of 6 days after surgery. The early-onset SSI group had a higher proportion of patients with Clavien–Dindo grade ≥IIIb SSI than the delayed-onset SSI. Patients who received adjuvant chemotherapy (AC) had earlier organ/space SSI onset than those who did not. The adjusted hazard ratio of 5-year RFS in the delayed-onset SSI was 2.58 (95% confidence interval: 1.43–4.65; p = 0.002): higher than that in the early-onset SSI, with the non-SSI as the reference.

Conclusions

Delayed-onset organ/space SSI worsened long-term prognosis compared to early-onset, and this may be due to delayed initiation of AC. Patients who are clinically suspected of having lymph node metastasis might need additional intervention to prevent delays in commencing AC due to the delayed SSI.
Appendix
Available only for authorised users
Literature
1.
go back to reference Coello R, Charlett A, Wilson J, Ward V, Pearson A, Borriello P. Adverse impact of surgical site infections in English hospitals. J Hosp Infect. 2005 60(2):93–103. CrossRefPubMed Coello R, Charlett A, Wilson J, Ward V, Pearson A, Borriello P. Adverse impact of surgical site infections in English hospitals. J Hosp Infect. 2005 60(2):93–103. CrossRefPubMed
2.
go back to reference Lawler J, Choynowski M, Bailey K, Bucholc M, Johnston A, Sugrue M. Meta-analysis of the impact of postoperative infective complications on oncological outcomes in colorectal cancer surgery. BJS Open. 2020 4(5):737–47. CrossRefPubMedPubMedCentral Lawler J, Choynowski M, Bailey K, Bucholc M, Johnston A, Sugrue M. Meta-analysis of the impact of postoperative infective complications on oncological outcomes in colorectal cancer surgery. BJS Open. 2020 4(5):737–47. CrossRefPubMedPubMedCentral
3.
go back to reference Matsuda S, Kitagawa Y, Okui J, Okamura A, Kawakubo H, Takemura R, et al. Old age and intense chemotherapy exacerbate negative prognostic impact of postoperative complication on survival in patients with esophageal cancer who received neoadjuvant therapy: a nationwide study from 85 Japanese esophageal centers. Esophagus 2023 Jul;20(3):445–454. Matsuda S, Kitagawa Y, Okui J, Okamura A, Kawakubo H, Takemura R, et al. Old age and intense chemotherapy exacerbate negative prognostic impact of postoperative complication on survival in patients with esophageal cancer who received neoadjuvant therapy: a nationwide study from 85 Japanese esophageal centers. Esophagus 2023 Jul;20(3):445–454.
4.
go back to reference Doeksen A, Tanis PJ, Vrouenraets BC, Lanschot van JJB, Tets van WF. Factors determining delay in relaparotomy for anastomotic leakage after colorectal resection. World J Gastroenterol. 2007;13(27):3721–5. CrossRefPubMedPubMedCentral Doeksen A, Tanis PJ, Vrouenraets BC, Lanschot van JJB, Tets van WF. Factors determining delay in relaparotomy for anastomotic leakage after colorectal resection. World J Gastroenterol. 2007;13(27):3721–5. CrossRefPubMedPubMedCentral
5.
go back to reference Okui J, Ueno R, Matsui H, Uegami W, Hayashi H, Miyajima T, et al. Early prediction model of organ/space surgical site infection after elective gastrointestinal or hepatopancreatobiliary cancer surgery. J Infect Chemother. 2020 26(9):916–22. CrossRefPubMed Okui J, Ueno R, Matsui H, Uegami W, Hayashi H, Miyajima T, et al. Early prediction model of organ/space surgical site infection after elective gastrointestinal or hepatopancreatobiliary cancer surgery. J Infect Chemother. 2020 26(9):916–22. CrossRefPubMed
6.
go back to reference Gessler B, Eriksson O, Angenete E. Diagnosis, treatment, and consequences of anastomotic leakage in colorectal surgery. Int J Colorectal Dis. 2017 32(4):549–56. CrossRefPubMedPubMedCentral Gessler B, Eriksson O, Angenete E. Diagnosis, treatment, and consequences of anastomotic leakage in colorectal surgery. Int J Colorectal Dis. 2017 32(4):549–56. CrossRefPubMedPubMedCentral
7.
go back to reference Morks AN, Ploeg RJ, Sijbrand Hofker H, Wiggers T, Havenga K. Late anastomotic leakage in colorectal surgery: a significant problem. Colorectal Dis. 2013 15(5):e271–5. CrossRefPubMed Morks AN, Ploeg RJ, Sijbrand Hofker H, Wiggers T, Havenga K. Late anastomotic leakage in colorectal surgery: a significant problem. Colorectal Dis. 2013 15(5):e271–5. CrossRefPubMed
8.
go back to reference Okui J, Obara H, Shimane G, Sato Y, Kawakubo H, Kitago M, et al. Severity of early diagnosed organ/space surgical site infection in elective gastrointestinal and hepatopancreatobiliary surgery. Ann Gastroenterol Surg. 2022 6(3):445–53. CrossRefPubMed Okui J, Obara H, Shimane G, Sato Y, Kawakubo H, Kitago M, et al. Severity of early diagnosed organ/space surgical site infection in elective gastrointestinal and hepatopancreatobiliary surgery. Ann Gastroenterol Surg. 2022 6(3):445–53. CrossRefPubMed
9.
go back to reference Kim IY, Kim BR, Kim YW. The impact of anastomotic leakage on oncologic outcomes and the receipt and timing of adjuvant chemotherapy after colorectal cancer surgery. Int J Surg. 2015 22:3–9. CrossRefPubMed Kim IY, Kim BR, Kim YW. The impact of anastomotic leakage on oncologic outcomes and the receipt and timing of adjuvant chemotherapy after colorectal cancer surgery. Int J Surg. 2015 22:3–9. CrossRefPubMed
10.
go back to reference Matsuda A, Maruyama H, Akagi S, Inoue T, Uemura K, Kobayashi M, et al. Do postoperative infectious complications really affect long-term survival in colorectal cancer surgery? A multicenter retrospective cohort study. Ann Gastroenterol Surg. 2023 Jan;7(1):110–120. Matsuda A, Maruyama H, Akagi S, Inoue T, Uemura K, Kobayashi M, et al. Do postoperative infectious complications really affect long-term survival in colorectal cancer surgery? A multicenter retrospective cohort study. Ann Gastroenterol Surg. 2023 Jan;7(1):110–120.
11.
go back to reference Cienfuegos JA, Baixauli J, Beorlegui C, Ortega PM, Granero L, Zozaya G, et al. The impact of major postoperative complications on long-term outcomes following curative resection of colon cancer. Int J Surg. 2018;52:303–8. CrossRefPubMed Cienfuegos JA, Baixauli J, Beorlegui C, Ortega PM, Granero L, Zozaya G, et al. The impact of major postoperative complications on long-term outcomes following curative resection of colon cancer. Int J Surg. 2018;52:303–8. CrossRefPubMed
12.
go back to reference Merkow RP, Bentrem DJ, Mulcahy MF, Chung JW, Abbott DE, Kmiecik TE, et al. Effect of postoperative complications on adjuvant chemotherapy use for stage III colon cancer. Ann Surg. 2013 ;258(6):847–53. CrossRefPubMed Merkow RP, Bentrem DJ, Mulcahy MF, Chung JW, Abbott DE, Kmiecik TE, et al. Effect of postoperative complications on adjuvant chemotherapy use for stage III colon cancer. Ann Surg. 2013 ;258(6):847–53. CrossRefPubMed
13.
go back to reference Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA. 2011;305(22):2335–42. CrossRefPubMed Biagi JJ, Raphael MJ, Mackillop WJ, Kong W, King WD, Booth CM. Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA. 2011;305(22):2335–42. CrossRefPubMed
14.
go back to reference Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Med. 2007;4(10):e297. CrossRefPubMedPubMedCentral Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, Mulrow CD, Pocock SJ, et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Med. 2007;4(10):e297. CrossRefPubMedPubMedCentral
15.
go back to reference Brierley JD, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours, 8th Wiley. 2017. Brierley JD, Gospodarowicz MK, Wittekind C. TNM Classification of Malignant Tumours, 8th Wiley. 2017.
16.
go back to reference Horan TC, Gaynes RP. Surveillance of nosocomial infections. In: MayhallCG, editor. Infect Control Hosp Epidemiol. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2004; p. 1659–1702. Horan TC, Gaynes RP. Surveillance of nosocomial infections. In: MayhallCG, editor. Infect Control Hosp Epidemiol. 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2004; p. 1659–1702.
17.
go back to reference Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13. CrossRefPubMedPubMedCentral Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13. CrossRefPubMedPubMedCentral
18.
go back to reference Nakamura K, Ogura K, Nakano H, Naraba H, Takahashi Y, Sonoo T, et al. C-reactive protein clustering to clarify persistent inflammation, immunosuppression and catabolism syndrome. Intensive Care Med. 2020;46(3):437–43. CrossRefPubMed Nakamura K, Ogura K, Nakano H, Naraba H, Takahashi Y, Sonoo T, et al. C-reactive protein clustering to clarify persistent inflammation, immunosuppression and catabolism syndrome. Intensive Care Med. 2020;46(3):437–43. CrossRefPubMed
19.
go back to reference Dayal V. Smoothers and Generalized Additive Models. In: Dayal V, editor. Quantitative Economics with R: A Data Science Approach. Singapore: Springer Singapore; 2020. p. 305–13. CrossRef Dayal V. Smoothers and Generalized Additive Models. In: Dayal V, editor. Quantitative Economics with R: A Data Science Approach. Singapore: Springer Singapore; 2020. p. 305–13. CrossRef
21.
go back to reference Malietzis G, Mughal A, Currie AC, Anyamene N, Kennedy RH, Athanasiou T, et al. Factors Implicated for Delay of Adjuvant Chemotherapy in Colorectal Cancer: A Meta-analysis of Observational Studies. Ann Surg Oncol. 2015;22(12):3793–802. CrossRefPubMed Malietzis G, Mughal A, Currie AC, Anyamene N, Kennedy RH, Athanasiou T, et al. Factors Implicated for Delay of Adjuvant Chemotherapy in Colorectal Cancer: A Meta-analysis of Observational Studies. Ann Surg Oncol. 2015;22(12):3793–802. CrossRefPubMed
22.
go back to reference Des Guetz G, Nicolas P, Perret GY, Morere JF, Uzzan B. Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis. Eur J Cancer. 2010;46(6):1049–55. CrossRefPubMed Des Guetz G, Nicolas P, Perret GY, Morere JF, Uzzan B. Does delaying adjuvant chemotherapy after curative surgery for colorectal cancer impair survival? A meta-analysis. Eur J Cancer. 2010;46(6):1049–55. CrossRefPubMed
23.
go back to reference Floodeen H, Hallböök O, Rutegård J, Sjödahl R, Matthiessen P. Early and late symptomatic anastomotic leakage following low anterior resection of the rectum for cancer: are they different entities? Colorectal Dis. 2013;15(3):334–40. CrossRefPubMed Floodeen H, Hallböök O, Rutegård J, Sjödahl R, Matthiessen P. Early and late symptomatic anastomotic leakage following low anterior resection of the rectum for cancer: are they different entities? Colorectal Dis. 2013;15(3):334–40. CrossRefPubMed
24.
go back to reference Kanemitsu Y, Shitara K, Mizusawa J, Hamaguchi T, Shida D, Komori K, et al. Primary Tumor Resection Plus Chemotherapy Versus Chemotherapy Alone for Colorectal Cancer Patients With Asymptomatic, Synchronous Unresectable Metastases (JCOG1007; iPACS): A Randomized Clinical Trial. J Clin Oncol. 2021;39(10):1098–107. CrossRefPubMedPubMedCentral Kanemitsu Y, Shitara K, Mizusawa J, Hamaguchi T, Shida D, Komori K, et al. Primary Tumor Resection Plus Chemotherapy Versus Chemotherapy Alone for Colorectal Cancer Patients With Asymptomatic, Synchronous Unresectable Metastases (JCOG1007; iPACS): A Randomized Clinical Trial. J Clin Oncol. 2021;39(10):1098–107. CrossRefPubMedPubMedCentral
25.
go back to reference Thoker M, Wani I, Parray FQ, Khan N, Mir SA, Thoker P. Role of diversion ileostomy in low rectal cancer: a randomized controlled trial. Int J Surg. 2014;12(9):945–51. CrossRefPubMed Thoker M, Wani I, Parray FQ, Khan N, Mir SA, Thoker P. Role of diversion ileostomy in low rectal cancer: a randomized controlled trial. Int J Surg. 2014;12(9):945–51. CrossRefPubMed
26.
go back to reference Hanna MH, Vinci A, Pigazzi A. Diverting ileostomy in colorectal surgery: when is it necessary? Langenbecks Arch Surg. 2015;400(2):145–52. CrossRefPubMed Hanna MH, Vinci A, Pigazzi A. Diverting ileostomy in colorectal surgery: when is it necessary? Langenbecks Arch Surg. 2015;400(2):145–52. CrossRefPubMed
27.
go back to reference Justiniano CF, Temple LK, Swanger AA, Xu Z, Speranza JR, Cellini C, et al. Readmissions With Dehydration After Ileostomy Creation: Rethinking Risk Factors. Dis Colon Rectum. 2018;61(11):1297–305. CrossRefPubMedPubMedCentral Justiniano CF, Temple LK, Swanger AA, Xu Z, Speranza JR, Cellini C, et al. Readmissions With Dehydration After Ileostomy Creation: Rethinking Risk Factors. Dis Colon Rectum. 2018;61(11):1297–305. CrossRefPubMedPubMedCentral
28.
go back to reference McCleary NJ, Meyerhardt JA, Green E, Yothers G, de Gramont A, Van Cutsem E, et al. Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database. J Clin Oncol. 2013;31(20):2600–6. CrossRefPubMedPubMedCentral McCleary NJ, Meyerhardt JA, Green E, Yothers G, de Gramont A, Van Cutsem E, et al. Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database. J Clin Oncol. 2013;31(20):2600–6. CrossRefPubMedPubMedCentral
29.
go back to reference Köhne CH, Folprecht G, Goldberg RM, Mitry E, Rougier P. Chemotherapy in elderly patients with colorectal cancer. Oncologist. 2008;13(4):390–402. CrossRefPubMed Köhne CH, Folprecht G, Goldberg RM, Mitry E, Rougier P. Chemotherapy in elderly patients with colorectal cancer. Oncologist. 2008;13(4):390–402. CrossRefPubMed
30.
go back to reference Morton D, Seymour M, Magill L, Handley K, Glasbey J, Glimelius B, et al. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol. 2023;41(8):1541–52. CrossRefPubMedPubMedCentral Morton D, Seymour M, Magill L, Handley K, Glasbey J, Glimelius B, et al. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol. 2023;41(8):1541–52. CrossRefPubMedPubMedCentral
31.
go back to reference Kim RH, Kavanaugh MM, Caldito GC. Laparoscopic colectomy for cancer: Improved compliance with guidelines for chemotherapy and survival. Surgery. 2017;161(6):1633–41. CrossRefPubMed Kim RH, Kavanaugh MM, Caldito GC. Laparoscopic colectomy for cancer: Improved compliance with guidelines for chemotherapy and survival. Surgery. 2017;161(6):1633–41. CrossRefPubMed
32.
go back to reference Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22(16):3408–19. CrossRefPubMed Benson AB 3rd, Schrag D, Somerfield MR, Cohen AM, Figueredo AT, Flynn PJ, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22(16):3408–19. CrossRefPubMed
33.
go back to reference Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol. 2012;23(10):2479–516. CrossRefPubMed Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol. 2012;23(10):2479–516. CrossRefPubMed
34.
go back to reference Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020;25(1):1–42. CrossRefPubMed Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T, et al. Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol. 2020;25(1):1–42. CrossRefPubMed
35.
go back to reference Kumar A, Kennecke HF, Renouf DJ, Lim HJ, Gill S, Woods R, et al. Adjuvant chemotherapy use and outcomes of patients with high-risk versus low-risk stage II colon cancer. Cancer. 2015;121(4):527–34. CrossRefPubMed Kumar A, Kennecke HF, Renouf DJ, Lim HJ, Gill S, Woods R, et al. Adjuvant chemotherapy use and outcomes of patients with high-risk versus low-risk stage II colon cancer. Cancer. 2015;121(4):527–34. CrossRefPubMed
36.
go back to reference Breugom AJ, Bastiaannet E, Boelens PG, Iversen LH, Martling A, Johansson R, et al. Adjuvant chemotherapy and relative survival of patients with stage II colon cancer - A EURECCA international comparison between the Netherlands, Denmark, Sweden, England, Ireland, Belgium, and Lithuania. Eur J Cancer. 2016;63:110–7. CrossRefPubMed Breugom AJ, Bastiaannet E, Boelens PG, Iversen LH, Martling A, Johansson R, et al. Adjuvant chemotherapy and relative survival of patients with stage II colon cancer - A EURECCA international comparison between the Netherlands, Denmark, Sweden, England, Ireland, Belgium, and Lithuania. Eur J Cancer. 2016;63:110–7. CrossRefPubMed
37.
go back to reference Kato Y, Shigeta K, Tajima Y, Kikuchi H, Hirata A, Nakadai J, et al. Comprehensive risk score of the E-PASS as a prognostic indicator for patients after elective and emergency curative colorectal cancer surgery: A multicenter retrospective study. Int J Surg. 2022;101:106631. CrossRefPubMed Kato Y, Shigeta K, Tajima Y, Kikuchi H, Hirata A, Nakadai J, et al. Comprehensive risk score of the E-PASS as a prognostic indicator for patients after elective and emergency curative colorectal cancer surgery: A multicenter retrospective study. Int J Surg. 2022;101:106631. CrossRefPubMed
38.
go back to reference Jung HW, Kim JW, Kim JY, Kim SW, Yang HK, Lee JW, et al. Effect of muscle mass on toxicity and survival in patients with colon cancer undergoing adjuvant chemotherapy. Support Care Cancer. 2015;23(3):687–94. CrossRefPubMed Jung HW, Kim JW, Kim JY, Kim SW, Yang HK, Lee JW, et al. Effect of muscle mass on toxicity and survival in patients with colon cancer undergoing adjuvant chemotherapy. Support Care Cancer. 2015;23(3):687–94. CrossRefPubMed
39.
go back to reference Lee J, Cho JR, Kim DW, Yang IJ, Suh JW, Oh HK, et al. Clinical impact of preoperative and postoperative sarcopenia on oncological outcomes in non-metastatic colorectal cancer. Colorectal Dis. 2023;25(4):775–86. CrossRefPubMed Lee J, Cho JR, Kim DW, Yang IJ, Suh JW, Oh HK, et al. Clinical impact of preoperative and postoperative sarcopenia on oncological outcomes in non-metastatic colorectal cancer. Colorectal Dis. 2023;25(4):775–86. CrossRefPubMed
Metadata
Title
Delayed-Onset Organ/Space Surgical Site Infection Worsens Prognosis in High-Risk Stage II and III Colorectal Cancer
Authors
Jun Okui
Kohei Shigeta
Yujin Kato
Shodai Mizuno
Kiyoaki Sugiura
Yuki Seo
Jumpei Nakadai
Hideo Baba
Hiroto Kikuchi
Akira Hirata
Akitsugu Makino
Takayuki Kondo
Shimpei Matsui
Ryo Seishima
Koji Okabayashi
Hideaki Obara
Yasunori Sato
Yuko Kitagawa
Publication date
22-09-2023
Publisher
Springer US
Published in
Journal of Gastrointestinal Surgery / Issue 11/2023
Print ISSN: 1091-255X
Electronic ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-023-05836-0

Other articles of this Issue 11/2023

Journal of Gastrointestinal Surgery 11/2023 Go to the issue