Skip to main content

C-reactive protein can predict anastomotic leak in colorectal surgery: a systematic review and meta-analysis

International Journal of Colorectal Disease volume 36, pages 1147–1162 (2021)Cite this article

Abstract

Background

Anastomotic leakage (AL) is one of the most significant complications after colorectal surgery, affecting length of stay, patient morbidity, mortality, and long-term oncological outcome. Serum C-reactive protein (CRP) level rises in infective and inflammatory states. Elevated CRP has been shown to be associated with anastomotic leak.

Objective

Perform a meta-analysis of current CRP data in AL after colorectal surgery.

Data sources

MEDLINE, EMBASE, CINAHL, CENTRAL databases

Study selection

Comparative studies studying serum CRP levels in adult patients with and without AL after colorectal surgery.

Intervention(s)

Elective and emergency open, laparoscopic or robotic colorectal excisions for cancer and benign pathology.

Main outcome measures

Mean serum CRP measurements between post-operative days (POD) 1 through 7 in patients with and without AL. Perform ROC analysis to determine cut-off CRP values to indicate AL.

Results

Twenty-three studies with 6647 patients (482 AL). Pooled mean time to diagnosis of AL was 7.70 days. AL associated with higher CRP on POD1 (mean difference (MD) 15.19, 95% CI 5.88–24.50, p = 0.001), POD2 (MD 51.98, 05% CI 37.36–66.60, p < 0.00001), POD3 (MD 96.92, 95% CI 67.96–125.89, p < 0.00001), POD4 (MD 93.15, 95% CI 69.47–116.84, p < 0.00001), POD5 (MD 112.10, 95% CI 89.74–134.45, p < 0.00001), POD6 (MD 98.38, 95% CI 80.29–116.46, p < 0.00001), and POD7 (MD 106.41, 95% CI 75.48–137.35, p < 0.00001) compared with no AL. ROC analysis identified a cut-off CRP of 148 mg/l on POD3 with sensitivity and specificity of 95%. On POD4 through POD7, cut-off levels were 123 mg/l, 115 mg/l, 105 mg/l, and 96 mg/l, respectively, with sensitivity and specificity of 100%.

Limitations

Study heterogeneity, some characteristics unreported, no RCT

Conclusions

AL is associated with higher CRP levels on each post-operative day compared to no AL after colorectal surgery. The cut-off CRP values can be used to predict AL to expedite investigation and treatment.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

References

  1. Thornton M, Joshi H, Vimalachandran C, Heath R, Carter P, Gur U, Rooney P (2011) Management and outcome of anastomotic leaks. Int J Color Dis 26:313–320

    Google Scholar 

  2. Bertelsen CA, Andreasen AH, Jorgensen T, Harling H (2010) Anastomotic leakage after curative anterior resection for rectal cancer: short and long-term outcome. Color Dis 12:e76–e81

    CAS  Google Scholar 

  3. Matthiessen P, Hallbrook O, Andersson M, Rutegard J, Sjodahl R (2004) Risk factors for anastomotic leakage after anterior resection of the rectum. Color Dis 6:462–469

    CAS  Google Scholar 

  4. Waterland P, Ng J, Jones A, Broadley G, Nicol D, Patel H, Pandey S (2016) Using CRP to predict anastomotic leakage after open and laparoscopic colorectal surgery: is there a difference? Int J Color Dis 31(4):861–868

    CAS  Google Scholar 

  5. Koedam TW, Bootsma B, Diejen C, van de Brug T, Kazemier G, Cuesta M, Furst A, Lacy A, Haglind E, Tuynman J, Daams F, Bonjer H (2020) Oncological outcomes after anastomotic leakage after surgery for colon or rectal cancer: increased risk of local recurrence. Ann Surg. https://doi.org/10.1097/SLA.0000000000003889

  6. Ni X, Jia D, Chen Y, Wang L, Suo J (2019) Is the Enhanced Recovery after Surgery (ERAS) program effective and safe in laparoscopic colorectal cancer surgery? A meta-analysis of randomized controlled trials. J Gastrointest Surg 23:1502–1512

    PubMed  Google Scholar 

  7. Brown JK, Singh K, Dumitru R, Chan E, Kim MP (2018) The benefits of enhanced recovery after surgery programs and their application in cardiothoracic surgery. Methodist Debakey Cardiovasc J 14(2):77–88

    PubMed  PubMed Central  Google Scholar 

  8. Macarthur DC, Nixon SJ, Aitken RJ (1998) Avoidable deaths still occur after large bowel surgery: Scottish audit of surgical mortality, Royal College of Surgeons of Edinburgh. Br J Surg 85(1):80–83

    CAS  PubMed  Google Scholar 

  9. Alves A, Panis Y, Pocard M, Regimbeau JM, Valleur P (1999) Management of anastomotic leakage after nondiverted large bowel resection. J Am Coll Surg 189(6):554–559

    CAS  PubMed  Google Scholar 

  10. Lasithiotakis K, Aghahoseini A, Alexander D (2016) Is early reversal of defunctioning ileostomy a shorter, easier and less expensive operation? World J Surg 40:1737–1740. https://doi.org/10.1007/s00268-016-3448-7

    Article  PubMed  Google Scholar 

  11. Bakx R, Busch ORC, van Geldere D, Bemelman WA, Slors JFM, van Lanschot JJB (2003) Feasibility of early closure of loop ileostomies: a pilot study. Dis Colon Rectum 46:1680–1684

    PubMed  Google Scholar 

  12. Menegaux F, Jordi-Galais P, Turrin N, Chigot J (2002) Closure of small bowel stomas on postoperative day 10. Eur J Surg 168:713–715

    PubMed  Google Scholar 

  13. Lane JC, Wright S, Burch J, Kennedy RH, Jenkins JT (2013) Early prediction of adverse events in enhanced recovery based upon the host systemic inflammatory response. Color Dis 15(2):224–230

    CAS  Google Scholar 

  14. Lagoutte N, Facy O, Ravoire A, Chalumeau C, Jonval L, Rat P, Ortega-Deballon P (2012) C-reactive protein and procalcitonin for the early detection of anastomotic leakage after elective colorectal surgery: pilot study in 100 patients. J Visc Surg 149:e345–e349

    CAS  PubMed  Google Scholar 

  15. Platt JJ, Ramanathan ML, Crosbie RA, Anderson JH, McKee RF, Horgan PG, McMillan DC (2012) C-reactive protein as a marker of postoperative infective complications after curative resection in patients with colorectal cancer. Ann Surg Oncol 19:4168–4177

    PubMed  Google Scholar 

  16. Paradis T, Zorigbaatar A, Trepanier M, Fiore JF Jr, Fried GM, Feldman LS, Lee L (2020) Meta-analysis of the diagnostic accuracy of C-reactive protein for infectious complications of laparoscopic versus open colorectal surgery. J Gastrointest Surg 24(6):1392–1401

    PubMed  Google Scholar 

  17. Singh PP, Zeng ISL, Srinivasa S, Lemanu DP, Connoly AB, Hill AG (2013) Systematic review and meta-analysis of use of serum C-reactive protein levels to predict anastomotic leak after colorectal surgery. Br J Surg 83(Suppl 1):23

    Google Scholar 

  18. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P (2009) Preferred reporting items for systematic reviews and meta analyses: the PRISMA statement. J Clin Epidemiol 62(7):1006–1012

    PubMed  Google Scholar 

  19. Wells G, Shea B, O’Connell D, Paterson J, Welch V, Losos M, Tugwell P (2019) The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analysis. Ottawa Hospital Research Institute http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 9 July 2020

  20. Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13

    PubMed  PubMed Central  Google Scholar 

  21. Review Manager (RevMan) [Computer Program]. Version 5.3 (2014) Copenhagen: the Nordic Cochrane Centre, The Cochrane Collaboration

  22. DeLong ER, DeLong DM, Clarke-Pearson DL (1988) Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 44(3):836–845

    Google Scholar 

  23. The Italian ColoRectal Anastomotic Leakage (iCral) Study Group (2020) Anastomotic leakage after elective colorectal surgery: a prospective multicentre observational study on the use of the Dutch leakage score, serum procalcitonin and serum C-reactive protein for diagnosis. BJS Open 4(3):499–507

    Google Scholar 

  24. Messias BA, Botelho RV, Saad SS, Mocchetti ER, Turke KC, Waisberg J (2020) Serum C-reactive protein is a useful marker to exclude anastomotic leakage after colorectal surgery. Sci Rep 10(1):1687

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Guevara-Morales G, Regalado-Torres MA, Cantarell-Castillo E, Castro-Salas R, Maldonado-Barron R, Castellanos-Juarez JC (2018) Utility of C-reactive protein in the early diagnosis of anastomotic leakage in colorectal surgery. Cirurgia y Cirujanos 86:381–385

    Google Scholar 

  26. Pantel HJ, Jasak LJ, Ricciardi R, Marcello PW, Roberts PL, Schoetz DJ Jr (2019) Should they stay or should they go? The utility of C-reactive protein in predicting readmission and anastomotic leak after colorectal resection. Dis Colon Rectum 62(2):241–247

    PubMed  Google Scholar 

  27. Sparreboom CL, Komen N, Rizopoulos D, Verhaar AP, Dik WA, Wu Z, van Westreenen HL, Doorneborsch PG, Dekker JWT, Menon AG, Daams F, Lips D, van Grevenstein WMU, Karsten TM, Bayon Y, Peppelenbosch MP, Wolthuis AM, D’Hoore A, Lange JF (2020) A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection. Color Dis 22(1):36–45

    CAS  Google Scholar 

  28. Stearns AT, Liccardo F, Tan K-N, Sivikroz E, Aziz O, Jenkins JT, Kennedy RH (2019) Physiological changes after colorectal surgery suggest that anastomotic leak is an early event: a retrospective cohort study. Color Dis 21(3):297–306

    CAS  Google Scholar 

  29. Fukada M, Matsuhashi N, Takahashi T, Imai H, Tanaka Y, Yamaguchi K, Yoshida K (2019) Risk and early predictive factors of anastomotic leakage in laparoscopic low anterior resection for rectal cancer. World J Surg Oncol 17(1):178

    PubMed  PubMed Central  Google Scholar 

  30. Munoz JL, Alvarez MO, Cuquerella V, Miranda E, Pico C, Flores R, Resalt-Pereira M, Moya P, Perez A, Arroyo A (2018) Procalcitonin and C-reactive protein as early markers of anastomotic leak after laparoscopic colorectal surgery within an enhanced recovery after surgery (ERAS) program. Surg Endosc 32(0):4003–4010

    PubMed  Google Scholar 

  31. Rybakov E, Shelygin Y, Tarasov M, Sukhina M, Zarodniuk I, Alexeev M, Chernyshov S (2018) Risk factors and inflammatory predictors for anastomotic leakage following total mesorectal excision with defunctioning stoma. Pol Przegl Chir 90(3):31–36

    PubMed  Google Scholar 

  32. Zawadzki M, Krzystek-Korpacka M, Gamian A, Witkievicz W (2018) Serum cytokines in early prediction of anastomotic leakage following low anterior resection. Videosurg Other Miniinvasive Tech 13(1):33–43

    PubMed  PubMed Central  Google Scholar 

  33. Bilgin IA, Hatipoglu E, Aghayeva A, Arikan AE, Incir S, Torun MM, Dirican A, Erguney S (2017) Predicting value of serum procalcitonin, C-reactive protein, drain fluid culture, drain fluid interleukin-6 and tumor necrosis factor-alpha levels in anastomotic leakage after rectal resection. Surg Infect 18(3):350–356

    Google Scholar 

  34. Mik M, Dziki L, Berut M, Trzcinski R, Dziki A (2018) Neutrophil to lymphocyte ratio and c-reactive protein as two predictive tools of anastomotic leak in colorectal cancer open surgery. Dig Surg 35(1):77–84

    CAS  PubMed  Google Scholar 

  35. Reynolds IS, Boland MR, Reilly F, Deasy A, Majeed MH, Deasy J, Burk JP, McNamara DA (2017) C-reactive protein as a predictor of anastomotic leak in the first week after anterior resection for rectal cancer. Color Dis 19:812–818

    CAS  Google Scholar 

  36. Kostic Z, Slavkovic D, Mijuskovic Z, Panisic M, Ignjatovic M (2015) C-reactive protein in drainage fluid as a predictor of anastomotic leakage after elective colorectal resection. Vojnosanitetski pregled 73:228–233. https://doi.org/10.2298/VSP141031017K

    Article  Google Scholar 

  37. Zawadzki M, Czarnecki R, Rzaca M, Obuszko Z, Velchuru VR (2015) C-reactive protein and procalcitonin predict anastomotic leaks following colorectal cancer resections—a prospective study. Videosurg Other Miniinvasive Tech 10(4):567–573

    PubMed Central  Google Scholar 

  38. Garcia-Granero A, Frasson M, Flor-Lorente B, Blanco F, Puga R, Carratala A, Garcia-Granero E (2013) Procalcitonin and C-reactive protein as early predictors of anastomotic leak in colorectal surgery: a prospective observational study. Dis Colon Rectum 56:475–483

    PubMed  Google Scholar 

  39. Almeida AB, Faria G, Moreira H, Pinto-de-Sousa J, Correia-da-Silva P, Maia JC (2012) Elevated serum c-reactive protein as a predictive factor for anastomotic leakage in colorectal surgery. Int J Surg 10(2):87–91

    CAS  PubMed  Google Scholar 

  40. Ortega-Deballon P, Radais F, Facy O, D’Athis P, Masson D, Charles PE, Cheynel N, Favre J-P, Rat P (2010) C-reactive protein is early predictor of septic complications after elective colorectal surgery. World J Surg 38:808–814

    Google Scholar 

  41. Woeste G, Muller C, Bechstein WO, Wullstein C (2010) Increased serum levels of C-reactive protein precede anastomotic leakage in colorectal surgery. World J Surg 34:140–146

    PubMed  Google Scholar 

  42. Leahy J, Schoetz D, Marcello P, Read T, Hall J, Roberts P, Rocco R (2014) What is the risk of clinical anastomotic leak in the diverted colorectal anastomosis? J Gastrointest Surg 18:1812–1816

    PubMed  Google Scholar 

  43. Alves A, Panis Y, Pocard M, Regimbeau JM, Valleur P (1999) Management of anastomotic leakage after nondivertied large bowel resection. J Am Coll Surg 189(6):554–559

    CAS  PubMed  Google Scholar 

  44. Adamina M, Steffen T, Tarantino I, Buetner U, Schmied BM, Warschkow R (2015) Meta-analysis of the predictive value of C-reactive protein for infectious complications in abdominal surgery. Br J Surg 102:590–598

    CAS  PubMed  Google Scholar 

  45. Warschkow R, Beutner U, Steffen T, Muller SA, Schmied B, Guller U, Tarantino I (2012) Safe and early discharge after colorectal surgery due to C-reactive protein: a diagnostic meta-analysis of 1832 patients. Ann Surg 256:245–250

    PubMed  Google Scholar 

  46. Gans SL, Atema JJ, van Dieren S, Groot Koerkamp B, Boermeester MA (2015) Diagnostic value of C-reactive protein to rule out infectious complications after minor abdominal surgery: a systematic review and meta-analysis. Int J Color Dis 30(7):861–873

    Google Scholar 

  47. Cousin F, Ortega-Deballon P, Bourredjem A, Doussot A, Giaccaglia V, Fournel I (2016) Diagnostic accuracy of procalcitonin and C-reactive protein for the early diagnosis of intra-abdominal infection after elective colorectal surgery: a meta-analysis. Ann Surg 264(2):252–256

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of General Surgery, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, UK

    Denise E. Yeung, Elizabeth Peterknecht, Shahin Hajibandeh & Andrew W. Torrance

  2. Department of General Surgery, Glan Clwyd Hospital, Rhyl, Denbighshire, UK

    Shahab Hajibandeh

  3. Department of General Surgery, Hereford County Hospital, Wye Valley NHS Trust, Hereford, UK

    Shahin Hajibandeh

Authors
  1. Denise E. Yeung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth Peterknecht
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shahab Hajibandeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shahin Hajibandeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Andrew W. Torrance
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Data acquisition: Peterknecht, Elizabeth; Yeung, Denise; Hajibandeh, Shahin; Hajibandeh, Shahab.

Drafting of manuscript: Yeung, Denise; Hajibandeh, Shahab; Hajibandeh, Shahin.

Critical revision of manuscript: Hajibandeh, Shahin; Torrance, Andrew.

Corresponding author

Correspondence to Denise E. Yeung.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(DOC 62 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yeung, D.E., Peterknecht, E., Hajibandeh, S. et al. C-reactive protein can predict anastomotic leak in colorectal surgery: a systematic review and meta-analysis. Int J Colorectal Dis 36, 1147–1162 (2021). https://doi.org/10.1007/s00384-021-03854-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00384-021-03854-5

Keywords

  • C-reactive protein
  • Anastomotic leak
  • Colorectal surgery