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International Journal of Colorectal Disease

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01-05-2020 | Rectal Cancer | Original Article

Prevention of anastomotic leak in rectal cancer surgery with local antibiotic decontamination: a prospective, randomized, double-blind, placebo-controlled single center trial

Published in: International Journal of Colorectal Disease | Issue 5/2020

Abstract

Purpose

Anastomotic leak and other infectious complications are septic complications of rectal cancer surgery caused by bacteria. Data from registry analysis show a beneficial effect of local antimicrobial administration on anastomotic leaks, but data are inconsistent in recent clinical trials. Therefore, our aim was to study the efficacy of topical antibiotic treatment on the incidence of anastomotic leaks in rectal cancer surgery.

Methods

A prospective, randomized, double-blind and placebo-controlled, single center trial was conducted. Patients received either placebo and amphotericin B or decontamination with polymyxin B, tobramycin, vancomycin, and amphotericin B four times per day starting the day before surgery until postoperative day 7. If a protective ileostomy was created, a catheter was placed transanally and the medication was administered locally to the anastomotic site. All patients received an intravenous perioperative antibiotic prophylaxis.

Results

The trial had to be stopped for ethical reasons after first interim analysis with 80 patients instead of the initially planned 280 patients. Of the 40 patients randomized to receive placebo, eight (20%) developed anastomotic leak compared to only 2 (5%) in the treatment group of 40 patients (decontamination) with significant difference in the χ² test (p = 0.0425). Twenty percent of the placebo group and 12.5% in the treatment group developed infectious complications not associated with anastomotic leak (p = 0.5312). One patient (2.5%) in the placebo group died (p = 0.3141).

Conclusion

Local decontamination with polymyxin, tobramycin, vancomycin, and amphotericin B is safe and effective in the prevention of anastomotic leak in rectal cancer surgery.

Shogan BD, Carlisle EM, Alverdy JC, Umanskiy K (2013) Do we really know why colorectal anastomoses leak? J Gastrointest Surg 17:1698–1707. https://doi.org/10.1007/s11605-013-2227-0 CrossRefPubMed

Paun BC, Cassie S, MacLean AR, Dixon E, Buie WD (2010) Postoperative complications following surgery for rectal cancer. Ann Surg 251:807–818. https://doi.org/10.1097/SLA.0b013e3181dae4ed CrossRefPubMed

Matthiessen P, Hallböök O, Rutegard J et al (2007) Defunctioning stoma reduces symptomatic anastomotic leakage after low anterior resection of the rectum for cancer: a randomized multicenter trial. Ann Surg 246:207–214. https://doi.org/10.1097/SLA.0b013e3180603024 CrossRefPubMedPubMedCentral

Slieker JC, Daams F, Mulder IM, Jeekel J, Lange JF (2013) Systematic review of the technique of colorectal anastomosis. JAMA Surg 148:190–201. https://doi.org/10.1001/2013.jamasurg.33 CrossRefPubMed

Jannasch O, Klinge T, Otto R et al (2015) Risk factors, short and long term outcome of anastomotic leaks in rectal cancer. Oncotarget 6. https://doi.org/10.18632/oncotarget.5170

Abis GSA, Stockmann HBAC, Bonjer HJ, van Veenendaal N, van Doorn-Schepens M, Budding AE, Wilschut JA, van Egmond M, Oosterling SJ, SELECT trial study group (2019) Randomized clinical trial of selective decontamination of the digestive tract in elective colorectal cancer surgery (SELECT trial): selective decontamination of the digestive tract in colorectal cancer surgery. Br J Surg 106:355–363. https://doi.org/10.1002/bjs.11117 CrossRefPubMed

Wirth U, Rogers S, Haubensak K, Schopf S, von Ahnen T, Schardey HM (2018) Local antibiotic decontamination to prevent anastomotic leakage short-term outcome in rectal cancer surgery. Int J Color Dis 33:53–60. https://doi.org/10.1007/s00384-017-2933-2 CrossRef

Eberhardt JM, Kiran RP, Lavery IC (2009) The impact of anastomotic leak and intra-abdominal abscess on cancer-related outcomes after resection for colorectal cancer: a case control study. Dis Colon Rectum 52:380–386. https://doi.org/10.1007/DCR.0b013e31819ad488 CrossRefPubMed

Mirnezami A, Mirnezami R, Chandrakumaran K, Sasapu K, Sagar P, Finan P (2011) Increased local recurrence and reduced survival from colorectal cancer following anastomotic leak: systematic review and meta-analysis. Ann Surg 253:890–899. https://doi.org/10.1097/SLA.0b013e3182128929 CrossRefPubMed

10.

Ashburn JH, Stocchi L, Kiran RP, Dietz DW, Remzi FH (2013) Consequences of anastomotic leak after restorative proctectomy for cancer: effect on long-term function and quality of life. Dis Colon Rectum 56:275–280. https://doi.org/10.1097/DCR.0b013e318277e8a5 CrossRefPubMed

11.

Allaix ME, Rebecchi F, Famiglietti F, Arolfo S, Arezzo A, Morino M (2019) Long-term oncologic outcomes following anastomotic leak after anterior resection for rectal cancer: does the leak severity matter? Surg Endosc:1–11. https://doi.org/10.1007/s00464-019-07189-9

12.

Cohn I, Rives JD (1955) Antibiotic protection of colon anastomoses. Ann Surg 141:707–717CrossRefPubMedPubMedCentral

13.

Schardey HM, Kamps T, Rau HG, Gatermann S, Baretton G, Schildberg FW (1994) Bacteria: a major pathogenic factor for anastomotic insufficiency. Antimicrob Agents Chemother 38:2564–2567. https://doi.org/10.1128/AAC.38.11.2564 CrossRefPubMedPubMedCentral

14.

Cohen SR, Cornell CN, Collins MH, Sell JE, Blanc WA, Altman RP (1985) Healing of ischemic colonic anastomoses in the rat: role of antibiotic preparation. Surgery 97:443–446PubMed

15.

Shogan BD, An GC, Schardey HM, Matthews JB, Umanskiy K, Fleshman JW Jr, Hoeppner J, Fry DE, Garcia-Granereo E, Jeekel H, van Goor H, Dellinger EP, Konda V, Gilbert JA, Auner GW, Alverdy JC (2014) Proceedings of the first international summit on intestinal anastomotic leak, Chicago, Illinois, October 4–5, 2012. Surg Infect 15:479–489. https://doi.org/10.1089/sur.2013.114 CrossRef

16.

Alverdy JC, Hyoju SK, Weigerinck M, Gilbert JA (2017) The gut microbiome and the mechanism of surgical infection: the gut microbiome and the mechanism of surgical infection. Br J Surg 104:e14–e23. https://doi.org/10.1002/bjs.10405 CrossRefPubMedPubMedCentral

17.

Schardey HM, Joosten U, Finke U, Staubach KH, Schauer R, Heiss A, Kooistra A, Rau HG, Nibler R, Lüdeling S, Unertl K, Ruckdeschel G, Exner H, Schildberg FW (1997) The prevention of anastomotic leakage after total gastrectomy with local decontamination: a prospective, randomized, double-blind, placebo-controlled multicenter trial. Ann Surg 225:172–180. https://doi.org/10.1097/00000658-199702000-00005 CrossRefPubMedPubMedCentral

18.

Roos D, Dijksman LM, Tijssen JG et al (2013) Systematic review of perioperative selective decontamination of the digestive tract in elective gastrointestinal surgery: perioperative selective decontamination of the digestive tract. Br J Surg 100:1579–1588. https://doi.org/10.1002/bjs.9254 CrossRefPubMed

19.

Koskenvuo L, Lehtonen T, Koskensalo S et al (2019) Mechanical and oral antibiotic bowel preparation versus no bowel preparation for elective colectomy (MOBILE): a multicentre, randomised, parallel, single-blinded trial. Lancet 394:840–848. https://doi.org/10.1016/S0140-6736(19)31269-3 CrossRefPubMed

20.

Rollins KE, Javanmard-Emamghissi H, Acheson AG, Lobo DN (2019) The role of oral antibiotic preparation in elective colorectal surgery: a meta-analysis. Ann Surg 270:43–58. https://doi.org/10.1097/SLA.0000000000003145 CrossRefPubMed

21.

Bothe MK, Maathuis AJH, Bellmann S et al (2017) Dose-dependent prebiotic effect of lactulose in a computer-controlled in vitro model of the human large intestine. Nutrients 9:E767. https://doi.org/10.3390/nu9070767 CrossRefPubMed

22.

Ruszkowski J, Witkowski JM (2019) Lactulose: patient- and dose-dependent prebiotic properties in humans. Anaerobe 59:100–106. https://doi.org/10.1016/j.anaerobe.2019.06.002 CrossRefPubMed

23.

Zhai S, Zhu L, Qin S, Li L (2018) Effect of lactulose intervention on gut microbiota and short chain fatty acid composition of C57BL/6J mice. MicrobiologyOpen 7:e00612. https://doi.org/10.1002/mbo3.612 CrossRefPubMedPubMedCentral

24.

MacFarlane JK, Ryall RD, Heald RJ (1993) Mesorectal excision for rectal cancer. Lancet 341(8843):457–460

25.

Rahbari NN, Weitz J, Hohenberger W et al (2010) Definition and grading of anastomotic leakagefollowing anterior resection of the rectum: a proposal by the International Study Group of Rectal Cancer. Surgery 147:339–351. https://doi.org/10.1016/j.surg.2009.10.012 CrossRefPubMed

26.

Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR (1999) Guideline for prevention of surgical site infection, 1999. Centers for disease control and prevention (CDC) hospital infection control practices advisory committee. Am J Infect Control 27(2):97–132

27.

Hermanek P, Sobin LH (1987) TNM classification of malignant Tumours. Springer Berlin Heidelberg, BerlinCrossRef

28.

Guenaga KF, Matos D, Castro AA, Atallah AN, Wille-Jørgensen P (2005) Mechanical bowel preparation for elective colorectal surgery. Cochrane Database Syst Rev 25:CD001544

29.

Zmora O, Mahajna A, Bar-Zakai B, Rosin D, Hershko D, Shabtai M, Krausz MM, Ayalon A (2003) Colon and rectal surgery without mechanical bowel preparation: a randomized prospective trial. Ann Surg 237:363–367PubMedPubMedCentral

30.

Soop M, Carlson GL, Hopkinson J, Clarke S, Thorell A, Nygren J, Ljungqvist O (2004) Randomized clinical trial of the effects of immediate enteral nutrition on metabolic responses to major colorectal surgery in an enhanced recovery protocol. Br J Surg 91:1138–1145CrossRefPubMed

31.

Wind J, Polle SW, Fung Kon Jin PH, on behalf of the Laparoscopy and/or Fast Track Multimodal Management Versus Standard Care (LAFA) Study Group; Enhanced Recovery after Surgery (ERAS) Group et al (2006) Systematic review of enhanced recovery programmes in colonic surgery. Br J Surg 93:800–809CrossRefPubMed

32.

Olivas AD, Shogan BD, Valuckaite V, Zaborin A, Belogortseva N, Musch M, Meyer F, Trimble WL, An G, Gilbert J, Zaborina O, Alverdy JC (2012) Intestinal tissues induce an SNP mutation in Pseudomonas aeruginosa that enhances its virulence: possible role in anastomotic leak. PLoS One 7:e44326. https://doi.org/10.1371/journal.pone.0044326 CrossRefPubMedPubMedCentral

33.

Shogan BD, Smith DP, Christley S, Gilbert JA, Zaborina O, Alverdy JC (2014) Intestinal anastomotic injury alters spatially defined microbiome composition and function. Microbiome 2:35. https://doi.org/10.1186/2049-2618-2-35 CrossRefPubMedPubMedCentral

34.

Shogan BD, Belogortseva N, Luong PM et al (2015) Collagen degradation and MMP9 activation by Enterococcus faecalis contribute to intestinal anastomotic leak. Sci Transl Med 7:286ra68CrossRefPubMedPubMedCentral

35.

Jacobson RA, Wienholts K, Williamson AJ, Gaines S, Hyoju S, van Goor H, Zaborin A, Shogan BD, Zaborina O, Alverdy JC (2020) Enterococcus faecalis exploits the human fibrinolytic system to drive excess collagenolysis: implications in gut healing and identification of druggable targets. Am J Physiol-Gastrointest Liver Physiol 318:G1–G9. https://doi.org/10.1152/ajpgi.00236.2019 CrossRefPubMed

36.

Bretagnol F, Panis Y, Rullier E, Rouanet P, Berdah S, Dousset B, Portier G, Benoist S, Chipponi J, Vicaut E, French Research Group of Rectal Cancer Surgery (GRECCAR) (2010) Rectal cancer surgery with or without bowel preparation: the French Greccar III multicenter single-blinded randomized trial. Ann Surg 252:863–868. https://doi.org/10.1097/SLA.0b013e3181fd8ea9 CrossRefPubMed

37.

Roos D, Dijksman LM, Oudemans-van Straaten HM, de Wit LT, Gouma DJ, Gerhards MF (2011) Randomized clinical trial of perioperative selective decontamination of the digestive tract versus placebo in elective gastrointestinal surgery. Br J Surg 98:1365–1372. https://doi.org/10.1002/bjs.7631 CrossRefPubMed

38.

Roos D, Dijksman LM, Sondermeijer BM, Oudemans-van Straaten HM, T de Wit L, Gerhards MF (2009) Perioperative selective decontamination of the digestive tract (SDD) in elective colorectal surgery. J Gastrointest Surg 13:1839–1844. https://doi.org/10.1007/s11605-009-0970-z CrossRefPubMed

39.

Althumairi AA, Canner JK, Pawlik TM, Schneider E, Nagarajan N, Safar B, Efron JE (2016) Benefits of bowel preparation beyond surgical site infection: a retrospective study. Ann Surg 264:1051–1057. https://doi.org/10.1097/SLA.0000000000001576 CrossRefPubMed

40.

Cannon JA, Altom LK, Deierhoi RJ, Morris M, Richman JS, Vick CC, Itani KM, Hawn MT (2012) Preoperative oral antibiotics reduce surgical site infection following elective colorectal resections. Dis Colon Rectum 55:1160–1166. https://doi.org/10.1097/DCR.0b013e3182684fac CrossRefPubMed

41.

Scarborough JE, Mantyh CR, Sun Z, Migaly J (2015) Combined mechanical and oral antibiotic bowel preparation reduces incisional surgical site infection and anastomotic leak rates after elective colorectal resection: an analysis of colectomy-targeted ACS NSQIP. Ann Surg 262:331–337. https://doi.org/10.1097/SLA.0000000000001041 CrossRefPubMed

42.

Kiran RP, Murray ACA, Chiuzan C et al (2015) Combined preoperative mechanical bowel preparation with oral antibiotics significantly reduces surgical site infection, anastomotic leak, and ileus after colorectal surgery. Ann Surg 262:416–425. https://doi.org/10.1097/SLA.0000000000001416 CrossRefPubMed

43.

Markwart R, Willrich N, Haller S, Noll I, Koppe U, Werner G, Eckmanns T, Reuss A (2019) The rise in vancomycin-resistant Enterococcus faecium in Germany: data from the German Antimicrobial Resistance Surveillance (ARS). Antimicrob Resist Infect Control 8:1–11. https://doi.org/10.1186/s13756-019-0594-3 CrossRef

44.

van der Bij AK, Frentz D, Bonten MJM (2016) Gram-positive cocci in Dutch ICUs with and without selective decontamination of the oropharyngeal and digestive tract: a retrospective database analysis. J Antimicrob Chemother 71:816–820. https://doi.org/10.1093/jac/dkv396 CrossRefPubMed

45.

Sciuto A, Merola G, De Palma GD, Sodo M, Pirozzi F, Bracale UM, Bracale U (2018) Predictive factors for anastomotic leakage after laparoscopic colorectal surgery. World J Gastroenterol 24:2247–2260. https://doi.org/10.3748/wjg.v24.i21.2247 CrossRefPubMedPubMedCentral

46.

Hamabe A, Ito M, Nishigori H, Nishizawa Y, Sasaki T (2018) Preventive effect of diverting stoma on anastomotic leakage after laparoscopic low anterior resection with double stapling technique reconstruction applied based on risk stratification. Asian J Endosc Surg 11:220–226. https://doi.org/10.1111/ases.12439 CrossRefPubMed

47.

Bonjer HJ, Deijen CL, Abis GA, Cuesta MA, van der Pas MHGM, de Lange-de Klerk ESM, Lacy AM, Bemelman WA, Andersson J, Angenete E, Rosenberg J, Fuerst A, Haglind E (2015) A randomized trial of laparoscopic versus open surgery for rectal cancer. N Engl J Med 372:1324–1332. https://doi.org/10.1056/NEJMoa1414882 CrossRefPubMed

48.

Alverdy JC, Hyman N (2020) Bowel preparation under siege. Br J Surg 107:167–170. https://doi.org/10.1002/bjs.11454 CrossRefPubMed

Title: Prevention of anastomotic leak in rectal cancer surgery with local antibiotic decontamination: a prospective, randomized, double-blind, placebo-controlled single center trial
Publication date: 01-05-2020
Keywords: Rectal Cancer
Rectal Cancer
Antibiotic
Ileostomy
Vancomycin
Published in: International Journal of Colorectal Disease / Issue 5/2020
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI: https://doi.org/10.1007/s00384-020-03544-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Prevention of anastomotic leak in rectal cancer surgery with local antibiotic decontamination: a prospective, randomized, double-blind, placebo-controlled single center trial

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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