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01-04-2018 | Original Scientific Report

Anti-inflammatory Effects of Enhanced Recovery Programs on Early-Stage Colorectal Cancer Surgery

Authors: Aurélien Venara, Emilie Duchalais, Anne Dariel, Philippe Aubert, Tony Durand, Guillaume Meurette, Malvyne Rolli-Derkinderen, Antoine Hamy, Michel Neunlist

Published in: World Journal of Surgery | Issue 4/2018

Abstract

Background

Postoperative ileus (POI) is observed in 20–30% of patients undergoing colorectal cancer surgery, despite enhanced recovery programs (ERPs). Cyclooxygenase (COX)-2 is identified as a key enzyme in POI, but other arachidonic acid pathway enzymes have received little attention despite their potential as selective targets to prevent POI. The objectives were to compare the expression of arachidonic acid metabolism (AAM) enzymes (1) between patients who underwent colorectal cancer surgery and followed an ERP or not (NERP), (2) and between ERP patients who experimented POI or not and (3) to determine the ability of antagonists of these pathways to modulate contractile activity of colonic muscle.

Methods

This was a translational study. Main outcome measures were gastrointestinal motility recovery data, mRNA expressions of key enzymes involved in AAM (RT-qPCR) and ex vivo motility values of the circular colon muscle. Twenty-eight prospectively included ERP patients were compared to eleven retrospectively included NERP patients that underwent colorectal cancer surgery.

Results

ERP reduced colonic mucosal COX-2, microsomal prostaglandin E synthase (mPGES1) and hematopoietic prostaglandin D synthase (HPGDS) mRNA expression. mPGES1 and HPGDS mRNA expression were significantly associated with ERP compliance (respectively, r2 = 0.25, p = 0.002 and r2 = 0.6, p < 0.001). In muscularis propria, HPGDS mRNA expression was correlated with GI motility recovery (p = 0.002). The pharmacological inhibition of mPGES1 increased spontaneous ex vivo contractile activity in circular muscle (p = 0.03).

Conclusion

The effects of ERP on GI recovery are correlated with the compliance of ERP and could be mediated at least in part by mPGES1, HPGDS and COX-2. Furthermore, mPGES1 shows promise as a therapeutic target to further reduce POI duration among ERP patients.

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Senagore AJ (2007) Pathogenesis and clinical and economic consequences of postoperative ileus. Am J Health-Syst Pharm 64:S3–S7CrossRefPubMed

Asgeirsson T, El-Badawi KI, Mahmood A, Barletta Luchtefeld M, Senagore AJ (2010) Postoperative ileus: it costs more than you expect. J Am Coll Surg 210:228–231CrossRefPubMed

Livingston EH, Passaro EP (1990) Postoperative ileus. Dig Dis Sci 35:121–132CrossRefPubMed

Traut U, Brügger L, Kunz R, Pauli-Magnus C, Haug K, Bucher HC, Koller MT (2008) Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults. Cochrane Database Syst Rev 23:CD004930

Chen J-Y, Ko T-L, Wen Y-R, Wu SC, Chu YH, Yien HW, Kuo CD (2009) Opioid-sparing effects of ketorolac and its correlation with the recovery of postoperative bowel function in colorectal surgery patients: a prospective randomized double-blinded study. Clin J Pain 25:485–489CrossRefPubMed

Schlachta CM, Burpee SE, Fernandez C, Chan B, Mamazza J, Poulin EC (2007) Optimizing recovery after laparoscopic colon surgery (ORAL-CS): effect of intravenous ketorolac on length of hospital stay. Surg Endosc 21:2212–2219CrossRefPubMed

Lubbers T, Buurman W, Luyer M (2010) Controlling postoperative ileus by vagal activation. World J Gastroenterol 16:1683–1687CrossRefPubMedPubMedCentral

Kobayashi T, Masaki T, Kogawa K, Matsuoka H, Sugiyama M (2015) Efficacy of gum chewing on bowel movement after open colectomy for left-sided colorectal cancer: a randomized clinical trial. Dis Colon Rectum 58:1058–1063CrossRefPubMed

Atkinson C, Penfold CM, Ness AR, Longman RJ, Thomas SJ, Hollingworth W, Kandiyali R, Leary SD, Lewis SJ (2016) Randomized clinical trial of postoperative chewing gum versus standard care after colorectal resection. Br J Surg 103:962–970CrossRefPubMedPubMedCentral

10.

Fujii T, Morita H, Sutoh T, Yajima R, Yamagushi S, Tsutsumi S, Asao T, Kuwano H (2014) Benefit of oral feeding as early as one day after elective surgery for colorectal cancer: oral feeding on first versus second postoperative day. Int Surg 99:211–215CrossRefPubMedPubMedCentral

11.

El Nakeeb A, Fikry A, El Metwally T, Fouda E, Youssef M, Ghazi H, Badr S, Khafagy W, Farid M (2009) Early oral feeding in patients undergoing elective colonic anastomosis. Int J Surg 7:206–209CrossRefPubMed

12.

Gustafsson UO, Scott MJ, Schwenk W, Demartines N, Roulin D, Francis N, McNaught CE, Macfie J, Liberman AS, Soop M, Hill A, Kennedy RH, Lobo DN, Fearon K, Ljunqvist O (2013) Guidelines for perioperative care in elective colonic surgery: enhanced Recovery After Surgery (ERAS(^®)) Society recommendations. World J Surg 37:259–284CrossRefPubMed

13.

Nygren J, Thacker J, Carli F, Fearon KC, Nordeval S, Lobo DN, Ljungqvist O, Soop M, Ramirez J (2013) Guidelines for perioperative care in elective rectal/pelvic surgery: enhanced Recovery After Surgery (ERAS(^®)) Society recommendations. World J Surg 37:285–305CrossRefPubMed

14.

Spanjersberg WR, Reurings J, Keus F, Van Laarhoven CJ (2011) Fast track surgery versus conventional recovery strategies for colorectal surgery. Cochrane Database Syst Rev 16:CD007635

15.

Barbieux J, Hamy A, Talbot MF, Casa C, Mucci S, Lermite E, Venara A (2016) Does enhanced recovery reduce postoperative ileus after colorectal surgery? J Visc Surg 2016:S1878–S7886

16.

van Bree SHW, van Bree S, Vlug MS, Hollmann MW, Ubbink DT, Zwinderman AH, de Jonge WJ, Snoek SA, Bolhuis K, van der Zanden E, The FO, Bennink RJ, Boeckxstaens GE (2011) Faster recovery of gastrointestinal transit after laparoscopy and fast-track care in patients undergoing colonic surgery. Gastroenterology 141:872–880CrossRefPubMed

17.

Wu Z, Boersema GSA, Jeekel J, Lange JF (2014) Nicotine gum chewing: a novel strategy to shorten duration of postoperative ileus via vagus nerve activation. Med Hypotheses 83:352–354CrossRefPubMed

18.

van den Heijkant TC, Costes LMM, van der Lee DGC, Aerts B, Osinga-de Jong M, Rutten HR, Hulsewe KW, de Jonge WJ, Buurman WA, Luyer MD (2015) Randomized clinical trial of the effect of gum chewing on postoperative ileus and inflammation in colorectal surgery. Br J Surg 102:202–211CrossRefPubMed

19.

Gong J, Xie Z, Zhang T, Gu L, Yao W, Guo Z, Li Y, Lu N, Zhu W, Li N, Li J (2016) Randomised clinical trial: prucalopride, a colonic pro-motility agent, reduces the duration of post-operative ileus after elective gastrointestinal surgery. Aliment Pharmacol Ther 43:778–789CrossRefPubMed

20.

Schwarz NT, Kalff JC, Türler A, Speidel N, Grandis JR, Billiar TR, Bauer AJ (2004) Selective jejunal manipulation causes postoperative pan-enteric inflammation and dysmotility. Gastroenterology 126:159–169CrossRefPubMed

21.

Berthoud HR, Carlson NR, Powley TL (1991) Topography of efferent vagal innervation of the rat gastrointestinal tract. Am J Physiol 260(1 Pt 2):R200–R207PubMed

22.

Schwarz NT, Kalff JC, Türler A, Engel DM, Watkins SC, Billiar TR, Bauer AJ (2001) Prostanoid production via COX-2 as a causative mechanism of rodent postoperative ileus. Gastroenterology 121:1354–1371CrossRefPubMed

23.

Kalff JC, Türler A, Schwarz NT, Schraut WH, Lee KK, Tweardy DJ, Billiar TR, Simmons RL, Bauer AJ (2003) Intra-abdominal activation of a local inflammatory response within the human muscularis externa during laparotomy. Ann Surg 237:301–315PubMedPubMedCentral

24.

Korolkiewicz RP, Sein-Anand J, Ruczyński J, Rekowski P, Bieniaszewski L, Chodrowski Z, Petrusewicz J, Ujda M, Dabkowski J, Bitel M, Kato S, Takeuchi K (2004) The role and interactions of nitric oxide (NO), carbon monoxide (CO), and prostanoids in the pathogenesis of postoperative ileus in rats. J Gastrointest Surg 8:346–357CrossRefPubMed

25.

Wattchow DA, De Fontgalland D, Bampton PA, Leach PL, Mclaughlin K, Costa M (2009) Clinical trial: the impact of cyclooxygenase inhibitors on gastrointestinal recovery after major surgery—a randomized double blind controlled trial of celeCOXib or diclofenac vs. placebo. Aliment Pharmacol Ther 30:987–998CrossRefPubMed

26.

Martinez-Cutillas M, Mañé N, Gallego D, Jimenez M, Martin MT (2014) EP2 and EP4 receptors mediate PGE2 induced relaxation in murine colonic circular muscle: pharmacological characterization. Pharmacol Res 90:76–86CrossRefPubMed

27.

Tajima T, Murata T, Aritake K, Urade Y, Michishita M, Matsuoka T, Narumiya S, Osaki H, Hori M (2012) EP2 and EP4 receptors on muscularis resident macrophages mediate LPS-induced intestinal dysmotility via iNOS upregulation through cAMP/ERK signals. Am J Physiol Gastrointest Liver Physiol 302:G524–G534CrossRefPubMed

28.

Kreiss C, Birder LA, Kiss S, VanBibber MM, Bauer AJ (2003) COX-2 dependent inflammation increases spinal Fos expression during rodent postoperative ileus. Gut 52:527–534CrossRefPubMedPubMedCentral

29.

Diener M, Gabato D (1994) Thromboxane-like actions of prostaglandin D2 on the contractility of the rat colon in vitro. Acta Physiol Scand 150:95–101CrossRefPubMed

30.

Shahbazian A, Heinemann A, Peskar BA, Holzer P (2002) Differential peristaltic motor effects of prostanoid (DP, EP, IP, TP) and leukotriene receptor agonists in the guinea-pig isolated small intestine. Br J Pharmacol 137:1047–1054CrossRefPubMedPubMedCentral

31.

van Bree SHW, Bemelman WA, Hollmann MW, Zwinderman AH, Matteoli G, El Temna S, The FO, Vlug MS, Bennink RJ, Boeckxstaens GE (2014) Identification of clinical outcome measures for recovery of gastrointestinal motility in postoperative ileus. Ann Surg 259:708–714CrossRefPubMed

32.

Vather R, Trivedi S, Bissett I (2013) Defining postoperative ileus: results of a systematic review and global survey. J Gastrointest Surg 17:962–972CrossRefPubMed

33.

Sista F, Schietroma M, Santis GD, Mattei A, Cecilia EM, Piccione F, Leardi S, Carlei F, Amicucci G (2013) Systemic inflammation and immune response after laparotomy vs laparoscopy in patients with acute cholecystitis, complicated by peritonitis. World J Gastrointest Surg 5:73–82CrossRefPubMedPubMedCentral

34.

Park SW, Lee SG, Song SH, Heo DS, Park BJ, Lee DW, Kim KH, Sung MW (2003) The effect of nitric oxide on cyclooxygenase-2 (COX-2) overexpression in head and neck cancer cell lines. Int J Cancer 107:729–738CrossRefPubMed

35.

Meile T, Glatzle J, Habermann FM, Kreis ME, Zittel TT (2006) Nitric oxide synthase inhibition results in immediate postoperative recovery of gastric, small intestinal and colonic motility in awake rats. Int J Colorectal Dis 21:121–129CrossRefPubMed

36.

Dandona P, Chaudhuri A, Mohanty P, Ghanim H (2007) Anti-inflammatory effects of insulin. Curr Opin Clin Nutr Metab Care 10:511–517CrossRefPubMed

37.

Paulasir S, Kaoutzanis C, Welch KB, Vandewarker JF, Krapohl G, Lampman RM, Franz MG, Cleary RK (2015) Nonsteroidal anti-inflammatory drugs: Do they increase the risk of anastomotic leaks following colorectal operations? Dis Colon Rectum 58:870–877CrossRefPubMed

38.

Kotagal M, Hakkarainen TW, Simianu VV, Beck SJ, Alfonso-Cristancho R, Flum DR (2016) Ketorolac use and postoperative complications in gastrointestinal surgery. Ann Surg 263:71–75CrossRefPubMedPubMedCentral

39.

Hakkarainen TW, Steele SR, Bastaworous A, Dellinger EP, Farrokhi E, Farjah F, Florence M, Helton S, Horton M, Pietro M, Varghese TK, Flum DR (2015) Nonsteroidal anti-inflammatory drugs and the risk for anastomotic failure: a report from Washington State’s Surgical Care and Outcomes Assessment Program (SCOAP). JAMA Surg 150:223–228CrossRefPubMedPubMedCentral

40.

Perrone L, Devi TS, Hosoya K, Terasaki T, Singh LP (2009) Thioredoxin interacting protein (TXNIP) induces inflammation through chromatin modification in retinal capillary endothelial cells under diabetic conditions. J Cell Physiol 221:262–272CrossRefPubMed

Title: Anti-inflammatory Effects of Enhanced Recovery Programs on Early-Stage Colorectal Cancer Surgery
Authors: Aurélien Venara
Emilie Duchalais
Anne Dariel
Philippe Aubert
Tony Durand
Guillaume Meurette
Malvyne Rolli-Derkinderen
Antoine Hamy
Michel Neunlist
Publication date: 01-04-2018
Publisher: Springer International Publishing
Published in: World Journal of Surgery / Issue 4/2018
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-017-4266-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Anti-inflammatory Effects of Enhanced Recovery Programs on Early-Stage Colorectal Cancer Surgery

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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