Abstract
Background and aims
There is controversy about the effect of the influence of hyperthermia and chemotherapeutic agents on the healing of intestinal anastomosis. The effects of hyperthermic intraperitoneal chemoperfusion (HIPEC) of wound healing after colonic anastomosis were investigated in a rat model.
Materials and methods
Thirty-six Wag/Rija rats were randomized into three groups of 12 animals each: group I: control (only colonic anastomosis was performed) (n = 12); group II: HIPEC (mitomycin C in a concentration of 20 mg/m2 (n = 12) colonic anastomosis was performed before HIPEC; group III: HIPEC (mitomycin C in a concentration of 20 mg/m2 (n = 12) colonic anastomosis was performed after HIPEC. Bursting pressure and bursting sites were recorded 4 and 10 days after intervention. Collagen deposits, inflammation and foreign body reactions were evaluated.
Results
Lower bursting pressure and lost of collagen were found in both HIPEC groups and compared with the control group. There was almost no difference between both HIPEC groups. They were noted overwhelmingly at the anastomosis in the HIPEC group. The degree of collagen accumulation was well-correlated with bursting pressure.
Conclusion
These results have shown that hyperthermic intraperitoneal chemoperfusion (HIPEC) impairs wound healing in colonic anastomosis in rats.
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References
Hendriks T, Mastboom WJ (1990) Healing of experimental intestinal anastomoses. Parameters for repair. Dis Colon Rectum 33:891–901
Simeon A, Monier F, Emonard H, Gillery P, Birembaut P, Hornebeck W et al (1999) Expression and activation of matrix metalloproteinase in wounds: modulation by the tripeptide-copper complex glycyl-l-histidyl-l-lysin-Cu2+. J Invest Dermatol 112:957–964
Nesbakken A, Nygaard K, Lunde OC, Blucher J, Gjertsen O, Dullerud R (2005) Anastomotic leak following mesorectal excision for rectal cancer: true incidence and diagnostic challenges. Colorectal Dis 7(6):576–581
Mann B, Kleinschmidt S, Stremmel W (1996) Prospective study of hand-sutured anastomosis after colorectal resection. Br J Surg 83:29–31
Pakkastie TE, Luukkonen PE, Jarvinen HJ (1994) Anastomotic leakage after anterior resection of the rectum. Eur J Surg 160:293–297
Biert J, Seifert W, de Man B, Wobbes T, Hoogenhout J, Hendriks T (1996) Combined preoperative irradiation and local hyperthermia delays early healing of experimental colonic anastomoses. Arch Surg 131(10):1037–1042
Uzunkoy A, Bolukbas C, Horoz M, Bolukbas FF, Kocyigit A (2005) The optimal starting time of postoperative intraperitoneal mitomycin-C therapy with preserved intestinal wound healing. BMC Cancer 5:31
Mansson P, Zhang XW, Jeppsson B, Thorlacius H (2002) Anastomotic healing in the rat colon: comparison between a radiological method, breaking strength and bursting pressure. Int J Colorectal Dis 17(6):420–425
Kanellos I, Mantzoros I, Demetriades H, Kalfadis S, Kelpis T, Sakkas L, Betsis D (2004) Healing of colon anastomoses covered with fibrin glue after immediate postoperative intraperitoneal administration of 5-fluorouracil. Dis Colon Rectum 47(4):510–515
Khoury GA, Waxman BP (1983) Large bowel anastomosis. I. The healing process and sutured anastomosis. A review. Br J Surg 70:61–63
Moran BJ, Meade B, Murphy E (2006) Hyperthermic intraperitoneal chemotherapy and cytoreductive surgery for peritoneal carcinomatosis of colorectal origin: a novel treatment strategy with promising results in selected patients. Colorectal Dis 8(7):544–550
Liberale G, Pocard M, Manganas D, Ducreux M, Lasser P, Elias D (2006) Hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis of digestive and peritoneal origin: rationale. Acta Chir Belg 106(3):291–296
Sugarbaker PH (2006) New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome? Lancet Oncol 7(1):69–76
Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, Zoetmulder FA (2003) Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 21(20):3737–3743
Glehen O, Kwiatkowski F, Sugarbaker PH, Elias D, Levine EA, De Simone M, Barone R, Yonemura Y, Cavaliere F, Quenet F, Gutman M, Tentes AA, Lorimier G, Bernard JL, Bereder JM, Porcheron J, Gomez-Portilla A, Shen P, Deraco M, Rat P (2004) Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study. J Clin Oncol 22(16):3284–3292
Esquivel J, Vidal-Jove J, Steves MA, Sugarbaker PH (1993) Morbidity and mortality of cytoreductive surgery and intraperitoneal chemotherapy. Surgery 113(6):631–636
Jacquet P, Stephens AD, Averbach AM, Chang D, Ettinghausen SE, Dalton RR, Steves MA, Sugarbaker PH (1996) Analysis of morbidity and mortality in 60 patients with peritoneal carcinomatosis treated by cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy. Cancer 77(12):2622–2629
Pelz JO, Doerfer J, Hohenberger W, Meyer T (2005) A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis. BMC Cancer 5(1):56
Du Bois D, Du Bois EF (1989) A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition (5):303–311
Fumagalli U, Trabucchi E, Soligo M, Rosati R, Rebuffat C, Tonelli C, Montorsi M (1991) Effects of intraperitoneal chemotherapy on anastomotic healing in the rat. J Surg Res 50(1):82–87
Salm R, Wullich B, Kiefer G, Fiebig HH, Farthmann EH (1991) Effects of a three-drug antineoplastic protocol of wound healing in rats: a biomechanical and histologic study on gastrointestinal anastomoses and laparotomy wounds. J Surg Oncol 47(1):5–11
Shen P, Levine EA, Hall J, Case D, Russell G, Fleming R, McQuellon R, Geisinger KR, Loggie BW (2003) Factors predicting survival after intraperitoneal hyperthermic chemotherapy with mitomycin C after cytoreductive surgery for patients with peritoneal carcinomatosis. Arch Surg 138(1):26–33
Sugarbaker PH, Stuart OA, Yoo D (2005) Strategies for management of the peritoneal surface component of cancer: cytoreductive surgery plus perioperative intraperitoneal chemotherapy. J Oncol Pharm Pract 11(3):111–119
Verwaal VJ, van Ruth S, Witkamp A, Boot H, van Slooten G, Zoetmulder FA (2005) Long-term survival of peritoneal carcinomatosis of colorectal origin. Ann Surg Oncol 12(1):65–71
Smeenk RM, Verwaal VJ, Zoetmulder FA (2005) Toxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei—a report of 103 procedures. Eur J Surg Oncol 32(2):186–90
Piso P, Dahlke MH, Loss M, Schlitt HJ (2004) Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from ovarian cancer. World J Surg Oncol 2(1):21
Averbach AM, Chang D, Koslowe P, Sugarbaker PH (1996) Anastomotic leak after double-stapled low colorectal resection. Dis Colon Rectum 39(7):780–787
Brasken P (1991) Healing of experimental colon anastomosis. Eur J Surg Suppl (566):1–51
el-Malt M, Ceelen W, Van den Broecke C, Cuvelier C, Van Belle S, de Hemptinne B, Pattyn P (2003) Influence of neo-adjuvant chemotherapy with 5-fluorouracil on colonic anastomotic healing: experimental study in rats. Acta Chir Belg 103(3):309–314
Acknowledgements
This study was supported by grants from the ELAN (Erlanger Leistungsbezogene Anschubfinanzierung und Leistungsförderung).
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Pelz, J.O.W., Doerfer, J., Decker, M. et al. Hyperthermic intraperitoneal chemoperfusion (HIPEC) decrease wound strength of colonic anastomosis in a rat model. Int J Colorectal Dis 22, 941–947 (2007). https://doi.org/10.1007/s00384-006-0246-y
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DOI: https://doi.org/10.1007/s00384-006-0246-y