Cytoreductive surgery (CRS) with subsequent hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising modality to treat and prevent peritoneal metastases. However, this treatment is associated with signficant morbidity and mortality. Whether or not CRS with HIPEC interferes with anastomotic healing has also been debated. This study was designed to investigate the effects of mitomycin C, cisplatin, oxaliplatin, and doxorubicin used in HIPEC treatment on colonic anastomosis healing in a rat model.
Methods
Sixty Wistar albino rats were employed in the study. Sigmoid resection and end-to-end colorectal anastomosis was performed in all rats. Group 1 rats underwent the surgical procedure alone, while group 2 rats were given hyperthermic intraperitoneal lavage with heated saline following surgery. Groups 3, 4, 5, and 6 had surgery with concomitant HIPEC treatment with mitomycin C, cisplatin, oxaliplatin, and doxorubicin, respectively. Anastomotic bursting pressures and hydroxyproline levels were evaluated.
Results
Regarding the hydroxyproline levels, groups 1 and 2 showed significantly higher values than other groups (p<0.001). However, there was no significant difference between the HIPEC treatment groups (groups 3, 4, 5, and 6) (p>0.05). When groups were compared regarding bursting pressure values, no significant differences were observed (p = 0.81).
Conclusions
This study demonstrated that the HIPEC procedure with mitomycin C, cisplatin, oxaliplatin and doxorubicin had negative effects on hydroxyproline levels, but had no detrimental effect on anastomotic bursting pressure in a rat model.
Get full access to this article
View all access options for this article.
References
1.
SugarbakerPHUpdate on the prevention of local recurrence and peritoneal metastases in patients with colorectal cancer. World J Gastroenterol. 2014;20 (28):9286–9291.
2.
BlairSLChuDZSchwarzREOutcome of palliative operations for malignant bowel obstruction in patients with peritoneal carcinomatosis from nongynecological cancer. Ann Surg Oncol. 2001;8 (8):632–637.
3.
JayneDGFookSLoiCSeow-ChoenFPeritoneal carcinomatosis from colorectal cancer. Br J Surg. 2002;89 (12):1545–1550.
4.
SadeghiBArvieuxCGlehenOPeritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study. Cancer. 2000;88 (2):358–363.
5.
MakrinVLev-CheloucheDEven SapirEParanHRabauMGutmanMIntraperitoneal heated chemotherapy affects healing of experimental colonic anastomosis: an animal study. J Surg Oncol. 2005;89 (1):18–22.
6.
SugarbakerPHPeritonectomy procedures. Ann Surg. 1995;221 (1):29–42.
7.
VerwaalVJvan RuthSde BreeERandomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003;21 (20):3737–3743.
8.
LosGSminiaPWondergemJOptimisation of intraperitoneal cisplatin therapy with regional hyperthermia in rats. Eur J Cancer. 1991;27 (4):472–477.
9.
HuangCQFengJPYangXJLiYCytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from colorectal cancer: a case-control study from a Chinese center. J Surg Oncol. 2014;109 (7):730–739.
10.
EliasDLefevreJHChevalierJComplete cytoreductive surgery plus intraperitoneal chemohyperthermia with oxaliplatin for peritoneal carcinomatosis of colorectal origin. J Clin Oncol. 2009;27 (5):681–685.
11.
SmeenkRMVerwaalVJZoetmulderFANToxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritoneia report of 103 procedures. Eur J Surg Oncol. 2006;32 (2):186–190.
12.
GlehenOOsinskyDCotteEIntraperitoneal chemohyperthermia using a closed abdominal procedure and cytoreductive surgery for the treatment of peritoneal carcinomatosis: morbidity and mortality analysis of 216 consecutive procedures. Ann Surg Oncol. 2003;10 (8):863–869.
13.
KusamuraSYounanRBarattiDCytoreductive surgery followed by intraperitoneal hyperthermic perfusion: analysis of morbidity and mortality in 209 peritoneal surface malignancies treated with closed abdomen technique. Cancer. 2006;106 (5):1144–1153.
14.
HanssonJGrafWPåhlmanLNygrenPMahtemeHPostoperative adverse events and long-term survival after cytoreductive surgery and intraperitoneal chemotherapy. Eur J Surg Oncol. 2009;35 (2):202–208.
15.
YoussefHNewmanCChandrakumaranKMohamedFCecilTDMoranBJOperative findings, early complications, and long-term survival in 456 patients with pseudomyxoma peritonei syndrome of appendiceal origin. Dis Colon Rectum. 2011;54 (3):293–299.
16.
YounanRKusamuraSBarattiDBowel complications in 203 cases of peritoneal surface malignancies treated with peritonectomy and closed-technique intraperitoneal hyperthermic perfusion. Ann Surg Oncol. 2005;12 (11):910–918.
17.
MirnezamiAMirnezamiRChandrakumaranKSasapuKSagarPFinanPIncreased local recurrence and reduced survival from colorectal cancer following anastomotic leak: systematic review and meta-analysis. Ann Surg. 2011;253 (5):890–899.
18.
FryeJBokeyELChapuisPHSinclairGDentOFAnastomotic leakage after resection of colorectal cancer generates prodigious use of hospital resources. Colorectal Dis. 2009;11 (9):917–920.
19.
BertelsenCAAndreasenAHJørgensenTHarlingHDanish Colorectal Cancer Group. Anastomotic leakage after curative anterior resection for rectal cancer: short and long-term outcome. Colorectal Dis. 2010;12 (7 Online):e76–e81.
20.
BertelsenCAAndreasenAHJørgensenTHarlingHDanish Colorectal Cancer Group. Anastomotic leakage after anterior resection for rectal cancer: risk factors. Colorectal Dis. 2010; 12 (1):37–43.
21.
RichardsCHCampbellVHoCHayesJElliottTThompson-FawcettMSmoking is a major risk factor for anastomotic leak in patients undergoing low anterior resection. Colorectal Dis. 2012;14 (5):628–633.
22.
SajidMSAhamdAMilesWFBaigMKSystematic review of oncological outcomes following laparoscopic vs open total mesorectal excision. World J Gastrointest Endosc. 2014;6 (5):209–219.
23.
DamenNSpilsburyKLevittMAnastomotic leaks in colorectal surgery. ANZ J Surg. 2014;84 (10):763–768.
24.
McDermottFDHeeneyAKellyMESteeleRJCarlsonGLWinterDCSystematic review of preoperative, intraoperative and postoperative risk factors for colorectal anastomotic leaks. Br J Surg. 2015;102 (5):462–479.
25.
GongJPYangLHuangXEOutcomes based on risk assessment of anastomotic leakage after rectal cancer surgery. Asian Pac J Cancer Prev. 2014;15 (2):707–712.
26.
BrownSRMathewRKedingAMarshallHCBrownJMJayneDGThe impact of postoperative complications on long-term quality of life after curative colorectal cancer surgery. Ann Surg. 2014;259 (5):916–923.
27.
YounanRKusamuraSBarattiDBowel complications in 203 cases of peritoneal surface malignancies treated with peritonectomy and closed-technique intraperitoneal hyperthermic perfusion. Ann Surg Oncol. 2005;12 (11):910–918.
28.
RullierELaurentCGarrelonJLMichelPSaricJParneixMRisk factors for anastomotic leakage after resection of rectal cancer. Br J Surg. 1998;85 (3):355–358.
29.
BuchsNCGervazPSecicMBucherPMugnier-KonradBMorelPIncidence, consequences, and risk factors for anastomotic dehiscence after colorectal surgery: a prospective monocentric study. Int J Colorectal Dis. 2008;23 (3):265–270.
30.
HymanNManchesterTLOslerTBurnsBCataldoPAAnastomotic leaks after intestinal anastomosis: its later than you think. Ann Surg. 2007;245 (2):254–258.
31.
KaranjiaNDCorderAPBearnPHealdRJLeakage from stapled low anastomosis after total mesorectal excision for carcinoma of the rectum. Br J Surg. 1994;81 (8):1224–1226.
32.
KhanAAWheelerJMCunninghamCGeorgeBKettlewellMMortensenNJThe management and outcome of anastomotic leaks in colorectal surgery. Colorectal Dis. 2008;10 (6):587–592.
33.
SümerAAltınlıESengerSEffect of pentoxifylline and vinpocetine on the healing of ischemic colon anastomosis: an experimental study. Ulus Travma Acil Cerrahi Derg. 2011; 17 (6):482–487.
34.
KanellosDPramateftakisMGMantzorosIThe effects of the intraperitoneal administration of oxaliplatin and 5-FU on the healing of colonic anastomoses: an experimental study. Tech Coloproctol. 2011;15 (Suppl 1):111–115.
35.
BlouhosKPramateftakisMGTsachalisTThe integrity of colonic anastomoses following the intraperitoneal administration of oxaliplatin. Int J Colorectal Dis. 2010;25 (7):835–841.
36.
PelzJODoerferJDeckerMDimmlerAHohenbergerWMeyerTHyperthermic intraperitoneal chemoperfusion (HIPEC) decrease wound strength of colonic anastomosis in a rat model. Int J Colorectal Dis. 2007;22 (8):941–947.
37.
CetinkayaKDincSGulcelikMAGranulocyte macrophage-colony stimulating factor improves impaired anastomotic wound healing in rats treated with intraperitoneal mitomycin-C. Surg Today. 2005;35 (4):290–294.
38.
KorudaMJRolandelliRHExperimental studies on the healing of colonic anastomoses. J Surg Res. 1990;48 (5):504–515.
39.
DincSAlagolHGulcelikMALocally applied granulocyte-macrophage colony-stimulating factor improves the impaired bowel anastomoses in rats with long-term corticosteroid treatment. World J Surg. 2002;26 (10):1208–1213.
40.
HabibiMOnerOZOrucMTEffects of a glutamine enema on anastomotic healing in an animal colon anastomosis model. Ann Coloproctol. 2015;31 (6):213–221.
41.
BraskénPHealing of experimental colon anastomosis. Eur J Surg Suppl. 1991;(566):1–51.
42.
BucknallTEThe effect of local infection upon wound healing: an experimental study. Br J Surg. 1980;67 (12):851–855.
43.
VerhofstadMHHendriksTDiabetes impairs the development of early strength, but not the accumulation of collagen, during intestinal anastomotic healing in the rat. Br J Surg. 1994; 81 (7):1040–1045.
44.
SugarbakerPHTechnical handbook for the integration of cytoreductive surgery and perioperative intraperitoneal chemotherapy into the surgical management of gastrointestinal and gynecologic malignancy. Grand Rapids, Michigan: Ludann Company2005; 12-24.
45.
Prada-VillaverdeAEsquivelJLowyAMThe American Society of Peritoneal Surface Malignancies evaluation of HIPEC with mitomycin C versus oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery. J Surg Oncol. 2014;110 (7):779–785.
46.
FumagalliUTrabucchiESoligoMEffects of intraperitoneal chemotherapy on anastomotic healing in the rat. J Surg Res. 1991;50 (1):82–87.
47.
MasoodIKianiMHAhmadMMasoodMISadaquatHMajor contributions towards finding a cure for cancer through chemotherapy: a historical review. Tumori. 2016;102 (1):6–17.
