Abstract
Hyperthermic intraperitoneal chemotherapy (HIPEC) causes delays in wound healing. Platelet-rich plasma (PRP) gel has been shown to be effective in facilitating wound healing. We examined the effect of PRP gel on the healing of colonic anastomosis in rats that received HIPEC. Twenty-four rats were subdivided into three groups. In group 1, the rats only underwent colonic anastomosis. In group 2, the rats underwent colonic anastomosis and cisplatin-paclitaxel-based HIPEC. In group 3, the rats underwent colonic anastomosis and cisplatin-paclitaxel-based HIPEC. Afterwards, PRP gel was administered to the colonic anastomosis region. The rats were sacrificed on the 7th postoperative day, the anastomotic bursting pressure (ABP) was recorded, and tissue samples were taken from the anastomotic line. Compared to that in group 2, ABP was higher in group 1 and group 3 (p= 0.002 and 0.048, respectively). Tissue hydroxyproline levels were higher in group 1 (p= 0.001) and group 3 (p = 0.043) than in group 2. Histopathological evaluation revealed a significant decrease in fibroblast activity in group 2 compared to that in group 1 (p= 0.006), with no significant difference between group 3 and group 1 (p= 0.585). Collagen accumulation was significantly lower in group 2 than in group 1 and group 3 (p= 0.001 and p= 0.019, respectively). PRP gel application may aid wound healing by increasing colon ABP, tissue fibroblast activity and collagen accumulation; therefore, its use may reduce the cytotoxic effects of HIPEC and facilitate the anastomotic wound healing process.
Similar content being viewed by others
References
Sugar baker PH, Van der Speeten K (2016) Surgical technology and pharmacology of hyperthermic perioperative chemotherapy. J Gastrointest Oncol 7(1):29–44. https://doi.org/10.3978/j.issn.2078-6891.2015.105
Auricchio A, Cardella F, Mabilia A, Basile N, Erario S, Del Sorbo G, Castellano P, Galizia G, Lieto E (2018) Fluorescence-guided surgery in the combined treatment of peritoneal carcinomatosis from colorectal cancer: preliminary results and considerations. World J Surg 42(4):1150–1160. https://doi.org/10.1007/s00268-017-4237-7
Van der Speeten K, Stuart OA, Sugarbaker PH (2009) Pharmacokinetics and pharmacodynamics of perioperative cancer chemotherapy in peritoneal surface malignancy. Cancer J 15(3):216–224. https://doi.org/10.1097/PPO.0b013e3181a58d95
Badrudin D, Dubé P, Sideris L (2016) Experimental studies in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: overview and future directions. J Rare Dis Res Treat 2(1):23–26
Pletcher E, Gleeson E, Labow D (2020) Peritoneal cancers and hyperthermic intraperitoneal chemotherapy. Surg Clin 100(3):589–613. https://doi.org/10.1016/j.suc.2020.02.009
Verwaal VJ, van Tinteren H, Ruth SV, Zoetmulder FA (2004) Toxicity of cytoreductive surgery and hyperthermic intra-peritoneal chemotherapy. J Surg Oncol 85(2):61–67. https://doi.org/10.1002/jso.20013
Aarts F, Bleichrodt RP, de Man B, Lomme R, Boerman OC, Hendriks T (2008) The effects of adjuvant experimental radioimmunotherapy and hyperthermic intraperitoneal chemotherapy on intestinal and abdominal healing after cytoreductive surgery for peritoneal carcinomatosis in the rat. Ann Surg Oncol 15(11):3299–3307. https://doi.org/10.1245/s10434-008-0070-4
Lopez-Lopez V, Lynn PB, Gil J, Garcia-Salom M, Gil E, Gonzalez A, Munoz IP, Cascales-Campos PA (2019) Effect of paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) on colonic anastomosis in a rat model. Clin Transl Oncol 21(4):505–511. https://doi.org/10.1007/s12094-018-1948-7
Passot G, Bakrin N, Roux AS, Vaudoyer D, Gilly FN, Glehen O, Cotte E (2014) Quality of life after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy: a prospective study of 216 patients. Eur J Surg Oncol 40(5):529–535. https://doi.org/10.1016/j.ejso.2013.11.019
Dodson RM, McQuellon RP, Mogal HD, Duckworth KE, Russell GB, Votanopoulos KI, Shen P, Levine EA (2016) Quality-of-life evaluation after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Ann Surg Oncol 23(Suppl 5):772–783. https://doi.org/10.1245/s10434-016-5547-y
Fresno L, Fondevila D, Bambo O, Chacaltana A, Garcia F, Andaluz A (2010) Effects of platelet-rich plasma on intestinal wound healing in pigs. Vet J 185(3):322–327. https://doi.org/10.1016/j.tvjl.2009.06.009
Göttgens KW, Vening W, van der Hagen SJ, van Gemert WG, Smeets RR, Stassen LP, Baeten CG, Breukink SO (2014) Long-term results of mucosal advancement flap combined with platelet-rich plasma for high cryptoglandular perianal fistulas. Dis Colon Rectum 57(2):223–227. https://doi.org/10.1097/DCR.0000000000000023
Landesberg R, Moses M, Karpatkin M (1998) Risks of using platelet rich plasma gel. J Oral Maxillofac Surg 56(9):1116–1117. https://doi.org/10.1016/s0278-2391(98)90286-5
Anitua E, Andia I, Ardanza B, Nurden P, Nurden AT (2004) Autologous platelets as a source of proteins for healing and tissue regeneration. Thromb Haemost 91(01):4–15. https://doi.org/10.1160/TH03-07-0440
Yamaguchi R, Terashima H, Yoneyama S, Tadano S, Ohkohchi N (2012) Effects of platelet-rich plasma on intestinal anastomotic healing in rats: PRP concentration is a key factor. J Surg Res 173(2):258–266. https://doi.org/10.1016/j.jss.2010.10.001
Cohen J (1992) A power primer. Psychol Bull 112(1):155–159. https://doi.org/10.1037//0033-2909.112.1.155
Erdem E, Dinç S, Erdem D, Üstün H, Caydere M, Alagöl H (2002) Effects of intraperitoneal chemotherapy and GM-CSF on anastomotic healing: an experimental study in rats. J Surg Res 108(1):1–6. https://doi.org/10.1006/jsre.2002.6425
Kusamura S, Younan R, Baratti D, Costanzo P, Favaro M, Gavazzi C, Deraco M (2006) Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion: analysis of morbidity and mortality in 209 peritoneal surface malignancies treated with closed abdomen technique. Cancer 106(5):1144–1153. https://doi.org/10.1002/cncr.21708
Sugarbaker PH (1998) Intraperitoneal chemotherapy and cytoreductive surgery for the prevention and treatment of peritoneal carcinomatosis and sarcomatosis. In: Seminars in surgical oncology, vol 3. Wiley Online Library, pp 254-261. doi:10.1002/(sici)1098-2388(199804/05)14:3<254::aid-ssu10>3.0.co;2-u
Moran B, Cecil T, Chandrakumaran K, Arnold S, Mohamed F, Venkatasubramaniam A (2015) The results of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in 1200 patients with peritoneal malignancy. Color Dis 17(9):772–778. https://doi.org/10.1111/codi.12975
Blaj S, Nedelcut S, Mayr M, Leebmann H, Leucuta D, Glockzin G, Piso P (2019) Re-operations for early postoperative complications after CRS and HIPEC: indication, timing, procedure, and outcome. Langenbeck's Arch Surg 404(5):541–546. https://doi.org/10.1007/s00423-019-01808-8
Younan R, Kusamura S, Baratti D, Oliva GD, Costanzo P, Favaro M, Gavazzi C, Deraco M (2005) Bowel complications in 203 cases of peritoneal surface malignancies treated with peritonectomy and closed-technique intraperitoneal hyperthermic perfusion. Ann Surg Oncol 12(11):910–918. https://doi.org/10.1245/ASO.2005.11.030
Roviello F, Marrelli D, Neri A, Cerretani D, de Manzoni G, Pedrazzani C, Cioppa T, Nastri G, Giorgi G, Pinto E (2006) Treatment of peritoneal carcinomatosis by cytoreductive surgery and intraperitoneal hyperthermic chemoperfusion (IHCP): postoperative outcome and risk factors for morbidity. World J Surg 30(11):2033–2040; discussion 2041-2032. https://doi.org/10.1007/s00268-006-0038-0
Etulain J (2018) Platelets in wound healing and regenerative medicine. Platelets 29(6):556–568. https://doi.org/10.1080/09537104.2018.1430357
Scherer SS, Tobalem M, Vigato E, Heit Y, Modarressi A, Hinz B, Pittet B, Pietramaggiori G (2012) Nonactivated versus thrombin-activated platelets on wound healing and fibroblast-to-myofibroblast differentiation in vivo and in vitro. Plast Reconstr Surg 129(1):46e–54e. https://doi.org/10.1097/PRS.0b013e3182362010
Sozutek A, Colak T, Cetinkunar S, Reyhan E, Irkorucu O, Polat G, Cennet A (2016) The effect of platelet-rich-plasma on the healing of left colonic anastomosis in a rat model of intra-abdominal sepsis. J Investig Surg 29(5):294–301. https://doi.org/10.3109/08941939.2015.1111473
Blair P, Flaumenhaft R (2009) Platelet alpha-granules: basic biology and clinical correlates. Blood Rev 23(4):177–189. https://doi.org/10.1016/j.blre.2009.04.001
Yol S, Tekin A, Yilmaz H, Kucukkartallar T, Esen H, Caglayan O, Tatkan Y (2008) Effects of platelet rich plasma on colonic anastomosis. J Surg Res 146(2):190–194. https://doi.org/10.1016/j.jss.2007.05.015
Liu Y, Kalén A, Risto O, Wahlström O (2002) Fibroblast proliferation due to exposure to a platelet concentrate in vitro is pH dependent. Wound Repair Regen 10(5):336–340. https://doi.org/10.1046/j.1524-475x.2002.10510.x
Aghayeva A, Benlice C, Bilgin IA, Atukeren P, Dogusoy G, Demir F, Atasoy D, Baca B (2017) The effects of hyperthermic intraperitoneal chemoperfusion on colonic anastomosis: an experimental study in a rat model. Tumori 103(3):307–313. https://doi.org/10.5301/tj.5000610
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethics Approval
This study was conducted at Adiyaman University Experimental Animal Application and Research Center (Adiyaman, Turkey) after obtaining the approval of the Experimental Animals Local Ethics Committee of the university (Reference No: 2018/034).
Conflict of Interest
The authors declare no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Alakuş, H., Göksu, M., Ertan, S. et al. Does Platelet-Rich Plasma (PRP) Improve Colonic Anastomotic Healing in Rats Undergoing Cisplatin-Paclitaxel-Based HIPEC?. Indian J Surg 84, 157–163 (2022). https://doi.org/10.1007/s12262-021-02871-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12262-021-02871-6