The influence of platelet-rich plasma (PRP) on colonic anastomosis healing impaired by intraperitoneal 5-flourouracil application. An experimental study

Abstract

Purpose 5-flourourasil (5-FU) is commonly used for early intraperitoneal chemotherapy in colorectal or appendiceal cancer patients with peritoneal carcinomatosis. Due to its effect, anastomosis healing can be impaired and leads to anastomotic leakage. In this study, we aimed to investigate the potential healing effect of platelet-rich plasma (PRP) on colonic anastomosis impaired by intraperitoneal 5-flourouracil application. Methods After ten rats were sacrificed for preparing PRP, forty Wistar-albino rats were subjected to colonic anastomosis, and randomly allocated into four groups including 10 rats each. According to receiving PRP and/or 5-FU application, the groups were formed as control (C), 5-FU without PRP (CT), anastomosis with PRP (C-PRP), and 5-FU with PRP (CT-PRP). CT and CT-PRP groups also received 5-FU intraperitoneally on postoperative day 1 (POD 1). All animals were euthanized on pod 7. The body weight change, anastomotic bursting pressure (ABP), tissue hydroxiprolin (TH) and histopathological examination of each group were analyzed. Results 5-FU application significantly reduced ABP levels when compared with group C, C-PRP and CT-PRP (for each comparison, p<0,01). PRP application in CT-PRP group raised the measure of ABP up to the levels of C group. Although tissue hydroxyproline levels (THL) levels of CT-PRP group were found higher than CT group, it was not significant (p=0.112). Microscopically, comparing with CT group, PRP application significantly promoted the healing of colonic anastomosis subjected to 5-FU application by improving tissue edema, necrosis, submucosal bridging and collagen formation (p<0.05). Tissue healing in CT-PRP group was observed as good as the control groups. (C, C-PRP, p=0.181, p=0.134; respectively). Conclusion PRP administration on colonic anastomosis significantly promotes the healing process of anastomosis in rats receiving 5-FU. This result encourages further clinical use of PRP to reduce the frequency of AL in patients receiving EPIC.

Platelet rich plasma effectiveness in bowel anastomoses: A systematic review

“…Although 50% (9/18) of the included studies reported no statistically significant changes in the anastomosis bursting pressure in PRP-treated compared to control groups, five studies reported that the application of PRP in the presence of an underlying medical or surgical condition, improved the anastomosis bursting pressure. Furthermore, the application of PRP in the open abdomen, ischemic /reperfusion injury, peritonitis, intraperitoneal 5-fluorouracil (5-FU) infusion, and hyperthermic intraperitoneal chemotherapy with 5-FU animal models was associated with statistically significant improved anastomosis bursting pressure[ 16 , 29 , 30 , 32 , 36 ]. Among, the other four studies, Dauser et al [ 26 ] investigated the application of PRF, which presents some component differences compared to PRP.…”

“…In two studies the anastomotic bursting pressure was significantly increased in the PRP-treated group while anastomotic tissue hydroxyproline levels did not show any significant changes[ 17 , 34 ]. Gorur et al [ 32 ] reported that PRP application was associated with increased tissue hydroxyproline levels in the intraperitoneal 5-FU infusion animal model.…”

“…Similarly, anastomotic wound inflammatory cellular infiltration in control compared to PRP groups did not show any statistically significant changes among the included studies. However, it was reported that in the presence of an underlying detrimental condition like intraperitoneal chemotherapy or infection, PRP application significantly decreased the inflammatory cellular infiltration in bowel anastomosis[ 30 - 32 , 34 - 36 ]. Theoretically, enhanced anastomosis strength associated with PRP application could partially be attributed to decreased inflammatory cell-mediated collagen degradation[ 42 ].…”

“…The amount of peripheral blood required for PRP preparation depends on the technique or commercial kit that are used during the isolation process[ 14 , 58 ]. Furthermore, its autologous nature increases biocompatibility[ 9 , 32 ]. However, some technical issues and concerns were raised among the included studies.…”

The protective effect of sildenafil on colon anastomosis in a rat model undergoing hypertermic intraperitoneal chemotherapy

“…Oral and topical agents are being used to prevent anastomotic leakage. For example, studies have shown that platelet-rich plasma applied topically to the anastomosis in rats treated with 5uorouracil and HIPEC strengthens tissue healing 15,16 . Sildena l was used similarly in our study.…”