Effects of Oral Pirfenidone on Colon Anastomosis Healing and Adhesion Formation in Rats.

INTRODUCTION: Many experimental studies have examined multiple drugs or treatments to improve the healing of intestinal anastomoses. Synthetic prostacyclin analogs, immunosuppressants, erythropoietin, growth hormone, insulin-like growth factor type 1, synthetic metalloproteinases inhibitors, and hyperbaric oxygen therapy have produced promising results in low-risk models of anastomosis dehiscence. However, in high-risk models, only hyperbaric oxygen therapy has been shown to be useful. Pirfenidone (PFD), a commonly used antifibrosing drug, has not been shown to be effective for this purpose. Our objective was to evaluate the effects of PFD on anastomosis healing and adhesion genesis in a low-risk rat model of dehiscence of colonic anastomosis. METHODS: An experimental study was conducted on 40 healthy Wistar rats randomly assigned to the control group or PFD experimental group (20 rats in each group). Colon anastomosis was performed 3 cm above the peritoneal reflection using the same technique in all animals. Mechanical resistance was studied by measuring bursting pressure. Adhesions were evaluated macroscopic and histologically using common staining techniques. Animals received the first PFD dose 12 h after surgery at a dose of 500 mg/kg one a day (SID) for 5 consecutive days. On day 6, the animals were reoperated on to measure the bursting pressure in situ and to classify adhesions macroscopically, and the anastomosed colon was resected for histological analysis. RESULTS: There were no deaths, complications, or anastomosis dehiscence in either group. The mean bursting pressure was 120.8 ± 11 mm Hg and 135.5 ± 12.4 in the control and PFD groups, respectively (p < 0.001). The adhesions were less dense and had less inflammatory cell infiltration in the PFD group (p < 0.02 and 0.002, respectively). Collagen content was slightly higher in the PFD group (p = 0.04). CONCLUSIONS: Our results revealed favorable effects of PFD in this low-risk colon anastomosis model; for example, the bursting pressure was higher, and the macroscopic adhesions were soft and exhibited less inflammatory infiltration and higher collagen content in the PFD group than in the control group. The results showing that PFD treatment was associated with better healing of minor adhesions seem to be paradoxical because the therapeutic indications for this drug are directed at treating fibrosing diseases.

Differences in Postoperative Pain, Nausea, and Vomiting After Elective Laparoscopic Cholecystectomy in Premenopausal and Postmenopausal Mexican Women.

BACKGROUND: Postoperative symptoms and pain after laparoscopic cholecystectomy (LC) are common in women. However, there is no evidence of differences in incidence and severity among different age groups. We evaluated whether adverse postoperative symptoms were more common in younger than in older women after LC. METHODS: One hundred and fifty premenopausal (mean age 37.6 ± 3.6 y) and 145 postmenopausal women (59 ± 5.2 y) were included in this retrospective cohort study. Clinical and anthropometric parameters were analyzed. Study endpoints were the incidences of postoperative nausea and vomiting (PONV) and pain, and the additional analgesics and antiemetics needed after surgery. RESULTS: Body mass index was normal in 42.7% of patients in the younger group and 64.8% in the older group (P < 0.001). Reported pain was more frequent and intense in the younger group throughout the study period (P < 0.01). Additional narcotics were required in 18% of premenopausal versus 7.6% of postmenopausal women (P = 0.001), and the doses used to reduce pain were higher for premenopausal women (P = 0.02). PONV was more frequent in the younger group at 1 and 6 h after surgery (P < 0.005). Rescue antiemetics were required in 29 premenopausal and 13 postmenopausal women (P = 0.01). Hospital stay was shorter for the older patients (P = 0.01). Minor morbidity was observed in both groups (0.7% and 2.1%). There was no mortality. CONCLUSIONS: Early PONV and pain after LC were more frequent in premenopausal women, who also required more rescue analgesic and antiemetic medication.