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Hepatopancreatobiliary surgery has a high incidence of postoperative morbidity, including incisional surgical site infection. Although several studies showed that subcuticular sutures reduced incisional surgical site infection in other fields of surgery, their impact on hepatopancreatobiliary surgery remains unknown. The aim of this study was to assess whether subcuticular sutures could reduce incisional surgical site infection in patients undergoing hepatopancreatobiliary surgery.A total of 436 consecutive patients underwent laparotomy and surgical resection for hepatopancreatobiliary tumors in our department from May 2013 to December 2015. We excluded among them, 8 patients with a follow-up period <30 days and 1 patient with unclear operative information. The incidence of incisional surgical site infection was compared between use of subcuticular sutures and of stapling, using propensity score analyses.In the baseline cohort (n=427), abdominal skin closure was performed by subcuticular sutures in 245 patients (57.4%) and by stapling in 182 patients (42.6%). The incidence of incisional surgical site infection was 5/245 (2.0%) in the subcuticular suture group and 21/182 (11.5%) in the stapling group (P <. 01). In the propensity score–matched cohort (n=318), patient demographics were well balanced between the two groups, and the incidence of incisional surgical site infection was 3/159 (1.8%) in the subcuticular suture group and 16/159 (10.0%) in the stapling group (P < .01). Propensity score analyses, as well as simple regression analyses, showed subcuticular sutures could consistently reduce incisional surgical site infection (with odd ratios of about 0.20).Use of subcuticular sutures is preferred to stapling for the prevention of incisional surgical site infection in hepatopancreatobiliary surgery.