Transection Speed and Impact on Perioperative Inflammatory Response - A Randomized Controlled Trial Comparing Stapler Hepatectomy and CUSA Resection

Abstract

Background: Parenchymal transection represents a crucial step during liver surgery and many different techniques have been described so far. Stapler resection is supposed to be faster than CUSA resection. However, whether speed impacts on the inflammatory response in patients undergoing liver resection (LR) remains unclear.

Materials and methods: This is a randomized controlled trial including 40 patients undergoing anatomical LR. Primary endpoint was transection speed (cm2/min). Secondary endpoints included the perioperative change of pro- and anti-inflammatory cytokines, overall surgery duration, length of hospital stay, morbidity and mortality.

Results: Mean transection speed was significantly higher in patients undergoing stapler hepatectomy compared to CUSA resection (CUSA: 1 (0.4) cm2/min vs. Stapler: 10.8 (6.1) cm2/min; p<0.0001). Analyzing the impact of surgery duration on inflammatory response revealed a significant correlation between IL-6 levels measured at the end of surgery and the overall length of surgery (p<0.0001, r = 0.6188). Patients undergoing CUSA LR had significantly higher increase of interleukin-6 (IL-6) after parenchymal transection compared to patients with stapler hepatectomy in the portal and hepatic veins, respectively (p = 0.028; p = 0.044). C-reactive protein levels on the first post-operative day were significantly lower in the stapler cohort (p = 0.010). There was a trend towards a reduced overall surgery time in patients with stapler LR, especially in the subgroup of patients undergoing minor hepatectomies (p = 0.020).

Conclusions: Liver resection using staplers is fast, safe and suggests a diminished inflammatory response probably due to a decreased parenchymal transection time.

Trial registration: ClinicalTrials.gov NCT01785212.

Conflict of interest statement

Competing Interests: The study was funded by a research grant from Covidien (Covidien AG, Victor von Bruns-Strasse 19, CH8212 Neuhausen Am Rheinfall. Switzerland). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have no other financial interests in Covidien or their products. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Fig 1. Enrollment and randomization.

Forty-six patients were enrolled for this study. In five patients liver resection was not performed due to tumor progression. The remaining 41 patients were randomized intraoperative and assigned to CUSA resection (n = 21) or stapler hepatectomy (n = 20). One patient from the CUSA group was excluded after randomization, as the patient emerged to be non-resectable.

Fig 2. Perioperative alteration of pro- (IL-6, IL-8) and anti-inflammatory cytokines (IL-10).

Systemic IL-6 (A), IL-8 (C) and IL-10 (E) levels significantly increased perioperatively compared to baseline values. Graphs show mean cytokine concentrations [pg/ml] ± SEM. There was a significant increase in IL-6 during liver resection in the portal vein (PV; p = 0.0001) and hepatic vein (HV; p<0.0001) respectively (B). Similar to that IL-10 increased significantly in the PV (p = 0.008) but not HV (F). IL-8 levels measured in the in and out flow remained virtually unchanged (D). Statistical significance compared to baseline values is abbreviated with * (p = 0.010–0.050), ** (p = 0.001–0.010), *** (p = 0.0001–0.001) or **** (p < 0.0001).

Fig 3. Stapler liver resection leads to a decreased IL-6 response compared to CUSA transection.

(A) IL-6 production was numerical higher in patients undergoing CUSA resection, though the observed difference did not reach statistical significance. Cytokines levels are shown as means ± SEM. (B) Calculating the specific IL-6 response during liver resection revealed a significantly higher increase in the portal vein (PV) (p = 0.028) and hepatic vein (p = 0.044) but not systemically in patients in the CUSA group. (C) There was a strong correlation between systemic IL-6 measured immediately after skin closure and length of operation (CUSA: p = 0.029, r = 0.489; Stapler: p<0.0001, r = 0.797; Overall: p<0.0001, r = 0.6188).

Fig 4. Perioperative course of IL-8, TNFa, IL-10 and C-reactive protein (CRP).

There was no significant difference between both groups in perioperative IL-8 (A), TNFa (B) or IL-10 (C) levels. CRP measured on the first postoperative day (POD) was significantly higher in patients undergoing CUSA resection than in patients with stapler hepatectomy (3.1 (0.3) vs. 4.8 (0.5); p = 0.010). Graphs show mean values ± SEM.