Which approach is preferred in left hepatocellular carcinoma? Laparoscopic versus open hepatectomy using propensity score matching

This study included patients who underwent surgical resection of solitary HCC based on preoperative radiological images between December 2012 and October 2016. This study was approved by the Samsung Medical Center Institutional Review Board (SMC-2017-05-090). A total of 139 patients underwent left hepatectomy because of HCC. The diagnosis of HCC was proved based on pathology after hepatectomy. Ruptured HCC cases (n = 5); those with a the history of locoregional therapies such as transarterial embolization (TACE) (n = 11), radiofrequency ablation (RFA) (n = 2), or the combination of TACE and RFA (n = 2); and open conversion cases because of uncontrolled bleeding during laparoscopic procedure (n = 1) were excluded. Two clinically comparable groups of patients were studied: those undergoing laparoscopic left hepatectomy (n = 40) and those undergoing open left hepatectomy (n = 80). The study included hepatectomy from four surgeons. Selection criteria for laparoscopic approach were surgeon dependent. One surgeon did not perform any laparoscopic approach, but three surgeons performed both approaches. Open hepatectomy was performed in cases with previous abdominal surgery or large tumor and in patients who did not agree to undergo LLH because of the expense.

Demographic, preoperative laboratory, and pathologic data were prospectively collected in the electrical medical records. None of the patients received postoperative adjuvant therapy before recurrence. The procedures used for surveillance after liver resection have been described previously [14].

All liver resections were intended to be totally laparoscopic and were performed according to the described procedures and the surgeon’s usual practice. The patient was placed in a supine position with the legs apart. Pneumoperitoneum was created by carbon dioxide insufflation at a pressure of 11–12 mmHg, and a 0-degree flexible laparoscope camera was used. When the tumor was located in segment 4, an intraoperative sonographic examination was performed to confirm the exact tumor location and its relationship to major blood vessels. Parenchymal transection was performed with the different types of energy devices (Sonicison, Medtronics or Harmonic Ace, Ethicone or Ligasure, Medtronics) in accordance with the surgeon’s usual practice; devices used were advanced bipolar device, and/or cavitron ultrasonic surgical aspirator (CUSA. EXcel, Valleylab, Boulder, CO). The corresponding Glissonean branch was managed using individual vessel ligation or temporary inflow control of the Glisson (TICGL) method according to the surgeon’s preference [15]. A temporary increase of intra-abdominal pressure of up to 15 mmHg was used to balance the central venous pressure in case of hepatic vein bleeding. Small vessels were controlled with bipolar coagulation and larger vessels were clipped or electively stapled. Pedicle clamping was not used routinely, but only when there was bleeding or when a long operation time was anticipated. The specimen was removed through in a small low-midline incision followed vertical extension of umbilical port trochar site or a Pfannenstiel incision unless there was a previous laparotomy scar, in which case the previous incision was used. Drain catheter was routinely placed at left upper quadrant.

Open left hepatectomy was performed through a reverse L-incision. After exploration of the abdominal cavity, the anterior approach was applied to dissect and clamp the left Glissonean pedicle below the hilar plate. When the tumor was located in segment 4, intraoperative sonographic examination was performed to confirm the exact tumor location and its relationship to major blood vessels. Parenchymal transection was achieved using a cavitron ultrasound surgical aspirator (CUSA EXcel; Valleylab, Boulder, CO, USA). Individual vessel ligation of hepatic artery and portal vein before parenchymal transection was performed and intermittent inflow control was done when necessary. Hemostasis was achieved by monopolar electrocoagulation, argon beam, clips, or non-absorbable sutures. Systematic routine placement of an abdominal drain was performed during surgery.

Postoperative histological assessment included maximal tumor size, encapsulation, intrahepatic metastasis, multicentric occurrence, microvascular invasion, serosal involvement, and cirrhosis. The histologic grade of HCC was assigned according to the Edmonson-Steiner system as well differentiated (grade I), moderately differentiated (grade II), or poorly differentiated (grade III, IV).

All statistical analyses were performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA). Continuous variables are described as median with range. Categorical variables are expressed as number and percentage of patients. Fisher’s exact test was conducted to evaluate differences in the frequencies of categorical variables between the groups. Mann-Whitney U analysis was conducted to evaluate differences in continuous variables between the two groups. The Kaplan-Meier survival method was performed to evaluate differences in patient survival between the two groups. Prognostic factors of patient survival were identified by Cox regression analysis. To overcome possible selection bias, 1:1 propensity score matching between the laparoscopic left hepatectomy and open left hepatectomy cohorts was applied using multiple logistic regression and a 1:1 matching requirement via the nearest-neighbor matching method. Statistical matching was executed using R 3.2.1 (Vienna, Austria; http://​www.​r-prject.​org/). We matched patients with regard to tumor size and presence of microvascular invasion. All tests were two-sided, and statistical significance was defined as P < 0.05.

The LLH group contained 40 patients, and the OLH group contained 80 patients. All patients underwent curative hepatectomy. Patient baseline and preoperative characteristics of the two groups are summarized in Table 1. Gender, age, etiology, white blood cell count, neutrophil-lymphocyte ratio, hemoglobin level, platelet count, total bilirubin, alkaline phosphatase (ALP), international normalized ratio (INR), albumin, creatinine, C-reactive protein (CRP), alpha-fetoprotein (AFP), and indocyanine green retention rate at 15 min (ICG-R15) were not different between the two groups before and after matching. The median aspartate transaminase (AST) and protein induced by vitamin K absence/antagonism-II (PIVKA-II) were higher in the OLH group than in the LLH group (31 U/L vs. 28 U/L; P = 0.041 and 278.5 mAU/mL vs. 32.5 mAU/mL; P = 0.001), but there were no statistically significant differences between the two groups after matching. There was no difference in alanine transaminase (ALT) level between the two groups before matching, but ALT was higher in the OLH group than in the LLH group after matching.

The median operation time in the LLH group was longer than that in the OLH group (266 min vs. 239 min; P = 0.005), but no statistically significant difference was found between the two groups after matching (Table 2). Blood loss was not different between the two groups before and after matching. Two patients (2.5%) in the OLH group and three patients (7.5%) in the LLH group received red blood cells before matching. The median postoperative hospital stay was significantly shorter in the LLH group than in the OLH group before and after matching (9 days vs. 13 days; P < 0.001).

The overall complication rate was 10.0% (n = 8) in the OLH group and 7.5% (n = 3) in the LLH group (P = 0.468). Atrial fibrillation (n = 1), ascites (n = 1), increased total bilirubin level (n = 1), nausea (n = 2), pleural effusion (n = 1), and pulmonary artery embolization (n = 1) developed in the OLH group and ascites (n = 1), cardiac enzyme elevation (n = 1), and pleural effusion (n = 1) in the LLH group. However, none of the patients had complications greater than Clavien–Dindo classification III. All complications were controlled with pharmacologic treatment or conservative management.

Median tumor size in the OLH group was larger than that in the LLH group (4.2 cm vs. 2.6 cm; P < 0.001). The incidence of microvascular invasion was higher in the OLH group was higher than in the LLH group (81.0% vs. 61.5%; P = 0.027). However, tumor size and microvascular invasion were not different between the two groups after matching. Free resection margin, tumor necrosis, tumor hemorrhage, encapsulation, portal vein tumor thrombosis (PVTT), bile duct tumor thrombosis (BDTT), serosal involvement, intrahepatic metastasis, multicentric occurrence, and cirrhosis were not different between the two groups before and after matching (Table 2).

The median follow-up period was 26.0 months (range, 2.5–48.2 months) for the OLH group and 22.8 months (range, 2.8–48.4 months) for the LLH group before matching (P = 0.226). Recurrence of HCC was observed in 13 patients (16.3%) in the OLH group and 8 patients (20.0%) in the LLH group. Initial recurrence sites were liver (n = 12) and synchronous liver and lung (n = 1) in the OLH group. The initial recurrent site in the LLH group was liver in seven patients and peritoneum in one patient. However, no trocar-site deposits were observed in the LLH group. Two patients (2.5%) in the OLH group and two patients (5.0%) in the LLH group died of HCC recurrence. The disease-free survival (DFS) and patient survival (PS) in the LLH group were similar to those in the OLH group before matching (P = 0.570 and P = 0.452, respectively, Fig. 1). The DFS and PS at 3 years were 79.6 and 93.9% in the LLH group and 91.1 and 93.8% in the OLH group, respectively. The DFS in the LLH group was worse than that in the OLH group after matching, but there was no statistically significant difference between the two groups (P = 0.189). The PS in the LLH group was similar to that in the OLH group (P = 0.545; Fig. 2).

No risk factors for predicting HCC recurrence were revealed after propensity score matching (Table 3). Laparoscopic approach was not a risk factor of HCC recurrence in univariate and multivariate analysis.