Study patients and protocol
Initially, 225 patients aged ≥70 years with newly diagnosed HCC and who underwent LLR and OLR in our department between January 1, 2010, and December 31, 2018, were enrolled in the study. Collected data were retrieved from prospectively maintained databases. Three patients were excluded from the analysis because of hybrid laparoscopic surgery, and four underwent combined procedures, including venous reconstruction and biliary reconstruction. Finally, the remaining 218 patients were evaluated. Tumor-related variables, including tumor location, maximum tumor size, vascular invasion, tumor thrombus, tumor number, presence of ascites, lymph node metastasis, and extrahepatic metastases, were evaluated using imaging techniques, such as ultrasonography, multidetector-row computed tomography (CT), and dynamic contrast-enhanced magnetic resonance imaging. HCC was diagnosed in all patients based on pathology after hepatectomy. None of the patients received preoperative chemotherapy or postoperative adjuvant therapy before recurrence.
The indication for and extent of liver resection were determined as follows: tumor number ≤4, general condition fulfilling a performance status of 0–2, and Child-Pugh classification A or B. Indocyanine green retention rate at 15 minutes (ICG-R15) was used for decision-making for the liver resection volume. The estimated liver resection volume and future remnant liver volume were calculated by CT; if the remnant liver volume was <30% of the total liver volume, liver resection was not performed. The exclusion criteria for LLR were as follows: HCC with tumor size >10 cm, HCC with the appearance of tumor thrombus in the main portal and main hepatic veins, or HCC necessary for liver resection of more than three contiguous segments. The selection criteria for laparoscopic approach were dependent on the surgeon’s judgment.
This study was conducted in accordance with the Declaration of Helsinki and was approved by the institutional review board of Fukuyama City Hospital (permission number 452). The need to obtain informed consent from patients was waived based on the aim and methods of this study. All procedures in this study were carried out in accordance with relevant guidelines and regulations.
Operative technique: laparoscopic liver resection
LLR was performed with the patient in supine position for tumor location in the left lobe and left hemi-lateral position for tumor location in the right lobe. The pneumoperitoneum was kept by carbon dioxide maintained at approximately 10 mmHg and all patients underwent intraoperative ultrasonography (IOUS) to clarify the locations of tumor and vascular structures. A 10-mm flexible camera was placed above the umbilicus, and 2–3 additional trocars, sized 5 or 12 mm, were placed on this arrangement in each case. The parenchymal dissection was performed using ultrasonic coagulating shears and the Cavitron ultrasonic surgical aspirator (CUSA; Valleylab, Boulder, CO, USA). Vessels with diameters of >3 mm were occluded using titanium clip, and the major hepatic vessels or hilar structures were divided by vascular stapling techniques. Temporary vascular inflow occlusion (Pringle maneuver) was applied during parenchymal transection depending on the situation in each case. The specimen was extracted through a small median incision with a plastic bag. A local drainage tube was placed during the operation and removed within 48–72 hours.
Operative technique: open liver resection
For OLR, the patient was placed in supine position and the usual skin incision was an upward midline or reversed L-shaped laparotomy. Similar to LLR, IOUS was routinely performed and hepatic parenchymal dissection was performed using ultrasonic coagulating shears and CUSA with the Pringle maneuver. Vessels with diameters of >3 mm were ligated or sutured. An abdominal drain was placed during surgery and removed within 48–72 h, similar to LLR.
Data collection
We evaluated the following patient demographic data: age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, and comorbid diseases (diabetes mellitus, hypertension, cardiovascular disease, respiratory disease, renal failure). We also obtained the medication history of antiplatelet therapy and of aspirin prescription for the primary and secondary prevention of thromboembolic morbidity in the year before date of surgery. With increasing age, elderly people are more likely to be prescribed antiplatelet therapy. Our institution has continued aspirin therapy perioperatively in patients undergoing liver resection to reduce thrombotic morbidity and has collected morbidity data on postoperative hemorrhage complications.
Blood samples for evaluating the operative liver function are as follows: aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum platelet count, prothrombin time, serum concentrations of albumin, total bilirubin, protein induced by vitamin K absence, alpha-fetoprotein, ICG-R15, and Child-Pugh score.
Perioperative data, including surgical procedure, operative time, blood loss, blood transfusion rate, time to start oral intake, length of hospital stay, morbidity, and mortality, were evaluated. To classify the degree of chronic hepatitis, the degree of liver fibrosis and necroinflammation was classified based on the New Inuyama classification [16].
Surgical complication was defined according to Clavien-Dindo classification, which defines major complications as those graded greater than III [17]. Clinicopathological staging was determined based on the tumor/nodes/metastasis (TNM) classification.
Statistical analysis
Propensity score matching
As this study was not randomized for surgical procedure between LLR and OLR, it was necessary to achieve comparability between both groups regarding potential confounding variables. Therefore, we used PSM with a multivariable logistic regression model. The covariates included in this model were age, sex, BMI, comorbid diseases, history of aspirin prescription, ASA classification, hepatitis status, Child-Pugh classification, maximum tumor size, preoperative blood test, and surgical procedures (Table 1).
These covariates were chosen because they were previously used in other similar studies [14,18,19] due to their clinical relevance. The nearest-neighbor matching algorithm was employed to form pairs of patients undergoing LLR and OLR to mitigate the potential for selection bias across surgical approaches. Case matching was performed one-to-one with a caliper width of 0.2 standard deviation n of logit of the propensity score.
Statistical analyses were performed using the JMP software version 14 (SAS Institute, Inc., Cary, NC, USA). Continuous variables before matching are described as median with range, whereas categorical data are expressed as number or frequency (%). Comparisons between the two groups were conducted using Mann-Whitney U test. Differences in categorical outcomes were analyzed using chi-square test, Yates’ test, Poisson distribution analysis, or Fisher’s exact test. Post-matching variables between the groups were assessed using the paired t-test or Mann-Whitney U test for continuous variables and the McNemar test for categorical variables. The level of statistical significance was set at 0.05.