Repeat Hepatic Resection Combined with Intraoperative Radiofrequency Ablation Versus Repeat Hepatic Resection Alone for Recurrent and Mutiple Hepatocellular Carcinoma Patients Meeting the Milan Criteria: A Propensity Score-Matched Analysis

Repeat Hepatic Resection Combined with Intraoperative Radiofrequency Ablation Versus Repeat Hepatic Resection Alone for Recurrent and Mutiple Hepatocellular Carcinoma Patients Meeting the Milan Criteria: A Propensity Score-Matched Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Repeat Hepatic Resection Combined with Intraoperative Radiofrequency Ablation Versus Repeat Hepatic Resection Alone for Recurrent and Mutiple Hepatocellular Carcinoma Patients Meeting the Milan Criteria: A Propensity Score-Matched Analysis Yang Huang, Liangliang Xu, Min Huang, Li Jiang, Mingqing Xu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1702329/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The surgical indications and therapeutic strategies for early-stage multifocal and recurrent hepatocellular carcinomas (rHCC) remain controversial. The purpose of this study was to compare the long-term outcomes of patients with recurrent and multifocal HCC meeting the Milan criteria with repeat hepatectomy (RH) and RH combined with intraoperative radiofrequency ablation (RFA). Methods A total of 109 consecutive patients with intrahepatic early-stage multifocal rHCC within Milan criteria following RH or RH + RFA were retrospectively collected from April 2010 to May 2020. Propensity score matching (PSM), subgroup analysis, and univariate and multivariate analyses were performed. Overall survival after recurrence (rOS) and recurrence-free survival after recurrence (rRFS) were calculated. Results The 1-, 3-, and 5-year rOS and rRFS of the combination group and the RH group were similar (p = 0.699; P = 0.587, respectively). The similar results are also appeared in matched population. Subgroup analyses showed that there was no significant difference between patients with 2 tumors and 3 tumors, but the RH group was associated with better rRFS than the combination group for patients whose tumors were located in the same lobe (p = 0.045). Multivariate analysis revealed that time to recurrence (TTR) ≤ 2 years and IM pathologically were independent risk factors. Conclusions For multifocal rHCC patients meeting the Milan criteria, RH combined with RFA may offer similar OS and RFS as RH alone; however, RH may be more suitable for patients with tumors located in the same lobe than RH combined with RFA. recurrent hepatocellular carcinoma multifocal tumors hepatic resection radiofrequency ablation survival outcome Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction HCC is one of the most common primary malignancies of the liver and is the third leading cause of cancer-related death worldwide (Bray et al. 2018 ; Li et al. 2022 ). At present, partial hepatectomy is the recommended first-line treatment for primary HCC, where curative treatment is deemed possible(Chang et al. 2016 ). Nevertheless, the postoperative tumor recurrence rate is not acceptable; the 5-year recurrence rate is 60–80% following primary resection with curative intent, and 80–95% of recurrences are confined to the remnant liver (Huang et al. 2012 ; Fan et al. 2011 ; 'EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma' 2012; Bruix and Sherman 2011 ). Future treatment for HCC will mainly focus on recurrent hepatocellular carcinoma (rHCC). Many studies have deemed that 5-year survival after RH resembles that after initial hepatectomy (Choi et al. 2008 ; Chan et al. 2012 ; Xia et al. 2020 ). However, guidelines for the management of early-stage rHCC remain controversial and poorly defined. Improvements in recurrence surveillance and medical imaging have led to the diagnosis of rHCC at an early stage when various treatments may still be available. rHCC usually originates from intrahepatic metastasis (IM) or multicentric occurrence (MO) (Dong et al. 2020 ). IM refers to HCC foci developing from tumor cells that have spread into the remnant liver via the portal vein before or during hepatic resection, usually occurring early. MO refers to new HCC foci developing due to the existence of chronic active hepatitis, cirrhosis, or other HCC-relevant risk factors after resection, appearing later. Most studies regard the 2-year recurrence interval as the critical value of early recurrence and late recurrence, which indicates that the clinical progression and outcomes of these two types of recurrence are significantly different(Imamura et al. 2003 ; Wu et al. 2009 ; Lu et al. 2020 ; Xu et al. 2019 ). Most early-stage rHCC patients can benefit from surgical intervention on the premise of good liver function. The therapeutic principles used for rHCC are essentially the same as those used for primary HCC (Tabrizian et al. 2015 ). In that way, the mainstay treatments of early-stage rHCC include salvage liver transplantation (SLT), RH, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), or systemic treatment using targeted therapy or chemotherapy. SLT is the most beneficial option, but it is of limited use in regions with liver donor shortages and disease progression on waiting lists (Poon et al. 2002). TACE combined with systemic treatment was managed for patients who had poor general performance and liver function, severe cirrhosis and unresectable conditions (size, number, and location of rHCC). RFA and RH are the next-most efficacious treatment options for early-stage rHCC. Many studies have shown that the long-term survival outcome of resection is similar to that of radiofrequency therapy for early-stage single recurrent hepatocellular (Chan et al. 2012 ; Liang et al. 2008 ; Song et al. 2015 ; Xia et al. 2020 ; Erridge et al. 2017 ). Currently, many centers use RH as the first-line treatment for rHCC and have claimed that it is preferable because its survival benefit is acceptable (Chan et al. 2012 ; Chua et al. 2021 ). Unfortunately, RH can be carried out only in rHCC patients within 13.4–22.9% because of poor liver function and multiple intrahepatic recurrence (Karabulut et al. 2012 ). RFA is now the new first-line locoregional treatment due to its therapeutic effectiveness, stable safety and minimal liver damage. Some studies have shown that RFA was as effective as RH in the treatment of small rHCC (≤ 3 cm in diameter) in terms of long-term survival outcome (Song et al. 2015 ; Yang et al. 2020 ). In addition, RFA had advantages over RH in terms of lower mortality and compilation rates (Feng et al. 2020 ). To the best of our knowledge, most studies focused on early-stage single rHCC, and there have been no reports published in the medical literature comparing the efficacy of RH and/or RFA for early-stage multifocal rHCC. Whether RH combined with RFA could make up for the vacancy that could not be achieved by RH alone in the treatment of early-stage multifocal rHCC. The aim of this retrospective study was to compare the outcomes of patients with multifocal rHCC meeting the Milan criteria (2–3 nodules, each ≤ 3 cm in diameter without vascular invasion or extrahepatic metastases) after RH combined with intraoperative RFA or RH alone. Meanwhile, to compare the differences between the two surgical methods, prognostic factors and subgroup analyses were performed. Method This present study was designed as a retrospective review, approved by the West China Hospital Ethics Committee, and conducted in accordance with the ethical guidelines of the Declaration of Helsinki. Patients A total of 3542 patients with HCC underwent curative hepatectomy (i.e., R0/R1 resection) from May 2008 to July 2018 at the Department of Hepato-Biliary-Pancreatic Surgery, West China Hospital, Sichuan University. In all, 2197 patients subsequently suffered tumor recurrence from April 2010 to May 2020, and 237 patients who underwent nonsurgical treatments such as TACE and anti-tumor drug therapy after initial resection and before the first recurrence were excluded. Meanwhile, 576 patients who received the above nonsurgical treatments after the first recurrence were also excluded. Then, 1017 patients with single recurrent tumor or not up to the Milan criteria were excluded. Next, 246 patients who were combined with other therapies, such as SLT and tyrosine kinase inhibitor administration, as well as 12 patients who were lost to follow-up, were excluded. Finally, a consecutive series of 109 patients conforming to inclusion criteria were finally enrolled in this study. They were divided into two groups according to surgical procedures: the combination group (n = 43), which consisted of those who underwent open RH combined with RFA, and the RH group (n = 66), which consisted of those patients who underwent open HR alone (Fig. 1 ). The follow-up data were updated in January 2021 or until death. Preoperative Evaluation Hepatologists, surgeons and radiologists jointly participated in the preoperative evaluation. The potential for resection was evaluated by ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Liver function was assessed by a combination of Child–Pugh score, liver biochemistry, and indocyanine green test. RH was undertaken in the presence of endurable cardiopulmonary and renal function, Child–Pugh grade A or B, which could be returned to Child–Pugh grade A by routine treatment, and a normal indocyanine green test at 15 min. Every patient enrolled in this study followed the following criteria: 1. Multiple intrahepatic recurrence of HCC after initial hepatectomy. 2. Received no treatment except for the initial hepatectomy. 3. Number of recurrent tumors ≤ 3 with the largest tumor ≤ 3 cm in diameter. 4. No radiologic evidence of invasion into major portal/hepatic vein branches. 5. There were no extrahepatic metastases, severe liver dysfunction, or significant coagulopathy (prothrombin activity < 40%, platelet count < 40×10 9 /L). 6. There was no history of encephalopathy, refractory ascites or variceal bleeding. Treatments The treatment scheme used for early-stage multifocal rHCC was essentially the same as that used for primary multifocal HCC with a small modification in liver function requirement. RH was assigned when there was the possibility for the complete removal of all tumors while retaining a sufficient remnant liver volume. On the basis of well-preserved liver function, if ICG-R15 is less than 10%, anatomical extended hepatectomy is permitted. For lesions ≤ 3 cm in diameter, RFA was also deemed to be the radical therapeutic method. In addition, the reasons for performing intraoperative RFA include insufficient remnant volume, deep location in liver parenchyma and distant anatomical location between tumors. However, RFA is sometimes inadequate for lesions on the liver surface or near large vessels. Otherwise, other factors affecting the treatment choice come from the experience and skills of the surgeon. Significant adhesions and ambiguous anatomical structures increase the difficulty of RH and the uncertainty of RFA. All treatments were reported to the patients or their relatives, and written informed consent was obtained. Surgical Procedure All operations were performed using the open approach, starting with an exploration, separating the adhesions caused by the initial operation thereafter. Intraoperative ultrasound was routinely performed to assess the tumor burden, the liver remnant, and the possibility of a negative resection margin. Parenchyma transection was carried out using a Cavitron Ultrasonic Surgical Aspiration (CUSA; Valleylab Corporation, Boulder, CO, USA) or clamping crush. The Pringle manoeuvre was routinely performed with a 15-min occlusion and 5-min reperfusion cycle when necessary. Experienced ultrasound doctors and surgeons should jointly locate the tumor by conventional ultrasound or contrast-enhanced ultrasonography (CEUS). A Cool-tip RFA system (Valleylab Corporation) was used for ablation. The numbers of overlapping ablations and ablation points were determined by the number and size of tumors. After completing the RFA procedure, we cauterized the electrode path to avoid bleeding and track seeding of the tumor. Diagnostic criteria and definitions The clinical diagnosis of HCC at both its initial and recurrent stages was based on the criteria of the American Association for the Study of Liver Diseases (AASLD) (Bruix and Sherman 2011 ). The diagnosis of recurrent HCC was confirmed by histopathology for resection. Some suspicious lesions were pathologically confirmed by ultrasound-guided biopsy for RFA. The presence of adhesions was defined when extensive adhesiolysis was necessary during surgery (Chua et al. 2021 ). Curative resection was defined as complete resection of all macroscopically detectable tumors with histological tumor-free margins along the parenchymal transection line. Complete RFA ablation was defined as an area equal to or larger than the ablated tumor without contrast enhancement after the RFA procedure at 1 month. Moreover, based on Couinaud’s segmentation, the right lobe of the liver is composed of segments V, VI, VII, and VIII, while the left lobe of the liver is composed of segments II, III, and IV (Pang 2002 ). According to the Liver Cancer Study Group of Japan with modifications (Matsuda et al. 2001 ). Multicentric occurrence (MO) was diagnosed when the resected recurrent tumors met one of the following modified criteria: 1. The recurrent tumor consists of well-differentiated HCC only; 2. The recurrent tumor has precancerous lesions or well-differentiated HCC around the less differentiated HCC and shows a ‘‘nodule-in-nodule’’ form; 3. All components of recurrent HCC show higher differentiation than the primary resected tumors. Recurrent HCC showing either the same or less differentiation than the primary resected tumors was diagnosed as intrahepatic metastasis (IM). Follow-up In both groups, enhanced CT was conducted one month after the treatment to evaluate whether the tumor was completely controlled. Thereafter, ultrasonography was carried out in the outpatient clinic once every 2 months within the first 2 years and then once every 3 months thereafter, while the CT scan was performed every 6 months. At each follow-up session, blood tests, serum liver function tests and AFP, as well as MRI or CEUS, if necessary, were carried out. Regardless of the serum HBV deoxyribonucleic acid, all patients with hepatitis-related HCC in our hospital were consulted by a hepatologist for antiviral therapy. Once the second recurrence was confirmed, patients were treated with third resection, re-RFA, TACE, sLT, or anti-tumor drugs. Statistical Analysis Categorical variables are expressed as numbers and percentages (%), and continuous variables are expressed as medians (ranges). Univariate analysis was performed to use Student’s t test or the Mann–Whitney U test, Chi-square test or Fisher’s exact test, as appropriate. rOS was defined as the period from the date of RH or RH + RFA to the date of death or the last follow-up until May 2021. rRFS was defined as the interval between the date of RH or RH + RFA and the date of second recurrence when medical tests confirmed. The rOS and rRFS rates were measured by using the Kaplan–Meier method and compared by using the log-rank test. The relative prognostic significance of the variables in predicting survival was assessed by Cox proportional hazards regression analysis. To minimize confounding bias between RH group and combination group, a 1:1 matching method using propensity score was performed by R software (Version 2.12x). All tests for differences were two-tailed, and p values were considered statistically significant when the associated probability was less than 0.05. Statistical analysis was performed using the SPSS software program (Version 20). Results Baseline Data at Recurrence The demographic characteristics of the pre- and post-PSM cohorts are summarized in Table 1 . Before PSM, the number of patients who underwent RH combined with RFA and RH alone was 43 and 66, respectively. Among them, 39 (90.7%) were male, and the mean age was 54.28 years (range, 31–78 years) in the combination group, while 54 (81.8%) were male, and the mean age was 56.23 years (range, 27–85 years) in the RH group. Hepatitis B positive was detected in 38 patients (88.4%) and 56 patients (84.8%) in the combination and RH group, respectively. ICG-R15 < 10% was tested in 36 patients (83.7%) and 55 patients (83.3%) in the combination and RH group, respectively. While 40 patients (93.0%) and 55 patients (93.9%) in the combination and RH group, respectively, had Child’s A liver function. Other indicators, such as HBV DNA ≥ 1000 IU/mL, serum AFP ≥ 100 ng/mL, total bilirubin, ALT, AST, albumin, prothrombin time, platelet count, total tumor size, and time to recurrence ≤ 2 y, revealed no significant difference between the two groups. However, more patients in RH group had two tumors than patients in combination group (p = 0.034), the largest tumor size was larger in combination group than in RH group (p = 0.026), and more patients in combination group had tumors located in the different lobes than patients in RH group (p = 0.049). The above parameters revealed no significant difference between the two groups after PSM. Table 1 Baseline characteristics of HCC patients with recurrent and mutifocal tumors meeting the Milan criteria at the time of recurrence Variable Before propensity matching After propensity matching Combination (n = 43) RH alone (n = 66) P value Combination (n = 37) RH alone (n = 37) P value Age, years, median (range) 52(31–78) 56(27–85) 0.400 52(31–78) 54(27–79) 0.871 Male, n (%) 39(90.7) 54(81.8) 0.200 33(89.2) 34(91.9) 1.000 Uderlying liver disease HBV, n (%) 38(88.4) 56(84.8) 0.602 36(97.3) 32(86.5) 0.199 HCV, n (%) 5(11.6) 8(12.1) 0.938 1(2.7) 4(10.8) 0.358 HBV DNA ≥ 1000, IU/mL, median (range) 5(11.6) 4(6.1) 0.302 4(10.8) 3(8.1) 1.000 Serum AFP ≥ 100, ng/mL, median (range) 14(32.6) 20(30.3) 0.804 12(32.4) 12(32.4) 1.000 Total bilirubin level, umol/L, median (range) 14.5(5.9–28.7) 14.1(6.1–30.3) 0.552 15.6(5.9–28.7) 12.9(7-30.3) 0.611 ALT level, IU/L, median (range) 30(9–79) 28(6-152) 0.125 30(9–79) 30(8–71) 0.634 AST level, IU/L, median (range) 28(16–70) 28(14–157) 0.322 28(18–70) 32(15–88) 0.957 Serum albumin, g/L, median (range) 42.6(31.8–52.1) 43.4(32.5–51.4) 0.579 42.6(31.8–52.1) 43.6(38.2–51.4) 0.294 Prothrombin time, s, median (range) 11.8(10.1–17.4) 11.9(10.3–14.6) 0.598 11.7(10.2–14.2) 12.1(10.3–14.4) 0.176 Platelet count, 10 9 /L, median (range) 105(64–310) 119.5(60–238) 0.422 105(64–218) 108(60–194) 0.970 Child - Pugh class A, n (%) 42(97.7) 64(97.0) 1.000 35(94.6) 35(94.6) 1.000 ICG-R15 < 10%, n (%) 36(83.7) 55(83.3) 0.958 32(86.5) 33(89.2) 1.000 Patients with two tumors, n (%) 22(51.2) 47(71.2) 0.034 20(54.1) 26(70.3) 0.150 Largest tumor size, cm, median (range) 2.7(1.4-3) 2.4(1.1-3) 0.026 2.7(1.4-3) 2.4(1.2-3) 0.050 Total tumor size, cm, median (range) 4.9(2.2-8) 4.8(2.1–7.3) 0.665 4.8(2.5-8) 4.8(2.1–7.3) 0.897 Time to recurrence ≤ 2y, n (%) 19(44.2) 32(48.5) 0.660 12(32.4) 15(40.5) 0.469 Located the different lobe, n (%) 28(65.1) 23(34.8) 0.049 23(62.2) 16(43.2) 0.103 HCC hepatocellular carcinoma, RH repeat hepatectomy, SD standard deviation, HBV hepatitis B virus, HCV hepatitis C virus, HBV DNA hepatitis B virus deoxyribonucleic acid, AFP a-fetoprotein, ALT alanine aminotransferase, AST aspartate aminotransferase, ICG-R15 indocyanine green retention rate at 15 min Clinicopathologic and Operative Data at Initial Resection As shown in Table 2 , the two groups were similar in the number of cases with AFP ≥ 400 ng/ml, Child–Pugh class A, BCLC stage, major tumor size and tumor number at their initial hepatectomy. The postoperative pathological results showed no significant differences in complete tumor capsule present, vascular invasion, satellites present, tumor grade, liver cirrhosis present, Ishak score, or resected margin positive present between the two groups. Blood loss, number of intraoperative blood transfusion and major resections during the initial resection were comparable between the two groups. Table 2 Clinical characteristics of patients with HCC for the initial resection Variable Combination (n = 43) HR alone (n = 66) P value Serum AFP ≥ 400ng/ml, n (%) 9(20.9) 14(21.2) 0.972 Major tumor size, cm, median (range) 4.5(1.6–14) 3.8(1–12) 0.076 Tumor number, solitary, n (%) 32(74.4) 56(84.8) 0.177 Complete tumor capsule present, n (%) 21(48.8) 30(45.5) 0.729 Vascular invasion Micro, n (%) 24(55.8) 34(51.5) 1.000 Macro, n (%) 3(7.0) 5(7.6) 0.660 Satellites present, n (%) 13(30.2) 14(21.2) 0.286 Tumor grade, n (%) G1 2(4.7) 3(4.5) 1.000 G2 23(53.5) 32(48.5) 0.610 G3-G4 18(41.9) 31(47.0) 0.600 Liver cirrhosis, n (%) 21 (48.8) 31(47.0) 0.849 Ishak score, median (range) 5(2–6) 5(1–6) 0.878 Resected margin positivity, n (%) 1(2.3) 0 (0) 0.394 BCLC stage, n (%) 0-A 31(72.1) 55(83.3) 0.160 B 9(20.9) 6(9.1) 0.079 Estimated blood loss, ml, median (range) 305(35-2100) 260(30-1980) 0.194 Intraoperative blood transfusion, n (%) 6(14.0) 4(6.1) 0.163 Extent of liver resection (Major), n (%) 10(23.3) 10(15.2) 0.285 HCC hepatocellular carcinoma, HR hepatic resection, RFA radiofrequency ablation, AFP alpha-fetoprotein Operative and Postoperative Data of Second Surgery There was no significant difference in the types of excision between the two groups (Table 3 ). Patients in RH group had a longer duration of operation than patients in combination group (before PSM: p < 0.001; after PSM: p < 0.001). The RH group had more patients with intraoperative blood loss of 501–1000 ml than the combination group (p = 0.034), and the opposite was true for blood loss of ≤ 200 ml (p = 0.042) for all populations. These differences were disappeared after PSM. There were no significant differences in the percentage of patients who received intraoperative blood transfusions or new tumors found by intraoperative ultrasound between the two groups before and after PSM. Table 3 Operative and postoperative data of HCC patients with recurrent and mutiple tumors meeting the Milan criteria at the time of recurrence Variable Before propensity matching After propensity matching Combination (n = 43) HR alone (n = 66) P value Combination (n = 37) HR alone (n = 37) P value Type of excision All tumors en bloc resection, n (%) --- 34(51.5) --- --- 22(59.5) --- Local resection 38(88.4) 51(77.3) 0.391 32(86.5) 26(67.6) 0.090 Hemi-hepatectomy 4(9.3) 10(15.2) 0.372 2(5.4) 7(21.6) 0.152 Extended resection 1(2.3) 5(7.6) 0.400 1(2.7) 4(10.8) 0.358 Operation time, h, mean ± SD (range) 4.4(3.7–6.2) 4.9(4.4–6.8) <0.001 4.3(3.7–6.2) 5.0(4.6–6.8) <0.001 Estimated blood loss, mL ≤ 200 9(20.9) 5(7.6) 0.042 6(16.2) 3(8.1) 0.479 201–500 27(62.8) 32(48.5) 0.143 25(67.6) 18(48.6) 0.099 501–1000 7(16.3) 23(34.8) 0.034 6(16.2) 13(35.1) 0.062 ≥ 1000 0(0) 6(9.1) 0.079 0(0) 3(8.1) 0.240 Adhesions present, n(%) 29(67.4) 39(59.1) 0.379 24(64.9) 22(59.5) 0.632 Intraoperative blood transfusion, n (%) 5(11.6) 11(16.7) 0.468 3(8.1) 5(13.5) 0.711 New tumor found by intraoperative ultrasound, n (%) 6(5.6) 11(7.3) 0.703 5(13.5) 7(18.9) 0.528 Data of resected tumor Resected tumor number, n (%) 58(54.2) 151(100) --- 51(56.0) 85(100) --- Resected tumor size, cm 2.5(0.5-3) 2(0.5-3) 0.022 2.6(0.5-3) 2.2(0.5-3) 0.113 Surgical margin for resected tumor, cm 2(1.5–2.5) 1.75(1-2.5) 0.085 2(1.5–2.5) 1.75(1-2.5) 0.213 Resected margin positivity, n (%) 0(0) 1(0.6) 1.000 0(0) 0(0) 1.000 Microvascular invasion 17(29.3) 27(17.9) 0.070 13(35.1) 12(32.4) 0.806 Liver cirrhosis 30(69.8) 37(56.1) 0.151 27(73.0) 21(56.8) 0.144 Ishak score, median(range) 6(2–6) 6(2–6) 0.155 6(2–6) 6(3–6) 0.243 Tumor grade of resected tumor, n (%) G1 4(6.9) 8(5.3) 0.656 3(5.9) 4(4.7) 1.000 G2 38(65.6) 103(68.2) 0.710 33(64.7) 60(70.6) 0.475 G3-G4 16(27.6) 40(26.5) 0.873 15(29.4) 21(24.7) 0.547 MO pathologically, n (%) 14(32.6) 28(42.4) 0.301 11(29.7) 14(37.8) 0.461 Data of ablated tumor Ablated tumor number, n (%) 49(45.8) --- --- 40(44.0) --- --- Ablated tumor size, cm 1.2(0.5-3) --- --- 1.3(0.5-3) --- --- Local tumor control after RFA, n (%) 49(100) --- --- 40(100) --- --- Complication grade, n (%) Grade Ⅰ 9(20.9) 10(15.2) 0.437 8(21.6) 7(18.9) 0.772 Grade Ⅱ 8(18.6) 7(10.6) 0.236 5(13.5) 4(10.8) 0.722 Minor complication 17(39.5) 17(25.8) 0.129 13(35.1) 11(29.7) 0.619 Grade Ⅲa 5(11.6) 15(22.7) 0.256 4(10.8) 6(16.2) 0.496 Grade Ⅲb 2(4.7) 7(10.6) 0.478 1(2.7) 3(8.1) 0.304 Grade Ⅳa 1(2.3) 3(4.5) 1.000 1(2.7) 3(8.1) 0.304 Grade Ⅳb 1(2.3) 1(2.3) 1.000 1(2.7) 1(2.7) 1.00 Grade Ⅴ 0 0 --- 0 0 --- Major complication 9(20.9) 26(39.4) 0.044 7(18.9) 13(35.1) 0.116 Duration of postoperative hospital stay, day 6(5–14) 7(5–18) 0.115 6(5–14) 7(5–17) 0.078 30-day mortality 0 0 --- 0 0 --- HCC hepatocellular carcinoma, HR hepatic resection, MO multicentric occurrence, IM intrahepatic metastasis. For resected tumors, there were 58 and 151 tumors in the RH group and combination group, respectively. Smaller tumors were present in RH group than in combination group in all patients (p = 0.022), however, no significant difference was found after PSM. There were also no significant differences in surgical margin, Ishak score, microvascular invasion present, liver cirrhosis present and tumor grade of Edmondson and Steiner between the two groups. For ablated tumors, a total of 48 tumors were ablated in combination group. All tumors undergoing RFA were locally controlled under the certification of CEUS or CT. Treatment-related complications are summarized in Table 3 . Complications were reported according to the Clavien–Dindo grade (Clavien et al. 2009 ). Minor complications, classified as Clavien–Dindo grade I or II, were developed in most patients and were similar between the two groups before and after PSM. Major complications were classified as grade III or higher. There were no significant differences among the subgrades of major complications between the two groups before and after PSM. Nevertheless, the RH group had a higher incidence of major complications than the combination group in general (p = 0.044). After PSM, the difference was disappeared between the two groups. In addition, no difference was observed between them regarding the duration of postoperative hospital stay before and after PSM. There were no deaths in either group during the perioperative period. Long-Term Survival Analysis During a median follow-up period of 38 months (range 7–97) for all objects, 27 (62.8%) patients in the combination group and 38 (57.6%) patients in the RH group died, and 28 (65.1%) patients in the combination group and 39 (59.1%) patients in the RH group experienced recurrence. The estimated rOS at 1, 3, and 5 years was 88.4%, 67.6% and 37.5%, respectively, for the patients in the combination group and 92.4%, 75% and 42.1% for the patients in the RH group (Fig. 2 A). The cumulative rRFS at 1, 3, and 5 years was 86%, 44.2% and 26%, respectively, for the patients in the combination group and 86.4%, 47.7% and 29.7% for the patients in the RH group (Fig. 2 B). Neither the rOS nor rRFS was significantly different between the two groups (p = 0.699 and p = 0.587, respectively). After PSM, the estimated rOS at 1, 3, and 5 years was 89.2%, 67.6% and 37.8%, respectively, for matched patients in the combination group and 89.2%, 70% and 43.5% for matched patients in the RH group (Fig. 2 C). The cumulative rRFS at 1, 3, and 5 years was 83.8%, 48.4% and 28.5%, respectively, for matched patients in the combination group and 83.8%, 45.8% and 35% for matched patients in the RH group (Fig. 2 D). The rOS and rRFS were still not significantly different between the two groups (p = 0.550 and p = 0.835, respectively). Subgroup Analysis According to Tumor Number In the subgroup analyses, the 1-, 3-, and 5-year rOS rates were similar between the combination group and the RH group in patients with two recurrent tumors (90.9%, 68.2% and 54.6% versus 93.6%, 78.9% and 49.9%, respectively; P = 0.682) (Fig. 3 A). The 1-, 3-, and 5-year rRFS was also similar between the combination group and the RH group in patients with two recurrent tumors (90.9%, 36.6% and 30.5% versus 87.2%, 45.4% and 29.3%, respectively; P = 0.692) (Fig. 3 B). Similar results emerged in patients with three recurrent tumors; the 1-, 3-, and 5-year rOS rates were 85.7%, 66.7%, and 21.2% and 89.5%, 66.2%, and 32.6% in the combination group and the RH group, respectively; P = 0.642) (Fig. 3 C). The 1-, 3-, and 5-year rRFS rates were 81%, 37.5%, and 20% and 84.2%, 52.9%, and 30.2% in the combination group and the RH group, respectively; P = 0.596) (Fig. 3 D). Subgroup Analysis According to Tumors’ Anatomic Locations In the other subgroup analyses, the 1-, 3-, and 5-year rOS rates were similar between the combination group and the RH group in patients with tumors located in the same lobe (86.7%, 70.6% and 42.4% versus 93%, 74.1% and 40.2%, respectively; P = 0.948) (Fig. 4 A). However, patients with all lesions in the same lobe who underwent RH had a significantly higher rRFS rate than those who underwent RH + RFA (1-, 3-, and 5-year rRFS rates of 86%, 50.4% and 36.2% versus 73.3%, 35% and 17.5%, respectively; P = 0.045) (Fig. 4 B). Meanwhile, for patients with tumors located in different lobes, there was no significant difference in the 1-, 3-, and 5-year OS rates between the two groups (89.3%, 66.6%, and 35.3% in the combination group vs. 91.3%, 77%, and 45.4% in the RH group, respectively; p = 0.840) (Fig. 4 C). Similarly, the 1-, 3-, and 5-year rRFS rates were also similar between the two groups (89.3%, 43.9%, 34.2% and 87%, 41.9%, 19.6%, respectively; p = 0.290) (Fig. 4 D). Risk-factor Analysis for Survival Outcome In univariate analysis, we found that three variables, albumin at recurrence ≤ 3.5 mg/dl, time to recurrence ≤ 2 years and IM pathologically, were poor prognostic factors for survival before and after PSM. Variables with p < 0.1 in univariate analysis and operative method were included in multivariate analysis, and we found that time to recurrence ≤ 2 years and IM pathologically were independent risk factors before and after PSM (Table 4 ). Table 4 Univariate and multivariate analysis of prognostic factors for survival Variable Univariate analysis Before propensity matching After propensity matching HR 95% CI P value HR 95% CI P value Sex (M) 1.015 0.629–1.854 0.397 1.213 0.710–1.689 0.764 Age (≥ 60 y) 0.875 0.604–1.328 0.206 0.945 0.453–1.563 0.535 HBsAg (+) 1.131 0.499–2.564 0.768 1.341 0.782–1.993 0.883 Tumor number at initial resection (n ≥ 2) 0.987 0.526–2.505 0.487 1.110 0.498–1.536 0.268 BCLC stage at initial resection (stage ≥ B) 1.453 0.159–4.543 0.119 1.421 0.453–3.879 0.212 MVI present at initial resection 1.234 0.913–1.924 0.300 1.118 0.793–2.034 0.542 HBV DNA at recurrence (≥ 1,000 IU/mL) 1.178 0.753–2.077 0.325 1.335 0.634–2.314 0.237 AFP at recurrence (≥ 100 ng/mL) 1.216 0.832–1.821 0.289 1.256 0.689–1.775 0.456 Albumin at recurrence (≤ 3.5mg/dL) 1.827 1.046–2.354 0.010 1.945 1.210–3.021 0.023 Time to recurrence (≤ 2y) 1.931 1.141–2.214 < 0.001 2.467 1.233–3.648 < 0.001 IM pathologically 2.137 1.178–3.874 0.002 2.373 1.034–4.569 < 0.001 Number of tumors (= 3) 1.356 0.959–1.757 0.140 1.328 0.836–2.540 0.221 Site of recurrence (different lobe) 1.582 0.991–2.730 0.085 1.684 1.113–3.235 0.078 Operative method (RH + RFA) 1.067 0.730–1.726 0.752 1.095 0.873–1.987 0.783 Multivariate analysis Before propensity matching After propensity matching HR 95% CI P value HR 95% CI P value Albumin at recurrence (≤ 3.5mg/dL) 1.434 1.034–2.118 0.098 1.459 1.112–2.349 0.139 Time to recurrence (≤ 2y) 2.234 1.328–4.213 < 0.001 2.678 1.122–5.034 < 0.001 IM pathologically 1.985 1.023–4.928 < 0.001 2.523 1.168–4.760 < 0.001 Site of recurrence (different lobe) 1.407 0.986–2.324 0.112 1.345 0.812–1.983 0.220 Operative method (RH + RFA) 1.103 0.680–1.873 0.576 0.987 0.770–1.523 0.874 N number, M male, HBsAg hepatitis B surface antigen, BCLC Barcelona clinic liver cancer, MVI microvascular invasion, HBV DNA hepatitis B virus deoxyribonucleic acid, AFP alpha-fetoprotein, IM intrahepatic metastasis, RH repeat hepatectomy, RFA radiofrequency ablation, HR hazard ratio, CI confidence interval. Discussion In the future, the treatment of HCC will tend to recurrent HCC due to the characteristic of high recurrence rate. Furthermore, under scheduled supervision after initial hepatic hepatectomy and advancement in imaging technology. Most recurrent HCC was found in the early and multifocal periods, making surgical treatment beneficial in these patients (Chua et al. 2021 ; Meniconi et al. 2015 ), and multifocal HCC at the 2nd resection was not a risk factor (Minagawa et al. 2003 ). Although the overall survival outcome of recurrent HCC after surgical intervention has improved tremendously recently, the optimal treatment for early-stage and multifocal intrahepatic rHCC is still not unifying. Nonsurgical treatment methods, such as TACE and systemic therapies are usually proposed for the treatment of recurrent HCC because of late tumor stage or insufficient preserved liver function (Poon et al. 2002; Tabrizian et al. 2015 ). However, for early-stage recurrent HCC, nonsurgical therapeutic effect is far lower than that of surgical treatment. The median survival time for recurrent patients treated with TACE was 19 months, and that for patients treated with sorafenib was 9.9 months (Tabrizian et al. 2015 ). SLT is the best theoretical solutions to treat both the tumor and the underlying hepatic disease for recurrent HCC fulfilling the Milan criteria (Chan et al. 2013 ). However, the shortage of organ donors, strict screening criteria of patients, and well-preserved liver function often relegate patients with recurrent HCC to the lowest priority to receive a graft before the disease progressing. In addition, taking into account the relatively low preoperative MELD score, outcomes for transplant must be reported on an intention-to-treat basis (Llovet, Fuster, and Bruix 1999 ). RH could attain similar survival outcomes as the first resection in selected patients. Meanwhile, RFA is recommended as a curative treatment, which is applicable in selected patients with two or three nodules ≤ 3 cm and with borderline liver function. Previous analyses revealed that RH and RFA were both effective treatments for early-stage recurrent HCC, and 5-year survival after RH was from 31–56% (Minagawa et al. 2003 ; Chan et al. 2013 ; Poon et al. 1999 ; Tralhão et al. 2007 ; Wang et al. 2015 ) and after RFA was from 37–45.4% (Xia et al. 2020 ; Liang et al. 2008 ; Wang et al. 2015 ), suggesting that excellent outcome could be present in selected patients with recurrent HCC. However, controversies have been seen in previous studies. On account of benefits in long-term survival outcome, others showed that the tumor might remain partially active after ablation, causing a higher local recurrence rate with the increase of tumor size (Sofocleous et al. 2012; Li et al. 2012 ). Since RH is sometimes inadequate for patients with poor liver function, multiple lesions and insufficient residual liver volume, and not all recurrent early-stage tumors are good candidates for RFA because some tumors are on the liver surface or near large vessels or critical organs. Therefore, it would be better to recognize RH and RFA as complementary treatment modalities rather than totally competitive modalities. In this regard, to overcome the limitations of each when used alone, we compared the long-term outcomes of patients with multifocal rHCC meeting the Milan criteria with RH and RH combined with intraoperative RFA. This combined treatment has been proven to be reliable and advantageous in initial resection of early-middle-stage multifocal HCC (Huang et al. 2020 ). Although many studies of recurrent HCC meeting the Milan criteria have been carried out (Wang et al. 2015 ), few of them referred to the combination means of multifocal rHCC meeting the Milan criteria. For such patients, treatment courses are determined by various clinical factors of the initial surgery. Therefore, we collected some important clinical characteristics of patients with HCC for the initial resection (Table 2 ), including tumor clinical stage, intraoperative circumstances and pathological results, which revealed no significant differences at the initial resection between the two groups. Meanwhile, PSM was performed to reduce the influence of confounding factors. Ultimately, we obtained statistical consistency from the data of demographic characteristics, laboratory evaluation and tumor-related information. Repeat hepatectomy is more complicated than initial resection because of the progression of hepatitis, the presence of adhesions and anatomical modifications by previous operations (Kawano et al. 2009 ; Shimada et al. 1996 ). Abdominal adhesion was present in 29 of the 43 patients in the combination group and 39 of the 66 patients in the RH group. Neovascular structures and ambiguous anatomy resulted in an unplanned increase in intraoperative blood transfusion, operation time, risk of bowl injury and perioperative complications. As shown in Table 3 , there was a significantly shorter operation time, less intraoperative blood loss, and a lower rate of major complications in the combination group than in the RH group. Major complications were mainly postoperative bleeding, liver dysfunction and bile leak, which mainly arose in the RH groups, probably due to limitations of RH in the treatment of tumors with special locations (Vitale et al. 2017 ). For example, a tumor located near critical structures receives RH, which frequently brings about large areas of parenchymal transection, subsequently prolonged operation time, increased blood loss and, inherently increased incidence of major complications. Our results of the combination therapy are consistent with findings of recently published studies of RFA with less trauma in treating recurrent HCC (Feng et al. 2020 ; Chua et al. 2021 ). No deaths occurred within 30 days after surgery, which may be attributed to rigorous preoperative evaluation of liver reserve function and appropriate postoperative management. Hepatectomy combined with RFA has the advantage of less surgical trauma on the premise of ensuring a favorable survival outcome, as for the particularity of recurrent multifocal HCCs mentioned above, RH combined with RFA is a complementary means theoretically. However, relevant studies only concentrated on recurrent single tumors or did not provide a targeted exploration of multifocal rHCC meeting the Milan criteria (Chan et al. 2013 ; Chen et al. 2020 ; Wang et al. 2015 ). Our study indicated that there was no difference in rOS and rRFS between patients treated with RH combined with RFA and RH alone. To reduce the bias resulting from the surgeon's choice of surgical method during the procedure as much as possible, we performed PSM to produce similar results in terms of tumor location, number and largest tumor size, which were significantly different before PSM. The outcomes of the two groups were also compared in subgroup analyses. We investigated the effectiveness of tumor number for recurrent multifocal tumors on postoperative survival after RH + RFA and RH alone. The combination group and the RH group had similar rOS and rRFS rates in patients with two recurrent tumors (Fig. 3 A, B), which is different from our previous results of initial resection for early-middle-stage multifocal HCC (Huang et al. 2020 ). One reason is that we narrowed the tumor criteria from the University of California San Francisco (UCSF) criteria to the Milan criteria. Tumor size is an important risk factor for survival outcome of patients with HCC. The other reason may be that the extent of resection of the recurrent tumor was smaller than that of the initial resection when considering the residual liver volume. Moreover, for patients with three recurrent tumors, no significant difference existed in either rOS or rRFS after RH + RFA and RH alone (Fig. 3 C, D). The potential explanation is that the number of recurrent tumors played a dominant role in effecting patients’ prognosis. Further subgroup analysis of the anatomic location of tumors was performed according to Couinaud’s segmentation. In the subgroup of tumors located in the same lobe, RH provided better rRFS than RH combined with RFA for patients with all lesions in the same lobe (Fig. 4 B), but in the subgroup of tumors located in different lobes, the difference of rRFS was eliminated between the two groups (Fig. 4 D). There are several reasons that could account for this phenomenon. First, 30 patients (88.2%) in the RH subgroup of tumors located in the same lobe underwent en bloc resection, which removed more nonneoplastic liver parenchyma closer to anatomical resection than the combination subgroup. Second, it was possibly attributable to frequent presence of microlesions that would likely have been resected following an en bloc resection in RH groups, not in combination group because some microlesions may grow slowly, especially in less biologically aggressive tumors (Roayaie et al. 2011 ). In other words, recurrent tumors may not be completely controlled by RFA. Third, if tumors were located in different lobes, theoretically, there would be more intrahepatic metastases in the wider liver region, thus causing no significant difference in either rOS or rRFS in the subgroup of tumors located in the different lobes. Time to recurrence ≤ 2, also called early recurrence (ER), and IM pathologically were identified as two risk factors in multivariate Cox model analyses. Many studies have clearly demonstrated that patients with ER had significantly worse survival than those with late recurrence (LR) after the second surgery (Imamura et al. 2003 ; Liang et al. 2008 ). Intrahepatic metastasis (IM), characterized by ER, is associated with more aggressive tumor behavior, whereas LR is more likely to be associated with MO with a beneficial survival outcome. The diagnosis of IM and MO is mainly based on histopathological findings as reported by the Liver Cancer Study Group of Japan with modifications. Although it is relatively subjective, it is still the most convenient and effective clinical identification method. In our study, 29 patients (67.4%) were defined as IM in the combination group, and 38 patients (57.6%) were defined as IM in the RH group. The difference in tumor biological behavior between IM and MO leads to the different prognosis (Imamura et al. 2003 ; Xu et al. 2019 ). We can also explain that the IM cases might be a consequence of the so-called recurrent multifocal HCC from clinically latent multiple intrahepatic metastases, which might have already been present at the time of initial surgery. In other words, these cases might be “latent Stage IV” at the time of initial surgery, mistaken for recurrence at the next operation. The major limitations were the following: First, it was a single-center retrospective study, and the outcomes of both RH and RFA partly depend on the expertise and experience of the operators. Second, we failed to consider the effects of different antiviral drugs that were associated with tumor recurrence during the follow-up periods. It was difficult to balance and adjust them between the two groups in this retrospective study. Finally, the chief among these is that the study spans a period of more than 10 years, during which HCC treatment has changed significantly. We have witnessed the development of comprehensive therapy for HCC. Despite its limitations, our study does provide some valuable references that can aid clinicians in confronting patients with early-stage multifocal rHCC. In conclusion, both RH combined with RFA and RH alone are safe and can achieve similar excellent results in selected patients with multifocal rHCCs meeting the Milan criteria, but RH combined with RFA had a relatively shorter operative time and fewer postoperative major complications. Moreover, RH may be more suitable for patients whose tumors are located in the same lobe because of better rRFS. How to treat these patients with a optimal means still worth looking forward to. Declarations Founding This work was supported by grants from the National Natural Science Foundation of China (81400636), Sichuan Province Key Research and Development Project (2019YFS0203), Key Clinical Research Incubation Project of West China Hospital of Sichuan University (2020HXFH028), and the Key R&D Support Plan of Chengdu Science and Technology Bureau (2021-YF05-00703-SN). Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author Contributions All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Yang Huang and Min Huang. The first draft of the manuscript was written by Yang Huang, Liangliang Xu. Mingqing Xu and Li Jiang conducted and corrected previous versions of the manuscript. All authors read and approved the final manuscript. 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'Risk Factors, Patterns, and Outcomes of Late Recurrence After Liver Resection for Hepatocellular Carcinoma: A Multicenter Study From China', JAMA Surg, 154: 209–17. Yang, D., B. Zhuang, Y. Wang, X. Xie, and X. Xie. 2020. 'Radiofrequency ablation versus hepatic resection for recurrent hepatocellular carcinoma: an updated meta-analysis', BMC Gastroenterol, 20: 402. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1702329","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":109470118,"identity":"c5658c45-f580-40bf-9755-09d702238500","order_by":0,"name":"Yang Huang","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Huang","suffix":""},{"id":109470119,"identity":"3cebe4dd-baa3-4268-b98f-64a7ce5cd645","order_by":1,"name":"Liangliang Xu","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Liangliang","middleName":"","lastName":"Xu","suffix":""},{"id":109470120,"identity":"3107459e-2050-4e2d-8163-75d8e3473800","order_by":2,"name":"Min Huang","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Min","middleName":"","lastName":"Huang","suffix":""},{"id":109470121,"identity":"54698dc4-3903-4c15-bc81-4ff87d6d206e","order_by":3,"name":"Li Jiang","email":"","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Jiang","suffix":""},{"id":109470122,"identity":"b63df256-b31e-44c1-9aa7-b1fcb242fade","order_by":4,"name":"Mingqing Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3klEQVRIiWNgGAWjYFADCcYGBoYKCTl5ojVAtJyxMDZsIF4LkGRsq0hkOEBAqcG1wxuYeSrq6vhnN7c9+DlPIoGxgfnhoxt4tEjOTitg5jlzWELizsF2w95tEnnsDGzGxjl4tPBL5xgw57YdkDCQSGyT4N0mUczYwMMmjU8LG1jLvzqwFsm/cyQSGw4Q0AKxpYEZrEWat4EILWC//Dl2WHLGDaAWmWMSxobNBPxicDt5A+OMmjp+/hnpzyTf1NTJybM3P3yMTwsQmP9A5TPjVw62iLCSUTAKRsEoGNkAAG2AQ/X5kGzqAAAAAElFTkSuQmCC","orcid":"","institution":"West China Hospital of Sichuan University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Mingqing","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2022-05-28 09:44:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1702329/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1702329/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22136911,"identity":"c26cfccd-e74b-4624-804c-4b2133a003bc","added_by":"auto","created_at":"2022-06-01 16:04:30","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":230604,"visible":true,"origin":"","legend":"\u003cp\u003eFlow of study participants. HCC hepatocellular carcinoma, HR hepatic resection, RFA radiofrequency ablation, RH repeat hepatectomy\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1702329/v1/e9fef7bf0014fadf65525142.jpg"},{"id":22136910,"identity":"38dd6e96-18fb-44ce-ab1d-81d83a5852c7","added_by":"auto","created_at":"2022-06-01 16:04:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":652559,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Overall survival after recurrence and (B) recurrence-free survival rates after recurrence for all study patients who underwent RH combined with RFA or RH alone. (C) Overall survival after recurrence and (D) recurrence-free survival rates after recurrence for propensity-matched patients who underwent RH combined with RFA or RH alone. RH repeat hepatectomy, RFA radiofrequency ablation\u003c/p\u003e","description":"","filename":"figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-1702329/v1/69357c367496405de4d6cb95.png"},{"id":22136913,"identity":"a031bb58-512b-4ef9-a359-bb03b3376ccc","added_by":"auto","created_at":"2022-06-01 16:04:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":608255,"visible":true,"origin":"","legend":"\u003cp\u003e(A)\u003cstrong\u003e \u003c/strong\u003eOverall survival after recurrence and (B) recurrence-free survival after recurrence of patients with two tumors who underwent RH combined with RFA or RH alone. (C) Overall survival after recurrence and (D) recurrence-free survival after recurrence of patients with three tumors who underwent RH combined with RFA or RH alone. RH repeat hepatectomy, RFA radiofrequency ablation\u003c/p\u003e","description":"","filename":"figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-1702329/v1/acab434f0090b6ce5fe4c41e.png"},{"id":22137279,"identity":"ea86df2b-e6c2-47aa-abdd-6cd43d92d6b6","added_by":"auto","created_at":"2022-06-01 16:09:30","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":626865,"visible":true,"origin":"","legend":"\u003cp\u003e(A)\u003cstrong\u003e \u003c/strong\u003eOverall survival after recurrence and (B) recurrence-free survival after recurrence of patients with tumors located in same lobe who underwent RH combined with RFA or RH alone. (C) Overall survival after recurrence and (D) recurrence-free survival after recurrence of patients with tumors located in different lobe who underwent RH combined with RFA or RH alone. RH repeat hepatectomy, RFA radiofrequency ablation\u003c/p\u003e","description":"","filename":"figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-1702329/v1/017cfc0ecd27f1e7f6f3af4f.png"},{"id":22137305,"identity":"aa7a8377-f1a0-43c6-a446-378f882d994b","added_by":"auto","created_at":"2022-06-01 16:09:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1294952,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1702329/v1/e90afbc4-f960-4d37-a285-61f0a9312ed9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Repeat Hepatic Resection Combined with Intraoperative Radiofrequency Ablation Versus Repeat Hepatic Resection Alone for Recurrent and Mutiple Hepatocellular Carcinoma Patients Meeting the Milan Criteria: A Propensity Score-Matched Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHCC is one of the most common primary malignancies of the liver and is the third leading cause of cancer-related death worldwide (Bray et al. \u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e2018\u003c/span\u003e; Li et al. \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e2022\u003c/span\u003e). At present, partial hepatectomy is the recommended first-line treatment for primary HCC, where curative treatment is deemed possible(Chang et al. \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e2016\u003c/span\u003e). Nevertheless, the postoperative tumor recurrence rate is not acceptable; the 5-year recurrence rate is 60\u0026ndash;80% following primary resection with curative intent, and 80\u0026ndash;95% of recurrences are confined to the remnant liver (Huang et al. \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Fan et al. \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e2011\u003c/span\u003e; 'EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma' 2012; Bruix and Sherman \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). Future treatment for HCC will mainly focus on recurrent hepatocellular carcinoma (rHCC). Many studies have deemed that 5-year survival after RH resembles that after initial hepatectomy (Choi et al. \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2008\u003c/span\u003e; Chan et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Xia et al. \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). However, guidelines for the management of early-stage rHCC remain controversial and poorly defined.\u003c/p\u003e \u003cp\u003eImprovements in recurrence surveillance and medical imaging have led to the diagnosis of rHCC at an early stage when various treatments may still be available. rHCC usually originates from intrahepatic metastasis (IM) or multicentric occurrence (MO) (Dong et al. \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). IM refers to HCC foci developing from tumor cells that have spread into the remnant liver via the portal vein before or during hepatic resection, usually occurring early. MO refers to new HCC foci developing due to the existence of chronic active hepatitis, cirrhosis, or other HCC-relevant risk factors after resection, appearing later. Most studies regard the 2-year recurrence interval as the critical value of early recurrence and late recurrence, which indicates that the clinical progression and outcomes of these two types of recurrence are significantly different(Imamura et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2003\u003c/span\u003e; Wu et al. \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Lu et al. \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Xu et al. \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2019\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMost early-stage rHCC patients can benefit from surgical intervention on the premise of good liver function. The therapeutic principles used for rHCC are essentially the same as those used for primary HCC (Tabrizian et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). In that way, the mainstay treatments of early-stage rHCC include salvage liver transplantation (SLT), RH, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), or systemic treatment using targeted therapy or chemotherapy. SLT is the most beneficial option, but it is of limited use in regions with liver donor shortages and disease progression on waiting lists (Poon et al. 2002). TACE combined with systemic treatment was managed for patients who had poor general performance and liver function, severe cirrhosis and unresectable conditions (size, number, and location of rHCC). RFA and RH are the next-most efficacious treatment options for early-stage rHCC. Many studies have shown that the long-term survival outcome of resection is similar to that of radiofrequency therapy for early-stage single recurrent hepatocellular (Chan et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Liang et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2008\u003c/span\u003e; Song et al. \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Xia et al. \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Erridge et al. \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2017\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCurrently, many centers use RH as the first-line treatment for rHCC and have claimed that it is preferable because its survival benefit is acceptable (Chan et al. \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e2012\u003c/span\u003e; Chua et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Unfortunately, RH can be carried out only in rHCC patients within 13.4\u0026ndash;22.9% because of poor liver function and multiple intrahepatic recurrence (Karabulut et al. \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). RFA is now the new first-line locoregional treatment due to its therapeutic effectiveness, stable safety and minimal liver damage. Some studies have shown that RFA was as effective as RH in the treatment of small rHCC (\u0026le;\u0026thinsp;3 cm in diameter) in terms of long-term survival outcome (Song et al. \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e2015\u003c/span\u003e; Yang et al. \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). In addition, RFA had advantages over RH in terms of lower mortality and compilation rates (Feng et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, most studies focused on early-stage single rHCC, and there have been no reports published in the medical literature comparing the efficacy of RH and/or RFA for early-stage multifocal rHCC. Whether RH combined with RFA could make up for the vacancy that could not be achieved by RH alone in the treatment of early-stage multifocal rHCC. The aim of this retrospective study was to compare the outcomes of patients with multifocal rHCC meeting the Milan criteria (2\u0026ndash;3 nodules, each \u0026le;\u0026thinsp;3 cm in diameter without vascular invasion or extrahepatic metastases) after RH combined with intraoperative RFA or RH alone. Meanwhile, to compare the differences between the two surgical methods, prognostic factors and subgroup analyses were performed.\u003c/p\u003e"},{"header":"Method","content":"\u003cp\u003e This present study was designed as a retrospective review, approved by the West China Hospital Ethics Committee, and conducted in accordance with the ethical guidelines of the Declaration of Helsinki.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eA total of 3542 patients with HCC underwent curative hepatectomy (i.e., R0/R1 resection) from May 2008 to July 2018 at the Department of Hepato-Biliary-Pancreatic Surgery, West China Hospital, Sichuan University. In all, 2197 patients subsequently suffered tumor recurrence from April 2010 to May 2020, and 237 patients who underwent nonsurgical treatments such as TACE and anti-tumor drug therapy after initial resection and before the first recurrence were excluded. Meanwhile, 576 patients who received the above nonsurgical treatments after the first recurrence were also excluded. Then, 1017 patients with single recurrent tumor or not up to the Milan criteria were excluded. Next, 246 patients who were combined with other therapies, such as SLT and tyrosine kinase inhibitor administration, as well as 12 patients who were lost to follow-up, were excluded. Finally, a consecutive series of 109 patients conforming to inclusion criteria were finally enrolled in this study. They were divided into two groups according to surgical procedures: the combination group (n\u0026thinsp;=\u0026thinsp;43), which consisted of those who underwent open RH combined with RFA, and the RH group (n\u0026thinsp;=\u0026thinsp;66), which consisted of those patients who underwent open HR alone (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The follow-up data were updated in January 2021 or until death.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003ePreoperative Evaluation\u003c/h2\u003e \u003cp\u003eHepatologists, surgeons and radiologists jointly participated in the preoperative evaluation. The potential for resection was evaluated by ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Liver function was assessed by a combination of Child\u0026ndash;Pugh score, liver biochemistry, and indocyanine green test. RH was undertaken in the presence of endurable cardiopulmonary and renal function, Child\u0026ndash;Pugh grade A or B, which could be returned to Child\u0026ndash;Pugh grade A by routine treatment, and a normal indocyanine green test at 15 min. Every patient enrolled in this study followed the following criteria: 1. Multiple intrahepatic recurrence of HCC after initial hepatectomy. 2. Received no treatment except for the initial hepatectomy. 3. Number of recurrent tumors\u0026thinsp;\u0026le;\u0026thinsp;3 with the largest tumor\u0026thinsp;\u0026le;\u0026thinsp;3 cm in diameter. 4. No radiologic evidence of invasion into major portal/hepatic vein branches. 5. There were no extrahepatic metastases, severe liver dysfunction, or significant coagulopathy (prothrombin activity\u0026thinsp;\u0026lt;\u0026thinsp;40%, platelet count\u0026thinsp;\u0026lt;\u0026thinsp;40\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L). 6. There was no history of encephalopathy, refractory ascites or variceal bleeding.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eTreatments\u003c/h2\u003e \u003cp\u003eThe treatment scheme used for early-stage multifocal rHCC was essentially the same as that used for primary multifocal HCC with a small modification in liver function requirement. RH was assigned when there was the possibility for the complete removal of all tumors while retaining a sufficient remnant liver volume. On the basis of well-preserved liver function, if ICG-R15 is less than 10%, anatomical extended hepatectomy is permitted. For lesions\u0026thinsp;\u0026le;\u0026thinsp;3 cm in diameter, RFA was also deemed to be the radical therapeutic method. In addition, the reasons for performing intraoperative RFA include insufficient remnant volume, deep location in liver parenchyma and distant anatomical location between tumors. However, RFA is sometimes inadequate for lesions on the liver surface or near large vessels. Otherwise, other factors affecting the treatment choice come from the experience and skills of the surgeon. Significant adhesions and ambiguous anatomical structures increase the difficulty of RH and the uncertainty of RFA. All treatments were reported to the patients or their relatives, and written informed consent was obtained.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eSurgical Procedure\u003c/h2\u003e \u003cp\u003eAll operations were performed using the open approach, starting with an exploration, separating the adhesions caused by the initial operation thereafter. Intraoperative ultrasound was routinely performed to assess the tumor burden, the liver remnant, and the possibility of a negative resection margin. Parenchyma transection was carried out using a Cavitron Ultrasonic Surgical Aspiration (CUSA; Valleylab Corporation, Boulder, CO, USA) or clamping crush. The Pringle manoeuvre was routinely performed with a 15-min occlusion and 5-min reperfusion cycle when necessary. Experienced ultrasound doctors and surgeons should jointly locate the tumor by conventional ultrasound or contrast-enhanced ultrasonography (CEUS). A Cool-tip RFA system (Valleylab Corporation) was used for ablation. The numbers of overlapping ablations and ablation points were determined by the number and size of tumors. After completing the RFA procedure, we cauterized the electrode path to avoid bleeding and track seeding of the tumor.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eDiagnostic criteria and definitions\u003c/h2\u003e \u003cp\u003eThe clinical diagnosis of HCC at both its initial and recurrent stages was based on the criteria of the American Association for the Study of Liver Diseases (AASLD) (Bruix and Sherman \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). The diagnosis of recurrent HCC was confirmed by histopathology for resection. Some suspicious lesions were pathologically confirmed by ultrasound-guided biopsy for RFA. The presence of adhesions was defined when extensive adhesiolysis was necessary during surgery (Chua et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). Curative resection was defined as complete resection of all macroscopically detectable tumors with histological tumor-free margins along the parenchymal transection line.\u003c/p\u003e \u003cp\u003eComplete RFA ablation was defined as an area equal to or larger than the ablated tumor without contrast enhancement after the RFA procedure at 1 month.\u003c/p\u003e \u003cp\u003eMoreover, based on Couinaud\u0026rsquo;s segmentation, the right lobe of the liver is composed of segments V, VI, VII, and VIII, while the left lobe of the liver is composed of segments II, III, and IV (Pang \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2002\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e According to the Liver Cancer Study Group of Japan with modifications (Matsuda et al. \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2001\u003c/span\u003e). Multicentric occurrence (MO) was diagnosed when the resected recurrent tumors met one of the following modified criteria: 1. The recurrent tumor consists of well-differentiated HCC only; 2. The recurrent tumor has precancerous lesions or well-differentiated HCC around the less differentiated HCC and shows a \u0026lsquo;\u0026lsquo;nodule-in-nodule\u0026rsquo;\u0026rsquo; form; 3. All components of recurrent HCC show higher differentiation than the primary resected tumors. Recurrent HCC showing either the same or less differentiation than the primary resected tumors was diagnosed as intrahepatic metastasis (IM).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eFollow-up\u003c/h2\u003e \u003cp\u003eIn both groups, enhanced CT was conducted one month after the treatment to evaluate whether the tumor was completely controlled. Thereafter, ultrasonography was carried out in the outpatient clinic once every 2 months within the first 2 years and then once every 3 months thereafter, while the CT scan was performed every 6 months. At each follow-up session, blood tests, serum liver function tests and AFP, as well as MRI or CEUS, if necessary, were carried out. Regardless of the serum HBV deoxyribonucleic acid, all patients with hepatitis-related HCC in our hospital were consulted by a hepatologist for antiviral therapy. Once the second recurrence was confirmed, patients were treated with third resection, re-RFA, TACE, sLT, or anti-tumor drugs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eCategorical variables are expressed as numbers and percentages (%), and continuous variables are expressed as medians (ranges). Univariate analysis was performed to use Student\u0026rsquo;s t test or the Mann\u0026ndash;Whitney U test, Chi-square test or Fisher\u0026rsquo;s exact test, as appropriate. rOS was defined as the period from the date of RH or RH\u0026thinsp;+\u0026thinsp;RFA to the date of death or the last follow-up until May 2021. rRFS was defined as the interval between the date of RH or RH\u0026thinsp;+\u0026thinsp;RFA and the date of second recurrence when medical tests confirmed. The rOS and rRFS rates were measured by using the Kaplan\u0026ndash;Meier method and compared by using the log-rank test. The relative prognostic significance of the variables in predicting survival was assessed by Cox proportional hazards regression analysis.\u003c/p\u003e \u003cp\u003eTo minimize confounding bias between RH group and combination group, a 1:1 matching method using propensity score was performed by R software (Version 2.12x). All tests for differences were two-tailed, and p values were considered statistically significant when the associated probability was less than 0.05. Statistical analysis was performed using the SPSS software program (Version 20).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv class=\"Section2\" id=\"Sec11\"\u003e\n \u003ch2\u003eBaseline Data at Recurrence\u003c/h2\u003e\n \u003cp\u003eThe demographic characteristics of the pre- and post-PSM cohorts are summarized in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Before PSM, the number of patients who underwent RH combined with RFA and RH alone was 43 and 66, respectively. Among them, 39 (90.7%) were male, and the mean age was 54.28 years (range, 31\u0026ndash;78 years) in the combination group, while 54 (81.8%) were male, and the mean age was 56.23 years (range, 27\u0026ndash;85 years) in the RH group. Hepatitis B positive was detected in 38 patients (88.4%) and 56 patients (84.8%) in the combination and RH group, respectively. ICG-R15\u0026thinsp;\u0026lt;\u0026thinsp;10% was tested in 36 patients (83.7%) and 55 patients (83.3%) in the combination and RH group, respectively. While 40 patients (93.0%) and 55 patients (93.9%) in the combination and RH group, respectively, had Child\u0026rsquo;s A liver function. Other indicators, such as HBV DNA\u0026thinsp;\u0026ge;\u0026thinsp;1000 IU/mL, serum AFP\u0026thinsp;\u0026ge;\u0026thinsp;100 ng/mL, total bilirubin, ALT, AST, albumin, prothrombin time, platelet count, total tumor size, and time to recurrence\u0026thinsp;\u0026le;\u0026thinsp;2 y, revealed no significant difference between the two groups. However, more patients in RH group had two tumors than patients in combination group (p\u0026thinsp;=\u0026thinsp;0.034), the largest tumor size was larger in combination group than in RH group (p\u0026thinsp;=\u0026thinsp;0.026), and more patients in combination group had tumors located in the different lobes than patients in RH group (p\u0026thinsp;=\u0026thinsp;0.049). The above parameters revealed no significant difference between the two groups after PSM.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab1\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eBaseline characteristics of HCC patients with recurrent and mutifocal tumors meeting the Milan criteria at the time of recurrence\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eBefore propensity matching\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eAfter propensity matching\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCombination\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;43)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRH alone\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCombination\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRH alone\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge, years, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52(31\u0026ndash;78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56(27\u0026ndash;85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52(31\u0026ndash;78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54(27\u0026ndash;79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.871\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(90.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54(81.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33(89.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(91.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eUderlying liver disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBV, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38(88.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56(84.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.602\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(97.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(86.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.199\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHCV, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(12.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.938\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.358\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBV DNA\u0026thinsp;\u0026ge;\u0026thinsp;1000, IU/mL, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.302\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSerum AFP\u0026thinsp;\u0026ge;\u0026thinsp;100, ng/mL, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(32.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(30.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.804\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal bilirubin level, umol/L, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.5(5.9\u0026ndash;28.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.1(6.1\u0026ndash;30.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.552\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.6(5.9\u0026ndash;28.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.9(7-30.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.611\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eALT level, IU/L, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30(9\u0026ndash;79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(6-152)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30(9\u0026ndash;79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30(8\u0026ndash;71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.634\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAST level, IU/L, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(16\u0026ndash;70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(14\u0026ndash;157)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.322\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(18\u0026ndash;70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(15\u0026ndash;88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.957\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSerum albumin, g/L, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.6(31.8\u0026ndash;52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.4(32.5\u0026ndash;51.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.6(31.8\u0026ndash;52.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43.6(38.2\u0026ndash;51.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.294\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProthrombin time, s, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.8(10.1\u0026ndash;17.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.9(10.3\u0026ndash;14.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.598\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.7(10.2\u0026ndash;14.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.1(10.3\u0026ndash;14.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.176\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlatelet count, 10\u003csup\u003e9\u003c/sup\u003e /L, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e105(64\u0026ndash;310)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e119.5(60\u0026ndash;238)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.422\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e105(64\u0026ndash;218)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e108(60\u0026ndash;194)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.970\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChild - Pugh class A, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42(97.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64(97.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35(94.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e35(94.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eICG-R15\u0026thinsp;\u0026lt;\u0026thinsp;10%, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36(83.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55(83.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.958\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(86.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33(89.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients with two tumors, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(51.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e47(71.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20(54.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(70.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.150\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLargest tumor size, cm, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7(1.4-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4(1.1-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.7(1.4-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.4(1.2-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal tumor size, cm, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.9(2.2-8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8(2.1\u0026ndash;7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.665\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8(2.5-8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8(2.1\u0026ndash;7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.897\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime to recurrence\u0026thinsp;\u0026le;\u0026thinsp;2y, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19(44.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(48.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.660\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(40.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.469\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLocated the different lobe, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(65.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(34.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.049\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(62.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(43.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.103\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eHCC\u003c/em\u003e hepatocellular carcinoma, \u003cem\u003eRH\u003c/em\u003e repeat hepatectomy, \u003cem\u003eSD\u003c/em\u003e standard deviation, \u003cem\u003eHBV\u003c/em\u003e hepatitis B virus, \u003cem\u003eHCV\u003c/em\u003e hepatitis C virus, \u003cem\u003eHBV DNA\u003c/em\u003e hepatitis B virus deoxyribonucleic acid, \u003cem\u003eAFP\u003c/em\u003e a-fetoprotein, \u003cem\u003eALT\u003c/em\u003e alanine aminotransferase, \u003cem\u003eAST\u003c/em\u003e aspartate aminotransferase, \u003cem\u003eICG-R15\u003c/em\u003e indocyanine green retention rate at 15 min\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec12\"\u003e\n \u003ch2\u003eClinicopathologic and Operative Data at Initial Resection\u003c/h2\u003e\n \u003cp\u003eAs shown in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, the two groups were similar in the number of cases with AFP\u0026thinsp;\u0026ge;\u0026thinsp;400 ng/ml, Child\u0026ndash;Pugh class A, BCLC stage, major tumor size and tumor number at their initial hepatectomy. The postoperative pathological results showed no significant differences in complete tumor capsule present, vascular invasion, satellites present, tumor grade, liver cirrhosis present, Ishak score, or resected margin positive present between the two groups. Blood loss, number of intraoperative blood transfusion and major resections during the initial resection were comparable between the two groups.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab2\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical characteristics of patients with HCC for the initial resection\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCombination (n\u0026thinsp;=\u0026thinsp;43)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHR alone (n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSerum AFP\u0026thinsp;\u0026ge;\u0026thinsp;400ng/ml, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(20.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.972\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMajor tumor size, cm, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5(1.6\u0026ndash;14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.8(1\u0026ndash;12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.076\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTumor number, solitary, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(74.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56(84.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.177\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComplete tumor capsule present, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(48.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30(45.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.729\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eVascular invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMicro, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24(55.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(51.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMacro, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.660\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSatellites present, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(30.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(21.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.286\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eTumor grade, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(53.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(48.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.610\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG3-G4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(41.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31(47.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.600\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLiver cirrhosis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (48.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31(47.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.849\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIshak score, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(2\u0026ndash;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(1\u0026ndash;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.878\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eResected margin positivity, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.394\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eBCLC stage, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0-A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31(72.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55(83.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.160\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(20.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEstimated blood loss, ml, median (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e305(35-2100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e260(30-1980)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.194\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntraoperative blood transfusion, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(14.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.163\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtent of liver resection (Major), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(23.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(15.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.285\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cem\u003eHCC\u003c/em\u003e hepatocellular carcinoma, \u003cem\u003eHR\u003c/em\u003e hepatic resection, \u003cem\u003eRFA\u003c/em\u003e radiofrequency ablation, \u003cem\u003eAFP\u003c/em\u003e alpha-fetoprotein\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec13\"\u003e\n \u003ch2\u003eOperative and Postoperative Data of Second Surgery\u003c/h2\u003e\n \u003cp\u003eThere was no significant difference in the types of excision between the two groups (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). Patients in RH group had a longer duration of operation than patients in combination group (before PSM: p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; after PSM: p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The RH group had more patients with intraoperative blood loss of 501\u0026ndash;1000 ml than the combination group (p\u0026thinsp;=\u0026thinsp;0.034), and the opposite was true for blood loss of \u0026le;\u0026thinsp;200 ml (p\u0026thinsp;=\u0026thinsp;0.042) for all populations. These differences were disappeared after PSM. There were no significant differences in the percentage of patients who received intraoperative blood transfusions or new tumors found by intraoperative ultrasound between the two groups before and after PSM.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab3\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eOperative and postoperative data of HCC patients with recurrent and mutiple tumors meeting the Milan criteria at the time of recurrence\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eBefore propensity matching\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eAfter propensity matching\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCombination\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;43)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHR alone\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;66)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCombination\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHR alone\u003c/p\u003e\n \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eType of excision\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAll tumors en bloc resection, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34(51.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(59.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLocal resection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38(88.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51(77.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.391\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(86.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(67.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.090\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHemi-hepatectomy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(9.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(15.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.372\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.152\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExtended resection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.400\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.358\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOperation time, h, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.4(3.7\u0026ndash;6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.9(4.4\u0026ndash;6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.3(3.7\u0026ndash;6.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.0(4.6\u0026ndash;6.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003eEstimated blood loss, mL\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le; 200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(20.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(7.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.042\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.479\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e201\u0026ndash;500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(62.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e32(48.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25(67.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18(48.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.099\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e501\u0026ndash;1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(16.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23(34.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026ge;\u0026thinsp;1000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(9.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.240\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAdhesions present, n(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29(67.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39(59.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24(64.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22(59.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.632\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntraoperative blood transfusion, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(16.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.468\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.711\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNew tumor found by intraoperative ultrasound, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(5.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(7.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.703\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.528\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eData of resected tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eResected tumor number, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58(54.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e151(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51(56.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eResected tumor size, cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5(0.5-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(0.5-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.6(0.5-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.2(0.5-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.113\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgical margin for resected tumor, cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1.5\u0026ndash;2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.75(1-2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(1.5\u0026ndash;2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.75(1-2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.213\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eResected margin positivity, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0(0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMicrovascular invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(29.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(17.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.070\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12(32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.806\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLiver cirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30(69.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e37(56.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27(73.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(56.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.144\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIshak score, median(range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(2\u0026ndash;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(2\u0026ndash;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.155\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(2\u0026ndash;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(3\u0026ndash;6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.243\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003eTumor grade of resected tumor, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(6.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.656\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(5.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38(65.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e103(68.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.710\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33(64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60(70.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.475\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG3-G4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16(27.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40(26.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.873\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(29.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21(24.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.547\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMO pathologically, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(32.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28(42.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.301\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14(37.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.461\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003eData of ablated tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAblated tumor number, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49(45.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40(44.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAblated tumor size, cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2(0.5-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3(0.5-3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLocal tumor control after RFA, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40(100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003eComplication grade, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade Ⅰ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(20.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10(15.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(21.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.772\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade Ⅱ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8(18.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(10.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.236\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.722\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMinor complication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(39.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17(25.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.129\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11(29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.619\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade Ⅲa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5(11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15(22.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.256\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4(10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(16.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.496\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade Ⅲb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(10.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.478\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.304\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade Ⅳa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(4.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3(8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.304\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade Ⅳb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1(2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGrade Ⅴ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMajor complication\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9(20.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26(39.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(18.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13(35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDuration of postoperative hospital stay, day\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(5\u0026ndash;14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(5\u0026ndash;18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6(5\u0026ndash;14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7(5\u0026ndash;17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30-day mortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e---\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eHCC\u003c/em\u003e hepatocellular carcinoma, \u003cem\u003eHR\u003c/em\u003e hepatic resection, \u003cem\u003eMO\u003c/em\u003e multicentric occurrence, \u003cem\u003eIM\u003c/em\u003e intrahepatic metastasis.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/div\u003e\n \u003cp\u003eFor resected tumors, there were 58 and 151 tumors in the RH group and combination group, respectively. Smaller tumors were present in RH group than in combination group in all patients (p\u0026thinsp;=\u0026thinsp;0.022), however, no significant difference was found after PSM. There were also no significant differences in surgical margin, Ishak score, microvascular invasion present, liver cirrhosis present and tumor grade of Edmondson and Steiner between the two groups. For ablated tumors, a total of 48 tumors were ablated in combination group. All tumors undergoing RFA were locally controlled under the certification of CEUS or CT.\u003c/p\u003e\n \u003cp\u003eTreatment-related complications are summarized in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. Complications were reported according to the Clavien\u0026ndash;Dindo grade (Clavien et al. \u003cspan class=\"CitationRef\"\u003e2009\u003c/span\u003e). Minor complications, classified as Clavien\u0026ndash;Dindo grade I or II, were developed in most patients and were similar between the two groups before and after PSM. Major complications were classified as grade III or higher. There were no significant differences among the subgrades of major complications between the two groups before and after PSM. Nevertheless, the RH group had a higher incidence of major complications than the combination group in general (p\u0026thinsp;=\u0026thinsp;0.044). After PSM, the difference was disappeared between the two groups. In addition, no difference was observed between them regarding the duration of postoperative hospital stay before and after PSM. There were no deaths in either group during the perioperative period.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec14\"\u003e\n \u003ch2\u003eLong-Term Survival Analysis\u003c/h2\u003e\n \u003cp\u003eDuring a median follow-up period of 38 months (range 7\u0026ndash;97) for all objects, 27 (62.8%) patients in the combination group and 38 (57.6%) patients in the RH group died, and 28 (65.1%) patients in the combination group and 39 (59.1%) patients in the RH group experienced recurrence. The estimated rOS at 1, 3, and 5 years was 88.4%, 67.6% and 37.5%, respectively, for the patients in the combination group and 92.4%, 75% and 42.1% for the patients in the RH group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eA). The cumulative rRFS at 1, 3, and 5 years was 86%, 44.2% and 26%, respectively, for the patients in the combination group and 86.4%, 47.7% and 29.7% for the patients in the RH group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eB). Neither the rOS nor rRFS was significantly different between the two groups (p\u0026thinsp;=\u0026thinsp;0.699 and p\u0026thinsp;=\u0026thinsp;0.587, respectively).\u003c/p\u003e\n \u003cp\u003eAfter PSM, the estimated rOS at 1, 3, and 5 years was 89.2%, 67.6% and 37.8%, respectively, for matched patients in the combination group and 89.2%, 70% and 43.5% for matched patients in the RH group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eC). The cumulative rRFS at 1, 3, and 5 years was 83.8%, 48.4% and 28.5%, respectively, for matched patients in the combination group and 83.8%, 45.8% and 35% for matched patients in the RH group (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eD). The rOS and rRFS were still not significantly different between the two groups (p\u0026thinsp;=\u0026thinsp;0.550 and p\u0026thinsp;=\u0026thinsp;0.835, respectively).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec15\"\u003e\n \u003ch2\u003eSubgroup Analysis According to Tumor Number\u003c/h2\u003e\n \u003cp\u003eIn the subgroup analyses, the 1-, 3-, and 5-year rOS rates were similar between the combination group and the RH group in patients with two recurrent tumors (90.9%, 68.2% and 54.6% versus 93.6%, 78.9% and 49.9%, respectively; P\u0026thinsp;=\u0026thinsp;0.682) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA). The 1-, 3-, and 5-year rRFS was also similar between the combination group and the RH group in patients with two recurrent tumors (90.9%, 36.6% and 30.5% versus 87.2%, 45.4% and 29.3%, respectively; P\u0026thinsp;=\u0026thinsp;0.692) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eB). Similar results emerged in patients with three recurrent tumors; the 1-, 3-, and 5-year rOS rates were 85.7%, 66.7%, and 21.2% and 89.5%, 66.2%, and 32.6% in the combination group and the RH group, respectively; P\u0026thinsp;=\u0026thinsp;0.642) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eC). The 1-, 3-, and 5-year rRFS rates were 81%, 37.5%, and 20% and 84.2%, 52.9%, and 30.2% in the combination group and the RH group, respectively; P\u0026thinsp;=\u0026thinsp;0.596) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eD).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec16\"\u003e\n \u003ch2\u003eSubgroup Analysis According to Tumors\u0026rsquo; Anatomic Locations\u003c/h2\u003e\n \u003cp\u003eIn the other subgroup analyses, the 1-, 3-, and 5-year rOS rates were similar between the combination group and the RH group in patients with tumors located in the same lobe (86.7%, 70.6% and 42.4% versus 93%, 74.1% and 40.2%, respectively; P\u0026thinsp;=\u0026thinsp;0.948) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eA). However, patients with all lesions in the same lobe who underwent RH had a significantly higher rRFS rate than those who underwent RH\u0026thinsp;+\u0026thinsp;RFA (1-, 3-, and 5-year rRFS rates of 86%, 50.4% and 36.2% versus 73.3%, 35% and 17.5%, respectively; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.045) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eB). Meanwhile, for patients with tumors located in different lobes, there was no significant difference in the 1-, 3-, and 5-year OS rates between the two groups (89.3%, 66.6%, and 35.3% in the combination group vs. 91.3%, 77%, and 45.4% in the RH group, respectively; p\u0026thinsp;=\u0026thinsp;0.840) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eC). Similarly, the 1-, 3-, and 5-year rRFS rates were also similar between the two groups (89.3%, 43.9%, 34.2% and 87%, 41.9%, 19.6%, respectively; p\u0026thinsp;=\u0026thinsp;0.290) (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eD).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv class=\"Section2\" id=\"Sec17\"\u003e\n \u003ch2\u003eRisk-factor Analysis for Survival Outcome\u003c/h2\u003e\n \u003cp\u003eIn univariate analysis, we found that three variables, albumin at recurrence\u0026thinsp;\u0026le;\u0026thinsp;3.5 mg/dl, time to recurrence\u0026thinsp;\u0026le;\u0026thinsp;2 years and IM pathologically, were poor prognostic factors for survival before and after PSM. Variables with p\u0026thinsp;\u0026lt;\u0026thinsp;0.1 in univariate analysis and operative method were included in multivariate analysis, and we found that time to recurrence\u0026thinsp;\u0026le;\u0026thinsp;2 years and IM pathologically were independent risk factors before and after PSM (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003ctable border=\"1\" id=\"Tab4\"\u003e\n \u003ccaption\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eUnivariate and multivariate analysis of prognostic factors for survival\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"3\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eUnivariate analysis\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eBefore propensity matching\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eAfter propensity matching\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex (M)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.015\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.629\u0026ndash;1.854\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.397\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.710\u0026ndash;1.689\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.764\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (\u0026ge;\u0026thinsp;60 y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.875\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.604\u0026ndash;1.328\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.206\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.945\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.453\u0026ndash;1.563\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.535\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBsAg (+)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.131\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.499\u0026ndash;2.564\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.768\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.341\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.782\u0026ndash;1.993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.883\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTumor number at initial resection (n\u0026thinsp;\u0026ge;\u0026thinsp;2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.987\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.526\u0026ndash;2.505\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.487\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.498\u0026ndash;1.536\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.268\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCLC stage at initial resection (stage\u0026thinsp;\u0026ge;\u0026thinsp;B)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.453\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.159\u0026ndash;4.543\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.119\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.421\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.453\u0026ndash;3.879\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.212\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMVI present at initial resection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.913\u0026ndash;1.924\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.300\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.793\u0026ndash;2.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.542\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHBV DNA at recurrence (\u0026ge;\u0026thinsp;1,000 IU/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.178\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.753\u0026ndash;2.077\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.335\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.634\u0026ndash;2.314\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.237\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAFP at recurrence (\u0026ge;\u0026thinsp;100 ng/mL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.216\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.832\u0026ndash;1.821\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.289\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.256\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.689\u0026ndash;1.775\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.456\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlbumin at recurrence (\u0026le;\u0026thinsp;3.5mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.827\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.046\u0026ndash;2.354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.945\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.210\u0026ndash;3.021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime to recurrence (\u0026le;\u0026thinsp;2y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.931\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.141\u0026ndash;2.214\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.467\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.233\u0026ndash;3.648\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIM pathologically\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.178\u0026ndash;3.874\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.373\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.034\u0026ndash;4.569\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNumber of tumors (=\u0026thinsp;3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.356\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.959\u0026ndash;1.757\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.328\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.836\u0026ndash;2.540\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.221\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSite of recurrence (different lobe)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.582\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.991\u0026ndash;2.730\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.085\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.684\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.113\u0026ndash;3.235\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.078\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOperative method (RH\u0026thinsp;+\u0026thinsp;RFA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.067\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.730\u0026ndash;1.726\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.752\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.873\u0026ndash;1.987\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.783\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eMultivariate analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eBefore propensity matching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eAfter propensity matching\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAlbumin at recurrence (\u0026le;\u0026thinsp;3.5mg/dL)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.434\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.034\u0026ndash;2.118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.459\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.112\u0026ndash;2.349\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.139\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTime to recurrence (\u0026le;\u0026thinsp;2y)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.234\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.328\u0026ndash;4.213\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.678\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.122\u0026ndash;5.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIM pathologically\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.985\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.023\u0026ndash;4.928\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.523\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.168\u0026ndash;4.760\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSite of recurrence (different lobe)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.407\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.986\u0026ndash;2.324\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.345\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.812\u0026ndash;1.983\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.220\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOperative method (RH\u0026thinsp;+\u0026thinsp;RFA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.103\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.680\u0026ndash;1.873\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.987\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.770\u0026ndash;1.523\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.874\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"7\"\u003e\n \u003cp\u003e\u003cem\u003eN\u003c/em\u003e number, \u003cem\u003eM\u003c/em\u003e male, \u003cem\u003eHBsAg\u003c/em\u003e hepatitis B surface antigen, \u003cem\u003eBCLC\u003c/em\u003e Barcelona clinic liver cancer, \u003cem\u003eMVI\u003c/em\u003e microvascular invasion, \u003cem\u003eHBV DNA\u003c/em\u003e hepatitis B virus deoxyribonucleic acid, \u003cem\u003eAFP\u003c/em\u003e alpha-fetoprotein, \u003cem\u003eIM\u003c/em\u003e intrahepatic metastasis, \u003cem\u003eRH\u003c/em\u003e repeat hepatectomy, \u003cem\u003eRFA\u003c/em\u003e radiofrequency ablation, \u003cem\u003eHR\u003c/em\u003e hazard ratio, \u003cem\u003eCI\u003c/em\u003e confidence interval.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the future, the treatment of HCC will tend to recurrent HCC due to the characteristic of high recurrence rate. Furthermore, under scheduled supervision after initial hepatic hepatectomy and advancement in imaging technology. Most recurrent HCC was found in the early and multifocal periods, making surgical treatment beneficial in these patients (Chua et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2021\u003c/span\u003e; Meniconi et al. \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e2015\u003c/span\u003e), and multifocal HCC at the 2nd resection was not a risk factor (Minagawa et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2003\u003c/span\u003e). Although the overall survival outcome of recurrent HCC after surgical intervention has improved tremendously recently, the optimal treatment for early-stage and multifocal intrahepatic rHCC is still not unifying.\u003c/p\u003e \u003cp\u003eNonsurgical treatment methods, such as TACE and systemic therapies are usually proposed for the treatment of recurrent HCC because of late tumor stage or insufficient preserved liver function (Poon et al. 2002; Tabrizian et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). However, for early-stage recurrent HCC, nonsurgical therapeutic effect is far lower than that of surgical treatment. The median survival time for recurrent patients treated with TACE was 19 months, and that for patients treated with sorafenib was 9.9 months (Tabrizian et al. \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). SLT is the best theoretical solutions to treat both the tumor and the underlying hepatic disease for recurrent HCC fulfilling the Milan criteria (Chan et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2013\u003c/span\u003e). However, the shortage of organ donors, strict screening criteria of patients, and well-preserved liver function often relegate patients with recurrent HCC to the lowest priority to receive a graft before the disease progressing. In addition, taking into account the relatively low preoperative MELD score, outcomes for transplant must be reported on an intention-to-treat basis (Llovet, Fuster, and Bruix \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e1999\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRH could attain similar survival outcomes as the first resection in selected patients. Meanwhile, RFA is recommended as a curative treatment, which is applicable in selected patients with two or three nodules\u0026thinsp;\u0026le;\u0026thinsp;3 cm and with borderline liver function. Previous analyses revealed that RH and RFA were both effective treatments for early-stage recurrent HCC, and 5-year survival after RH was from 31\u0026ndash;56% (Minagawa et al. \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2003\u003c/span\u003e; Chan et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Poon et al. \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e1999\u003c/span\u003e; Tralh\u0026atilde;o et al. \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e2007\u003c/span\u003e; Wang et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2015\u003c/span\u003e) and after RFA was from 37\u0026ndash;45.4% (Xia et al. \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Liang et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2008\u003c/span\u003e; Wang et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2015\u003c/span\u003e), suggesting that excellent outcome could be present in selected patients with recurrent HCC. However, controversies have been seen in previous studies. On account of benefits in long-term survival outcome, others showed that the tumor might remain partially active after ablation, causing a higher local recurrence rate with the increase of tumor size (Sofocleous et al. 2012; Li et al. \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e2012\u003c/span\u003e). Since RH is sometimes inadequate for patients with poor liver function, multiple lesions and insufficient residual liver volume, and not all recurrent early-stage tumors are good candidates for RFA because some tumors are on the liver surface or near large vessels or critical organs. Therefore, it would be better to recognize RH and RFA as complementary treatment modalities rather than totally competitive modalities. In this regard, to overcome the limitations of each when used alone, we compared the long-term outcomes of patients with multifocal rHCC meeting the Milan criteria with RH and RH combined with intraoperative RFA. This combined treatment has been proven to be reliable and advantageous in initial resection of early-middle-stage multifocal HCC (Huang et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2020\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAlthough many studies of recurrent HCC meeting the Milan criteria have been carried out (Wang et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2015\u003c/span\u003e), few of them referred to the combination means of multifocal rHCC meeting the Milan criteria. For such patients, treatment courses are determined by various clinical factors of the initial surgery. Therefore, we collected some important clinical characteristics of patients with HCC for the initial resection (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), including tumor clinical stage, intraoperative circumstances and pathological results, which revealed no significant differences at the initial resection between the two groups. Meanwhile, PSM was performed to reduce the influence of confounding factors. Ultimately, we obtained statistical consistency from the data of demographic characteristics, laboratory evaluation and tumor-related information.\u003c/p\u003e \u003cp\u003eRepeat hepatectomy is more complicated than initial resection because of the progression of hepatitis, the presence of adhesions and anatomical modifications by previous operations (Kawano et al. \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2009\u003c/span\u003e; Shimada et al. \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e1996\u003c/span\u003e). Abdominal adhesion was present in 29 of the 43 patients in the combination group and 39 of the 66 patients in the RH group. Neovascular structures and ambiguous anatomy resulted in an unplanned increase in intraoperative blood transfusion, operation time, risk of bowl injury and perioperative complications. As shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, there was a significantly shorter operation time, less intraoperative blood loss, and a lower rate of major complications in the combination group than in the RH group. Major complications were mainly postoperative bleeding, liver dysfunction and bile leak, which mainly arose in the RH groups, probably due to limitations of RH in the treatment of tumors with special locations (Vitale et al. \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e2017\u003c/span\u003e). For example, a tumor located near critical structures receives RH, which frequently brings about large areas of parenchymal transection, subsequently prolonged operation time, increased blood loss and, inherently increased incidence of major complications. Our results of the combination therapy are consistent with findings of recently published studies of RFA with less trauma in treating recurrent HCC (Feng et al. \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Chua et al. \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e2021\u003c/span\u003e). No deaths occurred within 30 days after surgery, which may be attributed to rigorous preoperative evaluation of liver reserve function and appropriate postoperative management.\u003c/p\u003e \u003cp\u003eHepatectomy combined with RFA has the advantage of less surgical trauma on the premise of ensuring a favorable survival outcome, as for the particularity of recurrent multifocal HCCs mentioned above, RH combined with RFA is a complementary means theoretically. However, relevant studies only concentrated on recurrent single tumors or did not provide a targeted exploration of multifocal rHCC meeting the Milan criteria (Chan et al. \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e2013\u003c/span\u003e; Chen et al. \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e2020\u003c/span\u003e; Wang et al. \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). Our study indicated that there was no difference in rOS and rRFS between patients treated with RH combined with RFA and RH alone. To reduce the bias resulting from the surgeon's choice of surgical method during the procedure as much as possible, we performed PSM to produce similar results in terms of tumor location, number and largest tumor size, which were significantly different before PSM.\u003c/p\u003e \u003cp\u003eThe outcomes of the two groups were also compared in subgroup analyses. We investigated the effectiveness of tumor number for recurrent multifocal tumors on postoperative survival after RH\u0026thinsp;+\u0026thinsp;RFA and RH alone. The combination group and the RH group had similar rOS and rRFS rates in patients with two recurrent tumors (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, B), which is different from our previous results of initial resection for early-middle-stage multifocal HCC (Huang et al. \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). One reason is that we narrowed the tumor criteria from the University of California San Francisco (UCSF) criteria to the Milan criteria. Tumor size is an important risk factor for survival outcome of patients with HCC. The other reason may be that the extent of resection of the recurrent tumor was smaller than that of the initial resection when considering the residual liver volume. Moreover, for patients with three recurrent tumors, no significant difference existed in either rOS or rRFS after RH\u0026thinsp;+\u0026thinsp;RFA and RH alone (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC, D). The potential explanation is that the number of recurrent tumors played a dominant role in effecting patients\u0026rsquo; prognosis. Further subgroup analysis of the anatomic location of tumors was performed according to Couinaud\u0026rsquo;s segmentation. In the subgroup of tumors located in the same lobe, RH provided better rRFS than RH combined with RFA for patients with all lesions in the same lobe (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB), but in the subgroup of tumors located in different lobes, the difference of rRFS was eliminated between the two groups (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD). There are several reasons that could account for this phenomenon. First, 30 patients (88.2%) in the RH subgroup of tumors located in the same lobe underwent en bloc resection, which removed more nonneoplastic liver parenchyma closer to anatomical resection than the combination subgroup. Second, it was possibly attributable to frequent presence of microlesions that would likely have been resected following an en bloc resection in RH groups, not in combination group because some microlesions may grow slowly, especially in less biologically aggressive tumors (Roayaie et al. \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). In other words, recurrent tumors may not be completely controlled by RFA. Third, if tumors were located in different lobes, theoretically, there would be more intrahepatic metastases in the wider liver region, thus causing no significant difference in either rOS or rRFS in the subgroup of tumors located in the different lobes.\u003c/p\u003e \u003cp\u003eTime to recurrence\u0026thinsp;\u0026le;\u0026thinsp;2, also called early recurrence (ER), and IM pathologically were identified as two risk factors in multivariate Cox model analyses. Many studies have clearly demonstrated that patients with ER had significantly worse survival than those with late recurrence (LR) after the second surgery (Imamura et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2003\u003c/span\u003e; Liang et al. \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e2008\u003c/span\u003e). Intrahepatic metastasis (IM), characterized by ER, is associated with more aggressive tumor behavior, whereas LR is more likely to be associated with MO with a beneficial survival outcome. The diagnosis of IM and MO is mainly based on histopathological findings as reported by the Liver Cancer Study Group of Japan with modifications. Although it is relatively subjective, it is still the most convenient and effective clinical identification method. In our study, 29 patients (67.4%) were defined as IM in the combination group, and 38 patients (57.6%) were defined as IM in the RH group. The difference in tumor biological behavior between IM and MO leads to the different prognosis (Imamura et al. \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2003\u003c/span\u003e; Xu et al. \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). We can also explain that the IM cases might be a consequence of the so-called recurrent multifocal HCC from clinically latent multiple intrahepatic metastases, which might have already been present at the time of initial surgery. In other words, these cases might be \u0026ldquo;latent Stage IV\u0026rdquo; at the time of initial surgery, mistaken for recurrence at the next operation.\u003c/p\u003e \u003cp\u003eThe major limitations were the following: First, it was a single-center retrospective study, and the outcomes of both RH and RFA partly depend on the expertise and experience of the operators. Second, we failed to consider the effects of different antiviral drugs that were associated with tumor recurrence during the follow-up periods. It was difficult to balance and adjust them between the two groups in this retrospective study. Finally, the chief among these is that the study spans a period of more than 10 years, during which HCC treatment has changed significantly. We have witnessed the development of comprehensive therapy for HCC. Despite its limitations, our study does provide some valuable references that can aid clinicians in confronting patients with early-stage multifocal rHCC.\u003c/p\u003e \u003cp\u003eIn conclusion, both RH combined with RFA and RH alone are safe and can achieve similar excellent results in selected patients with multifocal rHCCs meeting the Milan criteria, but RH combined with RFA had a relatively shorter operative time and fewer postoperative major complications. Moreover, RH may be more suitable for patients whose tumors are located in the same lobe because of better rRFS. How to treat these patients with a optimal means still worth looking forward to.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFounding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by grants from the National Natural Science Foundation of China (81400636), Sichuan Province Key Research and Development Project (2019YFS0203), Key Clinical Research Incubation Project of West China Hospital of Sichuan University (2020HXFH028), and the Key R\u0026amp;D Support Plan of Chengdu Science and Technology Bureau (2021-YF05-00703-SN).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Yang Huang and Min Huang. The first draft of the manuscript was written by Yang Huang, Liangliang Xu. Mingqing Xu and Li Jiang conducted and corrected previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003e\u003cspan\u003eBray, F., J. Ferlay, I. Soerjomataram, R. L. Siegel, L. A. Torre, and A. 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Xie. 2020. \u0026apos;Radiofrequency ablation versus hepatic resection for recurrent hepatocellular carcinoma: an updated meta-analysis\u0026apos;, BMC Gastroenterol, 20: 402.\u003c/span\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"recurrent hepatocellular carcinoma, multifocal tumors, hepatic resection, radiofrequency ablation, survival outcome","lastPublishedDoi":"10.21203/rs.3.rs-1702329/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1702329/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe surgical indications and therapeutic strategies for early-stage multifocal and recurrent hepatocellular carcinomas (rHCC) remain controversial. The purpose of this study was to compare the long-term outcomes of patients with recurrent and multifocal HCC meeting the Milan criteria with repeat hepatectomy (RH) and RH combined with intraoperative radiofrequency ablation (RFA).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA total of 109 consecutive patients with intrahepatic early-stage multifocal rHCC within Milan criteria following RH or RH\u0026thinsp;+\u0026thinsp;RFA were retrospectively collected from April 2010 to May 2020. Propensity score matching (PSM), subgroup analysis, and univariate and multivariate analyses were performed. Overall survival after recurrence (rOS) and recurrence-free survival after recurrence (rRFS) were calculated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe 1-, 3-, and 5-year rOS and rRFS of the combination group and the RH group were similar (p\u0026thinsp;=\u0026thinsp;0.699; P\u0026thinsp;=\u0026thinsp;0.587, respectively). The similar results are also appeared in matched population. Subgroup analyses showed that there was no significant difference between patients with 2 tumors and 3 tumors, but the RH group was associated with better rRFS than the combination group for patients whose tumors were located in the same lobe (p\u0026thinsp;=\u0026thinsp;0.045). Multivariate analysis revealed that time to recurrence (TTR)\u0026thinsp;\u0026le;\u0026thinsp;2 years and IM pathologically were independent risk factors.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eFor multifocal rHCC patients meeting the Milan criteria, RH combined with RFA may offer similar OS and RFS as RH alone; however, RH may be more suitable for patients with tumors located in the same lobe than RH combined with RFA.\u003c/p\u003e","manuscriptTitle":"Repeat Hepatic Resection Combined with Intraoperative Radiofrequency Ablation Versus Repeat Hepatic Resection Alone for Recurrent and Mutiple Hepatocellular Carcinoma Patients Meeting the Milan Criteria: A Propensity Score-Matched Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-06-01 16:04:28","doi":"10.21203/rs.3.rs-1702329/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"54e44e09-c708-4b2f-9424-ae82429eabf0","owner":[],"postedDate":"June 1st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-06-01T16:04:29+00:00","versionOfRecord":[],"versionCreatedAt":"2022-06-01 16:04:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1702329","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1702329","identity":"rs-1702329","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}