Despite that surgical resection is widely regarded as the most effective approach to the treatment of liver cancer, its safety and efficacy upon centrally located hepatocellular carcinoma (HCC) remain unsatisfactory. In consequence, seeking an integrated treatment, like combined with adjuvant radiotherapy, to enhance the prognosis of patients is of critical importance. By recruiting patients undergoing surgical resection for centrally located HCC ranging from June 2015 to 2020, they were divided into liver resection combined with adjuvant radiotherapy (LR + RT) and mere liver resection (LR) groups. The calculation of propensity score and model of Cox proportional hazards regression were utilized. 193 patients were recruited in aggregation, containing 88 ones undergoing LR + RT, while 105 handled with LR. RT was verified to be an independent factor of prognosis for relapse (HR 0.60). In propensity-score analyses, significant association existed between adjuvant radiotherapy and better disease-free survival (DFS) (Matched, HR 0.60; Adjustment of propensity score, HR 0.60; Inverse probability weighting, HR 0.63). The difference of DFS was apparent within two groups (p value = 0.022), and RT significantly down-regulated early relapse (p value < 0.05) in subgroup analysis. The calculation of E-value revealed robustness of unmeasured confounding. The combination of liver surgical resection with RT is safe and effective towards patients with centrally located HCC, which would notably enhance the prognosis and decrease the early relapse of HCC.

Centrally located hepatocellular carcinoma (HCC) is difficult to be radically resected due to its special location close to major hepatic vessels. Thus, we aimed to assess whether stereotactic body radiation therapy (SBRT) can be an effective and safe approach for centrally located HCC. This retrospective study included 172 patients with centrally located HCC who were treated with SBRT. Overall survival (OS) was analyzed as the primary endpoint. Rates of progression-free survival (PFS), local control, intrahepatic relapse, extrahepatic metastasis and toxicities were analyzed as secondary endpoints. The OS rates of 1-, 3-, and 5-year were 97.7%, 86.7%, and 76.3%, respectively. The PFS/local control rates of 1-, 3-, and 5-year were 94.1%/98.2%, 76.8%/94.9%, and 59.3%/92.3%, respectively. The cumulative incidence of intrahepatic relapse/extrahepatic metastases of 1-, 3-, and 5-year were 3.7%/2.9%, 25.0%/7.4%, and 33.3%/9.8%, respectively. Both univariate and multivariate analyses revealed that patients received BED10 at 100 Gy or more had better OS. Radiation-related adverse events were mild to moderate according to Common Terminology Criteria for Adverse Events, and no toxicities over grade 3 were observed. Patients with centrally located HCC in our cohort who received SBRT had similar OS and PFS rates compared to those reported in literatures who received surgery with neoadjuvant or adjuvant intensity-modulated radiation therapy. These results indicate that SBRT is an effective and well-tolerated method for patients with centrally located HCC, suggesting that it may serve as a reasonable alternative treatment for these kind of patients.

UNASSIGNED: Centrally located hepatocellular carcinoma (HCC) typically presents challenges in surgical intervention and is associated with a bleak prognosis. In order to address this pressing issue, it is imperative to identify a comprehensive treatment approach, such as neoadjuvant radiotherapy (neoRT), that can enhance the prognosis of patients diagnosed with centrally located HCC.
UNASSIGNED: Patients who had surgical resections for HCC between March 2015 and December 2020 were included in the study. Patients were assigned to either the neoRT combined with liver resection (neoRT+LR) group or the liver resection alone (LR) group. The study employed propensity-score analysis and Cox proportional-hazards regression models as research methodologies. Using the Kaplan-Meier method, overall survival (OS) and disease-free survival (DFS) were estimated in patients.
UNASSIGNED: During the study, 162 patients were enrolled, with 41 receiving neoRT+LR and 121 receiving LR. The duration of the median follow-up period was 45 months. The 1-year, 3-year, and 5-year OS rates were 95, 70, and 70% for patients in the neoRT+LR group, and 82, 64, and 54% for patients in the LR group, respectively. The 1-year, 3-year, 5-year DFS rates were 71, 53, and 37% for patients in the neoRT+LR group, and 52, 38, and 34% for patients in the LR group, respectively. A successful matching of 37 patients was achieved through propensity-score analysis. OS and DFS after matching analysis was statistically different between the two groups ( P=0.0099, P=0.034, respectively). neoRT was an independent prognostic factor for OS and DFS [hazard ratio (HR)=0.47, 95% CI: 0.24-0.93; HR=0.56, 95% CI: 0.34-0.92, respectively]. According to matching analysis, there were no statistically significant differences observed in terms of baseline characteristics, surgical safety, and complications between the groups.
UNASSIGNED: Liver resection and neoRT can be advantageous for patients with centrally located HCC.

UNASSIGNED: Although surgical resection is one of the most effective way to treat liver cancer, its efficacy and safety in treatment of centrally located hepatocellular carcinoma (HCC) remains elusive. Therefore, it is very important to find a comprehensive treatment mode, such as radical resection combined with neoadjuvant radiotherapy (neoRT).
UNASSIGNED: The centrally located HCC patients who underwent radical resection from July 2015 to April 2021 were enrolled. According to whether the neoRT was implemented or not, these patients were allocated into neoadjuvant radiotherapy combined with liver resection (neoRT+LR) and liver resection alone (LR) group. The research method used propensity-score analysis and Cox proportional-hazards regression models. We generated an E-value to assess the sensitivity to unmeasured confounding. This study is a real-world, retrospective study based on phase II clinical trial.
UNASSIGNED: A total of 168 patients were enrolled, including 38 patients treating with neoRT+LR and 130 patients with LR. The 1-, 3-, 5-year disease free survival (DFS) rates were 74%, 55% and 39% in the neoRT+LR group, and 44%, 28%, and 24% in the LR group, respectively. Neoadjuvant radiotherapy was an independent prognostic factor for postoperative recurrence ([HR]0.42, 95% CI [0.25, 0.69]). There was significant association between neoRT+LR and longer disease-free survival (Match, [HR] 0.43, 95% CI [0.24, 0.76]; GenMatch, [HR] 0.32, 95% CI [0.23, 0.43]; Adjusted for propensity score, [HR] 0.41, 95% CI [0.23, 0.73]; Inverse probability weighting, [HR] 0.38, 95% CI [0.22, 0.65], respectively). DFS before and after matching analysis was statistically different in two groups (p-value=0.005, p-value=0.0024, respectively). Neoadjuvant radiotherapy can significantly reduce the postoperative early recurrence (p-value <0.05). E-value analysis suggested robustness to unmeasured confounding.
UNASSIGNED: Liver resection combined with neoadjuvant radiotherapy was effective and safe for treatment of centrally located HCC patients, which improved the prognosis of patients and reduced the incidence of early recurrence.

Objective: To explore a novel method for preoperative precision assessment of centrally located hepatocellular carcinoma(HCC) with blood vessel as axis based on three-dimensional(3D) visualization and virtual reality(VR) technology and its application values. Methods: High-quality thin-layer enhanced CT data were collected from 20 patients with centrally located HCC who treated at First Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University from March 2017 to August 2018 diagnosed by preoperative examination. There were 18 males and 2 females, aged 28 to 69 years, all of Child-Pugh grade A. First of all, 3D reconstruction was performed by a 3D visualization software; then, the reconstructed 3D image was imported into VR development engine for VR research; afterwards, the analysis and evaluation system with blood vessel as axis was established based on 3D visualization classification of centrally located HCC; therefore, the relationship of the tumor to its major peripheral blood vessels was accurately judged and the surgical planning was formulated. Two images were brought into the operating room for navigation in surgery. The assessments results of preoperative data (CT and (or) MRI) and three-dimensional visualization of blood vessels in VR environment were compared; the values of the preoperative and postoperative hemoglobin, serum albumin and bilirubin were recorded and compared. Chi-square test, t-test and non-parametric test were used for the analysis of counting data, continuous measurement data and non-normal distribution measurement data, respectively. Results: 3D visualization modeling was completed in all of the 20 patients with centrally located HCC. According to the results of 3D visualization classification of centrally located HCC, there were 3 cases of type Ⅰ,1 case of type Ⅱ,4 cases of type Ⅲ,7 cases of type Ⅳ and 5 cases of type Ⅴ; according to the assessment and classification based on blood vessel as the axis, there were 6 cases of type Ⅰa,2 cases of type Ⅰb,2 cases of type Ⅱa,9 cases of type Ⅱb and 1 case of type Ⅱc. All patients underwent successful resection of tumor under the guidance of 3D visualization and VR technology. There were 15 cases whose assessment results based on preoperative CT/MRI were consistent with intraoperative findings, with a coincidence rate of 75.0%(15/20); while in VR environment, the assessment results of 3D visualization with blood vessel as axis were all consistent with the intraoperative findings, with coincidence rate of 100%(20/20). There was a statistically significant difference between the groups (χ(2)=5.714, P=0.017). There was no red blood cell transfusion in all patients during the operation. The preoperative hemoglobin was (128.8±14.9)g/L, and it was (119.8±12.5)g/L on postoperative day 1. There was no significant difference between these two sets of data (t=2.07, P=0.054). No death during the perioperative period and no complications such as hepatic failure, hemorrhage and biliary fistula after operation occurred. Conclusion: Preoperative evaluation based on 3D visualization and VR technology with blood vessel as the axis has significant clinical value for preoperative planning and surgical navigation of centrally located HCC.
目的： 研究一种基于三维可视化及虚拟现实（VR）的以血管为轴心的术前精确评估中央型肝癌的新方法及其应用价值。 方法： 回顾性收集2017年3月至2018年7月南方医科大学珠江医院肝胆一科收治的经术前检查诊断为中央型肝癌的20例患者的高质量CT图像数据。男性18例，女性2例，年龄28~69岁。所有患者肝功能Child-Pugh分级均为A级。首先采用三维可视化软件对影像学资料进行三维重建，然后导入VR开发引擎进行VR的研究，在三维可视化中央型肝癌分型基础上建立以血管为轴心的分析和评估体系，精确判断肿瘤与周围主要血管的关系，制定手术规划，并将二者图像带入手术室用于指导导航手术。比较20例患者术前资料评估结果及VR环境中以血管为轴心的三维可视化评估结果，记录术前术后血红蛋白、血清白蛋白、胆红素数值并进行对比。计数资料分析采用χ(2)检验，符合正态分布的计量资料比较采用t检验，非正态分布的计量资料比较采用非参数检验。 结果： 20例中央型肝癌患者均成功进行了三维重建，按照中央型肝癌三维可视化分型结果如下：Ⅰ型3例，Ⅱ型1例，Ⅲ型4例，Ⅳ型7例，Ⅴ型5例。以血管为轴心评估分型结果如下：Ⅰa型6例、Ⅰb型2例、Ⅱa型2例、Ⅱb型9例、Ⅱc型1例。所有患者均在三维可视化及VR指导下成功切除肿瘤，术前CT和（或）MRI评估结果与术中所见相符15例，符合率为75.0%（15/20）；在VR环境中以血管为轴心的三维可视化评估与术中探查所见均一致，符合率为100%（20/20），两者差异有统计学意义（χ(2)=5.714，P=0.017）。本组所有患者手术过程中均未输红细胞，术前血红蛋白为（128.8±14.9）g/L，术后第1天血红蛋白为（119.8±12.5）g/L，术前术后血红蛋白的差异无统计学意义（t=2.07，P=0.054）。患者围手术期无死亡，术后未发生肝功能衰竭、出血、胆瘘等并发症。 结论： 基于三维可视化及VR的以血管为轴心的术前评估对中央型肝癌术前规划及手术导航有重要的临床应用价值。.

The prognostic prediction for centrally located hepatocellular carcinoma (CL-HCC) after hepatectomy has not been well established. We aimed to develop prognostic nomograms for patients undergoing hepatectomy for CL-HCC.
A cohort of 380 patients who underwent curative hepatectomy for CL-HCC at our hospital between 2009 and 2015 were retrospectively studied. We randomly divided the subjects into training (n = 210) and validation (n = 170) groups. Univariate and multivariate survival analysis were used to identify prognostic factors. Visually orientated nomograms were constructed using Cox proportional hazards models. The performance of the nomogram was evaluated by the area under the ROC curve (AUC), calibration curve and compared with the conventional staging systems.
The statistical nomogram for OS built on the basis of ALBI grade, tumor number, tumor size, classification, hepatectomy methods, capsule formation and microvascular invasion (MVI) had good calibration and discriminatory abilities, with AUC of 0.746 (65-month survival). The nomogram for DFS was based on tumor number, tumor size, classification, HBV-DNA load, capsule formation and MVI, with AUC of 0.733 (65-month survival). These nomograms showed satisfactory performance in the validation cohort (AUC, 0.733 for 65-month OS; and 0.702 for 65-month DFS). The AUC of our nomograms were greater than those of conventional staging systems in the validation cohort.
The established nomograms might be useful for estimating survival for patients with CL-HCC after liver resection.

Centrally located hepatocellular carcinoma (HCC) is sited in the central part of the liver and adjacent to main hepatic vascular structures. This special location is associated with an increase in the difficulty of surgery, aggregation of the recurrence disease, and greater challenge in disease management. This review summarizes the evolution of our understanding for centrally located HCC and discusses the development of treatment strategies, surgical approaches and recurrence prevention methods. To improve patient survival, a multi-disciplinary modality is greatly needed throughout the whole treatment period.