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Abstract Background Liver transplantation (LT) is offered as a cure for Hepatocellular carcinoma (HCC), however 15–20% develop recurrence post-transplant which tends to be aggressive. In this study, we examined the transcriptome profiles of patients with recurrent HCC to identify differentially expressed genes (DEGs), the involved pathways, biological functions, and potential gene signatures of recurrent HCC post-transplant using deep machine learning (ML) methodology. Materials and methods We analyzed the transcriptomic profiles of primary and recurrent tumor samples from 7 pairs of patients who underwent LT. Following differential gene expression analysis, we performed pathway enrichment, gene ontology (GO) analyses and protein-protein interactions (PPIs) with top 10 hub gene networks. We also predicted the landscape of infiltrating immune cells using Cibersortx. We next develop pathway and GO term-based deep learning models leveraging primary tissue gene expression data from The Cancer Genome Atlas (TCGA) to identify gene signatures in recurrent HCC. Results The PI3K/Akt signaling pathway and cytokine-mediated signaling pathway were particularly activated in HCC recurrence. The recurrent tumors exhibited upregulation of an immune-escape related gene, CD274, in the top 10 hub gene analysis. Significantly higher infiltration of monocytes and lower M1 macrophages were found in recurrent HCC tumors. Our deep learning approach identified a 20-gene signature in recurrent HCC. Amongst the 20 genes, through multiple analysis, IL6 was found to be significantly associated with HCC recurrence. Conclusion Our deep learning approach identified PI3K/Akt signaling as potentially regulating cytokine-mediated functions and the expression of immune escape genes, leading to alterations in the pattern of immune cell infiltration. In conclusion, IL6 was identified to play an important role in HCC recurrence.

Background: Liver transplantation (LT) is offered as a cure for Hepatocellular carcinoma (HCC), however 15–20% develop recurrence post-transplant which tends to be aggressive. In this study, we examined the transcriptome profiles of patients with recurrent HCC to identify differentially expressed genes (DEGs), the involved pathways, biological functions, and potential gene signatures of recurrent HCC post-transplant using deep machine learning (ML) methodology. Materials and methods: We analyzed the transcriptomic profiles of primary and recurrent tumor samples from 7 pairs of patients who underwent LT. Following differential gene expression analysis, we performed pathway enrichment, gene ontology (GO) analyses and protein-protein interactions (PPIs) with top 10 hub gene networks. We also predicted the landscape of infiltrating immune cells using Cibersortx. We next develop pathway and GO term-based deep learning models leveraging primary tissue gene expression data from The Cancer Genome Atlas (TCGA) to identify gene signatures in recurrent HCC. Results: The PI3K/Akt signaling pathway and cytokine-mediated signaling pathway were particularly activated in HCC recurrence. The recurrent tumors exhibited upregulation of an immune-escape related gene, CD274, in the top 10 hub gene analysis. Significantly higher infiltration of monocytes and lower M1 macrophages were found in recurrent HCC tumors. Our deep learning approach identified a 20-gene signature in recurrent HCC. Amongst the 20 genes, through multiple analysis, IL6 was found to be significantly associated with HCC recurrence. Conclusion: Our deep learning approach identified PI3K/Akt signaling as potentially regulating cytokine-mediated functions and the expression of immune escape genes, leading to alterations in the pattern of immune cell infiltration. In conclusion, IL6 was identified to play an important role in HCC recurrence. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis was conducted to assess the survival benefits of repeat hepatectomy (RH) and thermal ablation therapy (TAT) in managing recurrent hepatocellular carcinoma (HCC). Methods: A comprehensive search was conducted in the PubMed, SinoMed, Embase, Cochrane Library, Medline, and Web of Science databases using relevant keywords to identify all studies published on this specific topic. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were estimated using a fixed-effects model. Results: This meta-analysis included a total of 21 studies, comprising 2580 patients with recurrent HCC, among whom 1189 underwent RH and 1394 underwent TAT. Meta-analysis results demonstrated that the RH group exhibited superior overall survival (OS) (HR=0.85, 95%CI 0.76~0.95, P=0.004) and recurrence-free survival (RFS) (HR=0.79, 95%CI 0.7~0.9, P<0.01) compared to the TAT group. Regarding postoperative complications, the TAT group experienced fewer complications than the RH group (OR=3.23, 95%CI 1.48~7.07, P=0.003), while no significant difference in perioperative mortality was observed between the two groups (OR=2.11, 95%CI 0.54~8.19, P=0.28). Conclusion: The present study demonstrates that, in comparison to TAT, RH may confer superior survival benefits for patients with recurrent HCC. [ABSTRACT FROM AUTHOR]

Background: Radiofrequency ablation (RFA) is the primary curative treatment for hepatocellular carcinoma (HCC) patients who are not eligible for surgery. However, the effects of RFA on the global tumor immune response remain unclear. Method: In this study, we examined the phenotypic and functional changes in peripheral blood mononuclear cells (PBMCs) from recurrent HCC patients who had undergone two RFA treatments using mass cytometry and high-throughput mRNA assays. Results: We observed significant increase in monocytes and decrease in T cell subpopulations three days after the first RFA treatment and three days after the second RFA treatment. The down-regulation of GZMB, GZMH, GZMK, and CD8A, which are involved in the cytotoxic function of T cells, was observed following RFA. Furthermore, the population of CD8 effector and memory T cells (CD8 Teff and CD8 Tem) significantly decreased after RFA. The expression of CD5 and CD161 in various T cell subpopulations also showed significant reductions. Additionally, elevated secretion of VEGF was observed in monocytes, B cells, regulatory T cells (Tregs), and CD4 naive T cells. Conclusion: In recurrent HCC patients, serum components derived from radiofrequency therapy can enhance the antigen-presenting capacity of monocytes. However, they also inhibit the anti-cancer immune response by reducing the population of CD8 effector and memory T cells and suppressing the activation of T cells, as well as down-regulating the expression of CD161 and CD5 in various T cell subpopulations. These tumor-derived components also contribute to an immunosuppressive microenvironment by promoting the secretion of VEGF in monocytes, Tregs, B cells, and CD4 naive T cells. [ABSTRACT FROM AUTHOR]

Abstract Purpose To summarize our single-center experience with percutaneous ultrasound (US)-guided radiofrequency ablation (RFA) for pediatric recurrent hepatocellular carcinoma (RHCC). Methods From September 2007 to September 2021, patients under 18 who underwent percutaneous US-guided RFA for RHCC were retrospectively enrolled in this study. Local effectiveness, complications, local tumor progression (LTP), progression free survival (PFS), and overall survival (OS) were evaluated. Results A total of 10 patients (9 male and 1 female; mean age, 11.7 ± 4 years ; age range, 6–17 years) with 15 intrahepatic RHCC lesions were enrolled in this study. Complete ablation (CA) was achieved in 14 out of 15 lesions (93.3%) after the first RFA. During the follow-up (mean, 63.1 ± 18 months; range, 5.3-123.3 months), LTP did not occur. Five patients died including three with tumor progression and one with liver failure. The accumulative one- and three-year PFS rates were 30% and 10%, respectively. The accumulative one- and three-year OS rates were 77.8% and 44.4%, respectively. Conclusions Our single-center experience suggests the safety and feasibility of percutaneous US-guided RFA for pediatric RHCC.

Abstract Objective The effectiveness and security of radiofrequency ablation (RFA) in combination with toripalimab (anti‐PD‐1) for the treatment of recurrent hepatocellular carcinoma (HCC) was studied in this article. Methods Total of 40 patients were enrolled in the study between September 2019 and November 2021. Data follow‐up ends in April 2022. The study’s main focus is on recurrence free survival (RFS), while the secondary objectives was safety. Chi‐square tests, Kaplan‐Meier, and Cox proportional hazards models were utilized to analyze the data. Results The median follow‐up period was 21.40 months, and the median RFS was 15.40 months in the group that received combination therapy, which was statistically significantly different (HR: 0.44, p = 0.04) compared with the RFA group (8.2 months). RFS rates (RFSr) at 6, 12 and 18 months in the combination therapy groups and RFA groups were 80% vs 65%, 62.7% vs 35% and 48.7% vs 18.8%, respectively. Between the two groups, significant difference of RFSr was found at 18 months (p = 0.04). No statistical differences were observed between the two groups in terms of safeness (p > 0.05). The subgroup analysis indicated that the combination of RFA and anti‐PD‐1 led to better RFS than RFA alone. Moreover, patients benefited more from combination therapy in the groups younger than 60 years (HR: 0.26, p = 0.018), male (HR: 0.32, p = 0.028) and Child‐Pugh grade A (HR: 0.38, p = 0.032). Conclusions Combining RFA with anti‐PD‐1 showed improved RFS and was deemed safe for patients with recurrent HCC who had previously undergone RFA treatment alone.

Purpose: To summarize our single-center experience with percutaneous ultrasound (US)-guided radiofrequency ablation (RFA) for pediatric recurrent hepatocellular carcinoma (RHCC). Methods: From September 2007 to September 2021, patients under 18 who underwent percutaneous US-guided RFA for RHCC were retrospectively enrolled in this study. Local effectiveness, complications, local tumor progression (LTP), progression free survival (PFS), and overall survival (OS) were evaluated. Results: A total of 10 patients (9 male and 1 female; mean age, 11.7 ± 4 years ; age range, 6–17 years) with 15 intrahepatic RHCC lesions were enrolled in this study. Complete ablation (CA) was achieved in 14 out of 15 lesions (93.3%) after the first RFA. During the follow-up (mean, 63.1 ± 18 months; range, 5.3-123.3 months), LTP did not occur. Five patients died including three with tumor progression and one with liver failure. The accumulative one- and three-year PFS rates were 30% and 10%, respectively. The accumulative one- and three-year OS rates were 77.8% and 44.4%, respectively. Conclusions: Our single-center experience suggests the safety and feasibility of percutaneous US-guided RFA for pediatric RHCC. [ABSTRACT FROM AUTHOR]

Purpose: Recurrent hepatocellular carcinoma (rHCC) patients with early recurrence usually suffer a poorer prognosis than those with late recurrence. We aimed to compare the treatment efficacy of repeat hepatectomy (RH) and percutaneous ablation (PA) in early-stage rHCC patients with early or late recurrence. Methods: This retrospective study enrolled 268 patients diagnosed with early-stage rHCC who received RH and PA. Overall survival (OS) and repeat recurrence-free survival (rRFS) were compared using log-rank analysis. Propensity score matching (PSM) was used to reduce the confounding bias. Results: Among the 268 patients with early-stage rHCC, 79 underwent RH and 189 underwent PA. Early (n = 174) and late (n = 94) recurrence was defined as recurrence within and after 2 years following initial hepatectomy, respectively. For patients with early recurrence, RH and PA provided similar 5-year OS (71.5% versus 74.4%, P = 0.87) and rRFS rates (24.7% versus 24.9%, P = 0.73). For patients with late recurrence, RH resulted in comparable 5-year OS (73.1% versus 86.1%, P = 0.62) and rRFS rates (36.6% versus 27.8%, P = 0.34) as PA. After PSM, RH continued to share similar 5-year OS and rRFS rates with PA in patients with early recurrence, and comparable efficacy of RH and PA was also observed in patients with late recurrence. Conclusion: RH can offer comparable OS and rRFS rates as PA for early-stage rHCC patients, regardless of whether they experience early or late recurrence. Therefore, both RH and PA are feasible treatment options for early-stage rHCC patients. [ABSTRACT FROM AUTHOR]

Objective: The effectiveness and security of radiofrequency ablation (RFA) in combination with toripalimab (anti‐PD‐1) for the treatment of recurrent hepatocellular carcinoma (HCC) was studied in this article. Methods: Total of 40 patients were enrolled in the study between September 2019 and November 2021. Data follow‐up ends in April 2022. The study's main focus is on recurrence free survival (RFS), while the secondary objectives was safety. Chi‐square tests, Kaplan‐Meier, and Cox proportional hazards models were utilized to analyze the data. Results: The median follow‐up period was 21.40 months, and the median RFS was 15.40 months in the group that received combination therapy, which was statistically significantly different (HR: 0.44, p = 0.04) compared with the RFA group (8.2 months). RFS rates (RFSr) at 6, 12 and 18 months in the combination therapy groups and RFA groups were 80% vs 65%, 62.7% vs 35% and 48.7% vs 18.8%, respectively. Between the two groups, significant difference of RFSr was found at 18 months (p = 0.04). No statistical differences were observed between the two groups in terms of safeness (p > 0.05). The subgroup analysis indicated that the combination of RFA and anti‐PD‐1 led to better RFS than RFA alone. Moreover, patients benefited more from combination therapy in the groups younger than 60 years (HR: 0.26, p = 0.018), male (HR: 0.32, p = 0.028) and Child‐Pugh grade A (HR: 0.38, p = 0.032). Conclusions: Combining RFA with anti‐PD‐1 showed improved RFS and was deemed safe for patients with recurrent HCC who had previously undergone RFA treatment alone. [ABSTRACT FROM AUTHOR]

Sizhe Liu, Le Kang, Yagang Song, Mingsan Miao School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of ChinaCorrespondence: Mingsan Miao, School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450046, People’s Republic of China, Tel/Fax +86-371-65962546, Email miaomingsan@163.comAbstract: Recurrence of hepatocellular carcinoma (HCC) negatively affects the quality of life of patients and leads to death. Studies have shown that recurrent hepatocellular carcinoma (RHCC) is closely related to tissue hypoxia and autophagy. It has been shown that hypoxia-inducible factor-1α (HIF-1α) and its downstream factor BCL-2 19 kDa-interacting protein 3 (BNIP3) promote cellular autophagy under hypoxic conditions, resulting in metastasis and RHCC. In this article, the molecular structures of HIF-1α and BNIP3 are described, and the significance of the HIF-1α/BNIP3 signaling pathway in RHCC is explained. Moreover, the role and mechanism of traditional Chinese medicine (TCM) in treating RHCC by modulating the HIF-1α/BNIP3 signaling pathway is discussed. Studies have shown that the HIF-1α/BNIP3 signaling pathway is a potential target of TCM in the treatment of RHCC. The mechanism of the HIF-1α/BNIP3 signaling pathway in RHCC and the progress achieved in TCM research on targeting and regulating this pathway are also reviewed in this article. The objective was to provide a theoretical basis for the prevention and treatment of RHCC, as well as further drug development.Keywords: recurrent hepatocellular carcinoma, HIF-1α/BNIP3 signaling pathway, traditional Chinese medicine, hypoxia, autophagy

Abstract Background The surgical indications and therapeutic strategies for early‐stage multifocal and recurrent hepatocellular carcinoma (rHCC) remain controversial. This study compared the long‐term outcome of patients with recurrent and multifocal HCC meeting the Barcelona Clinic Liver Cancer (BCLC) stage A 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 BCLC stage A following RH or RH + RFA were retrospectively collected from April 2010 to May 2020. Propensity score matching, subgroup analysis, and univariate and multivariate analyses were performed. Overall survival after recurrence (rOS) and recurrence‐free survival after recurrence (rRFS) were calculated by Kaplan–Meier analysis. Results The 1‐, 3‐, and 5‐year rOS and rRFS of the combination group and the RH group were similar (p = .699; p = .587, respectively). The similar results also appeared in matched population. Subgroup analyses indicated that there was no significant difference between patients with two tumors and three 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 = .045). Multivariate analysis revealed that time to recurrence (TTR) ≤ 2 years and intrahepatic metastasis (IM) pathologically were independent risk factors. Conclusions For multifocal rHCC patients meeting the BCLC stage A, tumor which is difficult to be surgically resected could be treated by RFA in order to avoid complications or bleeding. Tumors which were located in the same lobe may be more suitable to be treated by RH alone.

Laparoscopic hepatectomy is safely performed with minimal invasiveness on patients with recurrent liver tumors after previous hepatectomy. However, it is still difficult to dissect and expose the operative field at the transected edge or plane after open right hepatectomy, even for limited resection by a laparoscopic approach, due to severe adhesion to the surrounding peritoneum or organs. We herein applied the retroperitoneal laparoscopic approach to limited resection of the dorsal surface at the transected edge of Couinaud's segment 6 after previous repeated hepatectomies in a patient with recurrent hepatocellular carcinoma (HCC) by avoiding severe intra‐abdominal adhesion. We safely resected recurrent HCC via the retroperitoneal space. This approach is a useful and alternative option for laparoscopy which minimizes the dissecting time and avoids organ injury on the right side of the transected area of the liver after hepatectomy in patients with liver malignancies. [ABSTRACT FROM AUTHOR]

Purpose: To explore the safety and efficacy of lenvatinib in combination with trans-arterial chemoembolization (TACE) and programmed death receptor 1 (PD-1) antibody in the treatment of unresectable recurrent hepatocellular carcinoma (urHCC). Patients and methods: The clinical data of 16 patients with unresectable recurrent hepatocellular carcinoma admitted to the Department of Liver Surgery and Liver Transplantation Center, West China Hospital, Sichuan University, and received the conversion therapy of lenvatinib + TACE + PD-1 antibody between January 2019 and January 2022 were retrospectively analyzed. Results: There were 25% (4/16) patients suffering from grade 3 adverse events and no patients suffering from grade 4 or higher adverse events. After 4 months of treatment of 16 patients, according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), two, five, three, and six cases were in complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively, and the objective response rate (ORR) was 43.8% (7/16). The 1-year overall survival (OS) rate and 1-year progressionfree survival (PFS) rate were 86.2% and 46.9%, respectively. In our subgroup analysis, the ORR of patients with multiple lesions reached up to 60%, which was higher than that of patients with single lesions. Conclusions: Lenvatinib in combination with TACE and PD-1 antibody is safe and effective in the treatment of unresectable recurrent hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: The surgical indications and therapeutic strategies for early‐stage multifocal and recurrent hepatocellular carcinoma (rHCC) remain controversial. This study compared the long‐term outcome of patients with recurrent and multifocal HCC meeting the Barcelona Clinic Liver Cancer (BCLC) stage A 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 BCLC stage A following RH or RH + RFA were retrospectively collected from April 2010 to May 2020. Propensity score matching, subgroup analysis, and univariate and multivariate analyses were performed. Overall survival after recurrence (rOS) and recurrence‐free survival after recurrence (rRFS) were calculated by Kaplan–Meier analysis. Results: The 1‐, 3‐, and 5‐year rOS and rRFS of the combination group and the RH group were similar (p =.699; p =.587, respectively). The similar results also appeared in matched population. Subgroup analyses indicated that there was no significant difference between patients with two tumors and three 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 =.045). Multivariate analysis revealed that time to recurrence (TTR) ≤ 2 years and intrahepatic metastasis (IM) pathologically were independent risk factors. Conclusions: For multifocal rHCC patients meeting the BCLC stage A, tumor which is difficult to be surgically resected could be treated by RFA in order to avoid complications or bleeding. Tumors which were located in the same lobe may be more suitable to be treated by RH alone. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the efficacy and safety of microwave ablation (MWA) as a treatment for recurrent hepatocellular carcinoma (HCC) after initial successful surgical resection. Methods: This retrospective study included 40 patients (11 women and 29 men; mean age: 62.3 ± 11.7 years) with 48 recurrent lesions of HCC after initial surgical resection that were treated by percutaneous MWA. Several parameters including complications, technical success, local tumor progression (LTP), intrahepatic distant recurrence (IDR), overall survival (OS), and progression-free survival (PFS) were evaluated in order to investigate the safety and efficacy of MWA for these recurrent HCC lesions after surgical treatment. Results: All MWA treatments were performed without complications or procedure-related deaths. Technical success was achieved in all cases. Two cases developed LTP at a rate of 5%, and IDR occurred in 23 cases at a rate of 57.5% (23/40). The 1-, 2-, 3-, 4-, and 6-year OS rates were 97%, 89.2%, 80.3%, 70.2%, and 60.2%, respectively. The 1- and 3-year PFS rates were 50.2% and 34.6%, respectively. Conclusion: MWA is effective and safe as a local treatment for recurrent HCC after initial surgical resection. [ABSTRACT FROM AUTHOR]

Objective: The effectiveness of laparoscopic repeat hepatectomy (LRH) versus open repeat hepatectomy (ORH) on recurrent hepatocellular carcinoma (RHCC) is unclear. We compared the surgical and oncological outcomes of LRH and ORH in patients with RHCC with a meta-analysis of studies based on propensity score-matched cohorts. Methods: A literature search was conducted on PubMed, Embase, and Cochrane Library with Medical Subject Headings terms and keywords until 30 September 2022. The quality of eligible studies was evaluated with the Newcastle-Ottawa Scale. Mean difference (MD) with a 95% CI was used for the analysis of continuous variables; odds ratio (OR) with 95% CI was used for binary variables; and hazard ratio with 95% CI was used for survival analysis. A random-effects model was used for meta-analysis. Results: Five high-quality retrospective studies with 818 patients were included; 409 patients (50%) were treated with LRH and 409 (50%) with ORH. In most surgical outcomes, LRH was superior to ORH: less estimated blood loss, shorter operation time, lower major complication rate, and shorter length of hospital stay (MD= - 225.9, 95% CI= [-360.8 to -91.06], P= 0.001; MD=66.2, 95% CI =[5.28-127.1], P =0.03; OR=0.18, 95% CI=[0.05-0.57], P=0.004; MD= -6.22, 95% CI=[ -9.78 to -2.67], P =0.0006). There were no significant differences in the remaining surgical outcomes: blood transfusion rate and overall complication rate. In oncological outcomes, LRH and ORH were not significantly different in 1-year, 3-year, and 5-year overall survival and diseasefree survival. Conclusions: For patients with RHCC, most surgical outcomes with LRH were superior to those of ORH, but oncological outcomes with the two operations were similar. LRH may be a preferable option for the treatment of RHCC. [ABSTRACT FROM AUTHOR]

BackgroundPostoperative recurrence of hepatocellular carcinoma (HCC) is associated with low survival rates. While HCC treatment options have expanded substantially, they are accompanied by several challenges. This study assessed the outcomes of repeated hepatectomy (RH) for postoperative intrahepatic recurrence of HCC among patients undergoing initial hepatectomy (IH) as well as independent risk factors for HCC recurrence among patients undergoing repeated hepatectomy (RH).MethodsClinical data from 84 patients undergoing both IH and RH and 66 recurrent HCC patients who had received radiofrequency ablation (RFA) from July 2011 to September 2017 were retrospectively reviewed. The following groups were compared: (1) RH Group A (n = 84), (2) IH Group (n = 84, same individuals as RH Group A), (3) RH Group B (n = 45/84 from RH Group A), and (4) RFA Group (n = 66). The clinical pathology and operative characteristics of the patients in RH Group A were compared to those in the IH Group. Meanwhile, the clinical pathology and pre- and post-treatment features of the patients in RH Group B were compared to those in the RFA Group. The tumor-free survival time was compared between patients in RH Group A and the IH Group as well as between patients in RH Group B and the RFA Group. The independent risk factors for the 1-year postoperative tumor-free survival of RH Group A patients were investigated using univariate and multivariate analysis.ResultsMeasures of clinical pathology, including AFP, Child-Pugh score, HBV-DNA, tumor number, liver cirrhosis, tumor differentiation, surgical approach, and TNM stage differed significantly between patients in RH Group A and the IH Group (all P < 0.05), with the exception of tumor number and tumor size (both P > 0.05). No significant differences were found in these measures between the patients in RH Group B and the RFA Group (all P > 0.05). While patients in the RH Group A had a longer operation time than those in the IH Group (4.35 ± 1.25 h vs. 3.55 ± 0.92 h, P < 0.001), the level of intraoperative bleeding was similar (400.00 ± 199.25 ml vs. 359.40 ± 213.37 ml, P = 0.204). RH Group B patients had a longer hospitalization time than those in the RFA Group (6.5 ± 0.8 d vs. 5.5 ± 1.1 d, P < 0.001), however, the difference in hospitalization costs was not statistically significant (29,009 ± 3,806 CNY vs. 29,944 ± 3,752 CNY, P = 0.202). Five-day post-operative serum biomarker levels, including direct bilirubin (DB) and albumin (ALB), were significantly higher in RH Group B than in the RFA Group (all P < 0.05), with the exception of ALT, AST, and total bilirubin (TB) (all P > 0.05). Patients in RH Group A had a lower tumor-free survival time than those in the IH Group (median: 12 vs. 22 months, P < 0.001), and patients in the RH Group B had a significantly higher tumor-free survival time than those in the RFA group (median: 15 months vs. 8 months, P < 0.001). Age ≥50 y, Child-Pugh class A, and negative HBV-DNA were independent risk factors that positively impacted the 1-year postoperative tumor-free survival rate of postoperative intrahepatic recurrent HCC patients undergoing RH (P < 0.001, respectively).ConclusionDue to the potential of harm related to relapse of recurrent HCC for cancer patients, RH is a superior option. RH could offer better outcomes for recurrent HCC patients undergoing IH. Compared with lesion pathology, the better target organ of the liver will be key to ameliorating tumor-free survival for recurrent HCC patients undergoing RH.

Simple Summary: Among primary liver cancers, hepatocellular carcinoma (HCC) is the most common. Surgical resection and liver transplantation both represent potentially curative treatments not only in the case of the first occurrence, but also in those cases of disease recurrence if a proper selection of patients is performed ahead. Incidentally, the type and the time of relapse carry important weight on patient prognosis and overall survival. For these cases, proper management has still not been exactly defined. If precise indications for HCC first occurrence are quite clear, very few clear indications have been reported in those cases of relapse. The authors, after an extensive review of the published literature, aimed to summarize the modalities and the histopathological patterns of HCC recurrence, their prognostic value, and the main surgical strategies to deal with HCC relapse. At this point, either for redo hepatectomy or salvage liver transplantation, the pros and the cons have been detailed with the aim of characterizing the most suitable patients for receiving one or another. Some studies where such treatments were compared have been reported as well. Hepatocellular carcinoma (HCC) is the most common primary liver cancer, and both liver resection and liver transplantation are considered potentially curative options. However, high recurrence rates affect the prognosis depending both on the primary HCC pathology characteristics or on the type and time of the relapse. While great attention has been usually posted on treatment algorithms for the first HCC, treatment algorithms for recurrent HCC (rHCC) are lacking. In these cases, surgery still represents a curative option with both redo hepatectomy and/or salvage liver transplantation, which are considered valid treatments in selected patients. In the current era of personalised medicine with promises of new systemic-targeted immuno-chemotherapies, we wished to perform a narrative review of the literature on the role of surgical strategies for rHCC. [ABSTRACT FROM AUTHOR]

Abstract Aim This study aimed to evaluate the indications of laparoscopic repeat liver resection (LRLR) for recurrent hepatocellular carcinoma from the viewpoint of its difficulty. Methods One hundred and one patients who underwent LRLR and 59 patients who underwent open repeat liver resection (ORLR) were included. The difficulty was classified according to the preoperative predictive factors for difficult LRLR, including an open approach during previous liver resection, history of two or more previous liver resections, history of previous major liver resection, tumor near the resected site of the previous liver resection, and intermediate or high difficulty with the difficulty scoring system. We compared the surgical outcomes between the LRLR and ORLR groups based on the difficulty class (low‐ or intermediate difficiulty class, 0 to 3 predictive factors; high difficiulty class, 4 or 5 factors). Results In the low‐ or intermediate difficiulty class, intraoperative blood loss and the proportion of patients with postoperative complications were significantly lower in LRLR than in ORLR, and the duration of the postoperative hospital stay was significantly shorter in LRLR than in ORLR. In the high difficiulty class, total operative time and operative time before starting hepatic parenchymal resection were significantly longer in LRLR than in ORLR, and there were no significant differences in other surgical outcomes between the two groups. Conclusion LRLR is recommended for patients in the low or intermediate difficulty class. However, LRLR does not have an advantage with longer operative time for patients in the high difficulty class compared with ORLR.

Summary: Background: The evidence of radiofrequency ablation (RFA) following transarterial chemoembolisation (TACE) combined with sorafenib for intermediate-stage recurrent hepatocellular carcinoma (RHCC) is limited. Patient responses to this treatment vary because of the heterogeneous nature of RHCC, making it important to identify patients who are most likely to benefit from this combination therapy. The aim of this study was to evaluate the efficacy of RFA following TACE and sorafenib for the intermediate-stage RHCC. Methods: This retrospective, multicentre, cohort study included 363 patients with intermediate-stage RHCC underwent TACE combined with sorafenib (TACE-sorafenib group) or RFA following TACE and sorafenib (TACE-sorafenib + RFA group) between January 01, 2009 to December 31, 2015 from four institutions in China. Overall survival (OS), progression-free survival (PFS) and efficacy of patients were compared between the two groups by propensity score–matching (PSM). Findings: The 1-, 3-, and 5-year OS rates were 97.7%, 83.7%, 54.7% in TACE-sorafenib + RFA group, and 93.3%, 57.0%, 32.7% in TACE-sorafenib group. The 1-, 2-, and 3-year PFS rates were 85.3%, 58.0%, 26.9% in TACE-sorafenib + RFA group, and 55.3%, 30.7%, 15.3% in TACE-sorafenib group. Compared with the TACE-sorafenib group, the TACE-sorafenib + RFA group had significantly longer OS (HR, 0.54; 95%CI, 0.40–0.73; P

Background: To compare the perioperative and short-term outcomes of laparoscopic liver resection (LLR) and open liver resection (OLR) in recurrent hepatocellular carcinoma (rHCC) based on propensity score matching (PSM) to investigate therapeutic safety, efficacy, and value for clinical application. Methods: Forty-nine patients with rHCC who underwent surgery at Wenzhou People's Hospital between January 2017 and March 2022 were retrospectively analyzed and classified into LLR (n=30) and OLR (n=22) cases based on the surgical method. Thirty-eight patients were screened using PSM for data analysis to compare basic clinical characteristics, perioperative outcomes, and postoperative recurrence in both groups. Results: Before PSM, the tumour diameter was larger, tumor staging (BCLC staging system), intraoperative blood loss, units of blood transfused, constituent ratio of liver cirrhosis, incidence of MVI and intravascular tumour thrombus and postoperative complication were higher, and duration of hospital stay was significantly longer in the OLR group compared to those in the LLR group (p < 0.05). After PSM, there were no significant differences regarding tumour diameter, MVI incidence, blood transfusion amount or postoperative complication rate in the LLR and OLR groups. The tumor staging, incidence of vascular cancer thrombus, intraoperative blood loss and postoperative duration of hospitalisation were significantly higher in the OLR group than in the LLR group (p<0.05). The difference in recurrence-free survival (RFS) between the two groups was not statistically significant (p = 0.383). Conclusion: LLR for recurrent hepatocellular carcinoma can reduce intraoperative blood loss and postoperative complication rate, shorten the duration of hospitalisation, and is superior to OLR regarding perioperative and short-term efficacy, demonstrating good safety and feasibility. [ABSTRACT FROM AUTHOR]

This study aimed at analyzing and comparing the clinical efficacy and prognosis of repeat laparoscopic hepatectomy (r-LH) and radiofrequency ablation (RFA) in treating recurrent hepatocellular carcinoma (RHCC). Clinicopathological data of RHCC patients who underwent r-LH or RFA as treatment from three medical centers were retrospectively reviewed. Baseline characteristics at the recurrence time after initial hepatectomy and clinical outcomes following treatment of RHCC were compared between the two groups. Using the Kaplan-Meier method, survival curves for the two groups of patients were generated, and the log-rank test was used to compare survival differences. Propensity score matching (PSM) analysis was used to match patients of the r-LH and RFA groups in a 1:1 ratio. A total of 272 patients were enrolled, including 133 patients who underwent r-LH and 139 patients who received RFA. After PSM, 76 patients were matched in each study group. Compared with the r-LH group, the RFA group had shorter hospitalization and fewer postoperative complications. However, the r-LH group had significantly better overall survival (OS) and disease-free survival (DFS) than the RFA group before and after PSM. Subgroup analysis demonstrated that RHCC patients with solitary tumor or those with tumors located near the diaphragm, visceral surface or vessels, had survival benefits from r-LH. When tumor diameter ≤ 5 cm, r-LH appears to be an effective priority to RFA with a significantly higher OS and DFS rate in treating RHCC patients, especially for patients with solitary tumor and those with tumors located near the diaphragm, visceral surface or vessels.

The therapy of recurrent hepatocellular carcinoma (RHCC) remains poorly defined. Repeat hepatectomy (RH) and radiofrequency ablation (RFA) have offered as alternative therapy choices. Our study aims to assess survival benefits of RFA versus reresection for RHCC after resection. The electronic databases were used in order to explore the researches analyzing the efficacy of RH vs. RFA in treating RHCC updated to June 2020. After strict evaluation on quality, the interested results were extracted from articles. Totally, a total of 11 publications involving 1515 subjects were included, with 645 conducted RH and 870 taking RHA. We found that RH was associated with better 3-year OS (OR = 1.58, 95% CI = 1.22–2.05, P = 0.0005), while no difference with 1-year (OR = 1.03, 95% CI = 0.07–1.51, P = 0.90) or 5-year OS (OR = 1.66, 95% CI = 0.88–3.14, P = 0.12) in comparison with RFA for RHCC. In terms of DFS, RH was associated with better 3-year DFS (OR = 1.51, 95% CI = 1.11–2.06, P = 0.009) and 5-year DFS (OR = 1.54, 95% CI = 1.14–2.09, P = 0.005) than RFA. Moreover, RH had more morbidity compared with patients who underwent RFA for RHCC patients (OR = 5.61, 95% CI = 3.02–10.42, P

Background: Radiofrequency ablation (RFA) is considered as a convenient treatment with mild damage in treating recurrent hepatocellular carcinoma (RHCC). However, for patients with high risk of progression after RFA still needs new strategies to decrease the repeat recurrence.Methods: A total of 460 patients with RHCC within Milan criteria in four institutions were enrolled. 174 pairs were enrolled after propensity score matching (PSM). Overall survival (OS) and tumor-free survival (TFS) were compared between the two groups. A quantitative score system was established to screen out the beneficial population from RFA-sorafenib treatment.Results: The 1-, 3-, and 5-year OS rates were 97.7%, 83.7%, 54.7% for RFA-sorafenib group, and 93.1%, 61.3%, 30.9% for RFA group after PSM, respectively. Compared with the RFA group, the RFA-sorafenib group had significantly better OS (P < 0.001). The 1-, 3-, and 5-year TFS rates were 90.8%, 49.0%, 20.4% for RFA-sorafenib group, and 67.8%, 28.0%, 14.5% for RFA group after PSM. The difference was observed significantly between RFA-sorafenib group and RFA group (P < 0.001). A quantitative risk score system was established to precisely screen out the beneficial population from RFA-sorafenib treatment.Conclusions: Adjuvant sorafenib after RFA was superior to RFA alone in improving survival outcomes in patients with recurrent HCC within Milan criteria after initial hepatectomy. Subgroup analyses concluded that patients with high risk score had significantly longer survival from sorafenib administration. [ABSTRACT FROM AUTHOR]

The results of treatment for early stage recurrent hepatocellular carcinoma (HCC) remain controversial. This study aimed to analyze the clinical outcomes of recurrent HCC within the Milan criteria following different treatment modalities except liver transplantation. From January 2006 to December 2016, 272 consecutive HCC patients who developed intrahepatic recurrence after hepatectomy that satisfied the Milan criteria and Child–Pugh class A or B liver function were retrospectively enrolled. The outcomes of repeat resection (RR), local ablative therapy (LAT), or transarterial chemoembolization (TACE) were reported, and the prognostic factors of survival were investigated. Among the 272 patients, 136 (50.0%), 71 (26.1%), and 65 (23.9%) received TACE, LAT, and RR treatments, respectively. Treatment-related complications were 9.5%, 11.3%, and 10.7%, respectively, in the three groups. No patient died of treatment-related complication. The 1-, 3-, and 5-year overall survival rates after recurrence were 95.0%, 54.2%, and 45.8%, respectively, in the RR group; 86.6%, 51.7%, and 42.4%, respectively, in the LAT group; and 77.2%, 46.5%, and 38.4%, respectively, in the TACE group. On multivariate analysis, three independent factors related to survival after recurrences were identified. A single tumor nodule and AFP < 200 ng/mL predicted better survival, while a disease-free interval ≤ 1 year was associated with poor outcomes. RR and LAT could achieve good survival outcomes in well-selected patients with recurrent HCC within the Milan criteria, while TACE was the main form of treatment when curative therapy was not considered feasible and the clinical outcomes were satisfactory. [ABSTRACT FROM AUTHOR]

Abstract Background Repeat hepatectomy and radiofrequency ablation (RFA) are widely used to treat early recurrent hepatocellular carcinoma (RHCC) located in the subcapsular region, but the optimal treatment strategy remains to be controversial. Methods A total of 126 RHCC patients in the subcapsular location after initial radical hepatectomy were included in this study between Dec 2014 and Jan 2018. These patients were divided into the RFA group (46 cases) and the repeat hepatectomy group (80 cases). The primary endpoints include repeat recurrence-free survival (rRFS) and overall survival (OS), and the secondary endpoint was complications. The propensity-score matching (PSM) was conducted to minimize the bias. Complications were evaluated using the Clavien-Dindo classification, and severe complications were defined as classification of complications of ≥grade 3. Results There were no significant differences in the incidence of severe complications were observed between RFA group and repeat hepatectomy group in rRFS and OS both before (1-, 2-, and 3-year rRFS rates were 65.2%, 47.5%, and 33.3% vs 72.5%, 51.2%, and 39.2%, respectively, P = 0.48; 1-, 2-, and 3-year OS rates were 93.5%, 80.2%, and 67.9% vs 93.7%, 75.8%, and 64.2%, respectively, P = 0.92) and after PSM (1-, 2-, and 3-year rRFS rates were 68.6%, 51.0%, and 34.0% vs 71.4%, 42.9%, and 32.3%, respectively, P = 0.78; 1-, 2-, and 3-year OS rates were 94.3%, 82.9%, and 71.4% vs 88.6%, 73.8%, and 59.0%, respectively, P = 0.36). Moreover, no significant differences in the incidence of severe complications were observed between the RFA group and repeat hepatectomy group. Conclusion Both repeat hepatectomy and RFA are shown to be effective and safe for the treatment of RHCC located in the subcapsular region.

Background: The efficacy of radiofrequency ablation (RFA) for patients with early-stage recurrent hepatocellular carcinoma (HCC) with microvascular invasion (MVI) at the initial hepatectomy is limited. Our study aimed to explore whether adjuvant sorafenib following RFA could improve the situation. Methods: We retrospectively included 211 patients with early-stage (tumor number of ≤3 and tumor size of 2–5 cm) recurrent HCC with MVI at the initial hepatectomy who underwent adjuvant sorafenib following RFA or RFA alone in 13 centers from June 2013 to June 2020. In the combination group, sorafenib of 400 mg twice daily was administered within 7 days after RFA. Overall survival (OS) and recurrence-free survival (RFS) were compared. Subgroup analysis based on MVI grade was performed. MVI grade was based on the practice guidelines for the pathological diagnosis of HCC and included M1 (≤5 MVI sites, all located within adjacent peritumoral liver tissues 0–1 cm away from the tumor margin) and M2 (>5 MVI sites, or any MVI site located within adjacent peritumoral liver tissues > 1 cm away from the tumor margin). Results: A total of 103 patients received the combination therapy and 108 patients received RFA alone. The combination therapy provided better survival than RFA alone (median RFS: 17.7 vs. 13.1 months, P < 0.001; median OS: 32.0 vs. 25.0 months, P = 0.002). Multivariable analysis revealed that treatment allocation was an independent prognostic factor. On subgroup analysis, the combination therapy provided better survival than RFA alone in patients with M1 along with either a tumor size of 3–5 cm, tumor number of two to three, or alpha-fetoprotein (AFP) > 400 μg/L, and in those with M2 along with either a tumor size of 2–3 cm, one recurrent tumor, or AFP ≤ 400 μg/L. Conclusions: Adjuvant sorafenib following RFA was associated with better survival than RFA alone in patients with early-stage recurrent HCC with MVI at the initial hepatectomy. Moreover, MVI grade could guide the application of adjuvant sorafenib. [ABSTRACT FROM AUTHOR]

The efficacy and safety of CT-Guided Iodine-125 Radioactive Seed Implantation (RSI) for the treatment of intrahepatic recurrent hepatocellular carcinoma (rHCC) were analyzed in this multicenter retrospective study. We reviewed the medical records of patients with rHCC treated with I-125 seed implantation at four different hospitals in China from December 2011 and January 2021. The local progression-free survival (LPFS),liver PFS, and overall survival (OS) were calculated, and the short-term efficacy and treatment-related toxicities were evaluated. A total of 82 patients were enrolled; the median follow-up time was 46 months (range, 3–80 months). The 1-, 3- and 5-year LPFS rates were 63.8%, 27.1%, and 7.9%, respectively, and the corresponding OS rates were 74.8%, 32.9%, and 12.6%, respectively. Univariate analysis showed that factors influencing LPFS included the maximum lesion diameter, Barcelona Clinic Liver Cancer (BCLC) stage, interval between treatment and recurrence, and D90. Multivariate analyses revealed that the BCLC stage, interval between treatment and recurrence, and D90 were independent factors influencing LPFS, whereas BCLC stage, D90, and short-term efficacy were independent factors influencing OS. In summary, I-125 seed implantation is a safe and effective treatment for rHCC. The BCLC stage, interval, and D90 were found to influence the local control. A larger, prospective study is required to confirm the dose-response curve for Iodine-125 RSI of rHCC. [ABSTRACT FROM AUTHOR]

BackgroundThe efficacy of radiofrequency ablation (RFA) for patients with early-stage recurrent hepatocellular carcinoma (HCC) with microvascular invasion (MVI) at the initial hepatectomy is limited. Our study aimed to explore whether adjuvant sorafenib following RFA could improve the situation.MethodsWe retrospectively included 211 patients with early-stage (tumor number of ≤3 and tumor size of 2–5 cm) recurrent HCC with MVI at the initial hepatectomy who underwent adjuvant sorafenib following RFA or RFA alone in 13 centers from June 2013 to June 2020. In the combination group, sorafenib of 400 mg twice daily was administered within 7 days after RFA. Overall survival (OS) and recurrence-free survival (RFS) were compared. Subgroup analysis based on MVI grade was performed. MVI grade was based on the practice guidelines for the pathological diagnosis of HCC and included M1 (≤5 MVI sites, all located within adjacent peritumoral liver tissues 0–1 cm away from the tumor margin) and M2 (>5 MVI sites, or any MVI site located within adjacent peritumoral liver tissues > 1 cm away from the tumor margin).ResultsA total of 103 patients received the combination therapy and 108 patients received RFA alone. The combination therapy provided better survival than RFA alone (median RFS: 17.7 vs. 13.1 months, P < 0.001; median OS: 32.0 vs. 25.0 months, P = 0.002). Multivariable analysis revealed that treatment allocation was an independent prognostic factor. On subgroup analysis, the combination therapy provided better survival than RFA alone in patients with M1 along with either a tumor size of 3–5 cm, tumor number of two to three, or alpha-fetoprotein (AFP) > 400 μg/L, and in those with M2 along with either a tumor size of 2–3 cm, one recurrent tumor, or AFP ≤ 400 μg/L.ConclusionsAdjuvant sorafenib following RFA was associated with better survival than RFA alone in patients with early-stage recurrent HCC with MVI at the initial hepatectomy. Moreover, MVI grade could guide the application of adjuvant sorafenib.

The efficacy and safety of CT-Guided Iodine-125 Radioactive Seed Implantation (RSI) for the treatment of intrahepatic recurrent hepatocellular carcinoma (rHCC) were analyzed in this multicenter retrospective study. We reviewed the medical records of patients with rHCC treated with I-125 seed implantation at four different hospitals in China from December 2011 and January 2021. The local progression-free survival (LPFS),liver PFS, and overall survival (OS) were calculated, and the short-term efficacy and treatment-related toxicities were evaluated. A total of 82 patients were enrolled; the median follow-up time was 46 months (range, 3–80 months). The 1-, 3- and 5-year LPFS rates were 63.8%, 27.1%, and 7.9%, respectively, and the corresponding OS rates were 74.8%, 32.9%, and 12.6%, respectively. Univariate analysis showed that factors influencing LPFS included the maximum lesion diameter, Barcelona Clinic Liver Cancer (BCLC) stage, interval between treatment and recurrence, and D90. Multivariate analyses revealed that the BCLC stage, interval between treatment and recurrence, and D90 were independent factors influencing LPFS, whereas BCLC stage, D90, and short-term efficacy were independent factors influencing OS. In summary, I-125 seed implantation is a safe and effective treatment for rHCC. The BCLC stage, interval, and D90 were found to influence the local control. A larger, prospective study is required to confirm the dose-response curve for Iodine-125 RSI of rHCC.

Objective To evaluate the clinical efficacy of complete laparoscopic hepatectomy (LH) and open hepatectomy (OH） on recurrent hepatocellular carcinoma (r HCC） by meta-analysis. Methods The Cochrane Library, Pub Med, Embase, Web of Science and CNKI Databases were searched for eligible literature published up to 31 st March 2021.Statistical analysis was performed with Review Manager 5.3 software. Results A total of 655（313 in the LH group and 342 in the OH group） patients included in eight articles were eligible for this study. Compared with the OH group, the LH group had significant better results in the following aspects: operative duration[standard mean deviation (SMD）=-0.71,95% confidence interval（95%CI）（-0.91,-0.52）,P<0.000 01],intraoperative bleeding [SMD=-1.62,95%CI（-1.99,-1.25）,P<0.000 01],first passage of gas by anus[SMD =-0.89,95%CI（-1.35,-0.43）,P=0.000 2],postoperative activity time (days） [SMD =-1.44,95%CI（-2.08,-0.79）,P<0.000 1],and postoperative hospital stay time [SMD =-1.54,95%CI（-2.18,-0.89）,P<0.000 01].Conclusion The LH is feasible for r HCC, and the LH is safer than the OH. Therefore, it is recommended to be regarded as the preferred therapy of patients with r HCC. [ABSTRACT FROM AUTHOR]

Background: Both transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective methods for the treatment of recurrent hepatocellular carcinoma (RHCC). Thus far, it is unclear which method is more satisfactory in short- and long-term survival benefits. Purpose: To compare the overall survival (OS) and complications of TACE and RFA used for the management of RHCC. Material and Methods: A literature search was carried out using PubMed, the Cochrane Library and, Embase databases, and Google Scholar, keywords including "RHCC," "TACEC," and "RFA" with a cutoff date of 30 April 2021. Used Review Manager software was to calculate short- and long-term OS. The clinical outcomes are major complications and complete response (CR). Results: Finally, nine clinical trials met the research standard, including 1326 subjects, of which 518 received RFA and 808 received TACE. The analysis showed that patients who underwent RFA had significantly higher 1-, 3-, and 5-year OS (OR1-year = 1.92, 95% confidence interval (CI) = 1.27–2.91, p =.002; OR3-year = 1.64, 95% CI = 1.30–2.08, p <.0001; OR5-year = 3.22, 95% CI = 1.34–7.72, p =.009). Besides, the patients who chose RFA had an obvious higher rate of CR than those receiving TACE (OR = 33.75, 95% CI = 1.73–658.24, p =.002). However, the major complications were consistency between these two groups. Conclusion: Our study discovered that RFA had greater CR and incidence in both the short-term and long-term OS than TACE. In addition, obvious difference was not found in major complications in these two methods. [ABSTRACT FROM AUTHOR]

This paper evaluates the efficacy and safety of repeat hepatic resection and radiofrequency ablation in the treatment of recurrent hepatocellular carcinoma We retrieved and collected all relevant articles from the inception to 8 March 2020. After data extraction, we conducted meta-analysis and carried out the heterogeneity test, sensitivity analysis, and publication bias test to evaluate reliability A total of 12 studies with 1746 patients (rHR 837, RFA 909) were included. rHR was similar to RFA in a one-year overall survival rate (OS), while rHR was superior to RFA in 3- and 5-year OS and 1-, 3-, and 5-year disease-free survival rates (DFS), but the procedure-related complications of RFA were significantly less than those of rHR. Among the subgroups with Milan criteria, rHR was similar to RFA in 1-, 3-, and 5-year OS and 1-year DFS, but superior to RFA in 3- and 5-year DFS. RFA is the first choice for recurrent HCC meeting Milan criteria. When it does not meet the Milan criteria, minimally invasive treatment should not be carried out at the cost of survival, and rHR should be the first choice. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate the indications of laparoscopic repeat liver resection (LRLR) for recurrent hepatocellular carcinoma from the viewpoint of its difficulty. Methods: One hundred and one patients who underwent LRLR and 59 patients who underwent open repeat liver resection (ORLR) were included. The difficulty was classified according to the preoperative predictive factors for difficult LRLR, including an open approach during previous liver resection, history of two or more previous liver resections, history of previous major liver resection, tumor near the resected site of the previous liver resection, and intermediate or high difficulty with the difficulty scoring system. We compared the surgical outcomes between the LRLR and ORLR groups based on the difficulty class (low‐ or intermediate difficiulty class, 0 to 3 predictive factors; high difficiulty class, 4 or 5 factors). Results: In the low‐ or intermediate difficiulty class, intraoperative blood loss and the proportion of patients with postoperative complications were significantly lower in LRLR than in ORLR, and the duration of the postoperative hospital stay was significantly shorter in LRLR than in ORLR. In the high difficiulty class, total operative time and operative time before starting hepatic parenchymal resection were significantly longer in LRLR than in ORLR, and there were no significant differences in other surgical outcomes between the two groups. Conclusion: LRLR is recommended for patients in the low or intermediate difficulty class. However, LRLR does not have an advantage with longer operative time for patients in the high difficulty class compared with ORLR. [ABSTRACT FROM AUTHOR]

Objectives: To preliminarily evaluate the clinical effectiveness and safety of computed tomography (CT) image-guided irreversible electroporation (IRE) for the treatment of recurrent hepatocellular carcinoma (HCC) after surgical resection. Methods: From January 2016 to February 2018, 18 patients diagnosed with recurrent HCC after surgical resection received IRE under CT image guidance for 22 tumors. Patients were enrolled for IRE when ineligible for thermal ablation due to tumor location. Clinical records and imaging data were reviewed to assess complete ablation rate, local tumor progression free rate (LTPFR), local tumor progression free survival (LTPFS) and complications after a median follow-up time of 14 months. Results: Successful complete ablations were achieved in 20/22 (90.1%) tumors. Mean LTPFS was 10.5 ​± ​9.4 months. Overall 3-, 6- and 12-months LTPFR in 22 tumors following IRE were 68.2% (95% confidence interval [CI]: 45%–83%), 59.1% (95% CI: 33%–76%) and 36.4% (95% CI: 17%–56%), respectively. Complications included pneumothorax (2/18, 11.1%), localized pain (3/18, 16.7%), bile duct dilation (1/18, 5.6%) and transient hypertension (1/18, 5.6%). No major complications or treatment-related deaths were observed. The alpha-fetoprotein levels of two patients decreased to the normal range at 3 and 4 months, respectively. Conclusions: This study showed that percutaneous CT image-guided IRE can serve as a safe and effective treatment for recurrent HCC not suitable for thermal ablation.

Chunhou Qi,1 Shankai Li,1 Lei Zhang2 1Department of Interventional Medicine, Linyi City Central Hospital, Yishui, Shandong, People’s Republic of China; 2Department of Interventional Radiology, Shandong Medical Imaging Research Institute, Affiliated to Shandong University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Lei ZhangDepartment of Interventional Radiology, Shandong Medical Imaging Research Institute, Affiliated to Shandong University, 324 Jingwu Road, Jinan, Shandong, People’s Republic of ChinaTel +86-531-68776767Fax +86-531-87938550Email zhanglei0422@yeah.netAim: To develop and validate a nomogram for predicting the overall survival (OS) in patients with recurrent hepatocellular carcinoma (HCC) after hepatectomy who underwent microwave ablation (MWA).Methods: The training cohort included 299 patients with recurrent HCCs after hepatectomy who met the Milan criteria and received MWA from April 2007 to December 2017. Baseline characteristics were collected to identify risk factors for the determination of death after MWA. A multivariate Cox proportional hazards model based on significant risk factors was used to develop the nomogram, which was then assessed for its predictive accuracy using Harrell’s C-index and the area under the curve (AUC). The nomogram was validated by internal (n = 240) and external cohorts (n = 205) from another hospital.Results: After a median follow-up of 32.3 months, 38.8% (116/299) of patients had died. Multivariate Cox proportional hazards analyses showed that comorbid disease, early recurrence, and albumin-bilirubin (ALBI) grades 2– 3 were independent prognostic factors for poor OS. This nomogram accurately stratified patients into subgroups with low or high risk. The 1-, 3- and 5-year OS rates in the low-risk subgroup were 99.4%, 97.2%, and 86.1%, respectively, and they were 92.8%, 70.3%, and 45.8% in the high-risk subgroup (P < 0.001). The nomogram predicted OS in the training cohort with a C-index score of 0.801 (95% CI 0.761– 0.841). The nomogram was validated by internal and external cohorts, with C-index scores of 0.792 (95% CI 0.738– 0.846) and 0.744 (95% CI 0.703– 0.785), respectively.Conclusion: The nomogram provides individualized risk estimates for long-term OS for patients with recurrent HCC after hepatectomy who underwent MWA.Keywords: recurrent hepatocellular carcinoma, microwave ablation, overall survival, nomogram, hepatectomy

Abstract Background and aims The optimal treatment strategy for recurrent hepatocellular carcinoma (HCC) remains unclear. Therefore, we aimed to compare the outcomes of repeat hepatic resection (RHR) and radiofrequency ablation (RFA) for recurrent HCC. Method From December 2004 to December 2015, 138 patients who underwent RHR and 194 patients who underwent RFA were enrolled. Propensity score matching (PSM) was performed to establish 1:1 RHR‐RFA group matching. Clinical outcomes were compared before and after matching. Results Before matching, the 1‐, 3‐, and 5‐year postrecurrence survival (PRS) rates were 91.8%, 82.0%, and 72.9% for the RHR group (n = 138) and 94.4%, 75.4%, and 61.7% for the RFA group (n = 194), respectively (P = .380). After matching, the PRS rates at 1, 3, and 5 years were 90.5%, 81.5%, and 71.8% for the RHR group (n = 120) and 91.0%, 61.0%, and 41.7% for the RFA group (n = 120), respectively (P = .002). In the subgroup analysis, the PRS rates for the RHR group were better than those for the RFA group for patients who relapsed within 2 years (P = .004) or patients with primary tumor burden beyond the Milan criteria (P = .004). Multivariate analysis showed that treatment allocation was identified as an independent prognostic factor for PRS. Conclusion Compared with RFA, RHR provided a survival advantage for recurrent HCC, especially for patients who relapsed within 2 years and those with primary tumor burden beyond the Milan criteria.

Abstract Background Tumor recurrence in patients after surgery severely reduces the survival rate of surgical patients. Targeting and killing recurrent tumor cells and tissues is extremely important for the cancer treatment. Results Herein, we designed a nano-biomimetic photothermal-controlled drug-loading platform HepM-TSL with good targeting ability and immunocompatibility for the treatment of recurrent hepatocellular carcinoma. HepM-TSL can accurately target the recurrent tumor area with the aid of the cloaked homotypic cell membrane and release the chemotherapy drugs in a controlled manner. In vivo results have confirmed that HepM-TSL loaded with drugs and photosensitizer achieves the synergistic treatment of recurrent hepatocellular carcinoma with good therapeutic effect and slight side effects. Conclusion Accordingly, HepM-TSL provides a sound photothermal-chemotherapy synergistic strategy for the treatment of other recurrent cancers besides of recurrent hepatocellular carcinoma.

Purpose To evaluate the feasibility, effectiveness, and treatment outcomes of percutaneous radiofrequency ablation (RFA) in the application of intrahepatic recurrent hepatocellular carcinoma (r-HCC) after liver transplantation (LT). Methods From April 2008 to December 2019, a total of 37 patients (34 male and 3 female, mean age: 48.7 ± 10.5 years) with 61 r-HCCs after LT treated by RFA as a first-line option were enrolled. The technical success, recurrence-free survival (RFS), overall survival (OS) and complications were evaluated. Results After the first session of RFA, three patients were detected with residual foci. All of them received additional session of RFA and two tumors were successfully ablated. Therefore, the technical success was 97.3% (36/37). During the follow-up period, a total of 7 tumors developed local tumor progression (LTP) after 2.2–10.8 months. The LTP rate was 11.7% for r-HCC in the transplanted liver. The median RFS was 4.8 months (95% confidence interval [CI]: 2.2–7.3 months). The 1-, 3-, and 5-year cumulative OS rates were 68.5%, 40.3%, and 40.3%, respectively. Multivariate analyses revealed that tumor size was the only independent predictor for RFS (hazard ratio [HR] = 2.557, 95% CI, 1.015–6.444; p = .046) and limited extrahepatic metastasis was the only independent prognostic factors of OS after RFA for post-LT r-HCC (HR = 4.031, 95%CI, 1.218–13.339; p = .022). Major complications after RFA occurred in two patients (2/37, 5.4%). Conclusion Percutaneous RFA is safe and effective for intrahepatic r-HCC after LT, especially for those without limited extrahepatic metastasis.

BackgroundThe purpose of this study was to compare the efficacy and safety of transarterial chemoembolization (TACE) in combination with radiofrequency ablation (RFA) (TACE-RFA) and repeat hepatectomy in the treatment of recurrent hepatocellular carcinoma (HCC) after curative resection.MethodsThis retrospective study evaluated consecutive medical records of patients who received either TACE-RFA or repeat hepatectomy between January 2010 and May 2021. Overall survival (OS), progression-free survival (PFS), and complications were compared.ResultsOf the 2672 patients who received either TACE-RFA or repeat hepatectomy, 111 eligible patients were included in our study, 63 in the TACE-RFA group and 48 in the repeat hepatectomy group. The median OS was 38 months in the TACE-RFA group and 42 months in the repeat hepatectomy group, with no statistically difference between the two groups (P=0.45). Meanwhile, there was also no statistically significant difference in PFS between the two groups (P=0.634). Although both groups achieved similar outcomes, the rate of major complications was significantly higher in the repeat hepatectomy group (P=0.003).ConclusionsPatients with recurrent HCC in the TACE-RFA group and the repeat hepatectomy group had similar OS and PFS regardless of the patient’s tumor diameter, but the TACE-RFA group was safer and more minimally invasive.

Background: The purpose of this study was to compare the efficacy and safety of transarterial chemoembolization (TACE) in combination with radiofrequency ablation (RFA) (TACE-RFA) and repeat hepatectomy in the treatment of recurrent hepatocellular carcinoma (HCC) after curative resection. Methods: This retrospective study evaluated consecutive medical records of patients who received either TACE-RFA or repeat hepatectomy between January 2010 and May 2021. Overall survival (OS), progression-free survival (PFS), and complications were compared. Results: Of the 2672 patients who received either TACE-RFA or repeat hepatectomy, 111 eligible patients were included in our study, 63 in the TACE-RFA group and 48 in the repeat hepatectomy group. The median OS was 38 months in the TACE-RFA group and 42 months in the repeat hepatectomy group, with no statistically difference between the two groups (P =0.45). Meanwhile, there was also no statistically significant difference in PFS between the two groups (P =0.634). Although both groups achieved similar outcomes, the rate of major complications was significantly higher in the repeat hepatectomy group (P =0.003). Conclusions: Patients with recurrent HCC in the TACE-RFA group and the repeat hepatectomy group had similar OS and PFS regardless of the patient's tumor diameter, but the TACE-RFA group was safer and more minimally invasive. [ABSTRACT FROM AUTHOR]

Background: Repeat hepatectomy and radiofrequency ablation (RFA) are widely used to treat early recurrent hepatocellular carcinoma (RHCC) located in the subcapsular region, but the optimal treatment strategy remains to be controversial. Methods: A total of 126 RHCC patients in the subcapsular location after initial radical hepatectomy were included in this study between Dec 2014 and Jan 2018. These patients were divided into the RFA group (46 cases) and the repeat hepatectomy group (80 cases). The primary endpoints include repeat recurrence-free survival (rRFS) and overall survival (OS), and the secondary endpoint was complications. The propensity-score matching (PSM) was conducted to minimize the bias. Complications were evaluated using the Clavien-Dindo classification, and severe complications were defined as classification of complications of ≥grade 3. Results: There were no significant differences in the incidence of severe complications were observed between RFA group and repeat hepatectomy group in rRFS and OS both before (1-, 2-, and 3-year rRFS rates were 65.2%, 47.5%, and 33.3% vs 72.5%, 51.2%, and 39.2%, respectively, P = 0.48; 1-, 2-, and 3-year OS rates were 93.5%, 80.2%, and 67.9% vs 93.7%, 75.8%, and 64.2%, respectively, P = 0.92) and after PSM (1-, 2-, and 3-year rRFS rates were 68.6%, 51.0%, and 34.0% vs 71.4%, 42.9%, and 32.3%, respectively, P = 0.78; 1-, 2-, and 3-year OS rates were 94.3%, 82.9%, and 71.4% vs 88.6%, 73.8%, and 59.0%, respectively, P = 0.36). Moreover, no significant differences in the incidence of severe complications were observed between the RFA group and repeat hepatectomy group. Conclusion: Both repeat hepatectomy and RFA are shown to be effective and safe for the treatment of RHCC located in the subcapsular region. [ABSTRACT FROM AUTHOR]

Background: We compared surgical outcomes, with a focus on tumor characteristics, of laparoscopic repeat hepatectomy (LRH) and open repeat hepatectomy (ORH) to identify recurrent hepatocellular carcinoma (HCC) cases where the LRH procedure would be more favorable than ORH.Methods: Eighty-one HCC patients who underwent repeat hepatectomy in our hospital from 2008 to 2019 were retrospectively analyzed in this study. Of these patients, 30 and 51 patients underwent LRH and ORH, respectively. We analyzed surgical outcomes of LRH and ORH, focusing on tumor characteristics such as tumor size, location, distance from major vessels, and contralateral or ipsilateral tumor recurrence to determine what factors could affect surgical outcomes. Subsequently, using a propensity-matched cohort, we compared the impact of those factors on LRH and ORH outcomes.Results: In the entire cohort, the LRH operation time was significantly shorter in contralateral recurrent HCC cases than in ipsilateral recurrent HCC cases (252 vs. 398 min, P = 0.008); however, such a difference was not observed in the ORH operation time. We subsequently compared the surgical outcomes, in terms of the location of tumor recurrence, between the LRH and ORH groups in a propensity-matched cohort. In total, 23 patients were included in each of these groups. We found that the LRH procedure had significantly shorter operative time than the ORH procedure in the contralateral recurrent HCC cases (253 vs. 391 min, P = 0.018); however, we did not observe such a difference in the ipsilateral recurrent HCC cases (372 vs. 333 min, P = 0.669). LRH had lower blood loss, similar postoperative complications and shorter hospital stay than ORH in both contralateral and ipsilateral recurrent HCC cases.Conclusions: LRH is likely considered a more favorable approach than ORH in treating patients with contralateral recurrent HCC. [ABSTRACT FROM AUTHOR]

Background/aim: This study aimed to evaluate the utility of the albumin-bilirubin grade for predicting the prognosis after repeat liver resection for patients with recurrent hepatocellular carcinoma., Patients and Methods: Ninety patients with intrahepatic recurrent hepatocellular carcinoma who underwent repeat liver resection at our institution between 2005 and 2019 were retrospectively analyzed. Cox proportional-hazards regression models evaluated independent preoperative prognostic factors, including the albumin-bilirubin grade. Prognosis differences between patients with albumin-bilirubin grades 1 and 2 were analyzed using the Kaplan-Meier method., Results: Cox proportional-hazards regression analysis revealed that albumin-bilirubin grade 2 (p=0.003) and early recurrence within one year from the initial surgery (p=0.001) were independently associated with poor recurrence-free survival, and albumin-bilirubin grade 2 (p=0.020) was independently associated with poor overall survival. The five-year recurrence-free (31% and 17%, respectively) and overall (86% and 60%, respectively) survival rates after repeat liver resection for patients with albumin-bilirubin grades 1 and 2 were significantly different between groups (both p=0.003)., Conclusion: The albumin-bilirubin grade is useful for preoperatively predicting favorable survival rates after repeat liver resection for patients with recurrent hepatocellular carcinoma. Patients with an albumin-bilirubin grade 1 are better candidates for surgical treatment of recurrent hepatocellular carcinoma., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Ischemic cholangiopathy (IC) has a known poor prognosis. However, the risks and outcomes of this complication after transcatheter arterial chemoembolization (TACE) in hepatectomized patients are poorly documented. This study aimed to evaluate the incidence of and to identify the predictive factors for IC following TACE for recurrent hepatocellular carcinoma (HCC) after hepatectomy.Method: From a cohort with a total of 486 patients who underwent resection for HCC, we included all consecutive patients who were treated with TACE for recurrent HCC after hepatectomy between 2000 and 2017. IC was defined by the coexistence of biological cholestasis and morphological lesions.Results: A total of 156 patients underwent TACE for the treatment of HCC recurrence after hepatectomy. Of them, eight (5.1%) developed IC. Their prognosis was poor compared with patients without IC (3-year survival 23.4% vs 76.2%; P = 0.008). Two factors, namely, time between hepatectomy and TACE (4.8 months vs. 16.0 months, P = 0.001) and TACE for a remnant liver mobilized during hepatectomy (P = 0.001), were associated with IC. Receiver operating characteristic (ROC) curve analysis showed that 7 months was the more discriminant cutoff for the time period. IC occurred in 33.3% of the patients with the two factors, in 5.0% of those with one factor, and 0% in the absence of any factors.Conclusion: TACE for treating HCC recurrence carries a high risk of IC when performed early after hepatectomy in a previously mobilized liver. Our results might aid in identifying candidates for TACE for recurrent HCC, considering the major effect on patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: To explore prognostic factors by comparing the efficacy of salvage liver transplantation (sLT) and rehepatectomy (RH) for the treatment of recurrent hepatocellular carcinoma after hepatectomy. Methods: Clinical data were collected for 124 patients treated at our center from January 2012 to August 2018. The median follow‐up time for the patients was 39 months. By analyzing the clinical data between the sLT group (46 cases) and RH group (78 cases), the factors affecting the prognosis of patients were compared. Results: The proportion of alpha‐fetoprotein (AFP) ≥ 100 µg/L in the recurrence group was significantly higher than that in the recurrence‐free group (70.0% vs 22.2%, P =.014). The postoperative overall survival (OS) and recurrence‐free survival (RFS) were better in the sLT group than in the RH group (81.2% vs 36.9%, P <.01; 77.1% vs 55.6%, P =.019). In the sLT group, the OS and RFS in the AFP < 100 µg/L group were superior to those in the AFP ≥ 100 µg/L group (P =.046 and P =.002). Conclusion: The sLT group had achieved better efficacy than RH group, but when AFP ≥ 100 µg/L, sLT did not achieve better efficacy than RH. [ABSTRACT FROM AUTHOR]

Background and aims: The optimal treatment strategy for recurrent hepatocellular carcinoma (HCC) remains unclear. Therefore, we aimed to compare the outcomes of repeat hepatic resection (RHR) and radiofrequency ablation (RFA) for recurrent HCC. Method: From December 2004 to December 2015, 138 patients who underwent RHR and 194 patients who underwent RFA were enrolled. Propensity score matching (PSM) was performed to establish 1:1 RHR‐RFA group matching. Clinical outcomes were compared before and after matching. Results: Before matching, the 1‐, 3‐, and 5‐year postrecurrence survival (PRS) rates were 91.8%, 82.0%, and 72.9% for the RHR group (n = 138) and 94.4%, 75.4%, and 61.7% for the RFA group (n = 194), respectively (P =.380). After matching, the PRS rates at 1, 3, and 5 years were 90.5%, 81.5%, and 71.8% for the RHR group (n = 120) and 91.0%, 61.0%, and 41.7% for the RFA group (n = 120), respectively (P =.002). In the subgroup analysis, the PRS rates for the RHR group were better than those for the RFA group for patients who relapsed within 2 years (P =.004) or patients with primary tumor burden beyond the Milan criteria (P =.004). Multivariate analysis showed that treatment allocation was identified as an independent prognostic factor for PRS. Conclusion: Compared with RFA, RHR provided a survival advantage for recurrent HCC, especially for patients who relapsed within 2 years and those with primary tumor burden beyond the Milan criteria. [ABSTRACT FROM AUTHOR]

Background: Tumor recurrence in patients after surgery severely reduces the survival rate of surgical patients. Targeting and killing recurrent tumor cells and tissues is extremely important for the cancer treatment. Results: Herein, we designed a nano-biomimetic photothermal-controlled drug-loading platform HepM-TSL with good targeting ability and immunocompatibility for the treatment of recurrent hepatocellular carcinoma. HepM-TSL can accurately target the recurrent tumor area with the aid of the cloaked homotypic cell membrane and release the chemotherapy drugs in a controlled manner. In vivo results have confirmed that HepM-TSL loaded with drugs and photosensitizer achieves the synergistic treatment of recurrent hepatocellular carcinoma with good therapeutic effect and slight side effects. Conclusion: Accordingly, HepM-TSL provides a sound photothermal-chemotherapy synergistic strategy for the treatment of other recurrent cancers besides of recurrent hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Background: This meta-analysis was conducted to assess the survival benefits of repeat hepatectomy (RH) and thermal ablation therapy (TAT) in managing recurrent hepatocellular carcinoma (HCC)., Methods: A comprehensive search was conducted in the PubMed, SinoMed, Embase, Cochrane Library, Medline, and Web of Science databases using relevant keywords to identify all studies published on this specific topic. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were estimated using a fixed-effects model., Results: This meta-analysis included a total of 21 studies, comprising 2580 patients with recurrent HCC, among whom 1189 underwent RH and 1394 underwent TAT. Meta-analysis results demonstrated that the RH group exhibited superior overall survival (OS) (HR=0.85, 95%CI 0.76∼0.95, P=0.004) and recurrence-free survival (RFS) (HR=0.79, 95%CI 0.7∼0.9, P<0.01) compared to the TAT group. Regarding postoperative complications, the TAT group experienced fewer complications than the RH group (OR=3.23, 95%CI 1.48∼7.07, P=0.003), while no significant difference in perioperative mortality was observed between the two groups (OR=2.11, 95%CI 0.54∼8.19, P=0.28)., Conclusion: The present study demonstrates that, in comparison to TAT, RH may confer superior survival benefits for patients with recurrent HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Dong, Zhang, Wan and Zhang.)