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Hepatocellular carcinoma (HCC), the most prevalent malignancy of the digestive tract, is characterized by a high mortality rate and poor prognosis, primarily due to its initial diagnosis at an advanced stage that precludes any surgical intervention. Recent advancements in systemic therapies have significantly improved oncological outcomes for intermediate and advanced‐stage HCC, and the combination of locoregional and systemic therapies further facilitates tumor downstaging and increases the likelihood of surgical resectability for initially unresectable cases following conversion therapies. This shift toward high conversion rates with novel, multimodal treatment approaches has become a principal pathway for prolonged survival in patients with advanced HCC. However, the field of conversion therapy for HCC is marked by controversies, including the selection of potential surgical candidates, formulation of conversion therapy regimens, determination of optimal surgical timing, and application of adjuvant therapy post‐surgery. Addressing these challenges and refining clinical protocols and research in HCC conversion therapy is essential for setting the groundwork for future advancements in treatment strategies and clinical research. This narrative review comprehensively summarizes the current strategies and clinical experiences in conversion therapy for advanced‐stage HCC, emphasizing the unresolved issues and the path forward in the context of precision medicine. This work not only provides a comprehensive overview of the evolving landscape of treatment modalities for conversion therapy but also paves the way for future studies and innovations in this field. [ABSTRACT FROM AUTHOR]

Background & Aims: With the rising prevalence of non-alcoholic fatty liver disease (NAFLD) as a significant etiology for hepatocellular carcinoma (HCC), lean NAFLD-HCC has emerged as a specific distinct subtype. This study sought to investigate long-term outcomes following curative-intent hepatectomy for early-stage NAFLD-HCC among lean patients compared with overweight and obese individuals., Methods: A multicenter retrospective analysis was used to assess early-stage NAFLD-HCC patients undergoing curative-intent hepatectomy between 2009 and 2022. Patients were stratified by preoperative body mass index (BMI) into the lean (<23.0 kg/m 2 ), overweight (23.0-27.4 kg/m 2 ) and obese (≥27.5 kg/m 2 ) groups. Study endpoints were overall survival (OS) and recurrence-free survival (RFS), which were compared among groups., Results: Among 309 patients with NAFLD-HCC, 66 (21.3 %), 176 (57.0 %), and 67 (21.7 %) were lean, overweight, and obese, respectively. The three groups were similar relative to most liver, tumor, and surgery-related variables. Compared with overweight patients (71.3 % and 55.6 %), the lean individuals had a worse 5-year OS and RFS (55.4 % and 35.1 %, P = 0.017 and 0.002, respectively), which were comparable to obese patients (48.5 % and 38.2 %, P = 0.939 and 0.442, respectively). After adjustment for confounding factors, multivariable Cox-regression analysis identified that lean bodyweight was independently associated with decreased OS (hazard ratio: 1.69; 95 % confidence interval: 1.06-2.71; P = 0.029) and RFS (hazard ratio: 1.72; 95 % confidence interval: 1.17-2.52; P = 0.006) following curative-intent hepatectomy for early-stage NAFLD-HCC., Conclusions: Compared with overweight patients, individuals with lean NAFLD-HCC had inferior long-term oncological survival after hepatectomy for early-stage NAFLD-HCC. These data highlight the need for examination of the distinct carcinogenic pathways of lean NAFLD-HCC and its potential consequences in HCC recurrence., Competing Interests: Declaration of competing interest All authors have no conflicts of interest to declare., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Background: Hepatectomy is the preferred treatment for solitary hepatocellular carcinoma (HCC) without macrovascular invasion and distant metastasis, but long-term survival remains unsatisfactory in certain patients. We sought to identify whether the grading severity of microscopic vascular invasion (MVI) was associated with recurrence and survival among patients with solitary HCC., Methods: Consecutive patients who underwent hepatectomy for solitary HCC were identified from a multicenter prospectively-collected database. Patients were categorized into three groups according to the MVI grading system proposed by the Liver Cancer Pathology Group of China: M0 (no MVI), M1 (1-5 sites of MVI occurring ≤1.0 cm away from the tumor), and M2 (>5 sites occurring ≤1.0 cm or any site occurring >1 cm away from the tumor). Recurrence-free survival (RFS) and overall survival (OS) were compared among the groups., Results: Among 227 patients, 97 (42.7%), 83 (36.6%), and 47 (20.7%) patients had M0, M1, and M2, respectively. Median RFS rates among patients with M0, M1, and M2 were 38.3, 35.1, 11.6 months, respectively, while OS rates were 66.8, 62.3, 30.6 months, respectively (both P<0.001). Multivariate Cox-regression analyses demonstrated that both M1 and M2 were independent risk factors for RFS (hazard ratio 1.20, 95% CI: 1.03-1.89, P=0.040; and hazard ratio 1.67, 95% CI: 1.06-2.64, P=0.027) and OS (hazard ratio 1.28, 95% CI: 1.05-2.07, P=0.035; and hazard ratio 1.97, 95% CI: 1.15-3.38, P=0.013)., Conclusions: Grading severity of MVI was independently associated with RFS and OS after hepatectomy for solitary HCC. Enhanced surveillance for recurrence and potentially adjuvant therapy may be considered for patients with MVI, especially individuals with more severe MVI grading (M2)., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-22-411/coif). T.M.P. serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare., (2024 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Background: Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma (HCC). Based on age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II) with/without AFP-L3, ASAP and GALAD models are potential diagnostic panels. The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases (CLDs)., Methods: A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chinese hospitals. The etiologies of CLDs included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Using area under the receiver operating characteristic curve (AUC) values, the diagnostic performances of ASAP and GALAD models were compared to detect HCC among patients with various etiologies of CLDs., Results: Among 248 HCC patients and 722 CLD controls, the ASAP model demonstrated the highest AUC (0.886) to detect HCC at any stage, outperforming the GALAD model (0.853, P = 0.001), as well as any individual biomarker (0.687-0.799, all P < 0.001). In the subgroup analysis of various CLDs etiologies, the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology. In addition, the ASAP model performed better in detecting early-stage (BCLC stage 0/A) HCC versus the GALAD model., Conclusions: Despite using one less laboratory variable (AFP-L3), the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various etiologies of CLDs-related HCC., (Copyright © 2024 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Background: A solitary hepatocellular carcinoma (HCC) without macrovascular invasion and distant metastasis, regardless of tumor size, is currently classified as early-stage disease by the latest Barcelona Clinic Liver Cancer (BCLC) staging system. While the preferred treatment is surgical resection, the association of tumor morphology with long-term survival outcomes after liver resection for a solitary huge HCC of ≥10 cm has not been defined., Methods: Patients who underwent curative liver resection for a solitary huge HCC were identified from a multicenter database. Preoperative imaging findings were used to define spherical- or ellipsoidal-shaped lesions with smooth edges as balloon-shaped HCCs (BS-HCCs); out-of-shape lesions or lesions of any shape with matt edges were defined as non-balloon-shaped HCCs (NBS-HCCs). The two groups of patients with BS-HCCs and NBS-HCCs were matched in a 1:1 ratio using propensity score matching (PSM). Clinicopathologic characteristics, long-term overall survival (OS) and recurrence-free survival (RFS) were assessed., Results: Among patients with a solitary huge HCC, 74 pairs of patients with BS-HCC and NBS-HCC were matched. Tumor pathological features including proportions of microvascular invasion, satellite nodules, and incomplete tumor encapsulation in the BS-HCC group were lower than the NBS-HCC group. At a median follow-up of 50.7 months, median OS and RFS of all patients with a solitary huge HCC after PSM were 27.8 and 10.1 months, respectively. The BS-HCC group had better median OS and RFS than the NBS-HCC group (31.9 vs. 21.0 months, P=0.01; and 19.7 vs. 6.4 months, P=0.015). Multivariate analyses identified BS-HCC as independently associated with better OS (HR =0.592, P=0.009) and RFS (HR =0.633, P=0.013)., Conclusions: For a solitary huge HCC, preoperative imaging on tumor morphology was associated with prognosis following resection. In particular, patients with BS-HCCs had better long-term survival following liver resection versus patients with large NBS-HCCs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-21-423/coif). TMP and WYL serve as the unpaid editorial board members of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare., (2023 Hepatobiliary Surgery and Nutrition. All rights reserved.)