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Backgrounds/Aims: Patients undergoing liver resection for hepatocellular carcinoma (HCC) often possess good liver reserve, which may limit the prognostic effectiveness of existing liver function scores. This study aimed to develop a novel liver function score and a preoperative prognostic model specifically for HCC resection patients. Methods: Eight hundred twenty-seven HCC patients undergoing initial liver resection were segregated into training and validation cohorts in a 6:4 ratio. Cox regression analysis was employed to identify significant parameters influencing overall survival. The efficacy of the liver function score and prognostic model was evaluated using metrics such as the area under the receiver operating characteristic curve. Results: Aspartate aminotransferase (AST) and albumin emerged as significant prognostic indicators. The AST-albumin (ASAL) score, calculated as exp [AST (IU/L) × 0.005 - albumin (g/dL) × 1.043] × 100, outperformed existing scores such as Child-Turcotte-Pugh, albumin-bilirubin, platelet-albumin, and AST-platelet ratio index in both training and validation cohorts. Additionally, a scoring model that combined the ASAL score with alpha-fetoprotein and the up-to-seven criterion exhibited superior discriminatory capabilities compared to the American Joint Committee on Cancer tumor, node, metastasis stage, and Barcelona Clinic Liver Cancer stage. Conclusions: The proposed prognostic model that integrates the novel ASAL score offers promising prognostic potential for HCC patients undergoing liver resection.
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OBJECTIVES: This study aimed to evaluate the potential of deep learning (DL)-assisted automated three-dimensional quantitative tumor burden at MRI to predict postoperative early recurrence (ER) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This was a single-center retrospective study enrolling patients who underwent resection for BCLC A and B HCC and preoperative contrast-enhanced MRI. Quantitative total tumor volume (cm3) and total tumor burden (TTB, %) were obtained using a DL automated segmentation tool. Radiologists' visual assessment was used to ensure the quality control of automated segmentation. The prognostic value of clinicopathological variables and tumor burden-related parameters for ER was determined by Cox regression analyses. RESULTS: A total of 592 patients were included, with 525 and 67 patients assigned to BCLC A and B, respectively (2-year ER rate: 30.0% vs. 45.3%; hazard ratio (HR) = 1.8; p = 0.007). TTB was the most important predictor of ER (HR = 2.2; p < 0.001). Using 6.84% as the threshold of TTB, two ER risk strata were obtained in overall (p < 0.001), BCLC A (p < 0.001), and BCLC B (p = 0.027) patients, respectively. The BCLC B low-TTB patients had a similar risk for ER to BCLC A patients and thus were reassigned to a BCLC An stage; whilst the BCLC B high-TTB patients remained in a BCLC Bn stage. The 2-year ER rate was 30.5% for BCLC An patients vs. 58.1% for BCLC Bn patients (HR = 2.8; p < 0.001). CONCLUSIONS: TTB determined by DL-based automated segmentation at MRI was a predictive biomarker for postoperative ER and facilitated refined subcategorization of patients within BCLC stages A and B. CLINICAL RELEVANCE STATEMENT: Total tumor burden derived by deep learning-based automated segmentation at MRI may serve as an imaging biomarker for predicting early recurrence, thereby improving subclassification of Barcelona Clinic Liver Cancer A and B hepatocellular carcinoma patients after hepatectomy. KEY POINTS: Total tumor burden (TTB) is important for Barcelona Clinic Liver Cancer (BCLC) staging, but is heterogenous. TTB derived by deep learning-based automated segmentation was predictive of postoperative early recurrence. Incorporating TTB into the BCLC algorithm resulted in successful subcategorization of BCLC A and B patients.
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OBJECTIVES: To compare the diagnostic accuracy of 3D contrast-enhanced ultrasound (CEUS)/MRI-CEUS fusion imaging with 2D-CEUS in assessing the response of hepatocellular carcinoma (HCC) to locoregional therapies in a multicenter prospective study. MATERIALS AND METHODS: A consecutive series of patients with HCC scheduled for locoregional treatment were enrolled between April 2021 and March 2023. Patients were randomly divided into 3D-CEUS/MRI-CEUS fusion imaging group (3D/fusion group) or 2D-CEUS group (2D group). CEUS was performed 1 week before and 4-6 weeks after locoregional treatment. Contrast-enhanced MRI (CE-MRI) 4-6 weeks after treatment was set as the reference standard. CEUS images were evaluated for the presence or absence of viable tumors. Diagnostic performance criteria, including sensitivity, specificity, accuracy, and area under the curve (AUC), were determined for each modality. RESULTS: A total of 140 patients were included, 70 patients in the 2D group (mean age, 60.2 ± 10.4 years) and 70 patients in the 3D/fusion group (mean age, 59.8 ± 10.6 years). The sensitivity of the 3D/fusion group was 100.0% (95% CI: 75.9, 100.0), higher than that of the 2D group (55.6%, 95% CI: 22.7, 84.7; p = 0.019). The specificity of the 3D/fusion group was 96.3% (95% CI: 86.2, 99.4), which was comparable to that of the 2D group (98.4%, 95% CI: 90.0, 99.9; p = 0.915). The AUC of the 3D/fusion group was 0.98 (95% CI: 0.95, 1.00), higher than that of the 2D group (0.77, 95% CI: 0.56, 0.98; p = 0.020). CONCLUSION: 3D-CEUS/MRI-CEUS fusion imaging exhibits superior diagnostic accuracy in evaluating the treatment response to locoregional therapies for HCC. CLINICAL RELEVANCE STATEMENT: 3D-CEUS/MRI-CEUS fusion imaging can be applied for post-treatment assessment of residual tumors in HCC undergoing locoregional treatment, offering potential benefits in terms of accurate diagnosis and clinical management. KEY POINTS: Evaluating for HCC recurrence following locoregional therapy is important. 3D-CEUS/MRI-CEUS fusion imaging achieved a higher sensitivity than 2D-CEUS in assessing residual tumors after locoregional therapies. 3D-CEUS/MRI-CEUS fusion imaging can help clinicians intervene early in residual HCC lesions after locoregional treatment.
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OBJECTIVE: To examine the influence of Saponin I from Shuitianqi (Rhizoma Schizocapasae Plantagineae) (SSPH I) on hepatocellular carcinoma (HCC) metastasis, and to elucidate the underlying mechanism. METHODS: The intrahepatic metastasis Bagg's Albino/c (BALB/c) mouse model was established with human hepatocellular carcinomas (HepG2) cells, then treated with normal saline (once per day), cisplatin (2 mg/kg, once every 2 d), and SSPH â (25, 50, and 75 mg/kg, once per day). Then, we assessed alterations in the hepatic pathology and target protein expressions in the intrahepatic metastasis BALB/c mouse model using a series of molecular biology techniques. RESULTS: Based on our analysis, SSPH â significantly alleviated hepatocyte necrosis and tumor cells infiltration. Moreover, SSPH â suppressed extracellular matrix (ECM) degradation and angiogenesis viaa decrease in matrix etalloproteinase-2 (MMP-2), MMP-9, CD31, CD34, and vascular endothelial growth factor (VEGF) levels. Furthermore, SSPH â repressed invasion and meta-stasis by suppressing the transforming growth factor-ß1 (TGF-ß1)/Smad7 axis and epithelial-mesenchymal transition (EMT), as evidenced by the scarce TGF-ß1, N-cadherin, and Vimentin expressions, and elevated Smad7 and E-cadherin expressions. CONCLUSION: The SSPH â -mediated negative regulation of the TGF-ß1/Smad7 axis and EMT are critical for the inhibition of HCC invasion and metastasis.
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Medicamentos Herbarios Chinos , Transición Epitelial-Mesenquimal , Neoplasias Hepáticas , Saponinas , Proteína smad7 , Factor de Crecimiento Transformador beta1 , Animales , Humanos , Masculino , Ratones , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Células Hep G2 , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Metástasis de la Neoplasia , Saponinas/farmacología , Proteína smad7/metabolismo , Proteína smad7/genética , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
OBJECTIVE: To investigate the effect of Ganoderma Lucidum Spore Oil (GLSO) on the tumor growth and survival of H22 tumor-bearing mice treated with cyclophosphamide (CTX), and explore the underlying mechanism. METHODS: Allograft H22 hepatocellular carcinoma mouse model was applied to investigate the effect of GLSO on the tumor growth and survival of animals, and Kaplan-Meier survival analysis was used to analyze the life span. Plasma biochemical examination was used to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (UREA) and creatinine (CRE). Western blot analysis was performed to detect Programmed Death-1 (PD-1), Programmed Death Ligand 1 (PD-L1), Janus Kinase 2 (JAK2), phosphorylated Signal Transducer and Activator of Transcription 3 (p-STAT3), and Signal Transducer and Activator of Transcription 3 (STAT3) expression. RESULTS: GLSO increased the anti-tumor effect of CTX and prolonged the survival of H22 tumor-bearing mice treated with CTX. Meanwhile, GLSO increased the thymus index and showed no obvious toxicity to liver functions of animals. GLSO also decreased the level of UREA in H22 tumor-bearing mice treated with CTX. Furthermore, GLSO could inhibit the expression of PD-1 in spleen, which was independent of JAK2 expression and STAT3 phosphorylation. However, GLSO did not affect the expression of PD-L1, JAK2, and p-STAT3 in tumor tissue. CONCLUSION: GLSO could strengthen the anti-tumor effect of CTX and prolong the life span of H22 tumor-bearing mice, while the underlying mechanism might be relevant to the amelioration effect of thymus function and inhibition of PD-1 expression in spleen. Furthermore, these findings implied the promising role of GLSO in combination with CTX to extend the survival of patients in clinical chemotherapy of hepatocellular carcinoma.
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Ciclofosfamida , Neoplasias Hepáticas , Receptor de Muerte Celular Programada 1 , Animales , Humanos , Masculino , Ratones , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Ciclofosfamida/efectos adversos , Medicamentos Herbarios Chinos/administración & dosificación , Janus Quinasa 2/metabolismo , Janus Quinasa 2/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Receptor de Muerte Celular Programada 1/metabolismo , Receptor de Muerte Celular Programada 1/genética , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genéticaRESUMEN
Backgrounds/Aims: Although access to proton beam therapy (PBT) is limited worldwide, its use for the treatment of hepatocellular carcinoma (HCC) is gradually increasing with the expansion of new facilities. Therefore, we conducted a systematic review and meta-analysis to investigate the updated evidence of PBT for HCC. Methods: The MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were systematically searched for studies that enrolled patients with liver-confined HCC that were treated with PBT for a cure up to February 2024. Results: A total of 1858 HCC patients receiving PBT from 22 studies between 2004 and 2023 were selected for this meta-analysis. The median proportion of Child-Pugh class A was 86% (range: 41-100%), and the median tumor size was 3.6 cm (range: 1.2-9 cm). The median total dose ranged from 55 GyE to 76 GyE (median, 69 GyE). The pooled rates of 3- and 5-year local progression-free survival after PBT were 88% (95% confidence interval [CI], 85-91%) and 86% (95% CI, 82-90%), respectively. The pooled 3- and 5-year overall rates were 60% (95% CI, 54-66%) and 46% (95% CI, 38-54%), respectively. The pooled rates of grade 3 hepatic toxicity, classic radiation-induced liver disease (RILD), and non-classic RILD were 1%, 2%, and 1%, respectively. Conclusions: The current study supports PBT for HCC and demonstrates favorable long-term survival and low hepatic toxicities compared with other published studies on other radiotherapy modalities. However, further studies are needed to identify the subgroups that will benefit from PBT.
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PURPOSE: Nivolumab and regorafenib are second-line therapies for patients with advanced hepatocellular carcinoma (HCC). We aimed to compare the effectiveness of nivolumab and regorafenib. MATERIALS AND METHODS: We retrospectively reviewed patients with HCC treated with nivolumab or regorafenib after sorafenib failure. Progression-free survival (PFS) and overall survival (OS) were analyzed. An inverse probability of treatment weighting using the propensity score (PS) was performed to reduce treatment selection bias. RESULTS: Among the 189 patients recruited, 137 and 52 patients received regorafenib and nivolumab after sorafenib failure, respectively. Nivolumab users showed higher Child-Pugh B patients (42.3% vs. 24.1%) and shorter median sorafenib maintenance (2.2 months vs. 3.5 months) compared to regorafenib users. Nivolumab users showed shorter median OS (4.2 months vs. 7.4 months, p=0.045) than regorafenib users and similar median PFS (1.8 months vs. 2.7 months, p=0.070). However, the median overall and PFS did not differ between the two treatment groups after the 1:1 PS matching (log-rank p=0.810 and 0.810, respectively) and after the stabilized inverse probability of treatment weighting (log-rank p=0.445 and 0.878, respectively). In addition, covariate-adjusted Cox regression analyses showed that overall and PFS did not significantly differ between nivolumab and regorafenib users after 1:1 PS matching and stabilized inverse probability of treatment weighting (all p>0.05). CONCLUSION: Clinical outcomes of patients treated with nivolumab and regorafenib after sorafenib treatment failure did not differ significantly.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Nivolumab , Compuestos de Fenilurea , Piridinas , Sorafenib , Humanos , Nivolumab/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéutico , Sorafenib/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Adulto , Supervivencia sin ProgresiónRESUMEN
OBJECTIVES: To investigate the utility of deep learning (DL) automated segmentation-based MRI radiomic features and clinical-radiological characteristics in predicting early recurrence after curative resection of single hepatocellular carcinoma (HCC). METHODS: This single-center, retrospective study included consecutive patients with surgically proven HCC who underwent contrast-enhanced MRI before curative hepatectomy from December 2009 to December 2021. Using 3D U-net-based DL algorithms, automated segmentation of the liver and HCC was performed on six MRI sequences. Radiomic features were extracted from the tumor, tumor border extensions (5 mm, 10 mm, and 20 mm), and the liver. A hybrid model incorporating the optimal radiomic signature and preoperative clinical-radiological characteristics was constructed via Cox regression analyses for early recurrence. Model discrimination was characterized with C-index and time-dependent area under the receiver operating curve (tdAUC) and compared with the widely-adopted BCLC and CNLC staging systems. RESULTS: Four hundred and thirty-four patients (median age, 52.0 years; 376 men) were included. Among all radiomic signatures, HCC with 5 mm tumor border extension and liver showed the optimal predictive performance (training set C-index, 0.696). By incorporating this radiomic signature, rim arterial phase hyperenhancement (APHE), and incomplete tumor "capsule," a hybrid model demonstrated a validation set C-index of 0.706 and superior 2-year tdAUC (0.743) than both the BCLC (0.550; p < 0.001) and CNLC (0.635; p = 0.032) systems. This model stratified patients into two prognostically distinct risk strata (both datasets p < 0.001). CONCLUSION: A preoperative imaging model incorporating the DL automated segmentation-based radiomic signature with rim APHE and incomplete tumor "capsule" accurately predicted early postsurgical recurrence of a single HCC. CRITICAL RELEVANCE STATEMENT: The DL automated segmentation-based MRI radiomic model with rim APHE and incomplete tumor "capsule" hold the potential to facilitate individualized risk estimation of postsurgical early recurrence in a single HCC. KEY POINTS: A hybrid model integrating MRI radiomic signature was constructed for early recurrence prediction of HCC. The hybrid model demonstrated superior 2-year AUC than the BCLC and CNLC systems. The model categorized the low-risk HCC group carried longer RFS.
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Background/Aims: The enhancing "capsule" (EC) in hepatocellular carcinoma (HCC) diagnosis has received varying degrees of recognition across major guidelines. This study aimed to assess the diagnostic utility of EC in HCC detection. Methods: We retrospectively analyzed patients who underwent pre-surgical computed tomography (CT) and hepatobiliary agent-enhanced magnetic resonance imaging (HBA-MRI) between January 2016 and December 2019. A single hepatic tumor was confirmed based on the pathology of each patient. Three radiologists independently reviewed the images according to the Liver Imaging Reporting and Data System (LIRADS) v2018 criteria and reached a consensus. Interobserver agreement for EC before reaching a consensus was quantified using Fleiss κ statistics. The impact of EC on the LI-RADS classification was assessed by comparing the positive predictive values for HCC detection in the presence and absence of EC. Results: In total, 237 patients (median age, 60 years; 184 men) with 237 observations were included. The interobserver agreement for EC detection was notably low for CT (κ=0.169) and HBA-MRI (κ=0.138). The presence of EC did not significantly alter the positive predictive value for HCC detection in LI-RADS category 5 observations on CT (94.1% [80/85] vs. 94.6% [88/93], P=0.886) or HBA-MRI (95.7% [88/92] vs. 90.6% [77/85], P=0.178). Conclusions: The diagnostic value of EC in HCC diagnosis remains questionable, given its poor interobserver agreement and negligible impact on positive predictive values for HCC detection. This study challenges the emphasis on EC in certain diagnostic guidelines and suggests the need to re-evaluate its role in HCC imaging.
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Introduction: Hepatocellular carcinoma constitutes for approximately 75% of primary cancers of liver. Around 80- 90% of patients with HCC have cirrhosis at the time of diagnosis. Use of AI has recently gained significance in the field of hepatology, especially for the detection of HCC, owing to its increasing incidence and specific radiological features which have been established for its diagnostic criteria. Objectives: A systematic review was performed to evaluate the current literature for early diagnosis of hepatocellular carcinoma in cirrhotic patients. METHODS: Systematic review was conducted using PRISMA guidelines and the relevant studies were narrated in detail with assessment of quality for each paper. RESULTS: This systematic review displays the significance of AI in early detection and prognosis of HCC with the pressing need for further exploration in this field. CONCLUSIONS: AI can have a significant role in early diagnosis of HCC in cirrhotic patients.
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Carcinoma Hepatocelular , Detección Precoz del Cáncer , Cirrosis Hepática , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/diagnóstico por imagen , Detección Precoz del Cáncer/métodos , Inteligencia ArtificialRESUMEN
Background: Diacylglycerol O-acyltransferase 2 (DGAT2) synthesizes triacylglycerol (TG) from diacylglycerol; therefore, DGAT2 is considered as a therapeutic target for steatosis. However, the consequence of inhibiting DGAT2 is not fully investigated due to side effects including lethality and lipotoxicity. In this article, we observed the role of DGAT2 in hepatocarcinoma. Methods: The role of DGAT2 is analyzed via loss-of-function assay. DGAT2 knockdown (KD) and inhibitor treatment on HepG2 cell line was analyzed. Cumulative analysis of cell metabolism with bioinformatic data were assessed, and further compared with different cohorts of liver cancer patients and non-alcoholic fatty liver disease (NAFLD) patients to elucidate how DGAT2 is regulating cancer metabolism. Results: Mitochondrial function is suppressed in DGAT2 KD HepG2 cell along with the decreased lipid droplets. In the aspect of the cancer, DGAT2 KD upregulates cell proliferation. Analyzing transcriptome of NAFLD and hepatocellular carcinoma (HCC) patients highlights negatively correlating expression patterns of 73 lipid-associated genes including DGAT2. Cancer patients with the lower DGAT2 expression face lower survival rate. DGAT2 KD cell and patients' transcriptome show downregulation in estrogen- related receptor alpha (ESRRA) via integrated system for motif activity response analysis (ISMARA), with increased dimerization with corepressor prospero homeobox 1 (PROX1). Conclusion: DGAT2 sustains the stability of mitochondria in hepatoma via suppressing ESRRA-PROX1 transcriptional network and hinders HCC from shifting towards glycolytic metabolism, which lowers cell proliferation.
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Approximately 80% of hepatocellular carcinoma (HCC) cases arise in sub-Saharan Africa and Eastern Asia, following a similarly high prevalence of chronic hepatitis B virus (HBV) carriers in these regions. The etiology and epidemiology of HCC have recently changed worldwide. Although HBV infection is the main contributor to HCC development, a slow but continuous decline in HBV infection rates has been reported since 1990. Owing to the widespread use of direct-acting antivirals, the incidence of hepatitis C virus-related HCC has remarkably decreased in Japan and European countries. In Korea, Taiwan, and Singapore, the incidence of HBV-related HCC has significantly decreased owing to vaccination against HBV. Globally, while HBV accounted for more than half of HCCs in 1990, this had decreased to 42% in 2019. In contrast, the proportion of patients with alcoholic- and nonalcoholic steatohepatitis (NASH) increased from 13% to 18% and from 5% to 6%, respectively. NASH-related HCC has characteristics that differ from those of virus-associated HCC. Compared with other etiologies, patients with NASHassociated HCC are older, have a higher body mass index, and have higher rates of type 2 diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular disease. Nonalcoholic fatty liver disease (NAFLD)-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related and autoimmune liver diseases. Because patients with NAFLD usually have diabetes or obesity, surveying this population is challenging. Optimal selection of the target population and surveillance tools among patients with NAFLD needs to be determined.
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This review examines the transformative role of external beam radiotherapy (EBRT) in managing hepatocellular carcinoma (HCC), spotlighting the progression from traditional EBRT techniques to advanced modalities like intensity-modulated radiotherapy (RT), stereotactic body RT (SBRT), and innovative particle therapy, including proton beam therapy and carbon ion RT. These advancements have significantly improved the precision and efficacy of RT, marking a paradigm shift in the multimodal management of HCC, particularly in addressing complex cases and enhancing local tumor control. The review underscores the synergistic potential of integrating RT with other treatments like transarterial chemoembolization, systemic therapies such as sorafenib, and emerging immunotherapies, illustrating enhanced survival and disease control outcomes. The efficacy of RT is addressed for challenging conditions, including advanced HCC with macrovascular invasion, and RT modalities, like SBRT, are compared against traditional treatments like radiofrequency ablation for early-stage HCC. Additionally, the review accentuates the encouraging outcomes of particle therapy in enhancing local control and survival rates, minimizing treatment-related toxicity, and advocating for continued research and clinical trials. In conclusion, the integration of RT into multimodal HCC treatment strategies, coupled with the emergence of particle therapy, is crucial for advancing oncologic management, emphasizing the need for relentless innovation and personalized treatment approaches.
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Management of hepatocellular carcinoma (HCC) is challenging due to the complex relationship between underlying liver disease, tumor burden, and liver function. HCC is also notorious for its high recurrence rate even after curative treatment for early-stage tumor. Liver transplantation can substantially alter patient prognosis, but donor availability varies by each patient which further complicates treatment decision. Recent advancements in HCC treatments have introduced numerous potentially efficacious treatment modalities. However, high level evidence comparing the risks and benefits of these options is limited. In this complex situation, multidisciplinary approach or multidisciplinary team care has been suggested as a valuable strategy to help cope with escalating complexity in HCC management. Multidisciplinary approach involves collaboration among medical and health care professionals from various academic disciplines to provide comprehensive care. Although evidence suggests that multidisciplinary care can enhance outcomes of HCC patients, robust data from randomized controlled trials are currently lacking. Moreover, the implementation of a multidisciplinary approach necessitates increased medical resources compared to conventional cancer care. This review summarizes the current evidence on the role of multidisciplinary approach in HCC management and explores potential future directions.
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Hepatocellular carcinoma (HCC) presents a substantial public health challenge in South Korea as evidenced by 10,565 new cases annually (incidence rate of 30 per 100,000 individuals), in 2020. Cancer registries play a crucial role in gathering data on incidence, disease attributes, etiology, treatment modalities, outcomes, and informing health policies. The effectiveness of a registry depends on the completeness and accuracy of data. Established in 1999 by the Ministry of Health and Welfare, the Korea Central Cancer Registry (KCCR) is a comprehensive, legally mandated, nationwide registry that captures nearly all incidence and survival data for major cancers, including HCC, in Korea. However, detailed information on cancer staging, specific characteristics, and treatments is lacking. To address this gap, the KCCR, in partnership with the Korean Liver Cancer Association (KLCA), has implemented a systematic approach to collect detailed data on HCC since 2010. This involved random sampling of 10-15% of all new HCC cases diagnosed since 2003. The registry process encompassed four stages: random case selection, meticulous data extraction by trained personnel, expert validation, anonymization of personal data, and data dissemination for research purposes. This random sampling strategy mitigates the biases associated with voluntary reporting and aligns with stringent privacy regulations. This innovative approach positions the KCCR and KLCA as foundations for advancing cancer control and shaping health policies in South Korea.
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BACKGROUND: Multi-b-value diffusion-weighted imaging (DWI) with different postprocessing models allows for evaluating hepatocellular carcinoma (HCC) proliferation, spatial heterogeneity, and feasibility of treatment strategies. We assessed synergistic effects of bufalin+sorafenib in orthotopic HCC-LM3 xenograft nude mice by using intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI), a stretched exponential model (SEM), and a fractional-order calculus (FROC) model. METHODS: Twenty-four orthotopic HCC-LM3 xenograft mice were divided into bufalin+sorafenib, bufalin, sorafenib treatment groups, and a control group. Multi-b-value DWI was performed using a 3-T scanner after 3 weeks' treatment to obtain true diffusion coefficient Dt, pseudo-diffusion coefficient Dp, perfusion fraction f, mean diffusivity (MD), mean kurtosis (MK), distributed diffusion coefficient (DDC), heterogeneity index α, diffusion coefficient D, fractional order parameter ß, and microstructural quantity µ. Necrotic fraction (NF), standard deviation (SD) of hematoxylin-eosin staining, and microvessel density (MVD) of anti-CD31 staining were evaluated. Correlations of DWI parameters with histopathological results were analyzed, and measurements were compared among four groups. RESULTS: In the final 22 mice, f positively correlated with MVD (r = 0.679, p = 0.001). Significantly good correlations of MK (r = 0.677), α (r = -0.696), and ß (r= -0.639) with SD were observed (all p < 0.010). f, MK, MVD, and SD were much lower, while MD, α, ß, and NF were higher in bufalin plus sorafenib group than control group (all p < 0.050). CONCLUSION: Evaluated by IVIM, DKI, SEM, and FROC, bufalin+sorafenib was found to inhibit tumor proliferation and angiogenesis and reduce spatial heterogeneity in HCC-LM3 models. RELEVANCE STATEMENT: Multi-b-value DWI provides potential metrics for evaluating the efficacy of treatment in HCC. KEY POINTS: ⢠Bufalin plus sorafenib combination may increase the effectiveness of HCC therapy. ⢠Multi-b-value DWI depicted HCC proliferation, angiogenesis, and spatial heterogeneity. ⢠Multi-b-value DWI may be a noninvasive method to assess HCC therapeutic efficacy.
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Bufanólidos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/tratamiento farmacológico , Sorafenib/farmacología , Sorafenib/uso terapéutico , Ratones Desnudos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológicoRESUMEN
PURPOSE: To explore the predictive potential of intratumoral and multiregion peritumoral radiomics features extracted from multiparametric MRI for predicting pathological differentiation in hepatocellular carcinoma (HCC) patients. METHODS: A total of 265 patients with 277 HCCs (training cohort n = 193, validation cohort n = 84) who underwent preoperative MRI were retrospectively analyzed. The risk factors identified through stepwise regression analysis were utilized to construct a clinical model. Radiomics models based on MRI (arterial phase, portal venous phase, delayed phase) across various regions (entire tumor, Peri_5mm, Peri_10mm, Peri_20mm) were developed using the LASSO approach. The features obtained from the intratumoral region and the optimal peritumoral region were combined to design the IntraPeri fusion model. Model performance was assessed using the area under the curve (AUC). RESULTS: Larger size, non-smooth margins, and mosaic architecture were risk factors for poorly differentiated HCC (pHCC). The clinical model achieved AUCs of 0.77 and 0.73 in the training and validation cohorts, respectively, while the intratumoral model achieved corresponding AUC values of 0.92 and 0.82. The Peri_10mm model demonstrated superior performance to the Peri_5mm and Peri_20mm models, with AUC values of 0.87 vs. 0.84 vs. 0.73 in the training cohort and 0.80 vs. 0.77 vs. 0.68 in the validation cohort, respectively. The IntraPeri model exhibited remarkable AUC values of 0.95 and 0.86 in predicting pHCC in the training and validation cohorts, respectively. CONCLUSIONS: Our study highlights the potential of a multiparametric MRI-based radiomic model that integrates intratumoral and peritumoral features as a tool for predicting HCC differentiation. CRITICAL RELEVANCE STATEMENT: Both clinical and multiparametric MRI-based radiomic models, particularly the intratumoral radiomic model, are non-invasive tools for predicting HCC differentiation. Importantly, the IntraPeri fusion model exhibited remarkable predictiveness for individualized HCC differentiation. KEY POINTS: ⢠Both the intratumoral radiomics model and clinical features were useful for predicting HCC differentiation. ⢠The Peri_10mm radiomics model demonstrated better diagnostic ability than other peritumoral region-based models. ⢠The IntraPeri radiomics fusion model outperformed the other models for predicting HCC differentiation.
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This review explores the evolution of cancer staging, focusing on intermediate hepatocellular carcinoma (HCC), and the challenges faced by physicians. The Barcelona Clinic Liver Cancer (BCLC) staging system, introduced in 1999, was designed to address the limitations associated with providing accurate prognostic information for HCC and allocating specific treatments, to avoid overtreatment. However, criticism has emerged, particularly regarding the intermediate stage of HCC (BCLC-B) and its heterogeneous patient population. To overcome this limitation, various subclassification systems, such as the Bolondi and Kinki criteria, have been proposed. These systems are aimed at refining categorizations within the intermediate stage and have demonstrated varying degrees of success in predicting outcomes through external validation. This study discusses the shift in treatment paradigms, emphasizing the need for a more personalized approach rather than strictly adhering to cancer stages, without dismissing the relevance of staging systems. It assesses the available treatment options for intermediate-stage HCC, highlighting the importance of considering surgical and nonsurgical options alongside transarterial chemoembolization for optimal outcomes. In conclusion, the text advocates for a paradigm shift in staging systems prioritizing treatment suitability over cancer stage. This reflects the evolving landscape of HCC management, where a multidisciplinary approach is crucial for tailoring treatments to individual patients, ultimately aiming to improve overall survival.
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PURPOSE: Combining angiogenesis inhibitors may enhance therapeutic efficacy synergistically after TACE refractoriness. The purpose of this study was to compare the outcomes of transarterial chemoembolization (TACE) plus a tyrosine kinase inhibitor (TACE-TKI) with TKI only for patients with TACE-refractory hepatocellular carcinoma (HCC). METHODS: From January 2019 to March 2022, 101 HCC patients confirmed with TACE-refractory were retrospectively reviewed in the study. Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were evaluated between groups. RESULTS: Fifty-two patients undergoing TACE-TKI, while 32 patients receiving TKI alone were included. The objective response rate (ORR) was higher in the TACE-TKI group compared with the TKI group (55.8% vs. 25.0%, P = 0.006). The median PFS in the TACE-TKI group was significantly longer than that in the TKI group (7.6 months vs. 4.9 months, P = 0.018). The median OS was non reach to statistical longer than that in the TKI alone group (19.5 months vs. 17.7 months, P = 0.055). Subgroup analysis showed that TACE-TKI treatment resulted in a significantly longer median PFS and OS for Barcelona Clinic Liver Cancer (BCLC) stage B patients (PFS 11.8 months vs. 5.1 months, P = 0.017; OS 30.3 months vs. 19.4 months, P = 0.022). CONCLUSION: For patients with TACE-refractory HCC, TACE-TKI appeared to be superior to TKI monotherapy with regard to tumor control and PFS. Furthermore, for the BCLC stage B subgroup, TACE-TKI therapy was superior to TKI monotherapy in both OS and PFS.
Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Inhibidores de Proteínas Quinasas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Estudios Retrospectivos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Persona de Mediana Edad , Anciano , Terapia Combinada , Adulto , Resultado del TratamientoRESUMEN
BACKGROUND: Highly aggressive hepatocellular carcinoma (HCC) is characterized by high tumor recurrence and poor outcomes, but its definition and imaging characteristics have not been clearly described. PURPOSE: To develop and validate a fusion model on gadobenate dimeglumine-enhanced MRI for identifying highly aggressive HCC. STUDY TYPE: Retrospective. POPULATION: 341 patients (M/F = 294/47) with surgically resected HCC, divided into a training cohort (n = 177), temporal validation cohort (n = 77), and multiscanner validation cohort (n = 87). FIELD STRENGTH/SEQUENCE: 3T, dynamic contrast-enhanced MRI with T1-weighted volumetric interpolated breath-hold examination gradient-echo sequences, especially arterial phase (AP) and hepatobiliary phase (HBP, 80-100 min). ASSESSMENT: Clinical factors and diagnosis assessment based on radiologic morphology characteristics associated with highly aggressive HCCs were evaluated. The radiomics signatures were extracted from AP and HBP. Multivariable logistic regression was performed to construct clinical-radiologic morphology (CR) model and clinical-radiologic morphology-radiomics (CRR) model. A nomogram based on the optimal model was established. Early recurrence-free survival (RFS) was evaluated in actual groups and risk groups calculated by the nomogram. STATISTICAL TESTS: The performance was evaluated by receiver operating characteristic curve (ROC) analysis, calibration curves analysis, and decision curves. Early RFS was evaluated by using Kaplan-Meier analysis. A P value <0.05 was considered statistically significant. RESULTS: The CRR model incorporating corona enhancement, cloud-like hyperintensity on HBP, and radiomics signatures showed the highest diagnostic performance. The area under the curves (AUCs) of CRR were significantly higher than those of the CR model (AUC = 0.883 vs. 0.815, respectively, for the training cohort), 0.874 vs. 0.769 for temporal validation, and 0.892 vs. 0.792 for multiscanner validation. In both actual and risk groups, highly and low aggressive HCCs showed statistically significant differences in early recurrence. DATA CONCLUSION: The clinical-radiologic morphology-radiomics model on gadobenate dimeglumine-enhanced MRI has potential to identify highly aggressive HCCs and non-invasively obtain prognostic information. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 2.