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Background & Aims: Combined 18F-fluorodeoxyglucose (FDG) and 11C-acetate (dual-tracer) positron-emission tomography/computed tomography (PET/CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels. Methods: We retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020. For staging, we recorded new lesion detection rates, changes in the Barcelona Clinic Liver Cancer (BCLC) classification, and treatment allocation due to dual-tracer PET/CT. To characterize indeterminate lesions and unexplained elevation of serum AFP levels, the sensitivity and specificity of dual-tracer PET/CT in diagnosing HCC were evaluated. A multidisciplinary external review and a cost-benefit analysis of patients for metastatic screening were also performed. Results: Dual-tracer PET/CT identified new lesions in 14.3% of 273 staging patients, resulting in BCLC upstaging in 11.7% and treatment modifications in 7.7%. It upstaged 8.1% of 260 patients undergoing metastatic screening, with estimated savings of US$495 per patient. It had a sensitivity and specificity of 80.7% (95% CI 71.2-88.6%) and 94.8% (95% CI 90.4-98.6%), respectively, for diagnosing HCC in 201 indeterminate lesions. It detected HCC in 45.1% of 51 patients with unexplained elevations in serum AFP concentrations. External review revealed substantial agreement between local and external image interpretation and patient assessment (n = 273, κ = 0.822; 95% CI 0.803-0.864). Conclusions: Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP. Impact and implications: Compared to CT or MRI, dual-tracer positron-emission tomography/computed tomography (PET/CT) led to upstaging in 12% of patients with hepatocellular carcinoma (HCC) undergoing staging, resulting in treatment modification in 8% of cases and a cost saving of US$495 per patient. It also accurately detected HCC in high-risk cases where CT or MRI were equivocal or normal. Dual-tracer PET/CT provides added value beyond conventional imaging in patients with HCC by improving staging, confirming HCC diagnosis with high accuracy in patients with indeterminate lesions, and detecting HCC in patients with unexplained elevation of serum AFP.
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The prognosis of patients with decompensated cirrhosis is poor, with significantly increased liver-related mortality rates. With the rising tide of decompensated cirrhosis associated with metabolic dysfunction-associated steatotic liver disease (MASLD), the role of metabolic bariatric surgery (MBS) in achieving hepatic recompensation is garnering increasing attention. However, the complexity of preoperative assessment, the risk of postoperative disease recurrence, and the potential for patients to experience surgical complications of the MBS present challenges. In this opinion article we analyze the potential of MBS to induce recompensation in MASLD-related cirrhosis, discuss the mechanisms by which MBS may affect recompensation, and compare the characteristics of different MBS procedures; we highlight the therapeutic potential of MBS in MASLD-related cirrhosis recompensation and advocate for research in this complex area.
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BACKGROUND: Intraoperative indocyanine green (ICG) fluorescence imaging has been shown to be a new and innovative way to illustrate the optimal resection margin in hepatectomy for hepatocellular carcinoma. This study investigated its accuracy in resection margin determination by looking into the correlation of ICG intensity gradients with pathological examination results of resected specimens. METHODS: This was a prospective, single-center, non-randomized controlled study. Patients who had liver tumors indicating liver resection were recruited. The hypothesis was that the use of intraoperative near-infrared/ICG fluorescence imaging would be a promising guiding tool for removing hepatocellular carcinoma with a better resection margin. Patients were given ICG (0.25 mg/kg) 1 day before operation. Resected specimens were inspected under a fluorescent imaging system. Biopsies were taken from tumors and normal tissue. Color signals obtained from ICG fluorescence imaging were compared with biopsies for analysis. RESULTS: Twenty-two patients were recruited for study. The median size of their tumors was 2.25 cm. One patient had resection margin involvement. Under ICG fluorescence, the tumors typically lighted up as yellow color, wrapped by a zone of green color. Tumors of 17 patients (77.3%) displayed yellow color and were confirmed malignancy, while tumors of 12 patients (54.5%) displayed green color and were confirmed malignancy. Receiver operating characteristic curve was used to measure the sensitivity and specificity of the green color to look for a clear resection margin. The area under the curve was 85.3% (p = 0.019, 95% confidence interval 0.696-1.000), with a sensitivity of 0.706 and specificity of 1.000. CONCLUSION: The use of ICG fluorescence can be helpful in determining resection margins. Resection of tumor should include complete resection of the green zone shown in the fluorescence image.
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Carcinoma Hepatocelular , Corantes , Hepatectomia , Verde de Indocianina , Neoplasias Hepáticas , Margens de Excisão , Humanos , Estudos Prospectivos , Masculino , Feminino , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Hepatectomia/métodos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Imagem Óptica/métodos , AdultoRESUMO
In the study by Wu et al, patients with unresectable hepatocellular carcinoma were subjected to transarterial chemoembolization (TACE) as a conversion therapy in order to render their tumors suitable for resection. A nomogram was devised and shown to be effective in predicting the survival of these patients. Generalization of the results, however, is questionable since the study subjects consisted of patients who had resection after TACE while excluding patients with the same disease but not suitable for TACE. Immunotherapy can be considered to be an option for conversion therapy. However, markers for determining responses to a conversion therapy and for guiding the decision between TACE and sequential immunotherapy have been lacking. The question of whether effective conversion therapy can truly enhance overall survival remains unanswered.
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Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Quimioembolização Terapêutica/métodos , Quimioembolização Terapêutica/mortalidade , Resultado do Tratamento , Hepatectomia , Nomogramas , Imunoterapia/métodosRESUMO
BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a heterogeneous cancer with varying levels of liver tumor initiating or cancer stem cells in the tumors. We aimed to investigate the expression of different liver cancer stem cell (LCSC) markers in human HCCs and identify their regulatory mechanisms in stemness-related cells. METHODS: We used an unbiased, single-marker sorting approach by flow cytometry, fluorescence-activated cell sorting, and transcriptomic analyses on HCC patients' resected specimens. Knockdown approach was used, and relevant functional assays were conducted on the identified targets of interest. RESULTS: Flow cytometry on a total of 60 HCC resected specimens showed significant heterogeneity in the expression of LCSC markers, with CD24, CD13, and EpCAM mainly contributing to this heterogeneity. Concomitant expression of CD24, CD13, and EpCAM was detected in 32 HCC samples, and this was associated with advanced tumor stages. Transcriptomic sequencing on the HCC cells sorted for these individual markers identified epidermal growth factor receptor kinase substrate 8-like protein 3 (EPS8L3) as a common gene associated with the 3 markers and was functionally validated in HCC cells. Knocking down EPS8L3 suppressed the expression of all 3 markers. To search for the upstream regulation of EPS8L3, we found SP1 bound to EPS8L3 promoter to drive EPS8L3 expression. Furthermore, using Akt inhibitor MK2206, we showed that Akt signaling-driven SP1 drove the expression of the 3 LCSC markers. CONCLUSIONS: Our findings suggest that Akt signaling-driven SP1 promotes EPS8L3 expression, which is critical in maintaining the downstream expression of CD24, CD13, and EpCAM. The findings provide insight into potential LCSC-targeting therapeutic strategies.
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Antígeno CD24 , Carcinoma Hepatocelular , Molécula de Adesão da Célula Epitelial , Neoplasias Hepáticas , Células-Tronco Neoplásicas , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Molécula de Adesão da Célula Epitelial/metabolismo , Molécula de Adesão da Célula Epitelial/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Antígeno CD24/metabolismo , Antígeno CD24/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Citometria de Fluxo , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: This study is to examine the impact of perioperative (intraoperative/postoperative) blood transfusion on the outcomes of curative hepatectomy for hepatocellular carcinoma. Hepatectomy is a well-established curative treatment for hepatocellular carcinoma, and blood transfusion cannot always be avoided in treating the disease. METHODS: A retrospective study of patients having curative hepatectomy for hepatocellular carcinoma from January 2010 to December 2019 at a single center was conducted. The patients were stratified by their disease stage. Patients with and without perioperative blood transfusion were matched by propensity-score matching and compared for each disease stage. Univariate and multivariate analyses were performed to identify prognostic factors for overall survival for each stage. RESULTS: A total of 846 patients were studied. Among them, 125 received perioperative blood transfusion and 720 did not. Patients with blood transfusion had worse disease-free and overall survival. After stratification and matching, the ratios of transfusion to non-transfusion were 33:165 (stage 1), 28:140 (stage 2), and 45:90 (stage 3). Perioperative blood transfusion was associated with a higher incidence of postoperative complications in all three disease stages (p = 0.004/0.006/0.017), and hence longer hospitalization (p < 0.001 in all stages), but had no significant impact on hospital mortality (p = 0.119/0.118/0.723), 90-day mortality (p = 0.259/0.118/0.723), disease-free survival (p = 0.128/0.826/0.511), or overall survival (p = 0.869/0.122/0.122) in any disease stage. Prognostic factors for overall survival included tumor size, tumor number, alpha-fetoprotein level, and postoperative complication of grade ≥ 3A. CONCLUSION: Perioperative blood transfusion was associated with a higher incidence of complications but had no significant impact on survival after curative hepatectomy for hepatocellular carcinoma.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Estudos Retrospectivos , Hepatectomia , Neoplasias Hepáticas/cirurgia , Transfusão de Sangue , Complicações Pós-Operatórias/epidemiologiaRESUMO
Introduction: Immunotherapy has resulted in pathologic responses in hepatocellular carcinoma (HCC), but the benefits and molecular mechanisms of neoadjuvant immune checkpoint blockade are largely unknown. Methods: In this study, we evaluated the efficacy and safety of preoperative nivolumab (anti-PD-1) in patients with intermediate and locally advanced HCC and determined the molecular markers for predicting treatment response. Results: Between July 2020 and November 2021, 20 treatment-naive HCC patients with intermediate and locally advanced tumors received preoperative nivolumab at 3 mg/kg for 3 cycles prior to surgical resection. Nineteen patients underwent surgical resection on trial. Seven (36.8%) of the 19 patients had major pathologic tumor necrosis (≥60%) in the post-nivolumab resection specimens, with 3 having almost complete (>90%) tumor necrosis. The tumor necrosis was hemorrhagic and often accompanied by increased or dense immune cell infiltrate at the border of the tumors. None of the patients developed major adverse reactions contradicting hepatectomy. RNA-sequencing analysis on both pre-nivolumab tumor biopsies and post-nivolumab resected specimens showed that, in cases with major pathologic necrosis, the proportion of CD8 T cells in the HCC tissues predominantly increased after treatment. Moreover, to investigate noninvasive biomarker for nivolumab response, we evaluated the copy number variation (CNV) using target-panel sequencing on plasma cell-free DNA of the patients and derived a CNV-based anti-PD-1 score. The score correlated with the extent of tumor necrosis and was validated in a Korean patient cohort with anti-PD-1 treatment. Conclusion: Neoadjuvant nivolumab demonstrated promising clinical activity in intermediate and locally advanced HCC patients. We also identified useful noninvasive biomarker predicting responsiveness.
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Background: The tumor microenvironment of cancers has emerged as a crucial component in regulating cancer stemness and plays a pivotal role in cell-cell communication. However, the specific mechanisms underlying these phenomena remain poorly understood. Methods: We performed the single-cell RNA sequencing (scRNA-seq) on nine HBV-associated hepatocellular carcinoma (HCC) patients. The heterogeneity of the malignant cells in pathway functions, transcription factors (TFs) regulation, overall survival, stemness, as well as ligand-receptor-based intercellular communication with macrophages were characterized. The aggressive and stemness feature for the target tumor subclone was validated by the conduction of in vitro assays including sphere formation, proliferation, Annexin V apoptosis, flow cytometry, siRNA library screening assays, and multiple in vivo preclinical mouse models including mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection. Results: Our analysis yielded a comprehensive atlas of 31,664 cells, revealing a diverse array of malignant cell subpopulations. Notably, we identified a stemness-related subclone of HCC cells with concurrent upregulation of CD24, CD47, and ICAM1 expression that correlated with poorer overall survival. Functional characterization both in vitro and in vivo validated S100A11 as one of the top downstream mediators for tumor initiation and stemness maintenance of this subclone. Further investigation of cell-cell communication within the tumor microenvironment revealed a propensity for bi-directional crosstalk between this stemness-related subclone and tumor-associated macrophages (TAMs). Co-culture study showed that this interaction resulted in the maintenance of the expression of cancer stem cell markers and driving M2-like TAM polarization towards a pro-tumorigenic niche. We also consolidated an inverse relationship between the proportions of TAMs and tumor-infiltrating T cells. Conclusions: Our study highlighted the critical role of stemness-related cancer cell populations in driving an immunosuppressive tumor microenvironment and identified the S100A11 gene as a key mediator for stemness maintenance in HCC. Moreover, our study provides support that the maintenance of cancer stemness is more attributed to M2 polarization than the recruitment of the TAMs.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Vírus da Hepatite B , Neoplasias Hepáticas/patologia , Macrófagos/metabolismo , Técnicas de Cocultura , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
BACKGROUND: Our clinical practice of laparoscopic liver resection (LLR) had achieved better short-term and long-term benefits for patients with hepatocellular carcinoma (HCC) over open liver resection (OLR), but the underlying mechanisms are not clear. This study was to find out whether systemic inflammation plays an important role. METHODS: A total of 103 patients with early-stage HCC under liver resection were enrolled (LLR group, n = 53; OLR group, n = 50). The expression of 9 inflammatory cytokines in patients at preoperation, postoperative day 1 (POD1) and POD7 was quantified by Luminex Multiplex assay. The relationships of the cytokines and the postoperative outcomes were compared between LLR and OLR. RESULTS: Seven of the circulating cytokines were found to be significantly upregulated on POD1 after LLR or OLR compared to their preoperative levels. Compared to OLR, the POD1 levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), IL-8, and monocyte chemoattractant protein-1 (MCP-1) in the LLR group were significantly lower. Higher POD1 levels of these cytokines were significantly correlated with longer operative time and higher volume of blood loss during operation. The levels of these cytokines were positively associated with postoperative liver injury, and the length of hospital stay. Importantly, a high level of IL-6 at POD1 was a risk factor for HCC recurrence and poor disease-free survival after liver resection. CONCLUSIONS: Significantly lower level of GM-CSF, IL-6, IL-8, and MCP-1 after liver resection represented a milder systemic inflammation which might be an important mechanism to offer better short-term and long-term outcomes in LLR over OLR.
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Carcinoma Hepatocelular , Laparoscopia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Neoplasias Hepáticas/patologia , Citocinas , Interleucina-6 , Interleucina-8 , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Hepatectomia/efeitos adversos , Laparoscopia/efeitos adversos , Inflamação , Tempo de InternaçãoRESUMO
BACKGROUND: Hepatectomy is an established treatment for colorectal liver metastasis (CLM) or neuroendocrine liver metastasis. However, its role in non-colorectal non-neuroendocrine liver metastasis (NCNNLM) is controversial. This study aims to compare long-term survival outcomes after hepatectomy between NCNNLM and CLM in a population-based cohort. METHODS: From 2009 to 2018, curative hepatectomy were performed in 964 patients with NCNNLM (n â= â133) or CLM (n â= â831). Propensity score (PS) matching was performed. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival. RESULTS: There were 133 patients in the NCNNLM group and 266 patients in the CLM group. The mortality (1.5 â% vs 1.5 â%) and morbidity (19.5 â% vs 20.3 â%) rates were comparable between the two groups. There was no statistically significant difference in 5-year overall (48.9 â% vs 39.8 â%) and recurrence-free (25.1 â% vs 23.4 â%) survival rates between NCNNLM and CLM groups. A high pre-operative serum bilirubin level, severe postoperative complications and multiple tumors were independent prognostic factors for poor survival. CONCLUSION: Hepatectomy for selected patients with NCNNLM can achieve similar long-term oncological outcomes as those with CLM. High serum bilirubin, severe postoperative complication and multiple tumors are poor prognostic factors for survival.
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Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Hepatectomia , Pontuação de Propensão , Neoplasias Colorretais/patologia , Estudos Retrospectivos , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/cirurgia , Taxa de Sobrevida , Bilirrubina , Resultado do TratamentoRESUMO
BACKGROUND: Mutation and downregulation of FAT atypical cadherin 4 (FAT4) are frequently detected in HCC, suggesting a tumor suppressor role of FAT4. However, the underlying molecular mechanism remains elusive. METHODS: CRISPR-Cas9 system was used to knockout FAT4 (FAT4-KO) in a normal human hepatic cell line L02 to investigate the impact of FAT4 loss on the development of HCC. RNA-sequencing and xenograft mouse model were used to study gene expression and tumorigenesis, respectively. The mechanistic basis of FAT4 loss on hepatocarcinogenesis was elucidated using in vitro experiments. RESULTS: We found that FAT4-KO disrupted cell-cell adhesion, induced epithelial-mesenchymal transition, and increased expression of extracellular matrix components. FAT4-KO is sufficient for tumor initiation in a xenograft mouse model. RNA-sequencing of FAT4-KO cells identified PAK6-mediated WNT/ß-catenin signaling to promote tumor growth. Suppression of PAK6 led to ß-catenin shuttling out of the nucleus for ubiquitin-dependent degradation and constrained tumor growth. Further, RNA-sequencing of amassed FAT4-KO cells identified activation of WNT5A and ROR2. The noncanonical WNT5A/ROR2 signaling has no effect on ß-catenin and its target genes (CCND1 and c-Myc) expression. Instead, we observed downregulation of receptors for WNT/ß-catenin signaling, suggesting the shifting of ß-catenin-dependent to ß-catenin-independent pathways as tumor progression depends on its receptor expression. Both PAK6 and WNT5A could induce the expression of extracellular matrix glycoprotein, laminin subunit alpha 4. Laminin subunit alpha 4 upregulation in HCC correlated with poor patient survival. CONCLUSIONS: Our data show that FAT4 loss is sufficient to drive HCC development through the switching of canonical to noncanonical Wingless-type signaling pathways. The findings may provide a mechanistic basis for an in-depth study of the two pathways in the early and late stages of HCC for precise treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Camundongos , Animais , beta Catenina/genética , beta Catenina/metabolismo , Via de Sinalização Wnt/genética , Proteínas Wnt/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Carcinogênese/genética , Laminina , RNA , Caderinas/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
Background: The finding of pancreatic cystic lesions (PCL) on incidental imaging is becoming increasingly common. International studies report a prevalence of 2.2-44.7% depending on the population, imaging modality and indication for imaging, and the prevalence increases with age. Patients with PCL are at risk of developing pancreatic cancer, a disease with a poor prognosis. This publication summarizes recommendations for the diagnosis and management of PCL and post-operative pancreatic exocrine insufficiency (PEI) from a group of local specialists. Methods: Clinical evidence was consolidated from narrative reviews and consensus statements formulated during two online meetings in March 2022. The expert panel included gastroenterologists, hepatobiliary surgeons, oncologists, radiologists, and endocrinologists. Results: Patients with PCL require careful investigation and follow-up due to the risk of malignant transformation of these lesions. They should undergo clinical investigation and pancreas-specific imaging to classify lesions and understand the risk profile of the patient. Where indicated, patients should undergo pancreatectomy to excise PCL. Following pancreatectomy, patients are at risk of PEI, leading to gastrointestinal dysfunction and malnutrition. Therefore, such patients should be monitored for symptoms of PEI, and promptly treated with pancreatic enzyme replacement therapy (PERT). Patients with poor response to PERT may require increases in dose, addition of a proton pump inhibitor, and/or further investigation, including tests for pancreatic function. Patients are also at risk of new-onset diabetes mellitus after pancreatectomy; they should be screened and treated with insulin if indicated. Conclusions: These statements are an accurate summary of our approach to the diagnosis and management of patients with PCL and will be of assistance to clinicians treating these patients in a similar clinical landscape.
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Background: Currently, surgical resection is the mainstay for colorectal liver metastases (CRLM) management and the only potentially curative treatment modality. Prognostication tools can support patient selection for surgical resection to maximize therapeutic benefit. This study aimed to develop a survival prediction model using machine learning based on a multicenter patient sample in Hong Kong. Methods: Patients who underwent hepatectomy for CRLM between 1 January 2009 and 31 December 2018 in four hospitals in Hong Kong were included in the study. Survival analysis was performed using Cox proportional hazards (CPH). A stepwise selection on Cox multivariable models with Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to a multiply-imputed dataset to build a prediction model. The model was validated in the validation set, and its performance was compared with that of Fong Clinical Risk Score (CRS) using concordance index. Results: A total of 572 patients were included with a median follow-up of 3.6 years. The full models for overall survival (OS) and recurrence-free survival (RFS) consist of the same 8 established and novel variables, namely colorectal cancer nodal stage, CRLM neoadjuvant treatment, Charlson Comorbidity Score, pre-hepatectomy bilirubin and carcinoembryonic antigen (CEA) levels, CRLM largest tumor diameter, extrahepatic metastasis detected on positron emission-tomography (PET)-scan as well as KRAS status. Our CRLM Machine-learning Algorithm Prognostication model (CMAP) demonstrated better ability to predict OS (C-index =0.651), compared with the Fong CRS for 1-year (C-index =0.571) and 5-year OS (C-index =0.574). It also achieved a C-index of 0.651 for RFS. Conclusions: We present a promising machine learning algorithm to individualize prognostications for patients following resection of CRLM with good discriminative ability.
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Background and Objective: Hong Kong, like many parts of Asia, faces a high burden of hepatocellular carcinoma (HCC) caused by high endemic rates of hepatitis B virus infection. Hong Kong clinicians have developed a high level of expertise in HCC treatment across surgical, transarterial, ablative, radiotherapeutic and systemic modalities. This publication summarizes the latest evidence-based recommendations on how these modalities should be used. Methods: In two meetings held in 2020, a multidisciplinary panel of surgeons, oncologists and interventional radiologists performed a narrative review of evidence on the management of HCC, with an emphasis on treatment of HCC not amenable to surgical resection. Close attention was paid to new evidence published since the previous version of these statements in 2018. Key Content and Findings: The expert panel has formulated 60 consensus statements to guide the staging and treatment of unresectable HCC. Since the previous version of these statements, considerable additions have been made to the recommendations on use of targeted therapies and immunotherapies because of the large volume of new evidence. Conclusions: Our consensus statements offer guidance on how to select HCC patients for surgical or non-surgical treatment and for choosing among non-surgical modalities for patients who are not candidates for resection. In particular, there is a need for more evidence to aid physicians in the selection of second-line systemic therapies, as currently most data are limited to patients with disease progression on first-line sorafenib.
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Background: The use of laparoscopic (LLR) and robotic liver resections (RLR) has been safely performed in many institutions for liver tumours. A large scale international multicenter study would provide stronger evidence and insight into application of these techniques for huge liver tumours ≥10 cm. Methods: This was a retrospective review of 971 patients who underwent LLR and RLR for huge (≥10 cm) tumors at 42 international centers between 2002-2020. Results: One hundred RLR and 699 LLR which met study criteria were included. The comparison between the 2 approaches for patients with huge tumors were performed using 1:3 propensity-score matching (PSM) (73 vs. 219). Before PSM, LLR was associated with significantly increased frequency of previous abdominal surgery, malignant pathology, liver cirrhosis and increased median blood. After PSM, RLR and LLR was associated with no significant difference in key perioperative outcomes including media operation time (242 vs. 290 min, P=0.286), transfusion rate rate (19.2% vs. 16.9%, P=0.652), median blood loss (200 vs. 300 mL, P=0.694), open conversion rate (8.2% vs. 11.0%, P=0.519), morbidity (28.8% vs. 21.9%, P=0.221), major morbidity (4.1% vs. 9.6%, P=0.152), mortality and postoperative length of stay (6 vs. 6 days, P=0.435). Conclusions: RLR and LLR can be performed safely for selected patients with huge liver tumours with excellent outcomes. There was no significant difference in perioperative outcomes after RLR or LLR.