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Background and Objectives: Transarterial chemoembolization (TACE) and 125I seed implantation are methods used to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), PVTT often associated with arterioportal shunts(APS), there are few reports on the combined use of TACE and 125I seed implantation for such patients. This study aimed to evaluate the efficacy and safety of TACE combined with PVTT 125I seed implantation in the treatment of HCC patients with APS. Methods: Forty-two patients diagnosed with HCC combined with PVTT and APS between January 2020 and December 2021 were included. Appropriate materials were selected to transarterial embolization of the APS, and 125I seeds were implanted into the PVTT. The occlusion effect was observed and recorded after 3 months, the efficacy of intrahepatic lesions and PVTT was evaluated, and the patient survival, prognostic factors affecting APS recanalization were analyzed. Results: All 42 patients completed the follow-up three months after treatment. The immediate APS improvement rate was 100%, and the APS improvement rate at the three-month follow-up was 64.29%. The disease control rates of PVTT and intrahepatic lesions were 81.00% and 78.60%, respectively. The patients' 6-month and 12-month survival rates were 78.6% and 46.8%. The median OS for all patients was 11.90 months, and the median OS was 13.30 months in the APS effective treatment group and 8.30 months in the ineffective group. The PVTT type is the only independent factor affecting APS recanalization. (P=0.02). Conclusion: For HCC patients with PVTT and APS, TACE combine with 125I seed implantation in PVTT is a potentially effective and safe method that contributes to prolonging patient survival.

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Background: Vascular invasion is a major risk factor for poor prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC), and this study aimed to evaluate the feasibility and efficacy of deceased donor LT (DDLT) for the treatment of microvascular invasion (MVI) and segmental portal vein tumor thrombus (PVTT). Methods: We retrospectively analyzed 141 patients who received DDLT for HCC combined with vascular invasion from January 2016 to December 2023 at Shulan (Hangzhou) Hospital. To assess the risk of vascular invasion associated with the LT prognosis, we evaluated various clinicopathologic variables. The recurrence-free survival (RFS) and overall survival (OS) based on different types of vascular invasion were also analyzed. Results: A total of 141 patients were enrolled in this study, including patients with MVI (MVI group, n=60), segmental PVTT with segmental branches of the portal vein or above (segmental PVTT group, n=13), and lobar PVTT involving the left and right branches of the portal vein or the main portal vein (lobar PVTT group, n=68). Between the tumor recurrence group and the no recurrence group, there were significant differences in alpha-fetoprotein (AFP) level, tumor total diameter, pretransplant treatment, histological grade, and types of vascular invasion. Subgroup analyses were performed according to the types of vascular invasion, the lobar PVTT group had a significantly higher recurrence rate (lobar vs. MVI: 88.2% vs. 35.0%, lobar vs. segmental: 88.2% vs. 30.8%, both P<0.001), but there was no difference in recurrence rate between the MVI group and the segmental PVTT group (35.0% vs. 30.8%, P>0.99). The 3-year RFS rate and OS rate were as low as 9.1% and 45.9% in the lobar PVTT group, compared with 65.5% and 76.0% in the MVI group, 58.3% and 75.0% in the segmental PVTT group. Multivariate analysis showed that Child-Pugh classification, tumor total diameter, histological grade, and lobar PVTT were the main risk factors affecting RFS, whereas Child-Pugh classification, tumor total diameter, and lobar PVTT were the main risk factors affecting OS. Finally, analysis of the segmental PVTT group revealed that RFS was significantly higher in well and moderately-differentiated patients than in poor-differentiated patients (P=0.01). Conclusions: Lobar PVTT remains a contraindication to LT, whereas segmental PVTT can still be considered for LT after careful screening.

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Objective: This study aimed to investigate the feasibility of the efficacy and safety of TACE combined with Lenvatinib and PD-1 blockade in HCC with portal vein tumor thrombus (PVTT). Methods: Patients with HCC and PVTT who underwent TACE combined with Lenvatinib and PD-1 blockade as first-line therapy in clinical practice were retrospectively included. All subjects were followed-up regularly to obtain prognostic outcomes. The safety profile observed during the combination therapy was collected and documented. The Log rank test was used for exploratory analysis of prognosis and baseline characteristics and Cox regression analysis was used for multivariate analysis. Results: A total of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockade were included in this study. The best therapeutic response during treatment suggested that 4 patients achieved complete response, 30 patients showed partial response, 25 patients were stable disease, 5 patients had disease progression and 3 patients were not available. Objective response rate of this regimen was 50.7% [95% confidence interval (CI): 38.2-63.2%] and disease control rate was 88.1% (95% CI: 77.8-94.7%). The median progression-free survival of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockades was 9.3 months (95% CI: 5.85-12.75), and the median overall survival was 24.4 months (95% CI: 19.11-29.69). The safety profile highlighted that 65 patients experienced adverse reactions regardless of grade during treatment (97.0%), among whom 34 patients were deemed as grade ≥3 adverse reactions (50.7%). The most common adverse reactions were hypertension, fatigue, abnormal liver function, nausea, vomiting, and diarrhea. Overall adverse reactions were acceptable and controllable. Conclusion: TACE combined with Lenvatinib and PD-1 blockades as first-line therapy for HCC with PVTT demonstrated potential feasibility and encouraging clinical outcomes, providing long-term survival benefits for HCC patients. This conclusion should be confirmed in prospective large-scale clinical trials.

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BACKGROUND/AIM: The prognosis of hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombus (PVTT) is extremely poor. This study investigated whether local ablation-a curative treatment similar to resection-could improve the prognosis of patients with Child-Pugh B/C PVTT. PATIENTS AND METHODS: Between January 2020 and December 2023, 25 patients with Child-Pugh B/C PVTT HCC were enrolled, and their overall survival with radiofrequency ablation treatment and the associated drivers were investigated. RESULTS: Overall survival (median 282 days) differed between the group treated with transarterial chemoembolization (TACE, 285 days) and the group without it (159 days, p=0.0151). The median survival in the esophagogastric variceal exacerbation group (120.5 days) was shorter than that in the non-exacerbation group (284.0 days, p=0.00964). In multivariate analysis, concomitant TACE had a hazard ratio (HR) of 0.121 (p=0.0097), and the exacerbation of esophagogastric varices had a HR of 6.761 (p=0.01). CONCLUSION: Local ablation for PVTT may promote patient survival specifically by inhibiting the exacerbation of portal hypertension in patients with hepatocellular carcinoma.

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Carcinoma Hepatocelular , Neoplasias Hepáticas , Vena Porta , Humanos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Masculino , Femenino , Vena Porta/patología , Vena Porta/cirugía , Persona de Mediana Edad , Anciano , Pronóstico , Trombosis de la Vena/mortalidad , Trombosis de la Vena/etiología , Trombosis de la Vena/cirugía , Trombosis de la Vena/terapia , Trombosis de la Vena/patología , Resultado del Tratamiento , Quimioembolización Terapéutica/métodos , Ablación por Radiofrecuencia/métodos , Ablación por Catéter/métodos , Adulto

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Background: Portal vein tumor thrombus (PVTT) is a major risk factor of recurrence of hepatocellular carcinoma (HCC) after hepatectomy. Whether postoperative adjuvant immunotherapy and molecular targeted therapy (I-O and MTT) is effective in reducing the risk of recurrence of HCC with minimal portal invasion after hepatectomy and improving prognosis is unknown. Methods: We collected the data of HCC with Vp1 or Vp2 PVTT patients who underwent hepatectomy at our center between January 2019 and June 2022 from the hospital database. We utilized propensity score matching (PSM) to establish a 1:1 match between the postoperative group treated with I-O and MTT and the postoperative group without I-O and MTT. To compare the recurrence-free survival (RFS) and overall survival (OS) between the two groups, we employed the Kaplan-Meier method. Additionally, we conducted Cox regression analysis to identify the prognostic factors that influence patient prognosis. To account for different high-risk factors, subgroup analyses were carried out. Results: Among the 189 patients included in the study, 42 patients received postoperative adjuvant I-O and MTT. After PSM, the 1, 2-years RFS were 59.2%, 21.3% respectively in the I-O and MTT group and 40.8%, 9.6% respectively in the non-I-O and MTT group. The median RFS was 13.2 months for the I-O and MTT group better than 7.0 months for the non-I-O and MTT group (P = 0.028). 1, 2-years OS were 89.8%, 65.8% respectively in the I-O and MTT group and 42.4%, 27.7% respectively in the non-I-O and MTT group. The median OS was 23.5 months for the I-O and MTT group better than 17.2 months for the non-I-O and MTT group (P = 0.027). Multivariate analysis showed that postoperative adjuvant I-O and MTT was a prognostic protective factor associated with OS and RFS. The most frequent AE observed in this study was pruritus, and rare AEs included decreased platelet, hypothyroidism, proteinuria, myocarditis and hypoadrenocorticism. The incidence of GRADE ≥3 AE with no deaths recorded. Conclusion: The study suggested that postoperative adjuvant I-O and MTT strategy was beneficial to improve the prognosis of HCC patients with PVTT patients, while the therapy was safe and reliable.

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Aims/Background: Portal vein tumor thrombus (PVTT) is a common complication of primary hepatocellular carcinoma (HCC). HCC typically infiltrates intrahepatic vessels, particularly the portal vein, leading to the formation of PVTT, marking advanced-stage HCC and correlating with poor prognosis. PVTT often complicates local treatment strategies such as surgical resection and affects the efficacy of interventions. Combination therapy, including immunotherapy and targeted therapy, shows promise in HCC treatment, but management options for HCC patients with PVTT are incompletely characterized. This study aims to investigate the efficacy and safety of camrelizumab + apatinib in treating HCC patients with PVTT. Case Presentation: Two cases of HCC with PVTT were presented. Patient 1, a 51-year-old male with a history of hepatitis B virus, was diagnosed with stage IIIA HCC and treated with camrelizumab + apatinib, achieving complete response (CR) after six cycles. Patient 2, a 50-year-old male with stage IIIA HCC, also underwent the same treatment and achieved CR after four cycles but died due to acute cardiac disease. Results: Our research found that camrelizumab + apatinib effectively shrank the size of filling defects and significantly prolonged patients' progression-free survival. In addition, no adverse effects were observed during the treatment process. However, despite the manageable safety profile demonstrated by combination therapy, further clinical research is needed to validate its long-term efficacy and safety. Conclusion: Camrelizumab + apatinib produced satisfactory efficacy and safety among the HCC patients with PVTT, providing clinical evidence for future treatment.

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Anticuerpos Monoclonales Humanizados , Carcinoma Hepatocelular , Neoplasias Hepáticas , Vena Porta , Piridinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/patología , Masculino , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Persona de Mediana Edad , Piridinas/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Vena Porta/patología , Trombosis de la Vena/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico

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Vascular invasion of hepatocellular carcinoma involves tumor plugs in the main trunk of the portal vein, bile ducts, and veins, and it indicates poor prognosis. It is often associated with portal hypertension, which requires evaluation and management. Treatment includes hepatic resection, systemic pharmacotherapy, hepatic arterial infusion chemotherapy, and radiation therapy. Recurrence rates post-hepatic resection are high, and systemic drug therapy often has limited therapeutic potential in patients with a poor hepatic reserve. Single therapies are generally inadequate, necessitating combining multiple therapies with adjuvant and systemic pharmacotherapy before and after hepatectomy. This narrative review will provide an overview of the treatment of hepatocellular carcinoma with vascular invasion.

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BACKGROUND: There is no report resolving whether microvascular invasion (MVI) affects the prognosis of hepatectomy for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). The present study aimed to investigate the effect of MVI on HCC with PVTT after hepatectomy. METHODS: 362 HCC patients with PVTT were included in this retrospective study. Diagnostic criteria of PVTT in HCC patients were based on typical preoperative radiological features on imaging studies. The log-rank test was utilized to differentiate overall survival (OS) and recurrence-free survival (RFS) rates between the two groups. Univariate and multivariate Cox proportional hazard regression was utilized to detect independent factors. RESULTS: PVTT without MVI accounted for 12.2% (n = 44). PVTT without MVI groups was significantly superior to PVTT with MVI groups in OS (the median survival = 27.1 months vs 13.7 months) and RFS (the median survival = 6.4 months vs 4.1 months). The 1-, 3-, and 5-year OS rates (65.5%, 36.8%, 21.7% vs 53.5%, 18.7%, 10.1%, P = .014) and RFS rates (47.0%, 29.7%, 19.2% vs 28.7%, 12.2%, 6.9%, P = .005) were significant different between two groups. Multivariate analysis showed that MVI was an independent risk factor for OS (hazard ratio (HR) = 1.482; P-value = .045) and RFS (HR = 1.601; P-value = .009). CONCLUSIONS: MVI was an independent prognostic factor closely linked to tumor recurrence and poorer clinical outcomes for HCC patients with PVTT after hepatectomy. MVI should be included in current PVTT systems to supplement to the PVTT type.

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Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Invasividad Neoplásica , Vena Porta , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/complicaciones , Masculino , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/complicaciones , Femenino , Estudios Retrospectivos , Vena Porta/patología , Persona de Mediana Edad , Pronóstico , Trombosis de la Vena/patología , Trombosis de la Vena/etiología , Adulto , Anciano , Recurrencia Local de Neoplasia/patología

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Background: This study aimed to assess the effectiveness and safety of vascular intervention combined with lenvatinib versus vascular intervention alone in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT), and to identify prognostic factors associated with the treatment outcomes. Methods: We conducted a retrospective analysis of data from 92 patients with advanced HCC and PVTT who were treated between February 2016 and February 2023. Among them, 56 patients underwent vascular intervention alone (transarterial chemoembolization, TACE), while 36 patients received vascular intervention (TACE or hepatic arterial infusion chemotherapy [HAIC]) combined with lenvatinib. The primary outcomes included progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Survival rates were estimated by the Kaplan-Meier method, and confounders were adjusted using inverse probability of treatment weighting (IPTW). Prognostic factors were determined through the Cox regression model. Results: The median follow-up duration was 20.07 months (interquartile range: 6.41-25.36). The combination therapy group had a significantly longer median PFS (11.00 vs. 5.00 months, P<0.05) and OS (12.91 vs. 6.83 months, P<0.05) in comparison to the monotherapy group, and these findings remained consistent after IPTW matching. Moreover, the combination therapy group showed a higher ORR (55.56% vs. 26.79%, P<0.05) based on mRECIST criteria. Cox multivariate analysis identified extrahepatic metastasis and maximum tumor diameter as risk factors for PFS, while age, tumor number, and maximum tumor diameter influenced OS. Combined treatment emerged as a protective factor for OS. In the combination therapy group, hypertension was the most frequent adverse event, with grade 3 or 4 adverse events occurring rarely. Conclusion: The combination of vascular intervention with lenvatinib has demonstrated improved PFS and OS in advanced HCC patients with PVTT, and its safety profile appears to be acceptable. Adoption of this combined treatment strategy at an earlier stage may enhance patient outcomes.

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Purpose: This study aimed to assess the effectiveness and safety of combining hepatic arterial infusion chemotherapy (HAIC) with lenvatinib (LEN) and PD-1 inhibitors in treating arterioportal shunt (APS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Patients and Methods: Conducted retrospectively, the study enrolled 54 HCC patients with APS and PVTT treated with HAIC, LEN, and PD-1 inhibitors at our center between January 2021 and October 2023. APS improvement, APS recanalization, tumor response, PVTT response rate, overall survival (OS), intrahepatic progression-free survival (InPFS), and adverse events were evaluated. Results: APS improvement was observed in 42 patients (77.8%), with all improvement occurring within two treatment sessions. Complete APS occlusion was achieved in 40 patients (74.1%), and no recanalization occurred. The best objective response rate (ORR) and ORR after two HAIC sessions were 74.1% and 66.7%, respectively. The best PVTT response and PVTT response after two HAIC sessions were 98.1% and 94.4%, respectively. The median OS and InPFS were 10.0 months and 5.0 months, respectively. OS and InPFS were longer in patients with APS occlusion compared to those without (OS 12.1 vs 4.4 months, P<0.001, InPFS 6.2 vs 2.3 months, P=0.049). ALBI grade, extrahepatic spread, APS disappearance were potential prognostic factors for OS, while APS grade and extrahepatic spread being independently associated with InPFS. No treatment-related mortality occurred. Conclusion: Combining HAIC with LEN and PD-1 inhibitors proves to be both effective and safe in managing APS in HCC with PVTT, potentially improving patient survival.

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BACKGROUND: The objectives of this study were to assess the safety and efficacy of drug-eluting bead transarterial chemoembolization (DEB-TACE) as neoadjuvant therapy before liver transplantation (LT) for advanced-stage hepatocellular carcinoma (HCC) and to analyze the prognostic factors. AIM: To determine whether DEB-TACE before LT is superior to LT for advanced-stage HCC. METHODS: A total of 99 individuals diagnosed with advanced HCC were studied retrospectively. The participants were categorized into the following two groups based on whether they had received DEB-TACE before LT: DEB-TACE group (n = 45) and control group (n = 54). The participants were further divided into two subgroups based on the presence or absence of segmental portal vein tumor thrombus (PVTT). The DEB-TACE group consisted of two subgroups: Group A (n = 31) without PVTT and group B (n = 14) with PVTT. The control group also had two subgroups: Group C (n = 37) without PVTT and group D (n = 17) with PVTT. Data on patient demographics, disease characteristics, therapy response, and adverse events (AEs) were collected. The overall survival (OS) and recurrence-free survival (RFS) rates were assessed using Kaplan-Meier curves. Univariate and multivariate Cox regression analyses were conducted to determine the parameters that were independently related to OS and RFS. RESULTS: The DEB-TACE group exhibited an overall response rate of 86.6%. Following therapy, there was a significant decrease in the median alpha-fetoprotein (AFP) level (275.1 ng/mL vs 41.7 ng/mL, P < 0.001). The main AE was post-embolization syndrome. The 2-year rates of RFS and OS were significantly higher in the DEB-TACE group than in the control group (68.9% vs 38.9%, P = 0.003; 86.7% vs 63.0%, P = 0.008). Within the subgroups, group A had higher 2-year rates of RFS and OS compared to group C (71.0% vs 45.9%, P = 0.038; 83.8% vs 62.2%, P = 0.047). The 2-year RFS rate of group B was markedly superior to that of group D (64.3% vs 23.5%, P = 0.002). Results from multivariate analyses showed that pre-LT DEB-TACE [hazard ratio (HR) = 2.73, 95% confidence interval (CI): 1.44-5.14, P = 0.04], overall target tumor diameter ≤ 7 cm (HR = 1.98, 95%CI: 1.05-3.75, P = 0.035), and AFP level ≤ 400 ng/mL (HR = 2.34; 95%CI: 1.30-4.19, P = 0.009) were significant risk factors for RFS. Additionally, pre-LT DEB-TACE (HR = 3.15, 95%CI: 1.43-6.96, P = 0.004) was identified as a significant risk factor for OS. CONCLUSION: DEB-TACE is a safe and efficient therapy for advanced-stage HCC and also enhances patient survival after LT.

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Purpose: To evaluate the efficacy and safety of mFOLFOX-based hepatic arterial infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in the treatment of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). Methods: This retrospective study included patients who received mFOLFOX-based HAIC combined with TKIs and ICIs from January 2021 to January 2023. The primary outcome was the objective response rate of PVTT response, and the secondary outcomes were 6-month, 1-year survival rate, overall survival (OS), and corresponding adverse events and complications were also evaluated. PVTT responses were assessed using ITK-SNAP software. Results: A total of 37 patients were included in the analysis, 18.92% achieved a complete response and 56.76% achieved a partial response in PVTT response. The objective response rate (ORR) of PVTT was 75.68%. The 6-month survival rate was 89%, the 1-year survival rate was 66%, and the median OS was 15.8 months. In univariate analysis, Child-Pugh score (P=0.010) was important factor for predicting OS; in multivariate analysis, Child-Pugh score (P=0.015, HR= 3.089, 95%CI: 1.250-7.633) was the important factor for predicting OS. In terms of adverse reactions, the most common adverse reactions associated with HAIC are pain and thrombocytopenia associated with oxaliplatin. Conclusion: FOLFOX-based HAIC combined with TKIs and ICIs induced an objective response rate of 75.68% in PVTT. Clinical signicance: FOLFOX-based HAIC combined with TKIs and ICIs provides more treatment options for PVTT.

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BACKGROUND: Hepatic infarction is a rare liver condition. The purpose of this study is to report a case of hepatic infarction caused by thrombus formation following portal vein stent implantation in a patient with hepatocellular carcinoma and portal vein tumor thrombus, and to explore the underlying causes. CASE REPORT: The patient in this study was a 52-year-old male admitted with diffuse hepatocellular carcinoma involving the right lobe and portal vein tumor thrombus. After undergoing portal vein stent implantation and 125I particle strand implantation treatment, the portal vein was patent, and the pressure decreased. However, multiple instances of hepatic artery chemoembolization combined with targeted immunotherapy resulted in gradual reduction in the diameter of the hepatic artery and affecting hepatic arterial blood flow. Two months post-stent implantation, thrombus formation within the stent was noted, and the patient's condition did not improve with anticoagulant therapy, as evidenced by follow-up CT scans showing an increase in thrombi. Six months later, the patient suffered from gastrointestinal bleeding and, despite emergency esophagogastric variceal ligation and hemostatic treatment, developed hepatic parenchymal infarction and liver function failure. CONCLUSIONS: We reveal the underlying cause is that (1) thrombus formation within the portal vein stent, leading to portal vein embolism and obstructed blood flow due to exacerbate portal hypertension after various treatments; and (2) the effect of hepatic artery chemoembolization, immunotherapy, and targeted therapy on tumor angiogenesis, causing reduced hepatic artery diameter and impaired arterial blood flow. These factors disrupt the liver's dual blood supply system, ultimately contributing to hepatic infarction. To our knowledge, this is the first report of hepatic infarction as a complication following portal vein stent implantation for hepatocellular carcinoma with portal vein tumor thrombus, and it holds significant reference value for guiding the treatment of hepatocellular carcinoma with concurrent portal vein tumor thrombus in a clinical setting.

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Carcinoma Hepatocelular , Infarto , Radioisótopos de Yodo , Neoplasias Hepáticas , Vena Porta , Stents , Humanos , Masculino , Carcinoma Hepatocelular/terapia , Persona de Mediana Edad , Neoplasias Hepáticas/terapia , Vena Porta/patología , Stents/efectos adversos , Radioisótopos de Yodo/administración & dosificación , Infarto/etiología , Trombosis de la Vena/etiología , Trombosis de la Vena/terapia , Quimioembolización Terapéutica/efectos adversos , Quimioembolización Terapéutica/métodos

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Purpose: Portal vein tumor thrombosis (PVTT) is one of the hallmarks of advanced Hepatocellular carcinoma (HCC). Platelet (PLT) function parameters and CD8+T cells (CD8+Ts) play an important role in HCC progression and metastasis. This study is committed to establishing an efficient prognosis prediction model and exploring the combined effect of PLT and CD8+Ts on PVTT prognosis. Patients and Methods: This retrospective study collected 932 HCC patients with PVTT from 2007 to 2017 and randomly divided them into a training cohort (n = 656) and a validation cohort (n = 276). We performed multivariable Cox and Elastic-net regression analysis, constructed a nomogram and used Kaplan-Meier survival curves to compare overall survival and progression-free survival rates in different substrata. Relationships between indicators involved were also analyzed. Results: We found tumor number, size, treatment, PLT, γ-glutamyl transferase, alpha-fetoprotein, mean platelet volume, and CD8+Ts were related to the 5-year OS of patients with PVTT, and established a nomogram. The area under the receiver operating characteristic curve (AUCs) for predicting the 1-year OS rates were 0.767 and 0.794 in training and validation cohorts. The calibration curve and decision curve indicated its predictive consistency and strong clinical utility. We also found those with low PLT (<100*10^9/L) and high CD8+Ts (>320 cells/µL) had a better prognosis. Conclusion: We established a well-performing prognostic model for PVTT based on platelet functional parameters and CD8+Ts, and found that PT-8 formed by PLT and CD8+Ts was an excellent predictor of the prognosis of PVTT.

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BACKGROUND/AIM: The landscape of treatments for hepatocellular carcinoma (HCC), including immune checkpoint inhibitors, has expanded significantly. However, unresectable HCC patients with portal vein tumor thrombus (PVTT) continue to face a poor prognosis. This investigation examined the survival outcomes and determinants influencing survival rates in advanced HCC patients with PVTT undergoing treatment with atezolizumab plus bevacizumab (ATZ+BEV) or hepatic arterial infusion chemotherapy (HAIC). PATIENTS AND METHODS: Between December 2003 and June 2023, 48 advanced HCC with PVTT underwent treatment with either ATZ+BEV (16 patients) or HAIC (32 patients). RESULTS: The analysis revealed no significant disparities in overall survival (OS) or treatment efficacy between the ATZ+BEV and HAIC groups (ATZ+BEV: 10.0 months, HAIC: 15.3 months). Treatment with either ATZ+BEV or HAIC resulted in minimal alterations in the ALBI score and preserved hepatic function. Independent prognostic factors for OS, identified via multivariate logistic regression, included serum α-fetoprotein levels >400 ng/ml [hazard ratio (HR)=1.94; p=0.001], the existence of more than five tumors (HR=1.55; p=0.043), and the Child-Pugh score (HR=2.53; p=0.002). CONCLUSION: This investigation revealed no significant variance in OS and response rates between patients receiving ATZ+BEV and those treated with HAIC. The survival of advanced HCC patients with PVTT is intricately linked to the preservation of liver function, emphasizing the necessity for additional research to enhance treatment approaches for this patient population.

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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carcinoma Hepatocelular , Infusiones Intraarteriales , Neoplasias Hepáticas , Vena Porta , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/patología , Bevacizumab/administración & dosificación , Bevacizumab/uso terapéutico , Masculino , Femenino , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Vena Porta/patología , Estudios Retrospectivos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resultado del Tratamiento , Arteria Hepática , Pronóstico , Adulto

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Background: The presence of portal vein tumor thrombus (PVTT) is a significant indicator of advanced-stage hepatocellular carcinoma (HCC). Unfortunately, the prediction of PVTT occurrence remains challenging, and there is a lack of comprehensive research exploring the underlying mechanisms of PVTT formation and its association with immune infiltration. Methods: Our approach involved analyzing single-cell sequencing data, applying high dimensional weighted gene co-expression network analysis (hdWGCNA), and identifying key genes associated with PVTT development. Furthermore, we constructed competing endogenous RNA (ceRNA) networks and employed weighted gene co-expression network analysis (WGCNA), as well as three machine-learning techniques, to identify the upstream regulatory microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) of the crucial mRNAs. We employed fuzzy clustering of time series gene expression data (Mfuzz), gene set variation analysis (GSVA), and cell communication analysis to uncover significant signaling pathways involved in the activation of these important mRNAs during PVTT development. In addition, we conducted immune infiltration analysis, survival typing, and drug sensitivity analysis using The Cancer Genome Atlas (TCGA) cohort to gain insights into the two patient groups under study. Results: Through the implementation of hdWGCNA, we identified 110 genes that was closely associated with PVTT. Among these genes, TMEM165 emerged as a crucial candidate, and we further investigated its significance using COX regression analysis. Furthermore, through machine learning techniques and survival analysis, we successfully identified the upstream regulatory miRNA (hsa-miR-148a) and lncRNA (LINC00909) that targeted TMEM165. These findings shed light on the complex regulatory network surrounding TMEM165 in the context of PVTT. Moreover, we conducted CIBERSORT analysis, which unveiled correlations between TMEM165 and immune infiltration in HCC patients. Specifically, TMEM165 exhibited associations with various immune cell populations, including memory B cells and CD8+ T cells. Additionally, we observed implications for immune function, particularly in relation to immune checkpoints, within the context of HCC. Conclusions: The regulatory axis involving TMEM165, hsa-miR-148a, and LINC00909 emerges as a crucial determinant in the development of PVTT in HCC patients, and it holds significant implications for prognosis. Furthermore, alterations in the TMEM165/hsa-miR-148a/LINC00909 regulatory axis exhibit a strong correlation with immune infiltration within the HCC tumor microenvironment, leading to immune dysfunction and potential failure of immunotherapy.

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Background: Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT). Methods: The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts. Results: Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively). Conclusion: Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT.

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Background: Patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) present a poor prognosis. Current systemic therapies offer limited benefits. Hepatic artery infusion chemotherapy (HAIC) is a local regional treatment for advanced HCC, particularly in selected patients such as patients with PVTT or high intrahepatic tumor burden. Objectives: The purpose of this study is to retrospectively evaluate the efficacy and safety of HAIC combined with anti-PD-1 immunotherapy for HCC patients with PVTT, and explore factors related to survival prognosis, providing clues for treatment decisions for HCC patients. Design: This is a single-center retrospective study conducted over 2 years on consecutive PVTT patients receiving HAIC combined anti-PD-1 antibodies. Methods: The primary endpoint was overall survival (OS). Univariate and multivariate analyses were performed to identify prognostic factors affecting OS. Treatment-associated adverse events were evaluated as well. Results: A total of 119 patients were analyzed. The median OS and PFS were 14.9 months and 6.9 months. A total of 31.1% of grade 3-4 adverse events were reported, with elevated transaminase and total bilirubin being the most common. The independent variables correlated with survival include treatment-related alpha-fetoprotein (AFP) response, the presence of extrahepatic organ metastasis, absolute value of platelet (PLT), neutrophil-to-lymphocyte ratio, and combined usage of tyrosine kinase inhibitors (TKIs). Conclusion: In HCC patients with PVTT, combination therapy with HAIC and anti-PD-1 antibodies might be a promising therapy. The efficacy and safety of this combination protocol on patients with HCC complicated by PVTT warrants further investigation prospectively, especially in combination with TKIs.

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BACKGROUND: Portal vein tumor thrombus is an important indicator of poor prognosis in patients with hepatocellular carcinoma. Transarterial chemoembolization is recommended as the standard first-line therapy for unresectable hepatocellular carcinoma. Portal vein stent placement is a safe and effective therapy for promptly restoring flow and relieving portal hypertension caused by tumor thrombus. AIM: To assess the clinical significance of transarterial chemoembolization plus stent placement for the treatment of hepatocellular carcinoma with main portal vein tumor thrombosis. METHODS: We searched English and Chinese databases, assessed the quality of the included studies, analyzed the characteristic data, tested heterogeneity, explored heterogeneity, and tested publication bias. RESULTS: In total, eight clinical controlled trials were included. The results showed that the pressure in the main portal vein after stent placement was significantly lower than that with no stent placement. The cumulative stent patency and survival rates at 6 and 12 months were lower in the transarterial chemoembolization + stent placement group than in the transarterial chemoembolization + stent placement + brachytherapy/radiotherapy group. The survival rates of patients treated with transarterial chemoembolization + stent placement for 6 and 12 months were higher than those of patients treated with transarterial chemoembolization alone. CONCLUSION: For Chinese patients with hepatocellular carcinoma with main portal vein tumor thrombosis, transarterial chemoembolization plus stenting is effective. Transarterial chemoembolization + stent placement is more effective than transarterial chemoembolization alone. Transarterial chemoembolization + stent placement + brachytherapy/radiotherapy is more effective than transarterial chemoembolization + stenting.

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BACKGROUND: Liver transplantation (LT) for hepatocellular carcinoma (HCC) has been widely researched and is well established worldwide. The cornerstone of this treatment lies in the various criteria formulated by expert consensus and experience. The variations among the criteria are staggering, and the short- and long-term out comes are controversial. AIM: To study the differences in the current practices of LT for HCC at different centers in India and discuss their clinical implications in the future. METHODS: We conducted a survey of major centers in India that performed LT in December 2022. A total of 23 responses were received. The centers were classified as high- and low-volume, and the current trend of care for patients und ergoing LT for HCC was noted. RESULTS: Of the 23 centers, 35% were high volume center (> 500 Liver transplants) while 52% were high-volume centers that performed more than 50 transplants/year. Approximately 39% of centers had performed > 50 LT for HCC while the percent distribution for HCC in LT patients was 5%-15% in approximately 73% of the patients. Barring a few, most centers were divided equally between University of California, San Francisco (UCSF) and center-specific criteria when choosing patients with HCC for LT, and most (65%) did not have separate transplant criteria for deceased donor LT and living donor LT (LDLT). Most centers (56%) preferred surgical resection over LT for a Child A cirrhosis patient with a resectable 4 cm HCC lesion. Positron-emission tomography-computed tomography (CT) was the modality of choice for metastatic workup in the majority of centers (74%). Downstaging was the preferred option for over 90% of the centers and included transarterial chemoembolization, transarterial radioembolization, stereotactic body radiotherapy and atezolizumab/bevacizumab with varied indications. The alpha-fetoprotein (AFP) cut-off was used by 74% of centers to decide on transplantation as well as to downstage tumors, even if they met the criteria. The criteria for successful downstaging varied, but most centers conformed to the UCSF or their center-specific criteria for LT, along with the AFP cutoff values. The wait time for LT from down staging was at least 4-6 wk in all centers. Contrast-enhanced CT was the preferred imaging modality for post-LT surveillance in 52% of the centers. Approximately 65% of the centers preferred to start everolimus between 1 and 3 months post-LT. CONCLUSION: The current predicted 5-year survival rate of HCC patients in India is less than 15%. The aim of transplantation is to achieve at least a 60% 5-year disease free survival rate, which will provide relief to the prediction of an HCC surge over the next 20 years. The current worldwide criteria (Milan/UCSF) may have a higher 5-year survival (> 70%); however, the majority of patients still do not fit these criteria and are dependent on other suboptimal modes of treatment, with much lower survival rates. To make predictions for 2040, we must prepare to arm ourselves with less stringent selection criteria to widen the pool of patients who may undergo transplantation and have a chance of a better outcome. With more advanced technology and better donor outcomes, LDLT will provide a cutting edge in the fight against liver cancer over the next two decades.