Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis

Although the current standard treatment for hepatocellular carcinoma(HCC) with portal vein tumor thrombosis(PVTT) is sorafenib, many previous studies have established the need for a reliable local modality for PVTT control, which is a major cause of liver function deterioration and metastasis. Additionally, there is growing evidence for the prognostic significance of PVTT classification according to the location of tumor thrombosis. Favorable outcomes can be obtained by applying local modalities, including surgery or transarterial chemoembolization, especially in second-order or distal branch PVTT. Rapid control of PVTT could maintain or improve liver function and reduce intrahepatic as well as distant metastasis. Radiotherapy(RT) is one of the main locoregional treatment modalities in oncologic fields, but has rarely been used in HCC because of concerns regarding hepatic toxicity. However, with the development of advanced techniques, RT has been increasingly applied in HCC management. Randomized studies have yet to definitively prove the benefit of RT, but several comparative studies have justified the application of RT in HCC. The value of RT is especially noticeable in HCC with PVTT; several prospective and retrospective studies have reported favorable outcomes, including a 40% to 60% objective response rate and median overall survival of 15 mo to 20 mo in responders. In this review, we evaluate the role of RT as an alternative local modality in HCC with PVTT.

Treatment of hepatocellular carcinoma in patients with portal vein tumor thrombosis: Beyond the known frontiers

Hepatocellular carcinoma is one of the most frequent malignant tumors worldwide:Portal vein tumor thrombosis(PVTT)occurs in about 35%-50%of patients and represents a strong negative prognostic factor,due to the increased risk of tumor spread into the bloodstream,leading to a high recurrence risk.For this reason,it is a contraindication to liver transplantation and in several prognostic scores sorafenib represents its standard of care,due to its antiangiogenetic action,although it can grant only a poor prolongation of life expectancy.Recent scientific evidences lead to consider PVTT as a complex anatomical and clinical condition,including a wide range of patients with different prognosis and new treatment possibilities according to the degree of portal system involvement,tumor biological aggressiveness,complications caused by portal hypertension,patient’s clinical features and tolerance to antineoplastic treatments.The median survival has been reported to range between 2.7 and 4 mo in absence of therapy,but it can vary from 5 mo to 5 years,thus depicting an extremely variable scenario.For this reason,it is extremely important to focus on the most adequate strategy to be applied to each group of PVTT patients.

Efficacy of different treatment strategies for hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the efficacy of different treatment strategies for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) and investigate factors influencing prognosis.METHODS: One hundred and seventy-nine HCC patients with macroscopic PVTT were enrolled in this study. They were divided into four groups and underwent different treatments: conservative treatment group (n = 18),chemotherapy group (n = 53), surgical resection group (n = 24) and surgical resection with postoperative chemotherapy group (n = 84). Survival rates of the patients were analyzed by the Kaplan-Meier method. A log-rank analysis was performed to identify group differences. Cox's proportional hazards model was used to analyze variables associated with survival.RESULTS: The mean survival periods of the patients in four groups were 3.6, 7.3, 10.1, and 15.1 mo respectively.There were significant differences in the survival rates among the groups. The survival rates at 0.5-, 1-, 2-, and 3-year in surgical resection with postoperative chemotherapy group were 55.8%, 39.3%, 30.4%, and 15.6% respectively, which were significantly higher than those of other groups (P＜0.001). Multivariate analysis revealed that the strategy of treatment (P＜0.001) and the number of chemotherapy cycles (P = 0.012) were independent survival predictors for patients with HCC and PVTT.CONCLUSION: Surgical resection of HCC and PVTT combined with postoperative chemotherapy or chemoembolization is the most effective therapeutic strategy for the patients who can tolerate operation.Multiple chemotherapeutic courses should be given postoperatively to the patients with good hepatic function reserve.

Risk factors of poor prognosis and portal vein tumor thrombosis after curative resection of solitary hepatocellular carcinoma

BACKGROUND:Predictors of poor prognosis of solitary hepatocellular carcinoma(SHCC),a subgroup encompassing most patients with the malignancy,are still controversial.Hence,risk factors for portal vein tumor thrombosis(PVTT) in SHCC are obscure.The present study was designed to address this issue.METHOD:Clinicopathological and follow-up data for 156 consecutive patients with SHCC following curative hepatic resection were analyzed using uni-and multi-variate analyses.RESULTS:Univariate analysis showed that PVTT,tumornode-metastasis(TNM) stage,Edmondson-Steiner grade and preoperative serum alpha-fetoprotein(AFP) level were associated with the overall and disease-free survival,whereas tumor size only influenced the overall survival.In multivariate Cox regression tests,Edmondson-Steiner grade and TNM stage were independent prognostic markers for both overall and diseasefree survival.In addition,the Chi-square test showed that AFP level and Edmondson-Steiner grade were correlated with PVTT.Among them,only Edmondson-Steiner grade was shown to be of independent significance for PVTT in multi-variate logistic regression analysis.Additionally,AFP,the sole preoperative factor for PVTT,was not adequately sensitive and specific.CONCLUSIONS:Factors relating to post-surgical prognosis and PVTT in SHCC are all tumor-related.Of these,EdmondsonSteiner grade and TNM stage might be of particular importance in survival analysis.In addition,accurate prediction of PVTT by clinicopathological parameters before surgery remains difficult.

Hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate the prognostic factors and efficacy of hepatic arterial infusion chemotherapy in hepatocellular carcinoma with portal vein tumor thrombosis. METHODS: Fifty hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) were treated using hepatic arterial infusion chemotherapy (HAIC) via a subcutaneously implanted port. The epirubicin-cisplatin-5-fluorouracil (ECF) chemotherapeutic regimen consisted of 35 mg/m 2 epirubicin on day 1, 60 mg/m 2 cisplatin for 2 h on day 2, and 500 mg/m 2 5-fluorouracil for 5 h on days 1-3. The treatments were repeated every 3 or 4 wk. RESULTS: Three (6%) of the 50 patients achieved a complete response (CR), 13 (26%) showed partial responses (PR), and 22 (44%) had stable disease (SD).The median survival and time to progression were 7 and 2 mo, respectively. After 2 cycles of HAIC, CR was achieved in 1 patient (2%), PR in 10 patients (20%) and SD in 26 patients (52%). Significant pre-treatment prognostic factors were a tumor volume of < 400 cm 3 (P = 0.01) and normal levels of protein induced by vitamin K absence or antagonist (PIVKA)-Ⅱ (P = 0.022). After 2 cycles of treatment, disease control (CR + PR + SD) (P = 0.001), PVTT response (P = 0.003) and α-fetoprotein reduction of over 50% (P = 0.02) were independent factors for survival. Objective response (CR + PR), disease control, PVTT response, and combination therapy during the HAIC were also significant prognostic factors. Adverse events were tolerable and successfully managed. CONCLUSION: HAIC may be an effective treatment modality for advanced HCC with PVTT in patients with tumors < 400 cm 3 and good prognostic factors.

Hepatocellular carcinoma associated with tumor thrombosis in the portal vein: the effects of different treatments

OBJECTIVES: To compare the effects of different treatments for hepatocellular carcinoma (HCC) with tumor thrombosis in the portal vein (TTPV) and evaluate the factors influencing the prognosis. METHODS: One hundred and thirty-eight patients with HCC associated with TTPV, whose liver function was compensative and the tumor with TTPV can probably be resected together, were divided into four groups: conservative treatment group (n=14); chemotherapy group (n=19); surgical resection group (n=19); and surgical resection with postoperative chemotherapy group (n=64). RESULTS: The median survivals of the four groups were 3.5, 7.1, 10.1 and 13.4 months, respectively. The 0.5-, 1-, 2-, and 3-year cumulative survival rates of the surgical resection with postoperative chemotherapy group were 53.7%, 37.6%, 30.7% and 14.0% respectively, which were significantly higher than those of the other three groups (P<0.05). Both univariate and multivariate analysis revealed that postoperative chemotherapeutic course was the most important factor affecting the surgical results. CONCLUSIONS: If patients' liver fimction is compensative and tumors with TTPV can be removed together, exploration should be done. Surgical resection combined with postoperative chemotherapy can achieve the best results. More chemotherapeutic courses after surgical resection can be prescribed if the patients have good hepatic functional reserve.

Percutaneous electrochemotherapy in the treatment of portal vein tumor thrombosis at hepatic hilum in patients with hepatocellular carcinoma in cirrhosis: A feasibility study

AIMTo treated with electrochemotherapy (ECT) a prospective case series of patients with liver cirrhosis and Vp3-Vp4- portal vein tumor thrombus (PVTT) from hepatocellular carcinoma (HCC), in order to evaluate the feasibility, safety and efficacy of this new non thermal ablative technique in those patients.METHODSSix patients (5 males and 1 female), aged 61-85 years (mean age, 70 years), four in Child-Pugh A and two in Child-Pugh B class, entered our study series. All patients were studied with three-phase computed tomography (CT), contrast enhanced ultrasound (CEUS) and ultrasound-guided percutaneous biopsy of the thrombus before ECT. All patients underwent ECT treatment (Cliniporator Vitae®, IGEA SpA, Carpi, Modena, Italy) of Vp3-Vp4 PVTT in a single session. At the end of the procedure a post-treatment biopsy of the thrombus was performed. Scheduled follow-up in all patients entailed: CEUS within 24 h after treatment; triphasic contrast-enhanced CT and CEUS at 3 mo after treatment and every six months thereafter.RESULTSPost-treatment CEUS showed complete absence of enhancement of the treated thrombus in all cases. Post-treatment biopsy showed apoptosis and necrosis of tumor cells in all cases. The follow-up ranged from 9 to 20 mo (median, 14 mo). In 2 patients, the follow-up CT and CEUS demonstrated complete patency of the treated portal vein. Other 3 patients showed a persistent avascular non-tumoral shrinked thrombus at CEUS and CT during follow-up. No local recurrence was observed at follow-up CT and CEUS in 5/6 patients. One patient was lost to follow-up because of death from gastrointestinal hemorrage 5 wk after ECT.CONCLUSIONIn patients with cirrhosis, ECT seems effective and safe for curative treatment of Vp3-Vp4 PVTT from HCC.

Management of hepatocellular carcinoma patients with portal vein tumor thrombosis:A narrative review

Background: Hepatocellular carcinoma(HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis(PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. Data sources: We have reviewed literature from Pub Med on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. Results: Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can beneft from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also benefcial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classifcation models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival.

Alpha-fetoprotein and 18F-FDG standard uptake value predict tumor recurrence after liver transplantation for hepatocellular carcinoma with portal vein tumor thrombosis:Preliminary experience

Background:Portal vein tumor thrombosis(PVTT)is regarded as a contraindication for liver transplantation(LT)in hepatocellular carcinoma(HCC).However,some of these patients may have a favorable prognosis after LT.In this study,we evaluated the biological behavior of HCC with PVTT using tumor biomarker(alpha-fetoprotein,AFP)and 18 F-FDG positron emission tomography(tumor standard uptake value)to identify a subset of patients who may be suitable for LT.Methods:Seventy-five HCC-PVTT liver recipients transplanted during February 2016 and June 2018 were analyzed.Different pre-transplant prognostic factors were identified by univariate and multivariate analyses.PVTT status was identified following Vp classification(Vp1-Vp4).Results:Three-year recurrence-free survival and overall survival rates were 40%and 65.4%in Vp2-Vp3 PVTT patients,21.4%and 30.6%in Vp4 PVTT patients(P<0.05).Total tumor diameter>8 cm,pretransplant AFP level>1000 ng/m L and intrahepatic tumor maximal standard uptake value(SUVmaxtumor>5)were independent risk factors for HCC recurrence and overall survival after LT in Vp2-3 PVTT patients.Low risk patients were defined as total tumor diameter≤8 cm;or if total tumor diameter more than 8 cm,with both pre-transplant AFP level less than 1000 ng/m L and intrahepatic tumor SUVmax less than 5,simultaneously.Twenty-two Vp2-3 PVTT HCC patients(46.8%)were identified as low risk patients,and their 3-year recurrence-free and overall survival rates were 67.6%and 95.2%,respectively.Conclusions:Patients with segmental or lobar PVTT and biologically favorable tumors defined by AFP and 18 F-FDG SUVmax might be suitable for LT.

Prognostic value of the neutrophil-to-lymphocyte ratio for hepatocellular carcinoma patients with portal/hepatic vein tumor thrombosis

AIM To investigate whether the preoperative neutrophil-tolymphocyte ratio(NLR) could predict the prognosis of hepatocellular carcinoma(HCC) patients with portal/hepatic vein tumor thrombosis(PVTT/HVTT) after hepatectomy.METHODS The study population included 81 HCC patients who underwent hepatectomy and were diagnosed with PVTT/HVTT based on pathological examination. The demographics, laboratory analyses, and histopathology data were analyzed.RESULTS Overall survival(OS) and disease-free survival(DFS) were determined in the patients with a high(> 2.9) and low(≤ 2.9) NLR. The median OS and DFS duration in the high NLR group were significantly shorter than those in the low NLR group(OS: 6.2 mo vs 15.7 mo, respectively, P = 0.007; DFS: 2.2 mo vs 3.7 mo, respectively, P = 0.039). An NLR > 2.9 was identified as an independent predictor of a poor prognosis of OS(P = 0.034, HR = 1.866; 95%CI: 1.048-3.322) in uni-and multivariate analyses. Moreover, there was a significantly positive correlation between the NLR and the Child-Pugh score(r = 0.276, P = 0.015) and the maximum diameter of the tumor(r = 0.435, P < 0.001). Additionally, the NLR could enhance the prognostic predictive power of the CLIP score for DFS in these patients. CONCLUSION The preoperative NLR is a prognostic predictor after hepatectomy for HCC patients with PVTT/HVTT. NLR > 2.9 indicates poorer OS and DFS.

Efficacy of 5-Fluorouracil and High-Concentration Cisplatin Suspended in Lipiodol by Short-Term Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

Background: Since advanced hepatocellular carcinoma (HCC) is potentially fatal, and patients’ quality of life (QOL) often deteriorates during their treatment, improving the prognosis and QOL of patients given chemotherapy is very important. In addition, cost-effective treatments are highly desirable when chemotherapy must be given repeatedly. The aim of this study was to evaluate the efficacy and usefulness of 5-fluorouracil (5-FU) and high-concentration cisplatin by short-term hepatic arterial infusion chemotherapy (3-day FPL) in advanced HCC patients. Methods: Thirty patients with unresectable advanced HCC were enrolled. The patients underwent hepatic arterial infusion chemotherapy via the implanted port system with 5-FU on days 1 - 3 and a fine-powder formulation of cisplatin in suspended pre-warmed lipiodol on day 2 every 4 to 10 weeks. Tumor response was assessed one month later with CT. Results: All patients had evidence of portal vein invasion (Vp2-4). Four patients achieved a complete response (CR), 8 patients achieved a partial response (PR), and 7 patients had stable disease (SD). The median progression-free survival (PFS) and overall survival (OS) were 198 days and 452 days, respectively. The OS was significantly longer in the successful disease control group (CR, PR, and SD) than in the progressive disease group (P < 0.005). Conclusions: Three-day FPL was effective and tolerable in advanced HCC patients due to its shorter time of administration than conventional FP therapy. Therefore, repetitive 3-day FPL appears useful and contributes to improving the prognosis and QOL of patients with advanced HCC. In addition, this protocol is a cost-effective treatment.

Factors influencing the short-term and long-term survival of hepatocellular carcinoma patients with portal vein tumor thrombosis who underwent chemoembolization

BACKGROUND The factors affecting the short-term and long-term prognosis of hepatocellular carcinoma(HCC) patients with portal vein tumor thrombosis(PVTT) receiving transarterial chemoembolization(TACE) are still unclear.AIM To clarify the predictors correlated with the short-term and long-term survival of HCC patients with PVTT who underwent TACE.METHODS The medical records of 181 HCC patients with PVTT who underwent TACE at the Second Affiliated Hospital of Chongqing Medical University from January 2015 to July 2019 were retrospectively analyzed. We explored the short-term and longterm prognostic factors by comparing the preoperative indicators of patients who died and survived within 3 mo and 12 mo after TACE. Multivariate analyses were conducted using logistic regression. The area under the receiver operating characteristic curve(area under curve) was used to evaluate the predictive ability of the factors related to the short-term and long-term prognosis.RESULTS The median survival time was 4.8 mo(range: 2.5-8.85 mo). The 3 mo, 6 mo, and 12 mo survival rates were 68.5%, 38.7%, and 15.5%, respectively. In multivariable analysis, total bilirubin, sex, and aspartate aminotransferase(AST) were closely linked to short-term survival. When AST ≥ 87 U/L and total bilirubin ≥ 16.15 μmol/L, the 3-mo survival rate after TACE was reduced significantly(P < 0.05). AST had the best predictive ability, followed by total bilirubin, while sex had the worst predictive ability for short-term survival area under curve: 0.763(AST) vs 0.707(total bilirubin) vs 0.554(sex)]. The long-term survival outcome was significantly better in patients with a single lesion than in those with ≥ three lesions(P = 0.009). Patients with massive block HCC had a worse long-term survival than patients with nodular and diffuse HCC(P = 0.001).CONCLUSION AST, total bilirubin, and sex are independent factors associated with short-term survival. The number of tumors and the gross pathological type of tumor are related to the long-term outcome.

Positron emission tomography/computed tomography with ^(18)F-fluorodeoxyglucose identifies tumor growth or thrombosis in the portal vein with hepatocellular carcinoma

Patients suffering from hepatocellular carcinoma (HCC) with tumor thrombus in the portal vein generally have a poor prognosis. Portal vein tumor thrombus must be distinguished from portal vein blood thrombus, and this identification plays a very important role in management of HCC. Conventional imaging modalities have limitations in discrimination of portal vein tumor thrombus. The application of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for discrimination between tumor extension and blood thrombus has been reported in few cases of HCC, while portal tumor thrombosis and portal vein clot identified by 18F-FDG PET/CT in HCC patients has not been reported so far. We present two HCC cases, one with portal vein tumor thrombus and one thrombosis who were identified with 18F-FDG PET/CT. This report illustrates the complimentary value of combining the morphological and functional imaging in achieving a correct diagnosis in such clinical situations.

Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is very poor although sorafenib is recommended as the first-line treatment. Therefore, an effective treatment regime is needed for treating HCC with PVTT. This review summarized seven potential treatment regimes which including transarterial chemoembolization (TACE), TACE combined with sorafenib, TACE combined with radiotherapy (RT), hepatectomy, hepatic arterial infusion chemotherapy (HAIC), HAIC combined with sorafenib and HAIC combined with RT in the treatment of HCC with PVTT. In conclusion, hepatectomy or the combination of HAIC and sorafenib may be a more effective modality in the treatment of HCC patients with type I - II PVTT. HAIC combined with or without sorafenib/RT or the combination of RT and TACE is an alternative treatment choice for HCC patients with type III - IV PVTT. Further randomized controlled studies are warranted.

Transjugular intrahepatic portosystemic shunt with radioactive seed strand for main portal vein tumor thrombosis with cirrhotic portal hypertension

BACKGROUND Patients with hepatocellular carcinoma complicated with main portal vein tumor thrombosis(mPVTT) and cirrhotic portal hypertension(CPH) have an extremely poor prognosis, and there is a lack of a clinically effective treatment paradigm.AIM To evaluate the efficacy and safety of transjugular intrahepatic portosystemic shunt(TIPS)combined with radioactive seed strand for the treatment of mPVTT patients with CPH.METHODS The clinical data of 83 consecutive patients who underwent TIPS combined with 125I seed strand placement for mPVTT and CPH from January 2015 to December 2018 were retrospectively reviewed. Procedure-related data(success rate, relief of portal vein pressure and CPH symptoms,and adverse events), PVTT response, and patient survival were assessed through a 2-year followup.RESULTS The success rate was 100.0% without perioperative death or procedure-related severe adverse events. The mean portal vein pressure was significantly decreased after the procedure(22.25 ± 7.33mmHg vs 35.12 ± 7.94 mmHg, t = 20.61, P < 0.001). The symptoms of CPH were all effectively relieved within 1 mo. The objective response rate of PVTT was 67.5%. During a mean follow-up of 14.5 ± 9.4 mo(range 1-37 mo), the cumulative survival rates at 6, 12 and 24 mo were 83.1%, 49.7%,and 21.8%, respectively. The median survival time was 12.0 ± 1.3 mo(95% confidence interval: 9.5-14.5). In multivariate Cox regression analysis, body mass index, Child-Pugh grade, cTNM stage,and PVTT response were independent prognostic factors(P < 0.05).CONCLUSION TIPS combined with radioactive seed strand might be effective and safe in treating mPVTT patients with CPH.

Observation of Stereotactic Radiosurgery (Cyberknife) on Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

The purpose of the study was to analyze the clinical effect of stereotactic radiosurgery(SRS)(Cyberknife)on hepatocellular carcinoma with portal vein tumor thrombosis(HCC-PVTT).Data from 50 patients with HCC-PVTT who received Cyberknife from August 2013 to April 2016 was collected for efficacy analysis.Moreover,survival correlation was evaluated by Cox proportionalhazards model.The total effective rate in 1-3 months after treatment was 64.00%,including 7 cases in complete remission,12 cases in partial remission,13 cases in stable conditions,and 18 cases with enlargement;a 4-24-months follow-up(with an average of 11.58±2.58 months)showed that median survival,1-year cumulative survival rate,and 2-year cumulative survival rate were,respectively,11.86±1.79 months,48.00%,and 20.00%.Moreover,the Cox proportional-hazards model indicates that it was with no correlation between lesion diameter,classification of liver function,pre-operative alphafetoprotein,types of hepatitis,number of tumors,ascites,types of tumor emboli,total dose,and survival rate.SRS is effective for HCC-PVTT and serves as an ideal treatment clinically to help preserve patients’lives,which is worthy of clinical promotion and application.

Appropriate treatment strategies improve survival of hepatocellular carcinoma patients with portal vein tumor thrombus

AIM: To evaluate the survival benefits of different treatment strategies for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to determine the prognosis factors.

Experimental study on enhancement of the metastatic potential of portal vein tumor thrombus-originated hepatocellular carcinoma cells using portal vein serum

Objective： Portal vein metastasis of hepatocellular carcinoma（HCC） results in a poor prognosis and seriously affects the survival rate of patients. The mechanism underlying the formation of portal vein tumor thrombus（PVTT） is complex and is not yet fully understood. This study was conducted to investigate the impact of portal vein blood on the proliferation, metastasis, invasion and apoptosis of PVTT cells and to explore its possible mechanisms, which was expected to lay a foundation for ascertaining the mechanism underlying the portal vein metastasis of HCC.Methods： Peripheral blood and portal vein blood were collected from patients with HCC, and the sera from these two sources were used to culture the PVTT-originated HCC cell line CSQT-2. The cells were collected after 24 h, and flow cytometry was performed to detect cell proliferation, cell cycle stages and apoptosis. Transwell migration and invasion assays were applied to detect the metastasis and invasion of the cells in each group. The changes in the expression of MMP-2 and MMP-9 in cells were detected via Western blotting. The contents of IL-12, IFN-γ, IL-1β, IL-2 and TNF-α in the two groups of sera were quantified using corresponding kits. Results： Compared with the group of cells cultured with peripheral serum, the cells cultured with portal vein serum showed significantly lower apoptosis（P〈0.01）, significantly enhanced cell metastasis and invasion（P〈0.01）, whereas cell proliferation and the stages of the cell cycle did not differ significantly（P〉0.05）. A significantly increased expression level of MMP-2 has been observed in tumor cells treated portal vein serum. In addition, compared with peripheral serum, the content of IL-12 was significantly decreased in portal vein serum（P〈0.05）, while the contents of IFN-γ, IL-1β, IL-2, and TNF-α did not differ significantly（P〈0.05）. Conclusions： Portal vein serum from HCC patients could inhibit the apoptosis of PVTT-originated HCC cells and promote cell metastasis and invasion. This effect may be related to the lower level of IL-12 in portal vein serum.

Treatment of hepatocellular carcinoma with portal venous tumor thrombosis: A comprehensive review

The natural history of hepatocellular carcinoma(HCC)with portal vein tumor thrombosis(PVTT)is dismal(approximately 2-4 mo),and PVTT is reportedly found in 10%-40%of HCC patients at diagnosis.According to the Barcelona Clinic Liver Cancer(BCLC)Staging System(which is the most widely adopted HCC management guideline),sorafenib is the standard of care for advanced HCC(i.e.,BCLC stage C)and the presence of PVTT is included in this category.However,sorafenib treatment only marginally prolongs patient survival and,notably,its therapeutic efficacy is reduced in patients with PVTT.In this context,there have been diverse efforts to develop alternatives to current standard systemic chemotherapies or combination treatment options.To date,many studies on transarterial chemoembolization,3-dimensional conformal radiotherapy,hepatic arterial chemotherapy,and transarterial radioembolization report better overall survival than sorafenib therapy alone,but their outcomes need to be verified in future prospective,randomized controlled studies in order to be incorporated into current treatment guidelines.Additionally,combination strategies have been applied to treat HCC patients with PVTT,with the hope that the possible synergistic actions among different treatment modalities would provide promising results.This narrative review describes the current status of the management options for HCC with PVTT,with a focus on overall survival.

Portal vein tumor thrombosis in hepatocellular carcinoma patients: Is it the end?

Hepatocellular carcinoma(HCC)is the sixth most prevalent form of cancer globally and the third leading cause of cancer-related mortality.The incidence of portal vein tumor thrombosis(PVTT)in HCC patients is 21%at one year and 46%at three years.The presence of PVTT has consistently been associated with a poor prognosis for HCC patients over the past decades.Notably,HCC prognosis is influenced not only by the presence of PVTT but also by the degree or extent of PVTT.Currently,there is a lack of global consensus or established protocols regarding the optimal management of HCC with associated PVTT.The Barcelona Clinic for Liver Cancer classifies HCC patients with PVTT as stage C,indicating an advanced stage,and limiting treatment recommendations for these patients to systemic therapy.In recent years,there has been an increase in the availability of therapeutic options for HCC patients with PVTT.Treatment modalities include systemic therapy,transarterial chemoembolization,surgical resection,stereotactic body radiotherapy,transarterial radioembolization,and liver transplantation.An ideal therapy for each patient necessitates a multidisciplinary approach.This review article presents the latest updates in managing HCC patients with PVTT.