Transcatheter arterial chemoembolization combined with PD-1 inhibitors and Lenvatinib for hepatocellular carcinoma with portal vein tumor thrombus

BACKGROUND Hepatocellular carcinoma(HCC)patients complicated with portal vein tumor thrombus(PVTT)exhibit poor prognoses and treatment responses.AIM To investigate efficacies and safety of the combination of PD-1 inhibitor,transcatheter arterial chemoembolization(TACE)and Lenvatinib in HCC subjects comorbid with PVTT.METHODS From January 2019 to December 2020,HCC patients with PVTT types Ⅰ-Ⅳ were retrospectively enrolled at Beijing Ditan Hospital.They were distributed to either the PTL or TACE/Lenvatinib(TL)group.The median progression-free survival(mPFS)was set as the primary endpoint,while parameters like median overall survival,objective response rate,disease control rate(DCR),and toxicity level served as secondary endpoints.RESULTS Forty-one eligible patients were finally recruited for this study and divided into the PTL(n=18)and TL(n=23)groups.For a median follow-up of 21.8 months,the DCRs were 88.9%and 60.9%in the PTL and TL groups(P=0.046),res-pectively.Moreover,mPFS indicated significant improvement(HR=0.25;P<0.001)in PTL-treated patients(5.4 months)compared to TL-treated(2.7 months)patients.There were no treatment-related deaths or differences in adverse events in either group.CONCLUSION A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types Ⅰ-Ⅳ.

Comprehensive review of hepatocellular carcinoma with portal vein tumor thrombus:State of art and future perspectives

Background:Despite advances in the diagnosis of patients with hepatocellular carcinoma(HCC),70%-80%of patients are diagnosed with advanced stage disease.Portal vein tumor thrombus(PVTT)is among the most ominous signs of advanced stage disease and has been associated with poor survival if untreated.Data sources:A systematic search of MEDLINE(PubMed),Embase,Cochrane Library and Database for Systematic Reviews(CDSR),Google Scholar,and National Institute for Health and Clinical Excellence(NICE)databases until December 2022 was conducted using free text and MeSH terms:hepatocellular carcinoma,portal vein tumor thrombus,portal vein thrombosis,vascular invasion,liver and/or hepatic resection,liver transplantation,and systematic review.Results:Centers of surgical excellence have reported promising results related to the individualized surgical management of portal thrombus versus arterial chemoembolization or systemic chemotherapy.Critical elements to the individualized surgical management of HCC and portal thrombus include precise classification of the portal vein tumor thrombus,accurate identification of the subgroups of patients who may benefit from resection,as well as meticulous surgical technique.This review addressed five specific areas:(a)formation of PVTT;(b)classifications of PVTT;(c)controversies related to clinical guidelines;(d)surgical treatments versus non-surgical approaches;and(e)characterization of surgical techniques correlated with classifications of PVTT.Conclusions:Current evidence from Chinese and Japanese high-volume centers demonstrated that patients with HCC and associated PVTT can be managed with surgical resection with acceptable results.

Better surgical treatment method for hepatocellular carcinoma with portal vein tumor thrombus

Hepatocellular carcinoma(HCC) with portal vein tumor thrombus(PVTT) is a disease that is not uncommon, but the treatments vary drastically between Eastern and Western countries. In Europe and America, the first line of treatment is systemic therapy such as sorafenib and the surgical treatment is not a recommend option. While an increasing number of studies from China and Japan have suggested that surgical treatment results in better outcomes when compared to transcatheter arterial chemoembolization(TACE), sorafenib, or other nonsurgical treatments, and two classification systems, Japanese Vp classification and Chinese Cheng's classification, were very useful to guide the surgical treatment. We have also found that surgical treatment may be more effective, as we have performed surgical treatment for HCC-PVTT patients over a period of approximately 15 years and achieved good results with the longest surviving time being 13 years and onward. In this study, we review the efficacy and principles of current surgical treatments and introduce our new, more effective surgical technique named "thrombectomy first", which means the tumor thrombus in the main portal vein, the bifurcation or the contralateral portal vein should be removed prior to liver resection. Thus, compression and crushing of PVTT during the operation could be avoided and new intrahepatic metastases caused by tumor thrombus to the remnant liver minimized. The new technique is even beneficial to the prognosis of Cheng's classification Types Ⅲ and Ⅳ PVTT. The vital tips and tricks for the surgical approach are described.

Application of cystoscope in surgical treatment of hepatocellular carcinoma with portal vein tumor thrombus

Development of portal vein tumor thrombus deteriorates the prognosis of hepatocellular carcinoma, while surgical treatment can offer a promising prognosis for selected patients. However, the possibility of residual lesions in portal vein after conventional thrombectomy is a main risk factor leading to postoperative recurrence. Therefore, ensuring the complete removal of tumor thrombus during operation is critical to improve prognosis. For the first time, we report here one case of hepatocellular carcinoma with portal vein tumor thrombus in which cystoscope was successfully applied as a substitute of intravascular endoscope to visualize the cavity of the portal vein. The patient was a 61-year-old man with a 7-cm tumor in the right lobe of the liver, with tumor thrombus invading the right branch and adjacent to the conjunction of the portal vein. After removal of the tumor, the Olympus CYF-VA2 cystoscope was used to check the portal vein from the opening stump of the right branch of the portal vein. In this case, residual thrombus tissue was found near the opening stump and the conjunction of the portal vein. The residual lesion was carefully retrieved from the stump after retraction of the cystoscope. The procedure was repeated until no residual lesion was found. The whole duration time of thrombectomy was 22.5(15 + 7.5) min. The patient was free from recurrence at 8 months after the procedure. Our work indicated that the cystoscope is a suitable substitute, with a proper size and function to check the portal vein system and ensure the curability of thrombectomy. Although welldesigned clinic trails are still needed, this procedure may further improve the postoperative prognosis of hepatocellular carcinoma with portal vein tumor thrombus.

Hepatectomy for hepatocellular carcinoma with portal vein tumor thrombus

Despite surgical removal of tumors with portal vein tumor thrombus(PVTT) in hepatocellular carcinoma(HCC) patients, early recurrence tends to occur, and overall survival(OS) periods remain extremely short. The role that hepatectomy may play in long-term survival for HCC with PVTT has not been established. The operative mortality of hepatectomy for HCC with PVTT has also not been reviewed. Hence, we reviewed recent literature to assess these parameters. The OS of patients who received hepatectomy in conjunction with multidisciplinary treatment tended to be superior to that of patients who did not. Multidisciplinary treatments included the following: preoperative radiotherapy on PVTT; preoperative transarterial chemoembolization(TACE); subcutaneous administration of interferon-alpha(IFN-α) and intra-arterial infusion of 5-fluorouracil(5-FU) with infusion chemotherapy in the affected hepatic artery; cisplatin, doxorubicin and 5-FU locally administered in the portal vein; and subcutaneous injection of IFN-α, adjuvant chemotherapy(5-FU + Adriamycin) administration via the portal vein with postoperative TACE, percutaneous isolated hepatic perfusion and hepatic artery infusion and/or portal vein chemotherapy. The highest reported rate of operative mortality was 9.3%. In conclusion, hepatectomy for patients affected by HCC with PVTT is safe, has low mortality and might prolong survival in conjunction with multidisciplinary treatment.

Combined pancreatoduodenectomy and orthotopic liver transplantation for hepatocellular carcinoma with portal vein tumor thrombus:A case report

Hepatocellular cancer(HCC) is the most common primary malignant hepatic tumor that accounts for over 80% of primary liver tumors.The outlook for HCC is dismal if it is left untreated and the treatment for patients with HCC evolved into a complex task.The treatments for HCC are mainly surgical therapies including hepatic resection(HR) and liver transplantation.Although HR is a well accepted therapy for HCC,it is not suitable for patients with advanced cirrhosis.Orthotopic liver transplantation(OLT) is considered more appropriate in cases with HCC related to cirrhosis,because it may eliminate both the tumor and the underlying liver disease.In this study,we reported a patient with HCC and portal vein tumor thrombus underwent combined pancreatoduodenectomy with OLT and survived 23 months in our center.

Transjugular intrahepatic portosystemic shunt for esophagogastric variceal bleeding in patients with hepatocellular carcinoma and portal vein tumor thrombus

BACKGROUND Whether hepatocellular carcinoma(HCC)with portal vein tumor thrombus(PVTT)and acute esophagogastric variceal bleeding(EGVB)can improve the success rate of endoscopic hemostasis and overall survival(OS)from transjugular intrahepatic portosystemic shunt(TIPS)remains controversial.AIM To compare the clinical outcomes between TIPS and standard treatment for such HCC patients.METHODS This monocenter,retrospective cohort study included patients diagnosed as HCC with PVTT and upper gastrointestinal bleeding.Patients were grouped by the treatment(TIPS or standard conservative treatment).The success rate of en-doscopic hemostasis,OS,rebleeding rates,and main causes of death were ana-lyzed.RESULTS Between July 2015 and September 2021,a total of 77 patients(29 with TIPS and 48 with standard treatment)were included.The success rate of endoscopic hemostasis was 96.6%in the TIPS group and 95.8%in the standard treatment group.All the 29 patients in TIPS group successful underwent TIPS procedure and had a better OS compared with standard treatment within the first 160 days after treatment(68 days vs 43 days,P=0.022),but shorter OS after 160 days(298 days vs 472 days, P = 0.022). Cheng’s Classification of PVTT, total bilirubin and Child-Pugh class wereindependently negative associated with OS (all P < 0.05). The main causes of death were liver failure or hepaticencephalopathy (75.9%) in the TIPS group and rebleeding (68.8%) in the standard treatment.CONCLUSIONTIPS could reduce the risk of early death due to rebleeding and prolong short-term survival in HCC patients withPVTT and acute EGVB, which deserves further investigation.

Conversion therapy of a giant hepatocellular carcinoma with portal vein thrombus and inferior vena cava thrombus:A case report and review of literature

BACKGROUND The prognosis of hepatocellular carcinoma(HCC)combined with portal and hepatic vein cancerous thrombosis is poor,for unresectable patients the combination of targeted therapy and immune therapy was the first-line recommended treatment for advanced HCC,with a median survival time of only about 2.7-6 months.In this case report,we present the case of a patient with portal and hepatic vein cancerous thrombosis who achieved pathologic complete response after conversion therapy.CASE SUMMARY In our center,a patient with giant HCC combined with portal vein tumor thrombus and hepatic vein tumor thrombus was treated with transcatheter arterial chemoembolization(TACE),radiotherapy,targeted therapy and immunotherapy,and was continuously given icaritin soft capsules for oral regulation.After 7 months of conversion therapy,the patient's tumor shrank and the tumor thrombus subsided significantly.The pathology of surgical resection was in complete remission,and there was no progression in the postoperative follow-up for 7 months,which provided a basis for the future strategy of combined conversion therapy.CONCLUSION In this case,atezolizumab,bevacizumab,icaritin soft capsules combined with radiotherapy and TACE had a good effect.For patients with hepatocellular carcinoma combined with hepatic vein/inferior vena cava tumor thrombus,adopting a high-intensity,multimodal proactive strategy under the guidance of multidisciplinary team(MDT)is an important attempt to break through the current treatment dilemma.

Transarterial chemoembolization plus stent placement for hepatocellular carcinoma with main portal vein tumor thrombosis:A meta-analysis

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.

Liver transplantation and resection in patients with hepatocellular cancer and portal vein tumor thrombosis: Feasible and effective?

Patients with locally advanced hepatocellular cancer(HCC)and portal vein tumor thrombosis(PVTT)have a dismal prognosis since limited treatment options are available for them.In recent years,effective systemic therapy,and advances in the understanding of technicalities and effectiveness of ablative therapies especially radiotherapy,have given some hope to prolong survival in them.This review summarized recent evidence in literature regarding the possible role of liver resection(LR)and liver transplantation(LT)in patients with locally advanced HCC and PVTT with no extrahepatic disease.Downstaging therapies have helped make curative resection or LT a reality in selected patients.This review emphasizes on the key points to focus on when considering surgery in these patients,who are usually relegated to palliative systemic therapy alone.Meticulous patient selection based on tumor biology,documented downstaging based on imaging and decrease in tumor marker levels,and an adequate waiting period to demonstrate stable disease,may help obtain satisfactory long-term outcomes post LR or LT in an intention to treat strategy in patients with HCC and PVTT.

Application of radioactive iodine-125 microparticles in hepatocellular carcinoma with portal vein embolus

BACKGROUND Radioactive iodine-125(125I)microparticle therapy is a new type of internal radiation therapy that has shown unique advantages in the treatment of malignant tumors,especially hepatocellular carcinoma.Patients with hepatocellular carcinoma frequently experience portal vein embolism,which exacerbates the difficulty and complexity of treatment.125I particles,used in local radiotherapy,can directly act on tumor tissue and reduce damage to surrounding healthy tissue.Through retrospective analysis,this study discussed the efficacy and safety of radioactive 125I particles in portal vein embolization patients with hepatocellular carcinoma in order to provide more powerful evidence supporting clinical treatment.AIM To investigate the effect of transcatheter arterial chemoembolization combined with portal vein 125I particle implantation in the treatment of primary liver cancer patients with portal vein tumor thrombus and its influence on liver function.METHODS The clinical data of 96 patients with primary liver cancer combined with portal vein tumor thrombus admitted to our hospital between January 2020 and December 2023 were retrospectively analyzed.Fifty-two patients received treatment with transcatheter arterial chemoembolization and implantation of 125I particles in the portal vein(combination group),while 44 patients received treatment with transcatheter arterial chemoembolization alone(control group).The therapeutic effects on tumor lesions,primary liver cancer,and portal vein tumor embolisms were compared between the two groups.Changes in relevant laboratory indexes before and after treatment were evaluated.The t test was used to compare the measurement data between the two groups,and the χ^(2) test was used to compare the counting data between groups.RESULTS The tumor lesion response rate in the combination group(59.62%vs 38.64%)and the response rate of patients with primary liver cancer complicated with portal vein tumor thrombus(80.77%vs 59.09%)were significantly greater than those in the control group(χ^(2)=4.196,5.421;P=0.041,0.020).At 8 wk after surgery,the serum alpha-fetoprotein,portal vein main diameter,and platelet of the combined group were significantly lower than those of the control group,and the serum alanine aminotransferase,aspartate aminotransferase,and total bilirubin were significantly greater than those of the control group(t=3.891,3.291,2.330,3.729,3.582,4.126;P<0.05).The serum aspartate aminotransferase,alanine aminotransferase,and total bilirubin levels of the two groups were significantly greater than those of the same group 8 wk after surgery(P<0.05),and the peripheral blood platelet,alphafetoprotein,and main portal vein diameter were significantly less than those of the same group before surgery(P<0.05).CONCLUSION In patients with primary liver cancer and a thrombus in the portal vein,transcatheter arterial chemoembolization plus portal vein 125I implantation is more effective than transcatheter arterial chemoembolization alone.However,during treatment it is crucial to pay attention to liver function injury caused by transcatheter arterial chemoembolization.

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.

Comprehensive treatments for hepatocellular carcinoma with tumor thrombus in major portal vein

AIM: To evaluate the efficacy of transcatheter arterial chemoembolisation (TACE) compared with surgical intervention and sorafenib for treatment of hepatocellular carcinoma (HCC) in patients with tumor thrombus extending to the main portal vein.METHODS: From 2009 to 2013, a total of 418 HCC patients with tumor thrombus extending to the main portal vein were enrolled in this study and divided into four groups. These groups underwent different treatments as follows: TACE (n = 307), surgical intervention (n = 54), sorafenib (n = 15) and palliative treatment (n = 42). Overall survival rates were determined by Kaplan-Meier method, and differences between the groups were identified through log-rank analysis. Cox&#x02019;s proportional hazard model was used to identify the risk factors for survival.RESULTS: The mean survival periods for patients in the TACE, surgical intervention, sorafenib and palliative treatment groups were 10.39, 4.13, 5.54 and 2.82 mo, respectively. For the TACE group, the 3-, 6-, 12- and 24-mo survival rates were 94.1%, 85.9%, 51.5% and 0.0%, respectively. The corresponding rates were 60.3%, 22.2%, 0.0% and 0.0% for the surgical intervention group and 50.9%, 29.5%, 0.0% and 0.0% for the sorafenib group. Evidently, the results in the TACE group were significantly higher than those in the other groups (P &#x0003c; 0.0001). Furthermore, no significant difference among survival rates was observed between TACE with/without sorafenib (10.22 mo vs 10.52 mo, P = 0.615). No significant difference in survival rates was also found among the surgical intervention, sorafenib and palliative treatment groups (P &#x0003e; 0.05). These values significantly increased after TACE with/without sorafenib compared with other treatments (P &#x0003c; 0.05).CONCLUSION: For HCC patients with tumor thrombus extending to the main portal vein, TACE can yield a higher survival rate than surgical intervention or sorafenib treatment.

Combined endovascular brachytherapy, sorafenib, and transarterial chemobolization therapy for hepatocellular carcinoma patients with portal vein tumor thrombus

AIM To evaluate the safety and efficacy of combined endovascular brachytherapy(EVBT),transarterial chemoembolization(TACE),and sorafenib to treat hepatocellular carcinoma(HCC) patients with main portal vein tumor thrombus(MPVTT).METHODS This single-center retrospective study involved 68 patients with unresectable HCC or those who were unfit for liver transplantation and percutaneous frequency ablation according to the BCLC classification. All patients had Child-Pugh classification grade A or B,Eastern Cooperative Oncology Group(ECOG)performance status of 0-2,and MPVTT. The patients received either EVBT with stent placement,TACE,and sorafenib(group A,n = 37),or TACE with sorafenib(group B,n = 31). The time to progression(TTP) and overall survival(OS) were evaluated by propensity score analysis.RESULTS In the entire cohort,the 6-,12-,and 24-mo survival rates were 88.9%,54.3%,and 14.1% in group A,and 45.8%,0%,and 0% in group B,respectively(P < 0.001). The median TTP and OS were significantly longer in group A than group B(TTP: 9.0 mo vs 3.4 mo,P < 0.001; OS: 12.3 mo vs 5.2 mo,P < 0.001). In the propensity score-matched cohort,the median OS was longer in group A than in group B(10.3 mo vs 6.0 mo,P < 0.001). Similarly,the median TTP was longer in group A than in group B(9.0 mo vs 3.4 mo,P < 0.001). Multivariate Cox analysis revealed that the EVBT combined with stent placement,TACE,and sorafenib strategy was an independent predictor of favorable OS(HR = 0.18,P < 0.001). CONCLUSION EVBT combined with stent placement,TACE,and sorafenib might be a safe and effective palliative treatment option for MPVTT.

New Evidence and Perspectives on the Management of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus

Portal vein tumor thrombosis (PVTT) is an intractable condition but common phenomenon in hepatocellular carcinoma (HCC).HCC patients with PVTT may have worse liver function,a higher chance of comorbidity related to portal hypertension,lower tolerance to treatment and poorer prognoses.In Western guidelines,patients are offered palliative treatment with sorafenib or other systemic agents because HCC with PVTT is grouped together with metastatic HCC during the planning of its management.In recent years,various treatment options have become available for patients with HCC and PVTT.Therapy has also shifted toward evidencebased treatment.However,policies for the management of HCC with PVTT have not been established.This comprehensive literature review aims to present current and available management options for patients with HCC and PVTT.Evidence is mainly based on studies published after 2010.

Transarterial embolization and low-dose continuous hepatic arterial infusion chemotherapy with oxaliplatin and raltitrexed for hepatocellular carcinoma with major portal vein tumor thrombus

AIM To determine the efficacy and safety of transarterial embolization and low-dose continuous hepatic arterial infusion chemotherapy with oxaliplatin and raltitrexed in hepatocellular carcinoma(HCC) with major portal vein tumor thrombus(MPVTT).METHODS eighty-six patients with MPVTT accepted routine embolization. The catheter was kept in the hepatic artery and oxaliplatin(50 mg in 250 m L of glucose) was infused by pump for 4 h,followed by raltitrexed(2 mg in 100 m L of 0.9% saline) infusion by pump for the next 1 h. The efficacy and safety were evaluated afterthe transarterial chemoembolization(TACe).RESULTS Full or partial embolization was achieved in 86 cases,where all the cases received low dose continuous hepatic arterial infusion chemotherapy. Complete responses(CRs),partial responses(PRs),stable disease(SD),and disease progression(PD) for intrahepatic disease were observed in 0,45,20,and 21 patients,respectively. The 1-,2-and 3-year overall survival rates of the 86 patients were 40.7%,22.1%,and 8.1% respectively,and the median survival time was 8.7 mo. Complication was limited. CONCLUSION TACE with low dose continuous hepatic arterial infusion of oxaliplatin and raltitrexed could be an option in MPVTT patient; it was shown to be effective in patients with advanced HCC with MPVTT with less toxicity.

Neoadjuvant radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus:a systematic review

Background:The prognosis of hepatocellular carcinoma(HCC)with portal vein tumor thrombus(PVTT)is extremely poor.The clinical outcome of preoperative radiotherapy(RT)is still controversial.This study aimed to compare the clinical outcomes of combined neoadjuvant RT and hepatectomy with hepatectomy alone for HCC with PVTT.Methods:Comprehensive database searches were performed in PubMed,the Cochrane Library,EMBASE,and the Web of Science to retrieve studies published from the database creation to July 1,2020.Only comparative studies that measured survival between neoadjuvant RT followed by hepatectomy and hepatectomy alone were included.The characteristics of the included studies and patients were extracted,and the included data are presented as relative ratio(RR)estimates with 95%confidence intervals(CIs)for all outcomes.The RRs of each study were pooled using a fixed or random effects model with Review Manager(the Cochrane Collaboration,Oxford,UK)version 5.3.The response rate to RT and the overall survival(OS)rate in neoadjuvant RT followed by hepatectomy and hepatectomy alone were measured.Results:One randomized and two non-randomized controlled trials with 302 patients were included.Most patients were classified as Child-Pugh A,and Type II and III PVTT were the most common types.After RT,29(22.8%)patients were evaluated as partial response(PR)and had a positive RT response,but nine(7.1%)had progressive disease(PD).Neoadjuvant RT followed by hepatectomy was received by 127(42.1%)patients after excluding 15(5.0%)patients with severe complications or PD after RT,and 160(53.0%)patients received hepatectomy alone.In the randomized controlled trial(RCT),the 1-year OS rate in the neoadjuvant RT group and the surgery alone group was 75.2%and 43.1%,respectively(P<0.001).In the two non-randomized studies,a meta-analysis with a fixed effects model showed a longer OS in patients undergoing neoadjuvant RT followed by hepatectomy compared with hepatectomy alone at 1-year follow-up(RR=2.02;95%CI:1.45-2.80;P<0.0001).Conclusions:This systematic review showed that neoadjuvant RT followed by hepatectomy in patients with resectable HCC and PVTT was associated with a longer OS than patients who received hepatectomy alone.

Treatments of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus:Current Status and Controversy

The proportions of patients with hepatocellular carcinoma(HCC)involving portal vein tumor thrombus(PVTT)varies greatly in different countries or regions,ranging from 13%to 45%.The treatment regimens for PVTT recommended by HCC guidelines in different countries or regions also vary greatly.In recent years,with the progress and development of surgical concepts,radiotherapy techniques,systematic therapies(for example,VEGF inhibitors,tyrosine kinase inhibitors and immune checkpoint inhibitors),patients with HCC involving PVTT have more treatment options and their prognoses have been significantly improved.To achieve the maximum benefit,both clinicians and patients need to think rationally about the indications of treatment modalities,the occurrence of severe adverse events,and the optimal fit for the population.In this review,we provide an update on the treatment modalities available for patients with HCC involving PVTT.Trials with large sample size for patients with advanced or unresectable HCC are also reviewed.

Identification of portal vein tumor thrombus with an independent clonal origin in hepatocellular carcinoma via multi-omics data analysis

Objective: Multiple mechanisms underlying the development of portal vein tumor thrombus(PVTT) in hepatocellular carcinoma(HCC) have been reported recently. However, the origins of PVTT remain unknown. Increasing multi-omics data on PVTTs in HCCs have made it possible to investigate whether PVTTs originate from the corresponding primary tumors(Ts).Methods: The clonal relationship between PVTTs and their corresponding primary Ts was investigated using datasets deposited in public databases. One DNA copy number variations dataset and three gene expression datasets were downloaded for the analyses.Clonality analysis was performed to investigate the clonal relationship between PVTTs and Ts from an individual patient.Differential gene expression analysis was applied to investigate the gene expression profiles of PVTTs and Ts.Results: One out of 19 PVTTs had no clonal relationship with its corresponding T, whereas the others did. The PVTTs with independent clonal origin showed different gene expression and enrichment in biological processes from the primary Ts. Based on the unique gene expression profiles, a gene signature including 24 genes was used to identify pairs of PVTTs and primary Ts without any clonal relationship. Validation in three datasets showed that these types of pairs of PVTTs and Ts can be identified by the 24-gene signature.Conclusions: Our findings show a direct evidence for PVTT origin and consolidate the heterogeneity of PVTTs observed in clinic.The results suggest that PVTT investigation at a molecular level is clinically necessary for diagnosis and treatment.

SpyGlass in Diagnosis of Hepatocellular Carcinoma with Right Hepatic Duct Tumor Thrombus Hemorrhage: A Case Report

Hepatocelluar carcinoma presenting as a biliary duct tumor thrombus is a relatively rare entity, with poor prognosis. The primary clinical manifestation of this disease is obstructive jaundice, which can often be misdiagnosed. A 59-year-old female patient was admitted with sudden onset of abdominal pain. Laboratory tests suggested obstructive jaundice, and enhanced magnetic resonance imaging of the upper abdomen did not show obvious biliary dilatation. Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography suggested an occupying lesion in the upper bile duct. SpyGlass and biopsy finally confirmed hepatocellular carcinoma with right hepatic duct tumor thrombus hemorrhage. The SpyGlass Direct Visualization System, as an advanced biliary cholangioscopy device, showed the advantages of single-person operation as well as easy access to and visualization of the lesion.