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.

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.

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.

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.

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.

Treatment of hepatocellular carcinoma accompanied by portal vein tumor thrombus

The prognosis of patients with hepatocellular cardnorna （HCC） accompanied by portal vein tumor thrombus （PVTT） is generally poor if leo untreated： a median survival time of 2.7-4.0 mo has been reported. Furthermore, while transcatheter arterial chemoembolization （TACE） has been shown to be safe in selected patients, the median survival time with this treatment is still only 3.8-9.5 mo. Systemic single-agent chemotherapy for HCC with PVTT has failed to improve the prognosis, and the response rates have been less than 20%. While regional chemotherapy with low-dose cisplatin and 5-fluorouracil or interferon and 5-fluorouracil via hepatic arterial infusion has increased the response rate, the median survival time has not exceeded 12 （range 4.5-11.8） mo. Combined treatment consisting of radiation for PVTT and TACE for liver tumor has achieved a high response rate, but the median survival rates have still been only 3.8-10.7 mo. With hepatic resection as monotherapy, the 5-year survival rate and median survival time were reportedly 4%-28.5% and 6-14 mo. The most promising results were reported for combined treatments consisting of hepatectomy and TACE, chemotherapy, or internal radiation. The reported 5-year survival rates and median survival times were 42% and 31 mo for TACE followed by hepatectomy; 36.3% and 22.1 mo for hepatectomy followed by hepatic arterial infusion chemotherapy; and 56% for chemotherapy or internal radiation followed by hepatectomy.

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.

Highly metabolic thrombus of the portal vein:^(18)F fluorodeoxyglucose positron emission tomography/computer tomography demonstration and clinical significance in hepatocellular carcinoma

AIM： To assess the ability of ^18F-fluorodeoxyglucose positron emission tomography/computer tomography （^18F-FDG PET/CT） to differentiate between benign and malignant portal vein thrombosis in hepatocellular carcinoma （HCC） patients.METHODS： Five consecutive patients who had HBV cirrhosis, biopsy-proven HCC, and thrombosis of the main portal vein and/or left/right portal vein on ultrasound （US）, computer tomography （CT） or magnetic resonance imaging （MRI） were studied with ^18F-FDG PET/CT. The presence or absence of a highly metabolic thrombus on ^18F-FDG PET/CT was considered diagnostic for malignant or benign portal vein thrombosis, respectively. All patients were followed-up monthly with US, CT or MRI. Shrinkage of the thrombus or recanalization of the vessels on US, CT or MRI during follow-up was considered to be definitive evidence of the benign nature of the thrombosis, whereas enlargement of the thrombus, disruption of the vessel wall, and parenchymal infiltration over follow-up were considered to be consistent with malignancy. ^18SF-FDG PET/CT, and US, CT or MRI results were compared.RESULTS： Follow-up （1 to 10 mo） showed signs of malignant thrombosis in 4 of the 5 patients. US, CT or MRI produced a true-positive result for malignancy in 4 of the patients, and a false-positive result in 1. ^18F-FDG PET/CT showed a highly metabolic thrombus in 4 of the 5 patients. ^18F-FDG PET/CT achieved a true-positive result in all 4 of these patients, and a true-negative result in the other patient. No false-positive result was observed using ^18F-FDG PET/CT.CONCLUSION： ^18F-FDG PET/CT may be helpful in discriminating between benign and malignant portal vein thrombi. Patients may benefit from ^18F-FDG PET/CT when portal vein thrombi can not be diagnosed exactly by US, CT or MRI.

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.

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.

Conversion hepatectomy for hepatocellular carcinoma with main portal vein tumour thrombus after lenvatinib treatment: A case report

BACKGROUND Hepatocellular carcinoma(HCC)accompanied by portal vein tumour thrombus(PVTT)presents an aggressive disease course,worsening liver function reserve,and a high recurrence rate.Clinical practice guidelines recommend systemic therapy as the first-line option for HCC with portal invasion.However,to achieve longer survival in these patients,the treatment strategy should be concluded with removal of the tumour by locoregional therapy.We experienced a case of initially unresectable HCC with main PVTT converted to radical hepatectomy after lenvatinib treatment.CASE SUMMARY A 59-year-old male with chronic hepatitis C infection visited our clinic as a regular post-surgery follow-up.Contrast-enhanced abdominal computed tomography revealed a liver mass diffusely located at the lateral segment with a massive PVTT extending from the umbilical portion to the main and contralateral third-order portal branches.With the diagnosis of unresectable HCC with Vp4(main trunk/contralateral branch)PVTT,lenvatinib was started at 12 mg/d.The computed tomography taken 3 mo after starting lenvatinib showed regression of the PVTT,which had retreated to the contralateral first-order portal branch.He tolerated the full dose without major adverse effects.With cessation of lenvatinib for 7 d,radical left lobectomy and PVTT thrombectomy were conducted.The patient’s postoperative course was uneventful.Microscopically,the primary lesion showed fibrotic changes,with moderately to poorly differentiated tumour cells surrounded by granulation tissues in some areas.The majority of the PVTT showed necrosis.He was alive without recurrence for 8 mo.CONCLUSION This is the first case of HCC with Vp4 PVTT in which radical conversion hepatectomy was succeeded after lenvatinib 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.

Drug-eluting bead transarterial chemoembolization as neoadjuvant therapy pre-liver transplantation for advanced-stage hepatocellular carcinoma

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 DEBTACE(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.

Liver transplantation for hepatocellular carcinoma in India: Are we ready for 2040?

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 outcomes 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 undergoing 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 alphafetoprotein(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 downstaging 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.

Des-gamma-carboxy prothrombin and alpha-fetoprotein levels as biomarkers for hepatocellular carcinoma and their correlation with radiological characteristics

BACKGROUND Alpha-fetoprotein(AFP),a commonly used biomarker for hepatocellular carcinoma(HCC),is normal in up to one-third of patients.AIM To evaluate the diagnostic performance of des-gamma-carboxy-prothrombin(DCP)alone and in combination with AFP.METHODS In this study,202 patients with radiologically proven HCC were enrolled,and their DCP and AFP levels were evaluated for their diagnostic performance.RESULTS The mean age of the enrolled patients was 58.5 years;72.0%were male.DCP was elevated in 86.6%(n=175)of all patients,100.0%(n=74)of patients with portal vein thrombus,and 87.4%(n=111)of patients with multicentric HCC.AFP was elevated in 64.3%(n=130)of all the patients,74%(n=55)of the patients with portal vein thrombus,and 71.6%(n=91)of the patients with multicentric HCC(P=0.030,0.001,and 0.015,respectively).In tumors less than 2 cm in size(n=46),DCP was increased in 32(69.5%)patients,and AFP was increased in 25(54.3%)patients(P=0.801).There was good pairing between DCP and AFP for HCCs of 2 cm size or larger(P<0.001);however,the pairing among tumors<2 cm size was not significant(P=0.210).In 69 of the patients(34.1%),only one of the tumor markers was positive;DCP was elevated alone in 57/202(28.2%)of all patients,and AFP alone was elevated in 12/202(5.9%)of the patients.The areas under receiver operating characteristic curves(AUROC)for tumors>2 cm was 0.74 for DCP and 0.59 for AFP;combining both markers resulted in an AUROC of 0.73.For tumors<2 cm,the AUROC was 0.25 for DCP and 0.40 for AFP.CONCLUSION DCP,as an individual marker,had a better diagnostic performance in many cases of HCC.Hence,DCP may replace AFP as the primary HCC biomarker.

Transjugular intrahepatic portosystemic shunt with covered stents for hepatocellular carcinoma with portal vein tumor thrombosis

AIM: To evaluate transjugular intrahepatic portosystemic shunt (TIPS) with covered stents for hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (PVTT).

Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide,carboplatin,epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil:A pilo

AIM： To investigate the poor prognosis of HCC with PVTT, we evaluated the efficacy by a new combination chemotherapy for advanced hepatocellular carcinoma （HCC） with portal vein tumor thrombus （PVTT）. METHODS： From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil. RESULTS： The mean course of chemotherapy was 14.4 （range, 9-21） too. One patient showed complete response （CR） with disappearance of HCC and PVI-F after treatment, and the two patients showed partial response （PR）, response rate （CR ＋ PR/All cases 30%）. The median survival time after the therapy was 457.2 d. The one-year survival rate was 70%. Adverse reactions were tolerable.CONCLUSION： Although the prognosis of most patients with Stage IVA HCC by PVTT is poor, our combination chemotherapy may induces long-term survival and is an effective treatment and produced anti-tumor activity with tolerable adverse effects in patients for advanced Stage IVA HCC accompanied by PVTT.

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.

Lenvatinib for large hepatocellular carcinomas with portal trunk invasion:Two case reports

BACKGROUND In a phase III trial of lenvatinib as first-line treatment for advanced unresectable hepatocellular carcinoma(uHCC),the drug proved non-inferior to sorafenib in terms of the overall survival,but offered better progression-free survival.However,the effects of lenvatinib in uHCC patients with a tumor thrombus in the main portal vein and/or a high tumor burden(tumor occupancy more than 50%of the total liver volume),remain unclear,because these were set as exclusion criteria in the aforementioned trial.CASE SUMMARY A 53-year-old man(case 1)and 66-year-old woman(case 2)with uHCC presented to us with a tumor thrombus in both the main portal vein and inferior vena cava,a high tumor burden accompanied by a tumor diameter greater than>100 mm,and distant metastasis,with the residual liver function classified as grade 2A according to the modified Albumin–Bilirubin grading.We started both patients on lenvatinib.The therapeutic effect,as evaluated by the modified Response Evaluation Criteria in Solid Tumors,was rated as partial response in both case 1 and case 2(at 8 wk and 4 wk after the start of lenvatinib administration,respectively).The therapeutic effect was sustained for 6 mo in case 1 and 20 mo in case 2.Fever occurred as an adverse event in both case 1 and 2,and hyperthyroidism and thrombocytopenia in only case 2,neither of which,however,necessitated treatment discontinuation.CONCLUSION Even in hepatocellular carcinoma patients with poor prognostic factors,if the liver function is well-preserved,lenvatinib is effective and safe.

CT guided ^125iodine seed implantation for portal vein tumor thrombus in primary hepatocellular carcinoma

Background This study evaluated the clinical application of CT guided ^125iodine implantation in patients with portal vein tumor thrombus in primary hepatocellular carcinoma. Methods The ten patients （9 males and 1 female, aged from 36 to 72 years） with portal vein tumor thrombus accompanying hepatocellular carcinoma had been treated with comprehensive therapy including surgery, transcatheter arterial chemoembolization, radiotherapy ablation, microwave ablation or percutaneous ethanol injection. The average diameter of each tumor thrombus was 21.5 mm × 30.5 mm. Seeds of 30 MBq ^125I were implanted 5 mm apart within the portal vein tumor thrombus. The follow-up after 4 months included enhanced spiral CT. Results CT screening of the tumours indicated that 4 out of 10 patients showed complete response to the therapy, 5 partial response and 1 stable disease. Adverse effects included aggravated abdominal dropsy and temporarily increased transaminase, which were controlled by medical management. Severe complications such as haemorrhage, biliary fistula hepatic abscess, pancreatic fistula and hepatic function failure were not observed. Implanted seeds migrated to lung and left hepatic lobe in 1 case. Conclusion CT guided implantation of ^125iodine seeds, can effectively treat portal vein tumor thrombus accompanying hepatocellular carcinoma with minimal damage and few complications.