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Background and Aims: Portal vein tumor thrombus (PVTT) occurs frequently in hepatocellular carcinoma (HCC) patients. However, there is currently no satisfactory treatment. Radiotherapy (RT) and tyrosine kinase inhibitors (TKI) are currently commonly used. However, whether their combined use provides a survival benefit is debatable. This retrospective study compared the efficacy and safety between radiotherapy plus lenvatinib (RT + L) and radiotherapy plus sorafenib (RT + S) in the treatment of hepatocellular carcinoma with portal vein tumor thrombus (PVTT). Methods: Among patients with PVTT who received RT + L or RT + S between March 2017 and September 2022, the primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and incidence of treatment-related adverse effects. The prognostic factors were also assessed. Results: The analysis included 152 patients (RT + L: 48; RL: 25; RT + S: 55; S: 24). Compared with the RT + S group, the RT + L group had a longer OS and PFS. Among patients with type I/II PVTT, the median OS times were 19.8 months and 13.5 months (p = 0.047) and the median PFS was 12.3 months and 7.3 months (p = 0.042), respectively. And the median OS of the patients with type I/II PVTT were 14.4 months and 8.3 months (p = 0.030) and the median PFS was 8.3 months and 6.2 months (p = 0.026). ORR and DCR in RT + L group (25.0% and 75.0%) were also little higher than those in RT + S group (20.0% and 70.9%), but not statistically significant. In univariate analysis, etiology, Type of PVTT, alpha-fetoprotein (AFP) level, Child--Pugh score, and treatment method influenced OS. Multivariate analysis confirmed that treatment method, etiology, alpha-fetoprotein (AFP) level, and Child--Pugh score were independent prognostic factors for OS. Similar safety profiles were observed in the RT + L and RT + S groups. The most common adverse events were myelosuppression, decreased liver function, fatigue, diarrhea, nausea, and vomiting. Most adverse reactions were grade 1-2. Conclusion: The side effects of radiotherapy plus lenvatinib were acceptable. Compared to RT + S, RT + L had good efficacy in the treatment of hepatocellular carcinoma with PVTT. Validation is needed in prospective studies with larger sample sizes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the characteristic of blood supply of liver portal vein tumor thrombus (PVTT) using perfusion indexes and spectral parameters. Methods: Between July 2020 and December 2022, the study enrolled 25 liver cancer patients completed with PVTT (male=20, female=5; age 41-74 years (59.48 ± 9.12)) from the Interventional Department of Jiangsu Cancer Hospital. There were 11 cases of type III PVTT, 12 of type II PVTT, and 2 of type I PVTT (Cheng’s classification). All patients underwent spectral perfusion scans through dual-layer spectral detector computed tomography. The PVTTs were divided into proximal and distal groups based on the distance between the tumor thrombus and the main portal vein. The perfusion analysis was performed on the 120-kVp conventional images to generate hepatic perfusion index (HPI). The spectral based images (SBIs) during the artery and venous peak phases were extracted from the perfusion data. The iodine map and 40&100-keV virtual monoenergetic image (VMI) were generated from SBI data. HPI, iodine concentration (IC), CT value at 40 and 100-keV, and spectral slope (40- 100keV) of the primary lesion, proximal and distal PVTT, and liver parenchyma were measured and compared. The correlation between the primary lesion and proximal and distal PVTT was analyzed. Results: The IC and spectral slope during the arterial and venous peak phases and HPI of the primary lesion, proximal PVTT, and distal PVTT were highly correlated (P<0.001). The differences between the IC and spectral slope during the arterial and venous peak phases and HPI of the primary lesion, proximal PVTT were statistically significant (P<0.001). The differences between the IC during venous peak phase and HPI of primary lesion, distal PVTT were statistically significant (P<0.001), and there was no statistically significant difference in arterial phase IC, arterial and venous phase spectral slopes. Conclusion: The IC, slope, and HPI of the distal and proximal PVTT were highly correlated with the primary lesion, indicating that PVTT was similar to the primary lesion in the liver that they were both mainly supplied by the hepatic artery. However, there was still significant heterogeneity between the proximal PVTT and the primary lesion, while the difference in the distal PVTT was relatively small. [ABSTRACT FROM AUTHOR]

Yuan Tian,1,&ast; Wenbiao Jin,1,&ast; Honghua Sun,1 Dehao Jin,2 Dongxu Kang,1 Zhiyu Li,1 Longzhen Piao1 1Department of Oncology, The Affiliated Hospital of Yanbian University, Yanji City, Jilin Province, People’s Republic of China; 2Department of Radiology, Yanbian Maternal and Child Health Hospital, Yanji, Jilin Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyu Li; Longzhen Piao, Department of Oncology, The Affiliated Hospital of Yanbian University, No. 1327 Juzi Street, Yanji City, Jilin Province, People’s Republic of China, Tel +86 15526771578 ; +86 15526771162, Fax +86 433 2513610, Email 15526771578@163.com; plz1978@126.comBackground: Advanced-stage hepatocellular carcinoma (HCC), especially huge HCC or portal vein tumour thrombus (PVTT), is difficult to treat, and the prognosis is poor. The advantages of hepatic artery infusion chemotherapy (HAIC) combined with targeted therapy and immunotherapy for this complex disease are gradually becoming apparent. However, HAIC still has some inevitable disadvantages, such as arterial perfusion therapy requiring a long time, which results in many patients having difficulty completing the procedure. Modified HAIC (mHAIC)-based oxaliplatin and S-1 is a new treatment option for huge HCC or PVTT that can reduce complications and improve patient compliance. We report two cases of huge HCC or PVTT that were successfully treated with mHAIC combined with lenvatinib and camrelizumab. The clinical presentations, treatment strategies, and outcomes of these cases are presented.Case Presentation: Case 1: A 52-year-old female was found to have a huge HCC with a size of 14× 11 cm. She was treated with one cycle of mHAIC combined with transcatheter arterial chemoembolization (TACE), lenvatinib and camrelizumab and 3 cycles of mHAIC in combination with lenvatinib and camrelizumab. The patient’s follow-up maintenance therapy with lenvatinib and camrelizumab has been evaluated for efficacy in achieving complete response (CR). Case 2: A 57-year-old man was diagnosed with advanced HCC in combination with PVTT. He achieved partial remission (PR) after four cycles of mHAIC combined with lenvatinib and camrelizumab. This was followed by treatment with lenvatinib and camrelizumab with an efficacy assessment for CR, and progression-free survival (PFS) was 7 months.Conclusion: For advanced HCC with a large mass or PVTT, mHAIC combined with lenvatinib and camrelizumab is a safe and effective treatment with good patient compliance.Keywords: huge HCC, PVTT, mHAIC, case report

Background/purpose: The prognosis of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) is generally poor and hepatectomy is optional for these patients. This study aims to explore the survival benefits of neoadjuvant hepatic arterial infusion chemotherapy (HAIC) for resectable HCC with PVTT. Methods: This retrospective study included 120 resectable HCC patients with PVTT who underwent hepatectomy, from January 2017 to January 2021 at Sun Yat-sen University Cancer Center. Of these patients, the overall survival (OS) and recurrence-free survival (RFS) of 55 patients who received hepatectomy alone (Surgery group) and 65 patients who received neoadjuvant HAIC followed by hepatectomy (HAIC-Surgery group) were compared. Logistic regression analysis was conducted to develop a model predicting the response to neoadjuvant HAIC. Results: The OS rates for the HAIC-Surgery group at 1, 3, and 5 years were 94.9%, 78%, and 66.4%, respectively, compared with 84.6%, 47.6%, and 37.2% in the Surgery group (p < 0.001). The RFS rates were 88.7%, 56.2%, and 38.6% versus 84.9%, 38.3%, and 22.6% (p = 0.002). The subgroup analysis revealed that the survival benefit of neoadjuvant HAIC was limited to patients who responded to it. The logistic model, consisting of AFP and CRP, that predicted the response to neoadjuvant HAIC performed well, with an area under the ROC curve (AUC) of 0.756. Conclusion: Neoadjuvant HAIC followed by hepatectomy is associated with a longer survival outcome than hepatectomy alone for HCC patients with PVTT and the survival benefit is limited to patients who respond to neoadjuvant FOLFOX-HAIC. [ABSTRACT FROM AUTHOR]

Objective: To analyze the CT findings of hepatoid adenocarcinoma of the stomach (HAS) and improve the diagnosis accuracy of this condition. Methods: The CT images of 22 pathologically confirmed HAS patients were analyzed retrospectively. We investigated the location of lesions, morphology, enhancement features, area of invasion into surrounding organs, lymph node metastasis, and venous tumor thrombus. Results: Among the 22 patients (17 men and 5 women, the mean age was 61.41 ± 9.83 years ranging from 36 to 80 years) with HAS; the morphology of tumors included mass (n = 5), focal ulcer (n = 7), and infiltrating ulcer (n = 10). Extraserous fat was invaded in 12 cases. Enhancement scans showed continuous enhancement in all cases. The CT values of unenhanced scan, the arterial phase, and the portal venous phase are 30.36 ± 6.46, 60.91 ± 17.80, and 75.64 ± 22.09 (Hounsfield Unit, HU), respectively. In six cases, the tumor infiltrated the surrounding organs: liver (n = 1), pancreas (n = 2), and both liver and pancreas (n = 3). In 16 out of 22 patients (72.3%), suspicious lymph node metastasis at CT imaging has then been confirmed by pathological specimens. Intrahepatic metastasis was found in 14 cases. Seven patients had venous tumor thrombus: three patients developed tumor thrombus in the main trunk and intrahepatic branches of the portal vein and two patients in the portal vein, splenic vein, and superior mesenteric vein simultaneously. Conclusion: The CT scans of HAS often show a thickened gastric wall and infiltrating ulceration. Infiltration into extraserosal fat is often seen. Enhancement scans show a continuous and progressive enhancement of lesions. Lymph node metastasis, intrahepatic metastasis, and portal vein tumor thrombus are common in HAS patients. [ABSTRACT FROM AUTHOR]

Background: Surgical resection is a mainstay to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in east Asia. However, the postoperative recurrence rate is high. It is necessary to explore neo-adjuvant therapy to increase the surgical resection rate and improve overall survival. Evidence has shown that lenvatinib combined with PD-1 inhibitors is safe and effective in the treatment of advanced unresectable HCC. Radiotherapy is also an effective treatment method for PVTT and has a synergistic effect in combination with PD-1 inhibitors. Surgical resection after Lenvatinib and sintilimab combined with radiotherapy as a neoadjuvant treatment regimen may be a new exploration of HCC with PVTT, but there were not any reported. Methods: This open-label, single-arm, prospective, multi-center Phase I trial will enroll 20 HCC patients with PVTT who have a resectable primary tumor and no extra-hepatic metastasis. Eligible patients will be given radiotherapy, 3Gy*10 fraction, and will receive lenvatinib 8-12mg once daily and sintilimab 200mg once every three weeks. Surgical resection will be performed 6-8 weeks after radiotherapy. The primary endpoint is safety (number of patients ≥3G TRAE) and the number of patients who complete pre-op treatment and proceed to surgery. The secondary study endpoints include Major Pathological Response (MPR), 1-year tumor recurrence-free rate, Objective Response Rate (ORR), Imaging-Pathology Concordance Rate (IPCR), PVTT regression rate, Median Overall Survival (OS) and Recurrence Free Survival (RFS). Discussion: This trial may confirm that surgical resection following intensive neoadjuvant therapy can provide a safe and efficient regimen for BCLC stage C patients with PVTT. [ABSTRACT FROM AUTHOR]

Background and Aims: Portal vein tumor thrombus (PVTT) occurs frequently in hepatocellular carcinoma (HCC) patients. However, there is currently no satisfactory treatment. Radiotherapy (RT) and tyrosine kinase inhibitors (TKI) are currently commonly used. However, whether their combined use provides a survival benefit is debatable. This retrospective study compared the efficacy and safety between radiotherapy plus lenvatinib (RT + L) and radiotherapy plus sorafenib (RT + S) in the treatment of hepatocellular carcinoma with portal vein tumor thrombus (PVTT)., Methods: Among patients with PVTT who received RT + L or RT + S between March 2017 and September 2022, the primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), and incidence of treatment-related adverse effects. The prognostic factors were also assessed., Results: The analysis included 152 patients (RT + L: 48; RL: 25; RT + S: 55; S: 24). Compared with the RT + S group, the RT + L group had a longer OS and PFS. Among patients with type I/II PVTT, the median OS times were 19.8 months and 13.5 months ( p = 0.047) and the median PFS was 12.3 months and 7.3 months ( p = 0.042), respectively. And the median OS of the patients with type I/II PVTT were 14.4 months and 8.3 months ( p = 0.030) and the median PFS was 8.3 months and 6.2 months ( p = 0.026). ORR and DCR in RT + L group (25.0% and 75.0%) were also little higher than those in RT + S group (20.0% and 70.9%), but not statistically significant. In univariate analysis, etiology, Type of PVTT, alpha-fetoprotein (AFP) level, Child-Pugh score, and treatment method influenced OS. Multivariate analysis confirmed that treatment method, etiology, alpha-fetoprotein (AFP) level, and Child-Pugh score were independent prognostic factors for OS. Similar safety profiles were observed in the RT + L and RT + S groups. The most common adverse events were myelosuppression, decreased liver function, fatigue, diarrhea, nausea, and vomiting. Most adverse reactions were grade 1-2., Conclusion: The side effects of radiotherapy plus lenvatinib were acceptable. Compared to RT + S, RT + L had good efficacy in the treatment of hepatocellular carcinoma with PVTT. Validation is needed in prospective studies with larger sample sizes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Zheng, Ding, Su, Xin and Jiang.)

To explore the clinical efficacy and prognostic factors of the use of Gelfoam for drug-eluting bead (DEB) transarterial chemoembolization (GMD-TACE) in patients with unresectable large hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT). A retrospective analysis was conducted using the mRECIST standard to evaluate tumor response after GMD-TACE. Overall survival time, median survival time, time to progression (TTP) after the first intervention, and other treatment methods were recorded. The follow-up time was 2–110 months (mean 17.97 + 19.12 months), the median follow-up time was 12.5 months, and the first TTP after the first GMD-TACE was 4 months (95% CI 3.020–4.980). The median overall survival (OS) time was 14 months (95% CI 9.801–18.199). The 1-, 3-, and 5-year survival rates were 53.6%, 32.3%, and 8.9%, respectively. Multivariate analysis showed that the type of tumor thrombus was an independent factors affecting prognosis, and combination therapy was a protective factor affecting prognosis. GMD-TACE can be used as the core treatment for unresectable large HCC combined with a PVTT. This can improve the quality of life and further improve the median OS, and is worthy of clinical promotion and application. [ABSTRACT FROM AUTHOR]

The volumetric primary standard with a constant volume (pVTt) determines the flow rate from the rate of change of gas density in the defined measuring volume. The key element of the measuring system that uses the flying start–stop method is a diverter. This paper presents a time correction model that adapts the correction according to the diverting speed implemented in our pVTt system developed for flow rates smaller than 12 m g min − 1 . A detailed study of the diverter's effects on the effective collection time and two methods for determining the time correction are presented. One is based on the ISO 4185 standard and the other on measurements of the dynamic pressure upstream of the diverter. A set of correction time measurements were made at different diversion speeds to define the correction model at a flow rate of 9 m g min − 1 . The results show very good agreement between the measurements with both methods and the defined correction model. Additional measurements were made at smaller flow rates and the results indicate the independence of the time correction from the measured flow rate. [ABSTRACT FROM AUTHOR]

Background: Information about radiation-induced liver disease (RILD) in hepatocellular carcinoma (HCC) patients preexisting hepatitis B cirrhosis with portal vein tumor thrombus (PVTT) extended to the main portal vein treated with stereotactic body radiotherapy (SBRT) is still inadequate and the predictive markers for RILD have not been cleared in these patients. The aim of the study is to identify factors that can be used to predict RILD and to evaluate the influence of RILD in these patients. Methods: In our study, 59 patients were analyzed and evaluated from December 2015 to June 2019, according to the entry criteria. After treatment, 59 patients were followed up within the first month and then every 3 months. Hematology test, tumor markers, three-phasic CT scan of the lungs, and CT or MRI scan of the liver were performed at each follow up. Results: Median overall survival time was 10.7 months (range, 5.8 to 14.9). RILD appeared in 17 of the 59 patients (28.8%) at the 3rd month after SBRT. In the univariate analysis, not only the CP score class (A or B) but also each different pretreatment CP score (p < 0.05) was a significant predictive factor of RILD. More RILD cases were detected with the increase of CP score. The recovery rate decreased as the baseline CP score increased (p < 0.05). It was found that the overall survival time was affected by only baseline CP score and RILD (p < 0.05). Conclusions: The development of RILD has a dependency on the CP score in these patients. CP scores before treatment and RILD are significantly associated with overall survival. SBRT is an effective and safe method for patients with CP ≤ B7. For patients with CP-B8, liver function should be monitored more frequently. It is not safe enough for the SBRT treatment in CP-B9 patients. [ABSTRACT FROM AUTHOR]

BackgroundInformation about radiation-induced liver disease (RILD) in hepatocellular carcinoma (HCC) patients preexisting hepatitis B cirrhosis with portal vein tumor thrombus (PVTT) extended to the main portal vein treated with stereotactic body radiotherapy (SBRT) is still inadequate and the predictive markers for RILD have not been cleared in these patients. The aim of the study is to identify factors that can be used to predict RILD and to evaluate the influence of RILD in these patients.MethodsIn our study, 59 patients were analyzed and evaluated from December 2015 to June 2019, according to the entry criteria. After treatment, 59 patients were followed up within the first month and then every 3 months. Hematology test, tumor markers, three-phasic CT scan of the lungs, and CT or MRI scan of the liver were performed at each follow up.ResultsMedian overall survival time was 10.7 months (range, 5.8 to 14.9). RILD appeared in 17 of the 59 patients (28.8%) at the 3rd month after SBRT. In the univariate analysis, not only the CP score class (A or B) but also each different pretreatment CP score (p < 0.05) was a significant predictive factor of RILD. More RILD cases were detected with the increase of CP score. The recovery rate decreased as the baseline CP score increased (p < 0.05). It was found that the overall survival time was affected by only baseline CP score and RILD (p < 0.05).ConclusionsThe development of RILD has a dependency on the CP score in these patients. CP scores before treatment and RILD are significantly associated with overall survival. SBRT is an effective and safe method for patients with CP ≤ B7. For patients with CP-B8, liver function should be monitored more frequently. It is not safe enough for the SBRT treatment in CP-B9 patients.

ObjectiveThe aim of the current study was to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) in elderly patients diagnosed as advanced hepatocellular carcinoma (HCC) accompanied with different types of portal vein tumor thrombosis (PVTT).MethodsElderly HCC patients aged 70-year-old and above from January 2015 to December 2019 were included in this retrospective study. Efficacy data including OS, PFS, DCR, and ORR and safety data were collected in the indicated groups. Outcomes of HCC patients in the TACE group were compared with those patients in the best supportive care (BSC) group. Subgroup analyses were also conducted in the patients with different types of PVTT.ResultsAmong 245 elderly HCC patients, 124 were enrolled in this study. Out of these, 50.0% (n=62) underwent BSC treatment while 50.0% (n=62) underwent TACE. There were no major differences in the baseline characteristics of the two treatment groups. TACE treatment was associated with better median OS compared with BSC alone (11.30 m vs. 7.80 m; P5 cm vs. ≤5 cm) (HR: 1.94; 95%CI: 1.28-2.93; P=0.002), and treatment (TACE vs. BSC) (HR: 0.48; 95%CI: 0.32-0.72; P

Objective: The aim of the current study was to evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) in elderly patients diagnosed as advanced hepatocellular carcinoma (HCC) accompanied with different types of portal vein tumor thrombosis (PVTT). Methods: Elderly HCC patients aged 70-year-old and above from January 2015 to December 2019 were included in this retrospective study. Efficacy data including OS, PFS, DCR, and ORR and safety data were collected in the indicated groups. Outcomes of HCC patients in the TACE group were compared with those patients in the best supportive care (BSC) group. Subgroup analyses were also conducted in the patients with different types of PVTT. Results: Among 245 elderly HCC patients, 124 were enrolled in this study. Out of these, 50.0% (n=62) underwent BSC treatment while 50.0% (n=62) underwent TACE. There were no major differences in the baseline characteristics of the two treatment groups. TACE treatment was associated with better median OS compared with BSC alone (11.30 m vs. 7.80 m; P <0.001). Subgroup analyses showed that patients with type I and type II PVTT could benefit from TACE compared with BSC, based on that OS was 14.30 m vs. 7.80 m (P =0.007) and 13.00 m vs. 8.00 m (P =0.002), respectively. The DCR in the TACE group was 62.90%, and 17.74% in the BSC group (p<0.001). The proportion of ORR in TACE group was 35.48%, while 0.00% in the BSC group (p<0.001). Multivariable analyses showed that patients undergoing TACE treatment had 52% lower odds of mortality compared with patients undergoing BSC treatment (HR: 0.48; 95%CI: 0.32-0.72). Similarly, the media PFS was improved following TACE treatment (7.50 m vs. 4.00 m; P <0.001). TACE could significantly prolong the PFS in both type I and type II PVTT subgroups, without greatly significant improvement in type III PVTT patients (4.50 m vs. 2.70 m; P =0.103). Type III PVTT patients in the TACE group had more AEs than type I and type II PVTT patients. According to multivariable analyses, PVTT types (type III vs. type I-II) (HR: 2.18; 95%CI: 1.29-3.70; P =0.004), tumor diameter (>5 cm vs. ≤5 cm) (HR: 1.94; 95%CI: 1.28-2.93; P =0.002), and treatment (TACE vs. BSC) (HR: 0.48; 95%CI: 0.32-0.72; P <0.001) were independent indicators of overall survival. Conclusions: In elderly advanced HCC patients with PVTT, palliative TACE treatment can be an accessible effective measure to improve the OS and PFS for both type I and type II PVTT patients. [ABSTRACT FROM AUTHOR]

The volumetric primary standard with a constant volume (pVTt) determines the flow rate from the rate of change of gas density in the defined measuring volume. The key element of the measuring system that uses the flying start–stop method is a diverter. This paper presents a time correction model that adapts the correction according to the diverting speed implemented in our pVTt system developed for flow rates smaller than 12mgmin−1. A detailed study of the diverter’s effects on the effective collection time and two methods for determining the time correction are presented. One is based on the ISO 4185 standard and the other on measurements of the dynamic pressure upstream of the diverter. A set of correction time measurements were made at different diversion speeds to define the correction model at a flow rate of 9mgmin−1. The results show very good agreement between the measurements with both methods and the defined correction model. Additional measurements were made at smaller flow rates and the results indicate the independence of the time correction from the measured flow rate.

Locally advanced hepatocellular carcinoma includes the presence of portal tumor thrombosis. The prognosis and treatment options for these patients are limited. Radiation therapy allows portal recanalization and the combination of other treatments such as TACE or even surgery. There are different modalities of radiotherapy including conventional radiotherapy, 3DRT, IMRT or VMAT. SBRT allows high doses of radiation to be delivered to the tumor while limiting the dose to the nearby healthy tissues. This allows high doses of radiation to be delivered to the tumor in a few sessions with low side effects. This study aims to review the role of radiation therapy in hepatocellular carcinoma with portal tumour thrombosis, specifically the role of SBRT. [ABSTRACT FROM AUTHOR]

BackgroundHepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) has poor prognosis. Sorafenib/lenvatinib is recommended as the first-line therapy in these patients currently, with unsatisfactory response and survival benefit reported. Radiotherapy (RT) is increasingly utilized in advanced HCC and is considered an alternative option for HCC patients with PVTT. Combined treatment of RT and locoregional treatments such as transarterial chemoembolization shows promising results. However, the efficacy and safety for combined treatment of RT and systemic therapy have not been reported and thus warrant further studies. This prospective clinic trial aims at evaluating the efficacy and safety of stereotactic body RT (SBRT) combined with camrelizumab and apatinib in HCC patients with PVTT.MethodsThis multicenter, open-label, randomized controlled trial will enroll 264 HCC patients with PVTT who have not received systemic therapy previously. Stratification of patients will be based on the presence or absence of extrahepatic metastasis and level of AFP (AFP ≥ 400 or

Ming-Feng Li,1,2,* Henry WC Leung,3,* Agnes LF Chan,4 Shyh-Yau Wang2,* 1Department of Medical Imaging, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan; 2Department of Radiology, An-Nan Hospital, China Medical University, Tainan, Taiwan; 3Department of Radiation Oncology, An-Nan Hospital, China Medical University, Tainan, Taiwan; 4Department of Pharmacy, An-Nan Hospital, China Medical University, Tainan, Taiwan *These authors contributed equally to this work Purpose: We assessed the efficacy and safety of different modalities using the network meta-analysis for inoperable hepatocellular carcinoma (HCC) with portal vein invasion. The interested modalities included stereotactic body radiotherapy (SBRT) combined with transarterial chemoembolization (TACE), three-dimensional radiotherapy (3D-RT) combined with hepatic arterial infusion chemotherapy (HAIC) or TACE, TACE plus sorafenib, and use of SBRT, HAIC, sorafenib, and TACE alone. Methods: PubMed and Cochrane Library electronic databases were systematically searched for eligible studies published up to June 2017. We used network meta-analysis to compare the disease control rate (DCR) and severe adverse events for the eight interested regimens included in this analysis. Study quality was assessed following the Grading of Recommendations, Assessment, Development and Evaluations method. Results: Fifteen studies published between 2010 and 2016 involving a total of 2,359 patients were enrolled in this network meta-analysis. With indirect comparison of DCR and overall safety, the pooled results showed that RT plus HAIC was the most effective regimen in treating advanced HCC with portal vein tumor thrombosis, followed by RT plus TACE. HAIC alone and sorafenib combined with HAIC appeared least effective intervention regimens. The incidence of treatment-related adverse events of grade 3 or 4 occurred less in the patients who received SBRT alone compared with other interested regimens. Conclusion: 3D-RT combined with HAIC or TACE showed more favorable treatment responses compared with other regimens in advanced HCC patients with portal vein tumor thrombosis. Keywords: SBRT, HAIC, 3D-RT plus HAIC, sorafenib, network meta-analysis, PVTT

Background: Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) has poor prognosis. Sorafenib/lenvatinib is recommended as the first-line therapy in these patients currently, with unsatisfactory response and survival benefit reported. Radiotherapy (RT) is increasingly utilized in advanced HCC and is considered an alternative option for HCC patients with PVTT. Combined treatment of RT and locoregional treatments such as transarterial chemoembolization shows promising results. However, the efficacy and safety for combined treatment of RT and systemic therapy have not been reported and thus warrant further studies. This prospective clinic trial aims at evaluating the efficacy and safety of stereotactic body RT (SBRT) combined with camrelizumab and apatinib in HCC patients with PVTT. Methods: This multicenter, open-label, randomized controlled trial will enroll 264 HCC patients with PVTT who have not received systemic therapy previously. Stratification of patients will be based on the presence or absence of extrahepatic metastasis and level of AFP (AFP ≥ 400 or <400 ng/mL) and randomly assigned 1:1 to study and control groups. Patients in study group will receive SBRT (95% PTV 36–40 Gy/6–8 Gy), camrelizumab (200 mg every 3 weeks), and apatinib (250 mg every day), and patients in control group will receive camrelizumab (200 mg every 2 weeks) and apatinib (250 mg every day). Patients will be followed up for 1.5 to 3.5 years since the start of therapy. We will use overall survival as the primary endpoint and progression-free survival, objective response rate, disease control rate, adverse events, and quality of life as the secondary endpoints. Discussion: This study will be the first randomized controlled trial to assess the efficacy and safety of SBRT combined with camrelizumab and apatinib for HCC patients with PVTT. The results may help establish a new standard first-line therapy for these patients. Trial Registration: Chinese Clinical Trial Registration No. ChiCTR1900027102. Date of Registration: October 31, 2019. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the characteristic of blood supply of liver portal vein tumor thrombus (PVTT) using perfusion indexes and spectral parameters., Methods: Between July 2020 and December 2022, the study enrolled 25 liver cancer patients completed with PVTT (male=20, female=5; age 41-74 years (59.48 ± 9.12)) from the Interventional Department of Jiangsu Cancer Hospital. There were 11 cases of type III PVTT, 12 of type II PVTT, and 2 of type I PVTT (Cheng's classification). All patients underwent spectral perfusion scans through dual-layer spectral detector computed tomography. The PVTTs were divided into proximal and distal groups based on the distance between the tumor thrombus and the main portal vein. The perfusion analysis was performed on the 120-kVp conventional images to generate hepatic perfusion index (HPI). The spectral based images (SBIs) during the artery and venous peak phases were extracted from the perfusion data. The iodine map and 40&100-keV virtual monoenergetic image (VMI) were generated from SBI data. HPI, iodine concentration (IC), CT value at 40 and 100-keV, and spectral slope (40-100keV) of the primary lesion, proximal and distal PVTT, and liver parenchyma were measured and compared. The correlation between the primary lesion and proximal and distal PVTT was analyzed., Results: The IC and spectral slope during the arterial and venous peak phases and HPI of the primary lesion, proximal PVTT, and distal PVTT were highly correlated (P<0.001). The differences between the IC and spectral slope during the arterial and venous peak phases and HPI of the primary lesion, proximal PVTT were statistically significant (P<0.001). The differences between the IC during venous peak phase and HPI of primary lesion, distal PVTT were statistically significant (P<0.001), and there was no statistically significant difference in arterial phase IC, arterial and venous phase spectral slopes., Conclusion: The IC, slope, and HPI of the distal and proximal PVTT were highly correlated with the primary lesion, indicating that PVTT was similar to the primary lesion in the liver that they were both mainly supplied by the hepatic artery. However, there was still significant heterogeneity between the proximal PVTT and the primary lesion, while the difference in the distal PVTT was relatively small., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pan, Dai, Sheng, Li, Qiao, Kang and Zhang.)

To solve the problem of gradually prolonged gas stabilization time in container during the operation of pVTt gas flow standard device, the mechanism and approach of rapid stabilization for the temperature field in standard device tank were investigated. The two-way fluid-solid-thermal coupling mathematical model and the temperature field simulation models under natural constant temperature mode and water-jacket constant temperature mode were established. The COMSOL multiphysics software was used to simulate and test the intake and constant temperature processes. The results show that the water-jacket constant temperature mode can effectively eliminate the severe temperature gradient phenomenon in the natural constant temperature mode and shorten the gas stabilization time in the standard device tank. The main affecting factor on rapid gas stabilization in standard device tank is the temperature difference between the inlet air temperature of tank and the water temperature in water jacket. Keeping the water temperature in water jacket substantially the same as the inlet air temperature of standard device can effectively shorten the gas stabilization time in standard device tank and improve the efficiency of gas flow meter verification. [ABSTRACT FROM AUTHOR]

Venous invasion by hepatic tumors most commonly occurs with hepatocellular carcinoma and is associated with worse patient prognosis. Imaging plays an important role in the diagnosis of tumor thrombus in the liver. Moreover, differentiating between bland and tumor thrombus in the liver has important diagnostic, staging, therapeutic, and prognostic implications and may require a multimodal imaging approach including ultrasound, computed tomography, and/or magnetic resonance imaging. Treatment of hepatic malignancies with associated tumor thrombus is dependent on tumor type, disease extent within the liver, liver hemodynamics, and underlying liver function. Treatment of such tumors may involve surgical, locoregional and/or systemic therapies. The current review will focus on the imaging characteristics of venous invasion by hepatic tumors. The imaging findings most useful for differentiating hepatic venous tumor thrombus and bland thrombus will be highlighted and demonstrated with imaging examples. Imaging findings with implications for subsequent patient management will be described. [ABSTRACT FROM AUTHOR]

Aim To investigate the factors that influence survival of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) following transarterial chemoembolization (TACE). Methods Retrospectively enrolled HCC patients with PVTT ( n = 57). Patients received TACE, and the local tumor response was evaluated by modified response evaluation criteria in solid tumor (mRECIST). Overall survival and disease progression were evaluated using Kaplan-Meier survival curves. Prognostic factors were determined by multivariate Cox regression analysis. Results Following TACE, the median survival times was 8.3 months in HCC patients with PVTT. The median survival time was 3.1 months for patients with progressive disease following TACE and was 11.3 months for patients with complete response or partial response. The one-year rate of survival for patients with progressive disease was 5.0% and was lower than in patients with complete response or partial response (20.0%, P < 0.001). Multivariate analysis indicated that the presence of ascites, arteriovenous fistula and TACE response were significant factors for prognosis. The presence of early (<2 weeks) or late (≥2 weeks) PVTT was not a prognostic factor. Conclusion Our study indicates that TACE is feasible and potentially efficacious in HCC patients with PVTT, and identifies factors that may predict the prognosis of these patients. [ABSTRACT FROM AUTHOR]

Primary standards in the field of gas flow rate metrology determine the change of mass in the system for a given collection time. Standards using the fixed volume volumetric method (pVTt) determine the mass by measuring the gas density inside a fixed volume. These standards usually use the static method of mass determination and rarely use the dynamic method as the gas temperature changes due to the density change. An analytical model predicting the temperature in a pVTt system was developed. The static and the dynamic methods were implemented, with the dynamic method including the temperature correction based on the model. The model was first validated using the pressure response during the flow rate measurement, followed by validation using a comparison between the measured flow rates using the static and dynamic methods. Based on the results, we believe that the corrected dynamic method is an alternative to the static method. • Analytic model for prediction of temperature inside a pressure vessel during density change. • Only the processes of heat transfer, heat generation and heat accumulation are considered. • Dynamic method of mass determination and the model are implemented into the existing pVTt standard. • Validation of the analytic model made using measured pressure and measured flow rate. • Uncertainty of temperature correction and uncertainty of flow rate related to it were evaluated. [ABSTRACT FROM AUTHOR]

Background and Aim Portal vein tumor thrombus (PVTT) is not commonly used in the treatment of intrahepatic cholangiocarcinoma (ICC), and its impact on the prognosis of ICC is unclear. We aimed to assess the outcomes of ICC with or without PVTT after hepatic resection. Methods From January 2000 to December 2005, the data from all consecutive patients with ICC who underwent hepatic resection at our hospital were retrospectively analyzed. According to the Cheng's PVTT Classification (types I-IV), we compared the survival outcomes of ICC patients (with or without PVTT) and prognosis of patients with ICC with different types of PVTT. Results Three hundred and three patients with ICC were enrolled in this study (59 with PVTT). The incidence of PVTT was 19.4% (59/303). The median survival times were 12.68 and 28.91 months for ICC patients with and without PVTT, respectively ( P < 0.001). The multivariate analysis demonstrated that PVTT (hazard ratio [HR] 1.783; confidence interval 95% [1.279; 2.487]) was an independent risk factor for overall survival. Patients with type I PVTT exhibited significantly better survival than those with types II and III PVTT. Conclusion The ICC patients with PVTT exhibit a poorer prognosis compared with ICC patients without PVTT after hepatic resection. [ABSTRACT FROM AUTHOR]

Background: Surgical resection is a mainstay to treat hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in east Asia. However, the postoperative recurrence rate is high. It is necessary to explore neo-adjuvant therapy to increase the surgical resection rate and improve overall survival. Evidence has shown that lenvatinib combined with PD-1 inhibitors is safe and effective in the treatment of advanced unresectable HCC. Radiotherapy is also an effective treatment method for PVTT and has a synergistic effect in combination with PD-1 inhibitors. Surgical resection after Lenvatinib and sintilimab combined with radiotherapy as a neoadjuvant treatment regimen may be a new exploration of HCC with PVTT, but there were not any reported., Methods: This open-label, single-arm, prospective, multi-center Phase I trial will enroll 20 HCC patients with PVTT who have a resectable primary tumor and no extra-hepatic metastasis. Eligible patients will be given radiotherapy, 3Gy*10 fraction, and will receive lenvatinib 8-12mg once daily and sintilimab 200mg once every three weeks. Surgical resection will be performed 6-8 weeks after radiotherapy. The primary endpoint is safety (number of patients ≥3G TRAE) and the number of patients who complete pre-op treatment and proceed to surgery. The secondary study endpoints include Major Pathological Response (MPR), 1-year tumor recurrence-free rate, Objective Response Rate (ORR), Imaging-Pathology Concordance Rate (IPCR), PVTT regression rate, Median Overall Survival (OS) and Recurrence Free Survival (RFS)., Discussion: This trial may confirm that surgical resection following intensive neoadjuvant therapy can provide a safe and efficient regimen for BCLC stage C patients with PVTT., Clinical Trial Registration: https://clinicaltrials.gov/, identifier (NCT05225116)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Shu, Zheng, Yin, Zhang, Xiao, Yang, Yan, Zhang, Yang, Li and Dong.)

Portal vein tumor thrombus (PVTT) is a complication of liver disease, specifically hepatocellular carcinoma (HCC). It occurs secondary to direct invasion of tumor into the portal venous system. PVTT is associated with a poor prognosis, therefore identification and differentiation of malignant from benign thrombus is very important in the treatment of the patient. Sonography can be a useful tool in the detection of malignant thrombus. [ABSTRACT FROM AUTHOR]

Background: Portal vein tumour thrombus (PVTT) is highly associated with the progression and metastasis of hepatocellular carcinoma (HCC). However, there are no appropriate cell models of PVTT with which to study the biological and physiological characteristics of PVTT.Methods: Primary cell culture was performed by the use of a successive xenograft line called PVTT-#1, which was obtained from a 60-year-old male HCC patient accompanied by PVTT.Results: A successive cell line named CSQT-2 was established. The cell line showed aggressive phenotypes in terms of cell growth, survival, migration, xenograft and metastasis. Moreover, an orthotopic transplantation assay showed that PVTT can be generated in nude mice when CSQT-2 cells were inoculated in the liver and that it shows a typical migratory tendency in the vascular branches of portal vein. Moreover, the established CSQT-2 cells also showed varied expression of tumour-initiating cell (TIC) markers such as CD133, CD90 and EpCAM.Conclusion: Establishment of CSQT-2 may provide a suitable model with which to investigate the molecular mechanisms of PVTT-related HCC. [ABSTRACT FROM AUTHOR]

pVTt has been employed as the primary gas flow standard in many countries and the performance of the inlet valve significantly influences the verification. This paper not only proposes a hydraulically powered fast switching 3-way valve but also introduces its structure and working principle. Furthermore, it builds up the flow field simulation model and conducts the dynamic simulation of its working process. As shown by the results, the designed fast switching 3-way valve could achieve the fast switching of the critical flow. In addition, the "overlapping" mode and the "non-overlapping" mode of the 3-way valve are analysed contrastively. The result reveals that the flow field of the "non-overlapping" mode is more stable. Finally, the device is tested according to the pVTt verification procedure. As indicated by the results, the switching time of two fast switching 3-way valves corresponding to DN150mm and DN100mm caliber could be controlled within 55 ms, which is consistent with the simulation results. • We develop a hydraulically powered fast switching 3-way valve for pVTt gas flow standard device, which could achieve the fast switching of the critical flow. It adopts a hydraulic control method with a relatively high power per unit volume to achieve fast switching in a short time. • We build up the flow field simulation model and carry on the dynamic simulation of its working process. Then, the "overlapping" mode and the "non-overlapping" mode of the 3-way valve were analysed contrastively. The result showed that the flow field of the "non-overlapping" mode was more stable. • We carried on the experiments according to the pVTt verification procedure. The results showed the switching time of two fast switching 3-way valves corresponding to DN150mm and DN100mm caliber could be controlled within 55 ms, which was consistent with the simulation results. [ABSTRACT FROM AUTHOR]

Background: Type Ⅲ and Ⅳ portal vein tumor thrombi (PVTT) cannot be removed through surgery, and no effective therapeutic procedure is available. Type Ⅲ/Ⅳ PVTT can be downstage to type I/II PVTT by using Radiotherapy, and can further be can be removed surgically. Thus, radiotherapy may be an effective treatment for type Ⅲ/Ⅳ PVTT. This study aims to evaluate the efficacy and toxicity of radiotherapy for type III-IV PVTT., Methods: This prospective study was conducted from August 1, 2017, to September 30, 2019, for patients with type Ⅲ and Ⅳ PVTT. Patients received radiotherapy with a target dose of 50Gy/25f or 59.5Gy/17 f. Advanced radiological technique such as image fusion technique for CT image and MRI image were utilized to produce more precise lesion localization, and limit the dose to organs at risk in order to get a better downstage rate and less adverse complications., Results: Nine (9) patients with type Ⅲ PVTT and 5 patients with type Ⅳ PVTT were included in this study. 12 patients received a radiotherapy dose of 50Gy/25f, 2 patients received 59.50Gy/17 f. After radiotherapy, 92.9% of patients with PVTT were successfully downstage to type II/I. In patients with primary hepatocellular carcinoma, 8 patients (accounting 88.9%) achieved down-stage. 5 patients with other types of tumors achieved downstage which accounts 100%. In addition, none of the 14 patients observed radiation hepatitis and radiation liver failure. And none of the patients developed gastrointestinal ulcers and thrombocytopenia., Conclusion: Radiotherapy is a suitable treatment measure for type Ⅲ and Ⅳ PVTT to get downstage and make the opportunity for surgery. Image fusion technology for precise lesion location such as CT-MRI image fusion, and strict dose limitation of organ at risk, contributed to the improvement of radiotherapy efficiency and the significant decrease in adverse complications.

Background: The benefits of transarterial chemoembolization plus sorafenib (TACE-S) in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remain controversial. We compared the effectiveness and safety of TACE-S and TACE for HCC with PVTT., Methods: The Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure, VIP, Wan Fang, and Sino Med databases were systematically searched for studies of HCC with PVTT treated using TACE-S. Two authors independently extracted study outcomes, including overall survival (OS), time to progression (TTP), objective response (tumor response) and adverse events (AEs)., Results: Eight high-quality, retrospective studies with 1091 patients (TACE-S=356, TACE=735) were included in the review. Five retrospective studies with 973 patients (TACE-S=238, TACE=735) were included in the meta-analysis. The objective response rate (ORR, OR=3.59, 95% CI=1.74-7.39; I2=21%, P=0.0005 ) and disease control rate (DCR, OR=4.72, 95% CI=1.75-12.72; I2=56%, P=0.002) favored TACE-S. TACE-S significantly increased 6-month OS (OR=3.47; 95% CI=2.47-4.89; I2=0%, P < 0.00001) and 1-year OS (OR=3.10; 95% CI=2.22-4.33; I2=41%, P < 0.00001). The hazard ratio (HR) for OS (HR=0.62; 95% CI=0.51-0.75; I2=30%, P < 0.00001) also indicated that TACE-S was superior to TACE. TACE-S with PVTT had better outcomes in the first-order portal vein branch and lower-order portal vein branches than in the main portal vein and upper branches to superior mesenteric vein. The most common AEs were hand-foot skin reaction (HFSR, 178; 73%), diarrhea (142; 58%) and alopecia (76; 31%); AEs of grade 3/4 were rare., Conclusions: TACE-S may improve OS, ORR, TTP and DCR for HCC patients with PVTT compared to TACE.