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

Cerrito, Lucia; Annicchiarico, B.E.; Iezzi, Roberto; Gasbarrini, Antonio; Pompili, Maurizio; Ponziani, Francesca Romana

doi:10.3748/wjg.v25.i31.4360

Cited by 104 publications

(85 citation statements)

References 183 publications

(166 reference statements)

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“…The deficiency of powerful drugs and acquired drug resistance are the main reasons. Sorafenib is the only approved targeted drug for LIHC, and it is commonly reported that the drug resistance would be acquired in the process of therapy[ 31 ]. Although researchers have been trying their best to find underlying the mechanisms, there are much more unknown.…”

Section: Discussionmentioning

confidence: 99%

Identification of APEX2 as an oncogene in liver cancer

Ru¹,

Zhu²,

Hu³

et al. 2020

WJCC

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BACKGROUND DNA damage is one of the critical contributors to the occurrence and development of some cancers. APEX1 and APEX2 are the most important molecules in the DNA damage, and APEX1 has been identified as a diagnostic and prognostic biomarker in liver hepatocellular carcinoma (LIHC). However, the expression of APEX2 and its functional mechanisms in LIHC are still unclear. AIM To examine the expression of APEX2 and the potential mechanism network in LIHC. METHODS We conducted a pan-cancer analysis of the expression of APEX1 and APEX2 using the interactive TIMER tool. GEO datasets, including GSE14520, GSE22058, and GSE64041, were used to compare the APEX2 expression level in tumor tissues and adjacent non-tumor tissues. Then, we calculated the 5-year survival rate according to the web-based Kaplan-Meier analysis. We included the TCGA liver cancer database in GSEA analysis based on the high and low APEX2 expression, showing the potential mechanisms of APEX2 in LIHC. After that, we conducted Pearson correlation analysis using GEPIA2. Next, we performed quantitative polymerase chain reaction (qPCR) assay to examine the APEX2 levels in normal liver cell line LO2 and several liver cancer cell lines, including HepG2, Huh7, SMMC7721, and HCCLM3. APEX2 in HCCLM3 cells was knocked down using small interfering RNA. The role of APEX2 in cell viability was confirmed using CCK-8. Dual-luciferase reporter assay was performed to examine the promoter activity of CCNB1 and MYC . RESULTS APEX1 and APEX2 are both highly expressed in the tumor tissues of BLCA, BRCA, CHOL, COAD, ESCA, HNSC, LIHC, LUAD, LUSC, READ, and STAD. APEX2 overexpression in LIHC was validated using GSE14520, GSE22058, and GSE64041 datasets. The survival analysis showed that LIHC patients with high expression of APEX2 had a lower overall survival rate, even in the AJCC T1 patients. High level of APEX2 could indicate a lower overall survival rate in patients with or without viral hepatitis. The GSEA analysis identified that kinetochore and spindle microtubules are the two main cellular components of APEX2 in GO Ontology. APEX2 was also positively associated with molecular function regulation of chromosome segregation and DNA replication. The results of KEGG analysis indicated that APEX2 expression was positively correlated with cell cycle pathway and pro-oncogenic MYC signaling. Pearson correlation analysis showed that APEX2 had a significant positive correlation with CCNB1 and MYC. APEX2 level was higher in liver cancer cell lines than in normal liver LO2 cells. Small interfering RNA could knock down the APEX2 expression in HCCLM3 cells. Knockdown of APEX2 resulted in a decrease in the viability of HCCLM3 cells as well as the expression and promoter activity of CCNB1 and MYC . CONCLUSION APEX2 i...

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Section: Discussionmentioning

confidence: 99%

Identification of APEX2 as an oncogene in liver cancer

Ru¹,

Zhu²,

Hu³

et al. 2020

WJCC

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“…A summary of treatment strategies according to PVTT is provided in Figure 1 [26,34,35,38,41] . In terms of LDLT, within the scope of the present review, recent studies demonstrated LDLT is a viable option to improve [37] , Japan's PVTT portal vein invasion (VP) classification [34,35] . HAIC: hepatic arterial infusion chemotherapy; IFN-alpha 2b: interferon alfa-2b; LT: liver transplantation; RT: radiation therapy; TACE: transarterial chemoembolization; TARE: transarterial radioembolization; 5-FU: 5-fluorouracil.…”

Section: Vascular Invasionmentioning

confidence: 98%

“…However, two classifications are currently valid to effectively assess prognosis and provide guidance for surgical treatment [34] . The Liver Cancer Study Group of Japan differentiates PVTT in four main categories of portal vein invasion, VP1, VP2, VP3, and VP4 [34][35][36] . In a similar fashion, Cheng et al [34] proposed a four-category classification, with the distinction of a category for microscopic portal vein invasion and the allusion of the extension of PVTT involving the superior mesenteric vein or inferior vena cava [37,38] [ Figure 1].…”

Section: Vascular Invasionmentioning

confidence: 99%

“…HAIC: hepatic arterial infusion chemotherapy; IFN-alpha 2b: interferon alfa-2b; LT: liver transplantation; RT: radiation therapy; TACE: transarterial chemoembolization; TARE: transarterial radioembolization; 5-FU: 5-fluorouracil. *Under certain conditions; **not enough support [26,34,35,38,37,40,41] long-term survival outcomes among carefully selected patients under specific criteria such as: (a) PVTT in a segmental branch, (b) AFP level < 100ng/mL, (c) low AP score, and (d) patients with HCC and PVTT who were successfully downstaged [36,42,43] .…”

Section: Vascular Invasionmentioning

confidence: 99%

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Living donor liver transplantation for patients with advanced hepatocellular carcinoma

Cullen¹,

Vargas²,

Goldaracena³

2020

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Liver transplantation (LT) is the treatment of choice for patients with hepatocellular carcinoma (HCC) and underlying liver disease. Given the organ scarcity, LT for patients with HCC have been restricted to those patients associated with the highest survivals. However, many patients with extended criteria HCC can still benefit from LT, but due to deceased organ shortage, they are not offered that opportunity. Living donor liver transplantation (LDLT) emerged as a successful strategy to overcome organ shortage around the world and as LDLT experience grows, this technique might offer the opportunity to expand the indications of LT to patients with advanced HCC. Therefore, since LDLT is not competing for deceased donor organs, many patients with extended criteria HCC who could still benefit from transplantation may have access to this treatment option. In this review, we will discuss the role of LDLT for patients with advanced-stage HCC and how LDLT allows for safe expansion of HCC transplant criteria.

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“…In particular, HCC with portal vein tumor thrombosis (PVTT) is believed to be a negative prognostic factor because it increases the likelihood of tumor cell spread into the bloodstreams, resulting in higher chances of recurrence. 5 Previous studies have stated that HCC patients with portal vein invasion have a median survival period of 2.7-4 months without any treatment. 6,7 However, as per recent studies, depending on the patient's baseline performance status, hepatic function, tumor characteristics, the type of therapy could increase the survival duration from 5 months to 5 years.…”

Section: Introductionmentioning

confidence: 99%

Value of surgical resection compared to transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein tumor thrombus: A meta-analysis of hazard ratios from five observational studies

Kang

Song

Chung

et al. 2020

Ann Hepatobiliary Pancreat Surg

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Backgrounds/Aims: Although systemic therapy is recommended in advanced hepatocellular carcinoma (HCC), treatment options for advanced HCC with portal vein tumor thrombosis (PVTT) are debatable. Recent studies have recommended other treatments, such as surgical resection (SR) and transarterial chemoembolization (TACE). Therefore, we performed a meta-analysis of hazard ratio (HR) for overall survival (OS) between the two modalities using previous reports in order to compare the two treatment options. Methods: A systematic review was performed on previously reported data that compared the survival benefits of SR and TACE in patients with advanced HCC with PVTT. Thereafter, the meta-analysis was performed to determine the cumulative HR between the two different treatment groups. We used the HR and 95% CI directly from the original data, when available; however, if these data were unavailable, reconstruction was performed with the secondary data from the original Kaplan-Meier survival curve. Results: A total of seven studies were eligible; however, 2 were excluded from the meta-analysis. The remaining 5 studies that included 1422 patients (SR group=559, TACE group=863) were studied for the meta-analysis. The median OS was longer in the SR group (8.2-64 months in SR vs. 6.6-32 months in TACE), proving that SR offered survival benefits. Moreover, the HR for the OS in the TACE group was 1.64 (95% CI, 1.43-1.88) compared to SR group, depicting that TACE was a less favorable option compared to SR. Conclusions: There is evidence that SR may be a better viable option for advanced HCC with PVTT.

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

Cited by 104 publications

References 183 publications

Identification of APEX2 as an oncogene in liver cancer

Identification of APEX2 as an oncogene in liver cancer

Living donor liver transplantation for patients with advanced hepatocellular carcinoma

Value of surgical resection compared to transarterial chemoembolization in the treatment of hepatocellular carcinoma with portal vein tumor thrombus: A meta-analysis of hazard ratios from five observational studies

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