Dataset Information

Impact of splenomegaly and splenectomy on prognosis in hepatocellular carcinoma with portal vein tumor thrombus treated with hepatectomy.

ABSTRACT:

Background

Hepatocellular carcinoma (HCC) commonly occurs in patients with splenomegaly. This study aimed to investigate the impact of splenomegaly with or without splenectomy on long-term survival of HCC patients with portal vein tumor thrombus (PVTT) treated with liver resection (LR).

Methods

HCC patients with PVTT who underwent LR from 2005 to 2012 from 6 hospitals were retrospectively studied. The long-term overall survival (OS) and recurrence-free survival (RFS) were compared between patients with or without splenomegaly, and between patients who did or did not undergo splenectomy for splenomegaly. Propensity score matching (PSM) analysis was performed to match patients in a 1:1 ratio.

Results

Of 716 HCC patients with PVTT who underwent LR, 140 patients had splenomegaly (SM group) and 576 patients had no splenomegaly (non-SM group). The SM group was further subdivided into 49 patients who underwent splenectomy (SPT group), and 91 patients who did not received splenectomy (non-SPT group). PSM matched 140 patients in the SM group, and 49 patients in the SPT group. Splenomegaly was an independent risk factor of poor RFS and OS. The OS and RFS rates were significantly better for patients in the non-SM group than the SM group (OS: P<0.001; RFS: P<0.001), and for patients in the SPT group than the non-SPT group (OS: P<0.001; RFS: P<0.001).

Conclusions

Patients who had splenomegaly had significantly worse survival in HCC patients with PVTT. Splenectomy for splenomegaly significantly improved long-term survival in these patients.

SUBMITTER: Chai ZT

PROVIDER: S-EPMC7940905 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Impact of splenomegaly and splenectomy on prognosis in hepatocellular carcinoma with portal vein tumor thrombus treated with hepatectomy.

Chai Zong-Tao ZT Zhang Xiu-Ping XP Shao Min M Ao Jian-Yang JY Chen Zhen-Hua ZH Zhang Fan F Hu Yi-Ren YR Zhong Cheng-Qian CQ Lin Jian-Hua JH Fang Kun-Peng KP Wu Meng-Chao MC Lau Wan Yee WY Cheng Shu-Qun SQ

Annals of translational medicine 20210201 3

<h4>Background</h4>Hepatocellular carcinoma (HCC) commonly occurs in patients with splenomegaly. This study aimed to investigate the impact of splenomegaly with or without splenectomy on long-term survival of HCC patients with portal vein tumor thrombus (PVTT) treated with liver resection (LR).<h4>Methods</h4>HCC patients with PVTT who underwent LR from 2005 to 2012 from 6 hospitals were retrospectively studied. The long-term overall survival (OS) and recurrence-free survival (RFS) were compared ...[more]

PMID: 33708874

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Project description:Rationale: Hepatocellular carcinoma (HCC) is primarily characterized by a high incidence of vascular invasion. However, the specific mechanism underlying portal vein tumor thrombus (PVTT) in HCC remains unclear. As a consequence of myeloid cell developmental arrest, CD71+ erythroid progenitor cells (EPCs) and myeloid-derived suppressor cells play important roles in HCC; however, their roles in PVTT remain unclear. Methods: The role of CD71+ EPCs in the HCC tumor microenvironment (TME) was evaluated via morphological, RNA-sequencing, enzyme-linked immunosorbent assay, and flow cytometric analyses. Co-culture techniques were employed to assess the CD45+ EPCs and their vascular compromising effect. Additionally, the PVTT-promoting function of CD45+ EPCs was explored in vivo in a murine model. Results: The CD45+EPCs in HCC tissues exhibited increased myeloid cell features, including morphology, surface markers, transforming growth factor (TGF)-β generation, and gene expression, compared with those in circulation. Hence, a large proportion of CD45+EPCs, particularly those in TMEs, comprise erythroid-transdifferentiated myeloid cells (EDMCs). Additionally, the expression of C-C chemokine receptor type 2 (CCR2) mRNA was upregulated in CD45+EPCs within the TME. Tumor macrophages from HCC tissues induced substantial migration of CD45+EPCs in a dose-dependent manner. Meanwhile, results from immunofluorescence analyses revealed that these two cell types are positively associated in the TME and circulation. That is, EDMCs are chemoattracted by HCC macrophages mainly via CCR2 from CD45+ EPCs in the circulation. Additionally, the expressions of FX, FVII, FGB, C4b, CFB, and CFH were elevated in CD45+EPCs within the TME compared with those in the spleen. The CD45+EPCs from the HCC TME promoted vessel endothelial cell migration and compromised tube formation through TGF-β and FGB, respectively. Additionally, CD45+EPCs from the TME induced HCC cell migration. HCC macrophage-induced CD45+EPCs to exhibit higher levels of FX, FVII, FGB, and TGF-β. Meanwhile, upregulation of CCAAT/enhancer binding protein beta expression induced FGB and TGF-β generation in CD45+EPCs in the TME. WTAP, a major RNA m6A writer, stabilized FX and FVII mRNA and enhanced their nuclear export in CD45+EPCs from the TME. CD45+EPCs from the TME were positively associated with PVTT and poor prognosis. Splenectomy reduced the level of CD45+EPCs in the circulation and TME, as well as the incidence of microvascular invasion. The incidence of microvascular invasion increased following the transfer of HCC tissue CD45+EPCs to splenectomized HCC-bearing mice. Conclusions: The CD45+EPCs enriched in the HCC microenvironment are EDMCs, which are induced by HCC macrophages to migrate from the circulation to the TME. Subsequently, EDMCs promote PVTT by compromising the blood vessel endothelium, aggravating coagulation, and promoting HCC cell migration.

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

Dataset Information

Impact of splenomegaly and splenectomy on prognosis in hepatocellular carcinoma with portal vein tumor thrombus treated with hepatectomy.

Background

Methods

Results

Conclusions

Publications

Impact of splenomegaly and splenectomy on prognosis in hepatocellular carcinoma with portal vein tumor thrombus treated with hepatectomy.

Similar Datasets

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