In situ subtotal spleen resection combined with selective pericardial devascularization for the treatment of portal hypertension

BACKGROUND Hypersplenism and esophageal varices bleeding are the major complications of portal hypertension(PHT).In recent years,increasing attention has been given to spleen preservation operations.The mode and long-term effects of subtotal splenectomy and selective pericardial devascularization for PHT remain controversial.AIM To investigate the clinical efficacy and safety of subtotal splenectomy combined with selective pericardial devascularization for the treatment of PHT.METHODS This was a retrospective study of 15 patients with PHT who underwent subtotal splenectomy not preserving the splenic artery or vein combined with selective pericardial devascularization in the Department of Hepatobiliary Surgery,Qilu Hospital of Shandong University from February 2011 to April 2022.Fifteen propensity score-matched patients with PHT who underwent total splenectomy at the same time served as the control group.The patients were followed for up to 11 years after surgery.We compared the postoperative platelet levels,perioperative splenic vein thrombosis,and serum immunoglobulin levels between the two groups.Abdominal enhanced computed tomography was used to evaluate the blood supply and function of the residual spleen.The operation time,intraoperative blood loss,evacuation time,and hospital stay were compared between the two groups.RESULTS The postoperative platelet level of patients in the subtotal splenectomy group was significantly lower than that in the total splenectomy group(P<0.05),and the postoperative portal system thrombosis rate in the subtotal splenectomy group was also much lower than that in the total splenectomy group.The levels of serum immunoglobulins(IgG,IgA,and IgM)showed no significant differences after surgery compared with before surgery in the subtotal splenectomy group(P>0.05),but serum immunoglobulin IgG and IgM levels decreased dramatically after total splenectomy(P<0.05).The operation time in the subtotal splenectomy group was longer than that in the total splenectomy group(P<0.05),but there were no significant differences in the amount of intraoperative blood loss,evacuation time,or hospital stay between the two groups.CONCLUSION Subtotal splenectomy not preserving the splenic artery or vein combined with selective pericardial devascularization is a safe and effective surgical treatment for patients with PHT,not only correcting hypersplenism but also preserving splenic function,especially immunological function.

Management of hepatocellular carcinoma patients with portal vein tumor thrombosis:A narrative review

Background: Hepatocellular carcinoma(HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis(PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. Data sources: We have reviewed literature from Pub Med on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. Results: Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can beneft from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also benefcial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classifcation models can be used to design personalized treatments. The application of new treatment methods such as the atezolizumab plus bevacizumab scheme may increase survival.

Proteinase-activated receptor 2 promotes tumor cell proliferation and metastasis by inducing epithelialmesenchymal transition and predicts poor prognosis in hepatocellular carcinoma

AIM To clarify the role of proteinase-activated receptor 2(PAR2) in hepatocellular carcinoma, especially in the process of metastasis.METHODS PAR2 expression levels were assessed by qRT-PCR and immunohistochemistry(IHC) in patient tissues and in hepatocellular carcinoma cell lines SMMC-7721 and Hep G2. Cell proliferation and metastasis were assessed both in vitro and in vitro. Immunoblotting was carried out to monitor the levels of mitogen-activated protein kinase(MAPK) and epithelial-mesenchymal transition markers.RESULTS The prognosis was significantly poorer in patients with high PAR2 levels than in those with low PAR2 levels. Patients with high PAR2 levels had advanced tumor stage(P = 0.001, chi-square test), larger tumor size(P = 0.032, chi-square test), and high microvascular invasion rate(P = 0.037, chi-square test). The proliferation and metastasis ability of SMMC-7721 and Hep G2 cells was increased after PAR2 overexpression, while knockdown of PAR2 decreased the proliferation and metastasis ability of SMMC-7721 and Hep G2 cells. Knockdown of PAR2 also inhibited hepatocellular carcinoma tumor cell growth and liver metastasis in nude mice. Mechanistically, PAR2 increased the proliferation ability of SMMC-7721 and Hep G2 cells via ERK activation. Activated ERK further promoted the epithelial-mesenchymal transition of these cells, which endowed them with enhanced migration and invasion ability. CONCLUSION These data suggest that PAR2 plays an important role in the proliferation and metastasis of hepatocellular carcinoma. Therefore, targeting PAR2 may present a favorable target for treatment of this malignancy.

A novel oncolytic adenovirus inhibits hepatocellular carcinoma growth

Objective: To evaluate the inhibitory role of a novel oncolytic adenovirus(OA), GP73-SphK1 sR-Ad5, on the growth of hepatocellular carcinoma(HCC). Methods: GP73-SphK1 sR-Ad5 was constructed by integrating Golgi protein 73(GP73) promoter and sphingosine kinase 1(SphK1)-short hairpin RNA(shRNA) into adenovirus serotype 5(Ad5), and transfecting into HCC Huh7 cells and normal human liver HL-7702 cells. The expression of SphK1 and adenovirus early region 1(E1 A) was detected by quantitative real-time PCR(qRT-PCR) and western blot, respectively. Cell viability was detected by methylthiazolyldiphenyl-tetrazolium bromide(MTT) assay, and apoptotic rate was determined by flow cytometry. An Huh7 xenograft model was established in mice injected intratumorally with GP73-SphK 1 sR-Ad5. Twenty days after injection, the tumor volume and weight, and the survival time of the mice were recorded. The histopathological changes in tumor tissues were observed by hematoxylin-eosin(HE) staining and transmission electron microscopy(TEM). Results: Transfection of GP73-SphK1 sR-Ad5 significantly upregulated E1 A and downregulated SphK1 in Huh7 cells, but not in HL7702 cells. GP73-SphK1 sR-Ad5 transfection significantly decreased the viability and increased the apoptotic rate of Huh7 cells, but had no effect on HL7702 cells. Intratumoral injection of GP73-SphK1 sR-Ad5 into the Huh7 xenograft mouse model significantly decreased tumor volume and weight, and prolonged survival time. It also significantly decreased the tumor infiltration area and blood vessel density, and increased the percentages of cells with nucleus deformation and cells with condensed chromatin in tumor tissues. Conclusions: GP73-SphK1 sR-Ad5 serves as a novel OA and can inhibit HCC progression with high specificity and efficacy.