Long-term surgical outcomes of bile duct tumor thrombus versus portal vein tumor thrombus for hepatocellular carcinoma: a propensity score matching analysis.

Background: Portal vein tumor thrombus (PVTT) seriously affects the prognosis of hepatocellular carcinoma (HCC). However, whether bile duct tumor thrombus (BDTT) significantly affects the prognosis of HCC as much as PVTT remains unclear. We aimed to compare the long-term surgical outcomes of HCC with macroscopic PVTT (macro-PVTT) and macroscopic BDTT (macro-BDTT). Methods: The data of HCC patients with macro-BDTT or macro-PVTT who underwent hemihepatectomy were retrospectively reviewed. A propensity score matching (PSM) analysis was performed to reduce the baseline imbalance. The recurrence-free survival (RFS) and overall survival (OS) rates were compared between the cohorts. Results: Before PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.043 and P = 0.008, respectively). Multivariate analyses identified PVTT (hazard ratio [HR] = 1.835, P = 0.016) and large HCC (HR = 1.553, P = 0.039) as independent risk factors for poor OS and RFS, respectively. After PSM, the PVTT group had worse RFS and OS rates than the BDTT group (P = 0.037 and P = 0.004, respectively). The 3- and 5-year OS rates were significantly higher in the BDTT group (59.5% and 52.1%, respectively) than in the PVTT group (33.3% and 20.2%, respectively). Conclusion: Aggressive hemihepatectomy provides an acceptable prognosis for HCC patients with macro-BDTT. Furthermore, the long-term surgical outcomes of HCC patients with macro-BDTT were significantly better than those of HCC patients with macro-PVTT.

Surgical outcomes of hepatocellular carcinoma with extrahepatic bile duct tumor thrombus: a multicenter study.

Background: The long-term prognosis after surgery of patients with hepatocellular carcinoma (HCC) and extrahepatic bile duct tumor thrombus (Ex-BDTT) remains unknown. We aimed to identify the surgical outcomes of patients with HCC and Ex-BDTT. Methods: A total of 138 patients with Ex-BDTT who underwent hepatectomy with preservation of the extrahepatic bile duct from five large hospitals in China between January 2009 and December 2017 were included. The Cox proportional hazards model was used to analyze overall survival (OS) and recurrence-free survival (RFS). Results: With a median follow-up of 60 months (range, 1-127.8 months), the median OS and RFS of the patients were 28.6 and 8.9 months, respectively. The 1-, 3-, and 5-year OS rates of HCC patients with Ex-BDTT were 71.7%, 41.2%, and 33.5%, respectively, and the corresponding RFS rates were 43.5%, 21.7%, and 20.0%, respectively. Multivariate analysis identified that major hepatectomy, R0 resection, and major vascular invasion were independent prognostic factors for OS and RFS. In addition, preoperative serum total bilirubin ≥ 4.2 mg/dL was an independent prognostic factor for RFS. Conclusion: Major hepatectomy with preservation of the extrahepatic bile duct can provide favorable long-term survival for HCC patients with Ex-BDTT.

Should associating liver partition and portal vein ligation for staged hepatectomy be applied to hepatitis B virus-related hepatocellular carcinoma patients with cirrhosis? A multi-center study.

BACKGROUND: It is unclear whether associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can be performed in hepatitis B virus-related hepatocellular carcinoma (HCC) patients with cirrhosis. We explored the efficacy of ALPPS in HCC patients. METHODS: Data of 54 patients who underwent ALPPS between August 2014 and July 2020 at three centers were collected. Adverse factors affecting their prognosis were analyzed and subsequently compared with 184 patients who underwent transcatheter arterial chemoembolization (TACE). RESULTS: Overall survival rates of the ALPPS group at 1, 3, and 5 years were 70.6%, 38.4%, and 31.7%, respectively; corresponding disease-free survival rates were 50.5%, 22.4%, and 19.2%, respectively. The ALPPS group had a significantly greater long-term survival rate than the TACE group (before propensity score matching, P < 0.001; after propensity score matching, P = 0.002). Multivariate analysis demonstrated that multifocal lesions (P = 0.018) and macroscopic vascular invasion (P = 0.001) were prognostic factors for HCC patients who underwent ALPPS. After the propensity score matching, the multifocal lesions (P = 0.031), macroscopic vascular invasion (P = 0.003), and treatment type (ALPPS/TACE) (P = 0.026) were the factors adversely affecting the prognosis of HCC patients. CONCLUSION: ALPPS was feasible in hepatitis B virus-related HCC patients with cirrhosis and resulted in better survival than TACE.

Imaging Features of Hepatocellular Carcinoma With Bile Duct Tumor Thrombus: A Multicenter Study.

OBJECTIVES: There are still challenging problems in diagnosis of hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT) before operation. This study aimed to analyze the imaging features of HCC with B1-B3 BDTT. MATERIALS AND METHODS: The clinicopathological data and imaging findings of 30 HCC patients with B1-B3 BDTT from three high-volume institutions were retrospectively reviewed. A total of 631 patients without BDTT who were randomly collected from each of the enrolled centers were recorded as the control group to analyze the differences in clinicopathological characteristics and imaging features between the two groups. A total of 453 HCC patients who underwent surgical treatment in the three institutions from January 2020 to December 2020 were collected for a blinded reading test as the validation group. RESULTS: HCC patients with B1-B3 BDTT had more advanced tumor stages and adverse clinicopathological features. HCC lesions were detected in all patients, and intrahepatic bile duct dilation was observed in 28 (93.3%) patients with B1-B3 BDTT and 9 (1.43%) patients in HCC without BDTT. The intrahepatic bile duct dilation showed no enhancement at hepatic arterial phase (HAP) and no progressively delayed enhancement at portal venous phase (PVP), but it was more obvious at PVP on CT. In the reports of the 30 HCC patients with B1-B3 BDTT generated for the image when the scan was done, BDTT was observed in all 13 B3 patients and 3 of 12 B2 patients, but none of the 5 B1 patients. Fourteen patients were misdiagnosed before surgery. However, when using intrahepatic bile duct dilation in HCC patients as a potential biomarker for BDTT diagnosis, the sensitivity and specificity for BDTT diagnosis were 93.33% and 98.57%, respectively. The blinded reading test showed that intrahepatic bile duct dilation in CT and MRI scans could be for separating HCC patients with B1-B3 BDTT from HCC patients without BDTT. CONCLUSIONS: The HCC lesions and intrahepatic bile duct dilation on CT or MRI scans are imaging features of HCC with BDTT, which might facilitate the early diagnosis of B1-B3 BDTT.

[Significance of H3K27me3 and EZH2 in Predicting the Therapeutic Efficacy of Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the significance of H3K27me3 and its methyltransferase EZH2 in predicting the short-term and long-term outcome of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The paraffin wax speciments of 102 DLBCL patients in Fujian Medical University Cancer Hospital were collected. The expression of H3K27me3, EZH2 and BCL-2 protein were detected using tissue array made by tissue microarray(TMA) technique and immunohistochemistry method. The evaluation data after clinical treatment and follow-up results were collected and combined with expression levels of H3K27me3, EZH2 and BCL-2 detected by tissue array, then on the basis of these data, the survival of patients was analyzed by Kaplan-Meier method, the correlation of EZH2 with H3K27me3 and BCL-2 was analyzed by pearson correlation test, the correlation of above mentioned indicators with different therapeutic efficacy was analyzed by spearman correlation test. The relationship of H3K27me3 and EZH2 expression as well as co-expression of H3K27me3 and EZH2 with the therapeutic efficacy and prognosis of patients were compared. RESULTS: A total of 61.8% patients showed EZH2 high expression which positively correlated with high expression of H3K27me3 and BCL-2. The complete remission (CR) and overall remission (OR) rates in H3K27me3 high expression and co-expression of H3K27me3 EZH2 groups were lower than those in low expression groups (P<0.001), moreover OS and PFS rates also were lower than those in low expression (P<0.001). In the RCHOP subgroup, the patients with EZH2 low expression showed significantly better CR, OR OS and PFS in comparison with those of patients with higher expression (P=0.003,P=0.019). CONCLUSION: Part of DLBCL patients with H3K27me3 high expression or coexpression of both H3K27me3 and EZH2 exhibit a worse prognosis in comparison with those patients with H3K27me3 low expression or without coexpression. The patients with EZH2 low expression usually responde well to RCHOP regimen in the short-term or long-term survival.

Multiple verruciform xanthomas in the setting of congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome.

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome is a rare X-linked dominant disease characterized by peculiar cutaneous presentations and skeletal abnormalities. Verruciform xanthoma (VX)-like histologic changes occasionally occur in CHILD syndrome, but typical VX-like lesions coexisting with CHILD syndrome are rare. In this study we report a rare case of multiple, coexisting VXs on the vulva and left lower limb of an 11-year-old Chinese girl who also exhibited the typical clinical presentations and limb defects of CHILD syndrome. Histologic and immunohistochemical analyses showed that the lesions were typical VXs.

Reduced expression of autophagy markers correlates with high-risk human papillomavirus infection in human cervical squamous cell carcinoma.

Infection by an oncogenic human papillomavirus (HPV), in particular HPV16 and 18, is a high risk factor for developing cervical cancer; however, viral infection alone is not sufficient for cancer progression. Autophagy is hypothesized to be an important process during carcinogenesis. The aim of the present study was to investigate the association between autophagy and high-risk HPV (hrHPV) infection in human cervical squamous cell carcinomas (SCCs), and to analyze the clinical significance of this association. Quantum dot (QD)-based immunofluorescence histochemistry was used to detect the expression of autophagy markers, Beclin-1 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) proteins, in 104 cases of cervical cancer (including 80 SCCs and 24 adenocarcinomas) and 20 normal cervical tissues. hrHPV (HPV16/18) infection was detected by QDs based fluorescence in situ hybridization in cervical cancers. The results revealed that the expression levels of Beclin-1 and LC3B were significantly lower in cervical cancer cells when compared with those of normal cervical squamous epithelial cells, and were found to negatively correlate with hrHPV infection. The expression levels of Beclin-1 and LC3B were not associated with age, tumor grade, tumor stage, tumor node metastasis stage or lymph node metastasis. However, a positive correlation was identified between Beclin-1 and LC3B protein expression. In addition, the absence of autophagy in combination with hrHPV infection may accelerate the progression of cervical SCC. In conclusion, decreased expression of Beclin-1 and LC3B may be important in cervical carcinogenesis. The hrHPV-host cell interaction may inhibit autophagy, which may aid virus duplication and infection, as well as cervical cancer development.

Association between ERCC2 polymorphisms and glioma risk: a meta-analysis.

ERCC2 is an essential component of the nucleotide excision repair pathway which is involved in the effective maintenance of genome integrity. Association studies on ERCC2 polymorphisms and glioma risk have yielded inconclusive results. This meta-analysis was performed to gain a better insight into the relationship between ERCC2 polymorphisms and glioma risk. A systematic literature search updated to December 2, 2013 was performed in the Pubmed and EMBASE databases. Crude pooled odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were used to estimate the association between ERCC2 polymorphisms and glioma risk under a suitable effect model according to heterogeneity. All analyses were performed using Review Manager 5 (version 5.2) and STATA (version 12.0). The combined results demonstrated rs13181 to be significantly associated with glioma risk (G allele versus T allele: OR=1.15, 95% CI=1.05-1.26, P=0.002; dominant model: OR=1.22, 95% CI=1.07-1.39, P=0.002; recessive model: OR=1.18, 95% CI=0.98-1.41, P=0.070). We also found that rs13181 acts in an allele dose-dependent manner (GG versus TT: OR=1.30, 95% CI=1.07-1.57, P=0.009; TG versus TT: OR=1.20, 95%=CI 1.05-1.37, P=0.009; trend test, P=0.004). However, no evidence was found in analyses for the association between other 3 ERCC2 polymorphisms (rs238406, rs1799793, and rs1052555) and susceptibility to glioma development. Our meta-analysis suggests that rs13181 is significantly associated with glioma risk in an allele dose-dependent manner, whereas, 3 other ERCC2 polymorphisms (rs238406, rs1799793, and rs1052555) may have no influence.

Estrogen receptor α roles in breast cancer chemoresistance.

Resistance to chemotherapy treatment, which may lead to limited efficacy of systemic therapy in breast cancer patients, is multifactorial. Among the mechanisms of resistance to chemotherapy treatment, there are those closely related to estrogen receptor α, P-glycoprotein, multidrug resistance-related protein, glutathione S-transferase pi and topoisomerase-II. ERα is ligand-activated transcription factor that regulates gene expression and plays a critical role in endocrine signaling. In previous preclinical and clinical studies, positive ERα expression in breast cancer cells was correlated with decreased sensitivity to chemotherapy. This article reviews current knowledge on the predictive value of ERα with regard to response to chemotherapy. Better understanding of its role may facilitate patient selection of therapeutic regimens and lead to optimal clinical outcomes.

Prognostic significance of α5ß1-integrin expression in cervical cancer.

The purpose of this study was to evaluate the association of expression of α5ß1-integrin with clinicopathologic features and prognosis in cervical cancer. Levels of α5ß1-integrin in normal cervical mucosa and cervical cancer tissue were detected with immunohistochemistry. Survival analysis by the Kaplan-Meier method was performed to assess prognostic significance. α5ß1-integrin expression was detected in 84.6% (143/169) cervical cancer samples, significantly different from that in normal cervical mucosa (P < 0.05). Positive expression rates of α5ß1-integrin in patients with poor histologic differentiation, lymph node metastasis, and recurrence were elevated. Using Kaplan-Meier analysis, a comparison of survival curves of low versus high expression of α5ß1-integrin revealed a highly significant difference in human cervical cancer cases (P < 0.05), suggesting that overexpression of α5ß1-integrin is associated with a worse prognosis.The α5ß1-integrin promotes angiogenesis and associates with lymph node metastasis, vascular invasion and poor prognosis of cervical cancer. The current study indicated that α5ß1-integrin may be an independent prognostic factor for cervical cancer patients.

[Association between HLA-DQA1 gene copy number polymorphisms and susceptibility to gastric cancer].

OBJECTIVE: To explore the association between HLA-DQA1 gene copy number polymorphisms and gastric cancer risk in Chinese population, and the interaction of those genes and environmental factors. METHODS: The genotype of HLA-DQA1 gene copy number polymorphisms was determined in 343 patients with gastric cancer and 330 controls by quantitative polymerase chain reaction. Logistic regression model was used to evaluate the impact of this polymorphism on the risk of developing gastric cancer and the gene-environment interaction. RESULTS: Compared with 0 copy of HLA-DQA1 gene carriers, the 2 copies of HLA-DQA1 gene carriers had a significantly increased risk of gastric cancer (OR = 1.87, 95%CI = 1.15 - 3.06, P = 0.012). Gene-environment interaction of HLA-DQA1 gene copy number polymorphisms and Helicobacter pylori infection significantly increased the risk of gastric cancer in a multiplicative manner, with an OR of 3.89 (95%CI = 1.75 - 8.57, P = 0.001). CONCLUSIONS: HLA-DQA1 gene copy number polymorphism is associated with gastric cancer susceptibility, and there is a multiplicative gene-environment interaction between this polymorphism and Hp infection in the development of gastric cancer.

Association between genetic variations in tumor necrosis factor receptor genes and survival of patients with T-cell lymphoma.

The prognosis of T-cell lymphoma (TCL) has been shown to be associated with the clinical characteristics of patients. However, there is little knowledge of whether genetic variations also affect the prognosis of TCL. This study investigated the associations between single nucleotide polymorphisms(SNPs) in tumor necrosis factor receptor superfamily(TNFRSF) genes and the survival of patients with TCL. A total of 38 tag SNPs in 18 TNFRSF genes were genotyped using Sequenom platform in 150 patients with TCL. Kaplan-Meier survival estimates were plotted and significance was assessed using log-rank tests. Cox proportional hazard models were used to analyze each of these 38 SNPs with adjustment for covariates that might influence patient survival, including sex and international prognostic Index score. Hazard ratios (HRs) and their 95% confidence intervals(CIs) were calculated. Among the 38 SNPs tested, 3 were significantly associated with the survival of patients with TCL. These SNPs were located at LTßR (rs3759333C>T) and TNFRSF17(rs2017662C>T and rs2071336C>T). The 5-year survival rates were significantly different among patients carrying different genotypes and the HRs for death between the different genotypes ranged from 0.45 to 2.46. These findings suggest that the SNPs in TNFRSF genes might be important determinants for the survival of TCL patients.

[Managements of small thyroid nodules with contralateral papillary thyroid microcarcinoma].

OBJECTIVE: To study the diagnoses and treatments of small thyroid nodules (maximum diameter < 1 cm) with contralateral papillary thyroid microcarcinoma (PTMC). METHODS: A total of 253 patients with unilateral PTMC and contralateral thyroid benign nodules identified by ultrasound before thyroidectomy was retrospectively analysed. All patients underwent near-total or total thyroidectomy. Chi-square test was used for univariate analysis and logistic regression test for multivariate analysis. RESULTS: In 53 (20.9%) of 253 patients with unilateral PTMC, the contralateral thyroid benign nodules identified by ultrasound were confirmed pathologically as PTMC. Univariate analysis showed multifocality of the primary tumor and Hashimoto's thyroiditis were correlated with contralateral PTMC (χ(2) = 24.834, χ(2) = 5.182, P < 0.05). However, there were no significant differences for the existence of contralateral PTMC in age, sex, tumor size, capsule invasion, lymph node metastasis, the number of nodules and Tg-level. Multivariate analysis showed only multifocal PTMC was an independent predictive factor for contralateral PTMC (OR = 5.352, P < 0.05). CONCLUSIONS: The patients with unilateral multifocal PTMC have a high rate of PTMC in contralateral small thyroid nodules. However, it is very difficulty to define by ultrasonography preoperatively. The total thyroidectomy maybe serve as a useful treatment.

The role of tyrosine kinase Etk/Bmx in EGF-induced apoptosis of MDA-MB-468 breast cancer cells.

Etk/Bmx, a member of the Tec family of tyrosine kinases, mediates various signaling pathways and confers several cellular functions. In the present study, we have explored the functional role of Etk in mediating EGF-induced apoptosis, using MDA-MB-468 cell line as a model. We first demonstrated that EGF treatment induces Etk tyrosine phosphorylation in both HeLa and MDA-MB-468 cells. Overexpression of Etk by recombinant adenovirus in MDA-MB-468 cells potentiates the extent of EGF-induced cell apoptosis. The observed Etk-enhanced MDA-MB-468 cell apoptosis is associated with the Stat1 activation, as demonstrated by electrophoresis mobility shift assays and reporter gene assays. By contrast, a kinase domain deletion mutant EtkDeltaK, functioning as a dominant-negative mutant, ameliorates EGF-induced Stat1 activation and apoptosis in MDA-MB-468 cells. To explore whether the activated Etk alone is sufficient for inducing apoptosis, a conditionally activated Etk (DeltaEtk-ER), a chimeric fusion protein of PH domain-truncated Etk and ligand-binding domain of estrogen receptor, was introduced into MDA-MB-468 cells. Upon beta-estradiol ligand activation, the DeltaEtk-ER could stimulate Stat1 activity and confer cell apoptosis independent of EGF treatment. Taken together, our findings indicate that Etk is a downstream signaling molecule of EGF receptor and suggest that Etk activation is essential for transducing the EGF-induced apoptotic signaling.