Prognostic model for unresectable hepatocellular carcinoma treated with dual PD-1 and angiogenesis blockade therapy.

BACKGROUND AND AIMS: Dual programmed death 1 (PD-1) and angiogenesis blockade therapy is a frontline treatment for hepatocellular carcinoma (HCC). An accepted model for survival prediction and risk stratification in individual patients receiving this treatment is lacking. Aimed to develop a simple prognostic model specific to these patients. APPROACH AND RESULTS: Patients with unresectable HCC undergoing dual PD-1 and angiogenesis blockade therapy were included in training cohort (n=168) and validation cohort (n=72). We investigated the prognostic value of clinical variables on overall survival using a Cox model in the training set. A prognostic score model was then developed and validated. Predictive performance and discrimination were also evaluated. Largest tumor size and Alpha-fetoprotein concentration at baseline and Neutrophil count and Spleen volume change after 6 weeks of treatment were identified as independent predictors of overall survival in multivariable analysis and used to develop LANS score. Time-dependent receiver operating characteristic analysis, calibration curves, and C-index showed LANS score had favorable performance in survival prediction. Patients were divided into three risk categories based on LANS score. Median survival for patients with low, intermediate, and high LANS scores was 31.7, 23.5, and 11.5 months, respectively (p<0.0001). The disease control rates were 96.4%, 64.3%, and 32.1%, respectively (p<0.0001). The predictive performance and risk stratification ability of the LANS score were confirmed in validation and entire cohorts. CONCLUSION: The LANS score model can provide individualized survival prediction and risk stratification in patients with unresectable HCC undergoing dual PD-1 and angiogenesis blockade therapy.

Comparison of the Efficacy and Safety of Single-Session OK-432 and Multiple-Session 99% Ethanol Sclerotherapy for Symptomatic Simple Hepatic Cysts.

Purpose: This retrospective study aimed to compare the efficacy and safety of single-session OK-432 and multiple-session 99% ethanol sclerotherapy for symptomatic simple hepatic cysts. Methods: We reviewed patients who received aspiration sclerotherapy with OK-432 (group A) or 99% ethanol (group B) for symptomatic simple hepatic cysts at Guangdong Provincial People's Hospital from January 2013 to November 2019. Results: We included 42 patients in group A and 39 patients in group B. No significant difference was found in the mean volume of hepatic cysts between the two groups. The overall success rates were 92.9% (39 of 42 patients) in group A and 79.5% (31 of 39 patients) in group B (P = 0.08). The treatment success for cyst volumes <200 ml, 200-500 ml, and >500 ml was 100, 93.3, and 88.2% in group A, and 100, 84.6, and 57.1% in group B, respectively. The symptomatic relief rate in group A was higher than that in group B for cysts ≥500 ml (P = 0.049) and cysts <500 ml. For treatment-related complications, the incidence of pain at the injection site in group A was lower than that in group B. Conclusion: Single-session OK-432 sclerotherapy was safer and more effective than multiple-session 99% ethanol sclerotherapy for treating large cysts, although both treatments had similar effects on small cysts.

CircPOLR2A Promotes Proliferation and Impedes Apoptosis of Glioblastoma Multiforme Cells by Up-regulating POU3F2 to Facilitate SOX9 Transcription.

Glioblastoma multiforme (GBM) is the most common cancer in nervous system around the world. Little advancement has been achieved in promoting prognosis of GBM patients. Circular RNAs (circRNAs) are suggested as crucial effectors in modulating GBM development. Hsa_circRNA_092437 (circPOLR2A), an up-regulated circRNA in GBM cells, has not been studied yet. In this study, RT-qPCR and western blot assays were applied to detect RNA and protein levels. Cell proliferation and apoptosis were analyzed via functional assays. Subcellular fractionation assay was carried out to determine circPOLR2A distribution in cells. Bioinformatics analysis and mechanism assays were done for detecting relationships among different factors. Rescue assays were performed to confirm validity of circPOLR2A/SOX9 axis. According to experimental results, circPOLR2A was up-regulated in GBM cells and promoted GBM cell proliferation while inhibiting GBM cell apoptosis. CircPOLR2A mainly existed in cell cytoplasm and sponged miR-2113 to positively regulate POU3F2 expression. POU3F2 activated the transcription of SOX9 through interacting with SOX9 promoter (1-500). Rescue assays validated that circPOLR2A influenced GBM cell proliferation and apoptosis via SOX9. To conclude, circPOLR2A enhanced the transcription of SOX9 through miR-2113/POU3F2 axis, thus exacerbating GBM cells growth.

Feasibility and Clinical Value of CT-Guided 125I Brachytherapy for Pain Palliation in Patients With Breast Cancer and Bone Metastases After External Beam Radiotherapy Failure.

Objectives: To evaluate the feasibility and clinical value of CT-guided iodine-125 (125I) brachytherapy for pain palliation in patients with breast cancer and bone metastases after external beam radiotherapy failure. Methods: From January 2014 to July 2016, a total of 90 patients, who had received the standard therapies for bone metastases but still suffered moderate-to-severe pain, were retrospectively studied. About 42 patients were treated with both 125I brachytherapy and bisphosphonates (Group A), and 48 patients were treated with bisphosphonates alone (Group B). Results: In Group A, 45 125I brachytherapy procedures were performed in 42 patients with 69 bone metastases; the primary success rate of 125I seed implantation was 92.9%, without severe complications. Regarding pain progression of the two groups, Group A exhibited significant relief in "worst pain," "least pain," "average pain," and "present pain" 3-day after treatment and could achieve a 12-week-remission for "worst pain," "least pain," "average pain," and "present pain." The morphine-equivalent 24-h analgesic dose at 3 days, 4 weeks, 8 weeks, and 12 weeks was 91 ± 27, 53 ± 13, 31 ± 17, and 34 ± 12 mg for Group A, and 129 ± 21, 61 ± 16, 53 ± 15, and 105 ± 23 mg for Group B. Group A experienced a lower incidence of analgesic-related adverse events and better quality of life than Group B. Conclusion: The CT-guided 125I brachytherapy is a feasible and an effective treatment for the palliation of pain caused by bone metastases from breast cancer after external beam radiotherapy failure.

Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy for advanced biliary tract cancers with biliary obstruction: a multicentre, retrospective, controlled study.

OBJECTIVE: To evaluate the efficacy and safety of stent placement combined with intraluminal radiofrequency ablation (intra-RFA) and hepatic arterial infusion chemotherapy (HAIC) for patients with advanced biliary tract cancers (Ad-BTCs) and biliary obstruction (BO). METHODS: We retrospectively reviewed data for patients with Ad-BTCs and BO who underwent stent placement with or without intra-RFA and HAIC in three centres between November 2013 and November 2018. The stent patency time (SPT), overall survival (OS), and adverse events (AEs) were analysed. RESULTS: Of the 135 enrolled patients, 64 underwent stent placement combined with intra-RFA and HAIC, while 71 underwent only stent placement. The median SPT was significantly longer in the combination group (8.2 months, 95% confidence interval [CI]: 7.1-9.3) than in the control group (4.3 months, 95% CI: 3.6-5.0; p < 0.001). A similar result was observed for OS (combination: 13.2 months, 95% CI: 11.1-16.5; control: 8.5 months, 95% CI: 7.6-9.6; p < 0.001). The incidence of AEs related to biliary tract operation was not significantly different between the two groups (p > 0.05). The most common AE and serious AE related to HAIC were alanine aminotransferase elevation (24/64; 37.5%) and thrombocytopenia (8/64; 12.5%), respectively. All AEs were tolerable, and there was no death from AEs. CONCLUSIONS: Stent placement combined with intra-RFA and HAIC may be a safe, potential treatment strategy for patients with Ad-BTCs and BO. KEY POINTS: • Advanced biliary cancers (Ad-BTCs) with biliary obstruction (BO) can rapidly result in liver failure and cachexia with an extremely poor prognosis. • Stent placement combined with intraluminal radiofrequency ablation and hepatic arterial infusion chemotherapy may be safe and effective for patients with Ad-BTCs and BO. • The long-term efficacy and safety of the combined treatment is promising.

Microwave ablation after downstaging of hepatocellular carcinoma: outcome was similar to tumor within Milan criteria.

OBJECTIVES: The aim of this study was to evaluate the clinical outcome of patients receiving microwave ablation (MWA), either after downstaging of hepatocellular carcinoma (HCC) with transarterial chemoembolization (TACE), or without downstaging when meeting initially the Milan criteria. METHODS: From January 2012 to January 2018, 66 patients with HCC beyond the Milan criteria who were downstaged by TACE previous to MWA comprised the study group. The control group comprised 190 patients who underwent MWA as first-line treatment as they met initially the Milan criteria. Cumulative overall survival (OS) and recurrence-free survival (RFS) rates were compared. The propensity score analysis was performed to reduce potential bias. RESULTS: Baseline characteristics were balanced between the two groups after 1:1 propensity score matching. The OS rates were 100%, 79%, and 73% at 1, 3, and 5 years in the downstaging group and 95%, 83%, and 72%, respectively, in the Milan group. The corresponding RFS rate were 77%, 40%, and 31% in the downstaging group and 76%, 45%, and 34% in the Milan group. There were no significant differences in the OS and RFS rates between the two groups (p = 0.981 and p = 0.586). CONCLUSIONS: The long-term therapeutic outcomes of MWA for downstaged HCC with TACE were similar to HCC that initially met the Milan criteria. KEY POINTS: • Patients treated with MWA of HCC after downstaging with transarterial chemoembolization (TACE) were similar to those with HCC that initially met Milan criteria. • Microwave ablation (MWA) can be an effective treatment for hepatocellular carcinoma (HCC) that is downstaged to the Milan criteria.

MicroRNA-450b-3p inhibits cell growth by targeting phosphoglycerate kinase 1 in hepatocellular carcinoma.

Dysregulation of microRNAs frequently contributes to the occurrence and progression of human diseases, including hepatocellular carcinoma (HCC). In this study, the role of miR-450b-3p in HCC was investigated. Gene Expression Omnibus database and HCC specimens were used to evaluate the expression level of miR-450b-3p and the patient's prognosis. Cell functional analyses and tumor xenograft model were used to assess the role of miR-450b-3p in HCC. Bioinformatics was used to predict the downstream target gene of miR-450b-3p, which was verified by dual-luciferase reporter assay. MiR-450b-3p was found to be downregulated in HCC cell lines and tissues, compared with nontransformed immortal hepatic cells and adjacent normal liver tissues, respectively. Lower expression of miR-450b-3p was associated with poor overall survival and disease-free survival in patients with HCC. Ectopic expression of miR-450b-3p inhibited HCC cell viability, colony formation, and cell-cycle progression in vitro, and suppressed the growth of HCC xenograft tumors in vivo. Interestingly, a negative correlation between miR-450b-3p and phosphoglycerate kinase 1 (PGK1) protein was observed among HCC specimens. Additionally, miR-450b-3p inhibited PGK1 expression and phosphorylation of protein kinase B in HCC cell lines. Further experiments confirmed that PGK1 was a direct target of miR-450b-3p. Moreover, restoration of PGK1 abrogated the inhibitory effect of miR-450b-3p on HCC proliferation and cell division. In conclusion, miR-450b-3p is downregulated in human HCC and exerts tumor suppressive effects at least in part by inhibiting PGK1.

Microwave ablation versus radiofrequency ablation for the treatment of pulmonary tumors.

To retrospectively compare the efficacy and safety of radiofrequency ablation (RFA) and microwave ablation (MWA) in the treatment of pulmonary tumors, a total of 75 patients with lung tumor who underwent thermal ablation therapy in Guangdong General Hospital into the study from March 2007 to December 2014 were enrolled. Of the patients, 43 received radiofrequency ablation and 32 received microwaves ablation. The response rates, overall survival (OS), and complications rates between the RFA group and MWA group were compared. There were no significant differences in the baseline characteristics between two groups. The overall response rates of in RFA and MWA groups were 79% (34/43) and 69% (22/32), respectively, and there was no statistically significant difference between two groups (P = 0.309). The 1-, 2-, 3-, 5-year overall survival (OS) rates in RFA group and MWA group were 77%, 55%, 42%, 34% and 75%, 44%, 40%, 27%, respectively. No significant differences were found in the OS rates between two groups (P = 0.653). The complication rates were 49% (21/43) in RFA group and 50% (16/32) in MWA group; there was no significant difference between two groups (P = 0.921). No patients died during the perioperative period. Our study shows that no significant differences exist in efficacy and safety between RFA and MWA for the treatment of pulmonary tumors, which indicates that MWA could be a substitute therapy for RFA in terms of effectiveness and safety for treating pulmonary tumors.