It has been shown recently in China that arsenic trioxide (As2O3) is a very effective treatment for acute promyelocytic leukemia (APL). APL patients resistant to all-trans retinoic acid (ATRA) and conventional chemotherapy can still respond to AS2O3. In this study, we addressed the possible cellular and molecular mechanisms of this treatment by using NB4 cells as a model. The results show that: (1) As2O3 triggers relatively specific NB4 cell apoptosis at micromolar concentration, as proved by morphology, histogramic related nuclear DNA contents, and DNA gel eletrophoresis. (2) As2O3 does not influence bax, bcl-x, c-myc, and p53 gene expression, but downregulates bcl-2 gene expression at both mRNA and protein levels. (3) As2O3 induces a significant modulation of the PML staining pattern in NB4 cells and HL-60 cells. The micropunctates characteristic of PML-RAR alpha in NB4 cells dissappear after treatment with As2O3, whereas a diffuse PML staining occurs in the perinuclear cytoplasmic region. In addition, a low percentage of untreated NB4 cells exhibits an accumulation of PML positive particles in a compartment of cytoplasm. The percentage of these cells can be significantly increased after As2O3 treatment. A similar PML staining pattern is observed in apoptotic cells. (4) ATRA pretreatment does not influence As2O3-induced apoptosis. These results suggest that induction of cell apoptosis can be one of the mechanisms of the therapeutic effect of As2O3. Moreover, this apoptosis induction occurs independently of the retinoid pathway and may be mediated, at least partly, through the modulation of bcl-2, as well as PML-RAR alpha and/ or PML proteins.

Transarterial chemoembolisation combined with the endovascular implantation of an iodine-125 seed strand is feasible, safe and effective in the treatment for hepatocellular carcinoma with PVTT.

AIMTo evaluate the safety and efficacy of combined endovascular brachytherapy (EVBT), transarterial chemoembolization (TACE), and sorafenib to treat hepatocellular carcinoma (HCC) patients with main portal vein tumor thrombus (MPVTT).METHODSThis single-center retrospective study involved 68 patients with unresectable HCC or those who were unfit for liver transplantation and percutaneous frequency ablation according to the BCLC classification. All patients had Child-Pugh classification grade A or B, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and MPVTT. The patients received either EVBT with stent placement, TACE, and sorafenib (group A, n = 37), or TACE with sorafenib (group B, n = 31). The time to progression (TTP) and overall survival (OS) were evaluated by propensity score analysis.RESULTSIn the entire cohort, the 6-, 12-, and 24-mo survival rates were 88.9%, 54.3%, and 14.1% in group A, and 45.8%, 0%, and 0% in group B, respectively (P < 0.001). The median TTP and OS were significantly longer in group A than group B (TTP: 9.0 mo vs 3.4 mo, P < 0.001; OS: 12.3 mo vs 5.2 mo, P < 0.001). In the propensity score-matched cohort, the median OS was longer in group A than in group B (10.3 mo vs 6.0 mo, P < 0.001). Similarly, the median TTP was longer in group A than in group B (9.0 mo vs 3.4 mo, P < 0.001). Multivariate Cox analysis revealed that the EVBT combined with stent placement, TACE, and sorafenib strategy was an independent predictor of favorable OS (HR = 0.18, P < 0.001).CONCLUSIONEVBT combined with stent placement, TACE, and sorafenib might be a safe and effective palliative treatment option for MPVTT.

Purpose. The aim of this study was to evaluate the safety and efficacy of transcatheter arterial embolization (TAE) in patients with renal hemorrhage after percutaneous nephrolithotomy (PCNL) and evaluate the risk factors that may result in severe bleeding requiring TAE. Methods. We retrospectively reviewed 121 patients with post-PCNL renal hemorrhage. Thirty-two patients receiving endovascular embolization were compared with 89 patients only receiving conservative treatment. The demographic and clinical data were recorded and compared between the two groups. The values of estimated glomerular filtration rate (eGFR) and serum creatinine (SCr) were recorded preoperatively, postoperatively, and at last follow-up and analyzed to evaluate the safety and efficiency of TAE. Results. The successful hemostasis rate of conservative therapy was 73.6% (89/121) and that of TAE was 100% (32/32). SCr and eGFR were not significantly different before PCNL and after the last follow-up of TAE (SCr: 0.95 vs. 0.95 mg/dl, P=0.857; eGFR: 86.77 vs. 86.18 ml/min/1.73m2, P=0.715). The univariate analysis demonstrated that advanced age, urinary tract infection, and diabetes mellitus were significantly associated with severe bleeding during PCNL. Multivariate analysis further identified that diabetes mellitus was an independent risk factor for severe bleeding needing TAE [odds ratio (OR): 3.778, 95% confidence interval (CI):1.276-11.190, and P=0.016]. Conclusion. TAE is a safe and effective procedure to treat renal hemorrhage that cannot be resisted by conservative treatment after PCNL. Diabetes mellitus was associated with high risks of severe bleeding needing TAE after PCNL.