Results of computerized tomography guided percutaneous ablation of renal masses with nondiagnostic pre-ablation pathological findings

PURPOSE: Ablative therapy for renal masses has been criticized because the entire tumor cannot be evaluated pathologically after the procedure. Diagnosis depends on imaging findings and the results of percutaneous needle biopsies, which may be nondiagnostic in up to 21% of cases. We determined outcomes in patients undergoing ablation who had nondiagnostic biopsies at the time of the procedure. MATERIALS AND METHODS: A total of 79 patients (88 renal masses) underwent percutaneous computerized tomography guided biopsy and ablation of a renal mass under conscious sedation. Patients with nondiagnostic biopsies were identified and the medical records were reviewed retrospectively. All patients had an enhancing renal mass on preoperative computerized tomography or magnetic resonance imaging and all underwent postoperative contrast imaging to evaluate persistent viable tumor. RESULTS: A total of 19 patients (20 tumors) with nondiagnostic percutaneous biopsy (22.7% or 20 of 88) were included in the study. No serious complications occurred. Tumors were treated with frequency ablation (12) or cryoablation (7). In 17 patients (89.5%) post-procedure imaging confirmed the absence of contrast enhancement at a median followup of 27.3 months (range 3 weeks to 56 months). In 2 cases (10.5%) post-procedure imaging showed a residual renal mass or recurrence with enhancement, suggesting that the original percutaneous biopsy result was false negative. In 1 patient residual tumor was identified on initial post-ablation imaging and the patient underwent laparoscopic partial nephrectomy. In another patient recurrence was diagnosed 30 months after ablation and the patient underwent laparoscopic radical nephrectomy. Although there was a nondiagnostic percutaneous biopsy in each case, pathological findings in the subsequent surgical specimen confirmed renal cell carcinoma. CONCLUSIONS: Nondiagnostic percutaneous biopsy at renal tumor ablation does not obviate the need for standard post-procedure imaging followup. Of patients with nondiagnostic biopsies in this series 10.5% still harbored viable renal cell carcinoma after percutaneous ablation.     

Comparison of skin transport and metabolism of ethyl nicotinate in various species.

The skin transport and metabolism characteristics of ethyl nicotinate (EN) in rabbit, rat, guinea-pig, pig, shed snake skin and human were compared. In vitro skin transport using excised skin and hydrolysis experiments using skin homogenate were carried out. Flux of EN, a metabolite, nicotinic acid (NA), and the total (EN + NA), as well as kinetic parameters (V(max) and K(m)) for hydrolysis of EN were determined and compared among various species. The enzymatic conversion of EN to NA was observed for all skin permeation experiments. Total flux from EN-saturated solution between rabbit, rat, guinea-pig and human was significantly different (P < 0.05). A great difference between species was observed in skin esterase activity. The NA/total flux ratio of human was significantly lower than that of rabbit, rat or guinea-pig but lower than that of shed snake skin (P < 0.05). There is no significant difference in skin permeation and metabolism between human and pig (P > 0.05). Total flux increased linearly with an increase in EN donor concentration for all species. For pig, shed snake skin and human, NA flux increased with an increase in EN donor concentration and reached a plateau, suggesting the metabolic saturation was taking place in the skin. NA flux at plateau and EN donor concentration in which the NA flux reached a plateau were also affected by species difference. These findings indicated that the discrepancy in transdermal profiles of EN among species tested was predominantly due to the difference in the esterase activity in the skin.     

Combination chemotherapy and photodynamic therapy with fab' fragment targeted HPMA copolymer conjugates in human ovarian carcinoma cells

The biological activities of sequential combinations of anticancer drugs, SOS thiophene (SOS) and mesochlorin e 6 monoethylenediamine (Mce 6), in the form of free drugs, nontargeted N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-drug conjugates, P-GFLG-Mce 6 and P-GFLG-SOS (P is the HPMA copolymer backbone and GFLG is the glycylphenylalanylleucylglycine spacer), and Fab'-targeted HPMA copolymer-drug conjugates, P-(GFLG-Mce 6)-Fab' and P-(GFLG-SOS)-Fab' (Fab' from OV-TL16 antibodies complementary to CD47), were evaluated against human ovarian carcinoma OVCAR-3 cells. Mce 6, SOS, P-GFLG-Mce 6, P-GFLG-SOS, P-(GFLG-Mce 6)-Fab', and P-(GFLG-SOS)-Fab', when used as single agents or in binary combination, exhibited cytotoxic activities against OVCAR-3 cells, as determined using a modified MTT assay. The binding and internalization of P-(GFLG-Mce 6)-Fab' and P-(GFLG-SOS)-Fab' by OVCAR-3 cells were visualized by confocal microscopy and flow cytometry. The results confirmed an enhanced biorecognition by OVCAR-3 cells of Fab'-targeted HPMA copolymer conjugates over nontargeted conjugates. The median-effect analysis and the determination of the combination index (CI) were used to describe the drug interaction and quantify the synergism, antagonism, or additivity in anticancer effects. The sequential combinations of SOS+Mce 6 and P-GFLG-SOS+P-GFLG-Mce 6 displayed very strong synergism to synergism in the entire range of cell inhibition levels ( f a = 0.5 - 0.95). The P-(GFLG-SOS)-Fab'+P-(GFLG-Mce 6)-Fab' exhibited a strong synergism for f a values up to about 0.85, but showed synergistic effect and nearly additive effect at f a = 0.9 and 0.95, respectively. These observations support the continuation of in vivo investigations of these conjugates for the treatment of ovarian cancer.     

Analysis of naphthoquinone derivatives in the Asian medicinal plant Eleutherine americana by RP-HPLC and LC-MS

The first analytical procedure for the determination of a new naphthopyrone, eleutherinoside A, together with the known bioactive compounds eleuthoside B, isoeleutherin, eleutherin and eleutherol in Eleutherine americana was established. Optimum HPLC separation of these naphthoquinone derivatives was possible on RP-12 column material, using water and acetonitrile as mobile phase. Flow-rate, detection wavelength and temperature were adjusted to 1.0 mL/min, 254 nm and 40 degrees C, respectively. Validation results indicated that the HPLC method is well suited for the determination of naphthoquinone derivatives in the bulbs of E. americana with a good linearity (r2>0.9996), precision (intra-day R.S.D. <4.70%, inter-day R.S.D. <5.68%) and recovery rates from 96.26 to 103.48%. Limit of detection (LOD) was found to be below 0.84 microg/mL for all five compounds. LC-MS analyses performed in positive and negative electrospray ionization mode assured peak purity and identity. The analysis of different E. americana samples from Thailand revealed that eleutherol (0.10-0.20%) was dominant in all specimens, followed by isoeleutherin and eleutherin. The new natural product 2,5-dimethyl-10-hydroxynaphthopyrone 8-O-beta-d-glucopyranoside occurred in percentages of less than 0.05%.     

Temperature Measurements of the Low-Attenuation Radiographic Ice Ball During CT-Guided Renal Cryoablation

During renal cryoablation a low-attenuation area on CT develops around the cryoprobe. Knowledge of the temperature of the growing low-attenuation area can guide therapy and ensure lethal temperatures. Herein, we report thermocouple results and correlating CT images during the development of the low-attenuation “radiographic ice ball.” Five patients who underwent percutaneous CT-guided renal cryoablation were identified who had thermocouples inserted and serial intraprocedural CT images that included images with thermocouple measurements of 0° and sub-0°C. Thermocouples had been percutaneously placed just beyond the edge of the tumors either to ensure adequate cooling or to ensure safety to adjacent critical structures. Renal cryotherapy under CT guidance produced a growing low-attenuation area corresponding to the radiographic ice ball. When the thermocouple measured 0°C, CT images showed the thermocouple tip at the edge of the low-attenuation ice ball. At lower temperatures the tip was within the low-attenuation ice ball. We conclude that knowledge of the temperature at the ice ball edge during cryoablation can be used to predict the extent of tissue necrosis and thus provide an estimate of cryotherapy effectiveness during the procedure. Further work is necessary to establish a firm relationship between the thermal conditions and the zone of damage.     

Sexuality and Management of Benign Prostatic Hyperplasia with Alfuzosin: SAMBA Thailand

IntroductionBenign prostatic hyperplasia (BPH) is a common condition among elderly men. The aim of therapy is to improve lower urinary tract symptoms (LUTS) and quality of life (QoL) and to prevent complications.AimThe primary objective was to assess the effect on ejaculatory dysfunction (EjD) of 6 months treatment with alfuzosin (XATRAL) 10 mg once daily (OD) in men with LUTS suggestive of BPH in Thailand. Secondary objectives were to evaluate the efficacy of alfuzosin on LUTS, bother score (International Prostate Symptom Score [IPSS] 8th question), erectile dysfunction (ED), onset of action, and tolerability.MethodsOverall, 99 men with moderate to severe LUTS suggestive of BPH (mean IPSS 18.9, bother score 4.3) were enrolled in an open-label study. Sexual function was evaluated at baseline and after 6 months treatment, using the International Index of Erectile Function-5 and the Male Sexual Health Questionnaire (MSHQ) ejaculation score, a new validated questionnaire assessing seven EjD symptoms.Main Outcome MeasureThe main outcome measure is mean change from baseline to the end of treatment in the MSHQ Ejaculation score.ResultsMHSQ ejaculation score significantly improved from 23.09 at baseline to 21.54 at 6 months (P = 0.022). Overall, 70% of patients perceived an improvement in LUTS within 1 week (36.3% within 3 days). IPSS total score significantly improved from 18.93 at baseline to 9.59 at 6 months (P < 0.001). IPSS voiding and irritative subscores also significantly improved. The percentage of patients with moderate or severe ED decreased from 35.3% at baseline to 21.8% at 6 months. Most adverse events were dizziness (3%) and orthostatic hypotension (1%) with minor intensity. No significant change in blood pressure and heart rate was observed.ConclusionsAlfuzosin 10 mg OD administered for 6 months provides a marked and rapid (within 1 week) improvement in LUTS and bother score while improving both ED and EjD. Leungwattanakij S, Watanachote D, Noppakulsatit P, Petchpaibuol T, Choeypunt N, Tongbai T, Wanamkang T, Lojanapiwat B, Permpongkosol S, Tantiwong A, Pripatnanont C, Akarasakul D, Kongwiwatanakul S, and Chotikawanich E. Sexuality and management of benign prostatic hyperplasia with alfuzosin: SAMBA Thailand.     

Acute enhancing effect of a standardized extract of Centella asiatica (ECa 233) on synaptic plasticity: an investigation via hippocampal long-term potentiation

ContextECa 233 is the standardized extract of Centella asiatica (L.) Urban. (Apiaceae). It contains at least 85% of triterpenoid glycosides and yields neuroprotective and memory-enhancing effects. However, the exact molecules exerting the effects might be triterpenic acid metabolites reproduced through gut metabolism after orally ingesting C. asiatica, not triterpenoid glycosides.ObjectiveThis study demonstrates the effect of unmetabolized ECa 233 on hippocampal synaptic plasticity after directly perfusing ECa 233 over acute brain slices.Materials and methodsThe brain slices obtained from 7-week-old male Wistar rats were randomly divided into 4 groups. We perfused either artificial cerebrospinal fluid (ACSF), 0.01% DMSO, 10 µg/mL ECa 233, or 100 µg/mL on brain slices, and measured the long-term potentiation (LTP) magnitude to determine the synaptic plasticity of hippocampal circuits in each group.ResultsThe LTP magnitude of ACSF, DMSO, 10 ug/mL ECa 233, and 100 ug/mL ECa 233 groups increased from 100% to 181.26 ± 38.19%, 148.74 ± 5.40%, 273.71 ± 56.66%, 182.17 ± 18.61%, respectively. ECa 233 at the concentration of 10 µg/mL robustly and significantly enhanced hippocampal LTP magnitude. The data indicates an improvement of the hippocampal synaptic plasticity.Discussion and conclusionsThis study emphasizes the effectiveness of triterpenoid glycosides in ECa 233 on synaptic plasticity enhancement. Therefore, this study supported and complimented the known effects of C. asiatica extract on the enhancement of synaptic plasticity, and subsequently, learning and memory, suggesting that ECa 233 could be a promising memory enhancing agent.     

The maternal and offsprings’ characteristics associated with HOMA-IR in young adults: a prospective cohort study

International Journal of Diabetes in Developing Countries - Diabetes is an important chronic disease. Many studies from Western countries found that both maternal environment during pregnancy and...     

Analysis of allograft biopsy specimens from long-term surviving patients with stable renal function: predictive value of long-term graft prognosis

Abstract: Chronic allograft dysfunction is multi-factorial, and histology of long-term renal allograft shows variable findings. It is important to characterize the pathological features of graft kidneys with normal function to understand the natural course of transplants, which in turn would contribute to elucidate the causes of chronic allograft nephropathy (CAN). To address this issue, we performed 'non-episode' biopsies on well-functioning renal allografts, and evaluated the correlation between clinical outcome and histopathological findings. Patients who underwent a non-episode biopsy had a serum creatinine concentration less than 2.0 mg/dL, urinary protein of less than 500 mg/day and a stable clinical course. In total, 90 such biopsies were performed. Mean follow-up period after biopsy was 29 ± 16 months. We evaluated the histopathological findings and clinical outcome on each finding. Moreover, we compared the findings in the patients on tacrolimus with those of patients taking cyclosporin. Twenty-three biopsy specimens were essentially normal. Graft dysfunction during the follow-up period was recognized more frequently in patients showing more than one pathological process than in those with isolated findings. Graft outcome was not associated with drug-induced nephropathy, but with acute rejection ( P  = 0.0193) and CAN ( P  = 0.0032). Patients found to have CAN-b had a worse outcome than those with CAN-a. CAN-b was less common in the tacrolimus group than in the cyclosporin group. Non-episode biopsy has a predictive value of the long-term outcome of a renal allograft. CAN is associated with graft dysfunction; neither is drug-induced nephropathy. Patients treated with tacrolimus had lower rates of CAN-b than did cyclosporin-treated subjects.