The ameliorative effect of rosmarinic acid and epigallocatechin gallate against doxorubicin-induced genotoxicity.

Doxorubicin (Dox), an effective anticancer agent, is known for its genotoxic effects on normal cells. Phenolic compounds, renowned for their antitumor, antioxidant, and antigenotoxic properties, have gained prominence in recent years. This study investigates the individual and combined protective effects of rosmarinic acid (RA) and epigallocatechin gallate (EGCG) against Dox-induced genotoxicity using various in vitro test systems. The synergistic/antagonistic interaction of these combinations on Dox's chemotherapeutic effect is explored in breast cancer cell lines. Both RA and EGCG significantly mitigate Dox-induced genotoxicity in comet, micronucleus, and Ames assays. While Dox exhibits higher selectivity against MCF-7 cells, EGCG and RA show greater selectivity against MDA-MB-231 cells. The coefficient of drug interaction reveals a synergistic effect when RA or EGCG is combined with Dox in breast cancer cells. In conclusion, both EGCG and RA effectively reduce Dox-induced genetic damage and enhance Dox's cell viability-reducing effect in breast cancer cells.

Rosmarinic acid (RA) showed protective effect against doxorubicin-induced genotoxicity.Epigallocatechin gallate (EGCG) demonstrated pro-oxidant properties at high concentrations.EGCG and RA selectively targeted MDA-MB-231 cells.Synergistic effect was observed when EGCG or RA was administered together with Dox on breast cancer cells.

Giant left pheochromocytoma with vascular anomalies and pelvic horseshoe kidney: a case report.

BACKGROUND: Pheochromocytoma is a neuroendocrine tumor, and its treatment is dependent on surgical resection. Due to the wide availability of cross-sectional imaging, pheochromocytomas are commonly seen as small tumors less than 10 cm in size and are mostly treated with minimally invasive surgery. Their concomitant presence with horseshoe kidney or other anatomical and vascular anomalies is rare. Herein, we present a surgically complex giant pheochromocytoma case who underwent an open left radical adrenalectomy. CASE PRESENTATION: A 41-year-old Hispanic female presented with a 12 × 8 cm left hypervascular adrenal mass, pelvic horseshoe kidney, and severely dilated large left retro-aortic renal vein which branched into a left adrenal vein, congested left ovarian vein, and left uterine plexus. She was managed with insulin and metformin for uncontrolled diabetes with an A1c level of 9% and doxazosin for persistent hypertension. Clinical diagnosis of pheochromocytoma was confirmed with elevated urine and serum metanephrine and normetanephrine. The pre-operative ACTH was within normal range with a normal dexamethasone suppression test and 24-hour urine free cortisol. The adrenalectomy of the highly aggressive adrenal mass was performed via open approach to obtain adequate surgical exposure. Due to the large size of the tumor and its significant involvement with multiple adjacent structures, coordination with multiple surgical teams and close hemodynamic monitoring by anesthesiology was required for successful patient outcomes including preservation of blood supply to the pelvic horseshoe kidney. The histopathological diagnosis was pheochromocytoma with negative surgical margins. The patient was followed at 1, 4, 12, and 24 weeks postoperatively. She had a normal postoperative eGFR and was able to discontinue antihypertensive and antidiabetic medications at four weeks. She had transient adrenal insufficiency, which resolved at five months. The horseshoe kidney was intact except for a minimal area of hypo-enhancement in the left superior renal moiety due to infarction, which was significantly improved at six months. CONCLUSION: Our patient had a giant pheochromocytoma with anatomical variations complicating an already surgically challenging procedure. Nonetheless, with multiple provider collaboration, detailed pre-operative surgical planning, and meticulous perioperative monitoring, radical resection of the giant pheochromocytoma was safe and feasible with successful postoperative outcomes.

Resuscitating the resuscitation: A single-centre experience on extracorporeal cardiopulmonary resuscitation.

AIM: Extracorporeal cardiopulmonary resuscitation (ECPR) is the rapid deployment of venoarterial extracorporeal membrane oxygenation (ECMO) during active cardiopulmonary resuscitation or in patients with intermittent return of spontaneous circulation. This study aimed to describe the demographic characteristics and outcomes of patients undergoing ECPR to identify survival-associated factors. METHODS: The study was conducted in an extracorporeal life support centre of a tertiary hospital in Turkey and included all patients who underwent ECPR for in-hospital cardiac arrest between April 2013 and June 2021. Complications included bleeding, neurological injury, renal failure, hepatic failure, limb ischemia and bloodstream infections. The primary outcomes were survival of ECMO and survival to discharge. Neurological outcomes were assessed using the Pediatric Cerebral Performance Category Scale for children and the Category of Cerebral Performance Scale for adults. RESULTS: The study included 26 patients (24 paediatric, 2 adults), 22 (85%) of them had cardiac pathology. Bleeding was the most common complication. Twelve (46%) patients survived ECMO, 9 (35%) survived to discharge. Sex, age, primary diagnosis, cardiac arrest rhythm and ECMO duration were not significantly associated with the primary outcomes. Bleeding, neurological injury and renal failure were associated with poorer survival to discharge. The neurological outcomes of all survivors to discharge were good. CONCLUSIONS: ECPR is not commonly accessible. Sharing the experience of the few treating centres to date is crucial to accumulating sufficient knowledge about its efficiency and raising clinician awareness. This limited single-centre experience demonstrated the utility of ECPR.

Challenging a dogma: left ventriculotomy can be used safely in children.

OBJECTIVE: We aimed to discuss our unit's experience performing left ventriculotomies on children. METHODS: Between 2000 and 2022, we identified paediatric patients who required left ventriculotomy. Relevant information was gathered retrospectively. RESULTS: There were eight patients who underwent surgical procedure including left ventriculotomy. The range of weight and age was between 4.5 and 50 kg and 5 months to 17 years, respectively. Left ventriculotomy was primarily performed for the excision of cardiac masses in all but one who had pseudoaneurysm repair. There were no deaths that occurred early or late. Pre-operative and post-operative ejection fractions and fractional shortening values were comparable. There was no arrhythmia detected post-operatively. CONCLUSIONS: We conclude that an apical left ventriculotomy does not compromise the function of the left ventricle, even in young infants. In selected patients, it may be used safely for surgical access to the left ventricle.

The Design of Low-Cost Stand-Alone Microcontroller-Based Wireless Ultrasonic System for Process Monitoring and Analysis.

OBJECTIVES: Ultrasound technology is currently used in many areas, such as imaging, analysis, and process monitoring. The noninvasive implementation, nondestructive effect on the material to be applied, and low cost of the needed components give an advantage to the ultrasonic systems when compared to other methods for analysis and process monitoring studies. However, the current ultrasonic analysis setups used in the studies require additional devices such as a signal generator and oscilloscope. These devices used in the setup increase the cost, size, usage difficulty of the system and, most importantly, decrease the portability and stability. In order to prevent these disadvantages, an ultrasonic system that can work in real-time and its software are developed to be used in analysis and process monitoring without any additional devices. METHODS: This system was designed by using a microcontroller. The developed system is portable, has a small size, and a Bluetooth Low Energy connection. It has a battery for using standalone. RESULTS: Therefore, it can be easily used in different small and closed measurement environments such as incubators and controlled remotely. In addition, a mixture was analyzed with both the designed system and a commercial module. When the results are compared, two systems are found highly correlated r 2 = 1 . CONCLUSION: In this study, an embedded ultrasonic measurement system and its software are developed to be used in analysis studies, density measurements, and real-time process monitoring as a stand-alone device.

Pathological and Survival Outcomes Associated with Variant Histology Bladder Cancers Managed by Cystectomy with or without Neoadjuvant Chemotherapy.

PURPOSE: Although neoadjuvant chemotherapy is associated with a survival advantage in pure urothelial, muscle invasive bladder cancer, the role of neoadjuvant chemotherapy is less clear in variant histology or urothelial carcinoma with divergent differentiation. We compared chemotherapy response and survival outcomes of patients with nonpure urothelial carcinoma histology who were managed with neoadjuvant chemotherapy followed by cystectomy vs cystectomy alone. MATERIALS AND METHODS: We analyzed 768 patients with clinical muscle invasive bladder cancer (cT2-4N0M0) who were treated with cystectomy at a tertiary care center from 2007 to 2017. Patients were stratified by histology and treatment strategy. Adjusted logistic and Cox regression models were used to evaluate pathological downstaging, cancer specific survival and overall survival. RESULTS: The cohort consisted of 410 patients (53%) with pure urothelial carcinoma, 185 (24%) with urothelial carcinoma with divergent differentiation and 173 (23%) with variant histology. Overall, 314 patients (41%) received neoadjuvant chemotherapy prior to cystectomy. There were similar rates of complete (18% to 30%) and partial (37% to 46%) pathological downstaging with neoadjuvant chemotherapy across all histological subgroups (p=0.30 and p=0.40, respectively). However, while patients with pure urothelial carcinoma experienced an overall survival benefit (HR 0.71, 95% CI 0.51-0.98, p=0.0013) and those with variant histology experienced a cancer specific survival benefit (HR 0.55, 95% CI 0.30-0.99, p=0.0495) with neoadjuvant chemotherapy, patients with urothelial carcinoma with divergent differentiation did not experience overall or cancer specific survival benefits with the use of neoadjuvant chemotherapy prior to cystectomy. CONCLUSIONS: Among patients with muscle invasive bladder cancer those with nonpure urothelial carcinoma histology with variant histology achieved nearly equivalent response rates and survival benefits with the use of neoadjuvant chemotherapy as those with pure urothelial carcinoma, while patients with urothelial carcinoma with divergent differentiation experienced significantly worse survival outcomes regardless of the use of neoadjuvant chemotherapy prior to cystectomy.

Retroperitoneal Lymph Node Dissection Versus Surveillance for Adult Early Stage Pure Testicular Teratoma: A Nationwide Analysis.

PURPOSE: Following radical orchiectomy, surveillance and primary retroperitoneal lymph node dissection (RPLND) are acceptable options for the management of early stage pure testicular teratoma in adult patients; however, there is no uniform consensus. The aim of this study was to investigate survival outcomes of adults with early stage pure testicular teratoma based on management strategy. METHODS: Data was extracted from the National Cancer Database (NCDB) from testicular cancer patients diagnosed with clinical stage (CS) I pure teratoma (pT1-4N0M0S0) between 2004 and 2014. Kaplan-Meier and Cox regression analyses were used to assess clinical outcomes based on management strategy. RESULTS: Of the 61,167 patients diagnosed with testicular cancer, 692 (1.1%) had pure teratoma. Only individuals with CS I disease were considered (n = 237). The median age was 28 (23-35) years. Overall, 43 (18%) patients underwent RPLND and 194 (82%) patients were managed with surveillance. There was an increase in surveillance for CS I teratoma during the study period. Increasing distance from residence to treatment facility was an unadjusted predictor for undergoing primary RPLND (p < 0.001). Median follow-up was 54 months and there was no significant difference in overall survival between CS I teratoma patients managed with RPLND and those managed with surveillance (p = 0.13). CONCLUSIONS: There has been a trend toward increasing adoption of surveillance for the management of early stage pure testicular teratoma in adults. Our findings suggest that surveillance provides comparable survival outcomes to primary retroperitoneal lymph node dissection in this setting.

Ameliorating Effects of ß-Glucan on Epigastric Artery Island Flap Ischemia-Reperfusion Injury.

BACKGROUND: Ischemia-reperfusion injury has been one of the culprits of tissue injury and flap loss after island flap transpositions. Thus, significant research has been undertaken to study how to prevent or decrease the spread of ischemia-reperfusion injury. Preventive effects of ß-glucan on ischemia-reperfusion injury in the kidney, lung, and small intestine have previously been reported. In this study, we present the ameliorating effects of ß-glucan on ischemia-reperfusion injury using the epigastric artery island-flap in rats. MATERIALS AND METHODS: Thirty Wistar-Albino rats were equally divided into three groups: sham, experimental model, and treatment groups. In the sham group, an island flap was elevated and sutured back to the original position without any ischemia. In the experimental model group, the same-sized flap was elevated and sutured back with 8 h of ischemia and consequent 12 h of reperfusion. In the treatment group, 50 mg per kilogram ß-glucan was administered to the rats using an orogastric tube for 10 d before the experiment. The same-sized flap is elevated and sutured back to its original position with 8 h of ischemia and 12 h of consequent reperfusion in the treatment group. Tissue biopsies were taken on the first day of the experimental surgery. Tissue neutrophil aggregation and vascular responses were evaluated by histological examinations. Tissue oxidant and antioxidant enzyme levels are evaluated biochemically after tissue homogenization. Topographic follow-up and evaluation of the flaps were maintained, and photographs were taken on the first and seventh day of the experimental surgery. RESULTS: Topographic flap survival was significantly better in the ß-glucan administered group. The neutrophil number, malondialdehyde, and myeloperoxidase levels were significantly lower while glutathione peroxidase and superoxide dismutase levels were significantly higher in the ß-glucan administered group respective to the experimental model group. CONCLUSIONS: Based on the results of our study, we can conclude that ß-glucan is protective against ischemia-reperfusion injury. Our study presents the first experimental evidence of such an effect on skin island flaps.

Rerouting anomalous coronary artery origin in aortopulmonary window in newborn.

Coronary artery anomalies may accompany the aortopulmonary window and, if not noticed, may cause catastrophic consequences. The repair of the aortopulmonary window is quite straightforward; however, establishing a normal coronary pattern may challenge the repair. When the anomalous origin of the coronary artery is on the defect rim, right at the location where sutures are to be placed, it may interfere with proper suture placement. A technique to overcome such a technical obstacle and reroute the anomalous right coronary in such cases is described.

Bilateral thoracoscopic sympathectomy for cardiac denervation in pediatric population: Does Kuntz nerve cauterization have an impact on success?

INTRODUCTION: Cardiac sympathetic denervation (CSD) is an effective procedure for the treatment of inherited channelopathies. Left CSD has traditionally been recommended as neuromodulation to prevent arrhythmia episodes; however, it is thought that bilateral sympathectomy in combination with Kuntz ablation may have additional effects effective due to the anatomical variability of preganglionic sympathetic fibers. The aim of the study was to share our single-center clinical experience with bilateral thoracoscopic sympathectomy for cardiac denervation in different groups of pediatric patients with malignant arrhythmias. METHODS: Fourteen patients (seven with CPVT, five with LQTS, one with resistant ventricular tachycardia as a sequela of myocarditis, and one with cardiomyopathy and atrial tachycardia) underwent bilateral thoracoscopic sympathectomy for cardiac denervation. RESULTS: In all patients, arrhythmia episodes persisted despite medical therapy, and patients with implantable cardioverter-defibrillator received appropriate therapies. The rate of appropriate therapies was 3.25 per year (1-5 per year) in the year before sympathectomy. No major complications related to the procedure were observed in any of the patients. The QTc interval of LQTS patients decreased from 506.2 ± 16.9 ms before the procedure to 476 ± 28.8 ms after the procedure. The mean duration of follow-up after the procedure was 23.3 months (11-47 months). Only two patients received single episodes of therapy 12 and 22 months after CSD, and one patient had arrhythmic events due to noncompliance to medical therapy. CONCLUSION: Due to the anatomical variability of preganglionic fibers bilateral CSD with Kuntz nerve ablation effective treatment and is a safe option.

Toxicological evaluation of ergocalciferol, cholecalciferol, and their metabolites by a category approach.

Predictive toxicology plays an integral role in determining the toxicological profiles of chemicals for safety assessment. Vitamin D is an essential vitamin for the regulation of calcium absorption and homeostasis, as well as the treatment and prevention of several diseases such as rickets and osteomalacia. According to European Medicines Agency (EMA) Guideline on setting health-based exposure limits for use in risk identification in the manufacturing of different medicinal products in shared facilities, permitted daily exposure (PDE) calculation for active pharmaceutical ingredients (APIs) should be done by the medicinal product producers. PDE calculation is mainly based on critical toxicological endpoints such as repeated dose toxicity, genotoxicity, carcinogenicity, developmental and reproductive toxicity, and hypersensitivity potential. During this procedure, critical toxicological endpoints data of an API can be used to predict the PDE of another API that has a similar chemical structure. In the present paper, human toxicological endpoints of vitamin D2, D3, and their metabolites were evaluated and afterwards the data gaps in the toxicological endpoints were filled by forming a category. The read-across was justified by the structural and metabolic similarities. Molecular similarity and mechanistic relevance were found to be substantial, resulting in low uncertainty. The untested vitamin D analogs within the category can be read across with confidence to complete the data gaps related to the human health endpoints.

Protective Effect of Nigella sativa and Nigella damascena Fixed Oils Against Aflatoxin Induced Mutagenicity in the Classical and Modified Ames Test.

The antioxidant and mutagenic/antimutagenic activities of the fixed oils from Nigella sativa (NSO) and Nigella damascena (NDO) seeds, obtained by cold press-extraction from the cultivar samples, were comparatively investigated for the first time. The antimutagenicity test was carried out using classical and modified Ames tests. The fatty acid composition of the fixed oils was characterized by gas chromatography-mass spectrometry (GC-MS) while the quantification of thymoquinone in the fixed oils was determined by UPC2 . The main components of the NSO and NDO were found to be linoleic acid, oleic acid, and palmitic acid. The results of the Ames test confirmed the safety of NSO and NDO from the viewpoint of mutagenicity. The results of the three antioxidant test methods were correlated with each other, indicating NDO as having a superior antioxidant activity, when compared to the NSO. Both NSO and NDO exhibited a significant protective effect against the mutagenicity induced by aflatoxin B1 in Salmonella typhimurium TA98 and TA100 strains. When microsomal metabolism was terminated after metabolic activation of the mycotoxin, a significant increase in antimutagenic activity was observed, suggesting that the degradation of aflatoxin B1 epoxides by these oils may be a possible antimutagenic mechanism. It is worthy to note that this is the first study to assess the mutagenicity of NSO and NDO according to the OECD 471 guideline and to investigate antimutagenicity of NDO in comparison to NSO against aflatoxin.

Ultrasound based noninvasive real-time cell proliferation process monitoring.

The proliferation process's efficiency is related to the number of cells grown in culture and the maximum efficiency obtained at the stationary phase. Since the culture's growth speed is different for various cells and even for subgroups of the same cells, it is essential to monitor the process properly to obtain maximum efficiency. In this work, ultrasonic velocity measurement was performed noninvasively for wireless real-time monitoring of the suspension cell culture using a single integrated device to get maximum efficiency from the process by determining the phases. Using the advantage of the developed device's portability and wireless connectivity, the cells are monitored in the incubator without interfering with the actual process. Therefore, a real-time highly sampled growth curve is obtained, which was not possible to obtain with the currently used methods or the offline methods that are based on taking samples from the culture invasively. Filtering and curve fitting methods are also applied to the data to obtain a clean growth curve. The method developed as a result of this study ensures that the suspension cell culture was monitored most conveniently in the actual growth medium in real-time and noninvasively.

Ocular microemulsion of brinzolamide: Formulation, physicochemical characterization, and in vitro irritation studies based on EpiOcular™ eye irritation assay.

In recent years, the hydrophobic active substances have led researchers to develop new formulations to enhance bioavailability and dissolution rate; brinzolamide, a lipophilic drug belongs to carbonic anhydrase inhibitors, which cause reduction of intraocular pressure in patients suffering from glaucoma. Currently, the marketed product of brinzolamide is in the form of ocular drops; nonetheless, the conventional drops provide decreased therapeutic efficacy owing to their low bioavailability and pulsed drug release. Thus, the development of novel ocular formulations such as topical microemulsions is of high importance. In this work, the preparation of new microemulsions containing brinzolamide (0.2, 0.5 and 1% w/w) and comprised from isopropyl myristate, tween 80 and span 20 and Cremophor EL was performed. The obtained microemulsions were further characterized for their physicochemical properties. In addition, Fourier Transformed-Infrared spectroscopy was used touate the compatibility of active ingredients and components. In vitro release studies along with kinetic modeling were performed using the dialysis membrane method in simulated tear fluid. Bioadhesion studies were performed using Texture analysis. Finally, in vitro ocular irritation based on EpiOcular™ Eye Irritation Test and cytocompatibility studies was performed to examine any possible harm on ocular cells and predict in vivo safety profile.

Overcoming sociodemographic factors in the care of patients with testicular cancer at a safety net hospital.

BACKGROUND: The objective of this study was to determine whether standardized treatment of germ cell tumors (GCTs) could overcome sociodemographic factors limiting patient care. METHODS: The records of all patients undergoing primary treatment for GCTs at both a public safety net hospital and an academic tertiary care center in the same metropolitan area were analyzed. Both institutions were managed by the same group of physicians in the context of multidisciplinary cancer care. Patients were grouped by care center; clinicopathologic features and outcomes were analyzed. RESULTS: Between 2006 and 2018, 106 and 95 patients underwent initial treatment for GCTs at the safety net hospital and the tertiary care center, respectively. Safety net patients were younger (29 vs 33 years; P = .005) and were more likely to be Hispanic (79% vs 11%), to be uninsured (80% vs 12%; P < .001), to present via the emergency department (76% vs 8%; P < .001), and to have metastatic (stage II/III) disease (42% vs 26%; P = .025). In a multivariable analysis, an absence of lymphovascular invasion (odds ratio [OR], 0.30; P = .008) and an embryonal carcinoma component (OR, 0.36; P = .02) were associated with decreased use of adjuvant treatment for stage I patients; hospital setting was not (OR, 0.67; P = .55). For patients with stage II/III nonseminomatous GCTs, there was no difference in the performance of postchemotherapy retroperitoneal lymph node dissection between the safety net hospital and the tertiary care center (52% vs 64%; P = .53). No difference in recurrence rates was observed between the cohorts (5% vs 6%; P = .76). CONCLUSIONS: Sociodemographic factors are often associated with adverse clinical outcomes in the treatment of GCTs; they may be overcome with integrated, standardized management of testicular cancer.

Systematic Review and Meta-Analysis-Is there a Benefit in Using Neoadjuvant Systemic Chemotherapy for Locally Advanced Penile Squamous Cell Carcinoma?

PURPOSE: Neoadjuvant chemotherapy is a recommended treatment for patients with penile cancer with bulky inguinal lymphadenopathy or unresectable primary tumors, although there is no evidence of its benefit from randomized trials. MATERIALS AND METHODS: We conducted a systematic search in Embase® and MEDLINE® for studies reporting on patients who received preoperative neoadjuvant chemotherapy for locally advanced penile squamous cell carcinoma. Objective response rate, pathological complete response, grade 3 or greater toxicity and overall mortality were evaluated in terms of neoadjuvant chemotherapy type, which was dichotomized as nontaxane-platinum and taxane-platinum regimens. RESULTS: Overall 10 studies met the inclusion criteria, enrolling a total of 182 patients, with 66 (36.3%) and 116 (63.7%) treated with nontaxane-platinum and taxane-platinum regimens, respectively. The pooled results demonstrated an objective response rate of 53% (95% CI 42-64), pathological complete response rate of 16%, grade 3 or greater toxicity rate of 40% (95% CI 19-64) and overall mortality of 55% (95% CI 40-70) in patients treated with neoadjuvant chemotherapy. Stratified subanalysis revealed an objective response rate of 55% and 49%, a pathological complete response of 9% and 20%, a toxicity rate of 26% and 49%, and an overall mortality of 54% and 58% for nontaxane-platinum vs taxane-platinum regimens, respectively. CONCLUSIONS: The pooled findings in this study suggest that approximately 50% of the patients with bulky regional lymph node metastases from penile cancer respond to platinum based neoadjuvant chemotherapy and approximately 16% of patients achieve a pathological complete response. Nontaxane based regimens appear to be better tolerated than taxane regimens based on reported grade 3 or greater adverse events (26% vs 49%). Ultimately the robustness of these observations should be interpreted with an awareness of the inherent limitations of deriving data from a collection of small, heterogeneous series.

Prognostic significance of pre- and post-treatment PD-L1 expression in patients with primary high-grade non-muscle-invasive bladder cancer treated with BCG immunotherapy.

PURPOSE: Programmed cell death-1 ligand-1 (PD-L1) expression has been associated with prognostic implications in urologic malignancies. We aimed to investigate prognostic significance of pre- and post-treatment PD-L1 expression in patients treated with BCG for high-grade non-muscle-invasive bladder cancer (NMIBC). METHODS: We reviewed a total of 141 high-grade NMIBC cases treated with transurethral resection + ≥ 6 BCG instillations between 2004 and 2017. PD-L1 immunohistochemistry (IHC) scoring was done on 0-3 scale, and cut-off for positive and high-level PD-L1 expression was set to ≥ 1% and ≥ 5% staining of tumor-infiltrating immune cells (IC), respectively. Clinicopathologic characteristics and oncologic outcomes [recurrence-free (RFS) and progression-free survival (PFS)] were compared, stratified by PD-L1 positivity. The prognostic role of PD-L1 was assessed using Kaplan-Meier, and univariate and multivariate Cox regression analyses. RESULTS: Pre-treatment, 46.2% and 6.8% of high-grade NMIBC demonstrated positive and high-level PD-L1 expression, respectively. Positive PD-L1 expression was associated with submucosal invasion and refractory-tumor recurrence. PD-L1 expression was not associated with RFS or PFS in regression analysis. Post-treatment, 55.1% and 11.6% of recurrent tumors demonstrated positive and high-level PD-L1 expression, respectively. Down-regulation of PD-L1 expression was noted in patients with refractory recurrence (p = 0.012). CONCLUSION: Pre-treatment PD-L1 expression was associated with unfavorable pathological features in primary high-grade NMIBC and its expression level after BCG immunotherapy was significantly decreased in patients with refractory recurrence. PD-L1 expression did not have prognostic value for PFS or RFS; therefore, further research is necessary to identify novel biomarkers for prediction of disease outcomes in high-grade NMIBC.

Focal bipolar radiofrequency ablation for localized prostate cancer: Safety and feasibility.

OBJECTIVES: To evaluate the safety and feasibility of focal bipolar radiofrequency ablation in men with localized prostate cancer. METHODS: A review of 10 patients treated with a novel bipolar radiofrequency ablation probe integrated in a coil design (Encage; Trod Medical, Bradenton, FL, USA) between 2011 and 2017 in two prospective pilot trials. All men had clinical stage T1c prostate cancer, prostate-specific antigen <10 ng/mL and Gleason score ≤7. Ablation was carried out under general anesthesia, and bipolar probes were inserted transperineally under transrectal ultrasound guidance. Treatment-related adverse events, quality of life and negative biopsy rate were evaluated at 6 months after ablation. The Wilcoxon signed-rank test was used to compare baseline and post-treatment symptom scores. RESULTS: The median age was 58 years (range 50-64 years) and the median prostate volume was 49.65 cc (range 21-68 cc). Prostate cancer with a Gleason score of 6 (3 + 3) and 7 (3 + 4) was noted in seven and three patients, respectively. The median number of radiofrequency ablation cycles was 2.5 (range 2-5). All patients were catheter-free and able to void the day of surgery. Within 6 months after ablation, all adverse events were low grade, with the exception of one grade 3 hematuria that required cystoscopy without coagulation. Six months after ablation bowel, urinary and hormonal functions, and overall satisfaction remained stable. Erectile dysfunction occurred in two out of four patients who had normal sexual function before the procedure. Neither urinary incontinence nor urinary infection was noted. CONCLUSIONS: This first report on focal bipolar radiofrequency ablation documents a safe and feasible treatment option for selected patients with localized prostate cancer.

Uncommon Childhood Unilateral Cervical Giant Thymic Cyst.

Cervical thymic cysts are rare and present in the first decade of life. They constitute 0.3% to 1% of congenital neck masses. Thymic tissue foci, which exist between the mandible and the mediastinum, can be found at the descent of the thymic primordium. Thymic cysts should be considered in pediatric patients who present with cervical neck masses. The diagnosis of thymic cysts can only be made by histopathologic examinations. In recent years, the number of reports of thymic cyst cases have increased, one possible cause being the heightened awareness of thymic cysts among pathologists.

Tazarotene-loaded in situ gels for potential management of psoriasis: biocompatibility, anti-inflammatory and analgesic effect.

Psoriasis is a chronic autoinflammatory disorder characterized by patches of abnormal skin. For psoriasis management, the application of topical retinoids as Tazarotene is recommended. However, Tazarotene could induce skin irritation limiting its use. Herein, it is evaluated the possible usage of in situ gels for tazarotene skin delivery. The topical in situ gels were developed using thermosensitive poloxamers via cold method. They were examined for their appearance, sol-gel temperature, clarity, pH, viscosity, in vitro release, and stability. Their biocompatibility was evaluated by investigating their cytotoxicity and irritation inducing capacity. The possible anti-inflammatory and analgesic activities were determined by measuring the nitric oxide and prostaglandin E2 levels production in LPS-stimulated RAW264.7 murine macrophage cells. It was revealed that the in situ gels had no cytotoxic effect (∼95-100% cell viability) and nor irritation potential (∼97% cell viability), according to the in vitro EpiDerm™ reconstituted skin irritation test. Additionally, the 10% tazarotene-in situ gels showed possible analgesic activity since the production of prostaglandin E2 (PGE2) was decreased. In further, both concentrations of 5% and 10% tazarotene-in situ gels inhibited significantly the nitrite oxide production at 16% and 19%, respectively. Finally, the prepared in situ gels can act as a potential non-irritant alternative option for tazarotene topical skin delivery.