Body mass weighted PSA levels, new markers to predict locally advanced prostate cancer after prostatectomy.

BACKGROUND: PSA remains the most useful marker for screening, risk categorization, and follow-up in patients with prostate cancer. In the obese population, several studies have revealed that obesity may not only inversely interfere with the concentration of PSA, but also increase the risk of prostate cancer. Thus, we considered using the Body mass weighted PSA levels, presented as serum PSA concentration multiplied by body weight or BMI, instead of traditional PSA concentration, as potential markers to predict locally advanced prostate cancer after prostatectomy. METHODS: We retrospectively collected and analyzed data acquired from a single institute at which robot-assisted laparoscopic radical prostatectomy was performed. A total of 174 patients underwent radical prostatectomy, and the collected data included age, PSA level, body weight, BMI, and pathology results. RESULTS: A total of 174 patients diagnosed with adenocarcinoma of the prostate by needle biopsy, and most (N=165) were considered to have localized disease on preoperative multi-parameter magnetic resoanace imaging. After prostatectomy, 73% (N=127) of the patients remained in the localized disease group (group A) and 27%(N=47) of the patients were reclassified to the locally advanced prostate cancer (group B). The value of PSA was higher in Group B (16.9 vs 11.2 ng/dL; p= 0.062), but there was no statistically significant difference between the two groups. After using the numerical values of PSA x body weight and PSA x BMI, a statistically significant difference emerged between the two groups (p= 0.0198 in PSA × BW; p=0.0110 in PSA × BMI). CONCLUSION: The Body mass weighted PSA levels, instead of the traditional PSA concentration, may be better markers for predicting non-organ-confined disease after surgery. It may also be useful in screening and risk categorization.

Inhalable chitosan-based hydrogel as a mucosal adjuvant for hydroxychloroquine in the treatment for SARS-CoV-2 infection in a hamster model.

BACKGROUND: Effective therapy for COVID-19 remains limited. Hydroxychloroquine (HCQ) has been considered, but safety and efficacy concerns remain. Chitosan exhibits antiviral and immunomodulatory effects, yet how the combination of HCQ and chitosan performs in treating COVID-19 is unknown. METHODS: Male Syrian hamsters were inoculated intranasally with standardized stocks of the SARS-CoV-2 virus. Hamsters were allocated to saline (PBS), chitosan oligosaccharide (COS), HCQ, or COS + HCQ groups and received corresponding drugs. On days 1, 7, and 14 post-infection, two animals from each group were euthanized for sample collection. Viral loads were measured in lung homogenates. Biochemistry markers, cytokines, and immunoglobulins were analyzed from hamster sera. HCQ concentrations were compared between the blood, bronchoalveolar lavage, and lung tissues. All groups underwent histopathology exams of the lungs. Additional hamsters were treated with the same drugs to assess for toxicities to the heart and liver. RESULTS: Among all groups, viral loads in the COS + HCQ group were the lowest by day 8. The COS + HCQ group produced the highest interleukin (IL)-6 levels on day 4, and the highest IL-10, IgA and IgG levels on day 8. HCQ concentrations were higher in the COS + HCQ group's lungs than the HCQ group, despite having received half the dose of HCQ. Histopathology demonstrated earlier inflammation resolution and swifter viral clearance in the COS + HCQ group. There was no evidence of cardiac or hepatic injury in hamsters that received HCQ. CONCLUSION: In hamsters infected with the SARS-CoV-2 virus, the combination of intranasal COS and HCQ was associated with increased HCQ absorption in the lungs, more effective immune responses, without increasing the risk of hepatic or cardiac injuries.

Circulating Tumor Cells Predict Response of Neoadjuvant Chemotherapy in Patients with Bladder Cancer: A Preliminary Study.

This study aimed to explore the existence of circulating tumor cells (CTCs) in patients with muscle-invasive bladder cancer (MIBC) and their predictive potential for response to neoadjuvant chemotherapy (NAC). From 33 blood samples of MIBC patients, CTCs were isolated by cell surface markers and enriched by the IsoFlux™ device, followed by morphological and immunofluorescent identification. CTCs were detected at baseline in all samples. Immunofluorescence confirmed the tumor origin. MIBC patients were stratified by NAC response into the disease control (DC) and progressive disease (PD) groups. In the DC group, the number of CTCs decreased significantly after four courses of NAC (p < 0.0001). CTC counts in 7.5 mL after four NAC cycles were highly correlated with postoperative pathological T stage (p < 0.0001). Our study demonstrated that CTCs might represent a valuable predictive marker for NAC response in MIBC. CTC detection in MIBC patients could allow early arrangement of radical cystectomy for NAC non-responders to prevent disease progression while receiving the NAC courses.

Darolutamide for non-metastatic castration-resistant prostate cancer: Efficacy, safety, and clinical perspectives of use.

Darolutamide, a second-generation androgen receptor inhibitor (SGARI), has been shown to increase metastasis-free survival and overall survival among men with non-metastatic castration-resistant prostate cancer (nmCRPC). Its unique chemical structure potentially provides efficacy and safety advantages over the SGARIs apalutamide and enzalutamide, which are also indicated for nmCRPC. Despite a lack of direct comparisons, the SGARIs appear to have similar efficacy, safety, and quality of life (QoL) results. Indirect evidence suggests that darolutamide is preferred for its good adverse event profile, an attribute valued by physicians, patients, and their caregivers for maintaining QoL. Darolutamide and others in its class are costly; access may be a challenge for many patients and may lead to modifications to guideline-recommended regimens.

Molecular Pathophysiology and Potential Therapeutic Strategies of Ketamine-Related Cystitis.

Ketamine was first synthesized as a clinical medicine for anesthesia in 1970. It has been used as a recreational drug because of its low cost and hallucination effect in the past decade. Part of ketamine abusers may experience ketamine-related cystitis (KC) and suffer from lower urinary tract symptoms, including urinary frequency, urgency, and severe bladder pain. As the disease progression, a contracted bladder, petechial hemorrhage of the bladder mucosa, and ureteral stricture with hydronephrosis may occur. The pathophysiology of KC is still uncertain, although several hypotheses have been raised. Cessation of ketamine abuse is critical for the management of KC to prevent progressive disease, and effective treatment has not been established. Research has provided some theoretical bases for developing in vitro experiments, animal models, and clinical trials. This review summarized evidence of molecular mechanisms of KC and potential treatment strategies for KC. Further basic and clinical studies will help us better understand the mechanism and develop an effective treatment for KC.

Endoscopic Combined Intrarenal Surgery Versus Percutaneous Nephrolithotomy for Complex Renal Stones: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic combined intrarenal surgery (ECIRS) adds ureteroscopic vision to percutaneous nephrolithotomy (PCNL), which can be helpful when dealing with complex renal stones. Yet, there is still no consensus on the superiority of ECIRS. We aimed to critically analyze the available evidence of studies comparing efficacy, safety, bleeding risk, and efficiency of ECIRS and PCNL. METHODS: We searched for studies comparing efficacy (initial and final stone-free rate), safety (postoperative fever, overall and severe complications), efficiency (operative time and hospital stay) and bleeding risk between ECIRS and PCNL. Meta-analysis was performed. RESULTS: Seven studies (919 patients) were identified. ECIRS provided a significantly higher initial stone-free rate, higher final stone-free rate, lower overall complications, lower severe complications, and lower rate of requiring blood transfusion. There was no difference between the two groups in terms of postoperative fever, hemoglobin drop, operative time, and hospital stay. In the subgroup analysis, both minimally invasive and conventional ECIRS were associated with a higher stone-free rate and lower complication outcomes. CONCLUSIONS: When treating complex renal stones, ECIRS has a better stone-free rate, fewer complications, and requires fewer blood transfusions compared with PCNL. Subgroups either with minimally invasive or conventional intervention showed a consistent trend.

Phase I Targeted Combination Trial of Sorafenib and GW5074 in Patients with Advanced Refractory Solid Tumors.

BACKGROUND: Combination therapy with the administration of GW5074 and sorafenib significantly induced necrotic death in various cancer cells in vivo, as well as prolonging the survival of an animal disease model due to significant suppression of the primary and metastatic lesions. We sought to determine the safety, tolerability, pharmacokinetics, and anti-tumor activity of this co-administration therapy in patients with refractory advanced solid cancers. METHODS: Twelve patients were enrolled. Eligible subjects received different dosages of GW5074 in one of the three dose cohorts (Cohort 1: 750 mg daily, Cohort 2: 1500 mg daily, Cohort 3: 750 mg twice daily) plus 200 mg of sorafenib daily to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) at phase 1. Furthermore, the expression level of phosphorylated DAPKS308 in primary tumor, metastatic tumor, and circulating tumor cells (CTC) were evaluated to investigate the relationship between biomarker and the efficacy profile. RESULTS: Among the 12 enrolled patients in this phase 1 trial, most adverse effects (AE) were grade 1, with two being grade 3. The most frequent AE of all grades were weight loss and hypertension, occurring in 16.7% of participants. Eight patients (66.7%) had the disease controlled by receiving co-administration therapy of GW5074 and sorafenib. GW5074 was found to have poor absorption, as increasing the dosage did not result in a significant increase in the bioavailability of GW5074 in subjects. Furthermore, the expression level of phosphorylated DAPKS308 in tumor and CTCs were correlated with the disease control rate (DCR) and duration of response (DOR). CONCLUSIONS: Co-administration therapy of GW5074 and sorafenib demonstrated a favorable safety profile and showed anti-tumor activity in a variety of tumor types. However, the solubility of GW5074 is not satisfactory. A future phase 2a trial will be carried out using the new salted form that has been proven to be more effective.

Determining programmed cell death ligand 1 expression in circulating tumor cells of patients with clear cell renal cell carcinoma and its correlation with response to programmed cell death protein 1 inhibitors.

OBJECTIVE: There is a great interest in determining whether the expression of the programmed cell death ligand 1 is correlated with the efficacy of immune checkpoint inhibitors in patients with clear cell renal cell carcinoma; however, primary tumor biopsies can only provide limited information. Therefore, we explored the expression of programmed cell death ligand 1 on circulating tumor cells, which is a potential predictor of therapeutic response. METHODS: Circulating tumor cells were isolated from 20 clear cell renal cell carcinoma patients based on cell surface markers targeting clear cell renal cell carcinoma using IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. Programmed cell death ligand 1 expression status and clinical correlations were also analyzed. RESULTS: Before treatment with programmed cell death protein 1 inhibitors, circulating tumor cells were detected in all patients, ranging from 1 to 22 (median 7), with 75% (15/20) of the patients having programmed cell death ligand 1 + circulating tumor cells. Circulating tumor cell programmed cell death ligand 1 expression did not correlate with the immunohistochemical staining of programmed cell death ligand 1 in primary tumors. During treatment with programmed cell death protein 1 inhibitors, the disease control rate was much higher in the patients harboring programmed cell death ligand 1 + circulating tumor cells (73%, 11/15) than others (20%, 1/5). We also found that changes in total circulating tumor cell numbers and programmed cell death ligand 1 + circulating tumor cell counts correlated well with the disease outcome. CONCLUSION: We showed that the presence of programmed cell death ligand 1 + circulating tumor cells before programmed cell death protein 1 inhibition treatment could be a prognosis predictive factor and that the dynamic changes in circulating tumor cell numbers may be used to monitor the therapeutic response. Our study confirms the possibility of programmed cell death ligand 1 + circulating tumor cell detection in clear cell renal cell carcinoma patients' blood samples, which can potentially be used as an individualized immunotherapy molecular biomarker for real-time exploration.

DNA Hypomethylation Is Associated with the Overexpression of INHBA in Upper Tract Urothelial Carcinoma.

Urothelial carcinoma includes upper urinary tract cancer (UTUC) and bladder cancer. Although nephroureterectomy is the standard treatment for UTUC, the recurrence rate is approximately half and the tumor is associated with poor prognoses. Metastases are the most devastating and lethal clinical situation in urothelial carcinoma. Despite its clinical importance, few potential diagnostic biomarkers are suitable for early UC detection. We compared high-stage/high-grade urothelial carcinoma tissues to adjacent normal urothelial tissues using methyl-CpG binding domain protein capture for genome-wide DNA methylation analysis. Based on our findings, inhibin ßA (INHBA) might be associated with carcinogenesis and metastasis. Further, clinical UC specimens had significant INHBA hypomethylation based on pyrosequencing. INHBA was detected by real-time PCR and immunohistochemistry staining, and was found to be highly expressed in clinical tissues and cell lines of urothelial carcinoma. Further, INHBA depletion was found to significantly reduce BFTC-909 cell growth and migration by INHBA-specific small interfering RNA. Interestingly, a positive correlation was found between SMAD binding and extracellular structure organization with INHBA using gene set enrichment analysis and gene ontology analysis. Together, these results are the first evidence of INHBA promoter hypomethylation and INHBA overexpression in UTUC. INHBA may affect urothelial carcinoma migration by reorganizing the extracellular matrix through the SMAD pathway.

Detection of circulating tumor cells as therapeutic markers in patients with penile squamous cell carcinoma: A preliminary study.

BACKGROUND: This study aimed to investigate the presence of circulating tumor cells (CTCs) in patients with penile squamous cell carcinoma (PSCC). METHODS: CTCs were isolated from 14 patients with PSCC, 6 patients with balanoposthitis, and 6 healthy individuals. CTCs were enriched based on cell surface markers and filtered through the IsoFlux device, followed by identification according to cell morphology and immunofluorescence studies. RESULTS: CTCs were found in all PSCC blood samples but not in balanoposthitis samples and samples from healthy individuals. Immunofluorescence studies confirmed the tumor origin. When the patients with PSCC were stratified according to metastatic inguinal lymph node status, a statistically significant difference was observed in the number of detected CTCs. CONCLUSION: Our study showed that CTCs in PSCC may represent a valuable marker for differentiating PSCC from other tumors. Based on the correlation with some clinical parameters, CTC analysis is possibly relevant for noninvasive monitoring of disease progression and prognosis. The results also suggested a potential role of CTCs in preventing overtreatment, such as inguinal lymph node dissection.

Effects of robot-assisted versus hand-assisted nephroureterectomy on circulating tumor cells for upper urinary tract urothelial carcinoma.

To compare perioperative circulating tumor cells (CTC) in primary upper tract urothelial carcinoma (UTUC) patients who underwent hand-assisted retroperitoneoscopic nephroureterectomy (HANU) or robotic-assisted nephroureterectomy (RANU). A total of 29 patients received RANU (n = 10) or HANU (n = 19). Peripheral blood samples were collected before, 24 h after surgery (POh24) and on postoperative day 28 (POD28). The demographic and pathologic data are similar in both groups. RANU had a longer operative time (p = 0.031), less bleeding volume (p = 0.004), and comparable pain sore (p = 0.169). The mean CTC numbers before surgery (2.4 vs. 2.3, p = 0.482), POh24 (2.4 vs. 1.9, p = 0.668) and POD28 (0.5 vs. 0.6, p = 0.280) were not significant different among groups. The amount of CTCs in both groups decreased and reached similar level on POD28. No significant difference of overall and intravesical recurrence rate between the two approaches. In comparison to RANU, more surgical manipulation does not affect tumor cell translocation into the bloodstream in UTUC patients who received HANU. However, a longer follow-up would be needed for the final comparison of tumor recurrence.

Increased incidence of neurogenic bladder after radical hysterectomy for cervical cancer: A nationwide population-based cohort study.

BACKGROUND: The effect of radical hysterectomy for patients with cervical cancer on voiding function remains controversial. The purpose of this study was to examine the association between radical hysterectomy for patients with cervical cancer and the odds of developing neurogenic bladder by using data from the National Health Insurance Research Database (NHIRD) in Taiwan. METHODS: We identified 17 936 patients who underwent radical hysterectomy for cervical cancer between 2000 and 2013 among inpatients registered in the Longitudinal Health Insurance Database in Taiwan. Of the patients, those diagnosed as having cervical cancer without radical hysterectomy were selected and compared as a matched control group. Patients diagnosed as having cervical cancer before the index date, those with neurogenic bladder dysfunction before tracking, and those aged <20 years were excluded. The hazard ratios (HRs) of neurogenic bladder and other variants of interest were further calculated using a multivariate Cox regression analysis. The cutoff p value of <0.05 was regarded as statistically significant. RESULTS: The adjusted HR (aHR) of subsequent neurogenic bladder was higher in the hysterectomy group (aHR = 1.205; 95% CI, 1.086-1.440; p = 0.029) than in the control group during the follow-up period. As to the age subgroups, the patients aged 20 to 44 years (aHR = 3.321, p = 0.001) had a significantly increased risk of developing neurogenic bladder after radical hysterectomy as compared with those aged 45 to 64 years (aHR = 1.193, p = 0.012). CONCLUSION: Patients with cervical cancer undergoing radical hysterectomy have an increased risk of neurogenic bladder, which may result from nerve denervation caused by the operation. These patients should be informed of the potential risk of voiding dysfunction during discussion of the subsequent management for cervical cancer.

Programmed Cell Death Ligand 1 Expression in Circulating Tumor Cells as a Predictor of Treatment Response in Patients with Urothelial Carcinoma.

Programmed cell death ligand 1 (PD-L1) inhibitors are commonly used in treating advanced-stage urothelial carcinoma (UC). Therefore, this study evaluated the relationship between PD-L1 expression in circulating tumor cells (CTCs) and treatment response to PD-L1 inhibitors using blood samples collected from patients with UC (n = 23). Subsequently, PD-L1 expression and its clinical correlation were analyzed. All patients had CTCs before PD-L1 inhibitory treatment, of which 15 had PD-L1-positive CTCs. However, PD-L1-positive expression in CTCs was not correlated with PD-L1 expression in tumor biopsy samples. Patients with PD-L1-positive CTCs had better disease control (DC) rates than those without PD-L1-positive CTCs. Moreover, changes in the proportion of PD-L1-positive CTCs were associated with disease outcomes. Furthermore, the PD-L1-positive CTC count in 9 of 11 patients who achieved DC had significantly decreased (p = 0.01). In four patients with progressive disease, this was higher or did not change. PD-L1-positive CTCs at baseline could be used as a biomarker to identify patients suitable for PD-L1 blockade therapy. Dynamic changes in PD-L1-positive CTCs during the course of treatment are predictive factors of immunotherapy response and prognostic factors of disease control. Hence, PD-L1-positive CTCs could be employed as a real-time molecular biomarker for individualized immunotherapy.

Demethoxycurcumin induces apoptosis in HER2 overexpressing bladder cancer cells through degradation of HER2 and inhibiting the PI3K/Akt pathway.

Bladder cancer is the most common malignancy of the urinary tract and arising from the epithelial lining of the urinary bladder. Resistance to cytotoxic therapies is associated with overexpression of oncogenic proteins; including HER2, and Akt in chemotherapy resistance of bladder cancer. Various studies demonstrated that curcuminoids, the most important active phenolic compounds of turmeric (Curcuma longa), have anti-tumor activities in a wide range of human malignant cell lines. The aim of this study is to evaluate whether curcuminoids (curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin) could repress the expression of HER2 in HER2-overexpressing bladder cancer cells. Among the test compounds, DMC significantly suppressed the expression of HER2, and preferentially inhibited cell proliferation and induced apoptosis in HER2-overexpressing bladder cancer cells. DMC decreases HER2 level through inhibiting the interaction of HER2 and Hsp90. Our study also indicated that DMC showed additive activity in combination with chemotherapeutic agents, including paclitaxel and cisplatin. These findings show that DMC should be developed further as a new antitumor drug candidate for treatment of HER2-overexpressing bladder cancer.

Regulation of carcinogenesis and mediation through Wnt/ß-catenin signaling by 3,3'-diindolylmethane in an enzalutamide-resistant prostate cancer cell line.

Enzalutamide (ENZ) is an important drug used to treat castration-resistant prostate cancer (CRPC), which inhibits androgen receptor (AR) signaling. Previous study showed that 3,3'-diindolylmethane (DIM) is an AR antagonist that also inhibits Wnt signaling and epithelial-mesenchymal transition (EMT). To investigate whether combined treatment with ENZ and DIM can overcome ENZ resistance by regulating Wnt signaling to inhibit AR signaling and EMT in ENZ-resistant prostate cancer cells, 22Rv1 cells were cultured in normal medium and treated with ENZ, DIM, and DIM with ENZ. Exposure of ENZ-resistant cells to both DIM and ENZ significantly inhibited cell proliferation without cytotoxicity and invasion in comparison with the control. DIM significantly increased the E-cadherin expression and inhibited the expressions of Vimentin and Fibronectin, subsequently inhibiting EMT. Co-treatment with ENZ and DIM significantly increased the expressions of GSK3ß and APC and decreased the ß-catenin protein expression, causing inhibition of Wnt signaling and AR expression, it also significantly decreased the AR-v7 expression and down-regulated AR signaling. Via suppression of Wnt and AR signaling, co-treatment increased the E-cadherin and decreased the Vimentin and Fibronectin RNA and protein expressions, then inhibited EMT. Co-treatment with DIM and ENZ regulated Wnt signaling to reduce not only the AR expression, but also the AR-v7 expression, indicating suppression of EMT that inhibits cancer cell proliferation, invasion and migration to ameliorate ENZ resistance.

A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis/Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a painful recurrent condition characterized by the discomfort of the bladder, and current treatment options have limited effectiveness. Prolotherapy is a well-known treatment that involves the injection of non-biologic solutions to reduce pain and/or promote proliferation of soft tissue, and dextrose is the most common injectate. This study investigated the effects of dextrose prolotherapy in a rat model of IC/BPS and patients with IC/BPS. We used cyclophosphamide to induce IC/BPS in rats, and intravesical instillation of 10% dextrose solution was performed. After 1 week, we conducted a urodynamic test, bladder staining, and ECM-related gene expression analysis to examine the treatment's efficacy. We found that dextrose treatment could recover the instability of the bladder, reduce frequent urination, and improve the glycosaminoglycan layer regeneration and the bladder wall thickness along with a significant intense expression of CD44 receptors. Furthermore, we enrolled 29 IC/BPS patients with previous hyaluronic acid/Botox treatment for more than 6 months with remained unchanged condition. In this study, they received intravesical injections of 10% dextrose solution followed by assessments for up to 12 weeks. Patient characteristics and a 3-day voiding diary before treatment were recorded. Patient responses were examined using IC/BPS-related questionnaires. Moreover, expressions of growth factors and cytokines were analyzed. The results demonstrated that dextrose prolotherapy in patients with IC/BPS reduced the frequency of treatment over time, with the mean number of treatments being 3.03 ± 1.52, and significantly reduced the incidence of nocturia and questionnaire scores associated with symptoms. Dextrose prolotherapy significantly enhanced EGF level and, in contrast, reduced the level of HGF, PIGF-1, and VEGF-D after several weeks following treatment. The cytokine analysis showed that the expressions of IL-12p70 and IL-10 were significantly up-regulated after dextrose prolotherapy in IC/BPS patients. The levels of most growth factors and cytokines in IC/BPS patients had no significant difference and showed a similar tendency as time progressed when compared to healthy controls. Overall, the alteration of growth factors and cytokines exhibited safe treatment and potential stimulation of tissue remodeling. In summary, our study demonstrated that dextrose prolotherapy is a promising treatment strategy for IC/BPS disease management.

A High Phosphorus Diet Impairs Testicular Function and Spermatogenesis in Male Mice with Chronic Kidney Disease.

Hyperphosphatemia is a serious complication in chronic kidney disease (CKD) that occurs due to insufficient excretion of phosphorus during failure of renal function. Both CKD and an excessive phosphorus intake have been reported to increase oxidative stress and result in poor male fertility, but little is known about the reproductive function of the CKD under a poorly controlled phosphate intake. Eight-week-old C57BL/6 mice (n = 66) were randomly divided into four groups: a sham operation group received a chow diet as control (SC group, n = 14), CKD-induced mice received a chow diet (CKDC group, n = 16), control mice received a high phosphorus (HP) diet (SP group, n = 16), and CKD-induced mice received a HP diet (CKDP group, n = 20). CKD was induced by performing a 5/6 nephrectomy. The chow diet contained 0.6% phosphorus, while the HP diet contained 2% phosphorus. Impaired testicular function and semen quality found in the CKD model may result from increased oxidative stress, causing apoptosis and inflammation. The HP diet aggravated the negative effects of testicular damage in the CKD-induced mice.

Metformin Ameliorates Testicular Function and Spermatogenesis in Male Mice with High-Fat and High-Cholesterol Diet-Induced Obesity.

The aim of this study was to investigate the effects of metformin supplementation on metabolic dysfunction, testicular antioxidant capacity, apoptosis, inflammation and spermatogenesis in male mice with high-fat and high-cholesterol diet-induced obesity. Forty male C57BL/6 mice were fed a normal diet (NC group, n = 10) or a high-fat and high-cholesterol diet (HFC group, n = 30) for 24 weeks, and mice randomly chosen from the HFC group were later treated with metformin for the final 8 weeks of HFC feeding (HFC + Met group, n = 15). Compared with the HFC group, the obese mice supplemented with metformin exhibited improved blood cholesterol, glucose and insulin resistance. The HFC group diminishes in the sperm motility and normal sperm morphology, while the poorer maturity of testicular spermatogenesis was improved by metformin treatment. The HFC group exhibited a higher estradiol level and a lower 17ß-HSD protein expression. Further analyses showed that metformin treatment increased the activities of superoxide dismutase, catalase and glutathione peroxidase and reduced lipid peroxidation. Nevertheless, both the HFC and HFC + Met groups exhibited increased expressions of apoptosis and inflammation proteins in the testis. Metformin treatment ameliorated obesity-induced poor testicular spermatogenesis and semen quality through increasing the testosterone level and antioxidant capacity.

A survey for ketamine abuse and its relation to the lower urinary tract symptoms in Taiwan.

We aimed to explore the correlation between ketamine abuse and lower urinary tract symptoms (LUTS) and epidemiology of ketamine cystitis. Questionnaire records of ketamine abusers, such as sex, age, and details of using ketamine, including consumption method, amount, duration of ketamine use, and LUTS, were obtained from two private rehabilitation centers. We analyzed these factors and established a severity forecasting module. One hundred and six ketamine abusers completed the questionnaires. LUTS showed an onset time of 24.67 ± 26.36 months among ketamine abusers. Overactive bladder symptom score, international prostate symptom score-storage, interstitial cystitis symptom index, interstitial cystitis problem index, and visual analogue scale score were 5.25 ± 4.43, 5.95 ± 5.72, 10.96 ± 6.66, 9.73 ± 5.82, and 2.55 ± 3.18, respectively. All symptom scores were positively correlated with the duration of ketamine abuse. Ketamine snorting was significantly correlated with all symptom scores compared to smoking. Hydrodistention, intravesical hyaluronic acid instillation, intravesical injection with botulinum toxin, and hyperbaric-oxygen therapy showed better effect than oral treatment. Ketamine can induce severe storage symptoms, such as frequency or nocturia depending on the duration of abuse. Ketamine snorting may cause worse LUTS than smoking. Combining ketamine and other substances may exacerbate LUTS. Intravesical therapy may lead to better outcomes than oral treatment.

Anatomic mapping of the internal spermatic vein via subinguinal varicocelectomy with intraoperative vascular Doppler ultrasound.

BACKGROUND: Varicocele is believed to be a dilated vein of the pampiniform plexus along the spermatic cord. Surgical treatment should be considered in men with a symptomatic varicocele. To date, microsurgical varicocelectomy is the most effective method among various varicocelectomy techniques, according to the current evidence. This study aimed to evaluate the effectiveness of subinguinal varicocelectomy with intraoperative vascular Doppler for symptomatic varicocele and map the distributional trend of spermatic content simultaneously. METHODS: A total of 24 male patients underwent subinguinal varicocelectomy with intraoperative vascular Doppler ultrasound between March 2016 and October 2017, because of symptomatic varicocele or infertility. The numbers, sizes, and location of spermatic vessels in each site were recorded during operation. The visual analogue scale (VAS) score of scrotal pain was also obtained before and after surgery. RESULTS: The mean number of spermatic veins that were ligated in each spermatic unit was 4.70 (±2.06). The predominant distributional zone of spermatic veins was the medial upper zone on an axial view of the spermatic cord. Fifty-six (44.1%) spermatic veins were found in this zone. Normally, each spermatic cord has 1.33 (±0.61) spermatic arteries. The average VAS score prior to surgery was 1.95 (±0.89) and it decreased to 0.05 (±0.21) after the surgery. Complete resolution of pain was observed in almost all symptomatic patients (95.23%). A significant positive relationship between the number of veins ligated and improvement of VAS score was also noted (p < 0.05). CONCLUSION: Subinguinal varicocelectomy with intraoperative vascular Doppler ultrasound is an effective treatment for symptomatic varicocele. The more the internal spermatic veins are ligated, the more the VAS scores are improved. Determining the distributional trend of spermatic content is of great importance in the prevention of iatrogenic injury to the spermatic vessels and vas deferens.