Extracorporeal Shockwave Therapy Alleviates Inflammatory Pain by Down-Regulating NLRP3 Inflammasome in Experimental Chronic Prostatitis and Chronic Pelvic Pain Syndrome.

PURPOSE: To evaluate the anti-inflammatory and antioxidative effects of extracorporeal shockwave therapy (ESWT) on prostatitis and explore the mechanism of alleviating pain. MATERIALS AND METHODS: For in vitro testing, RWPE-1 cells were randomly divided into 5 groups: (1) RWPE-1 group (normal control), (2) LPS group (lipopolysaccharide inducing inflammation), (3) 0.1ESWT group (treated by 0.1 mJ/mm² energy level), (4) 0.2ESWT group (treated by 0.2 mJ/mm² energy level), and (5) 0.3ESWT group (treated by 0.3 mJ/mm² energy level). After ESWT was administered, cells and supernatant were collected for ELISA and western blot. For in vivo testing, Sprague-Dawley male rats were randomly divided into 3 groups: (1) normal group, (2) prostatitis group, and (3) ESWT group (n=12 for each). Prostatitis was induced by 17 beta-estradiol and dihydrotestosterone (DHT) administration. Four weeks after ESWT, the pain index was assessed for all groups and prostate tissues were collected for immunohistochemistry, immunofluorescence, apoptosis analysis and, western blot. RESULTS: Our in vitro studies showed that the optimal energy flux density of ESWT was 0.2 mJ/mm². In vivo, ESWT ameliorated discomfort in rats with prostatitis and inflammation symptoms were improved. Compared to normal rats, overexpressed NLRP3 inflammasomes triggered apoptosis in rats with prostatitis and this was improved by ESWT. TLR4-NFκB pathway was overactive after experimental prostatitis, compared to normal and ESWT groups, and prostatitis induced alterations in BAX/BAK pathway were inhibited by ESWT. CONCLUSIONS: ESWT improved CP/CPPS by reducing NLRP3 inflammasome and ameliorated apoptosis via inhibiting BAX/BAK pathway in a rat model. TLR4 may play a key role in bonding NLRP3 inflammasome and BAX/BAK pathways. ESWT might be a promising approach for the treatment of CP/CPPS.

Comparison of intrarectal heated lidocaine gel and periprostatic nerve block for pain control in transrectal ultrasound-guided prostate biopsy: A randomized controlled non-inferiority trial.

Background: To investigate whether intrarectal local anesthesia with heated lidocaine gel (IRLAH) is non-inferior to periprostatic nerve block (PNB) for reducing pain in patients undergoing transrectal ultrasound (TRUS)-guided prostate biopsy. Methods: We performed a randomized controlled non-inferiority trial with 100 participants who underwent systematic TRUS-guided, 12-core prostate biopsy from August 2019 to July 2020. These participants were randomly assigned to a group receiving intrarectal local anesthesia with 20 mL of heated (40°C) 2% lidocaine gel (n = 50) or PNB (n = 50). The primary outcome was a pain score on a 0-10 visual analogue scale (VAS) at four time points with the non-inferiority margin of 1; VAS-1: during local anesthesia application; VAS-2: during probe insertion; VAS-3: during biopsy; VAS-4: 30 minutes after the procedure. The secondary outcome included complications during and after the procedure. Results: The IRLAH group (0.1) met non-inferiority as well as superiority criteria for mean VAS-1 score vs. the PNB group (2.33) (P < 0.001), as the difference (95% confidence interval [CI]) between the two groups was -2.23 (-2.66 to -1.79) and the upper bound of the 95% CI were both below the prespecified non-inferiority margin and below zero. For mean VAS-3 score, the difference (95% CI) was 0.3 (-0.38 to 0.98) and the upper bound of the 95% CI did not exceed the predefined non-inferiority margin indicating that IRLAH was non-inferior (IRLAH group, 3.44; PNB group, 3.14). Also, non-inferiority was shown for pain scores at VAS-2 and VAS-4. There were no significant differences in complications. Conclusion: IRLAH is a noninvasive and non-inferior alternative to PNB for pain control in TRUS-guided prostate biopsy without increased risk of complications.

Trends of genital wart in Korea according to treatment method classification: Big data analysis of health care in 2010-2019.

PURPOSE: The purpose of this study is to investigate disease trend of genital wart through changes in each treatment method over the past 10 years in Korea. MATERIALS AND METHODS: From 2010 to 2019, surgical treatment including cauterization, excision, cryotherapy, and laser therapy, non-surgical treatment such as podophyllin, and surgical treatment for anorectal lesion were extracted and analyzed from 2010 to 2019. For each treatment method, characteristics such as sex, age, region, medical cost and average number of procedures were analyzed. RESULTS: The number of patients following all treatment modalities increased every year. Surgical treatment of genital wart and anorectal wart showed a significant increase in male patients. Number of non-surgical treatment decreased in males but increased in females. Surgical removal of the anorectal wart increased more than 250% in over 10 years, and males underwent surgery 4 times more than females. In both surgery and non-surgery, the mean session was higher in males. Most of them were carried out in primary medical institutions. In Seoul and Gyeonggi-do, the largest number of patients received treatment regardless of treatment method. CONCLUSIONS: Treatment for genital warts has increased rapidly over the past 10 years, and the increase in males is remarkable. The main treatment was surgery, and males mainly received surgical treatment, and females mainly received drug treatment. The primary medical institution was in charge of the most treatment. As the number of patients and related medical expenses are increasing rapidly, more attention and response to diseases are needed.

The change of antibiotic susceptibility in febrile urinary tract infection in childhood and adolescence during the last decade.

PURPOSE: The purpose of this study was to clarify the pattern of antibiotic resistance in pediatric urinary tract infections (UTIs). MATERIALS AND METHODS: We analyzed the data of entire urine culture tests and antibiotic susceptibility tests performed on hospitalized patients for febrile UTI at the Uijeongbu St. Mary's Hospital during 2010-2020. A retrospective analysis was performed using medical records of urine culture results and antibiotic susceptibility results in patients with UTIs. RESULTS: We performed urine cultures from 2,491 patients, and identified bacterial types in 1,651 cases. We found that the resistance rates to ampicillin, ampicillin/sulbactam, cefazolin, gentamicin, piperacillin, tobramycin, and trimethoprim/sulfamethoxazole were already over 20% in 2010. The resistance rates to many other antibiotics also steadily increased over time. Among the antibiotics tested in 2020, only amikacin, cefoxitin, imipenem, piperacillin/tazobactam, and tigecycline showed the resistance rates below 20%. Noticeably, ciprofloxacin also showed an increase in the resistance rate from 7.3% in 2010 (S 139 vs. R 11) to 27.78% in 2019 (S 104 vs. R 40) and even over 30% (33.96%) in 2020 (S 35 vs. R 18). CONCLUSIONS: Antibiotic resistance is a serious problem in pediatric UTIs. In the treatment of pediatric UTIs, more caution is needed in the use of antibiotics. It may be necessary to apply appropriate antibiotic management programs such as antibiotics steward program for pediatric patients. Failure of a proper response strategy coping with antibiotic resistance may accelerate the resistance crisis.

The effect of heated lidocaine gel on pain reduction during transrectal ultrasound-guided prostate biopsy: a randomized-controlled study.

PURPOSE: To determine whether intrarectal local anesthesia (IRLA) with heated lidocaine gel provides pain reduction during transrectal ultrasound (TRUS)-guided prostate biopsy. METHODS: We conducted a randomized-controlled study with 153 participants who underwent TRUS-guided, systematic 12-core prostate biopsy from May 2018 to June 2019. These participants were divided into three test groups. Before prostate biopsy, group A (51 patients) received no local anesthesia, group B (51 patients) received IRLA with 20 mL 2% lidocaine gel stored at room temperature, and group C (51 patients) received IRLA with heated (40 ℃) 20 mL 2% lidocaine gel. Pain was assessed using the 0-10 visual analogue scale (VAS) at three time points: VAS-1: during probe insertion, VAS-2: during biopsy, VAS-3: 30 min after the procedure. Complications during and after the procedure were evaluated. RESULTS: The mean VAS-2 score was significantly lower in group C compared to groups A and B (A, 4.6; B, 4.2; and C, 3.2; p < 0.05). There was no significant difference among the three groups in mean VAS-1 and VAS-3 scores. No significant difference was detected in incidence of complications between the three groups. No allergic reactions to lidocaine gel were observed. CONCLUSION: IRLA with heated lidocaine gel provides more effective pain control during TRUS-guided prostate biopsy than does conventional IRLA and no local anesthesia, without an increase of complications.

A Prospective Validation and Observer Performance Study of a Deep Learning Algorithm for Pathologic Diagnosis of Gastric Tumors in Endoscopic Biopsies.

PURPOSE: Gastric cancer remains the leading cause of cancer-related deaths in Northeast Asia. Population-based endoscopic screenings in the region have yielded successful results in early detection of gastric tumors. Endoscopic screening rates are continuously increasing, and there is a need for an automatic computerized diagnostic system to reduce the diagnostic burden. In this study, we developed an algorithm to classify gastric epithelial tumors automatically and assessed its performance in a large series of gastric biopsies and its benefits as an assistance tool. EXPERIMENTAL DESIGN: Using 2,434 whole-slide images, we developed an algorithm based on convolutional neural networks to classify a gastric biopsy image into one of three categories: negative for dysplasia (NFD), tubular adenoma, or carcinoma. The performance of the algorithm was evaluated by using 7,440 biopsy specimens collected prospectively. The impact of algorithm-assisted diagnosis was assessed by six pathologists using 150 gastric biopsy cases. RESULTS: Diagnostic performance evaluated by the AUROC curve in the prospective study was 0.9790 for two-tier classification: negative (NFD) versus positive (all cases except NFD). When limited to epithelial tumors, the sensitivity and specificity were 1.000 and 0.9749. Algorithm-assisted digital image viewer (DV) resulted in 47% reduction in review time per image compared with DV only and 58% decrease to microscopy. CONCLUSIONS: Our algorithm has demonstrated high accuracy in classifying epithelial tumors and its benefits as an assistance tool, which can serve as a potential screening aid system in diagnosing gastric biopsy specimens.

Effects of low-frequency intravaginal electrical stimulation on female urinary incontinence, quality of life, and urinary symptoms: A pilot study.

This study investigated the effects of a low-frequency home-based incontinence therapy device on quality of life (QoL) and urinary symptoms in women with urinary incontinence. From May 2017 to February 2018, 34 patients, aged ≥ 20 years, with involuntary urine leakage >2 times/week, were recruited to this study. Patients with severe pelvic organ prolapse, pregnancy, virgin status, and psychological problems were excluded. The incontinence home-care device treatments were administered in 12-minute sessions, twice daily for 8 weeks. Simultaneously, hyperthermic conditions of 35°C to 40°C and microvibrations were administered. All patients completed urinary incontinence questionnaires (King's Health Questionnaire [KHQ], Bristol Female Lower Urinary Tract Symptoms [BFLUTS] questionnaire, and the Overactive Bladder Symptom Score [OABSS]) before treatment, as well as 4 and 8 weeks into treatment. Changes in the questionnaire responses over time were compared. Two participants dropped out of the study and there was one screening failure, leaving 31 patients for analysis. After 4 weeks treatment, there were significant improvements in symptoms, such as role limitation, physical limitation, social limitation, personal relationship, emotion, sleep/energy, and severity measures. After 8 weeks treatment, almost all parameters on the KHQ revealed symptomatic improvement. On the BFLUTS, voiding times during activity, nocturia, urgency, urge incontinence, incontinence frequency, stress incontinence, volume leakage, strain to start, intermittency, reduced stream, acute retention, incomplete emptying, and stopping flow showed significant improvements. On the OABSS, almost all storage symptoms improved. Low-frequency electrical stimulation devices were effective at improving urinary incontinence, which became evident as the duration of treatment increased. Improvement of urgency and frequency was more evident after treatment.

Correlation between internal pudendal artery stenosis and erectile dysfunction in patients with suspected coronary artery disease.

BACKGROUND: Stenoses of internal pudendal arteries (IPAs) appear to be related to erectile dysfunction (ED). Nevertheless, the correlation between the severity of ED and stenosis of the IPAs is not well established. OBJECTIVES: To evaluate angiographic findings of IPAs in patients with suspected coronary artery disease (CAD) and to assess the correlation between the severity of ED and IPA stenosis. MATERIALS AND METHODS: Ninety-one patients who were scheduled for cardiac angiogram (CAG) because of suspected CAD participated. ED was assessed using the International Index of Erectile Function (IIEF) questionnaire. Erectile function (EF) domain scoring was used to assess the severity of ED: severe (EF score = 1-10); moderate (11-16); mild-moderate (17-21); mild (22-25); and no ED (26-30). Angiography was performed in bilateral common, internal iliac, and IPAs and the location and extent of stenoses were measured. We divided patients according to those with maximum stenosis of less than 50% (Group I) and those with more than 50% (Group II), regardless of direction. RESULTS: We diagnosed 88 patients (88/91, 96.70%) with ED. There was no correlation between increasing age and severity of ED (r = - 0.063, p = 0.555). There were 72 patients in Group I and 19 in Group II. In Group I, 62 patients were diagnosed with ED even though there was no stenosis. There was no significant correlation between the severity of ED and the extent of stenosis in IPAs (r = -0.118, p = 0.265). CONCLUSIONS: There was no significant correlation between the severity of ED and the extent of stenosis of IPAs. We believe that this is because the progression of ED is induced by endothelial cell dysfunction, not by mechanical obstruction leading to blood flow reduction.

Hemostatic effect and psychological impact of an oxidized regenerated cellulose patch after transrectal ultrasound-guided prostate biopsy: A prospective and retrospective study.

To investigate the usefulness of the oxidized regenerated cellulose patch (ORCP) for postbiopsy hemostasis, anxiety, and depression in patients undergoing transrectal ultrasound-guided prostate biopsy.This was a prospective-retrospective study of 300 patients who underwent systematic 12-core prostate biopsy from August 2016 through March 2018. The ORCP was inserted into the rectum immediately after prostate biopsy in the prospective group (n = 150), while the retrospective group (n = 150) underwent prostate biopsy alone. The frequency rate and duration of hematuria, rectal bleeding, and hematospermia were compared between the 2 groups. Anxiety and depression were assessed with the hospital anxiety and depression scale before and after prostate biopsy in the prospective group.The frequency rates of hematuria and hematospermia showed no significant differences between the prospective versus retrospective groups (64.7% vs 66.7%, P = .881; 18 vs 20%, P = .718; respectively). Frequency of rectal bleeding was significantly lower in the prospective group than in the retrospective group (26.7% vs 42.7%, P = .018). However, there were no significant differences in median duration of rectal bleeding, hematuria, or hematospermia between the 2 groups (2, 5, and 2 days vs 2, 7, and 1 day, P > .05, respectively, for the prospective vs retrospective group). Multivariate analysis found that ORCP insertion was a significant protective factor against postbiopsy rectal bleeding (P = .038, odds ratio 0.52). Only anxiety level in the prospective group before versus after prostate biopsy was significantly reduced (5 vs 4, P = .011).ORCP insertion after prostate biopsy is an effective and simple method for decreasing rectal bleeding. ORCP insertion may also alleviate anxiety in patients undergoing prostate biopsy.

Diffuse alveolar hemorrhage following sugammadex and remifentanil administration: A case report.

RATIONALE: Diffuse alveolar hemorrhage (DAH) is a rare life-threatening condition that accompanies general anesthesia. Negative-pressure pulmonary edema (NPPE) is a rare cause of DAH. PATIENT CONCERNS: A 25-year-old male patient developed hemoptysis following remifentanil administration by bolus injection with sugammadex at the emergence from general anesthesia. DIAGNOSIS: Chest x-ray and computed tomography showed DAH. INTERVENTIONS: Conservative care was provided with 4L of oxygen via nasal prong, 20 mg of Lasix and 2500 mg of tranexamic acid. OUTCOMES: The patient was discharged uneventfully. LESSONS: Muscle rigidity by remifentanil and the dissociated reversal of neuromuscular blockade by sugammadex was suspected as the cause of NPPE-related DAH. Therefore, the possibility NPPE-related DAH should be considered when using a bolus of remifentanil and sugammadex during emergence from general anesthesia.

Effects of a combination of herbal extracts (modified Ojayeonjonghwan (Wuzi Yanzong wan)) on partial urethral obstruction-induced detrusor overactivity in rats: impact on the nitric oxide pathway and oxidative stress.

BACKGROUND: We investigated the effects of a berry mixture formula (modified Ojayeonjonghwan (Wuzi Yanzong Wan, MO formula) on detrusor overactivity (DO). METHODS: The MO formula consisted of 5 seeds obtained from 5 types of berry plants. Twenty-four Sprague-Dawley rats were randomly assigned to four groups: sham-operated (control), partial urethral obstruction-induced DO (DO group), 0.03 mg/kg solifenacin-treated DO (solifenacin group) and 200 mg/kg MO formula -treated DO (berry mixture). The control and overactive groups were administered distilled water for 4 weeks, and the solifenacin and MO formula groups were treated with the respective medication for 4 weeks. After treatment, cystometrography was performed. At the endo of cystometrography, their bladder tissues were used for identifying the muscarinic receptors, endothelial nitric oxide synthase(eNOS), RhoA, Rock-I & II, 8-hydroxy-2' -deoxyguanosine(8-OHdG), superoxide dismutase(SOD), interleukin-6 &-8(IL-6, IL-8), and tumor necrosis factor-alpha(TNF-a). The tissues were stained and the muscle-to-collagen ratio was identified. RESULTS: The presence of the muscarinic receptors were not significantly different between the solifenacin and MO formula groups. However, significant differences were found between the solifenacin and MO formula groups in terms of eNOS, RhoA, Rock-I and -II levels. The muscle-to-collagen ratio was statistically lower in the DO and solifenacin groups; however, no significant difference was observed between the control and MO formula groups. Under oxidative stress, SOD showed a similar result as 8-OHgG. The MO formula group exhibited anti-inflammatory effects, showing that no significant difference was found between the control and MO formula groups regarding values of IL-6, IL-8, and TNF-a. However, the DO and solifenacin groups showed increased IL-6, IL-8, and TNF-a levels. Cystometrography showed that the OAB and solifenacin groups having a significantly lower value than the control and MO formula groups. The mean contraction interval was shorter in the DO, MO formula, and solifenacin groups and the highest in the control group. CONCLUSIONS: The MO formula exhibited a similar pharmacologic effect to that of solifenacin, with anti-inflammatory and antioxidant effects. Enhancement of the MO formula by the nitric oxide pathway affected DO including BPH-related DO. The MO formula may be one of the alternative choices of anticholinergics, a treatment for DO.

Long-Term Outcomes of Laparoendoscopic Single-Site Nephrolithotomy for Caliceal Diverticular Calculi: A Case Series.

OBJECTIVE: To evaluate the outcomes of laparoendoscopic single-site nephrolithotomy (LESS-NL) for symptomatic caliceal diverticular calculi. PATIENTS AND METHODS: From November 2009 to March 2014, 11 cases of LESS-NL with a homemade single-port device for caliceal diverticular calculi were performed by a single experienced laparoscopic surgeon. All patients were assessed at postoperative 1 month, 1 year, and 3 years for symptom-free status and by CT for stone-free and caliceal diverticular obliteration status. All complications were categorized by the Clavien-Dindo classification. Demographic parameters and postoperative outcomes were retrospectively analyzed. RESULTS: All procedures were effectively performed without conversion to open or conventional laparoscopic surgery. Median patient age was 53 years (range 22-73), and median diverticular size was 26 mm (range 15-58). Six patients (54.5%) had multiple stones, and five patients (45.5%) had a single stone; median stone size was 20.6 mm (range 12.1-66.4). The transperitoneal approach was used in seven patients (63.6%) and retroperitoneal approach in four patients (36.4%). Median operative time was 161 minutes (range 110-250), median estimated blood loss was 50 mL (range 20-400), and median hospital stay was 4 days (range 3-6). An additional needlescopic instrument was used in five cases (45.5%). There were three cases (27.3%) of grade I complications (two postoperative fever, one ileus), and no intraoperative or major complications. Median visual analog scale score significantly improved by discharge day (from 4.9 preoperatively to 1.4; p = 0.003). After a median follow-up of 38 months (range 36-41), all patients were symptom free with no evidence of stone or caliceal diverticulum on imaging. CONCLUSIONS: LESS-NL is a safe, feasible, and definitive treatment option for symptomatic caliceal diverticular calculi.

A useful method for assessing differences of compensatory hypertrophy in the contralateral kidney before and after radical nephrectomy in patients with renal cell carcinoma: ellipsoid formula on computed tomography.

OBJECTIVE: To investigate the usefulness of the ellipsoid formula for assessing compensatory hypertrophy of the contralateral kidney on pre-operative and post-operative CT in renal cell carcinoma (RCC) patients. METHODS: We retrospectively identified 389 patients who had radical nephrectomy for RCC between 2011  and 2015. Contrast-enhanced CT was performed within 3 months pre-operative and at 1 year post-operative. The kidney volumes were calculated from CT using the ellipsoid formula. We subdivided patients into three groups based on tumour size (I: ≤4 cm, II: 4-7 cm, III: >7 cm). Volumetric renal parameters were compared and multivariate analyses were performed to determine predictors associated with pre-operative  and post-operative compensatory hypertrophy. RESULTS: Kidney volume calculation using the ellipsoid  method took a median of 51 s. Group III had a significantly larger median pre-operative contralateral renal volume than Groups I and II (I:  140.4, II: 141.6, III: 166.7 ml, p < 0.05). However, the median ratio of post-operative contralateral renal volume change was significantly higher in Groups I and II than Group III (I: 0.36, II: 0.23, III: 0.12, p < 0.001). On multivariate analysis, tumour size revealed the strongest positive association with pre-operative contralateral kidney volume (partial regression coefficient: ß = 30.8, >7 cm) and ratio of post-operative contralateral kidney volume change (ß  = 0.214, I vs III; ß = 0.168, II vs III). CONCLUSION: Kidney volume calculation for assessing pre- and post-operative compensatory hypertrophy of the contralateral kidney in RCC patients can be easily and rapidly performed from CT images using the ellipsoid formula. Advances in knowledge: The ellipsoid formula allows reliable method for assessing pre-operative and post-operative compensatory hypertrophy of the contralateral kidney in RCC.

The effect of ultrasound-guided compression immediately after transrectal ultrasound-guided prostate biopsy on postbiopsy bleeding: a randomized controlled pilot study.

PURPOSE: To evaluate whether ultrasound-guided compression performed immediately after transrectal ultrasound (TRUS)-guided prostate biopsy decreases bleeding complications. METHODS: We prospectively evaluated a total of 148 consecutive patients who underwent TRUS-guided prostate biopsy between March 2015 and July 2016. Systematic 12-core prostate biopsy was performed in all patients. Of these, 100 patients were randomly assigned to one of two groups: the compression group (n = 50) underwent TRUS-guided compression on bleeding biopsy tracts immediately after prostate biopsy, while the non-compression group (n = 50) underwent TRUS-guided prostate biopsy alone. The incidence rate and duration of hematuria, hematospermia, and rectal bleeding were compared between the two groups. RESULTS: The incidence rates of hematuria and hematospermia were not significantly different between the two groups (60 vs. 64%, p = 0.68; 22 vs. 30%, p = 0.362, respectively, for compression vs. non-compression group). The rectal bleeding incidence was significantly lower in the compression group as compared to the non-compression group (20 vs. 44%, p = 0.01). However, there were no significant differences in the median duration of hematuria, hematospermia, or rectal bleeding between the two groups (2, 8, and 2 days vs. 2, 10, and 1 days, p > 0.05, respectively, for compression vs. non-compression group). TRUS-guided compression [p = 0.004, odds ratio (OR) 0.25] and patient age (p = 0.013, OR 0.93) were significantly protective against the occurrence of rectal bleeding after prostate biopsy in multivariable analysis. CONCLUSIONS: Although it has no impact on other complications, ultrasound-guided compression on bleeding biopsy tracts performed immediately after TRUS-guided prostate biopsy is an effective and practical method to treat or decrease rectal bleeding.

Initial Use of High-Dose Anticholinergics Combined with Alpha-Blockers for Male Lower Urinary Tract Symptoms with Overactive Bladder: A Prospective, Randomized Preliminary Study.

OBJECTIVES: To evaluate the clinical efficacy of initial combined treatment of alpha-blocker plus dose-dependent anticholinergic agent compared to the alpha-blocker monotherapy in benign prostatic hyperplasia patients with overactive bladder. METHODS: Male lower urinary tract symptoms (LUTS) patients with International Prostate Symptom Score (IPSS) of 8 or higher, total overactive bladder Symptom Score (OABSS) of 3 or higher, and 2 points or higher in the OABSS questionnaire number 2 were enrolled. Eligible subjects (total n = 146) were randomly assigned to receive tamsulosin 0.2 mg (Group I, n = 44), tamsulosin 0.2 mg plus solifenacin 5 mg (Group II, n = 55), or tamsulosin 0.2 mg plus solifenacin 10 mg (Group III, n = 47) for 12 weeks. Efficacy and safety assessments for each group were done using detailed questionnaires, and evaluating urinary parameters such as maximal urinary flow rate (Qmax) and postvoid residual volume (PVR) at 4 and 12 weeks. RESULTS: Groups II and III (combined use of tamsulosin and solifenacin) showed significant improvement in storage symptoms compared to group I (tamsulosin monotherapy), as reflected by IPSS storage subscore and OABSS (P < 0.05). Dry mouth developed in four (7%) and eight (17%) cases in group II and III, respectively, so that one (2%) and three (6%) cases dropped out in group II and III, respectively. Two cases (4%) of AUR developed in group III, and one of them was withdrawn (2%) from the study. CONCLUSIONS: Initial combined treatment of tamsulosin plus solifenacin for men with LUTS improves storage symptoms significantly, but dose modification is necessary to prevent adverse events.

Curcumin potentiates antitumor activity of cisplatin in bladder cancer cell lines via ROS-mediated activation of ERK1/2.

Resistance of bladder cancer to cisplatin is a major obstacle to successful treatment. In the current study, we investigated the apoptotic effects of curcumin and cisplatin co-treatment in 253J-Bv(p53 wild-type) and T24(p53 mutant) bladder cancer. We found that curcumin and cisplatin co-treatment primarily targets reactive oxygen species(ROS) and extracellular regulated kinase(ERK) signaling during the apoptosis induction in bladder cancer. The apoptosis rate in 253J-Bv and T24 cells co-treated with curcumin and cisplatin was increased compared to that in cells exposed to single-agent treatment conditions. Also, caspase-3 activation and ROS production were observed in both cells treated with curcumin and cisplatin, together with upregulation of p-MEK and p-ERK1/2 signaling. NAC(ROS scavenger) and U0126(ERK inhibitor) inhibited apoptosis induced by curcumin and cisplatin. In addition, when 253J-Bv cells were co-treated with curcumin and cisplatin, p53 and p21 expression levels were markedly increased when compared to controls. Unlike 253J-Bv cells, T24 cells were co-treated with curcumin and cisplatin revealed an induction of apoptosis through decreased p-signal transducer and activator of transcription 3(STAT3) expression. Moreover, pretreatment with U0126 suppressed curcumin and cisplatin-induced upregulation of p53, p21, and p-STAT3 and downregulation of survival proteins in both cells. In conclusion, co-treatment with curcumin and cisplatin synergistically induced apoptosis through ROS-mediated activation of ERK1/2 in bladder cancer.

Tumor size is associated with compensatory hypertrophy in the contralateral kidney after radical nephrectomy in patients with renal cell carcinoma.

PURPOSE: To assess the association between tumor size and postoperative compensatory hypertrophy of the contralateral kidney estimated with preoperative and postoperative CT in patients with renal cell carcinoma (RCC). METHODS: We prospectively identified 728 patients who underwent radical nephrectomy for RCC between 2012 and 2014. Contrast-enhanced CT was done within 3 months preoperatively and 1 year postoperatively. A tissue segmentation tool program with CT images was used to estimate kidney volume. We divided patients into three groups according to tumor size (A: ≤4 cm, B: 4-7 cm, C: >7 cm). Preoperative and postoperative volumetric kidney parameters were compared and multivariable linear regression model was used to analyze predictors associated with postoperative compensatory hypertrophy. RESULTS: The preoperative median contralateral kidney volume was significantly larger in group C than in groups A and B (A: 170.3, B: 176.9, C: 186.8 mL, p < 0.05); the median tumor-side renal parenchymal volume was smaller in group C than in the other groups (A: 168.4, B: 171.1, C: 139.0 mL, p < 0.001). However, the postoperative median contralateral kidney volume among the three groups was not significantly different; the median contralateral kidney volume change after surgery was significantly larger in groups A and B than in group C (A: 37.8, B: 37.5, C: 27.4 mL, p < 0.05). Tumor size (≤7 cm) (p = 0.001) and male gender (p < 0.001) were significantly correlated with increased contralateral kidney volume on multivariable analysis. Tumor size showed the strongest positive association with postoperative contralateral kidney volume (A vs. C, partial regression coefficient = 10.6; B vs. C, partial regression coefficient = 10.5). CONCLUSIONS: Tumor size (≤4 or 4-7 cm) and male gender are significant factors associated with compensatory hypertrophy after surgery.

Volumetric measurement of compensatory hypertrophy in the contralateral normal kidney by the tumor growth.

PURPOSE: We evaluated the association between tumor size and preoperative volumetric kidney parameters measured with CT in patients with renal cell carcinoma (RCC). METHODS: We prospectively identified 1118 patients who underwent radical or partial nephrectomy for RCC between 2011 and 2014. Contrast-enhanced CT was performed within three months before surgery. Kidney volume was measured using a tissue segmentation tool program from CT images. We classified patients into three groups depending on tumor size (A: ≤4 cm, B: 4-7 cm, C: >7 cm). The preoperative volumetric kidney parameters were compared and multivariable linear regression was used to analyze potential factors associated with compensatory hypertrophy of the contralateral normal kidney before surgery. RESULTS: Patients in group C had a significantly larger contralateral normal kidney volume than patients in A and B (A: 170.0 mL, B: 171.7 mL, C: 187.2 mL, p < 0.001). The contralateral kidney volume was not significantly different between groups A and B (p > 0.05). However, tumor-side real kidney volume in group C was significantly smaller than that of groups A and B (A: 168.8 mL, B: 164.9 mL, C: 150.9 mL, p < 0.001). On multivariable analysis, increased contralateral kidney volume was positively associated with male gender, higher BMI, DM, higher preoperative GFR, and tumor size (>7 cm), and negatively associated with older age (p < 0.05). Tumor size had the strongest positive association with contralateral kidney volume (>7 cm, partial regression coefficient = 30.2). CONCLUSIONS: Tumor size (>7 cm) is the strongest factor associated with compensatory hypertrophy in the contralateral normal kidney before surgery.

Immunoprofile-based subgrouping of urothelial bladder carcinomas for survival prediction.

One of the major challenges in bladder cancer management is in distinguishing aggressive from indolent tumors with similar clinicopathological factors, especially in cases of high-grade T1 stage tumors. To define a set of prognostic factors that can be easily assessed in clinical practice with a high cost-effectiveness, the expressions of 11 proteins were examined immunohistochemically in 403 cases of transurethral resection of bladder tumors, then correlated to clinical outcomes. Based on the protein immunoprofiles, urothelial carcinomas were divided into 4 intrinsic molecular subgroups with different clinical outcomes: subgroups 1 and 4 with the poorest survival, subgroup 2 with the best survival, and subgroup 3 with the intermediate survival outcome. The protein expression patterns of the 4 subgroups were mutually exclusive: overexpression of p53, EZH2, E2F1, and IMP3 and high Ki-67 proliferation index in subgroup 1; overexpression of cytoplasmic survivin in subgroup 4; overexpression of membranous TSP1 and cytoplasmic p27 in subgroup 2; and no representative protein overexpression in subgroup 3. Using these protein immunoprofiles, 3 risk groups were generated, which predicted disease-specific survival not only in total bladder carcinoma cases with 0.737 of predictive accuracy but also in high-grade stage T1 tumors with 0.658 of predictive accuracy. These results showed that urothelial carcinomas were composed of 4 clinically relevant molecular subgroups based on protein expression and that overall survival of those patients could be predicted using a set of a small number of protein expressions not only in total cases but also in high-grade stage T1 tumors.

Sphingosine-1-phosphate receptor 1 (S1PR1) expression in non-muscle invasive urothelial carcinoma: Association with poor clinical outcome and potential therapeutic target.

AIM: Sphingosine-1-phosphate receptor 1 (S1PR1) promotes tumour cell survival, invasion, anti-apoptosis, metastasis and radio/chemo-resistance in various cancers. However, the expression pattern and prognostic implications of S1PR1 in urothelial carcinoma remain unclear and thus were addressed here. METHODS: Tissue microarrays composed of 395 initially diagnosed and transurethral resected urothelial carcinomas of the urinary bladder were immunostained for S1PR1 and phosphor-signal transducer and activator of transcription 3 (pSTAT3). S1PR1 expression was analysed according to clinicopathological features, expression of several anti-apoptosis/proliferation-related markers and patient's survival. RESULTS: S1PR1 positivity was observed in 45.3% of urothelial carcinomas. Among patients with non-muscle invasive urothelial carcinoma (NMIC), S1PR1 positivity was associated with higher grade (P<0.001), higher subepithelial invasive component (P=0.006), lower papillary component (P=0.002), presence of metastasis (P=0.042) and high cancer-specific death (P<0.001). S1PR1 expression was correlated with pSTAT3 (P<0.001), survivin (P=0.008) and Ki-67 (P<0.001) expression. S1PR1 positivity predicted a shorter cancer-specific survival (CSS) in NMICs (P<0.001) and stage T1/high grade (T1HG) tumours (P=0.002). The Cox multivariate model was composed of S1PR1, survivin, lymphovascular invasion and age, and C-index was 0.781. S1PR1 positivity was correlated with shorter CSS in p53-positive T1HG carcinoma (P=0.003) in contrast to p53-negative T1HG carcinoma (P=0.205). In p53-overexpressing NMIC, S1PR1 was the only variable of the survival model and the C-index was 0.719. CONCLUSIONS: S1PR1 expression was associated with unfavourable clinicopathological features and the expression of several anti-apoptosis/proliferation-related markers in urothelial carcinoma. S1PR1 serves as an independent predictor of cancer-specific death in NMIC. The model including S1PR1 showed highly accurate prediction for CSS in NMIC patients regardless of the modality of adjuvant therapy.