Purpose: Vibegron, a novel, potent β3 agonist, has been approved for clinical use in overactive bladder (OAB) treatment in Japan and the Unites States. We performed a bridging study to investigate the efficacy and safety of a daily 50-mg vibegron (code name JLP-2002) dose in Korean patients with OAB. Methods: A multicenter, randomized, double-blind, placebo-controlled study was conducted from September 2020 to August 2021. Adult patients with OAB with a symptom duration of more than 6 months entered a 2-week placebo run-in phase. Eligibility was assessed at the end of this phase and selected patients entered a double-blind treatment phase after 1:1 randomization to either the placebo or vibegron (50 mg) group. The study drug was administered once daily for 12 weeks and follow-up visits were scheduled at weeks 4, 8, and 12. The primary endpoint was the change in mean daily micturition at the end of treatment. The secondary endpoints included changes in OAB symptoms (daily micturition, nocturia, urgency, urgency incontinence, and incontinence episodes, and mean voided volume per micturition) and safety. A constrained longitudinal data model was used for statistical analysis. Results: Patients who took daily vibegron had significant improvements over the placebo group in both primary and secondary endpoints, except for daily nocturia episodes. The proportions of patients with normalized micturition and resolution of urgency incontinence and incontinence episodes were significantly higher in vibegron group than in the placebo. Vibegron also improved the patients’ quality of life with higher satisfaction rates. The incidence of adverse events in the vibegron and placebo groups was similar with no serious, unexpected adverse drug reactions. No abnormality in electrocardiographs was observed as well as no significant increase in postvoid residual volume. Conclusions Once daily vibegron (50 mg) for 12 weeks was effective, safe, and well-tolerated in Korean patients with OAB.

Purpose: DA-8010 is a novel muscarinic M3 receptor antagonist with significant selectivity for bladder over salivary gland in preclinical studies. We evaluated the clinical efficacy and safety of DA-8010 in overactive bladder (OAB) patients. Methods: This phase 2, randomized, double-blind, parallel-group, active reference- and placebo-controlled trial was conducted at 12 centers in South Korea (NCT03566134). Patients aged ≥19 years with OAB symptoms for ≥3 months were enrolled. Three hundred six patients (30.07% male) were randomized to 12 weeks of treatment among 4 groups; 2 experimental groups (DA-8010 2.5 or 5 mg), an active reference group (solifenacin 5 mg), and a placebo group. The change from the baseline of (=∆) 24-hour frequency at 12 weeks (primary endpoint), episodes of urgency, overall/urgency urinary incontinence, average/ maximum voided volume, nocturia, and patients’ subjective responses were analyzed. Results: In the full analysis set, the mean (standard deviation) [median] values for ∆ 24-hour frequency at 12 weeks were -1.01 (2.44) [-1.33] for placebo, -1.22 (2.05) [-1.33] for DA-8010 2.5 mg, and -1.67 (2.25) [-1.67] for DA-8010 5 mg; DA-8010 5 mg showed a significant decrease compared with placebo (P=0.0413). At 4 and 8 weeks, both DA-8010 2.5 mg (P=0.0391 at 4 weeks, P=0.0335 at 8 weeks) and DA-8010 5 mg (P=0.0001 at 4 weeks, P=0.0210 at 8 weeks) showed significant decrease in ∆ 24-hour frequency compared with placebo. DA-8010 5 mg achieved a significant decrease in ∆ number of urgency episodes, compared with placebo at 4 (P=0.0278) and 8 (P=0.0092) weeks. Adverse drug reactions (ADRs) were observed in 3.95% of placebo, 6.67% of DA-8010 2.5 mg, 18.42% of DA-8010 5 mg, and 17.33% of solifenacin 5 mg groups. No serious ADRs were observed in any patient. Conclusions Both DA-8010 2.5 mg and 5 mg showed therapeutic efficacy for OAB without serious ADRs. Therefore, both dosages of DA-8010 can advance to a subsequent large-scale phase 3 trial.

PURPOSE: Many men are to some degree unsatisfied with the size of their penis, whether it is normal in size and appearance or not. We report a novel surgical technique for penile augmentation using a superficial external pudendal artery pedicle. MATERIALS AND METHODS: In total, 8 patients underwent penile augmentation from March 2003 to February 2004. Their mean age was 37.3 years. Five patients were unsatisfied about the size of their penis, and three patients had complications after insertion of foreign material. This penile augmentation technique was developed by using a low abdominal fat-flap where blood is supplied from the external pudendal artery. Spinal or epidural anesthesia was done during the operation, and the fat-flap was elevated and transpositioned to the site of lesion. RESULTS: All cases of patients were performed successfully by autografting using adipose tissue where blood flow was supplied from the external pudendal artery. There were no complications except one case of hematoma after the operation. The mean operative time was 80 min. The mean follow-up period after operation was about 6 months and all patients had a normal sexual life and no voiding dysfunctions. CONCLUSIONS: This novel surgical technique has several advantages. First, reconstruction without skin necrosis was possible even though the defect was large, because the blood supply was favorable. Second, there was no size limitation in augmentation with dermoplasty. Third, there was no evidence of atrophy of the flap.
Adipose Tissue ; Anesthesia, Epidural ; Arteries ; Atrophy ; Follow-Up Studies ; Hematoma ; Humans ; Male ; Necrosis ; Operative Time ; Penile Implantation ; Penis ; Skin ; Transplantation, Autologous

A 61-year-old man who had been diagnosed with prostate cancer 9 years ago and had been treated with pelvic irradiation and intermittent androgen deprivation therapy visited the emergency room because of back pain and weakness in both legs. Spine magnetic resonance imaging showed a lumbar epidural mass and spine metastasis. The whole-body workup revealed multiple metastases to the lymph nodes, bone, liver, and lung. The serum prostate-specific antigen was 0.02 ng/ml. He underwent laminectomy, posterior fixation, and epidural mass excision, and metastatic adenocarcinoma from the prostate was diagnosed. The patient underwent 1 cycle of docetaxel-based chemotherapy. More chemotherapy could not be done because of his general weakness. The patient died one month later of multiple organ failure.
Adenocarcinoma ; Back Pain ; Disease Progression ; Emergencies ; Humans ; Laminectomy ; Leg ; Liver ; Lung ; Lymph Nodes ; Magnetic Resonance Imaging ; Middle Aged ; Multiple Organ Failure ; Neoplasm Metastasis ; Prostate ; Prostate-Specific Antigen ; Prostatic Neoplasms ; Spine

BACKGROUND AND OBJECTIVES: Efonidipine hydrochloride, an L- and T-type dual calcium channel blocker, is suggested to have a heart rate (HR)-slowing action in addition to a blood pressure (BP)-lowering effect. The aim of this study was to determine the effect of efonidipine on HR and BP in patients with mild-to-moderate hypertension. SUBJECTS AND METHODS: In a multi-center, prospective, open-labeled, single-armed study, we enrolled 53 patients who had mild-to-moderate hypertension {sitting diastolic BP (SiDBP) 90-110 mmHg}. After a 2-week washout, eligible patients were treated with efonidipine (40 mg once daily for 12 weeks). The primary end point was the change in HR from baseline to week 12. The secondary end-point included the change in trough sitting BP and 24-hour mean BP between baseline and week 12. Laboratory and clinical adverse events were monitored at each study visit (4, 8, and 12 weeks). RESULTS: Fifty-two patients were included in the intention-to-treat analysis. After 12 weeks of treatment with efonidipine, the resting HR decreased significantly from baseline to week 12 {from 81.5+/-5.3 to 71.8+/-9.9 beats/minute (difference, -9.9+/-9.0 beats/minute), p<0.0001}. The trough BP {sitting systolic blood pressure (SiSBP) and SiDBP} and 24-hour mean BP also decreased significantly (SiSBP: from 144.6+/-8.2 to 132.9+/-13.5 mmHg, p<0.0001; SiDBP: from 96.9+/-5.4 to 88.3+/-8.6 mmHg, p<0.0001, 24-hour mean systolic BP: from 140.4+/-13.5 to 133.8+/-11.6 mmHg, p<0.0001; 24-hour mean diastolic BP: from 91.7+/-8.7 to 87.5+/-9.5 mmHg, p<0.0001). CONCLUSION: Efonidipine was effective in controlling both HR and BP in patients with mild-to-moderate hypertension.
Blood Pressure ; Calcium ; Calcium Channel Blockers ; Calcium Channels ; Dihydropyridines ; Heart ; Heart Rate ; Humans ; Hypertension ; Nitrophenols ; Organophosphorus Compounds ; Prospective Studies

OBJECTIVE: Free hand insertion of an external ventricular drain (EVD) is one of the most common emergency neurosurgical procedures, usually performed on critically ill patients. Complications such as infection and hemorrhage that accompany the placement of an EVD have been studied thoroughly, but few reports have focused on the accuracy of EVD positioning. As a result, the authors of this paper retrospectively studied the accuracy of tip positioning in the placement of an EVD. METHODS: One hundred and thirteen emergency EVDs were performed through Kocher's point during the past 3 years. All patients underwent the following procedures: at least one routine post-EVD computed tomographic (CT) scan that was retrospectively reviewed for accuracy of the EVD tip position, calculation of the Evan's index, and measurement of the intracranial length of the EVD. We divided the EVD tip position into 6 groups as follows:1) ipsilateral frontal horn of the lateral ventricle, 2) contralateral frontal horn of the lateral ventricle, 3) third ventricle, 4) body of the ipsilateral or contralateral lateral ventricle, 5) basal cisterns, or 6) brain parenchyma. Among the 6 groups, only the ipsilateral frontal horn group was considered to be the correct position for the EVD tip. RESULTS: The mean age of the patients was 55.6+/-15.3 years (age range, 12~90 years), and the most common indication for the EVD was supratentorial intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) (57.5%). Forty-five out of a total of 113 EVDs were placed by inexperienced neurosurgical trainees, and the remaining 68 were placed by experienced practitioners. Among 113 post-EVD CT scans, 48 EVD tips (42.5%) were in the ipsilateral frontal horn of the lateral ventricle (considered to be the correct position); 22 (19.5%) were in the third ventricle, 16 (14.1%) in the body of the ipsilateral or contralateral lateral ventricle, 14 (12.4%) in the contralateral frontal horn of the lateral ventricle, 11 (9.7%) within the brain parenchyma and 2 (1.8%) in the basal cistern. The mean estimated EVD length was 57+/-8.4mm. The mean length of EVDs that were positioned in the ipsilateral frontal horn was 55+/-4.3 mm, whereas the mean lengths of EVDs in the parenchyma and basal cistern were 64+/-14mm and 72+/-3.5mm, respectively. In addition, there was no statistically significant relationship between the surgeon's experience and the accuracy of the position of the EVD tip (p > 0.05). CONCLUSION: Emergency free hand placement of an EVD might be an inaccurate procedure. Further multi-institutional prospective studies are required to assess the accuracy and complications of free hand insertion of EVDs in an emergency setting. Studies are also needed on the feasibility of routine use of intra-operative neuro-navigation of other guidance tools, such as ultrasonography.
Animals ; Brain ; Cerebral Hemorrhage ; Critical Illness ; Emergencies ; Hand ; Hemorrhage ; Horns ; Humans ; Lateral Ventricles ; Neurosurgical Procedures ; Retrospective Studies ; Third Ventricle

PURPOSE: The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report here our experience with the CyberKnife(TM), demonstrating its efficacy, safety, and feasibility as a treatment modality for non-metastatic prostate cancer. MATERIALS AND METHODS: Between October 2002 and April 2006, 20 patients with biopsy-proven prostate cancer were treated with the CyberKnife(TM). The distribution of clinical risks, as assessed by using D'Amico's definition for risk grouping, was as follows: low (4), intermediate (5), and high (11). Three patients received 32 Gy, 7 patients received 34 Gy, and 10 patients received 36 Gy. All patients received the radiation doses in 4 fractions. The rectal and bladder toxicities were graded by using the criteria set forth by the Radiation Therapy Oncology Group (RTOG). RESULTS: The mean patient age was 71.4 years (range, 52-79 years), and the mean follow-up period was 35.5 months (range, 8-74 months). There were 2 acute and 1 late grade 2 gastrointestinal toxicities, and 1 acute and 2 late grade 2 urinary toxicities. The 5-year overall survival rate was 100%, respectively. The 5-year biochemical failure-free rate of the low-risk, intermediate-risk, and high-risk patients was 100%, 100%, and 90.9%, respectively. CONCLUSIONS: CyberKnife(TM) is a safe, well-tolerated, and rather effective treatment for non-metastatic prostate cancer. We obtained a 100% 5-year biochemical failure-free rate in low-risk and intermediate-risk patients. CyberKnife(TM) is a viable option for the treatment of non-metastatic prostate cancer.
Follow-Up Studies ; Humans ; Prostate ; Prostatic Neoplasms ; Radiobiology ; Radiosurgery ; Survival Rate ; Urinary Bladder

PURPOSE: The aim of this study was to evaluate the effectiveness and indication of radiofrequency ablation(RFA) using renal VX2 tumors by implantation of VX2 tumor cells under the renal capsule in rabbits. MATERIALS AND METHODS: Ten rabbits were injected with 30-40microliter VX2 tumor cells(1.2x10(7) viable cells/ml) under the renal capsule of the right kidney by right subcostal incision. On the 14th day after the tumor cells were implanted, we checked for the development of renal tumors, and the sizes and shapes(exophytic or central) of the tumors by the use of computed tomography. We performed RFA in the renal VX2 tumors with a 17G StarBurst electrode through kidney exposure. After the first and third day following RFA, renal function was checked. On the third day, we performed CT and harvested the kidneys for gross and microscopic evaluation. RESULTS: We confirmed the development of renal VX2 tumors in nine cases. Tumor shapes were exophytic in seven cases and central in two cases; the mean size of the tumors was 2.1 cm(range, 1.1-3.8cm). In all tumors, RFA was performed. From the use of enhanced CT after RFA on the third day, all of the lesions treated with RFA showed no enhancement. From the pathological findings, coagulative necroses were seen on all of the lesions treated with RFA. The necrotized tumor size after RFA was not different statistically as measured by CT and a pathological examination (p=0.833) CONCLUSIONS:: In centrally located renal tumors, we experienced thermal injury in pelvocalyceal systems. RFA is an effective method for nephron sparing surgery as the tumor cells completely disappear and there is preserved renal function and the procedure is easy to apply. We suggest that the RFA method for exophytic renal tumors is more effective than other procedures.
Rabbits ; Animals

PURPOSE: The purpose of this study was to compare the surgical outcomes of two different surgical methods for varicocelectomy, and to assess the effects of varicocelectomy on semen parameters in subinfertile men. MATERIALS AND METHODS: This study included 63 patients with clinically palpable varicocele and abnormal semen parameters who underwent varicocelectomy. Thirty-three patients underwent laparoscopic varicocelectomy, and 30 received microsurgical inguinal varicocelectomy. Semen analyses were performed 5.3 months later, and compared with the pre-operative data. RESULTS: The mean age of patients was 32.1+/-1.3 years old. Comparison of the semen parameters between pre and post-varicocelectomy revealed significant improvement in the sperm count (p<0.05). In laparoscopic and microsurgical inguinal varicocelectomy, the sperm counts were increased from 16.2+/-4.3 to 30.6+/-7.5 and from 15.4+/-3.8 to 37.5+/-7.7, respectively. Sperm motility also tended to improve. CONCLUSIONS: Varicocelectomy enhanced semen parameters after both laparoscopic and microsurgical methods. In subfertile men, early varicocelectomy is recommended.
Humans ; Male ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Varicocele

PURPOSE: The purpose of this study was to compare the surgical outcomes of two different surgical methods for varicocelectomy, and to assess the effects of varicocelectomy on semen parameters in subinfertile men. MATERIALS AND METHODS: This study included 63 patients with clinically palpable varicocele and abnormal semen parameters who underwent varicocelectomy. Thirty-three patients underwent laparoscopic varicocelectomy, and 30 received microsurgical inguinal varicocelectomy. Semen analyses were performed 5.3 months later, and compared with the pre-operative data. RESULTS: The mean age of patients was 32.1+/-1.3 years old. Comparison of the semen parameters between pre and post-varicocelectomy revealed significant improvement in the sperm count (p<0.05). In laparoscopic and microsurgical inguinal varicocelectomy, the sperm counts were increased from 16.2+/-4.3 to 30.6+/-7.5 and from 15.4+/-3.8 to 37.5+/-7.7, respectively. Sperm motility also tended to improve. CONCLUSIONS: Varicocelectomy enhanced semen parameters after both laparoscopic and microsurgical methods. In subfertile men, early varicocelectomy is recommended.
Humans ; Male ; Semen ; Semen Analysis ; Sperm Count ; Sperm Motility ; Varicocele