Inhibitory effects of the atypical antipsychotic, clozapine, on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells

To investigate the adverse effects of clozapine on cardiovascular ion channels, we examined the inhibitory effect of clozapine on voltage-dependent K+(Kv) channels in rabbit coronary arterial smooth muscle cells. Clozapine-induced inhibition of Kv channels occurred in a concentration-dependent manner with an halfinhibitory concentration value of 7.84 ± 4.86 µM and a Hill coefficient of 0.47 ± 0.06.Clozapine did not shift the steady-state activation or inactivation curves, suggesting that it inhibited Kv channels regardless of gating properties. Application of train pulses (1 and 2 Hz) progressively augmented the clozapine-induced inhibition of Kv channels in the presence of the drug. Furthermore, the recovery time constant from inactivation was increased in the presence of clozapine, suggesting that clozapineinduced inhibition of Kv channels is use (state)-dependent. Pretreatment of a Kv1.5 subtype inhibitor decreased the Kv current amplitudes, but additional application of clozapine did not further inhibit the Kv current. Pretreatment with Kv2.1 or Kv7 subtype inhibitors partially blocked the inhibitory effect of clozapine. Based on these results, we conclude that clozapine inhibits arterial Kv channels in a concentrationand use (state)-dependent manner. Kv1.5 is the major subtype involved in clozapineinduced inhibition of Kv channels, and Kv2.1 and Kv7 subtypes are partially involved.

Investigation of Information Acquisition Channel for Prostate Cancer High-Risk Group

Purpose@#The survey was conducted on Korean men to examine information acquisition channel for prostate cancer high risk group as part of the “Blue Ribbon Campaign” of the Korean Urological Oncology Society. @*Materials and Methods@#An online survey of 500 men aged 50 years old or older was completed to query investigation of the status of prostate cancer awareness and information acquisition from February 4 to February 9, 2021. @*Results@#Most men in their 50s and older are well aware that prostate cancer can also occur in young men in their 40s, so the rate of misunderstanding of the timing of prostate cancer screening after their 60s is very low. Two-thirds of all respondents (67.2%) were also confirmed that prostate cancer had no initial symptoms and was not included in the national cancer screening. Seventy-five percent of people look up information on their own in case of suspected prostate cancer, and 51.6% seek out knowledge on their own to prevent prostate cancer. Of the respondents, 27.4% of men contacted prostate cancer-related information within the past year, and the percentage of people contacted through ‘Internet/Phone,’ ‘People Around’ and ‘Television’ was high. The most trusted channel among prostate cancer information channels was ‘medical professionals,’ but the experience rate was not high, and the channel with high experience rate and reliability was shown as ‘television.’ @*Conclusions@#Much effort is still needed to understand the information acquisition behavior of Korean men and to improve awareness of early screening for prostate cancer.

Investigation of Information Acquisition Channel for Prostate Cancer High-Risk Group

Purpose@#The survey was conducted on Korean men to examine information acquisition channel for prostate cancer high risk group as part of the “Blue Ribbon Campaign” of the Korean Urological Oncology Society. @*Materials and Methods@#An online survey of 500 men aged 50 years old or older was completed to query investigation of the status of prostate cancer awareness and information acquisition from February 4 to February 9, 2021. @*Results@#Most men in their 50s and older are well aware that prostate cancer can also occur in young men in their 40s, so the rate of misunderstanding of the timing of prostate cancer screening after their 60s is very low. Two-thirds of all respondents (67.2%) were also confirmed that prostate cancer had no initial symptoms and was not included in the national cancer screening. Seventy-five percent of people look up information on their own in case of suspected prostate cancer, and 51.6% seek out knowledge on their own to prevent prostate cancer. Of the respondents, 27.4% of men contacted prostate cancer-related information within the past year, and the percentage of people contacted through ‘Internet/Phone,’ ‘People Around’ and ‘Television’ was high. The most trusted channel among prostate cancer information channels was ‘medical professionals,’ but the experience rate was not high, and the channel with high experience rate and reliability was shown as ‘television.’ @*Conclusions@#Much effort is still needed to understand the information acquisition behavior of Korean men and to improve awareness of early screening for prostate cancer.

Potential Utility of Prostate Health Index Density for Prostate Cancer Detection and Prediction in Korean Men: A Prospective Multicenter Study

Purpose@#We evaluated the clinical performance of Prostate Health Index (PHI) density with [-2]proPSA (p2PSA)and its derivatives in predicting the presence of prostate cancer (PCa) in Korean men. @*Materials and Methods@#A total of 706 men with total prostate-specific antigen (tPSA)≥2.5 ng/mL who underwenttheir first prostate biopsy were included in this prospective, multicenter, observational study. Diagnostic accuracyof tPSA, free-to-total PSA ratio (%fPSA), p2PSA, %p2PSA, the Beckman Coulter PHI, and PHI density wasassessed by receiver operating characteristic curve analyses and logistic regression analyses. PHI was calculatedas [(p2PSA/free PSA)×tPSA½], and density calculations were performed using prostate volume as determinedby transrectal ultrasonography. @*Results@#Overall, PCa was detected in 367 of all subjects (52%). In men with tPSA 2.5–10 ng/mL, the detectionrate of PCa was 41.1% (188 of 457). In this group, PHI and PHI density were the most accurate predictorsof PCa and significantly outperformed tPSA and %fPSA; area under the curve for tPSA, %fPSA, %p2PSA, PHI,and PHI density was 0.58, 0.68, 0.70, 0.75, 0.73 respectively. PHI and PHI density were also the strongestpredictor of PCa with Gleason score ≥7. @*Conclusions@#Based on the present prospective multicenter experience, PHI and PHI density demonstrate thesuperior clinical performance in predicting the presence of PCa in Korean men with tPSA 2.5–10 ng/mL.

De Novo Papillary Urothelial Carcinoma at a Previous Ureteroneocystostomy Site for Benign Ureteral Injury

Ureteroneocystostomy is a good treatment option for iatrogenic ureteral injury. Common complications at ureteroneocystostomy sites are strictures, stone formation, urinary infections, fistulas, and ureteral leaks. Here, we report a rare occurrence of urothelial carcinoma occurring at the site of a previous ureteral reimplantation. A 57-year-old female presented in the Emergency Department with left flank pain and chills. She had undergone a left ureteroneocystostomy with Boari flap due to iatrogenic ureteral obstruction during a laparoscopic left ovarian cystic mass excision 2 years ago. Computed tomography revealed left ureteral obstruction by the tumor at the neo-ureterovesical junction site. Both anterograde and retrograde ureteral catheterization approaches failed. We conducted a left percutaneous nephrostomy and administered antibiotics. Urine cytology was negative. We performed a left ureterovesical obstructive mass excision and Yang-Monti ileal ureter reconstruction. Biopsy of the ureteral-obstructing tumor revealed a low-grade papillary urothelial carcinoma. The patient’s symptoms and signs improved after surgery. To the best of our knowledge, this is the first report of a de novo urothelial carcinoma at the site of previous ureterovesical junction surgery. Urothelial carcinoma should be considered as one of the causes of stricture after ureteroneocystostomy. (Korean J Urol Oncol 2020;18:68-72)

Diagnostic Performance of %-2proPSA and Prostate Health Index for Prostate Cancer: Prospective, Multi-institutional Study

BACKGROUND: We evaluated the clinical performance of [-2]proPSA (p2PSA) and its derivatives in predicting the presence and aggressiveness of prostate cancer (PCa) in Korean men. METHODS: A total of 246 men with total prostate-specific antigen (tPSA) ≥ 3.5 ng/mL who underwent their first prostate biopsy were included in this prospective, multicenter, observational study. Diagnostic accuracy of tPSA, free-to-total PSA ratio (%fPSA), p2PSA, %p2PSA, and the Beckman Coulter prostate health index (PHI) was assessed by receiver operating characteristic curve analyses and logistic regression analyses. RESULTS: Overall, PCa was detected in 125 (50.8%) subjects. In men with tPSA 3.5–10 ng/mL, the detection rate of PCa was 39.4% (61/155). In this group, PHI and %p2PSA were the most accurate predictors of PCa and significantly outperformed tPSA and %fPSA; area under the curve for tPSA, %fPSA, %p2PSA, and PHI was 0.56, 0.69, 0.74, and 0.76, respectively. PHI was also the strongest predictor of PCa with Gleason score ≥ 7. CONCLUSION: This study demonstrates the superior clinical performance of %p2PSA and PHI in predicting the presence and aggressiveness of PCa in Korean men. The %p2PSA and PHI appear to improve detection of PCa and provide prognostic information.

Outcomes of Active Surveillance in Localized Prostate Cancer

Active surveillance (AS) is currently accepted as a good management option for men with low-risk prostate cancer (PCa). Moreover, given the grade migration following the 2005 International Society of Urologic Pathology consensus conference, AS may be appropriate for men presenting with favorable intermediate-risk PCa. Three contemporary experiences of AS for men with intermediate-risk features suggest that although these men are at higher risk for radical treatment, most of them are not significantly compromising chances for long-term cure. From the long-term randomized ProtectT trial, 10-year outcomes after active monitoring, surgery, or radiotherapy for localized PCa revealed that PCa specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Multiparametric magnetic resonance imaging, molecular biomarkers, and new Gleason grading system could enhance diagnostic accuracy and decrease the demerits of current AS protocols. Particularly, uniform recording of the percentage pattern 4 in Gleason 7 cancers will enable better understanding of prognostic risks and consideration of careful expansion of AS to populations with minimal Gleason pattern 4 disease.

Natural 10-year history of simple renal cysts

PURPOSE: To carry out long-term follow-up of patients diagnosed with asymptomatic simple renal cysts (SRCs). MATERIALS AND METHODS: One hundred fifty-eight adult patients in whom SRCs were incidentally diagnosed by abdominal ultrasonography or abdominopelvic computed tomography between August 1994 and June 2004 were followed up for over 10 years. The retrospective analysis investigated sequential changes in the size, shape, and Bosniak classification of the renal cyst and analyzed risk factors for increased size and growth rate of the cysts. RESULTS: The median follow-up period was 13.9 years (range, 10.0-19.8 years). Median patient age was 54.1 years (range, 22-86 years). Mean maximal cyst size was 33 mm (range, 2-90 mm). Among all patients, 120 (76%) showed a mean increase in maximum renal cyst diameter of 1.4 mm (6.4%) per year. Age at initial diagnosis was a risk factor for increased renal cyst maximum diameter. The probability of an increase in maximum diameter of an SRC was 7.1 times greater in patients aged 50 years or older at diagnosis than in those aged less than 50 years. However, among patients with an increased maximum diameter, the mean growth rate was lower in patients aged > or =50 years than in those aged <50 years. CONCLUSIONS: About three-quarters of adult patients with accidentally diagnosed SRCs presented with an increased maximum diameter. The only risk factor for an increase in maximum diameter was age. In patients with an increase in the maximum diameter, the growth rate of the maximum diameter was 6.4% per year during 10 years and decreased with age.

Osteoclast-Like Giant Cell Carcinoma of the Distal Ureter

Extraskeletal osteoclast-like giant cell (OGC) tumors are uncommon and have mainly been found in the breast and pancreas. OGC neoplasms of the urinary tract are extremely rare. Most cases found in the renal pelvis and bladder are associated with either an in situ urothelial malignancy or a conventional high-grade urothelial carcinoma. These malignancies tend to be associated with a poor prognosis and disease course. To our knowledge, no cases of OGC tumors of the distal ureter only have been published. Here, we present the case of a 76-year-old man who underwent hand-assisted laparoscopic nephroureterectomy because of painless gross hematuria with right flank pain. Pathologic examination showed OGC carcinoma of the right distal ureter. No local tumor recurrence or distant metastasis was found at the 5-month follow-up.

Efficacy of Dendritic Cells Matured Early with OK-432 (Picibanil(R)), Prostaglandin E2, and Interferon-alpha as a Vaccine for a Hormone Refractory Prostate Cancer Cell Line

Dendritic cells (DCs) are potent antigen-presenting cells. OK432 (Picibanil(R)) was introduced as a potent stimulator of DC maturation in combination with prostaglandin-E2 and interferon-alpha. We compared the efficacy of a DC-prostate cancer vaccine using early-mature DCs stimulated with OK432, PGE2 and INF-alpha (OPA) with that of vaccines using other methods. On days 3 or 7 of DC culture, TNF-alpha (T), TNF-alpha and LPS (TL) or OPA were employed as maturation stimulators. DU145 cells subjected to heat stress were hybridized with mature DCs using polyethyleneglycol. T cells were sensitized by the hybrids, and their proliferative and cytokine secretion activities and cytotoxicity were measured. The yields of early-mature DCs were higher, compared to yields at the conventional maturation time (P<0.05). In the early maturation setting, the mean fusion ratios, calculated from the fraction of dual-positive cells, were 13.3%, 18.6%, and 39.9%, respectively (P=0.051) in the T only, TL, and OPA-treated groups. The function of cytotoxic T cells, which were sensitized with the hybrids containing DCs matured early with OPA, was superior to that using other methods. The antitumor effects of DC-DU145 hybrids generated with DCs subjected to early maturation with the OPA may be superior to that of the hybrids using conventional maturation methods.

Management of Severe Bilateral Ureteropelvic Junction Obstruction in Neonates with Prenatally Diagnosed Bilateral Hydronephrosis

PURPOSE: The management of prenatally detected bilateral ureteropelvic junction obstruction (UPJO) remains controversial. We attempted to develop a treatment plan for patients with severe bilateral UPJO. MATERIALS AND METHODS: We evaluated the records of 13 patients with prenatally diagnosed grade 3 or more bilateral hydronephrosis that led to the postnatal diagnosis of severe bilateral UPJO. Ultrasonography and (99m)technetium mercaptoacetyltriglycine ((99m)Tc-MAG3) renal scans were performed within 1 month. Four renal units had grade 3 and 22 had grade 4 hydronephrosis. All 13 patients were managed by unilateral pyeloplasty, and the patients' mean age was 3 months. At 1 month postoperatively, we decided whether delayed surgery in the opposite renal unit was necessary according to the findings of ultrasonography and (99m)Tc-MAG3 scans. RESULTS: Of 13 patients, 11 underwent initial pyeloplasty on renal units with more severe hydronephrosis or lower relative renal function (RRF) on (99m)Tc-MAG3 scans. The remaining 2 patients simultaneously underwent percutaneous nephrostomy on renal units with a lower RRF and initial pyeloplasty on renal units with a higher RRF. In 5 patients, contralateral hydronephrosis had spontaneously improved at 1 month postoperatively, and 8 patients underwent delayed contralateral pyeloplasty at 2 months postoperatively. CONCLUSIONS: In children with severe bilateral UPJO, the non-operated renal units with grade 3 and some with grade 4 hydronephrosis improved spontaneously after unilateral pyeloplasty. Therefore, delayed pyeloplasty of the opposite side should be considered at 1 month following initial pyeloplasty.

Alteration of Antithrombin III and D-dimer Levels in Clinically Localized Prostate Cancer

PURPOSE: We performed a comparative analysis of the plasma levels of antithrombin (AT) III, plasminogen, fibrinogen, and D-dimer among patients with and without clinically localized prostate cancer to investigate the clinical significance of the coagulation profile in prostate cancer. MATERIALS AND METHODS: A prospective study was performed in which plasma levels of AT III, plasminogen, fibrinogen, and D-dimer were assessed in patients before they underwent prostate biopsy. According to the results of the biopsy, the patients were categorized into the cancer group or the control group. Levels of the four coagulation factors were then compared between the cancer and control groups. Also, levels of the four coagulation factors were correlated with tumor stage and grade in the cancer group. RESULTS: The cancer group had significantly lower levels of AT III activity and higher plasma D-dimer levels than did the control group (p=0.007 and p=0.018, respectively). Within the cancer group, no significant differences were observed in the levels of AT III, plasminogen, fibrinogen, or D-dimer between those with a pathological Gleason score of > or =7 and otherwise. Regarding pathologic stage of prostate cancer, the subjects with organ-confined disease and those with extraprostatic extension of a tumor demonstrated no significant differences in the preoperative levels of the four coagulation factors analyzed. CONCLUSIONS: Our results suggest that plasma levels of AT III and D-dimer are altered in patients with prostate cancer. Further study is needed to elucidate the underlying mechanism and clinical significances of such a phenomenon among patients with clinically localized prostate cancer.

Comparison of Laparoscopic and Open Partial Nephrectomies in T1a Renal Cell Carcinoma: A Korean Multicenter Experience

PURPOSE: We analyzed a series of patients who had undergone laparoscopic partial nephrectomies (LPNs) and open partial nephrectomies (OPNs) to compare outcomes of the two procedures in patients with pathologic T1a renal cell carcinomas (RCCs). MATERIALS AND METHODS: From January 1998 to May 2009, 417 LPNs and 345 OPNs were performed on patients with small renal tumors in 15 institutions in Korea. Of the patients, 273 and 279 patients, respectively, were confirmed to have pT1a RCC. The cohorts were compared with respect to demographics, peri-operative data, and oncologic and functional outcomes. RESULTS: The demographic data were similar between the groups. Although the tumor location was more exophytic (51% vs. 44%, p=0.047) and smaller (2.1 cm vs. 2.3 cm, p=0.026) in the LPN cohort, the OPN cohort demonstrated shorter ischemia times (23.4 min vs. 33.3 min, p<0.001). The LPN cohort was associated with less blood loss than the OPN cohort (293 ml vs. 418 ml, p<0.001). Of note, two patients who underwent LPNs had open conversions and nephrectomies were performed because of intra-operative hemorrhage. The decline in the glomerular filtration rate at the last available follow-up (LPN, 10.9%; and OPN, 10.6%) was similar in both groups (p=0.8). Kaplan-Meier estimates of 5-year local recurrence-free survival (RFS) were 96% after LPN and 94% after OPN (p=0.8). CONCLUSIONS: The LPN group demonstrated similar rates of recurrence-free survival, complications, and postoperative GFR change compared with OPN group. The LPN may be an acceptable surgical option in patients with small RCC in Korea.

Comparison of Laparoscopic and Open Partial Nephrectomies in T1a Renal Cell Carcinoma: A Korean Multicenter Experience

PURPOSE: We analyzed a series of patients who had undergone laparoscopic partial nephrectomies (LPNs) and open partial nephrectomies (OPNs) to compare outcomes of the two procedures in patients with pathologic T1a renal cell carcinomas (RCCs). MATERIALS AND METHODS: From January 1998 to May 2009, 417 LPNs and 345 OPNs were performed on patients with small renal tumors in 15 institutions in Korea. Of the patients, 273 and 279 patients, respectively, were confirmed to have pT1a RCC. The cohorts were compared with respect to demographics, peri-operative data, and oncologic and functional outcomes. RESULTS: The demographic data were similar between the groups. Although the tumor location was more exophytic (51% vs. 44%, p=0.047) and smaller (2.1 cm vs. 2.3 cm, p=0.026) in the LPN cohort, the OPN cohort demonstrated shorter ischemia times (23.4 min vs. 33.3 min, p<0.001). The LPN cohort was associated with less blood loss than the OPN cohort (293 ml vs. 418 ml, p<0.001). Of note, two patients who underwent LPNs had open conversions and nephrectomies were performed because of intra-operative hemorrhage. The decline in the glomerular filtration rate at the last available follow-up (LPN, 10.9%; and OPN, 10.6%) was similar in both groups (p=0.8). Kaplan-Meier estimates of 5-year local recurrence-free survival (RFS) were 96% after LPN and 94% after OPN (p=0.8). CONCLUSIONS: The LPN group demonstrated similar rates of recurrence-free survival, complications, and postoperative GFR change compared with OPN group. The LPN may be an acceptable surgical option in patients with small RCC in Korea.

The Prevalence of Benign Prostatic Hyperplasia in Elderly Men in Korea: A Community-Based Study

PURPOSE: The incidence of benign prostatic hyperplasia (BPH) is increasing in Korea. However, there are few reports about the prevalence of BPH in elderly men in Korea. We report the prevalence of BPH in elderly men through a community-based study. MATERIALS AND METHODS: We collected data from the Korean Longitudinal Study on Health and Aging (KLoSHA), which was designed as a population-based, prospective study in populations aged>65 years living in Seongnam, Korea. We selected 301 male participants by random sampling. The selected participants were interviewed with the International Prostate Symptom Score (IPSS) questionnaire and were evaluated by physical examination, blood tests, and transrectal ultrasound. The number of analyzed subjects was 236. The definition of BPH was a combination of moderate (8-19) to severe (>19) IPSS and prostate enlargement (>30 g on transrectal ultrasound). RESULTS: The prevalence of BPH was 40% overall and 36% in men in their late 60s (65-69 years), 43% in men in their 70s (70-79 years), and 53% in men over 80 (> or =80 years). BPH prevalence increased according to age but showed no statistically significant differences among the groups (p>0.05). CONCLUSIONS: The overall prevalence of BPH in this study was 40%, which was higher than in other previous epidemiologic studies in Korea. This study suggests an increasing tendency of BPH prevalence in Korea.

The Oncologic and Functional Results of the Ileal W-neobladder with a Serous-lined Extramural Tunnel / 대한비뇨기과학회지

PURPOSE: We wanted to analyze the oncologic and functional outcomes of radical cystectomy and creation of an orthotopic ileal neobladder with a serous-lined extramural tunnel. MATERIALS AND METHODS: There were 110 patients and 101 patients were male(mean age: 58.7 years, age range: 35-78 years). All these patients underwent radical cystectomy and creation of a ileal W-shaped neobladder with a serous-lined extramural tunnel, and all the procedures were done by one surgeon. The median period of follow-up was 28.9(range: 6-95) months. The Assessing the patients' clinical history, physical examinations, complete laboratory tests, CT scans and bone scans were performed postoperatively for the evaluation of recurrence and complications. The voiding patterns of 77 patients of the 110 patients were surveyed. RESULTS: Five-year-overall survival was 56% and the median survival period was 66.1 months. The tumor recurrence rate was 39.1%(43 patients) and 21(19.1%) patients died due to progression of cancer. The daytime and nighttime urinary continence rates at postoperative 1 year were 87% and 79%, respectively. Sixty three(81%) patients among the 77 patients had no voiding problems after the procedures. Nine patients still had severe incontinence and 5 patients still suffered from voiding difficulty. Renal functional deterioration developed in 3 patients(2.8%); however, no patients were on dialysis. Acute pyelonephritis was observed in 12 patients and recurrent pyelonephritis occurred in 6 patients. Ureter-ileal anastomosis site stricture was occurred in 5 renal units. No reflux from the ileal bladder into the ureter was observed. CONCLUSIONS: Radical cystectomy and an orthotopic ileal neobladder using a serous-lined extramural tunnel for patients with invasive bladder cancer were effective and durable procedures in terms of the oncologic and functional outcomes.

The Effect of Neoadjuvant Hormonal Treatment in Prostate Cancer on Biochemical Recurrence / 대한비뇨기과학회지

PURPOSE: When combined with surgery, neoadjuvant hormonal therapy (NHT) has not demonstrated a significant benefit for meaningful clinical endpoints such as progression-free survival or overall survival. We evaluated the effect of NHT on prostate cancer. MATERIALS AND METHODS: From 1995 to 2004, 519 patients underwent radical retropubic prostatectomy(RRP). One-hundred thirty of them were included in this retrospective case-control study and they were assessed for age, the preoperative prostate-specific antigen(PSA) level, the clinical stage and the biopsy Gleason score(GS). The subjects were divided into two groups: the RRP only group(n=65) and the NHT group(n=65), and these were matched for the 3 above mentioned parameters. The protocols for NHT were maximal androgen blockade(n=40), antiandrogen only(n=8), and LHRH analogue only(n=17). Biochemical recurrence was defined as a level of serum PSA of 0.2ng/ml or greater on 2 consecutive evaluations. RESULTS: The mean age of the RRP only group and the NHT group was 64.2 and 63.5, respectively(p>0.05). The rates of a positive surgical margin and biochemical recurrence in the NHT group were 49.2% and 42.5%, respectively, and they were 46.2% and 46.2%, respectively, in RRP only group, and there was no statistical difference between the two groups. In high risk patients(clinical stage> or =T3, biopsy GS> or =8, serum PSA>20ng/ml), NHT group was not differences compared with the RRP group. Neither the duration (3 months vs. 6 months) of NHT nor the regimens of NHT improved the clinical and surgical outcome. CONCLUSIONS: NHT did not improve biochemical recurrence and the positive surgical margin.