Effects of the beta-blocker carvedilol on arrhythmia and long-term clinical outcomes in benign prostate hypertrophy patients.

Benign prostatic hypertrophy (BPH) is associated with autonomic dysfunction and sympathetic nervous system mediated by the alpha receptor. However, limited data exist regarding the effects of the beta-blocker (BB) carvedilol on arrhythmia and urologic outcomes in BPH patients. Our database of patients diagnosed with BPH from 2015 to 2020 was used to obtain echocardiography and electrocardiogram data. Inclusion criteria were BPH patients taking BBs. International Prostate Symptom Score questionnaire were used to evaluate the urinary symptoms and quality of life. Among 448 patients with BPH (69.2 ± 10.9 years) taking BBs, 219 patients took carvedilol (48.9%) and 229 patients took a non-carvedilol BB (51.1%; bisoprolol, 184 patients, 80% or nebivolol, 45 patients, 20%). Difference in the baseline characteristics was not observed. During the median 36-month follow-up, a lower incidence of arrhythmic events (P = .029), total urologic events (P < .001), and less use of additive alpha-blocker was observed in the carvedilol group (P = .022). In multivariate analysis, less carvedilol use (P = .019), heart failure (P < .001), stroke (P < .001), and cardiomyopathy (P = .046) were independent risk factors for arrhythmic events. In addition, less carvedilol use (P = .009) and older age (P = .005) were independent risk factors for urologic events based on BB type at the median 36-month follow-up. The use of carvedilol was associated with less arrhythmic events in BPH patients with palpitation and decreased the incidence of urologic events in BPH compared with the use of non-carvedilol BBs in long-term follow-up.

Correlation between 5-α reductase type 2 protein expression and methylation of 5-α reductase type 2 promotor gene of benign prostatic hyperplasia.

PURPOSE: The enzyme 5-α reductase type 2 (5-AR 2) plays a key role in the development and maintenance of the prostate gland. We evaluated the level 5-AR 2 protein expression and the relationship between methylation of the 5-AR 2 gene-promoter and 5-AR 2 protein expression of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A total of 37 prostate samples were evaluated. These included 22 samples from men undergoing transurethral prostate resections and 15 non-cancerous transition-zone human prostate tissue samples taken following radical prostatectomy. We quantified 5-AR 2 protein expression and gene-promoter methylation status using common assay procedures. Clinical variables included age, body mass index (BMI), prostate-specific antigen (PSA) levels, lipid profiles, and prostate volumes. Univariate and multivariate statistical analyses were performed followed by stepwise logistic regression modeling. RESULTS: We were able to extract DNA from 36 of the 37 tissue samples and 10 of these (28%) did not express the 5-AR 2 protein. In total, 26 patients (72%) had methylated 5-AR 2 promoter-regions. There was a strong correlation between methylation of the 5-AR 2 promoter-regions and low-absent 5-AR 2 protein expression (p = 0.0003). Increasing age significantly predicted methylation status and protein expression level (p = 0.013). CONCLUSIONS: The level of 5-AR 2 protein expression varies among prostate tissue samples. Methylation of the 5-AR 2 gene-promoter may account for low or absent expression of 5-AR 2 in adult human prostate tissues. Increased age correlates with increased 5-AR 2 gene-promoter methylation and decreased protein expression in men with BPH.

A back-to-back tumor composed of papillary renal cell carcinoma and oncocytoma treated by laparoscopic partial nephrectomy: a case report.

BACKGROUND: Renal oncocytoma is the most common benign renal tumor, and papillary renal cell carcinoma is the second most common histologic subtype of renal cell carcinoma. Renal tumors containing different components such as papillary renal cell carcinoma and oncocytoma are extremely rare. CASE PRESENTATION: A renal mass was incidentally detected in a 52-year-old Korean woman, and a computed tomographic scan showed a 32-mm multicystic mass with some calcifications in the lower pole of the right kidney. She underwent laparoscopic partial nephrectomy without any perioperative complications. We found a papillary renal cell carcinoma and an oncocytoma in a tumor mass. CONCLUSIONS: The possibility of a mixed malignant tumor should be considered while treating benign tumors such as oncocytoma.

Laparoscopic -2port Varicocelectomy with Scarless Periumblical Mini-Incision: Initial Experience in Approach and Outcomes.

PURPOSE: As with other areas, there have been many efforts for minimally invasive surgery in varicocelectomy. We present our initial experience with laparoscopic varicocelectomy with a two-port scarless periumbilical mini-incision. MATERIALS AND METHODS: The study enrolled 18 patients who underwent laparoscopic varicocelectomy with a twoportscarless periumbilical mini-incision from February 2012 to April 2013. The laparoscopic varicocelectomy was performed using two 5-mm ports at periumbilical sites in skin creases. Here, the surgical procedure is introduced and the outcomes of the case series are summarized. We reviewed other laparoscopic techniques and compared them with our technique. RESULTS: The mean patient age was 34.8 years. Of the 18 patients, 15 had grade 3 varicoceles. The mean operatingtime was 62.5 minutes. Postoperatively, the scrotal pain level decreased immediately from a mean VAS score of 6.3 to 4.4 and then to 1.7 by 24 hours postoperatively. The mean hospital stay was 2.8 days. Complications included one hydrocele and two recurrent varicoceles. The operating time decreased as the surgeon's experience increased. CONCLUSION: Laparoscopic varicocelectomy with a two-port scarless periumbilical mini-incision is a feasible technique that can be mastered relatively easily. Prospective and comparative studies are required to validate this new technique.

Longitudinal changes in erectile function after thulium:YAG prostatectomy for the treatment of benign prostatic obstruction: a 1-year follow-up study.

This study aimed to evaluate the impact of thulium:yttrium-aluminum-garnet (Tm:YAG) (RevoLix®) laser prostatectomy for the treatment of benign prostatic obstructions on erectile function (EF). A total of 208 patients who underwent Tm:YAG laser prostatectomies participated in this study. All cases were evaluated preoperatively and at 3, 6, and 12 months postoperatively using the International Prostate Symptom Score (IPSS), quality of life (QoL) score, and the International Index of Erectile Function (IIEF-5) questionnaires. Patients were divided into groups A (severe erectile dysfunction [ED]), B (moderate ED), and C (mild-to-normal ED), according to their IIEF-5 scores. The median patient ages were 69, 65, and 62 years in groups A, B, and C, respectively. Significant improvements occurred in the IPSS and QoL score within the groups during the 12-month follow-up period. The IIEF-5 scores at 3 months postoperatively were lower than the preoperative scores in groups B and C. The IIEF-5 scores subsequently improved during the 12-month follow-up period. The slope of the relationship between the IIEF-5 score and the time since Tm:YAG laser prostatectomy had a ß value of 0.2210 (95% confidence interval 0.103 to 0.338, p = 0.0003); hence, each postoperative month was associated with an increase of 0.2210 in the IIEF-5 score. The IIEF-5 scores gradually increased and reached the preoperative levels by the 12-month follow-up assessment. Although the IIEF-5 score dropped significantly during the first 3 months postoperatively, it improved over the following 12 months. Tm:YAG laser prostatectomy did not impact on EF ultimately.

Correlation between postoperative prostate-specific antigen and biochemical recurrence in positive surgical margin patients: Single surgeon series.

BACKGROUND: To evaluate the relationship between postoperative prostate-specific antigen (PSA) levels and biochemical recurrence (BCR) after radical prostatectomy, especially in patients with positive surgical margins (PSMs). MATERIALS AND METHODS: A total of 144 patients who underwent radical prostatectomies performed by a single surgeon without any neoadjuvant or adjuvant treatment were analyzed. Differences in clinicopathological factors were compared by surgical margin status, and the relationship between postoperative PSA level and BCR in patients with PSMs was evaluated. RESULTS: Fifty of the 144 patients (34.7%) had PSMs. Of these, 74% experienced BCR. The negative surgical margins and PSMs groups differed significantly in terms of PSA level at diagnosis, clinical T stage, and risk group by the cancer of the prostate risk assessment score (P = 0.002, P = 0.002, and P = 0.004, respectively). Also, the nadir PSA level, tumor volume, and BCR rate differed between the two groups (P = 0.007, P = 0.015, and P = 0.005, respectively) On Kaplan-Meier analysis, BCR-free survival was better in the negative surgical margins than the PSMs group (64.1 vs. 55.4 months, log-rank test, P = 0.011). BCR-free survival did not differ significantly in PSMs patients according to whether PSA level was or was not detectable at 1 month postoperatively. However, BCR-free survival improved when the nadir PSA level was undetectable (compared to detectable) in PSMs patients (64.3 vs. 26.1 months, log-rank test, P < 0.001). In PSMs patients belonging to the high risk group by cancer of the prostate risk assessment score, BCR-free survival was significantly better when the PSA level attained the nadir within 3 months, compared to > 6 months, postoperatively (64.2 vs. 29.5 months, log-rank test, P = 0.022). CONCLUSION: If PSA is detectable in PSMs patients until 1 month after operation, cautious observation may be possible. If the nadir is attained within 3 months postoperatively in high-risk patients with PSMs, better BCR-free survival may be expected.

Wnt signaling promotes androgen-independent prostate cancer cell proliferation through up-regulation of the hippo pathway effector YAP.

Aberrant up-regulation of Wnt/ß-catenin signaling is associated with the development and progression of prostate cancer, but the underlying mechanism is unclear. Here we show that in the absence of androgens, the Wnt/ß-catenin pathway activates AR-mediated transcription through up-regulation of the Hippo pathway effector Yes-associated protein (YAP). Wnt3a-conditioned medium (Wnt3a-CM) promotes the growth of LNCaP cells and increases AR and YAP protein levels. Moreover, Wnt3a-CM induces the nuclear translocation of YAP and the AR, but not ß-catenin, thereby activating the expression of AR- and YAP-dependent genes, in an androgen-independent manner. In addition, depletion of YAP with small interfering RNA (siRNA) prevented Wnt3a-CM-mediated up-regulation of AR-dependent gene expression. Thus, our findings provide mechanistic insight into the proposed cross-talk between the Wnt/ß-catenin and Hippo pathways in androgen-independent prostate cancer development.

Computed Tomography Imaging Features and Changes in Hemostatic Agents After Laparoscopic Partial Nephrectomy.

PURPOSE: Urologists and radiologists should be aware of the CT scan appearance of laparoscopic partial nephrectomy (LPN) with the various hemostatic agents since they may confound the interpretation of these radiographic findings. We report the various postoperative CT scan appearance and changes after LPN. MATERIALS AND METHODS: We reviewed CT scans retrospectively (within 3 months) of 86 patients who underwent LPN using various hemostatic agents between March 2008 and July 2014. We analyzed the CT findings after LPN, including postoperative changes, tumor recurrence, and complications. We also discuss changes in abnormal features, such as mass-like lesions and gas formation, on follow-up CT scans. RESULTS: To categorize the postoperative changes, we classified them according to their specific CT findings: (1) a combination of perinephric stranding and postsurgical fluid collection (n = 46), (2) mass-like lesions (n = 35), (3) a parenchymal defect (n = 2), (4) local recurrence at the surgical site (n = 1), (5) a large hematoma as a complication after LPN (n = 2), (6) gas pockets, which may be a response to postsurgical fluid collection around soft tissue (n = 35), (7) fat at the excision site (n = 2; Fig. 7 ), and (8) contrast extravasation in the delayed phase (n = 1). Mass-like lesions were visible in 35 cases. The average change in size of bolster masses was -1.19 mm/month. However, the overall change in enhancement of mass-like lesions was not significant over time. Foci of gas were noted in 16 patients at the resection site in the first follow-up period (<3 months), as late as 40 days after the procedure. CONCLUSIONS: Knowledge of CT imaging features and changes in hemostatic agents following LPN is important in interpreting postoperative CT scans, as postoperative changes can be confused with tumor recurrence and can mimic abscesses.

Transutricular seminal vesiculoscopy in the management of symptomatic midline cyst of the prostate.

PURPOSE: To evaluate the utility of transutricular seminal vesiculoscopy as a diagnostic and therapeutic option for symptomatic midline cyst of the prostate in patients with hematospermia and symptoms associated with prostatitis. MATERIALS AND METHODS: From January 2005 to July 2013, 61 patients with symptomatic (hematospermia, pain on ejaculation, scrotal discomfort) midline cyst of the prostate, who did not improve with medication within a 4-week period, were included. Diagnosis of a midline cyst of the prostate was based on an anechoic round or spheroid-shaped lesion in the median, above the level of the verumontanum, extending into the prostatic base on transrectal ultrasonography (TRUS). All patients underwent transutricular seminal vesiculoscopy using a 9.0 Fr rigid ureteroscope and Bugbee electrode. Medical records, the Chronic Prostatitis Symptom Index (NIH-CPSI), and TRUS were used for assessment for more than 3 months after the procedure. RESULTS: Of the 61 patients, 32 (52.4 %) had hematospermia, 20 (32.7 %) had symptoms associated with chronic pelvic pain syndrome, such as perineal pain, scrotal discomfort, and testicular pain, and nine (14.7 %) patients had ejaculatory disturbances, such as painful or uncomfortable ejaculation and anejaculation as major complaints/symptoms. In endoscopic findings, hemorrhage was present in the dilation of the prostatic utricle and in the seminal vesicle in 11 (18.0 %) and 21 (34.4 %) of the patients, respectively. Calculi were found in the dilation of the prostatic utricle and in the seminal vesicle in 12 (19.7 %) and six (9.8 %), respectively. Hematospermia resolved in 29 of 32 (90.6 %) patients after transutricular seminal vesiculoscopy. In 29 patients with chronic pelvic pain syndrome and ejaculatory disturbances, NIH-CPSI scores improved, from 19.0 ± 3.8 to 11.8 ± 3.6 (p < 0.001), after treatment. The pain domain and quality-of-life domain scores of the NIH-CPSI were better postsurgery than presurgery (p < 0.001). Acute epididymitis, as a postoperative complication, was observed in two patients (3.3 %). CONCLUSIONS: There are various endoscopic findings in the dilation of prostatic utricle and seminal vesicle such as hemorrhage, calculi or/and purulent material in the patients with midline cyst of the prostate. The role of transutricular seminal vesiculoscopy in reducing symptoms may be mediated through the effects of endoscopic fenestration, removal of blood clots, calculi, or whitish debris and/or electrocautery of intracystic hemorrhage. This endoscopic technique enables useful diagnostic and therapeutic approaches for symptomatic midline cysts of the prostate.

Incidental abnormal FDG uptake in the prostate on 18-fluoro-2-deoxyglucose positron emission tomography-computed tomography scans.

18-fluoro-2-deoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) scans are commonly used for the staging and restaging of various malignancies, such as head and neck, breast, colorectal and gynecological cancers. However, the value of FDG PET/CT for detecting prostate cancer is unknown. The aim of this study was to evaluate the clinical value of incidental prostate 18F-FDG uptake on PET/CT scans. We reviewed 18F-FDG PET/CT scan reports from September 2009 to September 2013, and selected cases that reported focal/diffuse FDG uptake in the prostate. We analyzed the correlation between 18F-FDG PET/CT scan findings and data collected during evaluations such as serum prostate-specific antigen (PSA) levels, digital rectal examination (DRE), transrectal ultrasound (TRUS), and/or biopsy to confirm prostate cancer. Of a total of 18,393 cases, 106 (0.6%) exhibited abnormal hypermetabolism in the prostate. Additional evaluations were performed in 66 patients. Serum PSA levels were not significantly correlated with maximum standardized uptake values (SUVmax) in all patients (rho 0.483, p=0.132). Prostate biopsies were performed in 15 patients, and prostate cancer was confirmed in 11. The median serum PSA level was 4.8 (0.55-7.06) ng/mL and 127.4 (1.06-495) ng/mL in the benign and prostate cancer groups, respectively. The median SUVmax was higher in the prostate cancer group (mean 10.1, range 3.8-24.5) than in the benign group (mean 4.3, range 3.1-8.8), but the difference was not statistically significant (p=0.078). There was no significant correlation between SUVmax and serum PSA, prostatic volume, or Gleason score. 18F-FDG PET/CT scans did not reliably differentiate malignant or benign from abnormal uptake lesions in the prostate, and routine prostate biopsy was not usually recommended in patients with abnormal FDG uptake. Nevertheless, patients with incidental prostate uptake on 18F-FDG PET/ CT scans should not be ignored and should be undergo further clinical evaluations, such as PSA and DRE.

Cancer of the Prostate Risk Assessment (CAPRA) Preoperative Score Versus Postoperative Score (CAPRA-S): ability to predict cancer progression and decision-making regarding adjuvant therapy after radical prostatectomy.

The University of California, San Francisco, announced in 2011 Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score which included pathologic data, but there were no results for comparing preoperative predictors with the CAPRA-S score. We evaluated the validation of the CAPRA-S score in our institution and compare the result with the preoperative progression predictor, CAPRA score. Data of 130 patients were reviewed who underwent radical prostatectomy for localized prostate cancer from 2008 to 2013. Performance of CAPRA-S score in predicting progression free probabilities was assessed through Kaplan Meier analysis and Cox proportional hazards regression test. Additionally, prediction probability was compared with preoperative CAPRA score by logistic regression analysis. Comparing CAPRA score, the CAPRA-S score showed improved prediction ability for 5 yr progression free survival (concordance index 0.80, P = 0.04). After risk group stratification, 3 group model of CAPRA-S was superior than 3 group model of CAPRA for 3-yr progression free survival and 5-yr progression free survival (concordance index 0.74 vs. 0.70, 0.77 vs. 0.71, P < 0.001). Finally the CAPRA-S score was the more ideal predictor concerned with adjuvant therapy than the CAPRA score through decision curve analysis. The CPARA-S score is a useful predictor for disease progression after radical prostatectomy.

Thulium laser (RevoLix) vaporesection versus vapoenucleation with morcellator (Piranha) for the treatment of benign prostatic obstruction: a propensity-matched multicenter analysis.

OBJECTIVES: To compare the efficacy and safety of vaporesection without a morcellator, and vapoenucleation with a morcellator in thulium laser prostatectomy for the treatment of benign prostatic obstruction. METHODS: Between March 2010 and January 2013, 405 patients underwent thulium:yttrium-aluminium-garnet laser prostatectomy. Among these patients, 150 patients who underwent thulium:yttrium-aluminium-garnet laser prostatectomy without a morcellator (n = 75) or with a morcellator (n = 75) were analyzed in a propensity matching study. Outcome measures included International Prostate Symptom Score, quality of life score, maximum flow rate, postvoid residual, total operating time, laser time and resected tissue weight. RESULTS: No significant differences were noted between the thulium:yttrium-aluminium-garnet laser prostatectomy without a morcellator and thulium:yttrium-aluminium-garnet laser prostatectomy with a morcellator groups, including the prostate volume (50.3 vs 51.9 mL) and postoperative prostate volume (22.4 vs 18.7 mL). However, there were differences between the groups in total operating time (72.8 vs 61.0 min, P = 0.023) and laser activating time (24.5 vs 19.9 min, P = 0.037). Thulium:yttrium-aluminium-garnet laser prostatectomy with a morcellator showed greater resected tissue volume than thulium:yttrium-aluminium-garnet laser prostatectomy without a morcellator (9.0 vs 18.2 g, P = 0.029). There were also significant differences in total retrieval efficiency (1.14 vs 1.67 g/min, P = 0.031). There were no significant differences in improvement of International Prostate Symptom Score, quality of life scores and urodynamic findings between the two groups, except for the International Prostate Symptom Score (11.2 vs 7.3, P = 0.028) at 6 weeks after surgery. CONCLUSION: Thulium:yttrium-aluminium-garnet laser prostatectomy with a morcellator provides superior reduction of prostate volume and better short-term clinical outcomes than thulium:yttrium-aluminium-garnet laser prostatectomy without a morcellator in the treatment of patients with benign prostatic obstruction. Furthermore, thulium:yttrium-aluminium-garnet laser prostatectomy with a morcellator can offer a shorter operative time.

Predictive value of the cancer of the prostate risk assessment score for recurrence-free survival after radical prostatectomy in Korea: a single-surgeon series.

PURPOSE: To evaluate the validity of the cancer of the prostate risk assessment (CAPRA) score, a newly developed nomogram for preoperative prediction of recurrence after radical prostatectomy, in a single institution in Korea. MATERIALS AND METHODS: We retrospectively studied 115 men who had undergone radical prostatectomy as the first treatment for localized prostate cancer. The validity of the CAPRA score for the prediction of recurrence-free survival (RFS) and pathologic outcome was evaluated by using Kaplan-Meier analysis and a proportional hazards regression model. A seven-group model and a three-group model were used for the results. RESULTS: None of the variables of the CAPRA score was favorable compared with the previously reported data. The three-group model was significantly related with 3- and 5-year RFS (p<0.05), but the seven-group model was not. The concordance indices of the CAPRA score were 0.74 and 0.77. Of four components excluding the clinical T stage, three independently predicted RFS (age, Gleason sum, and percentage of positive biopsies). The CAPRA score was significantly related to the margin status, extracapsular extension, and seminal vesicle invasion in both the seven- and three-group models. In the three-group model, pathologic outcomes were more strongly related, especially a higher risk of seminal vesicle invasion. CONCLUSIONS: The CAPRA score showed high accuracy for predicting RFS. In particular, the three-group model was more useful for predicting RFS and pathologic outcomes. Therefore, the CAPRA score may be a useful prediction model for risk stratification and may help clinicians to develop localized prostate cancer treatment.

Primary androgen deprivation therapy for prostate cancer in koreans: a retrospective multicenter study.

PURPOSE: To evaluate the characteristics of patients who received primary androgen deprivation therapy (PADT) for prostate cancer and the clinical efficacy of this treatment. MATERIALS AND METHODS: Two hundred forty patients treated by PADT were reviewed. These patients could not receive definitive therapy owing to old age, patient need, and medical comorbidity. The patients were divided into three groups according to the extent of prostate cancer: localized, locally advanced, and metastatic. Then, prostate-specific antigen (PSA) progression in these groups was analyzed. RESULTS: The median age of the patients was 73.0 years, and the median pretreatment PSA level was 47.0 ng/mL. Of the patients, 91.7% were treated with combined androgen blockade, and 8.3% were treated with monotherapy. Clinical factors for PSA progression were a PSA nadir and a high clinical stage. Estimated PSA recurrence-free median survival time in each group was 57, 24, and 12 months, respectively. A PSA nadir of >0.2 ng/mL and metastatic stage were independent factors for expecting a poor response to PADT (hazard ratio 4.26, p<0.001; and 2.60, p<0.001). CONCLUSIONS: Patients with localized or locally advanced prostate cancer who did not receive definitive therapy had lower PSA progression rates than those at metastatic stage during PADT. Further, a PSA nadir of ≤0.2 ng/mL showed better progression-free survival. Therefore, PADT can be another therapeutic option in well-selected patients with localized or locally advanced prostate cancer and PSA change should be checked carefully.

Korean prostate cancer patients have worse disease characteristics than their American counterparts.

BACKGROUND: Although the PSA test has been used in Korea for over 20 years, the incidence of prostate cancer has risen, and the associated mortality has increased about 13-fold over the 20-year period. Also, several investigators have suggested that Asians in America are more likely to present with more advanced prostate cancer than Caucasians. We compared the characteristics of native Koreans and Americans (Caucasians and African- Americans) undergoing radical prostatectomies in Korea and the US. MATERIALS AND METHODS: Study subjects comprised patients at Korean and US hospitals from 2004 to 2012 who had undergone radical prostatectomies. We compared the characteristics of the subjects, including age, preoperative prostate-specific antigen (PSA) levels, body mass index (BMI), Gleason score, and pathological T stage. RESULTS: In total, 1,159 males (502 Koreans, 657 Americans) were included. The Korean and American patients had mean ages of 67.1 ± 6.6 and 59.2 ± 6.7 years, respectively. The mean preoperative PSAs were 15.4 ± 17.9 and 6.2 ± 4.6 ng/mL (p=0.0001) and the mean BMIs were 23.6 ± 2.6 and 28.7 ± 4.4 kg/m2 (p=0.0001), respectively. Pathological localized prostate cancer represented 71.7% of cases for Koreans and 77.6% for Americans (p=0.07). According to age, Koreans had higher T stages than Americans in their 50s (p=0.021) and higher Gleason scores than Americans in all age groups. According to PSA, Koreans had higher Gleason scores than Americans for PSA >10 ng/mL (p<0.05). According to prostate size and Gleason scores, Koreans had higher PSA values than Americans (p<0.01). CONCLUSIONS: These results show that Korean patients have elevated risk of malignant prostate cancers, as indicated by the significantly higher Gleason scores and PSAs, suggesting a need for novel prostate cancer treatment strategies in Korea.