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Glottic closure is essential for vocalization and airway protection. Several pathological conditions cause glottic insufficiency, such as vocal fold paralysis and presbylarynx, which is the age-related atrophy of laryngeal muscle. Injection laryngoplasty is common technique to treat glottic insufficiency, because it can be easily and inexpensively performed in an outpatient setting. Different injection material should be selected according to the purpose and patient condition before the procedure. Ideal material for injection laryngoplasty must be biocompatible, and the injected volume should be maintained for the desired duration without migration. Further, it will be better if it could be easily injected and removed. In this article, we reviewed the published research related to material for the injection laryngoplasty and tried to think about the limitations of current studies and the future direction of treatment.

PurposeThis study aims to evaluate the association of serum lipid profile on prostate cancer (PC) risk and aggressiveness.MethodsMen who underwent prostate biopsy between January 2005 and December 2015 were retrospectively analyzed. The association between lipid profile and the risk, stage, and Gleason grade group (GG) of the PC were investigated. Sensitivity analysis was conducted using univariate and multivariate quantile analysis for lipide profile on the risk and stage of PC.ResultsOf the 1740 study populations, 720 men (41.4%) were diagnosed as PC. From multivariate logistic regression analysis, age, prostate specific antigen, triglyceride (odds ratio (OR):1.05, confidence interval (CI):1.03-1.07, p-valuest, 2nd, 3rd and 4th quartile, p-valuest, 2nd, 3rd and 4th quartile, p-valueConclusionsThis study findings suggested increased in triglyceride level increased the risk PC. Increased in triglyceride level also associated with aggressive presentation of PC, with higher stage and GG.

Purpose:Statin use is reportedly associated with the risk of prostate cancer, outcomes after treatment, and prostate cancer-specific mortality. We sought to determine the efficacy of adjuvant atorvastatin in prostate cancer after radical prostatectomy.Patients and Methods:In this randomized, double-blind trial, we assigned patients with pathologic high-risk prostate cancer to receive either low-dose atorvastatin (20 mg/day, n = 183) or placebo (n = 181) for 1 year after radical prostatectomy. The primary endpoint was the 1-year biochemical recurrence rate. The secondary endpoints included the 5-year biochemical recurrence-free survival and changes in lipid, testosterone, and sex hormone binding globulin levels.Results:From October 2012 through January 2019, a total of 364 patients underwent randomization. Among 59 total primary end points, 30 (16.4%) and 29 (16.0%) occurred in the atorvastatin and placebo groups, respectively. Atorvastatin did not significantly reduce the primary endpoint of 1-year biochemical recurrence [HR, 0.96; 95% confidence interval (CI), 0.58–1.60]. During a median follow-up of 24 months, 131 patients experienced biochemical recurrence (68 in the atorvastatin group and 63 in the placebo group), representing Kaplan–Meier estimated event rates of 24.0% and 25.4% in the atorvastatin and placebo groups, respectively, at 24 months (HR, 1.00; 95% CI, 0.71–1.41). We observed no significant between-group differences in the testosterone and sex hormone binding globulin levels.Conclusions:Among patients with high-risk pathologic features after radical prostatectomy for prostate cancer, 1-year adjuvant use of atorvastatin was not associated with a lower risk of disease recurrence compared with that for placebo. (ClinicalTrials.gov number, NCT01759836).See related commentary by Murtola and Siltari, p. 4947

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To compare oncological outcomes in men with clinical T3b prostate cancer who underwent radical prostatectomy or a combination of radiation therapy plus androgen deprivation therapy.Men with clinical T3b prostate cancer who underwent radical prostatectomy or radiation therapy plus androgen deprivation therapy between 2007 and 2014 were evaluated. All patients were relatively healthy, with Eastern Cooperative Oncology Group performance status of 0 or 1 without nodal or distant metastasis. Cancer-specific survival was analyzed. Age, Charlson Comorbidity Index, biopsy Gleason score and pretreatment prostate-specific antigen were adjusted by propensity score matching. The Cox proportional hazards model was used to assess factors prognostic of cancer-specific survival.Of the 152 patients with clinical T3b prostate cancer, 45 underwent radical prostatectomy, and 107 underwent radiation therapy plus androgen deprivation therapy between 2007 and 2014. The mean cancer-specific survival was significantly longer in the radical prostatectomy than in the radiation therapy plus androgen deprivation therapy group (P = 0.029). Age, Charlson Comorbidity Index and pretreatment prostate-specific antigen were significantly higher in the radiation therapy plus androgen deprivation therapy group. In the propensity score matched population of 24 patients each, the median cancer-specific survival remained significantly longer in the radical prostatectomy than in the radiation therapy plus androgen deprivation therapy group (not reached vs 112.93 ± 11.94 months, P = 0.026). Multivariate analysis showed that undergoing radiation therapy plus androgen deprivation therapy was the only significant poor prognostic factor for cancer-specific survival (hazard ratio 6.694, 95% confidence interval 1.642-27.592, P = 0.008).Cancer-specific survival was significantly longer in men with clinical T3b prostate cancer who underwent radical prostatectomy than radiation therapy plus androgen deprivation therapy, suggesting that radical prostatectomy can be a better treatment option for the initial definitive treatment for these patients.

Purpose: This study was a prospective single-arm clinical trial aimed at assessing the efficacy and toxicity of subcutaneous interleukin (IL)-2 monotherapy in patients with metastatic renal cell carcinoma (RCC).Materials and Methods: We enrolled 26 patients with metastatic RCC in this multicenter controlled trial. The patients received subcutaneous injections of recombinant IL-2 (BMI-rh-IL2, an aldesleukin biosimilar, BMIKOREA Co., Ltd.) in 5-week cycles. In the first week, the patients received a subcutaneous IL-2 loading dose of 18×106 IU once on treatment days 1–5, followed by 2 days of rest. In the following 3 weeks, they received a dose of 18×106 IU via subcutaneous injection once on treatment days 1 and 2. Then, the patients received a dose of 9×106 IU via subcutaneous injection once on treatment days 3, 4, and 5, followed by 2 days of rest. The primary end point was the objective response rate; the secondary end points were progressionfree survival (PFS) and safety.Results: Overall, 22 patients were included in the final per-protocol analysis. The objective response and the disease control rates were 13.64% (3 of 22), and 90.9% (20 of 22), respectively. The mean PFS was 5.55 months (95% confidence interval, 2.71–8.4). The proportion of patients who experienced a treatment-related grade 3 or 4 adverse event was 3.85% (1 of 26). There were no treatment-related deaths.Conclusions: In this study, the subcutaneous IL-2 monotherapy regimen demonstrated efficacy and safety comparable to those reported in previous studies of subcutaneous IL-2 monotherapy and was effective in Korean patients with metastatic RCC.

Purpose: To identify the risk factors leading to radical cystectomy in patients who had undergone nephroureterectomy (NUx).Materials and Methods: We retrospectively reviewed the medical records of patients with upper tract urothelial carcinoma who underwent NUx during 2011–2019 and excluded patients with metastatic cancer. In total 646 patients were included in this study; of these, 532 had no previous bladder cancer history. Follow-up was performed every 3 months for 2 years after NUx was administered, and recurrence was confirmed using cystoscopy, urine cytology, computed tomography, and chest radiography. Bladder recurrence was confirmed through biopsy, urine cytology, or radiologic examination. Univariate and multivariate Cox regression analyzes were performed for statistical analysis of risk factors leading to radical cystectomy in patients undergoing NUx.Results: Lymphovascular invasion (LVI) (hazard ratio [HR], 4.728; 95% confidence interval [CI], 1.463–15.570; p=0.011), previous transurethral resection of bladder tumor history (HR, 3.825; 95% CI, 1.164–12.571; p=0.027), and intravesical recurrence (IVR) within 6 months (HR, 3.733; 95% CI, 1.091–12.778; p=0.036) in patients undergoing NUx are predictors of radical cystectomy implementation. In a multivariate analysis of patients without bladder cancer history, bladder recurrence was identified as a predictor of radical cystectomy implementation, if it occurred within 6 months of NUx (HR, 8.608; 95% CI, 1.545–47.976; p=0.014).Conclusions: LVI and IVR within 6 months and previous bladder cancer history are factors that can predict the need for radical cystectomy after NUx. Even in patients without bladder cancer history, early bladder recurrence within 6 months is a major predictor of radical cystectomy.

Purpose: To evaluate the association between microscopic hematuria (MH) detected by surveillance urinalysis and cancer recurrence in nonmuscle invasive bladder cancer (NMIBC) patients.Materials and Methods: A total of 1,082 NMIBC patients who underwent transurethral resection of bladder tumor (TURB) procedures at Asan Medical Center between January 2017 and December 2019 were included. We retrospectively reviewed the follow-up data for these cases including cystoscopy, urinalysis, and urine cytology. The association between urine testing and cancer recurrence was assessed by both univariable and multivariable logistic regression analysis.Results: The study patients had a median age of 68 years (interquartile range, 60–75 years) and comprised 898 men and 184 women. Among the 1,428 TURB procedures conducted in this series, 548 of the lesions (38.4%) were diagnosed as low-grade and 880 (61.6%) as highgrade cancers. A total of 3,309 follow-up cystoscopies were conducted during the study period and were divided into high-grade (HG) (2,011 cases) and low-grade (LG) (1,298 cases) groups according to the latest TURB pathology. MH was found to have a statistically significant association with NMIBC recurrence in both the LG (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.107–2.223; p=0.011) and HG (OR, 1.90; 95% CI, 1.434–2.517; p

Purpose: To construct a urologic cancer database using a standardized, reproducible method, and to assess preliminary characteristics of this cohort.Materials and Methods: Patients with prostate, bladder, and kidney cancers who were enrolled with diagnostic codes in the electronic medical record (EMR) at Asan Medical Center from 2007–2016 were included. Research Electronic Data Capture (REDCap) was used to design the Asan Medical Center-Urologic Cancer Database (AMC-UCD). The process included developing a data dictionary, applying branching logic, mapping clinical data warehouse structures, alpha testing, clinical record summary testing, creating “standards of procedure,” importing data, and entering data. Descriptive statistics were used to identify rates of surgeries and numbers of patients.Results: Clinical variables (n=407) were selected to develop a data dictionary from REDCap. In total, 20,198 urologic cancer patients visited our institution from 2007–2016 (bladder cancer, 4,616; kidney cancer, 5,750; prostate cancer, 10,330). The overall numbers of patients and surgeries increased over time, with robotic surgeries rapidly growing over a decade. The most common treatment for urologic cancer was surgery, followed by chemotherapy and radiation therapy.Conclusions: Using a standardized method, the AMC-UCD fosters multidisciplinary research. This constructed database provides access to clinical statistics to effectively assist research. Preliminary data should be refined through EMR chart review. The successful organization of data from 2007–2016 provides a framework for future periods of investigation and prospective models.

Background aims The efficacy of phosphodiesterase type 5 inhibitors (PDE5Is), which are commonly used to treat erectile dysfunction (ED), is not satisfactory in patients with denervation of the cavernous nerve due to pelvic surgeries and diabetes mellitus (DM). Pre-clinical studies using bone marrow-derived mesenchymal stem cells (BMSCs) to treat ED have shown promising results. The authors conducted a phase 1 clinical trial with autologous BMSCs in patients with ED due to radical prostatectomy or DM. Methods Ten patients (five with post-prostatectomy ED and five with DM-associated ED) who could not perform sexual activity despite taking the maximum dose of a PDE5I were enrolled. The brief clinical trial protocol was registered with the US National Institutes of Health on ClinicalTrials.gov (NCT02344849). The primary outcome was the safety of stem cell therapy, and the secondary outcome was the improvement of erectile function. Results Of the 13 patients screened, 10 were registered in the clinical trial and received autologous BMSCs and nine completed the clinical trial. One patient with post-prostatectomy ED experienced two treatment-emergent adverse events (TEAEs) (pyrexia and back pain), and two patients with DM-associated ED experienced a total of five TEAEs (one case each of viral upper respiratory tract infection, prostatitis and pruritus and two cases of hyperglycemia). Of these patients, one with DM-associated ED experienced two serious TEAEs (two instances of hyperglycemia). All TEAEs were considered not to be related to autologous BMSC therapy. In addition, no clinical significance was identified related to other safety measures, such as laboratory tests and vital signs. The mean International Index of Erectile Function score increased significantly at 1 month versus baseline (24.9 versus 18.1, P = 0.0222). Conclusions This phase 1 clinical trial confirmed the safety and potential efficacy of autologous BMSC therapy in patients with ED. The authors’ results need to be confirmed by a phase 2 clinical trial.

To investigate the impact of preoperative chemotherapy (pCTX) on pathologic nodal (pN) status and evaluate the optimal lymphadenectomy method according to clinical nodal (cN) status in patients with muscle-invasive bladder cancer who received pCTX. We retrospectively reviewed 449 patients with muscle-invasive bladder cancer who underwent radical cystectomy. Among them, 139 (31.0%) received pCTX. We analyzed overall survival among three groups (cN−pCTX−, cN−pCTX+, and cN+pCTX+); the impact of lymphadenectomy extent according to the history of pCTX in cN− patients (n = 393); and the pN status which includes number of positive lymph nodes, and lymph node density in cN− patients who underwent extended lymphadenectomy (n = 222). Overall survival was significantly dependent on cN status, and pCTX had no survival advantage although it decreased the percentage of pN+ patients and the number of positive lymph nodes in cN− patients. Lymph node density showed a significant prognostic effect on overall survival in Cox regression analysis both in cN− and cN+ patients. In cN− patients, there was no significant survival difference according to lymphadenectomy extent regardless of receiving pCTX. pCTX can control micrometastases but not overt metastases, despite decreasing the number of positive lymph nodes in patients with muscle-invasive bladder cancer. Although extended lymphadenectomy is a reasonable diagnostic strategy in the pCTX era, standard dissection is as therapeutic as extended dissection in patients with cN− disease.

Background We analyzed the relationship between biochemical recurrence (BCR) and the status of positive surgical margin (PSM) in patients with pT3a prostate cancer (PCa). Materials and methods Patients (n = 150) who underwent radical prostatectomy for pT3a PCa without nodal/distant metastasis were retrospectively reviewed between 2010 and 2013. The data regarding the status of PSM including the number, length, and margin Gleason score were collected. The predictors of BCR were analyzed using Cox regression hazard models. BCR-free survival was compared between the patients with negative surgical margin (NSM) and with PSM using Kaplan–Meier curves and log-rank tests. Results PSM was noted in 74 patients (49.3%). Seventy-six patients (50.7%) had NSM and 38 patients (25.3%) had single PSM. Twenty patients (13.3%) had two PSMs and 16 patients (10.7%) had ≥3 PSMs. In total patients, the multivariate analysis demonstrated that a pathological Gleason score of ≥8 was significantly associated with BCR [hazard ratio (HR), 2.173; 95% confidence interval (CI), 1.244–3.797; P = 0.038]. In patients with PSM, the number of PSM more than two was significantly associated with BCR (HR, 2.723; 95% CI, 1.256–5.902; P = 0.011). PSM length of ≥3 mm was also a significant predictive factor (HR, 1.024; 95% CI, 0.994–1.055, P = 0.042). Patients with the highest margin Gleason score of ≥4 had poorer BCR-free survival than those with that of 3/no surgical margin. Conclusions Number (more than one), length (≥3 mm), and higher margin Gleason score (≥4) of PSM were significantly associated with an increased likelihood of BCR in patients with pT3a PCa.

Purpose: Statin use is reportedly associated with the risk of prostate cancer, outcomes after treatment, and prostate cancer-specific mortality. We sought to determine the efficacy of adjuvant atorvastatin in prostate cancer after radical prostatectomy. Patients and Methods: In this randomized, double-blind trial, we assigned patients with pathologic high-risk prostate cancer to receive either low-dose atorvastatin (20 mg/day, n = 183) or placebo (n = 181) for 1 year after radical prostatectomy. The primary endpoint was the 1-year biochemical recurrence rate. The secondary endpoints included the 5-year biochemical recurrence-free survival and changes in lipid, testosterone, and sex hormone binding globulin levels. Results: From October 2012 through January 2019, a total of 364 patients underwent randomization. Among 59 total primary end points, 30 (16.4%) and 29 (16.0%) occurred in the atorvastatin and placebo groups, respectively. Atorvastatin did not significantly reduce the primary endpoint of 1-year biochemical recurrence [HR, 0.96; 95% confidence interval (CI), 0.58–1.60]. During a median follow-up of 24 months, 131 patients experienced biochemical recurrence (68 in the atorvastatin group and 63 in the placebo group), representing Kaplan–Meier estimated event rates of 24.0% and 25.4% in the atorvastatin and placebo groups, respectively, at 24 months (HR, 1.00; 95% CI, 0.71–1.41). We observed no significant between-group differences in the testosterone and sex hormone binding globulin levels. Conclusions: Among patients with high-risk pathologic features after radical prostatectomy for prostate cancer, 1-year adjuvant use of atorvastatin was not associated with a lower risk of disease recurrence compared with that for placebo. (ClinicalTrials.gov number, NCT01759836). See related commentary by Murtola and Siltari, p. 4947

Smoking is positively associated with multiple cancer types including head and neck cancer (HNC). We sought to confirm the effect of smoking in HNC and subtypes through big data analysis. All data used in this study originated from the Korean National Health Insurance Service database. We analyzed subjects who had undergone health check-ups in 2009 with follow-up until 2018 (n=10,585,852). We collected data on smoking and other variables that could affect the risk of HNC. The overall incidence of HNC was highest in current smokers (HR: 1.822, 95% CI: 1.729-1.920), followed by ex-smokers (HR: 1.242, 95% CI: 1.172-1.317). Laryngeal cancer, hypopharynx cancer, oral cancer, oropharyngeal cancer, and salivary gland cancer showed increasing incidence rates from ex-smokers to current smokers. Smoking duration and amount showed a dose-dependent relationship with the occurrence of HNC. However, the incidence of HNC did not increase significantly when smoking duration was less than 10 years, or when the smoking amount was less than 10 pack-years in ex-smokers. Smoking is associated with the risk of HNC. Smoking cessation before 10 years or 10 pack-years can prevent the development of HNC.

Purpose Decision-making for treatment of newly diagnosed prostate cancer (PCa) is complex due to the multiple initial treatment modalities available. We aimed to externally validate the SCaP (Severance Study Group of Prostate Cancer) Survival Calculator that incorporates a long short-term memory artificial neural network (ANN) model to estimate survival outcomes of PCa according to initial treatment modality. Materials and Methods The validation cohort consisted of clinicopathological data of 4,415 patients diagnosed with biopsy-proven PCa between April 2005 and November 2018 at three institutions. Area under the curves (AUCs) and time-to-event calibration plots were utilized to determine the predictive accuracies of the SCaP Survival Calculator in terms of progression to castration-resistant PCa (CRPC)–free survival, cancer-specific survival (CSS), and overall survival (OS). Results Excellent discrimination was observed for CRPC-free survival, CSS, and OS outcomes, with AUCs of 0.962, 0.944, and 0.884 for 5-year outcomes and 0.959, 0.928, and 0.854 for 10-year outcomes, respectively. The AUC values were higher for all survival endpoints compared to those of the development cohort. Calibration plots showed that predicted probabilities of 5-year survival endpoints had concordance comparable to those of the observed frequencies. However, calibration performances declined for 10-year predictions with an overall underestimation. Conclusion The SCaP Survival Calculator is a reliable and useful tool for determining the optimal initial treatment modality and for guiding survival predictions for patients with newly diagnosed PCa. Further modifications in the ANN model incorporating cases with more extended follow-up periods are warranted to improve the ANN model for long-term predictions.

Objective To evaluate the efficacy and tolerability of a self-expandable covered metallic stent in patients with malignant prostatic obstruction secondary to prostate cancer (PC). Methods We reviewed 22 cases of insertion of self-expandable covered metallic stents with barbs. Data were collected about PC status. Uroflowmetry variables, residual urine volume, International Prostate Symptom Score (IPSS), quality of life (QOL), and duration from stent insertion to removal were surveyed. These clinical parameters were compared before and after stent insertion. Results The patients with PC showed a mean age of 75.5 ± 6.5 years and mean 5.1 ± 1.9 Charlson comorbidity index. The average flow rate (2.4 ± 1.9 vs 5.9 ± 2.4 mL/s, P = .005), peak flow rate (6.9 ± 6.2 vs 14.1 ± 5.5 mL/s, P = .003), flow time (54.6 ± 29.1 vs 23.6 ± 13.7 s, P = .002), residual urine volume (178.7 ± 195.5 vs 7.0 ± 7.1 mL, P = .004), IPSS (26.2 ± 8.1 vs 8.0 ± 6.5 points, P = .001), and QOL (4.7 ± 1.3 vs 2.4 ± 2.1 points, P = .030) improved between before and after stent insertion, respectively. Pain was the most common complication, but 60% of the patients were managed without any intervention. There were hematuria, urinary retention, urinary frequency, obstruction, and urinary incontinence. However, there was no urinary tract infection due to the stent. The median time to stent removal was 5.7 months. Conclusions The stent was maintained for about 6 months with improved objective and subjective outcomes. The patients with PC, who had a poor comorbidity index and advanced PC status showed a tolerable maintenance period. Self-expandable covered metallic stents can be used for PC patients with a short life expectancy and unsuitability for general anesthesia.

It is important to focus on urgent needs in clinics and develop optimal materials. For successful augmentation of vocal folds, the ideal filler should be injectable through a syringe, and should stably maintain its volume for a long time without toxicity. To achieve these criteria, a click chemistry-based PEG (polyethylene glycol) hydrogel was developed and applied for vocal fold augmentation in vivo. The PEG hydrogel enables fast gelation in vivo after injection and provides long-term stability. Azide- and dibenzocyclooctyne (DBCO)-modified 4-arm PEG were cross-linked by chemical conjugation via click chemistry and yielded gelation within several minutes. After subcutaneous injection into mice and rats, the PEG hydrogel showed higher stability after 1 month compared to the traditionally used calcium hydroxyapatite–carboxymethyl cellulose (CaHA-CMC) filler. In rabbit models with vocal fold paralysis, the PEG hydrogel stably fixed the paralyzed vocal fold in 4 months and minimized the glottic gap. It was an improved therapeutic result compared to CaHA-CMC, demonstrating the potential of a click chemistry-based PEG hydrogel for vocal fold therapy.

We investigated the relationship between positive surgical margin (PSM)-related factors and biochemical recurrence (BCR) and the ability of intraoperative frozen sections to predict significant PSM in patients with prostate cancer. The study included 271 patients who underwent robot-assisted laparoscopic prostatectomy with bilateral nerve sparing and maximal urethral preservation. Intraoperative frozen sections of the periurethra, dorsal vein, and bladder neck were analyzed. The ability of PSM-related factors to predict BCR and significant PSM was assessed by logistic regression. Of 271 patients, 108 (39.9%) had PSM and 163 (60.1%) had negative margins. Pathologic Gleason score ≥8 (18.9% vs 7.5%, P = 0.015) and T stage ≥T3a (51.9% vs 24.6%, P < 0.001) were significantly more frequent in the PSM group. Multivariate analysis showed that Gleason pattern ≥4 (vs

The incidence of prostatic cancer has been reported to be low in Japan and Asia, compared with the USA and European countries. However, it is now on the increase in Japan. The possible etiological factors for the origin and development of prostatic cancer were examined on 187 patients with this malignancy who visited the Department of Urology, University of Tokyo during the past 16 years. No evidence that these factors were specifically related to prostatic cancer, was found. The possible etiology and differences in incidence between Japan, the USA, and European countries are discussed.

Background: Gamma-glutamyltransferase (GGT) is positively associated with several cancer types. The objective of this study was to investigate the association between GGT and head and neck cancer (HNC) incidence in a cohort of 10 million people, considering effects of smoking and alcohol consumption. Methods: All data used in this study were obtained from the Korean National Health Insurance Service database. We analyzed subjects who underwent health check-ups in 2009 and monitored them until 2018 (n = 9,597,952). Using proportional hazards models, quartiles of GGT as independent predictors for HNC incidence were evaluated. Results: The overall incidence of HNC increased in the highest quartile [r-GPT ≥ 40 U/L; HR, 1.452; 95% confidence interval (CI), 1.354–1.557]. Among HNC cases, the HR for hypopharyngeal cancer (HR, 2.364; 95% CI, 1.818–3.074) was significantly higher. HRs for HNC (larynx, sino-nasal, oropharynx, oral cavity, and nasopharynx, except salivary glands) were also significant. Conclusions: Elevated GGT was associated with the risk of some types of HNCs, such as hypopharyngeal, laryngeal, sinonasal, oropharyngeal, oral cavity, and nasopharyngeal cancer. Impact: Results of this study have implications for etiologic investigations and preventive strategies.

Background: Descriptive epidemiologists have repeatedly reported that males are more susceptible to head and neck cancers. However, most published data are those of cross-sectional studies, and no population-based cohort study has yet been published. The aim of this study was to compare the prevalence of head and neck cancers in healthy males with females. Methods: A retrospective cohort study using the Korean National Health Insurance Service database on 9,598,085 individuals who underwent regular health checkups from 1 January to 31 December 2009. We sought head and neck cancers developed during the 10-year follow-up. Results: A total of 10,732 (incidence rate (IR) per 1000 person-years 0.25) individuals were newly diagnosed with head and neck cancer among the 9,598,085 individuals during the 10-year follow-up. The IR was 0.19 in males (8500 affected) and 0.06 in females (2232 affected). Notably, the male–female ratio increased with age below 70 years but decreased thereafter. The male–female difference was most apparent for laryngeal cancer; the male IR was 11-fold higher in the 40 s and 20-fold higher in the 60 s, followed by hypopharyngeal cancer (6.8- and 24.2-fold). Males smoked more and drank more alcohol than females (p < 0.0001 *, p < 0.0001 *). When never-smokers/-drinkers (only) were compared, males remained at a 2.9-fold higher risk of head and neck cancer than females. The hazard ratios for head and neck cancers in males tended to increase in the lower part of the upper aerodigestive tract: larynx (13.9) > hypopharynx (10.9) > oropharynx (4.4) > nasopharynx (2.9) > sinonasal region (1.8) > oral (1.6). Only the salivary gland cancer incidence did not differ between the sexes; the gland is not in the upper aerodigestive tract. Conclusion: Males are much more susceptible to head and neck cancers than females regardless of whether they drink alcohol or smoke tobacco. Sex differences in the incidence of head and neck cancer are most evident in the 60 s in the lower part of the upper aerodigestive tract, such as the larynx and hypopharynx.

Patients with locally advanced HPV-positive tonsil cancer would benefit from prophylactic contralateral neck dissection (pCND).The aim of this study was to analyze rates of contralateral lymph node metastases (LNM) and their prognostic effects on locally advanced HPV-positive tonsillar squamous cell carcinoma.Medical records of 54 patients who underwent upfront primary surgery and pCND were retrospectively reviewed.Six (11.1%) patients had contralateral LNM in 54 locally advanced HPV-positive tonsil cancer. Of these, five patients had contralateral level II LNM and one patient had contralateral level II and III LNM. Contralateral LNM showed significant positive correlations with advanced T stage (This study demonstrated no advantage in performing pCND in early stage HPV-positive tonsil cancer.

A multiple receptor tyrosine kinase inhibitor, sunitinib, is a first-line therapy for clear cell renal cell carcinoma (CCRCC). Unfortunately, it has the major challenges of low initial response rate and resistance after about one year of treatment. Here we evaluated a microRNA (miRNA) and its target responsible for sunitinib resistance. Using miRNA profiling, we identified miR-96-5p upregulation in tumors from sunitinib-resistant CCRCC patients. By bioinformatic analysis, PTEN was selected as a potential target of miR-96-5p, which showed low levels in tumors from sunitinib-resistant CCRCC patients. Furthermore, PTEN and miR-96-5p levels were negatively correlated in a large The Cancer Genome Atlas kidney renal clear cell carcinoma cohort and high miR-96 and low PTEN represented poor prognosis in this cohort. Additionally, four-week sunitinib treatment increased miR-96-5p and decreased PTEN only in tumors from a sunitinib-resistant patient-derived xenograft model. We found a novel miR-96-5p binding site in the PTEN 3′ UTR and confirmed direct repression by luciferase reporter assay. Furthermore, we demonstrated that repression of PTEN by miR-96-5p increased cell proliferation and migration in sunitinib-treated cell lines. These results highlight the direct suppression of PTEN by miR-96-5p and that high miR-96-5p and low PTEN are partially responsible for sunitinib resistance and poor prognosis in CCRCC.

Cancer cell-derived extracellular vesicles (EVs) are promising biomarkers for cancer diagnosis and prognosis. However, the lack of rapid and sensitive isolation techniques to obtain EVs from clinical samples at a sufficiently high yield limits their practicability. Chimeric nanocomposites of lactoferrin conjugated 2,2-bis(methylol)propionic acid dendrimer-modified magnetic nanoparticles (LF-bis-MPA-MNPs) are fabricated and used for simple and sensitive EV isolation from various biological samples via a combination of electrostatic interaction, physically absorption, and biorecognition between the surfaces of the EVs and the LF-bis-MPA-MNPs. The speed, efficiency, recovery rate, and purity of EV isolation by the LF-bis-MPA-MNPs are superior to those obtained by using established methods. The relative expressions of exosomal microRNAs (miRNAs) from isolated EVs in cancerous cell-derived exosomes are verified as significantly higher than those from noncancerous ones. Finally, the chimeric nanocomposites are used to assess urinary exosomal miRNAs from urine specimens from 20 prostate cancer (PCa), 10 benign prostatic hyperplasia (BPH), patients and 10 healthy controls. Significant up-regulation of miR-21 and miR-346 and down-regulation of miR-23a and miR-122-5p occurs in both groups compared to healthy controls. LF-bis-MPA-MNPs provide a rapid, simple, and high yield method for human excreta analysis in clinical applications.

Background To evaluate the clinical outcomes of combination of androgen deprivation therapy (ADT), whole pelvic radiotherapy (WPRT), and stereotactic body radiotherapy (SBRT) boost in high-risk prostate cancer patients. Methods This prospective phase I/IIa study was conducted between 2016 and 2017. Following WPRT of 44 Gy in 20 fractions, patients were randomized to two boost doses, 18 Gy and 21 Gy, in 3 fractions using the Cyberknife system. Primary endpoints were incidences of acute toxicities and short-term biochemical recurrence-free survival (BCRFS). Secondary endpoints included late toxicities and short-term clinical progression-free survival (CPFS). Results A total of 26 patients were enrolled. Twelve patients received a boost dose of 18 Gy, and the rest received 21 Gy. The Median follow-up duration was 35 months. There were no grade ≥ 3 genitourinary (GU) or gastrointestinal (GI) toxicities. Sixty-one and 4% of patients experienced grade 1–2 acute GU and GI toxicities, respectively. There were 12% late grade 1–2 GU toxicities and 8% late grade 1–2 GI toxicities. Patient-reported outcomes of urinary symptoms were aggravated after WPRT and SBRT boost. However, they resolved at 1 month and returned to the baseline level at 4 months. Three-year BCRFS was 88.1%, and CPFS was 92.3%. Conclusions The present study protocol demonstrated that the combination of ADT, WPRT, and SBRT boosts for high-risk prostate cancer is safe and feasible, and may reduce total treatment time to 5 weeks. Boost dose of 21 Gy in 3 fractions seems appropriate. Trial registration ClinicalTrials.gov, ID; NCT03322020 - Retrospectively registered on 26 October 2017.

Purpose To investigate the relationship between the width of spared neurovascular bundle (NVB) measured during robot-assisted laparoscopic prostatectomy and postoperative sexual outcomes. Methods Patients with localized prostate cancer with erectile hardness score ≥2 (N = 105) who underwent NVB-sparing robot-assisted laparoscopic prostatectomy were included. Patients were divided into three groups [first (Q1) vs. second and third (Q2-3) vs. fourth (Q4) quartile] according to width of spared NVB measured with a flexible ruler after prostate removal. Preoperative and postoperative sexual function was evaluated according to erectile hardness score and Expanded Prostate Cancer Index Composite questionnaires. Results The proportion of patients with postoperative erectile hardness score ≥2 at postoperative 6 months was as follows: 38.9% (Q1), 48.6% (Q2–3), and 83.3% (Q4) (P = 0.016). The preoperative/postoperative 6-month sexual function score was 40.7/16.9 (Q1), 48.1/19.0 (Q2–3), and 51.2/28.1 (Q4). Postoperative sexual function was significantly associated with preoperative sexual function in Q4 (P = 0.006) and Q2–3 (P = 0.030) but not in Q1. On multivariate analysis, the width of spared NVB was a significant predictor for postoperative 6-month erectile hardness score ≥2. Limitation includes selection bias and short follow-up duration. Conclusions Not only the performance but also the degree and quality of NVB sparing thought to be important for postoperative sexual function. Measurement of the width of NVB during surgery could be an easy intraoperative method for assessing the quality of NVB sparing.

Purpose This study aimed to examine the causes of death in Korean patients who underwent radical prostatectomy for prostate cancer and investigate the relationship between comorbidity and mortality. Materials and methods We conducted a retrospective multicenter cohort study including 4,064 consecutive patients who had prostate cancer and underwent radical prostatectomy between January 1998 and June 2013. The primary endpoint of this study was all-cause mortality, and the secondary endpoints were cancer-specific mortality (CSM) and other-cause mortality (OCM). Charlson comorbidity index (CCI) was calculated to assess the comorbidities of each patient. Results Of 4,064 patients, 446 (11.0%) died during follow-up. The cause of death was prostate cancer in 132 patients (29.6%), other cancers in 121 patients (27.1%), and vascular disease in 57 patients (12.8%) in our cohort. The overall 10-year CSM rate was lower than the OCM rate (4.6% vs. 10.5%). The 10-year CSM rate was lower than the OCM rate in low- to intermediate-risk group patients (1.2% vs. 10.6%), whereas they were similar in high-risk group patients (11.8% vs. 10.1%). In the multivariable analysis, CCI was independently associated with all-cause mortality after radical prostatectomy, regardless of age and pathologic features. Conclusion Death from prostate cancer was rare in Korean men who underwent radical prostatectomy. Clinicians should be aware of the possibility of overtreatment of low-risk prostate cancer in men with significant comorbidity. Our findings may help to facilitate counseling and plan management in this patient group.

Purpose This study aims to systemically evaluate morphological printing errors between computer-aided design (CAD) and reference models fabricated using two different three-dimensional printing (3DP) technologies with hard and soft materials. Design/methodology/approach The reference models were designed to ensure simpler and more accurate measurements than those obtained from actual kidney simulators. Three reference models, i.e. cube, dumbbell and simplified kidney, were manufactured using photopolymer jetting (PolyJet) with soft and hard materials and multi-jet printing (MJP) with hard materials. Each reference model was repeatably measured five times using digital calipers for each length. These values were compared with those obtained using CAD. Findings The results demonstrate that the cube models with the hard material of MJP and hard and soft materials of PolyJet were smaller (p = 0.022, 0.015 and 0.057, respectively). The dumbbell model with the hard material of MJP was smaller (p = 0.029) and that with the soft material of PolyJet was larger (p = 0.020). However, the dumbbell with the hard material of PolyJet generated low errors (p = 0.065). Finally, the simplified kidney models with the hard material of MJP and soft materials of PolyJet were smaller (p = 0.093 and 0.021) and that with the hard material of PolyJet was opposite to the former models (p = 0.043). Originality/value This study, to the best of authors’ knowledge, is the first to determine the accuracy between CAD and reference models fabricated using two different 3DP technologies with multi-materials. Thus, it serves references for surgical applications as simulators and guides that require accuracy.

Objectives To document the management of advanced prostate cancer including diagnosis, prognosis, treatment, and care, in real‐world practice in Asia using the United in Fight against prOstate cancer (UFO) registry. Patients and Methods We established a multi‐national, longitudinal, observational registry of patients with prostate cancer presenting to participating tertiary care hospitals in eight Asian countries. A total of 3636 eligible patients with existing or newly diagnosed high‐risk localised prostate cancer (HRL), non‐metastatic biochemically recurrent prostate cancer (M0), or metastatic prostate cancer (M1), were consecutively enrolled and are being followed‐up for 5 years. Patient history, demographic and disease characteristics, treatment and treatment decisions, were collected at first prostate cancer diagnosis and at enrolment. Patient‐reported quality of life was prospectively assessed using the European Quality of Life‐five Dimensions, five Levels (EQ‐5D‐5L) and Functional Assessment of Cancer Therapy for Prostate Cancer questionnaires. In the present study, we report the first interim analysis of 2063 patients enrolled from study start (15 September 2015) until 18 May 2017. Results Of the 2063 enrolled patients, 357 (17%), 378 (19%), and 1328 (64%) had HRL, M0 or M1 prostate cancer, respectively. The mean age at first diagnosis was similar in each group, 56% of all patients had extracapsular extension of their tumour, 28% had regional lymph node metastasis, and 53% had distant metastases. At enrolment, 62% of patients had at least one co‐morbidity (mainly cardiovascular disease or diabetes), 91.8% of M1 patients had an Eastern Cooperative Oncology Group performance score of

The androgen receptor (AR) plays an important role in the pathogenesis and development of prostate cancer (PCa). Mostly, PCa progresses to androgen-independent PCa, which has activated AR signaling from androgen-dependent PCa. Thus, inhibition of AR signaling may be an important therapeutic target in androgen-dependent and castration-resistant PCa. In this study, we determined the anticancer effect of a newly found natural compound, sakurasosaponin (S-saponin), using androgen-dependent and castration-resistant PCa cell lines. S-saponin induces mitochondrial-mediated cell death in both androgen-dependent (LNCaP) and castration-resistant (22Rv1 and C4-2) PCa cells, via AR expression. S-saponin treatment induces a decrease in AR expression in a time- and dose-dependent manner and a potent decrease in the expression of its target genes, including prostate-specific antigen (PSA), transmembrane protease, serin 2 (TMPRSS2), and NK3 homeobox 1 (NKX3.1). Furthermore, S-saponin treatment decreases B-cell lymphoma-extra large (Bcl-xL) and mitochondrial membrane potential, thereby increasing the release of cytochrome c into the cytosol. Moreover, Bcl-xL inhibition and subsequent mitochondria-mediated cell death caused by S-saponin were reversed by Bcl-xL or AR overexpression. Interestingly, S-saponin-mediated cell death was significantly reduced by a reactive oxygen species (ROS) scavenger, N-acetylcystein. Animal xenograft experiments showed that S-saponin treatment significantly reduced tumor growth of AR-positive 22Rv1 xenografts but not AR-negative PC-3 xenografts. Taken together, for the first time, our results revealed that S-saponin induces mitochondrial-mediated cell death in androgen-dependent and castration-resistant cells through regulation of AR mechanisms, including downregulation of Bcl-xL expression and induction of ROS stress by decreasing mitochondrial membrane potential.

Purpose To retrospectively evaluate the safety and efficacy of the percutaneous obliteration of urinary leakage after partial nephrectomy (PN) using coils and N-butyl-cyanoacrylate (NBCA). Materials and Methods Data of 10 consecutive patients who underwent percutaneous obliteration of urinary leakage after PN using coil and NBCA between February 2016 and May 2018 were retrospectively reviewed. A urinary fistulography was performed via the drainage catheter. If the fistulous tract was clearly visualized, super-selective embolization of the fistulous tract with coils and urinoma cavity sealing with NBCA was performed. In cases where the fistulous tract could not be clearly visualized, only urinoma cavity sealing was performed. Outcomes and complications were assessed by reviewing medical records and computed tomography (CT). Results In 7 (70%) patients who showed obvious urinary fistulous tract, coil embolization of the urinary fistulous tract, followed by sealing of the urinoma cavity with NBCA, was performed. Obliteration of the urinoma without coil embolization of the fistula tract was performed in 3 patients (30%) in whom a distinct fistulous tract could not be visualized. The median number of treatment sessions required to achieve clinical success was 1 (range, 1–5). Four patients underwent multiple repeated procedure with successful results. All patients showed gradual decrease in size or complete disappearance of urinoma on follow-up CT without evidence of urinary leakage during the follow-up period (mean, 44.6 weeks; range, 11–117 weeks). There were no procedure-related complications. Conclusions Percutaneous obliteration of urinary leakage after PN using coils and NBCA is safe and effective.

We compared the efficacy and safety of human bone marrow-derived mesenchymal stem cells (hBMSC), delivered at different doses and via different injection routes in an animal model of chronic kidney disease.A total of ninety 12-week-old rats underwent 5/6 nephrectomy and randomized among nine groups: sham, renal artery control (RA-C), tail vein control (TV-C), renal artery low dose (RA-LD) (0.5×10Our findings confirm the efficacy and safety of high dose (2×10

The exposure of the prostate to high electric field strength during irreversible electroporation (IRE) has been extensively investigated. Multiple monopolar electrodes, however, have risks of organ piercing and bleeding when placing electrodes. A novel bipolar electrode made of pure platinum and stainless steel was developed for prostate cancer ablation. Voltages of 500 and 700 V were applied to the beagle prostate with this electrode to evaluate ablated tissues and their characteristics. IRE procedures were technically successful in all dogs without procedure-related complications. The current that flowed through the anode and cathode while applying 500 and 700 V were 1.75 ± 0.25 A and 2.22 ± 0.35 A, respectively. TUNEL assays showed that the estimated ablated areas when applying 500 and 700 V were 0.78 cm2 and 1.21 cm2, respectively. The minimum electric field strength threshold required for induction of IRE was 800 V/cm. The platinum electrode was resistant to corrosion. The IRE procedure for beagle prostates using a single bipolar electrode was technically feasible and safe. The novel bipolar electrode has great potential for treating human prostate cancer with fewer IRE-related complications.

To compare the outcomes of patients with high-risk prostate cancer treated by primary radical prostatectomy (RP) and primary androgen deprivation therapy (ADT). The study included patients with high-risk or very high-risk prostate cancer. Patients treated with definitive radiation therapy and those with clinical N1 and M1 disease were excluded. The RP group was divided into sub-cohorts of patients treated with ADT and those who received ADT after biochemical recurrence post-RP. Cancer-specific survival (CSS) and overall survival (OS) were analyzed using the Kaplan–Meier method and the Cox proportional hazards model. The study analyzed 859 patients divided into the RP group (n = 654) and ADT group (n = 205). Castration-resistant prostate cancer was detected in 23 (3.5%) patients in the RP group and 43 (21.0%) patients in the ADT group. Mortality cases included 63 (9.6%) patients in the RP group and 91 (44.4%) patients in the ADT group. CSS (P = .0002) and OS (P