The treatment of metastatic renal cell carcinoma (mRCC) has recently evolved from being predominantly cytokine-based treatment to the use of targeted agents, which include sorafenib, sunitinib, bevacizumab (plus interferon alpha [IFN-alpha]), temsirolimus, everolimus, pazopanib, and most recently, axitinib. Improved understanding of the molecular pathways implicated in the pathogenesis of RCC has led to the development of specific targeted therapies for treating the disease. In Korea, it has been 5 years since targeted therapy became available for mRCC. Thus, we now have broader and better therapeutic options at hand, leading to a significantly improved prognosis for patients with mRCC. However, the treatment of mRCC remains a challenge and a major health problem. Many questions remain on the efficacy of combination treatments and on the best methods for achieving complete remission. Additional studies are needed to optimize the use of these agents by identifying those patients who would most benefit and by elucidating the best means of delivering these agents, either in combination or as sequential single agents. Furthermore, numerous ongoing research activities aim at improving the benefits of the new compounds in the metastatic situation or their application in the early phase of the disease. This review introduces what is currently known regarding the fundamental biology that underlies clear cell RCC, summarizes the clinical evidence supporting the benefits of targeted agents in mRCC treatment, discusses survival endpoints used in pivotal clinical trials, and outlines future research directions.
Antibodies, Monoclonal, Humanized ; Biology ; Carcinoma, Renal Cell ; Hand ; Humans ; Imidazoles ; Indazoles ; Indoles ; Interferon-alpha ; Korea ; Molecular Targeted Therapy ; Niacinamide ; Phenylurea Compounds ; Prognosis ; Pyrimidines ; Pyrroles ; Sirolimus ; Sulfonamides ; TOR Serine-Threonine Kinases ; Vascular Endothelial Growth Factor A ; Bevacizumab ; Everolimus

PURPOSE: There is no consensus about a definition of benign prostatic hyperplasia, but there are various definitions based on a combination of clinical parameters used to describe the properties of BPH: symptoms of prostatism, increase of prostate volume, and bladder outlet obstruction. The prevalence of clinical BPH in Asian was believed to be lower than Caucasian. The lower urinary tract symptoms associated with BPH in Korea was reported by some authors and it was similar to the results of other studies in western countries. We report the prevalence of BPH in Korean men through a community-based study in Jeong-Eup county, Korea. MATERIALS AND METHODS: A total of 653 men aged 50 and over in Jeong-Eup area, Korea was randomly selected for determination of the prevalence of BPH. The definition of BPH in this study was combination of moderate(8-19) to severe(>19) I-PSS, enlargement of the prostate over 30gms on digital rectal examination by one board certified urologist, and decreased peak flow rate below 15ml/sec. Men with abnormal digital rectal examination(DRE) and elevated serum prostate specific antigen(PSA) above 3.5ng/ml were undergone sextant prostate biopsy to exclude the prostate cancer. RESULTS: I-PSS questionnaires were completed in 431 men and the response rate was 66.1%. Based on I-PSS, 162 men(37.6%) had moderate symptoms and 51 men(11.9%) severe symptoms. Of 213 men with moderate to severe symptoms, 35.7% had enlarged prostate by DRE, and 63.1% decreased flow rate. The prevalence of BPH by the definition in this study was 4.3% in their fifties, 13.2% in sixties and 16.3% in seventies and over eighty(overall, 11.1%). The population-adjusted prevalence of BPH in Korean men aged 50 and over was 8.7%. A good correlation was found between the total symptom score and the quality of life score that is included in the I-PSS. CONCLUSIONS: Men with moderate to severe I-PSS was 49.5%, which was similar to the results from other studies in Caucasian and Japanese. The prevalence of BPH in Korea by aforementioned definition was 8.7%, which seems to be lower than Caucasian. This results suggest that approximately 1,600,000 Korean men had moderate to severe urinary symptoms and 300,000 clinical BPH by the definition in this study.
Asian Continental Ancestry Group ; Biopsy ; Consensus ; Digital Rectal Examination ; Humans ; Jeollabuk-do* ; Korea ; Lower Urinary Tract Symptoms ; Male ; Prevalence* ; Prostate ; Prostatic Hyperplasia* ; Prostatic Neoplasms ; Prostatism ; Quality of Life ; Surveys and Questionnaires ; Urinary Bladder Neck Obstruction

One of the most significant risk factors for prostate cancer (PC) is a family history of the disease, with germ-line mutations in the breast cancer predisposition gene (BRCA) 2 conferring the highest risk. We here report a 56-year-old man presented with painful gait disturbance and diagnosed PC with multiple disseminated bone metastases. The patient had a strong family history of breast cancer with his 2 nieces affected. Furthermore, his aunts and uncles from both sides were diagnosed with stomach, ovarian, and colorectal cancers. His genomic sequencing analysis of the BRCA genes revealed the same BRCA2 deleterious mutation that his breast cancer-affected nieces carried. Previous studies have suggested that BRCA2-mutated PC is associated with a more aggressive phenotype and poor prognosis. Our experience in the present case also indicated the urgent needs for novel treatment modality and PC screening in this high-risk group of patients.
Breast ; Breast Neoplasms ; Colorectal Neoplasms ; Gait ; Germ-Line Mutation ; Humans ; Mass Screening ; Middle Aged ; Neoplasm Metastasis ; Phenotype ; Prognosis ; Prostate* ; Prostatic Neoplasms* ; Risk Factors ; Stomach

We report a case of vaginal leiomyoma in a female patient, which presented with a palpable paraurethral mass with several urinary symptoms such as frequency, urgency and dysuria. The physical examination revealed a localized, mobile, nontender mass in the anterior vaginal wall. Pelvic magnetic resonance (MR) imaging showed a malignant-looking vaginal mass co-existing with multiple uterine leiomyomas. The diagnosis was made through transvaginal ultrasound-guided needle biopsy. The surgical excision was accomplished without any complication. Despite the rarity, a few cases of malignant lesion presented with paraurethral mass were previously reported. The surgical excision and pathological confirmation of the benignancy is necessary.
Biopsy, Needle ; Diagnosis ; Dysuria ; Female ; Humans ; Leiomyoma* ; Magnetic Resonance Imaging* ; Physical Examination

Purpose: This study aimed to analyze the overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with either combination or only secondary hormone therapy (2ndHTx) or docetaxel chemotherapy. Materials and Methods: Between 2005 and 2018, 307 mCRPC patients’ medical records were retrospectively reviewed treated with either 2ndHTx (HTx [N=73, 23.8%] either abiraterone acetate or enzalutamide), docetaxel+2ndHTx (CTx-HTx [N=90, 29.3%]) or only docetaxel therapy (CTx-only [N=144, 46.9%]). The Cox proportional hazard model for risk factors of OS and Kaplan-Meier analysis with log-rank test for OS comparison among three therapeutic groups with a statistical significance of p＜0.05. Results: During a median 49.6-month follow-up and a median 22 months of OS, the worst OS was observed in CTx-only (17.7 months) followed by the CTx-HTx (22.9 months), and only-HTx (42.6 months) groups (p＜0.001). The baseline comparison showed that age, body mass index, TN stagings, and prostate specific antigen level were significantly different between groups (p＜0.05). In the multivariable analysis for the risk factors of OS, age (hazard ratio [HR], 0.978), cT3–4 stage (HR, 1.606), and HTx (HR, 0.482) were significant factors. With the HTx agents, enzalutamide was the only left risk factor for OS regardless of underlying diseases (HR, 0.511; p＜0.001). The group analyses for the OS showed that only-CTx group (HR, 2.696) and CTx-HTx group (HR, 1.434) were unfavorable factors for OS with a reference of HTx group (p＜0.001). Conclusions 2ndHTx was a significant prognostic factor for OS regardless of underlying diseases in patients with mCRPC and improved OS in comparison with docetaxel.

Eisenmenger's syndrome describes the elevation of pulmonary arterial pressure to the systemic level caused by an increased pulmonary vascular resistance with reversed or bi-directional shunt through an intracardiac or aortopulmonary communication. We report the case of 48-year-old woman with an elective total hip replacement arthroplasty for right femur neck fracture with Eisenmenger's syndrome secondary to large atrial septal defect. Anesthesia was induced with etomidate and rocuronium, maintained with desflurane 5 vol% and O₂ 3 L/min. Mirinone and norepinephrine were infused continuously to decrease right to left shunt. The patient was extubated after spontaneous breathing recovery and transferred to the intensive care unit. She was treated with mirinone, norepinephrine, dopamine, and dobutamine for hypoxemia and hypotension. After 3 hours of admission to intensive care unit, the patient had a cardiac arrest and died 30 minutes later.
Anesthesia ; Anoxia ; Arterial Pressure ; Arthroplasty ; Arthroplasty, Replacement, Hip* ; Dobutamine ; Dopamine ; Eisenmenger Complex* ; Etomidate ; Female ; Femoral Neck Fractures ; Heart Arrest ; Heart Septal Defects, Atrial ; Humans ; Hypertension, Pulmonary ; Hypotension ; Intensive Care Units ; Middle Aged ; Norepinephrine ; Respiration ; Vascular Resistance

Purpose: This study aimed to determine the prognostic roles of several immune-related laboratory parameters in patients with metastatic kidney and bladder cancer treated with immune checkpoint inhibitors (ICIs). Materials and Methods: Overall, 36 patients with either metastatic bladder (N=18) or kidney cancer (N=18) were enrolled retrospectively. Progression-free survival (PFS) and overall survival according to the pretherapeutic serum De Ritis ratio (DRR), neutrophil-to-lymphocyte ratio (NLR), and albumin level after ICI treatment, were analyzed. Treatment duration was adjusted using Contal and O’Quigley’s method to explore the cutoff and maximize the log-rank test statistic. Cox proportional hazards model was used to analyze the laboratory parameters. Results: A total of 9 patients received a combination therapy of multiple ICIs (N=9) and targeted agents (N=7). The median NLR, DRR, and albumin level at baseline were 1.7, 1.2, and 4.2 mg/dL, respectively. In the univariable analysis, combination of immunotherapies, total ICI cycles, baseline DRR, and albumin level were significant for PFS. Sex ratio, total ICI cycles, and baseline NLR and DRR were significant for cancer-specific survival (CSS). DRR and albumin levels, which were measured for up to 10 cycles, were significant in PFS and CSS. NLR was additionally significant in CSS. After adjusting total ICI cycles, DRR was significant in PFS and CSS, albumin level was significant only in PFS, and NLR was significant only in CSS in the multivariable analysis. Conclusions NLR, DRR, and albumin level are significant factors associated with the survival of patients with metastatic kidney and bladder cancer treated with ICI.

We investigated whether the detection of prostate specific membrane antigen (PSMA) in blood preoperatively has predictive value for biochemical recurrence (BCR) after radical prostatectomy in patients with prostate cancer. All 134 patients scheduled to receive radical prostatectomy for prostate cancer were prospectively enrolled. The authors used nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay to detect PSMA mRNA-bearing cells in peripheral blood, and analyzed the ability of PSMA mRNA positivity to predict BCR after surgery. PSMA-mRNA was detected in 24 (17.9%) patients by RT-PCR. Over a median follow-up of 20 months (range, 3 to 46 months), BCR developed in 15 patients (11.2%) and median time to BCR was 7 months (range, 3 to 25 months). Kaplan-Meier analysis revealed a significant difference between those positive or negative for PSMA in terms of recurrence-free actuarial probability (log rank P=0.0039). Multivariate analysis showed that positivity for PSMA mRNA (HR: 3.697, 95% CI 1.285-10.634, P=0.015) and a biopsy Gleason score of > or =7 (HR: 4.500, 95% CI 1.419-14.274, P=0.011) were independent preoperative predictors of BCR. The presence of PSMA mRNA in peripheral blood can be used to predict BCR after radical prostatectomy.
Aged ; Antigens, Surface/*blood/genetics ; Glutamate Carboxypeptidase II/*blood/genetics ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/blood/*diagnosis ; Predictive Value of Tests ; *Prostatectomy ; Prostatic Neoplasms/blood/*diagnosis/surgery ; RNA, Messenger/*blood ; Reverse Transcriptase Polymerase Chain Reaction ; Severity of Illness Index ; Time Factors

PURPOSE: The objective of this study was to determine Bcl-2 expression in localized prostate cancer and its potential role as a predictive factor for biochemical recurrence (BCR). MATERIALS AND METHODS: This study included 171 Korean patients with newly diagnosed adenocarcinoma of the prostate who underwent radical prostatectomy (RP) without neoadjuvant therapy at a single center between February 2005 and May 2009. RP specimens obtained from these patients were analyzed for the expression of Bcl-2 using tissue microarray. The values of Bcl-2 and other clinicopathologic factors were evaluated. Statistical analysis was performed with contingency table analysis, chi-square tests, and a Cox proportional hazard model. RESULTS: Bcl-2 expression was immunohistologically-confirmed in 42 patients (24.6%). Bcl-2 expression was not associated with conventional clinicopathologic factors. Bcl-2 negative patients had a significantly longer mean BCR-free survival than Bcl-2-positive patients (p=0.036). Among several variables, a high Gleason score in the RP specimen (> or =8), extraprostatic extension, seminal vesicle invasion (SVI), lymphovascular invasion (LVI), and Bcl-2 expression were significant predictors of BCR based on univariate analysis. Multivariate Cox proportional hazards analysis revealed that BCR was significantly associated with a high prostate specific antigen level (p=0.047), SVI (p<0.001), a positive surgical margin (p=0.004) and Bcl-2 expression (p=0.012). CONCLUSION: Bcl-2 expression in RP specimens is associated with a significantly worse outcome, suggesting a potential clinical role for Bcl-2. Post-operative Bcl-2 could be a significant predictor of outcome after RP.
Adenocarcinoma ; Humans ; Neoadjuvant Therapy ; Neoplasm Grading ; Proportional Hazards Models ; Prostate ; Prostate-Specific Antigen ; Prostatectomy ; Prostatic Neoplasms ; Proto-Oncogene Proteins ; Recurrence ; Seminal Vesicles

PURPOSE: The Gleason score of needle biopsies of the prostate and preoperative serum level of prostate-specific antigen(PSA) are two useful factors in predicting the final pathological staging of patients with prostate cancer treated by radical prostatectomy. Unfortunately, the Gleason score of the biopsy cores often differs from the Gleason score of radical prostatectomy specimen. We evaluated the role of Gleason scores of biopsy cores and the influence of PSA in predicting the Gleason scores of prostatectomy specimens and final pathological staging. MATERIALS AND METHODS: The records of 52 patients with prostate cancer treated by radical prostatectomy from June 1990 to June 1997 were reviewed. The patients were divided into three groups according to the sum of the Gleason scores, i.e. well differentiated(Gleason score 2-4), intermediate(5-7) and poorly differentiated tumors(8-10). The concordance between Gleason score of biopsy and prostatectomy specimen was analysed according to the Gleason score of tumor in biopsy specimen. Furthermore, we evaluated the different level of PSA could affect the concordance rate between Gleason scoreofbiopsyandprostatectomyspecimen. RESULTS: In well-differentiated tumors(Gleason score 2-4) in biopsy specimen, the concordance rate was 55.6%, In intermediate(5-7) differentiated cancers the Gleason score remained the same in 68%. In poorly differentiated tumors, the concordance rate was 72.2%. When PSA was less than 10ng/m1, concordance rate of well differentiated tumors and poorly differentiated tumors was 75%, 40%, respectively. Whereas the concordance rate of well differentiated tumors was 50% and that of poorly differentiated tumors was 90% when the PSA was higher than 20ng/m1. Using linear regression analysis, the preoperative PSA highly correlated with radical prostatectomy Gleason score(correlation coefficient(r)=0.38, p =0.005). CONCLUSIONS: The Gleason score of prostatectomy specimen was upgraded in 44.4% when the biopsy Gleason score was well differentiated, especially when preoperative PSA was higher than 20ng/m1. Therefore, the significance of biopsy Gleason score in the clinical application must be used cautiously when it is used to predict the pathological stage or biological potential of the cancer especially when it is low Gleason score with high PSA( > 20ng/m1). In the meantime, the level of PSA plays an significant role in determining organ confined disease, while high Gleason scone reflect the Iymph node positive disease.
Biopsy* ; Biopsy, Needle ; Humans ; Linear Models ; Neoplasm Grading* ; Prostate ; Prostatectomy* ; Prostatic Neoplasms