고위험 표재성 방광종양의 치료

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Establishment of patient-derived three-dimensional organoid culture in renal cell carcinoma

Purpose: Renal cell carcinoma is a heterogeneous kidney cancer, and over 403,000 cases were reported worldwide in 2018. Current methods for studying renal cell carcinoma are limited to two-dimensional (2D) culture of primary cell lines and patient-derived xenograft models. Numerous studies have suggested that 2D culture poorly represents the diversity, heterogeneity, and drug-resistance of primary tumors. The time and cost associated with patient-derived xenograft models poses a realistic barrier to their clinical utility. As a biomimetic model, patient-derived three-dimensional (3D) organoid culture can overcome these disadvantages and bridge the gap between in vitro cell culture and in vivo patient-derived xenograft models. Here, we establish a patient-derived 3D organoid culture system for clear cell renal cell carcinoma and demonstrate the biomimetic characteristics of our model with respect to both primary kidney cancer and conventional 2D culture. Materials and Methods: Normal renal tissues and tumor tissues were collected from patients with clear cell renal cell carcinoma. The dissociated cells were cultured as conventional 2D culture and 3D organoid culture. The biomimetic characteristic of the two cultures were compared. Results: Compared with 2D culture, the 3D organoid cultures retained the characteristic lipid-rich, clear cell morphology of clear cell renal cell carcinoma. Carbonic anhydrase 9 and vimentin were validated as biomarkers of renal cell carcinoma. Expression of the two validated biomarkers was more enhanced in 3D organoid culture. Conclusions: Patient-derived 3D organoid culture retains the characteristics of renal cell carcinoma with respect to morphology and biomarker expression.ope

The Association of A Number of Predictive Factors for The Recurrence of Papillary Urothelial Neoplasm of Low Malignant Potential: Prognostic Analysis From Multiple Academic Centers.

PURPOSE: To identify clinically useful predictors for the recurrence of papillary urothelial neoplasm of low malignant potential (PUNLMP), we reviewed the clinical information of patients who were diagnosed and treated in multiple tertiary-care academic facilities. MATERIALS AND METHODS: Between February 2007 and April 2015, 95 patients diagnosed with PUNLMP after transurethral resection of bladder (TURB) were included in this study. Age, gender, body mass index, smoking history, the presence or absence of previous history of urothelial neoplasm, the presence or absence of gross hematuria, cytological results at the time of diagnosis, tumor diameter, and multiplicity of tumor were estimated as variablesfor analysis. Cox regression tests were used for identifying predictive factors for recurrence of PUNLMP. RESULTS: Sixty-nine cases of PUNLMP were de novo primary bladder PUNLMPs without known urothelial lesions in the urinary tract, and 26 PUNLMPs were identified on surveillance biopsies of patients with a previous history of urothelial neoplasm. During the follow-up period, recurrences developed in 13 patients (13.7%). Recurrence rates were 4.2% and 9.5% at 12 and 24 months, respectively. On univariate and multivariate Cox regression analyses, previous history of urothelial neoplasm [95% confidence interval (CI): 0.057-0.604, hazard ratio (HR) = 0.185, P = .005] and multiplicity of tumors [95% CI = 0.064-0.584, HR = 0.193, P = .004] were identified as independent predictors for recurrence-free survival of patients with PUNLMP. CONCLUSION: Tumor multiplicity and previous history of urothelial neoplasm are independent prognostic factors forprediction of recurrence of PUNLMP. More careful and closer follow-up should be recommended for PULNMPpatients with tumor multiplicity or a previous history of urothelial neoplasm.ope

Radical Prostatectomy

Radical prostatectomy is mainly performed for the treatment of localized prostate cancer thanks to the early diagnosis using diagnostic tools, such as digital rectal examination, prostate specific antigen (PSA), transrectal ultrasonography and prostate biopsy. Retropubic approach or perineal approach can be used for open radical prostatectomy. Recently laparoscopic radical prostatectomy has become an acceptable alternative to open surgery. Indications for radical prostatectomy, the advantages and disadvantages of the each method, results of operation, complications and postoperative follow up will be described in this article.ope

Prognostic Factors for Recurrence and Progression in Korean Non-Muscle-Invasive Bladder Cancer Patients: A Retrospective, Multi-Institutional Study.

PURPOSE: To identify the prognostic factors related to tumor recurrence and progression in Korean patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data were collected and analyzed for 2412 NMIBC patients from 15 centers who were initially diagnosed after transurethral resection of bladder tumor (TURBT) from January 2006 to December 2010. Using univariable and multivariable Cox proportional hazards models, the prognostic value of each variable was evaluated for the time to first recurrence and progression. RESULTS: With a median follow-up duration of 37 months, 866 patients (35.9%) experienced recurrence, and 137 (5.7%) experienced progression. Patients with recurrence had a median time to the first recurrence of 10 months. Multivariable analysis conducted in all patients revealed that preoperative positive urine cytology (PUC) was independently associated with worse recurrence-free survival [RFS; hazard ratio (HR) 1.56; p<0.001], and progression-free survival (PFS; HR 1.56; p=0.037). In particular, on multivariable analysis conducted for the high-risk group (T1 tumor/high-grade Ta tumor/carcinoma in situ), preoperative PUC was an independent predictor of worse RFS (HR 1.73; p<0.001) and PFS (HR 1.96; p=0.006). On multivariable analysis in patients with T1 high-grade (T1HG) cancer (n=684), better RFS (HR 0.75; p=0.033) and PFS (HR 0.33; p<0.001) were observed in association with the administration of intravesical Bacillus Calmette-Guérin (BCG) induction therapy. CONCLUSION: A preoperative PUC result may adversely affect RFS and PFS, particularly in high-risk NMIBC patients. Of particular note, intravesical BCG induction therapy should be administered as an adjunct to TURBT in order to improve RFS and PFS in patients with T1HG cancer.ope

Impact of Cerebrovascular Disease on Survival Benefits from Local Treatment in Patients with De Novo Metastatic Hormone-Sensitive Prostate Cancer

PURPOSE: Local treatment has become a treatment option for patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC). Subgroup analyses based on a history of cerebrovascular disease (CVD) were performed to evaluate the impact thereof on overall survival (OS) after local treatment. MATERIALS AND METHODS: A retrospective analysis was performed for 879 patients with de novo mHSPC between August 2003 and November 2016. Patients were stratified according to prior CVD history and the type of initial treatment: androgen-deprivation therapy (ADT) alone versus local treatment consisting of radical prostatectomy (RP) or radiation therapy (RT) with ADT, with or without metastasis-directed therapy. The primary outcome was OS assessed by Kaplan-Meier analysis and Cox-regression models. RESULTS: Of 879 patients, 660 (75.1%) men underwent ADT alone, and 219 (24.9%) men underwent RP or RT with ADT, with or without metastasis-directed therapy. The median follow-up was 38 months. Multivariable analysis showed CVD history to be associated with a higher risk of overall mortality (p=0.001). In the overall cohort and in patients without a history of CVD, patients who underwent local treatment exhibited higher OS than men who received ADT alone (all p<0.001). However, the survival benefit conferred by local treatment was not seen in patients with a history of CVD (p=0.324). OS was comparable between patients who received RP and RT (p=0.521). CONCLUSION: Local treatment with or without metastasis-directed therapy may provide OS advantages for mHSPC patients without a history of CVD. Further prospective studies are needed to address these important concerns.ope

Predictive Variables of Progression to Androgen Independent Prostate Cancer after Combined Androgen Blockade

Purpose Despite of the effectiveness of androgen deprivation therapy for prostate cancer, it progress to androgen independent prostate cancer (AIPC) after various periods of time. The objective of this study was to analyze the clinical and pathological variables that predict progression to AIPC after combined androgen blockade (CAB). Materials and Methods We retrospectively reviewed the medical records of 343 patients who were treated with CAB for prostate cancer. Binary logistic regression test was used to analyze the independent predictors for the progression to AIPC. The time to AIPC, according to variables, was assessed by the Kaplan-Meier method and the variables were compared using the Log-Rank test. Results The mean follow-up was 42.1 months (range: 12-120). Seventy seven patients (33.3%) experienced progression to AIPC at a median of 20.2 months (range: 6-72). On univariate analysis, the percentage of positive prostate biopsies, the Gleason score, the T stage, the extent of bone metastasis, lymph node metastasis, the pretreatment PSA level, the nadir PSA and the PSA level at 3 and 6 months all had a significant relationship with the progression to AIPC. The receiver operating characteristic curve analysis for the nadir PSA showed that the optimal cut-off point to predict progression to AIPC was 0.5ng/ml with an area under curve of 0.769. A multivariate analysis demonstrated that the Gleason score (>7), the nadir PSA (>0.5ng/ml), and the PSA level at 6 months (>4.0ng/ml) were significantly correlated with the progression to AIPC. Conclusions This study suggested that Gleason score, the nadir PSA and the PSA level at 6 months were independent variables to predict progression to AIPC after CAB. The PSA level at 6 months may be the most accurate variable to predict progression to AIPC.ope

Effects of Soybean Metabolites on Prostate Cancer

Purpose: It has been postulated that soybean isoflavones act as inhibitory factors in several cancers. Recently, various in vitro and in vivo experimental studies have demonstrated that these isoflavones inhibit prostate cancer. Therefore, we investigated whether soybean isoflavones influenced the development of prostate cancer by comparing the levels of circulating isoflavones between prostate cancer patients and controls. Materials and Methods: The serum levels of genistein, daidzein and equol were determined using reverse-phase, high-performance liquid chromatography-multiple reaction ion monitoring mass spectrometry(HPLC-MS) and compared in 122 experimental subjects(61 prostate cancer patients and 61 cancer-free controls) from 6 hospitals. Results: The serum concentrations of genistein, daidzein and equol in the patients were 130.7⁑181.4ng/ml, 53.6⁑69.3ng/ml and 11.37⁑43.4ng/ml, with control values of 95.6⁑95.2ng/ml, 55.2⁑121.8ng/ml and 23.2⁑34.5ng/ml, respectively. There was no statistical difference between the 2 groups. Daidzein non-metabolizers who were unable to degrade daidzein into equol were compared between the patients and the controls, and were found to be significantly more common in the patient group (p=0.001, OR=3.44, 95% CI=1.6243-7.2855). However, the equol/daidzein ratio was significantly lower in the patients than in the controls(p=0.0072). No association between age, stage, Gleason score or isoflavone concentrations was found. Conclusions: These results suggest that the capability to produce equol (i.e., the mechanism for the metabolism of daidzein into equol) is closely involved in the lower incidence of prostate cancer, and that a diet based on soybean isoflavones would be useful in preventing prostate cancer.ope

Korean Nomogram for the Prediction of Recurrence-free Survival after Definitive Surgery for Renal Cell Carcinoma

Purpose: This multiinstitutional study was to investigate the accuracy of the Kattan nomograms for the prediction of recurrence after definitive surgery for renal cell carcinoma (RCC) in Korean patients and develop a nomogram revised to complement the shortcomings. Materials and Methods: Clinical and pathological data of 1,866 patients with RCC who had been followed for at least 2 years after surgery in each participating institutes were reviewed as well as evidence of disease recurrence, defined to include local recurrence and distant metastasis. Accuracy of the Kattan nomograms' predictability in tumors 7cm or less was tested by calculating the area under the receiver-operating characteristics curve (AUC) and actuarial recurrence-free survival by Kaplan-Meier method. We used the Cox proportional hazard analysis to identify significant variables and develop prediction nomogram, and internally validated by bootstrapping method. Mean follow-up was 56.5 months (24-184). Results: Recurrence occurred in 12.5% of the patients and correlated with the pathological stage, with 4.3%, 7.9%, 15.0%, 22.6%, 38.4%, 58.3% for stages T1a, T1b, T2, T3a, T3b/c and T4, respectively (p<0.001). The AUC of the Kattan nomograms was 0.276. Factors significantly predictive of recurrence were T stage (p<0.0001), presentation (p=0.006), preoperative hemoglobin (p=0.023) and gender (p=0.032). Actuarial 60-month recurrence-free survival was 87.9% and using the prognostic factors, nomogram predicting 60-month recurrence-free survival was constructed. Conclusions: Korean nomogram complementing the preexisting nomograms for the prediction of recurrence-free survival after definitive surgery for RCC has been constructed, which may be useful in patient prognostication, counseling and follow-up planning.ope

Safety and Efficacy of Intravesical Keyhole-Limpet Hemocyanin Therapy for Superficial Transitional Cell Carcinoma: A Prospective, Multicenter Study

Purpose: We wanted to determine the safety and efficacy 1 year after intravesical keyhole-limpet hemocyanin (KLH) therapy for the patients suffering with superficial transitional cell carcinoma. Materials and Methods: A total of 60 patients with bladder cancer who had undergone transurethral resection were treated with a one-year protocol (once a week for 6 weeks and 12 further treatments every 4 weeks) of KLH 20mg. The local and systemic safety and efficacy were evaluated. Results: In terms of the safety of KLH, 4 patients (6.7%) reported dizziness and slight fever, and 2 (3.3%) experienced urgency. The remaining 54 patients (90.0%) did not report any local side effects during the treatment period. In terms of efficacy, recurrence developed in 32 patients (53.3%) at a mean of 4.5 months after transurethral resection; 28 patients (46.7%) were disease free after 14 months. The univariate analysis showed a greater level of efficacy in the patients suffering with bacille Calmette-Guérin (BCG)-refractory disease (p=0.0150). No significant differences were found between the low, the intermediate-risk and the high-risk patients in terms of efficacy. Conclusions: The results of this study have confirmed the good tolerability of intravesical KLH and better efficacy in the BCG-refractory patients. However, in terms of overall efficacy, intravesical KLH therapy had no superiority over that of other intravesical treatments in terms of the overall efficacy.ope