Methylation Signature for Prediction of Progression Free Survival in Surgically Treated Clear Cell Renal Cell Carcinoma

BACKGROUND: Little is known about epigenetic silencing of genes by promoter hypermethylation in renal cell carcinoma (RCC). The aim of this study was to identify prognostic methylation markers in surgically treated clear cell RCC (ccRCC). METHODS: Methylation patterns were assayed using the Infinium HumanMethylation450 BeadChip array on pairs of ccRCC and normal tissue from 12 patients. Using quantitative PSQ analysis, tumor-specific hypermethylated genes were validated in 25 independent cohorts and their clinical relevance was also verified in 152 independent cohorts. RESULTS: Using genome-wide methylation array, Zinc finger protein 278 (ZNF278), Family with sequence similarity 155 member A (FAM155A) and Dipeptidyl peptidase 6 (DPP6) were selected for tumor-specific hypermethylated genes in primary ccRCC. The promoter methylation of these genes occurred more frequently in ccRCC than normal kidney in independent validation cohort. The hypermethylation of three genes were associated with advanced tumor stage and high grade tumor in ccRCC. During median follow-up of 39.2 (interquartile range, 15.4–79.1) months, 22 (14.5%) patients experienced distant metastasis. Multivariate analysis identified the methylation status of these three genes, either alone, or in a combined risk score as an independent predictor of distant metastasis. CONCLUSION: The promoter methylation of ZNF278, FAM155A and DPP6 genes are associated with aggressive tumor phenotype and early development of distant metastasis in patients with surgically treated ccRCC. These potential methylation markers, either alone, or in combination, could provide novel targets for development of individualized therapeutic and prevention regimens.

CDC6 mRNA Expression Is Associated with the Aggressiveness of Prostate Cancer

BACKGROUND: Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with oncogenic activities in human cancers; however, the clinical significance of CDC6 in prostate cancer (PCa) remains unclear. Therefore, we investigated whether the CDC6 mRNA expression level is a diagnostic and prognostic marker in PCa. METHODS: The study subjects included 121 PCa patients and 66 age-matched benign prostatic hyperplasia (BPH) patients. CDC6 expression was evaluated using real-time polymerase chain reaction and immunohistochemical (IH) staining, and then compared according to the clinicopathological characteristics of PCa. RESULTS: CDC6 mRNA expression was significantly higher in PCa tissues than in BPH control tissues (P = 0.005). In addition, CDC6 expression was significantly higher in patients with elevated prostate-specific antigen (PSA) levels (> 20 ng/mL), a high Gleason score, and advanced stage than in those with low PSA levels, a low Gleason score, and earlier stage, respectively. Multivariate logistic regression analysis showed that high expression of CDC6 was significantly associated with advanced stage (≥ T3b) (odds ratio [OR], 3.005; confidence interval [CI], 1.212–7.450; P = 0.018) and metastasis (OR, 4.192; CI, 1.079–16.286; P = 0.038). Intense IH staining for CDC6 was significantly associated with a high Gleason score and advanced tumor stage including lymph node metastasis stage (linear-by-linear association, P = 0.044 and P = 0.003, respectively). CONCLUSION: CDC6 expression is associated with aggressive clinicopathological characteristics in PCa. CDC6 may be a potential diagnostic and prognostic marker in PCa patients.

Prospective Factor Analysis of Alpha Blocker Monotherapy Failure in Benign Prostatic Hyperplasia

PURPOSE: We aimed to determine the treatment of choice criteria for benign prostatic hyperplasia (BPH) by analyzing the factors causing alpha-adrenergic receptor blocker (alpha-blocker) monotherapy failure. MATERIALS AND METHODS: This retrospective study enrolled 129 patients with BPH who were prescribed an alpha-blocker. Patients were allocated to a transurethral resection of prostate (TURP) group (after having at least a 6-month duration of medication) and an alpha-blocker group. We compared the differences between the two groups for their initial prostate volume, serum prostate-specific antigen (PSA), maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual urine volume (PVR). RESULTS: Of the 129 patients, 54 were in the TURP group and 75 were in the alpha-blocker group. Statistically significant differences (p<0.05) between the two groups were found in the prostate volume (50.8 ml vs. 34.4 ml), PSA (6.8 ng/ml vs. 3.6 ng/ml), Qmax (6.84 ml/sec vs. 9.99 ml/sec), and IPSS (27.3 vs. 16.8). According to the multiple regression analysis, the significant factors in alpha-blocker monotherapy failure were the IPSS (p<0.001) and prostate volume (p=0.015). According to the receiver operating characteristic (ROC) curve-based prediction regarding surgical treatment, the best cutoff value for the prostate volume and IPSS were 35.65 ml (sensitivity 0.722, specificity 0.667) and 23.5 (sensitivity 0.852, specificity 0.840), respectively. CONCLUSIONS: At the initial diagnosis of BPH, patients with a larger prostate volume and severe IPSS have a higher risk of alpha-blocker monotherapy failure. In this case, combined therapy with 5-alpha-reductase inhibitor (5-ARI) or surgical treatment may be useful.

Prospective Factor Analysis of Alpha Blocker Monotherapy Failure in Benign Prostatic Hyperplasia

PURPOSE: We aimed to determine the treatment of choice criteria for benign prostatic hyperplasia (BPH) by analyzing the factors causing alpha-adrenergic receptor blocker (alpha-blocker) monotherapy failure. MATERIALS AND METHODS: This retrospective study enrolled 129 patients with BPH who were prescribed an alpha-blocker. Patients were allocated to a transurethral resection of prostate (TURP) group (after having at least a 6-month duration of medication) and an alpha-blocker group. We compared the differences between the two groups for their initial prostate volume, serum prostate-specific antigen (PSA), maximum urinary flow rate (Qmax), International Prostate Symptom Score (IPSS), and postvoid residual urine volume (PVR). RESULTS: Of the 129 patients, 54 were in the TURP group and 75 were in the alpha-blocker group. Statistically significant differences (p<0.05) between the two groups were found in the prostate volume (50.8 ml vs. 34.4 ml), PSA (6.8 ng/ml vs. 3.6 ng/ml), Qmax (6.84 ml/sec vs. 9.99 ml/sec), and IPSS (27.3 vs. 16.8). According to the multiple regression analysis, the significant factors in alpha-blocker monotherapy failure were the IPSS (p<0.001) and prostate volume (p=0.015). According to the receiver operating characteristic (ROC) curve-based prediction regarding surgical treatment, the best cutoff value for the prostate volume and IPSS were 35.65 ml (sensitivity 0.722, specificity 0.667) and 23.5 (sensitivity 0.852, specificity 0.840), respectively. CONCLUSIONS: At the initial diagnosis of BPH, patients with a larger prostate volume and severe IPSS have a higher risk of alpha-blocker monotherapy failure. In this case, combined therapy with 5-alpha-reductase inhibitor (5-ARI) or surgical treatment may be useful.

Characteristics of Multiple Primary Malignancies in Renal Cell Carcinoma / 대한비뇨기과학회지

PURPOSE: This study aimed to evaluate the incidence, nature and prognosis of multiple primary malignancies in renal cell carcinoma. MATERIALS AND METHODS: From June 1995 to April 2004, we retrospectively reviewed the records of 578 patients who underwent an operation for renal cell carcinoma at Yonsei University. The incidence of other primary malignancies, in addition to the renal cell carcinoma, was determined and classified as antecedent, synchronous or metachronous. We analyzed the influence of the other primary malignancies on the prognosis, and the overall survival rates of the patients with multiple primary malignancies were compared to the remaining patients. RESULTS: Of the 578 patients, 62 patients (10.7%) had at least one malignancy beside renal cell carcinoma. In these cases, renal cell carcinoma was commonly incidental, small or low stage (75.8%). 22 patients (35.4%) had gastrointestinal cancer and 11 patients (17.7%) had hepatobiliary cancer. The malignancies were antecedent in 25 (40.3%), synchronous in 24 (38.1%), and metachronous in 14 patients (22.2%). On the analysis of overall survival with using the log rank test, there was no statistically significant factor for the presence of other antecedent or synchronous malignancies. CONCLUSIONS: Primary malignancy associated with renal cell carcinoma in the Korean population shows a different pattern from that of Western countries. The expected survival rate of patients suffering from renal cell carcinoma with tumor involvement of other organs, if surgically treated, is similar to that of renal cell carcinoma alone, so aggressive surgical treatment of renal cell carcinoma should be performed.

Perirenal Fat Invasion (pT3a) in Renal Cell Carcinoma Less Than 4cm in Size (cT1a): Analysis of the Prognostic and Pathological Implications / 대한비뇨기과학회지

PURPOSE: To investigate the incidence and histopathological factors of perirenal fat invasion (pT3a) in cT1a renal cell carcinomas. The implication for postoperative perirenal fat invasion, as a prognostic factor in patients with tumors less than 4cm tumor in size is also discussed. MATERIALS AND METHODS: Of 503 patients who underwent an operation for a renal cell carcinoma at our institution, between June 1995 and April 2004, we retrospectively reviewed the records of 176 with T1a renal cell carcinomas. We evaluated the pathological grade, cell type, tumor size, location and incidence of perirenal fat invasion using the Fisher's exact test. The overall survival was estimated using the Kaplan-Meier method and log-rank test, and the prognostic factors influencing the survival were estimated using the Cox proportional hazard regression model. RESULTS: In this study, a radical nephrectomy was performed in 128 men and 48 women, with a mean age of 54.6 years, ranging from 23 to 77. The mean follow-up was 31.3 months, ranging from 6 to 106 months. The average size of the renal cell carcinomas was 3.0cm, ranging from 1 to 4cm. The incidence of perirenal fat invasion in the T1a renal cell carcinomas was 5.7% (n=10). The nuclear grade (p<0.001) was a statistically significant factor in the incidence of postoperative perirenal fat invasion. CONCLUSIONS: In the patients with a renal cell carcinoma less than 4cm in size (cT1a), those in the postoperative perirenal fat invasion group had a significantly poorer prognosis. The tumor size and Fuhrman nuclear grade were implicated in the incidence of perirenal fat invasion in the T1a renal cell carcinomas. Therefore, in the case of nephron sparing surgery, more precise preoperative staging of the primary tumor is required.

Prognostic Influence of Coagulative Tumor Necrosis and the Tumor Location for T1a Renal Cell Carcinoma / 대한비뇨기과학회지

PURPOSE: The presence of histologic coagulative necrosis in the primary tumors of patients with renal cell carcinoma has been suggested to be an important predictor of survival. This study aimed to evaluate the relationship of tumor necrosis and tumor location as compared to the other clinical features. MATERIALS AND METHODS: From June 1995 to April 2004 we retrospectively reviewed the records of 204 patients who underwent unilateral radical nephrectomy for stage T1a renal cell carcinoma. The presence of histologic coagulative necrosis in the primary tumors was recorded and the location of tumor was classified based on the computed tomography (CT) scan. Overall survival was estimated using the Kaplan-Meier method and the log-rank test, and the prognostic factors that influenced on survival were estimated using the Cox proportional hazard regression model. RESULTS: In this study, radical nephrectomy was performed in 148 men and 56 women with a mean age of 54.9 years (age range: 23 to 77). The mean follow-up was 31.3 months (range: 6 to 106 months). The average size of the renal cell carcinoma was 3.0cm (range: 1 to 4). The tumor locations were categorized into 2 types according to the centrality and verticality. The incidence of necrosis in T1a renal cell carcinoma was 8.7% (n=18). On the analysis of the overall survival using the log rank test, tumor necrosis (p=0.01) was a statistically significant factor. CONCLUSIONS: For the patients with T1a renal cell carcinoma (2002 TNM stage), the presence of tumor necrosis was significantly associated with overall survival.

Scrotal Extramammary Paget's Disease Associated with Renal Cell Carcinoma / 대한비뇨기과학회지

A 62-year-old male presented with a longstanding right scrotal skin lesion. After a skin biopsy, the lesion was proven to be extramammary Paget's disease. The right scrotal skin was excised and a split thickness skin graft performed. After 16-months of follow up, the patient visited again, this time complaining of abdominal pain. On abdominal computerized tomography (CT) and whole body bone scans, the presence of a solid renal mass at the upper pole of the left kidney, with multiple metastatic lesions in the liver, bone and lymph nodes, were found. Under the impression of a malignant primary renal tumor, a radical nephrectomy was performed. A histological examination showed a conventional type renal cell carcinoma, with malignant Paget cells infiltrating and residing within the tumor mass. The patient died on the 50th postoperative day due to acute respiratory distress syndrome (ARDS) caused by aspiration pneumoniae.

Video Assisted Minilaparotomy Surgery (VAMS) - Live Donor Nephrectomy: 239 Cases

We have devised a new surgical method of video-assisted minilaparotomy surgery-live donor nephrectomy (VAMS- LDN), which is a hybridized form of laparoscopic and open surgeries that combines the advantages of both. We present the findings of our series of 239 consecutive patients. Since 1993 we have performed 239 successful VAMS-LND. All 239 healthy kidney donors' characteristics and their postoperative courses were retrospectively reviewed and the data were compared to 95 open donor nephrectomies performed during the same period. The mean age and weight of the patients were 37.9 +/- 11.0 years and 62.4 +/- 7.9 kg, respectively. The mean operating time was 154 +/- 41 minutes, which was similar to open donor nephrectomy but shorter than laparoscopic donor nephrectomy. There were no major intraoperative complications except two tears to lumbar veins which required transfusion. The mean warm ischemic time was 2.1 +/- 0.7 minutes, which was equal to open donor nephrectomy. The patients experienced less postoperative pain and recovered quicker than the open donor nephrectomy patients. VAMS-LDN is a safe and minimally invasive technique for live donor nephrectomy, incorporating advantages of both conventional open and laparoscopic methods. We suggest that VAMS-LDN is a viable option for living donor kidney transplantation.

Two Cases of Anterior Urethral Valve / 대한비뇨기과학회지

No abstract available.

Laparoscopy-Assisted Radical Nephrectomy Through Minilaparotomy / 대한비뇨기과학회지

No abstract available.

Retroperitoneoscopy-Assiste Extraperioneal Live Donor Nephrectomy Through Minilaparotomy / 대한비뇨기과학회지

No abstract available.

Inflammatory pseudotumor of urinary bladder

A previously healthy 44-year-old male was admitted with the chief complaint of intermittent gross hematuria. On initial ultrasonographic and CT examination, a grossly protruding intravesical tumor was noted and, under the impression of a malignant bladder tumor, transurethral resection was performed. The histological findings were spindle cells with elongated cytoplasm with rare mitotic figures distributed in myxoid stroma, consistent with diagnosis of inflammatory pseudotumor of the bladder. The benign nature of this tumor warrants conservative surgical management, usually consisting of transurethral resection or partial cystectomy. No reports of metastasis have been reported following complete excision. Therefore, any suspicion and recognition of this entity is imperative to avoid performing an irreversible radical procedure.

Laparoscopy-assisted urologic surgery through minilaparotomy

Minimally invasive surgery has gained wide acceptance as a method of reducing postoperative pain and curtailing the convalescence period. We have devised a modified surgical technique of laparoscopy-assisted surgery through minilaparotomy. It is a hybridized form of conventional open and laparoscopic surgery and it combines the benefits of both techniques by reducing postoperative pain and scarring as in laparoscopy, but at the same time maintaining the safety of conventional open surgery. From January 1992 to September 1999, we performed laparoscopy-assisted surgery through minilaparotomy in 167 patients. The operative time for laparoscopy-assisted surgery through minilaparotomy ranged from 79 to 290 minutes (mean 125). There was no conversion to open surgery, no peri- or postoperative complications, and only 3 patients needed a blood transfusion at any stage. Pain was significant on the first day but resolved quickly. All patients resumed consistent oral intake on the second day. All patients commenced ambulation by the second postoperative day and were able to resume full ambulatory activity by the fourth postoperative day. The final would size did not exceed 10 cm in size and all patients expressed satisfaction with their wounds. In conclusion, we believe that laparoscopy-assisted minilaparotomy surgery is a truly minimally invasive technique maintaining the advantages of conventional surgery. Our method could become a first-line approach for simple nephrectomy, living donor nephrectomy and radical nephrectomy, as well as surgery for kidney and ureter stones.