Magnetic resonance imaging/transrectal ultrasound fusion-targeted prostate biopsy using three-dimensional ultrasound-based organ-tracking technology: Initial experience in Japan.

OBJECTIVE: To evaluate the impact of magnetic resonance imaging/transrectal ultrasound fusion-targeted prostate biopsy on the diagnosis of clinically significant prostate cancer using real-time three-dimensional ultrasound-based organ-tracking technology. METHODS: The present study was a retrospective review of 262 consecutive patients with prostate-specific antigen of 7.1 ng/mL (interquartile range 4.0-19.8). All patients received pre-biopsy magnetic resonance imaging and had a suspicious lesion for clinically significant prostate cancer. All patients underwent a combination of systematic biopsy (6 cores) and three-dimensional ultrasound-based magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (2 cores). The positive rate of any cancer, positive rate of clinically significant prostate cancer, Gleason score and maximum cancer core length were compared between systematic biopsy versus magnetic resonance imaging/transrectal ultrasound fusion-targeted prostate biopsy. RESULTS: Overall, the positive rate of any cancer per patient was 61% (160/262) in systematic biopsy versus 79% (207/262) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001); and that of clinically significant prostate cancer per patient was 46% (120/262) in systematic biopsy versus 70% (181/262) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001). The positive rate of any cancer per core was 21.7% (330/1523) in systematic biopsy versus 68.6% (406/592) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001), and that of clinically significant prostate cancer per core was 12.7% (193/1423) in systematic biopsy versus 60.3% (357/592) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001). Adding systematic biopsy leads to 13 more cancer cases (5%). The distribution of Gleason score (6/7/8/9/10) was 59/71/23/6/1 in systematic biopsy versus 48/105/36/15/2 in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P = 0.005). The maximum cancer core length was 5 mm (0.5-16) in systematic biopsy versus 8 mm (1-19 mm) in magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy (P < 0.0001). CONCLUSIONS: Three-dimensional ultrasound-based magnetic resonance imaging/transrectal ultrasound fusion-targeted biopsy seems to be associated with a higher detection rate of clinically significant prostate cancer, with fewer cores than systematic random biopsy. However, significant cancer can still be detected by the systematic technique only. A combination of systematic biopsy with the targeted biopsy technique would avoid the underdiagnosis of clinically significant prostate cancer.

Morphometric analysis of prostate zonal anatomy using magnetic resonance imaging: impact on age-related changes in patients in Japan and the USA.

OBJECTIVES: To evaluate the impact of morphometric magnetic resonance imaging (MRI) analysis of the prostate zonal anatomy on aging, prostatic hypertrophy and lower urinary tract symptoms in patients from Japan and the USA. SUBJECTS AND METHODS: A retrospective analysis of 307 men, including 156 men from Japan and 151 from the USA, who consecutively underwent 3-Tesla MRI and International Prostate Symptom Score (IPSS) assessment because of elevated PSA levels. Using Synapse-Vincent (Fujifilm), the prostatic zones were segmented in each axial step-section of the T2-weighted MRI to reconstruct a three-dimensional model of the prostate, which was used to calculate: zonal volumes (whole-gland prostate, transition zone and peripheral zone volumes); the presumed circle area ratio (PCAR); and PZ thickness. Bivariate associations were quantified using Spearman's rank correlation coefficients. RESULTS: The USA subgroup had a greater prostate volume (49 vs 42 mL; P = 0.003) and TZ volume (26 vs 20 mL; P < 0.001) than the Japan subgroup, with no difference in PZ volume (19 vs 20 mL; P = 0.2). There was no age-related increase in PZ volume in either of the subgroups or in the entire cohort (P = 0.9, P = 0.2, P = 0.3, respectively). PZ thickness had a significant negative correlation with PCAR (P < 0.001) and TZ volume (P < 0.001). The greater the increase in the TZ volume with the increase in PCAR, which probably correlates with obstructive pressure, the thinner the PZ became. PCAR had a significant positive correlation with IPSS (P = 0.003) and obstructive symptoms (P = 0.007), while PZ thickness had a significant negative correlation (P = 0.018). CONCLUSIONS: No age-related increases and no differences between the Japanese and the US subgroups were found with regard to PZ volume. The more TZ volume increased, the higher the obstructive pressure and the thinner the PZ became; these changes were associated with increased obstructive symptoms. MRI analysis of prostate zonal anatomy enhanced our understanding of age-related changes in morphology and urinary symptoms.

Preoperative lipiodol marking and its role on survival and complication rates of CT-guided cryoablation for small renal masses.

BACKGROUND: Partial nephrectomy for small renal masses (SRM) may be useful for preserving renal function, but is technically more difficult than radical nephrectomy. Cryoablation may be performed under local anesthesia. The objective of the present study is to assess the safety and therapeutic efficacy of cryoablation with lipiodol marking for SRM. METHODS: Cryoablation therapy was performed on 42 patients under local anesthesia. Their median age was 74 years (31-91). The median tumor diameter was 21 mm (10-42). Responses to the treatment were evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST) by contrast-enhanced CT. In six patients (14.3%) for whom it was not possible to use contrast medium, plain CT findings were assessed according to Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Twenty-nine (69%) and five (12%) patients achieved complete responses (CR) and partial responses (PR), respectively, while four (10%) and four (10%) patients each had stable disease (SD) and progressive disease (PD) after the first course of therapy. A second course of cryoablation therapy with lipiodol marking was performed on three out of four patients with PD after the first course of therapy, and resulted in a total of 32 patients achieving CR (76%). Four (36.4%) out of 11 patients for whom lipiodol marking was not conducted had PD, whereas none of the 31 patients for whom lipiodol marking was conducted had PD. All grade complications were reported in 11 (24.4%) patients while grade 3 in two (4.4%) patients. 11 (24.4%) A significant difference was observed in postoperative hemorrhagic events in all grades (18% in patients undergoing cryoablation without lipiodol marking vs. 0% in patients undergoing cryoablation without lipiodol marking). CONCLUSIONS: Although further studies involving more patients are needed in order to evaluate long-term results, cryoablation therapy appears to be a useful treatment option for SRM. Preoperative marking with lipiodol was helpful for improving complication and survival rates with cryoablation.

Androgen suppresses testicular cancer cell growth in vitro and in vivo.

Silencing of androgen receptor (AR)-meditated androgen signaling is thought to be associated with the development of testicular germ cell tumors (TGCTs). However, the role of the androgen/AR signal in TGCT development has not been investigated. In this study, we show that the androgen/AR signal suppressed the cell growth of seminomas (SEs), a type of TGCT, in vitro and in vivo. Growth of SE cells was suppressed by DHT treatment and reduction of androgen levels by surgical castration promoted cancer cell growth in an in vivo xenograft model. Tryptophan hydroxylase 1 (TPH1), the rate limit enzyme in serotonin synthesis, was one of the genes which expression was reduced in DHT-treated SE cells. TPH1 was highly expressed in SE cancer tissues compared with adjacent normal tissues. Activation of androgen/AR signaling in SE cells reduced the expression of TPH1 in SE cells, followed by the reduction of serotonin secretion in cell culture supernatant. These results suggested that silencing of androgen/AR signaling may cause initiation and progression of SE through increase in TPH1 gene expression level.

Laparoendoscopic Single-Site Surgery for Pediatric Urologic Disease.

BACKGROUND: Laparoendoscopic single-site surgery (LESS) was performed for 31 cases of pediatric urologic disease in our department. OBJECTIVE: A retrospective chart review was performed on pediatric patients who underwent LESS. DESIGN, SETTING, AND PARTICIPANTS: Procedures included pyeloplasty (21), nephrectomy (4), varicocele ligation (3), orchiectomy (1), orchiopexy (1), and removal of female genitalia (1). In all 31 cases, an incision of 15 to 20 mm was made in the umbilical region, and a port for LESS was put in place. A 5-mm flexible scope and 5-mm forceps with a bending tip and regular laparoscopic forceps (3, 5 mm) were used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Intraoperative and postoperative outcomes were evaluated. RESULTS AND LIMITATIONS: For the 21 patients with pyeloplasty, the mean operation time was 240 minutes. Postoperative renal pelvis dilatation was relieved in all patients. For the 4 patients with nephrectomy, the mean operation time was 128 minutes. Postoperative urinary incontinence disappeared in all patients. The mean operation time of varicocele ligation was 73 minutes. Postoperation, varicocele disappeared and there was no testicular atrophy. The operation times of orchidectomy, bilateral orchidopexy, and removal of female genitalia mutilation were 60, 170, and 189 minutes, respectively. In all cases, there were no intraoperative or postoperative complications. CONCLUSIONS: The advantages of LESS include superior aesthetics with a smaller scar and less pain. LESS is considered as a less burdensome surgery for pediatric patients.

Post-chemotherapy laparoscopic retroperitoneal lymph node dissection is feasible for stage IIA/B non-seminoma germ cell tumors.

OBJECTIVE: To assess the efficacy, outcome and complications of post-chemotherapy laparoscopic retroperitoneal lymph node dissection (L-RPLND) for stage IIA/B testicular germ cell tumor (GCT) patients in comparison with open RPLND (O-RPLND). METHODS: L-RPLND was performed in 14 patients with stage IIA/B non-seminoma GCTs among 154 non-seminoma patients who received RPLND after completion of chemotherapy with tumor marker normalization at our institution between 1998 and 2013. Their outcomes were compared with those of 14 patients with stage IIA/B non-seminoma GCTs treated with O-RPLND during the same period. Clinical parameters were compared between L-RPLND and O-RPLND. RESULTS: There were no significant differences in the background characteristics of the two groups except for follow-up duration (36 months for L-RPLND, 70 months for O-RPLND; p = 0.02). Blood loss during surgery was significantly less for the L-RPLND group than for the O-RPLND group (155 mL for L-RPLND, 700 mL for O-RPLND; p < 0.001). Parameters related to post-operative recovery were significantly better for the L-RPLND group than for the O-RPLND group. Histopathological examination showed no difference between the two groups. Neither group had disease recurrence. CONCLUSION: Post-chemotherapy L-RPLND with a bilateral template and nerve-sparing method was safe, effective, and showed a high preservation rate of antegrade ejaculation with no deterioration of outcomes compared to O-RPLND.

Clinicopathological characteristics and oncological outcomes in patients with renal cell carcinoma registered in 2007: The first large-scale multicenter study from the Cancer Registration Committee of the Japanese Urological Association.

OBJECTIVES: To describe the clinicopathological features and oncological outcomes of renal cell carcinoma diagnosed in Japan in 2007, the results of the large-scale renal cell carcinoma registration study carried out by the Japanese Urological Association are reported. METHODS: The renal cell carcinoma survey was carried out by the Japanese Urological Association in 2012 to register newly diagnosed renal cell carcinoma cases in 2007 from 340 institutions nationwide. The survey included clinicopathological details, such as sex, age, family history, past history, smoking history, body mass index, reason for diagnosis, TNM classification, stage, histopathology, treatment and clinical outcomes. RESULTS: A total of 3663 cases diagnosed in 2007 were registered in this renal cell carcinoma registry program from 340 institutions. A total of 15 patients with a final diagnosis of oncocytoma were excluded, and 3648 cases of renal cell carcinoma were analyzed to evaluate oncological outcomes. The patients' median age was 63.9 years (range 5.9-95.1 years). Clear cell renal cell carcinoma was the most common histological subtype (77.2%), followed by papillary (5.0%) and chromophobe (3.2%) renal cell carcinoma. The most common initial treatment was radical nephrectomy (72.6%), and the most common secondary treatment was cytokine therapy (13.1%). Five-year overall survival rates in stages I, II, III, and IV were 94.8%, 90.2%, 78.8% and 39.6%, respectively. The 5-year overall survival rates for clear cell, papillary and chromophobe renal cell carcinomas, and carcinoma of the collecting ducts of Bellini were 88.6%, 79.8%, 93.0% and 40.0%, respectively. CONCLUSIONS: The present report is the first nationwide large-scale study to describe the clinicopathological characteristics and oncological outcomes of patients with renal cell carcinoma in Japan. Oncological outcomes depend on the clinical stage and histological subtype. Further investigations will be required to show improved oncological outcomes in the molecular targeted therapy era using the results of the present study as a baseline.

PAX2 promoted prostate cancer cell invasion through transcriptional regulation of HGF in an in vitro model.

Elucidating the mechanism of prostate cancer cell invasion may lead to the identification of novel therapeutic strategies for its treatment. Paired box 2 (PAX2) and hepatocyte growth factor (HGF) proteins are promoters of prostate cancer cell invasion. We found that PAX2 protein activated the HGF gene promoter through histone H3 acetylation and upregulated HGF gene expression. Deletion analysis revealed that the region from -637 to -314 of the HGF gene was indispensable for HGF promoter activation by PAX2. This region contains consensus PAX2 binding sequences and mutations of the sequences attenuated HGF promoter activation. Using an in vitro invasion model, we found that PAX2 and HGF promoted prostate cancer cell invasion in the same pathway. Knockdown of HGF expression attenuated the cells' invasive capacity. Moreover, in tissue samples of human prostate cancers, HGF and PAX2 expression levels were positively correlated. These results suggested that upregulation of HGF gene expression by PAX2 enhanced the invasive properties of prostate cancer cells. The PAX2/HGF pathway in prostate cancer cells may be a novel therapeutic target in prostate cancer patients.

Salvage brachytherapy for locally recurrent prostate cancer after external beam radiotherapy.

External beam radiotherapy (EBRT) is a standard treatment for prostate cancer. Despite the development of novel radiotherapy techniques such as intensity-modulated conformal radiotherapy, the risk of local recurrence after EBRT has not been obviated. Various local treatment options (including salvage prostatectomy, brachytherapy, cryotherapy, and high-intensity focused ultrasound [HIFU]) have been employed in cases of local recurrence after primary EBRT. Brachytherapy is the first-line treatment for low-risk and selected intermediate-risk prostate tumors. However, few studies have examined the use of brachytherapy to treat post-EBRT recurrent prostate cancer. The purpose of this paper is to analyze the current state of our knowledge about the effects of salvage brachytherapy in patients who develop locally recurrent prostate cancer after primary EBRT. This article also introduces our novel permanent brachytherapy salvage method.

The efficacy of radio-frequency ablation for metastatic lung or liver tumors of male germ cell tumors as an alternative minimally invasive therapy after salvage chemotherapy.

BACKGROUND: The aim of this study was to assess the efficacy of radio-frequency ablation (RFA) for metastatic lung or liver tumors of germ cell tumors (GCTs) after chemotherapy. METHODS: RFA with computed tomography guidance and monitoring was performed in 24 patients with 48 metastatic lung or liver tumors of GCTs. Group A consisted of 9 patients with tumor marker normalization after salvage chemotherapy and group B consisted of 15 patients without tumor marker normalization in spite ofintensive treatment. RESULTS: Out of 48 tumors, 41 tumors in 21 patients were evaluated for the efficacy of the RFA treatment. Of the 41 tumors, successful ablation was achieved in 34 (82.9 %). The patients in group A had significantly better survival than the patients in group B (p = 0.0003). In group A, all 9 patients are still alive with no evidence of disease (NED). Patients with a solitary tumor had significantly better survival than those with multiple tumors (p = 0.0247). In group B, 2 patients are alive with NED, 1 patient is alive with disease, and the remaining 12 patients have died a tumor-related death. Three cases of pneumothorax requiring intubation were observed. CONCLUSIONS: RFA is less invasive than surgery and is an effective treatment option for curative and palliative therapy as an alternative to invasive salvage surgery for post-chemotherapeutic metastatic lung or liver lesions from GCT.

Laparoscopic off-clamp partial nephrectomy using soft coagulation.

OBJECTIVES: To assess the effectiveness of soft coagulation in off-clamp laparoscopic partial nephrectomy. METHODS: A total of 32 patients with renal tumors underwent laparoscopic partial nephrectomy with off-clamp using soft coagulation between May 2012 and September 2013. Tumor resection was carried out using a combination of bipolar forceps and a ball electrode using the soft coagulation system without hilar clamping. The outcomes of these patients were compared with those of 30 patients treated with hilar clamping. RESULTS: This off-clamp procedure was successfully completed in 31 cases. No significant differences were observed in the mean age (60 vs 61 years), sex (male/female; 25/7 vs 20/10), mean RENAL nephrometry score (5.7 vs 5.8), mean body mass index (24.4 vs 23) or tumor size (15 mm vs 16 mm) between the two groups. No significant differences were noted in positive surgical margins (0 vs 0) or blood loss (104 vs 115 cc) as well. In contrast, a significant difference was noted in the total operative time (278 vs 238 min). Serum creatinine percentage changes at 3 months were 6.4 versus 7.3% in the off-clamp and hilum-clamp groups, respectively, which were not significantly different. CONCLUSIONS: Off-clamp laparoscopic partial nephrectomy can be safely carried out by using a soft coagulation technique.

Clinical outcomes and histological findings of patients with advanced metastatic germ cell tumors undergoing post-chemotherapy resection of retroperitoneal lymph nodes and residual extraretroperitoneal masses.

OBJECTIVES: To assess clinical outcomes of patients with advanced germ cell tumor undergoing post-chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection. METHODS: Between 1998 and 2013, 175 retroperitoneal lymph node dissections for advanced metastatic germ cell tumors were carried out at Kyoto Prefectural University of Medicine, Kyoto, Japan. Of patients receiving retroperitoneal lymph node dissections, 156 underwent post-chemotherapy retroperitoneal lymph node dissection with or without extraretroperitoneal mass resection as first surgery after completion of chemotherapy. Of these 156 patients, 47 underwent both post-chemotherapy retroperitoneal lymph node dissection and extraretroperitoneal mass resection. RESULTS: The histological findings were necrosis in 59.6%, teratoma in 31.4% and viable cancer in 9.0% at retroperitoneal lymph node. At extraretroperitoneal mass resection, necrosis was present in 59.6%, teratoma in 31.9% and viable cancer in 8.5%. Overall histological discordance between retroperitoneal lymph node and extraretroperitoneal mass was found in 31.9%. Five-year disease-free survival stratified by retroperitoneal lymph node histology in 156 patients was 91.3% for necrosis, 78.7% for teratoma and 63.5% for viable cancer (log-rank, P = 0.009). Antegrade ejaculation was preserved in 80.9%. In the worst histology of post-chemotherapy retroperitoneal lymph node dissection or extraretroperitoneal mass resection in 156 patients, 5-year disease-free survival was 93.2% for necrosis, 79.0% for teratoma and 63.4% for viable cancer (log-rank, P < 0.001). Independent prognostic factors for disease-free survival were presence of viable cancer in retroperitoneal lymph node histology and salvage chemotherapy. CONCLUSION: The presence of viable cancer at the retroperitoneal lymph node is an independent predictor of disease recurrence. In approximately one-third of cases, there is a histological discordance between retroperitoneal lymph node and extraretroperitoneal mass. Resection of residual retroperitoneal lymph node and extraretroperitoneal masses remains an important procedure in the management of advanced germ cell tumors.

Comprehensive assessment for novel prostate cancer markers in the prostate-specific antigen era: focusing on Asians and Asian countries.

We reviewed the current evidence for three novel prostate tumor markers (PCA3, TMPRSS2:ERG and proPSA) that have been recently reported predominantly in Western countries. We focus our attention on Asian men in both clinical and basic research studies. There have been no reports on the clinical usefulness of these three markers for Asians living in Western countries. In Asian countries, evidence for the clinical usefulness of PCA3 and proPSA-related indices including Prostate Health Index is being accumulated, mainly in Japan. The process for how a novel marker is approved in the clinical setting is also discussed.

Importance of continuous sequential chemotherapy and multimodal treatment for advanced testicular cancer: a high-volume Japanese center experience.

Patients with "difficult-to-treat" advanced testicular cancer can require multiple therapies. We retrospectively assessed our patients with advanced germ cell tumors (GCTs) and characterized the clinical efficacy, outcomes, and factors affecting overall survival (OS).Two hundred fifty-three patients with advanced GCTs were treated at Kyoto Prefectural University of Medicine, Kyoto, Japan, from June 1998 to September 2013. Of 253 patients, 142 patients had salvage chemotherapy.As first-line therapy, bleomycin, etoposide, and cisplatin, and etoposide and cisplatin therapies were performed in 234 cases (92.5%). As second-line therapy, etoposide, ifosfamide, and cisplatin/vinblastine, ifosfamide, and cisplatin, and paclitaxel, ifosfamide, and cisplatin/paclitaxel, ifosfamide, and nedaplatin therapies were carried out in 44 and 59 cases, respectively. Furthermore, 111, 72, 44, and 28 cases had third, fourth, fifth, and sixth-or-later-line chemotherapy, respectively. Five-year OS rate stratified by chemotherapy line was 95.5% in the first line, 89.4% in the second line, 82.1% in the third line, 45.1% in the fourth line, and 58.9% in the fifth or after line. A statistical significant difference was found when comparing fourth-or-after-line versus first to third-line therapy. Additional procedures were performed, including retroperitoneal lymph node dissection (RPLND) (n = 168), extra-RPLN resection (n= 114), and external beam radiotherapy/stereotactic radiotherapy (n = 78).Multivariate analysis showed that factors predicting better outcomes were in serum tumor marker (STM) normalization, RPLND, and extra-RPLN resection.Good outcomes were obtained in patients who completed chemotherapy up to third line. After fourth-line chemotherapy, approximately 50% of "difficult-to-treat" patients could be cured with normalization of STM levels and residual mass resection. Continuous or sequential chemotherapy with multimodality therapy is important for patients with "difficult-to-treat" advanced GCTs. Effective chemotherapy after third line should be developed.

Initial experience of combined use of photodynamic diagnosis and narrow band imaging for detection of flat urothelial lesion.

BACKGROUND: This preliminary study is the first report to compare photodynamic diagnosis (PDD) with narrow band imaging (NBI) in the same patients with flat urothelial lesions suspicious of carcinoma in situ (CIS) of the bladder. METHODS: Between November 26, 2012 and April 1, 2013, 10 patients underwent transurethral resection of bladder tumor using PDD and NBI simultaneously because of suspicion of CIS. The bladder was mapped first under white light (WL), then under NBI, and subsequently under blue light in odd-numbered patients. The bladder was mapped first under WL, then under blue light, and subsequently under NBI in even-numbered patients. Biopsies were carried out from all suspicious areas, noting whether NBI, PDD or both detected lesions. Random cold cup biopsies from healthy mucosa of bladder were performed from lesions negative on PDD and NBI. RESULTS: The sensitivity and specificity of PDD for detection of CIS and dysplasia were 0.916 and 0.827, respectively. The sensitivity and specificity of NBI for detection of CIS and dysplasia were 0.625 and 0.879. The area under the curve (AUC) for detection of CIS and dysplasia was 0.872 with PDD and 0.752 with NBI. The AUC with combined use of PDD and NBI was 0.918. There was no cancer or dysplasia identified in 43 lesions that were both PDD- and NBI-negative. CONCLUSION: When both PDD and NBI are negative, the possibility of CIS or dysplasia might be very low. The usefulness of the combination of PDD with NBI was suggested in this study.

Percutaneous nephrolithotripsy and antegrade ureterolithotripsy in a 10-month-old infant with urinary stones in both kidney and ureter.

The prevalence of urinary tract stones in the pediatric population is lower than that in adults. Although methods of surgery and medical equipment have developed, medical treatments for urinary tract stones are limited for pediatric cases. We report the case of a 10-month-old male infant with urinary stones in the left kidney and ureter who underwent percutaneous nephrolithotripsy and ureterolithotripsy using antegrade insertion of a ureteroscope through the same nephrostomy tract.

Salvage combined chemotherapy with paclitaxel, ifosfamide and nedaplatin for patients with advanced germ cell tumors.

OBJECTIVES: To investigate the efficacy of combined regimen with paclitaxel, ifosfamide and nedaplatin as salvage chemotherapy in patients with cisplatin-refractory or multiple relapsed germ cell tumors. METHODS: A total of 65 patients refractory to cisplatin-based chemotherapy or with relapse after induction or salvage chemotherapy received paclitaxel 210 mg/m(2) on day 1, ifosfamide 1.2 g/m(2) on days 2-6 and nedaplatin 100 mg/m(2) on day 2 of a 3-week cycle. The primary and secondary end-points were the response rate and overall survival, respectively. RESULTS: Paclitaxel, ifosfamide and nedaplatin therapy was carried out as second-line therapy in 17 patients, third-line in 31 and fourth-line or later in 17. Patients were pretreated with a median of six cycles of platinum-based chemotherapy (range 3-15 cycles). The overall response rate was 62.9%, including one patient with complete response and 38 with partial response. Serum tumor marker levels normalized in 35 (56.5%) patients. Overall survival at a median follow up of 34 months was 59.3%, and median time to progression was 12 months. Multivariate analysis showed that serum tumor marker normalization was the only independent predictor of better progression-free survival and overall survival. Grade 3/4 of neutropenia, anemia and thrombocytopenia was observed in 96.9%, in 81.5%, and in 90.8% of patients, respectively. CONCLUSION: Paclitaxel, ifosfamide and nedaplatin chemotherapy appears to be effective when used as first or second salvage treatment in advanced relapsed germ cell tumors. Even after fourth-line therapy, patients with serum tumor marker normalization might have a chance for a cure.

Comparison of diameter-axial-polar nephrometry and RENAL nephrometry score for treatment decision-making in patients with small renal mass.

INTRODUCTION: The aim of this study was to evaluate our institution's experience in performing laparoscopic radical nephrectomy (LRN) and partial nephrectomy (PN) in patients with small renal masses. METHODS: 142 patients with cT1aN0M0 lesions were identified. 68 of these subjects were treated with LRN and 74 were treated with laparoscopic PN (LPN). The clinicopathological characteristics of the two groups of patients, including diameter-axial-polar (DAP) nephrometry and RENAL nephrometry score (RENAL-NS), operative results, and outcomes, were retrospectively analyzed. RESULTS: A multivariate logistic regression analysis for the selection of PN as the treatment showed that tumor size, DAP nephrometry, RENAL-NS and imperative condition were all independent factors. The area under the curve receiver operating characteristics (ROC-AUC) of DAP and RENAL-NS for performing LPN were 0.897 and 0.825, respectively. CONCLUSIONS: Although LRN was performed in patients with a high nephrometry score in this study, open partial nephrectomy (OPN) should be considered for patients with a high nephrometry score in T1a renal cell carcinoma (RCC) because of better functional and similar oncological outcomes. Based on ROC analysis, when DAP is 6 or less, LPN should be considered and when DAP is 7 or more, OPN should be considered.

CDK1 and CDK2 activity is a strong predictor of renal cell carcinoma recurrence.

BACKGROUND: In renal cell carcinoma (RCC), the prediction of metastasis via tumor prognostic markers remains a major problem. The objective of our study was to evaluate the efficacy of cyclin-dependent kinase (CDK)1 and CDK2 activity as a prognostic marker in human RCC. METHODS: Surgical specimens were obtained from 125 patients with RCC without metastasis. Protein expression and kinase activity of CDKs were analyzed using a newly developed assay system named C2P (Sysmex, Kobe, Japan). We then examined the specific activities (SAs) of CDK1 and CDK2 and calculated CDK2SA-CDK1SA ratio in RCC. Also, risk score (RS) was examined. RESULTS: A total of 125 cases were tested, though 34 cases were excluded because of low sample quality (25 cases) and assay failure (9 cases). In total, 91 cases were analyzed. They included 68 male and 23 female patients, ranging in age from 19 to 83 years. At a median follow-up of 36 months (1-109M), tumor with low CDK2SA-CDK1SA ratio showed significantly better 5-year recurrence-free survival than those with high CDK2SA-CDK1SA ratio (88.7% vs. 54.7%, P = 0.00141). Also, RS enabled the classification of RCCs into high-risk and low-risk groups, and patients with tumors classified as low RS showed better recurrence-free survival than patients with tumors with high RS (88.7% vs. 54.7%, P = 0.0141). CONCLUSION: CDK1SA of tumors and the CDK2SA are both associated with recurrence and prognosis. IMPACT: CDK-based risk demonstrated is strongly associated with clinical outcome. CDK-based risk should be an accurate system for predicting recurrence and survival for planning follow-up.