Sarcopenia and the rate of change of the neutrophil/lymphocyte ratio as predictors of pembrolizumab efficacy in advanced urothelial carcinoma.

The objective was to evaluate the usefulness of sarcopenia and the neutrophil/lymphocyte ratio (NLR) as therapeutic efficacy predictors in patients who received pembrolizumab after platinum-based chemotherapy for advanced urothelial carcinoma (aUC). Forty-four patients with aUC were enrolled. Patients' background characteristics and clinical factors, the skeletal muscle index, and the psoas muscle index were evaluated. The NLR before and during treatment was calculated, and the rate of change of NLR was calculated. The median age was 70 years; the follow-up period was 13.2 months. The response rate was 54%. The nonresponding group had significantly more sarcopenia cases (P = 0.007) and a high rate of change of NLR (P = 0.0076). Progression-free survival (PFS) was significantly shorter in the group with sarcopenia (P = 0.002). Both PFS and overall survival were significantly shorter with an NLR rate of change greater than or equal to 1 (P = 0.001 and P = 0.002). On multivariate analysis, the presence of immune-related adverse events [hazard ratio (HR), 0.3723; 95% confidence interval (CI), 0.14-0.97; P = 0.04] and the NLR rate of change (HR, 3.986; 95% CI, 1.01-15.70; P = 0.048) were independent predictors of PFS. Sarcopenia and the rate of change of NLR appear to be useful as predictors of pembrolizumab efficacy in aUC.

Tadalafil 5 mg Once Daily Improved Each IPSS Subscore, QOL, and Nocturia in Elderly BPH Patients over 70 Years Old in a Real-World Clinical Setting.

OBJECTIVE: No reports have evaluated the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. The present study aimed to evaluate the treatment effects of tadalafil by age group in a positive, noninterventional observational study of Japanese men. We therefore divided patients into 2 groups about the age of 70 years and investigated the treatment effects of tadalafil regarding voiding and storage functions by age group. METHODS: Changes from baseline in each parameter (International Prostate Symptom Score [IPSS], quality of life [QOL] score, Overactive Bladder Symptom Score [OABSS], and residual urine volume) at 4, 12, and 24 weeks after initiating tadalafil for benign prostatic hyperplasia (BPH) patients were compared between groups (50-69 years vs. ≥70 years). In addition, side effects of tadalafil were investigated by age group. RESULTS: In the 50-69 years group, significant improvements from baseline were seen in IPSS total and QOL score for all time points. In addition, significant improvements in IPSS storage subscore from baseline were observed at the 4- and 24-week time points. In the ≥70 years group, significant improvements from baseline were seen in IPSS total, IPSS voiding and storage subscores, and QOL score at each time point. CONCLUSIONS: Tadalafil 5 mg once daily appeared effective in clinical settings for elderly BPH patients even over 70 years old.

Evaluation of a rapid one-step PSA test for primary prostate cancer screening.

BACKGROUND: To enhance the convenience and reduce the cost of prostate cancer (PC) screening, a one-step prostate-specific antigen (PSA) test was evaluated in a large population. The PSA SPOT test kit enables rapid detection of human PSA in serum or plasma at or above a cutoff level of 4 ng/mL to aid in the diagnosis of PC. METHODS: PC screening using the PSA SPOT test was offered to male participants in educational public lectures that we conducted in various cities. Test results were reported to participants at the end of the lectures. Blood samples from 1429 men were evaluated. Two independent observers interpreted the tests at 15 and 30 min. The remaining serum samples were subsequently tested using a conventional quantitative assay. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the test were 79.9, 93.0, 65.4, 96.6, and 91.2%, respectively. The sensitivity and specificity of the test changed with variations in the reading time. Quantitative assessment of the intensity of the band was correlated with the PSA value. CONCLUSIONS: PSA testing using this kit can be easily performed. The low cost and speed of the test make it a useful and convenient tool for primary PC screening.

Bilateral Xp11.2 translocation renal cell carcinoma: a case report.

BACKGROUND: Xp11.2 translocation renal cell carcinoma (RCC) is a rare variety of a kidney neoplasm. We report a case of bilateral Xp11.2 translocation RCC occurring metachronously and discuss this very rare entity with reference to the literature. CASE PRESENTATION: The patient was a 56-year-old woman who presented with a right renal tumor. The patient had undergone left radical nephrectomy 7 years previously, which resulted in a histopathological diagnosis of clear cell RCC. Open right partial nephrectomy was performed under the presumptive diagnosis of recurrence of clear cell RCC. The present right renal tumor was pathologically diagnosed Xp11.2 translocation RCC. More than 70% of the tumor cells in the present right tumor were strongly positive for transcription factor E3 (TFE3) expression by immunohistochemical analysis with an anti-TFE3 antibody. A break-apart of the TFE3 genes in the bilateral tumors was identified by fluorescence in situ hybridization analysis. Real time-polymerase chain reaction analysis for the alveolar soft part sarcoma locus-TFE3 fusion gene was performed, which gave a positive result in the bilateral tumors. Pathological comparison of each of the tumors might lead to a final diagnosis of Xp11.2 translocation RCC occurring metachronously. CONCLUSIONS: We present the bilateral Xp11.2 translocation RCC. A combination of immunohistochemical, cytogenetic and molecular biological approaches allowed the final diagnosis of such a rare RCC.

[Undifferentiated Prostate Cancer Treated with Radiation Therapy].

We describe a 75-year-old man with undifferentiated prostate cancer that was treated with radiation therapy. He presented at a nearby general hospital with dysuria and pain upon micturition. He was diagnosed with undifferentiated prostate cancer by a needle biopsy and referred to our hospital for further examination and treatment. Enhanced computed tomography and magnetic resonance images showed prostate cancer and right obturator lymph node metastasis measuring 2.5 cm. Cystoscopy and colonoscopy revealed direct invasion of the urinary bladder and rectum. We constructed a vesical fistula and an artificial anus, and then treated the primary tumor and lymph node metastasis with radiation. Undifferentiated prostate cancer is extremely rare and to our knowledge only a few cases have been reported. We suggest that radiation might be effective for treating undifferentiated prostate cancer with or without local invasion and/or metastasis along with total body control.

Combination with third-generation bisphosphonate (YM529) and interferon-alpha can inhibit the progression of established bone renal cell carcinoma.

The aim of this study was to investigate whether the third-generation nitrogen-containing bisphosphonate (YM529) can inhibit the progression of established bone renal cell carcinoma (RCC) and to elucidate its mechanism. Antiproliferative effect and apoptosis induction of RCC cells and mouse osteoclasts by YM529 and/or interferon-alpha (IFN-α) were evaluated in vitro using cell counting and in vivo using soft X-ray, the TUNEL method and tartrate-resistant acid phosphatase stain. For the in vivo study, male athymic BALB/cA Jc1-nu nude mice bearing human RCC cell line RBM1-IT4 cells were treated with YM529 and/or IFN-α. The biological activity of osteoclasts was evaluated using the pit formation assay. The antiangiogenetic effect by YM529 and/or IFN-α was analyzed using micro-vessel density and in situ mRNA hybridization. Osteoclast number in bone tumors was decreased in YM529-treated mouse. YM529 also inhibited osteoclast activity and proliferation in vitro, whereas basic fibroblast growth factor expressions and micro-vessel density within tumors were inhibited by IFN-α. Neither YM529 nor IFN-α alone significantly inhibited the growth of established bone metastatic tumors. Combined treatment with YM529 and IFN-α may be beneficial in patients with human RCC bone metastasis. Their effects are mediated by osteoclast recruitment inhibition and inactivation by YM529 and antiangiogenesis by IFN-α.

IgG4-related tubulointerstitial nephritis accompanied with cystic formation.

BACKGROUND: An immunoglobulin G4 (IgG4)-related disease is important disease in differential diagnosis of tumors in kidney, pancreas, lung and other organs. The imaging findings of IgG4-related kidney diseases are usually expressed as defect contrast region, while cystic formation in kidney is extremely rare. Here, we report a case of IgG4-related tubulointerstitial nephritis with renal cystic change caused by the narrowing or obstruction of collecting duct in renal medulla. CASE PRESENTATION: Abdominal contrasted CT scan showed a 31 × 24 mm cystic tumor at the upper pole of the right kidney and multiple low-attenuation areas in the left kidney. 18 F-fluorodeoxyglucose (FDG)-PET/CT scan showed moderate FDG accumulation of cystic tumor in marginal lesion. In addition, FDG-PET/CT scan also showed moderate FDG accumulation in the pancreatic body. Laparoscopic right nephrectomy was performed. Histological examination was revealed lymphoplasmacytic infiltrate with focal fibrosis and severe narrowing or obstruction of lumen of collecting duct in renal medulla. Furthermore, the IgG4 positive plasma cells infiltrated exceeding 10 cells per one high-power field in renal medulla. The ratio of IgG4-plasma cells to IgG-positive plasma cells was about 50%. The serum level of IgG4 was also elevated (218 mg/dl). Based on these findings, we finally diagnosed IgG4-related tubulointerstitial nephritis with renal cystic change. CONCLUSION: IgG4-related kidney disease might cause cystic formation by severe narrowing and obstruction of collecting duct.

[Clinical study on patients with renal-cell carcinoma accompanied with Von Hippel-Lindau disease treated with radiofrequency ablation].

We report 12 renal cell carcinomas in 6 patients with Von Hippel-Lindau (VHL) disease treated with radiofrequency ablation (RFA). The mean age of the patients was 46 (range 38-53) years (male : 4, female : 2). Computed tomography (CT)-guided transcutaneous RFA was performed under conscious sedation with local anesthetics. The mean size of the tumors was 2.4 (range 0.7-8.1) cm. Nine of the 12 tumors (75%) were locally well controlled. However, 3 tumors in 2 patients developed visceral metastases after RFA. While minimal flank pain, nausea, perinephritic hematoma and lumbago were observed, there was no major complication during or after the procedure. The therapy with CT-guided transcutaneous RFA is efficient and minimal invasive for renal cell carcinoma in patients with VHL, leading to preservation of renal function.

Investigation of risk factors for vaginal dehiscence and development of small bowel evisceration after robot-assisted radical cystectomy for female bladder cancer and an improved vaginal reconstruction technique to prevent its onset.

Transvaginal organ prolapse, such as small bowel evisceration, is a rare complication after radical cystectomy (RC) in female patients with invasive bladder cancer, However, it often requires emergency surgical repair. Here, we describe our experience with such a case and a review of similar previously reported cases, along with evaluation of the risk factors. We also propose a vaginal reconstruction technique to prevent this complication during robot-assisted laparoscopic radical cystectomy (RARC). A total of 178 patients who underwent laparoscopic radical cystectomy (LRC) or RARC were enrolled, 34 of whom (19%) were female. One of the 34 female patients had transvaginal small bowel evisceration after RARC. We evaluated our case and six such previously reported cases, to determine vaginal reconstruction techniques during RARC to prevent this complication postoperatively. Median age of these cases was 73 (51-80) years, and all patients were postmenopausal. The median time to small bowel evisceration was 14 (6-120) weeks postoperatively. In addition, we changed the methods of the vaginal reconstruction technique during RARC from the conventional side-to-side closure technique to the improved caudal-to-cephalad closure technique. Since implementing this change, we have not experienced any cases of vaginal vault dehiscence or organ prolapse. Transvaginal small bowel evisceration after RC can easily become severe. Therefore, all possible preventive measures should be taken during RARC. We believe that our vaginal reconstruction techniques might reduce the risk of developing this complication.

Intraoperative Blood Flow Evaluation Using Indocyanine Green Fluorescence Angiography for the Surgical Reconstruction of a Hilar Renal Artery Aneurysm.

Surgical reconstruction is one of the standard treatments for renal artery aneurysm. However, its intraoperative evaluation is sometimes difficult depending on the operative field, aneurysm morphology, and peripheral blood vessel distribution. This case demonstrated that after renal artery reconstruction, indocyanine green fluorescence angiography is used to evaluate the results of repairing. This method is useful in visceral aneurysm evaluation not only for assessing reconstructed blood flow but also for confirming tissue perfusion of the renal parenchyma.

Autologous rectus abdominis fascia sling surgery following unsuccessful synthetic midurethral sling.

Introduction: We performed autologous rectus abdominis fascia sling surgery using Advantage™ following an unsuccessful synthetic midurethral sling. Case presentation: At the age of 76 years, the patient experienced stress urinary incontinence recurrence. A 1-h pad test resulted in 259 g of leakage. A pressure flow study verified urine leakage while coughing and straining without detrusor overactivity. Abdominal leak point pressure was 10 cmH2O. Autologous rectus abdominis fascia sling surgery was performed using Advantage™. One month postoperatively, a 1-h pad test resulted in 0 g of leakage. Conclusion: We believe that this method will allow the fascia sling procedure to be performed reliably even if one is unfamiliar with conventional autologous rectus abdominis fascia sling surgery.

[First experiences of laparoscopic radical cystectomy].

PURPOSE: We determined whether laparoscopic radical cystectomy (LRC) was useful for the patients with bladder cancer. MATERIALS AND METHODS: We investigated the surgical outcome of LRC in the initial 30 patients with bladder cancer. RESULTS: Mean patients age was 68 (54-81) years old. Twenty six male and 4 female were enrolled. Lymphnode dissection was variably performed under aeroperitoneum. Twenty six patients were undergone ileal conduit and 4 patients were undergone ileal neobladder as urinary diversion. The urinary diversion of all cases was undergone extra-corporeally. Seventeen patients were received platinum based neo and adjivant-chemotherapy. Mean surgical time was 684 (398-950) min, and mean aeroperitoneum time was 418 (235-660) min. Intraoperative major complications were ureter injury and blood loss. Mean blood loss was 1,063 (150-2,730) ml intraoperatively. Ileus and acute pyeronephritis were observed in the 3 patients postoperatively. Seven patients relapsed and 2 patients died with bladder cancer in 14.9 months of median follow-up period (0.7-35.9) after the surgery. Progression free survival rate and overall survival rate at a year after surgery were 75.2% and 100%, respectively. CONCLUSIONS: The surgical therapy with LRC was well tolerated and successful in the patients with bladder cancer.

Primary adrenal Ewing's sarcoma family of tumors with tumor thrombus of the inferior vena cava: a case report.

BACKGROUND: Ewing's sarcoma is a malignant neoplasm that mainly occurs in skeletal tissue but can rarely arise in soft tissues. Recently, small round cell tumors (including Ewing's sarcoma) caused by chromosomal translocations have been collectively termed Ewing's sarcoma family of tumors. We report a rare case of primary adrenal Ewing's sarcoma family of tumors with tumor thrombus. CASE PRESENTATION: A 22-year-old Asian woman was referred to our hospital with a left retroperitoneal tumor 19 cm in diameter. Tumor thrombus was identified from the left adrenal vein to the inferior vena cava, infiltrating the right atrium. Total tumor excision with left adrenalectomy, nephrectomy, and thrombectomy was performed under hypothermic circulatory arrest, followed by seven courses of adjuvant chemotherapy. The patient has shown no signs of recurrence as of 26 months postoperatively. CONCLUSION: Radical surgery combined with systemic chemotherapy may contribute to good prognosis in patients with primary adrenal Ewing's sarcoma family of tumors.

Vibegron 50 mg Once Daily Improves OABSS, OAB-q SF Score in OAB Patients ≥80 Years Old in Real-World Clinical Settings and Switching from Other OAB Drugs May Reduce Residual Urine Volume.

Objective: The treatment effects of vibegron have not previously been evaluated in a prospective, non-interventional observational study of elderly Japanese patients, particularly those ≥80 years old. In addition, no reports have referred to residual urine volume in switching cases. We therefore grouped patients by condition and investigated the treatment effects of vibegron on Overactive Bladder Symptom Score (OABSS), Overactive Bladder Questionnaire Short Form (OAB-q SF), and residual urine volume in each group. Methods: This multicenter, prospective, non-interventional, observational study consecutively enrolled OAB patients with total OABSS score ≥3 and OABSS question 3 score ≥2. Sixty-three patients from six centers were recruited. Vibegron 50 mg once daily was administered for 12 weeks as first-line monotherapy (first-line group), monotherapy switching from antimuscarinics or mirabegron due to failure of prior therapy (no washout period), or combination therapy with antimuscarinics (second-line group). OABSS, OAB-q SF, and residual urine volume were collected after 4 and 12 weeks. Adverse events were also recorded at each visit. Results: Of the 63 patients registered, 61 were eligible for analysis (first line, n=36; second line, n=25). The OABSS, excluding daytime frequency scores, and OAB-q SF scale showed significant improvement in all conditions. Switching from mirabegron to vibegron significantly reduced residual urine volume. No serious treatment-related adverse events were encountered. Conclusion: Vibegron 50 mg once daily significantly improved OABSS and OAB-q SF even in patients ≥80 years old. Notably, switching from mirabegron to vibegron resulted in significant improvements to residual urine volume.

[The clinical value of 3 tesla diffusion-weighted magnetic resonance imaging in the diagnosis of prostate cancer].

Diffusion-weighted imaging (DWI) is a magnetic resonance imaging (MRI) method and is considered potentially useful for detecting prostate cancer. We evaluated the clinical value of DWI with apparent diffusion coefficient (ADC) maps in addition to T2-weighted imaging (T2WI) using 3 tesla (3 T) MRI. Thirty-three patients with elevated prostate specific antigen were evaluated by MRI with T2WI and DWI prior to transperineal template-guided mapping biopsy. The MRI findings were compared with the pathology of biopsy specimens in six parts of prostate : both sides of outer peripheral zones, inner peripheral zones, and transition zones. The sensitivities, specificities and accuracies were 42.1, 84.4 and 76.3％ in T2WI, 57.1, 84.7 and 80.8% in T2WI/DWI, and 87.5, 85.2 and 85.4% in DWI/ADC using 0.951×10 -3 mm2/s as cutoff ADC value. The hazard ratio of patients whose ADC values were under the cutoff was 25.86 by multivariate analysis. Mean ADC values were significantly different between cancer positive and negative cores (p＜0.001). The ADC value showed a negative correlation with increasing tumor length (p＝0.0047). Although further study with a large number of patients is necessary, DWI/ADC using 3 T MRI is a useful tool for detecting prostate cancer.

[Renal cell carcinoma with rhabdoid features and sarcomatoid change: a case report].

In Feb 2009, a-54-year-old female complained of left flank pain and macrohematuria. Computed tomography (CT) demonstrated the left renal tumor. In Mar 2009, she was referred to our hospital. On physical examination a hard mass was found in her left abdomen. CT demonstrated the left renal tumor and tumor thrombus of left renal vein, but we did not detect any remarkable metastasis in other organs. Thus, we performed left radical nephrectomy. The pathologic finding was renal cell carcinoma (RCC) with rhabdoid features and sarcomatoid change. Eight months postoperatively, she is alive without evidence of recurrence and metastasis. RCC with rhabdoid features and sarcomatoid change is rare. We discuss this case, and review the literature.

Synchronous bilateral renal cell carcinomas with differing histologies.

INTRODUCTION: Bilateral renal cell carcinomas with different histological types are rare. We report herein the first description of bilateral renal carcinomas with clear cell renal cell carcinoma and mucinous tubular and spindle cell carcinoma occurring synchronously. CASE PRESENTATION: A 62-year-old man was referred to our hospital with bilateral renal tumors. The tumors on each side showed different findings from both contrast-enhanced computed tomography and magnetic resonance imaging. The tumors were partially resected. Histopathological and immunohistochemical examination of the left renal tumor diagnosed clear cell renal carcinoma. Histopathological and immunohistochemical examination of the right renal tumor diagnosed mucinous tubular and spindle cell carcinoma. CONCLUSION: We encountered a case with clear cell renal cell carcinoma and mucinous tubular and spindle cell carcinoma occurring simultaneously in bilateral kidneys.

[A case of retroperitoneal solitary fibrous tumor].

Solitary fibrous tumor (SFT) is a common neoplasm of the pleura and rarely arises from the retroperitoneal space. We report a case of retroperitoneal SFT. A 54-year-old woman was admitted to the department of dermatology in our hospital for examination and treatment of malignant melanoma of the right lower leg. Computerized tomography (CT) showed the left adrenal mass measuring 6.0 x 4.5 x 10 cm. Because the tumor was thought to be left adrenal tumor or left adrenal metastasis of the malignant melanoma, she admitted to our department. Left radical adrenalectomy was performed. The histological examination of the specimen revealed that the spindle or oval cells proliferated patternless with hyalinized collagen cells and there were few mitotic figures. The tumor was not connected to the adrenal gland. The immunohistochemical examination showed that the tumor cells were diffusely positive for CD34, bcl-2 and vimentin. According to these findings, we diagnosed SFT arising from the retroperitoneum. At 5 years follow up she had no evidence of local recurrence and no distant metastasis.

[Clinical experience with transurethral resection of bladder tumor (TUR-Bt) guided by photodynamic diagnosis (PDD)].

PURPOSE: To report our clinical experience regarding transurethral resection of bladder tumor (TUR-Bt) guided by photodynamic diagnosis (PDD) with intravesical instillations of 5-aminolevulinic acid (ALA) and to assess the usefulness of the therapeutic method. MATERIALS AND METHODS: TUR-Bt guided by PDD was performed in 57 patients of which 47 were men and 10 women with a median age of 74.3 years (range 45-90), 36 were primary cases and 21 were recurrent cases with non-muscle invasive bladder cancer. Two to two and half hours prior to endoscopy 1.5 g ALA dissolved in 50 ml of 8.4% sodium hydrogen carbonate (NaHCO3) solution was instilled intravesically. For fluorescence excitation a blue light source (D-LIGHT System, Karl Storz Endoscopy Japan K.K.) was used. The tumorous lesions under white light guidance and the lesion with fluorescent excitation under blue (fluorescence) light guidance were taken by cold cup as a biopsy and also resected sequentially. To evaluate the accuracy of PDD, the levels in images of the ALA-induced fluorescence were compared with the pathological results. To evaluate the availability of TUR-Bt guided by PDD, survival Analysis regarding vesical recurrence was retrospectively examined compared to the cases underwent conventional TUR-Bt under white light guidance. Moreover, in these cases, multivariate analysis using Cox proportional-hazards model was performed to detect the clinico-pathological factor independently contribute to improving prognosis. (Results) In the 301 specimens obtained from 57 patients, the sensitivity and specificity of PDD were 92.5% and 60.1%, whereas the sensitivity and specificity of conventional endoscopic examination under white light guidance were 81.6% and 79.5%, respectively. Median follow-up period was 19.1 (range 8.6-49.9) months in 57 patients underwent TUR-Bt guided by PDD. Eight of 57 patients recurred and recurrence-free survival rate was 88.2 +/- 0.1% (at 12 months) and 76.2 +/- 0.1% (24-48 months). Median follow-up period was 49.9 (5.0-145.0) months in 149 patients underwent conventional TUR-Bt. Ninety-nine of 149 patients recurred and recurrence-free survival rate was 60.3 +/- 0.0% (12 months) and 31.6 +/- 0.0% (24-48 months). There was statistical significance in recurrence-free survival rate between these 2 therapeutic groups (p < 0.001). Moreover, multivariate analysis revealed the independent factor contribute to improving prognosis was only TUR-Bt guided by PDD (hazard ratio 0.279, p = 0.001). CONCLUSION: It was suggested that TUR-Bt guided by PDD might reduce the risk of vesical recurrence in the early stage after operation of non-muscle invasive bladder cancer.

Blockade of the vascular endothelial growth factor-receptor 2 pathway inhibits the growth of human renal cell carcinoma, RBM1-IT4, in the kidney but not in the bone of nude mice.

Primary and metastatic RCCs are consistently resistant to radiotherapy, chemotherapy, or immunotherapy. As recurrent or metastatic RCC after surgery is related with poor prognosis and cancer-related death, development of therapeutic modalities that can control RCC and improve patient survival is urgently needed. We determined whether blockade of the vascular endothelial growth factor-receptor 2 (VEGF-R2) signaling pathway inhibits the growth of human renal cell carcinoma cells in the kidney and bone of nude mice. Male nude mice implanted with 1x10(6) RBM1-IT4 cells in the kidney or in the tibia were treated with oral administrations of TSU-68, anti-VEGF-R2 tyrosine kinase inhibitor beginning 5 days after implantation. The tumor incidence, tumor weight and bone destruction were determined at twelve weeks after commencing the therapy. VEGF production by RCCs was determined by ELISA and alterations in VEGF production related with genetic instability were also analysed. VEGF-R expression of mouse osteoclast precursors (mOCPs) and human umbilical vascular endothelial cell (HUVEC) was determined by RT-PCR and Western immunoblotting. in vitro, the effects of TSU-68 on the cellular proliferation of HUVEC, normal human renal proximal tubule epithelial cell (RPTEC) and mOCPs were determined. RBM1-IT4 cells had loss of heterozygosity and frame shift mutation on chromosome 3p, inactivating the von Hippel-Lindau (VHL) tumor suppressor gene and resulting in the production of relatively higher levels of VEGF than the RCCs without VHL mutation. TSU-68 significantly inhibited the growth of RBM1-IT4 in the kidney (p<0.05). In contrast, TSU-68 did not inhibit the growth of RBM1-IT4 in the tibia or bone lysis. Although HUVEC, RPTEC and mOCPs expressed VEGF-R2, TSU-68 directly inhibited the VEGF-stimulated cell growth of HUVEC and RPTEC but not the mOCPs in vitro. These data indicate that the VEGF-VEGF-R2 pathway is not required for survival of the osteoclasts and anti-VEGF-R2 therapy did not contribute to the suppression of metastatic RCC growth in the bone.