Prognosis by cancer type and incidence of zoledronic acid-related osteonecrosis of the jaw: a single-center retrospective study.

PURPOSE: Survival time after bisphosphonate use has been increasingly recognized to be associated with the incidence of medication-related osteonecrosis of the jaw (MRONJ); however, this has not been elucidated sufficiently in the literature. This study aimed to clarify the incidence of MRONJ and the corresponding survival rate of patients treated with zoledronic acid (ZA) for each type of cancer and obtain useful information for the oral/dental supportive care of cancer patients. METHODS: We evaluated 988 patients who were administered ZA at our hospital; among them, 862 patients with metastatic bone tumors or myeloma were included. RESULTS: The median survival time (MST) after ZA initiation was 35, 34, 8, 41, 12, and 6 months for patients with breast, prostrate, lung, myeloma, renal, and other cancers, respectively. Patients with cancers that had a short survival time (lung and other cancers [MST = 8 and 6 months, respectively] and cancers with MST < 10 months) did not develop MRONJ; this could be attributed to the shorter duration of ZA administration. The cumulative incidence of MRONJ in breast cancer, prostate cancer, and multiple myeloma was related to the frequency of anti-resorptive drug use and the increased risk over time. In renal cancer, the cumulative incidence of MRONJ increased early, although the MST was 12 months. CONCLUSION: For the dentists in charge of dental management, it is essential to be aware of prognosis-related factors, predict MRONJ risk for each cancer treatment, and use risk prediction in dental management planning, particularly for cancers with non-poor prognosis.

Late recurrence in patients with non-muscle-invasive bladder cancer after 5-year cancer-free periods.

OBJECTIVES: There is no consensus about the follow-up schedule after 5-year cancer-free periods. In this study, we aimed to elucidate the risk factors for the recurrence in patients with non-muscle-invasive bladder cancer who remained cancer free for more than 5 years. METHODS: Data from six Japanese institutions were retrospectively reviewed. Among the patients with non-muscle-invasive bladder cancer who were treated with transurethral resection of bladder tumor between 1990 and 2013, those who had no recurrence for more than 5 years were included in this study. The Kaplan-Meier method and Cox hazards model were used to estimate recurrence-free survival and to determine the pathologic and clinical factors affecting late recurrence. RESULTS: In total, 434 patients were enrolled in this study. Of these patients, 55 patients (12.7%) experienced late recurrence. The median follow-up time was 8.9 years (interquartile range 6.9-11.3 years). Prior history of bladder cancer before the most recent transurethral resection was a significant predictor for late recurrence (hazard ratio 1.99 [95% confidence interval 1.13-3.47], P = 0.019), although other clinical factors including tumor grade, pathologic stage, tumor multiplicity, and current risk classification systems were not associated with late recurrence. CONCLUSIONS: Late recurrence after a long tumor-free period is not rare and it was not predicted by current risk classification systems. Only prior history of bladder cancer was a significant predictor for late recurrence in this study.

Prognostic impact of local radiotherapy on metastatic urothelial carcinoma patients receiving systemic chemotherapy.

OBJECTIVE: To clarify the prognostic impact of local radiotherapy on metastatic urothelial carcinoma patients treated by systemic chemotherapy. METHODS: Of the 228 metastatic urothelial carcinoma patients treated with systemic chemotherapy, 97 received radiotherapy mainly to metastatic sites. In patients for whom the purpose of radiotherapy was not specified, more than 50 Gy irradiation was considered to be for disease consolidation for survival analysis, while less than 50 Gy was categorized as palliation. According to the Kaplan-Meier method, we analysed overall survival from the initiation of treatment for metastatic urothelial carcinoma until death or the last follow-up, using the log-rank test to assess the significance of differences. The Cox model was applied for prognostic factor analysis. RESULTS: Overall, there was no significant difference in survival between patients with and those without radiotherapy (P = 0.1532). When analysing the patients undergoing consolidative radiotherapy separately, these 25 patients showed significantly longer survival than the 72 patients with palliative radiotherapy (P = 0.0047), with a 3-year overall survival of 43.3%. Of the present cohort, 22 underwent metastasectomy for disease consolidation, and there was no overlapping case between the metastasectomy cohort and cohort receiving consolidative radiotherapy. After controlling for four independent prognostic factors (sex, performance status, haemoglobin level and number of organs with metastasis) in our previous study, radiotherapy for disease consolidation showed a marginal value (hazard ratio = 0.666, P = 0.0966), while metastasectomy remained significant (hazard ratio = 0.358, P = 0.0006). CONCLUSIONS: In the selected patients, long-term disease control could be achieved after consolidative radiotherapy for metastatic urothelial carcinoma disease. Our observations suggest that local ablative therapy (surgery or radiotherapy) could facilitate long-term disease control. However, the treatment decision should be individualized because of the lack of randomized control trials.

Possibility for Dose Optimization of Pazopanib from Its Plasma Concentration in Japanese Patients with Cancer.

The currently approved dose of pazopanib (800 mg) is being re-examined owing to its adverse effects. The aim of this study was to evaluate the relationships among starting or maintenance doses of pazopanib, estimated pazopanib Cmin, and other clinical factors, including albumin and α-1 acid glycoprotein levels, in soft-tissue sarcoma and renal cell carcinoma. We also determined whether therapeutic drug monitoring of pazopanib concentrations may be used to improve its therapeutic efficacy and prevent adverse effects. Forty patients who received pazopanib for renal cancer or soft-tissue sarcoma at the Hokkaido Cancer Center were evaluated prospectively. Cmin for pazopanib was calculated based on the measured values from the plasma samples. The efficacy and time to treatment failure were then assessed. The pazopanib maintenance doses were 200 (n = 4), 400 (n = 34), 600 (n = 4), and 800 mg (n = 1). Most patients (65%) who received a 400 mg dose had an effective pazopanib concentration (≧20 µg/mL), whereas 35% of patients who received the 400 mg dose had ineffective concentrations (<20 µg/mL). Logistic regression analysis revealed that only the albumin level was significantly associated with effective pazopanib concentrations (odds ratio: 1.37, p = 0.0234). In conclusion, a dose of 400 mg had been effective and well tolerated in more than half of patients in this study. However, therapeutic drug monitoring is necessary during pazopanib therapy.

Health-related quality of life in Japanese patients with bladder cancer measured by a newly developed Japanese version of the Bladder Cancer Index.

INTRODUCTION: We validated a Japanese version of the Bladder Cancer Index (BCI) as a tool for measuring health-related quality of life (HRQOL) in bladder cancer patients treated with various surgical procedures. METHODS: The reliability and validity of the Japanese BCI were examined in 397 Japanese patients with bladder cancer via cross-sectional analysis. The patients simultaneously completed the Short Form (SF)-12, EQ-5D, and the Functional Assessment of Cancer Therapy-General and Bladder (FACT-G and FACT-BL). The differences in BCI subscales among various treatment groups were analyzed. RESULTS: This study involved 397 patients (301 males and 96 females), with a mean age of 70 years and a median disease duration of 29 months (IQR: 12-66 months). Of these patients, 221 underwent transurethral resection of a bladder tumor, and 176 patients underwent radical cystectomy (ileal conduit: 101 patients, ileal neobladder: 49, and ureterostomy: 26). Cronbach's alpha coefficient was ≥ 0.78 for all subscales, except the bowel bother subscale. Despite moderate correlations being detected between the function and bother score in urinary and bowel domains, the sexual function score was inversely correlated with the sexual bother score (r = - 0.19). A missing value percentage of > 15% was associated with old age (p < 0.05). The mean domain scores differed significantly among distinct clinically relevant treatment groups. CONCLUSIONS: Although revisions are needed to make it easier for elderly patients to comprehend, we confirmed the reliability and validity of the Japanese BCI. The Japanese BCI could be used for cross-cultural assessments of HRQOL in bladder cancer patients.

Cost comparison between open radical cystectomy, laparoscopic radical cystectomy, and robot-assisted radical cystectomy for patients with bladder cancer: a systematic review of segmental costs.

BACKGROUND: Robot-assisted radical cystectomy is becoming a common treatment for bladder carcinoma. However, in comparison with open radical cystectomy, its cost-effectiveness has not been confirmed. Although few published reviews have compared total costs between the two surgical procedures, no study has compared segmental costs and explained their impact on total costs. METHODS: A systematic review was conducted based on studies on the segmental costs of open, laparoscopic, and robot-assisted radical cystectomy using PubMed, Web of Science, and Cochrane Library databases to provide insight into cost-effective management methods for radical cystectomy. The segmental costs included operating, robot-related, complication, and length of stay costs. A sensitivity analysis was conducted to determine the impact of the annual number of cases on the per-case robot-related costs. RESULTS: We identified two studies that compared open and laparoscopic surgeries and nine that compared open and robotic surgeries. Open radical cystectomy costs were higher than those of robotic surgeries in two retrospective single-institution studies, while robot-assisted radical cystectomy costs were higher in 1 retrospective single-institution study, 1 randomized controlled trial, and 4 large database studies. Operating costs were higher for robotic surgery, and accounted for 63.1-70.5% of the total robotic surgery cost. Sensitivity analysis revealed that robot-related costs were not a large proportion of total surgery costs in institutions with a large number of cases but accounted for a large proportion of total costs in centers with a small number of cases. CONCLUSIONS: The results show that robot-assisted radical cystectomy is more expensive than open radical cystectomy. The most effective methods to decrease costs associated with robotic surgery include a decrease in operating time and an increase in the number of cases. Further research is required on the cost-effectiveness of surgeries, including quality measures such as quality of life and quality-adjusted life years.

Comparative study of lymph node dissection, and oncological outcomes of laparoscopic and open radical nephroureterectomy for patients with urothelial carcinoma of the upper urinary tract undergoing regional lymph node dissection.

OBJECTIVE: To assess the number of lymph nodes removed as a surrogate marker of the extent of lymph node dissection, and compare survival outcomes between laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) in patients undergoing standardized lymph node dissection. METHODS: We retrospectively analyzed the data of 214 cTanyN0M0 patients undergoing radical NU with regional lymph node dissection according to the tumor location. The Kaplan-Meier method and Cox hazards model were utilized for survival analyses, including recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: A total of 114 patients underwent LRNU and 100 underwent ORNU. There was no significant difference in the pT stage, pN stage, or tumor grade, but distal ureteral tumors were more frequent in the LRNU group. The number of lymph nodes removed did not differ between the two groups [LRNU: 12 (median), ORNU: 11.5, P = 0.3852]. Lymph node metastasis was pathologically identified in 19 patients (8.9%). The 5-year RFS (ORNU: 71.7%, LRNU: 74%, P = 0.7829), CSS (77.8 and, 80%, P = 0.8441) and OS (72.8, and 75.9%, P = 0.3456) did not differ between the two groups. In the sub-analysis of pT3/4 patients (n = 83), there were no significant differences in RFS, CSS, or OS between the two groups, although Kaplan-Meier survival curves were slightly better for those receiving ORNU. In the multivariate model, LRNU was not significantly correlated with a poorer RFS, CSS or OS. CONCLUSION: Our data support the feasibility of lymph node dissection with a laparoscopic approach and the equivalent oncological outcome of LRNU compared with ORNU when regional lymph node dissection is performed. However, LRNU should be performed after careful patient selection for advanced disease.

Outcome and prognostic factors in metastatic urothelial carcinoma patients receiving second-line chemotherapy: an analysis of real-world clinical practice data in Japan.

OBJECTIVES: The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. METHODS: Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan-Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. RESULTS: The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. CONCLUSIONS: The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.

Laparoscopic resection of paraaortic/paracaval neurogenic tumors: surgical outcomes and technical tips.

BACKGROUND: Due to variations in location and size, laparoscopic surgery for paraaortic or paracaval neurogenic tumors is challenging. We evaluated the surgical outcomes, as well as surgical tips and tricks. METHODS: Between 2000 and 2015, 25 procedures were performed in 24 patients. One patient underwent second surgery due to the recurrence of paraganglioma. Data were collected on the tumor diameter, tumor location, perioperative outcomes, pathology, and last-known disease status. Regarding the operative procedures, we reviewed the operative charts or videos to identify surgical tips and tricks. RESULTS: The median tumor diameter was 5.0 cm (range 1.5-10). The tumor location was suprahilar in 10, hilar in 6, and infrahilar in 9 cases. Regarding the approach, a transperitoneal approach was selected in 24 cases and retroperitoneal approach in 1. The median operative time and blood loss were 208 min (range 73-513) and 10 mL (range 0-1020), respectively. No patient required blood transfusion or conversion to open surgery. Pathological examination revealed paraganglioma in 12, ganglioneuroma in 7, and schwannoma in 6 cases. At the last follow-up, 23 patients were free of disease, while one patient developed metastatic multiple recurrence of paraganglioma 54 months after the second laparoscopic surgery. A review of the surgical records revealed several tips and tricks, including taping the vena cava/renal vein (n = 2) being helpful for detaching a retrocaval tumor from these great vessels, or rotating the kidney to provide a favorable operative view of tumors behind the renal hilum (n = 2). In recent cases, 3D-CT was helpful for preoperative planning. CONCLUSIONS: Laparoscopic resection of paraaortic or paracaval neurogenic tumors is feasible in experienced hands. Surgeons should be familiar with detaching maneuvers around great vessels and the mobilization of adjacent organs. Careful preoperative planning is mandatory.

Prospective mapping of lymph node metastasis in Japanese patients undergoing radical cystectomy for bladder cancer: characteristics of micrometastasis.

OBJECTIVE: To investigate node-disease prevalence including micrometastases and its survival impact on bladder cancer patients. METHODS: A total of 60 patients participated in this study, in which extended lymph node dissection was carried out according to the prospective rule (below aortic bifurcation). Radical cystectomy and extended lymph node dissection were performed by open surgery (n = 23) or laparoscopically (n = 37). Perioperative, pathological and follow-up data were collected. Micrometastasis in lymph nodes was investigated by pan-cytokeratin immunohistochemistry. Recurrence-free survival was estimated with the Kaplan-Meier method. RESULTS: The median number of lymph nodes removed was 29 (range: 10-103) and there was no significant difference between the two groups (open group: median 30, laparoscopic group: median 29). Routine pathological examination revealed that 10 patients had lymph node metastases. Immunohistochemistry revealed micrometastases in four additional patients (pNmicro+), who had been diagnosed with pN0 on routine pathological examination. After excluding the three patients with pure nonurothelial carcinoma on the final pathology (small cell carcinoma: n = 2, adenocarcinoma: n = 1), 10 out of the 57 urothelial carcinoma patients (17.5%) had node metastasis, and an additional 4 out of the 47 pN0 patients (4/47, 8.5%) had micrometastasis. The 2-year recurrence-free survival rates divided by pN stage were 82.4% for pN0, 66.7% for pNmicro+ and 12.5% for pN+ (three-sample log-rank test, P < 0.0001). Three out of the four patients with pNmicro+ were disease free at the last follow-up. CONCLUSIONS: We confirmed under extended lymph node dissection that a substantial proportion of the patients had node metastasis (pN+: n = 10 and pNmicro+: n = 4), and the pN stage influenced patient survival. Our observations of micrometastasis yielded additional evidence for the potential survival benefit of extended lymphadenectomy by eliminating microdisease.

Diagnostic outcome of ureteroscopy in urothelial carcinoma of the upper urinary tract: Incidence of later cancer detection and its risk factors after the first examination.

BACKGROUND: To determine the incidence of later cancer detection and its risk factors after the first diagnostic ureteroscopy. METHODS: One hundred and sixty-six patients undergoing diagnostic ureteroscopy based on the suspicion of urothelial carcinoma of the upper urinary tract (UC of the UUT) between 1995 and 2012 were included. We examined the diagnostic outcome of the initial ureteroscopy. Thereafter, we collected follow-up data on patients who had not been diagnosed with UC of the UUT at the first examination, and evaluated the incidence of later cancer detection and its risk factors using Cox hazard models. RESULTS: Of the 166 patients, 76 (45.8%) were diagnosed with UC of the UUT at the first diagnostic ureteroscopy. The remaining 90 (54.2%) were diagnosed with other malignancies (n = 22), non-malignant disorders (n = 18), or without disorders (n = 50). Of these 90 patients, follow-up data were available in 65 patients (median: 41 months, range: 3-170). During the follow-up, carcinoma was detected in 6 patients (6/65, 9.2%) at a median of 43.5 months (range: 10-59). Episodes of gross hematuria (p = 0.0048) and abnormal cytological findings (p = 0.0335) during the follow-up and a male sex (p = 0.0316) were adverse risk factors. CONCLUSION: Later cancer detection of UC of the UUT was not uncommon after the first examination. The risk analysis revealed the aforementioned characteristics.

Cross-sectional and longitudinal analyses of urinary extracellular vesicle mRNA markers in urothelial bladder cancer patients.

We designed this multi-center prospective study with the following objectives: (1) the cross-sectional validation of extracellular vesicles (EV) mRNA markers to detect urothelial bladder cancer (UBC) before transurethral resection of bladder cancer (TURBT), and (2) the longitudinal validation of EV mRNA markers to monitor non-muscle invasive bladder cancer (NMIBC) recurrence after TURBT. EV mRNA markers evaluated in this study were KRT17, GPRC5A, and SLC2A1 in addition to two additional markers from literatures, MDK and CXCR2, and measured by quantitative RT-PCR with normalization by a reference gene (ALDOB). Diagnostic performances of EV mRNA markers were compared to conventional markers. Regarding the first objective, we confirmed that EV mRNA biomarkers in urine were higher in UBC patients, particularly those with higher stage/grade tumors, than in those without UBC (n = 278 in total) and the diagnostic performance of EV mRNA MDK and KRT17 outperformed conventional biomarkers with AUC 0.760 and 0.730, respectively. Concerning the second objective, we prospectively analyzed the time courses of EV mRNA markers while NMIBC patients (n = 189) (median follow-up 19 months). The expression of EV mRNA KRT17 was significantly high in patients with recurrence, while it gradually decreased over time in those without recurrence (p < 0.01).

Influence of baseline renal function and dose reduction of nephrotoxic chemotherapeutic agents on the outcome of metastatic urothelial carcinoma: a retrospective study.

OBJECTIVES: To investigate the influence of baseline renal function and dose reduction of chemotherapeutic agents on the outcome of metastatic urothelial carcinoma patients with renal impairment. METHODS: A total of 57 patients with metastatic urothelial carcinoma treated by systemic chemotherapy were included in the present study. The 24 h-creatinine clearance was measured before each cycle and dose reduction was carried out according to our guidelines. Patients were divided into two groups according to baseline 24 h-creatinine clearance: fit group (60 mL/min/1.48 m(2) ≤) and unfit group (60 mL/min/1.48 m(2) >). Clinical characteristics and final outcomes were compared between the two groups. RESULTS: There was no significant difference in the total number of chemotherapy cycles of each patient between the two groups (fit group: median 5; unfit group: median 4; P=0.7466), although dose reduction was carried out significantly more often in the unfit group than in the fit group during treatment (fit group: median 0 cycles; unfit group: median 3.5 cycles; P=0.0016). Overall, the median survival was 16 months. There was a significant survival difference between the two groups (fit group: median 17 months; unfit group: median 10 months; P=0.0419). On multivariate analyses, impaired renal function at the baseline remained an adverse factor (HR 2.27, P=0.01). CONCLUSIONS: "Unfit" was a poor prognostic factor for metastatic urothelial carcinoma. The dose reduction strategy contributed to continuous treatment in the unfit group. However, its contribution to the prognosis of unfit patients is uncertain.

Validation of the Japanese version of the Body Image Scale for bladder cancer patients.

The Body Image Scale (BIS) is a 10-item tool that measures the body images of cancer patients. This study aims to validate the Japanese version of the BIS for bladder cancer patients. A multicenter cross-sectional survey was used to identify the participants, which included Japanese bladder cancer patients. The percentage of missing responses, internal consistency, and known-group validity were evaluated. The correlations between the BIS and two HRQOL instruments (the Bladder Cancer Index and the SF-12) were assessed to determine convergent validity. Among 397 patients, 221 patients were treated by transurethral resection of bladder tumor (TURBT) endoscopically, 49 patients underwent cystectomy with neobladder, and 127 patients underwent cystectomy involving stoma. The percentage of missing responses in the BIS ranged from 8.1 to 15.6%. Cronbach's α coefficient was 0.924. Higher BIS scores indicate negative body image, and the median BIS score for patients with native bladders after TURBT (0.5) was significantly lower than those of the patients with neobladder (4.0) and stoma formation (7.0), which indicated the discriminatory ability of the BIS. Each domain of the Bladder Cancer Index and the role summary score of the SF-12 correlated to the BIS scores, which confirmed the convergent validity. A range of BIS scores were identified among patients who reported similar physical summary scores and mental summary scores of the SF-12. This study confirmed the reliability and validity of the Japanese version of the BIS for bladder cancer patients.

Efficacy of nivolumab plus ipilimumab as first-line therapy for primary tumors in patients with renal cell carcinoma.

OBJECTIVES: With the emergence of several effective combination therapies, information on their effects at the primary site will be crucial for planning future cytoreductive nephrectomy (CN). The present study focused exclusively on changes in primary tumor sizes following treatment with nivolumab plus ipilimumab and investigated the clinical factors associated with a good response in primary tumors. METHODS AND MATERIALS: We retrospectively assessed 27 patients diagnosed with advanced renal cell carcinoma (RCC) who started treatment with nivolumab plus ipilimumab. Changes in tumor sizes at the primary site were described using waterfall and spider plots, respectively. We analyzed the correlation of tumor shrinkage between primary and metastatic site. The parameters analyzed between responders and non-responders according to primary tumor sizes were International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, peripheral blood markers, and CRP. RESULTS: The median age and follow-up period were 66 years and 9.3 months, respectively. The median IMDC risk score was 3 (range: 1-6). Nineteen patients were diagnosed with clear-cell RCC (ccRCC) and 8 patients with non-ccRCC. Among ccRCC patients, 9 (47.4%) achieved a significant response with a maximum reduction of 30% or more in the size of the primary tumor from baseline within 4 months, while 3 (37.5%) out of 8 patients with non-ccRCC achieved a significant response. Shrinkage of the primary tumor correlated with the metastatic tumors in both ccRCC and non-ccRCC cases. Of note, 6 patients underwent CN and no viable tumor cells were detected in the surgical specimens of 3 patients whose primary tumors shrank by approximately 50%-60% with a reduction to 4 cm or less. Among ccRCC patients, the neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio were slightly lower in responders than in non-responders (P = 0.0944 and P = 0.0691). The platelet-to-lymphocyte ratio was significantly lower in responders than in non-responder (P = 0.0391). CONCLUSIONS: Significant responses in primary tumors to nivolumab plus ipilimumab were observed in 50% of ccRCC patients, while responses varied among non-ccRCC patients. Inflammation markers may be predictive factors of treatment responses in primary tumors. Although further studies are needed, the present results suggest the importance of considering CN from radiological and pathological viewpoints.

Cytogenetic abnormalities of tumor-associated endothelial cells in human malignant tumors.

Tumor blood vessels are thought to contain genetically normal and stable endothelial cells (ECs), unlike tumor cells, which typically display genetic instability. Yet, chromosomal aberration in human tumor-associated ECs (hTECs) in carcinoma has not yet been investigated. Here we isolated TECs from 20 human renal cell carcinomas and analyzed their cytogenetic abnormalities. The degree of aneuploidy was analyzed by fluorescence in situ hybridization using chromosome 7 and chromosome 8 DNA probes in isolated hTECs. In human renal cell carcinomas, 22-58% (median, 33%) of uncultured hTECs were aneuploid, whereas normal ECs were diploid. The mechanisms governing TEC aneuploidy were then studied using mouse TECs (mTECs) isolated from xenografts of human epithelial tumors. To investigate the contribution of progenitor cells to aneuploidy in mTECs, CD133(+) and CD133(-) mTECs were compared for aneuploidy. CD133(+) mTECs showed aneuploidy more frequently than CD133(-) mTECs. This is the first report showing cytogenetic abnormality of hTECs in carcinoma, contrary to traditional belief. Cytogenetic alterations in tumor vessels of carcinoma therefore can occur and may play a significant role in modifying tumor- stromal interactions.