Fibroblast growth factor receptor 3 gene (FGFR3) mutations in high-grade muscle-invasive urothelial bladder cancer in a Brazilian population: evaluation and prevalence

ABSTRACT Objective To understand the feasibility of FGFR3 tests in the Brazilian public health context, and to sample the mutational burden of this receptor in high-grade muscle invasive bladder cancer. Methods A total of 31 patients with high-grade muscle-invasive bladder cancer were included in the present study. Either transurethral resection of bladder tumor or radical cystectomy specimens were analyzed. Formalin-fixed paraffin-embedded tissue blocks were sectioned, hematoxylin and eosin stained, and histologic sections were reviewed. Total RNA was extracted using the RNeasy DSP formalin-fixed paraffin-embedded kit. Qualitative results were displayed in Rotor-Gene AssayManager software. Results Six patients were excluded. From the samples analyzed, four (16.7%) were considered inadequate and could not have their RNA extracted. Two patients presented FGFR3 mutations, accounting for 9.5% of material available for adequate analysis. The two mutations detected included a Y373C mutation in a male patient and a S249C mutation in a female patient. Conclusion FGFR3 mutations could be analyzed in 84% of our cohort and occurred in 9.5% of patients with high-grade muscle invasive bladder cancer in this Brazilian population. FGFR3 gene mutations are targets for therapeutic drugs in muscle-invasive bladder cancer. For this reason, know the frequency of these mutations can have a significant impact on public health policies and costs provisioning.

Effect of 125I seeds on T24 transitional cell carcinoma of nude mouse / 中国介入影像与治疗学

Objective: To observe the effect of 125I on T24 transitional cell carcinoma of nude mouse. Methods: Totally 40 T24 transplanted tumor nude mice were divided into high, medium, low activity and control groups (each n=10), and 125I seeds with activity of 0.9 mCi (33. 3 MBq), 0.6 mCi (22. 2 MBq), 0.3 mCi (11. 1 MBq) and 0 mCi (nuclide free) were implanted in the tumor center, respectively. The 90% target absorbed dose (D90), tumor inhibition rate (IR), radiation reaction grade (RRG) of HE staining, apoptosis index and B-cell lymphoma-2 (Bcl-2) protein expression were analyzed and compared among groups 10 days and 20 days after implantation. Results: D90 and IR of nude mice with high, medium and low activity groups decreased gradually 10 and 20 days after 125I seed implantation (all P<0.05). The necrosis was obvious within 5 mm around the tumor, and the higher the seed activity, the longer the time, the wider the ranges of necrosis. RRG of high activity group 10 and 20 days after 125I seed implantation were higher than that in low activity group and control group (all P<0.05). Meanwhile, the apoptotic index of high, medium and low activity groups gradually decreased, the expression of Bcl-2 protein gradually increased (all P<0.05). Conclusion: 125I seeds can significantly inhibit the growth of T24 metastatic cell carcinoma in nude mouse. Promoting the apoptosis of tumor cells may be one of the mechanisms.

Trends in cancer incidence in Uruguay: 2002 -2015 / Tendencias de la incidencia de cáncer en Uruguay: 2002-2015

Abstract Background: Uruguay is the south American country which has the highest cancer incidence and mortality rates. The National Cancer Registry collects data on cancer cases nationwide since 1989 and has reached high quality standards in the last decades. This is the first report on incidence trends. Methods: Data from the National Cancer Registry of all new cases of invasive cancer from twelve sites diagnosed in 2002-2015 was analyzed. Age-standardized rates were calculated. Trends of incidence rates were analyzed using joinpoint regression models. Results: For both, men and women, incidence rates trends for all cancer sites, colo-rectal and bladder cancer remained stable. Esophageal and gastric cancers descended while thyroid and kidney cancer incidence increased. In men lung cancer decreased; testicular cancer increased, and prostate cancer increased at the beginning of the period and decreased in the final years. In women, lung cancer increased, breast cancer remained stable and cervical cancer presented a significant decline from 2005 to 2010 and reached a plateau since then. Conclusion: Cancer incidence dynamics are complex and affected not only by Public Health policies such as tobacco control, vaccination and screening programs, but also by environmental and life style changes and the attitude of the medical community towards the application of diagnostic and therapeutic tools. The aim of this paper is to analyze cancer incidence time trends in the country and provide possible explanations to them.

Resumen Introducción: Uruguay es el país de Sudamerica que tiene las mayores tasas de incidencia y mortalidad por cáncer. El Registro Nacional de Cáncer recoge los datos de cáncer de todo el país desde 1989 y en las últimas décadas ha alcanzado los más altos estándares de calidad. Este es el primer reporte de tendencias de incidencia de cáncer de Uruguay. Métodos: Se analizaron los datos de todos los casos de cáncer invasivo diagnosticados entre 2002 y 2015 incluidos en el Registro Nacional de Cáncer y los de once topografías en particular. Se calcularon las tasas de incidencia estandarizada y se analizaron las tendencias utilizando los modelos de regresión de Joinpoint. Resultados: Las tasas de incidencia de cáncer colorrectal, vejiga y todos los sitios reunidos se mantuvieron estables tanto en hombres como en mujeres. La tasa de incidencia de cáncer de estómago y esófago disminuyeron mientras que las de tiroides y riñón aumentaron. En los hombres, el cáncer de pulmón disminuyó, el cáncer de testículo aumentó y el de próstata aumentó en un lapso inicial y decreció en los últimos años. En las mujeres el cáncer de pulmón aumentó y el de mama se mantuvo estable mientras que el cáncer de cérvix presentó un descenso significativo entre 2005 y 2010 alcanzando una meseta desde entonces. Conclusión: La dinámica de la incidencia de cáncer es compleja y está afectada no sólo por las políticas de Salud Pública como las campañas de control de tabaco, vacunación y programas de tamizaje sino por los cambios ambientales y de los estilos de vida y la actitud de los médicos respecto a la aplicación de técnicas diagnósticas y terapéuticas. En este trabajo se analizan las tendencias de incidencia en el país y se plantean posibles explicaciones para los cambios.

Moderate or severe LUTS is associated with increased recurrence of non - muscle - invasive urothelial carcinoma of the bladder

ABSTRACT Purpose: Non - muscle - invasive bladder cancer (NMIBC) can recur despite transurethral resection (TURBT) and adjuvant intravesical therapy. Tobacco products excreted in the urine are hypothesized to cause tumor - promoting effects on urothelial cells through direct contact. We determined if moderate or severe lower urinary tract symptoms (LUTS) (defined as International Prostate Symptom Score [IPSS] ≥ 8) was associated with increased tumor recurrence. Materials and Methods: We retrospectively identified 70 consecutive men initially diagnosed with NMIBC at our institution from 2010 - 2016. Means were compared with independent T - test and proportions with chi - square analysis. Multivariate logistic regression was performed to determine independent predictors of recurrence. Results: The majority of patients had Ta disease (58.6%) followed by T1 (28.6%) and Tis (12.9%). Forty - one (58.6%) patients had moderate or severe LUTS upon presentation within 30 days of initial TURBT with mean IPSS of 13.2 vs. 5.2 in the control group (p < 0.01). Biopsy - proven tumor recurrence occurred in 24 (34.3%) patients at mean follow-up of 31.7 months. Mean time to recurrence was 14.6 months. Moderate or severe LUTS was an independent predictor of tumor recurrence (odds ratio [OR]: 19.1, 95% confidence interval [CI]: 2.86 - 127; p = 0.002). Voiding or storage symptoms based on the IPSS did not independently correlate with tumor recurrence (p = 0.08 and p = 0.31, respectively) although total mean IPSS score did (OR: 1.26, 95% CI: 1.07 - 1.47, p = 0.005). Conclusions: The presence of moderate or severe LUTS may be an important prognostic factor in NMIBC. Patients with significant urinary symptoms could be monitored more aggressively due to higher recurrence risk.

Prognostic Value of Lymphovascular Invasion in Node-Negative Upper Urinary Tract Urothelial Carcinoma Patients Undergoing Radical Nephroureterectomy

PURPOSE: This study aimed to evaluate the prognostic impact of lymphovascular invasion (LVI) in patients treated with radical nephroureterectomy (RNU) for upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: We collected data from 180 patients who were treated with RNU from 2005 to 2013 at our institution. The Kaplan-Meier method with log-rank test and Cox proportional hazards regression models were used for univariate and multivariate analyses. RESULTS: LVI was present in 28 patients (15.6%), which was associated with higher pathological tumor stage (p < 0.001), tumor necrosis (p=0.012), lymph node metastasis (p=0.017) and multifocality (p=0.012). On multivariate analysis, LVI was an independent prognostic factor of recurrence-free survival [RFS: hazard ratio (HR)=2.954; 95% confidence interval (CI)=1.539–5.671; p=0.001] and cancer-specific survival (CSS: HR=3.530; 95% CI=1.701–7.325; p=0.001) in all patients. In patients with node-negative UTUC, LVI was also a significant predictor of RFS (HR=3.732; 95% CI 1.866–7.464; p < 0.001) and CSS (HR=3.825; 95% CI=1.777–8.234; p=0.001). CONCLUSION: LVI status was an independent predictor in patients with UTUC who underwent RNU. The estimate of LVI could help physicians identify high-risk patients and make a better medication regimen of adjuvant chemotherapy.

The value of detection of circulating tumor cells in predicting lymph node metastasis of urothelial carcinoma / 中华泌尿外科杂志

Objective To discuss the application experience and predictive value of circulating tumor cells for urothelial carcinoma.Methods The clinical data of 96 patients with urothelial carcinoma treated by Beijing Cancer Hospital Urologic Department between September 2017 and September 2019 were analyzed retrospectively to evaluate relationship between the number of CTCs and pathological outcome.The mean age of the entire cohort was 62(40-87)years,with 74 males and 22 females.There were 13 cases of upper urinary tract tumors (pyelocarcinoma and ureteral carcinoma),83 cases of bladder carcinoma,and 12 cases of lymph node metastasis.There were 77 cases of primary onset and 19 cases of recurrence.68 cases in single focus group and 28 cases in multiple group.There were 29 cases in non infiltrative Ta stage,42 cases in infiltrative lamina propria T1 stage,16 cases in infiltrative muscle T2 stage,and 9 cases in extramuscular≥T3 stage.At least 3ml of peripheral blood was collected after fasting for at least 8 hours,After cleavage and centrifugation,immunomagnetic beads were added,folate probe was added,and then amplification was carried out.Then the copy number of CTCs in each ml of blood was calculated.Logistic linear regression was used to analyze the risk factors of lymph node metastasis.Results The mean CNC of all patients was 12.3 ±7.3;the mean CNC of ≤62 years old group was 10.8 ±4.2;the mean CNC of ＞62 years old group was 13.7 ±9.2;the mean CNC of initial cases was 11.5 ±5.3;the mean CNC of recurrent cases was 15.5 ± 12.2.Age (P =0.135) and frequency of onset (P =0.087) had no effect on the number of CTCs.The average CNC of single focus group was 10.5 ± 5.2,multiple focus group was 16.5 ± 9.7,Ta stage group was 8.2 ±2.3,T1 stage group was 12.0 ±4.4,T2 stage group was 16.4 ±6.8,and ≥T3 stage group was 19.5 ± 16.6.The number of lesions (P ＜ 0.001) was significantly correlated with pathological T stage (P ＜ 0.001) and the number of CTCs.Univariate regression analysis showed that T stage (P ＜ 0.001) and the number of CTCs (P =0.02) might be correlated with lymph node metastasis;multivariate analysis showed that only T stage could be used as an independent predictor of lymph node metastasis (P =0.002).Conclusions CTCs can be used to predict lymph node metastasis of urothelial carcinoma.

The value of detection of circulating tumor cells in predicting lymph node metastasis of urothelial carcinoma / 中华泌尿外科杂志

Objective@#To discuss the application experience and predictive value of circulating tumor cells for urothelial carcinoma.@*Methods@#The clinical data of 96 patients with urothelial carcinoma treated by Beijing Cancer Hospital Urologic Department between September 2017 and September 2019 were analyzed retrospectively to evaluate relationship between the number of CTCs and pathological outcome. The mean age of the entire cohort was 62(40-87)years, with 74 males and 22 females. There were 13 cases of upper urinary tract tumors (pyelocarcinoma and ureteral carcinoma), 83 cases of bladder carcinoma, and 12 cases of lymph node metastasis. There were 77 cases of primary onset and 19 cases of recurrence. 68 cases in single focus group and 28 cases in multiple group. There were 29 cases in non infiltrative Ta stage, 42 cases in infiltrative lamina propria T1 stage, 16 cases in infiltrative muscle T2 stage, and 9 cases in extra-muscular≥T3 stage. At least 3ml of peripheral blood was collected after fasting for at least 8 hours, After cleavage and centrifugation, immunomagnetic beads were added, folate probe was added, and then amplification was carried out. Then the copy number of CTCs in each ml of blood was calculated. Logistic linear regression was used to analyze the risk factors of lymph node metastasis.@*Results@#The mean CNC of all patients was 12.3±7.3; the mean CNC of ≤62 years old group was 10.8±4.2; the mean CNC of >62 years old group was 13.7±9.2; the mean CNC of initial cases was 11.5±5.3; the mean CNC of recurrent cases was 15.5±12.2. Age (P=0.135) and frequency of onset (P=0.087) had no effect on the number of CTCs. The average CNC of single focus group was 10.5±5.2, multiple focus group was 16.5±9.7, Ta stage group was 8.2±2.3, T1 stage group was 12.0±4.4, T2 stage group was 16.4±6.8, and ≥T3 stage group was 19.5±16.6. The number of lesions (P<0.001) was significantly correlated with pathological T stage (P<0.001) and the number of CTCs. Univariate regression analysis showed that T stage (P<0.001) and the number of CTCs (P=0.02) might be correlated with lymph node metastasis; multivariate analysis showed that only T stage could be used as an independent predictor of lymph node metastasis (P=0.002).@*Conclusions@#CTCs can be used to predict lymph node metastasis of urothelial carcinoma.

Overexpression of UHRF1 gene correlates with the major clinicopathological parameters in urinary bladder cancer

ABSTRACT Introduction Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). Objective The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients’ clinical outcome. Materials and Methods In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. Results UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. Conclusions The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.

Diffusion tensor imaging in differential diagnosis of clear cell renal cell carcinoma and transitional cell carcinoma / 中国介入影像与治疗学

Objective To evaluate the value of ADC and FA of diffusion tensor imaging (DTI) in differentiating clear cell renal cell carcinoma (ccRCC) and transitional cell carcinoma (TCC) of kidney pelvis.Methods Thirty-eight histopathology proven ccRCC and TCC patients (29 cases of ccRCC and 9 cases of TCC) were retrospectively enrolled.All the patients were performed abdominal MR fat saturation T1WI,fat saturation T2WI,LAVA and DTI (b=0,600 s/mm2).MR images were reviewed and analyzed by two radiologists in a double-blind manner with the value of ADC and FA measured using the Functool on AW 4.4 workstation.The data of two observers were analyzed with intra-class correlation coefficients (ICC) to assess inter-observer consistency.The differences of ADC values and FA values between ccRCC and TCC were compared by independent t-test.The ROC curves were used to analyze and compare the diagnostic value of DTI in differentiating ccRCC and TCC.Results The inter-observer agreements were good (ICC＞0.75).The ADC value of ccRCC was statistically higher than that of TCC ([2.03 ± 0.49] × 10-3 mm2/s vs [1.57 ± 0.43] × 10-3 mm2/s,P =0.015).But the FA value of ccRCC was statistically lower than that of TCC ([0.24±0.10] vs [0.42±0.22],P=0.002).The area under the ROC curve of ADC was 0.761 (P＜0.05),and the sensitivity and specificity were 79.3％ and 77.8％.The ADC threshold for differentiating ccRCC from TCC was 1.59× 10-3 mm2/s.The area under the ROC of FA was 0.762 (P＜ 0.05),and the sensitivity and specificity were 66.7 ％ and 93.1％.The FA threshold for differentiating ccRCC from TCC was 0.326.Conclusion MR DTI can effectively discriminate ccRCC and TCC.FA values has good diagnostic specificity in differentiating between ccRCC and TCC.

Methylation status of RASSF1A gene promoter in upper tract urothelial carcinoma and its clinical significance / 北京大学学报(医学版)

Objective:To investigate the methylation status of the RASSF1A gene promoter in upper tract urothelial carcinoma (UTUC)tissues and its correlation with clinicopathologic characteristics and postoperative recurrence of primary UTUC.Methods:In a retrospective design,a total of 687 patients who underwent surgeries for primary UTUC in the urology department of Peking University First Hospital were enrolled.The methylation status of the RASSF1A gene promoter was analyzed using methylation-sen-sitive polymerase chain reaction on tumor specimens.Results:Aberrant methylation for the RASSF1A gene promoter was detected in 183 (26.6%) DNA samples in total.Aberrant methylation of the RASSF1A gene was strongly associated with tobacco consumption (P =0.044),ipsilateral hydronephrosis (P <0.001 ),tumor location (P <0.001 ),tumor stage (P =0.001 ),tumor grade (P =0.007), lymph node metastasis (P =0.001 )and growth pattern (P =0.013).The methylated RASSF1A gene promoter was an independent risk factor for bladder recurrence (P <0.001,HR =0.471)and contrala-teral recurrence (P =0.030,HR =0.269)of UTUC after surgery.Hypermethylated RASSF1A was pre-dictive for improved bladder recurrence-free survival (BRFS)(P <0.001)and contralateral recurrence-free survival (CRFS)(P =0.021)in the UTUC patients.Compared with the patients with unmethylated RASSF1A,the patients containing tumors with hypermethylated RASSF1A had tendency toward longer re-currence-free survival time [(114.4 ±3.9)months vs.(84.0 ±3.2)months for BRFS,(138.1 ±1.8) months vs.(132.9 ±1.9)months for CRFS]and higher estimated cumulative recurrence-free survive rates (five-year survival rate for example,79.8% ±3.4% vs.57.4% ±2.6% for BRFS,98.9% ± 0.8% vs.93.0% ±1.4% for CRFS).Additionally,tumor multifocality (P =0.002,HR =1.538), and ureteroscopy before surgery (P =0.001,HR =1.725)were independent risk factors for bladder re-currence in postoperative UTUC patients.Conclusion:The methylation status of the RASSF1A gene pro-moter appears to be a promising epigenomic biomarker for assessing the aggressiveness of UTUC and a predictor predicting the urinary tract recurrence after surgery.

Current status of minimally invasive surgery for treatment of renal stones and tumors using a flexible ureteroscopy

Retrograde intrarenal surgery (RIRS) has been accepted as the first-line option for surgical treatment of upper urinary tract pathologies including stones and tumors. With the development of surgical instruments with improved deflection mechanisms, visualization, and durability, RIRS has taken on an expanding role in treating urinary calculi located in the upper urinary tract, as it compensates for the shortcomings of shockwave lithotripsy and percutaneous nephrolithotomy. RIRS can also be considered a conservative treatment option for upper urinary tract urothelial cancer or as a means of intensive postoperative surveillance after radical treatment of urinary tract urothelial cancer. RIRS has a steep learning curve and various surgical techniques can be utilized during operations. The use of particular surgical instruments should take into consideration of the gain in surgical efficiency, decrease in complications, and cost-benefit tradeoff.

Adjuvant chemotherapy for locally advanced upper tract urothelial carcinoma: updated results of the Seoul National university hospital experience

Objectives: The objective of this study was to update the long-term outcome in the treatment of locally advanced upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU) regarding the role of adjuvant chemotherapy. Materials and methods: Clinical data from 138 patients who underwent RNU for locally advanced UTUC (pT3/4 or pN+) were analyzed. Results: The adjuvant chemotherapy group comprised 66 patients, and other 72 patients did not receive adjuvant chemotherapy. Cisplatin-based chemotherapy was the most common regimen, depending on the patient's eligibility and renal function. The median follow-up period was 48.7 months (interquartile range: 29.2-96.9 months). The 3-and 5-year disease-specific survival (DSS) rates were 76.0% and 69.9% for the non-adjuvant chemotherapy group versus 74.6% and 54.5% for the adjuvant chemotherapy group (p=0.301, log-rank test). Overall survival (OS) rates for the same time period were 70.1% and 62.9% for the non-adjuvant chemotherapy group versus 73.8% and 53.2% for the adjuvant chemotherapy group (p=0.931, log-rank test). On multivariate analysis, adjuvant chemotherapy could not predict DSS and OS after surgery. When patients who received cisplatin-based adjuvant chemotherapy (n=59) were compared to those who did not receive adjuvant chemotherapy, similar results were found. Conclusions: There does not appear to be a significant DSS or OS benefit associated with adjuvant chemotherapy. Prospective randomized clinical trials are necessary to verify the effect of adjuvant chemotherapy on locally advanced UTUC.

Differential expression of P-gp in bladder cancer cell lines / 中华检验医学杂志

Objective The generation of drug resistance often leads to the failure of the bladder cancer chemotherapy.P-glycoprotein (P-gp) is an ATP-dependent drug efflux pump linked to development of multidrug resistance in cancer cells.The laboratory has successfully established adriamycin-resistant human bladder cancer cell line (pumc-91/ADM) from its parental cell line (pumc-91).According to the drug resistant spectrum analysis,pumc-91/ADM cell line exhibited the characteristics of multi-drug resistance.However,the expression of P-gp in two cell lines was still unknown.In this paper,there was a comparison between pumc-91/ADM and pumc-91 about the differential expression of P-gp.Methods To determine the expression and location of P-gp in pumc-91 and pumc-91/ADM,qRT-PCR,Western blot and immunocytochemistry were applied in the experiment.qRT-PCR was implemented to research the expression of P-gp mRNA in two cell lines (pumc-91/ADM and pumc-91).Western blot was adopted to investigate the expression of P-gp protein in pumc-91 and pumc-91/ADM cell lines.Immunocytochemistry technique was used to explore the cellular location of P-gp and affirm its expression in two cell lines visually.Student's t-test was employed for statistical analysis and P ＜ 0.05 was considered statistically significant.Results qRT-PCR analysis revealed that the expression of P-gp mRNA was upregulated in drug-resistant cell line pumc-91/ADM compared to parental cell line pumc-91.To normalize for differences in the amount of total RNA,GAPDH was selected as an endogenous RNA control.Compared with pumc-91,the expression of P-gp mRNA was upregulated 7.74 fold in pumc-91/ADM (t =11.97,P ＜ 0.05).Consistent with the qRT-PCR result,Western blot confirmed the protein of P-gp expressed differentially in two cell lines.The expression of P-gp protein was significantly increased in pumc-91/ADM compared to pumc-91.According to the results,the differences between pumc-91 and pumc-91/ADM had statistical significance (t =4.35,P＜0.05).Immunocytochemical analysis results demonstrated that P-gp was not only located in cell membrane but also in cytoplasm of the two cell lines.The expression of P-gp in pumc-91/ADM increased distinctly.The difference was statistically significant (t =11.41,P ＜ 0.05).Conclusion Compared with pumc-91,the expression of P-gp in pumc-91/ADM was significantly upregulated.

Preoperative Underweight Patients with Upper Tract Urothelial Carcinoma Survive Less after Radical Nephroureterectomy

The prognostic impact of body mass index (BMI) in patients with upper tract urothelial carcinoma (UTUC) is an ongoing debate. Our study aimed to investigate the prognostic role of BMI in patients treated with radical nephroureterectomy (RNU) for UTUC from a multi-institutional Korean collaboration. We retrospectively reviewed data from 440 patients who underwent RNU for UTUC at four institutions in Korea. To avoid biasing the survival estimates, patients who had previous or concomitant muscle-invasive bladder tumors were excluded. BMI was categorized into approximate quartiles with the lowest quartile assigned to the reference group. Kaplan-Meier and multivariate Cox regression analyses were performed to assess the influence of BMI on survival. The lower quartile BMI group showed significantly increased overall mortality (OM) and cancer specific mortality (CSM) compared to the 25%-50% quartiles and upper quartile BMI groups. Kaplan-Meier estimates showed similar results. Based on multivariate Cox regression analysis, preoperative BMI as a continuous variable was an independent predictor for OM and CSM. In conclusion, preoperative underweight patients with UTUC in Korea survive less after RNU. Preoperative BMI may provide additional prognostic information to establish risk factors.

Delayed Ureterectomy after Incomplete Nephroureterectomy for Upper Tract Urothelial Carcinoma: Pathologic Findings and Outcomes

Objectives To evaluate the pathologic findings and outcomes after distal ureterectomy for a retained ureteral segment following incomplete nephroureterectomy for urothelial carcinoma of the renal pelvis or ureter. Materials and Methods After IRB approval, an institutional database identified patients who underwent distal ureterectomy for a retained ureteral segment after assumed complete nephroureterectomy for urothelial carcinoma of the upper ureter or renal pelvis. Clinical and pathologic variables were analyzed. Results From January 1993 to July 2007, 12 patients were identified with median age at the time of ureterectomy of 60.5 years (41-85 years). Initial approach to surgery was open in 9 patients and laparoscopic in 3 patients. The median time from nephroureterectomy to distal ureterectomy was 23.5 months (range 2-66). At the time of initial surgery, pathologic stage was Ta, T1, T2, and T3 in 3,4,1, and 4 patients respectively. Initial pathology was urothelial carcinoma; grade 2 in 6 patients and grade 3 in six patients. Pathology from the subsequent surgery demonstrated urothelial carcinoma in the retained ureteral segment in 8 patients, dysplasia or atypia in 3 patients, and 1 patient with chronic inflammation. Local recurrence in 2 patients was present in a segment of ureter discontinuous with the bladder after laparoscopic nephroureterectomy. Three patients (25%), all with initial grade 3 renal pelvis lesions, developed metastatic disease. Conclusions Tumor recurrence in a retained ureteral segment after incomplete nephroureterectomy is a significant problem and may contribute to intravesical recurrence or metastatic disease. Complete, en bloc resection is imperative to minimize these risks. .

Radical nephroureterectomy for pathologic T4 upper tract urothelial cancer: can oncologic outcomes be improved with multimodality therapy?

Purpose To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU) and regional lymph node dissection (LND) on oncologic outcomes. Materials and Methods Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU. Results The study included 69 patients, 42 males (61%) with median age 73 (range 43-98). Median follow-up was 17 months (range: 6-88). Lymphovascular invasion was found in 47 (68%) and regional lymph node metastases were found in 31 (45%). Peri-operative chemotherapy was utilized in 29 (42%) patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08). In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01), and cancer specific mortality (HR: 0.5, P = 0.06). Conclusions Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC. .

Association between PSCA mRNA expression in bladder transitional cell carcinoma and rs2294008 polymorphism / 国际外科学杂志

Objective To evaluate the different expression level of prostate cell carcinoma antigen (PSCA)mRNA in bladder transitional cell carcinoma(BTCC) and normal bladder tissue,additionally analyse the relationship between PSCA mRNA expression level in BTCC and different rs2294008 (C ＞ T) genotypes and various clinicopathological features,including stage and grade.Methods Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was performed on 80 BTCC samples and 38 samples of normal bladder mucosal to measure the expression of PSCA mRNA.Genomic DNA were extracted from tumour tissue to sequence to determine the rs2294008 (C ＞ T) genotypes.Results PSCA mRNA expression was detected in all samples (100％).Tumor samples had significantly higher PSCA expression (M =0.22) than normal samples (M =0.12) (P =0.038).PSCA mRNA expression level was positively correlated with advanced histological grade (G1-2 vs.G3,P =0.001).However no significant difference was detected between patients with superficial tumors (Ta or T1) and those with (≥ pT2)muscle-invasive tumors (P =0.250).There was significantly higher PSCA mRNA expression in T allele carriers than CC homozygous (P =0.001).Conclusions PSCA mRNA expression is related to the BTCC and tumor histological grade,however it is unrelated to tumor stages.PSCA mRNA expression level is higher in patients with T allele carriers than CC homozygous,suggesting T allele may increase PSCA mRNA' s expression.

Immune expression of E-cadherin and α, β and γ-Catenin adhesion molecules and prognosis for upper urinary tract urothelial carcinomas

INTRODUCTION: Cell adhesion molecules (CAM) are required for maintaining a normal epithelial phenotype, and abnormalities in CAM expression have been related to cancer progression, including bladder urothelial carcinomas. There is only one study that correlates E-cadherin and α-, β- and γ-catenin expression with prognosis of upper tract urothelial carcinomas. Our aim is to study the pattern of immune expression of these CAMs in urothelial carcinomas from the renal pelvis and ureter in patients who have been treated surgically. Our goal is to correlate these expression levels and characteristics with well-known prognostic parameters for disease-free survival. MATERIALS AND METHODS: We evaluated specimens from 20 patients with urothelial carcinomas of the renal pelvis and ureter who were treated with nephroureterectomy or ureterectomy between June 1997 and January 2007. CAM expression was evaluated by immunohistochemistry in a tissue microarray and correlated with histopathological characteristics and patient outcomes after a mean follow-up of 55 months. RESULTS: We observed a relationship between E-cadherin expression and disease recurrence. Disease recurrence occurred in 87.5% of patients with strong E-cadherin expression. Only 50.0% of patients with moderate expression and 0% of patients with weak or no expression of E-cadherin had disease recurrence (p = 0.014). There was also a difference in disease-free survival. Patients with strong E-cadherin expression had a mean disease-free survival rate of 49.1 months, compared to 83.9 months for patients with moderate expression (p = 0.011). Additionally, an absence of α-catenin expression was associated with tumors that were larger than 3 cm (p = 0.003). CONCLUSIONS: We demonstrated for the first time that immune expression of E-cadherin is related to tumor recurrence and disease-free survival rates, and the absence of α-catenin expression is related to tumor size in upper tract urothelial carcinomas.

Clinicopathological characteristics of non-muscle-invasive bladder cancer patients association with chronic kidney disease / 中华泌尿外科杂志

Objective To explore the clinicopathological characteristics of non-muscle-invasive bladder cancer patients association with chronic kidney disease (CKD).Methods Between Jan 2009 and Dec 2010,536 patients (390 males and 146 females with mean age of 63 years) underwent surgical treatment at our institute for pathologically proven non-muscle-invasive bladder cancer.The clinical and pathological data of these patients were reviewed,and the relationships of these factors and CKD were analyzed.Presence of CKD was confirmed in patients with estimated glomerular filtration rate (eGFR)＜ 60ml/(min · 1.73 m2)calculated using the Modification of Diet in Renal Disease Study equation.Results Of the 536 consecutive cases,57 patients (10.6％) had CKD.Compared to the patients without CKD,there were more females and older patients in the patients with CKD (52.6％ vs 24.2％ and 69 years vs 62 years,both P ＜ 0.05).The patients with CKD proned to have multiple bladder tumor (71.9％ vs 50.9％,P ＜ 0.05) and synchronous upper urinary tract urothelial carcinoma (7.0％ vs 2.3％,P ＜0.05).The history of bladder cancer and upper urinary tract urothelial carcinoma were also predominated in these patients (43.9％ vs 29.0％ and 40.4％ vs 6.5％,both P ＜ 0.05).ConclusionConcurrent CKD in non-muscle-invasive bladder cancer patients is associated with greater risk of multiple tumors in urinary tract,particularly in female patients.

The safety of simultaneous transurethral green laser vaporization therapy in benign prostatic hyperplasia and nonmuscle-invasive bladder transitional cell carcinoma / 中国医师进修杂志

Objective To evaluate the safety of simultaneous transurethral green laser vaporization therapy in benign prostatic hyperplasia (BPH) and nonmuscle-invasive bladder transitional cell carcinoma (NMIBT).Methods The clinical data of 27 patients (observation group) who had undergone simultaneous transurethral green laser vaporization therapy in BPH and NMIBT between May 2004 and October 2010 were analyzed retrospectively.Meanwhile 27 patients(control group) only had undergone green laser vaporization therapy in NMIBT during the same period were selected.Clinicopathologic parameters,rate of recurrence and progression,rate of recurrence in the bladder neck and prostatic urethra were determined and compared.Results The time of follow-up in observation group and control group were (28.61 ± 19.53) and (30.20 ± 21.46) months.The rates of recurrence,progression and recurrence in the bladder neck and prostatic urethra between observation group and control group had no significant differences [ 18.5％ (5/27) vs.25.9％ (7/27),3.7％ (1/27) vs.0,0 vs.0] (P ＞0.05).Conclusion Simultaneous transurethral green laser vaporization of NMIBT and BPH can be safely performed without increasing the risk of tumor recurrence in the prostatic urethra.