Carcinoma Of Upper Urinary Tract Research Articles

Preliminary Results of a Novel Extraperitoneal LESS Nephroureterectomy for Urothelial Carcinoma of Upper Urinary Tract

Preliminary Results of a Novel Extraperitoneal LESS Nephroureterectomy for Urothelial Carcinoma of Upper Urinary Tract

HAS3 underexpression as an indicator of poor prognosis in patients with urothelial carcinoma of the upper urinary tract and urinary bladder.

Via data mining a published transcriptomic database of UBUC (GSE31684), we discovered hyaluronan synthase-3 (HAS3) as the most significant gene stepwise downregulated from early tumorigenesis to progression among those associated with hyaluronan synthase activity (GO:0050501). We consequently analyzed HAS3 protein expression and their association with clinicopathological factors and survival in our well-characterized cohort of urothelial carcinoma of upper urinary tract (UTUC) and urinary bladder (UBUC). HAS3 expression was assessed by immunohistochemistry and evaluated by using H score method in 295 UBUCs and 340 UTUCs, respectively. HAS3 protein expression statuses were further correlated with clinicopathological parameters and evaluated the prognostic significance for disease-specific survival (DSS) and metastasis-free survival (MeFS). HAS3 protein underexpression was significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular invasion, and frequent mitoses in both groups of UCs. HAS3 underexpression not only predicted poorer DSS and MeFS with univariate analysis, but also indicated dismal DSS and MeFS in multivariate analysis. HAS3 underexpression is associated with advanced tumor stage and adverse pathological features, as well as implies inferior clinical outcomes for both groups of patients with UTUCs and UBUCs, suggesting its critical role in tumor progression in UCs and may serve as a prospective prognostic biomarker and a novel therapeutic target in UCs.

Laparoscopic Distal Ureterectomy with Ureteroneocystostomy and Psoas Hitch

Abstract Introduction: In upper urinary tract carcinoma (UUTC), kidney-sparing surgery could represent a valid alternative1,2 to radical nephroureterectomy, even if long-term results remain a matte...

Expression of MLH1 and MSH2 in urothelial carcinoma of the renal pelvis.

In this study, we investigated microsatellite instability in urothelial carcinoma of the renal pelvis by lack of immunohistochemical staining for MLH1 and MSH2. The study included 44 cases of urothelial carcinoma of the renal pelvis obtained from radical nephroureterectomy specimens at our institution. We evaluated the loss of nuclear immunohistochemical staining of MLH1 and MSH2. Eight of 44 (18 %) patients had negative MLH1 expression and 25/44 (57 %) patients had negative MSH2 expression. Six of 8 (75 %) patients with negative MLH1 expression were male and 2/8 (25 %) patients were female. Nineteen of 25 (75 %) patients with negative MSH2 expression were male, and 6/25 (24 %) patients were female. Seven of 8 (88 %) cases with negative MLH1 expression were high-grade urothelial carcinoma, and 21/25 (84 %) cases with negative MSH2 expression were high-grade urothelial carcinoma. Twenty-one of 44 (48 %) cases had an inverted growth pattern, of which 3/21 (14 %) cases had negative MLH1 expression and 14/21 (67 %) cases had negative MSH2 expression. Our study showed that microsatellite instability based on negative expression of MLH1 and MSH2 was more common in male patients with high-grade urothelial carcinoma. There is a strong correlation between inverted growth pattern and negative MSH2 expression. Microsatellite instability testing should be performed in patients with upper urinary tract carcinoma and may have prognostic value.

1008 Long-term follow-up outcomes of conservative treatment of upper urinary tract carcinoma

1008 Long-term follow-up outcomes of conservative treatment of upper urinary tract carcinoma

Clinicopathological and prognostic significance of EZH2 expression in upper urinary tract carcinoma

Evidence suggests that overexpression of enhancer of zeste homologue 2 (EZH2) is associated with aggressive behavior in various cancers. However, the clinical, pathological, and prognostic associations of EZH2 expression in the upper urinary tract carcinoma have not been reported. This study aimed to investigate the significance of EZH2 expression in the upper urinary tract carcinoma by immunohistochemical analysis using a tissue microarray. High EZH2 expression was observed in 94 of 171 (55 %) cases and was significantly associated with several adverse prognostic factors, including sessile architecture, high histological grade, presence of lymphovascular invasion, concomitant carcinoma in situ, higher tumor stage, and higher Ki-67 expression (all P < 0.01). EZH2 expression status in primary and metastatic lesions was concordant in all 13 cases examined. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional hazards regression models. High EZH2 expression was significantly associated with a shorter metastasis-free survival (log-rank P = 0.005; multivariate hazard ratio, 1.85; 95 % confidence interval, 0.93-3.71) and cancer-specific survival (log-rank P = 0.006; multivariate hazard ratio, 3.08; 95 % confidence interval, 1.30-7.32) after nephroureterectomy. Our results suggest that EZH2 may serve as a novel prognostic biomarker and a potential therapeutic target in upper urinary tract carcinoma.

Impact pronostique de l’envahissement du parenchyme rénal dans la population des tumeurs de la voie excrétrice urinaire supérieure de stade pT3

Upper tract urinary carcinoma (UTUC) pT3 tumors are a heterogeneous entity including tumors invading the renal parenchyma, tumors with peripelvic fat invasion or peri-ureteral fat invasion. The aim of this study was to evaluate the prognostic significance of these three different groups of pT3 tumors. Between 1998 and 2012, 205 patients with UTUC were operated in two centers, including 52 patients with pT3 tumor stage. pT3 tumors were divided into three groups: peri-ureteral fat invasion (pT3U, n = 16), peripelvic fat invasion (pT3G, n = 21), and renal parenchyma invasion (pT3P, n = 15). The prognostic significance of the type of tumor infiltration was evaluated on specific and disease-free survival. Median follow-up was 18.9 months [6-133.4]. In univariate analysis, renal parenchyma invasion was associated with a better prognostic in both specific (P = 0.026) and disease-free survival (P = 0.031) compared with peripelvic or peri-ureteral fat invasion. Mutivariate analysis retained the pT3 subgroup as an independant prognostic factor in both specific and disease-free survival (P = 0.02). pT3 tumors with renal parenchyma invasion had a better prognosis than those with peripelvic or peri-ureteral fat invasion. The heterogeneity of the pT3 group should be taken into account to improve the care of patients.

Predictors of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma: an inflammation-based prognostic score.

PurposeSystemic inflammatory responses, which are defined in terms of the Glasgow prognostic score (GPS), have been reported to be independent predictors of unfavorable outcomes in various human cancers. We assessed the utility of the GPS as a predictor of intravesical recurrence after radical nephroureterectomy (RNU) in upper urinary tract carcinoma (UTUC).Materials and MethodsWe collected data for 147 UTUC patients with no previous history of bladder cancer who underwent RNU from 2004 to 2012. Associations between perioperative clinicopathological variables and intravesical recurrence were analyzed by using univariate and multivariate Cox regression models.ResultsOverall, 71 of 147 patients (48%) developed intravesical recurrence, including 21 patients (30%) diagnosed with synchronous bladder tumor. In the univariate analysis, performance status, diabetes mellitus (DM), serum albumin, C-reactive protein, GPS, and synchronous bladder tumor were associated with intravesical recurrence. In the multivariate analysis, performance status (hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.41-3.85; p=0.001), DM (HR, 2.04; 95% CI, 1.21-3.41; p=0.007), cortical thinning (HR, 2.01; 95% CI, 1.08-3.71; p=0.026), and GPS (score of 1: HR, 6.86; 95% CI, 3.69-12.7; p=0.001; score of 2: HR, 5.96; 95% CI, 3.10-11.4; p=0.001) were independent predictors of intravesical recurrence.ConclusionsOur results suggest that the GPS as well as performance status, DM, and cortical thinning are associated with intravesical recurrence after RNU. Thus, more careful follow-up, coupled with postoperative intravesical therapy to avoid bladder recurrence, should be considered in these patients.

S105 Epidemiological charactheristics of urothelial carcinoma of upper urinary tract in the kolubara district in the period 1983–2012.year

S105 Epidemiological charactheristics of urothelial carcinoma of upper urinary tract in the kolubara district in the period 1983–2012.year

Volumetric In Vivo Visualization of Upper Urinary Tract Tumors Using Optical Coherence Tomography: A Pilot Study

Knowledge of tumor stage and grade is paramount for treatment decision making in cases of upper urinary tract urothelial carcinoma but this condition cannot be accurately assessed by current techniques. Optical coherence tomography can hypothetically provide the urologist with real-time intraoperative information on tumor grade and stage. In this pilot study we report what are to our knowledge the first results of optical coherence tomography for grading and staging upper urinary tract urothelial carcinoma. Eight consecutive patients underwent ureterorenoscopy for suspicion or followup of upper urinary tract urothelial carcinoma. Optical coherence tomography data sets were intraoperatively obtained from the ureter and renal pelvis. All patients eventually underwent nephroureterectomy. Optical coherence tomography staging was done by visual inspection of lesions found on optical coherence tomography images. Optical coherence tomography grading was done by quantifying optical coherence tomography signal attenuation in mm(-1) on lesions and comparing results with the histopathological diagnosis. The Wilcoxon rank sum test was used for statistical analysis. For 7 in vivo optical coherence tomography diagnoses staging was in accordance with histology. In patient 8 tumor thickness transcended optical coherence tomography imaging depth range and, therefore, invasiveness findings were inconclusive. For grading the median attenuation coefficient for grade 2 and 3 lesions was 1.97 (IQR 1.57-2.30) and 3.53 mm(-1) (IQR 2.74-3.94), respectively (p<0.001). Healthy urothelium was too thin to reliably determine the attenuation coefficient. Optical coherence tomography is a promising, minimally invasive tool for real-time intraoperative optical diagnosis of tumors in the upper urinary tract. Our results warrant future research in a larger sample size to determine the accuracy of grading and staging by optical coherence tomography, and its possible implementation in the diagnostic algorithm for upper urinary tract urothelial carcinoma.

Human formalin-fixed paraffin-embedded tissues: an untapped specimen for biomonitoring of carcinogen DNA adducts by mass spectrometry.

DNA adducts represent internal dosimeters to measure exposure to environmental and endogenous genotoxicants. Unfortunately, in molecular epidemiologic studies, measurements of DNA adducts often are precluded by the unavailability of fresh tissue. In contrast, formalin-fixed paraffin embedded (FFPE) tissues frequently are accessible for biomarker discovery. We report here that DNA adducts of aristolochic acids (AAs) can be measured in FFPE tissues at a level of sensitivity comparable to freshly frozen tissue. AAs are nephrotoxic and carcinogenic compounds found in Aristolochia herbaceous plants, many of which have been used worldwide for medicinal purposes. AAs are implicated in the etiology of aristolochic acid nephropathy and upper urinary tract carcinoma. 8-Methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxole-5-carboxylic acid (AA-I) is a component of Aristolochia herbs and a potent human urothelial carcinogen. AA-I reacts with DNA to form the aristolactam (AL-I)-DNA adduct 7-(deoxyadenosin-N(6)-yl) aristolactam I (dA-AL-I). We established a method to quantitatively retrieve dA-AL-I from FFPE tissue. Adducts were measured, using ultraperformance liquid chromatography/mass spectrometry, in liver and kidney tissues of mice exposed to AA-I, at doses ranging from 0.001 to 1 mg/kg body weight. dA-AL-I was then measured in 10-μm thick tissue-sections of FFPE kidney from patients with upper urinary tract cancers; the values were comparable to those observed in fresh frozen samples. The limit of quantification of dA-AL-I was 3 adducts per 10(9) DNA bases per 2.5 μg of DNA. The ability to retrospectively analyze FFPE tissues for DNA adducts may provide clues to the origin of human cancers for which an environmental cause is suspected.

898 PREOPERATIVE ANEMIA IS A POWERFUL PREDICTOR FOR POOR OUTCOMES IN UPPER TRACT UROTHELIAL CARCINOMA TREATED WITH RADICAL NEPHROURETERECTOMY

You have accessJournal of UrologyUrothelial Cancer: Upper Tract Tumors (II)1 Apr 2013898 PREOPERATIVE ANEMIA IS A POWERFUL PREDICTOR FOR POOR OUTCOMES IN UPPER TRACT UROTHELIAL CARCINOMA TREATED WITH RADICAL NEPHROURETERECTOMY Michael Rink, Hans-Martin Fritsche, Nasim Sharifi, Atiqullah Aziz, Bikheet Al-Matar, Jens Hansen, Luis A. Kluth, Wolfgang Otto, Florian Miller, Roland Dahlem, Arnulf Stenzl, Margit Fisch, and Georgios Gakis Michael RinkMichael Rink Hamburg, Germany More articles by this author , Hans-Martin FritscheHans-Martin Fritsche Regensburg, Germany More articles by this author , Nasim SharifiNasim Sharifi Hamburg, Germany More articles by this author , Atiqullah AzizAtiqullah Aziz Regensburg, Germany More articles by this author , Bikheet Al-MatarBikheet Al-Matar Tübingen, Germany More articles by this author , Jens HansenJens Hansen Hamburg, Germany More articles by this author , Luis A. KluthLuis A. Kluth Hamburg, Germany More articles by this author , Wolfgang OttoWolfgang Otto Regensburg, Germany More articles by this author , Florian MillerFlorian Miller Tübingen, Germany More articles by this author , Roland DahlemRoland Dahlem Hamburg, Germany More articles by this author , Arnulf StenzlArnulf Stenzl Tübingen, Germany More articles by this author , Margit FischMargit Fisch Hamburg, Germany More articles by this author , and Georgios GakisGeorgios Gakis Tübingen, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.471AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Preoperative anemia is a predictor for unfavorable outcomes in different urological malignancies including prostate, renal cell and bladder cancer. The impact of preoperative anemia in upper urinary tract carcinoma (UTUC) treated with radical nephroureterectomy (RNU) remains unclear. METHODS We collected data of 314 UTUC patients treated with RNU from 1990 û 2011 without neoadjuvant chemotherapy at three German academic institutions. Anemia was defined as a preoperative hemoglobin (Hb) level of ≤12g/dL according to the WHO classification. A sensitivity analysis was performed adjusting for gender variances (anemia definitions: male≤13g/dL, female≤12g/dL) according to more recent classifications (Beutler et al, Blood 2006). Uni- and multivariable Cox regression models analyzed the impact of anemia on disease recurrence and cancer-specific survival. RESULTS Eighty-eight (28%) UTUC patients had pre-RNU anemia according to WHO classification and 120 (38%) according to more recent classifications. Presence of pre-RNU anemia was associated with advanced tumor stage (p≤0.03), nodal metastasis (p≤0.04) and presence of LVI (p≤0.007) independent of the classification used. At a median follow-up of 31 months (IQR 14; 73) 103 (33%) and 79 (25%) patients experienced disease recurrence and died cancer-specific, respectively. Preoperative anemia was significantly associated with disease recurrence (p=0.01) and cancer-specific mortality (p≤0.017) on Kaplan-Meier analyses, respectively, with no difference in either anemia definition. In multivariable analyses that adjusted for pathologic stage and grade, nodal status, LVI, ureter margin status and adjuvant chemotherapy, preoperative anemia was an independent predictor for disease recurrence (WHO: HR 1.84, p=0.049; recent classifications: HR 2.36, p=0.003) and cancer-specific mortality when using recent classifications (HR 1.91, p=0.04). CONCLUSIONS Preoperative anemia in UTUC is highly associated with features of aggressive tumor biology, and an independent predictor for disease recurrence and cancer-specific mortality. Hb-levels are frequently available and easy to achieve prior to RNU, thus representing a promising marker for follow-up scheduling and maybe adjuvant therapies. Our findings need to be confirmed in larger RNU cohorts. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e371 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Michael Rink Hamburg, Germany More articles by this author Hans-Martin Fritsche Regensburg, Germany More articles by this author Nasim Sharifi Hamburg, Germany More articles by this author Atiqullah Aziz Regensburg, Germany More articles by this author Bikheet Al-Matar Tübingen, Germany More articles by this author Jens Hansen Hamburg, Germany More articles by this author Luis A. Kluth Hamburg, Germany More articles by this author Wolfgang Otto Regensburg, Germany More articles by this author Florian Miller Tübingen, Germany More articles by this author Roland Dahlem Hamburg, Germany More articles by this author Arnulf Stenzl Tübingen, Germany More articles by this author Margit Fisch Hamburg, Germany More articles by this author Georgios Gakis Tübingen, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Impact pronostique de la localisation urétérale dans les tumeurs de la voie excrétrice supérieure

The aim of this study was to evaluate the prognostic significance of the ureteral location of the upper tract urinary carcinoma (UTUC). Between January 1998 and December 2007, 161 patients with UTUC were operated in our center. Tumors were located on renal pelvis in 51% of cases, on the ureter in 34% of cases and in both locations in 15% of cases. Nephroureterectomy was performed in 79.5% of cases (128/161) whereas a conservative treatment was performed in 20.5% of cases (33/161). In our series, 29.8% of patients had primary bladder cancer and 14.3% had synchronous bladder tumor. At a median follow-up of 42.5 months, 38.6% of patients developed bladder recurrence and 4.8% developed controlateral upper tract tumor. In multivariate analysis, ureteral location and existence of synchronous bladder tumor were independent prognostic factors of bladder recurrence (P=0.009 and P=0.025, respectively). Multivariate analysis retained T-stage and ureteral location as independent prognostic factors in both overall and disease-free survival (P=0.002 and P=0.0008 respectively for ureteral location). Ureteral location was an independent prognostic factor of bladder recurrence and was associated with a poorer prognosis.

Aristolochic acid nephropathy: Harbinger of a global iatrogenic disease

This review constitutes an overview of our investigations of aristolochic acid nephropathy, a chronic kidney disease associated with carcinomas of the upper urinary tract. Our studies began by confirming the hypothesis that chronic dietary poisoning by aristolochic acid was responsible for endemic (Balkan) nephropathy. A unique TP53 mutational signature in urothelial tumors and the presence of aristolactam-DNA adducts in the renal cortex, defined in the course of this research, proved to be robust biomarkers of exposure to this potent nephrotoxin and human carcinogen. Armed with this information, we used molecular epidemiologic approaches and novel mechanistic information to establish the causative role of aristolochic acid in upper urinary tract carcinoma in Taiwan, where one-third of the population had been prescribed herbal remedies containing Aristolochia, and the recorded incidence of upper urinary tract cancers is the highest in the world. As traditional Chinese medicine is practiced similarly in Taiwan and China, it is likely that upper urinary tract carcinomas and their attendant aristolochic acid nephropathy are prevalent in China and other Asian countries where Aristolochia herbs have been used for centuries in the treatment and prevention of disease, creating a potential public health problem of considerable magnitude.

Abstract 20: Whole exome sequencing of aristolochic acid induced upper urothelial carcinomas.

Abstract Aristolochic acid (AA), a human carcinogen and nephrotoxin, produced by Aristolochia plants and used extensively in traditional herbal medicines, was shown to be responsible for the clinical syndromes known as Chinese herb nephropathy and endemic (Balkan) nephropathy (EN), and to contribute to the high rate of upper urinary tract carcinoma (UUC) observed in certain Asian countries such as Taiwan. After bio-activation, AA gives rise to long-lived, pro-mutagenic aristolactam-DNA (AL-DNA) adducts that serve as specific biomarkers of exposure. Our studies of the TP53 gene in AA-induced UUC tumors detected a mutation spectrum that was dominated by A&amp;gt;T transversions located almost exclusively on the non-transcribed DNA strand, reflecting a failure to excise AL-DNA adducts by global genomic nucleotide excision repair. In the present study we undertook the whole exome sequencing of a set of AAN/UUC tumors from Taiwanese patients, and matching normal DNAs, to establish the genome wide consequence of AA-exposure. To establish that AA was critical in tumor formation we selected patients who had: 1) detectable AL-DNA adducts in kidney cortex DNA, and 2) the TP53 gene in tumor DNA contained an A&amp;gt;T mutation on the non-transcribed strand. The results indicate that these tumors indeed harbor a very high number of single base substitutions (SBS) in their coding exons (median of 545 SBS per tumor). Of these, 70% were A&amp;gt;T mutations with the majority of the mutated adenines on the non-transcribed strand. We are currently completing whole exome sequencing of an additional set of AA-induced UUC tumors, and ten smoking-induced UUC tumors for comparison. We will present an analysis of the driver mutations found in these tumors and the pathways harboring oncogenic mutations. Our goal is to define a panel of AA-specific mutations useful for developing biomarker screens for early detection of UUC in at risk populations. Citation Format: Thomas A. Rosenquist, Margaret Hoang, Maasaki Moriya, Victoriya S. Sidorenko, Kathleen Dickman, Chung-Hsin Chen, Lin Wu, Nickolas Papadopoulos, Yeong-Shiau Pu, Kenneth W. Kinzler, Bert Vogelstein, Arthur P. Grollman. Whole exome sequencing of aristolochic acid induced upper urothelial carcinomas. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 20.

Significance of ADC value for detection and characterization of urothelial carcinoma of upper urinary tract using diffusion-weighted MRI

To evaluate utility of diffusion-weighted magnetic resonance imaging (DWI) to detect and predict the histological characteristics of upper urinary tract urothelial carcinomas (UTUCs). We retrospectively evaluated 20 suspicious lesions from 19 patients. MRI study included conventional sequences and DWI with apparent diffusion coefficient (ADC) maps calculated between b=0 and b=1,000. ADC values were measured within two different regions of interest (ROI): a small identical ROI placed in the most restrictive part of the tumour and a larger ROI covering two-thirds of the mass surface. The mean ADC values of the tumours were compared with that of normal renal parenchyma using an unpaired Student's t test. Association between ADC values and histological features was tested using non-parametric tests. Overall, 18 tumours were confirmed histologically as UTUCs. DWI failed to detect two cases of UTUCs (one CIS and one small tumour of 5mm). There was no statistically significant difference in ADC values measured with the small or large ROI (p=0.134). The mean ADC value of UTUC was significantly lower than that of the normal renal parenchyma (p<0.001). No statistical association was found between ADC values and pathological features (location, p=0.35; grade, p=0.98; muscle-invasive disease, p=0.76 and locally advanced stage, p=0.57). DWI may be interesting tool for detecting UTUCs regarding the difference of ADC values between the tumours and surrounding healthy tissues. In regard to low frequency of UTUCs, the association of ADC values and histological characteristics need further investigations in a large prospective multi-institutional study.

Evidence of exposure to aristolochic acid in patients with urothelial cancer from a Balkan endemic nephropathy region of Romania

Recently, chronic Aristolochia poisoning was found responsible for the aetiology of Balkan endemic nephropathy (BEN) in Croatia, Serbia, and Bosnia, and diet was the likely route of exposure to aristolochic acid (AA). BEN, often associated with an increased incidence of upper urinary tract carcinoma (UUC), also affects residents of certain rural villages in Romania. AA is a nephrotoxin and human carcinogen that forms DNA adducts after metabolic activation, which induce characteristic TP53 mutations in urothelial tumours. Here we present the first evidence linking AA exposure to UUC in residents of an endemic region in the Romanian Mehedinti County. DNA was extracted from kidney and tumour tissue of seven patients who underwent nephroureterectomy for UUC and resided in BEN villages (endemic group). Five patients with UUC from nonendemic villages served as controls. AA-DNA adducts (7-(deoxyadenosin-N(6) -yl)-aristolactam I), established biomarkers of AA exposure, were identified by (32)P-postlabelling in renal DNA of six patients from the endemic group and in one of the nonendemic group (adduct levels ranged from 0.3 to 6.5 adducts per 10(8) nucleotides). Additionally, an A to T transversion in TP53, a base substitution characteristic of AA mutagenic activity was found in urothelial tumour DNA of one patient from the endemic group. Our results provide a molecular link to the cause of urothelial tumours in BEN regions of Romania indicating that AA is the common aetiological agent for BEN across its numerous geographical foci.

High-Grade Carcinomas Involving the Renal Sinus: Report of a Case and Review of the Differential Diagnosis and Immunohistochemical Expression

We report the case of a high-grade carcinoma involving the kidney in a young male with renal vein thrombosis and review the differential diagnosis and immunohistochemical workup. High-grade neoplasms involving the renal sinus include collecting duct carcinomas (CDCs), renal medullary carcinomas (RMCs), invasive high-grade urothelial carcinoma (UC) of the upper urinary tract, clear cell renal cell carcinoma, and type 2 papillary renal cell carcinoma. Distinguishing UC from CDC and RMC is problematic in small biopsy samples. The diagnosis of CDC (a rare, aggressive subtype of renal cell carcinoma) is challenging and requires the exclusion of UC. Renal medullary carcinoma is characterized by an appropriate clinical setting and consistent loss of nuclear expression of integrase interactor 1 (INI-1). A panel consisting of p63, paired box gene 8 (PAX8), and INI-1 is most optimal in distinguishing UC from CDC and RMC. A subset of urothelial carcinoma of upper urinary tract may be positive with PAX8.

Rôle pronostique des emboles vasculaires tumoraux dans les tumeurs des voies excrétrices urinaires supérieures : analyse rétrospective monocentrique

To analyze the prognostic impact of lymphovascular invasion (LVI) in case of urothelial carcinoma of upper urinary tract (UUT-UC).Retrospective study of 83 consecutive patients treated surgically for UUT-UC between January 1998 and October 2008. Prognostic interest of histopathological factors (stage, grade, LVI, CIS, tumor architecture, location, nodal status and surgical margins) was assessed in univariate and multivariate Cox regression model. Specific survival (SS), recurrence-free survival (RFS) and metastasis-free survival (MFS) were calculated using Kaplan-Meier method and Log-Rank test.LVI was observed in 26.5% of patients after histopathologic reviewing. The SS, RFS and MFS at 2 years were 93%, 76% and 96% respectively in group without LVI compared to 40%, 13% and 38% in group with LVI (P<0.001). In univariate analysis, pathological stage, LVI and margin status were predictive of SS (P<0.05). Pathological stage, LVI and surgical margin status were predictive of RFS (P<0.05). LVI, tumor architecture and status of surgical margins were predictive of MFS (P<0.05). LVI was the only independent predictive factor in multivariate analysis for all survival (P=0.002, 0.002 and 0.001 respectively for the SS, RFS and MFS).LVI was a poor prognostic factor in cases of UUT-UC. This criteria should be routinely sought and included in the pathology report.

Early Detection of Carcinoma In Situ of the Bladder: A Comparative Study of White Light Cystoscopy, Narrow Band Imaging, 5-ALA Fluorescence Cystoscopy and 3-Dimensional Optical Coherence Tomography

We compared the efficacy and potential limitations of white light cystoscopy, narrow band imaging, 5-ALA fluorescence cystoscopy and 3-dimensional optical coherence tomography for early diagnosis of bladder carcinoma in situ. By expressing simian virus 40T antigen in the urothelium carcinoma in situ typically develops in SV40T transgenic mice in about 8 to 20 weeks and then frank high grade papillary urothelial carcinoma starts to emerge. A total of 18 control and 29 SV40T mice were examined during weeks 8 to 22 by white light cystoscopy, fluorescence cystoscopy, narrow band imaging and 3-dimensional optical coherence tomography. Results were validated by histology. Newly improved algorithms for computer aided detection were applied to acquired 3-dimensional optical coherence tomography images to enhance the quantitative diagnosis of carcinoma in situ in near real time. Of 29 carcinoma in situ samples 27 were detected by 3-dimensional optical coherence tomography, 1 by white light cystoscopy, 26 by narrow band imaging and 13 by fluorescence cystoscopy. Of the 18 histologically confirmed benign cases 17 were detected by 3-dimensional optical coherence tomography, 14 by white light cystoscopy, 5 by narrow band imaging and 18 by fluorescence cystoscopy. The diagnostic sensitivity of white light cystoscopy (3.4%) and fluorescence cystoscopy (44.8%), and the specificity of narrow band imaging (27.8%) were significantly enhanced by 3-dimensional optical coherence tomography to 93.1% and 94.4%, respectively (p <0.01). Three-dimensional optical coherence tomography with quantitative computer aided detection can significantly enhance the sensitivity of white light cystoscopy and fluorescence cystoscopy, and the specificity of narrow band imaging for early diagnosis of carcinoma in situ. This suggests the potential of narrow band imaging guided 3-dimensional optical coherence tomography for future clinical detection of carcinoma in situ when effective image guidance is desirable.