Cancer Of Upper Urinary Tract Research Articles

MP2-04 PROGNOSTIC VALUE OF SERUM CYFRA 21-1 IN PATIENTS WITH G3 OR MUSCLE INVASIVE UPPER URINARY TRACT CANCER

You have accessJournal of UrologyBladder Cancer: Upper Tract TCC I1 Apr 2015MP2-04 PROGNOSTIC VALUE OF SERUM CYFRA 21-1 IN PATIENTS WITH G3 OR MUSCLE INVASIVE UPPER URINARY TRACT CANCER Akihiro Yano, Hironori Sugiyama, Eiken Cho, Hideki Takeshita, Yohei Okada, Hideki Nagamatsu, Makoto Morozumi, Satoru Kawakami, and Takumi Yamada Akihiro YanoAkihiro Yano More articles by this author , Hironori SugiyamaHironori Sugiyama More articles by this author , Eiken ChoEiken Cho More articles by this author , Hideki TakeshitaHideki Takeshita More articles by this author , Yohei OkadaYohei Okada More articles by this author , Hideki NagamatsuHideki Nagamatsu More articles by this author , Makoto MorozumiMakoto Morozumi More articles by this author , Satoru KawakamiSatoru Kawakami More articles by this author , and Takumi YamadaTakumi Yamada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.127AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES No serum prognosticator has been established in patients with potentially lethal upper urinary tract cancer (UUTC). The aim of this study is to evaluate the prognostic value of serum CYFRA 21-1 (CYFRA) in these patients. METHODS Serum levels of CYFRA and C-reactive protein (CRP) were measured in 30 patients with G3 or muscle invasive UUTC between Jan 2012 and Aug 2014. Cut-off values of CYFRA and CRP were determined by receiver operating characteristic analyses. Prognostic values of age, stage, CYFRA and CRP were evaluated using multivariate analysis with a Cox proportional hazards model. RESULTS The median (range) values of CYFRA, and CRP were 4.1 (1.4–177.3) ng/mL and 0.2 (0–5.2) mg/dL, respectively. The median (range) age and follow-up period was 75 (64–86) years and 7.7 (1.1–29.9) months. Prognostic values of age (< 75 vs. ≥ 75), stage (non-metastatic vs. metastatic), CYFRA (cut-off 3.9 ng/mL) and CRP (cut-off 1.5 mg/dL) were evaluated dichotomously. Multivariate analyses revealed that p-values for age, stage and CRP is 0.83, 0.17, 0.48, respectively, and only CYFRA (P = 0.037) is a significant and an independent prognosticator. In 21 patients with metastatic disease (CYFRA cut-off 5.8 ng/mL), those with elevated CYFRA had 20.9-fold higher risk of cancer-specific mortality than those with non-elevated CYFRA. CONCLUSIONS The current results indicate that serum CYFRA level can be a prognosticator for patients with potentially lethal UUTC. Further prospective analyses will be needed to confirm our results. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e11-e12 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Akihiro Yano More articles by this author Hironori Sugiyama More articles by this author Eiken Cho More articles by this author Hideki Takeshita More articles by this author Yohei Okada More articles by this author Hideki Nagamatsu More articles by this author Makoto Morozumi More articles by this author Satoru Kawakami More articles by this author Takumi Yamada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Substitution between Aristolochia and Bryonia genus in North-Eastern Morocco: Toxicological implications

Ethnopharmacological relevanceAlthough acknowledged as toxic herbs, Aristolochia species are still widely used worldwide. The aristolochic acids (AA) they contain can induce the so-called “aristolochic acid nephropathy”, leading to renal fibrosis and upper urinary tract cancer. Traditional Moroccan medicine still often uses Aristolochia species under the vernacular name of Bereztem for the treatment of numerous ailments, notably cancer, diabetes or digestive tract disorders. As the botanical identity and renal toxicity of used species remain unexplored, the safety of patients may be threatened. Material and methodsEthnopharmacological data were collected from herbalists from the provinces of Oujda and Berkane, located in North-Eastern Morocco. Samples of Bereztem were collected at herbalist shops and checked for their content in AA using TLC and LC-MS methods. The toxicity of crude methanolic extracts of each herb was assessed on a HK-2 cell-based in vitro model by measurement of the cell survival to evaluate cytotoxicity and by assessment of renal-specific toxicity via (i) the evaluation of genes (E-cadherin and α-smooth muscle actin) expression by RT-qPCR; (ii) the quantities of β-catenin and vimentin by immunofluorescence microscopy; (iii) the secretion of fibronectin; and (iv) the excretion of interleukin-6. ResultsThe survey indicated that, among 42 herbalists visited, 33 were retailers of Bereztem, which was generally sold as a cancer treatment. Botanical investigations revealed that Aristolochia longa was frequently substituted by Bryonia dioica, which was associated with a higher cytotoxicity. Parameters specific to renal toxicity were also found to be enhanced, as compared to Aristolochia baetica and A. longa: down-regulation of β-catenin and E-cadherin and up-regulation of vimentin and α-smooth muscle actin, and secretion of fibronectin and interleukin-6. ConclusionIn accordance with the Moroccan regulations, the use of so-called Aristolochia species should be discontinued. On one hand, the correctly identified aristolochia contain nephrotoxic aristolochic acids; on the other hand, aristolochia are massively substituted in North-Eastern Morocco and adulterated by a well-known toxic herb, B. dioica. Our data indicate that the bryony renal toxicity may be deleterious in shorter time periods than aristolochia. Reinforced on-site controls are needed to remind herbalists and harvesters that these herbs should be prohibited.

C133: A role of endourology in a treatment of urothelial cancer of upper urinary tract (UC-UUT)

C133: A role of endourology in a treatment of urothelial cancer of upper urinary tract (UC-UUT)

The ban on phenacetin is associated with changes in the incidence trends of upper‐urinary tract cancers in Australia

BackgroundPhenacetin is an analgesic that causes renal diseases and cancers of the upper‐urinary tract (UUT). It was banned in most countries from the late 1960s. This study aimed to evaluate, for the first time, the long‐term population impact of the phenacetin ban on UUT cancer rates. MethodsWe used cancer registry data from Australia, where phenacetin was widely used, to study age‐ and sex‐specific incidence trends of cancers of the renal pelvis and the ureter after the phenacetin ban (1979). Incidence rate ratios and average annual percentage change (AAPC) were calculated to quantify changes in rates over time. ResultsIncidence rates of renal pelvis cancer decreased by 52% in women and 39% in men between 1983–1987 and 2003–2007. The decline in women was stronger in states where the use of phenacetin was the most widespread, e.g. New South Wales (AAPC: −4.1%; 95% CI −5.3, −2.9) and Queensland (AAPC: −3.3%; 95% CI −4.9, −1.8), and after the mid‐1990s. Incidence rates of ureteral cancer remained stable for both sexes throughout the study period. ConclusionsOur findings strongly suggest a beneficial impact of the ban on phenacetin on the incidence of renal pelvis cancer in Australia, particularly among women.

Imaging of upper urinary tract cancer: using conventional MRI and diffusion-weighted MRI with different b values

Diffusion-weighted magnetic resonance imaging (DW-MRI) has been considered to be useful in diagnosing upper urinary tract (UUT) disease; however, the value of DW-MRI with different b values has not been reported. To evaluate the performance of using conventional MRI alone and in combination with DWI with different b values in diagnosing UUT cancer. Seventy patients with suspected UUT cancer underwent conventional MRI (T1-weighted and T2-weighted) and DW-MRI (b = 500 and 1500 s/mm(2)) on a 3 T-MRI scanner. The ureteroscopic and histopathologic findings were compared with the imaging findings. The utility of detecting UUT cancer using conventional MRI (set A), combined DW-MRI (b = 500 s/mm(2)) and conventional MRI (set B), and combined DW-MRI (b = 1500 s/mm(2)) and conventional MRI (set C) were independently evaluated by two readers. A total of 32 patients had verified cancer; 23 patients had benign UUT diseases, and 15 had no abnormality. Sets B and C had significantly improved diagnostic accuracy for UUT cancer compared with set A; the specificity in diagnosing UUT cancer was significantly improved when using set C compared with sets A and B. In patients without UUT obstructions, improved sensitivity and accuracy in diagnosis was achieved when using sets B and C compared with set A. Using DW-MRI in combination with conventional MRI provides increased diagnostic accuracy and sensitivity in patients without UUT obstruction. The combination of conventional MRI and DW-MRI with a higher b value (1500 s/mm(2)) improved the specificity in diagnosing UUT cancer compared to conventional sequences and DW-MRI with a lower b value (500 s/mm(2)).

Diffusion-weighted MRI as a potential imaging biomarker reflecting the metastatic potential of upper urinary tract cancer.

To evaluate the role of diffusion-weighted MRI (DW-MRI) as an imaging biomarker for upper urinary tract cancer (UUTC) that has already metastasized or will metastasize soon. 61 patients clinically diagnosed with UUTC were prospectively enrolled in this study. All the patients underwent MRI, including DW-MRI, prior to any interventions. Correlations between apparent diffusion coefficient (ADC) and other clinicopathological variables, including metastasis-free survival, were analysed. Median follow-up period was 938 days. Of the 61 patients, 12 had any metastases at the initial diagnosis. 11 patients developed metastases during the follow-up period. These 23 patients were categorized as "Metastatic". Of the remaining 38 patients, 35 with a follow-up period longer than 400 days were categorized as "Localized". ADC was significantly lower in the Metastatic category than in the Localized (p = 0.0002) category. Multivariate analysis of pre-operative variables identified ADC (cut-off value, 1.08 × 10(-3) mm(2) s(-1)) and clinical T stage based on T2 weighted MRI as an independent predictive factor of metastatic UUTC. 46 patients without any metastases during the initial diagnosis were stratified into a high-risk group (16 patients with low ADC and clinical T3-4) and a low-risk group (30 patients with high ADC or clinical Ta-2). The 3-year metastasis-free survivals were 45% and 93%, respectively. In the current study, UUTC with lower ADC value is more likely to have metastatic potential. Incorporating ADC with clinical T stage helps to differentiate metastatic UUTC at the initial diagnosis. DW-MRI is a potential imaging biomarker reflecting metastatic propensity of UUTC.

MP55-03 SARCOPENIA IS A PROGNOSTIC BIOMARKER OF ADVANCED UROTHELIAL CARCINOMA

You have accessJournal of UrologyBladder Cancer: Invasive II1 Apr 2014MP55-03 SARCOPENIA IS A PROGNOSTIC BIOMARKER OF ADVANCED UROTHELIAL CARCINOMA Hiroshi Fukushima, Minato Yokoyama, and Fumitaka Koga Hiroshi FukushimaHiroshi Fukushima More articles by this author , Minato YokoyamaMinato Yokoyama More articles by this author , and Fumitaka KogaFumitaka Koga More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1551AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Inoperable urothelial carcinoma (UC) patients due to metastatic and/or locoregionally advanced disease show poor prognosis despite recent improvements in multidisciplinary strategies. Pretreatment risk assessment based on prognosticators is required to offer such patients better therapeutic options including clinical trials. Sarcopenia, degenerative loss of skeletal muscle mass, is an objective indicator of cachexia. Few data exist on its prognostic value. Here, we investigated the role of sarcopenia as a prognostic biomarker in advanced UC patients. Methods This retrospective study consisted of 88 UC patients with cT4 or metastases to lymph nodes/distant organs, treated at our institution from 2004 to 2012. Variables included age, sex, performance status (PS), body mass index (BMI), hemoglobin, white blood cell count, creatinin, albumin, C-reactive protein (CRP), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), corrected calcium, presence of hydronephrosis, primary site, presence of lymph node or distant metastasis, prior curative surgery and any therapies for advanced disease. The L3 muscle index (cm2/m2) was calculated by normalizing skeletal muscle areas at the L3 vertebra level on CT images for height. Sarcopenia was defined as the L3 muscle index of 38.5 cm2/m2 for women and 52.4 cm2/m2 for men. We examined associations of sarcopenia with overall survival (OS) using Cox regression analysis. Results Of the 88 patients, 35 (40%) were assigned as sarcopenia. Sarcopenia was significantly associated with lower BMI (p < .0001), poorer PS (p = .002), advanced age (p = .01), lower albumin (p = .01), presence of distant metastasis (p = .02), higher ALP (p = .02) and higher CRP (p = .045). During the median follow-up of 13 m, 66 patients (75%) died. On multivariate analysis, sarcopenia was an independent predictor of shorter OS (HR 11.36, p < .0001), along with higher LDH (p = .001), higher ALP (p = .002), no therapies for advanced disease (p = .009), upper urinary tract cancer (p = .01), presence of lymph node metastasis (p = .02) and higher CRP (p = .04). Median OS was 10 and 33 m for patients with and without sarcopenia, respectively (p < .0001). Conclusions This is the first to show prognostic significance of sarcopenia in advanced UC. Sarcopenia, which is evaluated on routine CT scan, is a useful prognostic biomarker of advanced UC. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e556 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Hiroshi Fukushima More articles by this author Minato Yokoyama More articles by this author Fumitaka Koga More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

TERT Gene Promoter Mutations In Myelodysplastic Syndromes (MDS)

Mutations at the protein-coding region of TERT gene (chromosome 5p15.33) have been well characterized in patients affected by a constitutional telomere syndrome, including diskeratosis, aplastic anemia and pulmonary fibrosis (Calado RT, Hematology, ASH 2009:338). In rare cases somatic mutations may occur in de novo MDS/AML (Calado RT, Young NS. Blood 2008;111:4446). Mutations involving the regulatory region of TERT gene have been recently identified in a consistent proportion of familial and sporadic melanoma and in a subset of tumors originating from tissues with low rate of self-renewal (glioblastoma, liposarcoma, oligodendroglioma bladder cancer, upper urinary tract cancer). These mutations create new binding motifs for Ets/TCF transcription factors, thus increasing TERT gene transcription (Killela PJ et al, PNAS 2013;110:6021; Horn S et al, Science 2013;339:959). As far as we know TERT promoter mutations were never described in MDS. Material and MethodsIndex Case. A 52 years old woman was selected because of a complex phenotype including abnormal skin pigmentation, familial pulmonary fibrosis, osteoarthritis, and a refractory cytopenia with multilineage dysplasia (RCMD, WHO 2008) with a 47,XX,+8 karyotype.Screening Cases. Mutational analysis was extended to a cohort of 115 patients (72 males; 44 females, median age 69) referred to the Laboratory of Cytogenetics, Hematology Department,University of Perugia, Italy.Cytogenetics was normal in 49 cases (43%). Abnormalities included: isolated del(5q) (seven cases, 6%); del(5q) plus one additional change (three cases, 3%); isolated del(20q) (fourteen cases, 12%); trisomy 8 (five cases, 4%); monosomy 7 (two cases, 2%); -Y (three cases, 3%); del(11q) (two cases, 2%); complex karyotype (twenty-four cases, 21%); other aberrations (six cases, 5%).Genomic DNA was extracted from bone marrow (BM) of all cases and from peripheral blood T lymphocytes of index case using Salting out method. In all cases TERT promoter was screened using PCR based DHPLC assay (Wave system; MD Transgenomic Inc. Omaha, NE). The 274bp amplicon was amplified with forward primer 5'GTCCTGCCCCTTCACCTTC3' and reverse primer 5'AGCACCTCGCGGTAGTGG3' using Robust Start Taq KAPA2G (Biosystems, Woburn, MA). DNA from abnormal elution profiles were re-amplified and sequenced by Sanger method (ABI 3500 Genetic Analyzer, Applied Biosystems). Variations were detected using Finch TV v. 1.4.0. In the index case 23 amplicons encompassing all 16 exons of TERT gene were also screened (NC_000005.9). Mutations cloning was carried out after RNA extraction (Trizol, Invitrogen, Life Technologies, Paisley, UK), reverse transcription (ThermoscriptTM RT-PCR System, Invitrogen) and amplification (TERT_2CF (5'-CAGCGCTACTGGCAAATGCG-3' Ta-61,4°C; and TERT_2543R (5'-GGCACTGGACGTAGGACTTG-3' Ta-61,4°C). PCR products were sub-cloned into pGEM-T easy vector (Promega, Madison, WI, USA) and sequenced. ResultsIndex Case. Patient was a compound heterozygous for two germline variations: a nonsense mutation c.1209C>A p.C403* (exon 2) and a missense mutation c.2455C>T p.R819C (exon 8). A putative somatic A>C transition 57 bp before the ATG start codon was detected only in BM cells (Table).Screening Cases. DHPLC analysis showed three patients (2.6%) with a two-peak elution profile. Sequencing revealed a 10 bp duplication (c.1-110_1-101) in case 2; a c.1-124 C>T point mutation in case 3; a point mutation c.1-78 C>T in case 4 (Table). CommentWe showed that TERT gene promoter variations are recurrent events in 2.6% of MDS patients. Only low/int1 risk MDS (IPSS) were affected in this series. The c.1-57A>C, previously reported as a germline activating variation in familial melanoma (Horn S et al, Science 2013;339:959), was likely a somatic mutation in our index case, thus supporting its role in clonal MDS proliferation. We first found the melanoma activating c.1-124 C>T point mutation (Huang FW et al, Science 2013;339:957; Killela PJ et al, PNAS 2013;110:6021) in a MDS with isolated del(5q). The new variation of our case n.4 does not appear to introduce a new transcription factor binding site (http://www.cbrc.jp/research/db/TFSEARCH.html), whereas the 10bp duplication of case 2 indicates an hypothetical binding site for Ikaros. Further results from ongoing functional studies in these cases will be presented. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Assessment and Management of Renal Impairment in Chemotherapy for Urogenital Cancer

The method of diagnosing chronic kidney disease by simple estimated glomerular filtration rate equations has demonstrated a high prevalence of chronic kidney disease among the genitourinary cancer patients. Approximately 30-50% of urothelial cancer patients have Grade 3 chronic kidney disease before chemotherapy, and the rate increases to around 80% in upper urinary tract cancer patients who have undergone radical surgery. Several gold-standard treatments, including cisplatin for urothelial/testicular tumors and anti-vascular endothelial growth factor therapy for kidney cancers, are known to be associated with the development of renal impairment. However, which renal function assessments are best to select a chemotherapy regimen remain unknown. Most testicular tumor patients are cured by intensive combined chemotherapy with cisplatin, but chemotherapy can induce chronic kidney disease in testicular cancer survivors. The prevalence of Stage 3 chronic kidney disease among the testicular cancer survivors is between 10 and 20%. Thus, the estimated glomerular filtration rate assessment is a useful tool for monitoring the development of chronic kidney disease among the cancer survivors, and assessment of renal function is mandatory before the treatment of these genitourinary cancer patients.

Is aristolochic acid nephropathy a widespread problem in developing countries?: A case study of Aristolochia indica L. in Bangladesh using an ethnobotanical–phytochemical approach

Ethnopharmacological relevanceSpecies of Aristolochia are associated with aristolochic acid nephropathy (AAN), a renal interstitial fibrosis and upper urinary tract cancer (UUC). Aristolochic acid nephropathy has been reported in ten countries but its true incidence is unknown and most likely underestimated. By combining an ethnobotanical and phytochemical approach we provide evidence for the risk of AAN occurring in Bangladesh. More specifically, we assess the intra-specific variation of aristolochic acid analogues in medicinally used Aristolochia indica samples from Bangladesh. Materials and methodsEthnobotanical information was collected from 16 kavirajes (traditional healers) in different study locations in Bangladesh. Plant samples were obtained from native habitats, botanical gardens, herbal markets and pharmaceutical companies. The samples were extracted using 70% methanol and were analysed using LC-DAD-MS and 1H-NMR. ResultsRoots as well as leaves are commonly used for symptoms such as snake bites and sexual problems. Among the informants knowledge about toxicity or side effects is very limited and Aristolochia indica is often administered in very high doses. Replacement of Aristolochia indica with other medicinal plants such as Rauvolfia serpentina (L.) Benth. ex Kurz was common. Aristolochia indica samples contained a variety of aristolochic acid analogues such as aristolochic acid I, aristolochic acid II, cepharadione A and related compounds. ConclusionsAAN cases are likely to occur in Bangladesh and more awareness needs to be raised about the health risks associated with the use of Aristolochia indica and other species of Aristolochia as herbal medicines.

240 The ADC value is a prognostic biomarker of upper urinary tract cancer: Potential application to preoperative risk stratification

240 The ADC value is a prognostic biomarker of upper urinary tract cancer: Potential application to preoperative risk stratification

Molecular grading of tumors of the upper urothelial tract using FGFR3 mutation status identifies patients with favorable prognosis

BackgroundMutations in FGFR3 have been shown to occur in tumors of the upper urothelial tract and may be indicative of a good prognosis. In bladder tumors, the combination of FGFR3 mutation status and Ki-67 level has been used to define a tumor’s molecular grade and predict survival. Pathological evaluation of upper urothelial tumors is currently the best predictor of prognosis, but suffers from variability in pathological assessments. This study investigated the association with prognosis of FGFR3 mutations alone and in combination with Ki-67 in this patient population.MethodsGenomic DNA was isolated from tumor samples of 80 patients with upper urothelial cancer. The presence of mutation in FGFR3 was evaluated using real-time polymerase chain reaction. Ki-67 protein expression was determined by immunohistochemistry. Kaplan–Meier survival analysis evaluated the relationship of FGFR3 mutations and Ki-67 levels with survival.ResultsFGFR3 mutations were identified in 40% of tumors and were predominantly associated with noninvasive tumors. Overall survival was higher in patients with FGFR3 mutant tumors (P = 0.02) and in molecular grade 1 tumors as determined by FGFR3 and Ki-67 (P = 0.02).ConclusionIn this study, we confirm the occurrence of FGFR3 mutations in tumors of the upper urothelial tract and its association with a good prognosis. Both FGFR3 and molecular grading are predictors of overall survival. Molecular grading can help to assess the prognosis of patients with upper urinary tract cancer and may represent a new tool for managing this population of patients.

Clinical significance of preoperative peripheral blood neutrophil count in patients with non-metastatic upper urinary tract carcinoma

Preoperative elevation of markers of systemic inflammation is associated with a poor outcome in several cancers. The purpose of this study was to evaluate the prognostic significance of preoperative systemic inflammatory markers in patients with non-metastatic upper urinary tract cancer (UUTC). The records of 84 patients with non-metastatic UUTC who had undergone nephroureterectomy were reviewed, and the associations between preoperative clinical variables and recurrence-free survival (RFS) were analyzed by univariate and multivariate analyses. Clinical tumor stage, neutrophil count, and neutrophil-to-lymphocyte ratio were significantly associated with RFS in univariate analysis. Multivariate analysis showed that clinical T stage (hazard ratio [HR], 3.009; 95 % confidence interval [CI], 1.149-9.321; p = 0.024) and neutrophil count (HR, 3.521; 95 % CI, 1.423-9.108; p = 0.007) were independent predictors of RFS. The 3-year RFS in patients with a neutrophil count <4,000/μL was significantly higher than that in patients with a neutrophil count ≥ 4,000/μL (82.9 vs. 51.0 %, p = 0.004). Based on clinical T stage (T2 or less vs. T3 or greater) and neutrophil count (<4,000 vs. ≥ 4,000/μL), patients were stratified into 3 groups: low, intermediate, and high risk groups. RFS rates were significantly different between the 3 groups (p = 0.0005). Preoperative neutrophil count was an independent predictor of RFS in patients with non-metastatic UUTC. Stratification of patients based on neutrophil count and clinical T stage may be valuable for preoperative patient counseling and identifying patients with poor prognosis who may be candidates for neoadjuvant chemotherapy.

631 SEMI-QUANTIFICATION OF ANGIOGENESIS IN UROTHELIAL CANCER OF UPPER URINARY TRACT: A COMPARISON AMONG THREE ENDOTHELIAL MARKERS

You have accessJournal of UrologyUrothelial Cancer: Upper Tract Tumors1 Apr 2012631 SEMI-QUANTIFICATION OF ANGIOGENESIS IN UROTHELIAL CANCER OF UPPER URINARY TRACT: A COMPARISON AMONG THREE ENDOTHELIAL MARKERS Yasuyoshi Miyata, Tomohiro Matsuo, Kojiro Ohba, and Hideki Sakai Yasuyoshi MiyataYasuyoshi Miyata Nagasaki, Japan More articles by this author , Tomohiro MatsuoTomohiro Matsuo Nagasaki, Japan More articles by this author , Kojiro OhbaKojiro Ohba Nagasaki, Japan More articles by this author , and Hideki SakaiHideki Sakai Nagasaki, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.710AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Angiogenesis is the development of new blood vessels from preexisting capillaries. In numerous solid tumors, angiogenesis plays important roles for cell proliferation, progression, and survival. So, adequate method for quantification of angiogenesis is important to predict the prognosis and discuss the follow up strategy. However, there is no standard mothod of quantification of angiogenesis in urothelial cancer of upper urinary tract (UC-UUT). The purpose of this study was to evaluate the semi-quantification of angiogenesis by assessing microvessel density in UC-UUT, comparing the performance of three antibodies: anti-CD31, anti-CD34, and anti-CD105. METHODS Seventy-four patients diagnosed with UC-UUT undergoing radical operation were evaluated. There is no patient with metastasis because such UC-UUT patient was usefully treated with chemotherapy in our hospital. Formalin fixed specimens were analyzed by semi-quantitative immunohistochemical staining for CD31, CD34, and CD105. Microvessel density (MVD) “hot spots” were counted in three 200X high-power field (HPF). VEGF-A expression was also evaluated by immunohistochemical technique. Relationships between each MVD and pT stage, grade, and VEGF-A expression were evaluated. RESULTS Median MVDs estimated by anti-CD31, anti-CD34, and anti-CD105 were 48, 72, and 28/HPF, respectively. Although all MVDs were significantly associated with pT stage and grade, CD105-MVD showed most significant difference (p<0.001) between low (pTa+1) and high pT stage (pT2 - 4) compared to CD31-MVD or CD34-MVD. In addition, interestingly, CD105-MVD in tumor with pTa and Grade 1was extremely lower (median = 5/HPF) compared to that in pT1 tumors (median = 23/HPF). Such finding was not found in CD31-MVD and CD34-MVD. When relationship between each MVD and VEGF-A expression was investigated, CD105-MVD also showed most closely correlation (r=0.543, p<0.001). In survival analysis, all MVDs were associated with disease-free survival and cause-specific survival by Kaplan-Meier survival analyses. However, only CD105-MVD was identified as independent predictor for disease-free survival in multivariate analysis model including pT stage and grade. CONCLUSIONS In UC-UUT, MVD estimated by anti-CD105 antibody was most useful marker to reflect pathological status, malignant potential, and prognosis. In several cancers, CD105 was recognized as tumor-specific endothelial markers. We also suggest that CD105 is useful marker to detect tumor-specific angiogenesis in patients with UC-TCC. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e257 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuyoshi Miyata Nagasaki, Japan More articles by this author Tomohiro Matsuo Nagasaki, Japan More articles by this author Kojiro Ohba Nagasaki, Japan More articles by this author Hideki Sakai Nagasaki, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Tumour multiplicity as a risk factor for the development of bladder tumours after primary upper urinary tract cancer

Objective: To determine the independent risk factors for intravesical tumour recurrence in patients with primary urothelial cancer of the upper urinary tract. Patients and methods: Of the 60 patients who underwent nephroureterectomy for urothelial cancer of the upper urinary tract, the data from 49 patients were retrospectively reviewed. Patients with a previous history or concomitance of bladder cancer were excluded from the study. Multivariate analysis by Cox’s proportional hazards model was used to determine independent risk factors for intravesical tumour recurrence. Results: Of the 49 patients reviewed, 22 (44.9%) experienced subsequent intravesical tumour recurrence during a mean follow-up period of 26 months (range 3–103). On multivariate analysis, tumour multiplicity had a statistically significant impact on the risk of intravesical tumour recurrence ( P &lt; 0.01). Conclusion: Neither the pathology of the upper urinary tract cancers nor the method of treatment was associated with recurrent bladder cancers. Only tumour multiplicity had a significant impact on the incidence of intravesical tumour recurrence.

1392 ACCURACY AND LIMITATION OF URETEROSCOPY IN DIAGNOSIS OF UPPER URINARY TRACT CANCER

You have accessJournal of UrologyTechnology & Instruments: Ureteroscopy1 Apr 20111392 ACCURACY AND LIMITATION OF URETEROSCOPY IN DIAGNOSIS OF UPPER URINARY TRACT CANCER Norihiro Murahashi, Takashige Abe, Toru Harabayashi, Nobuo Shinohara, Ataru Sazawa, Satoru Maruyama, and Katsuya Nonomura Norihiro MurahashiNorihiro Murahashi Sapporo, Japan More articles by this author , Takashige AbeTakashige Abe Sapporo, Japan More articles by this author , Toru HarabayashiToru Harabayashi Sapporo, Japan More articles by this author , Nobuo ShinoharaNobuo Shinohara Sapporo, Japan More articles by this author , Ataru SazawaAtaru Sazawa Sapporo, Japan More articles by this author , Satoru MaruyamaSatoru Maruyama Sapporo, Japan More articles by this author , and Katsuya NonomuraKatsuya Nonomura Sapporo, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1239AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ureteroscopy can help to detect upper urinary tract cancer (UUTC) or to rule out malignancy. However, few reports examined the clinical course of patients considered free of disease at the first examination. The present study investigated the diagnostic accuracy of ureteroscopy for UUTC and the clinical course of patients who had not been diagnosed as UUTC by ureteroscopy. METHODS Study1 138 patients underwent diagnostic ureteroscopy based on suspected of having UUTC between 1995 and 2009. We reviewed the detection rate of carcinoma diagnosis. Study2 We focused on the patients who had not been diagnosed as UUTC at the first examination. We collected the follow-up data from these patients and examined the predictors of later cancer detection. RESULTS Of the138 pts, 59 (43%) were diagnosed as having cancer on the first examination. Thereafter, 37 underwent nephroureterectomy (NU), 2 did partial ureterectomy and 4 did endoscopic surgery, while 16 were treated by conservative therapy. Of the 37 with NU, carcinoma was not detected in surgical specimens in 3 (8.1%). All of them had concurrent bladder cancer. Of the 79 diagnosed as not having carcinoma at the first exam, 61 were followed for 3 months or longer. Of these, carcinoma was detected in 5 at a median of 55 months follow-up. As the clinical characteristic, the history of bladder cancer (yes/no=19/42, p=0.048) and gross hematuria episode after the exam (yes/no=11/50, p=0.004) were the predictors for the latter cancer detection. CONCLUSIONS Ureteroscopy is a useful modality for diagnosis of UTC. However, the ureteroscopic diagnosis might be carefully interpreted in case of concurrent bladder cancer. Patients, negative for ureteroscopy, who have a history of bladder cancer and continuous gross hematuria would be better under close follow-up because they have higher potential of later cancer detection. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e556 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Norihiro Murahashi Sapporo, Japan More articles by this author Takashige Abe Sapporo, Japan More articles by this author Toru Harabayashi Sapporo, Japan More articles by this author Nobuo Shinohara Sapporo, Japan More articles by this author Ataru Sazawa Sapporo, Japan More articles by this author Satoru Maruyama Sapporo, Japan More articles by this author Katsuya Nonomura Sapporo, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Risk of urothelial bladder cancer in Lynch syndrome is increased, in particular among MSH2 mutation carriers

BackgroundColorectal, endometrial and upper urinary tract tumours are characteristic for Lynch syndrome (hereditary non-polyposis colon carcinoma, HNPCC). The aim of the present study was to establish whether carriers of mutations...

Interest of methylated genes as biomarkers in urothelial cell carcinomas of the urinary tract

Urothelial cell carcinomas (UCC), including bladder cancer and upper urinary tract cancer, are the second most common malignancy of the urogenital tract after prostate cancer. It is a critical issue to differentiate accurately those patients whose tumour will recur and/or progress after initial treatment from those without recurrence and/or progression because tumours with a similar morphology behave differently. Patients undergo lifelong cystoscopic and cytology surveillance to detect subsequent tumour recurrence. New noninvasive methods for the diagnosis and surveillance of UCCs are required. DNA methylation is an important epigenetic mechanism of gene regulation and plays essential roles in tumour initiation and progression. Currently, aberrant promoter hypermethylation has been investigated in specific genes, i.e. tumour-suppressor genes, proto-oncogenes, genes involved in cell adhesion, and genes of cell cycle regulation. E-cadherin has been shown to be an independent marker of prognosis. Other genes, e.g. APC, RASSF1a, TNFRSF25, EDNRB, and p14, are implicated in tumour progression. IGFBP3 and APAF-1 are independent markers of recurrence. APAF-1 is also correlated with tumour stage and grade. In urine, hypermethylation of DAPK, RARβ, E-cadherin and p16 has been shown to have a good sensitivity and specificity for bladder cancer detection. Several studies found that analysis of hypermethylation using a panel of tumour-suppressor genes yielded superior results to cytology in the detection of bladder cancer and its progression. Hence, the different panels (e.g. RASSF1a/APC/p14, RAR_/DAPK/E-cadh/p16, p16/p14/MGMT/GSTP1, and RASSF1a/E-cadh/APC) are of interest in the detection of bladder cancer. The last panel and RASSF1a/E-cadh/APC/TNFRSF25/EDNRB are also interesting for tumour progression. There is evidence that the extent of the mutator and methylator phenotypes in UCCs differs with tumour location, perhaps suggesting that carcinogens affect the urinary tract in different ways. For all loci studied except DAPK, there was more frequent methylation in UUT-UCCs than in the bladder cancers; this difference was statistically significant for hMLH1, RARB, E-cadherin, p16 and MINT31. In contrast to UUT-UCCs, hMLH1 and MINT31 were rarely methylated in bladder tumours, suggesting that they play a role in UUT carcinogenesis but not bladder cancer.

Pathological characteristics and clinical course of bladder tumour developing after nephroureterectomy

To determine the pathological features and clinical course of intravesical recurrence after nephroureterectomy (NU) for upper urinary tract (UUT) cancer. Among 325 patients undergoing NU with bladder cuff excision for UUT cancer, in this retrospective multi-institutional study we evaluated 113 who developed bladder tumour after NU. Excluding patients with (i) perioperative systemic chemotherapy or radiotherapy for UUT cancer; (ii) a history of previous or synchronous bladder cancer at the time of NU; (iii) distant metastasis at the time of NU; (iv) a follow-up of <1 year after the initial bladder cancer recurrence; or (v) missing data, 74 patients were included in this study. We compared the pathology between UUT cancer and the first bladder cancer recurrence, using Fisher's exact test. Further intravesical recurrence and bladder cancer progression was analysed using the Kaplan-Meier method, with the log-rank test used to assess significance. A Cox proportional hazard model was used for multivariate analysis. The grade of the first bladder cancer recurrence strongly correlated with that of the UUT tumour (P < 0.001) and the carcinoma in situ (CIS) lesion with the first bladder cancer recurrence correlated with high grade (grade 3) UUT tumour (P < 0.001). In all, 56 of the assessable 70 patients further developed intravesical recurrence at a median interval of 7 months after the first bladder cancer recurrence. There were no clinicopathological factors that predicted the second recurrence. Progression occurred in 14 patients, at a median interval of 25 months. A CIS lesion with the first bladder cancer recurrence was a risk factor for progression on multivariate analysis. A large proportion of the patients who developed bladder tumour after NU had further intravesical recurrence, which indicated its refractory nature. Especially when a CIS lesion is detected in the initial intravesical recurrence, a careful follow-up is mandatory to detect bladder cancer progression.

The Protective Role of Renal Parenchyma as a Barrier to Local Tumor Spread of Upper Tract Transitional Cell Carcinoma and its Impact on Patient Survival

We investigated whether tumor location has independent prognostic significance in upper tract transitional cell carcinoma cases and which factor determines it. We reviewed data on 122 renal pelvis and 102 ureteral tumor cases, including the recurrence pattern. Tumor location and other clinicopathological variables were evaluated regarding cancer specific and recurrence-free survival. Stage pT3 tumors were stratified into those invading renal parenchyma or peripelvic/periureteral fat. Overall 5-year cancer specific survival and recurrence-free survival rates were 77.0% and 71.6%, respectively, at a mean followup of 60.7 months. Of the clinicopathological parameters T stage was the most significant prognosticator of the survival rate, while nodal involvement, high grade and ureteral tumor location were also significant for lower survival rates. Stratification analysis for matching pathological stage revealed that, while survival rates were similar in the renal pelvis and ureteral tumor groups at stage pT2 or less, renal pelvic tumors were associated with significantly higher survival rates than ureteral tumors for stage pT3. Specifically renal pelvic tumors invading the renal parenchyma were associated with a lower local failure rate, and higher cancer specific and recurrence-free survival rates than tumors invading peripelvic or periureteral fat, ie 77.5% vs 49.7% 5-year cancer specific survival and 75.6% vs 32.0% 5-year recurrence-free survival (p = 0.014 and 0.003, respectively). Tumor location is an independent prognostic factor for pT3 upper tract transitional cell carcinoma. The overall better prognosis of renal pelvic tumors was mainly attributable to pT3 tumor outcomes, specifically lesions invading the renal parenchyma. These findings may be due to the protective role of thick renal parenchyma against local tumor spread.