Tumors Of Upper Urinary Tract Research Articles

Potential Significance of EMP3 in Patients with Upper Urinary Tract Urothelial Carcinoma: Crosstalk with ErbB2-PI3K-Akt Pathway

Upper urinary tract (pyelocalyceal cavities and ureter) urothelial carcinoma is a relatively rare neoplastic disease. Although diagnosis and treatment of this tumor variant have improved significantly, accurate risk stratification remains a challenge. To identify the putative oncogene involved in urothelial carcinoma progression we performed bioinformatics guided experimental investigation targeting chromosome 19q13. We investigated the effects of EMP3 on cancer cell growth, migration and adhesion in transfection and siRNA experiments in vitro. Crosstalk of integrins or ErbB2 with EMP3 was examined by reverse transcriptase-polymerase chain reaction and immunoblot. The potential involvement of epigenetic alterations of EMP3 in vitro and in vivo was analyzed by methylation specific polymerase chain reaction. To validate clinical relevance we measured EMP3 expression at the mRNA and protein levels in a cohort of 77 patients with upper urinary tract urothelial carcinoma and compared prognostic significance in relation to that of ErbB2 expression. We noted functional crosstalk between ErbB2 and EMP3 in vitro. EMP3 over expression promoted cancer cell proliferation and migration but suppressed cell adhesion in vitro. EMP3 activated the ErbB2-PI3K-AKT pathway to increase cell growth in vitro. In the clinical cohort Kaplan-Meier survival estimates showed that ErbB2 and EMP3 co-expression was the most important indicator of progression-free and metastasis-free survival in patients with upper urinary tract urothelial carcinoma (log rank test p = 0.018 and 0.04, respectively). EMP3 is an important prognostic indicator for selecting patients with upper urinary tract urothelial carcinoma for more intensive therapy. EMP3 is an innovative co-targeting candidate for designing ErbB2 based cancer therapy.

Long-term follow-up of patients with tumours of the renal pelvis and ureter: How often is a bladder tumour diagnosed after five tumour-free years?

Objective. It is not known when cystoscopy follow-up should be terminated after surgery for tumours of the renal pelvis and ureter [upper urinary tract tumours (UUTTs)]. The aim of this study was to investigate the length of the interval from surgery to diagnosis of the first bladder tumour. Material and methods. A review was performed of all 930 patients who were diagnosed with a UUTT from 1971 to 1998 in western Sweden. The time to the first bladder tumour was estimated using Kaplan--Meier analyses. Univariate and multivariate analyses of potential risk factors for bladder recurrence were performed. Results. In total, 614 patients were treated surgically for a renal pelvic or ureteral tumour and underwent cystoscopy at least 3 months afterwards. Of these 614 patients,192 (31.3%) patients developed a bladder tumour after the upper tract surgery. The majority, 157 out of 192 patients (81.8%), were diagnosed during the first 2 years, an additional 24 patients (12.5%) during years 3--5 and 11 patients (5.7%) between years 5 and 20. A history of bladder tumours, large tumour diameter, carcinoma in situ and UUTT diagnosed during the last part of the study period were significant risk factors for bladder recurrence after upper tract surgery. Conclusion. Cystoscopy should be performed at short intervals during the first 2 years after surgery for a UUTT, in particular among patients with a history of bladder tumours. Late bladder recurrences are unusual; therefore, as a rule, follow-up cystoscopy should be terminated after 5 tumour-free years.

237 MicroRNA signature associated with poor outcome in upper urinary tract tumours

237 MicroRNA signature associated with poor outcome in upper urinary tract tumours

Contemporary evaluation of urography in diagnosis in patients with urothelial cell carcinoma.

312 Background: Upper urinary tract tumors (UUTT) can occur synchronous or metachronous (0.7 – 6%) with bladder tumors. The optimal imaging technique of the upper urinary tract is unclear. Studies on the accuracy of retrograde pyelography (RUP) and comparative studies on detection level are sparse. In this study we evaluated the effectiveness of a first RUP in patients with a first manifestation of urothelial cell carcinoma (UCC) in the urinary tract. Methods: In this retrospective study we evaluated all consecutive patients with pathologic proven UCC who underwent their first RUP between March 1998 and April 2008 in the University Medical Center Groningen, Netherlands. Data regarding patient and tumor characteristics, results from RUPs, use of alternative imaging techniques, treatment and outcome were collected from the electronically patient’s records. Follow up was calculated from the first RUP to the last registrated visit. Descriptive statistics have been used to evaluate the performance of the RUP. Results: A total of 156 patients underwent a first RUP because of a first manifestation of UCC of the bladder or upper urinary tract. A mean follow up of 5.09 years was achieved (range 0-13 years). On 17 RUPs (11%) abnormalities were detected. In 16 patients a malignancy was diagnosed. Except one renal cell carcinoma all tumors were UCC of the renal pelvis, ureters or both. Muscle invasive tumors were diagnosed in 7 of these 17 patients. In 30 patients (19%) no conclusive results were obtained because of failure of the RUP due to technical difficulties. In 19 of 30 patients alternative imaging was performed, with intravenous pyelography in 11 patients, computer tomography urography in 7 patients and with both in 1 patient. No UUTTs were diagnosed in this group. In 109 (70%) patients whit a negative RUP three patients developed a tumor after 8, 52, and 65 months. The latter two we consider as newly developed lesions. Conclusions: RUP in patients with a first manifestation of UCC is a very sensitive and accurate diagnostic tool in detecting UUTT.

Brain metastases in patients with urothelial carcinoma.

282 Background: Muscle invasive urothelial cancers are infrequent. Patients (pts) with metastatic disease have poor prognosis. Brain metastases (BM) are rare. The aim of this retrospective study is to analyse the characteristics, the treatment and the evolution of patients with BM treated in a single centre. Methods: Thirty pts with BM were identified among the 1591 pts with urothelial carcinoma seen at the Centre Léon Bérard, between 1994 and 2011. The study population was described, overall survival (OS) from diagnosis of BM was estimated by Kaplan-Meier method and prognostic factors were explored using a Cox model. Results: Twenty seven pts in our series were male. Median age at initial diagnosis was 60 years (range: 33.9-78.9 years). Twenty two pts had primary bladder tumours and 8 upper urinary tract tumours. Twenty four pts underwent surgery for their primary lesion, 2 received chemoradiotherapy and 4 did not receive any radical local treatment. Six pts had metastatic disease at initial presentation: 3 were operated on. Median delay between initial diagnosis and BM was 16.6 months (range: 0-56.4 months), 3 patients had BM at initial presentation. Median time between first metastases and BM was 10 months (range=0-52 months). Eleven patients developed BM as one of the first sites of metastases. BM were symptomatic in 28 pts: specific neurological symptoms (n=25), headaches (n=6), epilepsy (n=2). For the 2 other pts, they were discovered on a systematic brain MRI. Eighteen pts had cerebral metastases only, 5 pts had cerebellar metastases only, 6 had both; the last patient had cerebral, cerebellar and meningeal involvement. Half of the pts had only 1 brain lesion. Five pts were operated on: 4 received postoperative radiotherapy; 19 patients were given radiotherapy alone and 6 did not get any local therapy. In this series, median OS from diagnosis of BM was 3.4 months (IC95% [2.2-10.3]). Only the administration of chemotherapy after the diagnosis of BM was significantly associated with OS; probably because only fit enough patients were offered treatment. Conclusions: Prognosis of patients with urothelial carcinoma and BM is poor; however some patients have long survivals. Treatment is not codified as there is little data in the literature.

Distinct patterns and behaviour of urothelial carcinoma with respect to anatomical location: how molecular biomarkers can augment clinico-pathological predictors in upper urinary tract tumours

Upper urinary tract urothelial carcinoma (UTUC) shares many similarities with bladder-UC, but there is strong evidence on a clinical, aetiological, epidemiological and genetic level that key differences exist. In this review, we aim to highlight how UTUC differs from bladder-UC and report on the utility of molecular markers in the diagnosis and management of UTUC. A systematic literature search was conducted using the Medline and Embase databases and specific keyword combinations: 'urothelial carcinoma', 'bladder cancer', 'transitional cell carcinoma', 'upper tract', 'upper urinary tract', 'genetics', 'prognosis' and 'biomarkers'. UTUC has specific acquired (e.g. Balkans nephropathy, phenacetin abuse) and genetic hereditary non-polyposis colorectal cancer risk factors compared with bladder-UC. In general, the molecular biology of UC is broadly similar, irrespective of location in the urinary tract. However, there are distinct genetic (microsatellite instability) and epigenetic (hypermethylation) differences between some UTUC and bladder-UC. Clinical-pathological variables (e.g. hydronephrosis, tumour architecture, tumour location, stage and grade) have independent predictive power in UTUC, but tissue and urinary biomarkers can improve the clinical prediction of recurrence, invasion and survival in UTUC, though the evidence level is weak. UTUC shares many similarities with bladder-UC, but there is strong evidence that they should be considered as distinct urothelial entities. Prospective multi-institutional studies investigating molecular markers are urgently needed to augment clinic-pathological predictors in UTUC.

Breast cancer in Irish families with Lynch syndrome.

1543 Background: Breast cancer is not among the recognised malignant manifestations of Lynch Syndrome which include colorectal, endometrial, gastric, ovarian and upper urinary tract tumours. In this study we report the prevalence of breast cancer in Irish Lynch Syndrome families and determine immunohistochemical (IHC) expression of mismatch repair proteins (MMR) in available breast cancer tissue. Methods: Breast cancer prevalence was determined among Lynch Syndrome kindreds from two institutions in Ireland. One kindred was omitted due to a biallelic MMR and BRCA1 mutation.The clinicopathological data that was collected on breast cancer cases included age of onset, morphology, and hormone receptor status, and a genotype phenotype correlation was investigated. Immunohistochemical staining was performed for MLH1, MSH2, MSH6, and PMS2 on all available breast cancer tissue from affected individuals. Results: The distribution of MMR mutations seen in sixteen pedigrees were as follows; MLH1 (n=5), MSH2 (7), MSH6 (3), PMS2 (1). Sixty cases of colorectal cancer and 14 cases of endometrial cancer were seen. Seven breast cancers (5 invasive ductal and 2 invasive lobular cancers) and 1 case of ductal carcinoma in situ were reported in 7 pedigrees. This compared with 4 cases of prostate cancer. Of the 7 LS kindreds containing breast cancer, 6 MSH2 mutations and 1 MSH6 mutations were identified. Median age of breast cancer diagnosis was 49 years (range 38-57). Hormone receptor status is available on 3 breast cancer cases at time of abstract submission; all were ER positive and HER 2 negative. All cases had grade 2 or 3 tumours. 5 samples were available for IHC evaluation. 3 out of 5 cases showed loss of MMR expression, all showed loss of MSH2 and MSH6 expression. One of the two cases with normal IHC expression in breast tissue belonged to a kindred where 3 siblings with colorectal cancer and documented deleterious mutations demonstrated no IHC loss. Conclusions: Breast cancer occurred at an early age and was more common than prostate cancer in Irish Lynch Syndrome pedigrees. All identified breast cancer were in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer screening may be warranted in certain Lynch Syndrome kindreds.

Brain metastases in patients with urothelial carcinoma.

e15009 Background: Muscle invasive urothelial cancers are infrequent. Patients (pts) with metastatic disease have poor prognosis. Brain metastases (BM) are rare. The aim of this retrospective study is to analyse the characteristics, the treatment and the evolution of patients with BM treated in a single centre. Methods: Thirty pts with BM were identified among the 1591 pts with urothelial carcinoma seen at the Centre Léon Bérard, between 1994 and 2011. The study population was described, overall survival (OS) from diagnosis of BM was estimated by Kaplan-Meier method and prognostic factors were explored using a Cox model. Results: Twenty seven pts in our series were male. Median age at initial diagnosis was 60 years (range: 33.9-78.9 years). Twenty two pts had primary bladder tumours and 8 upper urinary tract tumours. Twenty four pts underwent surgery for their primary lesion, 2 received chemoradiotherapy and 4 did not receive any radical local treatment. Six pts had metastatic disease at initial presentation: 3 were operated on. Median delay between initial diagnosis and BM was 16.6 months (range: 0-56.4 months), 3 patients had BM at initial presentation. Median time between first metastases and BM was 10 months (range=0-52 months). Eleven patients developed BM as one of the first sites of metastases. BM were symptomatic in 28 pts: specific neurological symptoms (n=25), headaches (n=6), epilepsy (n=2). For the 2 other pts, they were discovered on a systematic brain MRI. Eighteen pts had cerebral metastases only, 5 pts had cerebellar metastases only, 6 had both; the last patient had cerebral, cerebellar and meningeal involvement. Half of the pts had only 1 brain lesion. Five pts were operated on: 4 received postoperative radiotherapy; 19 patients were given radiotherapy alone and 6 did not get any local therapy. In this series, median OS from diagnosis of BM was 3.4 months (IC95% [2.2-10.3]). Only the administration of chemotherapy after the diagnosis of BM was significantly associated with OS; probably because only fit enough patients were offered treatment. Conclusions: Prognosis of patients with urothelial carcinoma and BM is poor; however some patients have long survivals. Treatment is not codified as there is little data in the literature.

The role of positron emission tomography using carbon-11 and fluorine-18 choline in tumors other than prostate cancer: a systematic review

To systematically review published data on the role of positron emission tomography (PET) or PET/computed tomography (PET/CT) using either Carbon-11 ((11)C) or Fluorine-18 ((18)F) choline tracer in tumors other than prostatic cancer. A comprehensive literature search of studies published in PubMed/MEDLINE and Embase databases through January 2012 and regarding (11)C-choline or (18)F-choline PET or PET/CT in patients with tumors other than prostatic cancer was carried out. Fifty-two studies comprising 1800 patients were included and discussed. Brain tumors were evaluated in 15 articles, head and neck tumors in 6, thoracic tumors (including lung and mediastinal neoplasms) in 14, liver tumors (including hepatocellular carcinoma) in 5, gynecologic malignancies (including breast tumors) in 5, bladder and upper urinary tract tumors in 5, and musculoskeletal tumors in 7. Radiolabeled choline PET or PET/CT is useful to differentiate high-grade from low-grade gliomas and malignant from benign brain lesions, to early detect brain tumor recurrences and to guide the stereotactic biopsy sampling. The diagnostic accuracy of radiolabeled choline PET is superior compared to Fluorine-18 fluorodeoxyglucose ((18)F-FDG) PET in this setting. Radiolabeled choline PET or PET/CT seems to be accurate in differential diagnosis between malignant and benign thoracic lesions and in staging lung tumors; nevertheless, a superiority of radiolabeled choline compared to (18)F-FDG has not been demonstrated in this setting, except for the detection of brain metastases. Few but significant studies on radiolabeled choline PET and PET/CT in patients with hepatocellular carcinoma (HCC) and musculoskeletal tumors are reported in the literature. The combination of radiolabeled choline and (18)F-FDG PET increases the detection rate of HCC. The diagnostic accuracy of radiolabeled choline PET or PET/CT seems to be superior compared to (18)F-FDG PET or PET/CT and conventional imaging methods in patients with bone and soft tissue tumors. Limited experience exists about the role of radiolabeled choline PET and PET/CT in patients with head and neck tumors, bladder cancer and gynecologic malignancies including breast cancer.

Abstract 3679: Paired tumor and normal whole genome and transcriptome sequencing of transitional cell carcinoma of the upper urinary tract

Abstract Background: Transitional cell carcinoma of the upper urinary tract (UUT) is a rare urothelial cancer, which most often affects males ages 50-70. Previous studies have shown some overlap with genetic alterations frequently observed in bladder cancer, however complete molecular characterization of UUT tumors is currently limited. A 20-year-old woman with treated acute lymphoblastic leukemia (ALL) in remission for ∼13 years, presented with present with numerous metastatic lesions involving bone, adrenal, retrocaval lymph node, and kidney. Biopsy confirmed a second primary carcinoma originating from the ureter or kidney. After two lines of systemic chemotherapy, the patient enrolled in a whole-genome (WGS) and whole transcriptome sequencing (WTS) pilot study. Methods: Tumor DNA and RNA was isolated from fresh-frozen tissue obtained by needle core biopsy of the right kidney tumor. Germline DNA was isolated from the patient's whole blood. Commercial benign ureter tissue was used for normal RNA comparison. Whole-genome paired-end library and transcriptome sequencing were done on Illumina's HiSeq 2000 platform. Burrows-Wheeler Transform algorithm was used in alignment to human reference genome (build 36). Several short nucleotide variants (SNVs) were selected for further validation with Sanger sequencing. Quantitative PCR with specific primers to either amplified or deleted genomic regions and ΔΔCt method were used to validate chromosomal copy number abnormalities. Results: WGS yielded 46X and 55X uniquely mappable reads for the tumor and normal samples, respectively. Seventy-one damaging somatic SNVs and a number of chromosomal aberrations were identified in regions of cancer relevant genes. Most notably, truncating mutations were found in p53 and KDM6A (oncogenic histone demethylase) genes as well as a damaging mutation in E2F8 transcription factor. KDM6A and E2F8 mutations were confirmed with bi-directional Sanger sequencing. A homozygous deletion encompassing the tumor suppressor p16 and a prominent focal 2MB high-level amplification at 7p11.2 that includes the EGFR oncogene were also detected. WTS produced ∼1006 reads for each sample. Expression analysis revealed loss-of-heterozygosity in p53 wild-type locus and a significant upregulation of EGFR. Additionally, a number of genes (MKI67, AURKA, TOP2A, BUB, FOXM, and PLK1) associated with cell cycle progression had >4-fold tumor overexpression. Genomic qPCR confirmed a 10-fold reduction in p16 while EGFR was amplified >40 times. Conclusion: Through WGS and WTS, a number of common oncogenic targets to be deregulated in this UUT, including p53 mutation, EGFR and MYC amplifications, and p16 deletion. These targets have previously been implicated in urothelial cancers, most notably in bladder. Given, negative KRAS mutation status, EGFR targeted therapy may be a reasonable treatment option for this patient. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3679. doi:1538-7445.AM2012-3679

In the cystoscopic follow-up of non-muscle-invasive transitional cell carcinoma, NMP-22 works for high grades, but unreliable in low grades and upper urinary tract tumors

Two percent of the bladder non-muscle-invasive (NMI) transitional cell carcinomas (TCC) are associated with upper urinary tract (UUT) TCC. We evaluated the role of nuclear matrix protein-22 (NMP-22) (BladderChek) test in the diagnosis of lower urinary tract and UUT-TCC. From March 2009 to June 2011, 122 patients with bladder NMI-TCC underwent 205 control cystoscopy. A total of 95 (78 men and 17 women, mean age 60.7 years, range, 27-88) patients who were followed regularly with NMP-22 test and with follow-up cystoscopies (145 episodes; min. 1-max. 5) were included in this study. For routine monitoring of the UUT, IVU or CT urography was used once a year for high grades (HG), and once in every other year for low grades (LG). The sensitivity and specificity of NMP-22 were evaluated by ROC curves, and sensitivity, specificity, and positive and negative predictive values were calculated. Chi-square test was used for the differences between the subgroups. Cystoscopy and NMP-22 results of the patients included in the study revealed the sensitivity (44.4%) of the test was very low and the specificity (98.4%) was quite high (p < 0.001). Among the 10 cystoscopies where NMP-22 was negative, but cystoscopy was positive for tumor, 8 had LG and 2 had HG TCC. NMP-22 was never positive in low-grade tumors, in other words, all of the NMP-22-positive 8 tumors were high grade. On the other hand, in 20% (2/10) of the cases, NMP-22 can be negative although the tumor was high grade. Two (2.1%) HG UUT-TCC were detected in 95 patients. These 2 patients were within the 125 cystoscopies (75 patients) where both NMP-22 and cystoscopy were negative for tumor. Nuclear matrix protein-22 cannot detect LG TCC. However, it detects overwhelming majority of HG TCC. For this reason, positive NMP-22 test largely indicates HG TCC. NMP-22 is also not reliable in UUT-TCC, even in HG tumors.

Breast cancer in Irish families with Lynch syndrome.

413 Background: Breast cancer is not a recognised malignant manifestation of Lynch Syndrome which includes colorectal, endometrial, gastric, ovarian and upper urinary tract tumours. In this study we report the prevalence of breast cancer in Irish Lynch Syndrome families and determine immunohistochemical expression of mismatch repair proteins (MMR) in available breast cancer tissue. Methods: Breast cancer prevalence was determined among Lynch Syndrome kindreds from two institutions in Ireland, and a genotype phenotype correlation was investigated. One kindred was omitted due to the presence of a biallelic MMR and BRCA1 mutation. The clinicopathological data that was collected on breast cancer cases included age of onset, morphology, and hormone receptor status. Immunohistochemical staining was performed for MLH1, MSH2, MSH6, and PMS2 on all available breast cancer tissue from affected individuals. Results: The distribution of MMR mutations seen in 16 pedigrees was as follows; MLH1 (n=5), MSH2 (7), MSH6 (3), PMS2 (1). Sixty cases of colorectal cancer and 14 cases of endometrial cancer were seen. Seven breast cancers (5 invasive ductal and 2 invasive lobular cancers) and 1 case of ductal carcinoma in situ were reported in 7 pedigrees. This compared with 4 cases of prostate cancer. Six MSH2 mutations and 1 MSH6 mutation were identified in the 7 Lynch syndrome kindreds. Median age of breast cancer diagnosis was 49 years (range 38-57). Hormone receptor status is available on 3 breast cancer cases at time of abstract submission; all were ER positive and HER 2 negative. All cases had grade 2 or 3 tumours. Final results of immunohistochemistry for mismatch repair protein expression on breast cancer samples are pending and will be reported at the meeting. One breast cancer has been tested to date and demonstrated loss of MSH2 protein expression in an individual carrying an MSH2 mutation. Conclusions: Breast cancer occurred at an early age and was more common than prostate cancer in Irish Lynch Syndrome pedigrees. All reported breast cancer cases were in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer screening may be warranted in certain Lynch Syndrome kindreds.

UP-03.146 The Impact of Intravesical Recurrence on Prognosis After Nephroureterectomy for Upper Urinary Tract Urothelial Cancer

Bladder tumors have been reported to be found in a range of 15% to 50% after nephroureterectomy (NU) for patients with upper urinary tract tumor (UTT). Although many studies have reported clinicopathological features of UTT which affect bladder tumor development, these predictive factors are still controversial. The aim of this study was to identify predictive factors of intravesical recurrence after NU for UTT and verify prognosis of these patients.

UP-03.155 Results of BCG and MMC in Transitional Cell Carcinoma of Upper Urinary Tract: Spanish Cooperative Group Register of Upper Urinary Tract Tumors

Assessed the performance of instillations of bacillus Calmette-Guerin (BCG) and mitomycin C (MMC) in urothelial tumors of upper urinary tract treated with endourology approach and preservation of renal functional unit.

Computed Tomography-Urography for Upper Urinary Tract Imaging: Is It Required for All Patients Who Present with Hematuria?

To define in which patients who present with microscopic or macroscopic hematuria CT urography (CTU) is indicated as an imaging mode for the upper urinary tract (UUT). We conducted a prospective study on consecutive patients who attended a modern protocol-driven hematuria clinic from January 2006 to February 2010. Standard tests (history taking, physical examination, urinalysis via dipstick method, ultrasonography of kidneys and bladder performed by urologists, cystoscopy, and cytology) were directed to all patients, whereas the mode of additional UUT imaging (ultrasonography by a radiologist or four-phase CTU/magnetic resonance (MR) urography (MRU) when CTU was contraindicated) was selected according to a risk factor-based management algorithm. The added value of cross-sectional urography (CTU/MRU) supplementary to ultrasonography (by urologists) to detect renal masses, UUT tumors, and stones was assessed. Univariate and multivariate analysis on predictive factors for cross-sectional urography result were performed. From the total of 841 patients, lesions that might account for hematuria could not be identified in 462 (54.9%), whereas in 250 (29.7%) and 124 (14.7%) patients, hematuria was from benign and malignant disease, respectively. Cross-sectional urography revealed relevant UUT lesions in 73 of 525 (13.9%) patients. Only result of ultrasonography (odds ratio [OR] 7.7, 95% confidence interval [CI] 4.0-14.9), P<0.001) and type of hematuria (OR 2.6, 95% CI 1.3-5.1, P=0.01) were significant predictors for cross-sectional urography result. In 44 of 456 (9.6%) patients with no abnormalities on ultrasonography, CTU/MRU revealed that these were false negatives, with most lesions missed being stones. In 253 of 309 (81.9%) patients with macroscopic hematuria, no lesions were detected in the UUT on CTU/MRU, in contrast to 199 of 216 patients (92.1%) with microscopic hematuria. For patients who present with microscopic hematuria, ultrasonography is sufficient to exclude significant UUT disease. For patients with macroscopic hematuria, the likelihood of finding UUT disease is higher, and a CTU as a first-line test seems justified.

Conservative Endoscopic Retrograde Treatment of Upper Urinary Tract Tumors: Retrospective Analysis of the Last 105 Cases

Modern flexible ureterorenoscopy allows a retrograde approach to urothelial tumors in the upper urinary tract (UUTT) of small dimensions (<1.5 cm), of low grade and non-invasive. The percutaneous renal approach, although more invasive, provides an alternative treatment in case of larger dimension neoplasia or difficult retrograde access. The key to the success of endoscopic treatment of UUTT is an accurate patient selection. We will bring our experience in the treatment of UUTT by conservative endoscopic retrograde treatment. Treatment through endoscopic retrograde approach with rigid or flexible ureterorenoscopy has been applied to 105 patients; lesions were treated with electrocution or lasers using thin laser fibers type Ho:YAG. We evaluated the recurrence rate and the intra- and perioperative complications. The recurrence rate was equal to 30.4%. In no case was it necessary to recur to blood transfusion; 15% of wall perforations treated in a conservative manner occurred without following complications. Technological innovations, miniaturization and the increase of energy sources, such as fiber laser Holmium, have improved the management of endoscopic instruments for upper urinary tract tumors. The endoscopic retrograde conservative treatment is considered a valid alternative approach in the case of low-stage tumors, low-grading and small in dimensions.

Fluorescence In Situ Hybridisation in the Diagnosis of Upper Urinary Tract Tumours

Fluorescence In Situ Hybridisation in the Diagnosis of Upper Urinary Tract Tumours

Evaluation of upper urinary tract tumors by FISH in Chinese patients

Upper urinary tract tumor (UUTT) usually presents a high grade and stage, and recurs frequently. The aim of this study was to evaluate the utility of a fluorescence in situ hybridization (FISH) assay on chromosomes 3, 7, 9, and 17 as a reliable and noninvasive method for the diagnosis of Chinese patients with UUTT. Urine specimens from 50 patients with UUTT and 25 donors without evidence of urothelial tumors were analyzed by cytology and FISH. Voided urine samples from 20 normal individuals were used to establish the cut-off values for FISH assay. The McNemar test was applied for sensitivity and specificity. The overall sensitivity of FISH was statistically significantly greater than that of cytology (84.0 vs. 40.0%, P=0.000). The overall specificities of FISH and urine cytology were all 96.0% ( P=1.000). Polysomy in chromosomes 3, 7, and 17 were 38, 42, and 30%, respectively. Heterozygous and homozygous loss of the p16 locus was found in 36 and 32%, respectively. FISH analysis performed on cells collected from voided urine is feasible, and FISH could prove to be a reliable and less invasive ancillary test and improve the sensitivity of urine cytology in the diagnosis of UUTT.

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...

Evolution on experimental animal model for upper urothelium carcinogenesis

No optimal, well designed and reproducible animal model for upper urothelial carcinogenesis exists. This study characterized the histopathological features on top of immunolocalization of alpha-dystroglycans (alpha-DG) and matrix metalloproteinase (MMP-9) and cell turn-over in the upper urinary tract using a novel experimental model. Seventy-five female Fischer 344 rats were divided into three groups: the control group received a 0.30-ml dose of 0.9% physiological saline; the MNU group (chemical carcinogen N-methyl-N-nitrosourea) received 0.30 ml of MNU; and the MNU-citrate group received 0.30 ml of MNU plus sodium citrate, every one intravesically every other week for a total of 4 doses. After 15 weeks, bladder, ureters and renal pelvis were collected for morphological and molecular analysis. Associated management with MNU and sodium citrate was able to lead to 100% of both urinary bladder and upper urinary tract tumors, being the high-grade noninvasive papillary urothelial carcinoma the most frequent lesion. The upper urothelium showed reduced alpha-DG and increased MMP-9 and Ki-67 immunoreactivities in the MNU-citrate group in relation to the other groups. MNU group presented no upper urothelium tumor and 100% bladder tumor. This is a relevant evolution on experimental animal model for upper urinary tract carcinogenesis field. MMP-dependent disruption of the DG complex plays an important role in urothelial tumor carcinogenesis and showed the model applicability and significance. MNU-citrate model could contribute to a better understanding of human upper urothelial cancer development as well as to its local treatment strategies in a near future.