Ureteritis cystica mimicking upper tract urothelial cancer in a patient with bladder cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Muraki PH
PROVIDER: S-EPMC8403544 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundDifferent genomic characterization in urothelial carcinoma (UC) by site of origin may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether differences between upper tract UC (UTUC) and UC of the bladder (UCB) result from intrinsic biological diversity.Materials and methodsWe prospectively sequenced 118 tumors and matched blood DNA from Chinese patients with UC using next-generation sequencing techniques, including 45 UTUC and 73 UCB. Two hundred twenty-six patients with UTUC and 350 patients with UCB for The Cancer Genome Atlas were acquired from the cbioportal.ResultsThere were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid was only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared with UCB, UTUC had higher clonal and subclonal mutation numbers. TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. Patients with UTUC had lower PD-L1 than those with UCB. There was no significant difference in the number of DDR mutations, copy number variation counts, and tumor mutational burden between UTUC and UCB.ConclusionUTUC and UCB exhibit significant differences in the prevalence of genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may imply the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB.Implications for practiceThis study's findings lay the foundation for a deeper understanding of distinct molecular mechanisms and similar treatment opportunities between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) and had important implications for the site-specific management of patients with urothelial carcinoma. A comprehensive understanding of the biology of UTUC and UCB is needed to identify new drug targets in order to improve clinical outcomes.
| S-EPMC8342585 | biostudies-literature
Project description:PURPOSE:To investigate genomic differences between urothelial carcinomas of the upper tract (UTUC) and bladder (UCB), with a focus on defining the clonal relatedness of temporally distinct tumors. EXPERIMENTAL DESIGN:We prospectively sequenced tumors and matched germline DNA using targeted next-generation sequencing methods. The cohort included 195 UTUC patients and 454 UCB patients. For a subgroup of 29 patients with UTUC and a history of a subsequent UCB, both tumors were analyzed to assess their clonal relatedness. RESULTS:With the progression to higher UTUC clinical state, there were fewer alterations in the RTK/RAS pathway but more alterations in TP53/MDM2. Compared with UCB, TP53, RB1, and ERBB2 were less frequently altered in UTUC (26% vs. 46%, 3% vs. 20%, 8% vs. 19%, respectively; Q < 0.001), whereas FGFR3 and HRAS were more frequently altered (40% vs. 26%, 12% vs. 4%, respectively; Q < 0.001). On the basis of an integrated analysis of tumor mutational burden, MSIsensor score and mutational signature, 7.2% of UTUC tumors were classified as MSI-high/MMR-deficient (MSI-H/dMMR). The risk of bladder recurrence after UTUC was significantly associated with mutations in FGFR3, KDM6A, CCND1, and TP53. Comparison of UCB with corresponding UTUC tumors from the same patient supports their clonal relatedness. CONCLUSIONS:UTUC and UCB exhibit significant differences in the prevalence of common genomic alterations. In individual patients with a history of both tumors, UCB and UTUC were always clonally related. Genomic characterization of UTUC provides information regarding the risk of bladder recurrence and can identify tumors associated with Lynch syndrome.
| S-EPMC6359971 | biostudies-literature
Project description:PURPOSE:A better understanding of the molecular basis of urothelial carcinoma (UC) is needed to refine the clinical decision-making process. METHODS AND MATERIALS:We performed next-generation sequencing to investigate the mutational and transcriptional profiles of commonly mutated genes in UC using Ampliseq v2. Copy number variations (CNVs) were detected with nCounter assay. Genetic alterations between upper tract UC (UTUC) and urinary bladder UC (UBUC) were compared. RESULTS:Tumor samples from 31 UTUC and 61 UBUC patients were included in analysis. The two groups showed similar clinicopathologic features including tumor grade and stage. Median survival was longer in UTUC than UBUC patients, though this was statistically nonsignificant (59 vs 41 months, P=.137). In total, we found 982 genetic alterations from 92 samples: single nucleotide variants were the most common type of somatic mutation (479/508, 94.3%). Frequently detected somatic mutations included TP53 (68.5%), KDR (41.3%), and PIK3CA (17.4%). Notably, RB1 mutations were the only mutations significantly different between the UBUC and UTUC groups (19.7% vs. 0%, P=.020). The most common types of CNVs included amplifications (56/62, 90.3%): 17.7% of patients identified amplifications in NOTCH1. We also identified five translocations in the entire study population, including one case with FGFR3-TACC3 (Chr4) fusion. CONCLUSION:Within a small study population, we identified similar genetic alterations in both UTUC and UBUC patients, indicating a basis for similar management strategies.
| S-EPMC5699894 | biostudies-literature
Project description:BackgroundFollowing radical nephro-ureterectomy for urothelial carcinoma of the upper urinary tract (UUT), the reported bladder recurrence rate of urothelial carcinoma is 22-47%. A single intravesical instillation of chemotherapy within 10 days following nephro-ureterectomy has the potential to decrease the risk of a bladder recurrence significantly. Despite recommendation by the European Association of Urology guideline to administer a single instillation postoperatively, the compliance rate is low because the risk of extravasation of chemotherapy.AimTo reduce the risk of bladder cancer recurrence by a single intravesical instillation of Mitomycin immediately (within 3?h) before radical nephro-ureterectomy or partial ureterectomy.MethodsAdult patients (age???18 years) with a (suspicion of a) urothelial carcinoma of the UUT undergoing radical nephro-ureterectomy or partial ureterectomy will be eligible and will receive a single intravesical instillation of Mitomycin within 3?h before surgery. In total, 170 patients will be included in this prospective, observational study. Follow-up will be according to current guidelines.ResultsThe primary endpoint is the bladder cancer recurrence rate up to two years after surgery. Secondary endpoints are: a) the compliance rate; b) oncological outcome; c) possible side-effects; d) the quality of life; e) the calculation of costs of a single neoadjuvant instillation with Mitomycin and f) molecular characterization of UUT tumors and intravesical recurrences.ConclusionsA single intravesical instillation of Mitomycin before radical nephro-ureterectomy or partial ureterectomy may reduce the risk of a bladder recurrence in patients treated for UUT urothelial carcinoma and will circumvent the disadvantages of current therapy.
| S-EPMC5898538 | biostudies-literature
Project description:Urothelial carcinomas (UC) arise from the urothelium that covers the proximal urethra, urinary bladder, and the upper urinary tract. In daily routine and clinical trials UC originating from different locations are often treated and investigated in the same manner. However, differences between the two locations seem to be apparent and may question in handling them as a single oncologic entity. In this review we discuss similarities and differences between bladder and upper urinary tract UC and consider their potential impact on treatment strategies. Despite similarities of UC in the bladder (BC) and the upper urinary tract (UTUC), clinicopathologic and molecular differences may question to generally assemble both as a single tumor entity. Treatment standards for UTUC are often adopted from BC. However, a specific investigation in the former may still be meaningful as shown by the example of adjuvant cisplatin based chemotherapy. In conclusion, future investigations should prioritize the understanding of the tumor biology of both BC and UTUC. This may reveal which UTUC can be treated according to treatment standards of BC and in which cases, a separate approach may be more appropriate.
| S-EPMC8575564 | biostudies-literature
Project description:Upper tract urothelial carcinoma (UTUC) is rare but aggressive with poor prognosis. We aimed to find effective predictive markers for recurrence and prognosis in UTUC patients. In this retrospective study, we included 88 UTUC patients treated with radical neprhoureterectomy (RNU) and analyzed their clinicopathological parameters. For study of incidence of metachronous bladder tumor, models were adjusted with inclusion of prophylactic intravesical instillation chemotherapy. The mean follow-up was 28.59 months (2 to 82 mo). Lack of gross hematuria (RR 0.060, 95%CI 0.008-0.468), tumor located at ureter (RR 0.037, 95%CI 0.004-0.378), advanced stage and higher p53 expression were independent factors for worse survival. Recurrence of bladder cancer occurred 20% of patients at median follow-up of 37.65 months (5 to 82 mo). Higher tumor grade (RR 5.998, 95%CI 1.359-26.479) and presence of ipsilateral non-functioning kidney at diagnosis (RR 5.982, 95%CI 1.338-26.750) were predictors for recurrence. The present study identified several parameters with predictive value in the prognosis and intravesicle recurrence in UTUCand shed light on the better monitoring and management of the disease.
| S-EPMC3915316 | biostudies-other
Project description:ObjectiveTo assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery.Patients and methodsData from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post-treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0-Ta-Tis-T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer-specific survival (CSS) was evaluated using Cox regression analyses.ResultsA pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC (P < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC (P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27-0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89-2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64-0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49-0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45-0.82; P < 0.01), but not with OS.ConclusionsOur present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer.
| S-EPMC8246716 | biostudies-literature
Project description:This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.
| S-EPMC7935810 | biostudies-literature
Project description:The risk of developing urothelial carcinoma of the bladder (UCB) in patients treated by radical nephroureterectomy (RNU) for an upper urinary tract urothelial carcinoma (UTUC) is 22% to 47% in the 2 years after surgery. Subject of debate remains whether UTUC and the subsequent UCB are clonally related or represent separate origins. To investigate the clonal relationship between both entities, we performed targeted DNA sequencing of a panel of 41 genes on matched normal and tumor tissue of 15 primary UTUC patients treated by RNU who later developed 19 UCBs. Based on the detected tumor-specific DNA aberrations, the paired UTUC and UCB(s) of 11 patients (73.3%) showed a clonal relation, whereas in four patients the molecular results did not indicate a clear clonal relationship. Our results support the hypothesis that UCBs following a primary surgically resected UTUC are predominantly clonally derived recurrences and not separate entities.
| S-EPMC7821318 | biostudies-literature
Project description:IntroductionPrior studies have shown genetic similarities between upper tract and bladder urothelial carcinoma. However, upper tract urothelial carcinoma tends to be higher grade than bladder urothelial carcinoma and tends to form in patients with certain familial conditions (e.g. Lynch Syndrome), indicating there may be unique biologic processes in these tumors. The purpose of this study was to evaluate the differences in gene expression between upper tract and bladder urothelial carcinoma using microarray data.Design, setting, participantsA search of publicly available microarray datasets identified a clinically annotated dataset of 12 upper tract and 20 bladder urothelial carcinoma specimens. Gene expression analysis of data derived from the Affymetrix HGU133Plus2 chip was performed. Bioconductor packages were used to evaluate clustering, differential gene expression, pathways relevant to oncology, and a basal/luminal signature in upper tract versus bladder urothelial carcinoma.ResultsWhen separated by pathologic T stage, there was evidence of differential clustering among pT3 tumors and significant gene expression differences in 81 genes. Pathway analysis revealed differences in HGF and TNF signaling pathways. Upper tract tumors tended to have high expression of genes associated with a luminal subtype. One of the genes most highly expressed in upper tract tumors, SLITRK6, is the target of an antibody drug conjugate (AGS15E) currently in phase I clinical trials.ConclusionsThis study provides evidence for molecular differences between upper tract and bladder urothelial carcinoma, some of which contribute to oncologic-relevant pathways. Upper tract tumors tended to express genes consistent with a luminal subtype. We also identify a marker, SLITRK6, as a potential target for patients with advanced upper tract urothelial carcinoma.
| S-EPMC4552875 | biostudies-literature