Transurethral Resection Of Bladder Tumor Specimens Research Articles

Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder Cancer.

CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for a subset of these tumors. Interestingly, CD47 overexpression is associated with negative clinical outcomes in lung and gastric cancers; however, the expression and functional significance of CD47 in bladder cancer is not fully understood. We retrospectively studied patients with muscle invasion bladder cancer (MIBC) who underwent a transurethral resection of bladder tumor (TURBT) and subsequently underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). CD47 expression was examined by IHC in both TURBT and matched RC specimens. The difference in CD47 expression levels between TURBT and RC was also compared. The association of CD47 levels (TURBT) with clinicopathological parameters and survival outcomes was evaluated by Pearson's chi-squared tests and the Kaplan-Meier method, respectively. A total of 87 MIBC patients were included. The median age was 66 (39-84) years. Most patients were Caucasian (95%), male (79%), and aged >60 (63%) and most often (75%) underwent NAC prior to RC. Of those who received NAC, 35.6% were responders and 64.4% were non-responders. The final reported stages as per AJCC for all patients were as follows: stage 0 (32%), stage 1 (1%), stage 2 (20%), stage 3 (43%), and stage 4a (5%). A total of 60% of patients were alive; of those, 30% had disease recurrence and 40% died from bladder cancer at a median follow-up of 3.1 (0.2-14.2) years. CD47 levels were detectable in 38 (44%) TURBT samples. There was no association between CD47 levels and clinicopathological parameters such as age, gender, race, NAC, final stage, disease recurrence, and overall survival (OS). Patients aged >60 (p = 0.006), non-responders (p = 0.002), and at stage ≥ 3 (p < 0.001) were associated with worse OS by a univariate analysis and stage ≥ 3 remained significant even after a multivariate analysis. In patients managed with NAC, there were decreased CD47 levels in RC specimens compared to the TURBT specimens, but this did not reach statistical significance. CD47 expression was not a predictive nor prognostic marker for MIBC patients. However, expression of CD47 was detected in nearly half of MIBCs, and future studies are needed to explore the potential role of anti-CD47 therapy in these patients. Furthermore, there was a slight positive trend in decreased CD47 levels (from TURBT to RC) in patients receiving NAC. As a result, more research is needed to understand how NAC may modify immune surveillance mechanisms in MIBC.

Implications for diagnosis and treatment strategies in non-muscle invasive bladder cancer with variant histology: a systematic review.

The identification of variant histology (VH) has been recognized as a critical element in the diagnostic pathway of bladder cancer (BCa), both for prognostic and therapeutic implications. However, the current evidence on the oncological outcomes of patients harboring VH BCa mostly derives from studies including muscle-invasive disease. Consequently, the correct management of patients with non-muscle invasive bladder cancer (NMIBC) and VH is limited and conflicting, and the optimal therapeutic approach remains therefore controversial. In this review, we aimed at reporting the current evidence on NMIBC with VH. Despite a constant increase in VH reporting at transurethral resection of bladder tumor (TURBT) specimens as compared to previous decades, we found that the incidence of VH is still sparse among studies. Furthermore, the agreement between TURBT and radical cystectomy (RC) specimens in VH identification is another matter of debate. Currently, most of the included studies report a poor overall concordance, especially for the micropapillary variant. Finally, while squamous and micropapillary variants are those associated with the worst survival outcomes, immediate RC is mostly considered for micropapillary tumors. Conversely, the survival benefit of immediate RC as compared to bladder-sparing approaches (i.e., BCG immunotherapy) for the other types of VH BCa is still an open question owing to the paucity of data available. Thus, in these patients, BCG treatment could be proposed considering the need for more intensive oncological surveillance.

Surgical checklist adherence across urology expertise levels impacts transurethral resection of bladder tumour quality indicators.

To address the association of perioperative surgical checklist across variable surgical expertise with transurethral resection of bladder tumour (TURBT) accuracy and oncological outcomes in non-muscle-invasive bladder cancer. We relied on our prospective collaborative database of patients treated with TURBT between 2012 and 2017. Surgical experience was stratified into three groups: resident vs young vs expert consultants. The association of surgical experience with detrusor muscle (DM) presence and adherence to the standardised peri-procedural nine-items TURBT checklist was evaluated with logistic regression models. A Cox regression model was used to investigate the association of surgical experience with recurrence-free survival (RFS). A total of 503 patients were available for analysis. TURBT was performed by expert consultants in 265 (52.7%) patients, by young consultants in 149 (29.6%) and by residents in 89 (17.7%). Residents were more likely to have DM in the TURBT specimen than expert consultants (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.03-2.99, P= 0.04). Conversely, no differences in DM presence were seen between young vs expert consultants (OR 1.09, 95% CI 0.71-1.70, P= 0.69). The median checklist completion rate was higher for both residents and young consultants when compared to experts' counterparts (56% and 56% vs 44%, P= 0.009). When focusing on patients receiving a second-look TURBT, the persistent disease was associated with resident status (OR 4.24, 95% CI 1.14-17.70, P= 0.037) at initial TURBT. Surgical experience was not associated with 5-years RFS. Surgeon's experience in the case of adequate perioperative surgical checklist implementation was inversely associated with the presence of DM in the specimen but directly linked to higher probability of persistent disease at re-TURBT, although no 5-year RFS differences were noted.

Predictive molecular biomarkers for determining neoadjuvant chemosensitivity in muscle invasive bladder cancer.

Identifying neoadjuvant chemotherapy (NAC) response in patients with muscle invasive bladder cancer (MIBC) has had limited success based on clinicopathological features and molecular subtyping. Identification of chemotherapy responsive cohorts would facilitate delivery to those most likely to benefit. Develop a molecular signature that can identify MIBC NAC responders (R) and non-responders (NR) using a cohort of known NAC response phenotypes, and better understand differences in molecular pathways and subtype classifications between NAC R and NR. Presented are the messenger RNA (mRNA) and microRNA (miRNA) differential expression profiles from initial transurethral resection of bladder tumor (TURBT) specimens of a discovery cohort of MIBC patients consisting of 7 known NAC R and 11 NR, and a validation cohort consisting of 3 R and 5 NR. Pathological response at time of cystectomy after NAC was used to classify initial TURBT specimens as R (pT0) versus NR (≥pT2). RNA and miRNA from FFPE blocks were sequenced using RNAseq and qPCR, respectively. The discovery cohort had 2309 genes, while the validation cohort had 602 genes and 13 miRNA differentially expressed between R and NR. Gene set enrichment analysis identified mitochondrial gene expression, DNA replication initiation, DNA unwinding in the R discovery cohort and positive regulation of vascular associated smooth muscle cell proliferation in the NR discovery cohort. Canonical correlation (CC) analysis was applied to differentiate R versus NR. 3 CCs (CC13, CC16, and CC17) had an AUC &gt;0.65 in the discovery and validation dataset. Gene ontology enrichment showed CC13 as nucleoside triphosphate metabolic process, CC16 as cell cycle and cellular response to DNA damage, CC17 as DNA packaging complex. All patients were classified using established molecular subtypes: Baylor, UNC, CIT, Lund, MD Anderson, TCGA, and Consensus Class. The MD Anderson p53-like subtype, CIT MC4 subtype and Consensus Class stroma rich subtype had the strongest correlation with a NR phenotype, while no subtype had a strong correlation with the R phenotype. Our results identify molecular signatures that can be used to differentiate MIBC NAC R versus NR, salient molecular pathway differences, and highlight the utility of molecular subtyping in relation to NAC response.

Proposal for a New Vesical Imaging-Reporting and Data System (VI-RADS)-Based Algorithm for the Management of Bladder Cancer: A Paradigm Shift From the Current Transurethral Resection of Bladder Tumor (TURBT)-Dependent Practice.

Transurethral resection of bladder tumor (TURBT) is the essential first step in the current algorithm for the management of bladder cancer (BC). However, despite its necessity and significance, TURBT has several limitations, including cost, hospitalization, anesthesia, potential complications such as bladder perforation, and delay to radical cystectomy. The Vesical Imaging Reporting and Data System (VI-RADS) was developed to standardize the reporting of multiparametric magnetic resonance imaging for BC, and its diagnostic accuracy to predict muscle invasion has been validated. Given the high sensitivity of VI-RADS ≥ 3 and high specificity of VI-RADS ≥ 4 as clinically relevant cutoff values, we herein propose a new VI-RADS-based algorithm for the management of BC. Using this algorithm, patients with VI-RADS ≤ 2 may not need to undergo sampling of the detrusor muscle nor second TURBT even if there is no muscle in the initial TURBT specimen, whereas patients with VI-RADS ≥ 4 may skip conventional TURBT aimed at pathologic confirmation of muscle invasion and immediately undergo radical cystectomy. Our newly proposed algorithm enables the avoidance of unnecessary deep resection or second TURBT as well as delay to radical cystectomy. The VI-RADS-based algorithm enables a paradigm shift from the current TURBT-dependent practice in the management of BC.

SARCOMATOID UROTHELIAL CARCINOMA OF BLADDER - A RARE HISTOLOGICAL VARIANT

Introduction: Urothelial carcinoma (UC) is the most common histological type of bladder cancer. Around 75% of bladder cancers are classified as pure UC, and 25% are urothelial and nonurothelial histological variants. Sarcomatoid UC is a rare variant, accounts for 0.1%–0.3% of all urothelial carcinomas of bladder. It is a biphasic malignant neoplasm with morphologic and immunohistochemical evidence of both epithelial and mesenchymal differentiation. Objective: To study the histomorphological and immunohistochemical features of sarcomatoid urothelial carcinoma. Methods: We received TURBT (Trans Urethral Resection of Bladder Tumor) specimen for histopathological evaluation in the department of pathology, DY Patil medical college, Kolhapur. Routine tissue processing of bits was done and H &amp; E stained sections were subjected for detailed microscopic evaluation and various immunohistochemical markers were applied on the paraffin embedded tissue blocks. Results: A95years old female patient presented with hematuria and anemia.On cystoscopy polypoidal lesion seen in the lateral wall of urinary bladder.No history of previous surgery on urinary bladder.TURBT done. On gross, there were multiple, irregular, grey white strips of tissue altogether weighing 160gms. On microscopy, neoplasm with papillary architecture was seen invading lamina propria. Chondromyxoid, rhabdoid and malignant fibrohistiocytic tumor like areas noted. Immunohistochemical workup revealed positive staining with cytokeratin, vimentin and GATA3 and negative with H-Caldesmon, SMA and Myogenin. Conclusion: Sarcomatoid UC is seen in elderly. Morphologically, the lesion mimics sarcoma, immunohistochemistry workup aids in definitive diagnosis, as it has poor prognosis compared to pure UC.

Closed-loop audit of muscle sampling in Trans-Urethral Resection of Bladder Tumour

Introduction: Our experience with the presence of detrusor muscle (DM) following Trans-Urethral Resection of Bladder Tumour (TURBT). Objectives: To evaluate the presence of DM in primary TURBT specimens as a quality improvement exercise in Frimley Park Hospital, UK. And to assess if the level of the surgeon has impact on outcomes. Methods: Retrospective and prospective analysis of the electronic records from a single urology centre, servicing a group of urologists. Data collected over three consecutive audit loops between January 2014 and May 2018. Results: A total of 301 cases were performed under the care of seven consultant urologists. Analysis revealed a significant improvement in the overall quality of resections from 39% to 66% (50–84% for intermediate and high grade) after the introduction of the following interventions: (1) analysis and improved awareness of current practice; (2) introduction of European Association of Urology (EAU) guidelines by separating samples and sending a second specimen pot marked as bladder tumour base to look for DM; (3) dedicated urologists with an interest in bladder cancer performing en-bloc resection technique in appropriate cases. Conclusion: Through our closed-loop audits, we have demonstrated a considerable improvement in the quality of resections, resulting in accurate staging from the initial resection. This could in turn lead to improved over all prognoses and negating the need for re-resection in all cases of high-risk non-muscle invasive bladder cancer (NMIBC). Level of evidence: 3

English

BACKGROUND Urinary bladder cancer is associated with high morbidity and mortality rates if not treated optimally. One of the causes of tumour recurrence is undiscovered residual tumour, and the existence of macroscopically invisible premalignant and malignant lesions of urothelium during the primary resection which can be detected by taking biopsy from apparently normal mucosa in the vicinity of the tumour during trans urethral resection of bladder tumour (TURBT). The primary objective was to estimate the proportion of bladder tumour showing changes in adjacent non tumour mucosa in TURBT specimens, within a period of six months. The secondary objectives were to study the association between changes in non-tumour bladder mucosa with the recurrence, seen after six months, and to study the expression of P53 in adjacent non tumour mucosa of bladder cancer. METHODS All cases of bladder carcinoma from trans urethral resection of bladder tumour which were sent along with adjacent non tumour mucosa and received at Department of Pathology, MCH, Trivandrum, for a period of six months were included in the study. Adjacent mucosa sent along with TURBT specimen received at our department was collected. After processing, tissue is embedded in paraffin blocks and thin sections of 4 - 5 m thickness was taken and stained with haematoxylin and eosin (H &amp; E). Using light microscopy, changes in adjacent mucosa were assessed for any abnormal changes and findings were correlated with collected data. P53 expression was studied in the adjacent mucosa. All details were entered in the proforma. Details collected were entered in Excel and analysed using SPSS software. RESULTS Out of 37 TURBT cases that were sent along with adjacent mucosa, 12 cases showed changes in adjacent mucosa accounting for 32.4 %. P53 positivity accounting for 18.9 %, was seen in abnormal mucosa change with carcinoma in situ and dysplasia. On follow up, 8 % of cases with positive biopsy finding showed recurrence. CONCLUSIONS Multiple biopsies from adjacent non tumour mucosa is not necessary for all patients with superficial bladder tumour. Positive findings in adjacent mucosa does not have significant correlation with tumour stage / grade, and tumour size, number of lesions or histopathological findings. Adjacent mucosa may be useful in detecting concomitant carcinoma in situ (CIS), which can be helpful in therapeutic approach. KEY WORDS Normal Looking Mucosa, TURBT, Bladder Cancer

Association of immunohistochemical markers of tumor subtype with response to neoadjuvant chemotherapy and survival in patients with muscle-invasive bladder cancer.

PurposeA readily accessible biomarker to identify which patients with bladder cancer are more likely to respond to neoadjuvant chemotherapy (NAC) could help clinicians avoid unnecessary chemotherapy and prevent its subsequent complications in some patients. The primary objective of this study was to investigate the association of immunohistochemical markers of tumor subtype with response to NAC and survival of patients with muscle-invasive bladder cancer (MIBC).Materials and MethodsMIBC patients treated with NAC were retrospectively included. The tissue microarrays were assembled from transurethral resection of bladder tumor (TURBT) specimens and immunohistochemistry (IHC) was performed. The association of independent variables, including IHC markers, and clinical covariates with clinical complete response to NAC and with overall survival was assessed by using logistic regression and Cox proportional hazard regression analysis, respectively. Kaplan-Meier curves were plotted for different IHC-based tumor subtypes.ResultsData from 140 MIBC patients treated with NAC were retrospectively reviewed. A total of 63 patients with available TURBT specimens were eligible to be included in the analysis. Our results showed that the IHC signature of KRT5/6(+)/KRT20(−), as a combined marker of basal subtype, was the only covariate significantly associated with complete response to NAC (p=0.037). Moreover, we found no statistically significant differences in overall survival between different IHC-based subtypes (p=0.721).ConclusionsThe IHC expression of KRT5/6 and KRT20, as a readily accessible combined marker, may help us to identify the patients most likely to benefit from chemotherapy. The clinical utility of this marker needs to be established in larger prospective studies.

Assessing the Impact of the Absence of Detrusor Muscle in Ta Low-grade Urothelial Carcinoma of the Bladder on Recurrence-free Survival

BackgroundObtaining detrusor muscle (DM) in transurethral resection of bladder tumor (TURBt) specimen is considered a surrogate marker of resection quality. However, evidence was principally investigated in high-risk tumors. Therefore, DM sampling for low-grade (LG) urothelial carcinoma (UC) remains poorly investigated and certainly requires further investigation. ObjectiveTo assess whether the absence of DM in TURBt specimen has a negative impact on recurrence-free survival (RFS) in patients with a Ta LG UC. Design, setting, and participantsA multicenter TURBt database was queried for “LG, Ta, UC of the bladder.” All patients treated between 1996 and 2018 with tumor grade assessed according to both 1973 World Health Organization and 2004 WHO/International Society of Urological Pathology grading classifications and with a minimum follow-up of 1 yr were included. Patients with a previous history of high-grade UC, upper urinary tract UC, or bladder tumor differentiations other than UC were excluded. InterventionTURBt. Outcome measurements and statistical analysisBaseline demographic, clinical, and pathologic data were analyzed. The European Organization for Research and Treatment of Cancer (EORTC) risk group was recorded. Kaplan-Meier analysis was performed to assess the predictive role of clinical and pathologic data for RFS. Univariable and multivariable Cox regression analyses were performed to identify the predictors of recurrence. Results and limitationsOverall, 521 patients were included. At Kaplan-Meier analysis, the low-risk cohort displayed significantly higher RFS than the intermediate-risk cohort (1-yr RFS 87% vs 79%; log-rank p = 0.007). At univariable Cox regression analysis, only gender, multiple tumors, tumor diameter ≥3 cm, and EORTC risk group were significant predictors of recurrence. Absence of DM had no impact on RFS. Multivariable Cox regression analysis confirmed gender and EORTC risk group as independent predictors of recurrence. ConclusionsAbsence of DM in TURBt specimen has negligible role in RFS of patients with Ta LG tumors of the bladder. Patient summaryIn this study, we assessed the role that detrusor muscle (DM) in transurethral resection of bladder tumor specimen has in recurrence-free survival, in patients with a Ta low-grade urothelial carcinoma of the bladder. Absence of DM has no impact on tumor recurrence; therefore, it does not require additional attention.

Detrusor muscle in the initial TURBT specimen and recurrence rate at first check cystoscopy in non-muscle invasive bladder cancer

Introduction The presence of detrusor muscle (DM) is an essential component in “complete” transurethral resection of bladder tumour (TURBT) specimen. This study analyses patients who were subjected to a “complete” first TURBT to determine the presence/absence of DM in the specimen. Methodology Newly diagnosed non-muscle invasive bladder cancer (NMIBC) from 1-April-2007 to 31-March-2017(10-years) were retrospectively analysed at National Hospital of Sri Lanka. All TURBTs performed at initial diagnosis were analysed to determine the presence of DM in the specimen, the recurrence rate at first check cystoscopy (FCC) at 3 months and the association with surgeon's experience. Results Of 181 TURBT, 99(54.7%) were done by Consultant Urological Surgeon (CUS) and 82(45.3%) by senior registrars (SR). The overall DM positivity rate was 59.7% (n= 108/181), for CUS: 63.6% (n=63/99) and SRs 54.9% (n=45/82) (p=0.232); for pTa tumours:-CUS: 46.5%vs.SRs:50 %( p=0.751) and for pT1 tumours:-CUS: 76.8%vs.SRs:59.5 %( p=0.067). Analysis of those who were followed up (145/181, 80.1%) showed a positive recurrence at FCC in 27.1 %( 23/85) and 30.0 %( 18/60) when DM was present and absent in the first TURBT specimen respectively (OR=0.87(95%-CI: 0.41-1.8, p=0.7). Conclusion Clinically, DM positivity rate has prognostic significance only in the pT1 category of NMIBC. For pT1 tumours, the positive DM rates for the CUS and SRs were 76.8% and 59.5% respectively. The indifference in the recurrence rate may be due to the considerable proportion of lost to follow up in our study. Nevertheless, measures should be taken to enhance the DM positivity rates among urologists to achieve accurate staging and better prognosis.

A Rare Case of Polypoidal Cystitis in Adult without History of Prolong Catheterization

Introduction: Polypoidal cystitis is a rare lesion of the bladder mucosa characterized by benign exophytic inflammation,epithelial proliferation and development of polypoid mass without evidence of neoplasm histologically. Polypoid cystitis is rarely seen in patient without prolong used of indwelling catheter. Other cases of polypoidal cystitis are associated with post-radiation, post chemotherapy bladder reaction, colovesicular fistula are extremely rare. Case Report: 66 year old Malay male ,underlying hypertension and Benign Prostatic Hyperplasia (BPH) on treatment, complaining of difficulty in urination, straining on voiding for the past 6 months and on and off  hematuria for the past 2 months. He denied any history of CBD insertion or prolong cataheterization. Blood investigations are Normal. X-Ray KUB showed unremarkable. Ultrasound KUB revealed Prostatomegaly, no evidence of renal or ureteric calculi or evidence of Obstructive uropathy,No obvious bladder mass. Cystoscopy Examination (CE) showed enlarged occlusive prostate and noted bladder growth at base of bladder. The growth is malignant looking however no active bleeding seen. No bladder stone seen. Patient subsequently underwent TransUrethral Resection of Bladder Tumor (TURBT) and Trans-Urethral Resection of Prostate (TURP) in same setting. Intra operatively was uneventful. HistoPathological Examination (HPE) from TURBT specimens showed in favour of Polypoidal Cystitis and TURP revealed Nodular Hyperplasia. Discussion: Polypoidal Cystitis is a form or chronic cystitis characterized by exophytic inflammatory  lesion of bladder mucosa. The polypoidal mass is mimicking neoplasm. At the initial evaluation, it may be confused with transitional cell carcinoma of the urinary bladder, especially in patient without an indwelling catheter. The most common aetiology of this condition is long-standing indwelling catheterization.. There is also reported that any factors that irritates the bladder mucosa may result in Polypoidal Cystitis.  In our patient ,there was no history of such other causes, including prolong catheterization, fistula, urinary calculi or radiation therapy.

An insight into non transitional cell carcinoma of Bladder: A six year retrospective study

Non transitional cell carcinomas comprise 5 – 10% of all malignant bladder tumours. A retrospective study was done in 50 cases of TUR-BT (transurethral resection of bladder tumour) and radical cystectomy specimens for a period of 6 years at a tertiary care hospital. The various details analysed were the presenting complaints, age, sex, cystoscopy findings, radiological findings, urine cytology findings, gross morphology and microscopic findings. Non transitional cell carcinomas reported were squamous cell carcinoma, adenocarcinoma (papillary, mucinous and clear cell types) and sarcomatoid carcinoma.

Identifying predictors of pathologic complete response to neoadjuvant chemotherapy for muscle invasive bladder cancer.

e16015 Background: Pathologic complete response (pCR) to neoadjuvant chemotherapy is associated with improved outcome in patients (pts) with muscle invasive and/or lymph node positive (LN+) bladder cancer. Although molecular predictors are currently being evaluated, limited information is available regarding purely clinical parameters offering predictive information regarding pCR to neoadjuvant chemotherapy. Methods: We identified 189 unique pts within Kaiser Permanente Northern California diagnosed with bladder cancer during 1/1/10 through 12/31/17 who underwent chemotherapy with neoadjuvant intent with a plan for subsequent radical cystectomy. All pts had disease that was ≥cT2 and/or ≥cN1 and M0. Fourteen variables were examined for their association with pCR at radical cystectomy, using bivariate analysis and multivariate models. Results: Of the 189 pts in our cohort, 141 (74.6%) were male, 162 (85.7%) were white and the mean age was 66.4 years. 76 (40.2%) pts achieved pCR; of these, 59 (77.6%) had pre-treatment hemoglobin (hg) ≥ 13 g/dL (p = 0.0087), 69 (90.8%) did not have hydronephrosis (p &lt; 0.0001), 66 (86.8%) had no lymphovascular invasion (LVI) on transurethral resection of bladder tumor (TURBT) (p = 0.0506) and 69 (90.8%) had cT2 disease at time of diagnosis (p &lt; 0.0001). Logistic regression analysis showed that pCR was associated with hg ≥ 13 (OR 2.736, 95% CI 1.188-6.657), absence of hydronephrosis (OR 4.672, 95% CI 1.820-13.554), age ≤ 75 years (OR 3.410, 95% CI 1.263-10.057), absence of LVI on TURBT (OR 2.592, 95% CI 1.055-6.829), and clinical stage T2 vs. ≥T3 and/or N+ (OR 6.480, 95% CI 2.645-17.858). There was no statistically significant relationship between pCR and the following variables: cumulative cisplatin dose, split dose chemotherapy, chemotherapy regimen, history of tobacco use, race, gender, Charlson comorbidity score, baseline alkaline phosphatase, and percentage body weight loss during therapy. Conclusions: Pathologic CR was predicted by Hg &lt; 13 g/dL, absence of hydronephrosis, age ≤ 75 yrs, absence of LVI on TURBT specimen, and stage at diagnosis. These factors may influence selection of pts with muscle invasive and/or LN+ bladder cancer for neoadjuvant chemotherapy.

Diagnostic utility of GATA3 immunohistochemical expression in urothelial carcinoma.

This study aims to explore the utility of GATA binding protein 3, a zinc finger transcription factor, expression in genitourinary carcinoma, especially urothelial carcinoma. It is a prospective study where 74 consecutive cases of urothelial carcinoma along with 10 cases each of prostatic adenocarcinoma (PC) and conventional clear cell renal cell carcinoma were included between August 2016 and January 2017. All the cases were histopathologically evaluated and immunohistochemically stained for GATA binding protein 3. Only nuclear positivity was considered as positive. Immunoreactivity score for GATA expression was calculated based on the staining intensity as well as percentage. The statistical analysis was done using Statistical Package for Social Sciences Version 15.0 statistical analysis software. P value of <0.05 was considered statistically significance. GATA3 expressions were seen in 77% of the cases of urothelial carcinoma, whereas none of the clear cell renal cell carcinoma and prostatic adenocarcinoma cases was GATA3 positive. GATA3 expression significantly correlated with histological grade and muscle invasion with a weaker or negative expression in high-grade muscle invasive tumor as compared to low-grade and noninvasive neoplasm. Significantly weaker expression of GATA3 was found in cases with severe nuclear pleomorphism, mitosis >10/10 hpf, presence of necrosis, and tumor-infiltrating lymphocytes. No significant change in the status of GATA3 expression was seen in follow-up cases between initial Transurethral resection of bladder tumor (TURBT) and post-recurrence TURBT or radical cystectomy specimens. GATA3 as a sensitive and specific marker for urothelial carcinoma can be effectively used to exclude other genitourinary malignancies, PC, and renal cell carcinoma, at metastatic site. This marker can also be effectively used in predicting the probable grade and invasion in biopsy material with poor morphological characteristics, thereby helping in appropriate management in such cases.

Surgical checklist impact on recurrence-free survival of patients with non-muscle-invasive bladder cancer undergoing transurethral resection of bladder tumour.

To evaluate the impact of an eight-item surgical checklist (SC) on the recurrence-free survival (RFS) of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing transurethral resection of bladder tumour (TURBT). A group of urologists at two tertiary referral centres, with expertise in bladder cancer, identified eight critical items that should be performed in every high-quality TURBT. An eight-item SC was prospectively implemented into clinical practice and the operative reports of TURBTs performed before and after implementation were reviewed. Results from both institutions were combined to estimate the impact of introducing the SC on oncological outcomes. Multivariable logistic and Cox hazards regression analyses were performed to evaluate the impact of the SC on the presence of detrusor muscle in the TURBT specimen and on RFS, respectively. The operative reports of 266 TURBTs performed after the SC implementation were reviewed and compared to those of 281 TURBTs performed prior to the SC introduction. The SC was independently associated with a significant improvement in RFS (P = 0.02). However, the introduction of the SC was not significantly associated with the presence of detrusor muscle in the surgical specimen (P = 0.4). The use of an eight-item SC during TURBT in clinical practice increases the quality of operative reports thereby potentially improving individualised risk-stratification and care resulting in lower disease recurrence rates. Therefore, the introduction of a SC can be recommended to enhance oncological outcomes by improving surgical standardisation and operative reporting.

NACC1, as a Target of MicroRNA-331-3p, Regulates Cell Proliferation in Urothelial Carcinoma Cells.

The nucleus accumbens-associated protein 1 (NACC1) is a transcription factor constitutively expressed in the urothelium, where it regulates cell growth, senescence, autophagy, and epithelial-mesenchymal transition. microRNA (miRNA) constitutes a class of small non-coding RNAs which are involved in cell proliferation, differentiation, and progression of tumors. miRNAs and their target molecules are utilized for molecular diagnosis of urothelial carcinoma. NACC1 is one of several putative target molecules of miR-331-3p, and is associated with cell proliferation in cancers such as prostate and cervical cancer. Functional experiments involving miR-331-3p and its target molecule NACC1 were conducted using the urothelial carcinoma (UC) cell lines, T24, UMUC6, and KU7. Furthermore, quantitative reverse transcription polymerase chain reaction and immunostaining were performed to evaluate the expression of NACC1 in UC derived from transurethral resection of bladder tumor (TUR-Bt) specimens. The methane thiosulfonate (MTS) assay revealed that cell proliferation was significantly reduced after transient transfection of miR-331-3p precursor and/or NACC1 siRNA in UC cells. Cell senescence via cell cycle arrest at the G1 phase was induced by NACC1 inhibition. On the other hand, suppression of NACC1 induced cell migration and invasion abilities. Immunohistochemical analysis of TUR-Bt specimens revealed that over 70% of UC cells presented strongly positive results for NACC1. In contrast, normal urothelial cells were weakly positive for NACC1. It was also found that NACC1 expression was lower in invasive UC cells than in non-invasive UC cells. Loss of NACC1 induced vessel invasion in invasive UC tissues. The present results indicate that NACC1 regulated by miR-331-3p contributes to cell proliferation, and is involved in cell migration and invasion. This suggests that NACC1 can serve as a potential target molecule for the prediction and prognosis of UC, and can contribute to effective treatment strategies.

The pathologist's role in the detection of rare variants of bladder cancer and analysis of the impact on incidence and type detection.

Histology is one of the most important factors determining the prognosis of bladder cancers and rare variants are generally associated with decreased disease specific survival compared to pure transitional cell carcinomas. We believe that rare bladder cancer variants are likely underdiagnosed in the absence of a dedicated uro-pathologist in many centers. The objective of this study is to evaluate the contribution of a dedicated uro-pathologist on the identification of rare bladder cancer variants. We retrospectively analyzed the clinical and histological records of all patients which underwent a radical cystectomy and lymph node dissection between January 2000 and September 2015. The sample was divided in two groups: Group A, consists of patients who underwent radical cystectomy in the absence of a dedicated uro-pathologist at our institution, whereas the Group B consists of patients who underwent surgery when a dedicated uro-pathology service was available. We then evaluated the impact of a dedicated uro-pathologist on rare variants detection. One hundred thirty-seven out of 551 (24.9%) of patients who underwent RC had at least one rare variant. In Group A 38/238 (16%) of patients showed a rare variant, while 99/313 (31.6%; P<0.001) in group B. Furthermore, the diagnosis of sarcomatoid variant was statistically significantly less common in group A (P=0.0026). The concordance between final radical cystectomy histology and previous transurethral resection of bladder tumor (TURBT) histology was poor in both groups (overall 50.4%). The presence of a dedicated urological anatomical pathologist is of paramount importance and significantly increases the detection rate of non-transitional cell carcinoma bladder cancer types, but it does not increase the concordance rate between histological diagnoses in TURBT and radical cystectomy specimens.

Abstract 3423: Determining neoadjuvant cisplatin-based chemosensitivity in muscle invasive bladder cancer through differential gene and miRNA expression analysis

Abstract Background: Muscle invasive bladder cancer (MIBC) neoadjuvant responders as opposed to nonresponders demonstrated significantly improved 5-year cancer specific survival and reduced nodal positivity rates. Identification of chemo responsive cohorts would not only facilitate targeted delivery of chemotherapy to those most likely to benefit, but also avoid morbidity and delayed surgical intervention in patients unlikely to derive benefit. We evaluated the role of gene and miRNA expression profiles in initial TURBT (transurethral resection of bladder tumor) specimens of patients before undergoing neoadjuvant chemotherapy and subsequent radical cystectomy. Pathological response at time of cystectomy was used to classify initial TURBT specimens as responders (pT0) versus non-responders (≥pT2). Differential expression of gene and miRNA between the two groups may help stratify patients being considered for neoadjuvant chemotherapy. Methods: TURBT specimens from patients with MIBC were preserved in FFPE tissue blocks before patients subsequently received cisplatin-based neoadjuvant chemotherapy. A total of 13 pT0 and 17 ≥pT2 patients were selected and matched for age, gender and tumor stage. RNA was extracted from FFPE blocks using an Ambion total nucleic acid isolation kit. mRNA was sequenced using Illumina TruSeq RNA Access Library and NextSeq technology. Gene counts were assessed by ht-seq counts and differential expression using DESeq2. Pathway analysis was performed using GAGE. Differential expression of 754 miRNAs was analyzed using the TaqMan openarray miRNA panel. Results: In responders, a gene-set enrichment analysis revealed significant upregulation of genes in the hsa00190 pathway (implicated in oxidative phosphorylation), hsa03040(spliceosome function). In non-responders, there was significant upregulation of genes in the hsa04510 pathway (focal adhesion), hsa04512 (ECM-receptor interaction), hsa04310(Wnt signaling), hsa04350(TGF-beta signaling) and hsa04010 (MAPK signaling). For the miRNA analysis, significant upregulation of miR-23a, miR-27a, miR-135b, miR-145, miR-422a was seen in responders, and miR-93, miR-107, miR-339-3p, miR-532 in non-responders. Using a random forest classification, a significant proportion of non-responders were correctly identified compared to responders. Conclusion: Gene and miRNA expression in initial MIBC TURBT specimens may be used as an aid in predicting neoadjuvant non-responders. Increasing the sample size is needed to further validate our findings and may lead to a successful chemotherapy prediction model. Citation Format: Neal Murphy*, Paras Shah*, Annette Lee, Thomas Bradley, Manish Vira, Ilya Korsunsky, Andrew Shih, Oksana Yaskiv, Zachary Kozel, Anthony Liew, Houman Khalili, Xinhua Zhu. Determining neoadjuvant cisplatin-based chemosensitivity in muscle invasive bladder cancer through differential gene and miRNA expression analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3423.

MP10-18 CREATION OF A QUALITY-IMPROVEMENT DATABASE FOR TRANSURETHRAL RESECTION OF BLADDER TUMORS

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation II1 Apr 2017MP10-18 CREATION OF A QUALITY-IMPROVEMENT DATABASE FOR TRANSURETHRAL RESECTION OF BLADDER TUMORS Jason Cohen, Alex Glaser, Leslie Okorji, Daniel Oberlin, and Joshua Meeks Jason CohenJason Cohen More articles by this author , Alex GlaserAlex Glaser More articles by this author , Leslie OkorjiLeslie Okorji More articles by this author , Daniel OberlinDaniel Oberlin More articles by this author , and Joshua MeeksJoshua Meeks More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.346AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Presence of muscle in transurethral resection of bladder tumor (TURBT) specimens is an important indication of quality of endoscopic resection. The presence or absence of muscle should be noted by the pathologist, and a sample is usually only considered adequate if there is muscle present. The objective of this study is to create natural language processing to evaluate the quality of TURBT specimens amongst many surgeons at a large institution. METHODS The Enterprise Data Warehouse at Northwestern University was used to perform a retrospective analysis of patients undergoing TURBT over 10 years. Natural language processing was used to extract stage, grade, and muscle presence information from TURBT pathology reports. Initial construction of programming language was performed using a manually-created training set of 867 TURBTs. Outcomes included (1) rates of pathology reports mentioning the presence or absence of muscle, and (2) for pathology reports that mentioned muscle, rates of muscle presence in the surgical specimen. Since tumors that were cT2 involved muscle, these were excluded from the analysis. Logistic regression analysis was performed to determine associations with muscle being mentioned and present. RESULTS 3042 TURBTs from 1324 patients performed by 20 surgeons were included in the database. Validation of 150 randomly-selected data points generated with our algorithm revealed accuracy of 98.7%. Muscle was mentioned in 72% of all 2918 TURBTs stage <T2. Muscle was more likely to be mentioned in patients with T1 disease than Ta, CIS, or no cancer (Table 1). In the 2099 reports that mentioned muscle, only 50% of patients with T1 had muscle in the specimen, but patients with T1 disease were more likely to have muscle than Ta disease (Table 1). Mention of muscle in the pathology report was associated with T1 disease (OR 6.9, 95% CI 4.4-10.8, p<0.01) and oncology-fellowship-trained surgeon (OR 2.2, 95% CI 1.7-2.9, p<0.01). CONCLUSIONS Automated natural-language processing algorithm was used to create a TURBT database for quality improvement. Patients with T1 disease are more likely to have muscle mentioned and present in the report, and variations in muscle sampling exist amongst surgeons. This algorithm could be portable among medical systems and allow for large-scale quality initiatives between institutions. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e115 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Jason Cohen More articles by this author Alex Glaser More articles by this author Leslie Okorji More articles by this author Daniel Oberlin More articles by this author Joshua Meeks More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...