Non-muscle Invasive Bladder Tumors Research Articles

BCG immunotherapy response associated immune transcriptomic and spatial immune profiles of non-muscle invasive bladder tumors

Abstract Bladder cancer is a management-intensive disease that leads to ~200, 000 deaths worldwide every year. Upon initial diagnosis, approximately 75% of cases are categorized as non-muscle-invasive bladder cancer (NMIBC). Adjuvant Bacillus Calmette-Guérin (BCG) immunotherapy is the gold standard treatment for high risk NMIBC patients. Despite being used for over 40 years, many BCG patients exhibit tumor recurrence, a subset of which display progression to a muscle-invasive form of the disease that requires undesired bladder removal surgery. We recently demonstrated that the interferon response induced by BCG could be further complemented via synergistic activation of the Stimulator of Interferon Genes (STING) pathway. Towards clinical translation of this combinatorial immunomodulation and in order to determine immune biomarkers associated with response to BCG, we retrospectively investigated the immune transcriptomic profiles of tumors from BCG responders and non-responders. Interestingly, tumors from BCG non-responders showed a higher immune cell abundance and higher immune checkpoint gene expression. To further independently validate the transcriptomic findings at protein levels, we conducted spatial immune profiling of 12 immune cell markers (Ki-67+, CD8+ proliferating T cells, FoxP3+ T regulatory cells, CD79+ B cells, PD-1, PD-L1 and IDO1 immune checkpoints, CD68+ and CD163+ M1 and M2 macrophages) in a cohort of 571 NMIBC tumors. Preliminary findings showed that tumors from BCG non-responders are characterized by infiltration of immunosuppressive T regulatory cells. Findings from this study will have the potential to guide future immune biomarker guided immunomodulatory treatment combinations.

MP17-18 GEMCITABINE PROMOTING CCL2 SECRETION BY BLADDER CANCER CELL RECRUITED MDSCS INTO TUMOR MICROENVIRONMENT

INTRODUCTION AND OBJECTIVE:Bladder cancer (BC) is one of the most common malignant tumors of the urinary tract in China, 75% to 85% of which are grouped as non-muscle invasive bladder tumors. Gemci...

MP17-03 MICRORNA LET-7F-5P IS A NOVEL BIOMARKER OF RECURRENCE AND A POTENTIAL THERAPEUTIC OPPORTUNITY IN NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology II (MP17)1 Apr 2020MP17-03 MICRORNA LET-7F-5P IS A NOVEL BIOMARKER OF RECURRENCE AND A POTENTIAL THERAPEUTIC OPPORTUNITY IN NON-MUSCLE INVASIVE BLADDER CANCER Kevin Shee*, Carmen J Marsit, Alan R Schned, Jason Pettus, David A Armstrong, Margaret R Karagas, Todd W Miller, John D Seigne, and Angeline S Andrew Kevin Shee*Kevin Shee* More articles by this author , Carmen J MarsitCarmen J Marsit More articles by this author , Alan R SchnedAlan R Schned More articles by this author , Jason PettusJason Pettus More articles by this author , David A ArmstrongDavid A Armstrong More articles by this author , Margaret R KaragasMargaret R Karagas More articles by this author , Todd W MillerTodd W Miller More articles by this author , John D SeigneJohn D Seigne More articles by this author , and Angeline S AndrewAngeline S Andrew More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000842.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 50% to 75% of patients with non-muscle invasive bladder cancer (NMIBC) experience recurrences within 6 to 12 years of diagnosis, and the cost of screening makes bladder cancer one of the most expensive malignancies. The objective of this study was to identify reproducible prognostic miRNAs in resected non-muscle invasive bladder tumor tissue that are predictive of the recurrent tumor phenotype as potential biomarkers and molecular therapeutic targets. METHODS: NMIBC patient tumors from the New Hampshire Population Cohort (n=178) and Dartmouth Hitchcock Medical Center (n=38) were assayed for ∼800 miRNAs. Recurrence free survival (RFS) analyses using a multivariable model adjusted for sex, age, multiplicity, tumor size, stage, and grade were performed. Urine and plasma samples were obtained from available patients from the validation cohort and analyzed for miRNA expression. Lin28, a known negative regulator of Let-7f-5p, Lin28 primers and small molecule inhibitor Lin28 1632 were obtained and assayed using RT-PCR, cell viability, and scratch assays in NMIBC cell line HTB-2. RESULTS: miRNA Let-7f-5p showed the strongest association with recurrence across both the NH population cohort (p=0.039) and the DHMC TaHG/T1 cohort (p=0.065). Survival analyses stratified by median Let-7f-5p expression confirmed longer RFS in the patients with high Let-7f-5p for both discovery and validation cohorts (p=0.011 and 0.065; Figure 1A/B). Let-7f-5p was found to have potential clinical utility as a biomarker, and levels in urine and plasma were both found to be significantly correlated with levels in tumor tissue (P=0.0004 and 0.014, respectively). Finally, inhibition of Lin28 with Lin28 1632 significantly increased levels of Let-7f-5p expression (p=0.0003; Figure 1C) and led to significant inhibition of viability and migration of HTB-2 cells (both p<0.0001; Figures 1D/E). CONCLUSIONS: In this study, we have identified Let-7f-5p as a novel miRNA biomarker of recurrence in NMIBC tumors, and show that patients with high Let-7f-5p have longer RFS. We further show that targeting Lin28, a negative regulator of Let-7f-5p, represents a novel therapeutic opportunity in NMIBC. Source of Funding: Grant numbers R21CA182659, K07CA102327, CA182659, LM009012, GM103506 and GM103534, RR024475, RR028309, CA102327, CA121382, CA141017, CA099500, CA82354, CA078609, ES00002, 5P42ES05947, RR018787, and ES07373 from the National Cancer Institute, NIH, from the National Institute of Environmental Health Sciences, NIH, the National Center for Research Resources, NIH, and the National Institute of General Medical Sciences, NIH. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e226-e226 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kevin Shee* More articles by this author Carmen J Marsit More articles by this author Alan R Schned More articles by this author Jason Pettus More articles by this author David A Armstrong More articles by this author Margaret R Karagas More articles by this author Todd W Miller More articles by this author John D Seigne More articles by this author Angeline S Andrew More articles by this author Expand All Advertisement PDF downloadLoading ...

Evaluation of the Role of Early Second Look Cystoscopy after Complete Resection of Non-Muscle Invasive Bladder Tumors

Abstract Background most of the bladder cancers are non-muscle invasion at the time of diagnosis. Non-Muscle invasive tumors confined to the mucosa and invading the lamina propria are classified as stage Ta and T1, respectively, according to the Tumor, Node, Metastasis (TNM) classification system. Aim of the Study to determine the efficacy of early second look cystoscopy after complete resection of non-muscle invasive urinary bladder tumors and its impact on subsequent treatment policy. Patients and Methods this is a prospective clinical study that was done at Urology Department, Faculty of Medicine, Ain Shams University and Damanhur Oncology Centre. A total of 40 consecutive patients with newly diagnosed non-muscle invasive bladder cancer will be enrolled in this prospective study for second-look cystoscopy with TURBT in two to six weeks after initial TURBT and follow them up in one year. Results Single tumor was found in 22 cases (55%), while multiple tumors were recognized in 18 cases (45%) with average sizes ranging from 12mm to 70mm. Low-grade transitional cell carcinoma (TCC) was found in 26 cases (65%), whereas high-grade TCC was found in 14 cases (35%). Stage PTa tumors was found in 12 cases (30%) while 28 cases (70%) have had tumors of PT1 stage. All cases underwent an early second TURBT after (2-6) weeks which has reviled the following data. The majority of cases (28 cases) representing 70% of whole study population were free with no detection of any tumors either residual or recurrence. Residual tumors were detected in six cases (15%) all of which detected in patient with large primary tumor size exceeding 50mm or patients with multiple tumors. Whole detected residual tumors were found at edges of primary tumors ranging 2-5 mm in size which were completely resected and they were of the same stage and grade as the initial tumor. Conclusion Our findings in this study support the notion that second-look cystoscopy with or without TURBT is a prerequisite in patients with superficial bladder cancers except for patients with solitary, small low-grade pTa tumors. It is particularly highly recommended for patients with extensive and multiple tumors at the first TURBT

Retrograde en bloc resection for non-muscle invasive bladder tumor can reduce the risk of seeding cancer cells into the peripheral circulation

ObjectiveTo ascertain whether en bloc resection could reduce the risk of seeding cancer cells into the circulation during the resection of non-muscle invasive bladder cancer (NMIBC).MethodsPatients with primary NMIBC were enrolled in this prospective study from October 2017 to May 2018. Patients were allocated to receive conventional transurethral resection of the bladder (TURB) or retrograde en bloc resection technique of the bladder tumor (RERBT). Blood samples (1 ml) for circulating tumor cell (CTC) enumeration were drawn from the peripheral vein prior to resection (PV1), immediately after resection of the tumor base (PV2), and at 12 h after resection (PV3). Intra-group comparisons of the changes in the number of CTCs identified among the PV1, PV2, and PV3 blood samples were performed in each group.ResultsA total of 21 patients (12 in the RERBT group and 9 in the TURB group) were recruited. For patients receiving TURB, the level of CTCs identified in PV3 was significantly higher than that in PV1 (p = 0.047). However, there was no significant difference in CTC counts before and after resection in the RERBT group.ConclusionRERBT did not increase the number of tumor cells in the bloodstream.

How well do we manage non-muscle invasive bladder tumors? A UK audit of real-life practices.

The aim of this study was to assess the quality of TURBT (transurethral resection of bladder tumor) using surrogate parameters and evaluate adherence to the guidelines regarding the management of bladder tumors. A clinical audit of all new diagnosis of bladder cancer was undertaken from January 2016 to January 2017. A total of 101 new bladder cancer cases were included. Surrogates of TURBT quality including presence of detrusor in the specimen, rate of re-TUR, presence of carcinoma in situ, and 3-month recurrence rates were analyzed. Adherence to guidelines regarding management of non-muscle invasive bladder cancer including time to re-TUR and utilization of single instillation chemotherapy was evaluated. Absence of detrusor muscle in the specimen of the initial TURBT was noted in 22.8% of the cases. The chance of including muscle in the specimen was almost four-fold for tumors larger than 3 cm. A single instillation of intravesical chemotherapy following TURBT was administered in only 40% of eligible patients; 54.3% of patients had a re-TUR, the majority (61.3%) for high-grade non-muscle invasive bladder cancer on initial TURBT. Re-TUR was done on average 10 weeks after initial TURBT. The 3-month recurrence rate was 36.0% with larger tumors (>3 cm) being more prone to early recurrences. Early recurrences were not affected by intravesical instillations with bacillus Calmette-Guérin or mitomycin C although there was a positive association between the presence of carcinoma in situ on initial resection and early recurrences. One in two patients will have a re-TUR, and approximately one in two patients will have tumor on re-TUR. Single immediate chemotherapy instillations after TURBT are underutilized. The presence of carcinoma in situ on initial TURBT and tumor size were predictors of early recurrences.

Intravesical Bacillus Calmette-Guérin versus mitomycin C for Ta and T1 bladder cancer.

People with urothelial carcinoma of the bladder are at risk for recurrence and progression following transurethral resection of a bladder tumour (TURBT). Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) are commonly used, competing forms of intravesical therapy for intermediate- or high-risk non-muscle invasive (Ta and T1) urothelial bladder cancer but their relative merits are somewhat uncertain. To assess the effects of BCG intravesical therapy compared to MMC intravesical therapy for treating intermediate- and high-risk Ta and T1 bladder cancer in adults. We performed a systematic literature search in multiple databases (CENTRAL, MEDLINE, Embase, Web of Science, Scopus, LILACS), as well as in two clinical trial registries. We searched reference lists of relevant publications and abstract proceedings. We applied no language restrictions. The latest search was conducted in September 2019. We included randomised controlled trials (RCTs) that compared intravesical BCG with intravesical MMC therapy for non-muscle invasive urothelial bladder cancer. Two review authors independently screened the literature, extracted data, assessed risk of bias and rated the quality of evidence according to GRADE per outcome. In the meta-analyses, we used the random-effects model. We identified 12 RCTs comparing BCG versus MMC in participants with intermediate- and high-risk non-muscle invasive bladder tumours (published from 1995 to 2013). In total, 2932 participants were randomised. Time to death from any cause: BCG may make little or no difference on time to death from any cause compared to MMC (hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.79 to 1.20; participants = 1132, studies = 5; 567 participants in the BCG arm and 565 in the MMC arm; low-certainty evidence). This corresponds to 6 fewer deaths (40 fewer to 36 more) per 1000 participants treated with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Serious adverse effects: 12/577 participants treated with BCG experienced serious non-fatal adverse effects compared to 4/447 participants in the MMC group. The pooled risk ratio (RR) is 2.31 (95% CI 0.82 to 6.52; participants = 1024, studies = 5; low-certainty evidence). Therefore, BCG may increase the risk for serious adverse effects compared to MMC. This corresponds to nine more serious adverse effects (one fewer to 37 more) with BCG. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Time to recurrence: BCG may reduce the time to recurrence compared to MMC (HR 0.88, 95% CI 0.71 to 1.09; participants = 2616, studies = 11, 1273 participants in the BCG arm and 1343 in the MMC arm; low-certainty evidence). This corresponds to 41 fewer recurrences (104 fewer to 29 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations, imprecision and inconsistency. Time to progression: BCG may make little or no difference on time to progression compared to MMC (HR 0.96, 95% CI 0.73 to 1.26; participants = 1622, studies = 6; 804 participants in the BCG arm and 818 in the MMC arm; low-certainty evidence). This corresponds to four fewer progressions (29 fewer to 27 more) with BCG at five years. We downgraded the certainty of the evidence two levels due to study limitations and imprecision. Quality of life: we found very limited data for this outcomes and were unable to estimate an effect size. Based on our findings, BCG may reduce the risk of recurrence over time although the Confidence Intervals include the possibility of no difference. It may have no effect on either the risk of progression or risk of death from any cause over time. BCG may cause more serious adverse events although the Confidence Intervals once again include the possibility of no difference. We were unable to determine the impact on quality of life. The certainty of the evidence was consistently low, due to concerns that include possible selection bias, performance bias, given the lack of blinding in these studies, and imprecision.

Safety, feasibility, and quality of holmium laser en-bloc resection of nonmuscle invasive bladder tumors - A single-center experience.

Introduction:Conventional transurethral resection of bladder tumor (cTURBT), despite its piecemeal resection and associated limitations, remains the most widely practiced technique of TURBT. Resecting the tumor in a single piece would avoid most of the drawbacks of cTURBT. Our objective was to assess the feasibility, safety, and quality of Holmium (Ho) laser en-bloc resection (ERBT) for nonmuscle-invasive bladder cancer (NMIBC).Materials and Methods:We retrospectively studied 67 patients who underwent Ho laser EBRT for primary NMIBC. Data were collected regarding tumor size, number and location, intraoperative complications, and postoperative course. Patients were grouped as first 20, next 20 (21–40), and last 27 cases to assess how the quality of resection improved with increasing experience.Results:The mean tumor size was 28.7 ± 7.9 mm, with 34.3% of the patients having a tumor larger than 3 cm. While 43 patients (64.17%) had a single tumor, the rest had multiple tumors, ranging from 2 to 9 in number. The mean total duration of resection was 38.7 ± 11.6 min. No case required conversion to cTURBT. No patient experienced obturator reflex or bladder perforation. Detrusor muscle was present in 85.07% of the resections. With increasing experience, requirement for bladder irrigation and the incidence of postoperative clot evacuation decreased (P < 0.0001 and P = 0.31, respectively), and the detrusor-positive rate in the specimen increased (P = 0.24). The mean duration of catheterization was 1.76 ± 0.54 days.Conclusion:Ho laser ERBT is safe and feasible for complete resection of NMIBCs with no risk of obturator-nerve reflex and a high rate of detrusor-positive specimens.

Bipolar en Bloc Resection - Is it the Future in Non-Muscle Invasive Bladder Cancer?

Bladder cancer is among the most common urological malignancies. In this context, despite of all the technological advancements, transurethral resection of bladder tumour (TURBT) continues to represent the gold-standard diagnostic and treatment in non-muscle invasive bladder tumours (NMIBTs). The surgical technique of en bloc bipolar tumour resection could be performed using the hemispherical shape plasma-button electrode and saline irrigation fluid or using the laser fiber. The malignant formation is gradually pushed up and separated from the bladder wall. The final aspect of the bladder wall reveals the clean muscular fibers of the detrusor layer, free of malignant tissue, irregularities or debris. Concerning the outcomes, the operative parameters are heterogenous in the literature, because of the different resection devices utilized. However, there are few main points where all the studies agreed, concerning the lower recurrence rates comparing with classical resection and also the good quality resection samples. In conclusion, even if the general outcomes are favourable for the en bloc resection, there is still a lack of large multicentric comparative trials which establish the right place of the method in the urological armamentarium.

Re: Maheshwari PN, Arora AM, Sane MS, Jadhao VG. Safety, feasibility, and quality of holmium laser en bloc resection of nonmuscle invasive bladder tumors: A single-center experience. Indian J Urol 2020;36:106-11.

Re: Maheshwari PN, Arora AM, Sane MS, Jadhao VG. Safety, feasibility, and quality of holmium laser en bloc resection of nonmuscle invasive bladder tumors: A single-center experience. Indian J Urol 2020;36:106-11.

Authors Reply Re: Maheshwari PN, Arora AM, Sane MS, Jadhao VG. Safety, feasibility, and quality of holmium laser en bloc resection of nonmuscle invasive bladder tumors: A single-center experience. Indian J Urol 2020;36:106-11

Authors Reply Re: Maheshwari PN, Arora AM, Sane MS, Jadhao VG. Safety, feasibility, and quality of holmium laser en bloc resection of nonmuscle invasive bladder tumors: A single-center experience. Indian J Urol 2020;36:106-11

Comparative Outcomes of Bladder Cancer in Patients Under 40 Years of Age

Background and Objectives Bladder tumours are rare in young patients. Consequently, the literature is sparse and studies provide con-flicting reports on clinicopathological data and patient outcomes. This study examines, to our knowledge, the largest UK series of patients aged less than 40 years diagnosed with bladder cancer, and examines their risks and outcomes. Material and Methods A prospectively recorded database (2008-2018) was used to identify patients aged under 40 years diagnosed with bladder cancer. Data were retrospectively analyzed. Patients were then sub-divided into 2 groups based on age: group 1 was aged below 20 years and group 2 was aged 20–39 years. Results A total of 27 patients were identified with a median age of 34 years (range 14–39). Male to female ratio was 2.86:1. Median follow-up was 41.5 months (range 3–108). 61.9% presented with visible hematuria and 54.2% had one or more risk factors such as cigarette smoking. A total of 96.3% of patients had urothelial carcinoma and 92.3% of these were non-muscle invasive tumours. 7.7% presented with muscle invasive disease with 3.8% having positive nodes at diagnosis. Patients with non-muscle invasive urothelial tumours were risk-stratified according to the EAU-Guidelines Panel risk grouping with 39.1% low-risk, 4.3% intermediate-risk and 56.5% high-risk of recurrence and/or progression. During follow-up 30.4% recurred and 4.3% progressed to invasive disease. 23.1% underwent cystectomy and overall 11.5% died during follow-up, all due to metastatic disease. Patients in group one showed a statistically significant incidence of lower-grade disease at diagnosis with lower risk-group stratification but there was no significant difference in other parameters. Conclusion The majority of young patients in our series presented with non-muscle invasive urothelial bladder tumours but a significant proportion of these had high-risk disease. Some patients presented with aggressive, muscle invasive bladder cancer and consequently bladder cancer remains an important differential diagnosis in symptomatic patients regardless of age.

Surveillance of High-grade Non-muscle Invasive Bladder Tumours Using the Xpert Bladder Cancer Monitor

Surveillance of High-grade Non-muscle Invasive Bladder Tumours Using the Xpert Bladder Cancer Monitor

A Gencitabina como Alternativa Terapêutica na Ausência de BCG: A Experiência do CHLC (Hospital S. José)

Introdução: Os tumores não músculo invasivos da bexiga devem ser estratificados em grupos de risco de forma a adequar o tratamento após cirurgia a cada doente. Nos tumores de alto risco deve ser realizada terapêutica adjuvante com bacilo de Calmette-Guérin (BCG) intravesical durante 1 a 3 anos. Têm sido reportadas roturas de stock de BCG intravesical, tendo sido o Centro Hospitalar de Lisboa Central (CHLC) afectado nos anos 2014 e 2015, o que obrigou a uma reformulação no tratamento dos doentes que tinham indicação para realização desta terapêutica. A gencitabina poderá ser uma alternativa válida, dado que alguns estudos mostram que poderá ter um papel nos doentes de risco intermédio, como alternativa à mitomicina C, e nos de alto risco, refractários à BCG, com um perfil de toxicidade mais favorável.&#x0D; Material e Métodos: Trata-se de um estudo retrospectivo descritivo que incluiu doentes com tumores da bexiga não musculo-invasivos de alto risco, com início da doença em 2013/2014, afectados pelo período de escassez de BCG no Centro Hospitalar.&#x0D; Resultados: No CHLC, 11 doentes com tumores de alto risco foram submetidos a terapêutica com gencitabina, apenas dois exclusivamente, os restantes sequencialmente com BCG. Apenas dois doentes, tratados com BCG e gencitabina, apresentaram recidiva tumoral. No entanto, um número significativo (6 em 11) sofreram efeitos adversos, dois dos quais que levaram à interrupção da terapêutica.&#x0D; Conclusão: Aparentemente, a gencitabina foi uma boa alternativa de terapêutica adjuvante na ausência do tratamento gold standard (BCG), dada a existência de baixo número de recidivais tumorais, apesar do elevado número de efeitos adversos reportados.

Новые подходы к методике трансуретрального удаления опухолей мочевого пузыря большого размера единым блоком

to develop optimal techniques of en-bloc resection of large non-muscle invasive bladder tumors, determine the proper method of specimen extraction and assess the quality of specimens obtained by different techniques. A total of 12 patients with primary cT1 bladder cancer underwent transurethral en-bloc resection between January 2018 and March 2019 were enrolled into the study. Tumor size ranged from 3.5 cm to 6.2 cm. For removal and extraction of large bladder tumors using thulium fiber en-bloc laser three different techniques were developed: "swiss cheese technique", "crown and root technique" and "three steps technique" technique". The main pathologic criteria used for assessment of removal technique were tumor grade (G), depth of invasion (T), presence of carcinoma in situ (CIS), variant histology (VH), lymphovascular invasion (LVI), presence of detrusor muscle. Additional criteria were horizontal and vertical resection margin, subclassification of T1-stage and presence of focal necrosis in tumor. Among the techniques developed and tested, the best quality of specimens for morphological evaluation was obtained using the combined "crown and root technique". First step is electroresection of the exophytic part of the tumor into pieces, and the next step is en-bloc laser resection (using thulium fiber or holmium laser) of the tumor base. Overall, the quality of all specimens obtained using three techniques met the current requirements of pathologic study. En-bloc resection techniques of large bladder tumors allow obtaining specimen suitable for proper morphological evaluation and correct tumor staging. Further studies are required to evaluate the impact of these techniques on long-term results of treatment options.

TURBot: A System for Robot-Assisted Transurethral Bladder Tumor Resection

Staging and treatment of nonmuscle-invasive bladder tumors using transurethral resection of bladder tumors (TURBT) is challenging due to limitations in intravesicular tool dexterity, visualization and risk of bladder wall perforation. Currently, TURBT is achieved via a rigid resectoscope. This dexterity limitation is exacerbated when tumors are located in the bladder neck region. To address these limitations, an endoscopic robotic system called TURBot was developed. The paper presents the design considerations, modeling, and control challenges that were addressed to enable the first robot-assisted in vivo TURBT. The design and control of a slave robot comprised of a multisegment continuum robot capable of deploying a micro snake-like continuum robot for control of an ablation laser, a grasper, and a fiberscope is presented. A strategy for constrained telemanipulation is presented based on the redundancy resolution with varying task dimension that is commensurate with the level of constraint experienced by the robot during transurethral deployment. In addition to evaluation in animals, TURBot resection is compared against manual resection in a mockup user study using a human bladder phantom. The contributions of this paper present key steps that pave the way toward successful clinical robot-assisted TURBT.

EFFECTIVENESS OF SINGLE DOSE INTRAVESICAL MITOMYCIN C THERAPY AS PROPHYLAXIS TO PREVENT RECURRENCE AND PROGRESSION OF SUPERFICIAL NONMUSCLE INVASIVE BLADDER TUMOR.

Objectives: To determine the effectiveness of instillation of single dose of intravesical mitomycin C in patients with low grade non-muscle invasive bladder tumor (NMIBT). Study Design: Retrospective cross-sectional study. Setting: Tabba kidney institute Karachi. Period: 2016 to Jan-2018. Subject and Methods: A total of 76 patients with first time diagnosis of non-invasive bladder tumor were included. Data of patients of SNMIBT who underwent trans-uretheral resection of bladder tumor (TURBT) and received single dose instillation of mitomycin C (MMC, 40 mg) within 24 hours after resection from 2016 to Jan-2018 were included in this analysis. All these patients were followed for 6 months after TURBT, cystoscopy was performed at 3 and 6 monthly to check and record any recurrence or progression. Results: Out of 76 cases, 43 (56.57%) had one lesion, 27 (35.52%) had two lesion and 6 (7.89%) cases had three lesion. Single dose intravesical mitomycin C was effective in 81.57% (62/76) cases, recurrence occurred in 6 (7.89 %) cases and progression of disease in 8 (10.52%) cases. Conclusion: The results of present study confirmed the positive effect of instillation of single immediate dose of MMC in patients with low risk superficial bladder tumor. 81.57% patients will not require any further treatment if MMC-40 is given immediately following TURBT.

MicroRNA Dysregulation and Non-Muscle-Invasive Bladder Cancer Prognosis.

The high rate of non-muscle-invasive bladder cancer recurrence is a major challenge in patient management. miRNAs functionally regulate tumor cell proliferation and invasion, and have strong potential as biomarkers because they are robust to degradation. The objective of this project was to identify reproducible prognostic miRNAs in resected non-muscle-invasive bladder tumor tissue that are predictive of the recurrent tumor phenotype. We utilized patients diagnosed with primary non-muscle-invasive bladder cancer in three independent cohorts for a biomarker discovery/validation approach. Baseline tumor tissue from patients with the clinically challenging, non-muscle-invasive primary low stage (Ta), high grade, and T1 tumors (tumors extending into the lamina propria) comprised the discovery cohort (n = 38). We isolated the tumor tissue RNA and assessed a panel of approximately 800 miRNAs. miR-26b-5p was the top-ranking prognostic tumor tissue miRNA, with a time-to-recurrence HR 0.043 for levels above versus below median, (P adj = 0.0003). miR-26b-5p was related to a dose-response reduction in tumor recurrence, and levels above the median were also associated with reduced time-to-progression (P adj = 0.02). We used two independent longitudinal cohorts that included both low-grade and high-grade Ta and T1 tumors for validation and found a consistent relationship between miR-26b-5p and recurrence and progression. Our results suggest that miR-26b-5p levels may be prognostic for non-muscle-invasive bladder cancer recurrence, and can feasibly be assessed in baseline tumor tissue from a wide variety of clinical settings. Early identification of those non-muscle-invasive bladder tumor patients with refractory phenotypes would enable individualized treatment and surveillance.

Intravesical Therapies in Non-muscle Invasive Bladder Tumors

Intravesical Therapies in Non-muscle Invasive Bladder Tumors

The Diagnostic and Prognostic Significance of MicroRNA-21 in Non-muscle Invasive Bladder Tumors

The Diagnostic and Prognostic Significance of MicroRNA-21 in Non-muscle Invasive Bladder Tumors