Superficial Bladder Carcinoma Research Articles

Abstract 2816: Comparison of MB-49_luc bladder carcinoma cell clones in the orthotopic superficial bladder tumor model in C57BL/6 female mice

Abstract In preclinical research, cell inoculation via bladder wall injection is a standard for studying invasive bladder cancer into the bladder muscle wall. However, a subset of patients presents with non-muscle invasive (superficial) disease. The standard of care for these patients is excision coupled with BCG treatment via catheterization. There is a need to further establish mouse models of cell inoculation via bladder catheterization for early drug development. While the injection places cells into the bladder wall, catheterization coats the inside of the bladder by first instilling Poly-L-Lysine. After instilling Poly-L-Lysine, instillation of luciferase-tagged cell suspension occurs. MB49-luc cell lines were generated to determine the optimal cell lines for use in analyzing treatments for superficial bladder carcinoma. MB49-luc cells display varying degrees of luciferase activity and growth in vitro. A subset of cell lines were selected for further analysis in vivo, via bioluminescent imaging, survival analysis, flow cytometry and necropsy. The data provides a preclinical reference for the selection of a cell line for analysis of new drug candidates in C57BL/6 female mice inoculated via bladder catheterization. Citation Format: Mollie McArthur, Melissa Tran, Aliccia Koznecki, Helen Ketteringham, Corrine Silvio, Shannan Wenzel, Cheryl Davis, Shorena Nadaraia-Hoke, Chris Holding, Logan Salem, Victoria Caruso, Ben Hoerner, Madison Spencer, Marcus Josey, Alexa Tannu. Comparison of MB-49_luc bladder carcinoma cell clones in the orthotopic superficial bladder tumor model in C57BL/6 female mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2816.

Frequency of Complications Post-Intravesical BCG Instillation in Patients with Superficial Urinary Bladder Carcinoma

Objectives: To analyze patients who underwent intravesical BCG instillation for non-muscle invasive bladder tumor and to determine the frequency of complications after intravesical BCG instillation. Study Design: Cross-sectional study. Place and Duration of Study: Departments of Urology and General Surgery, Pakistan Ordinance Factories Hospital Wah Cantt from 1st January 2019 till 31st December 2020. Methodology: Fifty patients; Results: The mean age was 57.06±7.93 years. Forty two patients (84%) were male and 8 patients (16%) were female. Four patients (8%) were Ta stage, 34 patients (68%) were Tis stage and 12 patients (24%) were T1 stage. Mean time interval between TURBT and BCG instillation was 28.68±5.07 days, mean number of BCG instillation cycles was 6.80±2.06 days. Ten (20%) patients had urinary tract infection, 19 (38%) patients had bladder TB, 9 (18%) patients had BCG sepsis, 5 (10%) patients had miliary TB, 2 (4%) patients had epidimo-orchitis, 2 (4%) patients developed ophthalmic complications, 1 (2%) patient had polyarthralgia, 1 (2%) patient had septic arthritis and 1 (2%) patient developed spinal Conclusion: Bacillus Calmette-Guérin is most commonly used drug as chemotherapeutic agent for superficial bladder tumors after TURBT. Repeated cycles of BCG i.e. 6-12 cycles have been administered to patients. Previously most of symptoms i.e. LUTS, dysuria, hematuria were being associated with presence of tumor but now many case reports and few studies have associated these symptoms with BCG administration. Keywords: Superficial bladder carcinoma, Intravesical BCG, Lower urinary tract symptoms

Efficacy of High and Low Dose of BCG and Their Complications in Superficial Transtional Cell Carcinoma of Urinary Bladder

Background: Bladder cancer patients mostly (75%) present with non-muscle invasive bladder tumors. Aim: To compare tumor recurrence and side effects between high and low dose of BCG in NMIBC. Study Design: Randomized controlled trial. Methodology: Patients (n=30 each group) were enrolled with expected percentage of side effects with low dose (40 mg) as 2.5 % and high dose (80 mg) as 25.8%. Patients of all age groups with both genders having NMIBC (Ta, T1, Tis) and high grade tumors (G3) determined on histopathology of TURBT sample. Patients with history of renal transplant and chemotherapy were excluded. The difference between both groups was analyzed using Chi Square test with P- value of < 0.05 was considered statistically significant. Results: The mean age of patients in group A was 55.83 ± 9.17 and group B was 59.17 ± 8.13 years. There was no significant difference in the age of two groups (P= 0.142). There was no difference in gender distribution in two groups (P=0.688). Regarding the stage of tumor there were 13 cases of stage Ta and T1 in both groups. Conclusion: It was concluded that 40 mg dose of intra-vesical BCG in patients with NMIBC had lower recurrence and side effects as compared to higher dose of intra-vesical BCG. Key words: Recurrence, Side Effects, Low dose BCG and High Dose BCG.

Recurrence rate of superficial bladder cancer with intravesical BCG and mitomycin.

Objective: To compare the recurrence rate of superficial transitional cell carcinoma of urinary bladder using intravesical BCG and Mitomycin-C. Study Design: Randomized Controlled Trial. Setting: Urology Department, Teaching DHQ Hospital, Gujranwala. Period: November 2018, to Sep, 2019. Material & Methods: Was carried out on total 270 patients, admitted with suspicion of urothelial tumors. They were grouped in Group A and B, comprising 135 in each group. Group A received BCG and Group B received Mtiomycin-C intravesically following TUR-BT. Results: Out of 270 patients male to female ratio was 3:1. Age range of patients was between 30 to 70 years with mean of 50.0± 13.1 and 552.3 ± 12.9 years in Group A and B respectively. Recurrence was noted in 05.38% and 15.38% patients in Group A and B respectively. Regarding side effects pyrexia was associated with BCG in 27.40% patients which were self-limited in 26.66% cases however required anti-tuberculosis therapy for six months in 0.74%. Whereas only 06.67% patients receiving Mitomycin had pyrexia. Dysuria occurred in 74% and frequency in 68% patients who received BCG. Whereas Dysuria occurred in 20% and frequency in 36.29% patients who received Mitomycin-C. However genital skin rash was more common (08.14%) in Mitomycin group than BCG. Conclusion: Keeping in mind less recurrence rate and bearable toxicity, it is concluded that BCG is superior to Mitomycin. This study suggests long term follow up is required to establish recurrence in the management of superficial bladder cancer.

Immunostimulatory Response of RWFV Peptide-Targeted Lipid Nanoparticles on Bladder Tumor Associated Cells.

Bladder carcinoma is the most expensive tumor type to treat on a cost-per-patient basis from diagnosis to death. Treatment with Bacillus Calmette Guerin (BCG) instillation is the only approved immunotherapy in the clinic for the remission of superficial bladder carcinoma. Unfortunately, frequent relapses, high local morbidity, risk of systemic mycobacterial infection, and occasional supply chain interruptions limit the utility of BCG for bladder cancer treatment. It is well known that BCG utilizes an adhesin protein known as fibronectin attachment protein that possesses a crucial RWFV peptide sequence for binding to the bladder tumor microenvironment prior to the initiation of the immunotherapeutic response. We report a RWFV-targeted, pH-responsive stabilized lipid nucleic acid nanoparticle (LNP) vehicle for the effective delivery of an immunotherapeutic oligonucleotide, CpG, that is assembled using a glass microfluidic Chemtrix 3221 reactor. Our small-angle X-ray scattering studies revealed a layer-by-layer assembly of the oligonucleotides with a repeat distance of 6.04 nm within the LNP. Using flow cytometry to evaluate the different cell types found in the bladder tumor microenvironment, RWFV-targeted LNPs were found to attach specifically to fibronectin-secreting cells in culture during a 2 h incubation period. The trafficking and cellular fate of these targeted LNPs were revealed by confocal microscopy of RAW264.7 macrophages to enter the endocytotic pathway within 4 h post treatment. Importantly, control studies reveal that only the pH-sensitive LNP formulation is capable of efficiently releasing the payload within 12 h. As a result, the targeted pH-sensitive LNP resulted in higher expression levels of costimulatory molecules CD83, CD 86, and MHC II, while also inducing higher levels of TNF-α secretion from macrophages. These results demonstrate that RWFV-targeted, pH-sensitive LNP formulations are capable of maximum immunotherapeutic response, potentially making them a highly efficient, lower risk, and readily manufactured alternative to BCG immunotherapy.

Adjuvant Intravesical Chemotherapy in the Management of Superficial Transitional Cell Carcinoma of Urinary Bladder Following Transurethral Resection of Bladder Tumor- Result of Single Dose and Multiple doses of Mitomycin C

Background: Bladder cancer is the second most common cancer of the genitourinary tract. Mitomycin C has been commonly used in a perioperative fashion delivered intravesically immediately after TURBT Objective: To compare the results of post TURBT immediate single dose and multidose regimen of Mitomycin C therapy in the management of superficial transitional cell carcinoma of the urinary bladder. Method: The present prospective and comparative interventional study was conducted in the Department of Urology, National Institute of Kidney Diseases and Urology, Sher-E-Bangla Nagar, Dhaka from January 2015 to December 2016. Patients of superficial bladder cancer (tumor size ≤3 cm, number ≤3, grade I, II) were randomly included in the 2 groups. The sample size was seventy four (74). Thirty (30) patients were in each group and fourteen (14) were excluded from the study. In MMC single dose group (Group A), single dose of MMC 40mg/ 40ml was started immediately within 24 hours of TURBT. In MMC multi-dose group (Group B) 1st instillation of chemotherapy was started immediately within 24 hours of TURBT and additional instillation (5 instillations) were given as OPD basis and was continued weekly for 5 weeks. Follow-up was done on 3rd, 6th, 12th month of initial TURBT. Results: In this study mean age was 61.8±13.7 years in group A and 62.7±13.6 years in group B. Male was found 25 (83.3%) in group A and 26 (86.7%) in group B. Female was found 5 (16.7%) in group A and 4 (13.3%) in group B. Mean size of the tumor was found 2.13±0.78 cm in group A and 2.05±0.84 cm in group B. Mean number of tumor was found 1.8±0.8 in group A and 1.9±0.7 in group B. Tumor grade I was found 23 (76.7%) in group A and 25 (83.3%) in group B. Tumor status Ta of superficial bladder was found 25 (83.3%) in group A and 26 (86.7%) group B. Tumor status T1 of superficial bladder was found 5(16.7%) in group A and 4 (13.3%) group B. Five (16.7%) patients was found recurred in group A and 4 (13.3%) in group B at 6th month follow up. At 12th month follow up, 6 (20.0%) patients was found recurred in group A and 5 (16.7%) in group B. Side effect was found in 2 (6.7%) patients in group B and not found in group A. Conclusion: MMC single dose was similar to MMC multi-dose regimen with insignificant difference among the two. Bangladesh Journal of Urology, Vol. 23, No. 1, January 2020 p.62-66

A Comparative Study Between Single Dose & Multiple Doses of Mitomycin-C in the Management of Transitional Cell Carcinoma of Urinary Bladder

Objectives: To find out the efficacy of post TURBT immediate single dose adjuvant intravesical Mitomycin C therapy in comparison with multi-dose regimen of Mitomycin C therapy in the management of superficial transitional cell carcinoma of the urinary bladder. Methods: Total 76 patients of bladder mass were included in the study who had undergone transurethral resection followed by immediate single instillation of Mitomycin C. After availability of histopathological examination report of resected tumor, those fulfill the selection criteria were randomized into two groups. One group (Group A) was the odd numbers of the patients who already received immediate single intravesical instillation of Mitomycin C and another group (Group B) even number of the patients who received single dose of intravesical instillation of Mitomycin C immediately with additional 5 instillations (1 week interval for 5 weeks) and in whom prospective follow-up could be completed within next 12 months Results: The effect of single intravesical instillation of 40 mg of Mitomycin C (Group A) within 24 hours of TURBT with that of multiple doses (six doses) of Mitomycin C (Group B) in similar dose was insignificant. Conclusion: The efficacy of MMC single dose was similar to MMC multi-dose regimen with insignificant difference of side effect among the two groups (0% versus 6.25%). Bangladesh Journal of Urology, Vol. 20, No. 2, July 2017 p.74-77

Human papilloma virus DNA revelation in the superficial urothelial bladder carcinoma

Human papilloma virus DNA revelation in the superficial urothelial bladder carcinoma

Adjuvant intravesicular chemotherapy for superficial bladder carcinoma

Adjuvant intravesicular chemotherapy for superficial bladder carcinoma

Detection of the recurrence of superficial urothelial carcinoma of urinary bladder by combined urine cytology and cystoscopy

The study was aimed to evaluate the accuracy of combined urine cytology and cystoscopy for the detection of the recurrence of superficial urothelial carcinoma of urinary bladder without bladder biopsy. A total 60 patients [males 48, females 12; age range 41-80 years (mean age- 63.15 years)] were included. Urine cytology as well as cystoscopy were done with a targeted biopsy taken from any apparently visible growth in the bladder. The systematic biopsy was taken where there was no growth. Reports of the cytology and cystoscopy were compared with the histopathology reports. It was found that 18 patients were cytology positive (false positive 2) and 42 patients were cytology negative (false negative 10) with sensitivity 61.5% and specificity 94%. During cystoscopy 24 patients were found recurrent growth in the bladder (false positive 3) and 36 patients were negative (false negative 5) with sensitivity 80.7% and specificity 91%. But when combined urine cytology and cystoscopic findings evaluated, the sensitivity and specificity were found 100% and 91% respectively. In conclusion, combined urine cytology and cystoscopy can be used for the detection of recurrence of superficial urothelial carcinoma of urinary bladder.

Solid Tumors in Post-Polycythemia Vera and Post-Essential Thrombocythemia Myelofibrosis: A Study on 2220 Patients

Solid Tumors in Post-Polycythemia Vera and Post-Essential Thrombocythemia Myelofibrosis: A Study on 2220 Patients

Predicting 90-day and long-term mortality in octogenarians undergoing radical cystectomy

BackgroundRadical cystectomy bears a considerable perioperative mortality risk particularly in elderly patients. In this study, we searched for predictors of perioperative and long-term competing (non-bladder cancer) mortality in elderly patients selected for radical cystectomy.MethodsWe stratified 1184 consecutive patients who underwent radical cystectomy for high risk superficial or muscle-invasive urothelial or undifferentiated carcinoma of bladder into two groups (age < 80 years versus 80 years or older). Multivariable and cox proportional hazards models were used for data analysis.ResultsWhereas Charlson score and the American Society of Anesthesiologists (ASA) physical status classification (but not age) were independent predictors of 90-day mortality in younger patients, only age predicted 90-day mortality in patients aged 80 years or older (odds ratio per year 1.24, p = 0.0422). Unlike in their younger counterparts, neither age nor Charlson score or ASA classification were predictors of long-term competing mortality in patients aged 80 years or older (hazard ratios 1.07-1.10, p values 0.21-0.77).ConclusionsThis data suggest that extrapolations of perioperative mortality or long-term mortality risks of younger patients to octogenarians selected for radical cystectomy should be used with caution. Concerning 90-day mortality, chronological age provided prognostic information whereas comorbidity did not.

Pulmonary Metastasis Due to Superficial Transitional Cell Carcinoma of Urinary Bladder, A Rare Case Report and Literature Review

Pulmonary Metastasis Due to Superficial Transitional Cell Carcinoma of Urinary Bladder, A Rare Case Report and Literature Review

136 Eyelid Metastasis From Bladder Small Cell Carcinoma

Metastases to the eyelids are rare. The primary neoplasms are more frequently in breast, skin, digestive, and urological systems. There are very few reports related to bladder carcinomas. We present a unique case of small neuroendocrine cell carcinoma of the bladder metastatic to the eyelid. A 83-year-old man was treated for a high-grade superficial urothelial bladder carcinoma in August 2013 with endoscopic resection and intravesical BCG. In November 2014, he had an in situ bladder carcinoma (CIS). In November 2015, he presented a small cell neuroendocrine carcinoma in the bladder with invasion of muscular wall and areas of in situ carcinoma with focal neuroendocrine differentiation (immunostains positive for synaptophysin and partial for chromogranin A). In October 2016, he developed a skin metastasis of the back. In January 2017, a resective biopsy from a left superior eyelid nodule revealed a small cell carcinoma. The immunohistochemical reactions showed that tumor cells were positive for synaptophysin, chromogranin A, and CD56, and negative for cytokeratin 20. Metastases to the eyelids are rare. This is the first reported case of small cell neuroendocrine carcinoma of bladder metastasizing to the eyelid. The patient had a history of high-grade superficial urothelial carcinoma, later a CIS, and then the small cell neuroendocrine carcinoma. In the study, we need to discard Merkel cell carcinoma.

Case report: Mycobacterium bovis orchitis post intravesical Bacillus Calmette Guerin.

Bacillus Calmette-Guérin (BCG) therapy is a common adjunctive therapy for superficial bladder carcinoma but there has been noted to be complications from this treatment ranging from general disseminated infections to osteomuscular involvement. We report a case regarding a 63 year old gentleman who presented with right testicular swelling and pain and later found to have evidence consistent with Mycobacterium bovis orchitis. We also detail a literature review regarding genitourinary infections secondary to BCG therapy and discussion regarding current testing modalities.

Immunotherapy for Bladder Cancer

Urothelial carcinoma is the most common urological malignancy. Nonspecific immunotherapy using the Bacillus Calmette-Guerin vaccine has long been the mainstay for the treatment of high-risk superficial bladder carcinoma in an adjuvant setting after transurethral endoscopic resection. In metastatic disease, cisplatin-based chemotherapy remains the main therapeutic modality. In Europe, the standard second-line chemotherapy for patients with cisplatin-refractory tumours is vinflunine. Other systemic treatments with a lower level of evidence include paclitaxel and docetaxel. Studies of tumour microenvironment indicate a significant role for the immune system in the pathogenesis of urothelial tumours and the presence of a CD8 lymphocyte infiltrate is associated with better survival. In urothelial tumours, the correlation between PD-L1 expression in the tumour and the response to PD-1/PD-L1 inhibitors has been repeatedly demonstrated in clinical studies. Several inhibitors of PD-1/PD-L1 pathway are undergoing advanced-phase clinical trials and atezolizumab, nivolumab, pembrolizumab, durvalumab, and avelumab have already have received permanent or temporary registration status in the United States, mostly as second-line treatments for patients progressing on cisplatin-based chemotherapy. Three of these agents are currently registered in Europe: nivolumab for second line treatment and atezolizumab and pembrolizumab for first line treatment in patients not eligible for cisplatin as well as and for second line treatment. These novel immunotherapeutic agents for bladder cancer are relatively well tolerated and therefore potentially useful for patients with contraindications or intolerance to platinum regimens. The main toxicities include asthenia/fatigue, lymphopenia, anaemia, musculoskeletal pain, decreased appetite, and nausea.Key words: bladder cancer - imunotherapy - PD-1 receptor - antibodies - monoclonal This work was supported by the Czech Ministry of Health CR - RVO Thomayer Hospital - TN 0064190. The author declare he has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 29. 8. 2017Accepted: 3. 10. 2017.

A RARE COMPLICATION OF BCG IMMUNOTHERAPY

Intravesical Bacillus Calmette-Guérin immunotherapy is an effective agent for superficial bladder carcinoma. The main adverse effect of this treatment is cystitis. Arthralgia and migratory arthritis occur only in 0.5% of patients. Reiter syndrome is a very rare complication that can occur after intravesical apply of Bacillus Calmette-Guérin Immunotherapy. We report the first Albanian patient who developed Reiter’s syndrome, following intravesical Bacillus Calmette-Guérin. Diagnose of Reiter’s Syndrome was clinically based, excluding every other reason that could have caused it. Treatment was made with non-steroid and steroid anti-inflammatory drugs, followed by a full recovery result. Even though Reiter's Syndrome is a rare, but significant complication of BCG immunotherapy, it’s important to identify it in time, in order we to offer an adequate treatment.

BCG Immunotherapy for Bladder Carcinoma

Purpose: We reviewed the literatures to see history, regimen of BCG and how BCG become a standard therapy for bladder carcinoma.Materials and Methods: We reviewed the previous literature describing the bacillus Calmette-Guerin (BCG) vaccine as an anticancer agent and its success as the most effective immunotherapy used against human bladder cancer and its adverse effects.Results: The association between tuberculosis and carcinoma is well established, It demonstrate that Bacillus Calmette-Guerin have immunological reactivity, inhibiting the tumor growth and progression in experimental animal models, led to clinical trials showing that intravesical Bacillus Calmette-Guerin eradicate and prevent recurrence and progression of superficial bladder carcinoma The exact mechanism of action of intravesical BCG instillation is still under investigation. However, it appears that BCG is mediated by the local immune response, mainly through T-helper cell response. It reduces the recurrence rate by an average of 40% and progression by more than 20% in papillary tumors, Carcinoma-in-situ over the patients without BCG therapy.Conclusions: For the last 45 yrs Bacillus Calmette- Guerin therapy has remained first line intravesical immunotherapy for superficial bladder cancer, an outstanding example of successful immunotherapy.KYAMC Journal Vol. 8, No.-1, Jul 2017, Page 56-60

The role of immunohistochemical expression of OCT-4 and SOX2 as predictors of recurrence and progression in superficial urinary bladder carcinoma

BackgroundTumor recurrence and progression are two important landmarks in non-muscle-invasive bladder cancer (NMIBC) patients. Periodic cystoscopic follow-up visits of NMIBC patients are necessary after complete tumor resection as tumor recurrence occurs in nearly 70–80% of cases. Patients with a hi

Ruptured aortic aneurysm due to Mycobacterium bovis BCG with a delayed bacteriological diagnosis due to false negative result of the MPB 64 immunochromatographic assay

BackgroundAdjuvant therapy with bacillus Calmette–Guerin (BCG), a live attenuated strain of Mycobacterium bovis, has become the treatment of choice for low-risk superficial bladder carcinoma following transurethral resection of the bladder. Complications following vesical BCG instillations are uncommon but, in some cases, severe side-effects can occur such as sepsis or mycotic aneurysm. Besides usual laboratory techniques used for the diagnosis of Mycobacterium tuberculosis complex (MTBC) infections (smear microscopy and cultures), commercial immunochromatographic assays detecting MBP64, a 24 kDa M. tuberculosis complex-specific secretory protein, can rapidly distinguish MTBC and non-tuberculosis mycobacteria (NTM). MPB64 is found in M. tuberculosis, M. bovis and some but not all substrains of M.bovis BCG. Therefore, these immunochromatographic tests can lead to false negative results and delayed bacteriological diagnosis depending on the presence or absence of MPB64 protein in BCG substrains used for intravesical therapy.Case presentationWe report the case of a 78-year-old male patient who was admitted to the hospital because of a 1-month history of unexplained fever, thrill, weight-loss and general malaise. His past medical history was marked by a non-muscle-invasive bladder carcinoma treated by transurethral resection followed by BCG instillations (Oncotice, Merck, USA). The patient was initially treated for a urinary tract infection but as fever persists after 72 h of antibiotherapy, urinary tract ultrasound was performed and revealed a large abdominal aortic aneurysm confirmed by computed tomography. Surgery was performed after multidisciplinary discussion. Direct smear of perioperative samples revealed acid-fast bacilli and both solid and liquid cultures were massively positive. Rapid identification of the positive mycobacterial culture was performed using an immunochromatographic assay based on the detection of the Mycobacterium tuberculosis MPB 64 antigen. The result was negative for Mycobacterium tuberculosis complex. After review of the medical record, a polymerase chain reaction (PCR) was performed and gave a positive result for M. tuberculosis complex. Anti-tuberculosis therapy was started immediately and the patient evolved favorably.ConclusionsThrough this case, we showed how the utilisation of MPB64 immunochromatographic assays can provide misleading information due to the variable presence of this protein among the different BCG strains. This case further illustrates the utility of rapid TB complex-specific PCR assays which provide a more reliable identification of all MTBC species.