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Fulltext o-Vanillin Derived Schiff Bases and Their Organotin(IV) Compounds: Synthesis, Structural Characterisation, In-Silico Studies and Cytotoxicity

Yusof ENM, Latif MAM, Tahir MIM, Sakoff JA, Simone MI, Page AJ, et al.

Int J Mol Sci, 2019 Feb 15;20(4).
PMID: 30781445 DOI: 10.3390/ijms20040854

Six new organotin(IV) compounds of Schiff bases derived from S-R-dithiocarbazate [R = benzyl (B), 2- or 4-methylbenzyl (2M and 4M, respectively)] condensed with 2-hydroxy-3-methoxybenzaldehyde (oVa) were synthesised and characterised by elemental analysis, various spectroscopic techniques including infrared, UV-vis, multinuclear (¹H, 13C, 119Sn) NMR and mass spectrometry, and single crystal X-ray diffraction. The organotin(IV) compounds were synthesised from the reaction of Ph₂SnCl₂ or Me₂SnCl₂ with the Schiff bases (S2MoVaH/S4MoVaH/SBoVaH) to form a total of six new organotin(IV) compounds that had a general formula of [R₂Sn(L)] (where L = Schiff base; R = Ph or Me). The molecular geometries of Me₂Sn(S2MoVa), Me₂Sn(S4MoVa) and Me₂Sn(SBoVa) were established by X-ray crystallography and verified using density functional theory calculations. Interestingly, each experimental structure contained two independent but chemically similar molecules in the crystallographic asymmetric unit. The coordination geometry for each molecule was defined by thiolate-sulphur, phenoxide-oxygen and imine-nitrogen atoms derived from a dinegative, tridentate dithiocarbazate ligand with the remaining positions occupied by the methyl-carbon atoms of the organo groups. In each case, the resulting five-coordinate C₂NOS geometry was almost exactly intermediate between ideal trigonal-bipyramidal and square-pyramidal geometries. The cytotoxic activities of the Schiff bases and organotin(IV) compounds were investigated against EJ-28 and RT-112 (bladder), HT29 (colon), U87 and SJ-G2 (glioblastoma), MCF-7 (breast) A2780 (ovarian), H460 (lung), A431 (skin), DU145 (prostate), BE2-C (neuroblastoma) and MIA (pancreatic) cancer cell lines and one normal breast cell line (MCF-10A). Diphenyltin(IV) compounds exhibited greater potency than either the Schiff bases or the respective dimethyltin(IV) compounds. Mechanistic studies on the action of these compounds against bladder cancer cells revealed that they induced the production of reactive oxygen species (ROS). The bladder cancer cells were apoptotic after 24 h post-treatment with the diphenyltin(IV) compounds. The interactions of the organotin(IV) compounds with calf thymus DNA (CT-DNA) were experimentally explored using UV-vis absorption spectroscopy. This study revealed that the organotin(IV) compounds have strong DNA binding affinity, verified via molecular docking simulations, which suggests that these organotin(IV) compounds interact with DNA via groove-binding interactions.

Matched MeSH terms: Urinary Bladder Neoplasms
[A case of chronic schistosomiasis four years after infestation]

Pedalino M, Vercesi E, Manini C, Piras D, Di Primio OG, Vella R, et al.

Urologia, 2010 Oct-Dec;77 Suppl 17:38-41.
PMID: 21308673

Authors present a case of bilharziosis incidentally diagnosed in a patient undergoing TURB for suspected bladder cancer. The patient, who in 2005 had gone to Malaysia, had been suffering from recurrent hemorrhagic cystitis since 2007, which were treated with antibiotic therapy. In November 2009 he presented to our observation for persistent hematuria, underwent ultrasound examination, fibroscopy and TURB diagnostics for suspicious lesions. The histopathology diagnosis found granulomatous lesions with typical parasites eggs due to schistosomiasis eggs. As a consequence of that, the patient underwent medical therapy. The pathologist's role becomes nullifying not only for the diagnosis of parasitic infections but also for the exclusion or evidence of urothelial squamous neoplasia. The low incidence of this rare parasitic disease in European tourists and the presence of immigrants in our country require to spread the knowledge of these parasites and the most simple tests for early detection.

Matched MeSH terms: Urinary Bladder Neoplasms/diagnosis
Whole-genome multiparametric screening to identify modulators of epithelial-to-mesenchymal transition

Said NA, Gould CM, Lackovic K, Simpson KJ, Williams ED

Assay Drug Dev Technol, 2014 Sep;12(7):385-94.
PMID: 25181411 DOI: 10.1089/adt.2014.593

Metastasis accounts for the poor prognosis of the majority of solid tumors. The phenotypic transition of nonmotile epithelial tumor cells to migratory and invasive "mesenchymal" cells (epithelial-to-mesenchymal transition [EMT]) enables the transit of cancer cells from the primary tumor to distant sites. There is no single marker of EMT; rather, multiple measures are required to define cell state. Thus, the multiparametric capability of high-content screening is ideally suited for the comprehensive analysis of EMT regulators. The aim of this study was to generate a platform to systematically identify functional modulators of tumor cell plasticity using the bladder cancer cell line TSU-Pr1-B1 as a model system. A platform enabling the quantification of key EMT characteristics, cell morphology and mesenchymal intermediate filament vimentin, was developed using the fluorescent whole-cell-tracking reagent CMFDA and a fluorescent promoter reporter construct, respectively. The functional effect of genome-wide modulation of protein-coding genes and miRNAs coupled with those of a collection of small-molecule kinase inhibitors on EMT was assessed using the Target Activation Bioapplication integrated in the Cellomics ArrayScan platform. Data from each of the three screens were integrated to identify a cohort of targets that were subsequently examined in a validation assay using siRNA duplexes. Identification of established regulators of EMT supports the utility of this screening approach and indicated capacity to identify novel regulators of this plasticity program. Pathway analysis coupled with interrogation of cancer-related expression profile databases and other EMT-related screens provided key evidence to prioritize further experimental investigation into the molecular regulators of EMT in cancer cells.

Matched MeSH terms: Urinary Bladder Neoplasms/drug therapy
Wavelet energy-guided level set-based active contour: a segmentation method to segment highly similar regions

Achuthan A, Rajeswari M, Ramachandram D, Aziz ME, Shuaib IL

Comput Biol Med, 2010 Jul;40(7):608-20.
PMID: 20541182 DOI: 10.1016/j.compbiomed.2010.04.005

This paper introduces an approach to perform segmentation of regions in computed tomography (CT) images that exhibit intra-region intensity variations and at the same time have similar intensity distributions with surrounding/adjacent regions. In this work, we adapt a feature computed from wavelet transform called wavelet energy to represent the region information. The wavelet energy is embedded into a level set model to formulate the segmentation model called wavelet energy-guided level set-based active contour (WELSAC). The WELSAC model is evaluated using several synthetic and CT images focusing on tumour cases, which contain regions demonstrating the characteristics of intra-region intensity variations and having high similarity in intensity distributions with the adjacent regions. The obtained results show that the proposed WELSAC model is able to segment regions of interest in close correspondence with the manual delineation provided by the medical experts and to provide a solution for tumour detection.

Matched MeSH terms: Urinary Bladder Neoplasms/pathology; Urinary Bladder Neoplasms/radiography
Fulltext Validation of oligonucleotide microarray gene expression profiles by real-time PCR using SYBR-Green 1 fluorescence

Nik Norliza Nik Hassan, Rozita Rosli, Abdul Munir Abdul Murad, Nor Kaslina Kornain, Sabariah, A.R., Rohan Malek Johan, et al.

Buletin Persatuan Genetik Malaysia, 2008;14(1):1-16.
MyJurnal

DNA microarray technology has permitted large scale parallel analysis of gene expression of several diseases, including cancers. Real-time PCR has become a well-established procedure for
quantifying levels of gene expression. We evaluated Real-Time PCR to validate differentially expressed genes identified by DNA arrays. Gene expression of three different grade of transitional cell carcinoma (TCC) of human bladder cancer was determined using microarray slide containing cancer-related genes. Data obtained were sorted according based on the ratios between Cy3 and Cy5 dyes used and revealed 119, 235 and 183 differentially expressed genes in TCC WHO Grades I, II and III, respectively. Real-time PCR used SYBR Green-1 dye detection to validate relative change in gene expression. Real- Time PCR confirmed the change in gene expression of 17 of 28 (75%) genes identified by microarray. Real-Time PCR also suggest that genes identified by microarray with two or higher fold change cannot be eliminated as false nor be accepted as true without validation. Real-Time PCR based on SYBR Green- 1 is well-suited to validate DNA array results because it is quantitative, rapid and requires less RNA compared to the conventional assays.

Matched MeSH terms: Urinary Bladder Neoplasms
Urethral recurrence after radical cystectomy for urothelial carcinoma: A systematic review and meta-analysis

Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Kübler H, Stenzl A, et al.

Urol Oncol, 2018 02;36(2):54-59.
PMID: 29196179 DOI: 10.1016/j.urolonc.2017.11.007

PURPOSE: Currently, identified factors for urethral recurrence (UR) are based on individual reporting which has displayed controversy. In addition, risk of UR is one of the limiting factors to offer neobladder diversion during radical cystectomy (RC). We aim to systematically evaluate the incidence and risk factors of UR post-RC and its effect on survival.
MATERIALS AND METHODS: A systematic online search was conducted according to PRISMA statement for publications reporting on UR after RC. From initial 802 results, 14 articles including 6169 patients were included finally after exclusion of ineligible studies.
RESULTS: The incidence rate of UR was 4.4% (1.3%-13.7%). It was significantly lower with neobladder diversion (odds ratio = 0.44, 95% CI: 0.24-0.79, P = 0.006). Muscle invasion (hazard ratio = 1.18, 95% CI: 0.86-1.62, P = 0.31), carcinoma in situ (hazard ratio 0.97, 95% CI: 0.64-1.47, P = 0.88), prostatic stromal involvement (hazard ratio = 2.26, 95% CI: 0.01-627.75, P = 0.78), and prostatic urethral involvement (hazard ratio = 2.04, 95% CI: 0.20-20.80, P = 0.55) have no significant effect on UR. Men displayed tendency toward higher incidence of UR (odds ratio = 2.21, 95% CI: 0.96-5.06, P = 0.06). Absence of recurrence displayed tendency toward better disease specific survival, yet not significant (hazard ratio = 0.84, 95% CI: 0.66-1.08, P = 0.17). These results are limited by the retrospective nature of the included studies.
CONCLUSION: Muscle invasion, carcinoma in situ and prostatic stromal or urethral involvement at time of RC have no significant effect on UR. Orthotopic neobladder is associated with a significant lower risk of UR after RC.

Matched MeSH terms: Urinary Bladder Neoplasms/pathology; Urinary Bladder Neoplasms/surgery*
Fulltext Two Secreted Proteoglycans, Activators of Urothelial Cell-Cell Adhesion, Negatively Contribute to Bladder Cancer Initiation and Progression

Papadaki V, Asada K, Watson JK, Tamura T, Leung A, Hopkins J, et al.

Cancers (Basel), 2020 Nov 13;12(11).
PMID: 33202923 DOI: 10.3390/cancers12113362

Osteomodulin (OMD) and proline/arginine-rich end leucine repeat protein (PRELP) are secreted extracellular matrix proteins belonging to the small leucine-rich proteoglycans family. We found that OMD and PRELP were specifically expressed in umbrella cells in bladder epithelia, and their expression levels were dramatically downregulated in all bladder cancers from very early stages and various epithelial cancers. Our in vitro studies including gene expression profiling using bladder cancer cell lines revealed that OMD or PRELP application suppressed the cancer progression by inhibiting TGF-β and EGF pathways, which reversed epithelial-mesenchymal transition (EMT), activated cell-cell adhesion, and inhibited various oncogenic pathways. Furthermore, the overexpression of OMD in bladder cancer cells strongly inhibited the anchorage-independent growth and tumorigenicity in mouse xenograft studies. On the other hand, we found that in the bladder epithelia, the knockout mice of OMD and/or PRELP gene caused partial EMT and a loss of tight junctions of the umbrella cells and resulted in formation of a bladder carcinoma in situ-like structure by spontaneous breakdowns of the umbrella cell layer. Furthermore, the ontological analysis of the expression profiling of an OMD knockout mouse bladder demonstrated very high similarity with those obtained from human bladder cancers. Our data indicate that OMD and PRELP are endogenous inhibitors of cancer initiation and progression by controlling EMT. OMD and/or PRELP may have potential for the treatment of bladder cancer.

Matched MeSH terms: Urinary Bladder Neoplasms
Fulltext Tumoral cystitis in children

Zulfiqar MA, Zaleha AM, Zulkifli I, Chia WY, Samad SA

Med J Malaysia, 1998 Sep;53(3):284-7.
PMID: 10968168

Three children aged 3-11 years had ultrasonography of the urinary tract for the investigation of dysuria and haematuria. A bladder mass was seen in these 3 children. One child had computed tomography scan, cystoscopy and bladder biopsy because rhabdomyosarcoma was considered. The biopsy revealed an inflammatory process. The urine culture of the other 2 children revealed E. coli. On ultrasonography, the inflammatory mass may appear homogeneously hypoechoic or may contain moderate level echoes. The mucosal surface of the mass may be smooth or lobulated. It is important to consider an infective cause for a bladder mass in children because computed tomography, cystoscopy and biopsy may be avoided.

Matched MeSH terms: Urinary Bladder Neoplasms/ultrasonography*
Fulltext Tumor markers of bladder cancer: the schistosomal bladder tumors versus non-schistosomal bladder tumors

Abdulamir AS, Hafidh RR, Kadhim HS, Abubakar F

J Exp Clin Cancer Res, 2009;28:27.
PMID: 19243595 DOI: 10.1186/1756-9966-28-27

The aim of this study is to comparatively elucidate the underlying molecular pathways and clinicopathological criteria in schistosomal bladder tumor (SBT) versus non-schistosomal bladder tumor (NSBT).

Matched MeSH terms: Urinary Bladder Neoplasms/genetics; Urinary Bladder Neoplasms/metabolism; Urinary Bladder Neoplasms/parasitology*; Urinary Bladder Neoplasms/pathology
The prognostic impact of hexaminolevulinate-based bladder tumor resection in patients with primary non-muscle invasive bladder cancer treated with radical cystectomy

Renninger M, Fahmy O, Schubert T, Schmid MA, Hassan F, Stenzl A, et al.

World J Urol, 2020 Feb;38(2):397-406.
PMID: 31030231 DOI: 10.1007/s00345-019-02780-0

PURPOSE: To investigate whether hexaminolevulinate-based (HAL) bladder tumor resection (TURBT) impacts on outcomes of patients with primary non-muscle-invasive bladder cancer (NMIBC) who were eventually treated with radical cystectomy (RC).
METHODS: A total of 131 consecutive patients exhibiting NMIBC at primary diagnosis were retrospectively investigated whether they had undergone any HAL-guided TURBT prior to RC. Uni- and multivariable analyses were used to evaluate the impact of HAL-TURBT on cancer-specific (CSS) and overall survival (OS). The median follow-up was 38 months (IQR 13-56).
RESULTS: Of the 131 patients, 69 (52.7%) were managed with HAL- and 62 (47.3%) with white light (WL)-TURBT only prior to RC. HAL-TURBT was associated with a higher number of TURBTs prior to RC (p = 0.002) and administration of intravesical chemotherapy (p = 0.043). A trend towards a higher rate of tumor-associated immune cell infiltrates in RC specimens (p = 0.07) and a lower utilization rate of post-operative systemic chemotherapy (p = 0.10) was noted for patients who were treated with HAL-TURBT. The 5-year CSS/OS was 90.9%/74.5% for the HAL-group and 73.8%/55.8% for the WL-group (p = 0.042/0.038). In multivariable analysis, lymph node tumor involvement (p = 0.007), positive surgical margins (p = 0.001) and performance of WL-TURBT only (p = 0.040) were independent predictors for cancer-specific death.
CONCLUSIONS: The present data suggest that the resection of NMIBC under HAL exerts a beneficial impact on outcomes of patients who will need to undergo RC during their course of disease. This finding may be due to improved risk stratification as the resection under HAL may allow more patients to be treated timely and adequately.

Matched MeSH terms: Urinary Bladder Neoplasms/drug therapy*; Urinary Bladder Neoplasms/pathology; Urinary Bladder Neoplasms/surgery*
The impact of a modified ileal neobladder on the lifestyle and voiding patterns in Asian patients

Lee KT, Li MK, Cheng WS, Foo KT

Br J Urol, 1998 May;81(5):705-8.
PMID: 9634045 DOI: 10.1046/j.1464-410x.1998.00586.x

OBJECTIVE: To evaluate the impact of the modified ileal neobladder reconstruction on lifestyle, voiding habits and functional outcome in Asian patients.

PATIENTS AND METHODS: Twenty-seven Asian patients (25 men and two women, mean age 59 years, range 41-76) underwent modified ileal neobladder reconstruction after radical cystectomy for carcinoma of the bladder. The mean (range) follow-up was 21 (3-75) months. All patients were evaluated retrospectively using case notes, reviews, interviews and voiding charts; 18 patients underwent urodynamic studies.

RESULT: Twenty-five patients (93%) achieved diurnal and 23 (85%) nocturnal continence within 6 months. Of the 19 patients who were in employment before surgery, 15 continued to be economically active afterward; 26 patients (96%) reported no change in their daily living activities. Of 16 men who reported being potent pre-operatively only four retained some residual erectile function. Twenty-three patients were interviewed about their voiding habits and satisfaction with the outcome of surgery. Fourteen patients had no sensation of reservoir fullness and of the 21 men, 13 had to squat or sit to void effectively. The mean (range) voiding frequency was 5 (4-8) during the day and 2 (0-4) during sleep. Twenty-two patients were satisfied with the overall outcome.

CONCLUSIONS: The modified ileal bladder provides a high urinary continence rate with minimal changes in daily living activities and occupational status. The functional outcome was very satisfactory and accepted well, despite some changes in reservoir sensation, voiding posture and erectile function. The method is a viable option for reconstruction after cystectomy in Asian patients.

Matched MeSH terms: Urinary Bladder Neoplasms/ethnology; Urinary Bladder Neoplasms/psychology; Urinary Bladder Neoplasms/surgery*
The current status of checkpoint inhibitors in metastatic bladder cancer

Fahmy O, Khairul-Asri MG, Stenzl A, Gakis G

Clin. Exp. Metastasis, 2016 10;33(7):629-35.
PMID: 27380916 DOI: 10.1007/s10585-016-9807-9

For many decades, no significant improvements could be achieved to prolong the survival in metastatic bladder cancer. Recently, systemic immunotherapy with checkpoint inhibitors (anti-PD-L1/anti-CTLA-4) has been introduced as a novel treatment modality for patients with metastatic bladder cancer. We conducted a systematic review according to the PRISMA statement for data published on the clinical efficacy of checkpoint inhibitors in metastatic bladder cancer. Clinical efficacy of anti PD-L1 therapy was investigated in prospective trials in a total of 155 patients. Patients with positive expression for PD-L1 tended towards better overall response rates (ORR) compared to those with negative expression (34/76 vs 10/73, 45 vs 14 %; p = 0.21). Among patients with PD-L1 positive tumors, those with non-visceral metastases exhibited significantly higher ORR compared to those with visceral metastases (82 vs 28 %; p = 0.001). For anti-CTLA4 therapy, there were no data retrievable on clinical efficacy. Although data on clinical efficacy of checkpoint inhibitors in metastatic bladder cancer are currently limited, the efficacy of these drugs might depend mainly on the metastatic volume and immune system integrity. Patients with PD-L1 positive tumors and non-visceral metastases seem to derive the highest benefit from therapy.

Matched MeSH terms: Urinary Bladder Neoplasms/drug therapy*; Urinary Bladder Neoplasms/genetics; Urinary Bladder Neoplasms/pathology
Fulltext The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease

Fu YP, Kohaar I, Moore LE, Lenz P, Figueroa JD, Tang W, et al.

Cancer Res, 2014 Oct 15;74(20):5808-18.
PMID: 25320178 DOI: 10.1158/0008-5472.CAN-14-1531

A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (P(trend) = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models.

Matched MeSH terms: Urinary Bladder Neoplasms/genetics*; Urinary Bladder Neoplasms/pathology
Fulltext Targeting bladder cancer stem cells using Newcastle disease virus

Arcana Thirumorthy, De-Ming Chau, Khatijah Yusoff, Abhi Veerakumarasivam

Malaysian Journal of Medicine and Health Sciences, 2019;15(108):24-24.
MyJurnal

Introduction: Bladder cancer is associated with high risk of tumour recurrence and therapeutic resistance. Cancer stem cells (CSC) within a particular tumour are postulated to drive tumorigenesis and influence tumour behaviour. Recent studies have shown that Newcastle disease virus (NDV) is able to selectively kill and exert a strong oncolytic effect against various cancer types. However little is known about the oncolytic effect of NDV against CSC. In this study, the oncolytic effect of NDV against putative bladder CSC was examined. Methods: Putative bladder CSC was selectively grown in the form of 3D-spheroids from six different bladder cancer cell lines. The spheroid cells were characterised for their stemness properties to ensure that these cells truly represent CSC. This was conducted via the analysis of CSC associated genes and cell surface markers expression. Subsequently, the oncolytic effect of the wild-type NDV-AF2240 strain against the bladder cancer spheroids was investigated. Results: All the spheroids expressed significantly high levels of CSC-associated genes. Flow-cytometry analysis revealed that the expression pattern of the CSC-associated surface markers was different in the spheroid cells; suggesting heterogeneity in the expression signatures of these cells. The infection of spheroids with NDV showed that the NDV was able to target bladder cancer spheroids but there was a spectrum of response across the different spheroids. Intriguingly, NDV was able to persistently infect bladder cancer spheroids that were not sensitive towards NDV infection as the presence of NDV viral genes were detected in the spheroid cells. The NDV persistently infected bladder cancer spheroids were resistant to superinfection and developed an antiviral state by expressing low levels of interferon-beta (IFN-b). NDV persistency of infection affects the process of epithelial to mesenchymal transition (EMT) of cancer cells as the spheroid forming ability of an established NDV persistently infected bladder cancer cell line, EJ28-PI was shown to be impaired. The EJ28-PI cells expressed significantly high levels of the EN2 gene. Knockdown of the EN2 expression reduced the viability of EJ28-PI cells; suggesting a role for EN2 in mediating NDV persistency of infection in cancer cells. Conclusion: Bladder CSC gene expression signatures influence the efficacy of NDV-mediated oncolysis. Our current work is focused on identifying genes and signalling pathways that influence NDV-mediated oncolysis us-ing whole-transcriptomic sequencing. The findings of this study can potentially be used to enhance the efficacy of NDV-mediated oncolysis and accelerate the translation of NDV as an oncotherapeutic agent in the clinic.

Matched MeSH terms: Urinary Bladder Neoplasms
Systemic anti-CTLA-4 and intravesical Bacille-Calmette-Guerin therapy in non-muscle invasive bladder cancer: Is there a rationale of synergism?

Fahmy O, Khairul-Asri MG, Stenzl A, Gakis G

Med Hypotheses, 2016 Jul;92:57-8.
PMID: 27241256 DOI: 10.1016/j.mehy.2016.04.037

Although intravesical instillation of Bacille-Calmette-Guerin (BCG) immunotherapy was approved many decades ago as a first line therapy for intermediate to high-risk non-muscle invasive bladder cancer, its long-term efficacy is still arguable as a proportion of up to 30-40% of patients will develop recurrence or progression of their disease. Based on currently available data on the clinical application of checkpoint inhibitors in solid tumors, the mucosa-associated lymphoid tissue seems to be a main target for anti-CTLA-4 antibodies. In this manuscript we hypothesize that the combination of anti-CTLA-4 therapy with BCG might enhance the immune activity in the bladder submucosal tissue, and subsequently, improve oncological outcomes of NMIBC.

Matched MeSH terms: Urinary Bladder Neoplasms/immunology; Urinary Bladder Neoplasms/therapy*
Systematic Review and Meta-Analysis on the Impact of Hexaminolevulinate- Versus White-Light Guided Transurethral Bladder Tumor Resection on Progression in Non-Muscle Invasive Bladder Cancer

Gakis G, Fahmy O

Bladder cancer (Amsterdam, Netherlands), 2016 Jul 27;2(3):293-300.
PMID: 27500197

Introduction: Although there is evidence that hexaminolevulinate (HAL)-based transurethral bladder tumor resection (TURBT) improves the detection of Ta-T1 non-muscle-invasive bladder cancer (NMIBC) as well as carcinoma in situ there is uncertainty about its beneficial effects on progression. Material and Methods: A systematic literature search was conducted according to the PRISMA statement to identify studies reporting on HAL- vs. white-light (WL-) based TUR-BT in non-muscle invasive bladder cancer between 2000 and 2016. A two-stage selection process was utilized to determine eligible studies. Of a total of 294 studies, 5 (4 randomized and one retrospective) were considered for final analysis. The primary objective was the rate of progression. Results: The median follow-up for patients treated with HAL- and WL-TURBT was 27.6 (1-55.1) and 28.9 (1-53) months, respectively. Of a total of 1301 patients, 644 underwent HAL- and 657 WL-based TURBT. Progression was reported in 44 of 644 patients (6.8%) with HAL- and 70 of 657 patients (10.7%) with WL-TURBT, respectively (median odds ratio: 1.64, 1.10-2.45 for HAL vs. WL; p = 0.01). Data on progression-free survival was reported in a single study with a trend towards improved survival for patients treated with HAL-TURBT (p = 0.05). Conclusions: In this meta-analysis the rate of progression was significantly lower in patients treated with HAL- vs. WL-based TURBT. These results support the initiation of randomized trials on HAL with progression as primary endpoint.

Matched MeSH terms: Urinary Bladder Neoplasms
Stratifying patients with haematuria into high or low risk groups for bladder cancer: a novel clinical scoring system

Hee TG, Shah SA, Ann HS, Hemdan SN, Shen LC, Al-Fahmi Abdul Galib N, et al.

Asian Pac J Cancer Prev, 2013;14(11):6327-30.
PMID: 24377526

Haematuria is a common presentation of bladder cancer and requires a full urologic evaluation. This study aimed to develop a scoring system capable of stratifying patients with haematuria into high or low risk groups for having bladder cancer to help clinicians decide which patients need more urgent assessment. This cross- sectional study included all adult patients referred for haematuria and subsequently undergoing full urological evaluation in the years 2001 to 2011. Risk factors with strong association with bladder cancer in the study population were used to design the scoring system. Accuracy was determined by the area under the receiver operating characteristic (ROC) curve. A total of 325 patients with haematuria were included, out of which 70 (21.5%) were diagnosed to have bladder cancer. Significant risk factors associated with bladder cancer were male gender, a history of cigarette smoking and the presence of gross haematuria. A scoring system using 4 clinical parameters as variables was created. The scores ranged between 6 to 14, and a score of 10 and above indicated high risk for having bladder cancer. It was found to have good accuracy with an area under the ROC curve of 80.4%, while the sensitivity and specificity were 90.0% and 55.7%, respectively. The scoring system designed in this study has the potential to help clinicians stratify patients who present with haematuria into high or low risk for having bladder cancer. This will enable high-risk patients to undergo urologic assessment earlier.

Matched MeSH terms: Urinary Bladder Neoplasms/diagnosis*; Urinary Bladder Neoplasms/urine*
Self-perceived burden and its associations with health-related quality of life among urologic cancer patients

Ting CY, Teh GC, Yu KL, Alias H, Tan HM, Wong LP

Eur J Cancer Care (Engl), 2020 Jul;29(4):e13248.
PMID: 32495472 DOI: 10.1111/ecc.13248

OBJECTIVE: This study examined the prevalence of self-perceived burden (SPB) and its association with health-related quality of life (HRQoL) among urologic cancer patients.
METHODS: This was a prospective, cross-sectional study. A total of 429 respondents diagnosed with urologic cancers (prostate, bladder and renal cancer) from Sarawak General Hospital and Subang Jaya Medical Centre in Malaysia were interviewed by using a structured questionnaire. SPB and HRQoL were measured by the Self-perceived Burden Scale and the Functional Assessment of Cancer Therapy-General 7 Item Scale respectively.
RESULTS AND CONCLUSION: Self-perceived burden was experienced by 73.2% of the respondents. Respondents who had a lower education level, a monthly household income

Matched MeSH terms: Urinary Bladder Neoplasms/physiopathology; Urinary Bladder Neoplasms/psychology*
Fulltext Ruptured Aortic Aneurysm Secondary to Psoas abscess after Intravesical Bacilli Calmette-Guérin

Khandelwal A, Gupta A, Virmani V, Khandelwal K

Med J Malaysia, 2012 Oct;67(5):534-5.
PMID: 23770877

Bacillus Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis that has been used as effective treatment for early-stage transitional carcinoma of the urinary bladder. We present a case of a 68 year old man who had an abdominal aortic aneurysm following BCG therapy for bladder cancer. Contrast enhanced computerized tomogram (CECT) of abdomen and pelvis revealed bilateral hypodense lesions suggestive of psoas abscesses. In addition, a saccular abdominal aortic aneurysm measuring 4x3.6 cm involving infrarenal aorta with surrounding hematoma was seen. At surgery, he was found to have a psoas abscess and hemorrhage. He underwent ligation of the aorta and an axillary-bifemoral bypass. He was given one year of anti-tubercular therapy to which he responded clinically.

Matched MeSH terms: Urinary Bladder Neoplasms
Fulltext Reiter's syndrome postintravesical Bacillus Calmette-Guérin instillations

Ng KL, Chua CB

Asian J Surg, 2017 Apr;40(2):163-165.
PMID: 25183290 DOI: 10.1016/j.asjsur.2014.01.016

Intravesical Bacillus Calmette-Guérin (BCG) has been a proven and effective immunotherapy treatment for superficial transitional cell carcinoma (TCC) of the bladder, especially for high-grade tumors and carcinoma in situ. Nevertheless, significant side effects are associated with BCG instillations, including fever, myalgia, malaise, dysuria, hematuria, and irritable lower urinary tract symptoms. We herein report the case of a patient who developed Reiter's syndrome following intravesical BCG instillations. A 39-year-old Chinese man presented with a 3-week history of dysuria, suprapubic pain, and pain at the tip of the penis postmicturition. Initial investigations revealed that he had microhematuria, and an ultrasound with computed tomography scan of the abdomen showed a bladder mass. Transurethral resection of the bladder tumor was performed and the patient received a single dose of intravesical mitomycin postoperatively. Results of histopathological examination revealed high-grade bladder TCC (G3pT1), and the patient was managed with intravesical BCG for 2 weeks following the surgery. Four weekly cycles of BCG were administered uneventfully; however, before the fifth instillation, the patient complained of urethral discharge, bilateral conjunctivitis, and low back pain. Reiter's syndrome was diagnosed as a rare but known complication of BCG instillation and the BCG immunotherapy was withheld. The patient was treated with nonsteroidal antiinflammatory drugs (for back pain) and eye ointment (for conjunctivitis) and his condition improved. This case report of Reiter's syndrome should be highlighted as a rare but significant complication of BCG immunotherapy and urologists should have a high index of suspicion to diagnose this rare complication.

Matched MeSH terms: Urinary Bladder Neoplasms/drug therapy*; Urinary Bladder Neoplasms/pathology; Urinary Bladder Neoplasms/surgery

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