Displaying publications 1 - 20 of 61 in total

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  1. Md Akhir MKA, Hussin H, Veerakumarasivam A, Choy CS, Abdullah MA, Abd Ghani F
    Malays J Pathol, 2017 Dec;39(3):227-234.
    PMID: 29279584 MyJurnal
    Urothelial carcinoma is a common malignant neoplasm that has a poor prognosis and a high frequency of recurrence and metastasis. Constant disease surveillance with periodic and long term cystoscopy examination is necessary for management of the disease. However, the monitoring and therapy regimen is expensive, incurring a massive burden to patients and the government. Therefore, the development of specific biomarkers for urothelial carcinoma at an early stage and recurrence detection becomes a priority. Homeobox genes are a family of genes that are involved in tumourigenesis. They might be potential prognostic markers for urothelial carcinoma. The study investigated the expression pattern of NANOG which is one of a homeobox gene in different stages and grades of urothelial carcinoma. NANOG expressions were also correlated with patient demographic factors and clinicopathological parameters. The expression of NANOG in 100 formalin-fixed paraffin-embedded urothelial carcinoma tissues was determined by immunohistochemistry. Immunohistochemistry showed positive expression of NANOG in all specimens with detection in the cytoplasm, nuclei and the nuclear membrane of the cancer cells. The immunohistochemical expression of NANOG increased across stages and grades of the tumour. The expression of NANOG was not significantly associated with demographic factors; gender (p = 0.376), race (p = 0.718) and age (p = 0.058) as well as with most of the clinicopathological parameters; pathological stage (p = 0.144), grade (p = 0.625), lymph node involvement (p = 0.174) and distant metastasis (p = 0.228). However, NANOG expression showed significant correlation with tumour invasion (p = 0.019). We concluded that NANOG might be a potential biomarker for early diagnosis of urothelial carcinoma of the bladder.
    Matched MeSH terms: Urinary Bladder Neoplasms/pathology*
  2. Mohd Ariffin K, Abd Ghani F, Hussin H, Md Said S, Yunus R, Veerakumarasivam A, et al.
    Malays J Pathol, 2021 Apr;43(1):49-54.
    PMID: 33903305
    INTRODUCTION: Hedgehog (HH) pathway is an important signalling cascade for growth and patterning during embryonic development. Constitutive activation of Hedgehog pathway can be found in various types of malignancies including medulloblastoma, basal cell carcinoma, gastrointestinal, breast, pancreatic, prostate cancer and leukaemia. Little is known about the expression and role of Hedgehog signalling in bladder cancer.

    MATERIALS AND METHODS: The purpose of this study was to investigate the immunohistochemical expression of SMO in 112 bladder cancer cases and determine their association with demographic and clinicopathological parameters. Bladder cancer tissues were obtained from the Hospital Kuala Lumpur.

    RESULTS: SMO was expressed in the cytoplasm of all cases of bladder cancer. 6 cases (5.4%) showed low expression, while 106 cases (94.6%) showed high expression. Positive expression of SMO protein was correlated with a few variables which include grade and stage of tumour, lymph node metastasis and distant metastasis. SMO expression showed statistically significant association with higher grade (p=0.001) and higher stage (p=0.042) of bladder cancer. SMO expression also showed borderline association with lymph node metastasis (p=0.056).

    CONCLUSION: These findings indicate that SMO expression may be a poor prognostic marker in bladder cancer.

    Matched MeSH terms: Urinary Bladder Neoplasms
  3. Arcana Thirumorthy, De-Ming Chau, Khatijah Yusoff, Abhi Veerakumarasivam
    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
  4. Abdulamir AS, Hafidh RR, Kadhim HS, Abubakar F
    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
  5. Naqiyah I, Rohaizak M, Meah FA, Nazri MJ, Sundram M, Amram AR
    Singapore Med J, 2005 Jul;46(7):344-6.
    PMID: 15968447
    The occurrence of urinary bladder paragangliomas is rare. A 12-year-old Chinese girl who presented with history of blurring of vision was found to have grade IV hypertensive retinopathy. Investigations revealed a phaeochromocytoma on the posterior wall of the urinary bladder. A partial cystectomy with right ureter reimplantation was undertaken and her hypertension was promptly controlled. The diagnosis and management of this rare tumour is discussed.
    Matched MeSH terms: Urinary Bladder Neoplasms/diagnosis; Urinary Bladder Neoplasms/surgery*
  6. Teoh JY, Cho CL, Wei Y, Isotani S, Tiong HY, Ong TA, et al.
    World J Urol, 2019 Sep;37(9):1879-1887.
    PMID: 30560297 DOI: 10.1007/s00345-018-2602-2
    PURPOSE: The Asian Urological Surgery Training & Education Group (AUSTEG) has been established to provide training and education to young urologists in Asia. We developed and validated a porcine bladder training model for transurethral resection of bladder tumour (TURBT).

    METHODS: Urology residents and specialists were invited to test the training model. They were asked to complete a pre-task questionnaire, to perform piecemeal and en bloc resection of 'bladder tumours' within the training model, and to complete a post-task questionnaire afterwards. Their performances were assessed by faculty members of the AUSTEG. For the face validity, a pre-task questionnaire consisting of six statements on TURBT and the training model were set. For the content validity, a post-task questionnaire consisting of 14 items on the details of the training model were set. For the construct validity, a Global Rating Scale was used to assess the participants' performances. The participants were stratified into two groups (junior surgeons and senior surgeons groups) according to their duration of urology training.

    RESULTS: For the pre-task questionnaire, a mean score of ≥ 4.0 out of 5.0 was achieved in 5 out of 6 statements. For the post-task questionnaire, a mean score of ≥ 4.5 out of 5.0 was achieved in every item. For the Global Rating Scale, the senior surgeons group had higher scores than the junior surgeons group in 8 out of 11 items as well as the total score.

    CONCLUSION: A porcine TURBT training model has been developed, and its face, content and construct validity has been established.

    Matched MeSH terms: Urinary Bladder Neoplasms/surgery*
  7. Mahamooth Z, Awang H
    Med J Malaysia, 1983 Mar;38(1):4-8.
    PMID: 6633334
    One hundred and fifty patients with urothelial tumours were reviewed. They form the majority of patients with bladder cancer referred to the Institute of Urology over the past three years. From the study it becomes very apparent that the majority of patients are seen late in the course of their disease. The results of treatment of patients with early lesions have been satisfactory but the patients with late invasive lesions have very poor prognosis. A plea is made that one be more aware of this condition and that symptoms of haematuria and urinary tract infections should have a full urological assessment early.
    Matched MeSH terms: Urinary Bladder Neoplasms/pathology*; Urinary Bladder Neoplasms/therapy
  8. Ali F, Safawi EB, Zakaria Z, Basiron N
    Clin Ter, 2013;164(5):413-5.
    PMID: 24217827 DOI: 10.7417/CT.2013.1605
    Entero-cutaneous fistula resulting from a locally invasive large bowel carcinoma is a difficult surgical challenge. En-bloc resection of the involved organs and the entero-cutaneous fistula tract with a healthy tissue margin will result in a composite abdominal wall defect that requires closure. Reconstructive surgical options include primary closure, components separation and the use of local, regional or free flaps with or without prosthetic mesh. We report a case of an abdominal enterocutaneous fistula secondary to a locally invasive sigmoid carcinoma, which was reconstructed with a pedicled antero-lateral thigh perforator (ALT) flap. To our knowledge, this is the first case of a malignant entero-cutaneous fistula, which was reconstructed with an ALT flap.
    Matched MeSH terms: Urinary Bladder Neoplasms/diagnosis
  9. Chan LC, Kalyanasundram J, Leong SW, Masarudin MJ, Veerakumarasivam A, Yusoff K, et al.
    BMC Cancer, 2021 May 27;21(1):625.
    PMID: 34044804 DOI: 10.1186/s12885-021-08345-y
    BACKGROUND: Newcastle disease virus (NDV) is an oncolytic virus with excellent selectivity against cancer cells, both in vitro and in vivo. Unfortunately, prolonged in vitro NDV infection results in the development of persistent infection in the cancer cells which are then able to resist NDV-mediated oncolysis. However, the mechanism of persistency of infection remains poorly understood.

    METHODS: In this study, we established persistently NDV-infected EJ28 bladder cancer cells, designated as EJ28P. Global transcriptomic analysis was subsequently carried out by microarray analysis. Differentially expressed genes (DEGs) between EJ28 and EJ28P cells identified by the edgeR program were further analysed by Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) analyses. In addition, the microarray data were validated by RT-qPCR.

    RESULTS: Persistently NDV-infected EJ28 bladder cancer cells were successfully established and confirmed by flow cytometry. Microarray analysis identified a total of 368 genes as differentially expressed in EJ28P cells when compared to the non-infected EJ28 cells. GSEA revealed that the Wnt/β-catenin and KRAS signalling pathways were upregulated while the TGF-β signalling pathway was downregulated. Findings from this study suggest that the upregulation of genes that are associated with cell growth, pro-survival, and anti-apoptosis may explain the survivability of EJ28P cells and the development of persistent infection of NDV.

    CONCLUSIONS: This study provides insights into the transcriptomic changes that occur and the specific signalling pathways that are potentially involved in the development and maintenance of NDV persistency of infection in bladder cancer cells. These findings warrant further investigation and is crucial towards the development of effective NDV oncolytic therapy against cancer.

    Matched MeSH terms: Urinary Bladder Neoplasms
  10. 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
  11. Tan WS, Teo CH, Chan D, Ang KM, Heinrich M, Feber A, et al.
    BJU Int, 2020 05;125(5):669-678.
    PMID: 31975539 DOI: 10.1111/bju.15008
    OBJECTIVE: To determine patient experience and perception following a diagnosis of non-muscle-invasive bladder cancer (NMIBC).

    PATIENT AND METHODS: Patients were part of a prospective multicentre observational study recruiting patients with NMIBC for a urine biomarker study (DETECT II; ClinicalTrials.gov: NCT02781428). A mixed-methods approach comprising: (i) the Brief Illness Perception Questionnaire (Brief-IPQ) and (ii) semi-structured interviews to explore patients' experience of having haematuria, and initial and subsequent experience with a NMIBC diagnosis. Both assessments were completed at 6 months after NMIBC diagnosis.

    RESULTS: A total of 213 patients completed the Brief-IPQ. Patients felt that they had minimal symptoms (median [interquartile range, IQR] score 2 [0-5]) and were not particularly affected emotionally (median [IQR] score 3 [1-6]) with a minimal effect to their daily life (median [IQR] score 2 [0-5]). However, they remained concerned about their cancer diagnosis (median [IQR] score 5 [3-8]) and felt that they had no personal control over the cancer (median [IQR] score 2 [2-5]) and believed that their illness would affect them for some time (median [IQR] score 6 [3-10]). A significant association with a lower personal control of the disease (P 70 years. Many patients were uncertain about the cause of bladder cancer. Qualitative analysis found that at initial presentation of haematuria, most patients were not aware of the risk of bladder cancer. Patients were most anxious and psychologically affected between the interval of cystoscopy diagnosis and transurethral resection of bladder tumour (TURBT). Following TURBT, most patients were positive about their cancer prognosis.

    CONCLUSION: Patients with NMIBC have a poor perception of disease control and believe that their disease will continue over a prolonged period of time. This is particularly more pertinent in the elderly. Patients are most psychologically affected during the interval between cancer diagnosis following cystoscopy and TURBT. Health awareness about bladder cancer remained poor with a significant number of patients unaware of the causes of bladder cancer. Psychological support and prompt TURBT following bladder cancer diagnosis would help improve the mental health of patients with NMIBC.

    Matched MeSH terms: Urinary Bladder Neoplasms/diagnosis*; Urinary Bladder Neoplasms/psychology
  12. 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
  13. 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*
  14. 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*
  15. Fahmy O, Asri K, Schwentner C, Stenzl A, Gakis G
    J Surg Oncol, 2015 Sep;112(4):427-9.
    PMID: 26265262 DOI: 10.1002/jso.24007
    To investigate the current status and feasibility of robotic neobladder diversion after robotic assisted radical cystectomy. A Medline search was conducted resulting in identification of 423 articles. After exclusion of ineligible studies, 3 case series and 5 case reports were considered with a total number of reported cases of 203. Although robotic intracorporeal neobladder reconstruction is in its starting phase, initial perioperative results seem to be comparable to open series. However, randomized studies are needed to confirm non-inferiority.
    Matched MeSH terms: Urinary Bladder Neoplasms/surgery*
  16. 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*
  17. Fahmy O, Khairul-Asri MG, Schubert T, Renninger M, Malek R, Kübler H, et al.
    Urol Oncol, 2018 02;36(2):43-53.
    PMID: 29102254 DOI: 10.1016/j.urolonc.2017.10.002
    OBJECTIVE: This study aimed to comprehensively analyze the oncological long-term outcomes of trimodal therapy (TMT) and radical cystectomy (RC) for the treatment of muscle-invasive bladder cancer (BC) with or without neoadjuvant chemotherapy (NAC).

    PATIENTS AND METHODS: A systematic search was conducted according to the PRISMA guidelines for studies reporting on outcomes after TMT and RC. A total of 57 studies including 30,293 patients were included. The 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates for TMT and RC were assessed.

    RESULTS: The mean 10-year OS was 30.9% for TMT and 35.1% for RC (P = 0.32). The mean 10-year DSS was 50.9% for TMT and 57.8% for RC (P = 0.26). NAC was administered before therapy to 453 (13.3%) of 3,402 patients treated with TMT and 812 (3.0%) of 27,867 patients treated with RC (P<0.001). Complete response (CR) was achieved in 1,545 (75.3%) of 2,051 evaluable patients treated with TMT. A 5-year OS, DSS, and RFS after CR were 66.9%, 78.3%, and 52.5%, respectively. Downstaging after transurethral bladder tumor resection or NAC to stage ≤pT1 at RC was reported in 2,416 (29.1%) of 8,311 patients. NAC significantly increased the rate of pT0 from 20.2% to 34.3% (P = 0.007) in cT2 and from 3.8% to 23.9% (P<0.001) in cT3-4. A 5-year OS, DSS, and RFS in downstaged patients (≤pT1) at RC were 75.7%, 88.3%, and 75.8%, respectively.

    CONCLUSION: In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. Patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.

    Matched MeSH terms: Urinary Bladder Neoplasms/pathology; Urinary Bladder Neoplasms/therapy*
  18. 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*
  19. Schubert T, Renninger M, Schmid MA, Hassan FN, Sokolakis I, Fahmy O, et al.
    Urol Oncol, 2020 01;38(1):4.e7-4.e15.
    PMID: 31537484 DOI: 10.1016/j.urolonc.2019.08.013
    OBJECTIVES: To assess whether the presence and location of tumor-associated immune cell infiltrates (TAIC) on histological slides obtained from cystectomy specimens impacts on oncological outcomes of patients with bladder cancer (BC).

    MATERIAL AND METHODS: A total of 320 consecutive patients staged with cM0 bladder cancer underwent radical cystectomy (RC) between 2004 and 2013. The presence of TAIC (either located peritumorally [PIC] and/or intratumorally [IIC]) on histological slides was retrospectively assessed and correlated with outcomes. Kaplan-Meier analyses were used to estimate the impact of TAIC on recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS). Multivariable Cox-regression analysis was carried out to evaluate risk factors of recurrence. The median follow-up was 37 months (IQR: 10-55).

    RESULTS: Of the 320 patients, 42 (13.1%) exhibited IIC, 141 (44.1%) PIC and 137 (42.8%) no TAIC in the cystectomy specimens. Absence of TAIC was associated with higher ECOG performance status (P = 0.042), histologically advanced tumor stage (≥pT3a; P < 0.001), lymph node tumor involvement (pN+; P = 0.022), positive soft tissue surgical margins (P = 0.006), lymphovascular invasion (P < 0.001), and elevated serum C-reactive protein levels (P < 0.001). The rate of never smokers was significantly higher in the IIC-group (64.3%) compared to the PIC-group (39.7%, P = 0.007) and those without TAIC (35.8%, P = 0.001). The 3-year RFS/CSS/OS was 73.9%/88.5%/76.7% for patients with IIC, 69.4%/85.2%/70.1% for PIC and 47.6%/68.5%/56.1% for patients without TAIC (P < 0.001/<0.001/0.001 for TAIC vs. no TAIC). In multivariable analysis, adjusted for all significant parameters of univariable analysis, histologically advanced tumor stage (P = 0.003), node-positive disease (P = 0.002), and the absence of TAIC (P = 0.035) were independent prognosticators for recurrence.

    CONCLUSIONS: In this analysis, the presence and location of TAIC in cystectomy specimens was a strong prognosticator for RFS after RC. This finding suggests that the capability of immune cells to migrate into the tumor at the time of RC is prognostically important in invasive bladder cancer.

    Matched MeSH terms: Urinary Bladder Neoplasms/mortality; Urinary Bladder Neoplasms/surgery*
  20. 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
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