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Minimally invasive vs open radical cystectomy in patients with bladder cancer: A systematic review and meta-analysis of randomized controlled trials.
Hu, X, Xiong, SC, Dou, WC, Shao, YX, Yang, WX, Liu, JB, Li, X
European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2020;(1):44-52
Abstract
OBJECTIVE Minimally invasive surgical (MIS) approaches to radical cystectomy (RC) develop well in the past decades. We performed the present study to compare the perioperative outcomes, pathological outcomes, and oncologic outcomes between MIS approaches and open radical cystectomy (ORC) for bladder cancer. METHOD We conducted a comprehensive study search up to March 2019, searching the online database Embase, PubMed and Cochrane Library. RESULTS A total of 8 randomized controlled trials comprising 805 patients were included. We observed that MIS approaches were significantly associated with lower estimated blood loss (WMD = -343.21; 95%CI -431.34 to -255.08; P < 0.001), shorter length of stay (WMD = -0.76; 95%CI -1.28 to -0.24; P = 0.004), shorter time to flatus and diet (WMD = -0.46; 95%CI -0.64 to -0.27; P < 0.001; WMD = -0.92; 95%CI -1.58 to -0.28; P = 0.005; respectively), longer operation time (WMD = 61.38; 95%CI 34.89 to 87.88; P < 0.001), fewer 30-day overall complication (OR = 0.36; 95%CI 0.17 to 0.75; P = 0.007). And we did not detect significant difference in terms of 30-day (P = 0.278) and 90-day major complication (P = 0.899), positive surgical margins (P = 0.986), lymph node yield (P = 0.711), OS (P = 0.473), CSS (P = 0.778), RFS (P = 0.880), PFS (P = 0.324) between MIS approaches and ORC. CONCLUSION In the present studies, we demonstrated that MIS approaches improved perioperative outcomes and had similar pathological and oncological outcomes compared with ORC. Stratified by type of MIS approaches, the results are similar. In conclusion, MIS approaches could serve as an alternative choice in patients with bladder cancer. However, long-term clinical outcomes highlight the need for future studies.
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Management of cisplatin-associated toxicities in bladder cancer patients.
Desilets, A, Adam, JP, Soulières, D
Current opinion in supportive and palliative care. 2020;(3):286-292
Abstract
PURPOSE OF REVIEW Cisplatin remains the treatment cornerstone for bladder cancer, either in neoadjuvant or in metastatic (cisplatin-gemcitabine or dose-dense methotrexate, vinblastine, and doxorubicin). Timely and adequate management of cisplatin's adverse events is important in order to avoid dose reductions, treatment delays, or cessation. Over the last years, several randomized studies and updated guidelines have been published on this subject. RECENT FINDINGS The incidence, physiopathology, risk factors, preventive treatment, and optimal management of such complications will be presented, with special focus on cisplatin-associated nausea and vomiting, acute kidney injury (AKI), hypomagnesemia, neurotoxicity, and ototoxicity. SUMMARY Optimal prevention of cisplatin-associated nausea and vomiting requires an aggressive approach with the use of a four-drug prophylactic regimen (NK1 receptor antagonist, 5-HT3 receptor antagonist, dexamethasone, olanzapine). The use of intensive hydration before and after cisplatin infusion has been the mainstay of AKI prevention. The management of hypomagnesemia and neurotoxicity remains largely symptomatic. In an adult population, no therapy has yet demonstrated benefits in the prevention or treatment of platinum-related ototoxicity.
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Urothelial carcinoma of the bladder with abundant myxoid stroma: A case report and literature review.
Tao, TT, Chen, J, Hu, Q, Huang, XJ, Fu, J, Lv, BD, Duan, Y
Medicine. 2020;(28):e21204
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INTRODUCTION Abundant myxoid stroma rarely occurs in urothelial carcinomas (UCs). We report an 83-year-old woman with UC of the urinary bladder with abundant myxoid stroma. We summarized the clinicopathological features, immunophenotype, diagnosis, and differential diagnosis of this type of bladder cancer, in order to improve the understanding of surgeons and pathologists. PATIENT CONCERNS An 83-year-old female presented with hematuria and frequent micturition, without odynuria, hypogastralgia, or fever. DIAGNOSIS The computed tomography scan demonstrated extensive tumors in the anterior wall of the bladder and a soft tissue shadow anterior to the sacrum. Cystoscopy showed massive wide-based tumors located on the anterior and lateral walls of the bladder, with no tumor involving the bladder neck. Multiple punch biopsies were performed, the histologic evaluation of which revealed a poorly differentiated invasive UCs with myxoid stroma. INTERVENTIONS The patient underwent a laparoscopic radical cystectomy and cutaneous ureterostomy. OUTCOMES The patient discharged without any complications. Histologic evaluation revealed an invasive UC; the most prominent feature was an abundant myxoid stroma that covered approximately 80% of the lesion and the tumor cells were arranged in cords, small nests, or a sheet-like structure. Immunohistochemically, the tumor cells were positive for CK19, CK20, VEGF, EGFR, p63, 34βE12, MUC1, GATA3, uroplakin3, and TopII (rate = 15%), while the Ki-67 proliferation index was 10%. The myxoid stroma in the mesenchyme stained positively with AB-PAS and colloidal iron, and some tumor cells stained positive for colloidal iron. Considering the histologic, histochemical, and immunohistochemical findings, a diagnosis of UC with abundant myxoid stroma was made. After surgery, the regular follow-up was continued in clinic, and there was no recurrence for 2 years. CONCLUSION Morbidity associated with UC with abundant myxoid stroma is very low. The diagnosis mainly depends on histopathological and immunohistochemical findings.
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Assessments of frailty in bladder cancer.
Grimberg, DC, Shah, A, Molinger, J, Whittle, J, Gupta, RT, Wischmeyer, PE, McDonald, SR, Inman, BA
Urologic oncology. 2020;(9):698-705
Abstract
BACKGROUND AND AIMS The incidence of frailty is increasing as the population ages, which has important clinical implications given the associations between frailty and poor outcomes in the bladder cancer population. Due to a multi-organ system decline and decreased physiologic reserve, frail patients are vulnerable to stressors of disease and have poorer mortality and morbidity rates than their nonfrail peers. The association between frailty and poor outcomes has been documented across multiple populations, including radical cystectomy, creating a need for frailty assessments to be used preoperatively for risk stratification. We aim to provide a review of the common frailty assessments and their relevance to radical cystectomy patients. FINDINGS A variety of assessments for frailty exist, from short screening items to comprehensive geriatric assessments. The syndrome spans multiple organ systems, as do the potential diagnostic instruments. Some instruments are less practical for use in clinical practice by urologists, such as the Canadian Study of Health and Aging Frailty Index and Comprehensive Geriatric Assessment. The tool most studied in radical cystectomy is the modified Frailty Index, associated with high grade complications and 30-days mortality. Frailty often coexists with malnutrition and sarcopenia, stressing the importance of screening for and addressing these syndromes to improve patient's perioperative outcomes. CONCLUSIONS There is no universally agreed upon frailty assessment, but the most studied in radical cystectomy is the modified Frailty Index, providing valuable data with which to counsel patients preoperatively. Alterations in immune phenotypes provide potential future diagnostic biomarkers for frailty.
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Enhanced recovery after surgery (ERAS) protocols in patients undergoing radical cystectomy with ileal urinary diversions: A randomized controlled trial.
Vlad, O, Catalin, B, Mihai, H, Adrian, P, Manuela, O, Gener, I, Ioanel, S
Medicine. 2020;(27):e20902
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BACKGROUND Enhanced Recovery After Surgery (ERAS) protocols were introduced in clinical practice to reduce complication rates and hospital stay. We performed a randomized controlled single center study to evaluate perioperative benefits of an adapted ERAS protocol in patients with bladder cancer who underwent radical cystectomy (RC) and ileal urinary diversions (IUD). MATERIALS AND METHODS Forty five from 90 consecutive randomized patients were enrolled in an adapted ERAS protocol. Length of stay, diet issues, return of bowel function, readmission rates and complications were examined. RESULTS Among patients following ERAS protocol, we found a significant reduction in time to first flatus (1 vs 5 days, P < .001), time to first stool (2 vs 5 days, P < .001), time to normal diet (5 vs 6 days, P < .001) and length of stay (16 vs 18 days, P < .001). Also, postoperative ileus at less than 4 days was lower than in non-ERAS patients (15.6% vs 24.4%), but with a marginal trend toward significance (P = .05). Readmission rate was lower in the ERAS group, but the difference did not reach statistical significance. We also found a lower readmission and complication rate in patients with ERAS protocol (6.6% vs 11.1%, P = .23 and 46.6% vs 57.5%, P = .29, respectively). CONCLUSIONS Implementation of ERAS protocol for patients undergoing RC in our center was associated with a significant reduction in the time to the first flatus, time to the first stool, time to a normal diet, length of hospital stay.
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Comparative effectiveness of open, laparoscopic and robot-assisted radical cystectomy for bladder cancer: a systematic review and network meta-analysis.
Feng, D, Li, A, Hu, X, Lin, T, Tang, Y, Han, P
Minerva urologica e nefrologica = The Italian journal of urology and nephrology. 2020;(3):251-264
Abstract
INTRODUCTION Our aim is to compare feasibility and safety of open radical cystectomy (ORC), laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) for the treatment of bladder cancer through network meta-analysis. EVIDENCE ACQUISITION Eligible articles were identified from electronic databases including PubMed/Medline, Embase, the Cochrane Library and Web of Science up to August 2019 with no language limitations. Studies selection, quality assessment, data extraction and analysis were accomplished by two independent reviewers (DCF and AL) using Cochrane Collaboration's tools. EVIDENCE SYNTHESIS After screening 2528 articles, 27 studies were included in the final meta-analysis. In the network meta-analysis, both RARC (MD:83.09, 95% CI: 61.06 to 105.11) and LRC (MD: 49.68, 95% CI: 21.75 to 77.62) showed a longer operative time compared with ORC. Besides, RARC had a longer operative time than LRC (MD: 33.40, 95% CI: 1.35 to 65.45). RARC (MD:-591.86, 95% CI: -879.46 to -304.27) and LRC (MD: -435.28, 95% CI: -854.98 to -15.58) showed a less estimated blood loss (EBL) than ORC; however, the difference in EBL for RARC versus LRC was not significant. RARC (OR: 0.26, 95% CI: 0.14 to 0.50) and LRC (OR: 0.23, 95% CI: 0.13 to 0.43) had a higher blood transfusion rate than ORC; however, the OR between RARC and LRC was not significant. RARC (MD: -1.34, 95% CI: -2.55 to -0.12) and LRC (MD: -1.35, 95% CI: -2.38 to -0.32) took a shorter time to regular diet compared with ORC; however, there was no significant difference between RARC and LRC. Compared with ORC, RARC (MD: -2.37, 95% CI: -3.57 to -1.17) and LRC (MD: -2.22, 95% CI: -4.04 to -0.40) showed a shorter length of stay (LOS); however, the difference in LOS for RARC versus LRC was not significant. RARC, LRC and ORC were comparable with regard to minor complications, major complications, positive surgical margin and lymph node yields. CONCLUSIONS Current evidence indicates that minimally invasive approaches could be considered as a feasible and safe alternative to ORC when performed by experienced surgeons in selected patients. Notably, RARC may be more suitable for RC with extracorporeal urinary diversion. Larger well-designed trials are still needed to confirm these findings due to the observational nature of most studies.
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Ferumoxytol-Enhanced MR Lymphography for Detection of Metastatic Lymph Nodes in Genitourinary Malignancies: A Prospective Study.
Turkbey, B, Czarniecki, M, Shih, JH, Harmon, SA, Agarwal, PK, Apolo, AB, Citrin, DE, Gulley, JL, Harisinghani, M, Madan, RA, et al
AJR. American journal of roentgenology. 2020;(1):105-113
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OBJECTIVE. The objective of our study was to evaluate the utility of ferumoxytol-enhanced MR lymphography (MRL) in detection of metastatic lymph nodes (LNs) in patients with prostate, bladder, and kidney cancer. SUBJECTS AND METHODS. This phase 2 single-institution study enrolled patients with confirmed prostate (arm 1), bladder (arm 2), and kidney (arm 3) cancer and evidence of suspected LN involvement. Participants underwent ferumoxytol-enhanced MRL 24 and 48 hours after IV injection of 7.5 mg Fe/kg of ferumoxytol. A retrospective quantitative analysis was performed to determine the optimal timing for ferumoxytol-enhanced MRL using percentage change in normalized signal intensity (SI) from baseline to 24 and 48 hours after injection, which were estimated using the linear mixed-effects model in which time (24 vs 48 hours), diseases status, and time and disease status interaction were the fixed-effects independent variables. Differences in normalized SI values between subgroups of lesions were estimated by forming fixed-effects contrasts and tested by the Wald test. RESULTS. Thirty-nine patients (n = 30, arm 1; n = 6, arm 2; n = 3, arm 3) (median age, 65 years) with 145 LNs (metastatic, n = 100; benign, n = 45) were included. LN-based sensitivity, specificity, positive predictive value, and negative predictive value of ferumoxytol-enhanced MRL was 98.0%, 64.4%, 86.0%, and 93.5%, respectively. Sensitivity and specificity of ferumoxytol-enhanced MRL did not vary by LN size. Metastatic LNs showed a significantly higher percentage decrease of normalized SI on MRL at 24 hours after ferumoxytol injection than at 48 hours after ferumoxytol injection (p = 0.023), whereas the normalized SI values for nonmetastatic LNs were similar at both imaging time points (p = 0.260). CONCLUSION. Ferumoxytol-enhanced MRL shows high sensitivity in the detection of metastatic LNs in genitourinary cancers independent of LN size. The SI difference between benign and malignant LNs on ferumoxytol-enhanced MRL appears similar 24 and 48 hours after ferumoxytol injection, suggesting that imaging can be performed safely within 1 or 2 days of injection. Although ferumoxytol-enhanced MRL can be useful in settings without an available targeted PET agent, issues of iron overload and repeatability of ferumoxytol-enhanced MRL remain concerns for this method.
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Grain and dietary fiber intake and bladder cancer risk: a pooled analysis of prospective cohort studies.
Yu, EYW, Wesselius, A, Mehrkanoon, S, Brinkman, M, van den Brandt, P, White, E, Weiderpass, E, Le Calvez-Kelm, F, Gunter, M, Huybrechts, I, et al
The American journal of clinical nutrition. 2020;(5):1252-1266
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BACKGROUND Higher intakes of whole grains and dietary fiber have been associated with lower risk of insulin resistance, hyperinsulinemia, and inflammation, which are known predisposing factors for cancer. OBJECTIVES Because the evidence of association with bladder cancer (BC) is limited, we aimed to assess associations with BC risk for intakes of whole grains, refined grains, and dietary fiber. METHODS We pooled individual data from 574,726 participants in 13 cohort studies, 3214 of whom developed incident BC. HRs, with corresponding 95% CIs, were estimated using Cox regression models stratified on cohort. Dose-response relations were examined using fractional polynomial regression models. RESULTS We found that higher intake of total whole grain was associated with lower risk of BC (comparing highest with lowest intake tertile: HR: 0.87; 95% CI: 0.77, 0.98; HR per 1-SD increment: 0.95; 95% CI: 0.91, 0.99; P for trend: 0.023). No association was observed for intake of total refined grain. Intake of total dietary fiber was also inversely associated with BC risk (comparing highest with lowest intake tertile: HR: 0.86; 95% CI: 0.76, 0.98; HR per 1-SD increment: 0.91; 95% CI: 0.82, 0.98; P for trend: 0.021). In addition, dose-response analyses gave estimated HRs of 0.97 (95% CI: 0.95, 0.99) for intake of total whole grain and 0.96 (95% CI: 0.94, 0.98) for intake of total dietary fiber per 5-g daily increment. When considered jointly, highest intake of whole grains with the highest intake of dietary fiber showed 28% reduced risk (95% CI: 0.54, 0.93; P for trend: 0.031) of BC compared with the lowest intakes, suggesting potential synergism. CONCLUSIONS Higher intakes of total whole grain and total dietary fiber are associated with reduced risk of BC individually and jointly. Further studies are needed to clarify the underlying mechanisms for these findings.
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Coffee consumption and risk of bladder cancer: a pooled analysis of 501,604 participants from 12 cohort studies in the BLadder Cancer Epidemiology and Nutritional Determinants (BLEND) international study.
Yu, EYW, Dai, Y, Wesselius, A, van Osch, F, Brinkman, M, van den Brandt, P, Grant, EJ, White, E, Weiderpass, E, Gunter, M, et al
European journal of epidemiology. 2020;(6):523-535
Abstract
Recent epidemiological studies have shown varying associations between coffee consumption and bladder cancer (BC). This research aims to elucidate the association between coffee consumption and BC risk by bringing together worldwide cohort studies on this topic. Coffee consumption in relation to BC risk was examined by pooling individual data from 12 cohort studies, comprising of 2601 cases out of 501,604 participants. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel Weibull regression models. Furthermore, dose-response relationships were examined using generalized least squares regression models. The association between coffee consumption and BC risk showed interaction with sex (P-interaction < 0.001) and smoking (P-interaction = 0.001). Therefore, analyses were stratified by sex and smoking. After adjustment for potential confounders, an increased BC risk was shown for high (> 500 ml/day, equivalent to > 4 cups/day) coffee consumption compared to never consumers among male smokers (current smokers: HR = 1.75, 95% CI 1.27-2.42, P-trend = 0.002; former smokers: HR = 1.44, 95% CI 1.12-1.85, P-trend = 0.001). In addition, dose-response analyses, in male smokers also showed an increased BC risk for coffee consumption of more than 500 ml/day (4 cups/day), with the risk of one cup (125 ml) increment as 1.07 (95% CI 1.06-1.08). This research suggests that positive associations between coffee consumption and BC among male smokers but not never smokers and females. The inconsistent results between sexes and the absence of an association in never smokers indicate that the associations found among male smokers is unlikely to be causal and is possibly caused by residual confounding of smoking.
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The role of Protopine associated with Nuciferine in controlling adverse events during hyperthermic intravesical chemotherapy instillations. A nutraceutical approach to control adverse event during intravesical instillations.
Chiancone, F, Carrino, M, Fedelini, M, Fabiano, M, Persico, F, Meccariello, C, Fedelini, P
Archivio italiano di urologia, andrologia : organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica. 2020;(3)
Abstract
OBJECTIVES The aim of this study was to analyse the role of two alkaloid, Protopine and Nuciferine, in the prevention and the treatment of the low and mild grade adverse events related to the use of HIVEC® (Hyperthermic IntraVEsical Chemotherapy) instillations. MATERIALS AND METHODS From September 2017 to September 2019, 100 patients were prospectively randomized into two groups: Group A = Protopine and Nuciferine syrup, 10 ml, once a day, for 8 weeks; Group B = placebo (flavoured coloured water), 10 ml, once a day, for 8 weeks. The primary endpoint was the evaluation of the efficacy of the therapy with Protopine and Nuciferine in controlling of the irritative symptoms. The secondary endpoint was the evaluation of the influences of the treatment on the uroflowmetric parameters. RESULTS The patients of Group A showed a better International Prostatic Symptoms Score (IPSS) score, a better control of urgency symptoms (PPIUS) and tolerate well the pain (VAS score). The treatment doesn't modify Uroflow-Qmax and seems to improve the Uroflow-Voided Volume (ml) without influencing the Uroflow-Post Void Residual volume (PVR). Moreover, the treatment with Protopine and Nuciferine has been proven to be effective in the treatment of overactive bladder (OAB) symptoms. Patients' evaluation of the two different treatments assessed with Patient Global Impression of Improvement questionnaire (PGI-I), demonstrated improvements in the Group A, while the Group B showed a lower satisfaction. CONCLUSIONS Protopine and Nuciferine can be interesting nutraceutical compounds useful to control irritative and pain related symptoms of intravesical chemo/immunotherapy.