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European Urology Apr 2022Therapies based on immune checkpoint inhibitors (ICIs) are transforming the treatment landscape of urologic oncology. Nevertheless, an exhaustive overview of the... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Therapies based on immune checkpoint inhibitors (ICIs) are transforming the treatment landscape of urologic oncology. Nevertheless, an exhaustive overview of the toxicity spectrum of these novel therapies has yet to be provided.
OBJECTIVE
To comprehensively investigate the incidence and profile of ICI therapy-related adverse events (AEs) across urologic cancers.
EVIDENCE ACQUISITION
We searched for all clinical trials investigating the role of ICI therapy published between January 2010 and September 2021. Studies involving urologic cancers with reported overall incidence or tabulated data of treatment-related AEs (trAEs) or immune-related AEs (irAEs) were included. A systematic review and meta-analysis was performed after protocol registration in PROSPERO (CRD42021276435).
EVIDENCE SYNTHESIS
We identified 2638 records, of which 92 studies (including 22942 participants) met the inclusion criteria. The pooled overall incidence was 81.6% (95% confidence interval [CI] 78.0-84.7) for any-grade trAEs and 29.3% (95% CI 24.9-34.1) for grade ≥3 trAEs. The pooled overall incidence was 34.3% (95% CI 28.5-40.7) for any-grade irAEs and 10.2% (95%CI 8.2-12.7) for grade ≥3 irAEs. On a multivariable analysis, cancer type, therapy combination, clinical settings (perioperative vs advanced/metastatic), and drug exposure were independently associated with the occurrence of trAEs or irAEs. The overall rate of treatment-related mortality was 0.94% (140 of 14 899 participants), with pneumonitis (9.3%), pneumonia (7.9%), and respiratory failure (7.1%) being the most common causes. Immune-related mortality occurred in 0.26% (28 of 10 723) patients, with pneumonitis (35.7%), hepatic failure (10.7%), and hepatitis (7.1%) being most common.
CONCLUSIONS
Our study provides a comprehensive overview of ICI-associated AEs in urologic cancer patients. The spectrum and incidence of AEs vary across cancer types, ICI types, clinical settings, and therapy combinations. These findings provide important guidance to clinicians in counseling and management of patients with urologic cancers.
PATIENT SUMMARY
A high proportion of patients experience immune checkpoint inhibitor-associated toxicity. Physician and patient education is critical for early recognition and proper management.
Topics: Female; Humans; Immune Checkpoint Inhibitors; Incidence; Male; Radioimmunotherapy; Urologic Neoplasms
PubMed: 35101302
DOI: 10.1016/j.eururo.2022.01.028 -
JAMA Pediatrics Aug 2023Controversy exists on the clinical utility of kidney ultrasonography after first febrile urinary tract infection (UTI), and clinical practice guideline recommendations... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Controversy exists on the clinical utility of kidney ultrasonography after first febrile urinary tract infection (UTI), and clinical practice guideline recommendations vary.
OBJECTIVE
To determine the prevalence of urinary tract abnormalities detected on kidney ultrasonography after the first febrile UTI in children.
DATA SOURCES
The MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Central Register of Controlled Trials databases were searched for articles published from January 1, 2000, to September 20, 2022.
STUDY SELECTION
Studies of children with first febrile UTI reporting kidney ultrasonography findings.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently screened titles, abstracts, and full texts for eligibility. Study characteristics and outcomes were extracted from each article. Data on the prevalence of kidney ultrasonography abnormalities were pooled using a random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was prevalence of urinary tract abnormalities and clinically important abnormalities (those that changed clinical management) detected on kidney ultrasonography. Secondary outcomes included the urinary tract abnormalities detected, surgical intervention, health care utilization, and parent-reported outcomes.
RESULTS
Twenty-nine studies were included, with a total of 9170 children. Of the 27 studies that reported participant sex, the median percentage of males was 60% (range, 11%-80%). The prevalence of abnormalities detected on renal ultrasonography was 22.1% (95% CI, 16.8-27.9; I2 = 98%; 29 studies, all ages) and 21.9% (95% CI, 14.7-30.1; I2 = 98%; 15 studies, age <24 months). The prevalence of clinically important abnormalities was 3.1% (95% CI, 0.3-8.1; I2 = 96%; 8 studies, all ages) and 4.5% (95% CI, 0.5-12.0; I2 = 97%; 5 studies, age <24 months). Study recruitment bias was associated with a higher prevalence of abnormalities. The most common findings detected were hydronephrosis, pelviectasis, and dilated ureter. Urinary tract obstruction was identified in 0.4% (95% CI, 0.1-0.8; I2 = 59%; 12 studies), and surgical intervention occurred in 1.4% (95% CI, 0.5-2.7; I2 = 85%; 13 studies). One study reported health care utilization. No study reported parent-reported outcomes.
CONCLUSIONS AND RELEVANCE
Results suggest that 1 in 4 to 5 children with first febrile UTI will have a urinary tract abnormality detected on kidney ultrasonography and 1 in 32 will have an abnormality that changes clinical management. Given the considerable study heterogeneity and lack of comprehensive outcome measurement, well-designed prospective longitudinal studies are needed to fully evaluate the clinical utility of kidney ultrasonography after first febrile UTI.
Topics: Male; Humans; Child; Child, Preschool; Prospective Studies; Vesico-Ureteral Reflux; Kidney; Urinary Tract Infections; Ultrasonography
PubMed: 37252727
DOI: 10.1001/jamapediatrics.2023.1387 -
EBioMedicine Feb 2022Calcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for...
BACKGROUND
Calcium plays a role in a wide range of biological functions. Here we conducted a phenome-wide Mendelian randomisation (MR-PheWAS) analysis and a systematic review for MR studies to comprehensively investigate the health effects of serum calcium.
METHODS
One-hundred and thirty genetic variants strongly associated with serum calcium levels were used as instrumental variables. A phenome-wide association analysis (PheWAS) was conducted to examine the associations of genetically predicted serum calcium with 1473 distinct phenotypes in the UK Biobank including 339,197 individuals. Observed associations in PheWAS were further tested for replication in two-sample MR replication analysis. A systematic review for MR studies on serum calcium was performed to synthesize the published evidence and compare with the current MR-PheWAS findings.
FINDINGS
Higher genetically predicted calcium levels were associated with decreased risk of 5 diseases in dermatologic and musculoskeletal systems and increased risk of 17 diseases in circulatory, digestive, endocrine, genitourinary and immune systems. Eight associations were replicated in two-sample MR analysis. These included decreased risk of osteoarthritis and increased risk of coronary artery disease, myocardial infarction, coronary atherosclerosis, hyperparathyroidism, disorder of parathyroid gland, gout, and calculus of kidney and ureter with increased serum calcium. Systematic review of 25 MR studies provided supporting evidence on five out of the eight disease outcomes, while the increased risk of gout, hyperparathyroidism and disorder of parathyroid gland were novel findings.
INTERPRETATION
This study found wide-ranged health effects of high serum calcium, which suggests that the benefits and adversities of strategies promoting calcium intake should be assessed.
FUNDING
ET is supported by a CRUK Career Development Fellowship (C31250/A22804). XL is supported by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province. SCL acknowledges research funding from the Swedish Heart Lung Foundation (Hjärt-Lungfonden, 20210351), the Swedish Research Council (Vetenskapsrådet, 2019-00977), and the Swedish Cancer Society (Cancerfonden).
Topics: Calcium; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Phenomics; Phenotype; Polymorphism, Single Nucleotide
PubMed: 35134646
DOI: 10.1016/j.ebiom.2022.103865 -
Indian Journal of Urology : IJU :... 2017Ureteral endometriosis is a rare disease affecting women of childbearing age which presents with nonspecific symptoms and it may result in severe morbidity. The aim of... (Review)
Review
INTRODUCTION
Ureteral endometriosis is a rare disease affecting women of childbearing age which presents with nonspecific symptoms and it may result in severe morbidity. The aim of this study was to review evidence about incidence, pathogenesis, clinical presentation, diagnosis, and management of ureteral endometriosis.
MATERIALS AND METHODS
PubMed Central database was searched to identify studies reporting cases of ureteral endometriosis. "Ureter" or "Ureteral" and "Endometriosis" were used as key words. Database was searched for articles published since 1996, in English without restrictions regarding the study design.
RESULTS
From 420 studies obtained through database search, 104 articles were finally included in this review, including a total of 1384 patients with ureteral endometriosis. Data regarding age, location, pathological findings, and interventions were extracted. Mean patients' age was 38.6 years, whereas the therapeutic arsenal included hormonal, endoscopic, and/or surgical treatment.
CONCLUSIONS
Ureteral endometriosis represents a diagnostic and therapeutic challenge for the clinicians and high clinical suspicion is needed to identify it.
PubMed: 29021650
DOI: 10.4103/iju.IJU_84_17 -
European Journal of Surgical Oncology :... Nov 2016To perform a systematic review and meta-analysis of the comparative studies reporting oncological and renal function outcomes of segmental ureterectomy (SU) versus... (Comparative Study)
Comparative Study Meta-Analysis Review
A systematic review and meta-analysis of oncological and renal function outcomes obtained after segmental ureterectomy versus radical nephroureterectomy for upper tract urothelial carcinoma.
OBJECTIVE
To perform a systematic review and meta-analysis of the comparative studies reporting oncological and renal function outcomes of segmental ureterectomy (SU) versus radical nephroureterectomy (RNU) for upper tract urothelial carcinomas (UTUC).
MATERIALS AND METHODS
A literature search on Pubmed, Embase, and the Cochrane library was conducted according to the PRISMA guidelines, and a meta-analysis was performed to assess cancer-specific survival (CSS), overall survival (OS), recurrence-free survival (RFS), intravesical recurrence free survival (IVRFS) and surgery-related variations in estimated glomerular filtration rate (eGFR).
RESULTS
A total of 11 retrospective studies with 3963 patients who underwent either SU (n = 983; 24.8%) or RNU (n = 2980; 75.2%) were included. Although patients treated with SU were more likely to be diagnosed with favorable pathological features, the meta-analysis of unadjusted data revealed no significant difference between both groups in terms of CSS (HR 0.90, p = 0.33) and OS (HR 0.98, p = 0.93). Accordingly, the meta-analysis of adjusted data confirmed equivalent CSS (HR = 0.90, p = 0.47) between SU and RNU. Similarly, no significant difference was found in terms of RFS (HR 1.06, p = 0.72) and IVRFS (HR 1.35, p = 0.39). However, a significant decreased risk of impaired renal function was observed after SU when compared to RNU (mean eGFR difference = 9.32 ml/1.73 m, p = 0.007).
CONCLUSION
Although adverse patient and tumor characteristics were not equally balanced between treatment arms, our systematic review and meta-analysis supports similar oncological outcomes between SU and RNU, with better preservation of renal function after SU. As such, SU should be preferably used as the first-line treatment for low-risk ureter tumors, while considered for selected cases of high-risk disease.
Topics: Carcinoma, Transitional Cell; Glomerular Filtration Rate; Humans; Kidney Neoplasms; Nephrectomy; Treatment Outcome; Ureter; Ureteral Neoplasms
PubMed: 27612412
DOI: 10.1016/j.ejso.2016.08.008 -
Current Oncology (Toronto, Ont.) Dec 2022Upper tract urothelial carcinoma (UTUC) is a rare form of malignancy comprising only 5% of urothelial cancers. The mainstay of treatment is radical nephroureterectomy... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Upper tract urothelial carcinoma (UTUC) is a rare form of malignancy comprising only 5% of urothelial cancers. The mainstay of treatment is radical nephroureterectomy (RNU) with bladder cuff excision. Neoadjuvant or adjuvant chemotherapy is often used in locally advanced disease. The role of adjuvant radiotherapy (RT), however, remains controversial. To further explore the potential role of adjuvant RT, we performed a systematic review and meta-analysis of the literature from 1990 to present.
METHODS AND MATERIALS
We identified 810 candidate articles from database searches, of which 67 studies underwent full-text review, with final inclusion of 20 eligible studies. Among the included studies, there were no randomized controlled trials and a single prospective trial, with the remainder being retrospective series. We performed quantitative synthesis of the results by calculating the pooled odds ratios (OR) for the primary outcome of locoregional recurrence (LRR) and secondary outcomes of overall survival (OS), cancer-specific survival (CSS) and distant recurrence (DR).
RESULTS
Adjuvant RT, which was mostly prescribed for locally advanced or margin-positive disease following RNU, significantly reduced locoregional recurrence risk OR 0.43 (95% CI: 0.23-0.70), and the effect remained significant even following subgroup analysis to account for adjuvant systemic therapy. The effect of adjuvant RT on 3-year OS, 5-year CSS and DR was non-significant. However, 5-year OS was unfavourable in the adjuvant RT arm, but study heterogeneity was high, and analysis of small-study effects and subgroups suggested bias in reporting of outcomes.
CONCLUSIONS
Adjuvant RT in the setting of locally advanced UTUC improves locoregional control following definitive surgery, but does not appear to improve OS. Higher-quality studies, ideally randomized controlled trials, are needed to further quantify its benefit in this setting, and to explore multi-modal treatments that include systemic agents given concomitantly or sequentially with RT, which may offer an OS benefit in addition to the locoregional control benefit of RT.
Topics: Humans; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Radiotherapy, Adjuvant; Retrospective Studies; Prospective Studies; Neoplasm Recurrence, Local
PubMed: 36661651
DOI: 10.3390/curroncol30010002 -
Minerva Urologica E Nefrologica = the... Jun 2018Ureteral obstructions are managed by complex surgery not always feasible for surgical field complexity or poor patient conditions. Various surgical maneuvers, as... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ureteral obstructions are managed by complex surgery not always feasible for surgical field complexity or poor patient conditions. Various surgical maneuvers, as ureteral dilation, stenting and percutaneous nephrostomy, can be offered, but they are related to considerable failure rates and negative impact on quality of life. In selected cases, the positioning of long-term expandable metallic ureteral stents (EMUSs) may be an appropriate and successful choice.
EVIDENCE ACQUISITION
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria, a systematic review of the literature was performed in July 2017 using PubMed, Cochrane Library, Scopus and Web of Science databases. The search was conducted by typing the following terms: "Expandable metallic ureteral stent," "Memokath ureteral stent," "Allium ureteral stent," and "Uventa ureteral stent."
EVIDENCE SYNTHESIS
Twenty studies reported the safety, efficacy and clinical outcomes related to the common available EMUSs. Most studies were single-arm, retrospective and involving a low number of clinical cases, resulting in significant difficulties with outlining indications and drawing conclusions. Available papers showed EMUSs offered a high rate of patency, a long duration and a good quality of life, even if they are associated with significant complications.
CONCLUSIONS
Since the first description of ureteral stents 50 years ago, we have faced a significant evolution in stent design. The current generation of EMUSs offers many advantages, but the onset of adverse effects is still significant and limits their use to selected cases. Further research should be addressed to the realization of prospective, multi-institutional randomized clinical trials to highlight indications to manage appropriately ureteral obstructions.
Topics: Humans; Stents; Ureter; Ureteral Obstruction
PubMed: 29595037
DOI: 10.23736/S0393-2249.18.03035-7 -
European Urology Apr 2017Urothelial carcinoma is considered a pan-urothelial disease. As such, the remnant urothelium in the upper urinary tract and urethra following radical cystectomy (RC)... (Review)
Review
CONTEXT
Urothelial carcinoma is considered a pan-urothelial disease. As such, the remnant urothelium in the upper urinary tract and urethra following radical cystectomy (RC) remains at risk for secondary urothelial tumors (SUTs).
OBJECTIVE
To describe the incidence, diagnosis, treatment, and outcomes of patients with SUTs after RC.
EVIDENCE ACQUISITION
A systematic search was conducted using PubMed database according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines to identify studies between 1970 and 2016 reporting on malignant diseases of the urothelium after RC for bladder cancer. The search strategy separated between upper and lower tract urothelial tumors.
EVIDENCE SYNTHESIS
Of a total of 1069 studies, 57 were considered for evidence synthesis. SUTs occured in approximately 4-10% of patients after RC. Carcinoma in situ of the bladder, a history of nonmuscle invasive bladder cancer, and tumor involvement of the distal ureter are the strongest risk factors for secondary upper tract tumors. Risk factors for secondary urethral tumors represent urothelial malignancy in the prostatic urethra/prostate and bladder neck (in women), nonorthotopic diversions, and positive findings on permanent sections. The majority of patients (84%) with SUTs, presented with urothelial recurrence without evidence of metastasis. Of those, 84.0% were treated with surgery, 10.5% with systemic chemotherapy and/or radiotherapy, and 5.6% with topical chemotherapy and/or immunotherapy. After a median follow-up of 91 mo (range: 26-155), 65.9% of patients died of disease and 21.5% died of other causes. Detection and treatment of SUTs at an asymptomatic stage can reduce the risks of cancer-specfific and overall mortality by 30%. A limitation of the study is that the available data were retrospective.
CONCLUSIONS
SUTs are rare oncological events and most patients have an adverse prognosis despite absence of distant disease at diagnosis. Therefore, surveillance of the remnant urothelium should be implemented for patients with histological features of panurothelial disease as it may improve timely detection and treatment.
PATIENT SUMMARY
Secondary tumors of the renal pelvis, ureters, and urethra occur in approximately 4-10% of patients after radical removal of the bladder for bladder cancer. These patients' prognoses are reduced, likely due to delayed diagnosis. Therefore, routine surveillance might be important to detect tumors at an early stage.
Topics: Carcinoma, Transitional Cell; Cystectomy; Humans; Kidney Neoplasms; Neoplasms, Second Primary; Ureteral Neoplasms; Urethral Neoplasms; Urinary Bladder Neoplasms
PubMed: 27720534
DOI: 10.1016/j.eururo.2016.09.035 -
International Braz J Urol : Official... 2022The efficacy of alpha-blockers as medical expulsive therapy (MET) is well established. However, it is not known which of the three most commonly used alpha-blockers... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The efficacy of alpha-blockers as medical expulsive therapy (MET) is well established. However, it is not known which of the three most commonly used alpha-blockers (tamsulosin, alfuzosin and silodosin) is the most efficacious. With this study we aimed to assess the efficacy of the three commonly used alpha-blockers as MET for distal ureter stones.
MATERIALS AND METHODS
For this review, we searched multiple databases such as PubMed/Medline, Scopus, Embase, OviD SP, CINAHL, and web of science to identify all the relevant randomized studies comparing the efficacy of tamsulosin, alfuzosin, and silodosin. Preferred reporting items for systematic reviews for network meta-analysis (PRISMA-NMA) were followed while conducting this review and the study protocol was registered with PROSPERO (CRD42020175706).
RESULTS
In this review, 31 studies with 7077 patients were included. Compared to placebo all the treatment groups were more effective for both stone expulsion rate (SER) and stone expulsion time (SET). For both SER and SET, silodosin had the highest SUCRA (94.8 and 90.4) values followed by alfuzosin (58.8 and 64.9) and tamsulosin (46.2 and 44.5). The incidence of postural hypotension was similar with all the drugs, whereas, the incidence of retrograde ejaculation was significantly higher for silodosin. Overall confidence for each comparison group in this review ranged from "very low" to "moderate" according to the CINeMA approach.
CONCLUSION
Among the three commonly used alpha-blockers silodosin is the most efficacious drug as MET for lower ureter stones followed by alfuzosin and tamsulosin.
Topics: Adrenergic alpha-Antagonists; Humans; Male; Network Meta-Analysis; Tamsulosin; Treatment Outcome; Ureter; Ureteral Calculi
PubMed: 34003612
DOI: 10.1590/S1677-5538.IBJU.2020.0548 -
Urologia Internationalis 2023The aim of the study was to assess the effectiveness of the main classes of drugs used at reducing morbidity related to ureteric stents.
BACKGROUND
The aim of the study was to assess the effectiveness of the main classes of drugs used at reducing morbidity related to ureteric stents.
SUMMARY
After establishing a priori protocol, a systematic electronic literature search was conducted in July 2019. The randomized clinical trials (RCTs) selection proceeded in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered (PROSPERO ID 178130). The risk of bias and the quality assessment of the included RCTs were performed. Ureteral Stent Symptom Questionnaire (USSQ), International Prostate Symptom Score (IPSS), and quality of life (QoL) were pooled for meta-analysis. Mean difference and risk difference were calculated as appropriate for each outcome to determine the cumulative effect size. Fourteen RCTs were included in the analysis accounting for 2,842 patients. Alpha antagonist, antimuscarinic, and phosphodiesterase (PDE) inhibitors significatively reduced all indexes of the USSQ, the IPSS and QoL scores relative to placebo. Conversely, combination therapy (alpha antagonist plus antimuscarinic) showed in all indexes of the USSQ, IPSS, and QoL over alpha antagonist or antimuscarinic alone. On comparison with alpha blockers, PDE inhibitors were found to be equally effective for urinary symptoms, general health, and body pain parameters, but sexual health parameters improved significantly with PDE inhibitors. Finally, antimuscarinic resulted in higher decrease in all indexes of the USSQ, the IPSS, and QoL relative to alpha antagonist.
KEY MESSAGE
Relative to placebo, alpha antagonist alone, antimuscarinics alone, and PDE inhibitors alone have beneficial effect in reducing stent-related symptoms. Furthermore, there are significant advantages of combination therapy compared with monotherapy. Finally, PDE inhibitors are comparable to alpha antagonist, and antimuscarinic seems to be more effective than alpha antagonist alone.
Topics: Humans; Male; Adrenergic alpha-Antagonists; Muscarinic Antagonists; Pain; Quality of Life; Stents; Ureter
PubMed: 34818261
DOI: 10.1159/000518387