Role of Neoadjuvant Chemotherapy on Pathological, Functional, and Survival Outcomes of Upper Tract Urothelial Carcinoma Patients: A Systematic Review and Meta-Analysis.

The role of neoadjuvant chemotherapy (NAC) in upper tract urothelial cancer (UTUC) is not yet confirmed. Therefore, we conducted this review to pool the available evidence in this regard. We analyzed 14117 UTUC patients reported in 21 studies after searching 5 databases. The NAC was administered in 1983 patients and the remaining 12134 controls underwent radical nephroureterectomy (RNU) alone. Efficacy endpoints included pathological, functional, and survival outcomes. Safety was determined by overall and grade 3-4 complications. For dichotomous outcomes, the log odds ratio (logOR) was pooled, and for continuous variables, the crude mean difference was calculated along with its 95% CI. The NAC was associated with 10% complete pathological response (CPR), 42% pathological downstaging, 31% post-NAC advanced disease (pT3-4), 6% positive surgical margin, 18% lymph node metastasis (pN+), 24% lymphovascular invasion, and 29% mortality and recurrence at 5 years. Compared to controls, NAC resulted in increased risk of CPR [logOR=1.67; 95% CI, 0.11-3.23] and downstaging [logOR=1.30; 95% CI, 0.41-2.18] and reduced risk of advanced disease [logOR=-0.81; 95% CI, -1.51--0.11]. Renal function did not improve from baseline; however, it increased significantly after RNU. The NAC was associated with good survival/low mortality in the short term, with a sustained increase over time. Overall and grade 3-4 complications occurred in 25% and 7% of patients, respectively. Our findings support the potential benefits of NAC in enhancing pathological outcomes and possibly improving survival in UTUC patients undergoing RNU. The variability in response and associated complications underscore the importance of careful patient selection and tailored treatment approaches.

The Role of Lymph Node Dissection in the Management of Upper Urothelial Cancer: A Nodal Status-Based Meta-Analytical Study.

This systematic review was performed to study the prognostic value of lymph node dissection (LND) during nephroureterectomy in upper tract urothelial cancer (UTUC). Five databases were searched on September 11, 2022, to include studies that compared whether LND was performed, the extent of dissection (complete vs. incomplete), and the nodal status (positive "pN+" vs. negative "pN0"). Outcomes included prognosis (overall survival "OS," cancer-specific survival "CSS," disease-free survival "DFS," and recurrence-free survival "RFS") and complications. High-grade complications (≥ grade 3 according to the Clavien-Dindo classification). Data analysis were conducted through STATA. The pooled data are reported log odds ratio (logOR) with 95% CI. Thirty-three studies were analyzed. The LND resulted in improved 5-year OS [logOR=0.10; 95% CI: 0.06-0.15], 5-year CSS [logOR=0.10; 95% CI: 0.04- 0.17], and 10-year CSS [logOR=0.14; 95% CI: 0.06-0.21] when compared to non-LND. However, LND was associated with greater risk of high-grade complications [logOR=0.62; 95% CI: 0.26-0.98]. Complete LND was associated with lower risk of cancer-specific mortality than incomplete LND [logOR=-0.69; 95% CI: -1.22--0.16]. The pN0 patients had better 5-year OS; however, pN+ patients had better prognosis in DFS, RFS (at 2 and 5 years), and CSS (at 2, 5, and 10 years). Lymph node dissection provides a protective role in terms of 5-year OS and 5-year and 10-year CSS among UTUC patients. However, it is associated with higher risk of high-grade complications. The extent of dissection plays a minor prognostic role, while the positivity of resected nodes has great prognostic value in UTUC.

Perioperative, Functional, and Oncologic Outcomes of On-Clamp Versus Off-Clamp Partial Nephrectomy: An Updated Meta-analysis of 9027 Patients.

OBJECTIVE: The aim of this study was to determine the comparative efficacy and safety between on-clamp and off-clamp partial nephrectomy in patients with renal masses. MATERIALS AND METHODS: This systematic review was pre-registered on The International Prospective Register of Systematic Reviews (PROSPERO) (CRD42022339127). PubMed, Scopus, and Web of Science were searched. A manual search was also conducted to avoid missing relevant studies. All observational and experimental studies reporting the comparative efficacy and/or safety of on-clamp versus off-clamp partial nephrectomy were included. Outcomes were divided into 3 categories: perioperative, functional, and oncologic outcomes. Risk of bias was assessed using the The Risk Of Bias In Nonrandomized Studies of Interventions (ROBINS-I) and revised Cochrane ROB-II tool for nonrandomized and randomized studies, respectively. Fixed- and random-effect models were implemented to pool the mean difference and log odds ratio of continuous and dichotomous outcomes, respectively. A leave-one-out sensitivity analysis was conducted to determine if the effect size was driven by a single study, and Egger's regression test was used to assess publication bias. RESULTS: Forty-two studies were meta-analyzed. The on-clamping method showed greater benefit when compared to the off-clamping technique in terms of perioperative (estimated blood loss and blood transfusion), functional (estimated glomerular filtration rate), and oncologic outcomes (tumor resection time). However, it is associated with higher risk for complications. Most studies were of moderate-to-serious risk of bias. CONCLUSION: On-clamping shows superiority in terms of estimated blood loss, blood transfusion, estimated glomerular filtration rate, and tumor resection time. However, it is associated with increased risk of complications. The selection of the technique should be tailored per individual case based on their comorbidities and preoperative risk profile.

Prognostic Markers and Trials in Penile Cancer.

New tumor biomarkers open the potential for designing personalized therapy for penile squamous cell carcinoma. Despite the initial promising results of some biomarkers, controversy remains due to contradictory studies. Further robust research work is required before incorporating biomarkers in the personalized management of penile cancer. This narrative review aims to highlight some of the most commonly and recently investigated biomarkers of penile cancer and to summarize the ongoing registered clinical trials for the management of penile cancer patients.

The value of sestamibi single-photon emission computed tomography/computed tomography in differentiating and staging renal cell carcinomas: A systematic review.

Misdiagnosis of benign renal neoplasms can lead to unnecessary surgical resections, which increases the risk of other morbidities and mortality. Therefore, it is crucial to find a diagnostic modality for differentiation between benign and malignant renal masses. In the current study, we summarized published pieces of evidence concerning the use of technetium-99m (99mTc)-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) as a promising diagnostic nuclear imaging modality for the differentiation of renal neoplasms. The study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement for Systematic Reviews and Meta-Analyses. We conducted a systematic electronic database search for suitable studies from inception till February 20, 2020 in 9 databases. The risk of bias was assessed for the included studies using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. We identified 9373 records after exclusion of 8978 duplicates using EndNote software. Title and abstract screening resulted in 761 records for further full-text screening. Finally, four studies were included with total sample size of 80 patients. The overall risk of bias was low to moderate. The results of all the included studies supported using 99mTc-sestamibi SPECT/CT for the differentiation between benign and malignant renal neoplasms. The use of 99mTc-sestamibi SPECT/CT could be a rapid, less invasive, promising diagnostic modality for histological diagnosis and staging of renal neoplasm, as well as monitoring post-therapy tumor's response. However, more studies with large sample sizes are essential to confirm the reliability and accuracy of this modality for usage.

Surgical and Functional Outcomes of Artery Only Versus Artery and Vein Clamping in Patients Undergoing Partial Nephrectomy: A Systematic Review and Meta-Analysis.

Clamping of renal vessels during partial nephrectomy is usually performed to improve the visualization of tumor margins. However, clamping of renal vessels has been associated with detrimental effects on renal function after surgery. This study aimed to compare artery only versus artery and vein clamping as regards the surgical and functional outcomes in patients undergoing partial nephrectomy. The literature was searched for English published studies from January 1, 2000 to August 7, 2021. The search included MEDLINE/ PubMed, Cochrane Library, Scopus, Web of Science, Google Scholar, and ProQuest, using the terms {"par- tial nephrectomy"} OR {"nephron-sparing surgery"} AND {"renal artery and vein clamping} AND {"renal artery only clamping}. Nine studies were included. Meta-analysis showed the artery only clamping grouphad a significantly less percentage of change in glomerular filtration rate at last follow-up (standardizedmean difference: -0.42 [95% CI: -0.70, -0.13], P = .004) as well as a rate of postoperative complications(odds ratio: 0.64 [95% CI: 0.41, 0.98], P = .04). However, no significant difference was observed regarding the development of chronic kidney disease. There was no significant difference regarding the warm ischemiatime, blood loss, or positive surgical margin. Artery only clamping has a comparable safety to artery and vein clamping and may produce a renoprotective effect. Due to limitations of the included studies, the conduction of large-size randomized clinical trials with a long duration of follow-up is required before recommending the replacement of artery and vein clamping with artery only clamping during partial nephrectomy.

Pelvic lymph node dissection alone versus adjuvant radiotherapy in node positive penile cancer: A systematic review.

Introduction: The management options for regional lymph nodes (LNs) in men with penile cancer include surveillance, surgery, and chemotherapy. The use of radiotherapy (RT) for nodal disease follows tradition and single-institution policies. We aimed to analyse the existing evidence regarding the management of penile cancer patients with suspected or known metastatic pelvic LNs using pelvic LN dissection (PLND) with RT versus PLND or RT alone. Methods: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, with no filters for language or time. The search was conducted in EMBASE, MEDLINE/PubMed, and Cochrane Library. Inclusion criteria were adult men with penile cancer and suspected metastatic pelvic LNs, undergoing PLND with or without RT or RT alone. Primary outcomes included disease-specific survival and locoregional recurrence. Secondary outcomes included overall survival and complications of therapy. Results: A total of 552 articles were identified. Only eight retrospective studies were eligible for inclusion (including 406 patients). All studies had a high risk of bias. None of the studies reported the use of neoadjuvant RT. Indications for PLND varied but were usually two or more clinically positive inguinal nodes with or without extracapsular extension. Adjuvant RT was mainly used in positive pelvic LNs or pN2/pN3 stages. The rate of locoregional recurrence following adjuvant RT was 70%. Complications of treatment were reported in two studies only. Conclusions: There is insufficient evidence to recommend the use of adjuvant RT following PLND in penile cancer patients. The quality of evidence is low due to the retrospective design and high risk of bias. Randomized clinical trials are required to assess the efficacy and safety of adjuvant RT and PLND.

Chemoresection by mitomycin C compared to transurethral resection of bladder tumor in patients with recurrent nonmuscle-invasive bladder cancer: A systematic review and meta-analysis.

Some studies suggest that chemoresection with mitomycin C (MMC) is comparable to transurethral resection of bladder tumor (TURBT) in the management of recurrent nonmuscle-invasive bladder cancer (NMIBC). In this meta-analysis, we compared the efficacy and safety of MMC and TURBT in recurrent NMIBC. A search was conducted for studies published in English in the electronic databases of MEDLINE/PubMed, the Cochrane Library, Scopus, Web of Science, Google Scholar, ProQuest, System for information on Grey Literature, and ClinicalTrials.gov, with no publication date restrictions. Risk of bias was assessed using the Risk of bias 2 tool for randomized controlled trials and Risk of Bias inNon-Randomized Studies of Interventions-I tool for observational studies. Data analysis was performed using the RevMan 5.4 software. Three studies were included in this systematic review(total participants is 291); two studieswere included in themeta-analysis. The rate of complete response was significantly lower in MMC group compared with TURBT (relative risk [RR]: 0.55, 95% confidence interval (CI): 0.45-0.67, P< .001). The rates of local adverse events were lower inMMC, with a statistical significance for dysuria (RR: 0.55, 95% CI: 0.36-0.84, P » .006), urinary frequency (RR: 0.60, 95% CI: 0.43- 0.84, P» .003), cystitis (RR: 0.22, 95% CI: 0.06-0.81, P» .02), and incontinence (RR: 0.48, 95% CI: 0.24-0.96, P» .04). In terms of complete response, TURBT is superior to chemoresection withMMC. Currently, chemoresection withMMC should be restricted to patients unfit for surgery and in clinical trials. Future randomized controlled trials are recommended to confirm or refute the use ofMMC in treating recurrent NMIBC.

Radical nephrectomy and intracaval thrombectomy for advanced renal cancer with extensive inferior vena cava involvement utilising cardiopulmonary bypass and hypothermic circulatory arrest: Is it worthwhile?

OBJECTIVE: To report our long-term outcomes of surgical treatment of renal tumours with inferior vena cava (IVC) tumour thrombus above the hepatic veins, utilising cardiopulmonary bypass (CBP) and hypothermic circulatory arrest (HCA), as surgical resection remains the only effective treatment for renal cancers with extensive IVC tumour thrombus. PATIENTS AND METHODS: We retrospectively reviewed 48 consecutive patients (median age 58 years) who underwent surgical treatment for non-metastatic renal cancer with IVC tumour thrombus extending above the hepatic veins. Perioperative, histological, disease-free (DFS) and overall survival (OS) data were recorded. RESULTS: Tumour thrombus was level III in 23 patients and level IV in 25 patients. The median (range) CBP and HCA times were 162 (120-300) min and 35 (9-64) min, respectively. Three patients underwent synchronous cardiac surgical procedures. There were three (6.3%) perioperative deaths. American Society of Anesthesiologists grade and perioperative blood transfusion requirement were significant factors associated with perioperative death (P < 0.05). Despite extensive preoperative screening for metastases the median (range) DFS was only 10.2 (1.2-224.4) months. The median (range) OS was 23 (0-224.4) months. Cox regression analysis revealed that perinephric fat invasion conferred a significantly poorer DFS (P = 0.005). CONCLUSIONS: Radical surgery for patients with extensive IVC tumour thrombus has acceptable operative morbidity and mortality. It provides symptom palliation and the possibility of long-term survival. Improvements in preoperative detection of occult metastasis may improve case selection and newer adjuvant therapies may improve survival in this high-risk group.

Artificial urinary sphincters for treating postprostatectomy incontinence: A contemporary experience from the UK.

OBJECTIVES: To report a real-time contemporary practice and outcome of artificial urinary sphincter (AUS) in patients with postradical prostatectomy urinary incontinence (PPI) in the UK. METHODS: A retrospective observational study of patients who underwent AUS implantation (AMS 800) from 2007 to 2013. Data were collected on patients' demographics, infection and erosion rate, mechanical failure, reoperation, and continence rates. The study strictly included patients with postradical PPI only. Minimum follow-up was 15 months. RESULTS: Eighty-four AUSs were implanted over a period of 6 years. Patients' age ranged between 51 and 78 (median 69, mean 69.25) years. Median follow-up was 37 months, mean 39 months, and range 15-92 months. Among the 83 follow-up patients, 38.5% (32/83) reported that they were completely dry with no pads; 42.2% (35/83) of patients were socially continent (using 1 pad/day) and 19.3% (16/83) using ≥2 pads/day. One patient was lost to follow-up. Reoperation rate was 13.25% (11/83), including nine mechanical failures (10.8%). Two implant infections (2.4%) required explantation, out of which one had erosion (1.2%). Bladder overactivity developed in 6% of patients. Of the 83, 15 (18%) had pelvic radiotherapy. CONCLUSION: The implantation of AUS in patients with post-PPI has lower complications and reoperation rates than historical impression painted in the literature. This can be beneficial in counseling as well as during the education process of patients going through the decision process for prostate cancer treatment. Furthermore, these figures can add to our quest to increase the awareness of the success of anti-incontinence surgery among patients.