Segmental Ureterectomy for Upper Tract Urothelial Carcinoma: A Systematic Review and Meta-analysis of Comparative Studies

Radical nephroureterectomy (RNU) represents the standard of care for high-risk upper tract urothelial carcinoma (UTUC). In selected patients with ureteral UTUC, a conservative approach such as segmental ureterectomy (SU) can be considered. However, this therapeutic option remains controversial. The aim of this study was to perform a systematic review and meta-analysis of studies assessing the outcomes of SU versus RNU in patients with UTUC. Three search engines (Scopus, Embase, and Web of Science) were queried up to May 2019. The Preferred Reporting Items for Systematic Review and Meta-analysis Statement (PRISMA Statement) was used as a guideline for study selection. The clinical question was established as stated in the PICO (Population, Intervention, Comparator, Outcome) process. Patients in the SU group were more likely to have history of bladder cancer (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.12-3.51; P = .02), but less likely to present with preoperative hydronephrosis (OR, 0.52; 95% CI: 0.31-0.88; P = .02). A higher rate of ureteral tumor location was found in the SU group (OR, 7.54; 95% CI, 4.15-13.68; P < .00001). The SU group presented with a lower rate of higher (pT ≥ 2) stage (OR, 0.66; 95% CI, 0.53-0.82; P = .0002), and high-grade tumors (OR, 0.62; 95% CI, 0.50-0.78; P < .0001). The SU group was found to have shorter 5-year relapse-free survival (OR, 0.64; 95% CI, 0.43-0.95; P = .03), but higher postoperative estimated glomular filtration rate (weighted mean difference, 10.97 mL/min; 95% CI, 2.97-18.98; P = .007). Selected patients might benefit from SU as a therapeutic option for UTUC. In advanced high-risk disease, RNU still remains the standard of care

Radical penectomy, a compromise for life: Results from the PECAD study

Background: The use of organ sparing strategies to treat penile cancer (PC) is currently supported by evidence that has indicated the safety, efficacy and benefit of this surgery. However, radical penectomy still represents up to 15-20% of primary tumor treatments in PC patients. The aim of the study was to evaluate efficacy in terms of overall survival (OS) and disease-free survival (DFS) of radical penectomy in PC patients.Methods: Data from a retrospective multicenter study (PEnile Cancer ADherence study, PECAD Study) on PC patients treated at 13 European and American urological centers (Hospital "Sant'Andrea", Sapienza University, Roma, Italy; "G.D'Annunzio" University, Chieti and ASL 2 Abruzzo, Hospital "S. Pio da Pietrelcina", Vasto, Italy; Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA; Hospital of Budapest, Hungary; Department of Emergency and Organ Transplantation, Urology and Andrology Unit II, University of Bari, Italy; Hospital "Spedali Civil", Brescia, Italy; Istituto Europeo di Oncologia, University of Milan, Milan, Italy; University of Modena &amp; Reggio Emilia, Modena, Italy; Hospital Universitario La Paz, Madrid, Spain; Ceara Cancer Institute, Fortaleza, Brazil; Virginia Commonwealth University, Richmond, VA, USA; Aristotle University of Thessaloniki, Thessaloniki, Greece; Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland) between 2010 and 2016 were used. Medical records of patients who specifically underwent radical penectomy were reviewed to identify main clinical and pathological variables. Kaplan-Meier method was used to estimate 1- and 5-year OS and DFS.Results: Of the entire cohort of 425 patients, 72 patients (16.9%) treated with radical penectomy were extracted and were considered for the analysis. The median age was 64.5 (IQR, 57.5-73.2) years. Of all, 41 (56.9%) patients had pT3/pT4 and 31 (43.1%) pT1/pT2. Moreover, 36 (50.0%) were classified as pN1-3 and 5 (6.9%) MI. Furthermore, 61 (84.7%) had a high grade (G2-G3) with 6 (8.3%) positive surgical margins. The 1- and 5-year OS rates were respectively 73.3% and 59.9%, while the 1- and 5-year DFS rates were respectively 67.3% and 35.1%.Conclusions: PC is an aggressive cancer particularly in more advanced stage. Overall, more than a third of patients do not survive at 5 years and more than 60% report a disease recurrence, despite the use of a radical treatment

Radical penectomy, a compromise for life. Results from the PECAD study

Background: The use of organ sparing strategies to treat penile cancer (PC) is currently supported by evidence that has indicated the safety, efficacy and benefit of this surgery. However, radical penectomy still represents up to 15-20% of primary tumor treatments in PC patients. The aim of the study was to evaluate efficacy in terms of overall survival (OS) and disease-free survival (DFS) of radical penectomy in PC patients. Methods: Data from a retrospective multicenter study (PEnile Cancer ADherence study, PECAD Study) on PC patients treated at 13 European and American urological centers (Hospital “Sant'Andrea”, Sapienza University, Roma, Italy; “G.D'Annunzio” University, Chieti and ASL 2 Abruzzo, Hospital “S. Pio da Pietrelcina”, Vasto, Italy; Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA; Hospital of Budapest, Hungary; Department of Emergency and Organ Transplantation, Urology and Andrology Unit II, University of Bari, Italy; Hospital “Spedali Civili”, Brescia, Italy; Istituto Europeo di Oncologia, University of Milan, Milan, Italy; University of Modena &amp; Reggio Emilia, Modena, Italy; Hospital Universitario La Paz, Madrid, Spain; Ceara Cancer Institute, Fortaleza, Brazil; Virginia Commonwealth University, Richmond, VA, USA; Aristotle University of Thessaloniki, Thessaloniki, Greece; Maria Skłodowska-Curie Memorial Cancer Center, Warsaw, Poland) between 2010 and 2016 were used. Medical records of patients who specifically underwent radical penectomy were reviewed to identify main clinical and pathological variables. Kaplan-Meier method was used to estimate 1- and 5-year OS and DFS. Results: Of the entire cohort of 425 patients, 72 patients (16.9%) treated with radical penectomy were extracted and were considered for the analysis. The median age was 64.5 (IQR, 57.5-73.2) years. Of all, 41 (56.9%) patients had pT3/pT4 and 31 (43.1%) pT1/pT2. Moreover, 36 (50.0%) were classified as pN1-3 and 5 (6.9%) M1. Furthermore, 61 (84.7%) had a high grade (G2-G3) with 6 (8.3%) positive surgical margins. The 1- and 5-year OS rates were respectively 73.3% and 59.9%, while the 1- and 5-year DFS rates were respectively 67.3% and 35.1%. Conclusions: PC is an aggressive cancer particularly in more advanced stage. Overall, more than a third of patients do not survive at 5 years and more than 60% report a disease recurrence, despite the use of a radical treatment

食道扁平上皮癌におきてエンドセリンB受容体の高発現は腫瘍の血管新生と予後に関与する

BACKGROUND:The endothelin axis has been shown to have a pivotal role in several human malignancies. The aim of this study was to clarify the clinical importance of endothelin receptor type B (ETBR) in human oesophageal squamous cell carcinoma (OSCC). METHODS:We evaluated ETBR expression in 107 patients with OSCC by immunohistochemistry. Microvessel density (MVD) and lymphatic vessel density were assessed by CD31 and D2-40 immunostaining, respectively. Furthermore, CD4, CD8, and CD45RO+ tumour-infiltrating lymphocytes (TILs) were immunohistochemically analysed.RESULTS:Sixty-one (57%) cases showed high expression of ETBR. Endothelin receptor type B expression was correlated with several clinicopathological factors including tumour differentiation, tumour depth, and lymph node metastasis. The overall and disease-specific survival rates were significantly lower in patients with high ETBR expression than patients with low expression. Furthermore, multivariate analysis revealed that ETBR status was an independent prognostic factor for patient survival. Mechanistic analysis indicated that MVD was significantly higher in tumour tissues with high ETBR expression compared with those with low expression, suggesting that angiogenesis may be a key mechanism in tumour progression and metastasis of OSCC mediated by ETBR expression. By contrast, there were no significant correlations between TILs and ETBR expression.CONCLUSION: Endothelin receptor type B has a pivotal role in oesophageal cancer and may be therapeutic target for this intractable malignancy.博士（医学）・乙第1336号・平成26年5月28

Robotic versus other nephroureterectomy techniques: a systematic review and meta-analysis of over 87,000 cases

Purpose: To perform a systematic review and meta-analysis of the literature inherent robotic nephroureterectomy (RNU) and to compare its outcomes with those of other nephroureterectomy (NU) techniques. Methods: A systematic literature search was performed up to April 2019 using PubMed, Embase®, and Web of Science. The Preferred Reporting Items for Systematic Review and Meta-analysis Statement was followed for study selection. The following data were extracted for each study: baseline features, surgical outcomes, oncological outcomes, and survival outcomes. Stata® 15.0 was used for statistical analysis. Results: Literature search identified 80 studies eligible for the meta-analysis and overall 87,291 patients were included in the analysis: open NU (ONU; n = 45,601), hand-assisted laparoscopic NU (HALNU; n = 442), laparoscopic NU (LNU n = 31,093), and RNU (n = 10,155). RNU was more likely to be performed in those patients with multifocal tumor location (proportion: 0.19; 95% CI 0.14, 0.24) and high-grade disease (proportion: 0.70; 95% CI 0.53, 0.68). The lowest EBL was recorded in the RNU group (weighted mean (WM) 163.31 mL; 95% CI 88.94, 237.68), whereas the highest was in the ONU group (414.99 mL; 95% CI 378.52, 451.46). Operative time was shorter for ONU (224.98 mL; 95% CI 212.26, 237.69). RNU had lower rate of intraoperative complications (0.02; 95% CI 0.01, 0.05). ONU showed higher odds of transfusions (0.20; 95% CI 0.15, 0.25). LOS was statistically significantly shorter for the RNU group (5.35 days; 95% CI 4.97, 5.82). HALNU seemed to present lower risk of PSM (0.02; 95% CI − 0.01, 0.05), and lower risk of recurrence (0.22; 95% CI 0.15, 0.30), metastasis (0.07; 95% CI 0.05, 0.10), and cancer-related death (0.03; 95% CI 0.01, 0.06). ONU showed the lowest 5 years cancer specific survival (proportion: 0.77; 95% CI 0.74, 0.80). No correlation was found between the surgical technique and recurrence-free and cancer-specific survival. Conclusions: Evidence regarding RNU for the treatment of UTUC is increasing but it remains quite sparse and of low quality. Despite this, RNU seems to be safe, and to offer the advantages of a minimally invasive approach without impairing the oncological outcomes. Nevertheless, ONU, HALNU, and LNU still represent a valid, and commonly used surgical treatment option. As RNU becomes more popular, and concerns related to its use remain, the best surgical technique for NU remains to be determined

Ureteral location is associated with survival outcomes in upper tract urothelial carcinoma: A population-based analysis

Objectives: To evaluate the prognostic value of tumor location in patients with upper tract urothelial carcinoma. Methods: Within the Surveillance, Epidemiology and End Results Incidence Database, 6619 upper tract urothelial carcinoma cases were identified, including 3719 confined to the renal pelvis and 2971 to the ureter. Predictors of surgical technique (kidney sparing surgery versus radical nephroureterectomy), as well as 2- and 5-year cancer-specific survival and overall survival were evaluated. Results: Median follow-up time was 29 months (interquartile range 0–126 months) for both groups. Multivariate logistic analysis showed tumor dimension as the only factor associated with radical nephroureterectomy (odds ratio 1.02; P 3 cm was associated with the worst 2- and 5-year cancer-specific mortality (Pepe-Mori P < 0.001), and overall survival (log–rank P < 0.001). The 2- and 5-year cancer-specific mortality (Pepe-Mori P < 0.001) and overall survival were the worst for ureteral ≥T3 tumors (log–rank P < 0.001). The 2- and 5-year cancer-specific mortality (Pepe–Mori P < 0.001) and overall survival (log–rank P < 0.001) were the worst for ureteral grade III–IV cancers. Ureteral tumor location (subdistribution hazard ratio 1.18, P < 0.001), tumor dimension ≥3 (subdistribution hazard ratio 1.25, P < 0.001), T staging (T2–4 all P < 0.001), grading (grade III subdistribution hazard ratio 2.20, P = 0.001; grade IV subdistribution hazard ratio 2.39, P < 0.001) were found to be associated with higher cancer mortality. Conclusions: Ureteral tumor location in upper tract urothelial carcinoma seems to be associated with worse oncological outcomes, especially in the case of advanced disease. Although the type of surgical treatment does not seem to impact survival, surgeons should use caution in adopting a kidney-sparing surgery for patients with ureteral upper tract urothelial carcinoma

Ureteral location is associated with survival outcomes in upper tract urothelial carcinoma: A population-based analysis

Objectives: To evaluate the prognostic value of tumor location in patients with upper tract urothelial carcinoma. Methods: Within the Surveillance, Epidemiology and End Results Incidence Database, 6619 upper tract urothelial carcinoma cases were identified, including 3719 confined to the renal pelvis and 2971 to the ureter. Predictors of surgical technique (kidney sparing surgery versus radical nephroureterectomy), as well as 2- and 5-year cancer-specific survival and overall survival were evaluated. Results: Median follow-up time was 29 months (interquartile range 0–126 months) for both groups. Multivariate logistic analysis showed tumor dimension as the only factor associated with radical nephroureterectomy (odds ratio 1.02; P 3 cm was associated with the worst 2- and 5-year cancer-specific mortality (Pepe-Mori P < 0.001), and overall survival (log–rank P < 0.001). The 2- and 5-year cancer-specific mortality (Pepe-Mori P < 0.001) and overall survival were the worst for ureteral ≥T3 tumors (log–rank P < 0.001). The 2- and 5-year cancer-specific mortality (Pepe–Mori P < 0.001) and overall survival (log–rank P < 0.001) were the worst for ureteral grade III–IV cancers. Ureteral tumor location (subdistribution hazard ratio 1.18, P < 0.001), tumor dimension ≥3 (subdistribution hazard ratio 1.25, P < 0.001), T staging (T2–4 all P < 0.001), grading (grade III subdistribution hazard ratio 2.20, P = 0.001; grade IV subdistribution hazard ratio 2.39, P < 0.001) were found to be associated with higher cancer mortality. Conclusions: Ureteral tumor location in upper tract urothelial carcinoma seems to be associated with worse oncological outcomes, especially in the case of advanced disease. Although the type of surgical treatment does not seem to impact survival, surgeons should use caution in adopting a kidney-sparing surgery for patients with ureteral upper tract urothelial carcinoma

Impact of Perioperative Blood Transfusions on the Outcomes of Patients Undergoing Kidney Cancer Surgery: A Systematic Review and Pooled Analysis

The aim of the present study is to systematically review current evidence regarding the association between perioperative blood transfusions (PBT) and oncological outcomes of patients with renal cell carcinoma undergoing nephrectomy procedures. A computerized bibliographic search was conducted to identify pertinent studies. The Population, Intervention, Comparator, Outcome (PICO) study design approach was used to define study eligibility according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria. Only 7 studies were deemed fully eligible for analysis. Most series included both open and laparoscopic cases. The rate of PBT varied between 9.6% and 76.6%, and the median number of transfused units was 2 for most of the studies. At pooled analysis, a statistically significant association was found between PBT and disease recurrence (HR, 1.79; 95% CI, 1.32-2.41; P <.001), cancer-specific mortality (HR, 1.62; 95% CI, 1.29-2.05; P ≤.001), and all-cause mortality (HR, 1.45; 95% CI, 1.25-1.69; P <.001). Current evidence suggests that indeed the use of PBT may be associated with worse oncologic outcomes in patients with renal cell carcinoma undergoing nephrectomy procedures. Although presents findings should be interpreted within the intrinsic limitations of this type of pooled analysis, they emphasize the need for evidence-based strategies to minimize the use of PBT during kidney cancer surgery

Impact of metastasectomy on cancer specific and overall survival in metastatic renal cell carcinoma: Analysis of the REMARCC registry

Introduction & Objectives: As treatment paradigms for management of metastatic renal cell carcinoma (mRCC) have shifted, the role of surgical metastasectomy in management of mRCC has been in similar flux. We examined impact on survival of surgical metastatectomy stratified in the setting of different mRCC risk groups. Materials & Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. The cohort was subdivided utilizing Motzer RCC criteria (low, intermediate, and high risk), and impact of metastasectomy was analyzed via multivariable analysis (MVA) and Kaplan Meier analysis within each Motzer subgroup (KMA). Primary outcome was overall survival (OS) and secondary outcome was cancer specific mortality (CSM). Results: 431 patients (59 low risk, 274 intermediate risk, 98 high risk) with median follow-up of 19.2 months were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of low, intermediate and high risk groups (p=0.012). Risk groups differed significantly with respect to ECOG performance status (p<0.001) and number of metastases at diagnosis (low 2, intermediate 3.4, high 5.1, p<0.001). MVA for CSM revealed male sex (OR 1.77, p=0.015), number of metastases at diagnosis (OR 1.18, p<0.001), and higher risk category [low (referent) vs. intermediate OR 2.16, p=0.046, high OR 2.44, p=0.002] to be independent risk factors. MVA for OS demonstrated increasing number of metastases at diagnosis (OR 1.78, p<0.001) and higher risk category [low (referent) vs. intermediate OR 2.37, p=0.03, high OR 2.61, p=0.001] to be independent risk factors. KMA for CSM demonstrated that metastasectomy was associated with longer cancer-specific survival in low (32.78 vs. 76.09 months, p=0.004) but not intermediate (p=0.060) and high risk (p=0.595) groups. KMA for OS demonstrated that metastasectomy was associated with longer median OS in the low (25.8 vs. 92.7 months, p=0.003) and intermediate risk (20.1 vs. 26.3, p=0.038), but not high risk (p=0.911) groups (Figure). Conclusions: Metastasectomy was not associated with benefit in high risk mRCC patients, but was associated with improved CSM in low risk and improved OS in low and intermediate risk mRCC patients. Further investigation is requisite to refine criteria for employment of metastasectomy