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Artificial intelligence (AI) aims at simulating, or approximating, human intelligence in machines with the goal of reproducing, replacing or even improving brain tasks of perception, reasoning, and learning. For example, we have seen AI/ML models treating the ordinal variable Gleason Score as a continuous variable or age as any number between zero and infinity. And do the AI/ML models improve predictions above and beyond current standard of care and models based on already known predictors of the outcome?. [Extracted from the article]

The article discusses the use of artificial intelligence (AI) and machine learning (ML) in modern medicine. It highlights the potential applications of AI and ML in areas such as pathology, imaging interpretation, and data analysis. The article also raises concerns about the validation and clinical relevance of AI prediction models, citing examples of flawed models in sepsis prediction and COVID-19 diagnosis. The authors emphasize the need for standardized reporting and transparency in AI research, as well as the importance of considering biases and limitations in biomedical datasets. They conclude that the successful implementation of AI in clinical practice depends on rigorous methodology and replication of results. [Extracted from the article]

Purpose: To systematically review studies focused on screening programs for renal cell carcinoma (RCC) and provide an exhaustive overview on their clinical impact, potential benefits, and harms. Methods: A systematic review of the recent English-language literature was conducted according to the European Association of Urology guidelines and the PRISMA statement recommendations (PROSPERO ID: CRD42021283136) using the MEDLINE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases. Risk-of-bias assessment was performed according to the QUality In Prognosis Studies (QUIPS) tool. Results: Overall, nine studies and one clinical trials were included. Eight studies reported results from RCC screening programs involving a total of 159 136 patients and four studies reported screening cost-analysis. The prevalence of RCC ranged between 0.02 and 0.22% and it was associated with the socio-demographic characteristics of the subjects; selection of the target population decreased, overall, the screening cost per diagnosis. Conclusions: Despite an increasing interest in RCC screening programs from patients and clinicians there is a relative lack of studies reporting the efficacy, cost-effectiveness, and the optimal modality for RCC screening. Targeting high-risk individuals and/or combining detection of RCC with other health checks represent pragmatic options to improve the cost-effectiveness and reduce the potential harms of RCC screening. [ABSTRACT FROM AUTHOR]

Presurgical axitinib therapy increases fibrotic reactions within tumor thrombus in renal cell carcinoma with thrombus extending to the inferior vena cava. Keywords: neoadjuvant; thrombus; systemic treatment; tyrosine kinase inhibitor; cava thrombus EN neoadjuvant thrombus systemic treatment tyrosine kinase inhibitor cava thrombus 566 568 3 04/25/23 20230501 NES 230501 Abbreviations GRADE Grading of recommendations assessment, development and evaluation IO immunotherapies IVC inferior vena cava TKI tyrosine kinase inhibitor VTT venous tumour thrombus Renal cell carcinoma (RCC) with venous tumour thrombus (VTT) extension into the inferior vena cava (IVC) occurs in about 4%-15% of cases [[1]]. Neoadjuvant, thrombus, systemic treatment, tyrosine kinase inhibitor, cava thrombus. [Extracted from the article]

Historically, kidney cancer was approached in a siloed single-speciality way, with urological surgeons managing the localised stages of the disease and medical oncologists caring for patients if metastases developed. However, improvements in the management of localised kidney cancer have occurred rapidly over the past two decades with greater understanding of the disease biology, diagnostic options, and innovations in curative treatments. These developments are favourable for patients but provide a substantially more complex landscape for patients and clinicians to navigate, with associated challenging decisions about who to treat, how, and when. As such, the skill sets needed to manage the various aspects of the disease and guide patients appropriately outstrips the capabilities of one particular specialist, and the evolution of a multispeciality approach to the management of kidney cancer is now essential. In this Review, we summarise the current best multispeciality practice for the management of localised kidney cancer and the areas in need of further research and development. [ABSTRACT FROM AUTHOR]

Purpose: There is sparse evidence on outcomes of resected occult LN metastases at the time of nephrectomy (synchronous disease). We sought to analyse a large international cohort of patients and to identify clinico-pathological predictors of long-term survival. Materials and methods: We collected data of consecutive patients who underwent nephrectomy and LND for Tany cN0-1pN1 and cM0-1 RCC at 7 referral centres between 1988 and 2019. Patients were stratified into four clinico-pathological groups: (1) cN0cM0-pN1, (2) cN1cM0-pN1(limited, 1–3 positive nodes), (3) cN1cM0-pN1(extensive, > 3 positive nodes), and (4) cM1-pN1. Overall survival (OS) was estimated using the Kaplan–Meier method, and associations with all-cause mortality (ACM) were evaluated using Cox models with multiple imputations. Results: Of the 4370 patients with LND, 292 patients with pN1 disease were analysed. Median follow-up was 62 months, during which 171 patients died. Median OS was 21 months (95% CI 17–30 months) and the 5-year OS rate was 24% (95% CI 18–31%). Patients with cN0cM0-pN1 disease had a median OS of 57 months and a 5-year OS rate of 43%. 5-year OS (median OS) decreased to 29% (33 months) in cN1cM0-pN1(limited) and to 23% (23 months) in cN1cM0-pN1(extensive) patients. Those with cM1-pN1 disease had the worst prognosis, with a 5-year OS rate of 13% (9 months). On multivariable analysis, age (p = 0.034), tumour size (p = 0.02), grade (p = 0.02) and clinico-pathological group (p < 0.05) were significant predictors of ACM. Conclusion: Depending on clinico-pathological group, grade and tumour size, 5-year survival of patients with LN metastases varies from 13 to 43%. Patients with resected occult lymph node involvement (cN0/pN1 cM0) have the best prognosis with a considerable chance of long-term survival. [ABSTRACT FROM AUTHOR]

Objective: To evaluate intermediate‐ and long‐term oncological outcomes of active surveillance (AS) for localized renal masses (LRMs). Methods: This systematic literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement and registered on PROSPERO (CRD42021230416). Studies on AS for LRMs with at least 3 years' follow‐up were eligible. Two review authors independently screened the literature, extracted data, and assessed risk of bias. The primary outcomes were metastasis rate, renal cell carcinoma (RCC)‐specific mortality (RCC‐SM) and all‐cause mortality (ACM). Pooled estimates were obtained from random‐effects models. Subgroup analyses were performed for small renal masses (SRMs; ≤4 cm) and non‐SRMs (>4 cm). Results: We analysed 18 unique cohorts comprising 2066 patients. The pooled initial maximum tumour size was 2.8 cm (95% confidence interval [CI] 2.7–3.0) and the percutaneous biopsy rate was 28%. The pooled mean annual growth rate was 2.8 mm (95% CI 2.1–3.4). Within a pooled mean follow‐up of 53 months, 2.1% (95% CI 1.0–3.6) of patients developed metastatic disease, 1.0% (95% CI 0.3–2.1) died from RCC and 22.6% (95% CI 15.8–30.2) died from any cause. For patients with SRMs (nine studies, n = 987), the pooled metastasis rate was 1.8% (95% CI 0.5–3.7), RCC‐SM was 0.6% (95% CI 0–2.1), and ACM was 28.5% (95% CI 17.4–41.4). Across five studies reporting on outcomes of 239 patients with non‐SRMs, the pooled metastasis rate was 5.1% (95% CI 0–17.3), RCC‐SM was 2.1% (95% CI 0–8.9) and ACM was 29.1% (95% CI 13.6–47.3). This review is limited by non‐standardized inclusion criteria, definitions and follow‐up, data heterogeneity, limited patient numbers in sub‐analyses and absence of high‐quality studies. Conclusions: Active surveillance is a safe intermediate‐ and long‐term management option for well‐selected patients with LRMs, especially those with SRMs. Limited data are available for non‐SRMs, but current evidence would support further evaluation of this approach in selected patients. It is not possible to draw definitive conclusions until more high‐quality data become available. [ABSTRACT FROM AUTHOR]

Purpose: Patients with localised renal cell carcinoma (RCC) can expect excellent oncologic outcomes. As such, there has been a shift towards maximising health-related quality of life (HRQoL). A greater understanding of HRQoL outcomes associated with different treatment options for RCC can facilitate patient-centred care, shared decision-making and enable cost utility analyses to guide health policies. The aim of this literature review was to evaluate the evidence regarding HRQoL following different management strategies for localised RCC.Methods: Three databases were searched to identify studies reporting HRQoL in patients with localised renal cancer, including Medline, the Tuft's Medical Centre Cost Effectiveness Analysis registry and the EuroQol website.Results: Considerable methodological heterogeneity was noted. Laparoscopic nephrectomy was associated with significantly better short-term physical function compared to open surgery, although the effect on mental function was inconclusive. Nephron-sparing surgery was associated with better physical function compared to radical surgery. Patients' perception of remaining renal function was a significant independent predictor of HRQoL, rather than surgery type. Tumour size, stage, post-operative complications, age, body mass index, occupational status, educational level and comorbidities were significant predictors of HRQoL. Only three studies were available regarding non-surgical management options and very little data were available regarding the impact of follow-up protocols and long-term effects of "cancer survivorship."Conclusion: There is a need for validated and reproducible RCC-specific HRQoL instruments and standardisation amongst studies to enable comparisons. Increased awareness regarding determinants of poor HRQoL may enable high-risk patients to receive tailored support. [ABSTRACT FROM AUTHOR]

Purpose: Following curative treatment for localised renal cell carcinoma (RCC), up to 30% of patients develop tumour recurrence. Prognostic scores are essential to guide individualised surveillance protocols, patient counselling and potentially in the future to guide adjuvant therapy. In metastatic RCC, prognostic scores are routinely used for treatment selection in clinical practice as well as in all major trials.Methods: We performed a literature review on the current evidence based on prognostic factors and models for localised and metastatic RCC.Results: A number of prognostic factors have been identified, of which tumour node metastasis classification remains the most important. Multiple prognostic models and nomograms have been developed for localised disease, based on a combination of tumour stage, grade, subtype, clinical features, and performance status. However, there is poor level of evidence for their routine use. Prognostic scores for patients with metastatic RCC receiving targeted treatments are used routinely, but have limited accuracy. Molecular markers can improve the accuracy of established prognostic models, but frequently lack external, independent validation.Conclusion: Several factors and models predict prognosis of localised and metastatic RCC. They represent valuable tools to provide estimates of clinically important endpoints, but their accuracy should be improved further. Validation of molecular markers is a future research priority. [ABSTRACT FROM AUTHOR]

Purpose: The widespread use of abdominal imaging has affected the epidemiology of renal cell carcinoma (RCC). Despite this, over 25% of individuals with RCC have evidence of metastases at presentation. Screening for RCC has the potential to downstage the disease.Methods: We performed a literature review on the epidemiology of RCC and evidence base regarding screening. Furthermore, contemporary RCC epidemiology data was obtained for the United Kingdom and trends in age-standardised rates of incidence and mortality were analysed by annual percentage change statistics and joinpoint regression.Results: The incidence of RCC in the UK increased by 3.1% annually from 1993 through 2014. Urinary dipstick is an inadequate screening tool due to low sensitivity and specificity. It is unlikely that CT would be recommended for population screening due to cost, radiation dose and increased potential for other incidental findings. Screening ultrasound has a sensitivity and specificity of 82-83% and 98-99%, respectively; however, accuracy is dependent on tumour size. No clinically validated urinary nor serum biomarkers have been identified. Major barriers to population screening include the relatively low prevalence of the disease, the potential for false positives and over-diagnosis of slow-growing RCCs. Individual patient risk-stratification based on a combination of risk factors may improve screening efficiency and minimise harms by identifying a group at high risk of RCC.Conclusion: The incidence of RCC is increasing. The optimal screening modality and target population remain to be elucidated. An analysis of the benefits and harms of screening for patients and society is warranted. [ABSTRACT FROM AUTHOR]

Purpose: To test the hypothesis that cytoreductive nephrectomy (CN) improves overall survival (OS) of patients with synchronous metastatic renal cell carcinoma (mRCC), who subsequently receive targeted therapies (TT). Methods: We identified 261 patients who received TT for synchronous mRCC with or without prior CN. To achieve balance in baseline characteristics between groups, we used the inverse probability of treatment weighting (IPTW) method. We conducted OS analyses, including IPTW-adjusted Kaplan-Meier curves, Cox regression models, interaction term, and landmark and sensitivity analyses. Results: Of the 261 patients, 97 (37.2%) received CN and 164 (62.8%) did not. IPTW-adjusted analyses showed a statistically significant OS benefit for patients treated with CN (HR 0.63, 95% CI 0.46-0.83, P = 0.0015). While there was no statistically significant difference in OS at 3 months (P = 0.97), 6 months (P = 0.67), and 12 months (P = 0.11) from diagnosis, a benefit for the CN group was noted at 18 months (P = 0.005) and 24 months (P = 0.004). On interaction term analyses, the beneficial effect of CN increased with better performance status (P = 0.06), in women (P = 0.03), and in patients with thrombocytosis (P = 0.01). Conclusions: IPTW-adjusted analysis of our patient cohort suggests that CN improves OS of patients with synchronous mRCC treated with TT. On the whole, the survival difference appears after 12 months. Specific subgroups may particularly benefit from CN, and these subgroups warrant further investigation in prospective trials. [ABSTRACT FROM AUTHOR]

Objective To validate Caveolin-1 as an independent prognostic marker of biochemical recurrence (BCR) in a large multi-institutional cohort of patients with prostate cancer treated with radical prostatectomy (RP). Patients and Methods Caveolin-1 expression was evaluated by immunochemistry on a tissue microarray in 3 117 patients treated with RP for prostate cancer at five institutions. Univariable and multivariable Cox proportional hazards regression models assessed the association of Caveolin-1 status with BCR. Harrell's c-index quantified prognostic accuracy. Results Caveolin-1 was overexpressed in 644 (20.6%) patients and was associated with higher pathological Gleason sum ( P = 0.002) and lymph node metastases ( P = 0.05). Within a median (interquartile range) follow-up of 38 (21-66) months, 617 (19.8%) patients experienced BCR. Patients with overexpression of Caveolin-1 had worse BCR-free survival than those with normal expression (log-rank test, P = 0.004). Caveolin-1 was an independent predictor of BCR in multivariable analyses that adjusted for the effects of standard clinicopathological features (hazard ratio 1.21, P = 0.037). Addition of Caveolin-1 in a model for prediction of BCR based on these standard prognosticators did not significantly improve the predictive accuracy of the model. In subgroup analyses, Caveolin-1 was associated with BCR in patients with favourable pathological features (pT2pN0 and Gleason score = 6; P = 0.021). Conclusions We confirmed that overexpression of Caveolin-1 is associated with adverse pathological features in prostate cancer and independently predicts BCR after RP, especially in patients with favourable pathological features. However, it did not add prognostically relevant information to established predictors of BCR, limiting its use in clinical practice. [ABSTRACT FROM AUTHOR]

Context A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes. Objective To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN). Evidence acquisition A literature review was conducted. Evidence synthesis Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration. Conclusions Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications. Patient summary In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes. [ABSTRACT FROM AUTHOR]

Ureteral complications such as urinary leak, ureteral necrosis or ureteral stenosis are common complications after renal transplantation with major short- and long-term issues, including graft impairment and graft loss. At present, there is no agreement on the optimal management of ureteral complications. The aim of the current study was to evaluate the safety and efficacy of the self-expanding, large-caliber Allium ureteral stent in patients with ureteral complications following renal transplantation. In this retrospective study, the electronic database of Charité University Hospital was screened for patients receiving the self-expandable Allium ureteral stent in the transplant ureter after kidney transplantation between January 2016 and March 2022. Descriptive statistics were used to describe the outcomes. There were six men and four women with a median age of 61 years (interquartile range, 55 to 68 years). Nine out of 10 patients had ureteric stenosis, which was diagnosed at a median of two years (interquartile range 10 months to 9 years) following renal transplantation. The median operating time was 49 min (interquartile range, 30 to 60 min). Endoscopic Allium stent placement was successful in all patients with ureteric stenosis. The median length of stay in the hospital was four days (interquartile range 2 to 7 days). Only one patient (#5) had a postoperative grade IIIb Clavien–Dindo complication. Patients had follow-ups every 3 months with ultrasound and serum creatinine. Dislocation of the Allium stent was seen in four patients; all occurred within three months. Ultimately, three patients required ureteric re-implantation, two of which had early dislocation of the stent. Six patients are managed with a permanent Allium stent. The median dwell time was 11 months (interquartile range 3 to 20 months) and maximum dwell time was 23 months. The overall success rate was 60% (6 out of 10). According to our data, the Allium stent represents a safe and minimally invasive option with a success rate of 60%. It might, therefore, represent an alternative to DJ stents, nephrostomies or immediate re-implantation. As all dislocations occurred within three months, frequent early postoperative follow-up is required. [ABSTRACT FROM AUTHOR]

Abstract: Objective: ABO blood type is an inherited characteristic that has been associated with the prognosis of several malignancies, but there is little evidence in urothelial carcinoma of the bladder (UCB). The purpose of this study was to evaluate the effect of ABO blood type on mortality in patients with UCB treated with radical cystectomy (RC). Methods: Multi-institutional data from 7,906 patients with UCB treated with RC between 1979 and 2012 were retrospectively analyzed. The effect of ABO blood type on UCB-related mortality was evaluated with univariable and multivariable competing-risks regression models. Results: ABO blood type was O in 3,728 (47%), A in 2,748 (35%), B in 888 (11%), and AB in 532 (7%) patients. Blood type B was associated with a greater likelihood of lymphovascular invasion (P = 0.010) and positive soft tissue margins (P = 0.008). The median follow-up was 41 months. The 5-year cumulative UCB-related mortality rates for blood type O, A, B, and AB were 29.5%, 30.5%, 33.2%, and 25.8%, respectively. In univariable competing-risks regression, patients with blood type B had worse UCB-related mortality than those with blood type O (P = 0.026) and AB (P = 0.020). In multivariable analysis, however, blood type lost its statistical significance. Conclusions: Among patients treated with RC, ABO blood type is associated with a statistically significant but clinically insignificant difference in UCB-related mortality. This association was not present in multivariable analysis. Our data therefore suggest no relevant association of ABO blood type with UCB-related prognosis. [Copyright &y& Elsevier]

Introduction: Currently, most of renal tumors are small, low grade, with a slow growth rate, a low metastatic potential, and with up to 30 % of these tumors being benign on the final pathology. Moreover, they are often diagnosed in elderly patients with preexisting medical comorbidities in whom the underlying medical conditions may pose a greater risk of death than the small renal mass. Concerns regarding overdiagnosis and overtreatment of patients with indolent small renal tumors have led to an increasing interest in minimally invasive, ablative as an alternative to extirpative interventions for selected patients. Objective: To provide an overview about the state of the art in radiofrequency ablation (RFA), high-intensity focused ultrasound, and cryoablation in the clinical management of renal cell carcinoma. Methods: A PubMed wide the literature search of was conducted. Results: International consensus panels recommend ablative techniques in patients who are unfit for surgery, who are not considered candidates for or elect against elective surveillance, and who have small renal masses. The most often used techniques are cryoablation and RFA. These ablative techniques offer potentially curative outcomes while conferring several advantages over extirpative surgery, including improved patient procedural tolerance, faster recovery, preservation of renal function, and reduction in the risk of intraoperative and postsurgical complications. While it is likely that outcomes associated with ablative modalities will improve with further advances in technology, their application will expand to more elective indications as longer-term efficacy data become available. Conclusion: Ablative techniques pose a valid treatment option in selected patients. [ABSTRACT FROM AUTHOR]

Objective To validate high-sensitivity C-reactive protein (hs- CRP) serum levels as an independent marker for disease-free survival ( DFS) in clinically localised clear cell renal cell carcinoma ( ccRCC)., Patients and Methods In all, 403 consecutive patients with clinically localised ( T1-3N0M0) ccRCC treated by radical or partial nephrectomy were enrolled., Preoperative serum levels of hs- CRP were evaluated as both a continuous and categorical variables., Associations with clinical (age, gender) and pathological variables ( T classification, grade, tumour necrosis) were assessed with the chi-square and Kruskal- Wallis tests., Univariable and multivariable Cox proportional hazards models were fitted. The prognostic accuracy ( PA) was assessed with Harrell's C-index., Results The mean hs- CRP level was 1.32 mg/dL. The hs- CRP levels were associated with T classification ( P = 0.05), high-grade disease (P < 0.001) and tumour necrosis ( P = 0.003)., After a median follow-up of 43 months, 41 patients (10.1%) had developed disease recurrence. With each unit increase in hs- CRP levels, the risk of recurrence increased by 10% (hazard ratio 1.10, P = 0.015)., The thresholds of 0.5 and 0.75 mg/dL showed the best discrimination for stratification of patients according to the probability of recurrence., These categorically coded hs- CRP levels were identified as independent prognostic factors in multivariable analyses ( P < 0.001) and led to a significant increase in the PA of a multivariable base model containing the variables of the 'Stage, Size, Grade and Necrosis' ( SSIGN) score., Conclusions This study validates preoperative serum hs- CRP levels as independent prognostic factor after surgery for localised ccRCC., Hs-CRP may be included in standard prognostic modelling after surgery and may guide surveillance and inclusion in adjuvant clinical trials. [ABSTRACT FROM AUTHOR]

BACKGROUND: The short arm of chromosome 3 (3p) harbors the von Hippel-Lindau ( VHL) tumor suppressor gene, and the long arm of chromosome 14 (14q) harbors the hypoxia-inducible factor 1α ( HIF-1α) gene. The objective of this study was to evaluate the significance of 3p loss (loss VHL gene) and 14q loss (loss HIF-1α gene) in clear cell renal cell carcinoma (ccRCC). METHODS: In total, 288 ccRCC tumors underwent a prospective cytogenetic analysis for alterations in chromosomes 3p and 14q. Tumors were assigned to 1 of 4 possible chromosomal alterations: VHL +3p/+14q (VHL wild type [VHL-WT]), VHL +3p/−14q (VHL-WT plus HIF2α [WT/H2]), −3p/+14q (HIF1α and HIF2α [H1H2]), and −3p/−14q (HIF2α [H2]). RESULTS: Among patients who had loss of 3p, tumors with −3p/−14q (H2) alterations were larger ( P = .002), had higher grade ( P = .002) and stage ( P = .001), and more often were metastatic ( P = .029) than tumors that retained 14q (H1H2). All patients who had tumors with −3p/−14q (H2) had worse cancer-specific survival ( P = .014), and patients who had localized disease ( P = .012) and primary T1 (pT1) tumors ( P = .008) had worse recurrence-free survival. In patients who had pT1 tumors, combined 3p/14q loss was an independent predictor of recurrence-free survival (hazard ratio, 11.19; 95% confidence interval, 1.91-65.63) and cancer-specific survival (hazard ratio, 15.93; 95% confidence interval, 3.09-82.16). The current investigation was limited by its retrospective design, single-center experience, and a lack of confirmatory protein analyses. CONCLUSIONS: Loss of chromosome 3p (the VHL gene) was associated with improved survival in patients with ccRCC, whereas loss of chromosome 14q (the HIF-1α gene) was associated with worse outcomes. The results of the current study support the hypothesis that HIF-1α functions as an important tumor suppressor gene in ccRCC. Cancer 2013. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Introduction: Through evolution in technology, endoscopic treatment has gained popularity for the treatment of upper tract urothelial carcinoma (ENDO-UTUC). Methods: A total of 20 patients with ENDO-UTUC were compared to 178 treated by radical nephroureterectomy (RNU) for a pTa-1 UTUC, and a systematic review was performed. Results: Mean age for ENDO-UTUC was 71.9 ± 16.0 years, and tumor features were favorable (90 % papillary, 14 low grade, 11 pTa). All ENDO-UTUC were performed ureteroscopically. Mean follow-up was 20.4 ± 30 months. The 5-year overall survival (OS) rate was 45 %. Local (LR) and bladder recurrence (BR) was 25 and 15 %. Time to definitive treatment was longer, ASA higher, LR rates higher, OS lower for ENDO-UTUC (all p < 0.001), but no difference was recorded for BR ( p = 0.056) and cancer-specific survival (CSS) ( p = 0.364). Postoperative kidney function (KF) was better in the ENDO-UTUC ( p = 0.048), though preoperative KF showed no difference. The maximal level of evidence was 3b, patients were highly selected, numbers of patients were low, and ASA scores high. OS was rather low and CSS high. LR rate was high (61 %) and BR rate moderate (39 %) for ureteroscopic and 36 and 28 %, respectively, for percutaneous approach. Conclusions: LR for ENDO-UTUC is high. In high-grade UTUC, oncological outcome is worse. RNU is associated with a significant loss of KF, but LR is rare. ENDO-UTUC is reserved for selected cases if elective. In imperative cases, it has to be balanced between KF, morbidity of the procedure, risk of operation and tumor control. ENDO-UTUC is not necessarily underused in Austria, because of lack in evidence, but 41 % of all RNU were performed in pTa/pTis/pT1 lesions. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of this study was to evaluate the prevalence of chromosome 8q gain in clear cell renal cell carcinoma (CCRCC) and to correlate the findings with tumor phenotype and disease-specific survival (DSS). METHODS: The tumor karyotypes of 336 consecutive patients with CCRCC were prospectively evaluated with classical cytogenetic analysis. Chromosome 8q status was correlated with clinicopathological variables, and its impact on DSS was evaluated. RESULTS: Gain of 8q occurred in 28 tumors (8.3%). Gain of 8q was associated with a higher risk of regional lymph node (21.4% vs 6.2%, P = .011) and distant metastases (50.0% vs 24.4%, P = .006), and greater tumor sizes ( P = .030). Patients with gain of 8q had a 3.22-fold increased risk of death from CCRCC ( P < .001). In multivariable analysis, gain of 8q was identified as an independent prognostic factor (hazard ratio, 2.37; P = .006). The concordance index of a multivariable base model increased significantly following inclusion of 8q gain ( P = .0015). CONCLUSIONS: Gain of chromosome 8q occurs in a subset of CCRCCs and is associated with an increased risk of metastases and death from CCRCC. Because the proto-oncogene c-MYC is among the list of candidate genes located on 8q, our data suggest that these tumors may have unique pathways activated, which are associated with an aggressive tumor phenotype. If confirmed, defining tumors with gain of 8q may assist in identifying patients who would benefit for specific c-MYC inhibitors or agents that target the MAPK/ERK (mitogen-activated protein kinase) pathway. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the impact of age on PCA3 score and the utility of age-specific reference values in predicting initial prostate biopsy (pBx) outcomes. Patients and methods: This single-center, retrospective study included 205 men who underwent an initial 14-core TRUS-guided pBx due to PSA > 3.0 ng/ml or suspicious digital-rectal examination (DRE). PCA3 scores were measured with the Progensa assay. Linear regression models were fit to identify factors that impact PCA3 score and to determine age-specific reference values. Predictive accuracies of logistic regression models predicting presence of prostate cancer (PCa) were analyzed. Results: The positive biopsy rate was 37%. In multivariable linear regression, age ( P < 0.001), presence of PCa ( P < 0.001), and multifocal HG-PIN ( P = 0.012) were independent predictors of PCA3 score. Age showed the strongest impact on PCA3 score ( T = 4.77). The upper 95% confidence interval of PCA3 score in each age category was defined as the age-specific limit. A PCA3-score over the age-specific limit (PCA3-age) was associated with an 4.17-fold increased odds of being diagnosed with PCa ( P < 0.001). In multivariable logistic regression models predicting the presence of PCa, predictive accuracy of a base model (age, DRE, PSA, volume) increased from 69.6 to 75.4% ( P = 0.037) by adding the continuous PCA3 score, to 73.9% ( P = 0.098) with the 35 cutoff (PCA3-35) and to 77.1% ( P = 0.008) with PCA3-age. Conclusions: PCA3 score increases with age, independent of PCa presence. Age-specific PCA3 score reference values are superior to PSA, continuous PCA3 score, and PCA3-35 in predicting initial pBx outcome. Therefore, an age-adjusted PCA3 score should be used for interpretation of the results. [ABSTRACT FROM AUTHOR]

We studied the characteristics and prognosis of renal cell carcinoma (RCC) associated with Xp11.2 translocation and transcription factor E3 (TFE3) expression and determined the need for genetic analysis in routine diagnostics. Of 848 consecutive cases, 75 showed microscopic features suggestive of Xp11.2 translocation RCC or occurred in patients 40 years or younger. Of these cases, 17 (23%) showed strong nuclear TFE3 immunostaining, which was associated with more advanced tumors and inverse prognosis in univariate (P = .032) but not multivariate (P = .404) analysis. With fluorescence in situ hybridization and polymerase chain reaction, only 2 cases showed alterations of the X chromosome and the ASPL-TFE3 gene fusion, respectively. In our laboratory, the predictive value of TFE3 expression for the Xp11.2 translocation was 12%. Strong nuclear TFE3 expression is associated with metastatic spread and a poor prognosis. In our laboratory, TFE3 is not diagnostic for Xp11.2 translocation RCC. Diagnosis of Xp11.2 translocation RCC may be made only genetically. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of biphosphonate administration on subsequent Samarium-ethylene-diamine-tetramethyl-phosphonate (EDTMP) uptake in bone metastases of patients with castration-resistant prostate cancer. Patients and methods: The bone uptake of Sm-EDTMP was assessed in 40 consecutive patients with castration-resistant prostate cancer and multiple painful bone metastases and no prior bisphosphonate therapy. Sm-EDTMP was repeated after 3 months in the presence of bisphosphonates (zoledronic acid every 4 weeks, first administration 1 week after Sm-EDTMP administration). The retained activity in bone was evaluated 20 h after application using whole-body scintigraphy (acquisition 15 cm/min). Results: Mean patient age was 69 ± 4.8 years (range 57-77 years). Mean PSA level at study entry was 18.2 ± 21.0 ng/ml. Sm-EDTMP uptake ranged from 36.3 to 75.3% (mean 55.1 ± 10.9%) before bisphosphonate administration and 35.6 to 73.3% (mean 55.2 ± 10.4%) after bisphosphonate administration. No significant intra-individual difference with or without bisphosphonate treatment was observed ( P = 0.647). Conclusions: Bisphosphonate treatment does not affect Sm-EDTMP bone uptake in patients with castration-resistant metastatic prostate cancer. Thus, bisphosphonate treatment can be continued safely during samarium therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the impact of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC. METHODS: Eight hundred-two patients (457 nonsmokers and 345 smokers) who had up to 232 months of follow-up were compared for differences in their clinicopathologic features and survival outcomes. Immunohistochemical differences in p53 expression were correlated with smoking status. RESULTS: Smokers presented more commonly with pulmonary comorbidities ( P < .0001) and cardiac comorbidities ( P = .014) and with a worse performance status ( P = .031) than nonsmokers. Smoking was associated significantly with tumor multifocality ( P = .022), higher pathologic tumor classification ( P = .037), an increased risk of bulky lymph node metastases ( P = .031), and the presence of distant metastases ( P < .0001), especially lung metastases ( P < .0001). Both overall survival (OS) (62.37 months vs 43.64 months; P = .001) and cancer-specific survival (CSS) (87.43 months vs 56.57 months; P = .005) were significantly worse in patients who smoked. The number of pack-years was retained as an independent predictor of CSS and OS in patients with nonmetastatic disease. Mean expression levels of p53 were significantly higher in current smokers compared with former smokers and nonsmokers ( P = .012). CONCLUSIONS: In patients with RCC, a history of smoking was associated with worse pathologic features and survival outcomes and with an increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in patients with RCC who have a history of smoking is indicated. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently, there are no established diagnostic and prognostic serum markers for renal cell carcinoma (RCC). The objective of this study was to evaluate the putative significance of serum cell-free DNA. METHODS: Preoperative serum samples from 200 consecutive patients with sporadic, solid renal tumors were analyzed (157 patients with RCC and 43 patients with benign renal tumors). Quantitative real-time polymerase chain reaction was used to assess total cell-free DNA (ring finger protein 185 [ RNF185]) and CpG island methylation of Ras association domain family member 1A ( RASSF1A) von Hippel-Lindau ( VHL), prostaglandin-endoperoxidase synthase 2 ( PTGS2), and P16 (cyclin-dependent kinase inhibitor 2A). Associations with RCC, pathologic variables, and disease-specific survival were evaluated. RESULTS: Total cell-free DNA levels and CpG island methylation of RASSF1A and VHL were highly diagnostic for RCC with an area under the receiver operating characteristic curve of 0.755, 0.705, and 0.694, respectively. VHL methylation was detected more frequently in patients with clear cell RCC than in those with other subtypes ( P = .007). Total cell-free DNA levels were higher in patients with metastatic RCC ( P < .001) and necrotic RCC ( P = .003) and were associated with poorer disease-specific survival ( P < .001). In multivariate analysis, the tumor stage, size, grade, and necrosis (SSIGN) score ( P < .001) and categorized total cell-free DNA levels ( P = .028) were retained as independent prognostic factors. CONCLUSIONS: The current results indicated that cell-free DNA represents a novel serum-based diagnostic and prognostic biomarker for RCC. Total serum cell-free DNA levels and CpG island methylation of RASSF1A and VHL may be useful diagnostic biomarkers for RCC. VHL methylation of cell-free DNA is suggestive of clear cell RCC. Total serum cell-free DNA may be a useful prognostic biomarker that may assist in tailoring postoperative surveillance and therapy. External prospective validation of these data will be required. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Context: For small renal masses (SRMs), partial nephrectomy (PN) represents the therapeutic standard of care. Laparoscopic cryoablation (LCA) could be regarded as an alternative to surgical excision in selected patients, if perioperative complication rates and oncologic results are comparable. Objective: To perform a cumulative analysis of observational studies regarding oncologic outcomes and perioperative complications of both procedures. Evidence acquisition: Medline, Embase, and Web of Science searches were performed for clinically localized sporadic SRMs that were treated with PN or LCA. A total of 6785 lesions were analyzed for local and metastatic tumor progression and 10 906 procedures for perioperative complications. Evidence synthesis: Patients undergoing LCA were significantly older, mean tumor sizes were lower, and mean follow-up duration was shorter (each p <0.001). Following LCA and PN, 8.5% and 1.9% developed local tumor progression, respectively (p <0.001). In multivariable analysis, the relative risk for local tumor progression of LCA versus PN was 5.24-fold increased (p <0.001); the risk of metastatic progression was similar. The overall complication rate was higher following PN (23.5% vs 17.0%; p <0.001), especially the rate of major complications (19.2% vs 10.2%; p <0.001). In multivariable analysis, the total risk for complications and major complications for PN versus LCA was 4.6-fold (p =0.004) and 9.71-fold (p <0.001) increased, respectively. Limitations of this analysis include follow-up and selection bias, and lack of standardization reporting complications and outcomes. Conclusions: Both PN and LCA are viable options for the management of SRMs. Compared with PN, LCA results in a higher risk of local tumor progression. The risk of perioperative complications appears to be lower following LCA; however, this difference is strongly influenced by selection bias, and thus limited conclusions can be made regarding true differences in complications. Therefore, PN is the gold standard for SRMs, but LCA may be indicated in selected patients with significant comorbidity. [Copyright &y& Elsevier]

Objective. The purpose of the study was to evaluate the management and interpersonal variability of Bosniak classification and demonstrate the present diagnostic dilemmas. Material and methods. One-hundred and four patients with 113 complex renal cystic masses (26 Bosniak II,15 IIF,28 III and 44 IV) were included and analysed between April 1996 and May 2009.In total, 71 cystic masses were characterized by two radiologists in consensus initially as the first diagnosis (group 1), and then by a radiologist (group 2) and a urologist (group 3) independently in a blinded fashion. Results. Only 11 patients (10.6%) were symptomatic (one Bosniak IIF, six III and four IV). Only one had renal cell carcinoma (RCC) on final histology, whereas the others ( n == 10) had benign lesions. An overall pathological result was obtained in 71 masses (62.8%) (two Bosniak II, three IIF, 27 III and 39 IV). The overall incidence of RCC in surgically treated patients was 0%, 20%, 55.6% and 76.9% for each category, respectively. The interpersonal variability was significant among the three groups (especially in Bosniak II, IIF), and the overall category was changed in 54%, 20% and 41%, respectively ( p < 0.001). After correlation with final histology and presumed benign character of Bosniak II/IIF lesions (all patients having reached 5-year follow-up) the differences were not significant. Conclusion. It is challenging to minimize unnecessary surgical procedures in Bosniak category III. According to these results, it may make practical sense to group Bosniak II and IIF masses in one category. [ABSTRACT FROM AUTHOR]

AbstractPurpose:To directly compare perioperative, oncologic, and functional outcomes of laparoscopic renal cryoablation and open partial nephrectomy using a matched pair analysis.Patients and Methods:A total of 41 patients who underwent laparoscopic cryoablation for an incidental, solid clinical T1aN0M0renal tumor were matched with 82 patients who received partial nephrectomy in cold ischemia, using optimal matching based on propensity scores, which were created on the basis of preoperative aspects and dimensions used for an anatomic classification of renal tumors (PADUA) score, preoperative glomerular filtration rate, age-adjusted Charlson comorbidity index, and sex. Median follow-up was 33.6 months.Results:No differences in the overall incidence of complications (cryoablation, 20%; partial nephrectomy, 17%; P=0.739) and grade of complications (P=0.424) were observed. After cryoablation, local recurrence developed in four patients with renal-cell carcinoma (n=35) after a median duration of 14 months (range 6–18 mos), but none after partial nephrectomy. The 3-year recurrence-free survival probabilities after laparoscopic renal cryoablation vsopen partial nephrectomy were 83% vs100%, respectively (P=0.015). The average decrease of estimated glomerular filtration rate during follow-up was 7.8±3.1 mL/min/1.73 m2after laparoscopic cryoablation and 9.8±2.3 mL/min/1.73 m2after open partial nephrectomy, which was not statistically significant (P=0.602).Conclusions:Perioperative complications and renal functional outcomes of laparoscopic cryoablation and open partial nephrectomy are similar; however, laparoscopic cryoablation confers a substantially higher local recurrence risk of about 17% after 3 years. Therefore, laparoscopic renal cryoablation should be reserved for high-risk patients with decreased life expectancy. Careful patient counseling is advocated. Study limitations include the small sample size, the lack of randomization, and the short follow-up. [ABSTRACT FROM AUTHOR]

The article offers information on a study which determined whether deletion of chromosome 9p in clear cell renal cell carcinoma (ccRCC) predicted worse disease-specific survival (DSS) and recurrence-free survival (RFS). The study also investigated the possible association between the deletion and aggressive behavior in small renal masses. Methods used include fluorescence in situ hybridization and cytogenetics. A discussion on the research findings is detailed. The benefits of preoperative identification of patients with 9p deletions are mentioned.

Objectives: To compare the results of preoperative scrotal color Doppler ultrasonography (CDS) and final diagnosis of subsequent surgical exploration in cases of suspected testicular torsion (TT). Methods: This retrospective study included 298 boys with acute scrotum whose clinical presentation was suspicious of TT and who subsequently underwent emergency surgery regardless of CDS results. Results: Mean patient age was 11.4 ± 4.1 years. The mean time of duration of symptoms up to surgical exploration was 26.4 ± 37.3 hours. All patients had standardized CDS of the scrotum. At surgery, 62 boys (20.9%) were diagnosed with TT, 168 (56.4%) with torsion of a testicular appendage (TA), and 24 (8.1%) with epididymitis. In 34 patients (11.4%), the cause of pain could not be identified during surgery. Overall CDS sensitivity, specificity, positive predictive value, and negative predictive value for TT diagnosis was 96.8%, 97.9%, 92.1%, and 99.1%, respectively. The mean age for the occurrence of TA and TT was 11.2 and 13.4 years, respectively (P <.0001). The peak incidence of TT was between age 14 and 16. Boys with TT sought medical attention statistically significantly earlier than those with TA or epididymitis obviously because of more severe pain (P <.0001). At the time of exploration for TT the affected testicle could be preserved in 32 boys (85.5%). In the remaining 9 boys the testis was considered nonviable and removed. Conclusions: About 20% of boys presenting with an acute scrotum actually have TT. CDS is a reliable tool to identify TT. [Copyright &y& Elsevier]

Study Type – Therapy (case series) Level of Evidence 4 OBJECTIVE To outline the features and outcomes of renal cell carcinoma (RCC) in native kidneys of renal transplant recipients, who are at increased risk of developing this disease. PATIENTS AND METHODS We retrospectively studied the clinicopathological features and survival of 28 surgically treated RCCs, which developed in 24 renal transplant recipients. Features and outcomes were compared with 671 patients with RCC who had no renal transplant. RESULTS The median interval between renal transplantation and the occurrence of RCC was 5.6 years. Acquired cystic kidney disease was present in 83% of the transplanted patients. Compared with the patients with RCC and no renal transplant, RCCs of native kidneys in transplant recipients were more frequently incidental findings (92% vs 77%, P = 0.092), multifocal (39% vs 15%, P < 0.001), bilateral (17% vs 4%, P = 0.006), had lower T stages ( P = 0.040), were smaller ( P = 0.027), of lower grades ( P = 0.010), were more frequently papillary (43% vs 19%, P = 0.019) and occurred at a significantly younger age ( P = 0.022). After a median follow-up of 6.7 years, eight renal transplant recipients had died (33%), but only two deaths were due to RCC. Survival with metastatic RCC was only 4 months, if a full resection of all metastatic sites was not achieved. In multivariate analysis the presence of a renal transplant had no effect on survival. CONCLUSIONS Most RCCs in renal transplant recipients are incidental low-stage, low-grade tumours with a favourable prognosis. The outstanding pathological findings are bilateral occurrence, papillary subtype and multifocality. Prognosis of metastatic RCC is poor but might be favourable if all metastases are resected. Screening for early detection of asymptomatic RCC is advocated. [ABSTRACT FROM AUTHOR]

Abstract: Background: Modern histopathology is able to differentiate chromophobe renal cell carcinomas (cRCCs), oncocytomas, and chromophobe–oncocytic hybrid RCCs; however, the true frequency and clinical courses of these tumors remain unclear. Objective: To determine the clinical course of hybrid RCC. Design, setting, and participants: Ninety-one surgically treated tumors, originally classified as oncocytoma or cRCC, were slide reviewed and reclassified by an experienced uropathologist. Immunohistochemical cytokeratin-7 (CK7) staining was used to distinguish oncocytoma (CK7 positive in <10% of the cells) and hybrid RCCs (CK7 positive in >10% of the cells). Interventions: Radical tumor nephrectomy or nephron-sparing surgery. Measurements: Recurrence-free and tumor-specific survival. Results and limitations: Overall, 16 tumors (17.6%) were hybrid RCCs, 32 tumors were cRCCs, and 43 tumors were pure oncocytomas. Perinephric tissue invasion (pT3a) was found in one pure oncocytoma and in two hybrid RCCs. The pathologic stage for cRCC was pT1 in 50% of tumors (n =17), pT2 in 23.5% of tumors (n =8), and pT3a in 26.5% of tumors (n =9). Low-grade RCC was found in 76.5% of tumors (n =26), and vascular invasion was found in 11.8% of tumors (n =4). After a mean follow-up of 50 mo, no oncocytomas or hybrid RCCs were found, but two cRCCs had recurred. The 3-yr tumor-specific survival rates for patients with oncocytoma, hybrid RCCs, and cRCC were 100%, 100%, and 97%, respectively. Conclusions: Hybrid RCCs are more common than expected. The survival rate is 100% for both hybrid RCCs and oncocytomas. Hybrid RCCs may be candidates for active surveillance, and surgery may be unnecessary. CRCCs should be treated because a small proportion of these tumors exhibit aggressive clinical courses. [Copyright &y& Elsevier]

Abstract: Objectives: To analyze pathobiology and prognosis of chromophobe renal cell carcinoma (CRCC). Patients and methods: We studied 124 patients with CRCC who underwent nephrectomy from 1989 to 2006 at two institutions. Clinicopathological characteristics and survival were compared with 1,693 consecutive patients with clear-cell RCC. Results: Compared with clear cell RCC, patients with CRCC presented with less advanced tumors, but had a higher prevalence of concomitant sarcomatoid features (15% vs. 6%, P < 0.001). Metastatic CRCC showed a high incidence of sarcomatoid features (50%) and a predilection for liver metastases. The 5-year DSS rate for all patients with CRCC was 78% compared with 60% for patients with clear-cell RCC (P = 0.008). When adjusted for metastatic status, this survival difference disappeared. Nonmetastatic RCCs had similar prognosis (P = 0.157), whereas survival of metastatic CRCC was inferior to that of patients with metastatic clear-cell tumors (median: 6 vs. 19 months, P = 0.0095). In multivariate analysis, ECOG PS, symptomatic presentation, T stage, N stage, M stage, nuclear grade, and presence of sarcomatoid features, but not histological sub-type, were independent prognostic factors of DSS. Ten patients received immunotherapy, none of whom were responders. Conclusions: Compared with clear-cell RCC, patients with CRCC present with less advanced tumors, which lead to better survival rates on the whole. However, adjustment for metastatic status negates this difference. Patients with metastatic CRCC show a high prevalence of sarcomatoid features, predilection for liver metastases, no response to immunotherapy, and exhibit poor prognosis. [Copyright &y& Elsevier]

Objectives: To analyze risk factors, management, histology, and outcome of bilateral testicular germ cell tumors (TGCT) based on a 25-year single center experience. Methods: Out of 612 patients treated for TGCT between 1982 and 2007, 17 (3%) were found to have bilateral disease. Data of these patients were reviewed and analyzed. Results: Eleven patients (65%) were identified with metachronous and 6 (35%) with synchronous bilateral TGCT. One patient had a cryptorchism in childhood. Patients with metachronous bilateral disease presented at lower stages than those with synchronous bilateral disease (stage I: 82% vs 33%, P = 0.02). In metachronous bilateral TGCT, the interval between the tumors ranged from 4 months to 25 years with a median of 47 months. The risk of developing a TGCT in the contralateral testicle was 26-fold higher than the a-priori risk for a healthy individual to develop TGCT. Overall, 74% of the bilateral tumors were seminomas and >50% of the patients had similar histology on both sides. After a median follow up of 121 months for patients with synchronous and 95 months for patients with metachronous bilateral TGCT, all patients were alive with no evidence of disease. Conclusions: Most bilateral TGCT develop metachronously and are seminomas. Although patients with synchronous bilateral disease present at higher stages, both synchronous and metachronous bilateral TGCT carry a similar, excellent prognosis. Patients with unilateral TGCT require careful long-term monitoring of the remaining testicle due to a 26-fold increased risk of contralateral disease and a potentially long risk interval of up to 25 years. [ABSTRACT FROM AUTHOR]

Abstract: Patient''s history, physical examination, laboratory tests, and radiographic evaluation are the cornerstones of postoperative surveillance. It has been shown that localized renal cell carcinoma (RCC) can recur in nearly all organs of the body, but most commonly in the lung, bone, liver, brain, and renal fossa. Lung metastases can be sensitively detected through radiographic evaluation. Treatment of lung metastases might prolong survival, which supports surveillance x-ray or computed tomography scans. Surgical treatment of early detected liver metastases and local recurrences may also prolong survival, which supports a close abdominal surveillance program. Brain and bone metastases are usually symptomatic when they occur, and their treatment is generally palliative. Hence, surveillance protocols do not usually include their routine radiographic evaluation. Because partial nephrectomy does not increase the risk of local recurrence over radical nephrectomy, we recommend identical surveillance for completely resected tumors regardless of surgical approach. The risk of recurrence after nephrectomy is generally related to tumor stage, tumor grade, and patient performance status. The majority of recurrences occur within the first 5 years after surgery, supporting a more intense surveillance strategy within the first 5 years. The University of California Integrated Staging System (UISS) combines TNM stage, Fuhrman grade, and performance status, and categorizes patients into 3 different risk groups. The current surveillance protocol at our institution is based on the UISS. It is expected that molecular markers such as p53 will allow more individualized surveillance strategies in the future. [Copyright &y& Elsevier]

The article features the research conducted by Tobias Klatte and colleagues on the significance of carbonic anhydrase IX as a molecular marker in Los Angeles, California. Result shows carbonic anhydrase IX (CAIX) is a bladder cancer-specific antigen that is not expressed in normal urothelial tissue but is expressed in 70-90% of transitional cell carcinoma (TCC). It reveals that the expression is usually heterogeneous with a maximum staining seen on the luminal surfaces of the papillae.

Abstract: Over the past 2 decades, a greater understanding of the basic biology and genetics of kidney cancer has occurred. Surgical techniques have also evolved, and technological advances have made possible new methods of managing renal tumors. The most extensively used system to provide prognostic information for renal cell carcinoma (RCC) is currently the tumor, nodes, metastasis (TNM) staging system. Emerging data over the last few years has questioned whether further revisions are needed and if improvements can be made with the introduction of new, more accurate and predictive prognostic factors. The recent discovery of molecular tumor biomarkers are expected to revolutionize the staging of RCC and potentially lead to the development of new therapies based on molecular targeting. This review will examine the current staging modalities and prognostic factors associated with RCC as well as the selection of patients most likely to benefit from clinical trials. [Copyright &y& Elsevier]

Surveillance is a new management option for small renal masses (SRMs) in aged and infirm patients with short-life expectancy. The current literature on surveillance of SRM contains mostly small, retrospective studies with limited data. Imaging alone is inadequate for suggesting the aggressive potential of SRM for both diagnosis and followup. Current data suggest that a computed tomography (CT) or magnetic resonance imaging (MRI) every 3 months in the 1st year, every 6 months in the next 2 years, and every year thereafter, is appropriate for observation. The authors rather believe in active surveillance with mandatory initial and followup renal tumor biopsies than classical observation. Since not all SRMs are harmless, selection criteria for active surveillance need to be improved. In addition, there is need for larger studies in order to better outline oncological outcome and followup protocols. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the prognostic role of tumour size in pathological stage T3a renal cell carcinoma (RCC) with fat invasion only and to assess whether this subgroup maintains its relevance over the other pathological stages. Methods: We retrospectively studied 2113 patients from eight international institutions who were treated by surgical resection for T2–4 RCC. Disease-specific survival (DSS) was evaluated with univariate and multivariate analyses. Results: Univariate analysis of patients with T3a RCC showed that tumour size was significantly associated with DSS (HR: 1.09, 95% CI: 1.05–1.12, p <0.001). An ideal cut-off of 7cm for these patients was identified with a scatter plot of Martingale residuals and tumour size. The two T3a groups were distinctly different with respect to clinicopathologic parameters (performance status, metastases, grade, histological subtype) and survival (p <0.001). Median survival time was not reached for patients with T2 and T3a≤7cm disease with a 5- and 10-yr DSS rate of 70% and 59% and 63% and 53%, respectively. Median survival time for patients with T3a>7cm, T3b, T3c, and T4 disease was 54, 46, 21, and 11 mo, respectively, with 5- and 10-yr DSS rates of 46% and 36%, 46% and 36%, 34% and 0%, and 16% and 14%, respectively. Conclusions: Our data indicate that tumour size is an important factor for predicting outcome of patients with T3a RCC with fat invasion only. Our findings should merit consideration during the next revision of the TNM classification. [Copyright &y& Elsevier]

OBJECTIVE To evaluate peri-operative peripheral and renal venous plasma levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor type BB (PDGF-BB), transforming growth factor (TGF)-β1, endostatin, and thrombospondin-1 (TSP-1) in relation to pathological variables and prognosis, as pro- and anti-angiogenic factors are important for tumour growth and treatment of patients with renal cell carcinoma (RCC). PATIENTS AND METHODS The study included 74 consecutive patients with sporadic RCC who had tumour nephrectomy. Peripheral venous blood was drawn 1 day before, immediately and 1, 3 and 5 days after surgery. Renal venous blood was collected in a subgroup of 33 patients during surgery. The variables were analysed using quantitative enzyme-linked immunoassay kits, and associated with pathological variables and disease-specific survival. RESULTS Soon after surgery, peripheral venous VEGF, PDGF-BB and TGF-β1 levels were decreased, whereas endostatin levels were significantly increased. Renal venous VEGF, PDGF-BB and TGF-β1 levels were higher than in the general venous blood pool. Renal venous VEGF levels were correlated with tumour diameter and associated with grade and vascular invasion. After a mean follow-up of 30 months, higher peripheral preoperative, early peripheral postoperative and renal venous VEGF levels were associated with a poorer prognosis. However, in a multivariate analysis only Tumour-Node-Metastasis stage and Eastern Cooperative Oncology Group performance status were independent prognosticators of disease-specific survival. CONCLUSIONS Circulating pro- and anti-angiogenic factors change early after nephrectomy. VEGF, PDGF-BB and TGF-β1 are higher in the renal vein than in the general venous blood pool. Higher renal venous and peripheral levels of VEGF might be associated with a poorer prognosis. [ABSTRACT FROM AUTHOR]

An interesting group of papers in this section is headed by two papers on synchronous bilateral renal tumours, one from an international group of authors and one from Germany. The large series of patients are examined carefully by both groups, and the findings should be useful for all who are interested in this area. Authors from the UK examine the role of lactate dehydrogenase as a prognostic factor for testicular cancer. They found that it had limited sensitivity, specificity and positive predictive value for detecting relapse, with false-positive elevations being common. OBJECTIVE To present a multicentre experience and the largest cohort to date of nonmetastatic (N0M0) synchronous bilateral renal cell carcinoma (RCC), as because it is rare the single-institutional experience is limited. PATIENTS AND METHODS We retrospectively studied 10 337 patients from 12 urological centres to identify patients with N0M0 synchronous bilateral RCC; the clinicopathological features and cancer-specific survival were compared to a cohort treated for N0M0 unilateral RCC. RESULTS In all, 153 patients had synchronous bilateral solid renal tumours, of whom 135 (88%) had synchronous bilateral RCC, 118 with nonmetastatic disease; 91% had nonfamilial bilateral RCC. Bilateral clear cell RCC was the major histological subtype (76%), and papillary RCC was the next most frequent (19%). Multifocality was found in 54% of bilateral RCCs. Compared with unilateral RCC, patients did not differ in Eastern Cooperative Oncology Group performance status (ECOG PS) and T classification, but bilateral RCCs were more frequently multifocal (54% vs 16%, P < 0.001) and of the papillary subtype (19% vs 12%), and less frequently clear cell RCC (76% vs 83%, P = 0.005). For the outcome, patients with nonmetastatic synchronous bilateral RCC and unilateral RCC had a similar prognosis ( P = 0.63); multifocality did not affect survival ( P = 0.60). Multivariate analysis identified ECOG PS, T classification, and Fuhrman grade, but not laterality, as independent prognostic factors for cancer-specific survival. CONCLUSIONS Patients with N0M0 synchronous bilateral RCC and N0M0 unilateral RCC have a similar prognosis. The frequency of a familial history for RCC (von Hippel-Lindau disease or familial RCC) was significantly greater in bilateral synchronous than in unilateral RCC. The significant pathological findings in synchronous bilateral RCC are papillary subtype and multifocality. [ABSTRACT FROM AUTHOR]

OBJECTIVE To define the prognostic relevance of capsular involvement (invasion with no penetration) and collecting-system invasion in patients with stage I (pT1N0M0) and stage II (pT2N0M0) renal cell carcinoma (RCC), by evaluating the outcome of patients treated with nephrectomy. PATIENTS AND METHODS In all, 519 patients from a kidney cancer database treated with nephrectomy for stage I and II RCC between 1985 and 2005 were assessed retrospectively. The primary endpoint was recurrence-free survival time. The prognostic relevance of capsular involvement and collecting-system invasion were examined using univariate and multivariate survival analysis. RESULTS Capsular involvement and collecting-system invasion were evident in 112 (21.6%) and 39 (7.5%) patients, respectively. Capsular involvement was associated with higher Fuhrman grades and larger tumours. The incidence of collecting-system invasion was higher in patients with microvascular invasion. The median follow-up was 49 months. In univariate analysis, patients with capsular involvement and collecting-system invasion had a worse prognosis than patients without ( P = 0.007 and <0.001, respectively). In multivariate analysis, capsular involvement (hazard ratio 1.84, P = 0.036) and collecting-system invasion (3.78, P < 0.001) were independent prognostic factors of recurrence-free survival. Interestingly, there was no survival difference between patients with capsular involvement in stage I/II and patients with invasion of perinephric tissue (pT3aN0M0). CONCLUSIONS These findings suggest that capsular involvement and collecting-system invasion are poor prognostic findings in stage I and II RCC. They should both be considered when planning the follow-up. A revised pT3a stage including patients with capsular involvement could improve its prognostic validity. [ABSTRACT FROM AUTHOR]

OBJECTIVE To test the combination of docetaxel with two different doses of estramustine in patients with hormone-refractory prostate cancer (HRPC), to improve response rates and to lower side-effects, as docetaxel-based chemotherapy is an increasing option for men with advanced HRPC, and alone or combined with estramustine, docetaxel improves median survival. PATIENTS AND METHODS In all, 72 patients with metastatic HRPC were randomly assigned to receive docetaxel (70 mg/m2 intravenously, on day 2 every 21 days) and estramustine (3 × 280 mg/day oral starting 1 day before docetaxel, for 5 consecutive days) for arm A, or estramustine (3 × 140 mg/day oral starting 1 day before docetaxel, for 3 consecutive days) for arm B. Premedication with oral dexamethasone at a total daily dose of 16 mg, in divided doses twice a day was administered in arm A on day 1–5 and in arm B on day 1–3. Initially, six cycles were administered. Chemotherapy was restarted after a significant increase in prostate-specific antigen (PSA) level. Patients were monitored for any measurable PSA response and toxicity. RESULTS Between the arms there was no statistically significant difference in time to progression and overall survival. However, treatment B had less treatment-related toxicity than A. Independent prognostic variables were baseline factors like PSA level, haemoglobin level, Eastern Cooperative Oncology Group performance status, and bone pain at presentation. CONCLUSIONS In this randomized phase II study the combination of docetaxel and estramustine had substantial activity in HRPC, with a significant incidence of severe toxicity, both haematological and not. Nevertheless, treatment-related toxicity was predictable and manageable. There was no better effect with a higher dose of estramustine with docetaxel than for a lower dose. There was a slight tendency to higher toxicity for high-dose estramustine but this was not statistically significant. The present results support the assertion that estramustine is not necessary in docetaxel-based treatment regimens. [ABSTRACT FROM AUTHOR]

Out of 52 immune-related parameters in muscle-invasive bladder cancer, 39 were significant, and of these, 16 were independent prognostic parameters. The strongest prognostic factor was the density of intraepithelial CD8+ T cells, representing the terminal end route of tumor cell killing. Quantity and the spatial relationship of specific immune cell types can provide prognostic information in bladder cancer. The objective of the study was to characterize the spatial interplay and prognostic role of different immune cell subpopulations in bladder cancer. A total of 2463 urothelial bladder carcinomas were immunostained with 21 antibodies using BLEACH&STAIN multiplex fluorescence immunohistochemistry in a tissue microarray format and analyzed using a framework of neuronal networks for an image analysis. Spatial immune parameters were compared with histopathological parameters and overall survival data. The identification of > 300 different immune cell subpopulations and the characterization of their spatial relationship resulted in numerous spatial interaction patterns. Thirty-nine immune parameters showed prognostic significance in univariate analyses, of which 16 were independent from pT, pN, and histological grade in muscle-invasive bladder cancer. Among all these parameters, the strongest association with prolonged overall survival was identified for intraepithelial CD8+ cytotoxic T cells (time-dependent area under receiver operating characteristic curve [AUC]: 0.70), while stromal CD8+ T cells were less relevant (AUC: 0.65). A favorable prognosis of inflamed cancers with high levels of "exhaustion markers" suggests that TIM3, PD-L1, PD-1, and CTLA-4 on immune cells do not hinder antitumoral immune response in tumors rich of tumor infiltrating immune cells. The density of intraepithelial CD8+ T cells was the strongest prognostic feature in muscle-invasive bladder cancer. Given that tumor cell killing by CD8+ cytotoxic T lymphocytes through direct cell-to-cell-contacts represents the "terminal end route" of antitumor immunity, the quantity of "tumor cell adjacent CD8+ T cells" may constitute a surrogate for the efficiency of cancer recognition by the immune system that can be measured straightaway in routine pathology as the CD8 labeling index. Quantification of intraepithelial CD8+ T cells, the strongest prognosticfeature identified in muscle-invasive bladder cancer, can easily be assessed by brightfield immunohistochemistry and is therefore "ready to use" for routine pathology. [ABSTRACT FROM AUTHOR]

Purpose: Thioredoxins are major regulatory proteins of oxidative signaling. Trx1 is the most prominent thioredoxin and, therefore, the current study sought to evaluate the prognostic role of Trx1 in ccRCC. Methods and patients: A tissue micro-array (TMA) study was carried out to evaluate the association of Trx1 with clinicopathological features and survival outcome. Data from the Cancer Genome Atlas (TCGA) were evaluated for the association of characteristics in the Trx1 gene with clinicopathological features and survival outcome. Results: In the TMA, patients with ccRCC that had high Trx1 levels had lower T stages (p < 0.001), less often distant metastases (p = 0.018), lower nuclear grades (p < 0.001), and less often tumor necrosis (p = 0.037) or sarcomatoid features (p = 0.008). Patients with a combined score of ≥ 10 had better DSS than patients with a low combined score of < 10 (HR 95% CI 0.62 (0.39–0.98)). Interestingly, the survival outcome is compartment specific: ccRCC patients whose tumors had exclusively Trx1 expression in the cytoplasm had the worst survival outcome (HR 3.1; 95% CI 1.2–8.0). Genomic data from the TCGA demonstrated that patients with ccRCCs that had Trx1 losses had more advanced clinicopathological features and worse survival outcome in disease specific (p < 0.001), overall (p = 0.001), and progression free survival (p = 0.001) when compared to patients with ccRCCs without copy number variations (CNV) or gains. Conclusion: The current study suggests a possible role of Trx1 in the tumor biology of ccRCC and thus, the current study strongly advises in depth investigations of redox signaling pathways in ccRCC. [ABSTRACT FROM AUTHOR]

Abstract: The treatment of renal tumors with the technique of partial nephrectomy continues to evolve. The relevant literature reviewed confirmed the excellent oncological outcomes associated with partial nephrectomy in properly selected patients. In addition, much data is being accumulated regarding the safety and efficacy of this technique via a laparoscopic approach. With either approach, the chance for renal preservation would appear to be a major benefit while “non-hilar” clamping techniques during the open approach may maximize the likelihood for maintenance of long-term renal function. [Copyright &y& Elsevier]

Background: The current World Health Organization classification recognises 12 major subtypes of renal cell carcinoma (RCC). Although these subtypes differ on molecular and clinical levels, they are generally managed as the same disease, simply because they occur in the same organ. Specifically, there is a paucity of tools to risk-stratify patients with papillary RCC (PRCC). The purpose of this study was to develop and evaluate a tool to risk-stratify patients with clinically non-metastatic PRCC following curative surgery.Methods: We studied clinicopathological variables and outcomes of 556 patients, who underwent full resection of sporadic, unilateral, non-metastatic (T1-4, N0-1, M0) PRCC at five institutions. Based on multivariable Fine-Gray competing risks regression models, we developed a prognostic scoring system to predict disease recurrence. This was further evaluated in the 150 PRCC patients recruited to the ASSURE trial. We compared the discrimination, calibration and decision-curve clinical net benefit against the Tumour, Node, Metastasis (TNM) stage group, University of California Integrated Staging System (UISS) and the 2018 Leibovich prognostic groups.Results: We developed the VENUSS score from significant variables on multivariable analysis, which were the presence of VEnous tumour thrombus, NUclear grade, Size, T and N Stage. We created three risk groups based on the VENUSS score, with a 5-year cumulative incidence of recurrence equalling 2.9% in low-risk, 15.4% in intermediate-risk and 54.5% in high-risk patients. 91.7% of low-risk patients had oligometastatic recurrent disease, compared to 16.7% of intermediate-risk and 40.0% of high-risk patients. Discrimination, calibration and clinical net benefit from VENUSS appeared to be superior to UISS, TNM and Leibovich prognostic groups.Conclusions: We developed and tested a prognostic model for patients with clinically non-metastatic PRCC, which is based on routine pathological variables. This model may be superior to standard models and could be used for tailoring postoperative surveillance and defining inclusion for prospective adjuvant clinical trials. [ABSTRACT FROM AUTHOR]