Renal cancer Capitanio, Umberto, Dr; Montorsi, Francesco, Prof
The Lancet (British edition),
02/2016, Volume:
387, Issue:
10021
Journal Article
Peer reviewed
Summary The diagnosis and management of renal cell carcinoma have changed remarkably rapidly. Although the incidence of renal cell carcinoma has been increasing, survival has improved substantially. ...As incidental diagnosis of small indolent cancers has become more frequent, active surveillance, robot-assisted nephron-sparing surgical techniques, and minimally invasive procedures, such as thermal ablation, have gained popularity. Despite progression in cancer control and survival, locally advanced disease and distant metastases are still diagnosed in a notable proportion of patients. An integrated management strategy that includes surgical debulking and systemic treatment with well established targeted biological drugs has improved the care of patients. Nevertheless, uncertainties, controversies, and research questions remain. Further advances are expected from translational and clinical studies.
Abstract Context Erectile dysfunction (ED) is considered a vascular impairment that shares many risk factors with cardiovascular disease (CVD). A correlation between ED and CVD has been hypothesized, ...and ED has been proposed as an early marker of symptomatic CVD. Objective To analyze the relationship between ED and CVD, evaluating the pathophysiologic links between these conditions, and to identify which patients would benefit from cardiologic assessment when presenting with ED. Evidence acquisition A systematic literature review searching Medline, Embase, and Web of Science databases was performed. The search strategy included the terms erectile dysfunction, cardiovascular disease, coronary artery disease, risk factors, pathophysiology, atherosclerosis, low androgen levels, inflammation, screening , and phosphodiesterase type 5 inhibitors alone or in combination. We limited our search to studies published between January 2005 and May 2013. Evidence synthesis Several studies reported an association between ED and CVD. The link between these conditions might reside in the interaction between androgens, chronic inflammation, and cardiovascular risk factors that determines endothelial dysfunction and atherosclerosis, resulting in disorders of penile and coronary circulation. Because penile artery size is smaller compared with coronary arteries, the same level of endothelial dysfunction causes a more significant reduction of blood flow in erectile tissues compared with that in coronary circulation. Thus ED could be an indicator of systemic endothelial dysfunction. From a clinical standpoint, because ED may precede CVD, it can be used as an early marker to identify men at higher risk of CVD events. ED patients at high risk of CVD should undergo detailed cardiologic assessment and receive intensive treatment of risk factors. Conclusions ED and CVD should be regarded as two different manifestations of the same systemic disorder. ED usually precedes CVD onset, and it might be considered an early marker of symptomatic CVD.
Advanced glycation end-products (AGEs) are an assorted group of molecules formed through covalent bonds between a reduced sugar and a free amino group of proteins, lipids, and nucleic acids. ...Glycation alters their structure and function, leading to impaired cell function. They can be originated by physiological processes, when not counterbalanced by detoxification mechanisms, or derive from exogenous sources such as food, cigarette smoke, and air pollution. Their accumulation increases inflammation and oxidative stress through the activation of various mechanisms mainly triggered by binding to their receptors (RAGE). So far, the pathogenic role of AGEs has been evidenced in inflammatory and chronic diseases such as chronic kidney disease, cardiovascular disease, and diabetic nephropathy. This review focuses on the AGE-induced kidney damage, by describing the molecular players involved and investigating its link to the excess of body weight and visceral fat, hallmarks of obesity. Research regarding interventions to reduce AGE accumulation has been of great interest and a nutraceutical approach that would help fighting chronic diseases could be a very useful tool for patients' everyday lives.
Abstract Background Preoperative assessment of the risk of lymph node invasion (LNI) is mandatory to identify prostate cancer (PCa) patients who should receive an extended pelvic lymph node ...dissection (ePLND). Objective To update a nomogram predicting LNI in contemporary PCa patients with detailed biopsy reports. Design, setting, and participants Overall, 681 patients with detailed biopsy information, evaluated by a high-volume uropathologist, treated with radical prostatectomy and ePLND between 2011 and 2016 were identified. Outcome measurements and statistical analysis A multivariable logistic regression model predicting LNI was fitted and represented the basis for a coefficient-based nomogram. The model was evaluated using the receiver operating characteristic-derived area under the curve (AUC), calibration plot, and decision-curve analyses (DCAs). Results and limitations The median number of nodes removed was 16. Overall, 79 (12%) patients had LNI. A multivariable model that included prostate-specific antigen, clinical stage, biopsy Gleason grade group, percentage of cores with highest-grade PCa, and percentage of cores with lower-grade disease represented the basis for the nomogram. After cross validation, the predictive accuracy of these predictors in our cohort was 90.8% and the DCA demonstrated improved risk prediction against threshold probabilities of LNI ≤20%. Using a cutoff of 7%, 471 (69%) ePLNDs would be spared and LNI would be missed in seven (1.5%) patients. As compared with the Briganti and Memorial Sloan Kettering Cancer Center nomograms, the novel model showed higher AUC (90.8% vs 89.5% vs 89.5%), better calibration characteristics, and a higher net benefit at DCA. Conclusions An ePLND should be avoided in patients with detailed biopsy information and a risk of nodal involvement below 7%, in order to spare approximately 70% ePLNDs at the cost of missing only 1.5% LNIs. Patient summary We developed a novel nomogram to predict lymph node invasion (LNI) in patients with clinically localized prostate cancer based on detailed biopsy reports. A lymph node dissection exclusively in men with a risk of LNI > 7% according to this model would significantly reduce the number of unnecessary pelvic nodal dissections with a risk of missing only 1.5% of patients with LNI.
Several different stimuli may induce chronic prostatic inflammation, which in turn would lead to tissue damage and continuous wound healing, thus contributing to prostatic enlargement.
Patients with ...chronic inflammation and benign prostatic hyperplasia (BPH) have been shown to have larger prostate volumes, more severe lower urinary tract symptoms (LUTS) and a higher probability of acute urinary retention than their counterparts without inflammation.
Chronic inflammation could be a predictor of poor response to BPH medical treatment. Thus, the ability to identify patients with chronic inflammation would be crucial to prevent BPH progression and develop target therapies.
Although the histological examination of prostatic tissue remains the only available method to diagnose chronic inflammation, different parameters, such as prostatic calcifications, prostate volume, LUTS severity, storage and prostatitis‐like symptoms, poor response to medical therapies and urinary biomarkers, have been shown to be correlated with chronic inflammation.
The identification of patients with BPH and chronic inflammation might be crucial in order to develop target therapies to prevent BPH progression. In this context, clinical, imaging and laboratory parameters might be used alone or in combination to identify patients that harbour chronic prostatic inflammation.
Abstract Background The advent of molecular-based methods of identification and characterization of complex microbial populations has led to a new era of microbial discovery. A detailed and ...comprehensive analysis of the microbial ecosystem of the pathologic and healthy prostate tissues has not been yet reported. Objectives To characterize the microbiome possibly associated to the pathologic prostate microenvironment. Design, setting, and participants The microbiome profile of tumor, peri-tumor, and nontumor tissues was assessed on 16 radical prostatectomy-specimens. Outcome measurements and statistical analysis Microbiome analysis was assessed by massive ultradeep pyrosequencing. Bacteria load was expressed as a percentage of the total number of bacteria. The statistical significance of differences among specimen-groups was tested with Friedman's test (Dunn posthoc test) and Wilcoxon rank-sum test. Results and limitations Three phyla, six classes, nine orders, 14 families, and 11 genera were above the set threshold value of 1%, respectively. Significant differences in specific microbial populations among tumor/peri-tumor and nontumor prostate specimens were observed at certain taxonomic levels. Among genera, Propionibacterium spp. were the most abundant. Staphylococcus spp. were more represented in the tumor/peri-tumor tissues ( p < 0.05). The restricted number of specimens represents a potential limitation. Conclusions The prostate contains a plethora of bacteria, which set themselves within the gland with a distribution dependent on the nature of the tissue, thus suggesting a possible pathophysiological correlation between the composition of the local microbial niche and the presence of the tumor itself. Future studies will help to clarify the role of these specific bacteria and their potential to be exploited as new biomarkers. Patient summary The pathological prostate is populated by specific microbial populations, whose distribution varies according to the nature of the tissue. This finding opens interesting perspectives for the identification of novel therapeutic approaches and biomarkers.
To investigate the impact of Prostate Imaging Quality (PI-QUAL) scores on the diagnostic performance of multiparametric MRI (mpMRI) in a targeted biopsy cohort.
300 patients who underwent both mpMRI ...and biopsy were included. PI-QUAL scores were retrospectively assigned by two radiologists in consensus and were correlated to pre-biopsy PI-RADS scores and biopsy outcomes. Clinically significant prostate cancer (csPCa) was defined as ISUP grade ≥ 2.
Image quality was optimal (PI-QUAL ≥ 4) in 249/300 (83%) and suboptimal (PI-QUAL < 4) in 51/300 (17%). The proportion of PI-RADS 3 scores referred for biopsy was higher in scans of suboptimal vs optimal quality (51% vs 33%). For PI-QUAL < 4 scans, the positive predictive value (PPV) was lower compared to PI-QUAL ≥ 4 (35% 95%CI: 22, 48 vs 48% 95%CI: 41, 55; difference −13% 95%CI: −27, 2; p 0.090), as was the detection rate of csPCa in both PI-RADS 3 and PI-RADS 4–5 (15% vs 23% and 56 vs 63%, respectively). The overall MRI quality increased over time.
Scan quality may affect the diagnostic performance of prostate mpMRI in patients undergoing MRI-guided biopsy. Scans of suboptimal quality (PI-QUAL < 4) were associated with lower PPV for csPCa.
Abstract Context Robot-assisted radical prostatectomy (RARP) was proposed to improve functional outcomes in comparison with retropubic radical prostatectomy (RRP) or laparoscopic radical ...prostatectomy (LRP). In the initial RARP series, 12-mo urinary continence recovery rates ranged from 84% to 97%. However, the few available studies comparing RARP with RRP or LRP published before 2008 did not permit any definitive conclusions about the superiority of any one of these techniques in terms of urinary continence recovery. Objective The aims of this systematic review were (1) to evaluate the prevalence and risk factors for urinary incontinence after RARP, (2) to identify surgical techniques able to improve urinary continence recovery after RARP, and (3) to perform a cumulative analysis of all available studies comparing RARP versus RRP or LRP in terms of the urinary continence recovery rate. Evidence acquisition A literature search was performed in August 2011 using the Medline, Embase, and Web of Science databases. The Medline search included only a free-text protocol using the term radical prostatectomy across the title and abstract fields of the records. The following limits were used: humans; gender (male); and publication date from January 1, 2008. Searches of the Embase and Web of Science databases used the same free-text protocol, keywords, and search period. Only comparative studies or clinical series including >100 cases reporting urinary continence outcomes were included in this review. Cumulative analysis was conducted using the Review Manager v.4.2 software designed for composing Cochrane Reviews (Cochrane Collaboration, Oxford, UK). Evidence synthesis We analyzed 51 articles reporting urinary continence rates after RARP: 17 case series, 17 studies comparing different techniques in the context of RARP, 9 studies comparing RARP with RRP, and 8 studies comparing RARP with LRP. The 12-mo urinary incontinence rates ranged from 4% to 31%, with a mean value of 16% using a no pad definition. Considering a no pad or safety pad definition, the incidence ranged from 8% to 11%, with a mean value of 9%. Age, body mass index, comorbidity index, lower urinary tract symptoms, and prostate volume were the most relevant preoperative predictors of urinary incontinence after RARP. Only a few comparative studies evaluated the impact of different surgical techniques on urinary continence recovery after RARP. Posterior musculofascial reconstruction with or without anterior reconstruction was associated with a small advantage in urinary continence recovery 1 mo after RARP. Only complete reconstruction was associated with a significant advantage in urinary continence 3 mo after RARP (odds ratio OR: 0.76; p = 0.04). Cumulative analyses showed a better 12-mo urinary continence recovery after RARP in comparison with RRP (OR: 1.53; p = 0.03) or LRP (OR: 2.39; p = 0.006). Conclusions The prevalence of urinary incontinence after RARP is influenced by preoperative patient characteristics, surgeon experience, surgical technique, and methods used to collect and report data. Posterior musculofascial reconstruction seems to offer a slight advantage in terms of 1-mo urinary continence recovery. Update of a previous systematic review of literature shows, for the first time, a statistically significant advantage in favor of RARP in comparison with both RRP and LRP in terms of 12-mo urinary continence recovery.
The relationship between acute kidney injury (AKI) and long-term renal function is controversial. The influence of AKI duration on functional recovery after partial nephrectomy has never been ...investigated.
To investigate the association between AKI and renal function 1yr after partial nephrectomy, and whether this relationship is affected by the duration of AKI.
We analyzed the data of 1893 patients treated by partial nephrectomy for a single cT1 N0 M0 renal mass.
We defined three outcomes of interest: (1) recovery of at least 90% of baseline function 1yr after partial nephrectomy, (2) percentage change of 1-yr renal function compared with baseline function, and (3) chronic kidney disease (CKD) upstaging. AKI was defined according to the RIFLE criteria and recorded up to the 7th postoperative day. The association between AKI and each endpoint of interest was examined using regression models after adjustment for common predictors of renal function.
A total of 388 (20%) patients experienced AKI after surgery. The rate of patients recovering 90% of baseline function was lower in the AKI group (30% vs 61%), while the proportion of patients who had CKD upstaging was significantly higher (51% vs 23%; both p<0.0001). At multivariable analysis, AKI was associated with worse renal function 1yr after partial nephrectomy, regardless of the outcome of interest (all p<0.0001). Longer AKI increases the risk of functional deterioration, especially after the 3rd day of injury. The risk of CKD upstaging for an average patient who had 1–3 versus ≥4 d of AKI was 46% (95% confidence interval CI: 40%, 52%) versus 67% (95% CI: 55%, 78%; absolute risk increase of 21%; 95% CI: 8%, 34%).
AKI negatively affects long-term functional recovery after partial nephrectomy, and thus, modifiable factors associated with AKI should be identified and corrected preoperatively. The duration of injury is informative, and should be included in the assessment of AKI and in future studies addressing this topic.
Proper functional recovery after partial nephrectomy is jeopardized by acute kidney injury (AKI). Inclusion of the dimension of time into classification systems for AKI may be beneficial for postoperative risk stratification.
Acute kidney injury (AKI) negatively affects long-term functional recovery after partial nephrectomy and thus should be prevented. The duration of injury is informative, and should be included in the assessment of AKI and in future studies addressing this topic.
Abstract Context Although open radical cystectomy (ORC) is still the standard approach, laparoscopic radical cystectomy (LRC) and robot-assisted radical cystectomy (RARC) are increasingly performed. ...Objective To report on a systematic literature review and cumulative analysis of pathologic, oncologic, and functional outcomes of RARC in comparison with ORC and LRC. Evidence acquisition Medline, Scopus, and Web of Science databases were searched using a free-text protocol including the terms robot-assisted radical cystectomy or da Vinci radical cystectomy or robot* radical cystectomy . RARC case series and studies comparing RARC with either ORC or LRC were collected. A cumulative analysis was conducted. Evidence synthesis The searches retrieved 105 papers, 87 of which reported on pathologic, oncologic, or functional outcomes. Most series were retrospective and had small case numbers, short follow-up, and potential patient selection bias. The lymph node yield during lymph node dissection was 19 (range: 3–55), with half of the series following an extended template (yield range: 11–55). The lymph node–positive rate was 22%. The performance of lymphadenectomy was correlated with surgeon and institutional volume. Cumulative analyses showed no significant difference in lymph node yield between RARC and ORC. Positive surgical margin (PSM) rates were 5.6% (1–1.5% in pT2 disease and 0–25% in pT3 and higher disease). PSM rates did not appear to decrease with sequential case numbers. Cumulative analyses showed no significant difference in rates of surgical margins between RARC and ORC or RARC and LRC. Neoadjuvant chemotherapy use ranged from 0% to 31%, with adjuvant chemotherapy used in 4–29% of patients. Only six series reported a mean follow-up of >36 mo. Three-year disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates were 67–76%, 68–83%, and 61–80%, respectively. The 5-yr DFS, CSS, and OS rates were 53–74%, 66–80%, and 39–66%, respectively. Similar to ORC, disease of higher pathologic stage or evidence of lymph node involvement was associated with worse survival. Very limited data were available with respect to functional outcomes. The 12-mo continence rates with continent diversion were 83–100% in men for daytime continence and 66–76% for nighttime continence. In one series, potency was recovered in 63% of patients who were evaluable at 12 mo. Conclusions Oncologic and functional data from RARC remain immature, and longer-term prospective studies are needed. Cumulative analyses demonstrated that lymph node yields and PSM rates were similar between RARC and ORC. Conclusive long-term survival outcomes for RARC were limited, although oncologic outcomes up to 5 yr were similar to those reported for ORC. Patient summary Although open radical cystectomy (RC) is still regarded as the standard treatment for muscle-invasive bladder cancer, laparoscopic and robot-assisted RCs are becoming more popular. Templates of lymph node dissection, lymph node yields, and positive surgical margin rates are acceptable with robot-assisted RC. Although definitive comparisons with open RC with respect to oncologic or functional outcomes are lacking, early results appear comparable.
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