Notes

Data with regard to molecular characteristics models involving Escherichia coli cytochrome bd oxidase with the Silpada drive field.
To discuss treatment decisions in the first-line setting of metastatic renal cell carcinoma (mRCC).

Immune check point inhibitor (ICI) combinations have replaced sunitinib as the standard of care in the first-line treatment of mRCC. Dual ICI treatment with nivolumab and ipilimumab was shown to significantly improve overall survival and objective response rates. Tunicamycin Similarly, the ICI-tyrosine kinase inhibitor combinations pembrolizumab and axitinib and nivolumab and cabozantinib have demonstrated superiority in terms of overall survival, objective response rates and progression-free survival versus sunitinib. The lack of both comparative trials and predictive markers impedes individualized treatment decisions. Clinicians are left to make treatment choices based on clinical and biological factors. These factors may include differences in toxicity profiles, the rate of complete remission, a clinical situation that requires urgent tumor shrinkage, the presence of inflammation, histological or immune-histochemical features and others.

In the absence of comparative trials, clinical and biological factors may facilitate the choice between various treatment options in the first-line setting of mRCC. In addition, both the experience of the physician with a specific treatment together with patient's preferences and expectations of systemic therapy may be part of the decision-making process.
In the absence of comparative trials, clinical and biological factors may facilitate the choice between various treatment options in the first-line setting of mRCC. In addition, both the experience of the physician with a specific treatment together with patient's preferences and expectations of systemic therapy may be part of the decision-making process.
The aim of this review is to outline characteristics of the renal cell carcinoma (RCC) tumor immune microenvironment (TIME), the potential impact of tumor intrinsic alterations on the TIME and the value of metastatic tissue assessment in this context.

According to the latest European Association of Urology, European Society for Medical Oncology and National Comprehensive Cancer Network guidelines immune checkpoint inhibition represents a new core treatment strategy in advanced clear cell RCC (ccRCC). Despite its success, the prognosis of many RCC patients remains unsatisfactory most likely because of resistance mechanisms within the TIME. Moreover, most studies assess the primary tumor even though the advanced metastatic disease is targeted. Overall, metastatic RCC has hardly been investigated. First insights into the complexity of the genomic and immune landscape in RCC were recently provided. The functional impact of tumor intrinsic alterations on the TIME has just been described potentially contributing to therapy response in RCC.

The complexity of the RCC TIME and its potential interdependence with tumor intrinsic alterations has only just been recognized. A deeper understanding of the TIME may reveal predictive and prognostic biomarkers long-awaited in RCC, improve RCC patient stratification and could possibly be most instructive if assessed in metastatic tissue.
The complexity of the RCC TIME and its potential interdependence with tumor intrinsic alterations has only just been recognized. A deeper understanding of the TIME may reveal predictive and prognostic biomarkers long-awaited in RCC, improve RCC patient stratification and could possibly be most instructive if assessed in metastatic tissue.
Nephron-sparing partial nephrectomy is the state of the art for localized small renal mass and it is gaining attention also for more advanced cases. In the present narrative review, we discuss the new developments that have occurred in the advancement of this approach over the past few years.

Off-clamp, selective/superselective clamp and early-unclamping techniques are safe and feasible approaches, with potentially superior functional outcomes, and noninferior complications rate and oncological outcomes, when compared with main artery clamping. Renorrhaphy must preserve the physiological vascularization of residual parenchyma. Running sutures, particularly using barbed wires, shorten the operating and ischemia times. A further advantage could derive from avoiding a double-layer suture. Transperitoneal robot-assisted partial nephrectomy (RAPN) and retroperitoneal RAPN can be considered equivalent in terms of perioperative morbidity, functional and oncologic outcomes, regardless of tumor's location, thus the choice of the approach should be driven by the surgeon's expertise. Future improvements should be introduced by the single-port robotic surgery, which seems to be safe and feasibly also in an off-clamp manner.

Significant advances have recently been achieved in nephron-sparing surgery technique. However, future studies with standardized reporting of these new techniques are needed to assess the real impact of them on early and long-term functional outcomes.
Significant advances have recently been achieved in nephron-sparing surgery technique. However, future studies with standardized reporting of these new techniques are needed to assess the real impact of them on early and long-term functional outcomes.
The current treatment landscape of metastatic renal cell carcinoma has changed dramatically from the dominance of single-agent tyrosine kinase inhibitor (TKI) therapy to immune-checkpoint inhibitor (ICI)-based combinations in recent years. However, the optimal subsequent therapy remains ill-defined owing to the novelty of this approach.

Treatment with TKIs after failure of single or dual ICI therapies may result in robust clinical efficacy. Nonetheless, there is a trend toward lower efficacy of TKIs after previous ICI-TKI combination therapy. Currently, tivozanib is the only drug whose third- and later-line use after failure of TKI and ICI is supported by evidence, with significantly longer progression-free survival and higher objective response rates than sorafenib. Data from retrospective studies highlight the safety and clinical activity of ICI rechallenge.

Overall, the level of evidence remains low. Treatment after failure of dual ICI therapy is not well defined and may consist of any available TKI.
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