The percentage abundance of sarcomatoid component has a prognostic role in grade 4 non-metastatic clear cell-renal carcinoma

Purpose: Sarcomatoid dedifferentiation represents one of the most aggressive features of clear cell renal cell carcinoma (ccRCC). In this study we evaluated whether grade 4-ccRCC subclassification based on the intratumoral abundance of sarcomatoid features could have a prognostic impact. Methods: A cohort of 212 patients with localized or locally advanced sarcomatoid ccRCC was identified. This population was stratified according to abundance of sarcomatoid features in low-sarcomatoid (LS = < 20% sarcomatoid component; n = 117) and high-sarcomatoid (HS = ≥ 20% sarcomatoid component; n = 95). Estimates of cancer-specific survival (CSS) and recurrence-free survival (RFS) were calculated according to the Kaplan–Meier method and compared with the log-rank test. Multivariable analysis was performed using the Cox proportional hazards regression model to identify the most significant variables for predicting CSS and RFS. Results: Kaplan–Meier survival curves stratified by abundance of sarcomatoid component, showed that CSS and RFS were significantly decreased in patients with sarcomatoid component ≥ 20% (both P < 0.0001). At multivariable analysis by Cox regression modeling, the abundance of sarcomatoid component was an independent adverse prognostic factor for CSS (P < 0.0001) and RFS (P < 0.0001). Conclusion: ccRCC Subclassification based on the abundance of intratumoral sarcomatoid component has a clinical significance. Our study showed that ccRCC subclassification into HS versus LS groups had a prognostic impact in terms of CSS and RFS in non-metastatic ccRCC

Ischemia-Reperfusion Injury in Kidney Transplantation: Mechanisms and Potential Therapeutic Targets

: Kidney transplantation offers a longer life expectancy and a better quality of life than dialysis to patients with end-stage kidney disease. Ischemia-reperfusion injury (IRI) is thought to be a cornerstone in delayed or reduced graft function and increases the risk of rejection by triggering the immunogenicity of the organ. IRI is an unavoidable event that happens when the blood supply is temporarily reduced and then restored to an organ. IRI is the result of several biological pathways, such as transcriptional reprogramming, apoptosis and necrosis, innate and adaptive immune responses, and endothelial dysfunction. Tubular cells mostly depend on fatty acid (FA) β-oxidation for energy production since more ATP molecules are yielded per substrate molecule than glucose oxidation. Upon ischemia-reperfusion damage, the innate and adaptive immune system activates to achieve tissue clearance and repair. Several cells, cytokines, enzymes, receptors, and ligands are known to take part in these events. The complement cascade might start even before organ procurement in deceased donors. However, additional experimental and clinical data are required to better understand the pathogenic events that take place during this complex process

Novel Insights into Autophagy and Prostate Cancer: A Comprehensive Review

Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible

Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets

: Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs

A challenging surgical approach to locally advanced primary urethral carcinoma: A case report and literature review

Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches. A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and "en bloc" removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy. The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery. Patients with advanced stage tumors of the bulbomembranous urethra should be managed with radical surgery including the corporas up to the ischiatic tuberosity attachment, and membranous urethra in continuity with the prostate and bladder. Neo-adjuvant treatment may be advisable with the aim of improving the poor prognosis, even if the efficacy is not certain while it can delay the radical treatment of the disease

Erectile dysfunction

Pharmacological therapy and vacuum device don't provide satisfactory results or can be contraindicated in a limited number of patients with erectile dysfunction (ED). The sole available option to treat their condition is represented by surgery. Penile prosthetic surgery is the most common surgical approach to restore erectile function but within the other options available, venous ligation and penile arterial revascularization should be considered in selected patients. Penile prosthesis implant is recommended in patients with organ failure who don't respond to medical therapy, in case of severe corporal fibrosis due to priapism, or when both ED and Peyronie’s disease are diagnosed. In relatively young patients not affected by severe vascular disease and diabetes with a documented stenosis of the internal pudendal artery, penile arterial revascularization can be considered. In case of congenital venous leakage, a further surgical treatment is represented by venous ligation that can provide satisfactory results in young patients.</p