Differential expression of microRNA501-5p affects the aggressiveness of clear cell renal carcinoma

AbstractRenal cell carcinoma is a common neoplasia of the adult kidney that accounts for about 3% of adult malignancies. Clear cell renal carcinoma is the most frequent subtype of kidney cancer and 20–40% of patients develop metastases. The absence of appropriate biomarkers complicates diagnosis and prognosis of this disease. In this regard, small noncoding RNAs (microRNAs), which are mutated in several neoplastic diseases including kidney carcinoma, may be optimal candidates as biomarkers for diagnosis and prognosis of this kind of cancer. Here we show that patients with clear cell kidney carcinoma that express low levels of miR501-5p exhibited a good prognosis compared with patients with unchanged or high levels of this microRNA. Consistently, in kidney carcinoma cells the downregulation of miR501-5p induced an increased caspase-3 activity, p53 expression as well as decreased mTOR activation, leading to stimulation of the apoptotic pathway. Conversely, miR501-5p upregulation enhanced the activity of mTOR and promoted both cell proliferation and survival. These biological processes occurred through p53 inactivation by proteasome degradation in a mechanism involving MDM2-mediated p53 ubiquitination. Our results support a role for miR501-5p in balancing apoptosis and cell survival in clear cell renal carcinoma. In particular, the downregulation of microRNA501-5p promotes a good prognosis, while its upregulation contributes to a poor prognosis, in particular, if associated with p53 and MDM2 overexpression and mTOR activation. Thus, the expression of miR501-5p is a possible biomarker for the prognosis of clear cell renal carcinoma

Ultrasound diagnosis of unusual extratesticular mass: Case report and review of the literature

The adenomatoid tumor of the epididymis (EAT) is a neoplasm located in the paratesticular region. Mesothelial origin has been mentioned and inflammation has played some role in the development of these tumors. Physical examination and testicular ultrasound constituted important tools in the diagnosis. Some reports have mentioned malignant behavior, but it is very rare. Surgical treatment is the procedure of choice. We present the case of a 46-year-old patient with an adenomatoid tumour located in the head of the left epididymis that referred to our department with gradually enlarged intrascrotal mass

Ultrasound evaluation of the striated urethral sphincter as a predictive parameter of urinary continence after radical prostatectomy

Objectives: The purpose of this study was to evaluate preoperatively the results of transrectal ultrasound (TRUS) in the detection of morphological, vascularization status of urethral rhabdosphincter (RS) and evaluate the correlation with urinary continence after radical prostatectomy (RP). Methods: 211 patients who underwent RP were prospectively studied using TRUS scan of the RS thickness. At the end of the examination a study was performed with the use of colour-Doppler for the assessment of the RS vascularity pattern. The level of continence was graded on a 5 point scale as: 1 = complete continence, 2 = 1 pad daily, 3 = 2-3 pads daily, 4 = 4 or more pads daily, and 5 = complete incontinence. Results: It was possible to visualize the rhabdosphincter and its vascularity in all patients. Patients with normal continence (level 1 and 2) showed a sphincter-muscle thickness of 3.5 mm (± 0.4) and a hypoechoic ultrasound pattern. With respect to the other levels 3, 4 and 5 of urinary incontinence RS thickness was 2.8 mm (± 0.5), 2.1 mm (± 0.6), 1.7 (± 0.7) respectively. Incontinence after RP (≥ 3 level) was associated with urethral sphincter deficiency in the great majority of patients. Statistical significant differences were observed in the vascularity between continent and incontinent men in all measured vascularity variables (p < 0.005). Conclusions: This study suggests that RS integrity is a good predictor of urinary continence after RP and this information can be important during the preoperative phase as part of the informed consent

Lidocaine spray administration in transrectal ultrasound-guided prostate biopsy: Five years of experience

Objectives: We report in this singlecenter study our results of a five-year experience in the administration of lidocaine spray (LS) during ultrasound-guided prostate biopsy (TPB). Material and Methods: Between August 2008 and July 2013 a total of 1022 consecutive male patients scheduled for TPB with elevate PSA (≥ 4 ng/ml) and (or) abnormal digital rectal and (or) suspect TRUS were considered eligible for the study. Each patient was treated under local anaesthesia with LS (10 gr/100 ml), applied two minutes before the procedure. TPB was performed with the patient in the left lateral decubitus using multi-frequency convex probe “end-fire”. Two experienced urologists performed a 14-core biopsy, as first intention. After the procedure each patient was given a verbal numeric pain scale (VNS). The evaluation was differentiated in two scales VNS: VNS 1 for the insertion of the probe and the manoeuvres associated, while VNS 2 only for the pain during needle’s insertion. Results: Pain scores were not statistically significant different with regard to the values of PSA and prostate gland volume. Pain score levels during probe insertion and biopsy were significantly different: the mean pain score according to VNS was 3.3 (2-8) in the first questionnaire (VNS1) (p < 0.001) and 2.1 (1-7) in the second one (VNS2) (p < 0.125). The 8.2% of cases referred severe or unbearable pain (score ≥ 7), 74% of patients referred no pain at all. Only 21 patients would not ever repeat the biopsy or would request a different type of anaesthesia, while 82% of them would repeat it in the same way. In only eight patients we have not been able to insert TRUS probe. Conclusions: Our pain score data suggest that LS provides efficient patient comfort during TPB reducing pain both during insertion of the probe and the needle. This non-infiltrative anaesthesia is safe, easy to administer, psychologically well accepted by patients and of low cost

Relevance of prostate cancer in patients with synchronous invasive bladder urothelial carcinoma: a monocentric retrospective analysis

Objectives: We retrospectively reviewed data of patients with incidental prostate cancer (PCa) who underwent radical cystoprostatectomy (RCP) for invasive bladder cancer and we analyzed their features with regard to incidence, pathologic characteristics, clinical significance, and implications for management. Material and Methods: Clinical data and pathological features of 64 patients who underwent standard RCP for bladder cancer were included in this study. Besides the urothelial carcinoma of the urinary bladder, the location and tumor volume of the PCa, prostate apex involvement, Gleason score, pathological staging and surgical margins were evaluated. Clinically significant PCa was defined as a tumor with a Gleason 4 or 5 pattern, stage ≥ pT3, lymph node involvement, positive surgical margin or multifocality of three or more lesions. Postoperative follow-up was scheduled every 3 months in the first year, every 6 months in the second and third year, annually thereafter. Results: 11 out of 64 patients (17.2%) who underwent RCP had incidentally diagnosed PCa. 3 cases (27.3%) were diagnosed as significant PCa, while 8 cases (72.7%) were clinically insignificant. The positive surgical margin of PCa was detected in 1 patient with significant disease. The prostate apex involvement was present in 1 patient of the significant PCa group. Median follow-up period was 47.8 ± 29.2 (range 4-79). During the follow-up, biochemical recurrence occurred in 1 patient (9%). Concernig the cancer specific survival there was no statistical significance (P = 0.326) between the clinically significant and clinical insignificant cancer group. Conclusions: In line with published studies, incidental PCa does not impact on the prognosis of bladder cancer of patients undergoing RCP

A new ultrasound and clinical classification for management of prostatic abscess

Objectives: In literature, most of the published data regarding prostatic abscess (PA) are case reports, whereas there is no standardization of the diagnostic and therapeutic routines. The purpose of this study is a new classification of ultrasound imaging of PA with clinical features correlation. Material and Methods: We retrospectively analysed the ultrasound database archives and performed a MEDLINE® research of the peer reviewed literature on diagnosis and case reports of PA using the terms “prostate and abscess”. Results: PA can be classified into five Types: Type I - PA is present focally in a prostate lobe (≤ 10 mm). Type II - PA is present in a prostate lobe (> 10 mm) and/or partially overcrosses the border of the midline prostatic glandular. Type III - PA is present in both glandular lobes form of multifocal areas (≤ 10 mm). Type IV - PA is present in both glandular lobes form of multifocal areas (> 10 mm). Type V - PA involving intra or extraprostatic structures (bladder, urethra, seminal vesicles and prostatic capsule). The different ultrasound imaging and diagnostic criteria are listed for each type and subtype. Conclusions: The sonographic pattern of PA is usually characteristic and easily differentiated from other glandular lesions. The purpose of the study was to associate the use of TRUS to a clinical standardized classification in order to facilitate PA diagnosis and localization directing the clinician treatment to the correct management and adequate therapeutic treatment

Penile strangulation: An unusual sexual practice that often presents an urological emergency

Placement of constricting devices around the penis for autoerotic purposes or increasing of sexual performance represents a well-known challenge for urologists. Penile incarceration is a urologic emergency with potentially severe clinical consequences. In many cases a rapid intervention and a sudden removal of the foreign body it is enough so that patients need no further intervention. We report three different cases of strangulating objects (metallic ring, metal bearing and plumbing pipe) presented at our emergency department and three different methods of devices extraction practiced. Remove these devices can be challenging and often requires resourcefulness and multidisciplinary approach

Importance of an early diagnosis in primary adenocarcinoma of the seminal vesicle

The prognosis of seminal vesicle (SV) adenocarcinoma is often poor due to delayed diagnosis. About 95% of the patients die in less than 3 years. Diagnosis is difficult due to the absence of early clinical signs as hematuria, hematospermia and/or dysuria. We present the case of a 61-year-old Caucasian man with a left SV mass detected by transrectal ultrasound. SV ultrasound-guided biopsy showed an adenocarcinoma. The tumor was uniformly strongly immunoreactive for cytokeratin-7 and carcinoembryonic antigen. There was no immunoreactivity for prostate-specific acid phosphatase (PSAP) and CK-20. These tumors have been reported to be also positive for CA- 125. Therefore a combination of positive staining for CK-7, CEA and CA-125; with negative staining for CK-20, PSA and PSAP is the pattern of immunohistochemical findings noted for this rare tumor. The computed tomography of the abdomen-pelvis and chest X-ray was negative for metastases. The patient underwent a radical prostatectomy and lymphadenectomy. The prostate, rectum, bladder and lymph nodes were free from tumor involvement. The patient did not receive any adjuvant chemotherapy or radiation; and remains free of disease 3 years post-surgery

New Therapeutic Interventions for Kidney Carcinoma: Looking to the Future

Patients suffering from metastatic renal cell carcinoma (mRCC) show an overall survival rate of lower than 10% after 5 years from diagnosis. Currently, the first-line treatment for mRCC patients is based on antiangiogenic drugs that are able to inhibit tyrosine kinase receptors (TKI) in combination with immuno-oncology (IO) therapy or IO-IO treatments. Second-line therapy involves the use of other TKIs, immunotherapeutic drugs, and mTOR inhibitors. Nevertheless, many patients treated with mTOR and TK inhibitors acquire drug resistance, making the therapy ineffective. Therefore, the research of new therapeutic targets is crucial for improving the overall survival and quality of life of mRCC patients. The investigation of the molecular basis of RCC, especially in clear cell renal cell carcinoma (ccRCC), has led to the identification of different signaling pathways that are involved in renal carcinogenesis. Most of ccRCCs are associated with mutation in VHL gene, which mediates the degradation of hypoxia-inducible factors (HIFs), that, in turn, regulate the pathways related to tumorigenesis, including angiogenesis and invasion. Renal tumorigenesis is also associated with the activation of tyrosine kinases that modulate the PI3K-Akt-mTOR pathway, promoting cell proliferation and survival. In ccRCC, the abnormal activity of mTOR activates the MDM2 protein, which leads to the degradation of tumor suppressor p53 via proteasome machinery. In addition, p53 may be degraded by autophagy in a mechanism involving the enzyme transglutaminase 2 (TG2). Suppression of wild-type p53 promotes cell growth, invasion, and drug resistance. Finally, the activation of ferroptosis appears to inhibit cancer progression in RCC. In conclusion, these pathways might represent new therapeutic targets for mRCC

Prostatic calculi detected in peripheral zone of the gland during a transrectal ultrasound biopsy can be significant predictors of prostate cancer

Purpose: Prostatic calculi (PC) are usually associated with benign prostatic hyperplasia or chronic inflammation. However, in several studies prostatic inflammation and calcification have been implicated in the pathogenesis of prostate cancer (CaP). We evaluated the prevalence of PC during transrectal ultrasound (TRUS) and correlate the ultrasonographic patterns with histological findings. Methods: A prospective study of 664 patients undergoing TRUS and prostate biopsy was planned. A standardized reproducible technique was used with using a GE Logiq 7 machine equipped with a 5-9MHz multi-frequency convex probe “end-fire”. We defined marked presence of PC as multiple hyperechoic foci with significant area (≥ 3 mm in the largest diameter). PC were classified according to zone distribution into the gland: transitional zone (TZ), central zone (CZ), and peripheral zone (PZ). Results: No significant difference was noted between the patients with PC and without PC, when comparing age, preoperative PSA level, prostate volume, and biopsy number, except for DRE findings. 168 patients (25.3%) had marked presence of PC on TRUS: 50.6% in TZ, 20.2% in CZ, and 29.2% in PZ. 31 patients (63.3%) with presence of PC in PZ had CaP on biopsy. The correlation observed between CaP and the presence of PC in PZ was statistically significant (p < 0.001). However, among patients in the CaP group there was no statistical association between PC and moderate or high Gleason grade. Conclusions: This study suggests that chronic prostatic inflammation and PC have a role in the biogenesis of cancer. CaP was more frequent in patients with PC in PZ of the gland, but was not associated with higher Gleason grade among these patients (p < 0.001)