Predictors of Hospitalization After Ureteroscopy Plus Elective Double-J Stent as an Outpatient Procedure.

PURPOSE: To evaluate the safety and feasibility of ureteroscopy plus elective double-J stent as an outpatient procedure in an unselected population with regard to the treatment for ureteral calculi and to present a multivariate analysis of factors predict hospitalization. MATERIALS AND METHODS: Ureteroscopy was performed as an outpatient procedure on 308 consecutive patients with ureteral stones. Contraindication for day case surgery was the only exclusion criteria from the study. All causes that led to immediate hospitalization were recorded; at the same time, all causes of hospitalization that occurred within 72 h from the procedure were also recorded and included in the final analysis. RESULTS: The overall stone-free rate and the rate of hospitalization were 94.5 and 9.7% respectively. Intraoperative complications were observed in 16 patients (5.1%). In terms of the variables related to hospitalization, the univariate analysis showed a statistical significant association between the American Society of Anesthesiologists (ASA) score (p < 0.001) and operative time (p = 0.018). At multivariate analysis, the only independent factor predictor of hospitalization was the ASA score (p < 0.001). CONCLUSIONS: In our experience, semirigid ureteroscopy is a safe and effective treatment that is independent of intraoperative local conditions or stone size. Elective Double-J stenting avoids major complications as the first reason for hospitalization. We suggest that ASA score > 2 should be taken into account when ureterorenoscopy is planning as an outpatient procedure.

STAT3 Post-Translational Modifications Drive Cellular Signaling Pathways in Prostate Cancer Cells.

STAT3 is an oncoprotein overexpressed in different types of tumors, including prostate cancer (PCa), and its activity is modulated by a variety of post-translational modifications (PTMs). Prostate cancer represents the most common cancer diagnosed in men, and each phase of tumor progression displays specific cellular conditions: inflammation is predominant in tumor's early stage, whereas oxidative stress is typical of clinically advanced PCa. The aim of this research is to assess the correspondence between the stimulus-specificity of STAT3 PTMs and definite STAT3-mediated transcriptional programs, in order to identify new suitable pharmacological targets for PCa treatment. Experiments were performed on less-aggressive LNCaP and more aggressive DU-145 cell lines, simulating inflammatory and oxidative-stress conditions. Cellular studies confirmed pY705-STAT3 as common denominator of all STAT3-mediated signaling. In addition, acK685-STAT3 was found in response to IL-6, whereas glutC328/542-STAT3 and pS727-STAT3 occurred upon tert-butyl hydroperoxyde (tBHP) treatment. Obtained results also provided evidence of an interplay between STAT3 PTMs and specific protein interactors such as P300 and APE1/Ref-1. In accordance with these outcomes, mRNA levels of STAT3-target genes seemed to follow the differing STAT3 PTMs. These results highlighted the role of STAT3 and its PTMs as drivers in the progression of PCa.

Shmt2: A Stat3 Signaling New Player in Prostate Cancer Energy Metabolism.

Prostate cancer (PCa) is a multifactorial disease characterized by the aberrant activity of different regulatory pathways. STAT3 protein mediates some of these pathways and its activation is implicated in the modulation of several metabolic enzymes. A bioinformatic analysis indicated a STAT3 binding site in the upstream region of SHMT2 gene. We demonstrated that in LNCaP, PCa cells' SHMT2 expression is upregulated by the JAK2/STAT3 canonical pathway upon IL-6 stimulation. Activation of SHTM2 leads to a decrease in serine levels, pushing PKM2 towards the nuclear compartment where it can activate STAT3 in a non-canonical fashion that in turn promotes a transient shift toward anaerobic metabolism. These results were also confirmed on FFPE prostate tissue sections at different Gleason scores. STAT3/SHMT2/PKM2 loop in LNCaP cells can modulate a metabolic shift in response to inflammation at early stages of cancer progression, whereas a non-canonical STAT3 activation involving the STAT3/HIF-1α/PKM2 loop is responsible for the maintenance of Warburg effect distinctive of more aggressive PCa cells. Chronic inflammation might thus prime the transition of PCa cells towards more advanced stages, and SHMT2 could represent a missing factor to further understand the molecular mechanisms responsible for the transition of prostate cancer towards a more aggressive phenotype.

Analysis of STAT3 post-translational modifications (PTMs) in human prostate cancer with different Gleason Score.

Prostate Cancer (PCa) is a complex and heterogeneous disease. The androgen receptor (AR) and the signal transducer and activator of transcription 3 (STAT3) could be effective targets for PCa therapy. STAT3, a cytoplasmatic latent transcription factor, is a hub protein for several oncogenic signalling pathways and up-regulates the expression of numerous genes involved in tumor cell proliferation, angiogenesis, metastasis and cell survival. STAT3 activity can be modulated by several Post-Translational Modifications (PTMs) which reflect particular cell conditions and may be implicated in PCa development and progression. The aim of this work was to analyze STAT3 PTMs at different tumor stages and their relationship with STAT3 cellular functions. For this purpose, sixty-five prostatectomy, Formalin-fixed paraffin-embedded (FFPE) specimens, classified with different Gleason Scores, were subjected to immunoblotting, immunofluorescence staining and RT-PCR analysis. All experiments were carried out in matched non-neoplastic and neoplastic tissues. Data obtained showed different STAT3 PTMs profiles among the analyzed tumor grades which correlate with differences in the amount and distribution of specific STAT3 interactors as well as the expression of STAT3 target genes. These results highlight the importance of PTMs as an additional biomarker for the exactly evaluation of the PCa stage and the optimal treatment of this disease.

Neoadjuvant Chemotherapy in Neuroendocrine Bladder Cancer: A Case Report.

BACKGROUND: Small cell carcinoma of the urinary bladder is a rare and aggressive form of bladder cancer that mainly presents at an advanced stage. As a result of its rarity, it has been described in many case reports and reviews but few retrospective and prospective trials, showing there is no standard therapeutic approach. In the literature the best therapeutic strategy for limited disease is the multimodality treatment and most authors have extrapolated treatment algorithms from the therapy recommendations of small cell lung cancer. CASE REPORT: A 71-year-old male patient was referred to our hospital with gross hematuria and dysuria. Imaging and cystoscopy revealed a vegetative lesion of the bladder wall. A transurethral resection of the bladder was performed. Pathological examination revealed a pT2 high-grade urothelial carcinoma with widespread neuroendocrine differentiation. Multimodal treatment with neoadjuvant platinum-based chemotherapy was performed. A CT scan performed after chemotherapy demonstrated a radiological complete response. The patient underwent radical cystectomy and lymphadenectomy. The histopathological finding of bladder and node specimen confirmed a pathological complete response. A post-surgery CT scan showed no evidence of local or systemic disease. Six months after surgery, the patient is still alive and disease-free. CONCLUSIONS: A standard treatment strategy of small cell cancer of the urinary bladder is not yet well established, but a multimodal treatment of this disease is the best option compared to surgical therapy alone. The authors confirm the use of neoadjuvant chemotherapy in limited disease of small cell carcinoma of the urinary bladder.

Paraurethral leiomyoma.

Paraurethral leiomyoma is a rare, benign, hormone-dependent neoplasm of mesenchymal origin affecting women. The clinical evidence varies, but it tends to be asymptomatic or associated with the sensation of a foreign body; urinary symptoms are rarely described. The distinction among urethral, paraurethral, and anterior vaginal wall leiomyoma can be very difficult owing to their anatomic proximity. Excision of the mass is the recommended treatment, and the diagnosis is confirmed by the pathologic finding to rule out the presence of a sarcoma. A case of paraurethral leiomyoma associated with dysuria, dyspareunia, and obstructive voiding symptoms is reported.