Explorative surgery for acute scrotal pain: The importance of patient age, side affected, time to surgery and surgeon.

INTRODUCTION AND OBJECTIVE: Testicular torsion must be diagnosed quickly and accurately. The delay of the diagnosis and the subsequent delay of surgery may lead to loss testicular viability and orchidectomy. Aim of our retrospective evaluation was to define which element should be considered as major support to the clinician in distinguishing spermatic cord torsion from the other diseases mimicking this clinical emergency requiring surgical exploration. MATERIAL AND METHODS: We retrospectively reviewed all clinical and instrumental data of emergency scrotal exploration performed for acute scrotal pain at two different Urological Department in a 10 year period. Results of surgical exploration represented the four diagnostic categories in which patients were divided for statistical evaluation. We evaluated the relationship between diagnosis performed by testicular surgical exploration and the all clinical data available including surgeon involved in the procedures. RESULTS: A total of 220 explorative scrotal surgery were considered. We divided the cases in 4 categories according to the diagnostic results of each surgical procedure. Of all, spermatic cord torsion was diagnosed in 45% (99/220). The total testis salvage rate was of 78.8%. The patients with a diagnosis of spermatic cord torsion were older than patients with appendix torsion (15 vs 11 years in mean). When the affected side was the left, the probability to have a diagnosis of spermatic cord torsion was higher than the right side [χ2 (2, N = 218) = 11.77, p < 0.01]. Time elapsing between onset of symptoms and testicular salvagewas significantly lower even than in case of appendix torsion/necrosis (p < .0001), and of others pathologies diagnosed (p = .0383). CONCLUSION: In case of spermatic cord torsion, in addition to the clinical data, patient age and left side affected may represent an independent diagnostic predicting factor. The time elapsing between onset of symptoms and explorative surgery remain the only still prognostic factor for testicular viability.

May ultrasound probe size influence pain perception of needle piercing during transrectal prostate biopsy? A prospective evaluation.

INTRODUCTION AND OBJECTIVE: Transrectal ultrasound guided prostate biopsy (TRUS-Bx) is the definitive step in the diagnosis of prostate cancer (CaP). Patients (pts) generally experience significant pain during the procedure at the point that biopsy should be accompanied by some form of anesthesia. Several different factors influence pain perception (PP) during TRUS-Bx. In our study we want to assess that the use of an ergonomic smaller sized probe reduces PP during the procedure independently from the administration of local anesthesia or pain relieving drugs. MATERIALS AND METHODS: This was a prospective, randomized study in which 114 pts who underwent TRUS-Bx due to abnormal PSA and/or to digital rectal examination (DRE) suspicious findings were considered eligible. Pts were split in two TRUS-Bx groups into which we used two different sized ultrasound probes. In group 1, 61 pts underwent TRUS-Bx with ALOKA end fire probe (size 74 mm). In group 2, 53 pts underwent TRUS-Bx with B-K Type 8818 probe (size 58 mm). Both groups were treated with no local anesthesia or pain relieving drugs. Pain was evaluated three times using a 10-point visual analogue scale (VAS), during the DRE (VAS 1), during the insertion of the probe (VAS 2) and during the needle piercing (VAS 3). RESULTS: Mean age of pts was 68.03 (SD 8.51); mean tPSA and mean prostate volume was 7.75 (SD 4.83) and 45.17cc (SD 17.7), respectively. The two groups were homogeneous respect to tPSA (p = 0.675) and to prostate volume (p = 0.296); age was significantly different (p = 0.04) between Group 1 (65.93) and Group 2 (70.43), whereas no statistically significant correlation between VAS 3 and age was observed (p = 0.179). Analyzing pain perception, we found no statistically significant difference between the two groups in DRE (VAS 1; p = 0.839); on the contrary, patients in Group 1 experienced on average more pain than other in Group 2 both during the insertion of the probe (VAS 2 3.49 vs 1.09; p < 0.001) and during the needle piercing VAS 3 (2.8 vs 2.00; p < 0.05). The discomfort during probe insertion and manipulation was perceived as very high (VAS 2 > 5) in 42.6% of patients in Group 1 and in 9.4% in Group 2. Globally, the procedure was well tolerated (mean VAS score < 3) in 77% of patients in Group 1 and in 90% in Group 2. The proportion of patients who experienced more than moderate pain (VAS > 5) during needle piercing ranged 24.6 % in Group 1 to 18.9 % in Group 2. CONCLUSIONS: Patients who underwent a TRUS-Bx with the 58-mm circumference probe were found to experience lower degree of pain not only during the insertion of the probe through the anal sphincter, but also in the moment of needle piercing.

Adenomatous hyperplasia of the rete testis: A rare intrascrotal lesion managed with limited testicular excision.

INTRODUCTION: Testicular cancer is one of the most frequent in young men and its incidence is increasing in recent years because of incidental finding during routine ultrasound exams. Adenomatous hyperplasia of the rete testis is one of the benign and rare pathological types incidentally detected and very few cases are described in the literature. CASE REPORT: A 40 years old man come to our attention for a balanoposthitis without testicular pain. During andrological examination we performed palpation of the testes and we noticed a palpable nodule of hard consistency in the left testicle. We then performed an ultrasound exam of the testis which highlighted the presence of an intra-didymus neoformation with diameters of 1.2 x 1.6 cm and with the presence of cysts inside. We also performed blood tests to check tumor markers alpha fetoprotein, beta hCG and LDH which resulted inside the normal range. We then conducted a chest and abdomen CT scan that showed no pathological elements. Therefore, as we suspected that this tumor was benign, we performed an enucleation of the neoplasm. The definitive histological examination revealed the presence of dilated ducts lined with epithelial cubic-columnar cells with clear cytoplasm rich in glycogen and the pathologist so concluded that the tumor could be classified as adenomatous hyperplasia of the rete testis. At three months of follow up, the patient doesn't have any recurrent lesion to either testicles. DISCUSSION: Adenomatous hyperplasia of the rete testis is a very rare intrascrotal lesion. This histological type is the most frequent between benign lesion of the ovary, but few works in literature reported this histological type in the male gonad and, in most of these works, authors described these lesion at epididymis. CONCLUSION: We believe that a conservative approach must be considered mandatory in case of testicular lesions 1.5 cm in diameter. A radical approach might have alterate fertility of the patient and also have caused psychological trauma more than an enucleation. However a longer follow up is needed to understand if this was the right decision for the oncological point of view.

Buccal mucosa is a promising graft in Peyronie's disease surgery. Our experience and a brief literature review on autologous grafting materials.

AIM: Peyronie's Disease (PD) is an under reported acquired benign condition that, at the moment, is not curable with medical therapy. Surgery represent the gold standard of treatment. Surgical approaches are several and they consist in "plication techniques" or plaque incision/excision with grafting of resulting albuginea defect. Among grafting procedures, albuginea defect substitution with autologous materials demonstrated over the years not inferior results respect to heterologous grafts. Buccal mucosa graft (BMG) is not usually emphasized in many review articles and clinical series are yet limited. METHODS: We present our experience with seventeen plaque incision procedures and BMG in surgical correction of complex penile curvatures due to PD performed in a period of 30 months. Our analyses was focused on buccal mucosa graft characteristics as major determinant of the surgical success. We also conducted a brief literature review on autologous grafting materials used in reconstructive penile surgery for PD. RESULTS: Our cosmetics and functional results consists in a 100% of functional penile straightening with no relapses and 5,8% of de novo erectile dysfunction. Mean age was 56.4 years, mean follow-up of 22.5 (6-36) months. No complications graft related were observed. Operative time was 115.3 minutes in mean. Over 94% of patients referred they were "really much better" and "much better" satisfied based on PGI-I questionnaire administrated at the last follow- up visit. CONCLUSION: BMG is revealing as an optimal choice for reconstructive surgery in PD. Anatomical characteristics consisting in the great elasticity, the quick integration time and the easy harvesting technique lead to high cosmetics and functional success rate, without omitting economical and invasiveness aspects.

Painful ultrasound detected lesion in the proximal part of the corpus cavernosum: A case of so called "partial priapism"?

Partial priapism is a rare disorder generally described in literature as related to an idiopathic etiology leading to the thrombosis of the corpus cavernosum. Despite his rarity, this condition has been described in the last years with an increased frequency. It is characterized by thrombosis of the proximal segment of one corpus cavernosum with perineal pain as the more frequent clinical manifestation. Few cases were associated with perineal trauma. Instrumental appearance suggests for an hematoma in the interstitium of the proximal part of corpus cavernosum. Therapy is still controversial. We report a case of a 52-years old man referred to our Section of Urology suffering from a perineal pain occurred without trauma, sexual arousal or sexual intercourse, during the working office time. Laboratory revealed a slightly elevated white blood cells count. The full blood count, protein C reactive, electrolytes, international normalized ratio, activated partial thromboplastin time and urinalysis were within normal range. Tunica albuginea was normal. The partial thrombosis of the right corpus cavernosum was hypothesized. Treatment was conservative with non steroidal anti-inflammatory drug. Only the clinical presentation of symptoms and perineal ultrasound scan performed with color sonography leaded to the diagnosis. Eleven days later, at the clinical and ultrasonographic follow-up visit, the patient was asymptomatic with a total clinical and instrumental disappearance of signs of the corpus cavernosum involvement previously described. Considering the rarity of the condition, we performed a literature review.

An unusual case of primary intrascrotal lipoma.

In daily clinical practice, intrascrotal lesion are commonly detected, both by clinical examination either by ultrasound scan. While 95% of testicular lesions are malignant, most paratesticular lesions are benign. Among these, intrascrotal lipomas must be take into account in differential diagnosis. When they originate from scrotal wall, they named "primary scrotal lipoma". We describe a case of a primary intrascrotal lipoma diagnosed after surgical excision in a young man presented at our Urological Department complaining a painful left scrotal mass.

Ultrasound features of a metastatic seminal vesicle melanoma: A case report.

In this report we describe what we consider to be the second case of seminal vescicle (SV) metastasis from an unknown primary melanoma. only presenting symptom was a palpable firm nodule of the right prostate base on digital rectal examination (DRE). The diagnosis, after prostatic transrectal ultrasound examination (TRUS), was performed by ultrasound guided biopsy. We underline that prostatic TRUS evaluation is mandatory in case of abnormal digital rectal examination. Seminal vesicle must be always evaluated.

Intravesical BCG therapy as cause of miliary pulmonary tuberculosis.

Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) is considered the most effective adjuvant to endoscopic resection of bladder urothelial carcinoma in the therapeutic management of non-muscle invasive (NMIBC) at intermediate and high risk of recurrence and progression (pTa - pT1 and high-grade carcinoma in situ, CIS). Despite its proven efficacy, this type of treatment can determine local and systemic side effects of moderate or severe gravity, with the histological diagnosis of epithelioid granulomas in different organs, even in the absence of microbiological positivity of BCG. The immunotherapy with BCG is usually well tolerated and the virulence of the attenuated BCG is very low in immuno-competent patients, although only 16% of patients are able to receive all the instillations of the maintenance period (3 years) of treatment provided by the protocols, precisely because of side effects. Minor side effects usually resolve within a few hours or days. They develop in 3-5% of patients and usually consist of local infectious complications. Manifestations of BCG dissemination, such as vascular and ocular complications, are much less common, while BCG-disseminated infections, with granulomatous pneumonia or hepatitis present, are quite rare, representing 0.5-2% of the complications recorded. We present the clinical case of granulomatous lung and possibly liver infection caused by BCG in a patient aged 56 years being treated for several weeks with intravesical BCG for NIMBC pT1 high grade associated with CIS.

Testicular Nodules Suspected for Malignancy. Does the Pathologist Make the Difference for Organ-Sparing Surgery? .

OBJECTIVE: To evaluate the factors that influence decision-making after frozen section examination (FSE) when a urologist sends a surgical specimen of a testicular nodule to a pathologist. STUDY DESIGN: We retrieved, from surgical and pathological files of our center from 2008 to 2014, the clinical information of 15 patients who underwent an explorative inguinal testicular surgery for an intratesticular nodule suspected for malignancy and managed with intention of testicular-sparing surgery. We identify the factors that influenced the correlation between outcome of the FSE and final histopathological report. RESULTS: Mean diameter of the testicular nodules was 8.37 mm. Very small lesions (< 5 mm) were detected in 4 cases (27%), with definitive diagnosis of seminoma in 2 of those (50%). At clinical evaluation 2 nodules were palpable but not malignant at definitive diagnosis. Overall, at definitive histopathological nodule report, a pathologist diagnosed 5 Leydig cell tumors, 4 seminomas, 1 adenomatoid tumor, 1 Sertoli cell tumor, 1 malignant teratoma, and a hemorragic infiltrate in 3 cases. FSE on testicular biopsy reported intratesticular neoplasia only in all cases of definitive diagnosis of seminoma. We observed a concordance between nodule FSE and definitive pathologic report in 11 cases (73%) and in 87% of ancillary testicular biopsies. Discordance was observed in cases lacking the availability of a dedicated pathologist. CONCLUSION: In cases of small testicular nodule FSE may aid the surgery decision and avoid overtreatment. The close collaboration between urologist and a dedicated pathologist is very useful in reducing diagnostic and therapeutic errors.

Penile plaque as predictor of an advanced anorectal carcinoma: A case report.

The secondary involvement of the penis by tumors from others organs is a rare event representing only 0.8% of overall metastasis in the genitourinary tract. The most frequent clinical findings is priapism, but occasionally, solitary metastases to the penile skin, mucosa of the glans, corpus spongiosum or lesions of the albuginea mimicking an induratio penis have been reported. We report a case of penile plaque predicting the relapse of an anorectal carcinoma. The precise etiology of this particular manifestation is not well understood and the prognosis is poor. There are no individual treatments with curative intent.

Patch bulging after plaque incision and grafting procedure for Peyronie's disease. Surgical repair with a collagen fleece.

The incision/excision and grafting techniques (PIG) for surgical therapy of Peyronie's disease (PD) have gained popularity in recent years. Several different graft materials have been used but the ideal graft has yet to be established. The use of grafting materials could cause complications. In the daily clinical practice it will always be more frequent to manage complications arising from their use. We present herein the case of a patch bulging repaired with a ready-to-use collagen fleece (Tachosil®, Takeda, Linz, Austria, Europe) in a 61 years old man subjected to intervention of geometric corporoplasty with Paulo Egydio technique using an acellular collagen material (Xenform® patch, Boston Scientific, Natick, MA, USA) as graft. We also discuss the possible implications of PIG procedure.

Cross-talk between alpha1D-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation.

BACKGROUND: There is evidence that calcium (Ca(2+)) increases the proliferation of human advanced prostate cancer (PCa) cells but the ion channels involved are not fully understood. Here, we investigated the correlation between alpha(1D)-adrenergic receptor (alpha(1D)-AR) and the transient receptor potential vanilloid type 1 (TRPV1) expression levels in human PCa tissues and evaluated the ability of alpha(1D)-AR to cross-talk with TRPV1 in PCa cell lines. METHODS: The expression of alpha1D-AR and TRPV1 was examined in human PCa tissues by quantitative RT-PCR and in PCa cell lines (DU145, PC3 and LNCaP) by cytofluorimetry. Moreover, alpha(1D)-AR and TRPV1 colocalization was investigated by confocal microscopy in PCa cell lines and by fluorescence microscopy in benign prostate hyperplasia (BPH) and PCa tissues. Cell proliferation was assessed by BrdU incorporation. Alpha(1D)-AR/TRPV1 knockdown was obtained using siRNA transfection. Signalling pathways were evaluated by measurement of extracellular acidification rate, Ca(2+) flux, IP3 production, western blot and MTT assay. RESULTS: The levels of the alpha(1D)-AR and TRPV1 mRNAs are increased in PCa compared to BPH specimens and a high correlation between alpha(1D)-AR and TRPV1 expression levels was found. Moreover, alpha(1D)-AR and TRPV1 are co-expressed in prostate cancer cell lines and specimens. Noradrenaline (NA) induced an alpha(1D)-AR- and TRPV1-dependent protons release and Ca(2+) flux in PC3 cell lines; NA by triggering the activation of phospholipase C (PLC), protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways stimulated PC3 cell proliferation, that was completely inhibited by clopenphendioxan (WS433) and capsazepine (CPZ) combination or by alpha(1D)-AR/TRPV1 double knockdown. CONCLUSIONS: We demonstrate a cross-talk between alpha1D-AR and TRPV1, that is involved in the control of PC3 cell proliferation. These data strongly support for a putative novel pharmacological approach in the treatment of PCa by targeting both alpha1D-AR and TRPV1 channels.

Diagnostic and therapeutic utility of transrectal ultrasound in urological office prostatic abscess management: a short report from a single urologic center.

OBJECTIVES: Prostatic abscess (PA) is an infrequent condition in the modern antibiotic era. The everyday use of transrectal ultrasound (TRUS) during diagnostic work-up and the widespread recurrence to prostatic biopsies may lead to an increase of PA diagnosis. In this short report we analyze the patients characteristics and the management of seven recent cases of PA diagnosed in our institution. MATERIALS AND METHODS: The records of 7 patients admitted to our Center for LUTS associated to septic fever or acute urinary retention, was prospectively collected. Suspect of PA was done on digital rectal examination (DRE) and confirmed by TRUS performed after urinary system ultrasound (UUS) evaluation. Patients were admitted to hospital only in case of septic signs. A sovrapubic (SPC) or urethral catheter (UC) was placed depending on symptoms. A TRUS-guided aspiration of PA was performed with patient in lithotomic position, using a 18 gauge two-part needle, side/end fire needle access. Patient was discharged with antibiotic therapy and followed up until complete resolution of the PA and symptoms. RESULTS: Mean age was 62 years (range 24-82). Two patients were diabetics and one was affected by the immunodeficiency acquired syndrome (HIV). In one case, PA was detected after a persistent fever post TRUS guided prostate biopsy. Average prostate volume was 69 ml (range 19-118 ml). DRE was able to diagnose PA only in 2 cases (29%), UUS evaluation in 1 case (14%). All cases were confirmed by TRUS as hypo-anechoic areas with or without internal echoes in all patients. Mean PA dimension was 3.64 cm (range 1.5-8). SPC was placed in 3 cases (43%), UC in 3 patients (43%). Only 1 patient refused catheterization. Side fire needle aspiration was performed in all cases and in combination with end fire access in case of particular location of abscess cavities. Second look was needed in 2 cases (29%). Antibiotics were administered in all cases. The aspirated pus showed a positive culture for Escherichia coli (43%), Klebsiella pneumoniae (29%), Pseudomonas aeruginosa (14%) and Enterococcus faecalis (14%). PA resolution time mean was 9 days (range 3-24). CONCLUSIONS: TRUS evaluation in case of persistent LUTS associated with fever or acute urinary retention is determinant in the diagnosis of PA. Office or institutional management with TRUS needle aspiration is a good option in these cases.

Diagnostic ultrasound-guided excisional testicular biopsy for small (< 1 cm) incidental nodules. A single institution experience.

INTRODUCTION AND OBJECTIVES: The widespread use of scrotal ultrasound (SUS) has led to a marked increase in the number of incidentally detected testicular lesions. A small incidental nodule (STN) has defined as a non palpable (< 10 mm), asymptomatic solid lesion with normal levels of oncological testicular markers. Nowadays the lack of agreement on the topic causes managing problems to andrologists. We present our experience consisting in 8 cases of STN discovered by SUS performed for different clinical indications. MATHERIAL AND METHODS: We retrieved from our ultrasonographic files the clinical information about 717 patients evaluated for andrological problems. Patients with STN underwent to a complete clinical history and physical examination as well as oncological testicular markers measurement and ormonal assessment and then received a diagnostic ultrasound guided excisional biopsy (DEB). Surgical approach was performed through an inguinal incision. Using the coordinates previously obtained from preoperative SUS, STN was localized by intraoperative SUS. The lesion was enucleated and sent to the Pathology department for frozen section examination (FSE). Biopsies of affected testis (TB) were also performed. Post-excision ultrasound has been used to confirm the complete removal of the nodule. Whether pathological findings were benign, testis sparing surgery (TSS) was performed. Immediate radical orchidectomy (IRO) was performed if FSE and TB findings suggested a malignant lesion. RESULTS: STNs were discovered in 8 patients (1,1%). Very small lesions (< 5 mm) were detected in 50% of cases. We performed four IRO and four DEB with consequent TSS. In one case we performed a delayed radical orchidectomy (DRO). At FSE pathologist reported 3 Leydig cell tumor and 3 seminoma and an inflammatory regressive lesion in one case. FSE on TB reported intratesticular neoplasia (TIN) in three cases. In one case nodule wasn't sent to FSE. We observed a concordance between FSE and definitive pathologic report in six cases (75%). CONCLUSIONS: The management of STN is still a challenge for the surgical andrologist. A correct diagnosis has a crucial role in making the best treatment and patients outcome. Ultrasound guided excisional biopsy and the close collaboration with a dedicated pathologist are very useful in reducing errors.

The potential role of transrectal ultrasound as a tool for diagnosis or recurrence detection in bladder cancer. Two cases report.

OBJECTIVES: To demonstrate the potential role of transrectal ultrasound (TRUS) as a tool for diagnosis or recurrence detection in bladder cancer. MATERIAL AND METHODS: We report two cases of a primary lesion of bladder neck and trigone misdiagnosed by conventional sonographic abdominal evaluation and a case of bladder cancer recurrence diagnosed by TRUS performed before cystoscopy. RESULTS: The first patient presented at the Emergency Room of our Hospital for a flank pain with concurrent haematuria. The abdominal ultrasonography showed a right hydronephrosis and a thickened bladder wall without endoluminal projections. The end-fire probe with a longitudinal approach clearly showed a thickening of the bladder wall extended from the bladder neck to the posterior area. The patient was submitted to a transrectal prostate biopsy and to a urethrocystoscopy with a transurethral resection. The second patient was admitted to the Urology Unit for haematuria. Abdominal ultrasonography was unremarkable and urine cytology negative. The TRUS with an end-fire probe showed a 5 mm area of irregular thickening of the mucosa at the bladder neck. The uretrocystoscopy confirmed the presence of a perimeatal papillary lesion. CONCLUSION: We recommend the use of TRUS for bladder cancer detection in selected patients, as an easy, accurate and inexpensive tool. We need further study to validate the role of TRUS in the diagnosis and follow-up of bladder urothelial carcinoma.

Expression of transient receptor potential vanilloid-1 (TRPV1) in urothelial cancers of human bladder: relation to clinicopathological and molecular parameters.

AIMS: To evaluate the expression of transient receptor potential vanilloid type-1 channel protein (TRPV1) in normal and neoplastic urothelial tissues and to correlate TRPV1 expression with clinicopathological parameters and disease-specific survival. METHODS AND RESULTS: TRPV1 expression was analysed in normal and neoplastic urothelial samples at both mRNA and protein levels by quantitative real time polymerase chain reaction (qPCR) and immunohistochemistry, respectively. TRPV1 downregulation was found in urothelial cancer (UC) specimens, which correlated with tumour progression. Moreover, TRPV1 mRNA levels were associated with clinicopathological parameters to assess the role of TRPV1 downregulation as a negative prognostic factor for survival. Kaplan-Meier survival analysis demonstrated a significantly shorter survival in patients showing TRPV1 mRNA downregulation. Multivariate Cox regression analysis indicated further that TRPV1 mRNA expression retained its significance as an independent risk factor. CONCLUSIONS: The progression of UC of human bladder is associated with a marked decrease in TRPV1 expression, with a progressive loss in high-grade muscle invasive UC. Downregulation of TRPV1 mRNA expression may represent an independent negative prognostic factor for bladder cancer patients.

Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner.

Herein, we provide evidence on the expression of transient receptor potential vanilloid type 1 (TRPV1) on human urothelial cancer (UC) cells and its involvement in the apoptosis induced by the selective agonist capsaicin (CPS). We analyzed TRPV1 messenger RNA and protein expression on human UC cell lines demonstrating its progressive decrease in high-grade UC cells. Treatment of RT4 cells with CPS induced cell cycle arrest in G(0)/G(1) phase and apoptosis. These events were associated with rapid co-ordinated transcription of pro-apoptotic genes including Fas/CD95, Bcl-2 and caspase families and ataxia telangiectasia mutated (ATM)/CHK2/p53 DNA damage response pathway. CPS induced Fas/CD95 upregulation, but more importantly Fas/CD95 ligand independent, TRPV1-dependent death receptor clustering and triggering of both extrinsic and intrinsic mitochondrial-dependent pathways. Moreover, we observed that CPS activates ATM kinase that is involved in Ser15, Ser20 and Ser392 p53 phosphorylation as shown by the use of the specific inhibitor KU55933. Notably, ATM activation was also found to control upregulation of Fas/CD95 expression and its co-clustering with TRPV1 as well as RT4 cell growth and apoptosis. Altogether, we describe a novel connection between ATM DNA damage response pathway and Fas/CD95-mediated intrinsic and extrinsic apoptotic pathways triggered by TRPV1 stimulation on UC cells.

Transient receptor potential vanilloid type 2 (TRPV2) expression in normal urothelium and in urothelial carcinoma of human bladder: correlation with the pathologic stage.

OBJECTIVE: To evaluate the expression of transient receptor potential vanilloid type 2 (TRPV2) in normal human bladder and urothelial carcinoma (UC) tissues. METHODS: Bladder specimens were obtained by transurethral resection or radical cystectomy. TRPV2 mRNA expression in normal human urothelial cells (NHUCs), UC cell lines, and formalin-fixed paraffin-embedded normal (n=6) and cancer bladder tissues (n=58) was evaluated by polymerase chain reaction (PCR) and quantitative real-time PCR (RT-PCR). TRPV2 protein expression was assessed by cytofluorimetric and confocal microscopy analyses in NHUCs and UC cells and by Western blotting and immunohistochemistry in normal and UC tissues. RESULTS: Enhanced TRPV2 mRNA and protein expression was found in high-grade and -stage UC specimens and UC cell lines. Both the full-length TRPV2 (hTRPV2) and a short splice-variant (s-TRPV2) were detected in NHUC and normal bladder specimens, whereas a progressive decline of s-TRPV2 in pTa, pT1, and pT2 stages was observed, up to a complete loss in pT3 and pT4 UC specimens. CONCLUSIONS: Normal human urothelial cells and bladder tissue specimens express TRPV2 at both the mRNA and protein levels. A progressive loss of s-TRPV2 accompanied by a marked increase of hTRPV2 expression was found in high-grade and -stage UC tissues.