Urothelial Denudation Research Articles

Urothelial Functional Protein and Sensory Receptors in Patients With Interstitial Cystitis/Bladder Pain Syndrome With and Without Hunner's Lesion

To investigate the urothelium function and sensory receptors difference between interstitial cystitis/bladder pain syndrome (IC/BPS) patients with or without Hunner's lesion. Fourteen female IC/BPS patients with Hunner's lesion (Hunner IC) and 14 age-matched IC/BPS patients without Hunner's lesions (non-Hunner IC) were enrolled. Bladder mucosa biopsies were obtained. Bladder inflammation, eosinophil infiltration, and urothelial denudation were graded on a 4-point scale after staining with hematoxylin and eosin. Adhesive protein E-cadherin, tryptase, and zonula occuldens-1 in the bladder tissues were assessed with immunofluorescence staining. Urothelial muscarinic receptors M2, M3, endothelial nitric oxide synthase (eNOS), and purinergic receptor P2X3 were evaluated by Western blotting. Hunner IC patients had a significantly higher mean visual analog scale pain score and smaller cystometric bladder capacity than non-Hunner IC patients. The Hunner IC bladder specimens showed more severe or moderate eosinophilic infiltration and urothelial denudation than the non-Hunner IC bladder specimens did. The E-cadherin expression was significantly lower, and eNOS expression was significantly higher in the Hunner IC bladder samples than in the non-Hunner IC samples. The other functional proteins or sensory receptors did not differ between groups. Bladder inflammation and urothelial cell adhesion defects were more severe in the Hunner IC than that in the non-Hunner IC patients. eNOS was significantly higher in the Hunner IC than in the non-Hunner IC bladder samples, suggesting that eNOS expression difference may implicate different pathogenesis in 2 types of IC.

Metastatic renal cell carcinoma to the urinary bladder: a report of 11 cases.

Metastatic renal cell carcinoma (RCC) to the urinary bladder is rarely seen. Herein, we report the histologic subtypes, immunohistochemical characteristics, and prognosis of 11 patients with metastatic RCC to the urinary bladder. The mean age at the time of diagnosis of metastatic RCC to the bladder was 66 years (range, 58 to 79 y). There were 9 male and 2 female patients. Four patients presented with hematuria, 2 with urinary retention/obstruction, and 1 with bladder calculi. Four patients were asymptomatic and presented for surveillance cystoscopy, wherein they were found to have bladder masses. Nine patients had prior histories of RCC. The remaining 2 patients presented with metastatic clear cell RCC to the bladder and were subsequently found to have renal masses. The average time between nephrectomy and metastasis to the bladder was 20.7 months (range, 0 to 87 mo). Of the 10 patients with radical/partial nephrectomy, 7 cases were clear cell (2 with sarcomatoid features), 2 papillary, and 1 chromophobe with histologic fidelity between the primary and metastasis. Of cases with available data, the primaries' ISUP nucleolar grades were 2 (n=2), 3 (n=4), and 4 for the 2 cases with sarcomatoid features. In 8 cases, the bladder RCC undermined overlying urothelium with extensive urothelial denudation, and in 3 cases the RCC was free floating without attachment to the urothelium. The 1 chromophobe RCC metastasized with pagetoid spread to a preexisting urothelial papilloma. PAX8 immunohistochemistry was used to confirm the diagnosis in 2 cases. Three patients have no evidence of disease (7, 9, and 13 mo). Two are alive with disease after chemotherapy (30, 37 mo). Six patients are dead of disease with multiorgan metastases; 4 are dead after therapy (5, 8, 25, 28 mo), and two died without radiation or chemotherapy at 10 and 71 months. Metastatic RCC to the urinary bladder is uncommon, with most cases clear cell RCC. In some cases, evidence supports "drop metastases" as the mechanism of spread and patients have relatively long survival. However, in other cases spread to the bladder is in the setting of metastases to other sites, and these patients tended to die relatively shortly after their bladder metastases.

Histologic Impact of Dual-modality Intracorporeal Lithotripters to the Renal Pelvis

To test the hypothesis that dual-modality intracorporeal lithotripters used during percutaneous nephrolithotomy create a degree of tissue trauma in the dual-modality mode (ballistic and ultrasonic) similar to that in the single-modality mode (ultrasonic). The lithotripter devices tested were the Cyberwand and Swiss LithoClast Select. The activated probes, in both single- and dual-modality modes, were applied directly to the renal pelvis of 11 fresh nephrectomy specimens. The treated tissue sites were then processed for light microscopy and reviewed by a single genitourinary pathologist. Microscopic examination of the renal pelvis after 2 seconds of direct contact showed minimal denudation of the urothelium, with no changes noted in the subepithelial or muscle layers for the 2 devices evaluated. Direct contact for 4 seconds showed urothelial denudation and subepithelial changes (n= 13 of 23). Muscle injury was observed in some dual-modality specimens (n= 6 of 12). Increasing the contact time to 8 seconds resulted in fragmentation of the muscle layers more frequently with both settings (n= 15 of 22), except for when the Cyberwand was used at the small stone setting (n= 0 of 7). In the exvivo setting, minimal differences were noted in the degree of histologic trauma between the Cyberwand and Swiss LithoClast Select at 2 seconds. However, both dual-modality devices resulted in muscle damage at 4 and 8 seconds of contact time. Care should be taken during clinical procedures to avoid prolonged contact with the renal pelvis to minimize the potential for tissue trauma.

Intravesical Ultrasonography for Tumor Staging in an Orthotopically Implanted Rat Model of Bladder Cancer

Noninvasive and serial evaluation of tumor development and growth is important in an orthotopic animal bladder tumor model. However, to our knowledge a reliable method has not been established. We determined the usefulness of intravesical ultrasonography for tumor staging and volumetric assessment in an animal model. Tumors with various stages were formed in 20 female Fischer F344 rats by implanting AY-27 rat bladder carcinoma cells. Cells were implanted by instilling a suspension (4x10 cells) into the bladder cavity after urothelial denudation using hydrochloric acid or by directly injecting the cell suspension into the bladder wall. Tumor volume and invasion depth were measured by intravesical ultrasonography using an ultrathin 2.5Fr intraluminal ultrasound catheter via the urethra 7 to 10 days after cancer cell implantation. The rats were then sacrificed for histopathological examination. All rats showed bladder tumors 7 to 10 days after cancer cell implantation, of which stages varied from superficial to advanced disease. Intravesical ultrasonography showed a clear cross-sectional view of all layers of the bladder wall and enabled visualization of bladder tumors (minimal 0.5 mm in diameter). This approach also provided an accurate diagnosis of tumor invasion into muscle layers and perivesical tissues with precise invasion depth and tumor size. The positive predictive ratio regarding tumor staging reached 85%. Repeat examinations were feasible without noticeable adverse effects. Intravesical ultrasonography is a reliable and appropriate noninvasive method for evaluating tumor stage and size in an orthotopic rat bladder tumor model.

Significance of Denuded Urothelium in Papillary Urothelial Lesions

Flat urothelial carcinoma in situ (CIS) is often characterized by prominent dyscohesion with some cases having only a few clinging CIS cells remaining on biopsy. The finding of extensive denudation on urothelial biopsies is associated with a risk of CIS on either prior or subsequent biopsies. The significance of denudation in papillary urothelial lesions has not been formally studied. We identified from our surgical pathology files 31 specimens (from 28 patients) of papillary urothelial lesions with extensive denudation. In cases in which denudation was associated with low-grade urothelial neoplasms, follow-up of subsequent cytologic and histologic specimens was obtained. Of the 28 patients, 25 (89%) were men and 3 (11%) were women with an age range of 40 to 88 years old (mean age 62). Of 31 biopsies, 15 were from anatomically confined areas (ie, renal pelvis, ureter, and urethra). In 22/28 (79%) patients, prominent denudation was associated with high-grade papillary carcinomas, 4/28 (14%) low-grade papillary carcinomas, and 2/28 (7%) papillary urothelial neoplasms of low-grade malignant potential. The average extent of urothelial denudation was 82% with 61% of cases having > or =90% denudation. Prominent cautery artifact was present in 17/31 (55%) cases. In 13/28 patients with high-grade lesions, there was a concurrent biopsy of a second urothelial lesion that was either high-grade papillary urothelial carcinoma or invasive urothelial carcinoma. Five of the 6 patients in which the prominent denudation was associated with a low-grade papillary urothelial lesion have not progressed to a high-grade lesion. One patient with a denuded papillary urothelial neoplasm of low malignant neoplasm was subsequently diagnosed with a noninvasive low-grade papillary urothelial carcinoma in the bladder and a high-grade infiltrating urothelial carcinoma of the ureter. We conclude that (1) the majority of papillary urothelial lesions associated with prominent urothelial denudation are high grade; (2) a significant percentage of papillary urothelial lesions with denudation occur with either prominent cautery artifact or in anatomically confined areas, suggesting both iatrogenic and mechanical contributing factors, respectively; (3) a minority of cases with prominent urothelial denudation occur in association with low-grade papillary urothelial lesions and are not associated with progression to higher grade lesions on follow-up studies; and (4) prominent urothelial denudation in papillary lesions should prompt careful examination of these specimens for rare clinging high-grade carcinoma cells, although in a minority of cases the underlying lesion will be low grade.

Fast Liquid Ablation System for Prostatic Hyperplasia: A New Minimally Invasive Thermal Treatment

We determined patient tolerance and the sequence of histopathological changes of thermal injury and healing of the prostate after treatment with a novel, rapid, high temperature, liquid filled, flexible balloon thermotherapy system. A total of 17 patients scheduled for prostatic surgery received preoperative high temperature water balloon thermotherapy. In 13 patients intraprostatic, urethral and rectal temperatures were continuously monitored and determined using stereotactic thermal mapping with the patient under spinal anesthesia. The remaining 4 patients had lidocaine gel as the only method of pain control. Patient discomfort was recorded at all times during the procedure. After treatment a prostatic stent was left in place until surgery or spontaneous voiding. Serial sections of the resected prostates were evaluated pathologically with mapping. Treatment was well tolerated by all patients. Prostates were enucleated (in 12 patients) or entirely removed (in 5) at a mean of 35 days (range 15 to 173) after thermotherapy. The predominant pathological findings in the early phase were uniform periurethral hemorrhagic necrosis, extensive urothelial denudation and varying degrees of inflammation. The mean radial depth of necrosis (from the urethra to the viable tissue border) was 0.9 cm (range 0.6 to 1.5) involving a mean of 16% of the prostatic adenoma (range 7.8% to 32%). In the late (resolution) phase necrotic tissue had been replaced by scar tissue (fibrosis and hyalinization) with a mean radial depth of 0.13 cm (range 0.01 to 0.24), and the urothelium had largely regrown along the urethra. The fast liquid ablation system for hyperplasia is a new minimally invasive treatment that induces considerable thermal injury to the prostate with uniform necrosis and subsequent sloughing of dead tissue, allowing enlargement of the urethral lumen.

The pagetoid variant of bladder urothelial carcinoma in situ A clinicopathological study of 11 cases.

Pagetoid urothelial carcinoma in situ (CIS) is a rare variant of bladder cancer that is characterized by an intraepithelial proliferation of large cells arranged singly or in clusters and randomly distributed. These neoplasms deserve recognition and attention, chiefly because they may be overlooked or misdiagnosed as urothelial dysplasia, then causing unsuspected tumor recurrence after surgery. We report on the clinicopathological features and immunohistochemical findings of 11 (14.86%) cases of pagetoid CIS in a retrospective study of 74 cases of conventional carcinoma in situ. Most patients were male ( n=10). Their ages ranged from 31 years to 78 years. The lesion can be present with primary ( n=2) or secondary ( n=9) CIS. Pagetoid CIS is usually a focal lesion occurring in a clinical and histological setting of conventional CIS, and these patients essentially have the same progression and survival rates as patients without pagetoid changes and are treated in the same way. In cases with extensive urothelial denudation, pagetoid CIS may be focally present in otherwise normal-looking urothelium, thus alerting the pathologist to search for additional CIS elsewhere in the bladder. Given that primary extramammary Paget disease of the external genitalia and of the anal canal may extend to the bladder and, conversely, some bladder cases of pagetoid CIS may extend to the urethra, ureter, and beyond to the external genitalia, the differential diagnoses between these two entities represent an important therapeutic consideration. Our data suggest that a panel of immunostains including CK7+/CK20+/TM+ may assist in differentiating urothelial pagetoid CIS from extramammary Paget disease which is known to be CK7+/CK20-.

Transurethral hot-water balloon thermoablation for benign prostatic hyperplasia: patient tolerance and pathologic findings

Objectives. To determine the patient tolerance and thermal ablation pattern in human prostatic tissue after treatment with a hot water, catheter-based system. Methods. Twenty-seven men scheduled for surgery for symptomatic benign prostatic hyperplasia or adenocarcinoma of the prostate underwent water-induced thermotherapy. The patients were randomly assigned to one of four treatment groups. Lidocaine gel was the sole means of pain control. The patients and an observer recorded patient discomfort during therapy. A Foley catheter was left in place until surgery (n = 13) or successful voiding (n = 14). Prostates were subsequently enucleated or removed, whole mounted, and examined. Results. Patients reported mild treatment discomfort, the level of which did not correlate with the extent of necrosis, balloon diameter, or water temperature (all P >0.05). Distal penile burning was the most commonly reported discomfort. All 14 patients successfully voided within 12 days of treatment. Prostates were enucleated (n = 24) or removed (n = 3) at a mean of 27 days (range 4 to 120) after thermotherapy, except for a single adenectomy 17 months after therapy. Pathologic findings included periurethral hemorrhagic necrosis, with focal or extensive urothelial denudation and mild inflammation. The mean maximal depth of necrosis from the urethral lumen was 7, 9, 10.33, and 11 mm in groups 1, 2, 3, and 4, respectively. The extent of necrosis was similar in all groups ( P = 0.11), regardless of the water temperature; conversely, the balloon diameter correlated with the depth of necrosis ( P = 0.024). Conclusions. This system of tissue ablation appears to be well tolerated, and it produced consistent pathologic results.