Quantitative comparison of the renal pelvic urine and bladder urine to examine modifications of the urine proteome by the lower urinary tract.

PURPOSE: Urine proteome is a valuable reservoir of biomarkers for disease diagnosis and monitoring. Following formation as the plasma filtrate in the kidney, urine is progressively modified by the active reabsorption and secretion of the urinary tract. However, little is known about how the urine proteome changes as it passes along the urinary tract. EXPERIMENTAL DESIGN: To investigate this, we compared the proteome composition of the renal pelvis urine (RPU) and individually self-voided bladder urine (BU) collected from seven unilateral urinary tract obstruction male patients by LC-MS/MS screening. To our knowledge, this is the first proteomic comparison of RPU and BU samples from the same individual. RESULTS: Overall, RPU and BU proteomes did not exhibit proteins that were exclusively present in all samples of one urine type while in none of the other type. Nonetheless, BU had more overrepresented proteins that were observed at a higher frequency than RPU. Label-free quantitative analyses revealed BU-RPU differential proteins that are enriched in exosomes and extracellular proteins. However, the differences were not significant after corrections for multiple testing. Interestingly, we observed a significant increase of collagen peptides with hydroxyproline modifications in the BU samples, suggesting differences in protein modifications. CONCLUSIONS AND CLINICAL RELEVANCE: Our study revealed no substantial differences at the protein level between the BU and RPU samples. Future investigations with expanded cohorts would provide more insights about the urothelial-urinary interactions.

Surface analysis of ureteral stent before and after implantation in the bodies of child patients.

The aim of this work was to determine which part of a double-J ureteral stent (DJ stents) showed the highest tendency to crystal, calculi, and biofilm deposition after ureterorenoscopic-lithotripsy procedure (URS-L) to treat calcium oxalate stones. Additionally, the mechanical strength and the stiffness of DJ stents were evaluated before and after exposure to urine. Obtained results indicated that the proximal (renal pelvis) and distal (urinary bladder) part is the most susceptible for post-URS-L fragments and urea salt deposition. Both, the outer and inner surfaces of the DJ ureteral stents were completely covered even after 7 days of implantation. Encrustation of DJ stents during a 31-day period results in reducing the Young's modulus by 27-30%, which confirms the loss of DJ stent elasticity and increased probability of cracks or interruption. Performed analysis pointed to the need to use an antibacterial coating in the above-mentioned part of the ureteral stent to prolong its usage time and to prevent urinary tract infection.

Comprehensive Genomic Characterization of Upper Tract Urothelial Carcinoma.

BACKGROUND: Upper urinary tract urothelial cancer (UTUC) may have unique etiologic and genomic factors compared to bladder cancer. OBJECTIVE: To characterize the genomic landscape of UTUC and provide insights into its biology using comprehensive integrated genomic analyses. DESIGN, SETTING, AND PARTICIPANTS: We collected 31 untreated snap-frozen UTUC samples from two institutions and carried out whole-exome sequencing (WES) of DNA, RNA sequencing (RNAseq), and protein analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adjusting for batch effects, consensus mutation calls from independent pipelines identified DNA mutations, gene expression clusters using unsupervised consensus hierarchical clustering (UCHC), and protein expression levels that were correlated with relevant clinical variables, The Cancer Genome Atlas, and other published data. RESULTS AND LIMITATIONS: WES identified mutations in FGFR3 (74.1%; 92% low-grade, 60% high-grade), KMT2D (44.4%), PIK3CA (25.9%), and TP53 (22.2%). APOBEC and CpG were the most common mutational signatures. UCHC of RNAseq data segregated samples into four molecular subtypes with the following characteristics. Cluster 1: no PIK3CA mutations, nonsmokers, high-grade

Diagnostic utility of Ki-67 immunohistochemistry in small endoscopic biopsies of the ureter and renal pelvis.

Diagnosis of upper urinary tract urothelial carcinoma in ureteroscopic biopsies is challenging. Therefore, an immunohistochemical marker that can differentiate between malignant and benign urothelium and predict final pathological features is necessary. In this study, we investigated Ki-67 expression in 26 ureteroscopic biopsies of the ureter and renal pelvis diagnosed with urothelial carcinoma (UC) and in 13 biopsies with non-neoplastic urothelium, using digital image analysis. The median Ki-67 labeling index was 1.5% (range: 0.2-13.9%) in non-neoplastic urothelial specimens and 15.0% (range: 0.2-61.3%) in UC specimens (p=0.0001). In 12 of 26 (46%) UC specimens, the Ki-67 labeling index was more than 20%. By contrast, the Ki-67 labeling index was less than 5% in 11 of 13 (85%) non-neoplastic urothelial specimens. Ki-67 expression in ureteroscopic biopsies was significantly correlated with high tumor grade (p=0.013), concomitant carcinoma in situ (p=0.011), and stromal invasion (p=0.048) in surgical resection specimens. Our data suggested that Ki-67 may provide supplemental, objective evidence that can aid diagnosis of upper urinary tract UC in ureteroscopic biopsy specimens. Determination of Ki-67 expression in ureteroscopic biopsy specimens is potentially helpful in clinical decision making for patients with suspected upper urinary tract UC.

Urothelial carcinoma with oncocytic features: an extremely rare case presenting a diagnostic challenge in urine cytology.

Recognizing histological variants in urothelial carcinoma (UC) is important because some may be associated with different clinical outcomes and/or therapeutic approaches; being aware of unusual histological variants may also be crucial in preventing diagnostic misinterpretations. Histological variants based on cytoplasmic features, such as clear-cell, plasmacytoid, rhabdoid, and lipoid-rich variants, are described in invasive UC; however, these cytoplasmic features are not formally defined and not usually encountered in non-invasive UC. Oncocytic cytoplasm has not been well described in either invasive or non-invasive UC. Herein, we report an exceedingly rare case of UC with oncocytic features arising in the right renal pelvis, which presented a diagnostic challenge in urine cytology due to the relatively low nuclear-to-cytoplasmic ratio; however, it could definitively be diagnosed using histological specimens. UC diagnosis is based on the presence of papillary architecture and widespread p53 nuclear accumulation, suggesting malignancy. An oncocytic tumor is generally considered to be not actively dividing, as shown by the low Ki-67 labeling index in this case. In spite of the low proliferative activity, the possibility of intravesicle recurrence (IVR) should be considered since positive preoperative cytology of upper tract UC is a risk factor for IVR after nephroureterectomy.

Expression of VEGF in neonatal urinary obstruction: does expression of VEGF predict hydronephrosis?

BACKGROUND: In animal studies, the inhibition of VEGF activity results in high mortality and impaired renal and glomerular development. Mechanical stimuli, like mechanical stretch in respiratory and circulatory systems, results in an elevated expression of VEGF. In animal models, the experimental urinary obstruction is associated with stretching of tubular cells and activations of the renin-angiotensin system. This results in the upregulation of vascular endothelial growth factor (VEGF) and TNF-alfa. MATERIAL/METHODS: Tissue samples from urinary tract obstruction were collected and immunohistochemistry was performed in 14 patients (average age: 7.1±4.1 years). The control histology group consisted of ureteropelvic junction tissue from 10 fetuses after midtrimester artificial abortion. The fetuses did not have any failure at ultrasound screening and pathological examination. The mean gestational age was 20.6 weeks of gestation (±2.2SD). Expression of VEGF was detected with immunohistochemistry method. RESULTS: Expression of VEGF was found in varying intensity in the submucosa and subserosa layers, but only in the test tissue (placental tissue). The tissue of the patients with urinary obstruction and the tissue of the fetal ureteropelvic junction without urinary obstruction were negative for expression of VEGF. The repeated examination showed negative cells and no color staining. CONCLUSIONS: The pressure due to congenital urogenital obstruction resulting in mechanical stress in cells did not increase the expression of VEGF in young children in our study. To find a correlation between urogenital tract obstruction and increased expression of VEGF, we need to perform more examinations because the connection may be of therapeutic significance.

Does the histopathologic pattern of the ureteropelvic junction affect the outcome of pyeloplasty.

PURPOSE: To investigate the effects of the histopathologic pattern of obstructed ureteropelvic junction (UPJ) specimens, including collagen type 3, elastin, fibrosis and Cajal cells, on the outcome of pyeloplasty. MATERIALS AND METHODS: Histopathological specimens obtained following Anderson-Hynes pyeloplasty from 52 patients with intrinsic ureteropelvic junction obstruction (UPJO) between January 2005 and January 2008 were evaluated histopathologically. Patients with extrinsic or secondary UPJO were excluded. Preoperative and postoperative radiographic evaluations were performed either via diuretic renography or intravenous pyelography, or both. Six months post-surgery the patients were divided into 2 groups, as successful surgery (group 1) and unsuccessful surgery (group 2). Histopathological findings (collagen type 3, elastin, fibrosis and Cajal cells) in each group were statistically compared. RESULTS: The study included 52 patients (21 female and 31 male). Mean age of the entire study population was 39.42 ± 14.5 years, versus 39.63 ± 14.9 years in group 1 (n = 47) and 37.4 ± 10.0 years in group 2 (n = 5). Median follow-up was 18 months. There weren't any significant differences in collagen type 3, elastin, fibrosis, or Cajal cells between the 2 groups (P > .05). CONCLUSION: The histopathologic pattern of UPJ was not a factor associated with the success of pyeloplasty. Based on the present findings, we conclude that surgical technique is more important than the histopathologic pattern of UPJ for the successful treatment of UPJO.

Alpha adrenergic receptors in renal pelvis and calyces: can rat models be used?

We aimed, in this study, to determine the distribution of α-1 AR subtypes in rat and human pelvis and calyces, and to evaluate, by comparing these two species, the possibility of rats to be used as models for humans. Twenty patients with renal carcinoma were included into the study. The patients underwent radical nephrectomy for renal cell carcinoma (RCC). After nephrectomy, specimens were evaluated and excisional biopsies from healthy pelvis and calyces tissues were performed. When pathology confirmed the non-invasion of RCC, specimen was included into the study. A total of 7 adult Wistar Albino (250-300 g) female rats were used in this study. Specimens included renal pelvis and calyces. All specimens were evaluated under light microscope histopathologically. The concentrations of the receptor densities did not differ between the two groups. With the demonstration of the α receptors in rat kidneys and calyces, many receptor-based studies concerning both humans and rats can take place. Novel medication targeting these subtypes -in this matter α1A and α1D for renal pelvis and calyces- may be helpful for expulsive therapy and/or pain relief. With the demonstration of similar receptor densities between human and rat tissues, rat model may be useful for α-receptor trials for renal pelvis and calyces.

Alpha adrenergic receptors in renal pelvis and calyces: can rat models be used?

We aimed, in this study, to determine the distribution of α-1 AR subtypes in rat and human pelvis and calyces, and to evaluate, by comparing these two species, the possibility of rats to be used as models for humans. Twenty patients with renal carcinoma were included into the study. The patients underwent radical nephrectomy for renal cell carcinoma (RCC). After nephrectomy, specimens were evaluated and excisional biopsies from healthy pelvis and calyces tissues were performed. When pathology confirmed the non-invasion of RCC, specimen was included into the study. A total of 7 adult Wistar Albino (250-300 g) female rats were used in this study. Specimens included renal pelvis and calyces. All specimens were evaluated under light microscope histopathologically. The concentrations of the receptor densities did not differ between the two groups. With the demonstration of the α receptors in rat kidneys and calyces, many receptor-based studies concerning both humans and rats can take place. Novel medication targeting these subtypes -in this matter α1A and α1D for renal pelvis and calyces- may be helpful for expulsive therapy and/or pain relief. With the demonstration of similar receptor densities between human and rat tissues, rat model may be useful for α-receptor trials for renal pelvis and calyces.

Hydronephrosis promotes expression of hypoxia-inducible factor 1 alpha.

BACKGROUND: Obstructive uropathy is argued to involve an ischemia-type tissue injury. Further, hypoxia-inducible factor 1 alpha (HIF-1 alpha) constitutes a nuclear transcription factor normally upregulated under hypoxic conditions. We hypothesized that HIF-1 alpha is expressed in the hydronephrotic renal pelvis, as a result of tissue hypoxia. PATIENTS AND METHODS: Renal pelvis tissue specimens were obtained from 2 patient groups. Group 1 (controls, n = 10) consisted of patients who underwent nephrectomy due to nonobstructive renal malignancy. Group 2 (n = 18) consisted of patients who underwent open procedures due to intractable hydronephrosis, not amenable to conservative measures. HIF-1 alpha detection was conducted via immunohistochemical techniques, while histological alterations in both groups were also recorded. RESULTS: Smooth muscle hypertrophy and urothelial hyperplasia were major findings in group 2. HIF-1 alpha-positive cells (fibroblasts and occasionally macrophages), mainly localized in the stroma, were also found to a greater extent in group 2 (p = 0.0066). CONCLUSION: We conclude that HIF-1 alpha is mainly expressed in stroma fibroblasts of the hydronephrotic renal pelvis, implying the presence of significant tissue hypoxia at the dilated upper urinary tract.

Lipoid-cell variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of five cases.

Invasive urothelial carcinoma may present with many deceptive morphologic variants. We report the clinicopathologic and immunohistochemical features of 5 cases of the so-called lipid-cell variant of urothelial carcinoma. The tumors occurred in 4 men and 1 women aged from 56 to 80 years. Four cases were developed in the bladder and 1 case in the renal pelvis. All cases were revealed by a macroscopic hematuria. The tumors were composed of sheets and nests of large epithelial cells with an abundant clear multivacuolated cytoplasm mimicking lipoblasts. Nuclei were irregular, hyperchromatic, eccentric, and frequently indented by cytoplasmic vacuoles. Mucin stains (PAS, Alcian Blue) were negative. Tumor cells were strongly stained with cytokeratin 7, cytokeratin 20, and EMA but were negative with S-100 protein. In all cases, a usual high-grade urothelial carcinoma component was admixed with lipoid tumor cells. Two tumors infiltrated the bladder muscle, 2 cases invaded the bladder submucosa, and 1 case invaded the renal parenchyma. In the follow-up, despite appropriate surgical treatment, 4 patients died of the disease and 1 patient is alive without recurrence. Because of its rarity and the tumor cells' appearance, the lipoid-cell variant may be misdiagnosed and must be distinguished from liposarcoma or signet-ring cell carcinoma. In the present series, the lipoid-cell variant of urothelial carcinoma was associated with an aggressive behavior and a poor prognosis.

Overexpression of B7-H1 (PD-L1) significantly associates with tumor grade and postoperative prognosis in human urothelial cancers.

PURPOSE: The programmed death-1 (PD-1)/B7-H1 (also called PD-L1) pathway negatively regulates T cell activation and has been suggested to play an important role in regulating antitumor host immunity. To investigate the clinical significance of B7-H1 expression to the tumor grade and postoperative prognosis of patients with urothelial cancer, we analyzed the relationship between B7-H1 expression and various clinicopathological features and postoperative prognosis. EXPERIMENTAL DESIGN: Sixty-five urothelial cancer cases were examined. B7-H1 expression in tumors and the numbers and phenotypes of tumor-infiltrating lymphocytes were evaluated by immunohistochemistry and flow cytometry. RESULTS: A substantial expression of B7-H1 was observed in all urothelial cancers investigated. Tumor specimens from patients with higher WHO grade or primary tumor classifications showed significantly higher percentages of tumor-associated B7-H1. Tumor-associated B7-H1 expression was significantly associated with a high frequency of postoperative recurrence and poor survival rate. Furthermore, multivariate analysis indicated that tumor-associated B7-H1 was more significant prognostic factor than WHO grade. CONCLUSIONS: Our results demonstrate that the aberrant expression of B7-H1 in urothelial cancer is associated with aggressive tumors, suggesting a regulatory role of tumor-associated B7-H1 in antitumor immunity. Therefore, the manipulation of tumor-associated B7-H1 may become a beneficial target for immunotherapy in human urothelial cancer.

MET expression in sporadic renal cell carcinomas.

Although germline mutations of met proto-oncogene on human chromosome 7q31-34 have been known as useful molecular markers of hereditary papillary renal cell carcinoma (RCC), the expression of MET, a product of met proto-oncogene, has not been fully studied in sporadic RCC, along with its clinical significance. We investigated the expression of MET by immunohistochemistry in 182 cases of renal neoplasm encompassing 145 RCC, 25 urothelial carcinomas of renal pelvis, and 12 oncocytomas. MET was diffusely and strongly expressed in 90% of papillary RCC, all collecting duct carcinomas, and 92% of urothelial carcinomas of renal pelvis. On the contrary, clear cell RCC, chromophobe RCC, and oncocytomas were negative or focally positive for MET expression. In clear cell RCC, MET expression was positively correlated with high nuclear grade, presence of infiltrative growth, tumoral necrosis, papillary architecture, sarcomatoid component, tumoral involvement of the renal pelvis or ureter, involvement of the calyx, and lymphatic invasion. In conclusion, diffuse and strong expression of MET in papillary RCC and collecting duct carcinoma might be helpful in discriminating from the other subtypes of RCC with tubular or papillary growth. In case of MET expression observed in clear cell RCC, it might correlate with those clinicopathological parameters implying aggressive behavior.

[Reactive transformation of human urinary smooth muscular tissue in some diseases (structural-metabolic aspects of organization)].

Smooth muscular tissue (SMT) of human urinary system was studied at different levels (renal pelvis, proximal and distal parts of the ureter) in health and some urological diseases (vesicoureteral reflux, ureteral obstruction). The method of target cell dissociation was used. The volume of myocytes, nuclei, nuclear-cytoplasmic correlation were calculated. Content of DNA and cytoplasmic protein was studied cytospectrophotometrically. Electron-microscopic study was also made. Three types of myocytes with different structural-metabolic parameters were detected. There were significant differences in mean volumes of myocytes, cytophotometric indices of SMT in different parts of the urinary tracts related to the pattern of these zones functioning. A comparative analysis of intact and affected SMT of the distal ureter demonstrated changes in the structure of leiomyocytes population, optic density of cytoplasmic protein and proliferative activity of myocytes which correlated depending on the kind and change of functional load.

MET Expression in Sporadic Renal Cell Carcinomas

Although germline mutations of met proto-oncogene on human chromosome 7q31-34 have been known as useful molecular markers of hereditary papillary renal cell carcinoma (RCC), the expression of MET, a product of met proto-oncogene, has not been fully studied in sporadic RCC, along with its clinical significance. We investigated the expression of MET by immunohistochemistry in 182 cases of renal neoplasm encompassing 145 RCC, 25 urothelial carcinomas of renal pelvis, and 12 oncocytomas. MET was diffusely and strongly expressed in 90% of papillary RCC, all collecting duct carcinomas, and 92% of urothelial carcinomas of renal pelvis. On the contrary, clear cell RCC, chromophobe RCC, and oncocytomas were negative or focally positive for MET expression. In clear cell RCC, MET expression was positively correlated with high nuclear grade, presence of infiltrative growth, tumoral necrosis, papillary architecture, sarcomatoid component, tumoral involvement of the renal pelvis or ureter, involvement of the calyx, and lymphatic invasion. In conclusion, diffuse and strong expression of MET in papillary RCC and collecting duct carcinoma might be helpful in discriminating from the other subtypes of RCC with tubular or papillary growth. In case of MET expression observed in clear cell RCC, it might correlate with those clinicopathological parameters implying aggressive behavior.

Elastin content of the renal pelvis and ureter determines post-pyeloplasty recovery.

PURPOSE: We evaluated the collagen-to-smooth muscle tissue matrix ratio and percentage of elastin in the renal pelvis, ureteropelvic junction (UPJ) and ureter, and compared these findings with the degree of obstruction, patient age and post-pyeloplasty renal recovery. MATERIALS AND METHODS: We analyzed histological sections from 75 patients with UPJ obstruction. Nine patients were excluded owing to bilateral UPJ obstruction and an improper specimen. We divided the specimen obtained from pyeloplasty into 3 parts, namely the renal pelvis above the obstruction, the obstructed UPJ portion and the ureter below the obstruction. To examine the collagen and smooth muscle, sections were stained using Masson's trichrome, and elastic van Giesson stain was used for elastin, smooth muscle and collagen. Collagen, smooth muscle and elastin populations were identified, and the tissue matrix ratio and percentage of elastin were calculated by color image analysis. RESULTS: In patients with lower ratios of collagen-to-smooth muscle in the UPJ proper hydronephrosis was more improved postoperatively (p = 0.049). In patients with a lower percentage of elastin in the renal pelvis, UPJ and ureter hydronephrosis was more improved postoperatively (p <0.0001). CONCLUSIONS: Because the UPJ portion was resected during pyeloplasty, the renal pelvis and the ureter remaining after pyeloplasty are likely to be related to improved hydronephrosis. A higher percentage of elastin in the renal pelvis and ureter contributes to inelasticity and low compliance, and results in a slower recovery from hydronephrosis after pyeloplasty.

Elevation of CA 19-9 in giant hydronephrosis induced by a renal calculus.

CA 19-9 is a tumor marker of pancreatic and gastrointestinal cancer. Elevation in nonmalignant disease is rare. The case of a patient with a partial staghorn calculus, giant hydronephrosis, and elevated CA 19-9 serum levels is presented. Open transperitoneal right-sided nephrectomy was performed. In immunohistochemical analysis, CA 19-9 was expressed in the renal tubular epithelium and the renal pelvis. During postoperative follow-up, the CA 19-9 levels returned to normal. Hydronephrosis might cause false-positive results when CA 19-9 measurement is used to screen for malignant disease. Posttreatment CA 19-9 levels of patients with hydronephrosis have to be monitored closely to safely exclude malignant disease.

Altered expression of interstitial cells of Cajal in congenital ureteropelvic junction obstruction.

PURPOSE: Peristaltic contractions in the upper urinary tract serve to move urine from the kidney through the ureter to the bladder. Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis in children. To our knowledge the pathophysiology of UPJ obstruction is unknown. C-kit positive interstitial cells of Cajal (ICCs) are pacemaker cells that facilitate active propagation of electrical events and mediate neurotransmission. We investigated the expression of c-kit positive cells in the muscle layer of normal and obstructed UPJ specimens. MATERIALS AND METHODS: A total of 19 human formalin fixed, paraffin embedded specimens of intrinsic UPJ obstruction from children with a mean age of 2.3 years (range 2 months to 12 years) and 7 control samples from children with a mean age of 4.5 years (range 11 months to 9 years) were investigated immunohistochemically for the expression of c-Kit oncoprotein and peripherin by light and laser scanning microscopy. Quantification of immunolabeled structures was quantified using computerized image analysis. RESULTS: Peripherin immunoreactivity was strong in the muscle layer of normal UPJ specimens, while in UPJ obstructed specimens there was a decrease in peripherin positive nerve fibers. In normal UPJ specimens there were many c-Kit positive ICCs between the muscle bundles. The density of ICCs was markedly decreased in the muscle layers of UPJ obstructed specimens. CONCLUSIONS: To our knowledge this study shows for the first time the immuno-expression of c-Kit positive ICCs in the proximal part of the normal human upper ureter. The altered density of c-Kit positive cells in UPJ obstruction may have a role in the failure of transmission of peristaltic waves across the UPJ.

Potential role for the nuclear transcription factor NF-kappa B in the pathogenesis of ureteropelvic junction obstruction.

BACKGROUND AND PURPOSE: In an effort to better understand the pathophysiology of ureteropelvic junction (UPJ) obstruction and to determine possible predisposing factors for endopyelotomy failures, we compared the activation of the nuclear factor NF-kappa B and proinflammatory cytokines in patients who failed endopyelotomy and post-primary pyeloplasty patients. We hypothesized that an imbalance toward proinflammatory cytokines may promote fibrosis prior to and after endopyelotomy in patients with severe hydronephrosis. PATIENTS AND METHODS: The charts of patients who underwent open pyeloplasty at our institution were reviewed. Group I was the control group, consisting of 10 patients who had undergone radical nephrectomy for renal-cell carcinoma without involvement of the renal pelvis. Group II was the endopyelotomy failure group and included 11 patients over the age of 15 years treated for symptomatic UPJ obstruction. Group III included six patients who underwent primary pyeloplasty. Paraffin-embedded blocks of UPJ segments from each of these patients were obtained, and immunohistochemical detection of NF-kappa B activation, interleukin (IL)-6, and hypoxia-inducing factor (HIF) was performed. As an in-vitro model, activation of NF-kappa B and cytokine gene expression were also monitored in human bladder T24 urothelial cells 24 hours after exposure to hypoxia (1% O(2)) in the presence and absence of NF-kappa B inhibitor. The activation of NF-kappa B was determined by immunocytochemical analysis, whereas cytokine gene expression was measured using reverse transcriptase-polymerase chain reaction. RESULTS: Immunoreactivity to NF-kappa B was observed in the nuclei of the urothelium and muscle layer in all patients in group II. Such immunostaining suggests increased nuclear translocation and activation of this transcription factor. Those patients with increased expression of NF-kappa B demonstrated increases in IL-6 expression as well. Hypoxia-inducing factor was identified in all the tissue samples tested in group II. Stimulation of the human urothelial cells by hypoxia, known to activate NF-kappa B, resulted in an increase in the levels of IL-1 and IL-6 transcripts compared with hypoxia-exposed cells in the presence of NF-kappa B inhibitors. CONCLUSIONS: The NF-kappa B factor was upregulated and proinflammatory cytokines were activated in patients with UPJ obstruction who failed endopyelotomy. Proinflammatory cytokines upregulated by this nuclear factor can result in fibrosis and affect healing after endopyelotomy. Hypoxia appears to activate this nuclear factor. Further studies correlating the degree of hydronephrosis with the activation of HIF are necessary to clarify the role of severe hydronephrosis and its management in UPJ obstruction.

Cystic hamartoma of the renal pelvis: a rare pathologic entity.

We report a case of a rare cystic renal tumor previously termed cystic hamartoma of the renal pelvis. A 53-year-old woman presented to her gynecologist with menometorrhagia. She subsequently had a computed tomographic scan that demonstrated an incidental cystic mass in the lower pole of the left kidney. Histologically, the tumor was composed of a mixture of benign mesenchymal and epithelial components. The stroma consisted of spindle cells with monomorphic nuclei and abundant eosinophilic cytoplasm that resembled smooth muscle and that reacted positively with antibodies to alpha-smooth muscle actin, desmin, and vimentin. The epithelial component was composed mostly of cysts lined by cuboidal-to-columnar epithelium. Focal dilated cysts were lined by epithelium with oncocytic features. We think that this entity is distinct from other renal tumors, including mesoblastic nephroma, cystic nephroma, or a cystic, partially differentiated nephroblastoma, and that it is best classified as a cystic hamartoma of the renal pelvis.