Allelic Variants of the Complement Genes in Acute Postinfectious Glomerulonephritis.

Acute postinfectious glomerulonephritis (APIGN) is one of the most common causes of acute glomerulonephritis in children. It may lead to inflammation and proliferation of glomerular tissue through immunologic mechanisms (Balasubramanian R, Paediatr Int Child Health 2017;37:240-247).

Value of Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios in the Evaluation of Acute Rejection and Chronic Allograft Nephropathy in Children With Kidney Transplantation.

OBJECTIVES: Neutrophil-to-lymphocyte ratio and platelet (thrombocyte)-to-lymphocyte ratio have become accepted markers of inflammation in recent years and are used to assess disease activity in some diseases. In this study, we investigated the relationship between these values and acute rejection attacks, as well as their role in determining chronic allograft nephropathy, in follow-up of pediatric kidney transplant recipients. MATERIALS AND METHODS: Our study included 58 kidney transplant recipients (age 5-18 years) with at least 5-year follow-up at our center. Patients with history of secondary transplant, concomitant malignancy, and shorter follow-up were excluded. Medical history and laboratory parameters pretransplant and at 1, 3, and 6 months and 1, 2, 3, 4, and 5 years posttransplant, as well as kidney biopsy reports, were reviewed. RESULTS: Both neutrophil-to-lymphocyte (P = .003) and thrombocyte-to-lymphocyte (P = .002) ratios were significantly higher during acute rejection attacks. Although both values were higher in patients with chronic allograft nephropathy at 5 years posttransplant, differences were not statistically significant (P = .69 and P = .55). When patients with and without chronic allograft nephropathy within 5 years were compared, those who developed chronic allograft nephropathy had significantly higher neutrophil- tolymphocyte and thrombocyte-to-lymphocyte ratios at all periods in the first 2 and 4 years posttransplant, respectively. Among patients who had acute rejection attacks, those who subsequently developed chronic allograft nephropathy had higher neutrophil-tolymphocyte ratio in the first 3 years posttransplant, with higher thrombocyte-to-lymphocyte ratio at all posttransplant periods. CONCLUSIONS: This is the first study on neutrophil- tolymphocyte and thrombocyte-to-lymphocyte ratios in pediatric kidney transplant recipients. Our results indicated that both values can be useful and easily accessible markers in acute rejection diagnosis and determining chronic allograft nephropathy development risk, which are 2 major causes of kidney graft loss posttransplant. Pediatric studies with larger populations are needed to support our findings.

Which one is better for predicting extraprostatic extension on multiparametric MRI: ESUR score, Likert scale, tumor contact length, or EPE grade?

PURPOSE: To evaluate the European Society of Urogenital Radiology (ESUR) score, the Likert scale, tumor contact length (TCL) > 1 cm, and EPE (extraprostatic extension) grade in predicting EPE at multiparametric magnetic resonance imaging (mp-MRI). METHODS: Seventy-nine patients who underwent 3-T MRI and were histopathologically confirmed by microblocks were enrolled in this retrospective study. The index lesions were interpreted by two experienced radiologists. Apparent diffusion coefficient (ADC) values were also noted. Weighted κ statistics were used to compare interreader agreement. Univariate logistic regression analysis was performed to define independent predictors of EPE status. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to compare the MRI-based methods and clinical variables (ISUP grade, prostate volume and PSA density) + MRI-based methods for pathologic EPE prediction by using the area under the curve (AUC) value. RESULTS: The mean age was 64.5 years ± 6.2. 33/79 (41.8%) patients had pathologic EPE. As ESUR score showed weak interreader agreement (κ = 0.537), Likert scale, TCL, and EPE grade showed moderate agreement (κ = 0.608, κ = 0.747, κ = 0.647 respectively). Univariate ROC analysis result showed that all MRI-based score systems, mean ADC value, the ISUP grade, prostate volume, PSA density were the best variables in predicting EPE. ROC analysis results of four MRI-based methods showed good diagnostic performance. At multivariate analysis, all clinical models showed excellent diagnostic performance. CONCLUSION: All four MRI-based methods had good diagnostic performance. Furthermore, consisting of both qualitative and quantitative parameters and being less reader experience dependent, EPE grade was a promising method in predicting EPE. All clinical models showed excellent diagnostic performance.

Role of silymarin (Silybum marianum) in the prevention of colistin-induced acute nephrotoxicity in rats.

Silymarin (Silybum marianum) has some protective effects against drug toxicity (cisplatin, acetaminophen, adriamycin, gentamicin etc.). Colistin is a strong antimicrobial, which is frequently used in the treatment of resistant gram-negative bacterial infections in recent years although it has nephrotoxic potential. This study was aimed to determine the role of silymarin against colistin-induced acute nephrotoxicity (CIN). Rats were randomly divided into four groups. The control group was treated with tap water whereas groups 2 and 3 received silymarin (orally, 100 mg/kg/day) and colistin (intraperitoneally, 750.000 IU/kg/day) for seven days, respectively. Group 4 received both 750,000 IU/kg/day colistin and 100 mg/kg/day silymarin for seven days. After euthanasia, histopathological and biochemical examinations were completed for the kidney tissue specimens and blood samples. All parameters of the control and silymarin groups were similar. Severe weight loss was seen in the groups receiving colistin (groups 3 and 4). Silymarin significantly increased glutathione peroxidase and superoxide dismutase levels when administered with colistin in group 4 only. Acute tubular injury, tubular necrosis, meduller congestion, interstitial inflammation and apoptotic indices of colistin group were significantly higher than the control group. The administration of colistin with silymarin (group 4) was able to make some improvements in tubular necrosis and significant increase in antioxidant capacity. Silymarin increased antioxidant enzyme activity only when used in combination with colistin. The effects of silymarin may become more pronounced when used at higher doses or with a longer duration of treatment and may prevent nephrotoxicity.

The Histopathological Effect of Aloe Vera on the Wound Healing Process in a Surgically Created Tubularized Incised Plate Urethroplasty Model on Rats.

BACKGROUND: Hypospadias is a common congenital anomaly which is determined as an abnormal urethral opening on the ventral face of penis. The purpose of this rat model study was to research the effect of topically applied Aloe vera after a tubularized incised plate urethroplasty (TIPU). METHODS: The TIPU model was applied to male Wistar albino rats. A total of 30 rats were randomly grouped into 3 groups of 10. Group I was assigned as the control group, treated with 0.9% saline only twice a day for 15 days. Group II received topical Aloe vera gel once a day and Group III received Aloe vera gel twice a day. Spongiofibrosis was graded as 0: none, 1+:≤10% tissues involved, 2+:10%-49% tissues involved, 3+: ≥ 50% tissues involved. RESULTS: A higher degree of fibrosis and inflammation was determined in the Group I subjects than in Groups II and III. Fibrosis of grade 3+ was observed in 33% of the control group and not in any of the two Aloe groups (p = 0.043). Inflammation of grade 3+ was seen in 66.7% of the control group, in 10% of Group II, and in 33% of Group III (p = 0.02). CONCLUSIONS: The topical application of Aloe vera to a surgically created tubularized incised plate urethroplasty model decreased inflammation and fibrosis that may affect the success rates of this operation.

Case Report: A Human Case of Onchocerca lupi Mimicking Nodular Scleritis.

We report a case of human ocular onchocerciasis by zoonotic Onchocerca lupi presenting as nodular scleritis. Molecular analyses were used to confirm diagnosis at species level. In addition to few existing reports of human infection by O. lupi in Turkey, this case further suggests that the pathogen might be more common than previously reported, thus requiring further attention and investigations.

The role of histopathological and biochemical parameters for predicting metastatic disease on 68 Ga-PSMA-11 PET in prostate cancer.

BACKGROUND: The aim of this study was to evaluate the role of histopathological and biochemical parameters in the prediction of the presence and number of PSMA positive lesions consistent with the metastatic spread of prostate cancer on 68 Ga-PSMA PET images. METHODS: Biochemical, histopathological and imaging data of 302 prostate cancer patients who underwent 68 Ga-PSMA-11 PET/CT or PET/MR imaging for primary staging were retrospectively analyzed. Patients were divided into two groups as "PET positive" and "PET negative" according to the presence of pathologic extraprostatic PSMA involvement. "PET positive" patients were additionally divided into two groups: oligometastatic (1-3 metastatic lesion) and multimetastatic (>3 metastatic lesions). RESULTS: The mean age of patients was 66.8 ± 7.6 years. Imaging modality was PET/MR in 223 (73.8%) and PET/CT in 79 (26.2%) of patients. Total PSA, PSA density (PSAD), ALP, and tumor ratio in biopsy specimens were found to be significantly higher in "PET positive" group compared to "PET negative" group and in multimetastatic group compared to oligometastatic group. PET positivity was observed in 3.8% of the low-intermediate risk groups (ISUP 1-3 and total PSA ≤ 20 ng/ml and PSAD < 0.15 ng/ml/cc). This ratio was 46% in the high-risk group (ISUP 4-5 or total PSA > 20 ng/ml or PSAD ≥ 0.15 ng/ml/cc) with a relative risk of 12 (p < .001). The prediction models to predict the PET positivity and the presence of distant metastasis had AUCs of 0.901 and 0.925, respectively; with ALP, total PSA, and tumor ratio in needle biopsy specimen as significant independent predictors (p < .05). CONCLUSIONS: In this study, 68 Ga-PSMA-11 PET positivity was significantly higher in the high-risk patient group than in the low-intermediate risk groups. The prediction models used for predicting the PET positivity and the presence of distant metastasis on PET imaging were successful with high discriminatory powers. In addition to total PSA and ISUP GG, ALP and tumor ratio in biopsy specimens can be used to identify high-risk patients.

Relation between Cajal Cell Density and Radiological and Scintigraphic Outcomes in Patients with Ureteropelvic Junction Obstruction.

INTRODUCTION: In this study, we aimed to investigate the correlation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters in ureteropelvic junction obstruction (UPJO). METHODS: The study group consisted of 41 renal units (38 consecutive patients; 13 female and 25 male) surgically treated for UPJO. UPJ specimens from patients were immuno-stained with CD117 (c-kit) antibody for interstitial Cajal cells (ICCs). The relation between Cajal cell density and preoperative and postoperative radiological and scintigraphic parameters was evaluated. RESULTS: The mean age of the patients was 8.52 ± 8.86 (0-35) years. The density of Cajal cells was defined in 2 groups for convenient analysis as 0-5 cells (low) in 19 (46.3%) patients and >5 cells (moderate-high) in 22 (53.6%). There was significant difference between the preoperative and postoperative anteroposterior diameters of the related kidneys in both Cajal groups (p = 0.001-low, p = 0.000-moderate-high) independent of Cajal cell density. Regression in hydronephrosis postoperatively was determined in both Cajal groups (77.8%-low, 64.7%-moderate-high); however, there was no difference between them (p = 0.39). Preoperative T1/2 was significantly longer in the low Cajal group (p = 0.02). Postoperative T1/2 decreased in both low (p = 0.000) and moderate-high (p = 0.001) Cajal groups, but no difference was found between them (p = 0.24). There was significant improvement in the kidney differential function after surgery in the low Cajal density group (p = 0.015) while there was no correlation between the scintigraphic success or improvement and Cajal cell density (p = 0.51). DISCUSSION/CONCLUSION: ICC deficiency/density could not be shown as a predictive factor for the determination of success rate of pyeloplasty. Despite the lack of any evidence for the degree of deficiency as an indicator for the severity of obstruction and prediction of surgical success, further studies are needed for confirmation.

Ezrin is a prognostic biomarker in patients with clear cell metastatic renal cell carcinoma receiving sunitinib.

OBJECTIVE: Sunitinib is a novel oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities. This study evaluates ezrin expression in sunitinib-treated metastatic clear cell renal cell carcinoma (ccRCC) patients and elucidates its role as a possible marker for survival. MATERIALS AND METHODS: The expression of ezrin was measured by immunohistochemistry in 80 patients with ccRCC treated by first-line sunitinib between January 2007 and June 2012. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on the survival. RESULTS: In multivariate analysis, liver metastasis (P = 0.018; hazard ratio [HR]: 3.707 (1.257-10.931) and overexpression of ezrin (P = 0.006; HR: 2.993 (1.373-6.523 95% confidence interval) were remained significant factors influencing OS. Overexpression of ezrin in the patients who had progressed in the first 3 months was higher than in the patients who had progressed after 3 months (P = 0.003). The median OS was longer in patients with low levels of ezrin expression (27 months) compared to patients overexpressing ezrin (12 months) (P = 0.001). CONCLUSION: This is the first study in the literature showing that ezrin status is related with prognosis in patients with metastatic ccRCC.

Diagnostic accuracy of 68 Ga-PSMA PET/MRI and multiparametric MRI in detecting index tumours in radical prostatectomy specimen.

OBJECTIVE: To evaluate the diagnostic accuracy of the 68 gallium (68 Ga) prostate-specific membrane antigen (PSMA) positron emission tomography/magnetic resonance imaging (PET/MRI) and multiparametric MRI (mpMRI) by region-based comparison of index tumour localisations using histopathological tumour maps of patients who underwent radical prostatectomy because of clinically significant prostate cancer. PATIENTS AND METHODS: The study included 64 patients who underwent radical prostatectomy after primary staging with mpMRI and 68 Ga-PSMA PET/MRI. Diagnostic analysis was performed by dividing the prostate into four anatomic regions as left/right anterior and left/right posterior. The extension of the lesions in mpMRI and the pathological uptake in 68 Ga-PSMA PET/MRI were matched separately for each region with the extension of the index tumour into each region. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and the accuracy of mpMRI and 68 Ga-PSMA PET/MRI are shown as 55.7%, 91.8%, 80.6%, 77.2%, 78.1%, and 60.8%, 94.3%, 86.8% 79.8%, 83.5%, respectively. 68 Ga-PSMA PET/MRI has higher sensitivity and specificity compared with mpMRI. However, no statistically significant difference was found (P = .464). Combined imaging had significantly higher diagnostic accuracy compared with mpMRI and 68 Ga-PSMA PET/MRI (change in AUC: 0.084 and 0.046, P < .001 and P = .028, respectively), while no statistically significant difference was found between mpMRI and 68 Ga-PSMA PET/MRI (change in AUC: 0.038, P = .246). CONCLUSION: 68 Ga-PSMA PET/MRI had higher clinical diagnostic accuracy in prostate cancer compared with mpMRI. Diagnostic accuracy was significantly increased in the combined use of both imaging modalities.

Kidney biopsy in the elderly: diagnostic adequacy and yield.

PURPOSE: The number of kidney biopsies (KB) performed in elderly patients has been increasing. Safety and usefulness of elderly KB have been well established, whereas much less is known about diagnostic adequacy and yield in this patient population. METHODS: We performed a retrospective study of KBs in 428 patients from April 2015 to December 2017 at an academic institution. We compared KB from 50 patients aged over 64 (elderly) with KB from 378 patients aged between 18 and 64. RESULTS: Gender ratio, body mass index, systolic and diastolic BP, creatinine values, incidences of AKI at the time of biopsy, INR/aptt values, and platelets were similar between the two groups. eGFR and number of transplant biopsies were lower in the elderly biopsy group. The glomerular yield was similar between the two groups (22 ± 14 vs. 22 ± 13, p = 0.869). The likelihood of obtaining more than ten glomeruli was 87% and 88%, respectively, without a significant difference. Inadequate samples were encountered in 6% of the elderly and 5.6% of the non-elderly KB, again without a significant difference. Samples taken by nephrologist had higher glomerular yield for both groups (25 ± 13 vs. 18 ± 12 overall, 26 ± 14 vs. 18 ± 14 for elderly, p < 0.001 both). Inadequate biopsies were lower in the nephrologist group when all patients were considered (3% vs. 9%, p = 0.025). Results were numerically similar for the elderly patients, but the difference was not statistically significant (2% vs. 8%, p = 0.322). No deaths occurred in both arms. Minor complications were not different for each group (4.5% vs. 4%). There were no major complications in elderly patients. However, the difference did not reach statistical significance. CONCLUSION: The world is aging, leading to an increased number of KB in older patients. KB in the elderly is a safe, effective, and an indispensable tool for the nephrologist. This study suggests there is no need to fear lower diagnostic adequacy in the decision making of a KB for an elderly patient.

Clinicopathological significance of insulin-like growth factor-1 receptor expression in breast cancer.

OBJECTIVE: Insulin-like growth factor 1 receptor (IGF1R) is a receptor protein tyrosine kinase that is claimed to be related with tumor development and progression of breast cancer with some conflicting results in the literature. The aims of the study are to investigate expression of IGF1R, and correlate with clinicopathological parameters to clarify the significance of IGF1R on breast cancer. MATERIAL AND METHODS: IGF1R and Ki67 were applied immunohistochemically to the tissue microarray sections of 370 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings [ER, PR, HER2, CK5/6, and CK14] statistically. RESULTS: IGF1R overexpression showed direct correlation with Ki67 index (P=0.028), HER2 positivity (P=0.001), mitotic count (P=0.004), tumor grade (P=0.015), and geographic necrosis (P=0.023); and negative correlation with ER positivity (P=0.003). There was statistically significant difference between IGF1R expression and the molecular subtypes (P<0.001), mostly HER2+ phenotype. IGF1R expression was found to be higher in invasive ductal carcinoma (IDC) than invasive lobular carcinoma (ILC) (P=0.036). Both IGF1R and Ki67 expression were negatively correlated with disease-free survival (DFS) (P=0.020, P=0.023, respectively) and overall survival (OS) [P<0.001, each] rates. The inverse association between IGF1R overexpression and OS rate was also supported by multivariate analyses (P=0.025). CONCLUSIONS: Overexpression of IGF1R was found to be directly correlated with shorter DFS and OS as well as some clinicopathological features associated with adverse prognosis such as higher Ki67 index, mitotic count, tumor grade, presence of geographic necrosis, HER2 positivity, ER negativity, HER2+ molecular subtype, histological tumor type of IDC rather than ILC. Thus, IGF1R might be considered as an useful target for comprehensive future anti-tumor therapy investigations. Additionally, using IGF1R as well as Ki67 as a part of routine pathology practice might be fruitful in breast cancer therapy and prediction of prognosis. KEY WORDS: Breast carcinoma, IGF1R, Insulin-like growth factor-1 receptor, Immunohistochemistry, Prognosis.

Is it possible to prevent contrast-induced nephropathy with dexpanthenol?

PURPOSE: Contrast-induced nephropathy (CIN) is one of the side effects of diagnostic procedures. Oxidative stress plays an important role in CIN's pathophysiology. Dexpanthenol (Dexp) is a substance with antioxidant efficacy. We investigated the likely protective effects of dexpanthenol for CIN. METHODS: Twenty-four Sprague-Dawley rats were divided randomly into four groups of 6 rats; control (group 1), Dexp (group 2), CIN (group 3) and Dexp + CIN (group 4). All rats were restricted of water moderately to facilitate of nephrotoxicity. Dexp was administered into the intraperitoneally at a dose of 500 mg/kg for 5 days in groups 2 and 4. The same amount of saline was applied via intraperitoneally to group 1 and 3. In CIN and Dexp + CIN groups, L-NAME (10 mg/kg), tenoxicam (0.5 mg/kg) and sodium amidotrizoate (10 ml/kg) were administered on the 4th day via the tail vein for CIN. All rats were euthanized on the 6th day and samples for biochemical and pathological evaluations were collected. RESULTS: When the Dexp + CIN group and the CIN group were compared, it was found to be provide a significant decline at the level of acute tubular injury and necrosis in kidney biopsies by dexp. Furthermore Dexp significantly reduced the serum cystatin C (Cys-C) levels, not serum creatinine. There was no statistically significant difference between the groups in total oxidant and antioxidant levels. CONCLUSIONS: Dexpanthenol did not have significant effect on oxidative stress of acute kidney injury on this rat model. However, it has ameliorated serum Cys-C levels and histopathological findings of CIN.

The effect of adipocyte-macrophage crosstalk in obesity-related breast cancer.

Adipose tissue is the primary source of many pro-inflammatory cytokines in obesity. Macrophage numbers and pro-inflammatory gene expression are positively associated with adipocyte size. Free fatty acid and tumor necrosis factor-α involve in a vicious cycle between adipocytes and macrophages aggravating inflammatory changes. Thereby, M1 macrophages form a characteristic 'crown-like structure (CLS)' around necrotic adipocytes in obese adipose tissue. In obese women, CLSs of breast adipose tissue are responsible for both increase in local aromatase activity and aggressive behavior of breast cancer cells. Interlinked molecular mechanisms between adipocyte-macrophage-breast cancer cells in obesity involve seven consecutive processes: Excessive release of adipocyte- and macrophage-derived inflammatory cytokines, TSC1-TSC2 complex-mTOR crosstalk, insulin resistance, endoplasmic reticulum (ER) stress and excessive oxidative stress generation, uncoupled respiration and hypoxia, SIRT1 controversy, the increased levels of aromatase activity and estrogen production. Considering elevated risks of estrogen receptor (E2R)-positive postmenopausal breast cancer growth in obesity, adipocyte-macrophage crosstalk is important in the aforementioned issues. Increased mTORC1 signaling in obesity ensures the strong activation of oncogenic signaling in E2Rα-positive breast cancer cells. Since insulin and insulin-like growth factors have been identified as tumor promoters, hyperinsulinemia is an independent risk factor for poor prognosis in breast cancer despite peripheral insulin resistance. The unpredictable effects of adipocyte-derived leptin-estrogen-macrophage axis, and sirtuin 1 (SIRT1)-adipose-resident macrophage axis in obese postmenopausal patients with breast cancer are unresolved mechanistic gaps in the molecular links between the tumor growth and adipocytokines.

Ewing's sarcoma of kidney in a 60-year-old patient with local recurrence: A rare occurrence.

Ewing's family of tumors is aggressive tumors and frequently arises from bone and soft tissue. They might also arise from nonosseous structures such as gastrointestinal tract, adrenal glands, or kidney. Primary renal Ewing's sarcoma (ES)/primitive neuroectodermal tumor is an extremely rare entity which has aggressive clinical course. These high-grade malignant tumors predominantly affect adolescents and young adults. Patients mostly present with nonspecific symptoms such as pain, hematuria, mass, and sensitivity. It is confused with renal cell cancer in imaging techniques. The definitive diagnosis is based on the histopathological examination. Surgical or radiotherapy treatment is used for local control and multiagent chemotherapy used for systemic treatment. Despite all treatment options, prognosis is poor. We aimed to describe the diagnosis and follow-up and treatment of renal ES case that was considered as renal cell carcinoma in imaging but diagnosed as ES via histopathology.

Immunohistochemical expression profiles of MUC1 and MUC2 mucins in urothelial tumors of bladder.

BACKGROUND: Mucins may show aberrant expression, localization, and/or glycosylation in multiple malignancies. However, information regarding expression of these mucins is mostly unknown in urothelial tumors. AIM: This study was conducted for examining the expressions of membrane associated and secreted mucin (MUC1) and a secreted gel-forming mucin (MUC2) in urothelial tumors of the urinary bladder. SUBJECTS AND METHODS: Archival transurethral resection materials of 97 urothelial carcinoma cases were reexamined light microscopically and graded according to the 2004 WHO Classification. Pathological stage was given as pTa, pT1, and pT2. Demonstrative sections were recut for immunohistochemistry for MUC1 and MUC2. The results were statistically analyzed, and P < 0.05 was considered statistically significant. RESULTS: The positivity for MUC1 and MUC2 was 89.7% and 44.3%, respectively. Independent from pathological stage of the tumor, MUC1 expression showed statistically significant correlation with tumor grade (P < 0.05). We did not find any correlation between pathological stage and MUC1 and MUC2 expression (P > 0.05). MUC1 staining pattern in papillary urothelial neoplasm of low malignant potential cases was more commonly apical and superficial (luminal cell layer only). Intermediate cells ± basal cells or isolated cells or islands of tumor cells with cytoplasmic and/or circumferential membrane positivity for MUC1 and MUC2 were more commonly observed in both low- and high-grade carcinomas. The difference between groups in terms of MUC1 and MUC2 staining was statistically significant (P < 0.05). CONCLUSIONS: The staining patterns of both mucins are different between urothelial papillary tumors and may be used to make a differentiation, especially for low-grade papillary urothelial lesions. This difference may also be important in the carcinomatous transformation of urothelial neoplastic and preneoplastic lesions.