Low-Grade Injury following Testicular Torsion: A Multicenter Study Confirming a Disturbing Possibility.

INTRODUCTION: There is an ongoing debate whether to perform orchiectomy or orchidopexy following testicular torsion (TT) in cases where the testis seems non-viable. The main problem is lack of objective criteria defining testicular viability. The aim of this study was to investigate the grade of injury in orchiectomy specimens obtained from cases of TT and its association with clinical findings. METHODS: This multicenter retrospective study involved double-blinded reassessment of the patient files and the pathological specimens using Mikuz classification to analyze the relation between clinical and pathological findings. RESULTS: A total of 289 patient charts from 14 centers were reviewed and 228 were included in this study. Twenty (8.8%) patients had grade 1 injury which refers to reversible injury. The clinical findings of these 20 patients were compared to 208 patients with higher grades of injury. As expected, there was statistically significant difference regarding duration of symptoms (p < 0.001); however, range was wide in both groups (as long as 96 h for grade 1 and as short as 7 h for higher grades). There was no statistically significant difference in any other variable including age (median 14 for both, p = 0.531), symptoms (pain: 19/20 vs. 189/202, p = 0.801; swelling: 13/19 vs. 168/197, p = 0.094), absence of blood flow in Doppler US (15/19 vs. 164/197, p = 0.635), or degree of torsion (median 720° for both, p = 0.172). CONCLUSION: Our study revealed necessity for better criteria to define viability of testis following TT. Histopathological injury appeared to be reversible even in some patients with more severe perioperative findings, late admission, or high degree of twisting. Our findings support the tendency for testicular fixation instead of orchiectomy as none of the clinical or perioperative findings could be attributed to high-grade injury.

Modified histopathological classification with age-related glomerulosclerosis for predicting kidney survival in ANCA-associated glomerulonephritis.

BACKGROUND: The histopathological classification of ANCA-GN divides patients into four groups based on signs of glomerular injury. However, this classification did not consider age-related glomerulosclerosis. In this study, we aimed to compare the prediction of renal survival between Berden's ANCA-GN histopathological classification and ANCA-GN histopathological classification modified with age-related glomerulosclerosis. METHODS: Between January 2004 and December 2019, 65 patients diagnosed with ANCA-GN were enrolled. Demographic, laboratory, and histopathologic findings were retrospectively analyzed. Renal survival analyses were compared according to classical and modified ANCA-GN histopathological classifications. Multivariate Cox regression analysis for the factors affecting renal survival was performed. RESULTS: In Berden's ANCA-GN histopathological classification, 15 patients were in the focal group, 21 in the crescentic, 21 in the sclerotic, and 8 in the mixed group. The ANCA-GN histopathological classification model generated statistically significant predictions for renal survival (p = 0.022). When the histopathological classification was modified with age-related glomerulosclerosis, eight of the nine patients previously classified in the sclerotic group were classified in the mixed and one in the crescentic groups. Modification of histopathological classification with age-related glomerulosclerosis increases the statistical significance in renal survival analysis (p = 0.009). The multivariate Cox regression analysis showed that the disease-related global sclerotic glomeruli percentage and serum creatinine level were significant independent factors. CONCLUSION: Modification of Berden's ANCA-GN histopathological classification model with age-related glomerulosclerosis may increase the statistical significance of the histopathological classification model.

Investigation of VHL gene associated with miR-223 in clear cell renal cell carcinoma.

BACKGROUND: Clear cell type renal cell carcinoma (ccRCC) is the most common renal cell carcinoma (RCC). In this study, we examined the expressions of VHL and miR-223 in ccRCC patients׳ tissues to investigate the possible role in the development of ccRCC. METHODS AND RESULTS: This study collected five expression profiles (GSE36139, GSE3, GSE73731, GSE40435, and GSE26032) from Gene Omnibus Data. Expressions of VHL and miR-223 in paraffinized tumor and normal tissues of 100 Turkish patients' ccRCC tissues were determined by bioinformatic data mining and real-time quantitative polymerase chain reaction (qRT-PCR). The VHL gene was subjected to mutational analysis by DNA sequencing, and pVHL was analyzed using western blotting. Our study's t-test and Pearson correlation analysis showed that VHL gene expression in tumoral tissues with a - 0.39-fold decrease was not significantly lower than normal tissues (p = 0.441), and a 0.97-fold increase miR-223 (p = 0.045) was determined by real-time PCR. Also, as a result of DNA sequence analysis performed in the VHL gene, it was found that 26% of the patients have mutations. The mutations for (VHL):c.60C>A (p.Val20=) and (VHL):c.467delA (p.Tyr156Leu) was detected for the first time in Turkish patients. CONCLUSIONS: The present study demonstrated that the differences in the expression levels of miR-223 have the potential to be biomarkers to determine the poor prognosis in ccRCC.

RNA-based markers in biopsy cores with atypical small acinar proliferation: Predictive effect of T2E fusion positivity and MMP-2 upregulation for a subsequent prostate cancer diagnosis.

BACKGROUND: Atypical small acinar proliferation (ASAP) is a precursor lesion of prostate cancer (PC), and PC develops from this suspicious focus or an unsampled malignant gland nearby. However, PC-related molecular alterations that could guide the timing of repeat biopsies and help monitor PC risk in ASAP-diagnosed patients have not been investigated. The purpose of this study was to first investigate the expression of seven different PC-related RNAs that included serine 2 (TMPRSS2): erythroblastosis virus E26 oncogene homolog (ERG) gene (TMPRSS2-ERG, T2E) fusion, alpha-methylacyl-CoA racemase (AMACR), kallikrein related peptidase 3 (KLK3), androgen receptor (AR), prostate cancer specific antigen 3 (PCA3), and matrix metalloproteinases (MMP)-2 and 9. METHODS: PC-related RNAs were evaluated using a real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) system in pathologically ASAP-diagnosed prostate biopsy cores from 55 patients presenting with a normal digital rectal examination and a PSA level of 4-10 ng/mL. RESULTS: We detected that positive T2E fusion status (P = 0.013) and the expression of AMACR (P = 0.016), AR (P = 0.016) and MMP-2 (P = 0.013) were independently and significantly associated with PC risk in ASAP patients. There were also several statistically significant correlations between expression levels. Additionally, we demonstrated that T2E fusion positive ASAP patients with higher MMP-2 expression were more likely to be diagnosed with PC at a subsequent biopsy during the follow-up period (P = 0.003). CONCLUSIONS: Although, more clinical validations are needed for the stratification of PC risk in ASAP-diagnosed biopsy cores, our current results indicate that the coexistence of T2E fusion positivity with MMP-2 upregulation may help clinicians adjust their biopsy timetable and/or assessment of PC risk in ASAP-diagnosed patients with a PSA level of 4-10 ng/mL.

N-cadherin expression in primary and metastatic testicular germ cell tumors.

PURPOSE: Upregulation of N-cadherin in epithelial tumor cells has been reported to enhance the invasive process. Although the distribution of N-cadherin in the normal testis was demonstrated, there is no adequate information regarding its presence in testicular germ cell tumors (GCTs). Our purpose was to examine the expression and localization of N-cadherin in germ cell tumors of the testis and share our experience. METHODS: 104 adult cases of primary and metastatic testicular GCTs, 5 germ cell neoplasia in situ and 15 benign testicular tissues were included into the study and analyzed for immunoexpression of N-cadherin. Positive expression was evaluated according to intensity and localization of the staining. RESULTS: In 34 pure seminomas, 6 seminomas of mixed component and 16 metastatic seminomas, N-cadherin expression was observed with variable staining intensity. Two pure yolk sac tumors and 20 out of 34 mixed GCTs with yolk sac components were positive for N-cadherin. In contrast, neither the embryonal and chorionic carcinomas nor the teratomas showed N-cadherin expression. CONCLUSIONS: N-cadherin immunexpression should be interpreted considering both staining intensity and extent. In case of a metastatic tumor of unknown primary showing prominent N-cadherin expression, seminoma should be considered in the differential diagnosis. At the same time Ncadherin staining could be used to differentiate seminomas from embryonal carcinomas with solid components in metastatic GCTs, both having similar histopathological findings. On the other hand, the diagnostic value is not obvious for nonseminomatous tumors.

Hepatotoxicity associated with eculizumab in a patient with atypical hemolytic uremic syndrome / Hepatotoxicidad asociada con eculizumab en un paciente con síndrome urémico hemolítico atípico

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Urothelial Carcinoma of the Bladder in Pediatric Patient: Four Case Series and Review of the Literature

Background: Urothelial carcinoma of the bladder is a rare condition in children, and most cases in this age group are noninvasive and low-grade. However, no follow-up protocol has been defined for this patient group. The objective of this study was to draw attention to bladder tumors in children and focus on the current recommendations for postoperative follow-up along with a case study of four patients. Case Report: Four patients aged <18 years with urothelial carcinoma who were treated in our clinics between 2001 and 2015 were retrospectively evaluated. The results were compared with those of published pediatric case series in the literature. No abnormalities were found in the patients' physical examinations and laboratory analyses, except hematuria (microscopic or macroscopic). Ultrasonography was used in all the patients to detect lesions in the bladder. Surgical resections were performed endoscopically, except in one patient. Histopathological evaluations revealed low-grade superficial urothelial carcinoma. No recurrence or complication was observed for all patients. Conclusion: Although rarely encountered during childhood, urothelial carcinoma should be considered as a differential diagnosis in pediatric patients with hematuria.

Significance of amyloid A immunoexpression in the prognosis of renal cell carcinoma.

The study investigated immunoexpression of amyloid A (AA) in clear cell renal cell carcinoma (CCRCC) and evaluated its clinicopathologic correlation, particularly in disease progression. Expression of AA protein was evaluated in patients with CCRCC by immunohistochemistry. 146 cancerous tissue samples from 86 male and 60 female patients were studied. The relationship between AA protein expression and TNM stage, nuclear grade, renal capsule invasion, perirenal invasion, and survival of the patients were assessed. Thirty four percent of CCRCC cases were AA positive. The positive AA immunoexpression was related to higher Fuhrman nuclear grade, presence of perirenal invasion of the tumor, and poor survival of patients with CCRCC. There was not any statistically significant difference between patients' gender, status of capsule invasion, and stages of the tumor in terms of AA immunoexpression. Tumor stage (Hazard ratio (HR) = 7.76 (95% CI: 2.43-24.8) for stage 3 and HR = 29.9 (95% CI: 6.97-128.32) for stage 4) and AA immunoexpression (HR = 2.16 (95% CI: 1.01-4.64) were found to be associated with survival of the patients with CCRCC in Cox regression analysis. Immunoexpression of AA was increased in high grade CCRCCs. Immunoexpression of AA was associated with poor survival in patients with CCRCC. Thus, AA staining might be used as a useful immunohistological marker for the prediction of poor prognosis in renal cell cancer.

CDX2 immunostaining in primary and metastatic germ cell tumours of the testis.

Objective To evaluate the immunohistochemical staining pattern of caudal type homeobox 2 (CDX2) protein in germ cell tumours (GCTs) of the testis. Methods This study reassessed archival tissue samples collected from patients diagnosed with primary and metastatic testicular GCTs for CDX2 immunoreactivity using standard immunohistochemical techniques. Positive nuclear immunostaining was evaluated with regard to both the staining intensity and the extent of the staining. Results Tissue sections from primary and metastatic testicular GCTs ( n = 104), germ cell neoplasia in situ (GCNis) ( n = 5) and benign testicles ( n = 15) were analysed. The GCNis and benign testicular tissues showed no immunoreactivity for CDX2. Strong and diffuse staining of CDX2 was demonstrated only in the mature colonic epithelium of teratomas in both primary and metastatic GCTs. CDX2 positivity in other tumours (one pure yolk sac tumour, one yolk sac component of a mixed GCT and one pure seminoma) was infrequent, and was only weak and focal. Conclusions CDX2 immunostaining should be interpreted based on both the staining intensity and the extent of staining so as not to cause misdiagnosis. Teratomas with colonic-type epithelium should be considered in the differential diagnosis if a metastatic tumour with an unknown primary shows prominent CDX2 immunostaining.