Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (˃2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P<0.01). In network and toxicity analyses, these genes associated with activated mitogen-activated protein kinase, the Akt/phosphatidylinositol 3-kinase pathway, and proinflammatory cytokines that cause renal injury and oxidative stress. Additionally, expression of proinflammatory cytokines, numbers of immune cells, and cellular apoptosis increased in RP tissue. This study establishes an association between genes related to renal dysfunction, proinflammation, oxidative stress, and ion transport and RP development in CaOx SFs.
RESULTSIn the 63 non-palpable testes, MRI identified 22% (14/63) as intra-abdominal, 20% (13/63) as intra-canalicular, 29% (18/63) as testicular nubbins, and 29% (18/63) as unidentifiable. Although it was difficult to confirm their presence in the abdominal cavity using T1-and T2-weighted imaging alone, additional assessment, including fatsuppressed T2-weighted imaging and DWI facilitated the detection of intra-abdominal testes more easily because they were imaged at a markedly higher signal intensity. The sensitivity, specificity and positive and negative predictive values for the MRI vs the operative findings were 100, 97.3, 96.3, and 100%, respectively. The overall prediction accuracy was 98.4%. CONCLUSIONAdditional MRI assessments, fat-suppressed T2-weighted imaging and DWI are useful examinations to improve the preoperative diagnostic accuracy of non-palpable testes. KEYWORDS MRI, diffusion MRI, diagnostic imaging, cryptorchidism, vanishing testisWhat's known on the subject? and What does the study add? Both conventional magnetic resonance imaging (MRI) and ultrasonography (US) have been used for children with non-palpable testes to facilitate a preoperative diagnosis, but the accuracy of these examinations was not satisfactory. In the present study, to improve the diagnostic accuracy of non-palpable testes by MRI examination, we employed fatsuppressed T2-weighted imaging and DWI, as well as conventional MRI. Additional MRI assessments are useful methods to improve the accuracy of diagnosing non-palpable testes.Study Type -Diagnostic (exploratory cohort) Level of Evidence 2b OBJECTIVETo evaluate the magnetic resonance imaging (MRI) findings, diagnostic accuracy and clinical usefulness of fat-suppressed T2-weighted and diffusion-weighted imaging (DWI) in the management of non-palpable testes. PATIENTS AND METHODSIn all, 56 children (63 non-palpable testes) aged 8 months-11 years (mean 24.7 months) with non-palpable testes were enrolled. T1-and T2-weighted imaging, as well as fatsuppressed T2-weighted imaging and DWI were performed during MRI examination, and the imaging results were compared with surgical findings.
In cryptorchid testes there is a decreased number of spermatogonial stem cells in which FoxO1 is activated, indicating that failure of spermatogonial stem cell maintenance results in spermatogenesis alteration. We also noted interaction between miR-135a and FoxO1, and propose that miR-135a contributes to spermatogonial stem cell maintenance through modulation of FoxO1 activity.
What’s known on the subject? and What does the study add? Testicular torsion results in atrophy rates of more than 25% despite prompt surgical management, and there is no reliable intraoperative critieria to judge the viability of the testis, except the testicular appearance after scrotal incision. We demonstrated that less reduction of ITP after detorsion correlated with worse subsequent spermatogenesis. This result suggests that ITP can be the index to determine removal of the affected testis during surgery. OBJECTIVE • To assess the correlation between intratesticular pressure (ITP) after testicular torsion and subsequent testicular function using a rat model and to show that ITP at surgery is a useful predictor of future spermatogenesis. MATERIALS AND METHODS • Fourteen rats were divided into a torsion group (n= 7) and a control group with sham operation (n= 7). • Torsion was created by 720° rotation of the left testis in a counter‐clockwise direction. • Using a handheld compartment monitor, the ITP of the torsed testes was measured three times: before torsion (pre‐torsion), just before torsion repair (pre‐detorsion) and 5 min after torsion repair (post‐detorsion). • We evaluated the correlation between ITP and testicular weight, epididymal sperm count or pathological findings, such as the seminiferous tubule diameter (STD) and the modified Johnsen’s score, 4 weeks after surgery. RESULTS • Mean (se) pre‐torsion, pre‐detorsion and post‐detorsion ITP values in the torsion group were 5.9 (2.5), 19.7 (10.7) and 8.2 (4.8) cm H2O, respectively. • The ITP in torsed testes significantly increased after torsion (P < 0.01) and decreased after detorsion (P < 0.01). • Strong correlations were observed between the reduction of ITP after detorsion and testicular weight (r= 0.87, P < 0.05), epididymal sperm count (r= 0.94, P < 0.05), STD (r= 0.87, P < 0.05) or the Johnsen’s score (r= 0.99, P < 0.001). CONCLUSION • A smaller reduction in ITP after detorsion can be a risk factor for subsequent disturbance of spermatogenesis, suggesting that ITP can be an index for determining whether the affected testis should be removed after testicular torsion.
We report a case of recurrent advanced urachal carcinoma with right internal iliac node and left lung metastases in a 34-year-old man. After receiving partial cystectomy including en bloc resection of the urachus and with bilateral pelvic lymph node dissection, he was treated with five courses of S-1 and cisplatin combination chemotherapy. He remains free from the disease after a 30-month follow-up period. S-1/cisplatin combination chemotherapy is suggested to be a potent tool for controlling advanced urachal carcinoma.
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