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Small-molecule inhibitors of PD-L1 are postulated to control immune evasion in tumors similar to antibodies that target the PD-L1/PD-1 immune checkpoint axis. However, the identity of targetable PD-L1 inducers is required to develop small-molecule PD-L1 inhibitors. In this study, using chromatin immunoprecipitation (ChIP) assay and siRNA, we demonstrate that vitamin D/VDR regulates PD-L1 expression in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells. We have examined whether a VDR antagonist, MeTC7, can inhibit PD-L1. To ensure that MeTC7 inhibits VDR/PD-L1 without off-target effects, we examined competitive inhibition of VDR by MeTC7, utilizing ligand-dependent dimerization of VDR-RXR, RXR-RXR, and VDR-coactivators in a mammalian 2-hybrid (M2H) assay. MeTC7 inhibits VDR selectively, suppresses PD-L1 expression sparing PD-L2, and inhibits the cell viability, clonogenicity, and xenograft growth of AML cells. MeTC7 blocks AML/mesenchymal stem cells (MSCs) adhesion and increases the efferocytotic efficiency of THP-1 AML cells. Additionally, utilizing a syngeneic colorectal cancer model in which VDR/PD-L1 co-upregulation occurs in vivo under radiation therapy (RT), MeTC7 inhibits PD-L1 and enhances intra-tumoral CD8+T cells expressing lymphoid activation antigen-CD69. Taken together, MeTC7 is a promising small-molecule inhibitor of PD-L1 with clinical potential.

Context.— Intraductal carcinoma of the prostate (IDC-P) is considered a distinct form of aggressive prostate cancer where comedonecrosis, a grade 5 pattern, is occasionally present. Meanwhile, assigning a Gleason grade to IDC-P remains controversial. Objective.— To assess the clinical significance of necrosis associated with IDC-P. Design.— We compared radical prostatectomy (RP) findings and oncologic outcomes in men with prostate cancer exhibiting IDC-P with (IDC-P+/N+) versus without (IDC-P+/N−) comedonecrosis. Results.— Of the 558 RPs examined, IDC-P was present in 213 cases (38.2%), including 167 (78.4%) with IDC-P+/N− and 46 (21.6%) with IDC-P+/N+. When comparing IDC-P+/N− versus IDC-P+/N+ cases, the presence of necrosis was significantly associated with higher tumor grade, higher incidence of pT3/pT3b or pN1 disease, and larger estimated tumor volume. Outcome analysis revealed a significantly higher risk of disease progression in IDC-P+/N+ patients than in IDC-P+/N− patients (P < .001). Significant differences in progression-free survival between IDC-P+/N− and IDC-P+/N+ patients were also seen in subgroups, such as those without (P = .01) or with (P = .03) adjuvant therapy immediately after RP, those with pN0 disease (P < .001), and, more interestingly, those exhibiting conventional Gleason pattern 5 component (P = .02). Multivariate analysis showed significance for IDC-P+/N+ when IDC-P (grade 4) and IDC-P+/N+ (grade 5) were (hazard ratio, 1.768; P = .049) or were not (hazard ratio, 2.000; P = .008) incorporated into the Gleason score. Conclusions.— IDC-P+/N+ was found to be associated with worse histopathologic features on RP and poorer prognosis as an independent predictor. Pathologists may thus need to report the presence or absence of not only IDC-P but also comedonecrosis within IDC-P.

Context.— Seminal vesicle invasion (SVI) by prostate cancer (pT3b disease) has been considered as a key prognostic factor. Objective.— To assess the clinical impact of T3a lesions (ie, extraprostatic extension other than bladder neck invasion [BNI] or SVI [EPE], microscopic bladder neck invasion [mBNI]) in pT3b disease. Design.— We compared radical prostatectomy findings and long-term oncologic outcomes in 248 patients with pT3b disease, with versus without EPE/mBNI. Results.— Extraprostatic extension/mBNI was found in 219 (88.3%)/48 (19.4%) cases, respectively. Extraprostatic extension was significantly associated with higher preoperative prostate-specific antigen (PSA) level, higher rates of positive surgical margin (pSM) and lymphovascular invasion (LVI), and larger tumor volume. Similarly, mBNI was significantly associated with higher PSA level, higher rates of Grade Group(s) 4-5 or 5, pSM, LVI, and pN1, and larger tumor volume. Significant differences in all of these clinicopathologic features (except lymph node metastasis) between EPE−/mBNI+ or EPE+/mBNI− and EPE+/mBNI+ cases were also observed. Outcome analysis revealed that patients with EPE (P < .001) or mBNI (P < .001) had a significantly higher risk of disease progression than respective controls. Notably, there were significant differences in progression-free survival between EPE−/mBNI+ or EPE+/mBNI− cases and EPE−/mBNI− (P = .001) or EPE+/mBNI+ (P < .001) cases. In multivariate analysis, EPE (hazard ratio [HR] = 6.53, P = .009) and mBNI (HR = 2.33, P = .003), as well as EPE−/mBNI+ or EPE+/mBNI− (HR = 11.7, P = .01) and EPE+/mBNI+ (HR = 25.9, P = .002) versus EPE−/mBNI−, showed significance for progression. Conclusions.— From these significant findings, we propose a novel pT3b subclassification: pT3b1 (SVI alone without EPE or mBNI), pT3b2 (SVI with either EPE or mBNI), and pT3b3 (SVI with both EPE and mBNI).

BACKGROUND: Androgen receptor (AR) activation has been implicated in the pathogenesis of urothelial cancer. However, it remains controversial whether 5α-reductase inhibitors (5α-RIs), which are known for blocking the conversion of testosterone to the more potent androgen dihydrotestosterone and often prescribed for the treatment of, for instance, benign prostatic hyperplasia, contribute to preventing the development of bladder cancer. OBJECTIVE: To determine the role of 5α-RI therapy in urothelial tumorigenesis and tumor progression, using cell line models. METHODS: In a human non-neoplastic urothelial SVHUC subline stably expressing a full-length wild-type human AR (SVHUC-AR) with carcinogen/MCA challenge and human bladder cancer lines, we assessed the effects of three 5α-RIs, dutasteride (up to 100 nM), finasteride (up to 500 nM), and epristeride (up to 5μM), on neoplastic/malignant transformation and cell growth, respectively. RESULTS: In AR-positive bladder cancer UMUC3 and 5637-AR cells, an AR antagonist bicalutamide significantly inhibited their proliferation, whereas three 5α-RIs failed to do. Similarly, these 5α-RIs did not significantly inhibit the migration of bladder cancer cells induced by the treatment of testosterone which could be metabolized into dihydrotestosterone in culture medium. In MCA-SVHUC-AR cells, induction of their neoplastic transformation by testosterone, which was prevented by bicalutamide, was confirmed. However, no significant inhibitory effects of 5α-RIs on the neoplastic transformation of AR-positive urothelial cells treated with or without testosterone were observed. CONCLUSIONS: Using in vitro models for urothelial cancer, 5α-RI treatment even at supra-pharmacological doses was thus found to have no significant impact on the prevention of both tumorigenesis and tumor progression.

OBJECTIVE To evaluate the impact of cancer therapy on post-treatment ejaculation in patients with testicular cancer. METHODS A total of 74 testicular cancer survivors provided completed International Index of Erectile Function-15 questionnaires before and after treatment between 2010 and 2017. Sexual function, particularly ejaculatory function, was evaluated before and after treatment. In this study, patients who answered "1 = almost never/never" or "2 = a few times" for questionnaire number 9 (ejaculation frequency) were defined as having "ejaculation disorder." RESULTS Of 74 testicular cancer survivors, 50 (68%) had no ejaculation disorders before treatment. Four (44%) of nine survivors, who received chemotherapy and retroperitoneal lymph node dissection, developed ejaculation disorders after treatment. On multivariate analysis, retroperitoneal lymph node dissection was a significant predictor of post-treatment ejaculation disorder (P = 0.042). Of 60 survivors with evaluable ejaculation function after treatment, 24 (40%) did not attempt sexual intercourse, and multivariate analysis showed ejaculation disorder had a significant negative impact on having sexual intercourse (P = 0.035). Furthermore, the mean International Index of Erectile Function-15 scores in the groups with and without ejaculation disorders after treatment were 24.0 and 51.9, respectively (P

We found that FOXO1-shRNA sublines or FOXO1-positive cells co-treated with a FOXO1 inhibitor were significantly more resistant to cisplatin treatment at pharmacological concentrations, compared with respective control sublines or those with mock treatment. Western blot demonstrated considerable increases in the expression levels of a phosphorylated inactive form of FOXO1 (p-FOXO1) in cisplatin-resistant sublines established by long-term culture with low/increasing doses of cisplatin, compared with respective controls. Immunohistochemistry in surgical specimens from patients with muscle-invasive bladder cancer undergoing cisplatin-based neoadjuvant therapy further showed a strong trend to associate between p-FOXO1 positivity and unfavorable response to chemotherapy.

Perineural invasion (PNI) by prostate cancer detected on systematic sextant biopsy (S-Bx) has been considered as a key prognosticator. However, the clinical significance of PNI on magnetic resonance imaging-targeted biopsy (T-Bx) needs to be further investigated. We assessed 169 patients undergoing T-Bx with concurrent S-Bx, followed by radical prostatectomy (RP) from 2015 to 2019. In all cases where cancer was detected on T-Bx only (n = 34) or both S-Bx and T-Bx (B-Bx; n = 135), PNI was found in 33 (19.5%) T-Bxs. Compared with no PNI, PNI on T-Bx was associated with higher Grade Group on biopsy/RP, higher pT stage, and lymph node metastasis. Outcome analysis revealed a significant difference in the risk of biochemical recurrence after RP between cases with and without PNI on T-Bx (P = 0.021). Next, in the 135 B-Bx cases, PNI was found on S-Bx only (n = 31), T-Bx only (n = 15), or B-Bx (n = 16). Compared with PNI on S-Bx, B-Bx PNI was associated with higher preoperative prostate-specific antigen, higher biopsy GG, higher pT stage, and larger tumor volume. There were no significant differences in any of the clinicopathologic features examined between cases with PNI on T-Bx only vs. B-Bx. Moreover, in this subgroup of patients, PNI on B-Bx was associated with significantly higher risks of biochemical recurrence, compared with PNI on S-Bx only (P = 0.024) or T-Bx only (P = 0.033). In multivariate analysis, PNI on B-Bx showed significance for recurrence (hazard ratio = 2.787, P = 0.034). The presence of PNI on T-Bx, particularly B-Bx, associated with worse histopathologic features on RP and poorer outcomes might thus be useful for risk stratification.

INTRODUCTION AND OBJECTIVE:We and others have indicated that androgen receptor (AR) signaling plays a critical role in urothelial cancer outgrowth. Meanwhile, our DNA microarray data suggest that l...

Bladder cancer (BCa), mostly urothelial carcinoma (UCa), is often a highly aggressive disease. According to the Surveillance, Epidemiology, and End Results (SEER) database, the 5-year relative surv...

Testicular cancer occurs in the testes of the male reproductive system and is the most common cancer in adolescent and young adult (AYA) men. However, recently, there have been more cases of testicular cancer in men older than 40 years. Therefore, trends of testicular cancer during the past 40 years were retrospectively examined, focusing on age and histology. Patients who were diagnosed with testicular cancer at our institution between 1980 and 2019 were enrolled in this study. The patients were divided into groups by the year of diagnosis (1980s, 1990s, 2000s, and 2010s), age at diagnosis (14, 15 to 39, and older than 40 years), and histological type (seminoma and non-seminoma). A total of 563 patients were diagnosed with testicular cancer over the 40-year period. The median age at diagnosis increased continuously, from 28 years to 31 years, 34 years, and 38 years in each period, respectively (p < 0.001). Moreover, most testicular cancer patients were of the AYA generation, whereas the ratio of patients older than 40 years increased significantly since 2000 (p < 0.001). The relative proportion of seminoma also increased more than 50% since 2000. In the seminoma group, median age increased from 31 years to 41 years during the 40-year period (p < 0.001). In conclusion, the age at diagnosis is rising for testicular cancer patients. Clinicians should recognize that testicular cancer affects not only the AYA generation, but there has been a shift to older than 40 years, especially in seminoma.

Simple Summary It remains unclear why chemotherapy is often ineffective in patients with bladder cancer. Meanwhile, we previously reported that male sex hormones (i.e., androgens) could considerably reduce the efficacy of cisplatin, an anti-cancer drug used as the first-line treatment against advanced bladder cancer. The present study aimed to investigate how androgen receptor signaling, which is activated by binding of androgenic hormones, modulates sensitivity to cisplatin treatment in bladder cancer, using cell line models and surgical specimens. We found that the expression levels of the androgen receptor and a molecule (BXDC2) were inversely correlated and that loss of BXDC2 was associated with cisplatin resistance. We thus provide evidence to suggest an underlying molecular mechanism responsible for androgen receptor-induced chemoresistance in bladder cancer. Abstract Underlying mechanisms for resistance to cisplatin-based chemotherapy in bladder cancer patients are largely unknown, although androgen receptor (AR) activity, as well as extracellular signal-regulated kinase (ERK) signaling, has been indicated to correlate with chemosensitivity. We also previously showed ERK activation by androgen treatment in AR-positive bladder cancer cells. Because our DNA microarray analysis in control vs. AR-knockdown bladder cancer lines identified BXDC2 as a potential downstream target of AR, we herein assessed its functional role in cisplatin sensitivity, using bladder cancer lines and surgical specimens. BXDC2 protein expression was considerably downregulated in AR-positive or cisplatin-resistant cells. BXDC2-knockdown sublines were significantly more resistant to cisplatin, compared with respective controls. Without cisplatin treatment, BXDC2-knockdown resulted in significant increases/decreases in cell proliferation/apoptosis, respectively. An ERK activator was also found to reduce BXDC2 expression. Immunohistochemistry showed downregulation of BXDC2 expression in tumor (vs. non-neoplastic urothelium), higher grade/stage tumor (vs. lower grade/stage), and AR-positive tumor (vs. AR-negative). Patients with BXDC2-positive/AR-negative muscle-invasive bladder cancer had a significantly lower risk of disease-specific mortality, compared to those with a BXDC2-negative/AR-positive tumor. Additionally, in those undergoing cisplatin-based chemotherapy, BXDC2 positivity alone (p = 0.083) or together with AR negativity (p = 0.047) was associated with favorable response. We identified BXDC2 as a key molecule in enhancing cisplatin sensitivity. AR-ERK activation may thus be associated with chemoresistance via downregulating BXDC2 expression in bladder cancer.

Vitamin-D receptor (VDR) mRNA is enriched in malignant lung, ovarian and pancreatic tissues and showed poor prognoses. Calcitriol and stable or CRISPR-directed VDR upregulation increased PD-L1mRNA and protein expression in cancer cells in-vitro. A ChIP assay showed the binding of VDR with VDREPD-L1. Stattic, a STAT3 phosphorylation inhibitor blocked calcitriol or VDR overexpression induced PD-L1 upregulation. MeTC7, a VDR antagonist developed by us, reduced PD-L1 expression on macrophages, ovarian, lung, breast, and pancreatic cancer cells in-vitro. In radiotherapy inducible PD-L1 model of orthotopic MC38 murine colon cancer, MeTC7 decreased PD-L1 surface expression, suppressed inflammatory monocytes (IMs) population and increased intra-tumoral CD69+PD1+CD8+T-cells. Intriguingly, MeTC7 reduced TH-MYCN transgenic neuroblastoma tumor growth without affecting PD-L1 and tumor immune milieu. In summary, Vitamin-D/VDR drives PD-L1 expression on cancer cells via STAT-3. Inhibiting VDR exhibited anti-checkpoint effects in orthotopic colon tumors, whereas PDL1-independent and anti-VDR/MYCN effects controlled growth of transgenic neuroblastoma and xenografted tumors.SummaryVitamin-D/VDR induces PD-L1 expression on cancer cells via STAT-3; and targeting VDR by a novel small molecule antagonist MeTC7 exhibits both anti-PD-L1 and anti-VDR/MYCN effects in tumor models.

We recently demonstrated that silodosin, a selective α(1)-blocker often prescribed for the symptomatic treatment of benign prostatic hyperplasia (BPH), could inactivate a c-fos proto-oncogene regulator ELK1 in bladder cancer cells possessing a functional androgen receptor (AR). However, the clinical impact of α(1)-blockers on the development and progression of bladder cancer remained poorly understood. In the present study, we investigated if α(1)-blockers clinically used, including silodosin, tamsulosin, and naftopidil, could prevent the neoplastic/malignant transformation and cell growth, using non-neoplastic urothelial SVHUC sublines with carcinogen/MCA challenge and bladder cancer lines, respectively. Bladder cancers in men treated with silodosin, tamsulosin, or naftopidil for their BPH were then compared. Silodosin at 1-10 µM significantly inhibited the neoplastic transformation of MCA-SVHUC-AR cells, but not that of AR-negative MCA-SVHUC-control cells. In MCA-SVHUC-AR, silodosin significantly reduced the expression levels of oncogenes (c-fos/NF-κB1) and induced those of tumor suppressors (p27/PTEN). However, tamsulosin (up to 1 µM) or naftopidil (up to 10 µM) failed to significantly inhibit the neoplastic transformation of AR-positive or AR-negative urothelial cells. Similarly, cell proliferation/migration of AR-positive bladder cancer lines was considerably inhibited only by silodosin. Meanwhile, the incidence of bladder cancer in patients with silodosin [49/540 (9.1%)] was marginally lower, compared to those with tamsulosin [64/523 (12.2%); P=0.094] or tamsulosin or naftopidil [64+28/523+236 (12.1%); P=0.082]. There were no significant differences in tumor grade/stage among the 3 cohorts. Outcome analysis revealed lower risks for disease progression of non-muscle-invasive bladder tumors in the silodosin group than in the naftopidil group (P=0.011) or tamsulosin+naftopidil groups (P=0.035). Similarly, silodosin patients with muscle-invasive tumor had lower risks for disease progression, compared with tamsulosin (P=0.006) or tamsulosin+naftopidil (P=0.028) patients. Multivariate analysis further showed that silodosin treatment in those with non-muscle-invasive tumor was associated with improved progression-free survival, compared with naftopidil (hazard ratio=0.086; 95% confidence interval=0.008-0.905; P=0.041) or tamsulosin/naftopidil (hazard ratio=0.128; 95% confidence interval=0.016-1.036; P=0.054) treatment. Our in vitro studies thus indicate that both urothelial tumorigenesis and tumor growth are inhibited by silodosin, but not by tamsulosin or naftopidil. Clinical data further suggest that even pharmacological doses (e.g. 0.1 µM) of silodosin contribute to preventing bladder cancer progression.

The efficacy of cisplatin-based chemotherapy in patients with bladder cancer is often limited due to the development of therapeutic resistance. Our recent findings in bladder cancer suggested that activation of prostaglandin receptors (

A steroid hormone receptor, mineralocorticoid receptor (MR), is well known to play a critical role in maintaining normal homeostasis in the body primarily via regulating ionic and water transports. Indeed, MR antagonists have been prescribed to the patients as diuretic drugs. Meanwhile, emerging evidence has indicated that MR signaling, with or without functional interplay with glucocorticoid receptor or androgen receptor, contributes to modulating the development and progression of several types of neoplasms including genitourinary malignancies. This review summarizes the available data suggesting the involvement of MR signaling in renal cell carcinoma, prostatic adenocarcinoma, urothelial carcinoma, and other malignancies, and highlights potential underlying molecular mechanisms.

Background Many elderly men suffer from benign prostatic hyperplasia (BPH). Recently, chronic ischemia in the prostate has been suggested to be related to BPH. Thus, the impact of chronic ischemia on the development of prostatic hyperplasia and the efficacy of phosphodiesterase type 5 (PDE5) inhibitor for hyperplasia were evaluated in a rat model with chronic ischemia induced by local atherosclerosis. Methods Eighteen male Sprague-Dawley rats were divided into three groups: sham operation, regular diet, placebo (SRP); arterial endothelial injury, high cholesterol diet, placebo (AHP); or arterial endothelial injury, high cholesterol diet, and tadalafil as a PDE5 inhibitor (AHT). The endothelial injury in the common iliac arteries was performed using a 2-Fr Fogarty arterial embolectomy catheter through an incision in the femoral artery into the common iliac artery. Diet and oral drugs were administrated for 8 weeks after surgery. At 8 weeks, blood flow to the ventral prostate (VP) was measured using laser speckle blood flow analysis, and the VP was histologically evaluated. Results In the AHP group, prostatic blood flow was reduced, and mean VP weight and the interstitial area were significantly enlarged compared with the SRP group. In the AHT group, tadalafil administration obviously ameliorated the reduction of prostatic blood flow relative to the AHP group. Importantly, mean VP weight and the morphological changes in the AHT group were significantly smaller than those in the AHP group. Conclusions Enlargement of the VP resulted from chronic ischemia induced by local arteriosclerosis. Also, administration of tadalafil attenuated VP enlargement. Chronic ischemia in the prostate might thus contribute to the development of BPH, and PDE5 inhibitors might provide an innovative approach to preventing BPH.

Androgen receptor (AR) and estrogen receptor-β (ERβ) have been implicated in urothelial tumor outgrowth as promoters, while underlying mechanisms remain poorly understood. Our transcription factor profiling previously performed identified FOXO1 as a potential downstream target of AR in bladder cancer cells. We here investigated the functional role of FOXO1 in the development and progression of urothelial cancer in relation to AR and ERβ signals. In non-neoplastic urothelial SVHUC cells or bladder cancer lines, AR/ERβ expression or dihydrotestosterone/estradiol treatment reduced the expression levels of FOXO1 gene and induced those of a phosphorylated inactive form of FOXO1 (p-FOXO1). In chemical carcinogen-induced models, FOXO1 knockdown via shRNA or inhibitor treatment resulted in considerable induction of the neoplastic transformation of urothelial cells or bladder cancer development in mice. Similarly, FOXO1 inhibition considerably induced the viability, migration, and invasion of bladder cancer cells. Importantly, in FOXO1 knockdown sublines, an anti-androgen hydroxyflutamide or an anti-estrogen tamoxifen did not significantly inhibit the neoplastic transformation of urothelial cells, while dihydrotestosterone or estradiol did not significantly promote the proliferation or migration of urothelial cancer cells. In addition, immunohistochemistry in surgical specimens showed that FOXO1 and p-FOXO1 expression was down-regulated and up-regulated, respectively, in bladder tumor tissues, which was further associated with worse patient outcomes. AR or ERβ activation is thus found to correlate with inactivation of FOXO1 which appears to be their key downstream effector. Moreover, FOXO1, as a tumor suppressor, is likely inactivated in bladder cancer, which contributes in turn to inducing urothelial carcinogenesis and cancer growth.

Prostate cancer patients with initial PSA 100 ng/ml or greater who received transrectal ultrasoundguided prostate biopsy and were staged as M0 by imaging studies from 2011 to 2014 in seven hospitals, were enrolled in the study. Castration-resistant prostate cancer (CRPC)-free survival was compared between the two treatment groups : androgen deprivation therapy (ADT) alone and ADT plus local therapy. Of 142 prostate cancer patients with initial PSA 100 ng/ml or greater, 49 (34.5%) had no metastases and final analysis was performed on 46 patients. Thirty one M0 patients received ADT alone, and 15 received ADT plus local therapy. During follow-up (median 31 months, range 1-56 months) 13 patients (42%) in the ADT alone group progressed to CRPC. One- and two-year CRPC-free survival rates were 72.5 and 53%, respectively. No patients with ADT plus local therapy developed CRPC, and time to CRPC was prolonged significantly (p=0.002). On multivariate analysis for the group with ADT alone, PSA nadir of more than 0. 2 ng/ml and cN1 were independent predictors for progression to CRPC (p=0.009, 0.031). About one third of prostate cancer patients with initial PSA 100 ng/ml or greater had clinically no metastases. Local therapy to prostate combined with ADT may prolong time to CRPC compared with ADT alone. A subset of men with a PSA nadir of more than 0.2 ng/ml after ADT and cN1 could benefit from local therapy.

A 44-year-old man discovered a swollen right testis more than 4 years earlier. He was brought to our hospital because of abdominal pain and vomiting. Enhanced computed tomography (CT) showed a swollen right testis, lung nodules, and swollen retroperitoneal and mediastinal lymph nodes. The swollen lymph nodes compressed the duodenum, causing ileus. HCG, HCG-β, and AFP levels were normal, but the LDH level was high (2,933 IU/L). A diagnosis of testicular cancer with lung and lymph node metastases was made, and a right orchidectomy was performed. However, the pathological diagnosis was unclear, and it was necessary to consult another pathologist, but this took .6 weeks. While awaiting the pathological diagnosis, the patient was given chemotherapy with two 3-week courses of BEP. On pathological examination, the tumor consisted of small round cells with a rosette-like arrangement. Cartilage and keratinized tissues were also present. Immunohistochemical staining was positive for CD56, synaptophysin, vimentin, GFAP, and CD99 (MIC2), but negative for AE1/AE3, OCT-4, chromogranin, INI-1, and desmin. The patient was then diagnosed as having a primitive neuroectodermal tumor and teratoma. The metastatic lymph nodes decreased in size after chemotherapy; therefore, two further courses of BEP were added. However, CT showed disease progression. The patient refused further therapy and returned home. Eight months later, he was hospitalized because of swollen retroperitoneal and mediastinal lymph nodes and ileus. Despite treatment with radiation therapy, which resulted in decreased lymph nodes, the patient died. This was a very rare case, the first such case in Japan.

Retrospective study To compare the accuracy of estimated serum creatinine (Cre)–based glomerular filtration rates (eGFRcre) and serum cystatin C (CysC)–based eGFR (eGFRcys) for determining renal function in patients with spinal cord injury (SCI). Department of Urology, Tohoku Rosai Hospital, Japan Male patients with SCI for longer than 5 years after injury were eligible for inclusion in this study. eGFRcre and eGFRcys were calculated using the following formulas: eGFRcre = 194 × Cre-1.094 × age-0.287; eGFRcys = (104 × CysC-0.1019 × 0.996age) − 8. The eGFRcre/eGFRcys ratio between 0.8 and 1.2 was considered to be equal, and a relationship between them was investigated. Demographic data, degree of spinal cord damage, management of bladder emptying, post-injury period, and ambulatory status were evaluated. A total of 115 male patients were included. eGFRcre overestimated renal function in 87 (76%) patients with SCI compared with eGFRcys. On univariate analysis, renal function by eGFRcre was overestimated in patients with an eGFRcre of more than 60 ml min-1 per 1.73 m2 (P