Double Primary Cancer of the Prostate and Urothelial Cancer: A Single Institution Experience.

Prostate cancer (PCa) ranks as the second most common cancer in Japanese males, while bladder cancer (BC) holds the tenth spot. Among double urological cancers, the incidence of synchronous or metachronous BC and PCa is the highest. Reports on upper urinary tract (UUT) urothelial cancer (UC) in PCa patients are limited. Here, we present three cases of metachronous PCa and BC, with subsequent diagnosis of ureteral and renal pelvic cancer during the course of the disease. In the follow-up of patients with urological cancers, it is important to be aware not only of the progression of the initial cancer but also the potential development of a second cancer.

The role of advanced practice nurses in improving healthcare outcomes for patients with chronic kidney disease: A scoping review protocol.

INTRODUCTION: The number of patients with chronic kidney disease is increasing worldwide; previous studies have suggested that advanced practice nurses, including nurse practitioners and clinical nurse specialists, with expert practice skills can provide high-quality care and solve complex healthcare problems. In general, nurse practitioners are generalist nurses who work as autonomous clinicians with whole personal care. Clinical nurse specialists, in contrast, are nurses with advanced nursing knowledge and skills for individuals or specific populations. Their roles are independent and different; however, similarities exist in their role in potentially improving healthcare outcomes. Although two previous studies described the role of nephrology nurse practitioners, they were systematic reviews, and their outcomes were limited. To clarify the overall aspect of advanced practice nurses' role, it is necessary to extract the studies illustrating advanced practice nurses' practices for patients with chronic kidney disease. OBJECTIVE: This study aims to map the literature describing the role of advanced practice nurses in improving healthcare outcomes for patients with chronic kidney disease. MATERIALS AND METHODS: This scoping review will be conducted using the Joanna Briggs Institute methodology for scoping review. Online databases will be searched across MEDLINE (PubMed), CINAHL (EBSCOhost), Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Web of Science. Only studies published in English will be included, and no date limit will be set. Chronic kidney disease, renal replacement therapy, and advanced practice nurses as keywords and related search terms will be used. Two independent reviewers will screen the title and abstract/full-text; in case of discrepancy, a third reviewer will make the final decision. The results will be extracted and presented following the review question concerning the study characteristics, patients' characteristics, condition of chronic kidney disease, and role of advanced practice nurses.

Microdeletion at ESR1 Intron 6 (DEL_6_75504) Is a Susceptibility Factor for Cryptorchidism and Hypospadias.

CONTEXT: We have previously reported that a specific "AGATC" haplotype in a >34 kb tight linkage disequilibrium (LD) block within ESR1 is strongly associated with cryptorchidism and hypospadias in Japanese boys. OBJECTIVE: We aimed to determine the true susceptibility factor for cryptorchidism and hypospadias linked to the "AGATC" haplotype. METHODS: We performed various molecular studies in hitherto unreported 230 Italian boys (80 with cryptorchidism and 150 with normal genitalia) and previously reported and newly recruited 415 Japanese boys (149 with cryptorchidism, 141 with hypospadias, and 125 with normal genitalia). We also performed ESR1 expression analyses using breast cancer-derived MCF-7 cells. RESULTS: Haplotype analysis revealed the LD block and positive association of the "AGATC" haplotype with cryptorchidism in Italian boys. Whole genome sequencing identified an identical 2249-bp microdeletion (ΔESR1) generated by a microhomology-mediated replication error in both Japanese and Italian boys with the specific haplotype. ΔESR1 was found to be strongly associated with cryptorchidism and hypospadias by Cochran-Armitage trend test and was revealed to show nearly absolute LD with the "AGATC" haplotype. ESR1 expression was upregulated in MCF-7 cells with a homozygous deletion encompassing ΔESR1 and those with a homozygous deletion involving a CTCF-binding site within ΔESR1. CONCLUSION: The results reveal that ΔESR1, which has been registered as "DEL_6_75504" in gnomAD SVs v2.1, is the true susceptibility factor for cryptorchidism and hypospadias. It appears that ΔESR1 was produced in a single ancestral founder of modern humans and has been maintained within the genome of multiple ethnic groups by selection.

Clinical response in metastatic castration-resistant prostate cancer (mCRPC) cases treated with supra-physiological doses of testosterone: Bipolar androgen therapy.

Androgen deprivation therapy is a standard of care for metastatic prostate cancer. A paradoxical approach utilizing high doses of testosterone in castration-resistant prostate cancer patients demonstrated clinical responses. Here, we report on four heavily pretreated Japanese patients (including one patient on hemodialysis) successfully treated with supra-physiological doses of testosterone.

Familial testicular germ cell tumors in two brothers.

INTRODUCTION: Two percent of testicular germ cell tumors occur in family clusters. Here, we report metachronous testicular germ cell tumors in two brothers. CASE PRESENTATION: An elder brother was diagnosed at the age of 30 years old and the pathological diagnosis was mixed testicular germ cell tumor. A tumor in the younger brother was suspected during testicular self-examination. It was confirmed by ultrasound examination at the age of 30 years old, 3 years and 6 months after the diagnosis of the testicular tumor in elder brother. The pathological diagnosis was pure seminoma. Both brothers had stage 1 testicular germ cell tumors and no recurrence was observed during the follow-up period of 4 years and 4 months and 10 months, respectively. CONCLUSION: Various histological types of tumor can occur in members of one family. Besides genetic predisposition, shared diet, environmental exposure and other factors can contribute to the familial testicular cancer. Testicular self-examination is recommended for family members of a person with testicular germ cell tumor.

Bladder cancer metastasis producing beta-human chorionic gonadotropin, squamous cell carcinoma antigen, granulocyte-colony stimulating factor, and parathyroid hormone-related protein.

INTRODUCTION: In urothelial cancer, several paraneoplastic syndromes can be triggered by the aberrant expression of hormones, growth factors or lymphokines by tumor cells. CASE PRESENTATION: A 71-year-old female patient underwent radical cystectomy for muscle-invasive urothelial cancer. Shortly after the operation, the patient presented with a leukemoid reaction and hypercalcemia. Computed tomography scans revealed a rapidly progressing tumor on the left pelvic side, and serum levels of granulocyte-colony stimulating factor, parathyroid hormone-related protein, and beta human chorionic gonadotropin were elevated. The patient also tested positive for serum squamous cell carcinoma antigen. Hypercalcemia was successfully treated with denosumab. However, the patient's leukocyte counts steadily increased, her condition deteriorated and she passed away. CONCLUSION: To the best of our knowledge, this is the first report of urothelial cancer that tested positive for four tumor markers. The findings support the idea that poorly differentiated bladder carcinomas can ectopically secrete multiple proteins causing pleiotropic paraneoplastic syndromes.

Usefulness of multi-parametric MRI for diagnosis of invasive urothelial cancer: Case reports of bladder and ureteral cancer.

The presence or absence of metastasis has critical implications for therapeutic decision-making in urothelial cancer (UC). Conventional magnetic resonance imaging (MRI) utilizing anatomic T1- and T2-weighted images has modest efficacy in detecting lymph node and distant metastases in UC. However, incorporation of functional techniques including diffusion weighted imaging and dynamic contrast-enhanced imaging, may improve the accuracy of lesion detection and staging. Multiparametric (mp)MRI is widely used in the imaging of prostate and breast cancers, though its usefulness in UC has yet to be fully elucidated. The present study reports on mpMRI in the context of two cases of bladder and ureteral cancer, and imaging results with pathological diagnosis.

Updated recommendation on molecular-targeted therapy for metastatic renal cell cancer.

Molecular-targeted therapy was recommended for the systemic therapy of renal cell cancer (RCC) in the RCC guidelines, but these guidelines do not address the order of administration of the multiple presently available agents. There are several aspects that remain unknown regarding the optimal administration order and combination of molecular-targeted drugs. Until the optimal treatment sequence is determined by clinical trials, treatment individualization is required for each patient based on patient and disease characteristics. We herein investigate 12 cases of RCC patients who received axitinib. Axitinib was used as the first-line drug in 4 cases, second-line in 5 cases, third-line in 1 case and as a fourth-line drug in 2 cases. Partial response (PR) was observed in 4 cases (30%) and stable disease in 4 cases (30%) during axitinib treatment, with an overall response rate of 60%. The duration of PR ranged from 6 to 19 months. Based on our cases, axitinib exhibited reasonable therapeutic efficacy as first- as well as second-line treatment. However, more cases are required to draw firm conclusions.

Treatment sequence in castration-resistant prostate cancer: A retrospective study in the new anti-androgen era.

In recent years, abiraterone acetate (AA) and enzalutamide (EZL) have become available for the treatment of cancer. Prior clinical trials have demonstrated the benefits of these agents in males with castration-resistant prostate cancer (CRPC). The optimal sequencing of available therapies in the context of efficacy and known cross-resistance remains uncertain. Based on the mechanisms of action and accessible clinical data, AA and EZL may be indicated for the early stages of prostate cancer. Until clinical trials are conducted to determine the best treatment sequence, individualized therapy is required for each patient based on the clinicopathological characteristics. In the present study, 46 sequential patients (median age: 77, range 59-89; median serum PSA level: 56 ng/ml, range 1.5-3,211) with CRPC treated with EZL (160 mg/day) were retrospectively analyzed between June 2014 and July 2015 at the following institutions: Yamagata Prefectural Central Hospital (Yamagata, Japan); Yamagata Tokushukai Hospital (Yamagata, Japan); Ishinomaki Red Cross Hospital (Ishinomaki, Japan); Kan-etsu Hospital (Tsurugashima, Japan); Niigata Cancer Center Hospital (Niigata, Japan); Sakado Central Hospital (Sakado, Japan). A total of 18 patients were pre-treated with Docetaxel (DOC) and 28 patients were DOC-naïve. Once EZL therapy was initiated, increases in prostate specific antigen (PSA) levels were observed in 3/18 patients (17%) pre-treated with DOC and in 6/20 (30%) who were DOC-naïve. In total, 8/28 DOC-naïve patients were treated with AA without EZL. An increase in the PSA level was observed in only 1/8 (12%) cases following AA treatment in the DOC-naïve group. It was demonstrated that AA had a better efficacy in DOC-naïve patients. The efficacy of EZL was limited in AA-pre-treated patients following DOC administration.

Comparison of semi-extended and standard lymph node dissection in radical prostatectomy: A single-institute experience.

Standard lymphadenectomy for prostate cancer is limited to the obturator lymph nodes (LNs), although the internal and external iliac LNs represent the primary landing zone for prostatic lymphatic drainage. We performed anatomically semi-extended pelvic lymph node dissection (PLND) to assess the incidence of LN metastasis in cases of clinically localized prostate cancer. A total of 730 consecutive patients underwent radical prostatectomy with either semi-extended PLND, comprising 6 selective fields, namely the external iliac, internal iliac and obturator LNs bilaterally, or standard LND (obturator LNs alone). A total of 131 patients undergoing semi-extended PLND were compared with 599 patients undergoing standard LND. The patients were stratified into high-risk [prostate-specific antigen (PSA)>20 ng/ml, Gleason score (GS)≥8], intermediate-risk (PSA 10-20 ng/ml, GS=4+3) and low-risk (PSA<10 ng/ml, GS≤3+4) subgroups. Following semi-extended LND, positive LNs were detected in 12/61 (20%) of the high-risk, 1/30 (3%) of the intermediate-risk and 0/40 (0%) of the low-risk cases. Following standard LND, positive LNs were detected in 13/182 (7%) of the high-risk, 1/164 (0.6%) of the intermediate-risk and 0/253 (0%) of the low-risk cases. In high-risk patients, the detection rate of LN metastasis was significantly higher following extended LND compared with standard LND (P<0.01). In 9 of 13 patients (69%), metastases were identified in the internal and external iliac regions, despite negative obturator LNs. There were no significant differences regarding intraoperative and postoperative complications or blood loss in the two groups. There was no lymphocele formation in patients undergoing either standard or semi-extended LND. Extended pelvic LND (PLND) is associated with a high rate of LN metastasis detection outside the fields of standard LND in cases with clinically localized prostate cancer. Therefore, LND including the internal and external iliac LNs should be performed in all patients with high-risk prostate cancer; however, in the low-risk group, PLND may be omitted.

Remarkable response to neoadjuvant therapy with methotrexate, vinblastine, adriamycin, and Cisplatin for undifferentiated bladder carcinoma: a case report and literature review.

We report a case of primary undifferentiated bladder carcinoma, which revealed a remarkable response to methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) therapy. A 46-year-old Japanese woman presented at the hospital with the chief complaints of gross hematuria and pain during urination. Cystoscopy revealed a large smooth-surfaced tumor in the urinary bladder. The histopathological diagnosis was undifferentiated carcinoma. The patient then received 3 courses of MVAC over a 3-month period. Hydronephrosis disappeared after the first course, and the tumor shrank rapidly. After completion of the third MVAC course, radical cystectomy and ileal conduit surgery were performed. After 7 years, the patient has still had no recurrences or metastases. We retrospectively review the relative efficacy of the two popular chemotherapeutic regimens in the management of muscle-invasive bladder cancer in patients who had had radical cystectomy.

Long term survival in a case of concurrent retroperitoneal liposarcoma and renal cell carcinoma: a case report.

BACKGROUND: Liposarcoma is one of the most common soft tissue sarcomas found in adults. It has a predilection for retroperitoneal space. Renal cell carcinoma is the most common tumor of the kidney. CASE PRESENTATION: Concurrent retroperitoneal liposarcoma and renal cell carcinoma were found in a 34-year-old Japanese man. The renal tumor was first detected by ultrasonography, it was confirmed by computed tomography, which also identified a presumptive retroperitoneal liposarcoma, and the tumors were further assessed with magnetic resonance imaging. The patient was treated by surgical resection of retroperitoneal liposarcoma and left nephrectomy and has been disease-free for 10 years. CONCLUSIONS: The concomitant occurrence of a renal tumor and a primary primary liposarcoma is rare. The major factors promoting a good prognosis in this case were the favorable histology and the small size of the tumors.

[Three-year follow-up of 12 patients with prostate cancer treated with monthly degarelix in a phase II clinical trial].

The efficacy and safety of degarelix, a luteinizing hormone-releasing hormone(LH-RH)antagonist, in patients with prostate cancer(PCa)were evaluated in a phase II, open-label, multicenter clinical trial. In this trial, a total of 13 patients were accrued at the Yamagata Prefectural Central Hospital from 2007 to 2008. The median age was 80 years(range, 65-85 years), and clinical stages were T1c, T2, T3, and T4 in 1, 4, 6, and 2 patients, respectively. Nodal(N)status was N0 in 9 patients and N1 in 4 patients. Distant metastases were absent(M0)in 12 patients and present(M1b)in 1 patient. The median prostate- specific antigen(PSA)level was 29.1 ng/mL(range, 6.3-427 ng/mL). All but one patient, who died of an unrelated cause, received a monthly dose(80 or 160mg)of degarelix for 12 months and were followed-up for 3 years. The PSA level declined in all patients. One patient died of an unrelated cause during the phase II trial. After completion of the phase II trial, 5 patients were treated with combined and rogen blockade(CAB)(leuprolide plus anti-androgen therapy), 2 patients were treated with single-agent leuprolide, 2 patients received single-agent bicalutamide, and 1 patient was followed-up without additional treatment. Radical prostatectomy was performed in 2 patients. Among the 5 patients treated with CAB, 2 died of metastatic cancer. CAB was effective in suppressing PSA levels in 3 patients. In 1 patient with T3aN1M1b PCa, colon cancer with lung metastases was detected during the follow-up period. Treatment with chemotherapy for colon cancer was effective in suppressing PSA levels for 12 months. In 1 patient with cT3aN1M0 PCa, the PSA level declined to <0.02 ng/mL, and a reduction in size of the prostate gland and metastatic lymph nodes was observed. This effect persisted for 3.5 years after the completion of the 12-month degarelix regimen, and no additional treatment was required.

Efficacy of once or twice weekly administration of epoetin κ in patients receiving hemodialysis: A retrospective study.

Several clinically approved recombinant erythropoietin (rEPO) preparations, such as epoetin-ß, epoetin-δ and the epoetin-α derivative, darbepoetin-α, have been commercially produced. Since the expiration of patent protection, a number of novel rEPO biosimilars have been approved on the world market. In 2010, epoetin-κ, which is biosimilar to epoetin-α, was clinically approved. Epoetin-κ is a biopharmaceutical product that is based on serum-free media following master cell bank preparation. The present study analyzes the results obtained during a six-month observation period, in which the administration of epoetin-ß was switched to that of epoetin-κ. In a cohort of patients receiving chronic dialysis, who were clinically in a state of relative calm and were in control of their renal anemia, it was possible to sustain good control of the anemia by reducing the frequency of the epoetin-ß administration from the conventional and empirically determined three times a week to twice a week, and further to once a week. Furthermore, the good control was maintained upon changing from the administration of epoetin-ß to that of epoetin-κ. Moreover, three months subsequent to this switch, the degree of instability observed among the patients had decreased. Despite the fact that the situation following the changeover requires further investigation, it may be concluded that the results obtained in this study are indicative of the clinical equivalence and efficacy of epoetin-κ.

Laparoscopic Varicocelectomy Carried Out with the LigaSure Device in 52 Patients.

We describe the effective use of the bipolar vessel-sealing device: LigaSure for the division of the internal spermatic vessels in a laparoscopic varicocelectomy. A total of 52 males with varicocele (left-side n = 49, and bilateral n = 3) were included in this study. Blunt dissection was used to isolate the packet of spermatic vessels. The packet of spermatic vessels was divided using a bipolar diathermy system, the LigaSure Precise. It was clear that the operative time was significantly reduced compared to the method using clips, which was done before the development of this kind of device. In another experiment to examine the effect of vessel sealing, it was confirmed that the LigaSure has performance comparable to the clips. Despite the result that the Harmonic scalpel was less effective in vessel sealing, our study found it difficult to determine which is superior, LigaSure or clips, in terms of operative time, relapse rate and complication.

Haplotype analysis of the estrogen receptor 1 gene in male genital and reproductive abnormalities.

BACKGROUND: We have recently suggested that homozygosity for a specific 'AGATA' haplotype within a approximately 50 kb linkage disequilibrium (LD) block of the gene for estrogen receptor alpha (ESR1) may raise the susceptibility to cryptorchidism by enhancing estrogenic effects of environmental endocrine disruptors (EEDs). METHODS: Haplotype analysis of ESR1 was performed in 328 Japanese subjects, i.e. 70 patients with micropenis (MP), 43 patients with hypospadias (HS), 80 patients with spermatogenic failure (SF) and 135 control males. Genotyping was performed by the 5' nuclease assay. RESULTS: The LD block was identified in each of the patient groups and in the control males. The frequency of homozygotes for the specific 'AGATA' haplotype was markedly higher in the HS patients [P = 0.0000033, odds ratio [OR] = 11.26] and slightly higher in the MP patients (P = 0.034, OR = 3.64) than in the control males, and the 'AGATA' haplotype was strongly associated with HS (P = 0.0000022, OR = 11.26) and weakly associated with MP (P = 0.040, OR = 3.64) in a recessive mode. There was no significant difference between the SF patients and the control males. CONCLUSIONS: Our results support the hypothesis that homozygosity for the specific ESR1 'AGATA' haplotype may increase the susceptibility to the development of male genital abnormalities in response to estrogenic EEDs.

Functional glycosylation of human podoplanin: glycan structure of platelet aggregation-inducing factor.

Podoplanin (Aggrus) is a mucin-type sialoglycoprotein that plays a key role in tumor cell-induced platelet aggregation. Podoplanin possesses a platelet aggregation-stimulating (PLAG) domain, and Thr52 in the PLAG domain of human podoplanin is important for its activity. Endogenous or recombinant human podoplanin were purified, and total glycosylation profiles were surveyed by lectin microarray. Analyses of glycopeptides produced by Edman degradation and mass spectrometry revealed that the disialyl-corel (NeuAc alpha2-3Gal beta l-3(NeuAc alpha2-6)GalNAc alpha l-O-Thr) structure was primarily attached to a glycosylation site at residue Thr52. Sialic acid-deficient podoplanin recovered its activity after additional sialylation. These results indicated that the sialylated Corel at Thr52 is critical for podoplanin-induced platelet aggregation.

Mutation and polymorphism analyses of INSL3 and LGR8/GREAT in 62 Japanese patients with cryptorchidism.

BACKGROUND/AIMS: Although insulin-like factor 3 (INSL3) and its receptor leucine-rich repeat-containing G protein-coupled receptor 8/G protein-coupled receptor affecting testis descent (LGR8/GREAT) are essential for the gubernacular development, mutations of INSL3 and LGR8/GREAT are infrequent in patients with cryptorchidism (CO), and there is no report documenting a positive association of CO with a polymorphism in INSL3 or LGR8/GREAT. Here, we further examined the relevance of INSL3 and LGR8/GREAT mutations and polymorphisms to the development of CO. METHODS: Sixty-two Japanese CO patients and 60 fertile males were studied. INSL3 was analyzed by direct sequencing and restriction enzyme digestion, and LGR8/GREAT was examined by denaturing high-performance liquid chromatography followed by direct sequencing for exons with abnormal chromatogram patterns. RESULTS: No definitive mutation was identified in both genes. Six polymorphisms were detected in INSL3 or LGR8/GREAT and Thr/Thr genotype of Ala60Thr polymorphism in INSL3 was strongly associated with CO (p=0.0024, odds ratio=5.3, 95% confidence interval=1.7-17). CONCLUSION: The results, in conjunction with the previous data, suggest that mutations of INSL3 and LGR8/GREAT remain rare, and that the Thr/Thr genotype of Ala60Thr polymorphism in INSL3 may constitute a susceptibility factor for the development of CO.

Association of cryptorchidism with Gly146Ala polymorphism in the gene for steroidogenic factor-1.

Genotyping analysis was performed for Gly146Ala polymorphism in the gene for steroidogenic factor-1 (SF-1), which is known to reduce the transactivation function by approximately 20%, in 72 cryptorchid patients and 136 control males, revealing that the Ala allele, the Ala/Gly genotype, and the Ala/Ala plus Ala/Gly genotype frequencies were significantly higher in the patients than in the control males. The results suggest that the Gly146Ala polymorphism may be a susceptibility factor for the development of cryptorchidism (CO).

Association of cryptorchidism with a specific haplotype of the estrogen receptor alpha gene: implication for the susceptibility to estrogenic environmental endocrine disruptors.

CONTEXT: The prevalence of cryptorchidism (CO) has increased during the past few decades in several countries, and this event has primarily been ascribed to the estrogenic effects of environmental endocrine disruptors (EEDs). Little is known, however, about the role of genetic susceptibility to EEDs in this phenomenon. OBJECTIVE: The objective of this study was to determine whether CO is associated with a specific haplotype of the gene for estrogen receptor alpha (ESR1) that mediates the estrogenic effects of EEDs. DESIGN: This was a case-control study. SETTING: The study was performed at the National Research Institute and University Hospitals. SUBJECTS: Sixty-three cryptorchid males, aged 1-13 yr, and 47 control males, aged 4-12 yr, were studied. INTERVENTION: After genotyping 15 single nucleotide polymorphisms widely distributed in the greater than 300-kb genomic sequences of ESR1, haplotype analysis was performed. MAIN OUTCOME MEASURE: Identification of a specific ESR1 haplotype associated with CO was the main outcome measure. RESULTS: A haplotype block was identified for an approximately 50-kb region encompassing single nucleotide polymorphisms 10-14 in the 3' region of ESR1 in both groups. The frequency of the estimated AGATA haplotype within the block was higher in the patients than in the control males (34.0% vs. 21.3%; P = 0.037), and the association of this haplotype with CO phenotype was significant in a recessive mode (P = 0.0060). The homozygosity for this haplotype was identified only in the patients, and the frequency of the homozygotes was significantly different between the two groups (10 of 63 vs. zero of 47; P = 0.0042). CONCLUSIONS: The association of CO with homozygosity for the specific ESR1 haplotype suggests the relevance of genetic susceptibility to EEDs in the development of CO.