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1.
IJU Case Rep ; 7(3): 197-200, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38686072

RESUMO

Introduction: CHARGE syndrome is a rare disorder that causes congenital abnormalities in multiple organs, including secondary hypogonadism. We report, herein, a unique case of CHARGE syndrome with both primary and secondary hypogonadism and discuss the possible causes and pathogenesis in this patient. Case presentation: A 15-year-old boy with delayed secondary sexual characteristics and non-palpable testes was referred to our hospital. Physical examination and detection of a chromodomain-helicase-deoxyribonucleic acid-binding protein 7 gene mutation confirmed CHARGE syndrome. Hormone stimulation tests suggested both primary and secondary hypogonadism. Laparoscopic bilateral orchiectomy was performed because of decreased testosterone production and atrophy in both testes. Pathological examination of the testes revealed maturation arrest, germ cell neoplasm in situ, and decreased expression of steroid synthase. Conclusion: This appears to be the first report of CHARGE syndrome with both primary and secondary hypogonadism demonstrated in endocrinological and histological examinations.

2.
Fukushima J Med Sci ; 70(2): 57-64, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38346721

RESUMO

PURPOSE: We assessed the stiffness of unilateral undescended testes after orchiopexy, examining its value in tracking histopathological changes and fertility potential during postoperative follow-up. Additionally, we explored the optimal timing for surgery based on testicular stiffness. PATIENTS AND METHODS: Thirty-six boys who had been diagnosed with unilateral undescended testis and treated with orchiopexy were included in the study. Testicular stiffness was evaluated several times over respective follow-up periods by ultrasound strain elastography after orchiopexy. The strain ratios were measured as the ratios of the elasticities of the descended testis to those of the operated testes. The patients were divided into two groups based on the age at which they underwent orchiopexy:under < 2 years (Group A) and ≥ 2 years (Group B). RESULTS: The mean strain ratios were 0.90 ± 0.32 and 0.92 ± 0.20 in Groups A and B, respectively. In Group A, the strain ratio was constant regardless of postoperative months (r = 0.01, p = 0.99); however, in Group B, it tended to increase with postoperative months (r = 0.42, p = 0.07). CONCLUSIONS: Evaluation of testicular stiffness may be useful for the estimation of histopathological changes and fertility potential in boys with unilateral undescended testes at follow-up appointments after orchiopexy. Our data indicate that performing orchiopexy as early as possible may be recommended to avoid testicular damage.


Assuntos
Criptorquidismo , Técnicas de Imagem por Elasticidade , Orquidopexia , Testículo , Humanos , Masculino , Criptorquidismo/cirurgia , Criptorquidismo/diagnóstico por imagem , Lactente , Pré-Escolar , Testículo/diagnóstico por imagem , Criança
3.
Prostate ; 84(2): 203-211, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37876324

RESUMO

BACKGROUND: To elucidate the changes in activated complement pathway in the fibrous process of benign prostatic hyperplasia (BPH), we analyzed the correlation between complement component expression and histological types of fibrosis using human BPH tissue. METHODS: Fifty-six histological BPH patients who underwent prostate needle biopsy at our institution (mean age 68.6 ± 6.5 years), divided into two histological groups, fibromuscular and fibrous, were compared. Inflammatory cell infiltration in BPH tissue was evaluated by immunohistochemical staining using CD45, with complement expression analysis performed using C3, factor B, and C5b-9 antibody, and the occupancy ratio of the stained region was calculated. Further, correlation between the histological types of fibrous components in BPH tissue and lower urinary tract symptoms questionnaires was analyzed. RESULTS: Twenty-seven (48.2%) and 29 (51.8%) cases were classified in the fibromuscular and fibrous groups, respectively. The proportion of CD45-positive cells in BPH tissue was significantly higher in the fibromuscular group. In complement component analysis, factor B did not significantly differ between groups, while C3 (fibromuscular group; 10.7 ± 8.2%, fibrous group; 16.4 ± 12.7%) and C5b-9 (fibromuscular group; 15.9 ± 6.2%, fibrous group; 17.6 ± 9.2%) were significantly higher in the fibrous group (p = 0.04, p = 0.04, respectively). International Prostate Symptom Score Q5 subscore, indicating slow stream, was significantly higher in the fibrous group (p = 0.04). CONCLUSIONS: In fibrous BPH with abundant fibrosis, the late complement pathway in addition to alternative pathway was activated compared to fibromuscular BPH. These results suggested that the alternative and late complement pathways were involved in the histological fibrous process of BPH.


Assuntos
Hiperplasia Prostática , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Hiperplasia Prostática/patologia , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Próstata/patologia , Biópsia por Agulha , Fibrose
4.
IJU Case Rep ; 6(6): 465-467, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37928283

RESUMO

Introduction: We report a case of bilateral neonatal testicular torsion, with an extravaginal and a contralateral intravaginal testicular torsion. Case presentation: A 5-day-old boy with bilateral scrotal swelling and palpable induration was diagnosed with bilateral neonatal testicular torsion by color Doppler ultrasonography. The right testis was black with 360-degree extravaginal torsion of the spermatic cord, and the left testis was brown with 90-degree intravaginal torsion. We repaired the torsion and incised the tunica albuginea to reduce intratesticular pressure. The left testis became pink in color, but the right testis remained unchanged. Based on the pathological findings of the intraoperative biopsy of tissue specimens from both testes, we performed a right orchiectomy and preserved the left testis. Conclusions: Our experience suggests that testicular color improvement after fasciotomy and pathological findings of intraoperative testicular biopsy may indicate testicular preservation.

5.
BMC Endocr Disord ; 23(1): 243, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37932696

RESUMO

BACKGROUND: Patients with bilateral primary aldosteronism (PA) generally are treated with antihypertensive drugs, but optimal treatment for patients with complications due to refractory hypertension has not been established. In this report, we present a case with bilateral PA who presented with persistent hypertension, despite treatment with 6 drugs, and left-dominant heart failure, which was improved after unilateral adrenalectomy. CASE PRESENTATION: A 61-year-old man was admitted to our hospital because of severe left-dominant heart failure. His heart rhythm was atrial fibrillation and the left ventricle was diffusely hypertrophic and hypokinetic. Coronary arteries were normal on coronary arteriogram. Primary aldosteronism was suspected based on severe hypokalemia (2.5 mEq/L) and plasma aldosterone concentration (PAC; 1,410 pg/mL). Although computed tomography (CT) showed a single left cortical nodule, adrenal vein sampling (AVS) indicated bilateral PA. Early in the case, heart failure and hyperkalemia in this patient were improved by treatment with a combination of 6 antihypertensive drugs (spironolactone 25 mg/day, eplerenone 100 mg/day, azosemide 60 mg/day, tolvaptan 7.5 mg/day, enalapril 5 mg/day, and bisoprolol fumarate 10 mg/day); however, heart failure relapsed after four months of treatment. We hypothesized that hypertension caused by excess aldosterone was inducing the patient's heart failure. In order to reduce aldosterone secretory tissue, a laparoscopic adrenalectomy was performed for the left adrenal gland, given the higher level of aldosterone from the left gland compared to the right. Following surgery, the patient's heart failure was successfully controlled despite the persistence of high PAC. Treatment with anti-hypertensive medications was reduced to two drugs (eplerenone 100 mg/day and bisoprolol fumarate 10 mg/day). In order to elucidate the mechanism of drug resistance, immunohistochemistry (IHC) and real time-polymerase chain reaction (RT-PCR) assays were performed to assess the expression of steroidogenic factor 1 (SF-1), a regulator of steroid synthesis in adrenal tissue. IHC and RT-PCR demonstrated that the expression of SF-1 in this patient (at both the protein and mRNA levels) was higher than that observed in unilateral PA cases that showed good responsivity to drug treatment. CONCLUSIONS: Unilateral adrenalectomy to reduce aldosterone secretory tissue may be useful for patients with drug-refractory, bilateral PA. Elevated expression of SF-1 may be involved in drug resistance in PA.


Assuntos
Insuficiência Cardíaca , Hiperaldosteronismo , Hipertensão , Humanos , Masculino , Pessoa de Meia-Idade , Glândulas Suprarrenais , Adrenalectomia , Aldosterona , Anti-Hipertensivos/uso terapêutico , Bisoprolol/uso terapêutico , Eplerenona/uso terapêutico , Hiperaldosteronismo/complicações , Hipertensão/etiologia
6.
Cancer Med ; 12(22): 20677-20689, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37905674

RESUMO

OBJECTIVES: To investigate the efficacy of pharmacotherapy for metastatic non-clear cell renal cell carcinoma (nccRCC) in Japanese population. METHODS: In this retrospective analysis, we compared the time to treatment failure (TTF) for molecular-targeted agents as first-line therapy, or nivolumab therapy as sequential therapy between ccRCC and nccRCC using the data of Japanese metastatic RCC patients registered in the Michinoku Japan Urological Cancer Study Group database. RESULTS: In total, 511 cases of ccRCC and 77 cases of nccRCC were treated with pharmacotherapy. After excluding the patients who received cytokine therapy, chemotherapy, or others, there were 391 ccRCC patients and 60 nccRCC patients who were treated with tyrosine kinase inhibitors (TKIs), and 7 ccRCC patients and 7 nccRCC patients who were treated with mammalian-target of rapamycin inhibitors (mTORIs). In addition, 132 ccRCC patients and 16 nccRCC patients received nivolumab. There was no significant difference in IMDC risk classification before first-line therapy between ccRCC and nccRCC groups, or in each subgroup within the nccRCC group. TTF for TKIs (161 days, 95% CI: 75-212 days) and mTORIs (21 days, 95% CI: 9-31 days) didn't differ significantly between nccRCC and ccRCC groups (205 days, 95% CI: 174-243 days and 33 days, 95% CI: 8-113 days, respectively). TTF for TKIs was significantly longer than that for mTORIs in nccRCC group (p<0.01). There was no significant difference in TTF between the different TKIs in nccRCC group. In addition, no significant difference in TTF for nivolumab was seen between ccRCC and nccRCC groups. CONCLUSIONS: The results showed that the efficacy of molecular-targeted agents as first-line therapy was similar oncological outcomes between metastatic nccRCC and ccRCC in Japanese patients. TKIs may be more effective than mTORIs in metastatic nccRCC patients. Nivolumab administration might also be as effective in nccRCC patients as in ccRCC patients in Japanese population.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Nivolumabe/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Japão/epidemiologia , Estudos Retrospectivos , Terapia de Alvo Molecular , Resultado do Tratamento , Antineoplásicos/uso terapêutico
7.
Int J Clin Oncol ; 28(11): 1538-1544, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37740070

RESUMO

BACKGROUND: The Modified International Metastatic Renal Cell Carcinoma Dataset Consortium model (mIMDC) is a preoperative prognostic model for pT3cN0M0 renal cell carcinoma (RCC). This study aimed to validate the mIMDC and to construct a new model in a localized and locally advanced RCC (LLRCC). METHODS: A database was established (the Michinoku Japan Urological Cancer Study Group database) consisting of 79 patients who were clinically diagnosed with LLRCC (cT3b/c/4NanyM0) and underwent radical nephrectomy from December 2007 to May 2018. Using univariable and multivariable analyses, we retrospectively analyzed disease-free survival (DFS) and overall survival (OS) in this database, constructed a new prognostic model according to these results, and estimated the model fit using c-index on the new and mIMDC models. RESULTS: Independent poorer prognostic factors for both DFS and OS include the following: ≥ 1 Eastern Cooperative Oncology Group performance status, 2.0 mg/dL C-reactive protein, and > upper normal limit of white blood cell count. The median DFS in the favorable (no factor), intermediate (one factor), and poor-risk group (two or three factors) was 76.1, 14.3, and 4.0 months, respectively (P < 0.001). The 3-year OS in the favorable, intermediate, and poor-risk group were 92%, 44%, and 0%, respectively (P < 0.001). The c-indices of the new and mIMDC models were 0.67 and 0.60 for DFS (P = 0.060) and 0.74 and 0.63 for OS (P = 0.012), respectively. CONCLUSION: The new preoperative prognostic model in LLRCC can be used in patient care and clinical trials.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Prognóstico , Neoplasias Renais/patologia , Estudos Retrospectivos , Japão , Nefrectomia
8.
Urol Case Rep ; 51: 102546, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37692764

RESUMO

An isolated intravesical cavernous hemangioma of the bladder represents a rare occurrence, frequently posing challenges in distinguishing it from rhabdomyosarcoma. In this context, we present a case involving an 8-year-old male child diagnosed with a cavernous hemangioma of the bladder, which on MRI closely resembles the findings of rhabdomyosarcoma. Under such circumstances, the utilization of slow-flow images in contrast-enhanced MRI holds promise as a potentially valuable tool for discriminating between cavernous hemangioma and rhabdomyosarcoma in similar clinical scenarios.

9.
Curr Oncol ; 30(8): 7286-7302, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37623010

RESUMO

Theranostics (therapy + diagnosis) targeting prostate-specific membrane antigen (PSMA) is an emerging therapeutic modality that could alter treatment strategies for prostate cancer. Although PSMA-targeted radioligand therapy (PSMA-RLT) has a highly therapeutic effect on PSMA-positive tumor tissue, the efficacy of PSMA-RLT depends on PSMA expression. Moreover, predictors of treatment response other than PSMA expression are under investigation. Therefore, the optimal patient population for PSMA-RLT remains unclear. This review provides an overview of the current status of theranostics for prostate cancer, focusing on PSMA ligands. In addition, we summarize various findings regarding the efficacy and problems of PSMA-RLT and discuss the optimal patient for PSMA-RLT.


Assuntos
Neoplasias da Próstata , Humanos , Masculino , Imagem Molecular , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia
10.
IJU Case Rep ; 6(4): 248-252, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37405037

RESUMO

Introduction: Basal cell carcinoma of the prostate is rare, with no established treatment for its recurrence or metastasis. We report a case involving basal cell carcinoma of the prostate controlled using radiotherapy. Case presentation: A 57-year-old man complained of perineal pain. Although his prostate-specific antigen was 0.657 ng/mL, a digital rectal examination revealed his prostate was stone hard. Prostate needle biopsy showed basal cell carcinoma of the prostate. The patient then underwent radical prostatectomy. Local recurrence and sacral bone metastasis appeared 2 months after surgery. OncoGuide™ NCC Oncopanel System showed deletion of SMARCB1; however no recommended treatment was identified. Thus, we decided to perform radiotherapy, which reduced all lesions. Conclusion: Basal cell carcinoma of the prostate may have a poor prognosis with recurrence or metastasis, hence evaluation of prognostic factors is important. In this case, the genomic profiling test suggested that SMARCB1 deletion may be a prognostic factor associated with disease progression.

11.
Int J Mol Sci ; 24(14)2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37511400

RESUMO

Benign prostatic hyperplasia (BPH) is a chronic proliferative disease showing stromal-dominant proliferation. However, the detailed proliferation mechanism has remained unclear. Although aging and androgen have been reported as definitive risk factors for BPH, recent studies have focused on the involvement of androgen-independent factors. Androgen-independent factors include ischemia, oxidative stress, metabolic syndrome, infection, autoimmune reactions, and inflammation, with inflammation in BPH tissues playing a central role in the BPH proliferative process. Inflammation in BPH tissues by various factors finally leads to tissue remodeling and stromal proliferation through the wound healing process of the prostate. To elucidate the proliferative mechanism of BPH, a study using whole-genome gene expression analysis in a stromal-dominant BPH rat model was performed and showed that immune response-related pathways and complement classical pathways are activated. Furthermore, expression analysis using this BPH rat model showed that the autoimmune reaction triggered complement pathway activation in the proliferative process of BPH. BPH is a multifactorial disease, and understanding the role of androgen-independent factors including immune responses contributes to elucidating the pathogenesis of BPH. Androgen-independent factors may lead to new therapeutic targets for BPH, and further development of this research is expected.


Assuntos
Hiperplasia Prostática , Humanos , Masculino , Ratos , Animais , Hiperplasia Prostática/tratamento farmacológico , Androgênios/metabolismo , Próstata/patologia , Inflamação/metabolismo , Proliferação de Células
12.
Ther Adv Med Oncol ; 15: 17588359231182293, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37424944

RESUMO

In the treatment of cancer, understanding the disease status, or accurate staging, is extremely important, and various imaging techniques are used. Computed tomography (CT), magnetic resonance imaging, and scintigrams are commonly used for solid tumors, and advances in these technologies have improved the accuracy of diagnosis. In the clinical practice of prostate cancer, CT and bone scans have been considered especially important for detecting metastases. Nowadays, CT and bone scans are called conventional methods because positron emission tomography (PET), especially prostate-specific membrane antigen (PSMA)/PET, is extremely sensitive in detecting metastases. Advances in functional imaging, such as PET, are advancing the diagnosis of cancer by allowing information to be added to the morphological diagnosis. Furthermore, PSMA is known to be upregulated depending on the malignancy of the prostate cancer grade and resistance to therapy. Therefore, it is often highly expressed in castration-resistant prostate cancer (CRPC) with poor prognosis, and its therapeutic application has been attempted for around two decades. PSMA theranostics refers to a type of cancer treatment that combines both diagnosis and therapy using a PSMA. The theranostic approach uses a radioactive substance attached to a molecule that targets PSMA protein on cancer cells. This molecule is injected into the patient's bloodstream and can be used for both imaging the cancer cells with a PET scan (PSMA PET imaging) and delivering radiation directly to the cancer cells (PSMA-targeted radioligand therapy), with the aim of minimizing damage to healthy tissue. Recently, in an international phase III trial, the impact of 177Lu-PSMA-617 therapy was studied in patients with advanced PSMA-positive metastatic CRPC who had previously been treated with specific inhibitors and regimens. The trial revealed that 177Lu-PSMA-617 significantly extended both progression-free survival and overall survival compared to standard care alone. Although there was a higher incidence of grade 3 or above adverse events with 177Lu-PSMA-617, it did not negatively impact the patients' quality of life. PSMA theranostics is currently being studied and used primarily for the treatment of prostate cancer, but it has the potential to be applied to other types of cancers as well.

13.
J Clin Endocrinol Metab ; 108(10): 2550-2560, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37010083

RESUMO

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.


Assuntos
Criptorquidismo , Hipospadia , Humanos , Masculino , Criptorquidismo/genética , Homozigoto , Hipospadia/genética , Íntrons , Deleção de Sequência
15.
Int J Mol Sci ; 24(4)2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36835398

RESUMO

We aimed to investigate the relationship between mast cell (MC) infiltration into the bladder with urothelial barrier dysfunction and bladder hyperactivity in a chronic bladder ischemia (CBI) rat model. We compared CBI rats (CBI group; n = 10) with normal rats (control group; n = 10). We measured the expression of mast cell tryptase (MCT) and protease-activated receptor 2 (PAR2), which are correlated with C fiber activation via MCT, and Uroplakins (UP Ia, Ib, II and III), which are critical to urothelial barrier function, via Western blotting. The effects of FSLLRY-NH2, a PAR2 antagonist, administered intravenously, on the bladder function of CBI rats were evaluated with a cystometrogram. In the CBI group, the MC number in the bladder was significantly greater (p = 0.03), and the expression of MCT (p = 0.02) and PAR2 (p = 0.02) was significantly increased compared to that of the control group. The 10 µg/kg FSLLRY-NH2 injection significantly increased the micturition interval of CBI rats (p = 0.03). The percentage of UP-II-positive cells on the urothelium with immunohistochemical staining was significantly lower in the CBI group than in the control group (p < 0.01). Chronic ischemia induces urothelial barrier dysfunction via impairing UP II, consequently inducing MC infiltration into the bladder wall and increased PAR2 expression. PAR2 activation by MCT may contribute to bladder hyperactivity.


Assuntos
Isquemia , Receptor PAR-2 , Triptases , Bexiga Urinária Hiperativa , Bexiga Urinária , Animais , Ratos , Isquemia/metabolismo , Mastócitos/metabolismo , Receptor PAR-2/metabolismo , Triptases/metabolismo , Bexiga Urinária/irrigação sanguínea , Bexiga Urinária/metabolismo , Uroplaquina II/metabolismo , Urotélio/metabolismo , Bexiga Urinária Hiperativa/metabolismo
16.
Cancer Genomics Proteomics ; 20(1): 40-50, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36581342

RESUMO

BACKGROUND/AIM: Several cases of concurrent reduction of expression of polycystin 1 (PKD1) and Tuberous Sclerosis Complex 2 (TSC2) that are contiguous in chromosome 16p13 have been previously reported. This study newly addresses the concurrent reduction of expression of PKD1, TSC2 and NTHL1, which is adjacent to TSC2 and is a tumor suppressor gene. MATERIALS AND METHODS: We investigated the mRNA expression levels of PKD1, TSC2, PKD2, TSC1 and NTHL1 in blood and renal cell carcinoma (RCC) tissues in a proband with autosomal dominant polycystic kidney disease (ADPKD), tuberous sclerosis complex (TSC) and multiple pathologically diverse RCCs, including clear cell, papillary and chromophobe types. Additionally, we investigated germline variants in blood using whole exome sequencing (WES) in the proband and her four siblings. RESULTS: mRNA expression levels of PKD1, TSC2 and NTHL1 were reduced in the proband's blood and RCCs, compared with control groups. WES identified one novel variant with amino acid changes in the PKD1 exon in the three subjects with ADPKD, including the proband. Moreover, two variants in the TSC2 intron specific to the proband were also identified. CONCLUSION: In this study, we report a novel pathogenic variant in the PKD1 exon which likely led to ADPKD, and two variants in the TSC2 intron, which might have led to reduction in the expression of both TSC2 and NTHL1, consequently leading to TSC and multiple pathologically diverse RCCs.


Assuntos
Carcinoma de Células Renais , Desoxirribonuclease (Dímero de Pirimidina) , Neoplasias Renais , Rim Policístico Autossômico Dominante , Canais de Cátion TRPP , Proteína 2 do Complexo Esclerose Tuberosa , Feminino , Humanos , Carcinoma de Células Renais/genética , Desoxirribonuclease (Dímero de Pirimidina)/genética , Neoplasias Renais/genética , Rim Policístico Autossômico Dominante/genética , RNA Mensageiro/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteínas Supressoras de Tumor/genética , Canais de Cátion TRPP/genética
17.
Cancer Med ; 12(4): 4100-4109, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36200612

RESUMO

It remains unknown whether the early response to vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) management in malignancies links to long-term survival. The objective of this study was to investigate the survival rates and predictive factors of early response in patients with metastatic renal cell carcinoma (mRCC) managed by VEGFR-TKIs. From Jan. 2008 to Oct. 2018, 496 patients were treated with VEGFR-TKIs as first-line treatment at the eight Japanese hospitals (Michinoku RCC). Early cessation was defined as VEGFR-TKIs being given up within 3 months after their initiation. The number of patients in early cessation VEGFR-TKIs (Cohort I) was 173 (34.9%), and in long-term use (Cohort II) was 323 (65.1%). The cancer-specific survival (CSS) and overall survival (OS) were better in Cohort II. IMDC Poor-risk was at risk of early cessation of a first-line VEGFR-TKI. Axitinib was the most preferred drug for long-term treatment. On closer examination, both Cohort I and II were divided into two groups, the patients ceased VEGFR-TKI due to adverse events (Group A [67 from Cohort I] and Group C [51 from Cohort II]) and disease progression (Group B [106 from Cohort I] and Group D [272 from Cohort II]). Despite that the cessation was adverse events, CSS and OS in Group A were worse than both Group C and D. Axitinib was administered with the safer profile. IMDC Poor risk was the risk factor for the early disease progression. Managing early adverse events may contribute to a better prognosis in mRCC patients treated VEGFR-TKIs.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Estudos Retrospectivos , Neoplasias Renais/patologia , Axitinibe/efeitos adversos , Fator A de Crescimento do Endotélio Vascular , Inibidores de Proteínas Quinases/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular , Progressão da Doença
18.
Fukushima J Med Sci ; 68(3): 161-167, 2022 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-36372441

RESUMO

OBJECTIVE: To investigate the presence of bacteria in prostate tissue, and relationships between the bacteria and histopathological findings. METHODS: Samples were collected from prostate biopsy patients with no obvious lower urinary tract symptoms (LUTS). Detection and identification of bacterial species in the prostate tissues were performed with PCR for 16SrDNA and DNA sequencing. Histopathology was also evaluated. LUTS and lower urinary tract function were assessed by questionnaires, uroflowmetry, and ultrasonography. RESULTS: DNA was extracted from 97 prostate biopsies, with 5 bacterial species detected among samples from 7 patients (7.2%). The stroma-to-gland ratio in the prostate tissues from patients with bacteria was lower than in those without bacteria (p < 0.01). Glandular epithelial hyperplasia was also identified in the prostates harboring bacteria. International Prostate Symptom Score (IPSS), IPSS-quality of life (IPSS-QOL), Overactive Bladder Symptom Score (OABSS), maximum flow rate, urine volume by uroflowmetry, and post-voided residual urine were not significantly different when comparing patients with and without bacteria in their prostate samples. CONCLUSIONS: The present study demonstrated that 7.2% of men without obvious LUTS had bacteria in their prostate tissues. The presence of such bacteria might induce glandular hyperplasia and contribute to pathological changes in the early stages of benign prostate enlargement before affecting LUTS.


Assuntos
Sintomas do Trato Urinário Inferior , Próstata , Masculino , Humanos , Próstata/patologia , Qualidade de Vida , Hiperplasia/patologia , Sintomas do Trato Urinário Inferior/diagnóstico , Sintomas do Trato Urinário Inferior/patologia , Biópsia , Bactérias/genética
19.
In Vivo ; 36(5): 2384-2391, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36099112

RESUMO

BACKGROUND/AIM: The aim of the study was to evaluate the risk of venous thromboembolism (VTE) after robot-assisted radical prostatectomy (RARP) and discuss whether a uniform prophylaxis for VTE after radical prostatectomy is also suitable for robotic surgery. On this context, we investigated the incidence and risk factors of VTE, including asymptomatic events, after RARP compared to transurethral resection of bladder tumor (TUR-BT). PATIENTS AND METHODS: The participants were 209 patients with localized prostate cancer who underwent RARP, and 93 patients who underwent TUR-BT as controls. The incidence and risk factors of VTE, including deep vein thrombosis and pulmonary embolism, were systemically investigated seven days after surgery using contrast-enhanced computed tomography. RESULTS: Of the 209 RARP patients, 5.7% (12/209) patients had VTE. All events were asymptomatic and the incidence of VTE was not significantly different between the two surgeries (p=0.90). In multivariate analyses, neoadjuvant androgen deprivation therapy (ADT) (p=0.006), D-dimer value on postoperative day 1 (p=0.001) and lymphocele formation (p=0.043) were significantly associated with VTE after RARP. CONCLUSION: The risk of VTE after RARP might not be so high and uniform prophylaxis might not be suitable for RARP because it might be the same as that after transurethral resection for bladder tumors. However, neoadjuvant ADT, high D-dimer levels after surgery and lymphocele formation should be noted as risk factors of VTE after RARP.


Assuntos
Linfocele , Neoplasias da Próstata , Robótica , Neoplasias da Bexiga Urinária , Tromboembolia Venosa , Antagonistas de Androgênios , Humanos , Linfocele/etiologia , Linfocele/cirurgia , Masculino , Estudos Prospectivos , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Fatores de Risco , Neoplasias da Bexiga Urinária/cirurgia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle
20.
Int J Urol ; 29(10): 1132-1138, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35606052

RESUMO

OBJECTIVES: The aim of the present study was to clarify the relationships of intraoperative surgical position with the incidence of postoperative rhabdomyolysis and with postoperative renal function to safely perform robot-assisted radical prostatectomy. METHODS: The participants in the present study were 276 consecutive patients who underwent robot-assisted radical prostatectomy at our institutions between 2013 and 2020; 130 cases were performed in the opened legs position and 146 cases in the lithotomy position with a steep 23°-25° head-down position. Rhabdomyolysis was defined as creatine kinase values greater than 1000 IU/L. Propensity score matching including age, body mass index, the presence of comorbidities, preoperative creatine kinase, preoperative estimated glomerular filtration rate, and prostate-specific antigen was performed, resulting in a matched cohort of 146 patients (opened legs position group n = 73; lithotomy position group n = 73). RESULTS: After propensity score matching, creatine kinase values on the first day after surgery were significantly lower in the opened legs position group than in the lithotomy position group (opened legs position group: lithotomy position group = 246.9 ± 114.9 IU/L: 558.2 ± 114.9 IU/L, P = 0.034). There were significantly fewer patients diagnosed with postoperative rhabdomyolysis in the opened legs position group (opened legs position group: lithotomy position group = 0% (0/73): 9.6% (7/73), P < 0.001). In addition, fluid replacement volume was significantly less in the opened legs position group (opened legs position group: lithotomy position group = 5747 ± 180 mL: 6349 ± 0176 mL, P = 0.018). CONCLUSIONS: To prevent rhabdomyolysis after surgery, robot-assisted radical prostatectomy should be performed in the opened legs position.


Assuntos
Neoplasias da Próstata , Rabdomiólise , Procedimentos Cirúrgicos Robóticos , Robótica , Creatina Quinase , Humanos , Perna (Membro) , Masculino , Pontuação de Propensão , Antígeno Prostático Específico , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/complicações , Neoplasias da Próstata/cirurgia , Rabdomiólise/epidemiologia , Rabdomiólise/etiologia , Rabdomiólise/prevenção & controle , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos
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