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1.
World J Urol ; 42(1): 185, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38512511

RESUMO

PURPOSE: The International Bladder Cancer Group designated the subgroup that is resistant to Bacillus Calmette-Guérin (BCG) but does not meet the criteria for BCG-unresponsive NMIBC as "BCG-exposed high-risk NMIBC" to guide optimal trial design. We aimed to investigate the treatment patterns and prognoses of patients with BCG-exposed NMIBC. METHODS: We conducted a retrospective chart review of 3283 patients who received intravesical BCG therapy for NMIBC at 14 participating institutions between January 2000 and December 2019. Patients meeting the criteria for BCG-exposed and BCG-unresponsive NMIBC, as defined by the Food and Drug Administration and International Bladder Cancer Group, were selected. To compare treatment patterns and outcomes, high-risk recurrence occurring more than 24 months after the last dose of BCG was defined as "BCG-treated NMIBC." In addition, we compared prognoses between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. RESULTS: Of 3283 patients, 108 (3.3%), 150 (4.6%), and 391 (11.9%) were classified as having BCG-exposed, unresponsive, and treated NMIBC, respectively. BCG-exposed NMIBC demonstrated intermediate survival curves for intravesical recurrence-free and progression-free survival, falling between those of BCG-unresponsive and treated NMIBC. Among patients with BCG-exposed NMIBC, 48 (44.4%) received BCG rechallenge, which was the most commonly performed treatment, and 19 (17.6%) underwent early cystectomy. No significant differences were observed between BCG rechallenge and early cystectomy in patients with BCG-exposed NMIBC. CONCLUSIONS: The newly proposed definition of BCG-exposed NMIBC may serve as a valuable disease subgroup for distinguishing significant gray areas, except in cases of BCG-unresponsive NMIBC.


Assuntos
Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Vacina BCG/uso terapêutico , Estudos Retrospectivos , Adjuvantes Imunológicos/uso terapêutico , Prognóstico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Análise de Dados , Administração Intravesical , Invasividade Neoplásica , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/tratamento farmacológico
2.
Ann Surg Oncol ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38353798

RESUMO

BACKGROUND: This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. METHODS: The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. RESULTS: Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20 ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. CONCLUSION: The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.

3.
Sci Rep ; 14(1): 2397, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336798

RESUMO

Formaldehyde (H2CO) is a critical precursor for the abiotic formation of biomolecules, including amino acids and sugars, which are the building blocks of proteins and RNA. Geomorphological and geochemical evidence on Mars indicates a temperate environment compatible with the existence of surface liquid water during its early history at 3.8-3.6 billion years ago (Ga), which was maintained by the warming effect of reducing gases, such as H2. However, it remains uncertain whether such a temperate and weakly reducing surface environment on early Mars was suitable for producing H2CO. In this study, we investigated the atmospheric production of H2CO on early Mars using a 1-D photochemical model assuming a thick CO2-dominated atmosphere with H2 and CO. Our results show that a continuous supply of atmospheric H2CO can be used to form various organic compounds, including amino acids and sugars. This could be a possible origin for the organic matter observed on the Martian surface. Given the previously reported conversion rate from H2CO into ribose, the calculated H2CO deposition flux suggests a continuous supply of bio-important sugars on early Mars, particularly during the Noachian and early Hesperian periods.

4.
Asian J Endosc Surg ; 17(1): e13256, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37885361

RESUMO

INTRODUCTION: Holmium laser enucleation of the prostate (HoLEP) is an effective and safe surgery for patients with benign prostatic hyperplasia. However, some patients exhibit postoperative urinary incontinence. Here, we compared surgical outcomes and incidence of stress urinary incontinence between HoLEP with and without anterior prostatic urethral mucosa preservation (APUMP). METHODS: All patients in this study underwent HoLEP with APUMP technique (APUMP group) and without APUMP technique (no-APUMP group). Enucleation weight, enucleation time, max flow rate increase at 3 months, and urinary incontinence rates immediately after catheter removal and at 1 month after surgery were compared between the groups. RESULTS: In the APUMP (n = 340) and no-APUMP (n = 75) groups, the median enucleation weights were 34.5 and 35.0 g, respectively (p = .982). The corresponding median enucleation times were 33.0 and 46.5 min (p < .01), and median max flow rate increases at 1 month were 10.5 and 9.9 mL/s (p = .89). The urinary incontinence rates immediately after catheter removal were 4.1% and 14.7% (p < .01), and were 3.8% and 12.0% (p < .01) at 1 month after surgery. CONCLUSION: HoLEP using the APUMP technique could be performed with a shorter operative time while maintaining efficacy. The incidence of postoperative urinary incontinence could be decreased by APUMP, indicating that such preservation facilitates the maintenance of urinary continence after surgery.


Assuntos
Lasers de Estado Sólido , Hiperplasia Prostática , Incontinência Urinária por Estresse , Incontinência Urinária , Masculino , Humanos , Próstata , Incontinência Urinária por Estresse/cirurgia , Lasers de Estado Sólido/uso terapêutico , Hiperplasia Prostática/cirurgia , Mucosa , Resultado do Tratamento , Estudos Retrospectivos
5.
Int J Urol ; 31(4): 362-369, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38148124

RESUMO

OBJECTIVES: To compare the effectiveness and safety of gonadotropin-releasing hormone (GnRH) antagonist monotherapy to combined androgen blockade (CAB) with a GnRH agonist and bicalutamide in patients with advanced hormone-sensitive prostate cancer (HSPC). METHODS: The study was conducted as KYUCOG-1401 trial (UMIN000014243) and enrolled 200 patients who were randomly assigned to either group A (GnRH antagonist monotherapy followed by the addition of bicalutamide) or group B (CAB by a GnRH agonist and bicalutamide). The primary endpoint was PSA progression-free survival. The secondary endpoints were the time to CAB treatment failure, radiographic progression-free survival, overall survival, changes in serum parameters, including PSA, hormones, and bone and lipid metabolic markers, and adverse events. RESULTS: PSA progression-free survival was significantly longer in group B (hazard ratio [HR], 95% confidence interval [CI]; 1.40, 1.01-1.95, p = 0.041). The time to CAB treatment failure was slightly longer in group A (HR, 95% CI; 0.80, 0.59-1.08, p = 0.146). No significant differences were observed in radiographic progression-free survival or overall survival. The percentage of patients with serum testosterone that did not reach the castration level was higher at 60 weeks (p = 0.046) in group A. No significant differences were noted in the serum levels of bone metabolic or lipid markers between the two groups. An injection site reaction was more frequent in group A. CONCLUSIONS: The present results support the potential of CAB using a GnRH agonist and bicalutamide as a more effective treatment for advanced HSPC than GnRH antagonist monotherapy.


Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Antagonistas de Androgênios/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Anilidas/efeitos adversos , Nitrilas/efeitos adversos , Compostos de Tosil/efeitos adversos , Hormônio Liberador de Gonadotropina , Lipídeos/uso terapêutico
6.
J Histochem Cytochem ; 71(10): 555-563, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37675782

RESUMO

Thus far, several monoclonal antibodies directed against cell-surface carbohydrate antigens have been generated. Among them, R-10G reportedly reacts selectively with human embryonic stem and induced pluripotent stem cells, but not with embryonal carcinoma (EC) cells. However, EC cells derived from patients' EC tumors may exhibit varying levels of R-10G-reactive antigen expression. Thus, we asked whether human EC tissues or germ cell tumor (GCT) tissues other than EC express R-10G-reactive antigen. To do so, we quantitatively analyzed R-10G-reactive antigen expression in 83 testicular GCT surgical specimens containing a total of 125 various GCT components. Accordingly, in all EC components examined, the EC cell plasma membrane was immunolabeled with R-10G, while most seminoma components were R-10G-negative. In non-seminomatous GCT (NSGCT) other than EC (non-EC NSGCT), R-10G-reactive antigen expression was variable, but signal distribution was focal, and the average intensity was weaker than that seen in EC. The percentages of R-10G-positive cells in these three groups varied with high statistical significance (p<0.001 for all combinations). These findings indicate that the R-10G-reactive antigen is preferentially expressed in human testicular EC tissues and, thus, could be used as a diagnostic marker for this malignancy.


Assuntos
Carcinoma Embrionário , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , Biomarcadores Tumorais , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/metabolismo , Anticorpos Monoclonais
8.
Jpn J Clin Oncol ; 53(10): 984-990, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37496400

RESUMO

BACKGROUND: In men undergoing upfront active surveillance, predictors of adverse pathology in radical prostatectomy specimens, including intraductal carcinoma of the prostate and cribriform patterns, remain unknown. Therefore, we aimed to examine whether adverse pathology in radical prostatectomy specimens could be predicted using preoperative patient characteristics. METHODS: We re-reviewed available radical prostatectomy specimens from 1035 men prospectively enrolled in the PRIAS-JAPAN cohort between January 2010 and September 2020. We defined adverse pathology on radical prostatectomy specimens as Gleason grade group ≥3, pT stage ≥3, pN positivity or the presence of intraductal carcinoma of the prostate or cribriform patterns. We also examined the predictive factors associated with adverse pathology. RESULTS: All men analyzed had Gleason grade group 1 specimens at active surveillance enrolment. The incidence of adverse pathologies was 48.9% (with intraductal carcinoma of the prostate or cribriform patterns, 33.6%; without them, 15.3%). The addition of intraductal carcinoma of the prostate or cribriform patterns to the definition of adverse pathology increased the incidence by 10.9%. Patients showing adverse pathology with intraductal carcinoma of the prostate or cribriform patterns had lower biochemical recurrence-free survival (log-rank P = 0.0166). Increasing age at active surveillance enrolment and before radical prostatectomy was the only predictive factor for adverse pathology (odds ratio: 1.1, 95% confidence interval: 1.02-1.19, P = 0.0178; odds ratio: 1.12, 95% confidence interval: 1.02-1.22, P = 0.0126). CONCLUSIONS: Increasing age could be a predictive factor for adverse pathology. Our findings suggest that older men could potentially derive advantages from adhering to the examination schedule in active surveillance.


Assuntos
Carcinoma Intraductal não Infiltrante , Neoplasias da Próstata , Masculino , Humanos , Idoso , Próstata/patologia , Carcinoma Intraductal não Infiltrante/patologia , Conduta Expectante , Neoplasias da Próstata/patologia , Prostatectomia , Gradação de Tumores
9.
Plants (Basel) ; 12(11)2023 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-37299165

RESUMO

Pre-sowing seed priming is one of the methods used to improve the performance of tomato plants under salt stress, but its effect photosynthesis, yield, and quality have not yet been well investigated. This experiment aimed to alleviate the impact of sodium chloride stress on the photosynthesis parameters of tomato cv. Micro-Tom (a dwarf Solanum lycopersicum L.) plants exposed to salt stress conditions. Each treatment combination consisted of five different sodium chloride concentrations (0 mM, 50 mM, 100 mM, 150 mM, and 200 mM) and four priming treatments (0 MPa, -0.4 MPa, -0.8 MPa, and -1.2 MPa), with five replications. Microtome seeds were subjected to polyethylene glycol (PEG6000) treatments for 48 hours for priming, followed by germination on a moist filter paper, and then transferred to the germination bed after 24 h. Subsequently, the seedlings were transplanted into the Rockwool, and the salinity treatments were administered after a month. In our study salinity significantly affected tomato plants' physiological and antioxidant attributes. Primed seeds produced plants that exhibited relatively better photosynthetic activity than those grown from unprimed seeds. Our findings indicated that priming doses of -0.8 MPa and -1.2 MPa were the most effective at stimulating tomato plant photosynthesis, and biochemical contents under salinity-related conditions. Moreover, primed plants demonstrated relatively superior fruit quality features such as fruit color, fruit Brix, sugars (glucose, fructose, and sucrose), organic acids, and vitamin C contents under salt stress, compared to non-primed plants. Furthermore, priming treatments significantly decreased the malondialdehyde, proline, and hydrogen peroxide content in plant leaves. Our results suggest that seed priming may be a long-term method for improving crop productivity and quality in challenging environments by enhancing the growth, physiological responses, and fruit quality attributes of Micro-Tom tomato plants under salt stress conditions.

10.
Endocr Relat Cancer ; 30(7)2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37079309

RESUMO

Androgen-deprivation therapy (ADT) has been widely used for the treatment of advanced prostate cancer. However, prognosis and adverse events (AEs) vary among patients. This study aimed to identify genetic markers able to predict the outcome of ADT. Japanese patients treated with primary ADT for advanced prostate cancer in the KYUCOG-1401 trial were enrolled as a development set. A distinct population of advanced prostate cancer cases treated with ADT was included as a validation set. Single-nucleotide polymorphisms (SNPs) associated with radiographic progression-free survival (rPFS) at 1 year and AEs including de novo diabetes mellitus (DM), arthralgia, and de novo dyslipidemia were identified in the development set by a genome-wide association study (GWAS). The SNPs associated with rPFS in the development study were then genotyped in the validation set. GWAS followed by validation identified SNPs (rs76237622 in PRR27 and rs117573572 in MTAP) that were associated with overall survival (OS) in ADT. A genetic prognostic model using these SNPs showed excellent predictive efficacy for PFS and OS in ADT. In addition, GWAS showed that several SNPs were associated with de novo DM, arthralgia, and de novo dyslipidemia in ADT. This study identified novel multiple SNPs that correlated with outcomes in ADT. Future studies on correlations affecting the therapeutic efficacy of ADT-based combination therapies would make a valuable contribution to the development of personalized medicine.


Assuntos
Diabetes Mellitus , Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Estudo de Associação Genômica Ampla , Antagonistas de Androgênios/uso terapêutico , Prognóstico , Diabetes Mellitus/tratamento farmacológico
11.
Cancer Rep (Hoboken) ; 6(2): e1701, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36806727

RESUMO

BACKGROUND: Several treatment strategies use upfront chemotherapy or androgen receptor axis-targeting therapies for metastatic prostate cancer. However, there are no useful biomarkers for selecting appropriate patients who urgently require these treatments. METHODS: Novel patient-derived xenograft (PDX) castration-sensitive and -resistant models were established and gene expression patterns were comprehensively compared. The function of a gene highly expressed in the castration-resistant models was evaluated by its overexpression in LNCaP prostate cancer cells. Protein expression in the tumors and serum of patients was examined by immunohistochemistry and ELISA, and correlations with castration resistance were analyzed. RESULTS: Expression of the α2 chain of interleukin-13 receptor (IL13Rα2) was higher in castration-resistant PDX tumors. LNCaP cells overexpressing IL13Rα2 acquired castration resistance in vitro and in vivo. In tissue samples, IL13Rα2 expression levels were significantly associated with castration-resistant progression (p < 0.05). In serum samples, IL13Rα2 levels could be measured in 5 of 28 (18%) castration-resistant prostate cancer patients. CONCLUSION: IL13Rα2 was highly expressed in castration-resistant prostate cancer PDX models and was associated with the castration resistance of prostate cancer cells. It might be a potential tissue and serum biomarker for predicting castration resistance in prostate cancer patients.


Assuntos
Subunidade alfa2 de Receptor de Interleucina-13 , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/patologia , Subunidade alfa2 de Receptor de Interleucina-13/uso terapêutico , Xenoenxertos , Orquiectomia , Biomarcadores
12.
Cancer Sci ; 114(4): 1625-1634, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36602227

RESUMO

Genetic variations represented by single-nucleotide polymorphisms (SNPs) could be helpful for choosing an effective treatment for patients with prostate cancer. This study investigated the prognostic and predictive values of SNPs associated with the prognoses of pharmacotherapy for prostate cancer through their pharmacological mechanisms. Patients treated with docetaxel or androgen receptor pathway inhibitors (ARPIs), such as abiraterone and enzalutamide, for castration-resistant prostate cancer were included. The SNPs of interest were genotyped for target regions. The prognostic and predictive values of the SNPs for time to progression (TTP) were examined using the Cox hazard proportional model and interaction test, respectively. Rs1045642 in ABCB1, rs1047303 in HSD3B1, rs1856888 in HSD3B1, rs523349 in SRD5A2, and rs34550074 in SLCO2A1 were differentially associated with TTP between docetaxel chemotherapy and ARPI treatment. In addition to rs4775936 in CYP19A1, rs1128503 in ABCB1 and rs1077858 in SLCO2B1 might be differentially associated with TTP between abiraterone and enzalutamide treatments. Genetic predictive models using these SNPs showed a differential prognosis for treatments. This study identified SNPs that could predict progression as well as genetic models that could predict progression when patients were treated with docetaxel versus ARPI and abiraterone versus enzalutamide. The use of genetic predictive models is expected to be beneficial in selecting the appropriate treatment for the individual patient.


Assuntos
Docetaxel , Transportadores de Ânions Orgânicos , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Antagonistas de Receptores de Andrógenos/uso terapêutico , Androgênios , Docetaxel/uso terapêutico , Variação Genética , Proteínas de Membrana/genética , Nitrilas/uso terapêutico , Transportadores de Ânions Orgânicos/genética , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Taxoides , Resultado do Tratamento
13.
Int J Urol ; 30(2): 227-234, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36375045

RESUMO

OBJECTIVE: This study investigated the efficacy of docetaxel (DOC) and cabazitaxel (CBZ) and examined the factors associated with the prognosis of patients with castration-resistant prostate cancer (CRPC) receiving DOC-CBZ sequential treatment in Japanese real-world data. METHODS: We retrospectively evaluated data for 146 patients who received DOC followed by CBZ. The correlations of prostate specific antigen (PSA) decrease rate and time to progression between DOC and CBZ treatment were examined. Combined progression-free survival (PFS) of DOC-CBZ and overall survival (OS) from the initiation of DOC and the diagnosis of CRPC were evaluated and compared between patients with high and low PSA levels at the start of DOC and CBZ treatment. RESULTS: No correlations of PSA decrease rate and time to progression were observed between DOC and CBZ. The patients for whom DOC was started in higher PSA levels had significantly shorter combined PFS (p = 0.003) and OS from the initiation of DOC (p = 0.002). In patients who started DOC at high PSA levels, those who switched to CBZ at low PSA levels had longer OS than those who switched at high PSA levels (p = 0.048). The OS from CRPC of patients who started DOC at low PSA levels was significantly longer than those that started at high PSA levels (p = 0.030). CONCLUSIONS: For patients for whom DOC was not effective, sequential CBZ might have change to be effective. The PSA levels at the start of DOC and CBZ might be a potential prognostic biomarker.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Docetaxel/uso terapêutico , Estudos Retrospectivos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Antígeno Prostático Específico , Japão , Resultado do Tratamento
14.
Urology ; 172: 49-54, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36370770

RESUMO

OBJECTIVE: To examine the safety and efficacy of Endoscopic combined intrarenal surgery (ECIRS) between the lateral decubitus (LD) and Galdakao-modified supine Valdivia (GMSV) position. METHODS: We retrospectively reviewed the records of 226 patients with renal stones who underwent ECIRS in the LD and GMSV positions between 2018 and 2022. Surgeries early in the study period were mainly performed in the GMSV position, while later surgeries were mainly performed in the LD position. RESULTS: The number of patients in the LD and GMSV groups was 119 and 107, respectively. The proportion of patients who had no residual stone fragments >2 mm detected on radiography the day after surgery did not significantly differ between the LD group (91.6%) and the GMSV group (97.2%). Operation time was significantly shorter in the LD group (72 vs 81 minutes; P = .02). Total fluoroscopy time was significantly shorter in the LD group (92 vs 189 seconds; P<.001). Complication rates did not significantly differ between the groups. Among the variables analyzed, the patient position was independently impact on the fluoroscopy time (OR 0.309; 95% CI, 0.167-0.571; P<.001). CONCLUSION: ECIRS in the LD position is safe and effective and associated with shorter fluoroscopy than the GSMV position.


Assuntos
Cálculos Renais , Nefrostomia Percutânea , Humanos , Estudos Retrospectivos , Endoscopia , Cálculos Renais/cirurgia , Postura , Decúbito Dorsal
15.
Nat Commun ; 13(1): 6609, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329013

RESUMO

Dust storms on Mars play a role in transporting water from its lower to upper atmosphere, seasonally enhancing hydrogen escape. However, it remains unclear how water is diurnally transported during a dust storm and how its elements, hydrogen and oxygen, are subsequently influenced in the upper atmosphere. Here, we use multi-spacecraft and space telescope observations obtained during a major dust storm in Mars Year 33 to show that hydrogen abundance in the upper atmosphere gradually increases because of water supply above an altitude of 60 km, while oxygen abundance temporarily decreases via water ice absorption, catalytic loss, or downward transportation. Additionally, atmospheric waves modulate dust and water transportations, causing alternate oscillations of hydrogen and oxygen abundances in the upper atmosphere. If dust- and wave-driven couplings of the Martian lower and upper atmospheres are common in dust storms, with increasing escape of hydrogen, oxygen will less efficiently escape from the upper atmosphere, leading to a more oxidized atmosphere. These findings provide insights regarding Mars' water loss history and its redox state, which are crucial for understanding the Martian habitable environment.


Assuntos
Meio Ambiente Extraterreno , Marte , Hidrogênio , Oxigênio , Atmosfera , Água , Poeira/análise
16.
Anticancer Res ; 42(10): 4981-4987, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36191975

RESUMO

BACKGROUND/AIM: Radium-223 (Ra-223) therapy provides a survival benefit for castration-resistant prostate cancer (CRPC) patients with bone metastasis. The optimal timing of using Ra-223 has not been determined. We evaluated the efficacy and safety of Ra-223 before and after docetaxel (DOC) therapy. PATIENTS AND METHODS: We retrospectively reviewed 36 CRPC patients with bone metastasis who were treated with Ra-223 in our institution and satellite hospitals. Ra-223 was used before DOC (pre-DOC group) in 17 patients (47%) and after DOC (post-DOC group) in 19 patients (53%). The treatment completion rate of 6 cycles, progression-free survival (PFS), cause-specific survival (CSS) and occurrence rate of adverse events were compared between the groups. RESULTS: The median follow-up duration was 45 months. In the pre-DOC compared with the post-DOC group, treatment completion rate was significantly higher (94% vs. 52%, p<0.01), PFS was significantly longer (median: 8 vs. 5 months, p=0.024) and CSS was significantly longer (median: 32 vs. 15 months, p=0.028). The difference in CSS was significant in multivariate analysis. In the pre-DOC compared with the post-DOC group, the occurrence rate of grade ≥3 adverse events tended to be lower (6% vs. 36%, p=0.322), and the CSS tended to be longer (median: not reached vs. 45 months, p=0.208). CONCLUSION: Ra-223 could be used more safely and more effectively for CRPC patients with bone metastasis before than after DOC therapy.


Assuntos
Neoplasias Ósseas , Neoplasias de Próstata Resistentes à Castração , Rádio (Elemento) , Neoplasias Ósseas/induzido quimicamente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/radioterapia , Docetaxel/efeitos adversos , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Rádio (Elemento)/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
17.
Br J Cancer ; 127(9): 1680-1690, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35986085

RESUMO

BACKGROUND: The prognostic significance of germline variants in homologous recombination repair genes in advanced prostate cancer (PCa), especially with regard to hormonal therapy, remains controversial. METHODS: Germline DNA from 549 Japanese men with metastatic and/or castration-resistant PCa was sequenced for 27 cancer-predisposing genes. The associations between pathogenic variants and clinical outcomes were examined. Further, for comparison, DNA from prostate biopsy tissue samples from 80 independent patients with metastatic PCa were analysed. RESULTS: Forty-four (8%) patients carried germline pathogenic variants in one of the analysed genes. BRCA2 was most frequently altered (n = 19), followed by HOXB13 (n = 9), PALB2 (n = 5) and ATM (n = 5). Further, the BRCA1, BRCA2, PALB2 and ATM variants showed significant association with a short time to castration resistance and overall survival (hazard ratio = 1.99 and 2.36; 95% CI, 1.15-3.44 and 1.23-4.51, respectively), independent of other clinical variables. Based on log-rank tests, the time to castration resistance was also significantly short in patients with BRCA1, BRCA2, PALB2 or ATM somatic mutations and TP53 mutations. CONCLUSIONS: Germline variants in BRCA1, BRCA2, PALB2 or ATM are independent prognostic factors of the short duration of response to hormonal therapy in advanced PCa.


Assuntos
Mutação em Linhagem Germinativa , Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Proteína BRCA2/genética , Genes BRCA2 , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Mutação , Predisposição Genética para Doença , Proteína BRCA1/genética , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética
19.
J Clin Med ; 11(12)2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35743608

RESUMO

OBJECTIVES: To evaluate the management and outcome of idiopathic retroperitoneal fibrosis (iRPF) in Japan, and to identify its clinical biomarker. METHODS: We retrospectively analyzed 129 patients with iRPF treated between January 2008 and May 2018 at 12 university and related hospitals. Patients treated with glucocorticoid were analyzed to identify a predictive biomarker. These patients were classified into three groups according to overall effectiveness (no change: NC, complete response: CR, and partial response groups: PR), and each parameter was compared statistically. RESULTS: Male-female ratio was 5:1, and median age at diagnosis was 69 (33-86) years. Smoking history was reported in 59.6% of the patients. As treatment, 95 patients received glucocorticoid therapy with an overall response rate of 84%. As a result, serum concentration of IgG4 was significantly decreased in NC group compared with the other two groups (56.6 mg/dL vs. 255 mg/dL, 206 mg/dL, p = 0.0059 and 0.0078). ROC analysis was performed between the nonresponder (NC) and responder groups (CR + PR) to identify the cut-off value of serum IgG4 as a predictive marker. As a result, AUC of 0.793 was confirmed. CONCLUSIONS: Pre-treatment serum IgG4 concentration may have potential as a predictive biomarker of steroid treatment.

20.
Int J Urol ; 29(10): 1147-1154, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35613936

RESUMO

OBJECTIVE: This study aimed to assess survival outcomes in older patients with de novo metastatic prostate cancer who initially received androgen deprivation therapy. METHODS: The retrospective multicenter study included 2784 men with metastatic prostate cancer who were treated with androgen deprivation therapy between 2008 and 2017. Patients were classified into <75, 75-79, and ≥80 age groups. Propensity score matching was conducted to assess the cancer-specific survival of the groups. The 5-year net overall survival of each group was derived to evaluate relative survival compared with the general population using the Pohar-Perme estimator and the 2019 Japan Life Table. RESULTS: During the follow-up (median, 34 months), 1014 patients died, of which 807 died from metastatic prostate cancer progression. Compared with the <75 group, the cancer-specific survival of the 75-79 group was similar (hazard ratio 1.07; 95% confidence interval 0.84-1.37; P = 0.580), whereas that of the ≥80 group was significantly worse (hazard ratio 1.41; 95% confidence interval 1.10-1.80; P = 0.006). The 5-year net overall survival of the <75, 75-79, and ≥80 age groups were 0.678, 0761, and 0.718, respectively. The 5-year net overall survival of patients aged ≥80 years with low- and high-volume disease were 0.893 and 0.586, respectively, which was comparable with those in patients aged <75 years (0.872 and 0.586, respectively). CONCLUSIONS: Older metastatic prostate cancer patients aged ≥80 years had poorer cancer-specific survival compared with younger patients. Conversely, 5-year net overall survival in older patients aged ≥80 years was comparable with that in younger patients aged <75 years.


Assuntos
Neoplasias da Próstata , Idoso , Antagonistas de Androgênios/uso terapêutico , Androgênios , Humanos , Masculino , Modelos de Riscos Proporcionais , Neoplasias da Próstata/patologia , Estudos Retrospectivos
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