RESUMO
This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.
Assuntos
Inibidores da Agregação Plaquetária , Piridinas , Robótica , Masculino , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos de Coortes , Hemorragia/induzido quimicamente , Aspirina/efeitos adversos , Tienopiridinas , Prostatectomia/efeitos adversosRESUMO
Congenital hypogonadotropic hypogonadism (CHH) is a genetically and clinically diverse disorder encompassing Kallmann syndrome (KS) and normosmic CHH (nCHH). Although mutations in numerous genes account for nearly 50% of CHH cases, a significant portion remains genetically uncharacterized. While most mutations follow the traditional Mendelian inheritance patterns, evidence suggests oligogenic interactions between CHH genes, acting as modifier genes to explain variable expressivity and incomplete penetrance associated with certain mutations.In this study, the proband presented with nCHH, while his son exhibited KS. We employed whole-exome sequencing (WES) to investigate the genetic differences between the two, and Sanger sequencing was used to validate the results obtained from WES.Genetic analysis revealed that both the proband and his son harboured a mutation in FGFR1 gene. Notably, an additional rare mutation in PROKR2 gene was exclusively identified in the son, which suggests the cause of the phenotypic difference between KS and nCHH.
Assuntos
Hipogonadismo , Síndrome de Kallmann , Humanos , Síndrome de Kallmann/genética , Mutação de Sentido Incorreto , Hipogonadismo/genética , Mutação , Família , Receptores de Peptídeos/genética , Receptores Acoplados a Proteínas G/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genéticaRESUMO
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 farmacológicoRESUMO
Objective: To explore a morphometric grading system for blastocysts that is associated with ongoing pregnancy. Design: Cross-sectional study. Setting: None. Patientss: All consecutive vitrified blastocysts at our center from July 2018 to November 2021 that were transferred in single blastocyst transfer cycles until January 2022. Interventions: None. Main Outcome Measures: The ongoing pregnancy rate after a single vitrified-warmed blastocyst transfer. Interobserver agreement on morphometric values among embryologists. Results: Three morphometric variables (blastocyst diameter, area of inner cell mass [ICM], and the estimated trophectoderm cell count) were used to evaluate the expansion, ICM, and trophectoderm morphology. During the study period, 585 blastocysts were involved in this study. Of the 3 morphometric variables, ICM area (per 500 µm2, adjusted odds ratio, 1.19; 95% confidence interval, 1.09-1.30) and estimated trophectoderm cell count (per 10 cells, adjusted odds ratio, 1.25; 95% confidence interval, 1.12-1.39) were significantly associated with the ongoing pregnancy rate after adjustment for confounding factors. The ongoing pregnancy rate was 2.0% (1/49) with an ICM area of <2,500 µm2 and the estimated trophectoderm cell count <70. The ongoing pregnancy rate reached 47.8% (22/46) when the ICM area and the estimated trophectoderm cell count were >3,500 µm2 and >110, respectively. Interobserver agreement on the blastocyst diameter, ICM area, and the estimated trophectoderm cell count was excellent-to-good among 5 embryologists (intraclass correlation coefficients: 0.99, 0.87, and 0.91, respectively). Conclusions: Morphometric values of ICM and trophectoderm are promising predictors of pregnancy success. The high reproducibility suggests that the morphometric variables will contribute to identifying blastocysts with the highest developmental potential as well as those that will not result in a successful pregnancy.
RESUMO
Using new castration-resistant prostate cancer (CRPC) cell lines developed from LNCaP cells as a model for CRPC, we searched for novel biomarkers by analyzing the proteins secreted in culture supernatants. The results showed that the levels of secretory leukocyte protease inhibitor (SLPI) in these cell lines were 4.7-6.7 times higher than those secreted in parental LNCaP. Patients with localized prostate cancer (PC) and who expressed SLPI had a significantly lower prostate-specific antigen (PSA) progression-free survival rate than those who did not. Multivariate analysis revealed that SLPI expression was an independent risk factor for PSA recurrence. By contrast, when immunostaining of SLPI was performed on consecutive prostate tissue samples obtained from 11 patients, both in hormone naive (HN) and castration resistant (CR) conditions, only one patient expressed SLPI in the HNPC state; however, four of the 11 patients expressed SLPI in the CRPC state. In addition, two of these four patients were resistant to enzalutamide, and there was a discrepancy between their serum PSA levels and radiographic progression of the disease. These results suggest that SLPI can be a predictor of prognosis in patients with localized PC and disease progression in CRPC patients.
Assuntos
Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Próstata , Inibidor Secretado de Peptidases Leucocitárias , Regulação para Cima , Recidiva Local de NeoplasiaRESUMO
PURPOSE: This study investigated the associations of personality traits and preoperative lifestyle improvements with early weight loss after sleeve gastrectomy. METHODS: This was a single-center, retrospective study of 57 patients who underwent preoperative lifestyle intervention with a multidisciplinary team approach based on cognitive behavioral therapy before sleeve gastrectomy. All patients underwent preoperative psychological testing with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) and the Tokyo University Egogram New Version II (TEG II). We investigated the associations of psychological testing results and lifestyle improvements with percent total weight loss (%TWL) one year after surgery. RESULTS: The median %TWL at 1 year was 38.2% for patients with an improved lifestyle and 26.9% for those without improvement (P = 0.0008). Although TEG II factors were not associated with %TWL at 1 year, higher NEO-FFI extraversion (E) scores were significantly associated with a better %TWL at 1 year. The median %TWL at 1 year was 35.2% for patients with higher E scores and 25.4% for those with lower E scores (P = 0.0247). Lifestyle improvement and the NEO-FFI E score significantly influenced %TWL at 1 year based on a logistic regression analysis. CONCLUSION: The NEO-FFI E score and preoperative lifestyle improvement may be predictors of early weight loss after sleeve gastrectomy.
Assuntos
Laparoscopia , Obesidade Mórbida , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Estilo de Vida , Gastrectomia/métodos , Redução de Peso , Laparoscopia/métodos , PersonalidadeRESUMO
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 TratamentoRESUMO
This study aimed to evaluate the effects of jaw-opening exercises with and without pain on temporomandibular disorders (TMDs), specifically in relation to pain intensity and range-of-mouth opening in patients with TMDs. Participants were randomly assigned to either the jaw-opening exercise with pain (JE w/pain) or the jaw-opening exercise without pain (JE w/o pain) groups, and each exercise was performed for eight weeks. TMDs pain intensity was assessed using a 100-mm visual analog scale (VAS), and the range-of-mouth opening was evaluated at the baseline (T0), 2 weeks (T1), 4 weeks (T2), and 8 weeks (T3). Of the 61 participants, 57 (JE w/pain group, n = 30; JE w/o pain group, n = 27) were included in the analysis. The range-of-mouth opening and TMDs pain intensity improved from T1 to T3 in both groups. The JE w/pain group showed significant differences at T3 compared to T1 (pain-free unassisted mouth opening, p = 0.006; jaw-opening pain, p = 0.014; chewing pain, p = 0.018). In addition, the JE w/pain group showed significantly greater changes in the maximum unassisted mouth opening at T2 and T3 than the JE w/o pain group (T2, p < 0.001; T3, p = 0.003). Thus, jaw-opening exercises, until the occurrence of pain, may be effective in patients with TMDs.
Assuntos
Transtornos da Articulação Temporomandibular , Humanos , Projetos Piloto , Resultado do Tratamento , Dor , Terapia por ExercícioRESUMO
A 60-year-old man developed dyspnea without apparent limb weakness. He had cardiomyopathy in his 30s and was treated for chronic heart failure since 42. He was diagnosed as having four and a half LIM domains 1 (FHL1) mutation at 53 following the same diagnosis of his younger brother. He was first admitted to the cardiology department for possible worsening of chronic cardiac failure. Blood gas analysis showing respiratory acidosis prompted his treatment with a respirator. Neurological examination revealed that he had mild weakness limited to the shoulder girdle muscles and contracture at jaw, spine, elbows and ankles. Skeletal muscle CT showed truncal atrophy. He, as well as his younger brother, was diagnosed with FHL1 myopathy resulting in ventilation failure and was discharged after successful weaning from the respirator in the daytime. The present sibling cases are the first with FHL1 mutation to develop respiratory failure without limb weakness and suggest that FHL1 myopathy as a differentially diagnosis of hereditary myopathies with early respiratory failure.
Assuntos
Doenças Musculares , Insuficiência Respiratória , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas com Domínio LIM/genética , Masculino , Pessoa de Meia-Idade , Proteínas Musculares/genética , Músculo Esquelético , Doenças Musculares/etiologia , Doenças Musculares/genética , Mutação , Insuficiência Respiratória/etiologia , IrmãosRESUMO
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/genéticaAssuntos
Neoplasias das Glândulas Suprarrenais , Técnica de Fontan , Cardiopatias Congênitas , Laparoscopia , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Cardiopatias Congênitas/cirurgia , Humanos , Feocromocitoma/diagnóstico por imagem , Feocromocitoma/cirurgiaRESUMO
ObjectivesãThe purpose of this study was to clarify the issues behind the increasing number of solitary deaths of older people in central Tokyo.MethodsãIn this study a request was made to the national government for information on the 2016 vital statistics survey of ward A, one of the 23 wards of Tokyo. The entries in the death forms do not distinguish between death and post-mortem certificates. However, in the 23 wards where there is a medical examiner system, if the medical institution of the doctor who prepared the post-mortem certificate is the Tokyo-to Medical Examiner's Office, it is possible to identify that the postmortem examination was performed. If the hospital is listed, it is considered a death certificate. A descriptive analytical study was made on the relationship between the cause of death, sex, age and marital status with regard to postmortem examinations of deaths at home or in hospitals resulting from illnesses and home care deaths.ResultsãOf the 4,429 deaths in Ward A in 2016, 613 were found to be postmortem examinations, of which 436 (71.1%) were of individuals who were 65 years or older. Of the 757 deaths at home, 399 (52.7%) were postmortem examinations, of which 271 were deaths from illness. The number of home care deaths was 358 (47.3%). The mean age of death was 73.6 years for 145 males and 79.5 years for 123 females, out of 268 home deaths of 34 years or older identified as death from illness by postmortem examination. On the other hand, the mean age of death in 358 home care deaths was significantly older as compared to postmortem examination deaths. 65.3% of deaths at home and 54.1% of hospital deaths were due to sudden death-type diseases such as ischemic heart disease. Of the postmortem examination of home deaths from illness among the older people aged 65 years or older, 65.5% of the 110 males and 87.3% of the 110 females were single. Bereavement occurred in 27.3% of men and 52.7% of women, separation in 16.4% of men and 9.1% of women. 21.8% of men and 25.5% of women were never married.ConclusionsãIn the solitary deaths of older people in central Tokyo, sudden death disease is the direct cause of death and, in the background, there are bereavement from a spouse in women, separation or bereavement from a spouse in men, and being unmarried in both.
Assuntos
Morte Súbita , Idoso , Autopsia , Causas de Morte , Morte Súbita/etiologia , Feminino , Humanos , Masculino , Estado Civil , TóquioRESUMO
Background: Multiple common variants and also rare variants in monogenic risk genes such as BRCA2 and HOXB13 have been reported to be associated with risk of prostate cancer (PCa); however, the clinical setting in which germline genetic testing could be used for PCa diagnosis remains obscure. Herein, we tested the clinical utility of a 16 common variant-based polygenic risk score (PRS) that has been developed previously for Japanese men and also evaluated the frequency of PCa-associated rare variants in a prospective cohort of Japanese men undergoing prostate biopsy. Methods: A total of 1336 patients undergoing first prostate biopsy were included. PRS was calculated based on the genotype of 16 common variants, and sequencing of 8 prostate cancer-associated genes was performed by multiplex polymerase chain reaction based target sequencing. PRS was combined with clinical factors in logistic regression models to assess whether addition of PRS improves the prediction of biopsy positivity. Results: The top PRS decile was associated with an odds ratio of 4.10 (95% confidence interval = 2.46 to 6.86) with reference to the patients at average risk, and the estimated lifetime absolute risk approached 20%. Among the patients with prostate specific antigen 2-10 ng/mL who had prebiopsy magnetic resonance imaging, high PRS had an equivalent impact on biopsy positivity as a positive magnetic resonance imaging finding. Rare variants were detected in 19 (2.37%) and 7 (1.31%) patients with positive and negative biopsies, respectively, with BRCA2 variants being the most prevalent. There was no association between PRS and high-risk rare variants. Conclusions: Germline genetic testing could be clinically useful in both pre- and post-PSA screening settings.
Assuntos
Variação Genética , Mutação em Linhagem Germinativa , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Proteínas Mutadas de Ataxia Telangiectasia/genética , Biópsia por Agulha/estatística & dados numéricos , Intervalos de Confiança , Genes BRCA2 , Testes Genéticos , Genótipo , Proteínas de Homeodomínio/genética , Humanos , Japão , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Fatores de Risco , Sequenciamento Completo do Genoma/métodosRESUMO
PURPOSE: Although cell-free DNA (cfDNA) testing is expected to drive cancer precision medicine, little is known about the significance of detecting low-frequency variants in circulating cell-free tumor DNA (ctDNA) in castration-resistant prostate cancer (CRPC). We aimed to identify genomic profile including low-frequency variants in ctDNA from patients with CRPC and investigate the clinical utility of detecting variants with variant allele frequency (VAF) below 1%. EXPERIMENTAL DESIGN: This prospective, multicenter cohort study enrolled patients with CRPC eligible for treatment with abiraterone or enzalutamide. We performed targeted sequencing of pretreatment cfDNA and paired leukocyte DNA with molecular barcodes, and ctDNA variants with a VAF ≥0.1% were detected using an in-house pipeline. We investigated progression-free survival (PFS) and overall survival (OS) after different ctDNA fraction cutoffs were applied. RESULTS: One hundred patients were analyzed (median follow-up 10.7 months). We detected deleterious ATM, BRCA2, and TP53 variants even in samples with ctDNA fraction below 2%. When the ctDNA fraction cutoff value of 0.4% was applied, significant differences in PFS and OS were found between patients with and without defects in ATM or BRCA2 [HR, 2.52; 95% confidence interval (CI), 1.24-5.11; P = 0.0091] and TP53 (HR, 3.74; 95% CI, 1.60-8.71; P = 0.0014). However, these differences were no longer observed when the ctDNA fraction cutoff value of 2% was applied, and approximately 50% of the samples were classified as ctDNA unquantifiable. CONCLUSIONS: Detecting low-frequency ctDNA variants with a VAF <1% is important to identify clinically informative genomic alterations in CRPC.
Assuntos
Ácidos Nucleicos Livres , Neoplasias de Próstata Resistentes à Castração , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/uso terapêutico , Ácidos Nucleicos Livres/genética , Estudos de Coortes , Humanos , Masculino , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genéticaRESUMO
The altered levels of phospholipids (PLs) and lysophospholipids (LPLs) in prostate cancer (CaP) and benign tissues in our previous findings prompted us to explore PLs and LPLs as potential biomarkers for CaP. Urinary lipidomics has attracted increasing attention in clinical diagnostics and prognostics for CaP. In this study, 31 prostate tissues obtained from radical prostatectomy were assessed using high-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS). Urine samples were collected after digital rectal examination (DRE), and urinary lipids were extracted using the acidified Bligh-Dyer method. The discovery set comprised 75 patients with CaP and 44 with benign prostatic hyperplasia (BPH) at Kyoto University Hospital; the validation set comprised 74 patients with CaP and 59 with BPH at Osaka University Hospital. Urinary lipidomic screening was performed using MALDI time-of-flight MS (MALDI-TOF/MS). The levels of urinary lysophosphatidylcholine (LPC) and phosphatidylcholines (PCs) were compared between the CaP and BPH groups. The (PC [34:2] + PC [34:1])/LPC (16:0) ratio was significantly higher (P < .001) in CaP tissues than in benign epithelial tissues. The urinary PCs/LPC ratio was significantly higher (P < .001) in the CaP group than in the BPH group in the discovery and validation sets.
Assuntos
Biomarcadores Tumorais/urina , Lisofosfatidilcolinas/urina , Fosfatidilcolinas/urina , Hiperplasia Prostática/urina , Neoplasias da Próstata/urina , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Humanos , Lisofosfatidilcolinas/análise , Lisofosfolipídeos/urina , Masculino , Fosfatidilcolinas/análise , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/patologia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/química , Neoplasias da Próstata/patologia , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
Introduction. Intimal sarcoma is a very rare tumor arising within the intima of the pulmonary artery. Preoperative diagnosis of pulmonary artery sarcoma is difficult, and the tumor is sometimes misdiagnosed as pulmonary thromboembolism. We report a case of pulmonary artery intimal sarcoma successfully diagnosed by preoperative endovascular biopsy and treated via right pneumonectomy and pulmonary arterioplasty. Presentation of a Case. A 72-year-old woman was referred to our hospital with a low-attenuation defect in the lumen of the right main pulmonary artery by computed tomography. Pulmonary artery thromboembolism was suspected, and anticoagulation therapy was administered. However, the defect in the pulmonary artery did not improve. Endovascular catheter aspiration biopsy was performed. Histological examination revealed pulmonary artery sarcoma. The patient was treated with right pneumonectomy and arterioplasty with the use of cardiopulmonary bypass. Discussion. Preoperative biopsy by endovascular catheter is worth considering for a patient with a tumor in the pulmonary artery and can help in planning treatment strategies.
RESUMO
The prevalence of neuroendocrine prostate cancer (NEPC) arising from adenocarcinoma (AC) upon potent androgen receptor (AR) pathway inhibition is increasing. Deeper understanding of NEPC biology and development of novel therapeutic agents are needed. However, research is hindered by the paucity of research models, especially cell lines developed from NEPC patients. We established a novel NEPC cell line, KUCaP13, from tissue of a patient initially diagnosed with AC which later recurred as NEPC. The cell line has been maintained permanently in vitro under regular cell culture conditions and is amenable to gene engineering with lentivirus. KUCaP13 cells lack the expression of AR and overexpress NEPC-associated genes, including SOX2, EZH2, AURKA, PEG10, POU3F2, ENO2, and FOXA2. Importantly, the cell line maintains the homozygous deletion of CHD1, which was confirmed in the primary AC of the index patient. Loss of heterozygosity of TP53 and PTEN, and an allelic loss of RB1 with a transcriptomic signature compatible with Rb pathway aberration were revealed. Knockdown of PEG10 using shRNA significantly suppressed growth in vivo. Introduction of luciferase allowed serial monitoring of cells implanted orthotopically or in the renal subcapsule. Although H3K27me was reduced by EZH2 inhibition, reversion to AC was not observed. KUCaP13 is the first patient-derived, treatment-related NEPC cell line with triple loss of tumor suppressors critical for NEPC development through lineage plasticity. It could be valuable in research to deepen the understanding of NEPC.
Assuntos
Adenocarcinoma/patologia , Carcinoma Neuroendócrino/patologia , Linhagem Celular Tumoral/patologia , Neoplasias da Próstata/patologia , Animais , Proteínas Reguladoras de Apoptose/genética , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/secundário , Linhagem Celular Tumoral/metabolismo , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Ensaios de Seleção de Medicamentos Antitumorais , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Deleção de Genes , Expressão Gênica , Genes Neoplásicos , Genes do Retinoblastoma , Genes Supressores de Tumor , Genes p53 , Engenharia Genética , Xenoenxertos , Homozigoto , Humanos , Cariotipagem , Perda de Heterozigosidade , Masculino , Camundongos SCID , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Transplante de Neoplasias , PTEN Fosfo-Hidrolase/genética , Neoplasias Penianas/genética , Neoplasias Penianas/secundário , Neoplasias da Próstata/genética , Proteínas de Ligação a RNA/genética , Receptores AndrogênicosRESUMO
Radical prostatectomy is one of the major treatment options for patients with localized prostate cancer, and biochemical recurrence (BCR) after surgery is regarded as one of the representative indicators of the oncological outcome. The positive surgical margin (PSM) of the surgical specimen is considered to be one of the risk factors for BCR and its length (LPSM) was reported to be positively correlated with the risk for BCR. We retrospectively investigated the relationship between BCR and LPSM in 115 patients who underwent radical retropubic prostatectomy or laparoscopic radical prostatectomy without neoadjuvant hormone therapy at Shimada Municipal Hospital between 2008 and 2016. We found that the patients with a LPSM of 3 mm or longer had a higher risk for BCR than those with a LPSM shorter than 3 mm (HR 10.98, 95% confidence interval : 3.09-39.06, p <0.001), and patients with pT3 disease with a LPSM of 3 mm or longer had a higher risk for early BCR. Therefore, the LPSM may be a useful parameter to predict BCR after radical prostatectomy.
Assuntos
Margens de Excisão , Neoplasias da Próstata , Humanos , Masculino , Recidiva Local de Neoplasia , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos RetrospectivosRESUMO
Tempura is a dish of battered and deep-fried foods, and wheat flour is typically used; however, barley, buckwheat, and Job's tears have an antioxidant capacity. This study investigated whether replacing wheat flour with flours from these three crops in tempura affects the antioxidant capacity and deterioration of frying oil. Radical scavenging activity and polyphenol content of tempura were measured by chemiluminescence-based assay and the Folin-Denis method, respectively. The peroxide value, p-anisidin value, acid value, and polar compound of the oil used in frying were measured as indexes of oil deterioration post-frying due to oxidation. Although the frying oil of barley showed higher p-anisidin value than that of wheat, the oil samples' deterioration level measured in this study was low. The antioxidant capacity and polyphenol content in the three flours samples were higher than those in wheat sample, with buckwheat producing the greatest values, followed by Job's tears, and then barley. Thus, deep-fried products prepared using the three flours demonstrated superior antioxidant capacity owing to the abundance of antioxidant components. Therefore, tempura can be enjoyed in a healthier manner by using batter prepared using those flours, and substituting wheat flour with the three flours can increase the antioxidant capacity of deep-fried products.