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BACKGROUND: Chemotherapy is crucial for hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, and its survival benefits may outweigh adverse events. Oncotype DX (ODX) assesses this balance; however, it is expensive. Using nomograms to identify cases requiring ODX may be economically beneficial. We aimed to identify clinicopathological variables that correlated with the recurrence score (RS) and develop a nomogram that predicted the RS. METHODS: We included 457 patients with estrogen receptor-positive, HER2-negative breast cancer with metastases in fewer than four axillary lymph nodes who underwent surgery and ODX at our hospital between 2007 and 2023. We developed nomograms and internally validated them in 310 patients who underwent surgery between 2007 and 2021 and validated the model's performance in 147 patients who underwent surgery between 2022 and 2023. RESULTS: Logistic regression analysis revealed that progesterone receptor (PgR) level, histological grade (HG), and Ki67 index independently predicted the RS. A nomogram was developed using these variables to predict the RS (area under the curve [AUC], 0.870; 95% confidence interval [CI], 0.82-0.92). The nomogram was applied to the model validation group (AUC, 0.877; 95% CI, 0.80-0.95). When the sensitivity of the nomogram was 90%, the model was able to identify 52.3% low-RS and 41.2% high-RS cases not requiring ODX. CONCLUSIONS: This was the first nomogram model developed based on data from a cohort of Japanese women. It may help determine the indications for ODX and the use of nomogram to identify cases requiring ODX may be economically beneficial.
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BACKGROUND: The Chemotherapy-induced Alopecia Distress Scale (CADS) is a patient-reported outcome measure for assessing distress associated with Chemotherapy-induced alopecia (CIA). This study aimed to confirm the psychometric validity of the Japanese version of the CADS (CADS-J). METHODS: A total of 132 patients with breast cancer who developed CIA were asked to complete the CADS-J twice at 2 week intervals to confirm test-retest reliability. The body image domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) breast cancer-specific module, the self-esteem scale from the Rosenberg Self-Esteem Scale, and the emotional domain of the EORTC QLQ Core 30 were used to confirm the convergent validity of the CADS-J. The overall quality of life and physical domains of the EORTC QLQ Core 30 were used to confirm the discriminant validity of the CADS-J. RESULTS: In total, 125 participants provided valid responses. The mean age was 52.2 years. The overall Cronbach's alpha for the CADS-J was 0.903. The intraclass correlation coefficients of the first and second responses were r = 0.874, r = 0.952, r = 0.911, and r = 0.959 for the physical domain, emotional domain, activity domain, and relationship domain, respectively. In terms of convergent validity, the total CADS-J score was moderately correlated with body image (r = - 0.63), self-esteem (r = - 0.48), and the emotional domain (r = - 0.61). Regarding discriminant validity, the total CADS-J score was weakly correlated with the overall quality of life (r = - 0.34) and physical domain (r = - 0.24). CONCLUSIONS: The CADS-J is psychometrically reliable and valid for evaluating the distress caused by CIA. It is expected to be used in daily practice and as an endpoint in various studies.
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Antineoplásicos , Neoplasias da Mama , Humanos , Pessoa de Meia-Idade , Feminino , Qualidade de Vida , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/psicologia , Reprodutibilidade dos Testes , Japão , Alopecia/induzido quimicamente , Alopecia/diagnóstico , Alopecia/psicologia , Psicometria/métodos , Antineoplásicos/efeitos adversos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Invasive lobular carcinoma (ILC) grows diffusely in a single-cell fashion, sometimes presenting only subtle changes in preoperative imaging; therefore, axillary lymph node (ALN) metastases of ILC are difficult to detect using magnetic resonance imaging (MRI). Preoperative underestimation of nodal burden occurs more frequently in ILC than in invasive ductal carcinoma (IDC), however, the morphological assessment for metastatic ALNs of ILC have not fully been investigated. We hypothesized that the high false-negative rate in ILC is caused by the discrepancy in the MRI findings of ALN metastases between ILC and IDC and aimed to identify the MRI finding with a strong correlation with ALN metastasis of ILC. METHOD: This retrospective analysis included 120 female patients (mean ± standard deviation age, 57.2 ± 11.2 years) who underwent upfront surgery for ILC at a single center between April 2011 and June 2022. Of the 120 patients, 35 (29%) had ALN metastasis. Using logistic regression, we constructed prediction models based on MRI findings: primary tumor size, focal cortical thickening (FCT), cortical thickness, long-axis diameter (LAD), and loss of hilum (LOH). RESULTS: The area under the curves were 0.917 (95% confidence interval [CI] 0.869-0.968), 0.827 (95% CI 0.758-0.896), 0.754 (95% CI 0.671-0.837), and 0.621 (95% CI 0.531-0.711) for the FCT, cortical thickness, LAD, and LOH models, respectively. CONCLUSIONS: FCT may be the most relevant MRI finding for ALN metastasis of ILC, and although its prediction model may lead to less underestimation of the nodal burden, rigorous external validation is required.
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Neoplasias da Mama , Carcinoma Ductal de Mama , Carcinoma Lobular , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias da Mama/patologia , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/cirurgia , Carcinoma Lobular/patologia , Estudos Retrospectivos , Carcinoma Ductal de Mama/patologia , Linfonodos/patologia , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVE: We occasionally observed internal mammary lymph node metastases of breast cancer in a clinical setting. However, unlike a standard treatment in axillary metastasis, surgical resection for internal mammary lymph node metastasis is not prevalent because of unclear safety and benefits. Thus, we aimed to evaluate the diagnostic ability and clinical outcomes of positron emission tomography/computed tomography and video-assisted thoracoscopic surgery. METHODS: We retrospectively investigated 34 patients with breast cancer with abnormal 18F-fluorodeoxyglucose uptake in internal mammary lymph nodes, at a single centre, between January 2015 and June 2022 and identified 11 female patients (mean age ± SD, 51.5 ± 12.9 years) who underwent video-assisted thoracoscopic surgery resection. Positron emission tomography/computed tomography was used to determine the clinical stage. We reviewed the surgical pathology of eleven and two patients who underwent direct-view internal mammary lymph node resection to calculate the positive predictive value of positron emission tomography/computed tomography. RESULTS: Ipsilateral fluorodeoxyglucose accumulation was observed, with an average maximum standardized uptake value of 8.9 (range, 3.1-24.0). No perioperative complications occurred, and all patients who underwent video-assisted thoracoscopic surgery alone were discharged from the hospital on post-operative day 2 or 3. The estimated positive predictive value was 80%. All patients were alive, and seven of nine patients with metastasis were relapse-free, at a mean follow-up period of 17.9 months (range, 1-51). However, two patients had recurrence at 16 and 14 months after surgery for internal mammary lymph node relapse. CONCLUSIONS: Radiotherapy is the standard treatment for suspected internal mammary lymph node metastasis detected using positron emission tomography/computed tomography; however, we could safely perform minimally invasive video-assisted thoracoscopic surgery resection, leading to a definite pathological diagnosis.
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Neoplasias da Mama , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Feminino , Cirurgia Torácica Vídeoassistida , Metástase Linfática/patologia , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons/métodos , Recidiva Local de Neoplasia/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Fluordesoxiglucose F18 , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Compostos RadiofarmacêuticosRESUMO
BACKGROUND: Solitary fibrous tumors (SFT) are uncommon mesenchymal neoplasms which can arise in any anatomical location. Pleural SFTs have been most frequently documented; however, breast SFT is an exceedingly rare entity and seldom present in male breast, with only 8 previously reported cases. Recently, STAT6 immunostaining was considered to be a definitive marker of SFT, however, no case of the male breast SFT showing STAT6 positivity preoperatively has been reported. METHODS AND RESULTS: We describe a case of breast SFT in a 73-year-old male patient with a 12-month history of a palpable breast mass. The only associated clinical symptom was bilateral gynecomastia. An ultrasound scan examination revealed an oval, well-circumscribed and hypoechoic mass with hypervascularity. A core-needle biopsy was performed, and microscopic examination with immunohistochemistry confirmed the diagnosis of SFT. He underwent a complete surgical resection with clear margins, and there were no signs of high cellularity, remarkable mitotic activity, pleomorphism, hemorrhage or necrosis. CONCLUSION: A perioperative immunohistochemical evaluation for diffuse and intense nuclear expression of STAT6 was helpful to distinguish SFT from myofibroblastoma. We, herein, describe the first case of SFT in a male breast, confirmed by STAT6 immunostaining positivity. We also conducted a literature review of all previous cases of breast SFTs.
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Hemangiopericitoma , Febre Grave com Síndrome de Trombocitopenia , Tumores Fibrosos Solitários , Humanos , Masculino , Idoso , Tumores Fibrosos Solitários/diagnóstico por imagem , Tumores Fibrosos Solitários/cirurgia , Hemangiopericitoma/patologia , Ultrassonografia , Mama/patologia , Biomarcadores TumoraisRESUMO
Purpose: Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) are useful for detecting axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC); however, there is limited clinical evidence to demonstrate the effectiveness of the combination of PET/CT plus MRI. Further axillary surgery is not recommended against ALN micrometastasis (lesion ≤2 mm) seen in sentinel lymph nodes, especially for patients who received proper adjuvant therapy. We aimed to evaluate the efficacy of a prediction model based on PET/CT plus MRI for ALN macrometastasis (lesion >2 mm) and explore the possibility of risk stratification of patients using the preoperative PET/CT plus MRI and biopsy findings. Materials and methods: We retrospectively investigated 361 female patients (370 axillae; mean age, 56 years ± 12 [standard deviation]) who underwent surgery for primary IDC at a single center between April 2017 and March 2020. We constructed a prediction model with logistic regression. Patients were divided into low-risk and high-risk groups using a simple integer risk score, and the false negative rate for ALN macrometastasis was calculated to assess the validity. Internal validation was also achieved using a 5-fold cross-validation. Results: The PET/CT plus MRI model included five predictor variables: maximum standardized uptake value of primary tumor and ALN, primary tumor size, ALN cortical thickness, and histological grade. In the derivation (296 axillae) and validation (74 axillae) cohorts, 54% and 61% of patients, respectively, were classified as low-risk, with a false-negative rate of 11%. Five-fold cross-validation yielded an accuracy of 0.875. Conclusions: Our findings demonstrate the validity of the PET/CT plus MRI prediction model for ALN macrometastases. This model may aid the preoperative identification of low-risk patients for ALN macrometastasis and provide helpful information for PET/MRI interpretation.
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BACKGROUND: Current guidelines recommend the temporary discontinuation of anticoagulants before colonoscopic polypectomy, but the effect of this practice on reducing the risk of delayed bleeding after hot snare polypectomy (HSP) and endoscopic mucosal resection (EMR) remains unclear. Our aim was to assess the impact of anticoagulants on the risk of colorectal delayed bleeding after HSP and EMR, and evaluate the necessity of drug withdrawal. METHODS: We reviewed the clinical data of patients with colorectal polyps using antithrombotic drugs who underwent HSP and/or EMR between January 2016 and September 2020 at Nagaoka Red Cross Hospital. After excluding antiplatelet users, patients were classified into those who continued anticoagulants [continuation group: 50 patients (93 lesions)] and those who discontinued anticoagulants [discontinuation group: 87 patients (190 lesions)]. RESULTS: Delayed bleeding occurred in 12 lesions, and there was no significant difference in the incidence rates between the continuation and the discontinuation groups (3.2% vs. 4.7%; P=0.756). Logistic regression analysis showed that continued use of anticoagulants was not a significant risk factor for delayed bleeding compared to anticoagulant discontinuation (odds ratio, 0.670; 95% CI, 0.177-2.537; P=0.556). There was no significant difference in the incidence rate and risk of delayed bleeding, regardless of the length of the anticoagulant withdrawal period. CONCLUSIONS: Continued use of anticoagulants, compared to their discontinuation, did not increase the risk of colorectal delayed bleeding after HSP and EMR. Our results suggest that current guideline recommendations for anticoagulant withdrawal before colonoscopic polypectomy may be reconsidered. TRIAL REGISTRATION: UMIN000040449.
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Background: Sorafenib (SOR) is an anti-angiogenic chemotherapeutic that prolongs the survival rates of patients with hepatocellular carcinoma. However, SOR also damages normal vasculature and causes associated adverse events, including hand-foot syndrome and hypertension (HT). We previously reported in an animal study that vascular damage resulted in the narrowing of the normal vascular dimension area in medaka fish (Oryzias), and histidine (HIS), a major amino acid contained in dried bonito broth (DBB), prevented these changes. Therefore, in the study, we analyzed the effects of DBB and HIS on SOR-related vascular damages and associated adverse events in patients. Materials and methods: Three-dimensional (3D) vascular images of abdominal regions reconstituted from computed tomography were assessed to compare vascular diameter prior to and following SOR administration in groups receiving SOR monotherapy, DBB+SOR, and HIS+SOR. The clinical courses of hand-foot syndrome and HT and the toxicities of SOR in biochemical assays were monitored and compared between the groups. Correlations between hepatic function and SOR-related changes in the portal venous area dimension were also assessed. Results: SOR-related vascular damage revealed narrowing of the normal abdominal vasculature in the human body, which was monitored using 3D images. The damage was ameliorated by DBB and HIS, however, HIS had a more marked effect, particularly on the renal arteries and portal vein (PV). Maintenance of blood flow contributed to the maintenance of total cholesterol, prothrombin time, albumin (ALB), and renal functions. Changes in the 3D vascular area dimension of the PV and level of serum ALB were significantly correlated. The occurrences of the clinical symptoms of hand-foot syndrome and HT were lower in the DBB- and HIS-treated groups. Conclusion: Our results clearly demonstrate that DBB and HIS prevented SOR-related abdominal vascular damage and effectively maintained hepatic function, and prevented clinical symptoms and toxicity. Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000025937 and UMIN000026898).
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AIM: To investigate the associations between self-reported hearing loss and outdoor activity limitations, psychological distress and self-reported memory loss among older people. METHODS: We carried out a cross-sectional study using the data from the 2016 Comprehensive Survey of Living Conditions in Japan. The study population included people aged ≥65 years living at home, without a clinical diagnosis of dementia. The exposure of interest was self-reported hearing loss, whereas outcomes included outdoor activity limitations (Yes/No), psychological distress (Kessler Psychological Distress Scale score of ≥5) and self-reported memory loss (Yes/No). We carried out logistic regression analyses, adjusted for age, sex, smoking, alcohol, educational status, number of household members, household expenditure and number of clinical diagnoses requiring outpatient visits. RESULTS: Among 137 723 older people (mean age 74.5 years [standard deviation 7.4 years], 45.1% men), 12 389 (9.0%) reported hearing loss. People with hearing loss showed a higher prevalence of outdoor activity limitations (28.9% vs 9.5%, P < 0.001), psychological distress (39.7% vs 19.3%, P < 0.001) and memory loss (37.7% vs 5.2%, P < 0.001) than those without. The adjusted odds ratios comparing people with and without hearing loss were 2.0 (95% confidence interval 1.9-2.1), 2.1 (95% confidence interval 2.0-2.1) and 7.1 (95% confidence interval 6.8-7.4) for outdoor activity limitations, psychological distress and self-reported memory loss. CONCLUSIONS: This nationwide study suggested that older people with hearing loss were more likely to experience outdoor activity limitations, psychological distress and memory loss than those without. Early identification of and intervention in hearing loss might potentially reduce the risk of these poor health outcomes. Geriatr Gerontol Int 2019; 19: 747-754.
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Atividades Cotidianas/psicologia , Perda Auditiva , Vida Independente/estatística & dados numéricos , Transtornos da Memória , Angústia Psicológica , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Autoavaliação Diagnóstica , Feminino , Inquéritos Epidemiológicos , Perda Auditiva/epidemiologia , Perda Auditiva/psicologia , Humanos , Japão/epidemiologia , Masculino , Transtornos da Memória/epidemiologia , Transtornos da Memória/psicologia , Avaliação das Necessidades , Prevalência , Fatores de Risco , Apoio SocialAssuntos
Neoplasias Esofágicas/secundário , Estenose Esofágica/patologia , Neoplasias da Próstata/patologia , Idoso de 80 Anos ou mais , Biópsia , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/cirurgia , Estenose Esofágica/diagnóstico por imagem , Estenose Esofágica/cirurgia , Humanos , Masculino , Neoplasias da Próstata/tratamento farmacológicoRESUMO
The article "The search, coagulation, and clipping (SCC) method prevents delayed bleeding after gastric endoscopic submucosal dissection", written by Motoi Azumi, Manabu Takeuchi, Youhei Koseki, Masaru Kumagai, Yoko Kobayashi, Masafumi Takatsuna, Aiko Yoshioka, Seiichi Yoshikawa, Tsutomu Miura, and Shuji Terai, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 28 September 2018 without open access.
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BACKGROUND: Delayed bleeding is an important complication after gastric endoscopic submucosal dissection (ESD). The search, coagulation, and clipping (SCC) method can be used to prevent delayed bleeding after ESD. However, its safety and efficacy are unclear. We compared the SCC method with post-ESD coagulation (PEC) to clarify the safety and efficacy of the SCC method for preventing delayed bleeding after gastric ESD. METHODS: This retrospective study included 438 patients (478 lesions) who underwent gastric ESD. Multivariate logistic regression analysis was performed to identify the significant independent factors associated with delayed bleeding and we performed propensity-score matching (PSM) to reduce the effect of procedure-selection bias of SCC method. RESULTS: Of the 438 patients, 216 underwent PEC and 222 underwent SCC. Delayed bleeding was significantly less common in the SCC than in the PEC (2.6% vs. 7.2%; P = 0.013). Among patients treated with antithrombotic therapy, the delayed bleeding rate was lower in the SCC group than in the PEC group; however, the difference was not significant (P = 0.15). The SCC method was found to be a significant independent factor for the prevention of delayed bleeding. PSM was performed in 156 patients in the PEC group and SCC group. There was a significant difference in the incidence of bleeding in the PEC and SCC groups (P = 0.013). No patient had perforation/bleeding associated with the SCC method. CONCLUSIONS: Our findings suggest that the SCC method is a simple, safe, and effective approach for preventing delayed bleeding after gastric ESD.
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Dissecação/métodos , Ressecção Endoscópica de Mucosa/efeitos adversos , Fibrinolíticos/uso terapêutico , Hemorragia Pós-Operatória/prevenção & controle , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória/etiologia , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: Sorafenib (SOR) is a molecular medicine that prolongs the survival of patients with hepatocellular carcinoma (HCC). Therefore, the management of side effects is essential for the longer period of continuous medication. Among the various side effects, hand-foot syndrome (HFS) is the most common, occurring in 30%-50% of patients, and often results in discontinuation of the SOR medication. However, its mechanism has not been clarified, and no effective prevention method has been reported for the symptoms. Therefore, this study aimed to analyze its mechanism and to develop an effective prevention regimen for the symptoms. MATERIALS AND METHODS: To assess the mechanism of SOR-induced HFS, the peripheral blood flow in the hand and foot was carefully monitored by Doppler ultrasound, thermography, and laser speckle flowgraphy in the cases treated with SOR and its contribution was assessed. Then, the effect of dried-bonito broth (DBB), which was reported to improve peripheral blood flow, on the prevention of the symptom was examined by monitoring its occurrence and the peripheral blood flow. RESULTS: A total of 25 patients were enrolled in this study. In all, eight patients developed HFS, and all cases showed a significant decrease in the peripheral blood flow. DBB contributed to an increase in the flow (p = 0.009) and significantly decreased occurrence of HFS (p = 0.005) than control. Multivariable analysis showed that the ingestion of DBB is a significant independent contributor to HFS-free survival period (p = 0.035). CONCLUSION: The mechanism of SOR-induced HFS involves a decrease in the peripheral blood flow, and the ingestion of DBB effectively prevents the development of the syndrome by maintaining the flow.
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OBJECTIVE: Marfan syndrome (MFS) is a systemic connective tissue disorder caused by insufficient fibrillin-1 (FBN-1), a major component of microfibrils that controls the elasticity and integrity of connective tissues. FBN-1 insufficiency in MFS leads to structural weakness, which causes various tissue disorders, including cardiovascular and periodontal disease. However, the role of FBN-1 insufficiency in the destruction and regeneration of connective tissue has not yet been clarified. To investigate the role of FBN-1 insufficiency in tissue destruction and regeneration. DESIGN: We used a ligature-induced (LI) periodontal disease model in fbn-1-deficient mice (fbn-1c1039G/+ mice) with MFS and investigated the regeneration level of periodontal tissue and as an inflamatic marker, the expression of the matrix metalloproteinase (mmp)-9 and tumor necrosis factor (tnf)-α. RESULTS: Interestingly, fbn-1c1039G/+ mice exhibited slowed wound healing compared with wild type mice, but periodontal tissue destruction did not differ between these mice. Moreover, fbn-1c1039G/+ mice exhibited delayed bone healing in association with continuous mmp-9 and tnf-α expression. Furthermore, inflammatory cells were obvious even after the removal of ligatures. CONCLUSION: These data suggest that fibrillin-1 insufficiency in fbn-1c1039G/+ mice interfered with wound healing in connective tissue damaged by inflammatory diseases such as periodontal disease.
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Fibrilina-1/metabolismo , Fibrilina-1/farmacologia , Ligadura/efeitos adversos , Síndrome de Marfan/complicações , Doenças Periodontais/metabolismo , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia , Perda do Osso Alveolar/patologia , Animais , Linhagem Celular , Tecido Conjuntivo/patologia , Modelos Animais de Doenças , Expressão Gênica , Mandíbula , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Dente Molar , Doenças Periodontais/patologia , Periodontite , Periodonto/efeitos dos fármacos , Periodonto/lesões , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Sorafenib (SFN) is an anti-angiogenic chemotherapeutic that prolongs survival of patients with hepatocellular carcinoma (HCC); its side effects, including vascular damages such as hand-foot syndrome (HFS), are a major cause of therapy discontinuation. We previously reported that maintenance of peripheral blood flow by intake of dried bonito broth (DBB) significantly prevented HFS and prolonged the administration period. The amino acids contained in DBB probably contribute to its effects, but the mechanism has not been clarified. We hypothesized that histidine, the largest component among the amino acids contained in DBB, has effects on SFN-induced vascular damage, and evaluated this possibility using a novel medaka fish model. METHODS: The fli::GFP transgenic medaka fish model has a fluorescently visible systemic vasculature. We fed the fish with SFN with and without histidine to compare blood flow and vascular structure among the differently fed models. The vascular cross-sectional area of each fish was measured to determine vascular diameter changes. RESULTS: Our results demonstrated that SFN-fed medaka developed a narrower vascular diameter. In addition, this narrowing was counteracted by addition of histidine to the medaka diet. We observed no positive effect of histidine on regeneration of cut vessels or on cell growth of endothelial cells and HCC cell lines. CONCLUSION: We proved the efficacy of the medaka model to assess vascular changes after administration of specific chemicals. And our results suggest that SFN causes vascular damage by narrowing peripheral vessel diameter, and that histidine effectively counteracts these changes to maintain blood flow.
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Antineoplásicos/efeitos adversos , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/patologia , Histidina/farmacologia , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/efeitos adversos , Oryzias , SorafenibeRESUMO
Advances in treatment have resulted in a high rate of sustained virological response in patients with hepati- tis C, whereas many asymptomatic carriers of hepatitis C virus (HCV) remain untreated. Therefore, HCV antibody screening holds great significance. However, the measurement principles or types of antigen used in screening vary according to the manufacturer, leading to discrepancies in the results obtained using differ- ent screening reagents. In this study, the performances of five HCV antibody screening assays - ARCHITECT HCV, ECLusys Anti-HCV II assay, HISCL HCV Ab assay, LUMIPULSE II Ortho HCV, and LUMIPULSE Presto Ortho HCV- were compared using 2,042 serum samples. The positive rates for the various assays ranged from 3.6% to 4.5%, and 1,937 and 70 samples were determined as negative and positive, respectively. Discordant results were obtained for 35 samples (1.7%). Additional confirmatory testing was performed on 105 samples that tested positive with at least one reagent. Thus, of the 35 samples with discordant results, 24 single-positive samples were highly likely to be false-positive and 5 single-negative sam- ples were likely to be truly positive. Considering that HCV antibody would not be missed by any assay, those showing no or minimal non-specific or crossover reactions would be ideal for HCV antibody screening. Indeed, further improvement of screening reagents is also needed.
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Hepacivirus , Anticorpos Anti-Hepatite C , Hepatite C , Programas de Rastreamento , Hepacivirus/imunologia , Hepatite C/diagnóstico , Anticorpos Anti-Hepatite C/imunologia , Humanos , Testes SorológicosRESUMO
Aberrant production of proinflammatory cytokines is linked to many autoimmune diseases, and their inhibition by small molecule compounds is considered beneficial. Here, we performed phenotypic screening in IFNγ/LPS-activated RAW264.7, mouse macrophage cells, and discovered AS2677131 and AS2795440 as novel and potent inhibitors of IL-12p40, a subunit of IL-23. Interestingly, these compounds exhibited unique pharmacological activities in their inhibition of the production of IL-12p40, IL-6 and IL-1ß but not TNFα in activated macrophages or dendritic cells, and expression of IgM-induced MHC class II on B cells. To reveal these mechanisms, we synthesized two different activity probes which were structurally related to the AS compounds, and identified probe-specific binding proteins, including PIKfyve, a Class III PI kinase. The AS compounds inhibited PIKfyve activity and mimicked the properties of PIKfyve-deficient cells, eventually validating PIKfyve as target molecule. Regarding mechanism, AS2677131 regulated DNA binding activity of c-Rel on IL-12p40 and IL-1ß promoter. As expected, a PIKfyve inhibitor prevented the development of arthritis in rats. Taken together, our findings of the novel and potent PIKfyve inhibitors AS2677131 and AS2795440 reveal the critical role of PIKfyve in proinflammatory cytokine production and B cell activation, and may indicate a potential new therapeutic option for treatment of inflammatory diseases.
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Anti-Inflamatórios/farmacologia , DNA/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-rel/metabolismo , Animais , Artrite/prevenção & controle , Linfócitos B/citologia , Linfócitos B/efeitos dos fármacos , Citocinas/biossíntese , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Interferon gama/farmacologia , Subunidade p40 da Interleucina-12/genética , Lipopolissacarídeos/farmacologia , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Regiões Promotoras Genéticas/genética , Ligação Proteica/efeitos dos fármacos , Piridinas/farmacologia , Células RAW 264.7 , RatosRESUMO
Pseudomyxoma peritonei (PMP) is a condition characterized by production of a large amount of mucopolysaccharides by neoplastic epithelium, with intraabdominal cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) known to be viable treatment options. Pleural extension from an PMP is unusual and thought to be related to diaphragmatic perforation during surgery or transdiaphragmatic spreading of the disease through the lymphatic lacunae. Here, we report a patient with PMP with pleural extension of a mucinous tumor for whom CRS was performed twice. A 57-year-old female with PMP infiltrating the right chest cavity was scheduled for two separate CRS and hyperthermic chemotherapy procedures, because of the highly invasive characteristics of the surgery. For the first operation, we performed intra-abdominal surgery under general anesthesia combined with epidural anesthesia. To assess fluid and blood transfusion responsiveness, and reactions to vasoactive medication, we utilized an arterial pressure-based cardiac output monitor and central venous oximetry catheter. The second operation was performed 5 months later under general anesthesia with differential lung ventilation combined with epidural anesthesia. The operation and anesthesia for both surgical procedures were uneventful.
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Pleura/patologia , Pleura/cirurgia , Pseudomixoma Peritoneal/cirurgia , Anestesia Geral , Procedimentos Cirúrgicos de Citorredução , Diafragma , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Pseudomixoma Peritoneal/tratamento farmacológico , Cavidade TorácicaRESUMO
OBJECTIVE: To examine the consequences of early-onset hearing loss on several social and health measures and any related gender differences in Japanese populations. METHODS: Data from a 2007 nationally representative cross-sectional household survey of 136,849 men and women aged 20 to 39 years were obtained (prevalence of self-reported hearing loss: 0.74%). We focused particularly on four social and health measures: employment status (employed/unemployed), marital status (married/unmarried), smoking behavior (yes/no), and psychological distress (K6 instrument: ≥ 5 or not). We examined the association of hearing loss for each measure using generalized estimating equations to account for correlated individuals within households. FINDINGS: There was no significant association with employment status (p = 0.447). Men with hearing loss were more likely to be married, whereas women with hearing loss were less likely to be married (p < 0.001 for interaction). Although hearing loss was not associated with a current smoking status in men, women with hearing loss were more likely to be current smokers (p < 0.001 for interaction). Moreover, hearing loss was associated with psychological distress in men and women (both p < 0.001). CONCLUSION: These findings suggest that hearing loss is related to social and health issues in daily life, including a lower likelihood of marriage, more frequent smoking, and poorer mental health, especially in women. These issues may reflect a gap between the actual needs of women with hearing loss and the formal support received as a result of existing public health policies in Japan.
Assuntos
Perda Auditiva/epidemiologia , Perda Auditiva/psicologia , Estado Civil/estatística & dados numéricos , Saúde Mental , Fumar , Adulto , Estudos Transversais , Emprego/psicologia , Emprego/estatística & dados numéricos , Feminino , Perda Auditiva/complicações , Humanos , Japão/epidemiologia , Masculino , Distribuição por Sexo , Fumar/psicologia , Estresse Psicológico/complicações , Adulto JovemRESUMO
A 77-year-old woman with right aortic arch was diagnosed as aortic dissection (De Bakey IIIb) and hospitalized for conservative treatment. But, her respiratory condition deteriorated due to tracheal stenosis with aortic dissection. Surgical graft replacement of the descending aorta was performed to release tracheal stenosis. Six days after surgery, tracheoesophageal fistula (TEF) was noticed. The size of the fistula was 3 cm in diameter, located 3cm to the oral side from the carina and 23 cm from the incisors. Nineteen days after surgery, an esophageal stent was placed leading to temporary improvement of the respiratory status, but it aggravated again. Unfortunately, she died due to ventricular fibrillation 26 days after surgery. The case is extremely rare with dissection of the right aortic arch. Such a case is considered to be a high risk of TEF, and it is necessary to perform early preventive measures.