RESUMO
Malignant mesothelioma (MM) is uncommon in cats and dogs and can be challenging to diagnose. Adequate tissue sampling is required for superior diagnostic accuracy. Protoporphyrin IX, a metabolite of 5-aminolaevulinic acid (5-ALA), is a photosensitiser for photodynamic diagnosis (PDD). To the best of our knowledge, no study has reported the use of 5-ALA-PDD to detect MM in veterinary medicine. The present study describes the use of 5-ALA-PDD for MM diagnosis in a cat and dog, as well as the effectiveness of intracavitary chemotherapy. We evaluated the use of PDD with 5-ALA hydrochloride (5-ALA-PDD) in two cases of MM. A 12-year-old cat presented with a 1-month history of respiratory distress, and a 9-year-old dog presented with a 3-month history of mild abdominal distention. We endoscopically biopsied lesions in both the cases using 5-ALA-PDD. Histopathological examination revealed mesothelioma, and immunohistochemical staining was positive for calretinin. Both patients were treated with carboplatin. The cat died of respiratory failure. Although, the dog's condition improved 21 days after the first chemotherapeutic drug administration, the dog died on day 684 owing to cardiac-related issues. 5-ALA-PDD is thus, safe and feasible for the diagnosis of MM in veterinary medicine.
Assuntos
Doenças do Gato , Doenças do Cão , Mesotelioma Maligno , Gatos , Cães , Animais , Mesotelioma Maligno/veterinária , Ácido Aminolevulínico , Fármacos Fotossensibilizantes , Biópsia/veterináriaRESUMO
OBJECTIVES: Physical activity is recommended for disability prevention in the older adult population; however, the level of physical activity required for older adults with chronic kidney disease (CKD) remains unknown. This study aimed to examine the associations between daily physical activity and disability incidence in older adults with and without CKD to determine relevant daily physical activity levels. DESIGN: Prospective observational study. SETTING AND PARTICIPANTS: 3,786 community-dwelling older adults aged ≥65 years. MEASUREMENTS: Mean daily times spent in light- (LPA) and moderate-to-vigorous physical activity (MVPA) were measured using triaxial accelerometers. CKD was defined by a creatinine estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Disability incidence was identified as long-term care insurance certification during a 60-month follow-up period. Associations between physical activity and disability incidence were examined using Cox proportional hazard models stratified by the CKD status. Non-linear and linear associations were tested using the restricted cubic spline. RESULTS: A total of 1,054 individuals were identified to have CKD. Disability incidence was higher in the CKD group than in the non-CKD group. The adjusted cox proportional hazard models indicated that a 10-minute increase in MVPA time was associated with lower disability incidence in the non-CKD group (hazard ratio [HR], 0.838; 95% confidence interval [CI]: 0.764-0.918) and the CKD group (HR, 0.859; 95% CI: 0.766-0.960). Linear associations were observed in MVPA for the non-CKD and CKD groups. CONCLUSION: Increasing MVPA was associated with lower disability incidence in older adults with and without CKD. These findings can help devise disability prevention strategies for older CKD patients.
Assuntos
Pessoas com Deficiência , Insuficiência Renal Crônica , Idoso , Exercício Físico , Taxa de Filtração Glomerular , Humanos , Vida IndependenteRESUMO
OBJECTIVES: Recently, the standard of care for advanced urothelial cancer (UC) has been changed by developing immune-checkpoint inhibitors (ICIs). However, its response rate is limited to 20-30%. The identification of biomarkers to predict the therapeutic effects of ICIs is urgently needed. The present study explored the association between immunohistochemical biomarkers and clinical outcomes in UC patients treated with pembrolizumab. PATIENTS AND METHODS: A total of 85 patients with UC who received pembrolizumab after chemotherapy from January 2018 to May 2020 were retrospectively reviewed. Tumor tissues were obtained for immunohistochemical study from 47 out of 85 patients. The protein expressions of PD-L1, WT1, Nectin-4, CD4, CD8, Foxp3, and CD68 in tumor cells and/or tumor infiltrating lymphocytes were immunohistochemically examined. The associations between protein expressions and overall survival (OS), progression-free survival (PFS), and disease control rate (DCR) were statistically analyzed. RESULTS: Patients with positive PD-L1 in tumor cells showed significantly worse OS (Log-rank test: HR 5.146, p = 0.001, Cox regression analysis: HR 4.331, p = 0.014) and PFS (Log-rank test: HR 3.31. p = 0.022), along with significantly lower DCR (14.3%) compared to the PD-L1 negative patients (67.5%). In addition, patients with strong expression of Nectin-4 in tumor cells showed significantly higher DCR (100%) than the other patients (50%). CONCLUSION: PD-L1 expression in tumor cells was associated with poor prognosis (OS and PFS) and low DCR. Interestingly, the strong expression of Nectin-4 was correlated with high DCR. PD-L1 and Nectin-4 expression in tumor cells could be prognostic biomarkers useful for pembrolizumab in patients with advanced UC.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/biossíntese , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/metabolismo , Moléculas de Adesão Celular/biossíntese , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Migration Stimulating Factor (MSF) is a 70 kDa truncated isoform of fibronectin (FN); its mRNA is generated from the FN gene by an unusual two-stage processing. Unlike full-length FN, MSF is not a matrix molecule but a soluble protein which displays cytokine-like activities not displayed by any other FN isoform due to steric hindrance. There are two isoforms of MSF; these are referred to as MSF+aa and MSF-aa, while the term MSF is used to include both.MSF was first identified as a motogen secreted by foetal and cancer-associated fibroblasts in tissue culture. It is also produced by sprouting (angiogenic) endothelial cells, tumour cells and activated macrophages. Keratinocytes and resting endothelial cells secrete inhibitors of MSF that have been identified as NGAL and IGFBP-7, respectively. MSF+aa and MSF-aa show distinct functionality in that only MSF+aa is inhibited by NGAL.MSF is present in 70-80% of all tumours examined, expressed by the tumour cells as well as by fibroblasts, endothelial cells and macrophages in the tumour microenvironment (TME). High MSF expression is associated with tumour progression and poor prognosis in all tumours examined, including breast carcinomas, non-small cell lung cancer (NSCLC), salivary gland tumours (SGT) and oral squamous cell carcinomas (OSCC). Epithelial and stromal MSF carry independent prognostic value. MSF is also expressed systemically in cancer patients, being detected in serum and produced by fibroblast from distal uninvolved skin. MSF-aa is the main isoform associated with cancer, whereas MSF+aa may be expressed by both normal and malignant tissues.The expression of MSF is not invariant; it may be switched on and off in a reversible manner, which requires precise interactions between soluble factors present in the TME and the extracellular matrix in contact with the cells. MSF expression in fibroblasts may be switched on by a transient exposure to several molecules, including TGFß1 and MSF itself, indicating an auto-inductive capacity.Acting by both paracrine and autocrine mechanisms, MSF stimulates cell migration/invasion, induces angiogenesis and cell differentiation and alters the matrix and cellular composition of the TME. MSF is also a survival factor for sprouting endothelial cells. IGD tri- and tetra-peptides mimic the motogenic and angiogenic activities of MSF, with both molecules inhibiting AKT activity and requiring αvß3 functionality. MSF is active at unprecedently low concentrations in a manner which is target cell specific. Thus, different bioactive motifs and extracellular matrix requirements apply to fibroblasts, endothelial cells and tumour cells. Unlike other motogenic and angiogenic factors, MSF does not affect cell proliferation but it stimulates tumour growth through its angiogenic effect and downstream mechanisms.The epithelial-stromal pattern of expression and range of bioactivities displayed puts MSF in the unique position of potentially promoting tumour progression from both the "seed" and the "soil" perspectives.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Citocinas , Células Endoteliais , Humanos , Microambiente TumoralRESUMO
BACKGROUND: Nivolumab (NIVO) and irinotecan (IRI) are standard treatments for refractory advanced gastric cancer (AGC); however, it is unclear which drug should be administered first or in which cases. The tumor growth rate (TGR) during preceding treatment is reported to be associated with tumor response in metastatic colorectal cancer patients treated with regorafenib or trifluridine/tipiracil, suggesting that TGR may be useful for drug selection. Therefore, we evaluated the association between TGR during preceding treatment and the tumor response to NIVO or IRI. PATIENTS AND METHODS: We retrospectively evaluated consecutive AGC patients treated with NIVO or IRI and divided them into slow-growing (Slow) and rapid-growing (Rapid) groups according to TGR and the presence or absence of new lesions (NL+/NL-, respectively) during preceding treatment (Slow group: NL- with low TGR <0.30%/day; Rapid group: NL+ or high TGR ≥0.30%/day). RESULTS: A total of 117 patients (Rapid/Slow groups, 72/45; NIVO/IRI groups, 32/85) were eligible. All baseline characteristics except peritoneal metastases were similar between patients treated with NIVO and IRI in the Rapid and Slow groups. The response rate was significantly higher in patients treated with NIVO compared with IRI [31%/3%; odds ratio (OR), 13.8; P = 0.01; adjusted OR, 52; P = 0.002] in the Slow group, but there was no difference between patients treated with NIVO and IRI (5%/8%; OR, 0.68; P = 0.73; adjusted OR, 0.94; P = 0.96) in the Rapid group. Disease control rate, progression-free survival, and overall survival were consistent with these results. CONCLUSIONS: Our findings suggest that NIVO treatment is a more favorable option for patients with slow-growing tumors, and NIVO and IRI are similarly recommended for patients with rapid-growing tumors in refractory AGC. TGR and NL emergence during preceding treatment may be helpful for drug selection and warrant further investigation.
Assuntos
Irinotecano , Nivolumabe , Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Irinotecano/uso terapêutico , Nivolumabe/uso terapêutico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológicoRESUMO
The present study aimed to verify the changes in the expression levels of 13 candidate genes associated with chemotherapy resistance and to construct a scoring system to predict resistance to these drugs. The expression levels of the 13 candidate genes were compared between 20 dogs with lymphoma that were sensitive to drugs used in CHOP-based protocol and 16 dogs with lymphoma that were resistant to these drugs. The expression levels of six genes; ASNS, CCR3, CALCA, FCER1A, LOC448801, and EDNRB were significantly different between the two groups. A scoring system to predict resistance to cyclophosphamide, doxorubicin and vincristine, which are used in CHOP-based protocol, was constructed based on expression levels of the six genes in these 36 dogs using logistic regression models. After internal validation, sensitivity and specificity of the scoring system were 0.759 and 0.853, respectively. External validation was conducted in another cohort of 33 dogs with lymphoma, and sensitivity and specificity of the scoring system were 0.800 and 0.696, respectively. In conclusion, this study identified six genes associated with resistance to drugs used in CHOP-based protocol in canine lymphoma and proposed a novel scoring system to predict resistance to these drugs. This system might be beneficial in selecting the most appropriate chemotherapy protocol for individual dogs with lymphoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doenças do Cão/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Linfoma/veterinária , Transcriptoma , Animais , Estudos de Coortes , Ciclofosfamida/uso terapêutico , Cães , Doxorrubicina/uso terapêutico , Feminino , Linfoma/tratamento farmacológico , Masculino , Prednisona/uso terapêutico , Projetos de Pesquisa , Vincristina/uso terapêuticoRESUMO
A 5-year-old male toy poodle was referred for corrective surgery of an atrial septal defect. A sinus venosus-type atrial septal defect (ASD) with partial anomalous venous connection, suspected pulmonary hypertension, and pulmonary edema was confirmed by radiography, echocardiography, and cardiac computed tomography. Thoracic radiographs showed right heart enlargement. Echocardiography revealed right atrial and ventricular dilatation with mild flattening of the interventricular septum. Left-to-right shunt flow through the ASD was observed on color Doppler examination. Surgical correction of the sinus venosus ASD with a partial anomalous pulmonary venous connection was performed under cardiopulmonary bypass. A follow-up evaluation at 1 year after surgery showed resolution of the right-sided volume overload and no evidence of recurrence of ASD. Complications were not observed. Our findings indicate that surgical correction under cardiopulmonary bypass is a valid treatment option for an ASD with a partial anomalous pulmonary venous connection.
Assuntos
Doenças do Cão/cirurgia , Comunicação Interatrial/veterinária , Veias Pulmonares/anormalidades , Animais , Ponte Cardiopulmonar/veterinária , Doenças do Cão/congênito , Doenças do Cão/diagnóstico por imagem , Cães , Ecocardiografia/veterinária , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/cirurgia , Hipertensão Pulmonar/veterinária , Masculino , Veias Pulmonares/cirurgia , Tomografia Computadorizada por Raios X/veterinária , Resultado do TratamentoAssuntos
Prurigo/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Antineoplásicos Imunológicos/uso terapêutico , Fluordesoxiglucose F18 , Transportador de Glucose Tipo 1/metabolismo , Humanos , Queratinócitos/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Masculino , Melanoma/tratamento farmacológico , Melanoma/secundário , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Prurigo/metabolismo , Prurigo/patologia , Compostos Radiofarmacêuticos , Neoplasias Cutâneas/patologiaAssuntos
Melanoma/secundário , Doença de Paget Extramamária/patologia , Escroto/patologia , Neoplasias Cutâneas/patologia , Administração Intravenosa , Idoso , Povo Asiático/etnologia , Docetaxel/administração & dosagem , Docetaxel/uso terapêutico , Evolução Fatal , Humanos , Queratina-7/metabolismo , Antígeno MART-1/metabolismo , Masculino , Melanoma/patologia , Metástase Neoplásica/patologia , Segunda Neoplasia Primária/patologia , Doença de Paget Extramamária/metabolismo , Doença de Paget Extramamária/ultraestrutura , Moduladores de Tubulina/uso terapêuticoRESUMO
Weight loss after esophagectomy is common and is associated with unfavorable prognosis. However, the clinical features and surgical methods that influence postesophagectomy weight loss are not well characterized. This study aims to determine those features (especially the surgical methods) that may affect postoperative weight loss. We reviewed 221 esophageal cancer patients who had undergone esophagectomy at Kumamoto University Hospital (Kumamoto, Japan) between November 2012 and June 2015. Among these, we recruited 106 patients who had undergone transthoracic esophagectomy with gastric conduit reconstruction, had no cancer recurrence within 1 year, and no missing follow-up data. We tabulated the body weight changes and risk factors associated with weight loss exceeding 10% at 1-year postesophagectomy. The mean body weights at baseline and 1-year postsurgery were 60.3 kg (standard error (SE): 0.91) and 52.6 (SE: 0.91), respectively. One year postsurgery, the body weights had changed as follows: mean: -12.2%; median: -12.9%; standard deviation: 9.06; range: -36.1-18.56%; interquartile range: -10.5 to -14.0%. In the multivariate logistic regression analysis, the absence of pyloroplasty was the sole risk factor for more than 10% weight loss (OR: 3.22; 95% CI: 1.08-11.9; P = 0.036). Our data suggest that pyloroplasty with esophagectomy can overcome the post-surgical weight loss.
Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Gastroplastia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Piloro/cirurgia , Redução de Peso , Idoso , Peso Corporal , Neoplasias Esofágicas/fisiopatologia , Esofagectomia/métodos , Feminino , Gastroplastia/métodos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos RetrospectivosRESUMO
Evidence suggests that minimally invasive esophagectomy has several advantages with regard to short-term outcomes, compared to open esophagectomy in esophageal cancer patients. However, the impact of minimally invasive esophagectomy on long-term respiratory function remains unknown. The objective of this study is to assess the association between use of the minimally invasive esophagectomy and long-term respiratory dysfunction in esophageal cancer patients after esophagectomy. This retrospective single institution study using prospectively collected data included 87 consecutive esophageal cancer patients who had undergone esophagectomy. All patients underwent a respiratory function test before, and one year after esophagectomy. Logistic regression analysis was used to compute the hazard ratio for long-term respiratory dysfunction. Minimally invasive esophagectomies were performed in 53 patients, and open esophagectomies in 34 patients. The two groups showed no significant differences in terms of postoperative complications and postoperative course. Nor were any differences observed between the two groups in terms of volume capacity (L) and forced expiratory volume 1.0 (L) before esophagectomy (P > 0.34). However, one year after esophagectomy, the decreases in volume capacity and forced expiratory volume 1.0 were significantly less in the minimally invasive esophagectomy group than in the open esophagectomy group (P = 0.04 and P = 0.007, respectively). Multivariate analyses revealed that minimally invasive esophagectomy was an independent favorable factor for maintenance of forced expiratory volume 1.0 (hazard ratio = 0.17, 95% confidence interval 0.04-0.71; P = 0.01). Minimally invasive esophagectomy may be an independent favorable factor for maintenance of long-term respiratory function in esophageal cancer patients after esophagectomy.
Assuntos
Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Transtornos Respiratórios/etiologia , Idoso , Neoplasias Esofágicas/fisiopatologia , Esofagectomia/métodos , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Análise Multivariada , Período Pós-Operatório , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos , Tempo , Resultado do TratamentoRESUMO
Streptococcus thermophilus YIT 2001 (ST-1), a lactic acid bacterial strain, was shown to have inhibitory effects on the oxidation of low-density lipoprotein (LDL) and the development of aortic fatty lesions in an animal model, and lower the serum levels of malondialdehyde-modified LDL, an oxidative modification product of LDL, in a clinical trial. This study aimed to identify the intracellular active component of ST-1 associated with anti-oxidative activity against LDL oxidation. High-performance liquid chromatography-electrospray ionisation mass spectrometry analysis after fractionation of the cellular extract by reversed-phase chromatography demonstrated that the active fraction contained reduced glutathione (GSH). GSH showed anti-oxidative activity in a dose-dependent manner, while this activity disappeared following thiol derivatisation. ST-1 had the strongest anti-oxidative activity against LDL oxidation and the highest level of intracellular GSH among five strains of S. thermophilus. In addition, the anti-oxidative activity of ST-1 after thiol derivatisation decreased by about half, which was similar to that of three other strains containing poor or no intracellular GSH or thiol components. Moreover, anti-oxidative activity against LDL oxidation was observed in hyperlipidaemic hamsters fed with high GSH ST-1 cells but not in those given low GSH cells. These findings suggest that intracellular GSH in ST-1 may provide beneficial effects via anti-oxidative activity against LDL oxidation and excess oxidative stress in the blood.
Assuntos
Antioxidantes/farmacologia , Glutationa/farmacologia , Hiperlipidemias/fisiopatologia , Lipoproteínas LDL/metabolismo , Oxirredução/efeitos dos fármacos , Streptococcus thermophilus/química , Animais , Cromatografia Líquida de Alta Pressão , Cricetinae , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Streptococcus thermophilus/classificação , Espectrometria de Massas em TandemRESUMO
Pneumonia is a major cause of postesophagectomy mortality and worsens the long-term survival in resected esophageal cancer patients. Moreover, preoperative treatments such as chemotherapy or chemoradiotherapy (which have recently been applied worldwide) might affect the bacterial flora of the sputum. To investigate the association among preoperative treatments, the bacterial flora of sputum, and the clinical and pathological features in resected esophageal cancer patients, this study newly investigates the effect of preoperative treatments on the bacterial flora of sputum. We investigated the association among preoperative treatments, the bacterial flora of sputum, and clinical and pathological features in 163 resected esophageal cancer patients within a single institution. Pathogenic bacteria such as Candida (14.1%), Staphylococcus aureus (6.7%), Enterobacter cloacae (6.1%), Haemophilus parainfluenzae (4.9%), Klebisiella pneumoniae (3.7%), Methicillin-resistant Staphylococcus aureus (MRSA) (3.7%), Pseudomonas aeruginosa (2.5%), Escherichia coli (1.8%), Streptococcus pneumoniae (1.8%), and Haemophilus influenzae (1.2%) were found in the sputum. The pathogen detection rate in the present study was 34.3% (56/163). In patients with preoperative chemotherapy and chemoradiotherapy, the indigenous Neisseria and Streptococcus species were significantly decreased (P= 0.04 and P= 0.04). However, the detection rates of pathogenic bacteria were not associated with preoperative treatments (all P> 0.07). There was not a significant difference of hospital stay between the sputum-monitored patients and unmonitored patients (35.5 vs. 49.9 days; P= 0.08). Patients undergoing preoperative treatments exhibited a significant decrease of indigenous bacteria, indicating that the treatment altered the bacterial flora of their sputum. This finding needs to be confirmed in large-scale independent studies or well-designed multicenter studies.
Assuntos
Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Microbiota/efeitos dos fármacos , Microbiota/efeitos da radiação , Escarro/microbiologia , Idoso , Candida/isolamento & purificação , Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Enterobacter cloacae/isolamento & purificação , Escherichia coli/isolamento & purificação , Esofagectomia , Feminino , Haemophilus influenzae/isolamento & purificação , Haemophilus parainfluenzae/isolamento & purificação , Humanos , Klebsiella pneumoniae/isolamento & purificação , Tempo de Internação , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Pessoa de Meia-Idade , Neisseria/isolamento & purificação , Terapia Neoadjuvante , Período Pré-Operatório , Pseudomonas aeruginosa/isolamento & purificação , Estudos Retrospectivos , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
Primary malignant melanoma of the esophagus (PMME) is a highly malignant tumor with a poor prognosis. Because PMME is an extremely rare disease, therapeutic strategies against the tumor have yet to be established, and the efficacy of esophagectomy remains unclear. The objective of this study was to evaluate the post-esophagectomy survival of PMME patients. Ten patients who underwent esophagectomy for PMME between March 2005 and April 2013 at the Department of Gastroenterological Surgery, Cancer Institute Hospital, Tokyo, Japan, were identified from the institutional database. We retrospectively retrieved clinical information and data on the long-term outcomes from the patients' records. Survival rates after esophagectomy were calculated by the Kaplan-Meier method, and the hazard ratios of mortality were determined using the Cox's model. A follow-up study of the 10 patients revealed 7 cancer recurrences and 5 deaths. Median survival time was 34.5 months, and 5 of 10 patients survived longer than 2 years. The 1-year disease-free survival rate was 40%, and the 1- and 3-year overall survival rates were 70% and 60%, respectively. Importantly, all three of the non-relapsing patients were histologically confirmed as free of lymph node involvement. The four patients with lymph node metastasis relapsed within 1 year. The disease-free survival was significantly shorter in patients with lymph node involvement than in those without lymph node involvement (univariate hazard ratio = 13.3, 95% confidence interval 1.85-266.4; P = 0.009). In conclusion, esophagectomy might benefit PMME patients with no lymph node metastasis. Further large-scale cohort studies are needed to establish the treatment strategy for PMME.
Assuntos
Neoplasias Esofágicas , Esofagectomia/métodos , Efeitos Adversos de Longa Duração , Melanoma , Recidiva Local de Neoplasia , Idoso , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Japão , Estimativa de Kaplan-Meier , Efeitos Adversos de Longa Duração/epidemiologia , Efeitos Adversos de Longa Duração/etiologia , Excisão de Linfonodo/métodos , Metástase Linfática , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Estadiamento de NeoplasiasRESUMO
Recently, depletion of skeletal muscle mass (sarcopenia) has been linked to poor prognosis in several types of cancers, but has not been investigated in esophageal squamous cell carcinoma (ESCC). This retrospective study investigates the relationship between sarcopenia and clinical outcome in ESCC patients treated by surgical resection or definitive chemoradiation therapy (dCRT). The study was retrospectively conducted in a single academic hospital in Kumamoto, Japan, and involved 325 ESCC patients (256 surgical cases and 69 dCRT cases) treated between April 2005 and April 2011. Skeletal muscle mass was quantified by radiologic measures using standard computed tomography scans. The skeletal muscle tissue in the 325 ESCC patients was distributed as follows: mean: 47.10; median: 46.88; standard deviation (SD): 7.39; range: 31.48-71.11; interquartile range, 46.29-47.90. Skeletal muscle tissue was greater in male patients than in female patients (P < 0.0001), but was independent of other clinical and tumor features. Sarcopenia was not significantly associated with overall survival (log rank P = 0.54). Lymph node involvement significantly altered the relationship between sarcopenia and survival rate (P for interaction = 0.026). Sarcopenia significantly reduced the overall survival of patients without lymph node involvement (log rank P = 0.035), but was uncorrelated with overall survival in patients with lymph involvement (log rank, P = 0.31). The anastomosis leakage rate was significantly higher in the sarcopenia group than in the non-sarcopenia group (P = 0.032), but other surgical complications did not significantly differ between the two groups. Sarcopenia in ESCC patients without lymph node involvement is associated with poor prognosis, indicating sarcopenia as a potential biomarker for identifying patients likely to experience an inferior outcome. Moreover, sarcopenia was associated with anastomosis leakage but no other short-term surgical outcome.
Assuntos
Fístula Anastomótica/epidemiologia , Carcinoma de Células Escamosas/mortalidade , Quimiorradioterapia , Neoplasias Esofágicas/mortalidade , Esofagectomia , Sarcopenia/epidemiologia , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Japão/epidemiologia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Tomografia Computadorizada por Raios XAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Vulvares/tratamento farmacológico , Cetuximab/administração & dosagem , Feminino , Humanos , Neoplasias Pulmonares/secundário , Metástase Linfática , Pessoa de Meia-Idade , Paclitaxel/administração & dosagemRESUMO
BACKGROUND: Evaluation of myocardial function is clinically challenging in dogs with degenerative mitral valve disease (DMVD). Although myocardial dysfunction is caused by pathologic degeneration, histopathologic progression is poorly understood. OBJECTIVES: To characterize myocardial and pulmonary pathologic changes according to severity in dogs with naturally occurring DMVD, and to investigate whether or not pathologic degeneration is reflected by traditional clinical indices. ANIMALS: One hundred and seventeen dogs with naturally occurring DMVD. METHODS: Prospective observational study. Biopsied left atrium (LA), left ventricle (LV), and lung were evaluated histologically, and an attempt was made to correlate pathologic findings with clinical indices. RESULTS: Severe myocardial changes were observed in all International Small Animal Cardiac Health Council classes. In the lung, heart failure cell levels were significantly increased in class III patients (P < .0001). In a paired comparison, the LA showed significantly more severe degeneration than the LV, including myocardial fatty replacement, immune cell infiltration, and interstitial fibrosis (P < .0001). In contrast, myocardial cells were more hypertrophied in the LV than in the LA (P < .0001). Left ventricular end-diastolic dimension (LVEDd) was associated with fatty replacement (P = .033, R(2) = 0.584) and myocardial vacuolization (P = .003, R(2) = 0.588) in the LA. CONCLUSIONS AND CLINICAL IMPORTANCE: In DMVD, although severe pathologic changes may be evident even in early stages, there may be pathologic discrepancy between the LA and the LV. Myocardial degeneration may be reflected by clinical indices such as LVEDd and EF.
Assuntos
Doenças do Cão/patologia , Insuficiência da Valva Mitral/veterinária , Animais , Biópsia/veterinária , Doenças do Cão/diagnóstico , Cães , Ecocardiografia/veterinária , Feminino , Átrios do Coração/patologia , Ventrículos do Coração/patologia , Pulmão/patologia , Masculino , Valva Mitral/patologia , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/patologia , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
The effects of mitochondrial inhibitors (CN(-), a complex IV inhibitor and CCCP, protonophore) on catecholamine (CA) secretion and mitochondrial function were explored functionally and biochemically in rat and guinea-pig adrenal chromaffin cells. Guinea-pig chromaffin cells conspicuously secreted CA in response to CN(-) or CCCP, but rat cells showed a little, if any, secretory response to either of them. The resting metabolic rates in rat adrenal medullae did not differ from those in guinea-pig adrenal medullae. On the other hand, the time course of depolarization of the mitochondrial membrane potential (ΔΨm) in guinea-pig chromaffin cells in response to CN(-) was slower than that in rat chromaffin cells, and this difference was abolished by oligomycin, an F1F0-ATPase inhibitor. The extent of CCCP-induced decrease in cellular ATP in guinea-pig chromaffin cells, which was indirectly measured using a Mg(2+) indicator, was smaller than that in rat chromaffin cells. Relative expression levels of F1F0-ATPase inhibitor factor in guinea-pig adrenal medullae were smaller than in rat adrenal medullae, and the opposite was true for F1F0-ATPase α subunit. The present results indicate that guinea-pig chromaffin cells secrete more CA in response to a mitochondrial inhibitor than rat chromaffin cells and this higher susceptibility in the former is accounted for by a larger extent of reversed operation of F1F0-ATPase with the consequent decrease in ATP under conditions where ΔΨm is depolarized.
Assuntos
Medula Suprarrenal/fisiologia , Catecolaminas/metabolismo , Células Cromafins/fisiologia , Mitocôndrias/fisiologia , Consumo de Oxigênio/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Medula Suprarrenal/efeitos dos fármacos , Animais , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Hipóxia Celular , Células Cromafins/efeitos dos fármacos , Cobaias , Mitocôndrias/efeitos dos fármacos , Fosforilação Oxidativa , Ratos , Ratos Wistar , Especificidade da EspécieRESUMO
Odontogenic maxillary sinusitis (OMS) is an inflammatory disease caused by the spread of dental inflammation into the sinus. The long-term administration of antibiotic medicine and/or treatment of the causative tooth are the usual initial treatments. These initial treatments are not always effective, and the reason is not well understood. The purpose of this study was to identify factors of significance that may contribute to the results of the initial treatment of OMS. Thirty-nine patients were studied, divided into two groups according to the results of initial treatment: effective or non-effective. The effective group comprised 20 patients who were cured by initial treatment. The non-effective group comprised 19 patients who required an additional operation. The duration of symptoms, spread into the other sinuses, aperture width of the osteomeatal complex (OMC) on the side of the maxillary sinus, and anatomical variations in the sinuses were compared between the groups. The only significant difference found was in the aperture width of the OMC, which was significantly narrower in the non-effective group than in the effective group. The aperture width of the OMC may be a significant predictor of the effectiveness of initial treatment of OMS.