RESUMO
BACKGROUND: In critically ill patients, healthy vitamin C levels are important to avoid an imbalance in reactive oxygen species. To achieve this, oxidative stress levels in emergency patients need to be accurately measured in real-time. However, normally, reactive oxygen/nitrogen species are short-lived, rendering measurement difficult; moreover, measurement of relatively stable antioxidants and other oxidative stress markers in real-time is challenging. Therefore, we used electron-spin resonance spectrometry (ESR) to assess vitamin C levels, clarify their relationship with patients' severity, and establish more effective vitamin C therapy in critically ill patients. METHODS: We studied 103 severely ill emergency patients and 15 healthy volunteers. Vitamin C radical (VCR/dimethyl sulfoxide [DMSO]) values were analyzed in arterial blood samples by ESR at admission and once daily thereafter during the acute recovery phase. Severity scores were calculated. The relationship between these scores and VCR/DMSO values and chronological changes in VCR/DMSO values were analyzed. RESULTS: Serum VCR/DMSO values were significantly lower in critically ill patients than in healthy volunteers (0.264 ± 0.014 vs. 0.935 ± 0.052, p < 0.05), particularly in the severe trauma group and the cardiopulmonary arrest/post-cardiac arrest syndrome group. VCR/DMSO values and various severity scores did not correlate at admission; however, they correlated with SOFA scores from days 2-6. VCR/DMSO values remained low from the first measurement day through Day 6 of illness. CONCLUSIONS: Vitamin C levels were low at admission, remained low with conventional nutritional support, and did not correlate with the initial patient's severity; however, they correlated with patients' severity after admission. Some patients had normal vitamin C levels. Therefore, vitamin C levels should be measured in real-time and supplemented if they are below normal levels. TRIAL REGISTRATION: Retrospectively registered.
Assuntos
Estado Terminal , Dimetil Sulfóxido , Humanos , Estado Terminal/terapia , Elétrons , Ácido Ascórbico , Análise EspectralRESUMO
In a subgroup of Japanese patients in the ARCHER 1050 randomized phase 3 trial, we evaluated the efficacy and safety and determined the effects of dose modifications on adverse events (AE) and therapy management of first-line oral dacomitinib 45 mg compared with oral gefitinib 250 mg, each once daily in 28-d cycles, in patients with EGFR-activating mutation-positive (EGFR-positive; exon 19 deletion or exon 21 L858R substitution mutations) advanced non-small cell lung cancer (NSCLC). The primary endpoint was progression-free survival (PFS; RECIST, version 1.1, by blinded independent review). In 81 Japanese patients (40 dacomitinib, 41 gefitinib), PFS was longer with dacomitinib compared with gefitinib (hazard ratio [HR], 0.544 [95% confidence interval {CI}, 0.307-0.961]; 2-sided P = .0327; median 18.2 for dacomitinib [95% CI, 11.0-31.3] mo, 9.3 [95% CI, 7.4-14.7] mo for gefitinib). The most common Grade 3 AEs were dermatitis acneiform with dacomitinib (27.5%) and increased alanine aminotransferase with gefitinib (12.2%). A higher proportion of patients receiving dacomitinib (85.0%) compared with gefitinib (24.4%) had AEs leading to dose reduction. Incidence and severity of diarrhea, dermatitis acneiform, stomatitis and paronychia were generally reduced after dacomitinib dose reductions and dacomitinib treatment duration was generally longer in patients with a dose reduction in comparison with those without a dose reduction. Our results confirmed the efficacy and safety of first-line dacomitinib in Japanese patients with EGFR-positive advanced NSCLC.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinonas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Gefitinibe/administração & dosagem , Gefitinibe/efeitos adversos , Gefitinibe/uso terapêutico , Humanos , Japão , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Quinazolinonas/administração & dosagem , Quinazolinonas/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Disease/patient registries are underutilized despite their multiple advantages over clinical trials in the clinical evaluation of drugs, such as the capacity for long-term curation, provision of patient outcome data in routine clinical practice, and provision of benchmark data for comparison. Ensuring the fit-for-purpose quality of data generated from such registries is important to informing regulatory decision making. Here, we report the construction of a quality management system aiming to ensure regulatory-grade data quality for a registry of Japanese patients with glaucoma to evaluate long-term patient outcomes. METHODS: The quality management system was established by reference to the risk-based approach in the ICH-E6 (R2) recommendations. The following three-component approach was taken: establishment of governance, computerized system validation (CSV), and implementation of risk assessment and control. Compliance of the system with the recommendations of regulatory guidelines relevant to use of the registry was assessed. RESULTS: Governance by academic collaboration was established. This was followed by the development of a total of 15 standard operating procedures, including CSV, data management, monitoring, audit, and management of imaging data. The data management system was constructed based on a data management plan, which specified data/paper flow and data management procedures. The electronic data capture (EDC) system was audited by an external vendor, and configured and validated using the V-model framework as recommended in the GAMP5 guideline. Informed consent, eligibility assessment and major ophthalmology measurements were determined as Critical to Quality (CTQ) factors. A total of 22 risk items were identified and classified into three categories, and operationalized in the form of a risk control plan, which included training sessions and risk-based monitoring. The glaucoma registry addressed most quality recommendations in official guidelines issued by multiple health authorities, although two recommendations were not met. CONCLUSIONS: We established and configured a quality management system for a glaucoma registry to ensure fit-for-purpose data quality for regulatory use, and to curate long-term follow-up data of glaucoma patients in a prospective manner.
Assuntos
Confiabilidade dos Dados , Glaucoma , Humanos , Estudos Prospectivos , Glaucoma/terapia , Sistema de Registros , BenchmarkingRESUMO
BACKGROUND/AIMS: We aimed to clarify the clinicopathological features of gastric cancer in very elderly patients and to identify appropriate surgical therapy for them, focused particularly on their prognosis. METHODOLOGY: Patients who underwent gastrectomy for gastric cancer in Oita University Hospital were included in this study. The patients were divided into two groups: the very elderly group (80 years or older) (E group) and the middle-aged group (ranging from 40 to 79 years) (M group). Their clinicopathological features and postoperative survival were compared. RESULTS: Type 3,4 macroscopic types, INFγ and number of dissected lymph nodes were significantly less in the E group than in the M group (p=0.0092, p=0.0077, p=0.0475, respectively). Overall survival and disease-free survival were shorter for the E group (p=0.0898, p=0.0566, respectively). When other cause-related deaths were considered to be lost to follow-up, there was no significant difference between the E group and the M group. CONCLUSIONS: Whenever radical resection is possible, surgical resection for gastric cancer, even in the very elderly, should not be denied. Nevertheless, surgeons should try to do less invasive surgery, especially for the very elderly.
Assuntos
Gastrectomia , Neoplasias Gástricas/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Intervalo Livre de Doença , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/mortalidade , Hospitais Universitários , Humanos , Japão , Estimativa de Kaplan-Meier , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Seleção de Pacientes , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento , Carga TumoralRESUMO
BACKGROUND: The human homologue of Drosophila prune (PRUNE, which encodes h-prune) protein interacts with glycogen synthase kinase 3 and promotes cell motility. The aim of our study was to investigate the impact of immunohistochemically detected h-prune expression on the survival of patients with esophageal squamous cell carcinoma (ESCC). METHODS: Immunohistochemical staining of h-prune was performed for 205 surgically resected specimens of ESCC. RESULTS: In total, 43 (21%) of 205 ESCC cases were positive for h-prune. h-prune-positive ESCC cases showed a more-advanced T stage (P < 0.0001), N stage (P < 0.0001), and tumor stage (P < 0.0001) than h-prune-negative ESCC cases. In the group of 116 stage II and III ESCC cases, recurrence of ESCC was frequently found in h-prune-positive cases. In patients with lung recurrence, the tumors were more likely to be h-prune positive than h-prune negative. Univariate analysis revealed that T stage (P < 0.0001), N stage (P < 0.0001), tumor stage (P < 0.0001), and h-prune staining (P < 0.0001) were significant prognostic factors for survival. Multivariate analysis indicated that N stage (P = 0.0182) and h-prune staining (P < 0.0001) were independent predictors for survival. CONCLUSIONS: These results indicate that immunostaining of h-prune is useful to identify patients at high risk for recurrence or poor prognosis associated with ESCC.
Assuntos
Biomarcadores Tumorais/biossíntese , Carcinoma de Células Escamosas/metabolismo , Proteínas de Transporte/biossíntese , Neoplasias Esofágicas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/cirurgia , Esofagectomia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Monoéster Fosfórico Hidrolases , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
In this study, we examined the antitumor activities of isoprenoid derivatives conjugated with substrates of energy metabolism in human hepatoma-bearing athymic mice. Among these compounds, N-geranylpyruvic amide, N-geranyl-p-pyruvaminobenzoic amide, N,N'-digeranylmalic diamide and N,N'-digeranyl-O-acetylmalic diamide had strong antitumor effects. These geranylamine derivatives also inhibited in vitro cell growth. Sugar conjugates of geranylamine, geranic acid and mevalonic acid did not show any antitumor effect in vivo or in vitro. Although the geranylamine derivatives had no impact on the cell cycle distribution at 24 h, a sub-G1 (apoptotic) peak of varying magnitude was seen in DNA histograms of cells treated with the derivatives for 48 h. However, the geranylamine derivatives did not inhibit protein isoprenylation, which has been reported in cancer cells treated with several natural isoprenoids. These results suggest that the geranylamine derivatives conjugated with malic acid and pyruvic acid have a different mechanism of antitumor activity from that of natural isoprenoids.
Assuntos
Antineoplásicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Terpenos/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Citometria de Fluxo , Humanos , Injeções Intraperitoneais , Injeções Subcutâneas , Camundongos , Camundongos Endogâmicos BALB C , Transplante de Neoplasias , Relação Estrutura-Atividade , Terpenos/administração & dosagem , Terpenos/efeitos adversos , Terpenos/síntese química , Terpenos/química , Transplante HeterólogoRESUMO
Pins and wires offer the simplest and most effective tools for managing bone fractures and dislocations. Migration of these devices within the chest is rare, but can cause serious problems. The spontaneous migration of Kirschner wires from the right clavicle to the mediastinum resulted in penetrating injury of the esophagus and pseudo-aneurysm of the brachiocephalic artery in an 84-year-old patient. Two Kirschner wires were removed via a vertical incision on the right shoulder without thoracotomy and the brachiocephalic artery was replaced with a Dacron graft.
Assuntos
Fios Ortopédicos , Tronco Braquiocefálico/lesões , Esôfago/lesões , Migração de Corpo Estranho/complicações , Ferimentos Penetrantes/etiologia , Idoso , Idoso de 80 Anos ou mais , Falso Aneurisma/etiologia , Tronco Braquiocefálico/diagnóstico por imagem , Tronco Braquiocefálico/cirurgia , Clavícula/lesões , Esôfago/diagnóstico por imagem , Esôfago/cirurgia , Migração de Corpo Estranho/diagnóstico por imagem , Migração de Corpo Estranho/cirurgia , Fixação Interna de Fraturas , Fraturas Ósseas/cirurgia , Humanos , Masculino , Radiografia , Ferimentos Penetrantes/diagnóstico por imagem , Ferimentos Penetrantes/cirurgiaRESUMO
Macrophages have been reported to play an important role in suppressing tumor growth, and heat shock protein 70 (HSP70) in presenting tumor specific antigens. The objective of the present study was to investigate the relationship between lymph node metastasis and these two molecular biological markers in superficial esophageal carcinoma. Subjects were 37 patients with untreated submucosal esophageal carcinoma who underwent curative surgery. Among these patients, expression of CD68-positive macrophages in the tumor stroma and expression of HSP70 in tumor cells were analyzed. The results demonstrated that expression of CD68-positive macrophages was significantly greater among patients without lymph node metastasis (p<0.0001), and a significant correlation existed between HSP70 expression and CD68 expression (p=0.0125). In superficial esophageal carcinoma, lymph node metastasis is correlated with expression of CD68-positive macrophages in tumor stroma and expression of HSP70 in tumor cells. These two markers may therefore prove useful for therapy planning.
Assuntos
Carcinoma/metabolismo , Neoplasias Esofágicas/metabolismo , Proteínas de Choque Térmico HSP70/biossíntese , Metástase Linfática , Idoso , Antígenos CD/biossíntese , Antígenos de Diferenciação Mielomonocítica/biossíntese , Carcinoma/patologia , Carcinoma/terapia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Feminino , Humanos , Imuno-Histoquímica , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
A flexible nitinol stent was inserted to treat malignant stricture of the esophagus in 28 patients. Stenting was successful in all 28 patients, leading to an improved oral intake that was maintained for >80% of the survival period in 26 patients. Patients with tumors arising in the esophagus (n=24) were divided into two groups to compare complications and prognosis: patients who underwent stenting only (n=10); and patients who underwent stenting after radiochemotherapy (n=14). Fatal complications associated with stenting were seen in four patients (28.6%) who underwent stenting after radiochemotherapy and in one patient (10.0%) who underwent stenting only. Although survival was significantly longer for patients who underwent prior radiochemotherapy than for patients who did not, the incidence of fatal complications tended to be higher. No significant differences in background factors other than radiochemotherapy before stenting were observed between patients with fatal and non-fatal complications. Stenting was shown to represent a useful treatment for malignant stricture of the esophagus, as oral intake improved and was maintained for a long period of time in most patients. However, incidence of fatal complications was high among patients who underwent radiochemotherapy, and caution must be exercised due to the difficulty in predicting fatal complications.
Assuntos
Ligas , Carcinoma/terapia , Neoplasias Esofágicas/terapia , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/secundário , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/cirurgia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/secundário , Esofagoscopia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Stents/efeitos adversos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
This study divided patients with esophageal cancer and multiple primary cancers into two groups, a head and neck cancer (HNC) group and a non-head and neck cancer (NHNC) group. These groups were then evaluated on the basis of clinical and pathological studies. Among 92 patients with esophageal cancer as one of multiple primary cancers, 38 (41.8%) were assigned to the HNC group. The following characteristics distinguished patients in the HNC group from those in the NHNC group: (1) younger age; (2) shorter interval between diagnosis of metachronous cancers; (3) many displayed superficial esophageal cancer. Among the cases in which esophageal cancer was discovered synchronously with head and neck cancer, head and neck cancers were discovered before esophageal cancer; and (4) many patients displayed esophageal dysplasia, and many had multiple esophageal cancers. In the present study, we demonstrated the necessity of screening for multiple primary cancers in patients with esophageal cancer.
Assuntos
Neoplasias Esofágicas/epidemiologia , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias Primárias Múltiplas/epidemiologia , Causas de Morte , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Segunda Neoplasia Primária/epidemiologia , Medição de RiscoRESUMO
Primary adenocarcinoma of the esophagus is rare in Japan and, in most cases, arises from Barrett's esophagus epithelium. A 72-year-old man reporting heartburn and dysphagia and preoperatively diagnosed with adenosquamous carcinoma arising from Barrett's esophagus underwent thoracic esophagectomy and lymph node dissection in curative resection. Pathological diagnosis of the resected specimen showed adenosquamous carcinoma (coexistent adenocarcinoma and squamous cell carcinoma) invasive to the submucosal layer; metastasis was found in regional lymph nodes. Pathological staging was pT1bN1M0, stage II. Unfortunately, the man died of liver and lung metastasis 17 months postoperatively. To our knowledge, this rare case is only the fifth reported in the English literature on adenosquamous carcinoma arising from Barrett's esophagus.
Assuntos
Esôfago de Barrett/complicações , Carcinoma Adenoescamoso/etiologia , Neoplasias Esofágicas/etiologia , Idoso , Esôfago de Barrett/patologia , Esôfago de Barrett/cirurgia , Carcinoma Adenoescamoso/secundário , Carcinoma Adenoescamoso/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Humanos , Excisão de Linfonodo , Metástase Linfática , MasculinoRESUMO
The prognosis for brain metastasis from primary esophageal or gastric cancer is often poor because of late detection and a lack of effective treatments. We encountered two cases of long-term survival after resection of brain metastasis that was detected >1 year after primary esophagogastric junction adenocarcinoma resection. Both patients underwent total gastrectomy, middle to lower esophagectomy, and Roux-en-Y reconstruction using the jejunum, and intrathoracic anastomosis was performed via right thoracotomy and laparotomy for primary tumor resection as well as brain metastasis resection followed by CyberKnife irradiation. They remained recurrence free-one remains alive after 6.5 years, while the other died of myocardial infarction 4 years after surgery. The present cases emphasize that long-term survival in patients with brain metastasis from gastric cancer can be expected after resection and stereotactic radiosurgery of brain metastasis detected >1 year after the resection of primary gastric adenocarcinoma.
Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Neoplasias Esofágicas/patologia , Junção Esofagogástrica , Neoplasias Gástricas/patologia , Idoso , Intervalo Livre de Doença , Neoplasias Esofágicas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/cirurgia , Fatores de TempoRESUMO
BACKGROUND: Amplification of the chromosome 3q seems to occur frequently in esophageal squamous cell carcinoma (ESCC). This study analyzed the clinical effect of messenger RNA (mRNA) expression for PIK3CA (the gene that encodes phosphatidylinositol-3 kinase catalytic alpha-polypeptide) and TFRC (the gene that encodes the transferrin receptor), which map within chromosome 3q in ESCC. METHODS: Formalin-fixed, paraffin-embedded ESCC tissues were examined. Total RNAs were extracted, and reverse transcription products were subjected to polymerase chain reaction amplification of beta-actin, PIK3CA, and TFRC. RESULTS: Expression of beta-actin mRNA was detected in 67 (55.8%) of 120 samples, with PIK3CA mRNA expression in 22 (32.8%) of these 67 samples and TFRC mRNA expression in 15 (22.4%) of the 67 samples. PIK3CA mRNA expression correlated with regional lymph node metastasis (P = .04). TFRC mRNA expression correlated with distant metastasis (P = .04). Patients with positive results for either PIK3CA or TFRC mRNA displayed a significantly worse prognosis than patients with negative results (PIK3CA, P = .045; TFRC, P = .009). TFRC mRNA expression represented an independent prognostic factor in multivariate analysis (P = .0233), but PIK3CA did not (P = .7585). CONCLUSIONS: PIK3CA and TFRC mRNA represent prognostic factors in patients with ESCC. TFRC mRNA offers an independent prognostic factor, and expression may have clinically important implications.