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1.
Ther Innov Regul Sci ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32030692

RESUMO

BACKGROUND: Two issues in clinical trials with multiple endpoints were surveyed: (1) the terminology of multiple endpoints, the relationship between rare events and endpoints, and the differences in multiplicity adjustment between regions, and (2) the current practice on multiplicity adjustment and sample size calculation. This article summarizes the results of the survey on the second issue. METHODS: Eligible trials for this survey fulfilled the following conditions: (1) confirmatory phase 3 trial; (2) use of multiple primary endpoints, co-primary endpoints, key secondary endpoint(s) or composite endpoint(s); (3) inclusion of Japanese participants; and (4) protocols created in 2010 or later. The survey was conducted at member companies of the Japan Pharmaceutical Manufacturers Association from October 2017 to November 2017. RESULTS: Useable responses were obtained from 78 trials in 13 companies based in Japan and 9 companies based in other countries. The Bonferroni procedure was mostly used in clinical trials with multiple primary endpoints, while multiple testing procedures that consider a hierarchy of endpoints or a structure of hypotheses were used in clinical trials with key secondary endpoint(s). In sample size calculation, we can consider the probability of study success, such as the probability of statistical significance in at least one comparison of primary endpoints; however, other probabilities were also considered. This survey reveals that multiplicity adjustment and the correlation of endpoints were not always considered in sample size calculation. CONCLUSIONS: In clinical trials with multiple endpoints, clinical importance was considered when determining multiple testing procedures. Challenges remain with the definition of power, the consideration of multiple testing procedures and the correlation between endpoints in sample size calculation.

2.
Lung Cancer ; 141: 64-71, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31955002

RESUMO

OBJECTIVES: SPECTRA is a multicenter, randomized phase II study of chemotherapy with cisplatin (CDDP) plus S-1 versus CDDP plus pemetrexed (PEM) in combination with thoracic radiotherapy (TRT) for locally advanced non-squamous non-small cell lung cancer, in order to determine which of these two regimens might be preferable for comparison with standard therapies in a future phase III study. MATERIALS AND METHODS: Patients were randomly assigned to receive CDDP + S-1 (CDDP 60 mg/m2 on day 1 and S-1 80 mg/m2 on days 1-14, every 4 weeks, up to 4 cycles) or CDDP + PEM (CDDP 75 mg/m2 + PEM 500 mg/m2 on day 1, every 3 weeks, up to 4 cycles) combined with TRT (60 Gy in 30 fractions). The primary endpoint was the 2-year progression-free survival (PFS) rate. The sample size had been set at 100 patients. RESULTS: A total of 102 patients were randomized to receive CDDP + S-1 or CDDP + PEM (CDDP + S-1, n = 52; CDDP + PEM, n = 50) between January 2013 and October 2016. The results in the CDDP + S1 group and CDDP + PEM group were as follows: completion rates of TRT (60 Gy)/chemotherapy (4 cycles) was 92 %/73 % and 98 %/86 %, respectively; the response rates were 60 % and 64 %, respectively; median PFS after a median follow-up of 32.1 months, 12.7/13.8 months (hazard ratio [HR] = 1.16; 95 % confidence interval [CI], 0.73-1.84); 2-year PFS rate, 36.5 % (95 % CI, 23.5-49.6)/32.1 % (95 %CI, 18.9-45.4); median OS, 48.3/59.1 months (HR = 1.05; 95 %CI, 0.58-1.90); 2-year OS rate, 69.2 % (95 %CI, 56.7-81.8)/66.4 % (95 %CI, 53.0-79.9); Grade 3 toxicities: febrile neutropenia (12 %/2 %), anorexia (8 %/16 %), diarrhea (8 %/0 %), esophagitis (6 %/8 %), and neutropenia (35 %/50 %); Grade 2 or worse radiation pneumonitis, 15 % (8 patients)/4 % (2 patients). CONCLUSION: The 2-year PFS rate in the CDDP + S-1 arm was higher than that in the CDDP + PEM arm. Both treatments were safe, with manageable toxicities.

3.
Int J Clin Oncol ; 25(1): 1-42, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31203527

RESUMO

The number of deaths from colorectal cancer in Japan continues to increase. Colorectal cancer deaths exceeded 50,000 in 2016. In the 2019 edition, revision of all aspects of treatments was performed, with corrections and additions made based on knowledge acquired since the 2016 version (drug therapy) and the 2014 version (other treatments). The Japanese Society for Cancer of the Colon and Rectum guidelines 2019 for the treatment of colorectal cancer (JSCCR guidelines 2019) have been prepared to show standard treatment strategies for colorectal cancer, to eliminate disparities among institutions in terms of treatment, to eliminate unnecessary treatment and insufficient treatment and to deepen mutual understanding between healthcare professionals and patients by making these guidelines available to the general public. These guidelines have been prepared by consensuses reached by the JSCCR Guideline Committee, based on a careful review of the evidence retrieved by literature searches and in view of the medical health insurance system and actual clinical practice settings in Japan. Therefore, these guidelines can be used as a tool for treating colorectal cancer in actual clinical practice settings. More specifically, they can be used as a guide to obtaining informed consent from patients and choosing the method of treatment for each patient. Controversial issues were selected as clinical questions, and recommendations were made. Each recommendation is accompanied by a classification of the evidence and a classification of recommendation categories based on the consensus reached by the Guideline Committee members. Here, we present the English version of the JSCCR guidelines 2019.

4.
J Cancer Res Clin Oncol ; 146(1): 75-86, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31754833

RESUMO

PURPOSE: The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. METHODS: Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. RESULTS: While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29-5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/low FPGS and low GGH/high FPGS. Patients without adjuvant treatment showed no significant difference. CONCLUSION: GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/biossíntese , Peptídeo Sintases/biossíntese , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/enzimologia , gama-Glutamil Hidrolase/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Quimioterapia Adjuvante , Combinação de Medicamentos , Feminino , Mucosa Gástrica/enzimologia , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Peptídeo Sintases/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , gama-Glutamil Hidrolase/genética
5.
In Vivo ; 34(1): 461-467, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31882514

RESUMO

BACKGROUND/AIM: Endothelial cell-specific molecule-1 (ESM-1) is a soluble proteoglycan which has important role in various biological events. We investigated the impact of the ESM-1 expression in cancer tissues on outcomes in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy. PATIENTS AND METHODS: The ESM-1 mRNA expression in cancerous tissues and adjacent normal mucosa from 253 patients was measured. The associations between the ESM-1 gene expression and the survival and clinicopathological features were investigated. RESULTS: A significant association was observed between high ESM-1 expression and undifferentiated adenocarcinoma. The overall survival curve was significantly lower in patients with high ESM-1 expression than in those with low expression (p=0.005). High ESM-1 expression was a significant independent prognosticator (HR=2.291, p=0.007). CONCLUSION: ESM-1 gene expression in cancerous tissues is an important prognosticator in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy.

6.
Scand J Gastroenterol ; 54(11): 1331-1338, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31656106

RESUMO

Objectives: Transabdominal ultrasonography is a common and accurate tool for managing Crohn's disease (CD); however, the significance of the resulting data is poorly understood. This study was performed to determine the association between bowel wall thickness evaluated by water-immersion ultrasonography and macroscopic severity, namely, refractory inflammation and subsequent fibrosis in CD surgical specimens.Materials and methods: We retrospectively evaluated 100 segments of colon and small intestine from 27 patients with CD. The resected specimens were placed in saline postoperatively, and bowel wall thickness was measured by water-immersion ultrasonography and compared with macroscopic findings. Correlations between bowel wall thickness and macroscopic findings were assessed using analysis of variance and receiver operating characteristic curves.Results: According to the progression of macroscopic severity, the mean bowel wall thickness was increased as follows: macroscopically intact: 4.1 mm, longitudinal ulcer scars: 5.4 mm, longitudinal open ulcers: 6.0 mm, large ulcers: 6.4 mm, cobblestone-like lesions: 7.1 mm, and fibrotic strictures: 7.4 mm. For all lesions except longitudinal ulcer scars, the bowel wall thickness was significantly thicker than that of macroscopically-intact areas (p < .001). According to receiver operating characteristic curves, bowel wall thickness >4.5 mm was associated with CD lesions, and thickness >5.5 mm was associated with more severe lesions.Conclusions: The bowel wall thickness of CD lesions was evaluated by water-immersion ultrasonography correlated with macroscopic disease severity.

7.
Anticancer Res ; 39(10): 5715-5720, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570472

RESUMO

BACKGROUND/AIM: The PRKCI gene encodes Protein kinase C iota. The overexpression of protein kinase C iota is associated with poor outcomes in patients with gastric and other cancers, but the role of the PRKCI gene in gastric cancer is not fully understood. Thus, we evaluated the clinical significance of PRKCI gene expression in gastric cancer. MATERIALS AND METHODS: PRKCI mRNA expression levels in cancerous tissues and adjacent normal mucosa from 398 patients with gastric cancer were measured. Relationships between PRKCI gene expression and clinicopathological characteristics and outcomes were examined. RESULTS: Overall survival was lower in patients with a high expression of PRKCI than in those with low expression (p=0.016). No other relationships were observed. A high PRKCI expression was found to be an independent prognostic factor (p=0.036, HR=1.44, 95%CI=1.02-2.02). CONCLUSION: PRKCI gene expression in cancerous tissue might be a useful prognostic factor in patients with gastric cancer after gastrectomy.


Assuntos
Expressão Gênica/genética , Isoenzimas/genética , Proteína Quinase C/genética , Neoplasias Gástricas/genética , Gastrectomia/métodos , Mucosa Gástrica/patologia , Humanos , Prognóstico , RNA Mensageiro/genética , Neoplasias Gástricas/patologia
8.
BMC Cancer ; 19(1): 980, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640606

RESUMO

BACKGROUND: While denosumab has been shown to prevent skeletal-related events in patients with bone metastasis, there is a concern that it may cause atypical femoral fracture (AFF). While AFF has been reported in patients with osteoporosis receiving denosumab, data are scarce in the context of AFF occurring in patients with bone metastasis receiving monthly denosumab therapy. METHODS: To analyze the incidence of AFF in patients with bone metastasis, we reviewed the medical records of patients who had received monthly denosumab (120 mg) treatment from May 2012 to June 2017 at any of the three participant institutions. RESULTS: The study population consisted of 277 patients who had received a median of 10 doses (range, 1-79) of denosumab. Five patients were diagnosed as having AFF or symptomatic atypical femoral stress reaction (AFSR) needing surgical intervention, representing an incidence rate of 1.8% (95% confidence interval, 0.77-4.2). These patients had received 15, 45, 45, 46 or 47 doses of denosumab, respectively. Four of the patients had received prior zoledronic acid treatment. The results of our analysis suggested that long-term use of denosumab, especially for more than 3.5 years, and prior use of zoledronic acid were risk factors for the development of AFF. CONCLUSIONS: We found the AFF events in 5 patients (1.8%) among 277 cancer patients who had received monthly denosumab (120 mg) treatment. Long-term denosumab treatment and prior zoledronic acid treatment were identified as risk factors for the development of AFF.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Denosumab/uso terapêutico , Fraturas do Fêmur/epidemiologia , Fraturas do Fêmur/patologia , Osteoporose/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Denosumab/administração & dosagem , Denosumab/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Ácido Zoledrônico/efeitos adversos , Ácido Zoledrônico/uso terapêutico
9.
Auris Nasus Larynx ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31630851

RESUMO

OBJECTIVE: In this study, we examine the relationship between developmental insufficiency of mastoid air cells and abnormal morphology of the paranasal sinuses in patients with chronic otitis media (COM) and acquired middle ear cholesteatoma (AMEC) using precise image assessment, in order to evaluate whether the anatomical features of paranasal sinuses has any impact on the pathogenesis in COM and AMEC. METHODS: A total of 127 patients, including 45 COM patients and 82 AMEC patients, were enrolled for this study. The existence of nasal septal deviation, the existence of paranasal sinus opacification, the modified Lund-Mackay score, the diameters of the paranasal sinuses, the Vidic classification, mastoid development, and cranial size were assessed by CT examination. A further 76 adult patients who underwent high-resolution CT imaging of their skull bone for other diseases were enrolled as the control. RESULTS: The AMEC group showed a significantly shorter sphenoid length (P < 0.01) and lower Vidic classification score (P < 0.01) compared to the control group in this study. In addition, we observed that patients with AMEC had less pneumatization of the mastoid air cells compared to the control individuals, and that the sphenoid length of the poor MC score group was significantly shorter than that of the good MC score group. CONCLUSION: Our results suggested that the developmental deficiency in sphenoid length caused by long-standing pediatric rhinosinusitis might indicate the potential of chronic middle ear inflammation in childhood and impact the pneumatization of mastoid air cells. Therefore, chronic rhinosinusitis during the childhood and adolescence might play a role in the pathophysiology of AMEC.

10.
J Cancer ; 10(21): 5130-5138, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602266

RESUMO

Purpose: A comprehensive molecular analysis was conducted to identify prognostic and predictive markers for adjuvant S-1 chemotherapy in stage II/III Japanese gastric cancer (GC) patients and to evaluate their potential suitability for alternative cytotoxic or targeted drugs. Experimental Design: We investigated genetic polymorphisms of enzymes potentially involved in 5-fluoruracil (5-FU) metabolism as well as platinum resistance, previously identified genomic subtypes potentially predicting 5-FU benefit, and mRNA expression levels of receptor tyrosine kinases and KRAS as potential treatment targets in a single institution cohort of 252 stage II/III GC patients treated with or without S-1 after D2 gastrectomy. Results: 88% and 62% GC had a potentially 5-FU sensitive phenotype by SNP analyses of TS 3'UTR, and TS 5'UTR, respectively. 24%, 46%, 40%, 5%, and 44% GC had a potentially platinum sensitive phenotype by SNP analyses of GSTP1, ERCC1 rs11615, ERCC1 rs3212986, ERCC2, and XRCC1, respectively. High HER2, EGFR, FGFR2, or MET mRNA expression was observed in 49%, 66%, 72%, and 54% GC, respectively. High HER2 expression was the only significant prognosticator (HR=3.912, 95%CI: 1.706-8.973, p=0.0005). High HER2 (p=0.031), low EGFR (p=0.124), high MET (p=0.165) RNA expression, and TS 5'UTR subtype 2R/2R, 2R/3C, or 3C (p=0.058) were significant independent predictors for S-1 resistance. Conclusions: The present study suggests that platinum-based or RTK targeted agents could be alternative treatment options for a substantial subgroup of Japanese GC patients currently treated with S-1. HER2, EGFR, MET, and TS 5'UTR SNP appear to be promising predictive markers for S-1 resistance warranting validation in an independent GC series.

11.
BMJ Open ; 9(8): e028563, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31439602

RESUMO

OBJECTIVE: Few data regarding the incidence of cancer-associated thromboembolism (TE) are available for Asian populations. We investigated the incidence of TE (TEi) and its risk factors among gastric and colorectal cancer (GCC) patients received chemotherapy in a daily practice setting. DESIGN: A retrospective cohort study. SETTING: A single-institutional study that used data from Sapporo City General Hospital, Japan, on patients treated between January 2008 and May 2015. PARTICIPANTS: Five hundred Japanese GCC patients who started chemotherapy from January 2008 to May 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: TE was diagnosed by reviewing all the reports of contrast-enhanced CT performed during the follow-up period. All types of thrombosis detected by CT or additional imaging tests, such as venous TE, arterial TE and cerebral infarction, were defined as TE. Medical records of all identified patients were reviewed and potential risk factors for TE, including clinicopathological backgrounds, were collected. We defined the following patients as 'active cancer'; patients with unresectable advanced GCC, cancer recurrence during or after completing adjuvant chemotherapy and/or presence of other malignant tumours. RESULTS: Of the 500 patients, 70 patients (14.0%) developed TE during the follow-up period. TEi was 9.2% and 17.3% in GCC patients, 18.1% and 3.5% in active and non-active cancer patients, and 24.0% and 12.9% in multiple and single primary, respectively. Multivariate logistic regression analysis showed that colorectal cancer (CRC) (OR 2.371; 95% CI 1.328 to 4.233), active cancer (OR 7.593; 95% CI 2.950 to 19.543) and multiple primary (OR 2.527; 95% CI 1.189 to 5.370) were independently associated with TEi. CONCLUSION: TEi was 14.0% among Japanese GCC patients received chemotherapy, and was significantly higher among patients with CRC, active cancer and multiple primary than among those with gastric cancer, non-active cancer and single primary, respectively. TRIAL REGISTRATION NUMBER: UMIN000018912.

12.
Ther Innov Regul Sci ; : 2168479019855994, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31213076

RESUMO

BACKGROUND: Two issues on clinical trials with multiple endpoints were surveyed: (1) the terminology of multiple endpoints, relationship between rare events and endpoints, and differences in multiplicity adjustment between regions; and (2) the current practice on multiplicity adjustment and sample size calculation. This article provides a summary of the results of a survey on the first issue. METHODS: The survey was conducted among 63 members of the Japan Pharmaceutical Manufacturers Association from October to November 2017. RESULTS: Thirty-five companies based in Japan and 12 companies based in other countries, 47 companies in total, responded to the survey. The terms co-primary endpoints, secondary endpoint, and composite endpoint were used in a variety of ways. An endpoint for a clinically most important event that is expected to occur rarely differed between regions. Although the Pharmaceuticals and Medical Devices Agency did not demand multiplicity adjustment, it was considered in clinical trials with multiple endpoints for approval in Japan. CONCLUSIONS: The use of terminology differed from the definition in the Food and Drug Administration guidance and the European Medicines Agency guideline. There remain challenges on a clinically most important event that is expected to occur rarely and multiplicity adjustment in clinical trials with multiple endpoints.

13.
J Vasc Interv Radiol ; 30(6): 845-853.e6, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31126596

RESUMO

PURPOSE: Irreversible electroporation (IRE) differs from thermal radiofrequency (RF) ablation, especially in terms of the reparative process in the ablation zone induced. To elucidate this, the systemic immune responses after 2 mechanistically different types of ablation (IRE and RF ablation) were evaluated in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-one patients with HCC who underwent either RF ablation (n = 11) or IRE (n = 10) were studied. Peripheral blood samples were collected from all patients at 4 timepoints: before ablation, within 1 hour after ablation, 1 day after ablation, and 4 days after ablation. The phenotypes and functions of immune cells in peripheral blood and serum levels of cytokines and chemokines were monitored and analyzed using the mixed-effects model. Follow-up radiological images were also obtained to assess temporal changes in the ablation zone. RESULTS: The most significant difference was seen in the levels of macrophage migration inhibitory factor (MIF) in the IRE group compared to the RF ablation group (P = .0011): the serum levels of MIF in the IRE group significantly increased immediately after IRE and then rapidly decreased to the pre-ablation range 1 day after IRE, but, in contrast, no consistent trend was observed in the RF ablation group. The axial diameter (P = .0009) and area (P = .0192) of the ablation zone of IRE were significantly smaller than those of RF ablation 1 year after ablation. CONCLUSIONS: IRE was found to be associated with a significant early increase in MIF levels, which may facilitate the early reparative process and result in significant shrinkage of the ablation zone.


Assuntos
Técnicas de Ablação , Carcinoma Hepatocelular/cirurgia , Eletroporação , Oxirredutases Intramoleculares/sangue , Neoplasias Hepáticas/cirurgia , Fatores Inibidores da Migração de Macrófagos/sangue , Ablação por Radiofrequência , Técnicas de Ablação/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/imunologia , Feminino , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/imunologia , Masculino , Estudos Prospectivos , Ablação por Radiofrequência/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
14.
J Cancer ; 10(5): 1070-1076, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30854113

RESUMO

Background: In previous our phase III study to compare perioperative standard diet with or without Eicosapentaenoic acid (EPA)-enriched oral nutritional supplement (EPA-ON), additional EPA-ON did not contribute to prevent body weight loss after total gastrectomy. This report clarified whether EPA-ON could prevent loss of lean body mass (LBM) after total gastrectomy, a key secondary endpoint, in our phase III trial. Methods: This phase III study was designed as multicenter, open-label, superiority, randomized trial to confirm the preventive effect of EPA-ON body weight loss after total gastrectomy for gastric cancer. Eligible patients were randomized to either Standard-diet group or EPA-ON group by a centralized dynamic method. Standard-diet group was given no additional nutritional supplementation perioperatively (standard diet), while EPA-ON group was given an EPA-enriched supplement (ProSure®, Abbott Japan, Tokyo, Japan) in addition to their standard diet. This supplement included 600 kcal with 2.2 g/day of EPA. For both groups, patients underwent total gastrectomy with Roux-en Y reconstruction. Results: A total of 123 patients (Group A: 60, Group B: 63) were analyzed in the study. All background factors were well balanced between the both groups. Median loss of LBM was 6.74% (range -3.91% to 20.27%) in the Standard-diet group and 6.89% (range -5.11% to 20.04%) in the EPA-ON group at 1 month after surgery and was 8.59% (range -4.40% to 20.27%) in the Standard-diet group and 7.77% (range -5.57% to 23.35%) in the EPA-ON group at 3 months after surgery, which was not significantly different at the both (p=0.794 and p=0.393, respectively). Conclusions: The perioperative EPA-ON could not be recommended to prevent loss of LBM after total gastrectomy.

15.
Heart Vessels ; 34(6): 1002-1013, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30599063

RESUMO

Some experimental studies have shown that direct oral anticoagulants (DOACs) have anti-inflammatory effects. However, the interval changes in inflammatory markers in patients with non-valvular atrial fibrillation (AF) who receive DOACs remain unknown. Between July 2013 and April 2014, a total of 187 AF patients randomly assigned to receive rivaroxaban (n = 91) or dabigatran (n = 96) were assessed for eligibility. The levels of the following inflammatory markers were serially evaluated: high-sensitivity C-reactive protein, pentraxin-3, interleukin (IL)-1ß, IL-6, IL-18, tumor necrosis factor-α, monocyte chemotactic protein-1, growth and differentiation factor-15, and soluble thrombomodulin (sTM). The aim in this study was to evaluate the anti-inflammatory effects of rivaroxaban and dabigatran in patients with AF, in addition to the impact of markers on bleeding events. Finally, 117 patients (rivaroxaban: n = 55, dabigatran: n = 62) were included in the analysis at 12 months. Although the interval changes in sTM levels tended to be greater in the dabigatran group [0.3 (0-0.7) vs. 0.5 (0-1.0) FU/ml, p = 0.061], there were no significant differences in the interval changes in any inflammatory marker between 2 groups. There were no significant differences in bleeding events between 2 groups. The interval changes in sTM levels were significantly greater in patients with bleeding compared with those without [0.8 (0.5-1.3) vs. 0.4 (- 0.1-0.8) FU/ml, p = 0.017]. There were no significant differences in the interval changes in any inflammatory marker between rivaroxaban and dabigatran treatments in patients with AF. The increased levels of sTM after DOACs treatment might be related to bleeding events.


Assuntos
Fibrilação Atrial/tratamento farmacológico , Dabigatrana/uso terapêutico , Hemorragia/induzido quimicamente , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Dabigatrana/efeitos adversos , Feminino , Hemorragia/epidemiologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Análise de Regressão , Rivaroxabana/efeitos adversos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia
16.
Clin Exp Nephrol ; 23(2): 189-198, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30069609

RESUMO

BACKGROUND: Reliable prediction tools are needed to identify patients with chronic kidney disease (CKD) at greater risk of developing end-stage kidney failure (ESKF). We developed and validated clinical prediction models (CPMs) for CKD progression to ESKF under pre-dialysis nephrology care using CKD-Japan Cohort (CKD-JAC) data. METHODS: We prospectively followed up 2034 participants with CKD, defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2, aged 20-75 years for a mean of 3.15 years. We randomly divided the overall analysis set into development and validation cohorts. In the development cohort, CPMs were developed using Cox proportional hazard regression, and the goodness of fit was evaluated. In the validation cohort, discrimination and calibration of the developed CPMs were evaluated. We also validated developed CPMs in the dataset with the bootstrap method. RESULTS: ESKF onset was observed in 206 and 216 patients in the development (20.3%) and validation (21.2%) cohorts, respectively. Goodness of fit, discrimination, and calibration were worse for a simple model including age, sex, and eGFR than for a complicated model (plus albuminuria, systolic blood pressure, diabetes, serum albumin, and hemoglobin). The mean absolute difference between the observed and predictive probabilities of ESKF onset at 3 years was lower for the complicated model than for the simple model (1.57 vs. 1.87%). CONCLUSIONS: CPMs employing readily available data could precisely predict progression to ESKF in patients with CKD stage G3a to G5. These developed CPMs may facilitate more appropriate clinical care and shared decision-making between clinicians and patients.


Assuntos
Técnicas de Apoio para a Decisão , Taxa de Filtração Glomerular , Falência Renal Crônica/epidemiologia , Rim/fisiopatologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Adulto , Idoso , Biomarcadores/sangue , Bases de Dados Factuais , Progressão da Doença , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Japão/epidemiologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
17.
Breast Cancer Res Treat ; 173(1): 123-133, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30242578

RESUMO

PURPOSE: The Recurrence Score test is validated to predict benefit of adjuvant chemotherapy. TransNEOS, a translational study of New Primary Endocrine-therapy Origination Study (NEOS), evaluated whether Recurrence Score results can predict clinical response to neoadjuvant letrozole. METHODS: NEOS is a phase 3 clinical trial of hormonal therapy ± adjuvant chemotherapy for postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer, after six months of neoadjuvant letrozole and breast surgery. TransNEOS patients had tumors ≥ 2 cm and archived core-biopsy samples taken before neoadjuvant letrozole and subsequently sent for Recurrence Score testing. The primary endpoint was to evaluate clinical (complete or partial) response to neoadjuvant letrozole for RS < 18 versus RS ≥ 31. Secondary endpoints included evaluation of clinical response and rate of breast-conserving surgery (BCS) by continuous Recurrence Score result, ESR1 and PGR single-gene scores, and ER gene-group score. RESULTS: Of 295 TransNEOS patients (median age 63 years; median tumor size 25 mm; 66% grade 1), 53.2% had RS < 18, 28.5% had RS18-30, and 18.3% had RS ≥ 31. Clinical response rates were 54% (RS < 18), 42% (RS18-30), and 22% (RS ≥ 31). A higher proportion of patients with RS < 18 had clinical responses (p < 0.001 vs. RS ≥ 31). In multivariable analyses, continuous Recurrence Score result (p < 0.001), ESR1 score (p = 0.049), PGR score (p < 0.001), and ER gene-group score (p < 0.001) were associated with clinical response. Recurrence Score group was significantly associated with rate of BCS after neoadjuvant treatment (RS < 18 vs. RS ≥ 31, p = 0.010). CONCLUSION: The Recurrence Score test is validated to predict clinical response to neoadjuvant letrozole in postmenopausal patients with ER+, HER2-negative, clinically node-negative breast cancer.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Perfilação da Expressão Gênica/métodos , Letrozol/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Mastectomia/métodos , Mastectomia Segmentar , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/genética , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/metabolismo , Resultado do Tratamento
18.
J Matern Fetal Neonatal Med ; 32(1): 58-61, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28830259

RESUMO

OBJECTIVE: The objective of this study is to examine the effect of low-glucose value on the 1-h 50-g glucose challenge test (GCT) on neonatal body weight in low-risk Asian singleton pregnant women. METHOD: We retrospectively analyzed women who delivered a singleton neonate at term at a tertiary center and underwent GCT at 24-28 weeks of gestation between June 2001 and June 2015. The low GCT group was defined as <75 mg/dL and 75-139 mg/dL were control. We compared these two groups of maternal characteristics, small for gestational age neonate (SGA), large for gestational age neonate (LGA), low-birth weight, and macrosomia. The χ2 test, Fisher's exact test, and Student's t test were used. RESULTS: There were 313 low GCT groups and 4611 control. The low GCT group were younger, had lower prepregnancy body weight, higher stature, and lower prepregnancy body mass index (BMI). After adjusting these variables, the low GCT group had a lower rate of LGA and a higher rate of SGA. Neonatal body weight is more influenced by maternal physique than by low GCT result (standardized coefficient (ß); GCT 0.071, height 0.188, prepregnancy BMI 0.143). CONCLUSIONS: Neonatal body weight was only slightly influenced by low GCT result, but markedly influenced by maternal physique, such as height and prepregnancy BMI.


Assuntos
Peso ao Nascer , Glicemia , Hipoglicemia/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Feminino , Teste de Tolerância a Glucose , Humanos , Recém-Nascido , Japão/epidemiologia , Gravidez , Estudos Retrospectivos , Adulto Jovem
19.
Heart Vessels ; 34(6): 926-935, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30535756

RESUMO

Anatomical measurements obtained by intracoronary imaging devices are reported to correlate significantly with fractional flow reserve (FFR). Instantaneous wave-free ratio (iFR) is a nonhyperemic index of stenosis severity with discordant reports regarding its accuracy in relation to FFR. There is no information on the correlation of iFR with measurements derived from intracoronary imaging devices. The purpose of this study was to assess the relationship among iFR, intravascular ultrasound (IVUS), and optical frequency domain imaging (OFDI) parameters. Eighty lesions in 72 patients who underwent elective angiography and had intermediate lesions were enrolled. All lesions were assessed by iFR, FFR, IVUS, and OFDI. iFR was ≤ 0.89 in 21 (26%) lesions and FFR was ≤ 0.80 in 41 (51%) lesions. iFR correlated significantly with both IVUS-derived minimum lumen area (MLA) (r = 0.375, p = 0.003) and OFDI-derived MLA (r = 0.357, p = 0.005). FFR also correlated significantly with both IVUS-derived MLA (r = 0.472, p < 0.001) and OFDI-derived MLA (r = 0.445, p < 0.001). Among the lesions with FFR ≤ 0.80, iFR > 0.89 (mismatch) was observed in 20 lesions. There was no lesion with iFR ≤ 0.89 (reverse mismatch) among the lesions with FFR > 0.80. The lesion location among three major coronary vessels was related with the discrepancy between iFR and FFR (p = 0.007). In conclusion, iFR and FFR showed a significant correlation with IVUS and OFDI measurements. The discrepancy of iFR and FFR was associated with the lesion locations.


Assuntos
Cateterismo Cardíaco/instrumentação , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Reserva Fracionada de Fluxo Miocárdico , Idoso , Angiografia Coronária/métodos , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Tomografia de Coerência Óptica/métodos , Ultrassonografia de Intervenção/métodos
20.
Ann Surg Oncol ; 25(12): 3604-3612, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30178393

RESUMO

BACKGROUND: The technical feasibility and oncologic efficacy of reduced-port laparoscopic gastrectomy (RPG) for gastric cancer remain unclear. METHODS: A series of 767 patients with gastric cancer who underwent R0 laparoscopic gastrectomy were retrospectively matched for age, gender, American Society of Anesthesiology score, body mass index, surgeon, lymph node dissection, and pathologic stages by propensity scoring. Finally, data from 274 patients (74 conventional laparoscopic distal gastrectomy [CLDG] cases, 74 reduced-port distal gastrectomy [RPDG] cases, 63 conventional laparoscopic total gastrectomy [CLTG] cases, and 63, reduced-port total gastrectomy [RPTG] cases) were selected for analysis. RESULTS: Compared with the conventional group, the reduced-port group had significantly longer operation times (RPDG 265 min vs CLDG 239 min; p = 0.001 and RPTG 305 min vs CLTG 285 min; p = 0.012) and reduced blood loss (RPDG 48 ml vs CLDG 68 ml; p = 0.001 and RPTG 75 ml vs CLTG 110 ml; p = 0.026). The number of dissected lymph nodes was significantly higher in the CLDG group than in the RPDG group (38 vs 31; p = 0.002). Cosmetic satisfaction showed significant superiority in the reduced-port group compared with the conventional group. No significant difference was observed in overall survival (OS) (5-year OS: RPDG 100% vs CLDG 96.7%; p = 0.207 and RPTG 91.6% vs CLTG 91.8%; p = 0.615) or relapse-free survival (RFS) (5-year RFS: RPTG 92.3% vs CLTG 92.1%; p = 0.587). CONCLUSIONS: The study results suggest that RPG for gastric cancer by an experienced surgeon is a feasible and safe technique. The RPG procedure can be presented to patients as one of the effective treatment options.


Assuntos
Adenocarcinoma/mortalidade , Gastrectomia/mortalidade , Laparoscopia/mortalidade , Pontuação de Propensão , Neoplasias Gástricas/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Idoso , Perda Sanguínea Cirúrgica , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Resultado do Tratamento
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