Biomedical subjects

Yutaka Matsuyama

Publications and source records attributed to Yutaka Matsuyama.

18 recordsLinked to original sources

PubMed2006

Uracil-tegafur as an adjuvant for hepatocellular carcinoma: a randomized trial.

Frequent recurrence of hepatocellular carcinoma (HCC) after surgery remains a major clinical problem. This randomized controlled trial evaluated whether postoperative adjuvant therapy with oral uracil-tegafur (UFT) prevents recurrence of HCC. A total of 160 patients who underwent curative hepatic resection for HCC were randomly assigned to receive either 300 mg/day of UFT for 1 year after surgery (n = 79, UFT group) or surgery alone (n = 80, control group). The primary endpoint was recurrence-free survival, and the secondary endpoint was overall survival. Other study variables included liver function and type of recurrence. During a median follow-up of 4.8 years (range: 0.5-7.9), recurrence-free survival curves in the groups were similar (P = .87). Overall survival was slightly but not significantly worse in the UFT group than in the control group (P = .08). The rates of recurrence-free and overall survival at 5 years were 29% and 58%, respectively, in the UFT group, as compared with 29% and 73%, respectively, in the control group. The hazard ratio for recurrence in the UFT group, relative to the control, was 1.01 (95% confidence interval: 0.84-1.22, P = .87). The proportion of patients with advanced recurrence (i.e., multiple, extrahepatic, or associated with vascular invasion) was significantly higher in the UFT group (74%, 43 of 58 patients with recurrence) than in the control group (53%, 30 of 57) (P = .02). In conclusion, our results offer no evidence to support potential benefits of adjuvant chemotherapy with UFT after surgery in patients with HCC and suggest that such treatment may even worsen overall survival.

Adult↗

PubMed2006

A modified Japan Integrated Stage score for prognostic assessment in patients with hepatocellular carcinoma.

BACKGROUND: For patients with hepatocellular carcinoma (HCC), the selection of effective therapeutic options depends on a reliable prognostic assessment of both the tumor characteristics and liver impairment. This study sought to provide a modified Japan Integrated Stage (m-JIS) score to predict more accurately the survival of patients with HCC. METHODS: We analyzed the records of 42,269 patients diagnosed with HCC that were registered between 1992 and 1999 in a nationwide Japanese database. The m-JIS score was calculated from the tumor-node-metastasis stage and the grade of liver damage as defined by the Liver Cancer Study Group of Japan. The predictive accuracy for patient survival based on the m-JIS score was compared with that determined by the modified Cancer of the Liver Italian Program (m-CLIP) score using the cross-validation method. RESULTS: Patients were divided randomly into two groups, a training sample for construction of prediction models (n = 21,127 patients with 8,458 deaths) and a validation sample for assessment of those prediction models (n = 21,142 patients with 8,434 deaths). Both the m-JIS score and the m-CLIP score showed good discriminatory ability in the training sample. In the validation sample, the residuals of prediction based on the m-JIS score were smaller than those of the m-CLIP score (P < 0.0001). CONCLUSIONS: The m-JIS scoring system had better predictive accuracy than the m-CLIP score system for survival of Japanese patients with HCC.

Carcinoma, Hepatocellular↗

PubMed2006

Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients.

BACKGROUND & AIMS: To elucidate the survival of the patients with unresectable hepatocellular carcinoma (HCC) who underwent transcatheter arterial lipiodol chemoembolization (TACE) and to analyze the factors affecting the survivals. METHODS: During the last 8 years, a nationwide prospective cohort study was performed in 8510 patients with unresectable HCC who underwent TACE using emulsion of lipiodol and anticancer agents followed by gelatin sponge particles as an initial treatment. Exclusion criteria were extrahepatic metastases and/or any previous treatment prior to the present TACE. The primary end point was survival. The survival rates were calculated by the Kaplan-Meier method. The multivariate analyses for the factors affecting survival were evaluated by the Cox proportional hazard model. The mean follow-up period was 1.77 years. RESULTS: For overall survival rates by TACE, median and 1-, 3-, 5-, and 7-year survivals were 34 months, 82%, 47%, 26%, and 16%, respectively. Both the degree of liver damage and the tumor-node-metastasis (TNM) system proposed by the Liver Cancer Study Group of Japan demonstrated good stratification of survivals (P = .0001). The multivariate analyses showed significant difference in degree of liver damage (P = .0001), alpha-fetoprotein value (P = .0001), maximum tumor size (P = .0001), number of lesions (P = .0001), and portal vein invasion (P = .0001). The last 3 factors could be replaced by TNM stage. The TACE-related mortality rate after the initial therapy was .5%. CONCLUSIONS: TACE showed safe therapeutic modality with a 5-year survival of 26% for unresectable HCC patients. The degrees of liver damage, TNM stage, and alpha-fetoprotein values were independent risk factors for patient survival.

Aged↗

PubMed2006

Estimation of the average causal effect among subgroups defined by post-treatment variables.

BACKGROUND: In clinical trials, when comparing treatments in a subgroup of patients defined by an event that occurred after randomization is required, the standard estimator that adjusts for the post-treatment variable does not have a causal interpretation. PURPOSE: To address this problem, we formulate clinically relevant causal estimands using the principal stratification framework developed by Frangakis and Rubin, and propose a new estimation method for the principal causal effect. METHODS: We consider the comparison of the duration of response among patients who responded to chemotherapy in a cancer clinical trial. Our goal is to estimate the local average treatment effect, that is, the treatment difference among patients who would have responded to either treatment. In order to identify this estimand, we make the assumption that the value of the counterfactual indicator of response is independent of both the actual response status and the outcome variable of interest conditional on the covariates. The proposed estimator is a weighted average of the standard estimators for responders where weights are the probability that the response would have occurred had the patient received the other treatment. RESULTS: The proposed method is applied to data from a randomized phase III clinical trial in patients with advanced non-small-cell lung cancer. The average difference for the duration of response among responders estimated by the proposed method and the standard one was 16.1 (days) and 9.5 (days), respectively. We also evaluate the performance of the proposed method through simulation studies, which showed that the proposed estimator was unbiased, while the standard one was largely biased. CONCLUSIONS: We have developed an estimation method for the local average treatment effect. For any type of outcome variables, our estimator can be easily constructed and can be interpreted as the treatment effect among patients who would have had the event in either treatment group.

Carcinoma, Non-Small-Cell Lung↗

PubMed2005

Report of the 16th follow-up survey of primary liver cancer.

In the 16th nationwide follow-up survey of primary liver cancer, 19,920 patients were newly registered as patients with primary liver cancer at 795 medical institutions in Japan over a period of 2 years (from January 1, 2000 to December 31, 2001). Of these patients, 94.5% had hepatocellular carcinoma (HCC) and 3.6% had intrahepatic cholangiocarcinoma (ICC). In addition, 21,268 follow-up patients were registered, and a valid response rate of 75.6% was obtained in these follow-up patients. In this study, epidemiological and clinicopathological factors, diagnosis and treatment were investigated in patients who were newly registered in the 16th follow-up survey. As additional statistics, the cumulative survival rates of newly registered patients in the 11th to 16th follow-up surveys were calculated for each histological type (HCC, ICC and combined HCC and ICC) by background factor(s) and treatment, respectively. Furthermore, in patients with HCC, the cumulative survival rates were calculated for several types of treatment (hepatectomy, local ablation therapy and transcatheter arterial chemoembolization). It is anticipated that this follow-up survey will contribute to future research and medical practice for primary liver cancer.

Journal Article↗

PubMed2005

Intraoperative direct measurement of hepatic arterial buffer response in patients with or without cirrhosis.

The hepatic arterial buffer response (HABR) is an intrinsic regulatory mechanism of the hepatic artery (HA) that compensates for reductions in portal venous (PV) blood flow. Whether this response is maintained in patients with cirrhosis (LC) is unclear. The aim of the present study was to examine whether HABR is maintained in patients with LC using direct blood flow measurements. PV and HA blood flow were intraoperatively measured and compared in patients with (LC group, n = 39) or without (control group, n = 22) cirrhosis at baseline (baseline HABR) and after PV clamping (acute HABR) using an ultrasound transit-time flowmeter. In contrast to the proportional relationship between the baseline PV and HA blood flow observed in the control group, HA blood flow and the HA-PV flow ratio increased when PV blood flow decreased in the LC group, suggesting that the baseline HABR had already been activated. Acute HABR, evaluated by the absolute and relative changes in HA blood flow and by the buffer capacity, was blunted in the LC group (P < 0.001, P < 0.01, and P = 0.01, respectively). An association between the degree of acute HABR impairment and the level of baseline HABR activation (HA-PV flow ratio) could not be confirmed in the LC group. In conclusion, the baseline HABR appears to be continuously activated in patients with LC; this phenomenon probably results in the impairment of the acute HABR.

Blood Flow Velocity↗

PubMed2005

Prognostic impact of anatomic resection for hepatocellular carcinoma.

OBJECTIVES: To evaluate the prognostic impact of anatomic versus nonanatomic resection on the patients' survival after resection of a single hepatocellular carcinoma (HCC). SUMMARY OF BACKGROUND DATA: Anatomic resection is a reasonable treatment option for HCC; however, its clinical significance remains to be confirmed. METHODS: Curative hepatic resection was performed for a single HCC in 210 patients; the patients were classified into the anatomic resection (n = 156) and nonanatomic resection (n = 54) groups. In 84 patients assigned to the anatomic resection group, segmentectomy or subsegmentectomy was performed. We evaluated the outcome of anatomic resection, including segmentectomy and subsegmentectomy, in comparison with that of nonanatomic resection, by the multivariate analysis taking into consideration 14 other clinical factors. RESULTS: Both the 5-year overall survival and disease-free survival rates in the anatomic resection group were significantly better than those in the nonanatomic resection group (66% versus 35%, P = 0.01, and 34% versus 16%, P = 0.006, respectively). In the segmentectomy and subsegmentectomy group, the 5-year overall and disease-free survival rates were 67% and 28%, respectively, both of which were also higher than the corresponding rates in the nonanatomic resection group (P = 0.007 and P = 0.001, respectively). The results of multivariate analysis revealed that anatomic resection was a significantly favorable factor for overall and disease-free survivals: the hazard ratios were 0.57 (95% confidence interval, 0.32-0.99, P= 0.04), and 0.65 (0.43-0.96, P = 0.03). CONCLUSION: Anatomic resection for a single HCC yields more favorable results rather than nonanatomic resection.

Adolescent↗

PubMed2005

Overlap coefficient for assessing the similarity of pharmacokinetic data between ethnically different populations.

We developed a method to assess the similarity of pharmacokinetic data between ethnically different populations. An evaluation of confidence intervals for the mean difference in pharmacokinetic parameters, such as area under the concentration-versus-time curve (AUC), between populations is often used. We propose the use of the overlap coefficient (OC), which represents the proportion of overlap between two probability distributions, as a measure of the similarity between distributions. We considered five OC estimators--two parametric ones and three nonparametric ones. Simulation studies were conducted to compare the performance of the five OC estimators and their bootstrap confidence intervals. Results showed that nonparametric estimators with fixed-bandwidth kernel density estimation had a smaller mean squared error in almost all situations, and their coverage probabilities were close to the nominal level. The proposed method was applied to pharmacokinetic data from a bridging study of a combination therapy for metastatic colorectal cancer patients in the USA and Japan. From the analyses of this study, it was suggested that the distributions of the logarithmically transformed AUC for leucovorin and 5-fluorouracil were similar between the two populations.

Clinical Trials as Topic↗

PubMed2004

Reevaluation of prognostic factors for survival after liver resection in patients with hepatocellular carcinoma in a Japanese nationwide survey.

BACKGROUND: Advances in the diagnosis and surgical treatment of hepatocellular carcinoma (HCC) have improved the prognosis for patients with HCC who undergo liver resection. The objective of this study was to evaluate prognostic predictors for patients with HCC who underwent liver resection in a Japanese nationwide data base. METHODS: In this study, the authors analyzed 12,118 patients with HCC in a Japanese nationwide data base who underwent liver resection between 1990 and 1999 and compared them with a previous analysis of patients between 1982 and 1989. All patients were evaluated for prognostic factors. RESULTS: During the last decade, the increases in patients who were without hepatitis B virus surface antigen, who had small tumors, and who had portal vein invasion were noted. The 5-year overall survival rates for patients with HCC improved to 50.5%, compared with < 40% in the previous analysis. A multivariate analysis using a stratified Cox proportional hazards model according to associated liver disease indicated that age, degree of liver damage, alpha-fetoprotein level, maximal tumor dimension, number of tumors, intrahepatic extent of tumor, extrahepatic metastasis, portal vein invasion, hepatic vein invasion, surgical curability, and free surgical margins were independent prognostic predictors for patients with HCC. Operative mortality decreased from 2.3% in 1990-1991 to 0.6% in 1998-1999. CONCLUSIONS: Outcomes and operative mortality rates in patients with HCC improved during the last decade. Age, degree of liver damage, alpha-fetoprotein level, maximal tumor dimension, number of tumors, intrahepatic extent of tumor, extrahepatic metastasis, portal vein invasion, hepatic vein invasion, surgical curability, and free surgical margins were prognostic factors for patients with HCC who underwent liver resection.

Age Factors↗

PubMed2004

The effect of aging on functional decline among older Japanese living in a community: a 5-year longitudinal data analysis.

BACKGROUND AND AIMS: Using longitudinal data analyses, we examined the effects of aging on functional decline, based on activities of daily living (ADL) and instrumental activities of daily living (IADL) during a 5-year follow-up among older people living in a community in Japan. METHODS: The baseline survey in July 1988 involved all elderly residents aged 60 or older in Saku City, Nagano, Japan (N=13418). All survivors of this cohort were asked to participate in follow-up surveys conducted in 1989, 1990, 1991, 1992 and 1993. Five items of ADL and five of IADL were measured on each survey. A generalized estimating equations (GEE) analysis was used to examine the effects of aging on the increase of the proportion of subjects with functional dependence. RESULTS: These results indicated that the proportion of subjects who were dependent in ADL increased during the 5-year period by 2.2 times (p<0.001) and the proportion of those who were dependent in either ADL or IADL increased during the same period by 1.8 times (p<0.001). Gender did not appear to be significantly associated with functional decline. CONCLUSIONS: The GEE analysis in this study identified the statistically significant effect of aging on the increase of the proportion of subjects with functional dependence based on ADL and IADL.

Activities of Daily Living↗

PubMed2004

Individual patient-level and study-level meta-analysis for investigating modifiers of treatment effect.

BACKGROUND: In meta-analyses of clinical trials, clinicians are often interested in examining subset effects. Meta-regression of aggregated data is a usual approach for relating sources of variation in treatment effects to specific study characteristics. However, it is known that study-level analyses can lead to biased assessments and have some limitations in explaining the heterogeneity. An individual patient data (IPD) meta-analysis offers several advantages for this purpose. METHODS: We compared some regression analyses of IPD with meta-regression analyses of the summarized data using a real-world example in order to investigate whether a binary patient characteristic is related to treatment effect. We used data from 10 randomized trials for non-small-cell lung cancer (n = 1355). RESULTS: For treatment x stage interaction in IPD regression analysis, none of the tests of interactions was statistically significant. The meta-regression analysis gave a greater P-value than the IPD analysis. When excluding two studies, which had only stage I patients, the interaction was also not statistically significant in IPD analysis. On the other hand, the result of meta-regression analysis, though also showing no significant relationship, revealed a clear reversal in the direction of effect. CONCLUSION: We suggest that the results of meta-regression analyses would not be as robust as those of regression analyses using IPD in examining potential modifiers of treatment effects. To investigate whether patient characteristics are related to treatment effects, we suggest that interaction tests and sensitivity analyses using IPD should be employed whenever possible.

Carcinoma, Non-Small-Cell Lung↗

PubMed2003

Sensitivity analysis for the estimation of rates of change with non-ignorable drop-out: an application to a randomized clinical trial of the vitamin D3.

The vitamin D(3) trial was a repeated measures randomized clinical trial for secondary hyperparathyroidism in haemodialysis patients where the efficacy of the vitamin D(3) infusions for suppressing the secretion of parathyroid hormone (PTH) was compared among four dose groups over 12 weeks. In this trial, patients terminated the study before the scheduled end of the study due to their elevated serum calcium (Ca) level, that is, the administration of the vitamin D(3) was expected to cause hypercalcaemia as an adverse event. In this setting of monotone missingness, there is a potential for bias in estimation of mean rates of decline in PTH for each treatment group using the standard methods such as the generalized estimating equations (GEE) which ignore the observed past Ca histories. We estimated the treatment-group-specific mean rates of decline in PTH by the inverse probability of censoring weighted (IPCW) methods which account for the observed past histories of time-dependent factors that are both a predictor of drop-out and are correlated with the outcomes. The IPCW estimator can be viewed as an extension of the GEE estimator that allows for the data to be MAR but not MCAR. With missing data, it is rarely appropriate to analyse the data solely under the assumption that the missing data process is ignorable, because the assumption of ignorable missingness cannot be guaranteed to hold and is untestable from the observed data. We proposed a sensitivity analysis that examines how inference about the IPCW estimates of the treatment-group-specific mean rates of decline in PTH changes as we vary the non-ignorable selection bias parameter over a range of plausible values.

Bias↗

PubMed2003

Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy.

BACKGROUND/AIMS: We conducted a retrospective cohort study to investigate factors to early and late phase recurrence of hepatocellular carcinoma (HCC). METHODS: The study population consisted of 249 patients including 157 with cirrhosis who underwent hepatectomy for HCC. The endpoint was time-to-recurrence. Using a Cox regression model, factors to early and late phase recurrences were investigated censoring recurrence-free patients at the 2-year time point and in patients without recurrence at 2 years. RESULTS: Actuarial probability of overall recurrence at 1, 3, and 5 years were 0.301, 0.623, and 0.790, respectively, with a median follow-up of 624 days. Early recurrence was observed in 123 out of 249 patients; while late recurrence was found in 61 out of 113 patients. Factors to early recurrence were as follows: non-anatomical resection, presence of microscopic vascular invasion, and serum alpha-fetoprotein level >or=32 ng/ml. Those contributing to late phase recurrence were higher grade of hepatitis activity, multiple tumors, and gross tumor classification. CONCLUSIONS: Variables associated with metastatic recurrence were factors to early phase recurrence; whereas those related with elevated carcinogenesis contributed to late phase recurrence, thus providing an epidemiological evidence that different mechanisms, i.e. metastasis and de novo, are involved in intrahepatic recurrence after hepatectomy for HCC.

Adult↗

PubMed2003

A comparison of error detection rates between the reading aloud method and the double data entry method.

Data entry and its verification are important steps in the process of data management in clinical studies. In Japan, a kind of visual comparison called the reading aloud (RA) method is often used as an alternative to or in addition to the double data entry (DDE) method. In a typical RA method, one operator reads previously keyed data aloud while looking at a printed sheet or computer screen, and another operator compares the voice with the corresponding data recorded on case report forms (CRFs) to confirm whether the data are the same. We compared the efficiency of the RA method with that of the DDE method in the data management system of the Japanese Registry of Renal Transplantation. Efficiency was evaluated in terms of error detection rate and expended time. Five hundred sixty CRFs were randomly allocated to two operators for single data entry. Two types of DDE and RA methods were performed. Single data entry errors were detected in 358 of 104,720 fields (per-field error rate=0.34%). Error detection rates were 88.3% for the DDE method performed by a different operator, 69.0% for the DDE method performed by the same operator, 59.5% for the RA method performed by a different operator, and 39.9% for the RA method performed by the same operator. The differences in these rates were significant (p<0.001) between the two verification methods as well as between the types of operator (same or different). The total expended times were 74.8 hours for the DDE method and 57.9 hours for the RA method. These results suggest that in detecting errors of single data entry, the RA method is inferior to the DDE method, while its time cost is lower.

Data Collection↗

PubMed2003

Marginal structural models as a tool for standardization.

In this article, we show the general relation between standardization methods and marginal structural models. Standardization has been recognized as a method to control confounding and to estimate causal parameters of interest. Because standardization requires stratification by confounders, the sparse-data problem will occur when stratified by many confounders and one then might have an unstable estimator. A new class of causal models called marginal structural models has recently been proposed. In marginal structural models, the parameters are consistently estimated by the inverse-probability-of-treatment weighting method. Marginal structural models give a nonparametric standardization using the total group (exposed and unexposed) as the standard. In epidemiologic analysis, it is also important to know the change in the average risk of the exposed (or the unexposed) subgroup produced by exposure, which corresponds to the exposed (or the unexposed) group as the standard. We propose modifications of the weights in the marginal structural models, which give the nonparametric estimation of standardized parameters. With the proposed weights, we can use the marginal structural models as a useful tool for the nonparametric multivariate standardization.

Antineoplastic Agents, Hormonal↗

PubMed2002

Correcting for non-compliance of repeated binary outcomes in randomized clinical trials: randomized analysis approach.

We develop the randomized analysis for repeated binary outcomes with non-compliance. A break randomization-based semi-parametric estimation procedure for both the causal risk difference and the causal risk ratio is proposed for repeated binary data. Although we assume the simple structural models for potential outcomes, we choose to avoid making any assumptions about comparability beyond those implied by randomization at time zero. The proposed methods can incorporate non-compliance information, while preserving the validity of the test of the null hypothesis, and even in the presence of non-random non-compliance can give the estimate of the causal effect that treatment would have if all individuals complied with their assigned treatment. The methods are applied to data from a randomized clinical trial for reduction of febrile neutropenia events among acute myeloid leukaemia patients, in which a prophylactic use of macrophage colony-stimulating factor (M-CSF) was compared to placebo during the courses of intensive chemotherapies.

Drug-Related Side Effects and Adverse Reactions↗

PubMed2002

Fate of hepatocyte and sinusoidal lining cell function and kinetics after extended cold preservation and transplantation of the rat liver.

We investigated the chronological profile of graft damage and recovery after liver cold ischemia-reperfusion (I/R) injury, with particular attention to the role of apoptosis on hepatocyte and sinusoidal endothelial cell (SEC) damage. Male Lewis rats underwent rearterialized orthotopic liver transplantation using grafts subjected to a short (University of Wisconsin [UW] solution for 1 hour [UW1h]) and prolonged period (UW16h) of cold preservation. Experiments were performed immediately after preservation and 4 hours, 24 hours, 3 days, and 7 days after reperfusion. At each time, graft function, incidence of apoptotic cells, expression of the epitope recognized by a monoclonal antibody specific to rat SECs (SE-1), and incidence of proliferating cells were estimated. In the UW16h group, the proportion of apoptotic SECs was markedly elevated at 4 hours. The incidence of hepatocyte apoptosis was very low, although massive hepatocyte necrosis was evident at 24 hours. The incidence of proliferating hepatocytes and SECs peaked at 3 days, then returned to normal by 7 days. SE-1 expression was reduced immediately after preservation, followed by a marked reduction at 4 and 24 hours after reperfusion, and expression returned to normal by 7 days. Although SEC apoptosis was induced in the early phase of cold I/R injury, hepatocyte damage developed without the occurrence of apoptosis. Regeneration of both hepatocytes and SECs after cold I/R injury peaked at 3 days and was complete by 7 days, whereas functional recovery of these cell populations was complete 3 days after reperfusion.

Adenosine↗

PubMedDate not supplied

Pringle's manoeuvre in living donors.

The safety of the donor is paramount in living donor liver transplantation. The most important risk to the donor during hepatectomy is bleeding, and the inflow occlusion technique (Pringle's manoeuvre) has been reported to decrease bleeding without inducing liver injury in liver surgery. However, most transplant centres are doing donor hepatectomies without this technique for fear that it would result in ischaemic injury to the graft. We have done 46 living donor hepatectomies with Pringle's manoeuvre without any negative outcome on the quality of the graft. Surgeons should not hesitate to apply this technique in living donor hepatectomy.

Adult↗