Biomedical subjects
Publications and source records attributed to M Tabata.
Long-term cancer survivors risk development of second primary cancers (SPC). Vigilant follow-up may be required. We report outcomes of 92 patients who underwent chemoradiation for unresectable stage III non-small-cell lung cancer, with a median follow-up of 8.9 years. The incidence of SPC was 2.4 per 100 patient-years (95% confidence interval: 1.0-4.9).
Epidemiological evidence on gene-environment effects of the G-protein beta-3 subunit C825T polymorphisms and sodium on blood pressure in the free-living general population is limited. We examined the associations between the C825T polymorphism and blood pressure levels, stratified by the sodium variables estimated by 24-h urinary sodium excretion and a dietary questionnaire, among 1,471 men and women aged 30-74 from a community in Japan. Our a priori hypothesis was that individuals with the 825T allele have elevated blood pressure among subjects with a high sodium intake. Among the whole group, the systolic blood pressure level was +2.2 mmHg (p = 0.10) higher in TT than CC genotype individuals after adjustment for sex, age, antihypertensive medication use, body mass index, and alcohol consumption. This difference was more evident among individuals with low sodium excretion (+4.5 mmHg, p = 0.01), low present sodium intake (+3.2 mmHg, p = 0.11), and low past sodium intake (+4.8 mmHg, p = 0.02). No associations were observed among those with high sodium variables. Our results indicate that the G-protein beta-3 subunit C825T polymorphism is associated with higher systolic blood pressure levels in a large free-living Japanese population, and more specifically in women with a low sodium intake. This finding helps to explain part of the discrepancy between the previously reported genetic association among different ethnic groups.
BACKGROUND: The beta chain of the interleukin 2/15 receptor (IL-2/15Rbeta) is induced by the expression of the EWS-WT1. A case of desmoplastic small round cell tumour (DSRCT) expressing only an unusual EWS-WT1 treated by us is reported here. AIM: To characterise an unusual form of EWS-WT1. METHODS: Frozen tissue sections of the axillary tumour were examined using a laser-assisted microdissection technique and reverse transcriptase polymerase chain reaction. RESULTS: The novel fusion of exon 8 of EWS and the defective exon 10 of WT1 (-KTS) was detected. Although it was an unusual form, the coexpression of the present EWS-WT1, IL-2/15Rbeta and Janus kinase (JAK1) mRNA was detected in the tumour cells. IL-2 and signal transducers and activators of transcription (STAT5) mRNA were detected in both tumour and stromal cells. CONCLUSION: The induction of the IL-2/15 receptor signalling pathway may contribute to tumorigenesis in DSRCT through a paracrine or an autocrine system, even though the EWS-WT1 was an unusual form.
AIMS: To examine micrometastasis in node-negative hilar bile duct carcinoma (HBDC) using an immunohistochemical method and evaluated the clinical significance. METHODS: Four hundred and twenty three regional lymph nodes from 28 patients with node-negative HBDC who had undergone a resection were immunostained with an antibody against cytokeratins eight and 18 (CAM 5.2). RESULTS: Lymph node micrometastasis was detected in 11 of the 28 patients and 14 of the 423 lymph nodes. Lymph node micrometastasis was significantly correlated with the pT classification (p=0.03), the histopathological grading (p=0.01) and venous invasion (p=0.05). The 5-year survival rate of the patients with lymph node micrometastasis was 21.8%, as opposed to 66.5% in the patients without micrometastasis. Patients with micrometastasis showed a significantly poorer survival rate than those without micrometastasis (p=0.02). CONCLUSION: The results suggest that immunohistochemically detected lymph node micrometastasis has an impact on the outcome in HBDC.
BACKGROUND: This study aimed to investigate the survival outcome of patients with non-small-cell lung cancer (NSCLC) who had obtained disease stabilisation with gefitinib treatment and to clarify the effect of continued treatment with gefitinib on prognosis. PATIENTS AND METHODS: We reviewed the clinical records of 365 Japanese patients with NSCLC who received gefitinib (250 mg/day). RESULTS: Of 324 (89%) patients assessable for response, 147 (45%) obtained disease stabilisation and 71 (22%) patients achieved an objective response. Overall survival in patients obtaining disease stabilisation was significantly longer than in patients with progressive disease (median survival time 12.1 versus 4.4 months; P <0.0001). In patients obtaining disease stabilisation, those who continued gefitinib treatment until disease progression tended to have longer overall and progression-free survival compared with those discontinuing gefitinib treatment (1-year survival rate 52.1% versus 36.6%, P = 0.08; 1-year progression-free survival rate 31.8% versus 5.2%, P = 0.001). Multivariate analysis showed discontinuing gefitinib was an independent risk factor for progression-free survival (hazard ratio 1.66; 95% confidence interval 1.07-2.56; P = 0.022) but not for overall survival. CONCLUSIONS: Our findings indicate the importance of achieving disease stabilisation with gefitinib treatment and continued gefitinib treatment in Japanese patients with disease stabilisation, although further studies are required to confirm these findings.
The objective of this study was to assess the feasibility and effectiveness of an induction chemoradiotherapy regimen followed by surgery in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). A total of 22 patients with LA-NSCLC were treated with induction chemoradiotherapy consisting of cisplatin (40 mg m(-2)) and docetaxel (40 mg m(-2)) given on days 1, 8, 29 and 36 plus concurrent thoracic irradiation at a dose of 40-60 Gy (2 Gy fraction(-1) day(-1)). Surgical resection was performed within 6 weeks after completion of induction therapy. Objective response to the induction therapy was obtained in 16 patients (73%). In all, 20 patients (91%) underwent surgery and complete resection was achieved in 19 patients (86%). Pathological downstaging and pathological complete response were obtained in 14 (64%) and five (23%) patients, respectively. With a median follow-up period of 32 months, the calculated 3-year overall and progression-free survival rates were 66 and 61%, respectively. It is noteworthy that the 3-year overall survival rate in 14 patients achieving pathological downstaging was extremely high (93%). Toxicity was manageable with standard approaches. No treatment-related deaths occurred. This combined modality treatment is feasible and highly effective in patients with LA-NSCLC. The results warrant further large-scale study to confirm the effectiveness of this regimen.
BACKGROUND: The aim of this study was to clarify whether the results of surgical treatment of ruptured hepatocellular carcinoma (HCC) are poorer than the results of surgical treatment of non-ruptured HCC. METHODS: Out of a total of 224 HCC patients, the 6 patients with ruptured HCC were compared with 15 patients with non-ruptured HCC based on TNM stage IVA and having a Cancer of the Liver Italian Program (CLIP) score of 1 or 2. RESULTS: There were no significant differences in clinical and pathological features between the two groups. The 1-year and 3-year overall survival rates were 69.3% and 21.2%, respectively, in the ruptured HCC group and 51.3% and 20.5%, respectively, in the non-ruptured HCC group. The 1-year and 3-year disease-free survival rates were 33.0% and 0%, respectively, in the ruptured HCC group and 38.9% and 15.6%, respectively, in the non-ruptured HCC group. The differences in survival rates between these two groups did not reach statistical significance. CONCLUSION: Hepatic resection as definitive treatment after recovery from the initial insult of the rupture of HCC yields results similar to those obtained by surgical treatment of non-ruptured HCC at the same tumor stage and with the same degree of liver damage.
BACKGROUND: Single new agents reportedly produce promising response and survival effects, but platinum-based doublets remain the standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the effectiveness of platinum for advanced NSCLC by carrying out a meta-analysis of trials that compared platinum-based doublets with single new agent therapy alone. METHODS: We carried out a literature search to identify trials, conducted between 1994 and 2003, comparing a doublet of platinum plus a new agent with a new agent alone in previously untreated patients with advanced NSCLC. Outcomes analysed were response, survival and toxicity. RESULTS: Eight trials encompassing 2374 patients were identified. Platinum-based doublets produced an approximately two-fold higher overall (complete and partial) response rate than the new agent alone [odds ratio = 2.32; 95% confidence interval (CI)=1.68-3.20]. Platinum-based doublet therapy was also associated with a 13% prolongation of survival (hazard ratio = 0.87; 95% CI = 0.80-0.94, P <0.001). Despite significant increases in the frequencies of various toxic effects in patients receiving platinum-based doublets, no significant difference in treatment-related mortality was observed. CONCLUSION: This is the first published meta-analysis demonstrating the importance of combining platinum with single new agents in the treatment of advanced NSCLC.
In the present study, we tested whether the pineal organ of ayu (Plecoglossus altivelis), an osmerid teleost close relative of salmonids, harbours a circadian oscillator regulating rhythmic melatonin release using flow-through culture. The pineal organ maintained under light/dark cycles released melatonin in a rhythmic fashion with high levels during the dark phase. A circadian rhythm of melatonin release persisted in constant darkness for at least four cycles. Characteristics of the circadian rhythm (free-running period, phase and amplitude) exhibited small variations among cultures when the data was normalized, indicating that this system is sufficient for the analysis of the circadian rhythm both at qualitative and quantitative levels. Six-hour extension of the light phase from the normal onset time of the dark phase or exposure to constant light for 36 or 48 h before transfer to constant darkness significantly inhibited melatonin release. Phase shifts in the circadian rhythm of melatonin release were also observed. Thus, the ayu pineal organ contains all the three essential components of the circadian system (a circadian clock, the photoreceptor responsible for photic entrainment of the clock, and melatonin generating system as an output pathway). This system should provide a useful model for analysing the physiological and molecular basis of the vertebrate circadian system. In addition, further comparative studies using salmonids and related species including ayu will provide some insight into the evolution of the roles of the pineal organ in the vertebrate circadian system.
The excellent long-term patency rates achieved utilizing the internal thoracic arteries (ITAs) have stimulated a variety of approaches to expand the use of these conduits in coronary revascularization. The ITA divides at the level of the fifth or sixth intercostal space into the superior epigastric and musculophrenic branches. If these terminal branches of the ITA are large and long enough for grafting, they can be used to construct a "Y" anastomosis to the coronary arteries. We experienced 2 patients who underwent multivessel off-pump coronary artery bypass (OPCAB) using these ITA branches. In both patients the bilateral ITAs and the right gastroepiploic artery were taken down using the skeletonization technique as in situ grafts. One patient had 5 grafts including the right ITA terminal branches which were used for the left anterior descending branch (LAD) and diagonal branch. Another patient had 6 grafts including the left ITA terminal branches which were used for the posterolateral branch (PL)1 and PL2. Postoperative angiography revealed widely patent grafts in both patients. We believe that one of the advantages of applying the off-pump technique when the ITA branches are used is that it might be easier to arrange the angle of constructing a natural "Y" configuration compared with conventional coronary artery bypass grafting (CABG). In conclusion, the terminal branches of the ITA, if of suitable size, should be considered for "Y" grafts to diseased coronary arteries when performing complete arterial revascularization with only in situ grafts.
To improve the efficacy of fibreoptic bronchoscopy in the diagnosis of peripheral lung cancer, we evaluated the effectiveness of various techniques for obtaining samples for cytological examination. Between January 1984 and December 2000, flexible fibreoptic bronchoscopy under fluoroscopic guidance was performed in 1372 patients with lung cancer having no visible endoscopic findings. Histological examination of specimens obtained by forceps biopsy and cytological examinations on imprints of biopsy specimens, brushing, selective bronchial lavage, curettage, transbronchial needle aspiration, rinse fluids of the forceps, brush, curette, and aspiration needle, and all fluids aspirated during the bronchoscopic examinations were evaluated for diagnostic power. Using these techniques, the overall diagnostic rate with bronchoscopy was 93.4%. The sensitivity of the histological examination was 76.9%; additional imprint cytology increased the sensitivity to 84.8% (P<0.0001), while additional cytology on the rinse fluid of the forceps increased the sensitivity to 83.7% (P<0.0001). The addition of both imprint cytology and cytology on the rinse fluid of the forceps increased the diagnostic rate to 86.2% (P<0.0001). Our results indicate that cytological examinations of the imprints of biopsy samples and the rinse fluids of the forceps and the brush improve the efficacy of fibreoptic bronchoscopy in the diagnosis of peripheral lung cancer.
Recent studies have suggested the superiority of concomitant over sequential administration of chemotherapy and radiotherapy. Docetaxel and cisplatin have demonstrated efficacy in advanced non-small-cell lung cancer (NSCLC). This study evaluated the safety, toxicity, and antitumour activity of docetaxel/cisplatin with concurrent thoracic radiotherapy for patients with locally advanced NSCLC. Patients with locally advanced NSCLC (stage IIIA or IIIB), good performance status, age or=3 toxicities of 71, 60, 24, and 19%, respectively. Toxicity was significant, but manageable according to the dose and schedule modifications. Dose intensities of docetaxel and cisplatin were 86 and 87%, respectively. Radiotherapy was completed without a delay in 67% of 42 patients. The overall response rate was 79% (95% confidence interval (CI), 66-91%). The median survival time was 23.4+ months with an overall survival rate of 76% at 1 year and 54% at 2 years. In conclusion, chemotherapy with cisplatin plus docetaxel given on days 1, 8, 29, and 36 and concurrent thoracic radiotherapy is efficacious and tolerated in patients with locally advanced NSCLC and should be evaluated in a phase III study.
With the rapid advance of percutaneous catheter intervention, the direction taken by surgeons is not only to make coronary artery bypass grafting (CABG) less invasive but also to obtain better long-term results by using more arterial conduits. However, off-pump CABG (OPCAB) with only in situ arterial conduits such as the left and right internal thoracic arteries (ITAs) and the right gastroepiploic artery (RGEA) is technically demanding for the surgeon. The purpose of this study was to demonstrate the feasibility and safety of this technique. From January 2002 to December 2002, 57 patients underwent isolated CABG without cardiopulmonary bypass, excluding minimally invasive direct coronary artery bypass (MIDCAB) cases. There were 44 men and 13 women with a mean age of 64.1 years. Most of the patients (95%) underwent postoperative angiography within 1 month after surgery. The mean number of anastomoses was 3.8 +/- 1.4 (range 2-8). One patient suffered from mediastinitis and another from stroke. All patients were discharged from the hospital. Fifty patients (88%) received only in situ grafts for complete revascularization. Forty-one patients received bilateral ITAs and 27 received bilateral ITAs and RGEA. The mean number of anastomoses using bilateral ITAs and RGEA was 4.5 +/- 1.2 (range 3-8). The patency rate was 98%. Complete arterial revascularization with only in situ arterial conduits was associated with minimal operative risk and a high early graft patency rate, even in the off-pump situation. These results indicate that complete revascularization can be achieved in OPCAB with the exclusive use of in situ arterial conduits in patients with diffuse coronary arterial disease.
To investigate the problem of allogeneic bone marrow transplantation (allo-BMT) for advanced stage patients, we retrospectively analyzed 24 consecutive patients who underwent allo-BMT in the non-remission stage. Twenty-four patients (19 males and 5 females) with acute leukemia, chronic myelogenous leukemia, and malignant lymphoma underwent allo-BMT. The patients had a median age of 30 years. There were eight cases of acute myelogenous leukemia (AML), six cases acute lymphocytic leukemia (ALL), nine cases of chronic myelogenous leukemia (CML), and one case of Burkitt's lymphoma. The 3-year overall survival rate was 22.5%, with a median survival time of 206 days in AML, 345 days in ALL, and 363 days in CML. Overall survival was associated with a recovery of platelets of less than 30 days and an acute graft-versus-host disease (acute GVHD) presence of less than grade II ( p=0.042). Fourteen patients died of transplantation-related diseases. Our important problem is to decrease transplantation-related deaths in allo-BMT during the non-remission stage, and longer survival can be expected with better pretreatment and prophylaxis for GVHD. In addition, the selection of the source of hematopoietic stem cell transplantation at an optimal time is considered to be another problem to be approached.
We conducted a phase I/II study to investigate whether the surgical resection after induction chemotherapy with cisplatin and irinotecan was feasible and could improve the treatment outcome for patients with pathological N(2) non-small cell lung cancer. Fifteen patients with stage IIIA non-small cell lung cancer having mediastinal lymph node metastases proved by mediastinoscopy were eligible. Both cisplatin (60 mg m(-2)) and irinotecan (50 mg m(-2)) were given on days 1 and 8. Patients received two cycles of chemotherapy after 3-4 weeks interval. Induction was followed by surgical resection in 4-6 weeks. Patients who had documented tumour regression after preoperative chemotherapy received two additional cycles of chemotherapy and other patients received radiotherapy postoperatively. After the induction chemotherapy, the objective response rate was 73%. All the 15 patients received surgical resection and complete resection was achieved in 11 (73%) patients. There was no operation-related death and one death due to radiation pneumonitis during postoperative radiotherapy. The median time from entry to final analysis was 46.5 months, ranging from 22 to 68 months. The 5-year survival rate was 40% for all the 15 patients and it was 55% for the 11 patients who underwent complete resection. We conclude that the surgical resection after induction chemotherapy with cisplatin and irinotecan is feasible, and associated with low morbidity and high respectability.
Human T-cell leukaemia virus type I (HTLV-I) is a retrovirus that causes adult T-cell leukaemia (ATL). HTLV-I has existed in Japanese people for thousands of years. In order to prevent an epidemic of HTLV-I, it is important to explain the infection system by a mathematical approach. By considering the main infection routes in Japan, that is: (i) mother-to-child transmission; (ii) male (husband)-to-female (wife) transmission; and (iii) female (wife)-to-male (husband) transmission, a mathematical model for describing the time-dependent change of the infection proportion can be constructed. An upper bound of the present infection rate per year in male-to-female transmission and that in female-to-male transmission is given by the model, and theoretical results related to HTLV-I infection are also deduced from the mathematical model. A simulation study based on the present model demonstrates the theoretical results relating to the HTLV-I infection.
A phase II study of fractionated administration of irinotecan (CPT-11) and cisplatin (CDDP) in patients with non-small-cell lung cancer (NSCLC) was conducted. Between January 1996 and January 1998, 44 previously untreated patients with stage IIIB or IV NSCLC were enrolled. CDDP at a dose of 60 mg x m(-2) was given first and followed by CPT-11 at a dose of 50 mg x m(-2). Both drugs were given by 1-hour infusion on days 1 and 8, and repeated every 4 weeks up to 4 cycles. 42 patients were evaluated for response and 44 for survival and toxicity. 20 patients (48%: 95% confidence interval 32-63%) achieved an objective response. The median duration of responses was 8 months, and the median survival time and the 1-year survival rate were 12.5 months and 56.8%, respectively. Major toxicities were neutropenia and diarrhoea. Grade 3 or 4 neutropenia occurred in 70.5% of the patients and one patient died of sepsis. Grade 3 or 4 diarrhoea was experienced in 25.0%, but manageable by conventional therapy. In conclusion, fractionated administration of CPT-11 and CDDP was highly effective for advanced NSCLC with manageable toxicities.
To determine whether birth weight and childhood growth, especially rate of height increase, are independently related to major cardiovascular disease risk factors in adult life, the authors conducted a 20-year follow-up study in a Japanese population, using the record-linkage method. From medical checkup data for babies and for residents aged 20 years in Ishikawa, Japan, the authors obtained 20-year follow-up data (1985-1994) on 4,626 participants (2,198 men and 2,428 women) born in 1965-1974. Using multiple linear regression analysis, the authors estimated that a 1-standard-deviation higher birth weight was significantly associated with systolic blood pressure that was lower by 1.6 mmHg in men and by 1.0 mmHg in women, and with a serum cholesterol level that was lower by 0.07 mmol/liter in men and by 0.04 mmol/liter in women, after adjustment for current weight and rate of height increase. Moreover, after adjustment for birth weight and current weight, a 1-standard-deviation higher rate of height increase from age 3 years to age 20 years was significantly associated with systolic blood pressure that was lower by 0.7 mmHg in men and by 0.5 mmHg in women, and with serum cholesterol that was lower by 0.09 mmol/liter in men and by 0.05 mmol/liter in women. The results suggest that lower birth weight and lower rate of height increase during childhood are independently associated with increases in blood pressure and serum cholesterol in adult life.