Biomedical subjects
Publications and source records attributed to S Hiraki.
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).
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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.
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.
Spontaneous echo contrast in the descending aorta (DA-SEC) was examined as a possible risk factor for cerebral thromboembolism. In 19 patients (10 males, 9 females) in the chronic stage of cerebral infarction, abnormal findings by transesophageal echocardiography, flow dynamics of the common carotid artery (CCA), and hemostatic factors including blood coagulation and fibrinolysis were investigated. In nine patients, DA-SEC was detected, and SEC in left atrium (LA-SEC) was detected in nine patients. The DA-SEC positive group showed decreased blood-flow velocity (BFV) in bilateral CCA, high levels of thrombin-antithrombin III complex (TAT) and prothrombin fragment 1.2 (F1+2), a decrease in platelet count and a slight increase in D-dimer, which means an activated state of thrombin generation and resulting fibrinolysis, compared to the DA-SEC negative group. On the other hand, the LA-SEC positive group showed normal BFV in CCA and only a slight increase in D-dimer. We conclude that the condition producing DA-SEC is a stronger risk factor for cerebral infarction than that producing LA-SEC.
A recent meta-analysis and randomized studies have demonstrated that combined chemoradiotherapy is associated with a survival advantage for selected patients with locally advanced unresectable non-small-cell lung cancer (NSCLC). We conducted a phase II study of combined chemoradiotherapy to find a more effective combination of drugs and radiation than those previously reported for such patients. Between January 1994 and November 1996, 50 previously untreated patients with locally advanced unresectable NSCLC (stage IIIA with N2 or IIIB disease) were entered in this study. Patients were required to have Eastern Cooperative Oncology Group performance status < or = 2, age < or = 75 years and adequate organ function. Treatment consisted of three cycles of cisplatin (20 mg m(-2), days 1-5) and 5-fluorouracil (5-FU) (500 mg m(-2), days 1-5) every 4 weeks, and concurrent hyperfractionated thoracic radiation (1.25 Gy twice daily, with a 6-h interfraction interval; total radiation dose, 62.5-70 Gy). Of the 50 patients entered, 37 (74%) responded to this chemoradiotherapy, including two (4%) with complete response. By a median follow-up time of 41.0 months, 35 patients had died and 15 were still alive. The median time to progression for responding patients was 14.1 months (range, 2.6-51.3+ months). The median survival time was 18.7 months, with a survival rate of 66.0% at 1 year, 46.0% at 2 years and 27.6% at 3 years. Survival outcome was strongly affected by the extent of nodal involvement (median survival time, 27.4 months for N0-2 disease (n = 37) vs 10.7 months for N3 disease (n = 13); P = 0.007). The major toxicities of treatment were leukopenia and neutropenia (> or = Grade 3, 58% and 60% respectively). Other toxicities of > or = Grade 3 included thrombocytopenia (26%), anaemia (26%), nausea/vomiting (16%) and radiation oesophagitis (6%). Treatment-related death occurred for one patient. Our findings suggest that cisplatin and 5-FU in combination with concurrent hyperfractionated thoracic radiation is effective and feasible for the treatment of locally advanced unresectable NSCLC. The short-term survival in this study appeared to be more encouraging than those of similar chemoradiation trials. A randomized trial will be needed to compare the combination of cisplatin and 5-FU with other platinum-based regimens together with concurrent hyperfractionated thoracic radiation. In addition, in future studies, inclusion criteria for N3 disease with or without supraclavicular involvement should be reconsidered to correctly evaluate the effect of combined chemoradiotherapy for locally advanced unresectable NSCLC.
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A combination chemotherapy of irinotecan (CPT-11) and cisplatin (CDDP) has been reported to be active for lung cancer. In the previous trial, however, diarrhoea and leucopenia became the major obstacle for sufficient dose escalation of CPT-11 to improve the treatment outcome. We conducted a phase I study to investigate whether the fractionated administration of CDDP and CPT-11 at escalated dose was feasible and could improve the treatment outcome. Twenty-four previously untreated patients with unresectable non-small-cell lung cancer (NSCLC) or extensive disease of small-cell lung cancer (SCLC) were eligible. Both CDDP and CPT-11 were given on days 1 and 8, and repeated every 4 weeks. The dose of CDDP was fixed at 60 mg m(-2) and given by 1-h infusion before CPT-11 administration. The starting dose of CPT-11 was 40 mg m(-2), and the dose was escalated by an increase of 10 mg m(-2). The maximally tolerated dose of CPT-11 was determined as 60 mg m(-2) because grade 4 haematological or grade 3 or 4 non-haematological toxicities developed in six patients out of 11 patients evaluated. Diarrhoea became a dose-limiting toxicity. The objective response rates were 76% for NSCLC and 100% for SCLC. The recommended dose of CPT-11 and CDDP in a phase II study will be 50 mg m(-2) and 60 mg m(-2) respectively.
Monopolar cautery with irrigation forceps (CIF) was devised for use in liver resection that does not require occlusion of inflow to the remnant liver. However, a high power output is required to divide the hepatic parenchyma which boils the irrigation water. This study was performed to investigate the effects of using CIF on the hepatic parenchyma. Histologic and biochemical examination was performed in rats which had undergone hepatectomy using the CIF, irrigating bipolar (IB), Pringle's maneuver with blunt dissection (group P), or a sham operation. A greater cautery distance was obtained with the CIF than the IB. There was no significant difference in the remnant liver function after the 1st postoperative day in any of the groups. CIF is an effective instrument for anatomic or nonanatomic hepatic resection.
The purpose of the present study is to investigate the morphologic sites of breakdown in eyes pretreated with nilvadipine (a calcium channel blocker) that has been shown to inhibit the acute rise of aqueous flare induced by prostaglandin E2 (PGE2). Nilvadipine (100 microg/kg body weight) was injected intravenously in pigmented rabbits. Thirty minutes later, vehicle or PGE2 (10, 50 or 250 microg/ml) was applied on the cornea by use of a glass cylinder. Forty-five minutes later, the animals received horseradish peroxidase (HRP) intravenously and the eyes were enucleated. Distribution of HRP in the anterior segments was observed by electron microscopy. Without nilvadipine pretreatment, HRP was seen in the intercellular space of nonpigmented cells of the eyes treated with 50 microg/ml PGE2 and in the iris stroma of the eyes treated with 250 microg/ml PGE2. With nilvadipine pretreatment, HRP was not observed in these sites. Our results indicate that nilvadipine suppresses disruption of the different sites of the blood-aqueous barrier.
BACKGROUND: In an attempt to determine the efficacy of cyclophosphamide, doxorubicin, and vincristine (CAV)/cisplatin and etoposide (PVP) hybrid chemotherapy (HYB), a rapidly alternating chemotherapy, in patients with small cell lung carcinoma (SCLC), the authors conducted a randomized study to compare HYB with CAV-PVP sequential chemotherapy (SEQ). METHODS: Patients in the HYB group received the 3-drug CAV combination on Day 1 and the 2-drug PVP combination on Day 8, repeated every 4 weeks for up to 6 cycles. Patients in the SEQ group received 3 cycles each of CAV and PVP sequentially every 4 weeks, delivered on Days 1 and 8. All responding patients with limited disease (LD) received thoracic irradiation (50 gray) after chemotherapy. RESULTS: Between April 1988 and October 1992, 129 patients were evaluated fully. There were no significant differences in the treatment outcome between patients in the HYB and SEQ groups in terms of the complete response rate (59% for LD patients and 21% for extensive disease [ED] patients in the HYB group vs. 45% for LD patients and 16% for ED patients in the SEQ group), or median survival time (17.9 months for LD patients and 9.7 months for ED patients in the HYB group vs. 20.6 months for LD patients and 12.2 months for ED patients in the SEQ group). CONCLUSIONS: Hybrid CAV-PVP therapy is effective for the treatment of SCLC, but appears to be no better than sequential therapy with the same regimen.
We evaluated the effects of inflammation and physicochemical nature of selected agents on the intracameral levels of intravenously injected drugs in albino rabbits. Transcorneal diffusion of prostaglandin E2 (10, 50 or 250 micrograms/ml) using a glass cylinder was used to produce inflammation of the anterior segment in the right eyes. As a control, a vehicle was applied to the left cornea. Immediately, 2, 5, or 11 h after prostaglandin E2 administration, a mixed solution of fluorescein, cefmenoxime, and chloramphenicol (50 mg each/kg body weight) was injected intravenously. One hour after injection of the drugs, the primary aqueous humor was withdrawn. The intracameral levels of protein and these drugs after prostaglandin E2 administration increased at 1 h in a dose-dependent manner. These levels then gradually decreased. One hour after prostaglandin E2 administration, the intracameral levels of protein and these drugs in the prostaglandin E2-administered eyes were significantly higher than those in the vehicle-administered eyes, except chloramphenicol after administration of 10 micrograms/ml prostaglandin E2. Our findings indicate that the intracameral levels of intravenously administered drugs are altered not only by the severity of inflammation but also by the properties of drugs.
To evaluate the possible role of calcium channel blocker on changes in aqueous flare and intraocular pressure induced by prostaglandin E2 (PGE2) in pigmented rabbits, we examined the effects of nilvadipine and nicardipine (calcium channel blockers). PGE2, 25 micrograms/ml, was administered using a glass cylinder. Nilvadipine or nicardipine was injected intravenously. Aqueous flare was measured by a laser flare cell meter. Intraocular pressure was measured by a noncontact tonometer. After administration of PGE2, aqueous flare and intraocular pressure increased and then decreased. Increased flare and elevated intraocular pressure following PGE2 administration were inhibited by nilvadipine in a dose-dependent manner (5-500 micrograms/kg body weight). These responses were inhibited only slightly by nicardipine at the same concentration. Nilvadipine injected 30 min before PGE2 application inhibited the increase maximally. The inhibitory effect was found on days 1, 3, 5, and 7 by daily administration of nilvadipine. A good correlation between the inhibition of intraocular pressure and the inhibition of increased flare by nilvadipine was found. We believe that Ca2+, or calcium channel blocker-related substances may be involved in the mechanism of PGE2-induced elevation of aqueous flare and intraocular pressure in the pigmented rabbit.
In order to elucidate factors influencing the prognosis of small-cell lung cancer (SCLC), we reviewed the records of 253 patients with SCLC and evaluated 20 pretreatment prognostic factors by univariate analysis and Cox's multiple regression analysis. Recursive partitioning and amalgamation (RPA) was employed to identify subgroups with similar survival rates. Cox's multiple regression analysis identified five significant factors: extent of disease, number of metastatic sites, serum albumin, serum lactate dehydrogenase, and presence of weight loss. Among these, extent of disease was the most influential factor. RPA analysis revealed three subgroups predicting significantly different prognoses. The median survival time and 3-year survival rate were 18.4 months and 20.6%, respectively for the good-risk group (limited disease without weight loss), 13.5 months and 9.1%, respectively for the intermediate-risk group (limited disease with weight loss or extensive disease with less than two metastatic sites), and 9.2 months and 0%, respectively for the poor-risk group (extensive disease with two or more metastatic sites). These results will be useful for development of new staging system or subsequent stratification for randomized trials.
Chemotherapy is currently a primary treatment modality for small-cell lung cancer (SCLC). However, in the limited stage, a combination of chemotherapy and thoracic irradiation (TI) was found to be superior to chemotherapy alone by meta-analysis. Recently, concurrent administration of cisplatin and etoposide with TI may be an optimal treatment. The usefulness of prophylactic cranial irradiation in complete responders was also confirmed by meta-analysis. Dose-intensive weekly chemotherapy failed to improve the treatment outcome in the extensive stage. Randomized trials to verify the effectiveness of high-dose chemotherapy with peripheral blood stem cell transplantation are in progress.
BACKGROUND: Aminoaciduria is found in Lowe's syndrome. No studies of concentrations of ascorbic acid and amino acids in the aqueous humor of the syndrome have been performed. We examined these concentrations in a patient with Lowe's syndrome. METHODS: Ascorbic acid and amino acid levels in the aqueous humor and plasma of a male infant were measured by means of high-performance liquid chromatography. The patient, who had congenital cataract, miotic pupils, opaque corneas, glaucoma, aminoaciduria, normal levels of ascorbic acid and amino acid in the plasma, and renal tubular acidosis, underwent trabeculotomy, lensectomy, and anterior vitrectomy in both eyes. RESULTS: Intraocular pressure in both eyes decreased to within the normal range, but both corneas remained opaque. The amino acid levels in the aqueous humor were similar to those in the plasma, but intracameral ascorbic acid levels were decreased. After topical instillation of ascorbic acid, the corneas became transparent. The proband's mother had good visual acuity but paracentral lens opacities in both eyes. His maternal grandmother had scattered cortical opacities in both lenses. CONCLUSION: In this infant with Lowe's syndrome, we found intracameral levels of amino acids similar to those in the plasma. Levels of ascorbic acid in the aqueous humor were decreased.
We examined the disruption of the blood-aqueous barrier following prostaglandin (PG)-E2 application in rabbits. Vehicle or PGE2 in 10, 50 or 250 microg/ml concentration was applied to the cornea of pigmented rabbit with the use of a glass cylinder. After PGE2 administration, horseradish peroxidase (HRP) was injected intravenously. Then the eyes were enucleated, and distribution of HRP in the anterior segments was examined by electron microscopy. In control eyes, diffusion of HRP was blocked by vascular endothelial cells in the iris and by nonpigmented epithelial cells in the iridial and ciliary processes. In the iridial and ciliary processes of the eyes treated with 10 microg/ml PGE2, no HRP reaction product was seen in intercellular spaces of the nonpigmented epithelial cells, but it was found in pinocytotic vesicles. In the eyes treated with 50 microg/ml PGE2 HRP reaction product was found in intercellular spaces of the nonpigmented cells in the iridial processes. In the eyes treated with 250 microg/ml PGE2 HRP reaction product was further distributed in the iris stroma. The present study demonstrated that the sites of breakdown of the blood-aqueous barrier depended upon the doses of exogenous PGE2.
We evaluated a unilateral retinal vascular abnormality in a 34-year-old woman receiving bromocriptine mesylate for the suppression of postpartum lactation. After using bromocriptine, 2.5 mg twice daily for 1 week, the patient complained of metamorphopsia in the left eye. A central retinal vein occlusion was found. We believe that central retinal vein occlusion in patients receiving bromocriptine, as demonstrated in our patient, is rare.