Kumamoto Chuo Hospital

A non-contrast-enhanced three-dimensional (3D) magnetic resonance angiography (MRA) technique, which acquires images in a reasonably short scanning time and requires no contrast agent, is developed. An electrocardiographically (ECG) synchronized 3D half-Fourier fast spin-echo (FSE) technique with an appropriate ECG delay time for every slice encoding in 3D terms was used to examine the thoracic and iliac regions in 16 healthy volunteers at both 0.5 and 1.5 T. Prior to each 3D fresh blood imaging (FBI) experiment, an ECG preparation (ECG-prep) scan was acquired, and an appropriate ECG triggering time was selected for 3D FBI acquisition to optimize visualization of the vessel of interest. In the thoracic and abdominal regions, good-quality 3D MRA images were obtained. Furthermore, the weighted subtraction of two images in different phases provides contrast enhancement between arteries and veins.

BACKGROUND: In promoting tumour malignancy IL-6 signalling is considered to have an important role. However, the biological roles of IL-6 on radiosensitivity in oral squamous cell carcinoma (OSCC) remain largely unclear. The objective of this study is to determine the effects and molecular mechanisms of IL-6 on radiosensitivity in OSCC. METHODS: Two OSCC cell lines, and OSCC tissue samples with radioresistant cells were used. We examined the effects of IL-6, or tocilizumab, a humanised anti-human IL-6 receptor antibody, or both on radiosensitivity and DNA damage after X-ray irradiation in vitro. In addition, we investigated the involvement of the Nrf2-antioxidant pathway in IL-6-mediated radioresistant mechanisms using OSCC cell lines and tissues. RESULTS: Increased levels of IL-6 suppressed radiation-induced cell death, and the blockade of IL-6 signalling by tocilizumab sensitised tumour cells to radiation. The radioresistant effect of IL-6 was associated with decreased DNA damage after radiation. We also found that IL-6 promotes the activation of not only the downstream molecule STAT3 but also the Nrf2-antioxidant pathway, leading to a significant decrease in oxidative stress by upregulating Mn-SOD. CONCLUSIONS: These results indicate that the blockade of IL-6 signalling combined with conventional radiotherapy could augment the treatment response and survival rate in patients with radioresistant OSCC.

UNLABELLED: SUMMARY; A randomized placebo-controlled trial was conducted to examine the effect of daily oral 1 mg minodronate on vertebral fractures in 704 postmenopausal women with established osteoporosis for 24 months. Minodronate treatment reduced vertebral fractures by 59% without serious adverse events. Minodronate is a safe and effective bisphosphonate for osteoporosis treatment. INTRODUCTION: Minodronate increases bone mineral density (BMD) in postmenopausal osteoporotic patients. However, its efficacy in reducing osteoporotic fractures has not been tested. METHODS: To examine anti-fracture efficacy and safety of daily oral minodronate in postmenopausal women with established osteoporosis, a randomized, double-blind, placebo-controlled trial was conducted in 704 postmenopausal women (55 to 80 years) with one to five vertebral fractures and low BMD. Subjects were randomly assigned to receive daily oral 1 mg minodronate (n = 359) or placebo (n = 345) for 24 months, with daily supplements of 600 mg calcium and 200 IU vitamin D(3). RESULTS: Daily 1 mg minodronate for 24 months reduced the risk of vertebral fractures by 59% (95% CI, 36.6-73.3%). Furthermore, when fractures during the first 6 months were eliminated, the risk of vertebral fractures from 6 to 24 months was reduced by 74% in minodronate-treated group. Minodronate treatment also reduced height loss. Bone turnover markers were suppressed by about 50% after 6 months of minodronate treatment and remained suppressed thereafter. The overall safety profile including gastrointestinal safety was similar between the two groups. CONCLUSIONS: Daily oral minodronate is safe, well-tolerated, and is effective in reducing vertebral fracture risk in postmenopausal women with established osteoporosis.

We have developed a fully automated method for measuring LDL-cholesterol (LDL-C) in human serum without the need for prior separation, using a nonionic surfactant, polyoxyethylene-polyoxypropylene block copolyether (POE-POP), and a sodium salt of sulfated cyclic maltohexaose, alpha-cyclodextrin sulfate. Of the surfactants tested, POE-POP with a higher molecular mass of the POP block and a greater hydrophobicity reduced the reactivity of cholesterol in lipoprotein fractions; the reactivity in descending order was LDL >> VLDL > chylomicron approximately HDL. Gel filtration chromatographic studies revealed that POE-POP removed lipids selectively from the LDL fraction and allowed them to participate in the cholesterol esterase-cholesterol oxidase coupling reaction system. By contrast, alpha-cyclodextrin sulfate reduced the reactivity of cholesterol, especially in chylomicrons and VLDL. A combination of POE-POP with alpha-cyclodextrin sulfate provided the required selectivity for the determination of LDL-C in serum in the presence of magnesium ions and a small amount of dextran sulfate without precipitating lipoprotein aggregates. There was a good correlation between the results of LDL-C assayed by the proposed method and the beta-quantification reference method involving 161 sera with triglyceride concentrations ranging from 0.3 to 22.6 mmol/L.

We measured six apolipoproteins (apo AI, AII, B, CII, CIII, and E) by turbidimetric method using an automatic discrete biochemical analyzer and commercially available antisera. The turbidimetric method was compared with the single radial immunodiffusion method. Linearity for serum apolipoprotein assay by the automated turbidimetric method was better than by the single immuno-diffusion method. The linearity by the turbidimetric method was 2.5 G/L for AI, 1.0 G/L for AII, 4.5 G/L for B, 0.12 G/L for CII, 0.3 G/L for CIII, and 0.12 G/L for E. The presence of high concentrations of bilirubin (up to 0.15 G/L) and hemoglobin (up to 50 G/L) interfered with apolipoprotein measurement. Comparison of the immunoturbidimetric and the single radial immunodiffusion (SRID) methods showed excellent coefficients of correlation, r = 0.963, 0.896, 0.846, 0.936, 0.972, and 0.937 for apo AI, AII, B, CII, CIII, and E, respectively. Reference ranges for the six apolipoproteins were determined by using sera from 450 healthy subjects and were 1.4 +/- 0.3 G/L for AI and 0.3 +/- 0.01 for E. The observed levels of AII (P less than 0.001), B (P less than 0.01), and CIII (P less than 0.01) were significantly higher in males. The serum levels of apo B, CII, and E showed a gradual increase with age which was more prominent in females than in males. The levels of apo AI, AII decreased significantly over an 11 day period in 22 patients with myocardial infarction.

The advent of Deep Learning (DL) has significantly propelled the field of diagnostic radiology forward by enhancing image analysis and interpretation. The introduction of the Transformer architecture, followed by the development of Large Language Models (LLMs), has further revolutionized this domain. LLMs now possess the potential to automate and refine the radiology workflow, extending from report generation to assistance in diagnostics and patient care. The integration of multimodal technology with LLMs could potentially leapfrog these applications to unprecedented levels.However, LLMs come with unresolved challenges such as information hallucinations and biases, which can affect clinical reliability. Despite these issues, the legislative and guideline frameworks have yet to catch up with technological advancements. Radiologists must acquire a thorough understanding of these technologies to leverage LLMs' potential to the fullest while maintaining medical safety and ethics. This review aims to aid in that endeavor.

OBJECTIVE: Brain amyloidosis is a key feature of Alzheimer's disease (AD). It also incorporates cerebrovascular amyloid β (Aβ) in the form of cerebral amyloid angiopathy (CAA) involving neurovascular dysfunction. We have recently shown by retrospective analysis that patients with mild cognitive impairment receiving a vasoactive drug cilostazol, a selective inhibitor of phosphodiesterase (PDE) III, exhibit significantly reduced cognitive decline. Here, we tested whether cilostazol protects against the disruption of the neurovascular unit and facilitates the arterial pulsation-driven perivascular drainage of Aβ in AD/CAA. METHODS: We explored the expression of PDE III in postmortem human brain tissue followed by a series of experiments examining the effects of cilostazol on Aβ metabolism in transgenic mice (Tg-SwDI mice) as a model of cerebrovascular β-amyloidosis, as well as cultured neurons. RESULTS: We established that PDE III is abnormally upregulated in cerebral blood vessels of AD and CAA subjects and closely correlates with vascular amyloid burden. Furthermore, we demonstrated that cilostazol treatment maintained cerebral hyperemic and vasodilative responses to hypercapnia and acetylcholine, suppressed degeneration of pericytes and vascular smooth muscle cells, promoted perivascular drainage of soluble fluorescent Aβ1-40, and rescued cognitive deficits in Tg-SwDI mice. Although cilostazol decreased endogenous Aβ production in cultured neurons, C-terminal fragment of amyloid precursor protein expression was not altered in cilostazol-treated Tg-SwDI mice. INTERPRETATION: The predominant action of cilostazol on Aβ metabolism is likely to facilitate Aβ clearance due to the sustained cerebrovascular function in vivo. Our findings mechanistically demonstrate that cilostazol is a promising therapeutic approach for AD and CAA.

In a 2-year randomized, placebo-controlled study of 665 Japanese patients with primary osteoporosis, once-yearly administration of zoledronic acid (5 mg) reduced the risk of new morphometric vertebral fractures. INTRODUCTION: The purpose of this study was to determine the efficacy and safety of once-yearly intravenous infusion of ZOL in Japanese patients with primary osteoporosis. METHODS: This was a two-year multicenter, randomized, placebo-controlled, double-blind, parallel-group comparative study (ZONE Study). Subjects were 665 Japanese patients between the ages of 65 and 89 years who had prevalent vertebral fracture. Subjects were randomly assigned to receive once-yearly intravenous infusion of 5 mg of ZOL or placebo at baseline and 12 months. RESULTS: The 2-year incidence of new morphometric vertebral fracture was 3.0 % (10/330 subjects) in the ZOL group and 8.9 % (29/327) in the placebo group (p = 0.0016). The 24-month cumulative incidence of new morphometric vertebral fracture was 3.3 % in the ZOL group versus 9.7 % in the placebo group (log-rank test: p = 0.0029; hazard ratio: 0.35; 95 % confidence interval: 0.17-0.72). The cumulative incidence of any clinical fracture, clinical vertebral fracture, and non-vertebral fracture was significantly reduced in the ZOL group by 54, 70, and 45 %, respectively, compared to the placebo group. At 24 months, ZOL administration increased bone mineral density in the lumbar spine, femoral neck, and total hip (t test: p < 0.0001). No new adverse events or osteonecrosis of the jaw were observed in this study. CONCLUSIONS: Once-yearly administration of ZOL 5 mg to Japanese patients with primary osteoporosis reduced the risk of new morphometric vertebral fractures and was found to be safe.

Previously, it has been demonstrated that the neurotrophins and their receptors are present in human prostate tissue, but neither their functional role nor localization is clearly understood. We studied the expression of neurotrophins and their receptors in prostate cancer. Between 1990 and 1999, 48 prostate cancer specimens were obtained from patients undergoing radical prostatectomy, of whom 25 received neoadjuvant hormonal therapy (NHT) and 23 were untreated. The specimens were analyzed immunohistochemically for neurotrophins (nerve growth factor, brain derived neurotrophic factor, neurotrophin 3, neurotrophin 4/5) and their receptors (TrkA, TrkB, TrkC, p75NTR). Immunohistochemical studies revealed that both benign and malignant prostate gland epithelial cells expressed the neurotrophins and their receptors to various degrees, but no obvious immunopositive reaction was observed in stromal cells. In benign epithelial cells, the neurotrophins were localized to secretory cells and the receptors were localized to basal cells. The neurotrophins, TrkA and TrkC were expressed to a similar extent in prostate cancer specimens obtained from patients both with and without NHT. In contrast, the expression of TrkB was down-regulated and the expression of p75NTR was up-regulated in prostate cancer after hormonal therapy. These findings suggest that neurotrophins are secreted by prostate cancer cells in an autocrine fashion. Neurotrophins may be involved, through their receptors, in the escape mechanism from cell death after androgen depletion found in prostate cancer.

Colorectal adenoma is linked to metabolic dysfunction. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a precise definition and three subtypes, including non-obese MAFLD. We aimed to investigate the impact of MAFLD on the prevalence of colorectal adenoma by comparing it to non-alcoholic fatty liver disease (NAFLD) in health check-up examinees. This is a multicenter retrospective study. We enrolled 124 consecutive health check-up examinees who underwent colonoscopy. NAFLD and MAFLD were present in 58 and 63 examinees, respectively. Colorectal adenoma was diagnosed by biopsy. The impact of the MAFLD definition on the prevalence of colorectal adenoma was investigated by logistic regression, decision-tree, and random forest analyses. In logistic regression analysis, MAFLD was identified as the only independent factor associated with the presence of colorectal adenoma (OR 3.191; 95% CI 1.494–7.070; p = 0.003). MAFLD was also identified as the most important classifier for the presence of colorectal adenoma in decision-tree and random forest analyses (29 variable importance value). Among the three subtypes of MAFLD, non-obese MAFLD was the sole independent factor associated with the presence of colorectal adenoma (OR 3.351; 95% CI 1.589–7.262; p ≤ 0.001). Non-obese MAFLD was also the most important classifier for the presence of colorectal adenoma in decision-tree and random forest analyses (31 variable importance value). MAFLD, particularly non-obese MAFLD, is the most important factor associated with the presence of colorectal adenoma rather than NAFLD. Colonoscopy examination should be considered in patients with MAFLD, especially those who are non-obese.

This randomized, double-blind study assessed the antifracture efficacy and safety of intermittent intravenous (IV) ibandronate versus oral daily risedronate in Japanese patients with primary osteoporosis. Ambulatory patients aged ≥60 years were randomized to receive 0.5 or 1 mg/month IV ibandronate plus oral daily placebo or 2.5 mg/day oral risedronate, the licensed dose in Japan, plus IV placebo. The primary end point was noninferiority of ibandronate versus risedronate for first new or worsening vertebral fracture over 3 years. A total of 1,265 patients were randomized. A total of 1,134 patients formed the per-protocol set. Both ibandronate doses were noninferior to risedronate: 0.5 mg, hazard ratio (HR) 1.09 [95 % confidence interval (CI) 0.77-1.54]; 1 mg, HR 0.88 (95 % CI 0.61-1.27). The rate of first new vertebral fracture over 3 years was 16.8 % (95 % CI 12.8-20.8) for 0.5 mg ibandronate, 11.6 % (95 % CI 8.2-15.0) for 1 mg ibandronate, and 13.2 % (95 % CI 9.6-16.9) for risedronate. Significant increases in bone mineral density relative to baseline were observed with all treatments after 6 months, with substantial reductions in bone turnover markers after 3 months. Greatest efficacy was obtained with 1 mg ibandronate. Analyses in women only showed similar results to the overall population. No new safety concerns were identified. This study demonstrated the noninferiority of IV ibandronate to the licensed Japanese dose of oral risedronate and suggested that 1 mg/month is an effective dose in Japanese patients with primary osteoporosis.

Use of DLR at 80 kVp allows greater dose reduction for pediatric CT than do current IR techniques.

Monocyte chemoattractant protein-1 (MCP-1) plays a fundamental role in monocyte recruitment and has been implicated in atherosclerosis. The present study tested the hypothesis that increased levels of MCP-1 are associated with an increased risk for restenosis post stent implantation. The plasma MCP-1 antigen levels were measured pre-stenting, and at 24 and 48 h and 6 months post stenting in 41 patients with stable exertional angina (SEA) who had undergone successful stent implantation. Nineteen patients with chest pain syndrome were selected as a control group. Initial plasma MCP-1 antigen levels (mean +/- SE, pg/ml) in the patients with SEA were significantly higher than those in the control group (852.3+/-51.4 vs 418.2+/-26.7, p<0.001). The patients with SEA were divided into 2 groups based on follow-up angiographic findings: 17 patients with restenosis (R group); 24 patients without restenosis (N group). The lesion was significantly longer in the R group than in the N group (p<0.03). Plasma MCP-1 antigen levels at pre-stenting were not significantly different between the 2 groups (820.6+/-69.1 in the R group vs 874.7+/-73.8 in the N group). Serial changes of plasma MCP-1 levels were plotted as percent changes from the initial levels (mean +/- SE, %) and were significantly higher in the R group than in the N group at 48 h and at 6 months post stent implantation (104.6+/-4.8 vs 89.2+/-3.4, p<0.01, 109.6+/-11.2 vs 98.5+/-5.0, p<0.05). The study concludes that MCP-1 production at stented coronary arterial sites is associated with an increased risk for restenosis post stent implantation.

OBJECTIVE: Statin- and exercise-therapy are both clinically beneficial by preventing cardiovascular events in patients with coronary artery disease (CAD). However, there is no information on the vascular effects of the combination of statins and exercise on arterial wall stiffness in CAD patients. METHODS: The present study is a sub-analysis of PRESET study that determined the effects of 20-week treatment with statins (rosuvastatin, n=14, atorvastatin, n=14) combined with regular exercise on arterial wall stiffness assessed by measurement of brachial and ankle pulse wave velocity (baPWV) in CAD patients. RESULTS: The combination of statins and regular exercise significantly improved exercise capacity, lipid profile, including low- and high-density lipoprotein cholesterol, and high-sensitivity C-reactive protein (hs-CRP), baPWV (baseline: 1747 ± 355, at 20 weeks of treatment: 1627 ± 271 cm/s, p=0.008), and basophil count (baseline: 42 ± 32, 20 weeks: 26 ± 15 cells/µL, p=0.007), but had no effect on blood pressure (baseline: 125 ± 22, 20 weeks: 121 ± 16 mmHg). Changes in baPWV correlated significantly with changes in basophil count (r=0.488, p=0.008), but not with age, lipids profile, exercise capacity, or hs-CRP. CONCLUSION: In CAD patients, the combination treatment with statins and exercise resulted in significant amelioration of arterial wall stiffness, at least in part, through reduction of circulating basophils.

BACKGROUND: According to the Japanese Circulation Society guidelines, a bioprosthesis is recommended for aortic valve replacement (AVR) in patients aged ≥65 years who have no risk factors for thromboembolism. There are few data, however, regarding the actual durability of bioprosthetic valves in Japanese patients. The purpose of this study was to assess the long-term durability of Carpentier-Edwards pericardial (CEP) valves in Japanese AVR patients, and to assess the risk factors for reoperation due to structural valve deterioration (SVD). METHODS AND RESULTS: From 1986 to 2001, a total of 591 patients underwent AVR with CEP valves in 9 hospitals. Of these, 574 patients (mean age, 71.9±8.5 years) were analyzed in this study. There were 26 in-hospital deaths (4.5%). The 10-year follow-up rate was 82.6% and the median follow-up time was 9.2 years. Freedom from reoperation due to SVD was 99.5%, 96.7%, and 87.5% at 5, 10, and 15 years, respectively. Factors that raised the risk of reoperation due to SVD included younger age at operation and history of prior operation. In patients aged ≥65 years, freedom from reoperation due to SVD was 94.4% at 15 years. CONCLUSIONS: The durability of CEP valves in patients with AVR was excellent, especially in elderly patients. Thus, it seems appropriate to follow the current Japanese Circulation Society recommendations for the use of bioprosthetic valves.

Metabolic products of Aspergillus species may play a significant role in the pulmonary destructive process. We describe a patient who died of respiratory failure, in whom postmortem examination revealed aspergilloma and numerous calcium oxalate crystals around the aspergilloma, as well as extensive consolidation areas. An-87-year-old man with a history of pulmonary tuberculosis and asbestos exposure was admitted to our hospital with fever and hemosputum. Chest radiograph on admission showed several small cavities in the right upper lung fields, but did not indicate the presence of a fungus ball. The patient was treated with several antibiotics, but his symptoms, and findings for inflammatory indicators and findings on chest radiographs deteriorated, and he died of respiratory failure 45 days after admission. Postmortem examination of the thoracic cavities showed marked involvement with extensive adhesions, fibrosis, caseation, and necrotic tissue. Aspergillus niger formed a mass in the right upper cavity and a localized invasion surrounding the cavity wall, but no organisms were detected in the left consolidation area. Numerous calcium oxalate crystals were found in the cavity wall, as well as an extensive consolidation area. We consider that oxalic acid produced by Aspergillus was the main cause of the patient's respiratory failure.

OBJECTIVE: Encapsulating peritoneal sclerosis (EPS) is recognized as a serious complication of peritoneal dialysis. The aim of this study was to determine the incidence, clinical features, and variation in mortality rates for EPS. DESIGN: A prospective multicenter design was used, in which peritoneal dialysis patients were pre-registered by facilities across Japan and the incidence of EPS was observed in the registrants. The registrants were followed for a total of 4 years to accurately observe the onset of EPS. RESULTS: As of April 1999, 2216 peritoneal dialysis patients from 64 facilities were registered. By the end of March 2001, 332 patients had dropped out, and 17 of the dropouts had developed SEP. The incidence was 0.77%. After excluding 110 patients who died, the incidence in 2106 patients was 0.81%. The incidence of EPS increased with the duration of peritoneal dialysis. Of the 17 patients with EPS, 12 developed the condition after discontinuing peritoneal dialysis and changing to hemodialysis. During the 2-year survey period, 6 of the 17 EPS patients died. The interval from onset to death was 10.8 +/- 5.8 months (range: 3-19.5 months). CONCLUSIONS: From this prospective multicenter study, the current incidence of EPS is 0.77% (0.81% when dropout owing to death is censored). After a follow-up of 2 years, we conjecture that the incidence of EPS will increase. The incidence, etiology, and prognosis of EPS will be further clarified by periodic observation of dropouts until the end of March 2003.

BACKGROUND: We explored the usefulness of myocardial strain analysis on cardiac magnetic resonance imaging (CMR) scans for the identification of cardiac amyloidosis. METHODS AND RESULTS: The 61 patients with systemic amyloidosis underwent 3.0-T CMR, including CMR tagging and late-gadolinium enhanced (LGE) imaging. The circumferential strain (CS) of LGE-positive and LGE-negative patients was measured on midventricular short-axis images and compared. Logistic regression modeling of CMR parameters was performed to detect patients with LGE-positive cardiac amyloidosis. Of the 61 patients with systemic amyloidosis 48 were LGE-positive and 13 were LGE-negative. The peak CS was significantly lower in the LGE-positive than in the LGE-negative patients (-9.5±2.3 vs. -13.3±1.4%, P<0.01). The variability in the peak CS time was significantly greater in the LGE-positive than in the LGE-negative patients (46.1±24.5 vs. 21.2±20.1 ms, P<0.01). The peak CS significantly correlated with clinical biomarkers. The sensitivity, specificity, and accuracy of the diagnostic model using CS parameters for the identification of LGE-positive amyloidosis were 93.8%, 76.9%, and 90.2%, respectively. CONCLUSIONS: Myocardial strain analysis by CMR helped detect LGE-positive amyloidosis without the need for contrast medium. The peak CS and variability in the peak CS time may correlate with the severity of cardiac amyloid deposition and may be more sensitive than LGE imaging for the detection of early cardiac disease in patients with amyloidosis.

BACKGROUND: Although concern regarding patency and possible compromise of graft blood flow by routing the right internal thoracic artery (RITA) through the transverse sinus has been raised, little is known about long-term patency. METHODS AND RESULTS: To evaluate long-term patency of in situ RITA bypass via the transverse sinus, our first 115 patients (94 men, 21 women; mean age, 62.5 years; range, 13 to 77 years) who were alive in 1998 were enrolled for angiographic study. Only good-caliber grafts with no occlusion, string sign, or significant stenosis were considered patent. Early postoperative angiography had been performed 2 to 3 weeks after surgery in 114 patients. The early patency rates were 97.1% for RITA and 95.4% for left internal thoracic artery (LITA) grafts. Of 109 long-term survivors, 73 (67.0%) consented to have late angiographic restudy at a mean of 59 months (range, 9 to 93 months); 89.9% of RITA and 92.3% of LITA grafts were patent. Cumulative patency rates (actuarial curves) at 6 years were 89.3% (95% CI, 85% to 94%) for RITA and 94.5% (95% CI, 92% to 97%) for LITA, the differences not reaching statistical significance (multivariate Cox analysis). CONCLUSIONS: Our study demonstrated good long-term patency of in situ RITA bypass grafting via the transverse sinus for revascularization of the circumflex and diagonal arteries and supports its continued use.

To assess the effect and toxicity of hypotonic cisplatin treatment (HPT) consisting of the intrapleural administration of cisplatin in distilled water for malignant pleural effusion in patients with non-small-cell lung cancer (NSCLC). Non-small-cell lung cancer patients with cytologically proven and previously untreated malignant pleural effusion were enrolled into this study. Firstly, the lung was fully re-expanded by a tube thoracostomy, and then 25 mg cisplatin in 500 ml of distilled water was instilled through a chest tube and then the tube was clamped. After 1 h, the tube was declamped and allowed to drain. The chest tube was removed when the pleural effusion volume decreased to 200 ml or less per day. A complete response (CR) was considered to occur when the pleural effusion disappeared. A partial response (PR) was determined to occur when the volume of pleural effusion remained under (1/4) of hemithorax. The response at 4 weeks was evaluated by an extramural review. Out of 84 patients enrolled from February 1998 to August 2002, 80 patients were eligible and analysed in the present study. The toxicity of HPT was acceptable. Neither a haematological toxicity of any grade nor grade 4 nonhaematological toxicity was observed. Grade 3 nonhaematological toxicities were observed, including nausea (4%), vomiting (3%), pyothorax (1%) and dyspnoea (1%). The median time of drainage from HTP was 4 days. Twenty-seven (34%) and 39 (49%) patients achieved CR and PR, respectively, for an overall response rate of 83% (95% confidence interval, 74-91%). The median duration of the response was 206 days. The median survival time of all patients was 239 days. Hypotonic cisplatin treatment for malignant pleural effusion of NSCLC is therefore considered to be feasible and effective. A phase III study of HPT is thus warranted.