Cost-effectiveness analysis of screening for colorectal cancer in Japan.

To clarify the best cost-effective screening strategy for colorectal cancer in Japan, the cost-effectiveness ratio was compared among six currently performed procedures. The analysis was made using a simulation model to estimate long-term cost and effectiveness of the screening programs. In the screening by the immunological fecal occult blood test (FOBT), a comparison between the one- and two-day fecal collection methods indicated that the latter was more cost-effective than the former. A comparison was also made on the four workup methods: barium enema (BE) alone, a combination of BE and sigmoidoscopy (BE + SIG), total colonoscopy (TCF) alone, and a combination of BE and TCF (BE + TCF). The cost-effectiveness ratio was the lowest in the method using TCF alone, followed by those based on BE alone and BE + TCF, and the highest in the BE + SIG method. The superiority of TCF alone strategy was stable over a range of estimates such as the sensitivity of diagnostic tests, the probability of complications due to TCF, etc. It is concluded that a combination of the two-day FOBT and TCF yields the best cost-effectiveness.     

Diagnostic value of kinetic analysis using dynamic FDG PET in immunocompetent patients with primary CNS lymphoma

Purpose The purpose of this study was to investigate the accumulation of FDG in immunocompetent patients with primary central nervous system (CNS) lymphoma using qualitative and quantitative PET images and to compare baseline with follow-up PET after therapy. Methods Twelve immunocompetent patients with CNS lymphoma were examined. Dynamic emission data were acquired for 60 min immediately following injection of FDG. In seven patients, repeated PET studies were performed after treatment. Applying a three-compartment five-parameter model, K ₁, k ₂, k ₃, k ₄, vascular fraction (V _B ) and cerebral metabolic rate of glucose (CMR_Glc) were obtained. We evaluated the FDG uptake visually using qualitative and parametric images and quantitatively using parametric images. Results A total of 12 lesions were identified in ten patients with newly diagnosed CNS lymphoma. On visual analysis, ten lesions showed an increase on qualitative images, eight showed an increase on K ₁ images, 12 showed an increase on k ₃ images and ten showed an increase on CMR_Glc images. On quantitative analysis, k ₂, k ₃ and CMR_Glc values of the lesion were significantly different from those of the normal grey matter (p<0.02–0.0005). A total of three lesions were identified in two patients with recurrent tumour. All three lesions showed an increase on qualitative, k ₃ and CMR_Glc images. The K ₁, k ₂, k ₃ and CMR_Glc values after treatment were significantly different from those obtained before treatment (p<0.04–0.008). Conclusion Kinetic analysis, especially with respect to k ₃, using dynamic FDG PET might be helpful for diagnosis of CNS lymphoma and for monitoring therapeutic assessment.     

Effect of genetic polymorphisms of SLC28A1, ABCG2, and ABCC4 on bioavailability of mizoribine in healthy Japanese males

The aim of the present study was to investigate the genetic factors responsible for the interindividual variability in the bioavailability of mizoribine. Thirty healthy Japanese men aged 20-49 years and weighing 53-75 kg participated in the present study and took 150 mg of mizoribine. Urine samples were collected periodically for 12 h after the dose, and the bioavailability of mizoribine was calculated from the estimated total urinary excretion from time zero to infinity. The bioavailability of mizoribine in the 30 subjects ranged from 60.3% to 99.4%. The mean bioavailability of mizoribine in subjects with the concentrative nucleoside transporter 1 (SLC28A1) 565-A/A allele (75.4%) was significantly lower than that in subjects with the SLC28A1 565-G/G allele (90.1%). On the other hand, the bioavailability of mizoribine was not affected by polymorphisms of breast cancer resistance protein (ABCG2) C421A and multidrug resistance-associated protein 4 (ABCC4) G2269A. The findings in the present prospective study suggested that the genetic test for the SLC28A1 G565A polymorphism is promising for predicting the Japanese subjects with lower bioavailability of mizoribine.     

GROWTH HORMONE ATTENUATES MYOCARDIAL FIBROSIS IN RATS WITH CHRONIC PRESSURE OVERLOAD-INDUCED LEFT VENTRICULAR HYPERTROPHY

• 1 The role of growth hormone (GH) in cardiac remodelling and function in chronic and persistent pressure overload‐induced left ventricular hypertrophy has not been defined. The aim of the present study was to assess short‐term GH treatment on left ventricular function and remodelling in rats with chronic pressure overload‐induced hypertrophy.
• 2 Twenty‐six weeks after induction of ascending aortic stenosis (AAS), rats were treated with daily subcutaneous injections of recombinant human GH (1 mg/kg per day; AAS‐GH group) or saline (AAS‐P group) for 14 days. Sham‐operated animals served as controls. Left ventricular function was assessed by echocardiography before and after GH treatment. Myocardial fibrosis was evaluated by histological analysis.
• 3 Before GH treatment, AAS rats presented similar left ventricular function and structure. Treatment of rats with GH after the AAS procedure did not change bodyweight or heart weight, both of which were higher in the AAS groups than in the controls. After GH treatment, posterior wall shortening velocity (PWSV) was lower in the AAS‐P group than in the control group. However, in the AAS‐GH group, PWSV was between that in the control and AAS‐P groups and did not differ significantly from either group. Fractional collagen (% of total area) was significantly higher in the AAS‐P and AAS‐GH groups compared with control (10.34 ± 1.29, 4.44 ± 1.37 and 1.88 ± 0.88%, respectively; P < 0.05) and was higher still in the AAS‐P group compared with the AAS‐GH group.
• 4 The present study has shown that short‐term administration of GH to rats with chronic pressure overload‐induced left ventricular hypertrophy induces cardioprotection by attenuating myocardial fibrosis.

     

Heart remodeling produced by aortic stenosis promotes cardiomyocyte apoptosis mediated by collagen V imbalance

Cardiac remodeling (CR) is a structural change of the heart due to chronic hemodynamic overload related to changes in both myocyte and extracellular matrix (ECM). We investigated that the imbalance of collagen V promotes cardiomyocyte apoptosis that contributes to heart failure and cell death. Aortic stenosis was induced surgically and male Wistar rats were randomized to 18 weeks (Sham 18?w, n?=?12; AoS 18?w, n?=?12) and severe of heart failure (Sham HF, n?=?12; AoS HF, n?=?12) groups. Functional and structural echocardiogram, immunohistochemistry for Ki-67, TUNEL assay and Immunofluorescence for collagen were performed. Our main results were: (1) Progressive reduction of cardiac functional capacity due to cardiac remodeling with decreased eject fraction in heart failure; (2) Imbalance of collagen deposition with increased, crowded and irregular collagen I in situ expression; (3) Dysregulation of dynamic control of collagen fibers with exposed epitopes of collagen V; (4) Additional apoptosis that are dependent to cardiac injury. The collagen V expression in cardiac remodeling is for the first time described and may be related to additional apoptosis and autoimmune response. Our findings suggest a critical role of collagen V in cardiac remodeling to modulate and promote heart failure and death.     

Clinical usefulness of fusion of 131I SPECT and CT images in patients with differentiated thyroid carcinoma.

Precise localization of the foci of (131)I uptake for management of patients with differentiated thyroid carcinoma can be difficult because of a lack of anatomic landmarks. The objective of the present study was to demonstrate the clinical usefulness of (131)I SPECT/CT fusion images in patients with differentiated thyroid carcinoma. METHODS: CT and SPECT were performed 7 d after administration of a therapeutic dose of (131)I to 17 patients with differentiated thyroid carcinoma. External markers were placed at 3 locations on the skin of the patient to adjust the sections of CT and SPECT in the same geometric plane. Fusion images were constructed by combining the digital CT and SPECT images on a computer workstation. The data from both planar and SPECT (131)I images and CT images were first separately assessed by 2 nuclear medicine physicians. (131)I SPECT/CT fusion images were then interpreted. Fusion images were considered to improve image interpretation in comparison with CT and scintigraphy separately when they provided better localization of sites of increased radiopharmaceutical uptake. RESULTS: Both CT and (131)I SPECT showed the pathologic sites in 5 of 17 patients (29%). Fusion images were considered to be of benefit in 15 of 17 patients (88%). In 4 patients, CT showed normal-sized lymph nodes, whereas (131)I SPECT showed abnormal findings. In 3 patients with bone metastasis, fusion images confirmed the precision of the localization of abnormal (131)I uptake. Five bone metastases and 1 muscle metastasis were occult and were not seen on the CT images. Finally, (131)I scintigraphy findings were abnormal for 2 patients for whom the CT findings were initially considered normal. Fusion images confirmed the precision of the localization of physiologic (131)I uptake. CONCLUSION: For registration of anatomic and functional images in fusion imaging, the method using external markers was simple and practical. (131)I SPECT/CT fusion images using this technique may improve anatomically limited interpretation of (131)I scintigraphy alone in patients with differentiated thyroid carcinoma.     

Hepatic functional reserve in patients with biliary malignancies: an assessment by technetium 99m galactosyl human serum albumin hepatic scintigraphy.

PROBLEM: Technetium 99m galactosyl human serum albumin (99mTc-GSA) is a hepatic scintigraphy agent that binds to the asialoglycoprotein receptors. We evaluated the clinical use of the scintigraphy for the pre-operative assessment of biliary malignancies. PATIENTS AND METHODS: Scintigraphy was performed before operation in 56 patients with biliary malignancies. A hepatic uptake ratio of 99mTc-GSA (LHL15; the count ratio of the liver to the sum of the heart and liver 15 min after injection of 99mTc-GSA) was calculated. RESULTS: LHL15 was significantly associated with bilirubin half-life in patients treated before operation with percutaneous transhepatic biliary drainage (P = 0.007). After operation, 4 of 18 patients with LHL15 < 0.925 died within 30 days. The postoperative mortality was significantly greater in patients with LHL15 < 0.925 than in patients with LHL15 > or = 0.925 (P = 0.033). CONCLUSION: 99mTc-GSA scintigraphy is useful in evaluating the hepatic functional reserve in patients with biliary malignancies.