HCC in Japan has very different characteristics from that in other Asian countries. Because, among the Japanese HCC patients approximately 80% of the patients are HCV positive and they are aged over 60 years old. On the other hand, in many Asian countries HBVpositive HCC patients are dominant and their age is younger than the Japanese patients.
Early diagnosis of HCC is mainly performed by means of imaging diagnostic technique such as abdominal ultrasonography, dynamic CT, dynamic MRI and CT angiography. If small HCC less than 3 cm in diameter is found and liver function is well preserved, local ablation therapy or surgical treatment promises better than 5 years survival (over 60%). While, TAE or TACE is performed in cases of HCC larger than 3 cm in size, if liver failure is not complicated. In advanced HCC cases with multiple tumors, arterial infusion of anticancer drug has been applied. However, its efficacy is not estimated.
Chemoprevention is another modality for HCC. Eradication of HCV with an antiviral agent has proven to prevent hepatocarcinogenesis. As for chemoprevention of HCC, some trials are on going in Japan.

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Objective: The objective of this study was to elucidate the relationship between risk factors and the coronary artery disease (CAD) in young middleaged Japanese men.
Methods: A cohort study of 2,764 young middleaged Japanese men aged 3544 (mean±SD: 42.3±2.5) years based on a 10year followup to identify the risk factors for the occurrence of CAD was conducted. There were 35 cases of CAD during the follow up; 25 myocardial infarctions and 10 angina pectoris. The Cox Proportional hazard model was used to identify the independent risk factors for CAD. Adjustment was made for variables including age, body mass index, smoking habit, systolic blood pressure, total cholesterol (TC), highdensity lipoprotein cholesterol (HDLC), fasting plasma glucose (FPG), and triglyceride.
Results: TC, low HDLC, and FPG were identified as significant independent risk factors for CAD. Adjusted hazard ratio (HR) of a high level of TC≥220 (mg/dl) for CAD was 5.46 (95% confidence interval (CI): 1.9617.51) and that of a high level of HDLC<50(mg/dl) was 9.01 (95%CI: 1.1372.17), and a high level of FPG≥110 (mg/dl) was 2.94 (95%CI: 1.228.23). Considering the combination of these risk factors, adjusted HR for CAD of the subjects who had 2 risk factors was 8.37 (95%CI: 2.2131.65).
Conclusions: Using the database of young middleaged Japanese men, TC, low HDLC, and FPG were found to be important risk factors for CAD, and the combination of these risk factors was associated with CAD.

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Objective: Highdensity lipoprotein cholesterol (HDLC) levels are known to be reduced in the metabolic syndrome, but the HDLC profile of elderly patients with coronary artery disease (CAD) has not been well characterized. This study investigated the gender difference of HDLC levels in elderly Japanese patients with CAD.
Methods: Serum lipid data were analyzed retrospectively to assess sexrelated differences of the lipid profile, and to evaluate the effects of pharmacotherapy or physical exercise on hyperlipidemia.
Patients: A total of 163 elderly (≥65 years) outpatients with CAD (128 men aged 70.6±5.2 years and 35 women aged 74.1±6.0 years [mean±SD]) were investigated.
Results: The mean total cholesterol (TC), lowdensity lipoprotein cholesterol (LDLC), and triglyceride (TG) levels were similar in men and women, while the mean HDLC level was significantly higher in women than men (58.3±18.1 vs. 50.3±13.5 mg/dL; p=0.0064). The HDLC level was not significantly influenced by oral lipidlowering therapy or regular exercise in either sex. However, women without lipidlowering therapy had significantly higher HDLC levels than men with (p=0.0312) or without (p=0.0338) lipidlowering therapy, while women performing regular exercise had significantly higher HDLC levels than men with (p=0.0047) or without (p<0.001) regular exercise.
Conclusion: Elderly women with CAD have higher HDLC levels relative to their postmenopausal state than those of men with CAD. Low HDLC levels, unlike in men, may not be a major risk factor for CAD in elderly women.

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Objective: The International Prognostic Index (IPI) was reported in 1993 and it is now widely used for predicting the outcome in patients with aggressive nonHodgkin's lymphoma. It defines 5 risk factors and 4 distinct risk groups from retrospective data. In this study, we evaluated the outcome of riskadopted therapy for diffuse large Bcell lymphoma (DLBCL), the most common aggressive lymphoma, and assessed the possible prognostic factors.
Methods and Patients: We treated 177 consecutive patients newly diagnosed with DLBCL using therapies determined by putative risk factors. Therapies included CHOP followed by involved field irradiation; ACOMPB with the consolidation regimen MLY9; highdose chemotherapy supported by autologous peripheral blood stem cell transplantation; or performance status (PS) oriented CHOP. Statistical analysis was performed to determine the comprehensive risk factors in DLBCL.
Results: Overall, the complete response (CR), 3year overall survival (OS), and 3year relapsefree survival (RFS) rates for CR patients were 71%, 69%, and 75%, respectively. Male gender, high LDH, poor PS (≥2), more than one extranodal involvement site, and B symptoms were independent adverse prognostic factors for OS. High LDH and poor PS were independent, adverse prognostic factors for RFS.
Conclusion: In the 5 risk factors indicated by IPI, high LDH and poor PS remained for OS and RFS even after riskadopted therapy.

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Objective: We investigated the efficacy of edaravone in patients with cardioembolic stroke.
Methods: Cardioembolic stroke patients were treated with drip intravenous infusion of edaravone (ED group, n=141) for 7 days, and were retrospectively compared with a historicalcontrolled cohort of similar patients (control group, n=114).
Results: Early improvement (between day 0 and day 10), defined as change in National Institutes of Health Stroke Scale (NIHSS), was seen more frequently in mild patients (NIHSS on admission ≤7) among the ED group than in the control group (change in NIHSS +2 vs. -2, respectively, p=0.013). Similar efficacy was not seen in the moderate to severe (NIHSS >7) patients. Independent patients (modified Rankin Scale ≤2) 6 months after the onset were likely to be less frequent in the ED than the control group (28% versus 41%; p=0.066). Other clinical outcomes in the ED group were not significantly different from those in the control group.
Conclusion: The results suggest that edaravone may only be effective in mild patients with cardioembolic stroke.

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Objective: Invasive fungal infection is a major cause of morbidity and mortality in patients with febrile neutropenia unresponsive to antibacterial treatment. Empirical antifungal therapy with amphotericin B has been the standard of care for these patients; however, there remains a need for less toxic alternative drugs.
Patients and Methods: We conducted a prospective study to evaluate the efficacy and safety of micafungin (MCFG), a novel antifungal agent of the echinocandin class, in an empirical therapy setting for patients with febrile neutropenia.
Results: A total of 31 patients with acute leukemia who developed febrile neutropenia were enrolled in the study. Among them, 18 patients fulfilling the protocoldefined criteria, including 10 with persistent fever and 8 with recurrent fever, received MCFG empirically. Underlying diseases consisted of acute myeloid leukemia (n=15) and acute lymphoblastic leukemia (n=3). The median duration of neutropenia and drug administration was 22 and 9.5 days, respectively. Treatment success, defined as defervescence during the neutropenic period, absence of breakthrough fungal infections, and requiring no replacement of antifungal drugs, was achieved in 14 patients (78%). None of the patients required discontinuation or dose reduction due to adverse events except for one patient with severe hypokalemia.
Conclusions: Although the studied patients were limited in number, our results indicate that MCFG is an encouraging agent for empirical antifungal therapy in patients with febrile neutropenia, and deserves further investigation in largescale studies.

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Von HippelLindau (VHL) syndrome is a neoplastic syndrome caused by a mutation in the VHL gene. There is a discrepancy between the phenotypes of human VHL syndrome and VHL genedisrupted mouse models. A heterozygous VHL genedisrupted model (vhl +/-) developed hepatic vascular lesions; in contrast, hepatic hemangioma is a rare manifestation of human VHL syndrome. We identified a novel mutation (P154S) in the VHL gene in a Japanese family with pheochromocytoma. One of the members demonstrated hepatic hemangiomas, suggesting that there may be a relationship between the mutation of the VHL gene and hepatic vascular lesions, even in humans.

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We have encountered five hemodialysis patients who had received enteral nutrition and recovered from erythropoietinresistant anemia with neutropenia after the correction of copper deficiency. We reduced the required doses of recombinant human erythropoietin (rHuEPO) to maintain the target hematocrit levels and three patients were finally weaned from the rHuEPO therapy. Thus, copper deficiency is involved in erythropoietinresistant anemia in hemodialysis patients.

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A 41yearold woman with a history of epilepsy was referred for multiple nodular groundglass opacities on a chest computed tomography (CT) scan. They were initially suspected of representing atypical adenomatous hyperplasia or welldifferentiated adenocarcinoma. However, the subsequent brain CT and magnetic resonance imaging (MRI) scans revealed a coarse nodular calcification and cortical tubers. A subungual fibroma was also noted. Histological examination of a videoassisted thoracoscopic lung biopsy specimen disclosed multiple nodules of type II pneumocyte hyperplasia with septal thickening. Based on all of these findings taken together, a diagnosis of tuberous sclerosis complex with multifocal micronodular pneumocyte hyperplasia (MMPH) was made.

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A 50yearold woman was admitted to our hospital after computed tomography (CT) revealed renal masses and mediastinal lymphadenopathy. Uveitis had previously been diagnosed by a local ophthalmologist. Elevated levels of serum soluble IL2 receptor were observed. However, renal function was not compromised. Abdominal CT showed multiple low attenuation tumorlike nodules in both kidneys. As lymphoma was considered likely, CTguided renal biopsy was performed; however, histological examination of the excised specimens revealed noncaseating granulomas. Analysis of bronchoalveolar lavage fluid demonstrated a sarcoidosis pattern. The final diagnosis was sarcoidosis with renal involvement.

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Longterm observation with chest radiograph and computed tomography (CT) scan was performed for pulmonary amyloidosis. There are few reports of primary pulmonary amyloidosis with a longterm observation. We encountered three cases of nodular pulmonary amyloidosis observed by intermittent chest radiograph or CT for 5 years or more. The patients were a 54yearold man, and 67 and 68year old women. For diagnosis, transbronchial biopsy and percutaneous lung biopsy were performed. Amyloid nodules grew slowly and two cases showed findings of cavity and calcification.

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A 73yearold man with no symptoms was admitted to our hospital with a nodular shadow (>2 cm) in the left upper lung field on chest Xray. A histological diagnosis (small cell carcinoma) was obtained by bronchoscopic examination including a transbronchial lung biopsy (TBLB). The preoperative clinical staging was T1N0M0 (StageIA). After preoperative chemotherapy (CDDP + CPT11) was carried out, a nodule in the left S¹⁺² diminished remarkably, but a smaller nodule in the left S³ (>8 mm) remained unchanged. While the nodule in the left S¹⁺² (small cell carcinoma) had become completely necrotic by the time the final diagnosis was made after resection of the left upper lobe, histological diagnosis of the nodule in the left S³ revealed a well differentiated adenocarcinoma. Synchronous presentation of earlystage lung cancer consisting of small cell carcinoma and adenocarcinoma was identified in the same left upper division of the lung. Because there have been the few previous reports regarding cases of synchronous presentation of earlystage lung cancer in the same lung lobe, we also report on the clinical characteristics, thus adding this case to the five previously reported cases.

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A 76yearold man with a past history of pneumoconiosis visited the Department of Gastroenterology in our hospital suffering from dysphagia. Gastroscopy revealed an esophageal ulcer on the top of a torus lesion. Chest computed tomography (CT) revealed it was caused by a swollen lymph node in the mediastinum. Squamous cell carcinoma related antigen (SCC) was elevated to 1.8 ng/ml. To rule out malignancy, we performed fluorine18 deoxyglucose positron emission tomography (FDGPET) which revealed a significantly increased uptake in a nodular lesion in the right upper lobe and mediastinal lymph nodes. Biopsy and cytology of the nodular lesion revealed only pneumoconiosis. We must be careful when we interpret the findings of FDGPET in pneumoconiosis patients.

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A 66yearold woman who was positive for human Tlymphotropic virus type I (HTLVI) antibody developed mixed connective tissue disease (MCTD) with interstitial pneumonia, and was successfully treated with corticosteroid. One year later, under maintenance treatment of prednisolone (PSL), she contracted acute type adult Tcell leukemia/lymphoma (ATLL) without flaring of MCTD. MCTD is considered to be as one of the HTLVIrelated inflammatory diseases, however the development of ATLL during the treatment of HTLVIrelated MCTD has not been well studied. Here, we review the literature and raise the issue of the mutual interactions between MCTDcausative antiHTLVI immune response and antiATLL immune response.

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A 51yearold man with poliomyelitis was admitted to emergency because of a severe decubitus ulcer on his right hip that was associated with infection. His general condition deteriorated and he was malnourished and dehydrated. Despite adequate hyperalimentation and antibiotic administration, laboratory data indicated pancytopenia 4 days later. He was diagnosed as having secondary hemophagocytosis (HPS) associated with methicillinsensitive Staphylococcus aureus sepsis due to decubitus inflammation based on bone marrow aspiration and a blood culture. Although granulocyte colony stimulating factor, packed red blood cell transfusions, platelet transfusions, and antibiotics gradually improved the pancytopenia, the patient died of massive gastrointestinal tract bleeding.

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A 48yearold man was admitted to our hospital because of repeated episodes of epigastralgia. Endoscopy showed multiple whitish granules extending from the 2nd to 3rd portion of the duodenum. Biopsy specimens showed well circumscribed follicles with a monotonous population of predominantly small cleaved cells that were positive for CD20, CD10 and BCL2, but negative for CD5. A full staging study showed no abnormalities. The tumor was finally diagnosed according to the WHO classification as a stage I follicular lymphoma (FL), grade 1, of the duodenum and subsequently received irradiation to the involved area. After 3 years of followup, he is still in complete remission. Because FL arising in the duodenum has recently reported with increasing frequency, patients with multiple granules in the duodenum should be examined carefully.

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We have experienced a Takayasu arteritis (TA) patient, successfully treated with infliximab, who did not respond well to conventional therapy with glucocosteroid and methotrexate. Takayasu arteritis had developed in a 24yearold woman (March 2003) who had been treated with glucocorticoid including methylprednisolone pulse therapy and methotrexate; however, she relapsed during the tapering of the dosage of oral prednisolone. Nineteen months after the first administration of glucocorticoid, 3 mg/kg of infliximab was introduced to the patient. The therapeutic efficacy of infliximab was markedly demonstrated; the patient's Creactive protein (CRP) value returned to almost normal range with subsequent tapering of the dosage of oral prednisolone in the absence of further relapse. This is the first case presentation of TA in Japan successfully treated with infliximab.

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Vancomycin, an antibiotic to which methicillinresistant Staphylococcus aureus (MRSA) is sensitive, frequently induces hypersensitivity reactions. Lowering the vancomycin infusion rate and/or premedicating with antihistamine effectively reduce hypersensitivity in most cases. However, vancomycin desensitization is sometimes the only way to ensure safe use. Two types of desensitization protocols have been reported, and these utilize different infusion intervals; rapid desensitization and slow desensitization. We herein report a case of vancomycin hypersensitivity with methicillinresistant Staphylococcus aureus infection. A combination of the two desensitization protocols, rapid desensitization followed by slow desensitization, effectively inhibited the hypersensitivity reaction during vancomycin infusion, and methicillinresistant Staphylococcus aureus was successfully eradicated.

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A 23yearold woman with prolonged fever, rash, and pericarditis associated with high titers of antinuclear, antiSm, and antiRNP antibodies was suspected of having systemic lupus erythematosus (SLE). However, we also considered infectious diseases, particularly Q fever, as the Creactive protein level was elevated and the patient reported contact with zoo animals around two weeks before the onset. The condition responded rapidly to administration of minocycline; symptoms resolved without using steroids. Thereafter, no recurrence of the illness was observed. Titer of Coxiella burnetii antibody was high and the illness was accordingly diagnosed as acute Q fever rather than SLE.

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