Objective Interferon (IFN) therapy reduces the incidence of hepatocarcinogenesis in patients with hepatitis C viral (HCV) infection who achieve a sustained virological response (SVR). The aim of the present study was to determine the rate of hepatocarcinogenesis and the risk factor in sustained virological responders.
Patients and Method The study subjects were 1,193 patients with HCV-related chronic liver disease and IFN- or IFN plus ribavirin-induced SVR. The age, male/female ratio, and liver fibrosis stage [(F0-F3)/LC] were 15-83 years, 808/385, and 1106/41, respectively. Patients were followed-up for 8.3 years (range, 0 to 19.0 years) and the incidence of hepatocellular carcinoma was recorded.
Results Hepatocellular carcinogenesis was detected in 23 patients during the follow-up. The crude rates of hepatocarcinogenesis at 5, 10, and 15 years were 1.5%, 2.4% and 4.1%, respectively. Multivariate analysis identified cirrhosis, male sex and age older than 50 years as determinants of hepatocarcinogenesis with hazard ratios of 12.9 (p<0.001), 6.45 (p=0.012), and 20.2 (p=0.004), respectively.
Conclusion Long-term follow-up of patients with chronic HCV infection is necessary even in those who show SVR, especially in male elderly patients with cirrhosis.

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Background and Aims Myelosuppression observed in patients with inflammatory bowel disease (IBD) treated with azathioprine (AZA) has been attributed to low thiopurine S-methyltransferase (TPMT) activity. TPMT activity is dependent on the genetic polymorphism of high-versus low-metabolizing alleles. We investigated the association between TPMT genotypes and myelosuppression in Japanese IBD patients.
Methods Forty-one healthy volunteers and 70 IBD patients (UC, n = 50; CD, n = 20) were recruited. All IBD patients were treated with AZA. The TPMT genotypes were determined by polymerase-chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses.
Results One healthy volunteer showed a heterozygous mutation of TPMT*1/*3C. All other volunteers and the 70 IBD patients were of the wild alleleotype (TPMT*1/*1). In the IBD patients, 7 patients developed leucopenia (<3,000 /μL). One of them developed severe leucopenia (<1,000 μL) with agranulocytosis on day 14 after drug initiation.
Conclusion TPMT mutations are not associated with myelosuppression in Japanese IBD patients. Even in IBD patients with a wild TPMT genotype, clinicians should pay attention for the possible development of myelosuppression.

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Objective The incidence of colorectal cancer throughout the Republic of Korea has been rising over the last 25 years. The change in incidence is supposed to be due to the westernized life style. We evaluated the anatomical distribution of colorectal cancer and the properties of synchronous adenomatous polyps in the Korean population which were known to be different from those in Western countries.
Materials and Methods From January 1997 to December 2006, 896 cases of colorectal cancer were reviewed retrospectively.
Results A total of 25.1% were proximally located cancer with a modest female predominance (odds ratio 1.5). Synchronous adenomatous lesions were accompanied in 31.9% of all colorectal cancer cases. In the distal colorectal cancer patients, 18.8% had proximally located synchronous adenomas. In those with proximal colon cancer, only 20.5% of patients had distally located adenomas. The likelihood of a proximal colon cancer without distal sentinel lesions was higher in females (odds ratio 3.0).
Conclusion There has been a steep rise in the incidence of colorectal cancer in Korea and distal colon cancer is more prevalent than in Western countries. However, as over 20% of proximal colon cancers can exist without distal colonic synchronous or sentinel lesions, a total colonoscopic examination should be considered first in surveillance.

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Background As the reason for insufficient control of blood pressure (BP), poor compliance of taking antihypertensive agents is an important issue. In Japan, no prospective study on the compliance of antihypertensive agents has been done. In this study we prospectively investigated the details of the relationship between the compliance of taking antihypertensive agents and living style and situation in hypertensive patients.
Methods We prospectively examined 121 outpatients with essential hypertension treated with antihypertensive agents for 12 months. Using an oral interview based on the questionnaire sheet, the factors about living style and situations which worsen the compliance were assessed. Also we evaluated the relationship of BP control and season, which was compared between patients with poor compliance and those with good compliance.
Results As for the background of the poor compliance, many factors related to the patients' living style and situation were clarified. On average for 12 months the levels of the compliance and BP showed a significant negative correlation and BP was significantly higher in patients with poor compliance than those with good compliance. However, in the summer season BP did not differ between patients with poor and good compliance,
Conclusion Many factors regarding the patients' living style and situation were related to poor compliance. The development of strategy that changes these factors is a future task for improving compliance. This study may also imply that unnecessary antihypertensive agents are prescribed in some patients with poor compliance in the summer season. Determination of the suitable prescription by which to attain optimal individual patients' compliance is important in the treatment of hypertensive patients.

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Objective The aim of this study was to evaluate the initial and mid-term results of pulse infusion thrombolysis (PIT) using a unique pump system and stent placement for proximal deep vein thrombosis (DVT) in Japanese.
Methods Among the patients who were admitted to our institute under diagnosis of proximal DVT between April 2001 and March 2005, 11 patients (4 men, mean age 61 years) who underwent PIT and angioplasty followed by stent placement were enrolled in this retrospective analysis. Urokinase or monteplase was used as a thrombolytic agent. Venous or stent patency was assessed by color Doppler ultrasound or enhanced computed tomography for a mean follow-up duration of 54 months.
Results Sites of thrombus were left lower limbs in 10 cases and left upper limb in one case. Initial technical (complete venous flow recovery) and clinical (disappearance of pain and swelling of diseased leg or arm) success was achieved in all patients. Two of 11 patients showed stent occlusion with leg swelling and pain one month later and 3 years later, respectively. These patients had associated protein S deficiency.
Conclusion PIT and stent deployment for DVT is safe and effective with favorable initial and mid-term clinical results and without major complications in Japanese, except for cases of congenital coagulation abnormality.

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Background Pleural effusion is not a pathognomonic sign and distinguishing between transudates and exudates often presents a diagnostic dilemma.
Objective To examine whether the NT pro-brain natriuretic peptide (NT-proBNP) in pleural fluid is a diagnostic tool for determining the cardiac etiology of pleural effusions.
Methods We measured pleural fluid and serum NT-proBNP levels in a consecutive series of 98 patients with heart failure and in 142 patients with other causes.
Results The median pleural fluid NT-proBNP levels among the heart failure patients were significantly higher (3,310 pg/mL) than hepatic hydrothorax (16 patients, 531 pg/mL), malignant pleural effusion (38 patients, 733 pg/mL), parapneumonic pleural effusion (40 patients, 294 pg/mL), and tuberculous pleural effusion (64 patients, 214 pg/mL) (p<0.001). At a cut-off point of ≥1,714 pg/mL, the test had a sensitivity of 99%, a specificity of 99 % for the diagnosis of heart failure. There were 28 patients with pleural effusion due to heart failure misclassified as exudates by Light's criteria. Ten cases of misclassified heart failure (36% of 28 patients) showed serum-effusion protein gradient less than 3.1 g/dL; 26 of them exhibited pleural fluid NT-proBNP levels of ≥1,714 pg/mL. The 26 patients of misclassified heart failure received diuretics before thoracentesis. Pleural fluid NT-proBNP levels were correlated with serum NT-proBNP levels (R²=0.928, p<0.001).
Conclusion Pleural fluid NT-proBNP may be useful in the diagnosis of pleural effusion resulting from heart failure. The test may be especially useful in heart failure patients with exudates who have been treated with diuretics.

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Objective This study was to clarify the neuropathological findings of acute encephalomyelopathy with Sjögren's syndrome.
Methods We examined an autopsied case of acute encephalomyelopathy with Sjögren's syndrome.
Case Report A 40-year-old woman developed acute myelopathy and brainstem dysfunction. Magnetic resonance imaging (MRI) revealed high-intensity lesions on T2-weighted axial images (T2WI) in the medulla oblongata and cervical spinal cord. We established a diagnosis of Sjögren's syndrome (SjS) according to the European Community criteria. The patient was treated with intravenous methylprednisolone (500 mg/day) for three days, followed by oral prednisolone. Although her neurological symptoms improved, her general condition deteriorated after the onset of acute colonic pseudo-obstruction and she died of multiple organ failure associated with hemophagocytosis.
Results Autopsy showed atrophy of the secretory glands and an accumulation of lymphocytes around the ducts, confirming the diagnosis of Sjögren's syndrome. Neuropathological examination revealed multifocal lesions in the cervical spinal cord and medulla, along with scattered perivascular lymphocytic infiltration. In addition, there was demyelination, spongy change and axonal swelling in the white matter, but no remarkable vasculitic changes were seen in the central nervous system.
Conclusion Although the steroid therapy may have had a significant influence, the main pathological finding in this case was not vasculitis, but rather axonal degeneration with spongy change and axonal swelling.

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Objective Near infrared spectroscopy (NIRS) is a non-invasive optical technique to monitor cerebral tissue oxygen saturation (ScO₂). The purpose of this study was to reveal the usefulness of ScO₂ monitoring in evaluating cerebral circulation in patients with autonomic failure.
Methods Nineteen patients with multiple system atrophy (MSA), who had autonomic failure, and 10 age-matched normal control subjects participated. In addition to blood pressure monitoring, ScO₂ was recorded by a near-infrared spectroscopy instrument during head-up tilt (HUT) test.
Results HUT tests induced postural symptoms in 9 MSA patients (presyncopal group), but not in 10 MSA patients (non-presyncopal group) or in any of the controls. ScO₂, which decreased slightly in the controls and MSA patients, did not differ significantly between the MSA and control groups. With regard to MSA subgroups, the ScO₂ reduction in the presyncopal group (-3.1±1.7%) was significantly larger than in the non-presyncopal group (-0.9±0.5%, P<0.005) and controls (-1.1±1.0%, P<0.05). The systolic blood pressure decreases during HUT in the non-presyncopal (-35.2±16.1 mmHg, P<0.01) and presyncopal (-54.3±27.5 mmHg, P<0.0005) groups were significantly greater than that in the control group (4.0±10.7 mmHg), but the difference between presyncopal and non-presyncopal groups was not significant.
Conclusion In our study, ScO₂ reduction seemed to be associated with presyncopal symptoms. ScO₂ monitoring may be useful to detect cerebral hypoperfusion in MSA patients with autonomic failure.

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Sclerosing cholangitis with autoimmune pancreatitis (SC with AIP) takes a better clinical course than primary sclerosing cholangitis due to the effectiveness of steroid therapy. However, the morphological and functional changes in SC with AIP during long-term observation have not yet been reported. We encountered two cases of SC with AIP that resulted in liver atrophy and portal obstruction during long-term observation. One case was followed up without steroid therapy. The other case was treated with endoscopic biliary drainage initially. These cases may provide further information regarding steroid therapy for SC with AIP.

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A 70-year-old man who had aspirated an artificial tooth during treatment at a dental clinic visited our hospital. His symptoms and physical condition were not remarkable. CT of chest revealed a foreign body in the right middle bronchus; bronchoscopy revealed it was wedged there. First, the authors tried to remove it using a suction device attached to a bronchoscope, as well as by using a forcep; however, the attempt failed. Therefore, a second effort was made using a cap constructed of a nasogastric tube, based on the concept of attaching an endoscopic cap to a bronchoscope. The latter was successful.

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Acute systemic infections may involve the heart, mostly represented by myocarditis and pericarditis. We report the case of a likely myopericarditis in an adult, leading to the diagnosis of tuberculosis infection. The clinical presentation was an acute coronary syndrome with elevated troponin Ic. An alternative diagnosis of myopericarditis was considered. Chest X-ray depicted a miliary pattern and a CT-scan demonstrated bilateral micronodules with a "tree-in-bud" pattern associated with parenchymal consolidations in the apical segment of the left upper lobe, suggesting infectious bronchiolitis. As the direct microscopic examination of the bronchial expectoration revealed the presence of Koch's bacterium, a diagnosis of a tuberculous myocarditis was likely. The clinical, electrocardiographic and CT-scan findings are shown; cardiac effects associated with tuberculosis are discussed.

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Class 1a anti-arrhythmic drugs are often used for the treatment of atrial fibrillation (AF), but it is not well known that myasthenia gravis (MG)-like symptoms can be generated by their anti-cholinergic effects. We had a patient with MG who developed symptomatic MG aggravation after AF treatment with disopyramide. Symptomatic MG aggravation was followed by Takotsubo-shaped cardiomyopathy, QT prolongation, and Torsades de Pointes. We suggest that the anti-cholinergic effects of disopyramide can induce MG crisis and should therefore be carefully considered when disopyramide is used to treat AF in patients with MG.

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Multiple liver metastases were incidentally detected in the lobe of the liver of an 81-year-old woman following total thyroidectomy and ablative radioactive iodine administration for the treatment of papillary thyroid carcinoma. A biopsy specimen taken from the metastatic liver tumor was histologically diagnosed as anaplastic carcinoma. Immunohistochemical staining for p53 was positive in both the primary tumor and liver biopsy specimens. We considered this to have been caused by anaplastic transformation from papillary thyroid carcinoma during treatment. We report a rare case of multiple liver metastases from a papillary thyroid carcinoma, which we believe to be the result of anaplastic transformation during postoperative radioactive iodine-131 therapy.

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This report describes the case of a 57-year-old man who underwent a repeated renal biopsy 25 years after the first biopsy in which the diagnosis of IgA nephropathy was made. Although the patient exhibited gradually increasing proteinuria and a slowly progressive renal impairment, the histological findings of the repeat biopsy revealed no evidence of either glomerular inflammatory changes or IgA deposition. Instead, a marked decrease in the glomerular density and hypertrophy of the remnant glomeruli were noted. Almost a complete disappearance of urinary protein excretion by a calorie-restricted diet indicated that the patient's obesity and its related factors may have contributed to the present nephropathic development.

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A 47-year-old man was referred to our hospital because of dyspnea, cough and weight loss. On physical examination, marked dilatation of thoraco-superficial epigastric venous anastomosis was found. The chest wall collateral vessels revealed enlarged head-to-toe flow, suggesting complete obstruction of the SVC and one or more of the major caval tributaries, including the azygos system. Thoracic CT demonstrated that a huge anterior mediastinal tumor completely obstructed the superior vena cava. He was diagnosed with Hodgkin lymphoma of the nodular sclerosis type, StageIII_XB based on the biopsy specimen from the right subcutaneous lumbodorsal mass.

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This report describes a very rare case of a tracheal fibroepithelial polyp. A 69-year-old male had been treated in this department because of chronic obstructive pulmonary disease since 2006. In July 2007, chest computed tomography revealed a bronchial tumor located at the distal end of the trachea. A bronchoscopic examination revealed a multilocular polyp. An endobronchial resection was performed to remove the lesion. A tracheobronchial fibroepithelial polyp is very rare. We herein describe and discuss the appropriate therapeutic policy and also review the pertinent literature.

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Nontuberculous mycobacterium infection is rarely accompanied by pleural involvement. We describe a very rare occurrence of Mycobacterium (M) avium pleuritis with pleural effusion in a non-compromised 73-year-old woman patient who had been treated for sick sinus syndrome. She was admitted to our hospital with general malaise and left pleural effusion. To establish a definitive diagnosis, a biopsy specimen was obtained from the left parietal pleura by video-assisted thoracoscopic surgery. The pleural biopsy specimen revealed only diffuse lymphoid cell infiltration and neoplastic or granulomatous lesions were absent. Culture of the pleural biopsy specimen revealed M. avium, indicating that the pleuritis was caused by this organism. A course of anti-tubercular agents (rifampin, ethambutol and streptomycin sulfate) and clarithromycin gradually resolved the pleural effusion.

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Hepatitis-associated aplastic anemia (HAA) has been reported to show a successful outcome following immunosuppressive treatment. On the other hand, the long-term prognosis of HAA has not been sufficiently clarified. Herein we report a patient with HAA who had been treated with cyclosporine for one year, and maintained complete remission without treatment. Ten years later, acute non-A, non-B, and non-C hepatitis reccurred followed by bone marrow aplasia. A second immunosuppressive treatment with antithymocyte globulin and cyclosporine was effective. This case might provide useful information for the long-term follow-up of patients with HAA.

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We report here a very rare case of chronic myeloid leukemia (CML) following long-term chemotherapy with 5'-deoxy-5-fluorouridine (5'-DFUR) for gastric cancer. A 69-year-old man was diagnosed with the chronic phase of CML. Six years previously, he underwent radical subtotal gastrectomy for gastric cancer, and was subsequently treated with oral anti-metabolite 5'-DFUR as adjuvant chemotherapy for 6 years. He was placed on imatinib therapy, and achieved a major molecular response 10 months after the initiation of therapy. This is the first reported case of therapy-related CML following 5'-DFUR treatment.

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A 58-year-old woman presented with muscle weakness, whole body myalgia, and dyspnea. On admission, neurological examination showed proximal muscle weakness in the extremities. The weakness gradually extended to the bulbar and respiratory muscles, necessitating an artificial ventilator. Serum CK level was markedly increased (33,774 IU/L; normal <150 IU/L) and myoglobinuria was noted in urinalysis. There was no sign of renal failure. Nerve conduction study was normal, but needle EMG showed myopathic changes in the weak muscles. Serological studies for virus titers showed more than a four-fold increase of cytomegalovirus (CMV) antibody titer during the disease course. The IgM anti-GM2 antibody was also elevated in the acute phase and decreased in the recovery phase. The muscle weakness and respiratory failure gradually improved after intravenous methylprednisolone administration, and the serum CK level was normalized in several days. CMV infection was thought to have played a central role in the rhabdomyolysis, leading to critical but reversible respiratory muscle paralysis.

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We encountered a 54-year-old Japanese man who presented with painless swellings on his bilateral neck. Although ultrasonographic findings suggested metastatic lymphadenopathy, histological examination of the mass revealed non-caseous granulation lymphadenitis. He was subsequently diagnosed as having prostate carcinoma with metastasis to the multiple bones. The present case suggested that prostate carcinoma could cause cervical lymphadenopathy due to non-caseous granulation as an initial manifestation, and could be a sign for an impending clinical expression of metastasis to an area draining to the lymph nodes.

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This paper was withdrawn by the authors due to the inclusion of incorrect experimental data.

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