Objective The aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) genes have been implicated in the development of colorectal cancer (CRC). However, the results are inconsistent. In this study, a meta-analysis was performed to assess the associations between the ALDH2 and ADH1B polymorphisms and the risk of CRC.
Methods Relevant studies were identified using PubMed, Web of Science and CNKI up to February, 2013. The pooled odds ratio (OR) with a 95% confidence interval (CI) was calculated using the fixed- or random-effects model.
Results A total of 11 case-controlled studies were selected. Of these, 11 studies included 2,893 cases and 3,817 controls concerning the ALDH2 Glu487Lys polymorphism and six studies included 1,864 cases and 3,502 controls concerning the ADH1B polymorphism. The results indicated that there was a statistically significant link between the ALDH2 polymorphism and the risk of CRC (Glu/Lys+Lys/Lys vs. Glu/Glu: OR=0.87, 95%CI: 0.78-0.96, p=0.10; Glu/Lys vs. Glu/Glu: OR=0.87, 95%CI: 0.77-0.97, p=0.38); however, no significant associations were observed between the ADH1B polymorphism and the risk of CRC win any of the genetic models.
Conclusion This meta-analysis demonstrated that the ALDH2 polymorphism, but not the ADH1B polymorphism, significantly increases the risk of CRC in East Asians.

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Objective We attempted to elucidate the clinical features of chronic hepatitis C patients who develop hepatocellular carcinoma (HCC) after achieving a sustained viral response (SVR) to interferon (IFN) therapy.
Methods The clinical features of 130 patients at 19 hospitals who developed HCC after obtaining an SVR were retrospectively reviewed.
Results Overall, 107 (82%) of the 130 patients were men, with 92 (71%) being ≥60 years of age and 76, 38 and 16 developing HCC within 5, 5-10 and 10-16.9 years after IFN therapy, respectively. Before receiving IFN therapy, 92 (71%) patients had cirrhosis and/or a low platelet count (<15×10⁴ cells/μL). Lower albumin (<3.9 g/dL) and higher alpha fetoprotein (AFP) (≥10 ng/mL) levels were identified in a multivariate analysis to be independent variables of the development of HCC within five years after IFN therapy. Among 4,542 SVR patients, HCC occurred in 109 (2.4%) during a 5.5-year follow-up period, thus resulting in an occurrence rate of 4.6% for men and 0.6% for women.
Conclusion SVR patients with lower albumin or higher AFP levels require careful assessments to prevent early HCC development after IFN therapy. HCC occurrence within >10 years of IFN therapy is not uncommon, and the risk factors remain uncertain, thus suggesting that all SVR patients should undergo long-term follow-up examinations for HCC development.

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Objective Both increased serum levels of low-density lipoprotein cholesterol (LDLC) and metabolic syndrome (MetS) are associated with obesity and have been established to be risk factors of cardiovascular disease. However, studies on the relationship between LDLC and MetS have been limited.
Methods Cross-sectional (n=3,871) and longitudinal (n=2,558) associations between LDLC and MetS were examined in a Japanese health screening population.
Results The odds ratio (OR) [95% confidence interval (CI)] of coexisting MetS for each one SD increase in the LDLC level was 1.25 [1.12-1.40] (p<0.001) adjusted for body mass index (BMI) and other confounding covariates and 1.12 [0.97-1.28] (p=0.119) adjusted for numerical values of the components of MetS and other confounding covariates. The similarly adjusted ORs [95% CIs] for the highest quartile of LDLC (Q4) compared with the lowest quartile (Q1) were 1.76 [1.22-2.54] (p=0.002) and 1.46 (0.93-2.30) (p=0.101), respectively. The hazard ratio (HR) [95% CI] for developing MetS for each one SD increase in the LDLC level was 1.24 [1.10-1.40] (p<0.001) adjusted for BMI and other confounding covariates and 1.19 [1.05-1.34] (p=0.006) adjusted for the pre-existing dichotomous five components of MetS and other confounding covariates. The similarly adjusted HRs [95% CIs] for developing MetS for Q4 compared with Q1 were 1.71 [1.17-2.51] (p=0.006) and 1.61 [1.08-2.40] (p=0.020), respectively.
Conclusion The LDLC level is associated with coexisting MetS and functions as a predictor of the development of MetS, independent of BMI or the pre-existing components of MetS, in a Japanese health screening population.

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Objective Statins prevent cardiovascular events in patients with coronary artery disease (CAD). However, there is little information regarding the vascular effects of statins on arterial wall stiffness in CAD patients.
Methods A total of 36 patients were randomly assigned to receive rosuvastatin (10 mg per day) or simvastatin/ezetimibe (10/10 mg per day) for eight weeks. The aim of the present study was to determine the effects of rosuvastatin or simvastatin/ezetimibe on arterial wall stiffness measured according to the brachial and ankle pulse wave velocity (baPWV) in CAD patients.
Results Both treatments significantly improved the levels of total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hs-CRP) (p<0.05). The ROCK activity and baPWV were significantly improved in the rosuvastatin group compared with that observed in the simvastatin/ezetimibe group (p<0.05). The changes in baPWV were significantly correlated with the changes in the ROCK activity (r=0.488, p<0.01), but not with the changes in the lipid profile or the hs-CRP level.
Conclusion Compared with simvastatin/ezetimibe (10/10 mg), rosuvastatin (10 mg) appears to more effectively improve arterial wall stiffness that may be mediated by modulation of the ROCK activity.

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Objective To investigate the seasonal variation of severe hypoglycemia in hospitalized elderly patients.
Methods Among the patients hospitalized in our department between 2004 and 2010, we analyzed the records of 67 patients who required emergency admission for severe hypoglycemia and were aged 60 years or older. Comparisons were made between those admitted during the warm season (April-September) and those in the cold season (October-March).
Patients The mean age of the 67 patients was 76±8 years, including 45 men and 22 women. Twenty-four patients were admitted in the warm season and 43 patients were admitted in the cold season, with the average annual number being 3.4±1.9 and 6.1±2.8, respectively (p<0.05).
Results Admissions for patients taking insulin showed no significant difference between the warm and cold season. In contrast, significantly fewer patients taking oral hypoglycemic agents were admitted in the warm season than in the cold season (5 vs. 22, p<0.05). Among them, 26 patients (96%) were taking sulfonylurea, and anorexia associated with acute infections was the main cause of severe hypoglycemia. In the warm season, all of the patients were discharged without complications, while 8 patients had complications in the cold season.
Conclusion A seasonal variation regarding hospitalization was observed for severe hypoglycemia among the patients 60 years of age or older, with a higher incidence in the cold season than the warm season, and anorexia related to infections in patients taking sulfonylureas was responsible for this variation. Accordingly, careful management of acute illness is needed for patients using sulfonylureas, especially during the cold season.

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Objective Methotrexate (MTX) is a cytotoxic agent that is commonly employed as an alternative to corticosteroids to treat sarcoidosis, although the proper use and efficacy of MTX as a single agent remain unclear.
Methods The clinical records of patients newly diagnosed with sarcoidosis who were admitted to our institution between 2000 and 2009 were reviewed. Among these patients, 26 received 7.5 mg of MTX per week as a single agent, and the independent effects of MTX were analyzed.
Results Six of the 26 patients (23%) exhibited an improvement of sarcoidosis-related lesions. The skin lesions demonstrated a relatively higher response rate (37%) than the pulmonary lesions (9%). Ten of the 26 patients (39%) experienced adverse effects, mostly mild hepatotoxicity. No severe adverse effects, including irreversible hepatotoxicity, were observed.
Conclusion Although the efficacy of low-dose MTX monotherapy for sarcoidosis in this study was not high (23%), some patients exhibited definite improvements, and the drug proved to be safe, suggesting its possible benefits as a single agent for treating sarcoidosis.

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Objective The autoimmune mechanism is considered to play an important role in the development of acquired idiopathic generalized anhidrosis (AIGA), and muscarinic M3 receptors (M3Rs) on eccrine glands are possible autoimmune targets. We investigated the existence of autoantibodies against M3Rs in AIGA patients.
Methods We immunostained M3R-expressing cultured cells with the serum of 12 AIGA patients (mean age: 35.0±11.7 years, mean disease duration: 26.6±25.8 months) and 10 healthy subjects (mean age: 32.4±10.4 years).
Results The surface of the M3R-expressing cells was stained by the serum obtained from one of the 12 AIGA patients but not by the serum obtained from the remaining 11 patients or healthy subjects.
Conclusion The presence of M3R autoantibodies may therefore be related to the underlying mechanism of disease in a subset of AIGA patients.

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Objective Data regarding the frequency of fibromyalgia (FM) in patients with Takayasu's arteritis (TAK) have not been previously reported. We aimed to investigate the frequency of FM in TAK, defined according to the new 2010 ACR Preliminary Diagnostic Criteria for Fibromyalgia. The association between the ACR-1990 and 2010 FM criteria and the effects of patient-reported outcomes (PROs) on FM were also analyzed.
Methods We studied 55 patients (age: 42,30±12,37 years, F/M: 49/6) with TAK and 40 age- and sex-matched controls (age: 41±10.84 years, F/M: 31/9). All patients were examined for FM tender points by two observers and asked to complete the ACR 2010 FM questionnaire for FM. The SF-36, the Health Assessment Questionnaire (HAQ) and hospital anxiety and depression scales (HADS) were used to assess the quality of life. Thirty patients were reevaluated six months later.
Results Seven (12.7%) patients with TAK and four patients with HC (10%) fulfilled the 2010 FM criteria (p=0.682), while three (5.4%) TAK patients and no controls (0%) met the 1990 criteria (p=0.133). FM was found at a significantly higher rate in the active patients than in the inactive patients according to the ACR-2010 FM criteria (p=0.006). The SF-36 physical component scores were significantly lower (p=0.003) and the HAQ scores were significantly higher in the TAK (p=0.006) patients than in the controls.
Conclusion The frequency of FM is similar between the general population and patients with TAK. However, the incidence of FM is significantly higher in active patients. The new FM criteria subscales (WPI, SSS) are significantly correlated with scales such as the SF-36, anxiety and depression scales and HAQ in TAK patients, suggesting that, in a minority of patients with FM and TAK, PROs may be affected by the presence of FM.

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Objective Adverse skin reactions as a local side effect of nicotine patches sometimes interfere with smoking cessation therapy. We studied the effects of semipermeable membrane dressings (SMD) used under nicotine patches (NP) on nicotine absorption, as assessed according to the urinary cotinine levels, and skin symptoms.
Methods First, the urinary cotinine levels were compared in eight nonsmokers that applied NP over SMD and NP without SMD (Study 1). The urinary cotinine levels were measured using a highly sensitive competitive enzyme immunoassay. Second, 28 subjects undergoing NP therapy for diagnosed nicotine dependence were randomly assigned into two groups in a crossover design to receive NP over SMD and NP without SMD. The urinary cotinine levels and skin symptoms were compared between the two treatment groups. During the follow-up period of 48 weeks, the smoking cessation rate was evaluated (Study 2).
Results No statistical differences were observed in the urinary cotinine levels between the NP over SMD and NP without SMD groups. In Study 2, the skin symptoms improved with the use of SMD in 42.8% (6/14) of the patients and worsened in 28.5% (4/14) of the patients. No serious skin disorders were reported. The subjects followed in Study 2 exhibited smoking cessation rates of 92.8%, 78.5% and 64.2% at 12, 24 and 48 weeks, respectively.
Conclusion The use of NP over SMD is a safe and effective alternative application to NP treatment for preventing the skin symptoms caused by NP without interfering with nicotine absorption.

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The patient was a 35-year-old man who felt persistent hunger pain for five months. Upper gastrointestinal scope studies revealed a 20-mm polypoid lesion located in the middle body of the stomach. The pathological diagnosis revealed a granuloma in the biopsy specimens. The eradication of Helicobacter pylori had no effect on the patient's abdominal symptoms. Ultimately, the polypoid lesion was resected using endoscopy, and the patient was relieved of his hunger pain. The final diagnosis was a pyogenic granuloma in the stomach. This study is the first report of a pyogenic granuloma in the stomach in which the patient's abdominal pain disappeared after tumor resection performed via endoscopy.

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A 55-year-old man suffering from melena was admitted to our hospital. A blood test showed severe anemia. Contrast-enhanced computed tomography (CT) revealed a huge lesion in the duodenum and dilatation of the common bile duct. Upper gastrointestinal endoscopy also identified hemorrhaging from the tumor in the duodenum. Due to the low density of the tumor mass, we performed emergency pylorus-preserving pancreaticoduodenectomy. Histology revealed an area of well-differentiated liposarcoma as well as an area of high-grade spindle cells and pleomorphic sarcoma without obvious differentiation. The final pathological diagnosis was dedifferentiated liposarcoma. This is the first case report of primary liposarcoma of the duodenum.

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Polyarteritis nodosa (PAN) is a rare necrotizing vasculitis that occurs in small- to medium-sized muscular arteries. A 71-year-old man was admitted to our hospital for an evaluation of a sustained fever and he later died of cardiac arrest. The autopsy revealed that the patient had PAN and severe coronary vasculitis with no signs of cardiac ischemia. The reason for the patient's sudden death remains unclear; however, cardiac arrest due to coronary vasculitis was suggested. This is a rare case of PAN coronary vasculitis that led to sudden death without either stenosis or any embolism.

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A 70-year-old man complaining of exertional dyspnea was referred to our hospital for recurrence of mitral regurgitation (MR) after mitral valve repair. Echocardiography revealed the presence of a bulging subaortic septum with flow acceleration in the left ventricular outflow tract (LVOT) and systolic anterior motion of the mitral valve with moderate MR, consistent with LVOT obstruction. Since medical therapy was not sufficiently effective, we performed percutaneous transluminal septal myocardial ablation (PTSMA). After the procedure, the MR resolved, with a reduced LVOT pressure gradient. The patient's symptoms improved. PTSMA was effective for the treatment of MR that emerged after mitral valve repair.

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An 11-year and 3-month-old boy with a neuromuscular disorder was admitted for dyspnea. Echocardiography revealed severe left ventricular dysfunction with an ejection fraction (EF) of 17%. However, the EF had been 57% when the patient was 10 years and 9 months old. The patient's clinical condition became refractory, and he died on the 155th day of hospitalization. Speckle-tracking analysis was retrospectively performed, which demonstrated that the global radial strain was within the normal range; however, the global longitudinal and circumferential strains were lower -than -normal 10 years and 9 months of age. Adult neuromuscular disorder-related secondary cardiomyopathy generally progresses slowly, although progression depends on the age of onset of cardiomyopathy.

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We herein report the case of a patient with slowly progressive type 1 diabetes and insulin independence lasting for >10 years despite the detection of continuously elevated glutamic acid decarboxylase autoantibody titers. We monitored the patient's clinical course and analyzed his endogenous insulin secretion and sensitivity using an intravenous glucose tolerance test (IVGTT) and oral glucose tolerance test (OGTT). His body mass index remained at approximately 22, while his serum C-peptide immunoreactivity level gradually decreased. The level of insulin secretion was significantly higher on the OGTT than the IVGTT. The patient's insulin sensitivity was within the normal limits. These results suggest that maintaining a lifestyle sufficient to preserve insulin secretion and/or normal insulin sensitivity is important and that β-cell responsiveness to incretins may, in part, contribute to insulin independence.

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The leading subtype of lung cancer, adenocarcinoma, received a new classification in 2011 when multifocal, pneumonic-type mucinous tumors, formerly called mucinous bronchioloalveolar carcinomas, were reclassified as "invasive mucinous adenocarcinomas." These tumors appear to be less sensitive to chemotherapy than other non-small cell lung cancers. We herein report two cases of invasive mucinous adenocarcinoma that showed a dramatic radiologic response to combination therapy with cisplatin, pemetrexed and bevacizumab. Recent data suggest that the use of paclitaxel-based chemotherapy is an acceptable therapeutic strategy in cases of invasive mucinous adenocarcinoma. The cases reported here and preclinical findings suggest the therapeutic efficacy of cisplatin, pemetrexed and bevacizumab in treating such tumors.

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A 75-year-old man presented with the chief complaints of coughing and dyspnea. Chest computed tomography revealed narrowing of the trachea. A tumor measuring 40×33×15 mm in size that caused -90% reduction in the cross-sectional area of the trachea 4 cm above the carina was cauterized with high-frequency electrocautery via a rigid bronchoscope. A pathological examination revealed papillary squamous cell carcinoma with immunohistochemical p16 overexpression. Multiplex polymerase chain reaction confirmed human papillomavirus type 18 DNA in the tumor. At the 12-month follow-up visit following the administration of radiotherapy, the patient exhibited no local recurrence or distant metastasis.

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We herein report two cases of acute respiratory distress syndrome (ARDS) with high values of Chlamydophila pneumoniae-specific antibodies. In the first case (a 65-year-old man), high levels of anti-C. pneumoniae antibodies (IgG and IgA) were detected on admission, and the anti-C. pneumoniae IgA level rose by Day 30. The patient was successfully treated with quinolone and steroids. In the second case (an 85-year-old man), abnormally high levels of anti-C. pneumoniae IgM were detected on admission. The patient did not recover, despite receiving treatment with several antibiotics and anti-inflammatory agents. Neither of the patients displayed other pathogen-specific antigens or antibodies. Chlamydophila pneumonia is usually mild, although it can cause severe interstitial pneumonia and ARDS in reinfected patients and the elderly.

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The histological findings and clinical course of primary seasonal influenza viral pneumonia have not been fully elucidated. We herein report the case of a 65-year-old man with primary seasonal influenza viral pneumonia. The patient presented with fever, myalgia, general fatigue and dyspnea of seven days duration. Chest computed tomography showed bilateral ground-glass opacity and consolidation. A rapid influenza virus antigen test was positive for influenza A virus. We diagnosed him as having community-acquired influenza pneumonia and started therapy with antibiotics plus oseltamivir; however, his symptoms, respiratory condition and radiological findings deteriorated. Polymerase chain reaction following bronchoscopy showed the bronchoalveolar lavage fluid to be positive for the influenza A virus. A right lower lobe transbronchial lung biopsy revealed type II pneumocyte metaplasia, acute and chronic interstitial infiltrates and alveolar organization without hyaline membranes or fibrin thrombi in the vascular lumen. Treatment with prednisolone at a dose of 60 mg/day (1 mg/kg) resulted in an improvement. The patient was discharged on hospital day 15. Two weeks after admission, the serum antibody titer for influenza A (H3N2) had increased significantly. No other pathogens were found either serologically or in the respiratory samples, and we diagnosed the patient to therefore have primary influenza viral pneumonia.

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Extramedullary hematopoietic effusion (EHE) is recognized to be an unusual phenomenon accompanied by hematologic disorders. Only a few reports are available of EHE occurring in patients with lymphoma. We herein report the case of a 54-year-old man with follicular lymphoma. Bone marrow aspirates and biopsied specimens showed diffuse invasion of small cleaved atypical lymphoid cells that were positive for CD10, 20, bcl2, immunoglobulin lambda and Bcl-2-IgH rearrangement. The pleural effusion aspirates and a biopsied specimen obtained via thoracoscopy revealed megakaryocytes and immature myeloid cells in addition to lymphoma cells. To the best of our knowledge, this is the first report of EHE accompanied by lymphoma according to the World Health Organization classification.

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Histiocytic sarcoma (HS) is a rare malignancy of soft tissues with an unknown etiology. The CHOP (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride and prednisolone) regimen is often adopted as first-line chemotherapy; however, its therapeutic efficacy against HS is usually low. We herein first present the case of a patient with HS who was infected with human immunodeficiency virus-1 (HIV) in whom treatment with a combination of CHOP and antiretroviral therapy (ART) was successful. The patient has been in complete remission for 12 months following the discontinuation of chemotherapy under continuous ART. This case report may help to promote further investigation of both HS and HIV-related malignancy.

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We herein report the case of a 26-year-old woman with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis presenting with ophthalmoplegia and flaccid paraplegia. She developed disorientation and hallucination after fever and vomiting. Hypothermia, hypoventilation, hypertension, paralytic ileus and hyponatremia were present. Neurological examination showed mild consciousness disturbance and bilateral ophthalmoplegia on admission, flaccid paraplegia with leg areflexia on Day 4. Anti-NMDAR antibodies were detected in the serum and cerebrospinal fluid samples. Motor nerve conduction velocity was decreased in the tibial and peroneal nerves. F-wave amplitudes were reduced in the tibial nerve. MRI disclosed lesions in the callosal splenium, hippocampus and cerebral subarachnoid regions. In addition to various encephalitic symptoms, physicians should pay more attention to peripheral nerve damage in patients with anti-NMDAR encephalitis.

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Pineal cysts are a common incidental finding in imaging studies, and the majority of such cysts are asymptomatic. However, hemorrhaging pineal cysts, which are considered to be rare, are often associated with severe symptoms. We herein describe the case of a 58-year-old patient with the novel manifestation of a bleeding pineal cyst, who had a benign outcome without any surgical treatment. Although the clinical manifestations resembled those of bacterial meningitis, magnetic resonance images suggested chemical meningitis caused by an intracystic hemorrhage and rupture of the pineal cyst.

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Bilateral internal carotid artery dissection (ICAD) is a rare but important cause of stroke in young adults. Anticoagulant and/or antiplatelet agents are usually recommended for stroke prevention;however, such treatments remain highly controversial, and there are inadequate data to compare the efficacy of anticoagulation and antiplatelet therapy. We herein report the case of 30-year-old man presenting with progressive bilateral ICAD during antiplatelet treatment. This report suggests the possibility that intramural hematomas are enlarged by antiplatelet and anticoagulant agents and draws attention to the medications associated with ICAD.

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We herein report the first Japanese case of vertebral sarcoidosis diagnosed using multiple imaging modalities and a biopsy. CT, MRI and (18)F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) detected multiple vertebral lesions, and a vertebral biopsy guided by the PET findings confirmed the diagnosis of vertebral sarcoidosis. Although the disease was refractory to corticosteroids, treatment with methotrexate (MTX) achieved a good response. Our case suggests that MRI and 18F-FDG PET are useful for determining the site for a biopsy and that MTX is effective for treating vertebral sarcoidosis.

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