Objective Although gastroesophageal reflux disease (GERD), a very common disorder worldwide, is considered to be a lifestyle disease, the pathogenic role of lifestyle factors and consequently the efficacy of lifestyle interventions, remains controversial. Lifestyle factors associated with GERD and the beneficial effect of specific recommended lifestyle interventions in the primary care setting were evaluated as a post-hoc analysis of the LEGEND study which investigated the effect of lansoprazole in patients with GERD who reported dyspeptic symptoms.
Methods GERD patients with dyspepsia were treated with lansoprazole 15 mg or 30 mg daily for four weeks. Reflux and dyspeptic symptoms were evaluated using patient-reported questionnaires before and four weeks after the administration of lansoprazole.
Results Among 12,653 patients, "feelings of continued stress" was the most common lifestyle factor (45.6% of patients), and >30% of the patients reported "eating sweet foods at least once every two to three days," "eating greasy foods at least once every two to three days" and "drinking coffee almost daily." Introducing lifestyle interventions had a significant effect on both reflux and dyspeptic symptoms.
Conclusion Lifestyle interventions are thus considered to be important in GERD patients with dyspepsia who receive a proton pump inhibitor.

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Objective To compare the efficacy of sequential therapy, concomitant therapy and hybrid therapy for the treatment of Helicobacter pylori (H. pylori) infection.
Methods PubMed, Web of Science, Medline, Embase, the Cochrane Central Register of Controlled Trials and CNKI were searched up to the end of May 10, 2014 in order to identify all randomized controlled trials (RCTs) reporting the effects of sequential therapy, concomitant therapy and hybrid therapy on H. pylori eradication. The relative risk (RR) of eradicating H. pylori infection after sequential therapy compared with concomitant therapy or hybrid therapy was pooled. The eradication rates were considered both on an intention-to-treat (ITT) and per-protocol (PP) basis.
Results A total of 10 RCTs involving 3,501 patients were included. The pooled data suggested that the differences between the three groups were not statistically significant (ITT analysis: sequential therapy vs. concomitant therapy: RR=1.01, 95%confidence interval (CI): 0.97-1.04, sequential therapy vs. hybrid therapy: RR=1.02, 95%CI: 0.85-1.22, concomitant therapy vs. hybrid therapy: RR=1.03, 95%CI: 0.97-1.08; PP analysis: sequential therapy vs. concomitant therapy: RR=1.00, 95%CI: 0.96-1.03, sequential therapy vs. hybrid therapy: RR=0.97, 95%CI: 0.86-1.09, concomitant therapy vs. hybrid therapy: RR=1.01, 95%CI: 0.93-1.10). In the ITT and PP analyses, the overall eradication rates were 84.3% (95%CI: 79.1-89.4) and 86.4% (95%CI: 81.7-91.0) for the sequential therapy group, 86.7% (95%CI: 81.0-92.3) and 89.8% (95%CI: 85.1-94.5) for the concomitant therapy group and 86.6% (95%CI: 82.3-91.0) and 92.7% (95%CI: 90.5-94.9) for the hybrid therapy group, respectively. There were no significant differences among these therapies in terms of the rate of side effects.
Conclusion The pooled evidence suggests that sequential therapy, concomitant therapy and hybrid therapy are similar with respect to the treatment of H. pylori infection.

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Objective This study aimed to assess risk factors for mother-to-child transmission (MTCT) of hepatitis B virus (HBV) after immunoprophylaxis.
Methods Risk factors for MTCT were assessed using a multivariate logistic regression model.
Patients We enrolled 256 mother-child pairs with positive maternal hepatitis B surface antigens (HBsAg) between January 2010 and June 2013. All children received passive-active immunization after birth. The children were tested for HBsAg at birth and 6-12 months and/or 1-3 years of age.
Results Among 256 children, 10 (3.9%) developed HBV infection, all of whom were born to hepatitis B e antigen (HBeAg)-positive mothers with a high HBV DNA level (median, 7.36; range, 6.75-8.00 log₁₀ IU/mL). A total of 20 mothers received antiviral treatment during pregnancy. The maternal viral load decreased from an average of 7.16 to 3.08 log₁₀ IU/mL (p<0.0001) at delivery. The multivariate logistic regression analysis showed that a high maternal HBV DNA level [odds ratio (OR) for each log₁₀ IU/mL increase, 2.44; 95% confidence interval (CI), 1.13-5.29, p=0.023] and vaginal delivery (OR=6.96, 95% CI, 1.80-26.93, p=0.005) were risk factors for HBV immunoprophylaxis failure.
Conclusion Additional treatment strategies should be considered in HBeAg-positive mothers with an HBV DNA level above 6-7 log₁₀ IU/mL. In addition, our study supports the use of Cesarean section for infants born to HBsAg-positive mothers.

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Objective The aim of this study was to investigate the associations between the incidence of diabetes and the accumulation of markers of impaired glucose metabolism; i.e., pre-diabetes.
Methods This retrospective cohort study recruited 1,631 men without diabetes at baseline who attended more than two routine health check-ups at our institution between 2006 and 2012. The participants were divided into four groups based on the number of markers of impaired glucose metabolism exhibited at the initial examination. The following markers of impaired glucose metabolism were defined as risk factors for diabetes: a fasting plasma glucose level of ≥110 mg/dL, 2-hour plasma glucose level of ≥140 mg/dL and glycated hemoglobin (HbA1c) value of ≥6.0% (42 mmol/moL). The risk of developing diabetes was assessed using a multivariate analysis.
Results The median examination interval was 1,092 days. The incidence of diabetes rose in association with the number of markers. The subjects with two markers displayed a multivariate-adjusted odds ratio (OR) for diabetes of 19.43 [95% confidence interval (CI): 9.70-38.97] and the subjects with three markers displayed an OR of 48.30 (95% CI: 20.39-115.85) compared with the subjects with one or no markers.
Conclusion The present results demonstrate the impact of accumulating markers of impaired glucose metabolism on the risk of developing diabetes. Anti-diabetes intervention strategies should aim to comprehensively assess an individual's risk of developing diabetes at the pre-diabetes stage.

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Objective Distal renal tubular acidosis (dRTA) is a hyperchloremic metabolic acidosis disorder characterized by a normal anion gap with abnormal urinary hydrogen (H⁺) excretion. At present, there are few available reports regarding the clinical status of primary dRTA. The primary objective of this study was to analyze the clinical features and outcomes of primary dRTA.
Methods This was a retrospective study performed in patients with primary dRTA who were hospitalized at Ruijin Hospital between March 1996 and July 2009; the clinical features of these patients were analyzed.
Results This study included 95 consecutive inpatients: 40 men (42.11%) and 55 women (57.89%). Among them, 60 had hypokalemia (63.12%), 29 had complete dRTA and 66 had incomplete dRTA. The mean urine calcium levels of the patients with and without urinary lithiasis were 0.10±0.04 and 0.07±0.05 mmol/24 h・kg, respectively (p=0.04). The blood pH values of the patients with and those without bone disease were 7.37±0.06 and 7.32±0.06, respectively (p=0.01). A total of 8.33% (8/27) of the patients had tubular proteinuria.
Conclusion Hypokalemia is the most common clinical manifestation of primary dRTA. Primary dRTA can also be accompanied by proximal tubular dysfunction. Controlling the urine calcium and citrate levels is crucial for the treatment of nephrocalcinosis and/or nephrolithiasis, while restoring the blood pH to the normal level is essential for controlling bone disease.

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Objective Fibre-optic bronchoscopy with bronchoalveolar lavage (FOB-BAL) is an important tool for diagnosing and selecting treatment for acutely hypoxaemic patients with diffuse lung infiltrates. However, FOB-BAL carries a risk of significant hypoxaemia and subsequent tracheal intubation during and after the procedure. The application of FOB-BAL using a laryngeal mask airway (LMA) in combination with continuous positive airway pressure (CPAP) may minimize the incidence of hypoxaemia; however, the safety and efficacy of this procedure have not been investigated.
Methods A retrospective chart review was performed from April to September 2013. Data regarding the recovered volume of BAL fluid, incidence of tracheal intubation within eight hours after the completion of FOB-BAL, respiratory and haemodynamic parameters and treatment modifications were collected for the evaluation.
Results Ten trials of FOB-BAL using an LMA and CPAP were performed in nine patients with severe acute hypoxaemia associated with diffuse lung infiltrates. The BAL fluid recovery rate was 56%, and the procedure was completed without subsequent complications. In addition, the percutaneous arterial oxygen saturation decreased to 95.7%±3.8%, although it was never lower than 90.0% during the procedure, and no patients required intubation. Furthermore, the arterial blood pressure significantly but transiently decreased due to sedation, and the procedure yielded diagnostic information in all nine patients.
Conclusion FOB-BAL using LMA and CPAP appears to be safe and effective in patients who develop severe acute hypoxaemia.

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Objective Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting side effect of some anti-cancer drugs. However, medical staff frequently encounter difficulties in ascertaining the severity of CIPN. We sought to develop a questionnaire in order to accurately assess CIPN. The validity of this questionnaire was compared with that of free-style interviews.
Methods We developed the CIPN self-check sheet by analyzing existing self-assessment tools for CIPN and matching the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) grades. From August to December 2011, 77 cancer patients participated in this study. In order to evaluate the validity of the CIPN self-check sheet compared with a free-style interview assessment, the cross-classification and κ coefficients between the CTCAE grades from each assessment and those from a comprehensive assessment were analyzed. The comprehensive assessment utilized information obtained from the medical examination, free-style interview and CIPN self-check sheet.
Results Upon completion of the study, 248 CIPN self-check sheets were collected (median number of sheets per patient, 3; range, 1-14). The cross-classification analysis illustrated that the CIPN self-check sheet successfully identified all grade 3 cases. The coefficient of the CIPN self-check sheet was significantly higher than that of the free-style interviews [κ values: 0.988 (p<0.01) and 0.501 (p<0.01) for the self-check sheet and interviews, respectively].
Conclusion The CIPN self-check sheet can be used to assess the severity of CIPN based on the CTCAE grade more accurately than free-style interviews.

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A 68-year-old man presented with severe abdominal pain. Seven months earlier, he had received systemic chemotherapy for small-cell lung cancer with solitary metastasis to the spleen, followed by splenectomy. Abdominal computed tomography and abdominal arterial angiography showed diffuse ischemia of the mesenteric artery without apparent occlusion. The patient also suffered from septicemia caused by Enterococcus faecium. Therefore, a diagnosis of non-occlusive mesenteric ischemia (NOMI) induced by septicemia was supposed. Although treatment with antibiotics and papaverine hydrochloride was administered and the necrotic tissue in the intestinal tract was resected, the patient died.
Physicians should be aware that patients undergoing splenectomy are likely to be affected by septicemia, which may subsequently induce NOMI.

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We herein report the case of a 42-year-old man with a one-year history of ulcerative colitis who presented with exacerbated bloody diarrhea, a productive cough and increasing breathing difficulties. Colonoscopy revealed typical deep ulcers in the rectosigmoid colon and atypical multiple sucker-like ulcers in the transverse colon, and computed tomography of the chest demonstrated wall thickening of the trachea and bronchi. In addition, bronchoscopy showed ulcers in the trachea, and histopathology disclosed findings of necrosis and inflammation of the subepithelial tissue of the trachea. Based on these findings, the patient's respiratory symptoms were strongly suspected to be due to ulcerative colitis-related tracheobronchitis. Treatment with systemic corticosteroids subsequently resulted in a rapid clinical improvement.

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The patient was a 43-year-old man admitted to the hospital with intermittent epigastric pain and vomiting, without any evidence of trauma. Blood tests showed elevated lipase/amylase levels. Abdominal computed tomography (CT) revealed pancreatitis complicated by an intramural duodenal hematoma (IDH). He was conservatively treated, and one month after admission, follow-up panendoscopy showed normal duodenal mucosa without luminal narrowing. Non-traumatic IDH is typically associated with coagulation abnormalities. Abdominal CT is an excellent tool for diagnosis in cases of acute abdomen. However, the pathogenesis of and relationship between IDH and pancreatitis remain unknown.

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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Since our first report in 1998, approximately 30 families with multiple GISTs due to a germline gain-of-function mutation of c-kit have been reported. We herein present a case of a family with multiple GISTs that have a germline c-kit mutation in exon 11 (Del-Val560) in two siblings. One of the patients showed a fair response to treatment with a half-dose of imatinib (200 mg/day). There are few reports describing the response to imatinib in familial GISTs and this drug appears to be a promising therapeutic option.

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A 55-year-old man was annually followed up for a large hepatic cyst. In 2006, a 20-mm nodule was detected in contact with the cyst that gradually grew thereafter. By 2013, the mass had expanded to 90 mm, and a percutaneous biopsy revealed a solitary fibrous tumor (SFT). Surgical resection was subsequently performed, and the patient has since been doing well for 11 months, without recurrence. SFT of the liver is a rare neoplasm; only 44 cases have been reported to date. This is the first report to describe the long-term progression of hepatic SFT from the time of its development.

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Inflammatory pseudotumor (IPT) is a rare benign condition often misdiagnosed as malignancy. An 80-year-old man was referred to our clinic for an asymptomatic hepatic mass detected on plain abdominal CT. Abdominal ultrasonography identified the lesion as a poorly defined hypoechoic mass. Although a liver biopsy did not provide any evidence of malignancy, imaging modalities suggested a diagnosis of cholangiocarcinoma. The patient underwent left lobectomy, and the pathological findings were consistent with the features of xanthogranulomatous cholangitis. This case is the first report of hepatic IPT originating from xanthogranulomatous cholangitis without symptoms and illustrates the importance of obtaining a preoperative diagnosis in order to avoid a misdiagnosis of malignant tumor.

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Hepatitis C-associated osteosclerosis (HCAO) is an uncommon condition characterized by increased bone density, skeletal pain and elevated bone formation markers. Since 1992, only 17 cases have been reported. We herein describe the case of a 61-year-old woman affected by severe pain involving the lower limbs. The laboratory data showed an elevated serum alkaline phosphatase level, and the patient was found to be seropositive for hepatitis C virus infection. In addition, an X-ray skeleton survey showed marked cortical thickening of both femurs and tibias, and a whole-body bone scan revealed an increased cortical radionuclide uptake in the involved bones. These findings were consistent with a diagnosis of HCAO. In this report, we discuss the patient's clinical course over 16 years and, for the first time, show a normalized radioisotope uptake on bone scanning 10 years after the diagnosis.

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We herein report the first case of a nonfunctioning islet cell tumor that transformed into a proinsulinoma during the process of metastasis to the lungs. This phenomenon was confirmed in a 69-year-old woman with an advanced pancreatic islet cell tumor and multiple liver metastases who later developed multiple lung metastases. She underwent pancreatic resection followed by the administration of chemotherapy and survived for seven years. Although the patient initially had hyperglycemia due to diabetes mellitus, she conversely began to manifest hypoglycemic attacks 63 months postoperatively with the concomitant development of multiple lung metastases. An autopsy revealed that only the tumor in the lungs produced proinsulin; no other hormones were detected.

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Catheter ablation is an established treatment for atrial fibrillation (AF). The incidence of major complications related to the procedure is reported to be 4.5%, and delayed cardiac tamponade (DCT) is a rare, although recently recognized, complication. However, the mechanisms underlying the development of DCT remain unclear. We herein report the cases of two men, both 49 years of age, who developed cardiac tamponade requiring pericardiocentesis a few weeks after undergoing pulmonary vein isolation for persistent AF. Physicians should explain to the patient the potential for DCT as a complication prior to performing catheter ablation and provide careful follow-up for at least a few weeks after the session.

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We herein report the case of 34-year-old woman with acute tricuspid valve infective endocarditis (IE) associated with a ruptured sinus of Valsalva and multiple septic pulmonary emboli. She had no history of medical problems, except for atopic dermatitis (AD). Blood cultures identified methicillin-sensitive Staphylococcus aureus. Despite the administration of two months of antibiotic therapy, the patient experienced recurrent pulmonary emboli and developed heart failure due to a left-to-right shunt, whereas the area of vegetation did not change in size. She subsequently underwent surgery for shunt closure and tricuspid valve replacement. The AD was thought to be the cause of the patient's bacteremia, which consequently resulted in aggressive right-sided IE.

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A 60-year-old woman presented with ST-elevation myocardial infarction due to extrinsic compression of the left main coronary artery (LMCA) caused by a dilated pulmonary artery (PA) with idiopathic pulmonary hypertension and was successfully treated with intravascular ultrasound- and optical coherence tomography-guided stenting. Continuous subcutaneous epoprostenol infusion therapy was initiated immediately after the procedure and increased aggressively. Imaging modalities were extremely useful in making the diagnosis and providing follow-up of LMCA compression syndrome in this case. Over the one-year observation period, a sufficient hemodynamic improvement was obtained, without exacerbation of the PA dilatation, resulting in the absence of compression of the LMCA.

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An 84-year-old woman diagnosed with hypertrophic obstructive cardiomyopathy (HOCM) was referred to our hospital due to chest pain associated with an increased level of troponin T. Following the administration of cibenzoline, the left ventricular outflow pressure gradient (LVPG) completely disappeared. Left ventricular pressure pullback tracing subsequently demonstrated the "reappearance" of the LVPG. Left ventriculography showed apical ballooning with excessive contractions at the base of heart, and we therefore made a diagnosis of Takotsubo cardiomyopathy in a patient with HOCM. Hypercontractions of the base of the heart associated with Takotsubo cardiomyopathy may be responsible for the "reappearance" of LVPG in this case.

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A 55-year-old man presented with a rapidly enlarging thyroid. He had been diagnosed with lung adenocarcinoma nine months earlier. Computed tomography (CT) and ultrasound (US) detected reticular cord-like structures, but no nodules, in the thyroid. A fine-needle aspiration biopsy (FNAB) of the thyroid revealed thyroglobulin-negative adenocarcinoma cells, thus establishing the diagnosis of diffuse thyroid metastases of lung cancer. Moreover, the fluid demonstrated milky chyliform effusion. This case suggests that the presence of reticular cord-like structures on US and CT may be a key imaging finding for the clinical diagnosis of diffuse thyroid metastases and that chyliform effusion may contribute to rapid goiter formation.

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We herein describe a case of hypercalcemic crisis in a 52-year-old Japanese woman. She suffered from thirst and fatigue for one month. Her serum calcium (a) levels were 19.0 mg/dL, and she was diagnosed with hypercalcemic crisis. Circulating levels of parathyroid and thyroid hormones were elevated. She was diagnosed with primary hyperparathyroidism accompanied by Graves' disease. Thyroparathyroidectomy was performed after circulating levels of Ca and thyroid hormones were normalized. Both of primary hyperparathyroidism and Graves' disease can contribute and accelerate hypercalcemia, resulting in a state of crisis. The possibility of their coexistence should therefore be taken into consideration in cases of hypercalcemia.

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A 34-year-old man with a history of rectal cancer was receiving oral chemotherapy [tegafur-uracil (UFT) with leucovorin]. He visited our hospital due to nausea and abdominal pain, and his laboratory data revealed the presence of urinary ketones, hyperglycemia and high anion gap metabolic acidosis, and HbA1c level of 6.8%. Accordingly, we diagnosed fulminant type 1 diabetes. The development of fulminant type 1 diabetes during chemotherapy for malignancy is a rare, but potentially fatal condition. Therefore, clinicians should consider diabetic ketoacidosis in the differential diagnosis when examining chemotherapy patients who present with gastrointestinal symptoms.

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Minimal change nephrotic syndrome (MCNS) is a common form of nephrotic syndrome (NS). We herein present the case of a 57-year-old woman with advanced lung adenocarcinoma treated with the tyrosine kinase inhibitor (TKI) gefitinib who developed NS. A renal biopsy revealed minor glomerular abnormalities, and the patient's symptoms improved exclusively with the discontinuation of gefitinib. Therefore, we diagnosed her with MCNS associated with gefitinib treatment. A few months later, however, she developed recurrent lung tumors. Following the challenging initiation of the TKI erlotinib, she achieved remission without proteinuria. We thus conclude that erlotinib is a potential treatment option in patients with NS associated with gefitinib therapy.

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A 73-year-old man was admitted in respiratory failure that had subacutely progressed after five weeks of dapsone treatment for a skin rash. He also presented with fever, systemic erythroderma and liver dysfunction. Chest computed tomography showed diffuse reticular shadows with ground-glass opacity and bilateral mediastinal lymphadenopathy. Lymphocytes, but not eosinophils, were increased in the bronchoalveolar lavage fluid. Moreover, reactivation of human herpes virus-6 was confirmed on a paired serum test. Finally, we diagnosed the patient with dapsone hypersensitivity syndrome (DHS), a rare adverse event of this drug. Lung injury unaccompanied by eosinophilia in the bronchoalveolar lavage fluid is even more rare as a DHS-related lung manifestation.

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We herein describe a 67-year-old man with advanced adenocarcinoma of the lung who developed an alveolar hemorrhage (AH) associated with pemetrexed. He received four courses of pemetrexed therapy with carboplatin and seven courses of pemetrexed maintenance therapy. One week after the last pemetrexed administration, the patient developed hemoptysis with deteriorating dyspnea and anemia. Chest images showed diffuse ground-glass attenuation. The diagnosis of AH was based on findings of bloody bronchoalveolar lavage (BAL) fluid, hemosiderin-laden macrophages in the BAL fluid, and a transbronchial lung biopsy sample. This report is the first to describe AH associated with pemetrexed.

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A 51-year-old woman undergoing steroid treatment for systemic lupus erythematosus (SLE) was admitted to our hospital after developing a fever, consciousness disturbance and seizures, leading to a diagnosis of SLE-induced meningoencephalitis. Although steroid therapy improved her symptoms, she complained of post-lumbar puncture thunderclap headaches during follow-up, and cerebral venous thrombosis (CVT) was subsequently diagnosed on magnetic resonance venography and cerebral angiography. This is a rare case of neuropsychiatric SLE complicated by CVT during treatment for aseptic meningoencephalitis. The onset of aseptic meningoencephalitis and administration of the lumbar puncture and steroid therapy may have induced the development of the patient's CVT symptoms.

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Medullary hemorrhage is rare, and the causative role of hypertension still remains controversial. Cavernous angioma and other vascular malformations have been reported to cause medullary hemorrhage. A 53-year-old man was admitted to our hospital for vertigo. Medullary hemorrhage and multiple small hypointense lesions were detected on T2-star weighted magnetic resonance imaging (T2*W MRI). One and four months later, the appearance of new lesions confirmed the diagnosis of cerebral cavernous angioma. Cavernous angioma is often characterized by de novo appearance/progression on MRI. A follow-up MRI is required to diagnose cavernous angioma in patients with medullary hemorrhage.

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A 64-year-old neurologically asymptomatic woman with rheumatoid arthritis who was treated with the tumor necrosis factor (TNF)-α antagonist adalimumab developed disseminated tuberculosis (TB). After receiving anti-TB therapy and discontinuing adalimumab, she exhibited paradoxical worsening due to immune reconstitution inflammatory syndrome (IRIS) with the appearance of meningitis and brain tuberculomas. This case indicates that continuing anti-TNF therapy may be necessary to prevent IRIS in patients who develop TB, particularly disseminated TB, during the course of anti-TNF therapy. In addition, careful screening for central nervous system (CNS) TB should be performed prior to the initiation of therapy, as even neurologically asymptomatic patients can develop CNS manifestations of IRIS.

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Neisseria elongata, a normal resident in the human oral cavity, rarely causes invasive infections. We herein report a case of endocarditis caused by Neisseria elongata subsp. nitroreducens that occurred in a patient without any apparent cardiac complications. The patient received aortic valve replacement following the administration of intravenous beta-lactam for five weeks. To our knowledge, this is the first published case in Japan of N. elongata infection in a patient without a prosthetic device.

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