Objective Despite recent advances in endoscopic treatment and laparoscopic surgery for gastric cancers, an increase in the uptake of these therapeutic approaches has not yet been fully demonstrated. Therefore, the present study aimed to investigate the change in therapeutic approaches regarding the treatment of gastric cancers detected by cancer screening in Saga Prefecture, Japan between April 2002 and March 2011. Methods Gastric cancer screening by X-ray was performed on 311,074 subjects between April 2002 and March 2011. In total, 534 patients were thereafter diagnosed with gastric cancer. Eighteen subjects were excluded because precise details of their treatment were not available. To evaluate the changes in the therapeutic approach, the observation period was divided into three 3-year intervals: Period I: April 2002 to March 2005; Period II: April 2005 to March 2008; Period III: April 2008 to March 2011. Results The use of open laparotomy for the treatment of gastric cancer decreased, and laparoscopic surgery and endoscopic treatment increased markedly in a time-dependent manner. A 2.5-fold increase in endoscopic treatment, and a 18.4-fold increase in laparoscopic surgery were observed in Period III compared with Period I (after adjusting for age and tumor characteristics). Conclusion Endoscopic treatment and laparoscopic surgery for gastric cancer increased during the investigation period (2002-2011), although the tumor characteristics of the gastric cancers detected through cancer screening in Saga Prefecture, Japan did not show any changes.
Objective The aim of this study was to evaluate the vitamin D status and the relationship between the vitamin D status and hypertension in a relatively large cohort in northern China. Methods This study was a part of the Kailuan study, consisting of 3,788 coal mine workers (including 2,532 underground workers and 1,256 surface workers) who received periodic health examinations between September 13, 2012 and December 24, 2012. Information on demographic factors, personal history and medical history were collected. The height, weight, blood pressure and serum25-hydroxyvitamin D [25(OH)D] level of each patient were measured. Results The mean 25(OH)D level in this cohort was 21.73±15.82 nmol/L. The number (%) of patients with vitamin D deficiency, insufficiency, inadequacy and sufficiency were 2,509 (66.24%), 1,051 (27.75%), 201 (5.31%) and 27 (0.71%), respectively. In all the participants, after adjusting for the age, salt intake, physical activity, smoking status, alcohol drinking status, work type, work environment, body mass index, diabetes and hyperlipidemia, the odds ratios for hypertension with 25(OH)D level ≥50, 25-50 and <25 nmol/L were 1.00 (reference), 1.44 (95%CI, 0.99-2.11) and 1.39 (95%CI, 0.97-1.99), respectively. Logistic regression models to evaluate the odds ratios and 95% CIs of hypertension for each quintile of the 25(OH)D level did not determine significant associations between the vitamin D status and hypertension. No significant associations were found in the underground workers or in the surface workers. Conclusion There was a high proportion of coal mine workers with vitamin D deficiency and insufficiency in Kailuan. However, no significant association between low vitamin D levels and hypertension was found in this cohort. Further investigations are needed to determine the relationship between vitamin D levels and hypertension.
Objective Increased left ventricular mass (LVM) and LV fibrosis mass (LVFM) are characteristics of hypertrophic cardiomyopathy (HCM). Additionally, a substantial increase in the plasma B-type natriuretic peptide (BNP) level is observed. Therefore, we investigated the interrelationship and clinical significances of these parameters in a HCM cohort that underwent cardiac MRI (CMR). Methods Patients with HCM (n=109) receiving regular outpatient treatment underwent CMR and follow-up through 2015 from CMR examinations. The clinical outcome measures were all-cause mortality, admission for worsening heart failure, and ventricular tachycardia/fibrillation. Results The baseline body mass index (BMI), LV outflow tract (LVOT) obstruction, New York Heart Association (NYHA) class, and increased left atrial dimension (LAD) index were associated with the plasma BNP level. In the CMR analysis, LVM and LVFM indices significantly correlated with the BNP level (r=0.422 and 0.368, respectively), which were independent determinants according to a multivariate analysis (p=0.009 and 0.023, respectively). A Kaplan-Meier analysis during a median follow-up of 19.4 months showed that the baseline LVM or LVFM index was not associated with the clinical outcomes. However, the baseline BNP level was significantly associated with them (p<0.001). In addition, a multivariate Cox proportional hazard analysis showed that plasma BNP was an independent predictor for the clinical outcomes after adjusting for age, sex, LVM, and LVFM. Conclusion The LVM and LVFM are determinants of the BNP level independent of the BMI, LVOT obstruction, LAD, and NYHA class in patients with HCM. However, plasma BNP may be a more sensitive integrated-marker for the clinical outcomes than LVM or LVFM.
Objective To examine the serum levels of eicosapentaenoic acid (EPA) and the ratios of docosahexaenoic acid (DHA), and the EPA/arachidonic acid (AA) and DHA/AA and to clarify their association with the areas of subcutaneous and visceral fat separately by sex among patients with type 2 diabetes. Methods The study participants included 118 men and 96 women who were hospitalized to receive treatment for type 2 diabetes. We examined the serum levels of EPA and DHA and the ratios of EPA/AA and DHA/AA, and analyzed their association with the total fat area (TFA), subcutaneous fat area (SFA), and visceral fat area (VFA), as measured by computed tomography. Results The mean age of the study participants was 62.6±13.6 years. The mean HbA1c level was 9.37±2.27%. Among men, a multivariate regression analysis adjusted for age and BMI, revealed a significant negative association between VFA and the EPA/AA ratio. When the multivariate regression analysis was adjusted for age, BMI, and HbA1c level, VFA was still found to be significantly negatively associated with the EPA/AA ratio. Although a crude analysis revealed a significant negative association between SFA and the EPA/AA ratio in women, no association was observed in multivariate regression analyses. Conclusion These results suggest the possibility that EPA inhibits the accumulation of visceral fat in men. Furthermore, there appear to be marked differences in the relationships between EPA and DHA and visceral fat accumulation.
Objective We herein conducted a retrospective study to evaluate the long-term efficacy and safety of sitagliptin treatment in elderly patients with type 2 diabetes mellitus. Methods We analyzed the changes in glycemic control in 112 Japanese type 2 diabetes patients over 65 years of age treated with 50 mg/day sitagliptin. Hemoglobin A1c (HbA1c) levels, liver and kidney functions, and usage of hypoglycemic agents were recorded for 24 months. Results HbA1c levels were significantly decreased, and the significance of HbA1c reduction was maintained during the observation period [from 7.7±1.1% to 7.2±0.7% (p<0.001) at the end of observational period]. The %change in HbA1c levels was significantly and negatively correlated with the baseline HbA1c levels (r=-0.51, p<0.001), but not with age, duration of diabetes, or the estimated glomerular filtration rate (eGFR). No patient experienced severe hypoglycemia episodes, and aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, and the eGFR remained unchanged. The dose of sulfonylurea was finally decreased in 72% of patients treated with sulfonylurea. Conclusion Sitagliptin treatment continually decreases the HbA1c level for 24 months and is useful to reduce the dose of sulfonylurea in elderly patients with type 2 diabetes.
Objective Circulating microRNAs have been recognized as promising biomarkers for various diseases. The aim of the present study was to explore the potential role of circulating miR-107, miR-128b and miR-153 as non-invasive biomarkers in the diagnosis of ischemia stroke. Methods One hundred and fourteen ischemic stroke patients (61±11.3 years old) and 58 healthy volunteers (56±3.9 years old) matched for age and sex were enrolled in this study. Total RNA was isolated from plasma with TRIzol reagent. The circulating microRNAs levels were measured by quantitative real-time polymerase chain reaction. Results The circulating levels of miR-107, miR-128b and miR-153 significantly increased 2.78-, 2.13- and 1.83-fold in ischemia stroke patients in comparison to the healthy volunteers, respectively. Receiver operating characteristic (ROC) curves were analyzed using the SPSS software program and revealed the areas under the curve for circulating miR-107, miR-128b and miR-153 to be 0.97, 0.903 and 0.893 in ischemia stroke patients in comparison to healthy volunteers, respectively. The levels of circulating miR-107, miR-128b and miR-153 therefore positively correlated with the severity of stroke as defined by NIHSS classes. Conclusion Our results suggest that circulating miR-107, miR-128b and miR-153 might be used as potential novel non-invasive biomarkers for the diagnosis of ischemia stroke. However, future prospective trials in large-sized patient cohorts are needed before drawing any definitive conclusions.
Objective The use of intravenous in-line filters is effective for the mechanical removal of large particles, precipitates, bacteria, fungi, large lipid globules, and air. However, the routine use of in-line filters remains controversial. Many patients with hematological diseases frequently suffer from bloodstream infections (BSIs) with fatal outcomes. Methods The year before cessation of an in-line filter was defined as the "filter period" and the year after its cessation was defined as the "non-filter period." The number of central line-associated bloodstream infections (CLABSIs), which are defined through surveillance, the catheter utilization rate, the number of patient deaths within 7 days after removal of the central venous catheters (CVCs), and the overall survival rate following CVC insertion were measured. Results During both periods, 84 patients had a total of 140 CVCs with a total number of catheter days of 3,407. There were 10 CVCs with CLABSIs, and the overall CLABSI rate was 2.9/1,000 catheter days, including 4 CVCs with CLABSIs (2.5/1,000 catheter days) during the filter period and 6 CVCs with CLABSIs (3.3/1,000 catheter days) during the non-filter period. The CLABSI rate, catheter utilization rate, and mortality did not differ significantly between the two periods. The only independent variable that was found to be significantly associated with the development of CLABSIs was a neutrophil count of <500×106/L (p<0.05). Conclusion Our study revealed that the cessation of in-line filters from CVCs does not significantly influence the incidence of BSIs and mortality in patients with hematological disease. To confirm our results, however, a large-scale randomized controlled study is warranted.
A 64-year-old man seeking treatment for a common cold was admitted to our hospital due to symptoms of general fatigue and liver dysfunction. A thorough history review revealed that the patient had recently started taking an over-the-counter (OTC) drug. Drug-induced lymphocyte stimulation tests were positive. Serum markers for autoimmune hepatitis (AIH) were particularly elevated. Liver biopsy revealed spotty necrosis and ceroid-pigmented Kupffer cells and piecemeal necrosis with multiple plasma cells. He responded to corticosteroids, thus suggesting the presence of an immune-mediated component associated with the liver injury. Liver injury after using OTCs should be included in the differential diagnosis for chronic hepatitis with features of AIH.
Although high-quality cardiopulmonary resuscitation (CPR) is essential for survival from cardiac arrest, chest compressions can also sometimes lead to life-threatening chest injuries. In addition, post-cardiac arrest syndrome patients often have coagulopathy due to therapeutic hypothermia, mechanical hemodynamic support, or both. Therefore, when progressive anemia and prolonged shock are detected in patients who have received CPR, identifying the cause of hemorrhagic shock is crucial. We herein present an interesting case of hemorrhagic shock due to an internal mammary artery injury secondary to CPR that was detected by computed tomography and invasive angiography.
A sinus of Valsalva aneurysm (SVA) is a rare aortic anomaly. The most common complication is a rupture into the right ventricle and atrium. An SVA rupture into the left ventricle is a rare event. A 42-year-old man visited an outpatient clinic due to worsening exertional dyspnea. A loud to-and-fro heart murmur was detected, and echocardiography revealed a right SVA that had ruptured into the left ventricle, inducing acute heart failure. Computed tomography imaging allowed us to determine that the right SVA had been caused by asymptomatic Takayasu's arteritis. The patient was treated with prednisolone and the right SVA rupture was surgically repaired.
A 61-year-old woman with multiple metastatic and unresectable gastrointestinal stromal tumors (GISTs) was referred for investigation of refractory hypoglycemia that developed four months before this hospitalization. On admission, her fasting plasma glucose was 38 mg/dL despite 10% glucose infusion. Investigations revealed that her serum C-peptide, insulin and growth hormone levels were suppressed, and big insulin-like growth factor II was observed. She was diagnosed with non-islet cell tumor hypoglycemia, which resolved after glucocorticoid treatment. Clinicians should thus be vigilant to identify hypoglycemia in patients with large metastatic GISTs because glucocorticoid therapy is useful even if the GIST is inoperable.
A 16-year-old man was transferred to our emergency department seven hours after ingesting 486 aspirin tablets. His blood salicylate level was 83.7 mg/dL. He was treated with fluid resuscitation and sodium bicarbonate infusion, and his condition gradually improved, with a decline in the blood salicylate level. However, eight days after admission, he again reported nausea, a venous blood gas revealed metabolic acidosis with a normal anion gap. The blood salicylate level was undetectable, and a urinalysis showed glycosuria, proteinuria and elevated beta-2 microglobulin and n-acetyl glucosamine levels, with a normal urinary pH despite the acidosis. We diagnosed him with relapse of metabolic acidosis caused by renal tubular acidosis.
A 70-year-old woman was admitted to our hospital because of fatigue and renal dysfunction and was diagnosed with light chain deposition disease (LCDD) with multiple organ involvement (kidney, thyroid gland, heart and eyes). After chemotherapy with bortezomib, cyclophosphamide and dexamethasone, hepatobiliary enzyme levels increased abruptly. A liver biopsy showed light chain deposition in Disse spaces. After two years of treatment with bortezomib, melphalan and prednisone (VMP) administered at shorter intervals relative to regular cycles, the patient showed a hematological and organ response. This case indicates that a relatively low dose intensity VMP regimen is preferable for elderly patients with LCDD with multiple organ involvement.
A 79-year-old man on hemodialysis was hospitalized for further investigation. Early gastric cancer was diagnosed by gastrointestinal endoscopy and endoscopic submucosal dissection (ESD) was performed. Fever and abdominal pain thereafter developed, and a severe inflammatory response was observed on a blood test. Contrast computed tomography (CT) showed ulcer-like projections and soft tissue surrounding the aorta, from the celiac to left renal artery. An infected aneurysm was diagnosed. Although infected aneurysms developing after laparoscopic cholecystectomy or biopsy of contiguous esophageal duplication cyst have been reported, those developing after ESD have not. When fever and abdominal pain develop after ESD, an infected aneurysm should be considered and contrast CT performed.
A 75-year-old woman was referred to our hospital with the chief symptom of dyspnea. Chest computed tomography revealed lymphadenopathy, emphysema, and honeycombing. Sarcoidosis was diagnosed due to an elevated serum ACE level and the findings of a lymph-node biopsy. Her smoking history, radiography findings, and impaired gas exchange indicated combined pulmonary fibrosis and emphysema (CPFE). Raynaud's phenomenon gradually appeared, and we also diagnosed her with systemic sclerosis (SSc). Right heart catheterization revealed pulmonary hypertension (PH). Smoking was assumed to be the chief cause, but SSc may also induce the development of CPFE. Severe PH induced by CPFE or SSc was present, but the influence of sarcoidosis also could not be ignored.
Cushing's syndrome due to young small-cell lung cancer (SCLC) is recognized as being extremely rare. We herein present the case of a 35-year-old nonsmoking man who presented with thirst and polyuria. Laboratory examinations showed hyperglycemia, hypokalemia and liver enzyme elevation. Imaging examinations revealed the presence of multiple liver tumors and lymph node swelling. The levels of serum neuroendocrine tumor markers were elevated. The patient was diagnosed with SCLC based on the pathological examination of a biopsy specimen from the right supraclavicular lymph node. The physical findings, including proximal myopathy, truncal obesity and pigmentation suggested high levels of glucocorticoids. An immunohistochemical examination of the tumor showed that it was positive for adrenocorticotropin (ACTH). An endocrinological investigation allowed for the definitive diagnosis of SCLC with ectopic ACTH production.
Ruxolitinib is a useful treatment option for myelofibrosis since it effectively resolves splenomegaly and constitutional symptoms. After the widespread use of ruxolitinib outside of clinical trials, a series of case reports indicated a potential risk of ruxolitinib-associated opportunistic infections, including the reactivation of the hepatitis B virus (HBV). We herein report the case of a polycythemia vera patient who showed an elevation of HBV-DNA viral DNA with an elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after the initiation of ruxolitinib. Anti-viral therapy with entecavir was immediately started and the HBV viral load thereafter decreased with an improvement of the liver function. Physicians should thus be aware of the potential risk of ruxolitinib-associated HBV reactivation.
Adult T cell leukemia / lymphoma (ATL) is one of the most aggressive hematological malignancies caused by human T-lymphotropic virus type-I (HTLV-1). Mogamulizumab is a new defucosylated humanized monoclonal antibody agent which targets C-C chemokine receptor type 4 (CCR4) expressed occasionally on the surface of ATL cells. However, adverse events such as drug eruptions have also been highlighted, at least in part, via the dysfunction of regulatory T cells (Tregs). We herein report a pronounced recurrence of systemic psoriasis vulgaris accompanied by the treatment of mogamulizumab in a patient with ATL. Pathological examinations may suggest a mechanistic link between the recurrence of autoinflammatory diseases and anti-CCR4 antibody therapies.
We herein report a case of recurrent optic neuritis involving the cerebral white matter and brainstem in a patient positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. The patient had an initial attack at 24 years of age. Optic neuritis recurred over 14 years, and she was admitted to our neurology unit at 38 years of age. She showed bilateral optic neuritis, high-intensity lesions in the cerebral white matter and brainstem on T2 MRI with contrast enhancement, and elevated serum anti-MOG antibodies. Immunotherapy improved the MRI lesions. Recurrent optic neuritis in patients with anti-MOG antibodies may thus involve the cerebral white matter and brainstem.
A 68-year-old man was admitted because of weakness of the left leg, dysesthesiae of the extremities and bilateral lower extremity purpura. A neurological examination showed mononeuritis multiplex with laboratory evidence of hypocomplementemia, cryoglobulinemia and leukocytoclastic vasculitis in the biopsy of a skin specimen. The patient also exhibited bilateral submandibular gland swelling, elevated serum IgG4 levels and infiltration of a large number of IgG4-positive plasma cells in the submandibular glands. These findings were consistent with both cryoglobulinemic vasculitis and IgG4-related disease. The administration of oral prednisolone (1 mg/kg/day) resolved the neurological manifestations and the swelling of the submandibular glands and cryoglobulinemia.
A 78-year-old man presented with bilateral auricular and nasal chondritis and an inner ear disorder. Relapsing polychondritis (RPC) was diagnosed and corticosteroid therapy was initiated. Two years later, he developed abdominal pain and a fever. A contrast-enhanced computed tomography scan showed enhancement of the mesentery and massive ascites. The patient underwent emergency laparotomy, which revealed inflammation and thickening of the omentum. A microscopic examination of the omentum disclosed vasculitis, and corticosteroid and cyclophosphamide pulse therapies were administered. We herein report the first case of RPC complicated by pathologically proven vasculitis of the omentum, clearly indicating an association between the pathogenesis of these two conditions.
We report the findings of a 46-year-old man, who presented with fever and renal dysfunction while undergoing treatment for Crohn's disease with infliximab (IFX). Remittent fever and renal dysfunction with urinary casts developed and lasted for 3 weeks without deterioration of Crohn's disease. Renal biopsy revealed acute tubulointerstitial nephritis (ATIN). After the discontinuation of IFX, his fever and renal abnormalities resolved. We herein report the first known case of ATIN associated with IFX.
A 72-year-old man was diagnosed with rheumatoid arthritis (RA) and prior hepatitis B virus (HBV) infection. He began treatment with salazosulfapyridine (SASP). Several months later, his blood tests reflected a slightly elevated liver function. Serum tests were positive for hepatitis B surface antigen and HBV-DNA, and the diagnosis of de novo HBV hepatitis was made. A genetic analysis showed that he had polymorphisms of ABCG2 and NAT2, which could lead to high plasma concentrations of SASP and sulfapyridine. To the best of our knowledge, this is the first report of de novo hepatitis developing during SASP monotherapy for RA.
A 36-year-old Japanese woman with intestinal Behcet's disease was admitted to our hospital due to a recurrent ileocecal ulcer. Because infliximab (IFX) showed secondary failure, IFX was switched to adalimumab (ADA). After the third injection of ADA, she was unexpectedly 4-weeks pregnant. ADA was continued until 20 gestational weeks. Remission of the disease activity was maintained during pregnancy, and the birth was uneventful. The ileocecal ulcer disappeared after her delivery. ADA was detected in the umbilical blood after 119 days from the last infusion. The placental transition and timing of neonatal vaccination should be considered in cases of pregnancy with TNF antibody therapy.
An outbreak of dengue fever occurred in Japan in August 2014. We herein report the case of a 63-year-old man who presented with a persistent fever in September 2014. Acute parvovirus B19 infection led to a false positive finding of dengue fever on a rapid diagnostic test (Panbio Dengue Duo CassetteTM). To the best of our knowledge, there are no previous reports of a false positive result for dengue IgM with the dengue rapid diagnostic test. We believe that epidemiological information on the prevalence of parvovirus B19 is useful for guiding the interpretation of a positive result with the dengue rapid diagnostic test.
We herein report a 52-year-old man infected with human immunodeficiency virus (HIV) who was referred to our hospital due to the development of severe neurocognitive disorders and bilateral leukoencephalopathy. He has been treated with antiretroviral agents for 17 years, but low-level viremia has been detected consistently prior to admission. Drug resistant testing of the serum and the cerebrospinal fluid (CSF) both demonstrated a M184V mutation. A brain biopsy revealed perivascular CD8+ T-lymphocyte infiltration, leading to the diagnosis of CD8 encephalitis. The clinical symptoms improved drastically after changing to a nucleoside reverse transcriptase inhibitor sparing regimen, which subsequently decreased the HIV viral load to an undetectable level in both the serum and CSF.
A 63-year-old woman was referred to Fukushima Red Cross Hospital with an enlargement of the left submandibular gland and subcutaneous bleeding in the chest and legs. A diffuse enlargement of the pancreas was also detected by abdominal computed tomography, and laboratory data showed severe thrombocytopenia. She was diagnosed with IgG4-related disease (IgG4-RD) complicated with autoimmune thrombocytopenia and was treated with methylprednisolone, after which the number of platelets favorably increased. Further investigation for liver dysfunction revealed underlying primary biliary cirrhosis (PBC). We herein report a rare case of IgG4-RD overlapping PBC complicated with autoimmune thrombocytopenia.
Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe drug hypersensitivity reaction characterized by rash, fever and multi-organ failure. Limbic encephalitis (LE) is a rare disorder characterized by cognitive dysfunction with memory disturbance, seizures and psychiatric symptoms. We herein present an unusual case of DRESS syndrome due to lamotrigine with reactivation of Epstein-Barr virus, which developed autoimmune LE and syndrome of inappropriate antidiuretic hormone secretion. Discontinuation of lamotrigine, administration of methylprednisolone and intravenous immunoglobulin led to improvement. The LE in this case might have been caused by an autoimmune inflammatory mechanism associated with DRESS syndrome.