Genomic risk of hepatitis C-related hepatocellular carcinoma

To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), we conducted a genome-wide association study using 432,703 autosomal SNPs in 721 individuals with HCV-induced HCC (cases) and 2890 HCV-negative controls of Japanese origin. Eight SNPs that showed possible association (P <1 10(?5)) in the genome-wide association study were further genotyped in 673 cases and 2596 controls. We found a previously unidentified locus in the 50 flanking region of MICA on 6p21.33 (rs2596542, P(combined) = 4.21 10(?13), odds ratio = 1.39) to be strongly associated with HCV induced HCC. Subsequent analyses using individuals with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61) but is significantly associated with progression from CHC to HCC (P = 3.13 10(?8)). We also found that the risk allele of rs2596542 was associated with lower soluble MICA protein levels in individuals with HCV-induced HCC (P = 1.38 10(?13)).     

Plasma Level of Homocysteine Associated with Severe Vertebral Fracture in Postmenopausal Women

The aim of this cross-sectional cohort study was to clarify risk factors for severe vertebral fractures in postmenopausal Japanese women. Subjects were ambulatory volunteers age over 50 years who were recruited from a population of outpatients at a primary care institute. At registration, age, body mass index (BMI), bone mineral density (BMD), and present illness were investigated. Biochemical parameters including urinary levels of type I collagen cross-linked N-telopeptides (NTXs), and pentosidine and plasma levels of homocysteine were measured. Values were compared with different fracture grades (grade 0–3). A total of 1,475 postmenopausal women (66.6 ± 9.0 years) were included in the present study. Distributions of vertebral fracture grades were grade 1, 137 cases (9.3 %); grade 2, 124 cases (8.4 %); and grade 3, 162 cases (11.0 %). Age, BMI, BMD, NTX, pentosidine, and homocysteine were significantly associated with vertebral fracture in unadjusted analysis. In addition, a higher prevalence of hypertension was observed in patients with severe fracture. When comparing vertebral fracture grade 0 versus grade 2–3 by multiple regression analysis, pentosidine and homocysteine levels were a significant risk for moderate/severe vertebral fracture (odds ratio [OR] = 1.17, 95 % confidence interval [CI] 1.00–1.38, p = 0.049; OR = 1.22, 95 % CI 1.03–1.46, p = 0.013). Homocysteine levels were also a significant risk when comparing vertebral fracture grade 0 versus grade 3 (OR = 1.27, 95 % CI 1.04–1.58, p = 0.021). Plasma level of homocysteine was an independent risk for severe vertebral fractures.     

Pathophysiological analysis of nonalcoholic fatty liver disease by evaluation of fatty liver changes and blood flow using xenon computed tomography: can early-stage nonalcoholic steatohepatitis be distinguished from simple steatosis?

Introduction

Effective noninvasive tests that can distinguish early-stage nonalcoholic steatohepatitis (NASH) from simple steatosis (SS) have long been sought. Our aim was to determine the possibility of noninvasively distinguishing early-stage NASH from SS.

Materials and methods

We used Fick’s principle and the Kety–Schmidt equation to determine the hepatic tissue blood flow (TBF) in 65 NASH patients who underwent xenon computed tomography (Xe-CT). We calculated the lambda value (LV), i.e., Xe gas solubility coefficient, in liver and blood. We assessed the histological severity of fatty changes and fibrosis on the basis of Brunt’s classification. Liver biopsy revealed SS in 9 patients and NASH in 56 patients. NASH stages 1 and 2 were classified as early-stage NASH (Ea-NASH; 38 patients) and stages 3 and 4 as advanced-stage NASH (Ad-NASH; 18 patients). We evaluated the differences in LV and TBF among the 3 groups.

Results

LV was significantly lower in the Ad-NASH group than in the SS and Ea-NASH groups. Portal venous TBF (PVTBF) was significantly lower in the Ea-NASH group than in the SS group, and PVTBF was lower in the Ad-NASH group than in the Ea-NASH group. Total hepatic TBF (THTBF) was significantly different between the SS and Ea-NASH groups and between the SS and Ad-NASH groups.

Conclusions

In conclusion, measurements of TBF and LV are useful for evaluating the pathophysiological progression of NASH. In addition, these measurements can facilitate the differential diagnosis of SS and Ea-NASH, which may not be distinguishable by other means.     

Clinical outcomes of endoscopic submucosal dissection and endoscopic mucosal resection for laterally spreading tumors larger than 20 mm

Background and Aims: Colorectal laterally spreading tumors (LST) > 20 mm are usually treated by endoscopic submucosal dissection (ESD) or endoscopic mucosal resection (EMR). Endoscopic piecemeal mucosal resection (EPMR) is sometimes required. The aim of our study was to compare the outcomes of ESD and EMR, including EPMR, for such LST. Methods: A total of 269 consecutive patients with a colorectal LST > 20 mm were treated endoscopically at our hospital from April 2006 to December 2009. We retrospectively evaluated the complications and local recurrence rates associated with ESD, hybrid ESD (ESD with EMR), EMR, and EPMR. Results: ESD and EMR were performed successfully for 89 and 178 LST, respectively: 61 by ESD; 28 by hybrid ESD; 70 by EMR; and 108 by EPMR. Between‐group differences in perforation rates were not significant. Local recurrence rates in cases with curative resection were as follows: 0% (0/56) in ESD; 0% (0/27) in hybrid ESD; 1.4% (1/69) in EMR; and 12.1% (13/107) in EPMR; that is, significantly higher in EPMR. No metastasis was seen at follow up. The recurrence rate for EPMR yielding ≥ three pieces was significantly high (P < 0.001). All 14 local recurrent lesions were adenomas that were cured endoscopically. Conclusions: As for safety, ESD/hybrid ESD is equivalent to EMR/EPMR. ESD/hybrid ESD is a feasible technique for en bloc resection and showed no local recurrence. Although local recurrences associated with EMR/EPMR were seen, which were conducted based on our indication criteria, all local recurrences could obtain complete cure by additional endoscopic treatment.     

Risk Stratification for Serious Arrhythmic Events Using Nonsustained Ventricular Tachycardia and Heart Rate Turbulence Detected by 24‐Hour Holter Electrocardiograms in Patients with Left Ventricular Dysfunction

Background: Previous studies have described the clinical usefulness of the presence of nonsustained ventricular tachycardia (NSVT) and defined heart rate turbulence (HRT) in stratifying patients at risk. We prospectively assessed whether HRT can facilitate the predictive accuracy of NSVT for identifying patients at risk for serious arrhythmic events in patients with left ventricular (LV) dysfunction. Methods: We enrolled 299 consecutive patients with LV dysfunction (ejection fraction ≤ 40%) including ischemic (n = 184) and nonischemic causes (n = 115). The presence of NSVT was assessed on Holter electrocardiograms (ECGs). HRT was simultaneously measured from Holter ECGs, assessing two parameters: turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO and TS were abnormal. The end point was defined as of sudden cardiac death (SCD) and sustained ventricular tachyarrhythmias (VTs). Results: NSVT was documented in 93 patients (32.7%). For HRT assessment, 17 patients (5.6%) were not utilized. Of 282 patients, 68 (24.1%) were HRT positive. During follow‐up of 960 ± 444 days, 14 patients (5.0%) reached the end point. NSVT, HRT, and diabetes were significantly associated with the end point. On multivariate analysis, NSVT had the strongest value for the end point, with an HR of 4.4 (95%CI, 1.4–14.3; P = 0.0138). When NSVT combined with HRT, the predictive accuracy is more increased, with an HR of 8.2 (95%CI, 2.9–23.3; P < 0.0001). The predictive values of the combination were higher than single use of NSVT or HRT. Conclusions: HRT can facilitate the predictive accuracy of NSVT for identifying patients at risk for serious arrhythmic events in patients with LV dysfunction.     

Cancer‐associated ischemic stroke is associated with elevated d‐dimer and fibrin degradation product levels in acute ischemic stroke with advanced cancer

Aim: Although several studies have reported various causes of ischemic stroke in patients with cancer, only a few have evaluated the clinical relevance of ischemic stroke pathogenesis to cancer. The aim of the present study was to elucidate the clinical characteristics of cancer‐associated ischemic stroke. Methods: We evaluated 154 ischemic stroke patients without cancer and 57 ischemic stroke patients with cancer who had either received continuous treatment for cancer within 5 years before to the onset of ischemic stroke, or who had been diagnosed with cancer within 1 year after the onset of ischemic stroke. Cancer patients were grouped into “cancer‐associated ischemic stroke,” the “conventional ischemic stroke,” or “other.” Results: A total of 15 patients (26%) were classified into the cancer‐associated ischemic stroke in cancer patients. In univariate analysis of the cancer‐associated ischemic stroke and the others, there were significant differences in the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of d ‐dimer, fibrin degradation product and hemoglobin. With multivariate regression analysis of those factors, the prevalence of hypertension, hyperlipidemia and advanced cancer (clinical stage IV), and the levels of d ‐dimer and fibrin degradation product remained as statistically independent factors, which were associated with cancer‐associated ischemic stroke (n = 111, χ² = 67.21, P < 0.0001). Conclusion: In acute ischemic stroke, the cancer‐associated ischemic stroke is associated with elevated d ‐dimer and fibrin degradation products, even after controlling hypertension, hyperlipidemia and advanced cancer (clinical stage IV). Geriatr Gerontol Int 2012; 12: 468–474.     

Characterizing the need for tracheostomy placement and decannulation after cervical spinal cord injury

Purpose

There have been few reports on the risk factors for tracheostomy and the possibility of patients for decannulation. The purpose of this study was to identify factors necessitating tracheostomy after cervical spinal cord injury (SCI) and detect features predictive of successful decannulation in tracheostomy patients.

Methods

One hundred and sixty four patients with cervical fracture/dislocation were retrospectively reviewed. The patients comprised 142 men and 22 women with a mean age of 44.9 years. The clinical records were reviewed for patients’ demographic data, smoking history, level of cervical spine injury, injury patterns, neurological status, evidence of direct thoracic trauma and head injury, tracheostomy placement, and decannulation. Risk factors necessitating tracheostomy and factors predicting decannulation were statistically analysed.

Results

Twenty-five patients (15.2 %) required tracheostomy. Twenty-one patients were successfully decannulated. Smoking history (relative risk [RR], 3.05; p = 0.03) and complete SCI irrespective of injury level (C1–4 complete SCI: RR, 67.55; p < 0.001, C5–7 complete SCI: RR, 57.88; p < 0.001) were significant risk factors necessitating tracheostomy. C1–4 complete SCI was more frequent among those who could not be decannulated. However, even in patients with high cervical complete SCI at the time of injury, patients regaining sufficient movement to shrug their shoulders within 3 weeks after injury could later be decannulated.

Conclusions

The risk factors for tracheostomy after complete SCI were a history of smoking and complete paralysis irrespective of the level of injury. High cervical level complete SCI was found to be a risk factor for the failure of decannulation in patients without shoulder shrug within 3 weeks after injury.