Outcomes of EUS-FNA in patients receiving antithrombotic therapy.

Background and study aims To investigate bleeding risk and thromboembolic risk in patients receiving antithrombotic therapy who underwent endoscopic ultrasound-guided fine-needls aspiration (EUS-FNA). Patients and methods A single-center retrospective study of 908 consecutive patients undergoing EUS-FNA for pancreatic and non-pancreatic lesions patients between March 2013 and March 2017 was performed. Antithrombotic management was classified into three groups: continuous, discontinuation, and heparin replacement. Results A total of 114 patients (12.6 %) were on antithrombotic drugs and 794 (84.6 %) were not. There were six cases of significant bleeding (0.7 %) four in the antithrombotic group (0.4 %) and two (0.2 %) in the non-antithrombotic group, (odds ratio, 9.59; 95 % confidence interval, 2.12 - 43.1; P  = 0.006). Of the four cases in the antithrombotic group, two were on continuous treatment, one was on discontinuation treatment and one was on heparin replacement. All cases of non-significant bleeding occurred in the non-antithrombotic group (3 peri-tumoral hematomas, 1 submucosal hematoma, and 1 intraluminal bleed). The sole thromboembolic event (0.9 %) was a cerebral infarction in the antithrombotic group in a patient on thienopyridine who switched to aspirin before the procedure. Conclusions There was a slight increase in risk of bleeding in patients receiving antithrombotic therapy especially postoperative bleeding; however, there were no cases of severe bleeding was seen and only one case of cerebral infarction which occurred in a high-risk thromboembolic patients. We concluded that EUS-FNA in a safe procedure for patients on antithrombotics, even when antithrombotic therapy is not discontinued during EUS-FNA.

Slow-growing amelanotic malignant melanoma of the esophagus with long survival: a case report and review of the literature.

Background and study aims We report a case of amelanotic malignant melanoma of the esophagus (AMME), an exceedingly rare disease. A 77-year-old Japanese woman presented to our hospital with features suggestive of a middle esophageal submucosal tumor, which was diagnosed pathologically as AMME. The patient underwent thoracoscopic resection of the esophagus and laparoscopic gastric tube reconstruction. Three years after surgery, computed tomography showed no recurrence. Generally, the prognosis of malignant melanoma of the esophagus is very poor. However, our patient had no recurrence, and is alive 3 years after surgery and 5 years after the tumor was first detected.

Rapid skeletal muscle wasting predicts worse survival in patients with liver cirrhosis.

AIM: Sarcopenia impairs the outcome of patients with liver cirrhosis independently of liver function reserves. The aim of this study was to investigate whether the rate of skeletal muscle wasting predicts mortality in cirrhotic patients. METHODS: This retrospective study evaluated 149 cirrhotic patients who visited our hospital between March 2004 and September 2012. The skeletal muscle cross-sectional area at the level of the third lumbar vertebra was measured by computed tomography, from which the skeletal muscle index was obtained for diagnosis of sarcopenia. The relative change in skeletal muscle area per year (ΔSMA/y) was calculated in each patient. Cox proportional hazards regression analysis was performed to evaluate risk factors for mortality. RESULTS: Of the 149 cirrhotic patients, 94 (63%) were diagnosed with sarcopenia. The median of ΔSMA/y in all patients was -2.2%. For patients in Child-Pugh class A, B and C, ΔSMA/y was -1.3%, -3.5% and -6.1%, respectively. During a median follow-up period of 39 months (range, 1-110), 45 patients (30%) died. The optimal cut-off value of ΔSMA/y for predicting mortality was -3.1%; the survival rate in patients with ΔSMA/y of -3.1% or less was significantly lower than in patients with ΔSMA/y of more than -3.1% (P < 0.0001). The multivariate Cox proportional hazards model found ΔSMA/y of -3.1% or less to be significantly associated with mortality in cirrhotic patients (hazard ratio = 2.73, 95% confidence interval = 1.43-5.44, P < 0.01). CONCLUSION: ΔSMA/y is useful for predicting mortality in patients with liver cirrhosis. Management of skeletal muscle may contribute toward improving the outcome of cirrhotic patients.

Impact of serum glycosylated Wisteria floribunda agglutinin positive Mac-2 binding protein levels on liver functional reserves and mortality in patients with liver cirrhosis.

AIM: Serum glycosylated Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA(+) -M2BP) levels are a non-invasive and reliable marker to assess the degree of liver fibrosis. We investigated the use of WFA(+) -M2BP levels to predict mortality in patients with liver cirrhosis (LC). METHODS: This retrospective study consisted of 59 consecutive patients. Liver fibrosis was estimated by hyaluronic acid (HA), 7S fragment of type IV collagen (7S collagen), aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 index. The severity of liver disease was evaluated by Child-Pugh classification and the Model for End-Stage Liver Disease (MELD) score. Cox proportional hazards regression analysis was performed to evaluate risk factors for mortality, and the diagnostic accuracy of WFA(+) -M2BP levels to predict mortality was examined using receiver-operator curves. RESULTS: Serum WFA(+) -M2BP levels of Child-Pugh class A, B and C had cut-off indexes (COI) of 2.90, 6.15 and 9.45, respectively. WFA(+) -M2BP levels were positively correlated with HA, 7S collagen, APRI, FIB-4 index, Child-Pugh class and MELD score. Multivariate analysis identified WFA(+) -M2BP levels as an independent risk factor of mortality (hazard ratio = 1.19, 95% confidence interval = 1.02-1.41, P = 0.03), and the optimal cutoff point to predict mortality was 5.0 COI. The survival rate was significantly lower in patients with WFA(+) -M2BP levels 5.0 or more COI than in patients with WFA(+) -M2BP of less than 5.0 COI (P = 0.002). CONCLUSION: Serum WFA(+) -M2BP levels were significantly correlated with both liver function reserves and liver fibrosis, and were independently associated with mortality in patients with LC.

Sarcopenia impairs prognosis of patients with liver cirrhosis.

OBJECTIVE: Sarcopenia is characterized by the loss of skeletal muscle mass, and is reported to appear in patients with liver cirrhosis (LC). The aim of this study was to investigate the prevalence of sarcopenia in patients with LC, and to test the association between sarcopenia and patient outcomes. We also analyzed the effect of branched-chain amino acid (BCAA) supplementation on sarcopenic LC. METHODS: Clinical and blood biochemical data of 130 patients with LC who underwent abdominal computed tomography scan were analyzed in this retrospective study. The cross-sectional area of skeletal muscles was measured at the level of the third lumbar vertebra on the scan. The skeletal muscle index was calculated to identify sarcopenia. Cirrhotic patients who were treated with BCAA supplementation of 12 g/d for ≥ 1 y were defined as the BCAA group, and the effect of BCAA on sarcopenic LC was evaluated. RESULTS: Sixty-eight percent of all patients (82% of men and 50% of women) were diagnosed with sarcopenia. Male sex (P = 0.01) and body mass index (P < 0.0001) were predictors of sarcopenia. The multivariate Cox proportional hazards model found BCAA supplementation (hazard ratio [HR], 0.38; P = 0.01), sarcopenia (HR, 3.03; P < 0.01), and Child-Pugh classes B (HR, 2.39; P = 0.03) and C (HR, 5.49; P < 0.001) to be independently associated with mortality. The mortality of sarcopenic LC was significantly higher than that of non-sarcopenic LC (P = 0.01). Moreover, BCAA supplementation improved the survival of sarcopenic patients in subgroup analysis (P < 0.01). CONCLUSIONS: Sarcopenia is significantly associated with mortality in patients with LC. BCAA supplementation might be associated with improved survival of such patients.

Quercetin glucuronide inhibits cell migration and proliferation by platelet-derived growth factor in vascular smooth muscle cells.

Many epidemiologic studies have reported that dietary flavonoids provide protection against cardiovascular disease. Quercetin, a member of the bioflavonoids family, has been proposed to have anti-inflammatory, anti-atherogenic, and anti-hypertensive properties leading to the beneficial effects against cardiovascular diseases. Recent studies demonstrated that orally administered quercetin appeared in plasma as glucuronide-conjugated forms in rats and humans. Therefore, we examined the effect of chemically synthesized quercetin glucuronide on platelet-derived growth factor (PDGF)-induced cell migration and kinase activation in cultured rat aortic smooth muscle cells (RASMCs). PDGF-induced RASMC migration was inhibited by quercetin 3-O-beta-D-glucuronide (Q3GA). Q3GA also attenuated PDGF-induced cell proliferation in RASMCs. PDGF activated extracellular-signal regulated kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and Akt in RASMCs. PDGF-induced JNK and Akt activations were suppressed by Q3GA, whereas ERK1/2 and p38 MAP kinase activations were not affected. We also confirmed that PDGF-induced JNK and Akt activations were inhibited by antioxidants, N-acetylcysteine and diphenyleneiodonium chloride, in RASMCs. These findings suggest Q3GA would be an active metabolite of quercetin in plasma and may possess preventing effects for cardiovascular diseases relevant to vascular smooth muscle cell disorders.

Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan.

In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a difference in clinical features between the two genotypes remains unclear. This study compares the clinical features of patients infected with the two. From January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients with genotype 4 were enrolled. Patients with genotype 4 had significantly higher peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747-4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series, patients with genotype 4 had longer median duration of hospital stay (26.5 days, 18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection tended to have more severe clinical manifestations than those with genotype 3 infection.

Full-length sequences of six hepatitis E virus isolates of genotypes III and IV from patients with sporadic acute or fulminant hepatitis in Japan.

OBJECTIVE: Ranges of variation and conservation in sequence need to be defined for detecting and genotyping hepatitis E virus (HEV). METHODS: Six HEV isolates from Japanese patients were sequenced over the entire genome and compared phylogenetically along with 16 reported HEV isolates, including two from pigs. RESULTS: Three of the six HEV isolates were of genotype III, and the remaining three were of genotype IV. Local clusterings of Japanese HEV isolates were observed in the phylogenetic analyses, including a swine HEV isolate reported previously (swJ570). All six HEV isolates possessed three open reading frames (ORFs). The ORF3 in the three isolates of genotype III were in a different reading frame, while that in the three isolates of genotype IV were in the same reading frame as ORF1. A stretch of 46-96 nucleotides was identified, point mutations and deletions in which were specific for the four genotypes (I-IV). A polymerase chain reaction method was developed with 9 nested universal primers, deduced from conserved regions in the 5'-terminal sequences of the 22 HEV genomes. CONCLUSIONS: Conserved and genotype-specific variation in HEV sequences, identified in the comparison of 22 full-length genomes, would be useful in designing primers for sensitive detection and specific genotyping of HEV RNA.

A case report: two patients with fulminant hepatitis E in Hokkaido, Japan.

Hepatitis E virus (HEV) has been listed as one of the major agents that cause fulminant hepatitis in HEV-endemic areas, but not in non-endemic areas. Recently, however, we experienced two cases of fulminant hepatitis E in Hokkaido, Japan: case-1 was a 34-year-old woman and case-2, a 51-year-old man, neither having a history of travelling outside Japan or contact with travellers abroad or foreigners. HEV RNA was detected in their acute-phase serum and sequencing analyses indicated that they were infected with different strains of HEV: genotype III in case-1 and IV in case-2. Case-1 patient deceased after liver transplantation, while case-2 patient survived. Based on these cases, we suggest that HEV should be considered as an aetiologic agent for fulminant hepatitis, even in non-endemic areas.

Genetic heterogeneity of hepatitis E virus recovered from Japanese patients with acute sporadic hepatitis.

The recent discovery of a presumably Japan-indigenous hepatitis E virus (HEV) strain (JRA1) spurred analysis of additional isolates from 7 cases of acute sporadic hepatitis E infection. Comparison of a 326-nucleotide region from open-reading frame 1 indicated that 1, 3, and 3 isolates segregated to genotypes I, III, and IV, respectively. Six patients had not traveled abroad recently. One patient had traveled to Hawaii 1 month before becoming ill, and the nucleotide sequence of the HEV isolate infecting her resembled those of US isolates (89%-91% nucleotide identity). However, the isolate was even more homologous to 2 other Japanese isolates (95%-97% nucleotide identity), suggesting that it is more likely a domestic, rather than an imported, strain. Three genotype IV isolates from Japan also had a higher homology to each other (100% amino acid identity) than to 2 Chinese isolates (97%-98% amino acid identity). These findings suggest that HEV strains of at least 3 different genotypes have already made inroads and are spreading in Japan.