Yoshibumi Kaneko

Magnifying narrowband imaging is more accurate than conventional white-light imaging in diagnosis of gastric mucosal cancer.

BACKGROUND & AIMS It is difficult to accurately diagnose patients with depressed gastric mucosal cancer based on conventional white-light imaging (C-WLI) endoscopy. We compared the real-time diagnostic yield of C-WLI for small, depressed gastric mucosal cancers with that of magnifying narrow-band imaging (M-NBI). METHODS We performed a multicenter, prospective, randomized, controlled trial of patients with undiagnosed depressed lesions ≤10 mm in diameter identified by esophagogastroduodenoscopy. Patients were randomly assigned to groups that were analyzed by C-WLI (n = 176) or M-NBI (n = 177) immediately after detection; the C-WLI group received M-NBI after C-WLI. We compared the diagnostic accuracy, sensitivity, and specificity between C-WLI and M-NBI and assessed the diagnostic yield of M-NBI conducted in conjunction with C-WLI. RESULTS Overall, 40 gastric cancers (20 in each group) were identified. The median diagnostic values for M-NBI and C-WLI were as follows: accuracy, 90.4% and 64.8%; sensitivity, 60.0% and 40.0%; and specificity, 94.3% and 67.9%, respectively. The accuracy and specificity of M-NBI were greater than those of C-WLI (P < .001); the difference in sensitivity was not significant (P = .34). The combination of M-NBI with C-WLI significantly enhanced performance compared with C-WLI alone; accuracy increased from (median) 64.8% to 96.6% (P < .001), sensitivity increased from 40.0% to 95.0% (P < .001), and specificity increased from 67.9% to 96.8% (P < .001). CONCLUSIONS M-NBI, in conjunction with C-WLI, identifies small, depressed gastric mucosal cancers with 96.6% accuracy, 95.0% sensitivity, and 96.8% specificity. These values are better than for C-WLI or M-NBI alone.

Measurement of serum hepcidin-25 levels as a potential test for diagnosing hemochromatosis and related disorders

BackgroundIron overload syndromes include a wide spectrum of genetic and acquired conditions. Recent studies suggest suppressed hepcidin synthesis in the liver to be the molecular basis of hemochromatosis. However, a liver with acquired iron overload synthesizes an adequate amount of hepcidin. Thus, hepcidin could function as a biochemical marker for differential diagnosis of iron overload syndromes.MethodsWe measured serum iron parameters and hepcidin-25 levels followed by sequencing HFE, HJV, HAMP, TFR2, and SLC40A1 genes in 13 Japanese patients with iron overload syndromes. In addition, we performed direct measurement of serum hepcidin-25 levels using liquid chromatography–tandem mass spectrometry in 3 Japanese patients with aceruloplasminemia and 4 Italians with HFE hemochromatosis.ResultsOne patient with HJV hemochromatosis, 2 with TFR2 hemochromatosis, and 3 with ferroportin disease were found among the 13 Japanese patients. The remaining 7 Japanese patients showed no evidence for genetic basis of iron overload syndrome. As far as the serum hepcidin-25 was concerned, seven patients with hemochromatosis and 3 with aceruloplasminemia showed markedly decreased serum hepcidin-25 levels. In contrast, 3 patients with ferroportin disease and 7 with secondary iron overload syndromes showed serum hepcidin levels parallel to their hyperferritinemia. Patients with iron overload syndromes were divided into 2 phenotypes presenting as low and high hepcidinemia. These were then associated with their genotypes.ConclusionDetermining serum hepcidin-25 levels may aid differential diagnosis of iron overload syndromes prior to genetic analysis.

High prevalence of fulminant hepatic failure among patients with mutant alleles for truncation of ATP7B in Wilson's disease

Abstract Objective. Although many mutations of the Wilsons disease (WD) gene (ATP7B) have been reported, few data exist regarding the occurrence of fulminant hepatic failure (FHF). We sought to determine if genotypic assignment according to type of protein-product could be related to the prevalence of FHF among patients with WD. Material and methods. We performed gene analysis in Japanese patients with WD as well as genotype–phenotype analysis in 51 patients. We divided genotypes into two groups according to type of ATP7B product: truncated group [T] consisted of two truncated alleles including nonsense, insertion, deletion, or splice site mutation, and missense group [M] consisted of one or two missense alleles. We also divided phenotypes into two groups: [FHF] group and [non-FHF] group. Results. We were able to determine genotype in 42 patients. Genotypically, 11 patients were assigned to [T] group and 31 to [M] group. Phenotypically, 4 patients were [FHF] and 38 were [non-FHF]. All patients in [FHF] group belonged to [T] group. The prevalence of [FHF] in [T] group was 36.4% and was significantly higher than in [M] group (p < 0.003). Conclusions. These results demonstrated that genotypes for truncation of ATP7B are associated with high prevalence of FHF.

Detection of pharyngeal cancer in the overall population undergoing upper GI endoscopy by using narrow-band imaging: a single-center experience, 2009–2012

BACKGROUND Nonmagnifying observation by using narrow-band imaging (NBI) is useful for detecting pharyngeal lesions. Magnifying observation by using NBI can distinguish between cancerous and noncancerous lesions and is therefore useful for the early detection of pharyngeal cancer. OBJECTIVE To evaluate the usefulness of observation of the pharynx by using NBI in the overall population undergoing upper GI endoscopy. DESIGN Retrospective study. SETTING Single tertiary referral center. PATIENTS A total of 11,050 upper GI endoscopies between January 2009 and December 2012. INTERVENTIONS Observation of the pharynx by using NBI. MAIN OUTCOME MEASURES The rate of detection of pharyngeal cancer, the rates of detection according to the reason for endoscopy, and the types of cancers detected. RESULTS Thirty-eight cancerous lesions were detected in 29 patients (0.26%, 29/11,050). The rate of detection of pharyngeal cancer was significantly higher in patients with a history of head and neck cancer (9.7%, 3/31) or a history of esophageal cancer (3.5%, 10/282). In patients undergoing endoscopy for screening, pharyngeal discomfort, and a history of gastric cancer, the rates of detection of pharyngeal cancer were 0.11% (10/8872), 1.1% (3/265), and 0.19% (3/1600), respectively. Two patients (6.9%) were female. One had a history of esophageal cancer, and the other had pharyngeal discomfort. LIMITATIONS Single-center, retrospective study. CONCLUSIONS Observation of the pharynx by using NBI in patients with previous head and neck cancer or esophageal cancer or who have pharyngeal discomfort is very important. Moreover, pharyngeal cancer was certainly found in the male patients undergoing screening endoscopy, although the rate was lower.

Apolipoprotein B gene mutations and fatty liver in Japanese hypobetalipoproteinemia

BACKGROUND Familial hypobetalipoproteinemia (FHBL) is a hereditary disorder characterized by decreased plasma concentrations of low-density lipoprotein cholesterol. The best-characterized causes of FHBL are apolipoprotein B (apoB) gene mutations, which produce truncated apoB proteins. Fatty liver is thought to be frequent in FHBL, owing to impaired secretion of very-low-density lipoprotein from the liver. Homozygotes for FHBL present with extremely low concentrations of plasma lipids, and may suffer from deficiencies of fat-soluble vitamins. The objectives of this study were to identify apoB-defective FHBL subjects and investigate fatty liver in Japanese population. METHODS We screened 14 hypocholesterolemic subjects for apoB gene mutations by PCR-SSCP and performed liver ultrasonography in a Japanese population. RESULTS We identified an apoB-82 homozygote in one subject and an apoB-13.7 heterozygote in another subject. Four of 6 individuals with FHBL presented with fatty liver in those 2 FHBL families. Liver biopsy of the apoB-13.7 heterozygote, which had obesity and insulin resistance, showed severe fatty liver. The apoB-82 homozygote was asymptomatic with fat-soluble vitamin concentrations being normal, possibly due to spared secretion of apoB-48 from the intestine and increased plasma concentrations of high-density lipoprotein cholesterol. CONCLUSION ApoB gene mutations might not be rare and that fatty liver might be frequent in Japanese FHBL.

Impact of Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutation on the Occurrence of Chronic Pancreatitis in Japanese Patients

DNA analyses of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in Japanese patients with idiopathic chronic pancreatitis (ICP) were performed to determine the relationship between the CFTR mutation and ICP. The study included patients with alcoholic pancreatitis (n = 20), patients with ICP (n = 20) and healthy volunteers (controls; n = 110). The poly-T region in intron 8 of the CFTR gene was analysed by direct sequencing. The CFTR coding region was screened using single-strand conformational polymorphism and direct sequencing. In the controls, frequencies of the 5T genotype and 5T allele were 4.5% and 3.6%, respectively. The frequency of the 5T genotype was significantly higher in the ICP group (20%) versus controls, but was not significantly different in alcoholic chronic pancreatitis patients (5%). Thus, the CFTR gene mutation, especially the 5T genotype, appears to have some relationship to ICP prevalence in Japanese patients independent of cystic fibrosis.

Assessment of still and moving images in the diagnosis of gastric lesions using magnifying narrow-band imaging in a prospective multicenter trial.

Objectives Magnifying narrow-band imaging (M-NBI) is more accurate than white-light imaging for diagnosing small gastric cancers. However, it is uncertain whether moving M-NBI images have additional effects in the diagnosis of gastric cancers compared with still images. Design A prospective multicenter cohort study. Methods To identify the additional benefits of moving M-NBI images by comparing the diagnostic accuracy of still images only with that of both still and moving images. Still and moving M-NBI images of 40 gastric lesions were obtained by an expert endoscopist prior to this prospective multicenter cohort study. Thirty-four endoscopists from ten different Japanese institutions participated in the prospective multicenter cohort study. Each study participant was first tested using only still M-NBI images (still image test), then tested 1 month later using both still and moving M-NBI images (moving image test). The main outcome was a difference in the diagnostic accuracy of cancerous versus noncancerous lesions between the still image test and the moving image test. Results Thirty-four endoscopists were analysed. There were no significant difference of cancerous versus noncancerous lesions between still and moving image tests in the diagnostic accuracy (59.9% versus 61.5%), sensitivity (53.4% versus 55.9%), and specificity (67.0% versus 67.6%). And there were no significant difference in the diagnostic accuracy between still and moving image tests of demarcation line (65.4% versus 65.5%), microvascular pattern (56.7% versus 56.9%), and microsurface pattern (48.1% versus 50.9%). Diagnostic accuracy showed no significant difference between the still and moving image tests in the subgroups of endoscopic findings of the lesions. Conclusions The addition of moving M-NBI images to still M-NBI images does not improve the diagnostic accuracy for gastric lesions. It is reasonable to concentrate on taking sharp still M-NBI images during endoscopic observation and use them for diagnosis. Trial registration Umin.ac.jp UMIN-CTR000008048

New treatment for eradication of Helicobacter pylori: effective and inexpensive combination

Background: Proton pump inhibitors (PPIs) profoundly inhibit gastric acid secretion by irreversibly binding and inactivating H 1/K1 ATPase on the secretory canalicular surface of stimulated parietal cells. An understanding of the kinetics of H1/K1 ATPase turnover in humans is largely unknown. A model to examine the synthesis and activation of new pumps can be achieved by investigating the recovery of acid secretion following inhibition with an intravenous (IV) PPI such as Pantoprazole (Panto) under maximally stimulated conditions with Pentagastrin. Aims: To estimate proton pump recovery (PPR) in normal individuals receiving continuous IV Pentagastrin (1 mg/kg/hr) following single-dose IV Panto therapy. Methods: Gastric acid output was collected continuously for 24 hours after single 15 minute infusions of Panto (20–120 mg, n 524) or placebo (n 53). Acid secretion was constant in placebo-treated individuals reflecting an absence of tachyphylaxis to continuous Pentagastrin infusion. PPR was calculated using the following formula: dR/dt 5k*Cpanto.R1(ln2/ PPR)*(Ro2R); where R5acid production, Ro 5mean Pentagastrin-stimulated acid output [PSAO], k 5reaction constant between Panto and proton pumps and Cpanto 5Panto plasma concentration. Results:Of the 27 study subjects (mean age 31.2 yrs; range 21–45 yrs), 10 were male and 17 female. Twenty subjects were white, 7 were African American, 1 was Hispanic, and 1 was Asian. The mean PSAO, an indirect measure of parietal cell mass, was 21.6 618.4 mEq/hr (range 1.6–52.8) and mean PPR was 37.1 621 hr (6.7–75). PPR correlated inversely with PSAO (r50.55, p,0.009) with a slope of 1.01 mEq/hr/hr. PPR did not correlate with age, gender, weight or race. Conclusions: These results demonstrate for the first time that recovery rates for gastric acid secretion following PPI administration in normal subjects are variable with an inverse relationship between recovery of acid secretion and maximal secretory capacity. These findings may reflect a normal physiologic homeostatic mechanism whereby humans maintain acid secretion within appropriate levels. Disclosure:This research was funded by Wyeth Ayerst Research, Radnor, PA.