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

石川県立中央病院金沢大学医薬保健研究域医学系Iron 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. Methods We 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. Results One 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. Conclusion Determining serum hepcidin-25 levels may aid differential diagnosis of iron overload syndromes prior to genetic analysis. © Springer 2010

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

High-incidence spontaneous tumors in JF1/Ms mice: relevance of hypomorphic germline mutation and subsequent promoter methylation of Ednrb

PURPOSE: \nJF1/Ms mice, an inbred strain derived from Japanese wild mice, carry a germline hypomorphic mutation in the endothelin receptor type B gene (Ednrb). We observed that the JF1/Ms mice develop various spontaneous tumors at a high incidence late in life. The aim of this study was to elucidate the mechanism responsible for spontaneous tumors in these mice. Possible relevance of milk-borne mammary tumor virus and gene alterations in Ednrb to tumorigenesis was explored.\nMETHODS: \nExpression and methylation status of Ednrb were quantitatively analyzed in normal and cancer tissues of mammary gland, liver, submandibular gland as well as in a cultured cell line, MW1, established from a submandibular gland adenocarcinoma. The biological effects of EDNRB were examined in the MW1 cells transfected with wild-type Ednrb.\nRESULTS: \nTranscripts of Ednrb were barely detectable, and the promoter region of Ednrb was hypermethylated in tumor tissues and the MW1 cells. In contrast, normal counterpart tissues showed positive expression of Ednrb transcripts and had unmethylated promoter regions. Treatment of the MW1 cells with 5-Aza-dC restored transcription of Ednrb to normal levels. Transfection of the MW1 cells with Ednrb1 (MW1-Ednrb1) resulted in lower growth rates and morphological changes compared with the mock-transfected MW1 cells (MW1-mock1). Furthermore, the MW1-Ednrb1 cells transplanted in syngeneic mice showed a lower proliferation rate than the MW1-mock1 cells.\nCONCLUSIONS: \nGermline mutation and subsequent promoter methylation of Ednrb may be relevant to cancer susceptibility in the JF1/Ms mice. These data indicate that Ednrb acts as a tumor suppressor, as reported in human prostate, bladder, and clear cell renal carcinomas

Pseudolymphoma of the liver associated with primary biliary cirrhosis: A case report and review of literature

We report a case of two pseudolymphomas of the liver in a 63-year-old Japanese woman with primary biliary cirrhosis. One of the lesions was found incidentally during a medical examination, presenting as a 10 mm hypodense nodule that revealed hyperdensity in the early phase and hypodensity in the late phase in computed tomography (CT) after injection of contrast medium. Retrospectively, the 10 mm nodule had first been discovered as a 4 mm nodule during CT 4 years previously. Superparamagnetic iron oxide-enhanced MRI revealed another 4 mm hyperintense nodule in segment 6 in addition to the 10 mm hyperintense nodule in segment 7. CT during arterial portography revealed two hypointense nodules. Findings with other imaging modalities such as ultrasonography, magnetic resonance imaging, and hepatic angiography were consistent with hepatocellular carcinoma. A right posterior segmentectomy was performed, and the lesions were microscopically diagnosed as pseudolymphoma. To the best of our knowledge, only 31 other cases of this disease have ever been reported, with a highly asymmetrical male:female ratio of 1:9.7. Although we could find only one case of transformation of hepatic pseudolymphoma into lymphoma in the liver, the exact nature of development from benign pseudolymphoma to malignant lymphoma is still not fully understood and cases of hepatic lymphoma need to be followed carefully

Assessment of Still and Moving Images in the Diagnosis of Gastric Lesions Using Magnifying Narrow-Band Imaging in a Prospective Multicenter Trial

<div><p>Objectives</p><p>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.</p><p>Design</p><p>A prospective multicenter cohort study.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p><p>Trial registration</p><p>Umin.ac.jp <a href="https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000009477&language=E" target="_blank">UMIN-CTR000008048</a></p></div

Characteristics of 40 Gastric Lesions Used in Both Tests.

<p>Characteristics of 40 Gastric Lesions Used in Both Tests.</p