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Takefumi Kimura,
Akihiro Shinji,
Akira Horiuchi,
Naoki Tanaka, Tadanobu Nagaya,
Takashi Shigeno,
Naoshi Nakamura,
Michiharu Komatsu,
Takeji Umemura,
Norikazu Arakura,
Akihiro Matsumoto,
Eiji Tanaka
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ABSTRACT: Ischemic colitis (IC) typically develops in the elderly, where hypertension, cerebrocardiovascular disease, and past history of abdominal surgery are regarded as risk factors. Although there have been reports of younger patients with IC, its clinical features remain unclear.
The aim of this study was to clarify the clinical characteristics of IC in young adults.
Three hundred fifty-nine patients were diagnosed as having IC at five hospitals across Nagano prefecture, Japan. Clinical data were compared between the young patient group [20-45 years, n = 53 (15%)] and the elderly patient group [>45 years, n = 306 (85%)], as well as with age- and gender-matched healthy individuals (n = 156).
The presence of a smoking habit and hyperuricemia were significantly higher in the young patient group compared with the elderly patient group (42 vs. 19%, P = 0.001 and 8 vs. 1%, P = 0.019, respectively), which was confirmed by multiple logistic regression analysis (P = 0.001, odds ratio 3.239 and P = 0.028, odds ratio 16.907, respectively). Additionally, multiple logistic regression analysis of the young IC patient group and age- and gender-matched healthy individuals demonstrated that these two factors were strongly associated with IC development (P = 0.008, odds ratio 2.49 for smoking habit and P = 0.039, odds ratio 6.37 for hyperuricemia).
High prevalences of a smoking habit and hyperuricemia are characteristic features of IC in the young adult population.
Digestive Diseases and Sciences 03/2012; 57(6):1652-9. · 2.12 Impact Factor
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Naoki Tanaka,
Akira Horiuchi,
Takahide Yokoyama,
Gengo Kaneko,
Naoto Horigome,
Takahiro Yamaura, Tadanobu Nagaya,
Michiharu Komatsu,
Kenji Sano,
Shin-Ichi Miyagawa,
Toshifumi Aoyama,
Eiji Tanaka
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ABSTRACT: Hepatic steatosis may develop after pancreatic resection, but its clinicopathological features remain unclear. We explored the clinical characteristics of newly appearing nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD), designated as de novo NAFLD after PD.
Of 83 patients who underwent PD between 2001 and 2006, the patients with regular alcohol consumption after PD (n = 3), those who were unavailable for regular abdominal computed tomography follow-up (n = 12), and those who died within 6 months of PD (n = 8) were excluded from the study. In the remaining 60 patients, the prevalence and clinical features of de novo NAFLD after PD were examined.
NAFLD developed after PD in 14 (23%) patients in our cohort. Liver biopsy was performed in 8 patients and all showed typical steatohepatitis. Compared with the patients who had conventional nonalcoholic steatohepatitis (NASH), patients with post-PD de novo NASH demonstrated significant decreases in body mass index and lower levels of serum albumin, cholesterol, apolipoprotein B, and homeostasis model assessment for insulin resistance. Multivariate logistic regression analysis revealed that pancreatic head cancer was associated with an increased risk of developing NAFLD after PD (odds ratio 12.0, 95% confidence interval 2.0-71.4, P = 0.006). Increased dosage of oral pancreatic enzymes significantly ameliorated the steatosis, as well as leading to the recovery of body weight loss and resolution of the biochemical abnormalities.
De novo NAFLD/NASH after PD is characterized by non-obesity and lack of hyperlipidemia and insulin resistance and is associated with pancreatic exocrine insufficiency. In such patients, intensifying pancreatic enzyme supplementation may be useful.
Journal of Gastroenterology 01/2011; 46(6):758-68. · 4.16 Impact Factor
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Tomoko Hatta,
Yasunari Fujinaga,
Masumi Kadoya,
Hitoshi Ueda,
Hiroaki Murayama,
Masahiro Kurozumi,
Kazuhiko Ueda,
Michiharu Komatsu, Tadanobu Nagaya,
Satoru Joshita,
Ryo Kodama,
Eiji Tanaka,
Tsuyoshi Uehara,
Kenji Sano,
Naoki Tanaka
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ABSTRACT: To assess the degree of hepatic fat content, simple and noninvasive methods with high objectivity and reproducibility are required. Magnetic resonance imaging (MRI) is one such candidate, although its accuracy remains unclear. We aimed to validate an MRI method for quantifying hepatic fat content by calibrating MRI reading with a phantom and comparing MRI measurements in human subjects with estimates of liver fat content in liver biopsy specimens.
The MRI method was performed by a combination of MRI calibration using a phantom and double-echo chemical shift gradient-echo sequence (double-echo fast low-angle shot sequence) that has been widely used on a 1.5-T scanner. Liver fat content in patients with nonalcoholic fatty liver disease (NAFLD, n = 26) was derived from a calibration curve generated by scanning the phantom. Liver fat was also estimated by optical image analysis. The correlation between the MRI measurements and liver histology findings was examined prospectively.
Magnetic resonance imaging measurements showed a strong correlation with liver fat content estimated from the results of light microscopic examination (correlation coefficient 0.91, P < 0.001) regardless of the degree of hepatic steatosis. Moreover, the severity of lobular inflammation or fibrosis did not influence the MRI measurements.
This MRI method is simple and noninvasive, has excellent ability to quantify hepatic fat content even in NAFLD patients with mild steatosis or advanced fibrosis, and can be performed easily without special devices.
Journal of Gastroenterology 12/2010; 45(12):1263-71. · 4.16 Impact Factor
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ABSTRACT: Along with the growing elderly population, patients with gastric ulcers caused by low-dose aspirin have increased. Gastric cancer is also common among the elderly population, but is sometimes difficult to distinguish from gastric ulcers, especially those stemming from aspirin use. To differentiate the diagnostic symptoms of gastric ulcers and gastric cancers in elderly patients, we compared the endoscopic findings of 198 subjects (92 benign ulcers and 106 cancers) aged 65 years and older. Despite their benign nature, aspirin-induced ulcers tended to have more irregularity of the ulcer edge and heterogeneous formation of regenerating epithelium than ulcer unrelated to aspirin. Asking about the use of low-dose aspirin is therefore important when confronted with such lesions in elderly patients.
Nippon rinsho. Japanese journal of clinical medicine 11/2010; 68(11):2036-9.
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ABSTRACT: Non-steroidal anti-inflammatory drug (NSAID)-related small intestinal complications exist, since developed new diagnostic modalities, such as balloon and capsule endoscopies. Some experiments have shown rebamipide to protect from NSAID-induced small intestinal complications. The purpose of this study is to investigate whether the effective concentrations of rebamipide (COR) are present in the small intestine after taking an ordinary clinical dose and double dose of this drug. Twelve healthy male subjects were enrolled. After taking 100 or 200 mg of rebamipide, balloon enteroscopy was performed at 1 and 3 h, and biopsy samples were obtained from the jejunum and the stomach. Venous blood samples were taken simultaneously. Samples were analyzed by high-performance liquid chromatography. The mean COR in the jejunum was higher than 100 µM at 1 h and higher than 10 µM at 3 h in both the 100 and 200 mg groups. Mean COR in the stomach was less than 100 µM at 1 h in the 100 mg group; however it was higher than 100 µM in the 200 mg group. In conclusion, the COR level in the jejunum was sufficient to protect for NSAID-induced gastrointestinal complications.
Journal of Clinical Biochemistry and Nutrition 11/2010; 47(3):256-60. · 1.98 Impact Factor
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Tadanobu Nagaya,
Naoki Tanaka,
Takefumi Suzuki,
Kenji Sano,
Akira Horiuchi,
Michiharu Komatsu,
Takero Nakajima,
Tomoko Nishizawa,
Satoru Joshita,
Takeji Umemura,
Tetsuya Ichijo,
Akihiro Matsumoto,
Kaname Yoshizawa,
Jun Nakayama,
Eiji Tanaka,
Toshifumi Aoyama
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ABSTRACT: It is well-known that hepatic triglycerides (TG) diminish with the progression of non-alcoholic steatohepatitis (NASH), which has been designated as burned-out NASH, but its mechanism remains unclear. We aimed to explore the changes in hepatic fatty acid (FA) and TG metabolism with disease progression.
Hepatic expression of key genes in healthy individuals (n=6) and patients with simple steatosis (SS, n=10), mild NASH (fibrosis stage 1-2, n=20), and advanced NASH (fibrosis stage 3-4, n=20) were assessed by quantitative polymerase chain reaction.
Hepatic expression of genes related to FA uptake and oxidation and very-low-density lipoprotein synthesis/export did not differ among the groups. However, the mRNA levels of sterol regulatory element-binding protein (SREBP)-1c and its downstream genes FA synthase, acetyl-coenzyme A carboxylase 1, and diacylglycerol acyltransferase 1 were inversely correlated with fibrosis stage. Immunoblot analysis revealed a remarkable reduction in mature SREBP-1c levels in advanced NASH. Furthermore, hepatic expression of tumor necrosis factor-alpha increased in accordance with fibrosis progression, which was possibly related to the decrease in hepatic SREBP-1c expression.
Down-regulation of SREBP-1c and lipogenic enzymes may be associated with the development of burned-out NASH.
Journal of Hepatology 10/2010; 53(4):724-31. · 9.26 Impact Factor
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Takeshi Uehara,
Hideaki Hamano,
Shigeyuki Kawa,
Kenji Sano,
Keiko Oki,
Yukihiro Kobayashi, Tadanobu Nagaya,
Taiji Akamatsu,
Masahiro Kurozumi,
Yasunori Fujinaga,
Eiji Tanaka,
Takayuki Honda,
Hiroyoshi Ota
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ABSTRACT: Autoimmune pancreatitis (AIP) is a recently recognized disease entity. In some patients, this disease is associated with other inflammatory diseases. In this study, we aimed to elucidate the pathologic characteristics of AIP-associated gastritis (AIP-G). We evaluated and compared the pathologic findings and immunohistochemical expressions of immunoglobulin G (IgG)4 and IgG in gastric biopsy specimens from 13 AIP-G patients with those from patients of 2 control groups. We divided the AIP-G patients who did not receive steroid therapy [AIP-G-ST(-)] into the following 2 groups: without Helicobacter pylori (HP) infection [AIP-G-HP(-)] and with HP infection [AIP-G-HP(+)]. The control groups comprised 19 patients who were diagnosed with chronic active gastritis associated with HP infection and 7 patients with nonsteroidal anti-inflammatory drug-induced gastritis. We classified the findings for the gastric mucosa into those for the upper and the lower lamina propria. The characteristic finding of AIP-G groups was diffusely lymphoplasmacytic infiltration in the lamina propria. The IgG4-positive plasma cell/IgG-positive plasma cell ratios (IgG4/IgG ratios) in both the upper and lower lamina propria in the AIP-G-ST(-) groups were predominantly higher than the corresponding values in the other groups. In the AIP-G-ST(-) groups, the IgG4/IgG ratio in the lower lamina propria was predominantly higher than that in the upper lamina propria, irrespective of the HP status. In conclusion, diffuse lymphoplasmacytic infiltration in the lamina propria and increased IgG4/IgG ratio in the gastric mucosa (notably in the lower lamina propria) may be the characteristic findings of AIP-G.
The American journal of surgical pathology 09/2010; 34(9):1241-9. · 4.06 Impact Factor
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Masaru Tsutsui,
Naoki Tanaka,
Masatomo Kawakubo,
Yo Sheena,
Akira Horiuchi,
Michiharu Komatsu, Tadanobu Nagaya,
Satoru Joshita,
Takeji Umemura,
Tetsuya Ichijo,
Akihiro Matsumoto,
Kaname Yoshizawa,
Toshifumi Aoyama,
Eiji Tanaka,
Kenji Sano
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ABSTRACT: Reliable noninvasive biomarkers to assess the histologic activity of nonalcoholic fatty liver disease (NAFLD) have not been established. As the frequency of Mallory bodies is known to be closely associated with the disease severity, we hypothesized that serum levels of Mallory body-related proteins were correlated with NAFLD histologic activity and evaluated this possibility.
Serum levels of total and fragmented cytokeratin (CK) 18, heat shock protein (Hsp) 70, Hsp90alpha, ubiquitin+1, and p38alpha at the time of liver biopsy were measured in 118 NAFLD patients and their association with histologic findings and NAFLD histologic activity score (NAS) was investigated.
Serum levels of both forms of CK18 and Hsp90alpha were markedly higher in patients having nonalcoholic steatohepatitis (NASH) compared with non-NASH ones. Both forms of CK18 significantly correlated with degree of steatosis, lobular inflammation, and ballooning, and showed stronger positive correlations with NAS than serum aspartate and alanine aminotransferase (AST and ALT). Multiple regression analysis further revealed that fragmented CK18 and AST were effective predictors of NAS, with the former being the more definitive of the two (P<0.001 vs. 0.005). In 20 NAFLD patients who received a follow-up biopsy, changes in fragmented CK18 levels, but not AST or ALT levels, closely paralleled those in NAS.
These results establish the usefulness of fragmented CK18 measurement for assessing and monitoring the histologic activity of NAFLD.
Journal of clinical gastroenterology 07/2010; 44(6):440-7. · 2.21 Impact Factor
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Naoki Tanaka,
Akira Horiuchi,
Takahiro Yamaura,
Michiharu Komatsu,
Takahide Yokoyama,
Shinji Okaniwa, Tadanobu Nagaya,
Kaname Yoshizawa,
Kendo Kiyosawa,
Toshifumi Aoyama,
Eiji Tanaka
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ABSTRACT: Hepatoprotective therapies that include regular glycyrrhizin injections (GIs) are beneficial for chronic hepatitis C patients, but are sometimes insufficient for normalizing serum alanine aminotransferase (ALT) levels. Here, we evaluated whether the addition of minor bloodletting, named petit phlebotomy (PP), prior to each GI could further reduce serum ALT concentrations in such patients.
Seventy-six hepatitis C virus (HCV)-infected patients receiving regular GI, with persistently abnormal serum ALT levels, were randomly divided into GI + PP and GI groups and monitored for 12 months. PP was performed before every GI to a total 60 ml of blood a week. The primary PP endpoint was a serum ferritin level of less than 20 ng/ml. PP was suspended upon reaching the endpoint, but was resumed as needed. The efficacy of the addition of PP was evaluated by measuring changes in serum ALT levels.
Two patients in each group dropped out because of the appearance of hepatocellular carcinoma. The remainder completed the 12-month treatment with no serious adverse events. Serum ALT and ferritin levels were significantly decreased in the GI + PP group (from 67 +/- 34 to 44 +/- 14 U/l and from 163 +/- 127 to 25 +/- 21 ng/ml, respectively, both P < 0.001), but these changes were not seen in the GI group. Although 20 patients in the GI + PP group had compensated cirrhosis, no significant reductions in serum albumin concentrations were observed.
The addition of PP is effective and safe for improving serum aminotransferase levels in HCV-infected patients receiving regular GI, even in those with compensated cirrhosis.
Journal of Gastroenterology 04/2009; 44(6):577-82. · 4.16 Impact Factor
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Tadanobu Nagaya,
Naoki Tanaka,
Atsushi Kamijo,
Satoru Joshita,
Koh Nakazawa,
Hideharu Miyabayashi,
Suguru Yoneda,
Tetsuya Ito,
Michiharu Komatsu,
Eiji Tanaka,
Kiyoshi Kitano
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ABSTRACT: A 33-year-old Japanese man was referred to our hospital after a huge intrapelvic tumor with bilateral hydronephrosis was found following persistent lumbago. Natural killer/T-cell lymphoma was suspected due to positive immunostaining for CD56, but CHOP therapy was ineffective. Re-evaluation of the tumor cells showed that they were positive for CD99, neuron-specific enolase, and synaptophysin and had a t(11 ; 22) (q24 ; q12) translocation, leading to the revised diagnosis of primitive neuroectodermal tumor (PNET). Systemic chemotherapies and radiation therapy were added to surgical resection, and no recurrence has been detected for 3 years. Taken together, PNET may be considered in adult patients with CD56-positive tumors.
Internal Medicine 02/2009; 48(15):1267-72. · 0.94 Impact Factor
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Naoki Tanaka, Tadanobu Nagaya,
Michiharu Komatsu,
Akira Horiuchi,
Goro Tsuruta,
Haruaki Shirakawa,
Takeji Umemura,
Tetsuya Ichijo,
Akihiro Matsumoto,
Kaname Yoshizawa,
Toshifumi Aoyama,
Kendo Kiyosawa,
Eiji Tanaka
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ABSTRACT: Recent studies using transgenic mouse models have demonstrated that the presence of hepatitis C virus (HCV) singularly induces insulin resistance (IR). When evaluated in humans, the exclusion of other factors influencing IR, such as obesity, alcohol intake, hepatic inflammation and steatosis is needed, but only few studies have been performed to these ends. Therefore, we aimed at exploring the singular effects of HCV on glucose metabolism through analysis of HCV carriers with persistently normal serum aminotransferase.
Non-obese, non-diabetic and non-alcoholic HCV carriers (n=30) were enrolled with 30 hepatitis B virus carriers matched by age, gender, body mass index and waist-to-hip ratio. All patients maintained normal serum aminotransferase (<30 U/L), hyaluronic acid (<50 ng/ml) and platelet count (>150 x 10(3)/microl) for more than 5 years without additional treatments, and had no signs of steatosis. We then compared fasting plasma glucose, serum insulin and adiponectin, and homoeostasis model assessment of IR (HOMA-IR) and HOMA-beta indices between the groups.
There were no significant differences in IR/secretion-associated markers or serum adiponectin. Multivariate analysis demonstrated that the presence of HCV was not an independent predictor of IR. HOMA-IR was strongly correlated with waist circumferences and serum gamma-glutamyltransferase in HCV carriers, but not with serum aminotransferase, high-sensitivity C-reactive protein, hyaluronic acid or HCV core antigen.
These results suggest that the presence of HCV alone does not affect IR. Coexistence of hepatitis, steatosis and/or fibrosis may be important to the pathogenesis of IR induced by chronic HCV infection.
Liver international: official journal of the International Association for the Study of the Liver 04/2008; 28(8):1104-11. · 3.82 Impact Factor
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ABSTRACT: Here we report two patients with hematological malignancies associated with complications of fatal cardiac zygomycosis. The first case, a 72-year-old man with myelodysplastic syndrome being treated with low-dose cytarabine, died of sudden cardiac arrest. An autopsy revealed disseminated zygomycosis accompanied with occlusion of the coronary artery by fungal thrombi. The second case, a 52-year-old woman with acute lymphoblastic leukemia, developed febrile neutropenia and skin eruptions with induration on the face and extremities during the first induction chemotherapy. She experienced sudden bradycardia with unstable hemodynamics and died of acute myocardial infarction. Histological examination of a skin biopsy demonstrated zygomycosis. In light of the above, it should be kept in mind that cardiac zygomycosis might occur in hematologically compromised patients presenting with acute myocardial infarction.
Internal Medicine 02/2008; 47(9):839-42. · 0.94 Impact Factor
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Pancreas 09/2006; 33(2):203-5. · 2.39 Impact Factor
