Toru Shimosegawa

International consensus guidance statement on the management and treatment of IgG4-related disease

A. Khosroshahi, Z. S. Wallace, J. L. Crowe, T. Akamizu, A. Azumi, M. N. Carruthers, S. T. Chari, E. Della-Torre, L. Frulloni, H. Goto, P. A. Hart, T. Kamisawa, S. Kawa, M. Kawano, M. H. Kim, Y. Kodama, K. Kubota, M. M. Lerch, M. L€ ohr, Y. Masaki, S. Matsui, T. Mimori, S. Nakamura, T. Nakazawa, H. Ohara, K. Okazaki, J. H. Ryu, T. Saeki, N. Schleinitz, A. Shimatsu, T. Shimosegawa, H. Takahashi, M. Takahira, A. Tanaka, M. Topazian, H. Umehara, G. J. Webster, T. E. Witzig, M. Yamamoto, W. Zhang, T. Chiba, and J. H. Stone

The polymorphism interleukin 8 −251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population

Background:Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process. Aims: We investigated the effects of an interleukin 8 (IL-8) gene polymorphism on the risk of gastroduodenal diseases, the degree of H pylori induced gastritis, and IL-8 gene transcription. Subjects: The study was performed in 244 healthy control subjects and 690 H pylori positive patients with non-cardia gastric cancer, gastric ulcer, duodenal ulcer, or gastritis. Methods: We identified the IL-8 −251 A/T polymorphism by direct sequence analysis, and measured the gastritis score and serum pepsinogen (PG). The transcriptional promoter activity of the IL-8 gene was assessed by luciferase assay. Results:IL-8 −251A was associated with a higher risk of gastric cancer and gastric ulcer. Patients carrying IL-8 −251A showed an increased risk of gastric cancer (odds ratios (OR) 2.01 (95% confidence interval (CI) 1.38–2.92)) and gastric ulcer (OR 2.07 (95% CI 1.37–3.12)). Compared with patients younger than 49 years, atrophy and metaplasia scores in the antrum were significantly higher and the PG I/II ratio significantly lower in −251A carriers than in T/T carriers. In the in vitro assay, IL-8 −251A showed enhanced promoter activity in response to IL-1β or tumour necrosis factor α. Conclusions: The IL-8 −251A allele may be associated with progression of gastric atrophy in patients with H pylori infection, and may increase the risk of gastric cancer and gastric ulcer in Japanese people.

Helicobacter pylori infection prevents erosive reflux oesophagitis by decreasing gastric acid secretion

BACKGROUND Helicobacter pylori infection is less prevalent and atrophic gastritis is less extensive in patients with reflux oesophagitis than those without it, but few studies have examined this relationship directly. AIMS We investigated the relationship between H pylori infection, acid secretion, and reflux oesophagitis in Japanese subjects. SUBJECTS A total of 105 patients with erosive reflux oesophagitis were compared with 105 sex and age matched patients without reflux oesophagitis. METHODS The diagnosis of H pylori infection was made by histological examination of gastric mucosal biopsy specimens, rapid urease test, and detection of serum IgG antibodies. Acid secretion was assessed by the endoscopic gastrin test. RESULTS H pylori infection was present in 36 patients with erosive reflux oesophagitis (34.3%) and in 80 control subjects (76.2%) (odds ratio 0.163, 95% confidence interval 0.09–0.29). Overall acid secretion was significantly greater in patients with reflux oesophagitis. AmongH pylori positive patients, acid secretion was greater in patients with reflux oesophagitis than those without oesophagitis. CONCLUSION In Japan, erosive reflux oesophagitis occurs most often in the absence ofH pylori infection and gastric hyposecretion. Even in the presence of H pylori infection, reflux oesophagitis is more likely to develop in patients without gastric hyposecretion. H pylori infection may inhibit reflux oesophagitis by inducing hypoacidity.

Japanese clinical guidelines for autoimmune pancreatitis.

Objectives: As the patients with autoimmune pancreatitis (AIP) are increasing in Japan, the practical guideline for managing AIP is required to be established. Methods: Three committees (the professional committee for making clinical questions [CQs] and statements by Japanese specialists, the expert panelist committee for rating statements by the modified Delphi method, and the evaluating committee by moderators) were organized. Fifteen specialists for AIP extracted the specific clinical statements from a total of 871 literatures by PubMed search (∼1963-2008) and from a secondary database and made the CQs and statements. The expert panelists individually rated these clinical statements using a modified Delphi approach, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. Results: The professional committee made 13, 6, 6, and 11 CQs and statements for the concept and diagnosis, extrapancreatic lesions, differential diagnosis, and treatment, respectively. The expert panelists regarded them as valid after a 2-round modified Delphi approach. Conclusions: After evaluation by the moderators, the Japanese clinical guideline for AIP has been established. Further studies for the international guideline are needed after international consensus for diagnosis and treatment.

Changes in gastric acid secretion assayed by endoscopic gastrin test before and after Helicobacter pylori eradication.

BACKGROUND It remains controversial whether or not Helicobacter pyloriinfection causes altered gastric acid secretion. A novel test for evaluating gastric acid secretion (endoscopic gastrin test; EGT) has recently been developed. AIM To investigate by EGT the effects of H pylorieradication on the state of gastric acid secretion in patients with peptic ulcer. METHODS Twenty six patients with duodenal ulcer and 33 with gastric ulcer, for all of whomH pylori infection had been documented, were studied by EGT, histological examination of gastric mucosa, and measurement of plasma gastrin levels before and one and seven months after H pylori eradication. RESULTS In patients with duodenal ulcer, the mean EGT value beforeH pylori eradication was higher than that inH pylori negative controls, but it had decreased significantly seven months after the treatment. In contrast, the mean EGT value of patients with gastric ulcer beforeH pylori eradication was lower than that inH pylori negative controls, but it had increased one month after the treatment; this was followed by a slight decrease at seven months. In both groups, mean EGT values seven months after the treatment were not significantly different from the mean control value. CONCLUSIONS The reduced acid secretion in gastric ulcer patients and gastric acid hypersecretion in duodenal ulcer patients were both normalised after the clearance of H pylori.

The effects of lansoprazole on erosive reflux oesophagitis are influenced by CYP2C19 polymorphism

Background : The acid suppressive effect of lansoprazole is influenced by the P450 2C19 (CYP2C19) polymorphism.

Increased gastric acid secretion after Helicobacter pylori eradication may be a factor for developing reflux oesophagitis.

The role of acid secretion in reflux oesophagitis which may develop after H. pylori eradication is not well known.

In Vivo Raman Study of the Living Rat Esophagus and Stomach Using a Micro-Raman Probe under an Endoscope:

A small endoscope system equipped with a micro Raman probe is developed for in vivo Raman measurements in living rats. The measurements are done under anesthesia and artificial respiration to minimize the impact on the rats. Raman spectra of living rat esophagus and stomach are successfully measured. Our results suggest that the Raman spectra reflect subsurface tissue structure that cannot be distinguished in the endoscope image. After the experiments, rats recover without any aftereffects. It is verified that the Raman measurement using the present system is safe and noninvasive for rats.

Japanese consensus guidelines for management of autoimmune pancreatitis: II. Extrapancreatic lesions, differential diagnosis

• A variety of extrapancreatic lesions are reported to be complicated with AIP. Among those cited are close association with lachrymal and salivary gland lesions, hilar lymphadenopathy, interstitial pneumonitis, sclerosing cholangitis, retroperitoneal fibrosis, and tubulointerstitial nephritis. Description A variety of extrapancreatic lesions are reported to be complicated with AIP, and close associations have been pointed out with lachrymal and salivary gland lesions (Fig. 1) [1], hilar lymphadenopathy [2], sclerosing cholangitis [3, 4], retroperitoneal fibrosis (Fig. 2) [5], and tubulointerstitial nephritis [6]. Associations were also reported with hypophysitis [7], chronic thyroiditis [8], and prostatitis [9]. Other extrapancreatic involvements have been reported in a few cases [10–12]. Though it is not certain that all of them have a relation with AIP, extrapancreatic lesions are prevalent in the systemic organs (Table 1) [7–12], suggesting that AIP may be a member of IgG4related diseases. The extrapancreatic lesions appear synchronously or metachronously with the pancreatic lesion(s), share the same pathological conditions, and show favorable response to corticosteroid therapy; these characteristics indicate a common pathophysiological background. The lesions are usually detected by image tests and blood tests (CT, MRI, gallium scintigraphy, FDG-PET, and hormone assay); however, these should be confirmed by histological findings. Extrapancreatic lesions sometimes mimic, or are misdiagnosed as, primary lesions of the corresponding organs: lachrymal and salivary gland lesions for Sjogren’s syndrome, respiratory lesions for sarcoidosis, and sclerosing cholangitis for primary sclerosing cholangitis (PSC). Therefore, it is necessary to differentiate between IgG4related diseases and inherent diseases of the corresponding organs. When the pancreatic lesion is obscured, it may be difficult to detect these presumably IgG4-related extrapancreatic lesions. However, recognition of these extrapancreatic lesions should also aid in the correct diagnosis of AIP.

Cytochrome P450 2C19 polymorphism influences the preventive effect of lansoprazole on the recurrence of erosive reflux esophagitis

Background:  The efficacy of lansoprazole (LPZ) at inhibiting gastric acid secretion is influenced by cytochrome P450 2C19 (CYP2C19) polymorphism. The purpose of the present study was to investigate whether CYP2C19 polymorphism had an influence on the remission of erosive reflux esophagitis (RE) during maintenance therapy with LPZ.