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Dear Editor, In the paper by Akkaya N, et al., Helicobacter pylori (H. pylori) infection was evaluated in 65 patients with fibromyalgia syndrome (FM) and in 41 healthy controls, using two different serological methods [1]. In particular, the authors used anti-H. pylori IgA antibodies, a serological test with unacceptably low sensitivity (63.4%) and specificity (67.6%), yielding a poor overall accuracy of 67.2% in all ages [2]. Furthermore, it was demonstrated that this test possesses an even lower overall accuracy rate in the ages over 18 years (51.8%) [2], thereby rendering it practically useless and a waste of time and resources for the patients evaluated in the study by Akkaya N, et al. [1]. Therefore, this comes to no surprise why the authors found no significant difference in the prevalence of H. pylori IgA antibodies between their FM patients and controls (p=0.169) [1]. It would be interesting to know why the authors chose this particular test for their study in spite of its poor performance shown before. On another aspect, the authors reported that they found no statistically significant differences regarding mainly the clinical features (sleep disturbance, fatigue, stiffness, headache, subjective soft-tissue swelling, paresthesia, dysmenorrhea, female urethral syndrome, irritable bowel syndrome, and anxiety), anxiety and depression subscale of Fibromyalgia Impact Questionnaire, history of depression, and previous treatment for depression between the two study groups (FM patients and controls) [1]. We believe that this is a paradox, since one would expect that FM patients with a higher prevalence of H. pylori infection (according to the H. pylori IgG serology) should present with more profound clinical features compared with a group of healthy controls. This paradox, however, can be explained by the fact that although this serological test establishes the presence of previous H. pylori infection, it does not discriminate between current and old infections. Such a distinction is crucial because only current H. pylori infection induces both humoral and cellular immune responses that cross-react with host components, owing to the sharing of homologous epitopes (molecular mimicry), thereby contributing and/or perpetuating tissue damage [3], and possibly, the development of the clinical features of FM; immunological (cellular/humoral) responses are increasingly recognized as being essential in the initiation and progression of FM syndrome [4]. Moreover, eradicating H. pylori infection might delay the progression of this disease, particularly at earlier stages. Thus, it would be interesting to know why the authors chose a serological IgG test, instead of histology, the practical gold standard for the diagnosis of current H. pylori infection, or at least the C-urease breath test, the noninvasive test of choice for H. pylori infection. Although the latter test requires fasting, false-negative results may occur if antibiotics have been used within the previous 4 weeks and false-positive results can occur from urease present in the mouth [5], this is considered a reliable alternative to the histologic method for the detection of H. pylori infection. By using these two methods signifying active H. pylori infection, the authors C. Zavos : J. Kountouras : P. Katsinelos : S. A. Polyzos : G. Deretzi :N. Zavos : E. Gavalas : I. Pilpilidis :D. Tzilves Department of Gastroenterology, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece

Management of giant pedunculated polyps can be a challenge for therapeutic endoscopists, mainly because such polyps are not found in commonplace and experience from their management is limited. We describe a novel use of endoclips that induces significant polyp volume reduction, thereby facilitating the endoscopic removal of giant pedunculated polyps.

We read with interest the paper by Theoharides et al. (2008), who concluded that mast cells can be stimulated by corticotropin-releasing hormone, secreted under stress, to release mediators including histamine, interleukin (IL)-8, tryptase and vascular endothelial growth factor (VEGF), which disrupt the blood–brain barrier (BBB) permitting metastases of lung and mammary adenocarcinomas. Helicobacter pylori infection (Hp-I) appears to be a common denominator of lung, mammary and gastrointestinal (GI) tract cancers contributing to the mentioned stress–mast cell–BBB disruption–brain metastases sequence of these malignancies. Indeed, apart from GI malignancies (mainly gastric cancer), Hp-I has been involved in lung and breast cancers (Prelipcean et al., 2007; Moss and Malfertheiner, 2007; Kountouras et al., 2004), mainly via induction of the oncogenic growth factor gastrin which contributes to lung and breast carcinogenesis and metastasis (Yonemori et al., 2005; Gugger and Reubi, 1999); an elevated pro-gastrin-releasing peptide level before prophylactic cranial irradiation appears to be significantly related to the first failure event due to brainmetastases and survival of lung carcinoma (Yonemori et al., 2005). Physical and psychological stresses are accepted as triggers and/or modifiers of various GI disorders clinical course. Stress can also synergize with other pathogenic factors such as Hp to produce upper GI malignancies. The brain–gut axis provides the anatomical basis through which emotions and environmental influences modulate the GI function through the regulation of GI immune system and mucosal inflammation; in this regard, mucosal mast cells – at cellular level – and corticotropin releasing factor (CRF), at molecular level, appear to play a critical role (Caso et al., 2008).

Epplein and colleagues ([1][1]) reported that the overall Helicobacter pylori ( H. pylori ) seropositivity was not associated with colorectal cancer risk, and seropositivity to specific H. pylori proteins, particularly the toxin VacA antibodies, may be associated with a higher risk of colorectal

Helicobacter pylori might contribute to cancer and/or bone marrow-derived stem cell-related gastrointestinal oncogenesis

Dear Sir, In their recent article in the JCC, Calabrese et al.1 concluded that resumption of low-dose smoking in ex-smokers with refractory ulcerative colitis (UC) may ameliorate signs and symptoms and smokers should be followed for smoking-associated risks including cardiovascular disorders and cancers; they discussed only anecdotal data suggesting that smoking may be associated with a decreased risk of colon carcinoma in UC. Although their considerations might be partially correct, they probably reflect only one side of the coin. A considerable body of evidence has linked smoking with UC-associated colorectal cancer.2, …

Prevalence and Natural History of Low-Grade Dysplasia in Patients With Barrett’s Esophagus Christos Zavos*, Romy E. Verbeek, Max Leenders, Leon M. Moons, Frank P. Vleggaar, Peter D. Siersema Gastroenterology and Hepatology, UMC Utrecht, Utrecht, Netherlands Introduction: Previous studies have been inconsistent with regard to the prevalence of low-grade dysplasia (LGD) in patients with Barrett’s esophagus (BE) and the rate of progression of LGD to high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Aims: To assess the prevalence and natural history of LGD in patients with BE and LGD. Methods: All patients with a diagnosis of BE and LGD between 1985 and 2009 of whom pathology specimens were available in the nationwide pathology database (PALGA) were included and followed-up for progression to HGD and/or EAC. Median age at diagnosis and time to progression were assessed, as well as sex, p53 status and type of hospital where biopsies were taken. Patients were excluded if they had a prior diagnosis of HGD and/or EAC or if no follow-up endoscopic biopsies ( 3 months after the initial LGD diagnosis) were available. Results: In total, 10,152 diagnoses of BE were included in the database, of which 2,215 patients (21.8%) were diagnosed with LGD, mostly males (71.5%) with a median age of 62 years at diagnosis. A decreasing trend over time in LGD diagnoses as proportion of all BE diagnoses was observed using the Cochran-Armitage test (p 0.0001). At least one follow-up biopsy was available in 1,638 patients (73.9%). After a median follow-up of 6.7 years, 137 patients (8.4%) progressed to HGD and 72 (4.4%) progressed to EAC. Median time to progression to HGD was 8.42 (4.4113.62) years and to EAC was 8.28 (3.30-13.2) years. In 157 patients tested for p53 status, 104 (66.2%) were positive, of which 8 progressed to HGD and 3 to EAC. Of the patients having at least one follow-up biopsy, 213 (13.0%) had biopsies taken only at an academic hospital and 262 (16.0%) at both academic and nonacademic hospitals. Patients with biopsies coming from both academic, and academic and non-academic hospitals had a higher progression to HGD (53.3%) and EAC (33.3%) compared to non-academic hospitals. Conclusion: The prevalence of LGD in BE in a large cohort of patients with a diagnosis of BE is relatively high (21.8%), although the relative numbers of LGD are decreasing over time suggesting an increasing awareness for BE. Moreover, a considerable number of patients with LGD will develop HGD (8.4%) or EAC (4.4%) after a median follow-up of 6.7 years, demonstrating that endoscopic surveillance and/ or treatment should be considered in this subgroup of BE patients.

Induction of Interleukin-8 Expression by Helicobacter Pylori Infection in Patients with Endoscopy-Negative Gastroesophageal Reflux Disease

munohistochemistry colonic biopsy specimens, obtained by endoscopy, from 22 Greek patients (16 with Crohn’s disease and 6 with ulcerative colitis), which were stained for Bcl-2 and Bax [automatic immunostain (antibodies BioGenex)]. Ten out of 16 (62%) patients with Crohn’s disease and 3 out of 6 (50%) patients with ulcerative colitis demonstrated a Bax overexpression (>25% of cells stained). Moreover, Bcl-2 protein was overexpressed in 4 out of 16 (25%) patients with Crohn’s disease and in 3 out of 6 (50%) patients with ulcerative colitis. These preliminary results suggest a possible existence of a balance between cell pro-apoptotic and anti-apoptotic mechanisms in ulcerative colitis, indicated by Bax and Bcl-2 overexpression in 50% of the patients, and a great propensity of pro-apoptotic mechanisms in Crohn’s disease, indicated

Background: The degree of association between homocysteine metabolism and inflammatory bowel diseases (IBD) remains unknown and the association between hyperhomocysteinemia and thrombosis and oncogenesis remains controversial in IBD. The aim of this study was to investigate the serum homocysteine levels in patients with Crohn’s disease (CD) and ulcerative colitis (UC) and the potential folate therapeutic regimen against hyperhomocysteinemia. Methods: Serum levels of homocysteine were measured in 55 patients with (IBD) (28/55 CD and 31/55 UC patients). Patients with hyperhomocysteinemia received 15mg folate/day for 2 12 months. Levels of serum homocysteine were measured during folate treatment. Results: Hyperomocysteinemia was prevalent in 28/55 (50.90%) of patients studied (13 CD and 15 UC patients). Mean homocysteine levels among the patients with hyperhomocysteinemia were 17.72mmol/L with range 14.23 29.88mmol/L (normal values 3.7 13.9mmol/L) (Table 1). Folate was administered in 24/28 patients and serum levels of homocysteine were re-measured in 17 patients. In 14/17 patients lower levels of homocysteine were observed with a mean reduction of 5.25mmol/L by folate treatment. The baseline levels of homocysteine in these patients were 17.01 mmol/L and posttreatment 11.75mmol/L.

Summary is a complex immune response against the harmful effects of diverse stimuli within the nervous system; it is considered a characteristic and critical component in nearly all neuroinflammatory disorders and could be initiated by peripheral inflammatory conditions. Helicobacter pylori (H. pylori), a potential gastrointestinal pathogen, induces humoral and cellular immune responses that, owing to the sharing of homologous epitopes (molecular mimicry), cross-react with nervous system components, contributing and perpetuating neural tissue damage. current evidence implicates H. pylori in neurological disorders of the central nervous system (cerebrovascular diseases, mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, seizure, migraine, multiple sclerosis and neuromyelitis optica), the peripheral nervous system (Guillain Barre syndrome) and ophthalmic disorders (glaucoma) through various potential pathogenetic mechanisms. More clinical and experimental studies are required to attest the impact of H. pylori infection on neuroinflammatory disorders, thereby establishing H. pylori as a neurological pathogen. Immunogastroenterology 2013; 2:79-89

Jeon et al. (1) stated that infectious agents might have an impact on cardiovascular disease (CVD) and metabolic syndrome, potentially mediated by increased inflammatory markers, including C-reactive protein (CRP) and interleukin (IL)-6. However, epidemiological studies investigating the impact of pathogen burden on diabetes have been limited; cross-sectional studies examining systemic pathogens and insulin resistance (IR) or prevalent diabetes have produced equivocal findings, and Helicobacter pylori infection ( Hp -I) shows no association with IR or prevalent diabetes. We previously conducted a systematic review summarizing the epidemiological evidence regarding the association between Hp -I and IR quantitative-only indices (2). A positive association between Hp -I and homeostasis model assessment of insulin resistance …

Aims: An association between Helicobacter pylori (H. pylori) infection and glaucoma has been previously suggested. The aim of this study was to investigate the apoptotic and cell proliferation processes as potential common pathogenetic mechanisms underlying this association. Methods: Fifty-one glaucoma patients (33 female, mean age: 71.4±9.2 years) were initially enrolled. Biopsy specimens obtained on upper gastrointestinal (GI) endoscopy were evaluated for H. pylori presence, for expression of genes involved in apoptosis and cell proliferation (Ki-67, p53, Bcl-2), and for indices of cellular immune surveillance (T-lymphocytes (TLs) and B-lymphocytes (BLs)). Results: Of the 43 patients eligible for upper GI endoscopy, 90.7% were tested positive for H. pylori infection. Ki-67 was positively expressed in 81.25% patients with H. pylori infection and in 1 patient without H. pylori infection. p53 was positively expressed in 31.25% patients with H. pylori infection but not in the patients without H. pylori infection. Bcl-2 was positively expressed in 68.75% patients with H. pylori infection and in 1 patient without H. pylori infection. Ki-67, p53 and Bcl-2 were over-expressed in 19%, 25% and 37.5%, respectively, of the patients with H. pylori infection, but none of them was over-expressed in the patient without H. pylori infection. TL marker was positively expressed in all patients with H. pylori infection and in the one patient without H. pylori infection. BL marker was positively expressed only in one patient with this infection. Conclusion: H. pylori-induced oncogenes Ki-67, p53 and Bcl-2, and TLs involved in apoptotic and cell proliferation pathways might contribute to glaucomatous neuropathy, with an additional oncogenic potential. Immunogastroenterology 2012; 1:40-46

Aims: Serum ferritin and insulin resistance increase and adiponectin decreases with the severity of nonalcoholic fatty liver disease (NAFLD). The aims of this pilot study were: the evaluation of serum iron and ferritin, and ferritin/adiponectin ratio and ferritin by homeostatic model of assessment insulin resistance (HOMA-IR) product; ferritin relationship with adiponectin and HOMA- IR in NAFLD patients. Methods: Thirty patients with biopsy-proven NAFLD (15 with simple nonalcoholic fatty liver (NAFL), 15 with nonalcoholic steatohepatitis (NASH)) and 24 matched controls were recruited. Serum samples for ferritin, adiponectin and standard biochemical tests were obtained after overnight fasting. Results: Serum ferritin (ng/mL), ferritin/adiponectin ratio and ferritin by HOMA-IR product were higher in NAFL patients (96.9±12.4, 26.7±4.4, 245±50, respectively) than controls (58.3±11.0, 13.6±4.6, 92±31, respectively), and even higher in NASH patients (124.5±21.8, 35.5±9.6, 725±217, respectively). Serum ferritin was higher in more severe portal inflammation, without independently predicting it. However, both ferritin/adiponectin ratio (p=0.027) and ferritin by HOMA-IR product (p=0.017) could independent predict portal inflammation. Serum iron was similar irrespectively of the histological category. Serum ferritin (but not iron) correlated positively with HOMA-IR (rs=0.563; p

We read with interest the paper by Shiota et al. [1], who reported that older age and male sex were significantly associated with Alzheimer’s disease. Moreover, the authors reported a lack of association between Helicobacter pylori infection (Hp-I) status and Alzheimer’s disease in their Japanese cohort, suggesting that their findings might be explained by the much higher prevalence of Hp-I in the general Japanese than in the European population. We herein wish to emphasize two essential concerns regarding the methodological limitations which may render the results of this study highly debatable. The first is that both age and sex, found to be associated with Alzheimer’s disease, were not matched in the two study groups (p \ 0.001 and p = 0.01, respectively), and thus comparisons between the two study groups (i.e., Alzheimer’s disease patients and controls) cannot be expected to establish any firm conclusions. The second concern is that the very high Hp-I prevalence in the general Japanese population around 70 years old, reported by the authors, and, deductively, in the control group of the study, renders the study underpowered, meaning it requires probably thousands of participants in order to prove whether an association between Alzheimer’s disease and Hp-I can be established or excluded; it requires a very large population to be screened to prove or not a statistical difference in Hp-I among patients with Alzheimer’s disease and the general Japanese population. In view of the aforementioned methodological limitations, we deduce that this study can neither confirm the lack of association between the Hp-I status and Alzheimer’s disease in the Japanese population, nor is it comparable with the European studies indicating such an association [2–4].