Ultrasonographic diagnosis of ileo-ileal intussusception secondary to Vanek's tumor.

Intussusception is a common condition of bowel obstruction in pediatric patients. However, 5% of all cases occur in adults, mostly aged over fifty, with no difference based on sex, representing about 1% of all causes of bowel obstruction. Compared to pediatric population, it is triggered by a pathologic lead point in about 85% of cases, represented in 60% of cases by malignant and benign neoplasms. Among these neoplasms, an inflammatory fibroid polyp (IFP), a benign neoplastic submucosal lesion also known as Vanek's tumor, is considered a very uncommon cause of adult intussusception. Clinical presentation could differ by location and size of tumor, and may include abdominal pain, nausea, vomiting, diarrhea or constipation, bleeding, weight loss, palpable abdominal mass, bowel obstruction, and gastrointestinal bleeding. Considering its common and non-specific symptoms, radiologic imaging plays a key role in the diagnosis of an IFP, especially computed tomography (CT) scan, which represents the most sensitive modality to confirm intussusception. However, bowel sonography (BS) has become an accurate procedure in various pathological intestinal diseases, also including intussusception. In this paper, we report a rare case of ileo-ileal intussusception secondary to Vanek's tumor diagnosed by BS.

Neuromarketing empirical approaches and food choice: A systematic review.

Consumers' food choices are often driven by reasons of which consumers are not fully aware. Decision-making about food is influenced by a complex set of emotions, feelings, attitudes, and values that are impossible to assess simply by asking consumers their opinions. Indeed, traditional techniques, such as self-reports or interviews, mainly allow the measurement of conscious and rational reactions to a product or advertising. Recently, there has been a rapidly growing interest in the multidisciplinary field of "neuromarketing," which takes advantage of neuroscientific techniques to study consumer behavior. This discipline applies neuroscientific methods and tools that allow the measurement of consumers' emotional and spontaneous reactions in a more objective and observable way. The aim of this paper is (a) to describe neuromarketing's underlying assumptions, techniques, and the advantages of this perspective, examining the scientific literature on the use of neuromarketing in food studies; and (b) to suggest best practices to apply this novel approach in the food marketing domain, with a specific focus on non-invasive methods. Finally, although the perception of nutritional elements has already been explored, the health content of labels, the presence of additives, and the evaluation of the information conveyed by food packaging remain other possible elements of interest in future food neuromarketing research.

Hepatocellular carcinoma recurrence in patients with curative resection or ablation: impact of HCV eradication does not depend on the use of interferon.

BACKGROUND: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. AIM: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. METHODS: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. RESULTS: TTR by Kaplan-Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. CONCLUSION: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used.

Risk factors in gastric cancer.

STATE OF THE ART: Gastric cancer (GC) is still a major health problem worldwide due to its frequency, poor prognosis and limited treatment options. At present prevention is likely to be the most effective means of reducing the incidence and mortality from this disease. The most important etiological factors implicated in gastric carcinogenesis are diet and Helicobacter pylori (H. pylori) infection. High intake of salted, pickled or smoked foods, as well as dried fish and meat and refined carbohydrates significantly increased the risk of developing GC while fibers, fresh vegetables and fruit were found to be inversely associated with GC risk. Epidemiological investigations (retrospective, case-control and prospective) and several meta-analyses have demonstrated that concurrent or previous H. pylori infection is associated with an increased risk of GC in respect to uninfected people. H. pylori colonizes gastric mucosa where it induces a complex inflammatory and immune reaction that on time leads to a severe mucosal damage i.e., atrophy, intestinal metaplasia (IM) and dysplasia. The risk of GC is closely related to the grade and extension of gastric atrophy, IM and dysplasia. PERSPECTIVES AND CONCLUSIONS: Today a plausible program for GC prevention means: (1) a correct dietary habit since childhood increasing vegetables and fruit intake, (2) a decrease of H. pylori spread improving family and community sanitation and hygiene, (3) a search and treat H. pylori strategy in offspring of GC, (4) a search and treat H. pylori strategy in patients with chronic atrophic gastritis and intestinal metaplasia (IM), (5) a careful endoscopic and histologic follow-up if precancerous lesions persist irrespective of H. pylori eradication.

Increased mucosal nitric oxide production in ulcerative colitis is mediated in part by the enteroglial-derived S100B protein.

In the central nervous system glial-derived S100B protein has been associated with inflammation via nitric oxide (NO) production. As the role of enteroglial cells in inflammatory bowel disease has been poorly investigated in humans, we evaluated the association of S100B and NO production in ulcerative colitis (UC). S100B mRNA and protein expression, inducible NO synthase (iNOS) expression, and NO production were evaluated in rectal biopsies from 30 controls and 35 UC patients. To verify the correlation between S100B and NO production, biopsies were exposed to S100B, in the presence or absence of specific receptor for advanced glycation end-products (RAGE) blocking antibody, to measure iNOS expression and nitrite production. S100B and iNOS expression were evaluated after incubation of biopsies with lipopolysaccharides (LPS) + interferon-gamma (IFN-gamma) in the presence of anti-RAGE or anti-S100B antibodies or budesonide. S100B mRNA and protein expression, iNOS expression and NO production were significantly higher in the rectal mucosa of patients compared to that of controls. Exogenous S100B induced a significant increase in both iNOS expression and NO production in controls and UC patients; this increase was inhibited by specific anti-RAGE blocking antibody. Incubation with LPS + IFN-gamma induced a significant increase in S100B mRNA and protein expression, together with increased iNOS expression and NO production. LPS + IFN-gamma-induced S100B up-regulation was not affected by budesonide, while iNOS expression and NO production were significantly inhibited by both specific anti-RAGE and anti-S100B blocking antibodies. Enteroglial-derived S100B up-regulation in UC participates in NO production, involving RAGE in a steroid insensitive pathway.

Methodology and indications of H2-breath testing in gastrointestinal diseases: the Rome Consensus Conference.

BACKGROUND: Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. AIM: The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. METHODS: Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. RESULTS AND CONCLUSIONS: The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

Interleukin-13 mucosal production in Helicobacter pylori-related gastric diseases.

UNLABELLED: A shift from Th1 (IFN-gamma) towards Th2 (IL-4)-type immune response was found in patients with gastric cancer and dysplasia. Recently, IL-13 has been described as a central mediator of Th2-dominant immune response in different inflammatory diseases. AIM AND METHODS: to analyse, by Enzyme-Linked-Immuno-SPOT (ELISPOT) assay and immunohistochemistry, the IL-13 production of mononuclear cells obtained from gastric biopsies of 19 H. pylori-negative subjects and 23 H. pylori-positive patients. RESULTS: By ELISPOT, we did not find any significant variation of the spot range number of IL-13, IL-4 and IFN-gamma secreting cells, irrespective of H. pylori status. After antigenic exposition, the spot range for IL-13, IL-4 and IFN-gamma significantly increased (p<.0001) only in H. pylori-positive patients. A prevalent Th1 (IFN-gamma) immunoresponse was observed in 2/23 cases with active gastritis, while a prevalent Th2 (IL-13 and IL-4) was detected in 5/23 cases all with atrophic chronic gastritis of whom two with intestinal metaplasia. By immunohistochemistry, IL-13, IL-4 and IFN-gamma were detectable in all cases directly related to the inflammatory infiltrate. In the two cases with intestinal metaplasia, IL-13 and IL-4 were localised in both inflammatory and epithelial cells. This immunopattern was confirmed in selected additional 10 cases of H. pylori-positive chronic atrophic gastritis with intestinal metaplasia and 10 cases of intestinal type gastric cancer. CONCLUSION: These preliminary results suggest that IL-13 could be implicated in the different outcome of H. pylori infection.

Low-dose aspirin reduces the gene expression of gastrokine-1 in the antral mucosa of healthy subjects.

BACKGROUND: Gastrokine 1 (GKN1), one of the most abundant transcripts in normal stomach, is down-regulated by Helicobacter pylori infection. Aspirin (ASA), which is often used for secondary prevention of cardiovascular events, can damage gastric-duodenal mucosa within 1 or 2 h of ingestion. AIM: To study the gastric mucosal expression of GKN1 during acute low-dose ASA consumption. METHODS: Ten H. pylori-negative human volunteers took 100 mg ASA per day for 1 week, and underwent multiple upper GI endoscopies. GKN1 expression was analysed in antral and corpus mucosa by quantitative reverse-transcriptase polymerase chain reaction, western blot and immunohistochemistry (IHC). Gastric mucosal damage was detected endoscopically and histologically. RESULTS: Gastrokine 1 was similarly expressed in both antral and corpus mucosa. The use of low-dose ASA led to a significant decrease (3.07 a.u. vs. 0.23 a.u., P < 0.001) in antrum at day 7, while GKN1 transcript levels in corpus mucosa were slightly elevated (twofold, P < 0.005). Western blot and IHC confirmed these changes at the protein level. Furthermore, IHC revealed a vesicular staining pattern in the cytoplasm for GKN1 that was confirmed by transfected human gastric adenocarcinoma cell line expressing GKN1. CONCLUSION: Our data demonstrated that low-dose ASA downregulates GKN1 expression specifically in antral mucosa.

Gastrokine 1 expression in patients with and without Helicobacter pylori infection.

BACKGROUND: To understand the molecular changes underlying Helicobacter pylori-related gastric diseases is mandatory to prevent gastric cancer. Proteomic technology is providing a rapid expansion of the basic knowledge, particularly in the discovery of new biomarkers involved in the tumourigenesis. AIM: To characterise changes in protein expression level of the gastric mucosa in H. pylori-infected patients. METHODS: The population enrolled comprised 41 dyspeptic patients. Proteins extracted from gastric mucosal specimens were analysed by 2-dimensional electrophoresis, sequenced by MALDI-TOF and identified by Edman's degradation. RESULTS: Twenty-one out of 41 patients had H. pylori infection of whom 17 had anti-CagA IgG antibodies. Several proteins were identified, of which Rho guanosine diphosphatase dissociation inhibitor alpha and heat shock protein 27 increased and glutathione transferase and antrum mucosa protein-18 decreased in H. pylori-positive in respect to H. pylori-negative patients. Interestingly, antrum mucosa protein-18, currently referred as gastrokine-1, showed two isoforms differing in the first N-terminal amino acid residue. Both gastrokine-1 isoforms were observed in the H. pylori-negative group whereas a lower expression or even absence of the gastrokine-1 basic isoform was found in a subgroup (7/21) of H. pylori-positive patients with moderate-severe gastritis. CONCLUSION: Our study demonstrated the presence of gastrokine-1 isoforms of which the basic isoform was reduced in a subset of patients with H. pylori infection.

Gastric adenomas: relationship between clinicopathological findings, Helicobacter pylori infection, APC mutations and COX-2 expression.

Gastric adenomas are rare neoplastic growths characterized by localized polypoid proliferations of dysplastic epithelium that tend to progress to infiltrating adenocarcinoma. Therefore, the identification of molecular markers that could reliably recognize adenomas at risk of progression is advocated in the clinical management. In this study we investigated, in a series of gastric adenoma specimens from an area at high risk of gastric cancer, the relationship between clinicopathological characteristics of adenoma and Helicobacter pylori infection, APC mutational status, and COX-2 and the down-stream enzyme mPGES1 expression. Helicobacter pylori infection, detected in 24%, and 33% by histology and PCR analyses, respectively, did not show any relationship with growth pattern, localization, size, dysplasia grade and presence of synchronous cancer. Pathogenetic mutations of MCR region (codons 1269-1589) of the APC gene were detected only in one case corresponding to a single, small size, low grade, H. pylori-negative adenoma. The expression of COX-2 largely matched that of mPGES(1). Both were overexpressed in 79% of cases showing a relationship with high-grade dysplasia, size >10 mm and presence of a synchronous carcinoma. In conclusion, COX-2 may play a key role in the development and progression of gastric adenoma and could be an attractive target in the management of gastric adenoma at major risk of cancer development.

Twice-daily standard dose of omeprazole achieves the necessary level of acid inhibition for Helicobacter pylori eradication. A randomized controlled trial using standard and double doses of omeprazole in triple therapy.

Antibiotic resistances and level of acid inhibition may affect the outcome of eradicating regimens for H. pylori. To evaluate the impact of different degrees of acid inhibition on the efficacy of triple treatment, we treated 323 patients with H. pylori infection with clarithromycin and tinidazole plus omeprazole, either 20 mg bid or 40 mg bid. Gastric biopsies and antimicrobial susceptibility testing were performed. Eradication was evaluated by means of breath test. Eradication rates were (intention to treat and per protocol) 83.3 and 84.3% in patients receiving 40 mg omeprazole and 81.9 and 84.1% in those receiving 80 mg omeprazole. Culture was successful in 218 patients (68.7%). Resistance to clarithromycin and metronidazole were found in 13.7 and 20.6%, respectively. Eighteen further patients (8.2%) presented double resistance. Resistance was comparable across the two groups. In resistant patients the eradication rate was significantly lower (66.6% [95% CI, 56-76%], vs 86% [95% CI, 78-91%]; P = 0.001). Antibiotic resistance (OR, 2.73; 95% CI, 1.4-5.3) and smoking (OR, 2.68; 95% CI, 1.4-5.2) were independent predictors of eradication failure. Omeprazole, 20 mg bid, achieves the optimal acid inhibition in H. pylori eradication. Increasing antisecretory activity does not significantly enhance cure rates.

Review article: helicobacter pylori and molecular events in precancerous gastric lesions.

Gastric cancer can be divided into intestinal type and diffuse type that differ substantially in epidemiology and pathogenesis. The most important aetiological factor associated both with intestinal and diffuse gastric cancer, is Helicobacter pylori. Exposure of gastric epithelial cells to H. pylori results in an inflammatory reaction with the production of reactive oxygen species and nitric oxide that, in turn, deaminates DNA causing mutations. The complex interplay between H. pylori strain, inflammation and host characteristics may directly promote diffuse type gastric cancer or induce a cascade of morphological events, i.e. atrophy, intestinal metaplasia and dysplasia, finally leading to intestinal type gastric cancer. Two mechanisms, genetic and epigenetic have been held to play a role in the molecular alterations underlying gastric carcinogenesis. The former, comprising changes in the DNA sequence, is irreversible; the latter, involving DNA methylation, is potentially reversible by eliminating the triggering agents. If H. pylori is eradicated before development of stable mutations, the risk of gastric cancer will likely be prevented. Thus, eradication of H. pylori might immediately reduce the risk of diffuse type gastric cancer, whereas prevention of intestinal type gastric cancer may be less effective if patients are treated later in the evolution of the carcinogenic process.

Is there a link between environmental factors and a genetic predisposition to cancer? A lesson from a familial cluster of gastric cancers.

To determine the prevalence of gastric precancerous lesions and mucosal genetic alterations in relatives of a cluster of familial gastric cancer (FGC), we studied a kindred spanning two generations. The founder, daughter and niece underwent surgery for gastric cancer (GC); a son and other two daughters of the founder, presented with chronic dyspepsia. In all subjects, gastric mucosa samples were analysed for pathological features, Helicobacter pylori infection, microsatellite (MIN) and chromosomal (CIN) instability. The overexpression of mp53 and c-myc, and cytoplasmic beta-catenin delocalisation were found in the 2 younger cancer patients. All GC and gastritis patients had normal E-cadherin expression and were MIN-negative. Aneuploidy characterised all GC cases, and mixed euploid and aneuploid cell populations were present in the gastric biopsies from two of three 'at-risk' relatives. These two subjects, one of whom had severe active gastritis, and gastric mp53 and c-myc expression, were CagA-positive H. pylori-infected. DNA aneuploidy, p53 and c-myc expression disappeared after H. pylori eradication. In this FGC cluster, genetic abnormalities were found in first-degree relatives (3 patients) only in presence of H. pylori infection (2 cases H. pylori-positive versus 1 case H. pylori-negative) supporting the hypothesis that, besides the influence of a genetic profile, FGC may be, at least partly, mediated by intrafamilial clustering of H. pylori infection.

Acid exposure and altered acid clearance in GERD patients treated for Helicobacter pylori infection.

BACKGROUND: After the eradication of Helicobacter pylori, an increased incidence of gastroesophageal reflux disease and acid gastric secretion have been reported. AIM: To evaluate the effect of Helicobacter pylori-eradication on proximal and distal gastroesophageal reflux and acid clearance in patients with gastroesophageal reflux disease. PATIENTS AND METHODS: Sixty-eight gastroesophageal reflux disease patients (age range 18-61 years) were studied by upper endoscopy. All underwent esophageal manometry and dual probe 24-h pH-metry. RESULTS: Percent of time at pH<4 was significantly increased in the proximal esophagus of Helicobacter pylori-eradicated patients compared to Helicobacter pylori-negative (2.4+/-0.5 vs. 1.0+/-0.2; p<0.01); no differences were found in the distal esophagus (14.0+/-3.7 vs. 9.0+/-1.4%, NS). The total number of reflux episodes was significantly higher in the proximal oesophagus of Helicobacter pylori-eradicated patients (37+/-3 vs. 22+/-3, p<0.05). In the distal esophagus, acid clearance was significantly longer, both during total time (1.4+/-0.2 vs. 0.8+/-0.7 min, p<0.01), and in the supine period (8.5+/-2.7 vs. 2.7+/-0.4 min, p<0.05). No differences were reported in the manometric parameters of the two groups of patients. CONCLUSION: In patients with gastroesophageal reflux disease, Helicobacter pylori eradication is associated with increased acid exposure of the proximal esophagus and delayed distal acid clearance.

Review article: molecular basis of gastric carcinogenesis.

Gastric cancer is constituted by two histomorphological entities 'intestinal' and 'diffuse', however lesions with similar morphologies may differ in biological aggressiveness and response to therapy. Two distinct molecular pathways have been identified in gastric carcinogenesis: the microsatellite mutator phenotype and a phenotype associated with chromosomal and intrachromosomal instability. Mounting evidence suggests that microsatellite mutator phenotype alterations and expression of the products of cancer-related genes are early markers of cell transformation, and may serve to identify the gastric carcinoma histotypes. The lack of a clear genetic basis, lends weight to the notion that gastric cancer is not a monomorphic entity but may be affected by environmental factors. Helicobacter pylori is the most important environmental risk factor associated with sporadic gastric cancer. Exposure of gastric epithelial cells to bacterium results in the generation of reactive oxygen species and inducible nitric oxide synthase that in turn may cause genetic alterations leading to cancer in a subset of subjects. Thus, gastric cancer may be considered the result of an interplay between host genetic profile and environmental toxic agents. The new technologies of molecular analysis will help to establish an individual's risk of developing gastric cancer and will lead to novel biological therapeutic strategies.

Reflux oesophagitis in adult coeliac disease: beneficial effect of a gluten free diet.

BACKGROUND: Coeliac disease patients show a number of gastrointestinal motor abnormalities, including a decrease in lower oesophageal sphincter pressure. The prevalence of endoscopic oesophagitis in these subjects however is unknown. AIM: To evaluate whether untreated adult coeliac patients had an increased prevalence of reflux oesophagitis and, if so, to assess whether a gluten free diet exerted any beneficial effect on gastro-oesophageal reflux disease (GORD) symptoms. PATIENTS AND METHODS: We retrospectively studied 205 coeliac patients (females/males 153/52, median age 32 years) who underwent endoscopy for duodenal biopsy and 400 non-coeliac subjects (females/males 244/156, median age 37 years) referred for endoscopy for upper gastrointestinal symptoms. Each patient was given a questionnaire for evaluation of GORD symptoms prior to and 4-12 months after endoscopy. Coeliac patients were given a gluten free diet. Oesophagitis patients of both groups, following an eight week course of omeprazole, were re-evaluated for GORD symptoms at four month intervals up to one year. Significance of differences was assessed by Fisher's exact test. RESULTS: Oesophagitis was present in 39/205 (19%, 95% confidence interval (CI) 13.8-25.0%) coeliac patients and in 32/400 (8%, 95% CI 5.5-11.1%) dyspeptic subjects. At the one year follow up, GORD symptoms relapsed in 10/39 (25.6%, 95% CI 13-42.1%) coeliacs with oesophagitis and in 23/32 (71.8%, 95% CI 53.2-86.2%) non-coeliac subjects with oesophagitis. CONCLUSION: Coeliac patients have a high prevalence of reflux oesophagitis. That a gluten free diet significantly decreased the relapse rate of GORD symptoms suggests that coeliac disease may represent a risk factor for development of reflux oesophagitis.

An immunodominant DQ8 restricted gliadin peptide activates small intestinal immune response in in vitro cultured mucosa from HLA-DQ8 positive but not HLA-DQ8 negative coeliac patients.

BACKGROUND: Studies on intestinal T cell clones from the mucosa of patients with coeliac disease have led to the identification of immunogenic gliadin epitopes. One is HLA-DQ8 restricted, its recognition by T cells being increased by introduction of negatively charged residues operated by tissue transglutaminase. AIM: To test HLA-DQ8 restricted epitope in both native (QYPSGQGSFQPSQQNPQA) and deamidated (QYPSGEGSFQPSQENPQA) forms in an organ culture system of treated coeliac mucosa from HLA-DQ8 positive and HLA-DQ8 negative patients. PATIENTS AND METHODS: Jejunal biopsies obtained from 10 patients with coeliac disease (six HLA-DQ8 positive and four HLA-DQ8 negative) were cultured in vitro with a peptic-tryptic digest (PT) of gliadin, or with the native (peptide A) or deamidated (peptide B) peptide. Intraepithelial CD3(+) and lamina propria total CD25(+) and CD3(+)CD25(+) cells were counted, lamina propria intercellular adhesion molecule 1 (ICAM-1) expression was evaluated, as well as that of Fas molecules on epithelial cells. RESULTS: In HLA-DQ8 positive, but not in HLA-DQ8 negative, coeliacs the density of intraepithelial CD3(+) cells, lamina propria total CD25(+), and CD3(+)CD25(+) cells, as well as expression of ICAM-1 and Fas molecules were significantly increased in biopsies cultured with PT, peptide A, or peptide B compared with biopsies cultured in medium alone. CONCLUSION: These data show that the DQ8 restricted gliadin peptide is immunogenic only in the intestinal mucosa of HLA-DQ8 positive coeliac patients in both native and deamidated forms.

Long-lasting intestinal bleeding in an old patient with multiple mucosal vascular abnormalities and Glanzmann's thrombasthenia: 3-year pharmacological management.

A 75-year-old woman with Glanzmann's thrombasthenia was admitted because of persistent melaena. Endoscopic examination showed multiple angiodysplastic lesions, with active bleeding in small and large bowel. Electro-coagulation of some lesions, octreotide, conjugated oestrogens and selective embolization of jejunal vessels did not change transfusion requirements. After 8 month-transfusions, ethinylestradiol + norethisterone in association with octreotide was started, leading to no transfusion over the following 9 months. Bleeding recurred after withdrawing octreotide and substituting ethinylestradiol + norgestrel for the ethinylestradiol + norethisterone combination. Re-introduction of octreotide did not improve bleeding; however, a reduction of transfusion requirement was observed when the ethinylestradiol + norethisterone pill was re-administered. The association of octreotide and of an oestrogen-progesterone combination was helpful in the difficult management of recurrent bleeding in this patient with diffuse gastrointestinal vascular abnormalities and a severe condition predisposing to bleeding.

Up-regulation of heparin binding epidermal growth factor-like growth factor and amphiregulin expression in Helicobacter pylori-infected human gastric mucosa.

BACKGROUND: Host response plays a major role in pathogenesis of Helicobacter pylori-induced gastroduodenal disease including adenocarcinoma of distal stomach. Epidermal growth factor-related growth factors are important modulators of gastric homeostasis in normal and damaged gastrointestinal mucosa. AIM: To evaluate expression of heparin binding epidermal growth factor and amphiregulin in antral mucosa of Helicobacter pylori-infected and non-infected dyspeptic patients and to correlate levels of heparin binding-epidermal growth factor and amphiregulin mRNA with mitogenic activity of gastric epithelial cells. METHODS: A total of 10 Helicobacter pylori-infected and 15 Helicobacter pylori non-infected (10 with and 5 without gastritis) dyspeptic patients were studied. Diagnosis of Helicobacter pylori infection was based on rapid urease test and histology. Heparin binding-epidermal growth factor and amphiregulin mRNA expression in antral mucosa were assessed by reverse transcriptase-polymerase chain reaction. Protein expression and localization of both peptides were determined by immunohistochemistry. Mitogenic activity of antral gastric mucosa was assessed by determination of proliferating cell nuclear antigen labelling index by immunohistochemistry. RESULTS: Heparin binding-epidermal growth factor and amphiregulin mRNA expression increased in Helicobacter pylori-infected vs Helicobacter pylori non-infected patients. Heparin binding-epidermal growth factor and amphiregulin immunostaining was more intense and deeper in gastric gland compartment in infected mucosa than in non-infected mucosa. Increase in heparin binding-epidermal growth factor and amphiregulin mRNA expression significantly correlated with increase in proliferating cell nuclear antigen labelling index. CONCLUSIONS: Helicobacter pylori gastritis is associated with up-regulation of heparin binding-epidermal growth factor and amphiregulin which correlates with increased mitogenic activity of gastric mucosa. Increased heparin binding-epidermal growth factor and amphiregulin expression is postulated to contribute to reparative response of gastric mucosa to Helicobacter pylori infection.