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Rare truncating BRCA2 K3326X (rs11571833) and pathogenic CHEK2 I157T (rs17879961) variants have previously been implicated in familial pancreatic ductal adenocarcinoma (PDAC), but not in sporadic cases. The effect of both mutations in important DNA repair genes on sporadic PDAC risk may shed light on the genetic architecture of this disease. Both mutations were genotyped in germline DNA from 2,935 sporadic PDAC cases and 5,626 control subjects within the PANcreatic Disease ReseArch (PANDoRA) consortium. Risk estimates were evaluated using multivariate unconditional logistic regression with adjustment for possible confounders such as sex, age and country of origin. Statistical analyses were two-sided with p values

Background Although consensus guidelines suggest that patients with high-risk intraductal papillary mucinous neoplasms (IPMNs) should have surgery, a non-operative strategy is often selected in patients who are poor surgical candidates. The aim was to determine the risk of disease-related death from IPMN in patients with worrisome features or high-risk stigmata who were kept under observation. Methods A PubMed literature search was undertaken of articles published from August 1992 to June 2016 (updated October 2017). The methodology was developed from PRISMA and MOOSE checklists. Incidence proportions and rates of overall and IPMN-related deaths were calculated, with subgroup analyses for main-duct/mixed-type and branch-duct IPMNs. Quality of the studies, publication bias and heterogeneity were explored. Results Six studies reported data on overall mortality and eight described disease-specific mortality for 556 patients during follow-up ranging from 24·9 to 60·0 months. Pooled rates of overall and IPMN-related mortality were 30·9 (95 per cent c.i. 19·6 to 45·1) and 11·6 (6·0 to 21·2) per cent respectively. The pooled incidence rate for overall mortality was substantially higher than that for IPMN-related mortality: 78 (95 per cent c.i. 44 to 111) and 23 (9 to 37) per 1000 patient-years respectively. The pooled incidence rate for disease-specific mortality was considerably lower for branch-duct than for main-duct or mixed-type IPMNs: 5 (0 to 10) and 32 (12 to 52) per 1000 patient-years respectively. Conclusion In patients unfit for surgery, IPMN-related mortality among patients with worrisome features and high-risk stigmata is low, and the risk of death from other causes much higher.

Background: We investigated pretreatment fasting glucose as a predictor of patients’ important outcomes in breast and colorectal cancers undergoing targeted therapies. Patients and methods: In a historic cohort of 202 breast and 218 colorectal cancers treated with targeted agents from 1998 to 2009, we used the Kaplan–Meier method and the log-rank test to estimate survival through tertiles of fasting glucose and the Cox proportional hazards model for multivariate analysis stratified by primary site of cancer and including gender, age and body mass index. Results: The median follow-up was 20 months (1–128). At 60 months, 65% of patients in the lowest tertile of fasting glucose did not experiment disease progression compared with 34% in the highest tertile (P= 0.001). Seventy-six percent of females in the lowest tertile showed no progression compared with 49% in the top tertiles (P= 0.015). In multivariate analysis, fasting glucose was a significant predictor of time to disease progression only in breast cancer patients in the first tertile compared with the third (P= 0.017). Conclusions: We found evidence of a predictive role of pretreatment fasting glucose in the development of resistance in breast cancer patients treated with targeted agents. Prospective studies are warranted to confirm our findings.

Expression of the solute carrier (SLC) transporter SLC22A3 gene is associated with overall survival of pancreatic cancer patients. This study tested whether genetic variability in SLC22A3 associates with pancreatic cancer risk and prognosis. Twenty four single nucleotide polymorphisms (SNPs) tagging the SLC22A3 gene sequence and regulatory elements were selected for analysis. Of these, 22 were successfully evaluated in the discovery phase while six significant or suggestive variants entered the validation phase, comprising a total study number of 1,518 cases and 3,908 controls. In the discovery phase, rs2504938, rs9364554, and rs2457571 SNPs were significantly associated with pancreatic cancer risk. Moreover, rs7758229 associated with the presence of distant metastases, while rs512077 and rs2504956 correlated with overall survival of patients. Although replicated, the association for rs9364554 did not pass multiple testing corrections in the validation phase. Contrary to the discovery stage, rs2504938 associated with survival in the validation cohort, which was more pronounced in stage IV patients. In conclusion, common variation in the SLC22A3 gene is unlikely to significantly contribute to pancreatic cancer risk. The rs2504938 SNP in SLC22A3 significantly associates with an unfavorable prognosis of pancreatic cancer patients. Further investigation of this SNP effect on the molecular and clinical phenotype is warranted. © 2017 The Author(s).

Everolimus is a valid therapeutic option for neuroendocrine tumors (NETs); however, data in a real-world setting outside regulatory trials are sparse. The aim of this study was to determine everolimus tolerability and efficacy, in relation to previous treatments, in a compassionate use program. A total of 169 patients with advanced progressive NETs treated with everolimus were enrolled, including 85 with pancreatic NETs (pNETs) and 84 with nonpancreatic NETs (non-pNETs). Previous treatments included somatostatin analogs (92.9%), peptide receptor radionuclide therapy (PRRT; 50.3%), chemotherapy (49.7%), and PRRT and chemotherapy (22.8%). Overall, 85.2% of patients experienced adverse events (AEs), which were severe (grade 3–4) in 46.1%. The most frequent severe AEs were pneumonitis (8.3%), thrombocytopenia (7.7%), anemia (5.3%), and renal failure (3.5%). In patients previously treated with PRRT and chemotherapy, a 12-fold increased risk for severe toxicity was observed, with grade 3–4 AEs reported in 86.8% (vs. 34.3% in other patients). In addition, 63.3% of patients required temporarily everolimus discontinuation due to toxicity. Overall, 27.8% of patients died during a median follow-up of 12 months. Median progression-free survival (PFS) and overall survival (OS) were 12 months and 32 months, respectively. Similar disease control rates, PFS, and OS were reported in pNETs and non-pNETs. In the real-world setting, everolimus is safe and effective for the treatment of NETs of different origins. Higher severe toxicity occurred in patients previously treated with systemic chemotherapy and PRRT. This finding prompts caution when using this drug in pretreated patients and raises the issue of planning for everolimus before PRRT and chemotherapy in the therapeutic algorithm for advanced NETs.

Objective: The aim of this study was to develop a new international classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of published evidence, and worldwide consultation. Background: The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric descriptions of occurrences that are merely associated with severity. Methods: A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensive medicine specialists, and radiologists who are currently active in clinical research on acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global Web-based survey was conducted and a dedicated international symposium was organised to bring contributors from different disciplines together and discuss the concept and definitions. Result: The new international classification is based on the actual local and systemic determinants of severity, rather than descriptions of events that are correlated with severity. The local determinant relates to whether there is (peri)-pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri) pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity - mild, moderate, severe, and critical. Conclusions: This classification is the result of a consultative process amongst pancreatologists from 49 countries spanning North America, South America, Europe, Asia, Oceania, and Africa. It provides a set of concise up-to-date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research. This ensures that the determinant-based classification can be used in a uniform manner throughout the world.

Summary Background Long-term observational studies assessing the incidence of type I gastric carcinoid (typeIGC) in patients with chronic atrophic gastritis are few. Aim To evaluate the occurrence of typeIGC at diagnosis and during follow-up and to identify patient features associated with the presence of typeIGC in a cohort of chronic atrophic gastritis patients. Methods Three hundred and sixty-seven chronic atrophic gastritis patients [245 women, age 54 (18–79) years] underwent regular follow-up by gastroscopy. The incidence of typeIGC was determined in chronic atrophic gastritis patients with at least 2 years of follow-up (n = 214). Baseline clinical and histological features were analysed as factors associated with the presence of typeIGC by univariate analysis. Results Type I gastric carcinoid was diagnosed in nine (2.4%) patients at the moment when chronic atrophic gastritis was diagnosed. After 1463 person-years, six patients developed typeIGC with an annual incidence rate (person-year) of 0.4%. Patients with typeIGC had significantly higher levels of gastrin, chromogranin A and more frequently the presence of body polyps and ECL-dysplasia compared with chronic atrophic gastritis patients without typeIGC. Conclusions This cohort study shows that typeIGC is a rare complication in patients with chronic atrophic gastritis, and the presence of body polyps and ECL-dysplasia at gastroscopic/histologic evaluation is strongly associated with the presence of typeIGC.

Summary Background Due to suppression of gastric acidity during antisecretory therapy, an impaired absorption of co-administered drugs may occur. Aim To review evidence of impaired drug absorption related to the use of co-administered PPIs or H2RAs. Methods Systematic search of MEDLINE/EMBASE/SCOPUS databases (1980–September 2008) for English articles with keywords: drug malabsorption and absorption, stomach, anti-secretory/acid inhibitory drugs, histamine H2 antagonists, PPIs, gastric acid, pH, hypochlorhydria, gastric hypoacidity. From 2126 retrieved articles, 16 randomized crossover studies were identified investigating impaired absorption of nine different drugs in association with co-administration of PPIs or H2RAs. Information on investigated drug, study type, features of investigated subjects, study design, type of intervention, and study results were extracted. Results The identified studies investigated the absorption kinetics of nine drugs. Acid suppression reduced absorption of ketoconazole, itraconazole, atazanavir, cefpodoxime, enoxacin and dipyridamole (median Cmax reduction by 66.5%). An increased absorption of nifedipine and digoxin (median AUC increase by 10%) and a 2-fold-increase in alendronate bioavailability were observed. Conclusions Gastric pH appears relevant for absorption of some cardiovascular or infectious disease agents. Antisecretory treatment may significantly modify the absorption of co-administered drugs.

Summary Background Impaired acid secretion may affect drug absorption and may be consequent to corporal Heliocobacter pylori-gastritis, which may affect the absorption of orally administered drugs. Aim To focus on the evidence of impaired drug absorption associated with H. pylori infection. Methods Data sources were the systematic search of MEDLINE/EMBASE/SCOPUS databases (1980–April 2008) for English articles using the keywords: drug malabsorption/absorption, stomach, Helicobacter pylori, gastritis, gastric acid, gastric pH, hypochlorhydria, gastric hypoacidity. Study selection was made from 2099 retrieved articles, five studies were identified. Data were extracted from selected papers, investigated drugs, study type, main features of subjects, study design, intervention type and results were extracted. Results In all, five studies investigated impaired absorption of l-dopa, thyroxine and delavirdine in H. pylori infection. Eradication treatment led to 21–54% increase in l-dopa in Parkinon’s disease. Thyroxine requirement was higher in hypochlorhydric goitre with H. pylori-gastritis and thyrotropin levels decreased by 94% after treatment. In H. pylori- and HIV-positive hypochlorhydric subjects, delavirdine absorption increased by 57% with orange juice administration and by 150% after eradication. Conclusions A plausible mechanism of impaired drug absorption is decreased acid secretion in H. pylori-gastritis patients. Helicobacter pylori infection and hypochlorhydria should be considered in prescribing drugs the absorption of which is potentially affected by intragastric pH.

A panel of experts from Latin America convened in Brazil, in May of 2007, for consensus recommendations regarding the management of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas. The recently introduced World Health Organization classification of NETs represents a step forward, but the former classification of carcinoids into foregut, midgut and hindgut is still likely to be useful in the near future. Macroscopic description of the tumor should be followed by light microscopic examination and immunohistochemical staining, whereas other techniques might not be widely available in Latin America. Surgery remains the mainstay of treatment for patients with potentially curable tumors, and adequate selection is paramount in order to optimize treatment results. Regarding systemic therapy, patients with well-differentiated tumors or islet-cell carcinomas may be categorized as having indolent disease, while patients with poorly differentiated, anaplastic, and small-cell carcinomas, or with atypical carcinoids, may be approached initially as having aggressive disease. Somatostatin analogues play a cytostatic role in indolent tumors, and chemotherapy may play a role against other, more aggressive NETs. Obviously, there is an urgent need for novel therapies that are effective against NETs.

Summary Background Atrophic body gastritis patients are at increased risk for gastric cancer. IL-1B/IL-1RN polymorphisms have been associated with gastric cancer susceptibility. The relationship between these polymorphisms and the long-term outcome of atrophic body gastritis patients is not known. Aim To investigate whether the genotyping of IL-1B-511/IL-1RN polymorphisms is useful to characterize atrophic body gastritis patients at increased risk for gastric neoplasms. Methods IL-1B-511/IL-1RN polymorphisms were compared between 110 atrophic body gastritis patients and 110 age- and gender-matched controls, and patients were followed up (median 4.1 years) according to a cohort study design. Results Genotype frequencies of IL-1B-511/IL-1RN were similar between patients and controls. Atrophic body gastritis patients harbouring the wild type of IL-1B-511/IL-1RN polymorphisms were not different from those harbouring the proinflammatory pattern as far as regards gender, age, gastric cancer family history and metaplastic atrophy. Sixteen atrophic body gastritis patients developed a gastric neoplastic lesion at follow-up: eight were IL-1B-511-T carriers and eight were IL-1RN-allele-2 carriers. Harbouring the proinflammatory genotypes was not significantly associated with developing gastric neoplastic lesions. Conclusions In atrophic body gastritis patients, IL-1B-511 and IL-1RN polymorphisms do not appear to be associated either with specific clinical, biochemical or histological features or with the development of gastric neoplastic lesions at long-term follow-up.

SUMMARY Background A better understanding of predictors of risk for pancreatic ductal adenocarcinoma (PDAC) could inform preventive efforts against this lethal cancer. While aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDS) might protect against several gastrointestinal cancers, their role in the development of PDAC remains unclear. Aim To conduct a systematic review and meta-analysis on the relation between ASA ⁄ NSAIDs exposure and the risk of PDAC. Methods We searched Pubmed, Embase, Scopus, Cochrane database of systematic reviews and reference lists of identified papers and included observational (cohort or case-control) studies and randomized controlled trials examining exposure to ASA and ⁄ or NSAIDs and the incidence or mortality of PDAC. We defined three categories (low, intermediate, high), based on exposure duration and dose. Results Eight studies fulfilled our inclusion criteria (four cohort, three case controls, and one randomized controlled trial studies) enrolling 6301 patients between 1971–2004; all but one study took place in the US. The pooled OR were 0.99 (0.83–1.19), 1.11 (0.84–1.47) and 1.09 (0.67–1.75) in the low, intermediate and high exposure groups respectively, with considerable heterogeneity (I 2 ranging 60–86%). Sensitivity analysis by ASA use only, study design or sex did not reveal additional important information. Conclusions This study did not show an association between ASA ⁄ NSAIDs and PDAC. The large baseline exposure in controls in North-America may have obscured an association. There is need for additional studies, especially in Europe, to clarify this issue.

Patients with Crohn's disease may experience several non-digestive complications, including muscle disorders. Rabdomyolysis has rarely been reported in patients with inflammatory bowel disease, however a number of factors may cause muscular damage in this setting. We report the case of a young woman with Crohn's disease who developed a severe, symptomatic skeletal muscle damage associated with severe hypokaliemia. Reversal of the potassium levels to normal ranges led to clinical resolution. The possible causes that might have lead to hypokalemia development and subsequent rhabdomyolysis are discussed with special emphasis for the potential causative role of medical treatment, especially budesonide for which similar side effects have been previously reported. Physicians should be aware that hypokalemia is possible in the setting of Crohn's disease and muscle damage can present as a complication.

The efficacy and safety of omeprazole, in 241 patients with active recurrent duodenal ulcer from 21 Italian centres, was studied in a multicentre double-blind randomized trial comparing 20 mg omeprazole o.m. or 40 mg famotidine nocte with endoscopic examination, symptom recording, laboratory screening and gastrin assay. In a per protocol analysis, the duodenal ulcer healing rates for omeprazole and famotidine, documented by endoscopy, were 62% (68/109) and 33% (39/117) after 2 weeks of treatment (P less than 0.001), 92% (96/104) and 80% (86/108) cumulative after 4 weeks (P less than 0.05), and 99% (102/103) and 92% (96/104) after 6 weeks (P less than 0.05), respectively. The results of this trial demonstrate that 20 mg omeprazole o.m. is superior to 40 mg famotidine nocte in duodenal ulcer healing.

In most cases gastro-enteropancreatic neuroendocrine tumors grow slowly. Interferon-alpha and somatostatin analogs have shown symptomatic, biochemical, and, in a minority of cases, antiproliferative activity. Generally, they are proposed as single-agent therapy. However, based on in vitro and in vivo evidence, the combined use of these drugs was proposed in several non-randomized trials, indicating that there is an additive effect of the combination. Nevertheless, the three randomized trials published so far did not show a statistically significant survival benefit for the combination compared to the same agents alone, even though an advantage for the combination came out in all three studies. On the other hand, data from non-randomized trials would justify the sequential use of the two drugs or the combination after progression on single agent therapy. Therefore, at present the up-front combined use of interferon-alpha and somatostatin analog is not justified, whereas it could be indicated after progression to single-agent therapy. Further larger, international, prospective, randomized, multicentric clinical trials studying homogeneous populations would be necessary to give a final answer, but the rarity and heterogeneity of this malignancy does not assure that it will be possible.

Ulcerative Colitis (UC) is a chronic inflammatory disease of the colon of unknown etiology. Several clinical indexes have been proposed for UC disease activity evaluation, but none have been properly validated. Moreover, the reference parameter for the scores and their prognostic value is not clear. Mucosal healing has been recently proposed as an important end-point. Aim of the present study was to evaluate the correlation of four clinical indexes with objective diagnostic tools for UC evaluation, the discriminative ability in identifying patients with endoscopic mucosal healing, and to analyze the possible prognostic indication for disease course in 1 year of follow-up.We analyzed data of 75 patients recorded in regular follow-up visit in IBD clinic at S. Andrea Hospital, Rome, between 2007-2011. We recorded clinical data and lab tests at the time of the visit, and endoscopic/histological reports performed within 1 month. Clinical indexes (Seo' activity index, Simple Clinical Colitis Activity Index, partial Mayo score and Endoscopic-Clinical Correlation Index) were calculated and correlation to endoscopic and histologic activity, and to C-reactive protein increment, was assessed by mean of Spearman's rank correlation. Discriminative ability of the indexes for patients with and without endoscopic mucosal healing was tested by calculation of area under ROC curve (AUC). Patients with low and high clinical scores were compared for number of flares and increment of therapy during 1 year of follow-up.Clinical indexes had a good correlation with endoscopic activity (mean r = 0.73 ± 0.06), a fair correlation with CRP-increment (mean r = 0.55 ± 0.01) and a poor one with histologic activity (mean r = 0.35 ± 0.01). The discriminatory ability of the indexes for endoscopic mucosal healing was good for all the indexes (mean AUC = 0.87 ± 0.05). Patients with high clinical score had more flares and required more frequently increase of therapy at 1 year of follow up compared with patients with low score.Clinical indexes have a good correlation with endoscopic activity and can discriminate patients with and without mucosal healing. Patients with low and high score have different risk of disease flare and of need to increase therapy at 1 year. Clinical indexes may represent a useful tool for disease assessment in clinical practice in UC outpatients with mild-moderate disease.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and incurable disease. Poor prognosis is due to multiple reasons, including acquisition of resistance to gemcitabine, the first line chemotherapeutic approach. Thus, there is a strong need for novel therapies, targeting more directly the molecular aberrations of this disease. We found that chronic exposure of PDAC cells to gemcitabine selected a subpopulation of cells that are drug-resistant (DR-PDAC cells). Importantly, alternative splicing of the pyruvate kinase gene (PKM) was differentially modulated in DR-PDAC cells, resulting in promotion of the cancer-related PKM2 isoform, whose high expression also correlated with shorter recurrence free survival in PDAC patients. Switching PKM splicing by antisense oligonucleotides to favour the alternative PKM1 variant rescued sensitivity of DR-PDAC cells to gemcitabine and cisplatin, suggesting that PKM2 expression is required to withstand drug-induced genotoxic stress. Mechanistically, up-regulation of the polypyrimidine-tract binding protein (PTBP1), a key modulator of PKM splicing, correlated with PKM2 expression in DR-PDAC cell lines. PTBP1 was recruited more efficiently to PKM pre-mRNA in DR- than in parental PDAC cells. Accordingly, knockdown of PTBP1 in DR-PDAC cells reduced its recruitment to the PKM pre-mRNA, promoted splicing of the PKM1 variant and abolished drug resistance. Thus, chronic exposure to gemcitabine leads to up-regulation of PTBP1 and modulation of PKM alternative splicing in PDAC cells, conferring resistance to the drug. These findings point to PKM2 and PTBP1 as new potential therapeutic targets to improve response of PDAC to chemotherapy.

Summary Background Most adults with coeliac disease have a subclinical form of the disease and iron-deficiency anaemia may be the sole presenting symptom. Aim To evaluate demographic, clinical and biochemical characteristics of adult coeliac disease patients presenting with iron-deficiency anaemia. Patients A total of 108 iron-deficiency anaemia patients in whom coeliac disease has been diagnosed were studied. As a control group 108 non-coeliac iron-deficiency anaemia patients, comparable for sex and age, were studied. Results Of the 108 coeliac disease patients, 95 (88%) were female (mean age 34 years, range 19–72) and 13 (12%) were male (mean age 33 years, range 15–65). The median duration of iron-deficiency anaemia before diagnosis was 66 months in coeliac disease patients and 14 months in the iron-deficiency anaemia control group (P = 0.0001). The occurrence of at least one gastrointestinal symptom, not spontaneously reported, was observed in 92 (85%) patients with coeliac disease and in 67 (62%) patients in the control group (P = 0.001). The concomitant presence of diarrhoea, abdominal pain and abdominal bloating was detected in 14% patients with coeliac disease with respect to 3% in the control group (P = 0.005). Conclusions The vast majority of coeliac disease patients with iron-deficiency anaemia presentation were unaware of the gastrointestinal symptoms and this relationship is useful for diet compliance.

Background Knowledge of factors able to predict the clinical outcome of homogenous series of entero-pancreatic endocrine tumours treated with somatostatin analogues is poor. This study was aimed at identifying predictors for efficacy of somatostatin analogues at inhibiting tumour growth and modifying patients' survival during long-term follow-up. Patients and methods 31 patients with entero-pancreatic well-differentiated endocrine carcinoma received long-acting somatostatin analogues. All had progressive, metastatic disease (87% liver metastases, 38.7% distant extra-hepatic metastases). Results Response rate after 6 months of treatment was 45.2% (all disease stabilisation: 27.8% of pancreatic vs. 81.8% of intestinal tumours, P = 0.007). The predictors for non-response were: pancreatic tumour (OR 5.8), no previous surgery (OR 6.7), and the presence of distant extra-hepatic metastases, the latter being also confirmed by multivariate analysis (OR 10.0). Responders maintained stabilisation for 26.5 months, and none died during follow-up. Different survival curves were observed for patients, responding at 6 months compared to non-responders (P = 0.004), 3-year survival rate being 100% and 52.3%, respectively. Conclusions Distant extra-hepatic metastases are the major predictor of poor efficacy of somatostatin analogues in progressive, metastatic, well-differentiated entero-pancreatic endocrine carcinomas. Patients achieving response after 6 months of treatment, maintain it throughout a long-term follow-up. Non-responders after 6 months of treatment, have a worse survival, and should be considered for alternative treatments.

Summary Background : Benign epithelial gastric polyps have been reported to be more common in atrophic body gastritis. The role of Helicobacter pylori infection in the induction of gastric atrophy is well-known. The development of hyperplastic polyps may be in relation to H. pylori infection. Aim : To investigate occurrence of benign epithelial gastric polyps in atrophic body gastritis patients at diagnosis and follow-up, and the role of H. pylori and other risk factors for the development of benign epithelial gastric polyps. Methods : A total of 259 consecutive atrophic body gastritis patients included in a follow-up programme, of whom 202 were followed up for median period of 4 years (range: 2–11). At baseline and follow-up gastroscopies, the presence of benign epithelial gastric polyps was evaluated. Biopsies for histology were obtained from all detected benign epithelial gastric polyps. Results : Frequency of benign epithelial gastric polyps in atrophic body gastritis patients were 4.6% at baseline and 5.9% at follow-up. About 91.7% were hyperplastic polyps. H. pylori infection was detected in 79.2% atrophic body gastritis patients with benign epithelial gastric polyps, and in 70.8% without benign epithelial gastric polyps. Smoking was more frequent among patients with benign epithelial gastric polyps [42% vs. 20%, OR 2.8 (95% CI: 1.2–6.9)]. Conclusions : Benign epithelial gastric polyps occur in about 5% of atrophic body gastritis patients, and the vast majority are hyperplastic polyps. Smoking habit, but not H. pylori infection, increases the risk for benign epithelial gastric polyps in atrophic body gastritis patients.

Summary Background : Although large hiatal hernia may cause bleeding from Cameron erosions, its role in iron deficiency anaemia has been debated, and no data are available on the treatment of these patients with proton pump inhibitors. Aims : To determine the prevalence of large hiatal hernia in out-patients with iron deficiency anaemia and the role of proton pump inhibitors in the prevention of recurrence of anaemia. Methods : Two hundred and twenty-eight out-patients underwent upper/lower endoscopy. Those with large hiatal hernia were given an oesophagogram, discontinued iron supplementation and received proton pump inhibitor treatment with (group 1) or without (group 2) surgery. Anaemia was re-assessed during 1 year of follow-up. Results : Large hiatal hernia was the likely cause of anaemia in 21 patients (9.2%). The median haemoglobin and ferritin values at the diagnosis of anaemia were 7.9 g/dL and 6 µg/L, respectively. Cameron erosions were found in 33% of patients. Ten and eleven patients were included in groups 1 and 2, respectively. Haemoglobin values were 13.8 g/dL and 13.4 g/dL at 3 months of follow-up, and 13.4 g/dL and 13.8 g/dL at 1 year of follow-up, in groups 1 and 2, respectively. Conclusions : Large hiatal hernia may cause iron deficiency anaemia, even without Cameron erosions. Surgery in combination with proton pump inhibitor therapy is no better than proton pump inhibitor therapy alone in preventing the recurrence of anaemia.

and moderate-severe steatosis (OR 2.1; 95%CI, 1.1-4.1; p=0.03). SVR rates were not related to HOMA in the overall population [63% (220/351) vs 60% (29/48), p=0.75], nor in subgroup analysis by virus genotype [genotype 1: 43% (61/143) for ≤ 2 HOMA vs 53% (9/17) for > 2 HOMA (p=0.45); genotype 2 and 3: 83% (143/173) vs 80% (20/25), p=0.78, respectively]. In SVR patients, baseline and follow up HOMA values were similar (1.12±0.82 vs 1.17±1.1, p=0.25). Conversely, nonresponders had increased HOMA values trough 18 months follow up (from 1.17±0.7 to 1.49±1.3, p=0.007); IR de-novo occurred more frequently in non-SVR than in SVR patients [24% (25/106) vs 8% (16/198), p=0.0003]. Conclusions: While the outcome of Peg-IFN/Rbv therapy is not influenced by IR, the latter is prevented once SVR is achieved.

Background. The usefulness of small bowel investigation in iron deficiency anaemia (IDA) patients is controversial. Aim. To evaluate the presence of small bowel lesions likely to cause IDA in patients with unexplained IDA after negative gastroscopy with biopsies and colonoscopy (CS). Methods. A total of 117 outpatients, referred for unexplained IDA, underwent gastroscopy with biopsies and colonscopy. In 17 (14.5%) patients, endoscopic/histological investigations were negative. Of these patients, 13 underwent small bowel follow-through (SBFT) and if necessary to confirm the diagnosis, further gastrointestinal (GI) investigations. Results. Small bowel lesions likely to cause IDA were found in five (38%) patients. Four of these lesions were detected by SBFT, two of them were malignant. These findings, confirmed at surgery and ileoscopy (IS), led to the final diagnoses of jejunal and ileal adenocarcinoma, idiopathic ileal ulcers and ileal Crohn’s disease. In one case, after negative SBFT, jejunal angiodysplasia was detected by video capsule endoscopy (VCE). Faecal occult blood test (FOBT) was positive in four (31%) patients, all of whom presented lesions likely to cause IDA, detected in three cases by SBFT and in one case by VCE. Conclusions. This study shows the importance of investigating the small bowel in IDA patients after negative upper and lower GI endoscopy, particularly if FOBT is positive.

Until recently, the association of primary hyperparathyroidism and gastric carcinoid, with or without hypergastrinaemia, had been considered an incomplete form of multiple endocrine neoplasia type 1. This is because it seemed unlikely that the rare joint appearance of these diseases could occur only by chance. It is now possible to evaluate the pathogenetic involvement of the multiple endocrine neoplasia type 1 gene in many, apparently sporadic, clinical conditions. This is a case report of a female mimicking multiple endocrine neoplasia type 1 due to the presence of hyperparathyroidism, gastric carcinoid, and hypergastrinaemia. However, involvement of the MEN-1 gene (exons 2-10) was not detected, whereas hypergastrinaemia was attributed to a chronic atrophic gastritis.

Iron deficiency anaemia is generally considered a sign of occult bleeding from the gastrointestinal tract, and standard care therefore includes evaluation of the gastrointestinal tract to rule out possible bleeding sites. However, it is often overlooked that iron deficiency anaemia may be the result of an imbalance between iron loss and iron intake, and may also be due to reduced absorption of iron from food, i.e., coeliac disease. The absorption of alimentary iron is not a simple process and the stomach plays a major role in this process of iron "digestion". This review presents evidence linking iron deficiency anaemia to gastric conditions that lead to reduced acid secretion, such as, for example, gastric surgery, atrophic body gastritis and Helicobacter pylori gastritis.

Background: Seroepidemiological and clinical studies suggest that Helicobacter pylori may cause iron deficiency anaemia (IDA) in the absence of peptic lesions by undefined mechanisms, which still remain to be fully elucidated. Gastric acidity and ascorbic acid (AA) promote iron absorption. AA is lowered in the presence of H pylori infection. H pylori can cause atrophic body gastritis with achlorhydria, decreased iron absorption, and consequent IDA. Whether alterations in intragastric acidity and AA concentrations play a role in IDA developing in patients with H pylori gastritis remains to be determined . Aim: To evaluate gastric juice pH and gastric juice and plasma AA in patients with H pylori infection and unexplained IDA, compared with controls with IDA and a healthy stomach or with controls with H pylori infection and no IDA. Results: Patients with IDA and H pylori gastritis were characterised by concomitant increased intragastric pH (median value 7) and decreased intragastric AA (median value 4.4 μg/ml) compared with controls with a healthy stomach (median pH 2; median intragastric AA 17.5 μg/ml) and with H pylori positive controls without IDA (median pH 2.1; median intragastric AA 7.06 μg/ml). Intragastric AA was inversely related to pH ( r =−0.40, p=0.0059) and corporal degree of gastritis ( r =−0.53, p=0.0039). Plasma AA concentrations were lower in all infected groups than in healthy controls. Conclusions: Patients with unexplained IDA and H pylori gastritis present concomitant changes in intragastric pH and AA that may justify impaired alimentary iron absorption and consequent IDA.

A case of abdominal tuberculosis with pancreatic involvement is described. A 27-year-old Italian male, with no known cause of immunodeficiency and with no evidence of pulmonary tuberculosis, was admitted to our division because of acute pancreatitis. Abdominal imaging revealed a large ‘tumour-like’ mass in the pancreas head compressing the distal choledochous, and multiple adenopathy. Histological examination of multiple specimens removed during explorative laparotomy revealed granulomas with giant cells, caseous necrosis, and positive Ziehl-Neelsen staining. Tissue culture was positive for Mycobacterium tuberculosis. Once specific medical treatment was started, the pancreatic damage completely resolved.

Background In patients with digestive endocrine tumours, complete pre-operative staging is essential in planning proper management and evaluating treatment efficacy. To date, somatostatin receptor scintigraphy (SRS) is considered the ‘gold standard’ imaging procedure, and very few data are available concerning the use of helical computed tomography (hCT). This study aimed to determine the diagnostic accuracy and the ability to modify the surgical management of hCT, alone or combined with SRS. Patients and methods Sixty patients were staged before surgery by hCT, SRS and tumour markers, and included in group 1 if suitable for radical surgery, otherwise in group 2. All patients underwent laparotomy followed by subsequent re-staging. Results SRS sensitivity was 77%, 48% and 67% for primary, lymph-node and liver lesions, respectively. hCT sensitivity was 94%, 69% and 94% for primary, lymph-node and liver lesions, respectively (P = 0.02 versus SRS, for liver lesions). During pre-operative evaluation, hCT correctly staged 92% and SRS 75% of patients (P = 0.02). hCT provided additional information in 17% of patients. Conclusions Since hCT has been shown to be extremely accurate, providing essential information for the planning of surgical treatment compared with that of SRS, both techniques should be used in the pre-operative work-up of digestive endocrine tumours.

Summary Background : Helicobacter pylori infection induces atrophic body gastritis, but the long-term effect of its cure on body atrophy is unclear. Aim : To investigate the long-term effects of H. pylori cure on gastric morpho-functional parameters in patients with atrophic body gastritis. Methods : Forty patients with atrophic body gastritis were cured of H. pylori infection. Gastroscopy with biopsies, gastrin and pepsinogen I levels and basal and stimulated acid secretion were evaluated before and 6–12 months after treatment. Results : At eradication assessment (6–12 months), in eight of the 40 patients, body atrophy was no longer observed, whereas in 32 of the 40 it remained substantially unchanged (2.03 ± 0.12 vs. 1.83 ± 0.15). In the eight patients with reversed body atrophy, gastrinaemia decreased significantly with respect to pre-treatment values (265 ± 59.9 pg/mL vs. 51.8. ± 6.04 pg/mL), and basal and stimulated acid secretion increased significantly after cure. In the 32 patients still presenting body atrophy, gastrinaemia was similar topre-treatment values (457 ± 76.04 pg/mL vs. 335.1 ± 58.8 pg/mL). At follow-up (21–25 and 32–70 months), the eight patients with reversed body atrophy continued with normal gastrinaemia (35.3 ± 10.1 pg/mL vs. 38.5 ± 8.8 pg/mL), but in the 19 patients with continued atrophy, both corporal atrophy and intestinal metaplasia remained substantially unchanged. Conclusions : Following successful treatment in patients with atrophic body gastritis and H. pylori infection, long-term histological investigations are crucial in order to detect reversed body damage or to confirm continued body atrophy.

Background: It has been reported that 50% of patients with atrophic body gastritis have positive Helicobacter pylori antibody titres only. In atrophic body gastritis, a decrease in H. pylori antibodies after eradication treatment has been reported, suggesting that serology may indicate an active H. pylori infection. Aim: To investigate the time course of H. pylori antibodies and gastric inflammation after eradication treatment in patients with atrophic body gastritis, and to determine whether serology alone can be considered as a valid tool to assess the efficacy of eradication treatment in patients with atrophic body gastritis. Methods: Twenty-seven patients with atrophic body gastritis (12 serologically H. pylori-positive only, ABG-S+; 15 H. pylori-positive at histology and serology, ABG-H+) were included in the treatment group, and 17 patients (all ABG-S+) in the no treatment group. All patients had gastroscopy plus biopsies evaluated according to the updated Sydney system and H. pylori immunoglobulin G determination: in the treatment group, at baseline and 6 and 24 months after eradication (bismuth-based triple regimens); in the no treatment group, at baseline and after 3 years. Results: In the treatment group, in ABG-S+ patients, H. pylori antibodies decreased significantly 6 months after treatment [37.5 U/mL (16–100 U/mL) vs. 15 U/mL (0–100 U/mL), P

Background: Recent studies have reported an association between iron deficiency anaemia and Helicobacter pylori. Helicobacter pylori could cause iron deficiency anaemia by altering iron absorption. We observed that most patients with Helicobacter pylori infection and iron deficiency anaemia present a chronic superficial pangastritis. Aim: To investigate whether Helicobacter pylori-positive patients with iron deficiency anaemia have peculiar histological and functional features when compared with non-anaemic Helicobacter pylori-positive subjects. Patients: Fifty-one patients with iron deficiency anaemia, in whom chronic superficial Helicobacter pylori gastritis was the only gastrointestinal finding, and 103 non-anaemic Helicobacter pylori-positive controls were included in the study. Thirty-seven patients were randomly matched with 37 controls of the same sex and age. Methods: Gastroscopy, with antral (n=3) and body (n=3) biopsies, was performed. Gastrin and pepsinogen I levels and antiparietal cell antibodies were evaluated. Intragastric pH was also measured. Results: Gastritis involved the corporal mucosa in 90% of patients compared to 42.7% of controls (P

Background: Proton pump inhibitors are potent acid suppressants which, at normal doses, can result in hypergastrinaemia in patients with idiopathic oesophageal reflux disease and in the control of symptoms in most patients with gastrinomas. Therefore, their use could delay or mask the diagnosis of gastrinoma. Aim: To investigate whether the widespread use of proton pump inhibitors masks or complicates the diagnosis of gastrinoma. Subjects and methods: Data from two centres with different referral criteria for suspected gastrinomas were analysed (Gastroenterology Unit, Rome, Italy and National Institutes of Health, Bethesda, MD, USA). The number of referrals and the number of new patients with gastrinoma diagnosed in the years prior to the widespread use of proton pump inhibitors (1986–1992) were compared with the numbers since proton pump inhibitors became widely available (1993–1998). Results: The decrease in referral rate (P=0.0009) and the decrease in the annual rate of gastrinoma diagnosis (P=0.0020) at both centres correlated with the increased use of proton pump inhibitors. At the Italian centre, there was a 62% decrease in annual referrals (P