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Background/Aims To evaluate associations between delayed gastric emptying (GE) assessed by the octanoic acid breath test and upper gastrointestinal (GI) symptoms. Methods A historical, prospective study included 111 consecutive symptomatic adults referred for a GE breath test because of upper abdominal symptoms suggestive of delayed GE. Exclusion criteria included underlying organic disease associated with delayed GE. Patients completed a symptom questionnaire and underwent a GE octanoic breath test. Patients with delayed GE were compared with those with normal results, for upper GI symptoms. Results Early satiety was the only symptom significantly associated with delayed GE. It was observed in 52% of subjects with delayed GE compared to 33% patients with no evidence of delayed GE (P = 0.005). This association was seen for all degrees of severity of delayed GE. Patients with early satiety had a t1/2 of 153.9 ± 84.6 minutes compared to 110.9 ± 47.6 minutes in subjects without it (P = 0.002). In a logistic regression model, early satiety was significantly associated with delayed GE (OR, 2.29; 95% CI, 1.01-5.18; P = 0.048). Conclusions Early satiety is the only patient-reported GI symptom associated with delayed GE. The utility of GE tests as a clinical diagnostic tool in the work-up of dyspeptic symptoms may be overrated.

Background: Confirmation of Helicobacter pylori eradication by urea breath test (UBT) is currently performed 4–6 weeks after completion of therapy because of unacceptable false-negative results in UBTs performed earlier. Use of a high-dose citric acid test meal appears to enable accurate detection of H. pylori even during short term therapy with proton pump inhibitors. Aim: To evaluate if use of a high dose citric acid (4.0 g) test meal can decrease the interval required for confirmation of eradication after triple therapy. Methods: 233 patients positive for H. pylori were randomized to undergo UBT at 7 days or 14 days after triple therapy, and again at 6 weeks. The latter test was considered the gold standard test. Results: The UBT performed 6 weeks after the end of treatment found that 79.9% were cured. The same test 7 days after therapy found false-negative detection of H. pylori in 7.3% patients compared to 3.2% patients examined after 14 days. The sensitivity, specificity, positive and negative predictive values and accuracy for evaluation on day 14 were 80, 100, 100, 96.3 and 96.7%, respectively. Conclusions: High-dose citric acid-based UBT is a valid test for the assessment of H. pylori status 14 days after triple therapy. This may obviate the delay in instituting second-line eradication therapy, or further evaluation of the symptomatic patient unresponsive to therapy despite eradication.

Summary Background : The need to withhold acid suppression therapy while awaiting urea breath test results is a common clinical problem in symptomatic patients. It is unclear at present if the dose or type of proton pump inhibitor or the type of test meal govern the apparent masking effect of proton pump inhibitors on the urea breath test. Aim : To prospectively evaluate Helicobacter pylori detection rates during treatment with four different proton pump inhibitors, utilizing a high-dose citric acid-based 13C urea breath test. Methods : Patients positive for Helicobacter pylori by urea breath test were randomized to receive either omeprazole 20 mg/day, pantoprazole 40 mg/day, lansoprazole 30 mg/day or esomeprazole 40 mg/day for 14 days. A repeat breath test was performed on day 14 of treatment. Results : One hundred and seventy-nine patients, mean age 45.8 ± 16.8, completed the study. Treatment with omeprazole or pantoprazole prior to urea breath test (UBT) was associated with low false negative results, while lansoprazole and esomeprazole caused clinically unacceptable high false negative rates (pantoprazole 2.2% vs. lansoprazole 16.6%, P = 0.02, vs. esomeprazole 13.6%, P = 0.05; omeprazole 4.1% vs. lansoprazole 16.6%, P = 0.05). Conclusions : Proton pump inhibitor-induced false negative results on high-dose citric acid based urea breath test vary with the type of proton pump inhibitor used. Selection of the appropriate test meal and proton pump inhibitor may allow symptomatic individuals to continue their proton pump inhibitors prior to performing a urea breath test.

Laron-type dwarfism is an autosomal recessive disorder caused by deletions or mutations of the growth hormone receptor gene. It is characterized by high circulating levels of growth hormone (GH) and low levels of insulin-like growth factor I (IGF-I). Patients are refractory to both endogenous and exogenous GH, and present severe growth retardation and obesity. Therapy with recombinant human insulin-like growth factor-I (rhIGF-I) accelerates linear growth. We describe a 2-year old girl with Laron syndrome, who presented with postnatal growth failure and hypoglycaemic seizures. Her evaluation disclosed high GH values during a glucagon test (peak GH value 170 ng/ml) and very low IGF I value (0.1 ng/ml) with no rise following GH administration. The growth velocity improved considerably with the administration of IGF I. Molecular analysis showed a heterozygous mutation on exon 4 of the GH receptor gene, inherited from the mother, a rather puzzling finding considering the clinical findings in mother and infant. This case constitutes the first report of Laron syndrome from Greece.

Aim: To evaluate the sensitivity and specificity of a new 13C urea breath test, Oridion BreathID, for the diagnosis of Helicobacter pylori. Methods: A total of 97 consecutive symptomatic patients referred for upper endoscopy were included in the ‘pre-therapy’ part of the study. After endoscopy the patients were analysed for H. pylori by Oridion BreathID. BreathID continuously sampled the subject’s breath for 20 min, and displayed the results on the BreathID screen in real time. Results of the BreathID were compared with the ‘gold standard’ (rapid urease test and histology). We also prospectively tested the validity of BreathID in comparison to isotope ratio mass spectrometry, in 40 patients referred to monitor the efficacy of H. pylori eradication treatment. Results: Complete agreement was observed between the ‘gold standard’ and the Breath ID test in 96.9% (94 out of 97) of the patients. The sensitivity and specificity of BreathID were 97.8% and 96.1%, respectively. The correlation between BreathID and isotope ratio mass spectrometry breath test was 100%. Conclusions: The Oridion BreathID has comparable sensitivity and specificity to the claims of the currently available urea breath tests. Furthermore, BreathID has the potential advantages of ease of use with minimal medical staff requirement, and real time rapid results (20 min maximum) which may make the BreathID preferable to other urea breath test assays.

Background: Robust evaluation of induction therapies using both clinical and inflammatory outcomes in pediatric Crohn's disease (CD) are sparse. We attempted to evaluate clinical, inflammatory, and composite outcomes of induction of remission therapies (normal C reactive protein [CRP] remission) in a large pediatric prospective multicenter study. Methods: Patients enrolled at diagnosis into the growth relapse and outcomes with therapy in Crohn's disease study were evaluated for disease activity, CRP, and fecal calprotectin at 8, 12 and 52 weeks after starting treatment. The primary endpoint was week-12 steroid-free remission defined by pediatric Crohn's disease activity index and CRP

Before the development of efficient medications for peptic ulcer disease many patients were treated surgically by partial gastrectomy. The pathogenetic role of Helicobacter pylori was also not known yet. Some of these patients may therefore still harbor H. pylori in their remnant stomach as a carcinogenic agent for gastric cancer. This could be even more relevant for patients who were operated for tumors in the stomach. The efficacy of the urea breath test (UBT) is not clear in this population.To study the prevalence of H. pylori and to evaluate the sensitivity and specificity of the continuous UBT (BreathID) in postgastrectomized patients in Israel. In this system, the pH of the stomach is lowered by the addition of citric acid that may be beneficial in the smaller and more alkalic stomach.We compared retrospectively the results of our continous UBT with a rapid urease test (RUT) and the histology in all our patients who underwent gastroscopy for any clinical indication, and had a history of partial gastrectomy during the years 2002 to 2010. Only patients in whom H. pylori was tested by all the 3 methods during the same day were included in the study. We identified 76 such patients older than 18 years and performed a statistical analysis of all possibly related clinical data. The 3 methods were compared with each other.H. pylori was positive in 14/76 (18.4%) patients when histology was considered as the gold standard method. The positive predictive value of the continuous UBT and the RUT was 0.64 and 0.35, respectively. The negative predictive value was high by both the methods, 0.92 and 0.95, respectively. Weight loss was correlated with positivity for H. pylori (P=0.032) and a longer gastric stump was marginally related to H. pylori (P=0.071). There was no difference for H. pylori positivity between patients with Billroth I or Billroth II operations. Prevalence of H. pylori was not lower in patients who had partial gastrectomy several years earlier.The prevalence of H. pylori is considerable even several years after partial gastrectomy. The BreathID is reliable to exclude H. pylori after partial gastrectomy. The positive predictive value of the UBT is not very high but better than the RUT. We suggest that all positive patients found by the breath test should be treated. Our results support the view that alternative noninvasive methods, such as the stool antigen test should be further studied and compared with the BreathID in larger populations.

ObjectiveTo investigate whether congenital IGF1 deficiency confers protection against development of malignancies, by comparing the prevalence of malignancies in patients with congenital (secondary) deficiency of IGF1 with the prevalence of cancer in their family members.MethodOnly patients with an ascertained diagnosis of either Laron syndrome (LS), congenital IGHD, congenital multiple pituitary hormone deficiency (cMPHD) including GH or GHRHR defect were included in this study. In addition to our own patients, we performed a worldwide survey and collected data on a total of 538 patients, 752 of their first-degree family members, of which 274 were siblings and 131 were further family members.ResultsWe found that none of the 230 LS patients developed cancer and that only 1 out of 116 patients with congenital IGHD, also suffering from xeroderma pigmentosum, had a malignancy. Out of 79 patients with GHRHR defects and out of 113 patients with congenital MPHD, we found three patients with cancer in each group.Among the first-degree family members (most heterozygotes) of LS, IGHD and MPHD, we found 30 cases of cancer and 1 suspected. In addition, 31 malignancies were reported among 131 further relatives.ConclusionsOur findings bear heavily on the relationship between GH/IGF1 and cancer. Homozygous patients with congenital IGF1 deficiency and insensitivity to GH such as LS seem protected from future cancer development, even if treated by IGF1. Patients with congenital IGHD also seem protected.

Reviewing the prevalence of malignancies in our cohort of 64 Laron syndrome patients and of 102 of their first degree relatives we registered none in the homozygous patients with LS, but 11 instances of cancer in the heterozygous family members.

The association of hepatic haemangiomas with female sex hormones is not entirely clear. We prospectively evaluated the impact of female sex hormones on the natural history of liver haemangiomas.We followed 94 women with 181 haemangiomas diagnosed by ultrasound for a period of1-17 years (mean 7.3 (5.5) years). The location, number, size, and ultrasonographic pattern of the lesions were evaluated. Patients were also evaluated by questionnaire for gynaecological and reproductive history. We compared the change in number and size of haemangiomas in patients who received or did not receive exogenous hormonal treatment.Age at first period was inversely associated with the size of haemangiomas (r = 0.181, p = 0.015) while age at menopause was positively correlated with the number of haemangiomas detected at first ultrasound (r = 0.542, p0.0001). During follow up, no change in the ultrasonographic pattern or number of haemangiomas was observed. An increase in the size of the lesions was demonstrated in 5/22 (22.7%) hormone therapy exposed patients compared with 7/72 (9.7%) controls. Three variables (ultrasonographic pattern, number of haemangiomas, and hormone therapy) predicted whether or not a given haemangioma would increase in size. A hypoechoic pattern increased the risk of progression while a hyperechoic pattern decreases that risk (p = 0.003). The number of haemangiomas was inversely associated with the likelihood of progression (p = 0.006) and hormone therapy increased the risk of haemangioma enlargement (p = 0.05).Hepatic haemangiomas seem to be influenced by both endogenous and exogenous female sex hormones although significant enlargement occurs only in a minority of patients. Consequently, routine liver ultrasound follow up in women with hepatic haemangiomas receiving hormone therapy appears appropriate.

We prospectively evaluated a 13 C urea breath test (UBT) that involves passive continuous sampling for diagnosis of Helicobacter pylori in 72 children. Results were obtained within 10 minutes in 96% of patients. The test is rapid, user-friendly, and has 100% concordance with conventional diagnostic methods.

We describe here a 19 month-old girl with classical Laron syndrome (LS). Molecular analysis of the GH receptor gene in the patient and her parents was performed. The patient was found to be heterozygous for a mutation in exon 4 (R43X) and heterozygous for a polymorphism in exon 6 (Gly168Gly). Her mother was also heterozygous for R43X but homozygous for the polymorphism. In the father, a heterozygous polymorphism was found. Contrary to previous assumptions that only homozygous patients express the typical phenotype, this patient shows all the classical features of LS, despite being a heterozygote for a pathological defect.

Background The Maastricht 2-2000 guidelines on the current management of Helicobacter pylori infection were recently adopted by the Israeli Gastroenterological Association. Goal To determine the impact of these clinical guidelines on the current knowledge, attitudes, and management of H. pylori among primary care physicians, hospital internists, and gastroenterologists in Israel. Study Self-administered, voluntary, anonymous questionnaires were given personally to 229 physicians, 73 primary care physicians, 71 internists, and 85 gastroenterologists. The questions evaluated 4 main issues in the management of H. pylori: (1). the optimal diagnostic test, (2). indications for eradication, (3). combination and duration of triple therapy, and (4). the need for confirmation following eradication. Results There were significant variations in the adherence of those recommendations among gastroenterologists, internists, and primary care physicians. Specifically, 94.1% of gastroenterologists and 88.9% of internists consider the urea breath test the test of choice for H. pylori diagnosis compared with 60.0% of the primary care physicians. Significant differences in the eradication indications for mucosa-associated lymphoid tissue (MALT) lymphoma, first-degree relatives of gastric cancer patients, atrophic gastritis, functional dyspepsia, and concomitant use of nonsteroidal antiinflammatory drugs were demonstrated among gastroenterologists and the other groups. Conclusions Primary care physicians may not be aware of important indications for diagnosis and eradication of H. pylori related to the risk of gastric malignancy or concomitant use of nonsteroidal antiinflammatory drugs. Public health agencies may need to increase penetration of the Maastricht 2000 recommendations to primary care physicians.

Recently, several investigators have suggested that H. pylori may be a contributory factor in hyperemesis gravidarum. The purpose of this study was to evaluate whether seropositivity for IgG antibodies to H. pylori may also be related to nausea, vomiting, heartburn and epigastric pain in pregnancy.One hundred and eighty-five women, at term pregnancy, were included in the study. All women completed a questionnaire regarding information on the number of pregnancies and deliveries, weight gain, smoking and gastrointestinal complaints before and during pregnancy. The presence of H. pylori infection was determined by serology.The overall prevalence rate of H. pylori seropositivity was 45.9%. Women positive for H. pylori IgG were older (28.7+/-4.5 vs. 27.0+/-4.5, p=0.02), had more prior pregnancies (3.2+/-2.1 vs. 2.6+/-1.6, p=0.02) and deliveries (2.6+/-1.6 vs. 2.0+/-1.1, p=0.006) and reported vomiting in the first trimester more frequently than H. pylori negative patients (81.2% vs. 65%, p=0.004). On the other hand vomiting in the second trimester was reported more frequently among smokers during pregnancy compared to non-smokers.H. pylori seropositivity is significantly associated with emesis gravidarum but not with gastro-intestinal symptoms later in pregnancy. First trimester vomiting more than doubles the likelihood that the gravida is H. pylori IgG positive.