Michele Quitadamo

Randomized Study of Two "Rescue" Therapies for Helicobacter pylori-Infected Patients After Failure of Standard Triple Therapies

OBJECTIVES:A novel rifabutin-based therapy is able to cure Helicobacter pylori infection in most patients who have failed eradication after standard proton pump inhibitor (PPI)-based triple therapy. We compared this regimen with the quadruple therapy.METHODS:A total of 135 patients were randomized into three groups who were treated for 10 days with pantoprazole 40 mg b.i.d., amoxycillin 1 g b.i.d., and rifabutin 150 mg o.d. (RAP150 group), or 300 mg o.d. (RAP300 group), and pantoprazole 40 mg b.i.d., metronidazole 250 mg t.i.d., bismuth citrate 240 mg b.i.d., and tetracycline 500 mg q.i.d. (QT group). Before therapy, patients underwent endoscopy with biopsies for histology, culture and antibiotic susceptibility tests. H. pylori eradication was assessed by the 13C-urea breath test.RESULTS:On intention-to-treat analysis, eradication rates (with 95% confidence intervals [CI]) were 66.6% (53–80%) in the RAP150 and QT groups, respectively, and 86.6% (76–96%) in RAP300 group (p < 0.025). Most patients harboring metronidazole- and clarithromycin-resistant strains were eradicated at an equal rate by each of the three regimens. Side effects were observed in 9% and 11% of rifabutin-treated patients, and in 47% of those on quadruple therapy (p < 0.0001).CONCLUSIONS:In patients who failed standard eradicating treatments, a 10-day course of rifabutin with pantoprazole and amoxycillin is more effective and well tolerated than the quadruple therapy.

Aberrant DNA methylation in non-neoplastic gastric mucosa of H. Pylori infected patients and effect of eradication.

BACKGROUND:Gene promoter methylation is an epigenetic event leading to gene silencing. This mechanism is particularly relevant in cancer since it can interfere with the activity of specific “suppressor” genes.AIM:To evaluate promoter methylation of CDH1, p16, APC, MLH1, and COX2 in patients with H. pylori (Hp) infection before and after eradication.METHODS:Fifty-seven dyspeptic outpatients who had never performed previous endoscopy or Hp testing and treatment underwent clinical interview, endoscopy with three paired gastric biopsy specimens from the antrum, angulus, and corpus, and 13C-urea breath test (UBT). Biopsies were scored for the presence of Hp and intestinal metaplasia (IM). DNA methylation of five tumor-related genes (CDH1, p16, MLH1, APC, and COX2) was evaluated by methylation-specific PCR in each biopsy. Infected patients were given a standard eradicating treatment and, after 1 yr, underwent endoscopy with biopsies and UBT.RESULTS:Hp infection was found in 45 patients. IM was detected in 17 out of 45 (38%) infected patients. Mean number of methylated genes was 0, 1.1 ± 0.9, and 1.6 ± 0.9 among the 12 Hp−/IM−, the 28 Hp+/IM−, and the 17 Hp+/IM+ patients, respectively (P < 0.0001). Specifically, promoter hypermethylation of CDH1, p16, APC, MLH1, and COX2 was found in 68%, 25%, 7%, 0%, and 14% of Hp+/IM− patients and in 71%, 29%, 35%, 12%, and 12% of Hp+/IM+ patients. No significant difference was found among the three groups of patients as far as age, smoking, alcohol, meat and vegetable consumption, and family history of gastric cancer were considered. Twenty-three out of 45 (51%) infected patients underwent the 1-yr follow-up endoscopy: 17 out of 23 (74%) were successfully eradicated. After Hp eradication, CDH1, p16, and APC methylation significantly decreased while COX2 methylation completely disappeared. Conversely, MLH1 methylation did not change significantly in patients with IM.CONCLUSION:Hp infection is associated with promoter methylation of genes which are relevant in the initiation and progression of gastric carcinogenesis. While CDH1 methylation seems to be an early event in Hp gastritis, MLH1 methylation occurs late along with IM. Hp eradication is able to significantly reduce gene methylation thus delaying or reversing Hp-induced gastric carcinogenesis.

Patterns of symptoms in functional dyspepsia: role of Helicobacter pylori infection and delayed gastric emptying

Objective:Functional dyspepsia (FD) is a syndrome in which several causes are probably involved. Our aim was to investigate the association between specific dyspeptic symptoms and Helicobacter pylori infection or delayed gastric emptying.Methods:Nine hundred thirty-five consecutive outpatients with unexplained dyspepsia were studied. After appropriate investigation, 304 patients were diagnosed as affected by chronic FD and were tested for H. pylori infection and gastric emptying of solids by means of 13C-urea and 13C-octanoic acid breath tests. Four dyspeptic symptoms (epigastric pain or burning, postprandial fullness, nausea, and vomiting) were scored as absent, mild, moderate, or severe (0–3) according to their influence on the patients’ activities. Symptoms of irritable bowel syndrome and gastroesophageal reflux disease were also assessed. On the basis of symptom scores, three groups were identified: “prevalent pain” (10.5%), “prevalent discomfort” (32.6%), and “unclassifiable” dyspepsia (56.9%).Results:Of the 304 patients with FD, 208 (68.4%) were H. pylori–positive on urea breath test. Gastric emptying was delayed in 99 subjects (32.6%). Patients with “prevalent pain” were infected significantly more often (81.2%vs 59.6%; p= 0.026) and less frequently had delayed gastric emptying (6.2%vs 40.4%; p= 0.0001) than those with “prevalent discomfort.”H. pylori infection was independently associated with age ≥40 yr and epigastric pain or burning ≥2 (odds ratio [OR] and 95% confidence interval [CI] 4.09 [2.39–7.00] and 1.70 [1.04–2.77], respectively). Delayed gastric emptying was independently associated with a cumulative score ≥6 for postprandial fullness, nausea, and vomiting (OR [95% CI]: 3.13 [1.06–9.18]). H. pylori status had no influence on gastric emptying. Logistic regression analysis showed that delayed gastric emptying, female sex, and concomitant symptoms of inflammatory bowel syndrome were independently associated with a cumulative score ≥6 for postprandial fullness, nausea, and vomiting (p= 0.0281, p= 0.0387, and p= 0.0316, respectively). Moreover, concomitant symptoms of gastroesophageal reflux disease, female sex, and H. pylori infection were independently associated with epigastric pain or burning ≥2 (p= 0.002, p= 0.0001, and p= 0.0875, respectively).Conclusions:Two subsets of FD patients have been identified on the basis of symptoms. One subgroup is mainly characterized by “prevalent pain,”H. pylori infection, and normal gastric emptying; the other one demonstrates “prevalent discomfort” and delayed gastric emptying. These findings shed some light on possible etiopathogenetic mechanisms of FD.

Helicobacter pylori infection and growth delay in older children.

It is thought that Helicobacter pyloriinfection may influence growth rate in children. The aim of this study was to evaluate the prevalence of H pylori infection in healthy Italian children, and to look for differences in height between infected and non-infected subjects. Two hundred and sixteen children, aged 3 to 14 years, were tested for H pylori infection by13C-urea breath test. Centile values for height were calculated. Composite indices for socioeconomic class and household crowding were also determined. Forty nine of 216 children (22.7%) wereH pylori positive. The prevalence of infection increased with age. Eight of 49 H pylori positive children (16.3%) were below the 25th centile for height, compared with 13 of 167 H pylori negative children (7.8%). This difference became significant in children aged 8.5 to 14 years; in this group (n = 127), eight of 31 infected children (25.8%) were below the 25th centile for height, compared with eight of 96 non-infected children (8.3%). A significant correlation was found between socioeconomic conditions, household crowding, and H pylori status. By using stepwise logistic regression, only the centile value for height was significantly related to H pylori status in older children. Thus H pylori infection was associated with growth delay in older children, poor socioeconomic conditions, and household overcrowding. This finding is consistent with the hypothesis that H pylori infection is one of the environmental factors capable of affecting growth.

Predictors of failure of Helicobacter pylori eradication with the standard 'Maastricht triple therapy'.

Triple therapy with proton pump inhibitor, clarithromycin and amoxicillin has recently been proposed in Maastricht as first‐line treatment for H. pylori infection.

Proton-Pump Inhibitors and Outcome of Endoscopic Hemostasis in Bleeding Peptic Ulcers: A Series of Meta-analyses

OBJECTIVE:To perform metaanalyses of studies on outcome of bleeding ulcers of different proton-pump inhibitors (PPIs) regimens, after stratification of patients by endoscopic stigmata, and analysis of studies with and without endotherapy.METHODS:A total of 35 randomized trials comparing PPIs to placebo and/or H2-receptor antagonists (H2RAs) in 4,843 patients with high-risk endoscopic stigmata were retrieved. Outcomes were rebleeding, surgery, and mortality.RESULTS:Monotherapy with oral or bolus PPIs was superior to placebo and H2RAs in reducing rebleeding in both bleeders and nonbleeders at index endoscopy; the need for surgery was reduced only when compared to H2RAs. In nonbleeders, PPI monotherapy was as effective as a combination of endotherapy with H2RAs. A combination of endotherapy with PPIs was superior to monotherapy in reducing bleeding and surgery, and superior to endotherapy alone in minimizing rebleeding, but not surgery; the benefit was lost when confronted to endotherapy plus H2RAs, whether PPIs were given as infusion or bolus. By pooling data from studies comparing high doses of PPIs as continuous infusion versus regular doses as intermittent bolus, rebleeding, surgery, and mortality were not significantly different.CONCLUSIONS:Combination of endotherapy with either PPIs or H2RAs is indicated for nonbleeding ulcers at endoscopy with the intent to reduce rebleeding and surgery. Its value may extend to bleeding lesions, but current data are scanty. The benefit appears to be independent from route and doses of PPIs, as oral, bolus, or infusional methods are all effective.

helicobacter pylori Infection May Undergo Spontaneous Eradication in Children: A 2-year Follow-up Study

BACKGROUND Helicobacter pylori infection is generally acquired early in life. However, it is still unknown whether a spontaneous eradication can occur. The purpose of this study was to evaluate whether H. pylori infection can undergo spontaneous eradication in children. METHODS Three hundred and four Italian children (age range, 4.5 to 18.5 years) were tested for H. pylori by means of 13C-urea breath test. Infected children were followed up every 6 months for as long as 2 years. Parents were instructed to record consumption of antibiotics. At each visit, children underwent a repeat 13C-urea breath test. RESULTS Eighty-five out of 304 (27.9%) children were H. pylori infected. Forty-eight out of 85 infected children (56.4%) participated in the follow-up study. After 2 years, 8 (16.6%) infected children had negative results on 13C-urea breath tests; 2 of them were given antibiotics for concomitant infections. One child was negative at 6 months but became positive again at the next 6-month 13C-urea breath test. Forty children remained persistently positive; of them, 10 were treated with a short course of antibiotics. CONCLUSIONS Our findings support the hypothesis that, at least during childhood, H. pylori infection may be a fluctuating disease with spontaneous eradication and possible recurrence.

Gastric emptying of solids is delayed in celiac disease and normalizes after gluten withdrawal

Several gastrointestinal motor abnormalities have been detected in patients with celiac disease, but it is unclear whether they are able to influence the gastric emptying rate. The aim of this work was to evaluate the gastric emptying rate of solids in children with celiac disease before and after a gluten‐free diet. Nine children with celiac disease and nine healthy controls (age range 4‐16 y) underwent a 13C‐octanoic acid breath test to measure gastric emptying. Half emptying time (t1/2) and lag phase (tlag) were calculated. After 6 mo of a gluten‐free diet, all celiac children underwent a repeat 13C‐octanoic acid breath test. The gastric motility parameters, t1/2 and tlag, were significantly longer in patients than in controls. No significant correlation between abnormal gastric emptying and specific symptom patterns or severity of histological damage was found. On a gluten‐free diet, the gastric emptying rate normalized in all celiac patients. This finding supports the hypothesis that gluten‐driven mucosal inflammation might determine motor abnormalities by affecting smooth muscle contractility or impairing the release of neurotransmitters. Alternatively, nutrient malabsorption might determine significant changes in intraluminal milieu, which, in turn, may affect intestinal motor functions.

Ranitidine bismuth citrate‐based triple therapies after failure of the standard ‘Maastricht triple therapy’: a promising alternative to the quadruple therapy?

Triple therapy with proton pump inhibitor, clarythromycin, and amoxicillin has been proposed in Maastricht as the first‐line treatment of H. pylori infection.

Amoxicillin‐Tetracycline Combinations are Inadequate as Alternative Therapies for Helicobacter pylori Infection

Background. Triple therapy with proton pump inhibitors or ranitidine bismuth citrate, clarithromycin and either amoxicillin or nitroimidazole derivatives are the present gold standards for cure of Helicobacter pylori infection. However, primary resistance to either clarithromycin or nitroimidazole derivatives is increasing and alternative therapies are needed.