The syndrome of gastric carcinoid and hyperparathyroidism: a family study and literature review.

OBJECTIVE: To present evidence supporting the hypothesis that the coexistence of gastric carcinoids (GCs) and hyperparathyroidism may represent a distinct clinical entity, not related to multiple endocrine neoplasia type 1 (MEN1). METHODS: We studied a cohort of five young siblings (age range 26-42 years), one of whom had been found to have GC and hyperparathyroidism. All siblings underwent serial gastroscopies for the assessment of gastric neuroendocrine cell proliferations over a mean follow-up period of 31.2 months. Imaging, biochemical and hormonal as well as molecular genetic investigations were performed in the direction of MEN1 syndrome. The literature was searched for cases with coexistence of GCs and hyperparathyroidism not associated with MEN1. RESULTS: Four of the siblings, all male, were found to have GCs in a background of Helicobacter pylori-associated chronic atrophic gastritis and pernicious anaemia, with no serological evidence of gastric autoimmunity. In two of them, asymptomatic hyperparathyroidism was also present. Screening for MEN1 gene mutations or large deletions was negative, and hormone and imaging investigations did not support a diagnosis of familial MEN1 syndrome. A literature search revealed sporadic reports of cases with GC and hyperparathyroidism not attributable to MEN1. CONCLUSIONS: The association of GCs and hyperparathyroidism appears to constitute a distinct syndrome that can be encountered in genetically predisposed individuals, and should not be regarded as 'atypical' or 'incomplete' expression of MEN1. Its prevalence and aetiology should be the subject of future studies. Screening for hyperparathyroidism seems to be justified in patients with GC of any type.

Decreased expression of DNA-dependent protein kinase, a DNA repair protein, during human colon carcinogenesis.

DNA-dependent protein kinase (DNA-PK), consisting of a catalytic subunit (DNA-PKcs) and the Ku70 and Ku86 proteins, participates in the repair of DNA double-strand breaks (DSBs). We assessed its expression immunohistochemically in normal human colon tissue, colon adenomas, colon carcinomas, and normal tissue distant from carcinomas. Normal colonocytes expressed all DNA-PK proteins. Compared with the expression in normal tissue [176.62 +/- 18.56 (the intensity of expression x the percentage of cells expressing this protein), mean + SE], the expression of Ku70 was significantly reduced in adenomas (36.62 +/- 11.09; P < 0.001) and carcinomas (85.68 +/- 15.76; P < 0.01), as was the expression of Ku86 [(113.10 +/- 10.22 versus 41.66 +/- 14.71 in adenomas (P < 0.01) or versus 85.68 +/- 15.76 in carcinomas (P < 0.05)]. The expression of DNA-PKcs was not significantly changed. The marked underexpression of Ku70 and Ku86 starting at the adenoma stage may be crucial to the development of colon cancer.

"Reappearance" of Helicobacter pylori after eradication: implications on duodenal ulcer recurrence: a prospective 6 year study.

We estimated the rate of Helicobacter pylori "reappearance" and of duodenal ulcer relapse up to 6 years after eradication of H. pylori. Of 220 patients in whom H. pylori was eradicated, 165 were eligible at 12 months to follow-up. Endoscopy was scheduled every 12 months or whenever symptoms appeared. Baseline H. pylori eradication was confirmed by CLO test, histology (hematoxylin-eosin and Giemsa stain), and culture. H. pylori was tested for by the three methods at 12 months and subsequently by 2 methods (CLO, histology) on biopsies obtained from the gastric antrum and body. We reviewed 90 patients after 1 year, 32 after 2 years, 13 after 3 years, 12 after 4 years, 2 after 5 years, and 16 after 6 years (range, 12 to 72 months; average, 25.23 months; patient-years, 347). At 12 months after eradication, 16 of 165 patients (9.7%) were H. pylori positive and 5 had ulcer relapse. Of 75 patients evaluated at 24 months, 7 (9.3%) were H. pylori positive and 1 (1.3%) had ulcer relapse. At 36 months, 43 patients were seen and 1 (2.3%) was H. pylori positive and had ulcer relapse (2.3%). Thirty, 18, and 16 patients were seen at 48, 60, and 72 months, respectively. None was H. pylori positive and none had ulcer relapse. Overall, 24 H. pylori-positive patients were found, two thirds of them in the first year after eradication. In 7 of 24 (29%, 6 smokers), ulcer recurred. None of the H. pylori-negative patients had ulcer relapse. The H. pylori reappearance rate was 7% and the ulcer relapse rate was 2% per patient-year. If the 16 H. pylori-positive patients who were found the first year are considered as recrudescence, then the reinfection rate will be 2.3% per patient-year.

High eradication rate of Helicobacter pylori using a four-drug regimen in patients previously treated unsuccessfully.

The objective of this study was to assess the efficacy of a new regimen in eradicating Helicobacter pylori (Hp) in patients with duodenal ulcer (DU) who were previously treated unsuccessfully with standard triple therapy (tripotassium dicitratobismuthate [TDB] 120 mg QID, metronidazole 500 mg TID, and tetracycline 500 mg QID) or proton-pump inhibitor (PPI) dual therapy (omeprazole 20 mg BID and amoxicillin 500 mg QID). The study included 133 consecutive patients aged 17 to 83 years with endoscopically diagnosed DU (diameter > or = 5 mm) in whom standard triple therapy or PPI dual therapy had failed to eradicate Hp. A rapid urease (CLO) test was performed on four biopsy specimens at study entry and at least 1 month after the end of treatment to confirm Hp colonization and eradication, respectively. Patients were considered to be Hp positive if any CLO test was positive within 2 hours, and Hp was considered to be eradicated if all CLO tests were still negative after 24 hours. In 31 randomly selected patients, Hp eradication was confirmed histologically as well. Patients were given omeprazole 60 mg/d (20 mg in the morning and 40 mg in the evening) plus amoxicillin 500 mg QID for 10 days and subsequently were given metronidazole 500 mg TID for 10 days plus TDB 120 mg QID for 6 weeks. One hundred and twenty-four patients were followed up; five (4%) withdrew because of side effects (protracted diarrhea, stomatitis, skin rashes). Per-protocol analysis showed Hp eradication in 113 of 119 patients (95%) and ulcer healing in 118 of 119 (99%). Intent-to-treat analysis showed an Hp eradication rate of 85% (113 of 133 patients) and an ulcer healing rate of 89% (118 of 133 patients). In per-therapy analysis, the Hp eradication rate was 91% (113 of 124 patients), and the ulcer healing rate was 95% (118 of 124 patients). Side effects were observed in 39 of 119 patients (33%) and were generally mild. The four-drug regimen used in this study, when given to patients previously treated unsuccessfully with standard triple therapy or PPI dual therapy, was highly effective in eradicating Hp and healing DUs and had no major side effects.

One-week therapy with omeprazole, clarithromycin and metronidazole or ornidazole, followed by 3 weeks' treatment with omeprazole, eradicates Helicobacter pylori equally and heals duodenal ulcer.

OBJECTIVE: To estimate and compare the efficacy of 'triple' 1-week regimens--omeprazole, clarithromycin and a nitroimidazole (metronidazole or ornidazole)--followed by omeprazole, for an additional 3 weeks, on Helicobacter pylori eradication and duodenal ulcer (DU) healing, in a country with a high resistance rate of H. pylori to metronidazole. DESIGN: Open, prospective, two-centre study. METHODS: Patients older than 18 years with active duodenal ulcer (DU), diagnosed by endoscopy and found to be infected with H. pylori (modified Giemsa stain and CLO test, Delta West, Australia), were included in the study. Three triple-drug regimens, given for 7 days, were used. (1) omeprazole (Om) 20 mg once a day, plus clarithromycin (Cl) 250 mg twice daily, plus ornidazole (Or) 500 mg twice daily (O1COr); (2) Om 20 mg twice daily, plus Cl 250 mg twice daily, plus Or 500 mg twice daily (OCOr); and (3) Om 20 mg twice daily, plus Cl 250 mg twice daily, plus metronidazole (M) 500 mg twice daily (OCM). Two hundred and three consecutive H. pylori-positive patients were included in the study, randomly assigned as follows: 50 patients (group A1: 32 men, 18 women, age 23-77 years) on O1COr; 47 patients (group A2: 29 men, 18 women, age 27-77 years) on OCOr; and 106 (group B: 71 men, 35 women, age 18-83 years) on OCM. Ulcer healing and H. pylori eradication were assessed endoscopically, 8-9 weeks after the start of treatment. H. pylori was considered eradicated if both histology and rapid urease test (six biopsies, antrum-body) were negative. RESULTS: Eleven patients were lost to follow-up; 192 patients were analysed. Group A1: 48; group A2: 44; group B: 100. 'Per-protocol' analysis: H. pylori eradication, 90-93% (P = 0.901); ulcer healing, 90-98% (P = 0.300). 'Intention to treat' analysis: H. pylori eradication, 85-88% (P = 0.887); ulcer healing, 86-91% (P = 0.657). Compliance was excellent, no serious side effects were observed and no patients withdrew due to side effects. CONCLUSIONS: No differences were observed in the H. pylori eradication and the healing rate among the groups. It seems that twice daily omeprazole is no better than single daily dosage and that ornidazole is as effective as metronidazole. In addition, in the studied population which is believed to have a high prevalence of metronidazole resistance, all the regimens used were effective.

Triple therapy eradicated H. pylori equally in patients pretreated with omeprazole or ranitidine. A 12-month follow-up.

The aim of this study was twofold: first, to investigate the effectiveness of a standard triple therapy (tripotassium dicitrato bismuthate, 125 mg q.i.d., tetracycline hydrochloride 500 mg q.i.d., and metronidazole 500 mg t.i.d.) in eradicating Helicobacter pylori in patients with duodenal ulcer successfully healed with omeprazole or ranitidine; second, to examine the influence of the eradication on duodenal ulcer recurrence rate after 12 months. Two hundred forty-five consecutive H. pylori-positive patients with healed duodenal ulcer either with omeprazole (20 mg/day, 126 patients) or with ranitidine (150 mg b.i.d., 119 patients) given at random, began triple therapy for 15 days. H. pylori eradication was looked for 4-5 weeks later by culture of biopsy material, hematoxylin-eosin stain, and rapid urease test. H. pylori-eradicated patients were followed up for 12 months. Endoscopy was carried out at the end of the follow-up or whenever symptoms appeared. Five patients (2.0%) withdrew because of triple-therapy-related side effects. The eradication rate was 92% (220 of 240 patients); no difference was found between those healed with omeprazole (93%, 114 of 123 patients) or ranitidine (91%, 106 of 117 patients). Of 220 successfully treated patients, 132 completed the 12-month follow-up. The duodenal ulcer recurrence rate was 4% (5 of 132 patients); 3% (2 of 70) in the omeprazole group and 5% (3 of 62) in the ranitidine group healed. All the recurrences were asymptomatic. H. pylori recurrence rate was 11% (14 of 132 patients); no difference was found between patients healed with omeprazole (10%, 7 of 70 patients) or with ranitidine (11%, 7 of 62 patients). All the recurrent duodenal ulcers occurred in H. pylori-positive patients (36%, 5 of 14 patients). Standard triple therapy after duodenal ulcer healing with omeprazole or ranitidine eradicates H. pylori in comparable high rates. Side effects were mild and dropouts were only 2%. Ulcer recurrence rate 12 months after eradication was low and comparable between those healed with omeprazole or ranitidine.