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    ABSTRACT: Many gastric acid hypersecretory states (basal acid output of greater than 15.0 mEq/h) exist for which the etiology is known, such as Zollinger-Ellison syndrome, systemic mastocytosis, antral exclusion, antral predominant Helicobacter pylori gastritis (antral G cell hyperplasia), chronic gastric outlet obstruction, short gut syndrome and basophilic leukemias. However, many hypersecretory patients have no identified etiology for their acid hypersecretion and are designated as idiopathic gastric acid hypersecretors with a basal acid output of greater than 10 mEq/h and a normal serum gastrin level. Because of the gastric acid hypersecretion these patients also commonly have an increased frequency of stools. Idiopathic gastric acid hypersecretion represents a known cause of gastric acid hypersecretion that is far more common than Zollinger-Ellison syndrome and it has a markedly different treatment regimen and natural history. We report a case of a patient with idiopathic gastric acid hypersecretion previously misdiagnosed as having Crohn's disease because of a presenting complaint of diarrhea and mimicking Zollinger-Ellison syndrome because her fasting serum gastrin level was elevated when incorrectly measured in the presence of antisecretory treatment.
    European Journal of Gastroenterology & Hepatology 05/2005; 17(4):441-4. DOI:10.1097/00042737-200504000-00008 · 2.15 Impact Factor
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    ABSTRACT: To determine the frequency, mutation spectrum and phenotype of the recently described autosomal recessive MUTYH-associated polyposis (MAP), we performed a systematic search for MUTYH (MYH) mutations by sequencing the complete coding region of the gene in 329 unselected APC mutation-negative index patients with the clinical diagnosis of familial adenomatous polyposis (FAP) or attenuated FAP (AFAP). Biallelic germline mutations in MUTYH were identified in 55 of the 329 unselected patients (17%) and in another 9 selected index cases. About one-fifth (20%) of the 64 unrelated MAP patients harboured none of the 2 hot-spot missense mutations Y165C and/or G382D. Including 7 affected relatives, almost all MAP patients presented with either an attenuated (80%) or with an atypical phenotype (18%). Fifty percentage of the MAP patients had colorectal cancer at diagnosis. Duodenal polyposis was found in 18%, thyroid and stomach cancer in 1 case, other extraintestinal manifestations associated with FAP were not observed. In 8 families, vertical segregation was suspected; in 2 of these families, biallelic mutations were identified in 2 generations. Monoallelic changes with predicted functional relevance were found in 0.9% of the 329 patients, which is in accordance with the carrier frequency in the general population. In conclusion, biallelic MUTYH mutations are the underlying genetic basis in a substantial fraction of patients with adenomatous polyposis. The phenotype of MAP is best characterised as attenuated or atypical, respectively. Colorectal surveillance starting at about 18 years of age is recommended for biallelic mutation carriers and siblings of MAP patients, who refuse predictive testing.
    International Journal of Cancer 08/2006; 119(4):807-14. DOI:10.1002/ijc.21905 · 5.01 Impact Factor
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    ABSTRACT: Biallelic germline mutations in MYH are associated with colorectal neoplasms, which develop through a pathway involving somatic inactivation of APC. In this study, we investigated the incidence of the common MYH mutations in an Australian cohort of sporadic colorectal cancers, the clinicopathological features of MYH cancers, and determined whether inactivation of mismatch repair and base excision repair (BER) were mutually exclusive. The MYH gene was sequenced from lymphocyte DNA of 872 colorectal cancer patients and 478 controls. Two compound heterozygotes were identified in the cancer population and all three cancers from these individuals displayed a prominent infiltration of intraepithelial lymphocytes. In total, 11 heterozygotes were found in the cancer group and five in the control group. One tumour from an individual with biallelic germline mutation of MYH also demonstrated microsatellite instability (MSI) as a result of biallelic hypermethylation of the MLH1 promoter. Although MYH-associated cancers are rare in a sporadic colorectal population, this study shows that these tumours can develop through either a chromosomal or MSI pathway. Tumours arising in the setting of BER or mismatch repair deficiency may share a biological characteristic, which promotes lymphocytic infiltration.
    British Journal of Cancer 12/2006; 95(9):1239-43. DOI:10.1038/sj.bjc.6603421 · 4.82 Impact Factor