Lee J. Hixson

Regression of Barrett's esophagus by laser ablation in an anacid environment

SummaryConsistent regression of intestinal metaplasia in Barretts esophagus has not been achieved with medical or surgical interventions. In this case report, a patient with Barretts esophagus of stable length had half the circumference of the Barretts epithelium ablated with laser therapy while on a high-dose proton-pump inhibitor. In the absence of esophageal acid exposure and after laser ablation, the intestinal metaplasia was documented to reepithelialize with normal squamous mucosa, which has oersisted.

ASSESSMENT OF MUTATIONS IN KI-RAS AND P53 IN COLON CANCERS FROM AZOXYMETHANE- AND DIMETHYLHYDRAZINE-TREATED RATS

Mutations in the Ki‐ras oncogene and the p53 tumor suppressor gene are known to occur at high frequencies in human colon cancers. We measured the frequency of mutations in these two genes in colon adenocarcinomas obtained from a widely used experimental model of human colon carcinogenesis: F344 rats treated with the carcinogens azoxymethane (AOM) or dimethylhydrazine (DMH). We detected codon 12 mutations in Ki‐ras in approximately 60% of colon adenocarcinomas induced by either carcinogen. We characterized the rat p53 intron‐exon junctions to construct primers for polymerase chain reaction amplification of this gene. We discovered that the rat p53 gene was structurally different from the human p53 gene, as the rat gene was missing one intron between exons 6 and 7. Both single‐stranded DNA conformational polymorphism analysis and direct DNA sequencing of the highly conserved regions of rat exons 5–7 were conducted because the corresponding human regions (exons 5–8) have been reported as being mutated most frequently in human colon cancers. Using these methods, we were unable to identify any p53 mutations in the highly conserved regions of exons 5–7 in either AOM‐ or DMH‐induced colon adenocarcinomas. These data confirm that Ki‐ras was mutated in most colon cancers in AOM‐ or DMH‐treated rats but indicate that molecular alterations in the p53 gene, if they occur in this animal model, are different from most p53 mutations in human colon cancers. Mol. Carcinog. 19:137–144, 1997.

Preventing hypoxemia during colonoscopy a randomized controlled trial of supplemental oxygen

Hypoxia as measured by pulse oximetry is well recognized in patients undergoing colonoscopy. A single trial of supplemental oxygen therapy has been shown to diminish the observed desaturation during colonoscopy. We further defined the role of supplemental oxygen during colonoscopy in a randomized controlled trial. Ninety-four patients undergoing routine colonoscopy were randomized to oxygen (2 L by nasal prongs) or placebo (nasal prongs only) arms. The physician and patients were blinded to which arm they were in. Sixty-four percent of patients in the placebo arm desaturated (less than 90% saturation) versus 29% in the treatment arm (p less than 0.001). There were no complications observed in either arm. We conclude that supplemental oxygen will decrease but not prevent the incidence of arterial desaturation observed during colonoscopy.

False-positive secretin-KABI provocation test associated with achlorhydria

Two patients with chronic abdominal pain and fasting hypergastrinemia had increases in serum gastrin of 440 and 300 pg/ml after injection of 2 U/kg Secretin-KABI. Both subsequently proved to have pentagastrin-fast achlorhydria. Intragastric instillation of 0.1 N HCl suppressed serum gastrin concentration by greater than 60%. In both, the pancreas was normal by sonography or computed tomography (CT) scan and at laparotomy in one. Both are currently asymptomatic 12 and 18 months later. We conclude that achlorhydria may be associated after injection of Secretin-KABI with a false-positive rise in fasting serum gastrin concentration of greater than 200 pg/ml and that gastric analysis for hypochlorhydria should be performed before secretin provocation testing.

Dietary Fiber or Piroxicam as Potential Cancer Prevention Agents: Effects on Rectal Epithelial Cell Proliferation in Humans at Increased Risk of Colon Cancer

Over the past decade, there has been little improvement in outcome of treatment for advanced colon cancer. The best chance for cure remains early removal of a localized malignant tumor. Accordingly, much emphasis has been focused on screening, early detection and removal of recognized precursor lesions, namely adenomatous colon polyps. However, this approach is problematic in that current methods, such as testing of stool for occult blood and periodic examination of the rectum and colon by fiberoptic endoscopy, have either less than desired sensitivity or are expensive, entail some risk, detect only gross macroscopic lesions and do not address the persistence of abnormal colonic mucosal biology which imparts a continued cancer risk. However, the demonstration that colonic crypt epithelial cell proliferative activity (labeling index) which is increased in colon cancer was also abnormal in colon mucosa of patients with familial polyposis coli, who are known to be at high risk for developing cancer, provided a tool to assess for the presence of a subclinical or microscopic abnormality (Lipkin 1983, 1984). The subsequent reports that crypt cell proliferative activity was also increased in patients with sporadic colon adenomas, and that the labeling index in patients with familial polyposis could be changed toward normal by addition of calcium to the diet, provides evidence that this marker of crypt cell epithelial proliferative activity might be useful to evaluate cancer risk in certain patient groups and for assessing the effects of treatment interventions aimed at decreasing cancer risk (Lipkin 1985). We have used the tritiated thymidine labeling index to evaluate the effects of two proposed cancer prevention strategies, namely increased dietary fiber and treatment with the nonsteroidal anti-inflammatory drug (NSAID) piroxicam.