High-grade dysplasia associated with fundic gland polyposis in a familial adenomatous polyposis patient, with special reference to APC mutation profiles.

We report a patient with familial adenomatous polyposis who developed high-grade dysplasia against a background of fundic gland polyposis. Two large high-grade dysplasia lesions were found in the gastric body, where numerous fundic gland polyps were present. In both lesions, the dysplastic epithelium covered non-neoplastic oxyntic glands that occasionally exhibit cystic changes. A genetic analysis for APC (adenomatous polyposis coli) revealed a somatic 50-bp deletion involving codons 1502-1517 and 2-bp deletion at codon 1465 in each lesion of high-grade dysplasia. In contrast, six of the 18 fundic gland polyps were found to harbor an identical mutation: 1-bp insertion at codon 1556. Both lesions of high-grade dysplasia and the fundic gland polyps were similarly located in the fundic gland area and were caused by the inactivation of APC; however, their mutation profiles of APC were different. These results imply that fundic gland polyps and high-grade dysplasia of the stomach have distinct preferences for APC genotypes in their development.     

Identification of quantitative trait loci for cardiac hypertrophy in two different strains of the spontaneously hypertensive rat.

Cardiac hypertrophy and left ventricular hypertrophy are known to be substantially controlled by genetic factors. As an experimental model, we undertook genome-wide screens for cardiac mass in F2 populations bred from the stroke-prone spontaneously hypertensive rats (SHRSP) and normal spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) of a Japanese colony. Two F2 cohorts were independently produced: F2(SHRSP x WKY) (110 male and 110 female rats) and F2(SHR x WKY) (151 male rats). The ratio of heart weight to body weight (Hw/Bw) was evaluated at 12 months of age in F2(SHRSP x WKY) after salt-loading for 7 months, and at around 15 weeks of age in F2(SHR x WKY) who had been fed a normal rat chow diet. Subsequent to an initial screen with 251 markers in F2(SHRSP x WKY) male progeny, 170 and 161 markers were selected and characterized in F2(SHRSP x WKY) female progeny and F2(SHR x WKY) male progeny, respectively. Markers from four chromosomal regions showed suggestive or significant linkage to Hw/Bw. The strongest and the most consistent linkage was found in the vicinity of D3Mgh16 on rat chromosome (RNO) 3 (a maximal log of the odds score reached 4.0 to 6.6 across the F2 populations studied). In the other three regions on RNO6, RNO10 and RNO13, the degree of linkage was more prominent in either males or females. These data provide solid evidence for a "principal" RNO3 quantitative trait loci regulating Hw/Bw in SHRSP and SHR, and also suggest the possible presence of sexual dimorphism in regard to genetic susceptibility for cardiac hypertrophy.     

Molecular screening of the human melanocortin-4 receptor gene: identification of a missense variant showing no association with obesity, plasma glucose, or insulin

Summary Disruption of the melanocortin-4 (MC-4) receptor gene in mice results in maturity-onset obesity, hyperinsulinaemia and hyperglycaemia. These phenotypes are characteristic of human obesity that frequently accompanies non-insulin-dependent diabetes. It is therefore possible that human MC-4 receptor gene mutations contribute to human obesity. To test this possibility, we examined by DNA sequencing the entire coding region of the human MC-4 receptor gene in 40 morbidly obese (BMI > 35 kg/m²) white British males and examined the 5′- and 3′-flanking regions in 20 out of these obese subjects. We also sequenced all these regions in 10 lean (BMI < 18 kg/m²) white British males for a reference. We identified a single nucleotide substitution that replaces valine with isoleucine at codon 103, in two obese subjects in the heterozygous state. No other nucleotide alterations were found. The prevalence of this missense variant was studied in 322 white British males (190 with BMI > 28 kg/m² and 132 with BMI < 22 kg/m²) selected from a population-based epidemiological survey. In these subjects, no homozygotes for the isoleucine allele were found. The frequency of heterozygotes was similar (4.2 vs 4.5 %) in the two groups and there was no significant difference in BMI, total skinfold thickness, plasma insulin and glucose levels between heterozygotes and codon-103 valine homozygotes in either group. These results suggest that coding sequence mutations in the MC-4 receptor gene are unlikely to be a major cause of human obesity, at least in white British males. [Diabetologia (1997) 40: 976–979] Received: 10 March 1997 and in revised form 9 May 1997     

Endoscopic submucosal resection of rectal carcinoid tumors with a ligation device

BACKGROUND: Local endoscopic mucosal resection of rectal carcinoid tumors is often associated with margin involvement that requires further intervention. The efficacy of resection of these tumors with endoscopic submucosal resection with a ligation device (ESMR-L) was evaluated. METHODS: Fourteen rectal carcinoid tumors were treated by ESMR-L between 1999 and 2002. ESMR-L was performed with a conventional colonoscope with an attached band-ligator device. For comparison, 14 rectal carcinoid tumors, treated by either endoscopic mucosal resection or polypectomy between 1990 and 1997, were evaluated as historical controls. All tumors were estimated to be 1 cm or less in diameter. OBSERVATIONS: There were no differences between the 2 groups in terms of age, gender, or tumor size. For 6 (43%) patients in the control group, there was tumor involvement at the margin of the resection specimen, whereas all tumors removed by ESMR-L had histopathologically proven negative margins (p < 0.05). The mean vertical resection margin also was significantly deeper in the ESMR-L group (p < 0.05). There was no complication of any procedure. CONCLUSIONS: ESMR-L is technically simple, minimally invasive, and safe for treatment of small rectal carcinoid tumors contained within the submucosa. ESMR-L provides a deeper resection margin compared with that obtained with conventional endoscopic mucosal resection or polypectomy.     

Guidelines for sedation in gastroenterological endoscopy

Recently, the need for sedation in gastrointestinal endoscopy has been increasing. However, the National Health Insurance Drug Price list in Japan does not include any drug specifically used for the sedation. Although benzodiazepines are the main medication, their use in cases of gastrointestinal endoscopy has not been approved. This has led the Japan Gastrointestinal Endoscopy Society to develop the first set of guidelines for sedation in gastrointestinal endoscopy on the basis of evidence‐based medicine in collaboration with the Japanese Society for Anesthesiologists. The present guidelines comprise 14 statements, five of which were judged to be valid on the highest evidence level and three on the second highest level. The guidelines are not intended to strongly recommend the use of sedation for gastrointestinal endoscopy, but rather to indicate the policy as to the choice of appropriate procedures when such sedation is deemed necessary. In clinical practice, the final decision as to the use of sedation should be made by physicians considering patient willingness and physical condition.     

Width and depth of resection for small colorectal polyps: hot versus cold snare polypectomy

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