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Suppression of azoxymethane-induced colon cancer development in rats by a cyclooxygenase-1 selective inhibitor, mofezolac.

We demonstrated recently that mofezolac, a cyclooxygenase-1 (COX-1) selective inhibitor, suppresses the development of azoxymethane (AOM)-induced colonic aberrant crypt foci in F344 rats and intestinal polyps in APC1309 mice. In the present study, we therefore investigated the effects of mofezolac on colon cancer development. Male F344 rats were injected subcutaneously with 15 mg/kg body weight of AOM in the back twice at 7-day intervals from 5 weeks of age, and fed a diet containing 600 or 1200 ppm mofezolac for 32 weeks, starting 1 day before the first dosing of AOM. Treatment with 1200 ppm mofezolac significantly reduced the incidence, multiplicity and volume of colon carcinomas to 79%, 2.15 +/- 1.65 and 7.5 +/- 11.8 mm3, respectively, compared with 94%, 3.19 +/- 1.87 and 23.7 +/- 31.2 mm3 in the AOM treatment alone. Administration of 600 ppm mofezolac showed only a slight reduction. No side effects were observed in any of the groups. These results confirm that COX-1, as well as COX-2, contributes to colon carcinogenesis and that mofezolac may be a good chemopreventive agent for human colon cancer.

Animals↗

Development of gastric adenocarcinoma in Mongolian gerbils after long-term infection with Helicobacter pylori.

BACKGROUND AND AIM: The experimental evidence that long-term colonization of Helicobacter pylori results in the development of gastric cancer in Mongolian gerbils has been reported only by two Japanese groups to date. This study aimed to investigate the carcinogenicity of H. pylori infection in a Mongolian gerbil model. METHODS: Thirty-six Mongolian gerbils (inner Mongolian origin) were divided into two groups (male to female ratio, 1:1) and orally inoculated with a standard H. pylori strain (ATCC43504) or H. pylori161 (isolated from a Chinese patient with gastric adenocarcinoma), respectively, once a week for 5 weeks. Another 10 control gerbils were given phosphate-buffered saline. The animals were killed 8, 20, 28 and 84 weeks after inoculation for bacterial and histological examination. RESULTS: Seven inoculated gerbils died at the week 42. Overall, H. pylori colonization was detected in 24 (83%) of the 29 available inoculated gerbils. The gastric lesions were aggravated gradually over time. At week 84, moderate to severe gastritis, characterized by diffuse infiltration of mononuclear cells and formation of multiple lymphoid follicles in mucosa and submucosa, and even the lymphoepithelial lesions, were observed. Epithelial hyperplasia were dominant in almost all gerbils. Four (24%) of the 17 animals had hyperplastic polyps. Intestinal metaplasia were rarely seen (in three gerbils). Well-differentiated gastric adenocarcinomas developed in three (18%) of the 17 gerbils after 84 weeks. Of the three gerbils, one female gerbil was infected with H. pylori161 and the others (one male and one female) were infected with ATCC43504. CONCLUSIONS: The present study reconfirms that H. pylori infection alone can induce gastric adenocarcinoma in Mongolian gerbils and suggests that different species of gerbil and both standard and clinically isolated H. pylori strains can be used for investigating the carcinogenesis of H. pylori. This is the first report of the development of gastric cancer in female gerbils, which highlights the importance of using both sexes to investigate the pathogenesis of H. pylori and whether host susceptibility is influenced by sex.

Adenocarcinoma↗

Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers.

BACKGROUND: Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown. AIMS: To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue. METHODS: Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells. RESULTS: In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear beta-catenin. The number of H2RSP-positive cells in the invasive front of well-differentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones. CONCLUSION: In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers.

Adenocarcinoma↗

ACP Best practice no 159. Examination of large intestine resection specimens.

Macroscopic examination of large intestinal resection specimens by the surgical pathologist provides important diagnostic and prognostic information. This review summarises current recommended protocols and evidence based guidelines for gross description, dissection, and histological block selection in both neoplastic and non-neoplastic colorectal disease. Specific lesions discussed include colorectal cancer, polypectomies and polyposis syndromes, and inflammatory bowel disease. Microscopic examination is briefly described, with emphasis on certain pitfalls that might be encountered in routine practice. A section covering special techniques for the investigation of occult bleeding is included.

Clinical Protocols↗

Multiple radiopaque masses in the jaws.

In this report, the less common oral findings occurring in Gardner's syndrome are described, which occurred concurrently with colorectal polyposis. In addition, what clinically appeared as small intestinal polyps, microscopically represented nodular lymphoid hyperplasia, as reported in the literature. Review of the literature showed the oral findings reported here are not common and that enzyme assays can help detect polyps at an early stage of this complex syndrome.

Adenomatous Polyposis Coli↗

Difficult wounds: an update.

The purpose of this collective review is to describe revolutionary advances in the treatment of Gardner's syndrome (GS), pseudofolliculitis barbae, nasal septal perforation, factitious wounds, and hidradenitis suppurativa (HS). Gardner's syndrome or familial polyposis has various manifestations that appear to be controlled by a single genetic locus. Apart from the large bowel adenomas, which are always present, a common extracolonic symptom of Gardner's syndrome is the occurrence of epidermal cysts. These cysts can be seen before the intestinal polyps are evident. Because epidermal cysts in patients with Gardner's syndrome are always benign, we excise these cysts using incisions that are commonly used for rhytidectomy. Pseudofolliculitis barbae, a pseudofolliculitis caused by ingrown hairs, effects 85% of blacks who shave their beards. When this disease is allowed to progress to keloid formation, we use a surgical approach that includes excision of the keloidal scar, meticulous debridement of all residual ingrown hairs in the underlying wound, and coverage of the defect with a split-thickness skin graft. More recently, laser therapy has revolutionized the treatment of pseudofolliculitis barbae and has enabled a cure for the first time for those plagued with this disorder and for whom a beardless face is acceptable. Nasal septal perforation is a well recognized complication of septal surgery. Other iatrogenic causes of perforation include cryosurgery, electrocoagulation for epitaxis, nasotracheal intubation, or nose packing. In recent years drugs such as cocaine account for an increasing number of perforations. It has only been with the use of an external approach for the repair of the nasal septal defect that surgical closure has become easier and more reliable. The external approach allows for greater surgical closure and enables the surgeon to use both hands with the aid of binocular vision to mobilize and suture local mucosal advancement flaps and the intraseptal connective tissue grafts. More recently, surgeons have repaired large septal perforations with a radial forearm free flap. Because of its availability and deep emotional significance, the skin is a common site for self-destructive behavior with the development of factitious skin wounds. When suspected, psychiatric care must proceed immediately. Second, the ulcer can then be healed by appropriate techniques and wound repair. It is important to emphasize that the treating physician must first confront the patient, and then a psychiatrist should provide appropriate psychotherapy. Hidradenitis suppurativa is an inflammatory disease of the skin and subcutaneous tissue that occurs in apocrine-gland-bearing areas distributed in the axilla, mammary nipple areola, mons pubis, groin, scrotum, perineum, perianal region, and umbilicus. The condition has an insidious onset. The susceptibility of women's axillary skin to hidradenitis suppurativa may be related, in part, to the practice of axillary removal of hair with a safety razor. Consequently, the use of safety razors must be avoided and replaced with the use of an electric razor. The method of treatment will vary with the stage of the disease. Treatment of the chronic stage of axillary hidradenitis suppurativa is primarily surgical. More recently, carbon dioxide laser treatment, with healing by secondary intention, is proving to be a rapid, efficient, and economic treatment of this difficult wound.

Epidermal Cyst↗