An assessment of the risk of neoplasia in long-term ileal reservoirs using the DMH rodent model

Heppell, Jacques; Zubiria, M De; Brais, M.; Durh, M A; Carioto, S.; Boivin, Y; Potvin, Claude

doi:10.1007/bf02053197

Cited by 11 publications

(4 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study we lost 19.6% of rats, including those groups undergoing no procedure. Our postoperative mortality was low (17.6%), which also represents appropriate performance (7,18,35). Furthermore, we obtained better results in female versus male rats.…”

Section: Discussionmentioning

confidence: 56%

See 1 more Smart Citation

Effect of defunctionalization on colon carcinogenesis in the rat

Pérez-Holanda

Rodrigo

Salas

et al. 2006

Rev. esp. enferm. dig.

View full text Add to dashboard Cite

Objective: to examine the effect of fecal absence on experimental colon carcinogenesis in both male and female rats. Material and methods: a total of 138 10-week-old Sprague-Dawley, male and female rats were divided into five groups: A) 20 rats, no treatment; B) 26 rats, colonic defunctionalization; C) 30 rats, 18 weekly doses of dimethylhydrazine (DMH), 21 mg/kg body weight each, from the beginning of the study; D) 20 rats, ethylen-diamine-tetraacetic acid for 18 weeks; and E) 42 rats, same surgical procedure as rats in group B plus DMH injections at the same doses as rats in group C. Animals were sacrificed after 25-27 weeks. Number of tumors, their location, and pathological findings were all compared between groups. Results: no tumors developed in the dimethylhydrazine-free groups. No differences were obtained either in number of tumors or tumors per rat for group C as compared to group E. Fecal absence was associated with smaller-sized tumors (p = 0.007), greater numbers of non-mucinous tumors (p = 0.00009), better differentiation (p = 0.0054), and lesser penetration into the wall (p = 0.015) for group E as compared to group C. In the dimethylhydrazine group, fecal absence altered the number of tumors developing in males as compared to female rats (p = 0.025). Moreover, this fecal absence showed no inhibitory effect on right colonic tumors (p = 0.0065). Conclusions: fecal absence alters the DMH-carcinogenic pattern in the defunctionalized colon when using an experimental model in both male and female rats.

show abstract

Section: Discussionmentioning

confidence: 56%

“…-Localization and ileal section at 5 mm from the ileocecal valve (17), proximal and distal ligatures of the arterial branch, and ligature with a silk 4/0 suture (18).…”

Section: Methodsmentioning

confidence: 99%

Effect of defunctionalization on colon carcinogenesis in the rat

Pérez-Holanda

Rodrigo

Salas

et al. 2006

Rev. esp. enferm. dig.

View full text Add to dashboard Cite

show abstract

“…Furthermore, the histological changes that occur in functioning pouches were found not to increase the risk of malignant transformation in the 1,2dimethylhydrazine dihydrochloride model of intestinal carcinogenesis in rats. 43 Nevertheless, very few pouches have been functioning for more than 10 years so that the late effects of pouch formation remain unknown. This stresses the need for longterm follow up with regular endoscopic and histological assessments in these patients.…”

Section: Discussionmentioning

confidence: 99%

Effects of the faecal stream and stasis on the ileal pouch mucosa.

Silva

Millard

Soper

et al. 1991

Gut

View full text Add to dashboard Cite

This study aimed to investigate the effects of the faecal stream and stasis on the mucosa of ileal pouches. Nine patients were followed up. Two pouch biopsy specimens were obtained from each at the time of pouch formation, ileostomy closure, and three, six, and 12 months after operation. None developed pouchitis. Two pouch biopsy specimens each were also obtained from 20 patients (six with pouchitis), whose pouches had been functioning for at least a year and in whom pouch evacuation was assessed by radioisotope labelled artificial stool. Biopsy specimens were assessed for the degree of acute and chronic inflammation, mucin type (high iron diaminealcian blue stain), a morphometric index of villous atrophy (villous height:total mucosal thickness), and crypt cell proliferation (using the monoclonal antibody Ki67). Mean values from the two biopsy specimens were obtained for each parameter. After three months of pouch function, the scores for acute and chronic inflammation, the degree of sulphomucin, and crypt cell proliferation were significantly higher, and the index of villous atrophy was significantly lower (indicating a greater degree of villous atrophy), than at pouch formation or at ileostomy closure. The values at pouch formation and ileostomy closure were similar. For all parameters, the changes seen at six and 12 months were not significantly different from those at three months. There was no significant correlation between the efficiency of pouch evacuation and any of the mucosal changes. It is concluded that exposure to the faecal stream is necessary for changes to take place in the pouch mucosa, although the amount of stasis, as measured by radioisotopic evacuation studies, seems to be irrelevant. The mucosal changes occur soon after ileostomy closure and then remain stable for at least one year. The aims of this study were firstly, to investigate the early and delayed effects of the faecal stream on the pelvic ileal pouch mucosa by making serial observations over a period of one year from the time of pouch formation, and secondly to relate mucosal changes to efficiency of pouch emptying of an artificial stool.Patients and tissues Nine patients with pelvic ileal pouches (seven men, median age 30 years (range 19-54)) were followed up for a period of 12 months from the time of their pouch formation. All of them had originally had ulcerative colitis. Two pouch biopsy specimens, taken at least 10 cm from the anal verge, were obtained at the time of pouch formation, at ileostomy closure (median 14 weeks (range 7-28) after pouch formation), and then at three, six, and 12 months after operation from each patient. None of the patients developed pouchitis during the follow up period or were taking medication other than antidiarrhoeal drugs (loperamide or diphenoxylate) throughout the 12 months.Two mucosal biopsy specimens, taken at least 10 cm from the anal verge, were also obtained from 20 patients with pelvic ileal pouches (15 men, median age 32 (range 22-56)) who consented to pouch evacuation studies....

show abstract

“…Our understanding of the pathophysiologic mechanisms that underlie pouchitis has been hampered not only by the lack of widely accepted and consistent diagnostic criteria (14), but also by the lack of a small animal model with correlates analogous to acute clinical pouchitis. Although rodent models have been developed to investigate various aspects of ileal pouch morphology (21), pouch neoplasia (22), and even pouch inflammation (23), these models lacked many of the physical signs of pouchitis (i.e., diarrhea, rectal bleeding, etc. ), and therefore had little direct clinical relevance to the study of the pathophysiologic mechanisms of acute pouchitis.…”

Section: Introductionmentioning

confidence: 99%

Pouchitis in a Rat Model of Ileal J Pouch–Anal Anastomosis

Shebani

Stucchi

Fruin

et al. 2002

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

Endorectal ileal pouch-anal anastomosis (IPAA) has become the operation of choice for patients with chronic ulcerative colitis. Although this procedure improves the quality of life, pouchitis remains a significant postoperative complication. Because our understanding of the pathophysiology of pouchitis may, in part, be due to the lack of small animal model, our aim was to develop a model of IPAA in a rat that mimics its clinical counterpart. Colectomy, proctectomy, construction of an ileal J pouch, and ileal pouch-rectal anastomosis as a model of IPAA was performed in Sprague-Dawley and Lewis rats. Radiographic contrast studies were performed to quantitate intestinal transit. The presence of activated neutrophils was quantified by measuring mucosal myeloperoxidase (MPO) activity. Oxidative stress was quantitated by measuring urinary 8-isoprostane (8-IP) levels. Anaerobic and aerobic bacterial counts were determined on Brucella and tryptic soy agar plates, respectively. Dextran sulfate sodium (DSS) was used to exacerbate ileal J pouch inflammation. Mortality was low, and animals gained weight normally after recovery. Stasis was documented radiographically. MPO levels were elevated (p < 0.05) in the ileal J pouch 30 and 60 days after IPAA, indicating an inflammation that was associated with stasis and bacterial overgrowth. 8-IP levels were elevated by 80% compared with controls. Oral administration of 5% DSS to IPAA rats with further elevated MPO and 8-IP levels in concert with a pouchitis-like syndrome that included the physical, gross, and histologic characteristics of clinical pouchitis. An understanding of the pathophysiology of pouchitis is essential to the future development of new therapeutic modalities. This model is applicable to investigating several key etiologic mechanisms purportedly related to pouchitis.

show abstract

An assessment of the risk of neoplasia in long-term ileal reservoirs using the DMH rodent model

Cited by 11 publications

References 14 publications

Effect of defunctionalization on colon carcinogenesis in the rat

Effect of defunctionalization on colon carcinogenesis in the rat

Effects of the faecal stream and stasis on the ileal pouch mucosa.

Pouchitis in a Rat Model of Ileal J Pouch–Anal Anastomosis

Contact Info

Product

Resources

About