SHORT COMMUNICATION: The relationship between megacolon and carcinoma of the colon: an experimental approach

Abstract

'Carcinoma of the colon does not occur in cases of megacolon' is an axiom held by Brazilian physicians working in endemic areas for Chagas' disease. The objective of the present study was to test this axiom experimentally by submitting rats with experimental megacolon to a carcinogen which causes carcinoma of the colon. Eighty young male Wistar rats received serosal application of either saline (0.9% NaCl) or 2 mM benzalkonium chloride (BAC) to the distal colon. Ten months later randomly chosen saline and BAC rats were injected weekly with dimethylhydrazine (DMH) for 20 weeks. Non-DMH-treated rats from both original groups were maintained, for a total of four experimental groups. Three months after the injections all surviving rats were killed. At autopsy the presence of absence of carcinomas along the colon was recorded. The induction of megacolon was evaluated by morphometry of the wall from the distal colon and myenteric denervation was assessed by neuron counts. An increase of at least 2-fold in distal colon wall thickness confirmed the induction of megacolon in BAC-treated rats. Neuronal counts from BAC and control rats not treated with DMH showed an average denervation of 63%. The number of distal colon carcinomas in BAC+DMH-treated rats was significantly lower than that in DMH-treated rats. These findings appear to contradict the traditional concept of carcinogenesis of the colon. The clinical axiom was reproduced experimentally.

Association of uterine leiomyoma and Chagas' disease.

“…[1][2][3][4][5][6] It has been associated with a greater frequency of malignant neoplasias in Chagas' disease patients than in non-Chagas' disease patients; in a comparison of the tumor sites, a significantly greater frequency of esophagus cancer and uterine cervix in the Chagas group was observed. 3 A revision of necropsies showed that there was greater frequency of carcinomas of the esophagus among Chagas' disease patients with megaesophagus compared with non-Chagas' disease patients.…”

“…8 In an experimental study, rats with induced megacolon that were submitted to a carcinogenic substance had a significantly lower frequency of colon cancer compared with controls. 9 Adad and others 6 described a case involving an association of neoplasia of the smooth musculature of the esophagus with Chagas' disease. Taken together, these reports led us to questioning the frequency of uterine leiomyoma in Chagas' disease patients.…”

Chagasic megacolon and large bowel neoplasms: case series and literature review

“…On the other hand, the incidence of chagasic megacolon cancer in endemic regions for Chagas disease is only 0.1% 1 . Garcia and Garcia et al 13,14 experimentally induced megacolon with the topic application of benzalkonium chloride in the intestinal serosa of Wistar rats, and observed that these animals presented a lower incidence of tumors after being exposed to dimethylhydrazine. Oliveira and Oliveira et al 8,15 observed that Wistar rats chronically infected by Tripanossoma cruzi presented a lower frequency of benign and malignant chemically induced neoplastic colics.…”

“…Garcia 13 , on the other hand, found one rectal adenocarcinoma out of the 802 studied surgical specimens. Changes in the bacterial flora and intestinal pH, as well as in the composition of the affected intestinal wall that would lead to changes in the neurotransmitter and neuropeptide levels, have been studied as protective factors to the occurrence of neoplasms in these patients 13,14,17,18 . Concerning the described case series, mean age of our patients was 68.5 years, very close to that observed by Fagundes et al 12 , in 2002; it is also close to the age group of colorectal cancer incidence in non-chagasic patients.…”

Effects of myenteric denervation on extracellular matrix fibers and mast cell distribution in normal stomach and gastric lesions

“…The ENS importance for the regulation of the gastrointestinal functions is observed after the topical application of the cationic surfactant, benzalkonium chloride (BAC), on the serous layer that results in partial and selective destruction of myenteric plexus neurons [6]. The correlation between carcinogenesis and the ENS has been demonstrated in experimental models using the myenteric denervation by BAC and the induction of tumors by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) [7] and 1,2-dimethylhydrazine (DMH) [8] with a reduction in the incidence and size of gastrointestinal tumors.…”