A retrospective study of histopathological findings in 894 cases of megacolon: what is the relationship between megacolon and colonic cancer?

Patients with megaesophagus (ME) have increased prevalence of cancer of the esophagus. In contrast, a higher incidence of colorectal cancer is not observed in patients with megacolon (MC). MC is very common in some regions of Brazil, where it is mainly associated with Chagas disease. We reviewed the pathology records of surgical specimens of all patients submitted for surgical resection of MC in the Hospital das Clínicas of the Faculty of Medicine of Ribeirão Preto (HC-FMRP), from the University of São Paulo. We found that 894 patients were operated from 1952 until 2001 for MC resection. Mucosal ulcers, hyperplasia and chronic inflammation were frequently found, while polyps were uncommon. No patients with MC presented any type of colonic neoplasm. This observation reinforces the hypothesis that MC has a negative association with cancer of the colon. This seems to contradict the traditional concept of carcinogenesis in the colon, since patients with MC presents important chronic constipation that is thought to cause an increase in risk for colon cancer. MC is also associated with other risk factors for cancer of colon, such as hyperplasia, mucosal ulcers and chronic inflammation. In ME these factors lead to a remarkable increase in cancer risk. The study of mucosal cell proliferation in MC may provide new insights and useful information about the role of constipation in colonic carcinogenesis.

Bilateral paracoccidioidomycotic iliopsoas abscess associated with ileo-colonic lesion

This case report shows the clinical development of a patient with systemic paracoccidioidomycosis presenting with lymphatic-intestinalmanifestation. The patient initially had a substantial clinical improvement but had a recrudescence after six months of sulfamethoxazoletrimethoprim oral treatment, with the emergence of feverish syndrome, lumbar pain, and intermittent claudication, characterizing a bilateral iliopsoas muscle abscess, necessitating clinicosurgical therapeutics.

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients

The schistosomal parasite plays a critical role in the development of malignant lesions in different organs. The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for disease detection. The objective of this paper is to evaluate certain biochemical parameters as diagnostic tools to efficiently differentiate between colonic carcinoma and colonic carcinoma associated with schistosomal infection among Egyptian patients. The parameters under investigation are interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α), carcinoembryonic antigen (CEA) levels, tissue telomerase, pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase (LDH) enzyme activities. The results revealed a significant elevation in the level of the tumour markers IL-2, TNF-α and CEA as well as the activities of LDH, telomerase and G-6-PD among non-bilharzial and bilharzial colonic cancer groups, with a more potent effect in bilharzial infection-associated colonic cancer. A significant inhibition in PK activity was recorded in the same manner as compared to normal tissues. The efficacy of this biomarker was also evaluated through detecting sensitivity, specificity, negative and positive predictive values. In conclusion, schistosomal colonic carcinoma patients displayed more drastic changes in all parameters under investigation. The combination of the selected parameters succeeded in serving as biomarkers to differentiate between the two malignant types.

Influence of preoperative supplementation of omega-3 fatty acid in the healing of colonic anastomoses in malnourished rats receiving paclitaxel

OBJECTIVE: To evaluate the effect of preoperative supplementation of omega-3 fatty acids on the healing of colonic anastomoses in malnourished rats receiving paclitaxel. METHODS: we studied 160 male Wistar rats, divided in two groups: one subjected to malnutrition by pair feeding (M) for four weeks, and another that received food ad libitum (W). In the fourth week, the groups were further divided into two subgroups that received omega-3 or olive oil by gavage. The animals were submitted to colonic transection and end-to-end anastomosis. After the operation, each of the four groups was divided into two subgroups that received intraperitoneal isovolumetric solutions of saline or paclitaxel. RESULTS: mortality was 26.8% higher in the group of animals that received paclitaxel (p = 0.003). The complete rupture strength was greater in well-nourished-oil Paclitaxel group (WOP) compared with the the malnourished-oil Paclitaxel one (MOP). The collagen maturation index was higher in well-nourished-oil saline group (WOS) in relation to the malnutrition-oil-saline group (MOS), lower in malnourished-oil-saline group (MOS) in relation to malnourished-ômega3-saline one (M3S) and lower in the well-nourished-omega3-saline group (W3S) compared with the malnourished-omega3-saline (M3S). The blood vessel count was higher in the malnourished-oil-saline group (MOS) than in the malnourished-oil-paclitaxel group (MOP) and lower in the malnourished-oil-saline group (MOS) in relation to the malnourished-omega3-paclitaxel group (M3P). CONCLUSION: supplementation with omega-3 fatty acids was associated with a significant increase in the production of mature collagen in malnourished animals, with a reversal of the harmful effects caused by malnutrition associated with the use of paclitaxel on the rupture strength, and with a stimulus to neoangiogenesis in the group receiving paclitaxel.

Effect of Carapa guianensis Aublet (Andiroba) and Orbignya phalerata (Babassu) in colonic healing in rats

Objective: to evaluate the healing effect of the babassu aqueous extract and andiroba oil on open wounds in the cecum of rats. Methods: fifty-four Wistar rats were divided into three groups of 18: 1) babassu group with application of aqueous extract of babassu; 2) andiroba group with application of the oil; and 3) control group, with application of saline solution. All procedures were done by gavage. Each group was divided into three subgroups of six animals according to the observation period of 7, 14 or 21 days. From each animal was removed caecum fragment of 1.5cm² diameter. The areas of the lesions were analyzed macroscopically and resected specimens by light microscopy using hematoxylin-eosin and Masson's trichrome. Results: abscess and infection were observed in two aroeira group animals, and in one only hematoma. In relationship to adhesions degree, babassu group had higher incidence of grade II while in the control and aroeira groups predominated adhesions grade I. On microscopic examination on day 7 fibroblast proliferation was greater in aroeira and lower in babassu group (p=0.028). On the 14th day polymorphonuclear were less pronounced in babassu (p=0.007). As for the resistance test of air insufflation, it was observed that in all andiroba group in all tested days showed be higher. As for collagen, on the 7th day it was present in 100% of animals of aroeira group. On the 14th day was more pronounced in the control group and at day 21 similar results were found in the control and aroeira groups. Conclusion: animals in babassu and andiroba groups showed better cecum healing compared to the control group.

Total and segmental colonic transit time in constipated patients with Chagas’ disease without megaesophagus or megacolon

Manometric and pharmacological tests have shown that motor abnormalities may occur in the non-dilated colons of chagasic patients. In order to investigate the presence of abnormalities of colonic function in constipated patients with Chagas’ disease (ChC) without megaesophagus or megacolon, studies of total and segmental colonic transit time with radiopaque markers were performed on 15 ChC patients, 27 healthy volunteers and 17 patients with idiopathic constipation (IC). The values obtained for the control group were similar to those reported in the literature (total colonic time: 34.1 ± 15.6 h; right colon: 9.9 ± 7.3 h; left colon: 10.8 ± 10 h, and rectosigmoid: 12.6 ± 9.9 h). Colonic transit time data permitted us to divide both IC and ChC patients into groups with normal transit and those with slow colonic transit. Colonic inertia was detected in 41% of IC patients and in 13% of ChC patients; left colon isolated stasis (hindgut dysfunction) was detected in 12% of IC patients and 7% of ChC patients, and outlet obstruction was detected in 6% of IC patients and 7% of ChC patients. There were no significant differences in total or segmental colonic transit times between slow transit IC and slow transit ChC patients. In conclusion, an impairment of colonic motility was detected in about 30% of constipated patients with Chagas’ disease without megaesophagus or megacolon. This subgroup of patients presented no distinctive clinical feature or pattern of colonic dysmotility when compared to patients with slow transit idiopathic constipation.

Dietary fiber intake, stool frequency and colonic transit time in chronic functional constipation in children

The objective of the present study was to evaluate associations between fiber intake, colonic transit time and stool frequency. Thirty-eight patients aged 4 to 14 years were submitted to alimentary evaluation and to measurement of colonic transit time. The median fiber intake of the total sample was age + 10.3 g/day. Only 18.4% of the subjects presented a daily dietary fiber intake below the levels recommended by the American Health Foundation. In this group, the median left colonic transit time was shorter than in the group with higher dietary fiber intake (11 vs 17 h, P = 0.067). The correlation between stool frequency and colonic transit time was negative and weak for left colon (r = -0.3, P = 0.04), and negative and moderate for rectosigmoid and total colon (r = -0.5, P<0.001 and r = -0.5, P<0.001, respectively). The stool frequency was lower in the group with slow transit time (0.8 vs 2.3 per week, P = 0.014). In conclusion, most patients with chronic functional constipation had adequate dietary fiber intake. The negative correlation between stool frequency and colonic transit time increased progressively from proximal segments to distal segments of the colon. Patients with normal and prolonged colonic transit time differ in terms of stool frequency.

Trypanosoma cruzi infection and/or administration of the nonsteroidal anti-inflammatory nimesulide increase the number of colonic crypts overexpressing metallothioneins in rat colon carcinogenesis

Trypanosoma cruzi infection and nonsteroidal anti-inflammatory drugs inhibit colorectal carcinogenesis by mechanisms not completely known and metallothionein proteins (MTs) may be involved in this process. Sixty-six male Wistar rats weighing 90 to 120 g were randomly divided into seven groups (GI to GVII). GI, GII and GIII animals were subcutaneously infected with 200,000 trypomastigote forms of the Y strain of T. cruzi. After 8 weeks, GI, GII, GIV, and GVI were injected with one weekly subcutaneous dose of 12 mg/kg dimethylhydrazine for 4 weeks. In sequence, GI, GIV and GV were treated with nimesulide (10 mg/kg per dose, five times per week for 8 weeks). Groups I, III, IV, and VI had 12 animals, and each of the other groups had 6 animals. All the animals were euthanized 8 weeks after the last dimethylhydrazine injection. The colons were fixed and processed for MT immunohistochemistry. The index of MT-overexpressing colonic crypts (MTEC) was estimated as the percentage of MT-stained crypts in relation to the total number of crypts scored. Five hundred crypts per animal were scored. Data were analyzed by the Kruskal-Wallis test followed by the Dunn test. There was an increase in MTEC index in the groups either infected with T. cruzi or treated with nimesulide or both infected and treated when compared to control (401, 809, and 1011%, respectively). We suggest that the increased formation of MTEC may be related to the protection against carcinogenesis provided both by T. cruzi infection and nimesulide.

Intrinsic denervation of the colon is associated with a decrease of some colonic preneoplastic markers in rats treated with a chemical carcinogen

Denervation of the colon is protective against the colon cancer; however, the mechanisms involved are unknown. We tested the hypothesis that the denervated colonic mucosa could be less responsive to the action of the chemical carcinogen dimethylhydrazine (DMH). Three groups of 32 male Wistar rats were treated as follows: group 1 (G1) had the colon denervated with 0.3 mL 1.5 mM benzyldimethyltetradecylammonium (benzalkonium chloride, BAC); G2 received a single ip injection of 125 mg/kg DMH; G3 was treated with BAC + the same dose and route of DMH. A control group (Sham, N = 32) did not receive any treatment. Each group was subdivided into four groups according to the sacrifice time (1, 2, 6, and 12 weeks after DMH). Crypt fission index, ß-catenin accumulated crypts, aberrant crypt foci, and cell proliferation were evaluated and analyzed by ANOVA and the Student t-test. G3 animals presented a small number of aberrant crypt foci and low crypt fission index compared to G2 animals after 2 and 12 weeks, respectively. From the second week on, the index of ß-catenin crypt in G3 animals increased slower than in G2 animals. From the 12th week on, G2 animals presented a significant increase in cell proliferation when compared to the other groups. Colonic denervation plays an anticarcinogenic role from early stages of colon cancer development. This finding can be of importance for the study of the role of the enteric nervous system in the carcinogenic process.

Effects of bromopride on expression of metalloproteinases and interleukins in left colonic anastomoses: an experimental study

Anastomotic dehiscence is the most severe complication of colorectal surgery. Metalloproteinases (MMPs) and interleukins (ILs) can be used to analyze the healing process of anastomosis. To evaluate the effects of bromopride on MMP and cytokine gene expression in left colonic anastomoses in rats with or without induced abdominal sepsis, 80 rats were divided into two groups for euthanasia on the third or seventh postoperative day (POD). They were then divided into subgroups of 20 rats for sepsis induction or not, and then into subgroups of 10 rats for administration of bromopride or saline. Left colonic anastomosis was performed and abdominal sepsis was induced by cecal ligation and puncture. A colonic segment containing the anastomosis was removed for analysis of gene expression of MMP-1α, MMP-8, MMP-13, IL-β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). On the third POD, bromopride was associated with increased MMP-1α, MMP-13, IL-6, IFN-γ, and IL-10 gene expression. On the seventh POD, all MMP transcripts became negatively modulated and all IL transcripts became positively modulated. In the presence of sepsis, bromopride administration increased MMP-8 and IFN-γ gene expression and decreased MMP-1, TNF-α, IL-6, and IL-10 gene expression on the third POD. On the seventh POD, we observed increased expression of MMP-13 and all cytokines, except for TNF-α. In conclusion, bromopride interferes with MMP and IL gene expression during anastomotic healing. Further studies are needed to correlate these changes with the healing process.

Intestinal spirochetosis: first cases reported in Brazil and the use of immunohistochemistry as an aid in histopathological diagnosis

Colonization of the colon and rectum by intestinal spirochetes is detected for the first time in Brazil in 4 of 282 (1.41%) patients who had undergone sigmoidoscopy and/or colonoscopy with a histopathological diagnosis of chronic non specific-colitis. This frequency is probably understimated, since surgically obtained specimens were not considered in the present study. Histopathological diagnosis was performed using routine stains like hematoxylin-eosin which showed the typical, of 3-µm thick hematoxyphilic fringe on the brush border of the surface epithelium, and by silver stains like the Warthin-Starry stain. Immunohistochemical procedures using two, polyclonal, primary antibodies, one against Treponema pallidum and the other against Leptospira interrogans serovar copenhageni serogroup Icterohaemorrhagiae cross-reacted with spirochetal antigen/s producing a marked contrast of the fringe over the colonic epithelium, preserving the spiral-shaped morphology of the parasite. In one case with marked diarrhea, immunohistochemistry detected spirochetal antigen/s within a cell in an intestinal crypt, thus demonstrating that the infection can be more widely disseminated than suspected using routine stains. Immunohistochemical procedures, thus, greatly facilitate the histological diagnosis of intestinal spirochetosis and may contribute to a better understanding of the pathogenesis of the disease. Transmission and scanning electron microscopy performed in one case showed that the spirochete closely resembled the species designated as Brachyspira aalborgi.

Evaluation of WGA and Concanavalin A (Con A) lectin as biomarkers of hepatosplenic schistosomiasis in human biopsies with no evidence of egg-granuloma system

Introduction: Colonic lesions are predominant in patients with schistosomiasis. However, carbohydrate alterations in colonic schistosomiasis remain unclear. Lectin-ligands allow us to identify changes in the saccharide patterns of cells. Methods: Biopsies of descending and rectosigmoid colon of patients were submitted to WGA and Con A lectin histochemistry. Results: WGA stained stroma and gland cells of descending colon and rectosigmoid tissues in a granular strong cytoplasmatic pattern in schistosomiasis specimens differing from normal control and Con A failing to recognize all samples analyzed. Conclusions: WGA ligands are expressed differently in patients with hepatosplenic schistosomiasis and no evidence of egg-granuloma system.

HYPOXIC STRESS, HEPATOCYTES AND CACO-2 VIABILITY AND SUSCEPTIBILITY TO Shigella flexneri INVASION

SUMMARY Inflammation due to Shigella flexneri can cause damage to the colonic mucosa and cell death by necrosis and apoptosis. This bacteria can reach the bloodstream in this way, and the liver through portal veins. Hypoxia is a condition present in many human diseases, and it may induce bacterial translocation from intestinal lumen. We studied the ability of S. flexneri to invade rat hepatocytes and Caco-2 cells both in normoxic and hypoxic microenvironments, as well as morphological and physiological alterations in these cells after infection under hypoxia. We used the primary culture of rat hepatocytes as a model of study. We analyzed the following parameters in normoxic and hypoxic conditions: morphology, cell viability, bacterial recovery and lactate dehydrogenase (LDH) released. The results showed that there were fewer bacteria within the Caco-2 cells than in hepatocytes in normoxic and hypoxic conditions. We observed that the higher the multiplicity of infection (MOI) the greater the bacterial recovery in hepatocytes. The hypoxic condition decreased the bacterial recovery in hepatocytes. The cytotoxicity evaluated by LDH released by cells was significantly higher in cells submitted to hypoxia than normoxia. Caco-2 cells in normoxia released 63% more LDH than hepatocytes. LDH increased 164% when hepatocytes were submitted to hypoxia and just 21% when Caco-2 cells were in the same condition. The apoptosis evaluated by Tunel was significantly higher in cells submitted to hypoxia than normoxia. When comparing hypoxic cells, we obtained more apoptotic hepatocytes than apoptotic Caco-2 cells. Concluding our results contribute to a better knowledge of interactions between studied cells and Shigella flexneri. These data may be useful in the future to define strategies to combat this virulent pathogen.