Dietary risk factors for colorectal cancer in Brazil: a case control study.

BACKGROUND: High meat intake and low consumption of vegetables, fruits and whole grains have been associated with increased risk of colorectal cancer in some relevant cohort studies conducted in distinct ethnic populations. The role of the dietary pattern on the risk of sporadic colorectal adenocarcinoma (SCA) in Brazil is unknown; therefore, it was the aim of the present study. METHODS: The dietary patterns of 169 patients with SCA and 101 controls were analysed by food frequency recall. Crude odds ratios were calculated and given within 95 % confidence intervals. RESULTS: Patients reported higher average intakes of beef (32.0 ± 1.8 versus 23.7 ± 1.6, P = 0.0069), chicken (18.1 ± 0.9 versus 12.2 ± 0.8, P = 0.0002), and pork (8.9 ± 0.9 versus 3.4 ± 0.5, P < 0.0001). These individuals had a 1.025, 1.069, and 1.121-fold increased risk of SCA. Similar consumption of fish, vegetables, fruits and whole grains was reported by patients and controls. CONCLUSIONS: Meat consumption is greater in patients with SCA in the Brazilian population. Considering the study population - characterized by ethnic heterogeneity -, the environmental factor related to food habits may be associated with higher incidence of this disease in Brazil.

Effect of yogurt containing polydextrose, Lactobacillus acidophilus NCFM and Bifidobacterium lactis HN019: a randomized, double-blind, controlled study in chronic constipation.

BACKGROUND: Constipation is a frequent complaint and the combination of a prebiotic and probiotics could have a potentially synergic effect on the intestinal transit. The present study therefore aims to investigate the combination of polydextrose (Litesse), L. acidophilus NCFM® and B. lactis HN019 in a yogurt on intestinal transit in subjects who suffer from constipation. METHODS: Patients with constipation were randomly divided into two groups, Control Group (CG) and Treatment Group (TG), and had to eat 180 ml of unflavored yogurt every morning for 14 days. Those in the CG received only yogurt, while the TG received yogurt containing polydextrose, L. acidophilus NCFM (ATCC 700396) and B. lactis HN019 (AGAL NM97/09513). RESULTS: Favourable clinical response was assessed since Agachan score had a significant reduction at the end of the study in both groups and tended to be better in the TG. The subjects in the treatment group also had a shorter transit time at the end of the intervention compared to the control group (p = 0.01). CONCLUSION: The product containing yogurt with polydextrose, B. lactis HN019 and L. acidophilus NCFM® significantly shortened colonic transit time after two weeks in the TG compared to CG and may be an option for treatment of constipation.

Autophagy is decreased in mesenteric fat tissue but not in intestinal mucosae of patients with Crohn's disease.

Crohn's disease (CD) is a chronic intestinal disease with a multifactorial etiology. Recently, a role for mesenteric fat has been proposed in CD pathophysiology, since fat hypertrophy is detected close to the affected intestinal area; however, there are few studies regarding autophagy and the hypertrophied mesenteric tissue in CD. To evaluate autophagy-related proteins in intestinal mucosae and mesenteric fat of patients with CD and controls, patients with ileocecal CD (CD Group) and with non-inflammatory disease (FC Group) selected for surgery were studied. Expression of LC3-II was determined by immunoblotting of protein extracts. In addition, beclin-1, LC3 and Atg16-L1 RNA levels were measured using RT-PCR. The expression of LC3-II was significantly lower in the mesenteric tissue and higher in intestinal mucosae of CD when compared to controls. However, mRNA expression of autophagy-related proteins was similar when comparing the mesenteric fat groups. These findings suggest a defect in autophagy activation in the mesenteric fat tissue of CD individuals, which could be involved in the maintenance of the inflammatory process.

Temporal trends in the epidemiology of inflammatory bowel diseases in the public healthcare system in Brazil: A large population-based study.

Background: Population-based data on epidemiology of Inflammatory Bowel Diseases (IBD) in Brazil are scarce. This study aims to define temporal trends of incidence and prevalence rates of Crohn's disease (CD) and ulcerative colitis (UC) in Brazil. Methods: All IBD patients from the public healthcare national system were included from January 2012 to December 2020. Average Annual Percent Change (AAPC) and 95% confidence intervals (CI) were calculated using log-linear regression for incidence and binomial regression for prevalence. Moran's I autocorrelation index was used to analyse clustering of cities by level of prevalence. Findings: A total of 212,026 IBD patients were included. Incidence of IBD rose from 9.4 in 2012 to 9.6 per 100,000 in 2020 (AAPC=0.8%; 95% CI -0.37, 1.99); for UC, incidence increased from 5.7 to 6.9 per 100,000 (AAPC=3.0%; 95% CI 1.51, 4.58) and for CD incidence decreased from 3.7 to 2.7 per 100,000 (AAPC=-3.2%; 95% CI -4.45, -2.02). Prevalence of IBD increased from 30.0 in 2012 to 100.1 per 100,000 in 2020 (AAPC=14.8%; CI 14.78-14.95); for UC, from 15.7 to 56.5 per 100,000 (AAPC=16.0%; CI 15.94, 16.17); for CD from 12.6 to 33.7 per 100,000 (AAPC=12.1% CI 11.95, 12.02). A south-north gradient was observed in 2020 prevalence rates of IBD [I=0.40 (p<0.0001)], CD [I=0.22 (p<0.0001)] and UC [I=0.42 (p<0.0001)]. Interpretation: Incidence of CD is decreasing whereas of UC is increasing, leading to stabilization in the incidence of IBD from 2012 to 2020 in Brazil. Prevalence of IBD has been climbing with 0.1% of Brazilians living with IBD in 2020. Funding: None.

Detection of epithelial apoptosis in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is the surgical procedure of choice for patients with refractory ulcerative colitis (UC) and for familial adenomatous polyposis (FAP) with many rectal polyps. Pouchitis is one of the more frequent complications after IPAA in UC patients; however, it is rare in FAP. OBJECTIVE: Evaluate pro-apoptotic activity in endoscopically and histological normal mucosa of the ileal pouch in patients with UC and FAP. METHODS: Eighteen patients (nine with UC and nine with FAP) with J pouch after total rectocolectomy were studied. Biopsies were obtained from the mucosa of the pouch and from normal ileum. The specimens were snap-frozen and the expressions of Bax and Bcl-2 were determined by immunoblot of protein extracts and by immunohistochemistry analysis. FADD, Caspase-8, APAF-1 and Caspase-9 were evaluated by immunoprecipitation and immunoblot. RESULTS: Patients with UC had significantly higher protein levels of Bax and APAF-1, Caspase-9 than patients with FAP, but were similar to controls. The expressions of Bcl-2 and FADD, Caspase-8 were similar in the groups. Immunohistochemistry for Bax showed less intensity of immunoreactions in FAP than in UC and Controls. Bcl-2 immunostaining was similar among the groups. CONCLUSION: Patients with FAP present lower levels of pro-apoptotic proteins in all methods applied, even in the absence of clinical and endoscopic pouchitis and dysplasia in the histological analysis. These findings may explain a tendency of up-regulation of apoptosis in UC patients, resulting in higher rates of progression to pouchitis in these patients, which could correlate with mucosal atrophy that occurs in inflamed tissue. However, FAP patients had low pro-apoptotic activity in the mucosa, and it could explain the tendency to low cell turn over and presence of adenomas in this syndrome.

Evaluation of lateral lymph node metastases in advanced distal rectal cancer.

BACKGROUND/AIMS: The importance of lateral node dissection has not yet been fully investigated in advanced rectal cancer. To evaluate tumor cells in perirectal and lateral lymph nodes dissection from rectal adenocarcinomas considered free of disease by the hematoxylin-eosin test. METHODOLOGY: Fifteen patients submitted to neoadjuvant therapy and surgery for rectal adenocarcinoma with lateral node dissection were studied, retrospectively. The paraffin blocs of the nodes were analyzed with a immunohistochemical study and multiples cross section of the nodes. RESULTS: A total of 331 lymph nodes from these 15 patients were assessed, distributed as 258 perirectal nodes, 73 non perirectal, and 27 lateral nodes. The average was 22.1 lymph nodes per patient. Three patients out of 15 (20%) with histological negative lateral lymph node had occult metastasis detected by pancytokeratins AE1 and AE3. One of these cases didn't present tumor in the surgical specimen of the rectum. A case of positive lateral node identified by hematoxylin-eosin was also identified by immunohistochemical study. CONCLUSIONS: Although we had a small number of patients in the present study, lateral node dissection is important in selected cases of advanced cancer. Pancytokeratins AE1 and AE3 had a potential to improve study for detection of occult node metastasis, being helpful in rectal cancer prognosis.

Family history of cancer in Brazil: is it being used?

In developing countries, low budgets make the issue of integrating genetics into clinical practice a challenge, a situation in which the use of family history (FH) becomes important for patient care, as it is a low cost strategy and a risk assessment tool. The purpose of this study was to review medical records of patients with colorectal cancer (CRC) seen in a public University Hospital and evaluate how often FH of cancer is registered. Initially we searched a database for patients who were seen in our hospital between 2002 and 2004 with the diagnosis of CRC. We found 415 patients, 104 of whom were excluded. A total of 311 charts were reviewed and classified into 3 groups. Group A: no FH documented; group B: FH was documented, but FH of cancer was not collected; and group C: FH of cancer was documented. We also investigated what type of information was recorded, in order to verify if important elements were assessed. Ninety-eight charts (31.5%) were classified in group A, 20 (6.5%) in group B, and 193 (62%) in group C. In addition, we observed that important information regarding affected relatives was not collected in most of the charts. In conclusion, we found that although FH of cancer was recorded in 62% of charts of patients with CRC, information that could be relevant for risk assessment and management of at-risk families was missing. Our findings expose an important problem in health education that could reflect negatively in the quality of medical assistance to individuals at risk for familial cancer.

A Retrospective Analysis of Colorectal Serrated Lesions from 2005 to 2014 in a Single Center: Importance of the Establishment of Diagnostic Patterns.

BACKGROUND: Serrated colorectal lesions are increasingly recognized as an important process in the development of colorectal cancer. Endoscopic and histological diagnosis may be difficult, and knowledge of the serrated lesions is important for the establishment of strategies for treating colorectal lesions. We aimed to analyze serrated lesions diagnosed at a single center and evaluate if there was an increase in their identification over the years. DESIGN AND SETTING: A retrospective analysis of colonoscopy reports was performed at a specialized center from 2005 to 2014. METHODS: Colonoscopy reports about any resected endoscopic lesions were reviewed and subjected to histological diagnosis from 2005 to 2014. Then, serrated lesions were evaluated based on morphological characterization, location, size, occurrence of synchronous lesions, and the patient's history of colorectal cancer and polyps. RESULTS: A total of 2126 colonoscopy examination reports were reviewed, and 3494 lesions were analyzed. On histopathological examination, 1089 (31.2%) were classified as hyperplastic polyps, 22 (0.6%) as sessile serrated adenomas, and 21 (0.6%) as traditional serrated adenomas. There was an increase in the number of cases of sessile and traditional serrated adenomas diagnosed after 2010. Before 2010, two cases of sessile serrated adenomas and seven cases of traditional serrated adenomas were diagnosed; after 2010, 20 cases of sessile serrated adenoma and 14 cases of traditional serrated adenomas were diagnosed. CONCLUSION: There was an increase in the diagnosis of sessile serrated adenomas over the years, which can be attributed to better accuracy in colonoscopy and histological classification.

Comparative study of eosinophil chemotaxis, adhesion, and degranulation in vitro in ulcerative colitis and Crohn's disease.

BACKGROUND: Eosinophils have been identified in tissues from patients with Crohn's disease (CD) and ulcerative colitis (UC) but whether they contribute to IBD pathogenesis is unknown. This study aimed to investigate the functional activity and morphological aspects of peripheral-blood eosinophils from IBD patients compared to those from healthy volunteers (HVs). METHODS: Eosinophils from HVs and CD and UC patients were purified using a Percoll gradient and then a immunomagnetic cell separator. Functional activity in inactivated and previously activated cells was investigated by measuring adhesion to fibronectin and chemotaxis to fMLP, and degranulation was measured by release of eosinophil peroxidase (EPO). Cell morphology was investigated using electron microscopy. RESULTS: Eosinophil adhesion to human fibronectin in both inactivated and PAF-stimulated and PMA-stimulated eosinophils was markedly higher in patients with CD than in either patients with UC or HVs. Similarly, the chemotactic response was markedly higher in eosinophils isolated from CD patients than in those isolated from UC patients or HVs. Baseline EPO release was higher in eosinophils isolated from UC patients than in those isolated from HVs or CD patients. Stimulation with fMLP or PMA did not further increase EPO release in cells from UC or CD patients. Comparable expression of MAC- 1 and VLA-4 adhesion molecules was observed on the surfaces of eosinophils from all groups, and an greater number of granules was noted in the eosinophils from UC patients than in those from CD patients. CONCLUSIONS: Our results indicate that peripheral-blood eosinophils are potentially primed and activated in IBD patients. Whether the differences in the morphology and functional responses of eosinophil from UC and CD patients reflect differences in disease phenotype remains to be elucidated.

Toll-like receptor 4, F4/80 and pro-inflammatory cytokines in intestinal and mesenteric fat tissue of Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a chronic intestinal ailment with a multifactorial etiology, whose incidence has increased during the last three decades. Recently, a role for mesenteric fat has been proposed in CD pathophysiology, since fat hypertrophy is detected nearby the affected intestinal area; however, there are few studies on this aspect. AIM: To evaluate inflammatory activity in intestinal mucosa and mesenteric fat tissue of patients with CD and controls. MATERIALS AND METHODS: Ten patients with ileocecal CD and 16 patients with non-inflammatory disease (control groups) were studied. The specimens were snap-frozen and the expression of TLR-4, F4/80, IL1-ß and IL-6 were determined by immunoblot of protein extracts. TLR4 RNA level were measured using RT-PCR. The t Test was applied (p<0.05). The local ethical committee approved the study. RESULTS: The intestinal mucosa of CD group had significantly higher protein levels of TLR-4, F4/80, IL-1ß and IL-6 than the controls. The gene expression of TLR4 was lower in the intestinal mucosa of CD compared to the control group. Regard the mesenteric fat tissue, there was no statistical difference related to TLR-4, F4/80, IL-1ß and IL-6 proteins expression. CONCLUSIONS: These findings may result from an up-regulation of macrophage activation and intracellular pathways activated by bacterial antigens, which are more important in intestinal mucosa than fat tissue in CD patients. This may represent an anomalous regulation of innate immunity and could contribute to the production of proinflammatory mediators and disease development.

Differential expression of TLR2, TLR4 and JNK in mucosa of ileal pouches for ulcerative colitis. Is there a role for bacterial antigen pathway in asymptomatic patients?

INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) is the preferred surgical procedure for patients with refractory ulcerative colitis (UC) and familial adenomatous polyposis (FAP). However, pouchitis is the most common complication after IPAA in UC patients and only occurs after ileostomy closure. Therefore, it is important to get more information about the role of the ileal pouch microbiota and mucosa susceptibility to inflammation in UC patients. Therefore, we evaluated Toll-like receptors (TLRs) expression in normal endoscopic and histological mucosa of the ileal pouch in patients with UC and FAP, in order to find any abnormality in this pathway in asymptomatic patients, which may contribute to pouchitis. MATERIALS AND METHODS: Twelve patients (six with UC and six with FAP) with "J" pouch reconstruction, after total rectocolectomy, were studied. Biopsies were obtained from the mucosa of the pouch. Normal ileum biopsies were obtained from six patients submitted to ileocolonoscopy with no abnormalities. The specimens were snap-frozen and the expressions of TLR2, TLR4 and JNK (nuclear signalization factor) were determined by immunoblot protein extract. RESULTS: Patients with UC had significantly higher protein levels of TLR4 than controls and FAP. The expressions of TLR2 and JNK were similar in the groups. CONCLUSION: Patients with UC had higher levels of TLR4, even in the absence of clinical, endoscopic and histological pouchitis. These findings may explain a tendency towards the up-regulation of intracellular pathways activated by bacterial antigens in UC patients, which could contribute to the production of proinflammatory mediators and pouchitis development.

Polymorphisms in methylenetetrahydrofolate reductase gene (MTHFR) and the age of onset of sporadic colorectal adenocarcinoma.

BACKGROUND AND AIMS: Evidence is accumulating for a role of folate in the aetiology of colorectal cancer (CRC). The methylenetetrahydrofolate reductase (MTHFR) gene, involved in folate metabolism, is polymorphic in humans. Since it is unknown whether the MTHFR C677T and A1298C polymorphisms alter the risk for CRC, this was the aim of our study. MATERIALS AND METHODS: Genomic DNA from 102 sporadic colorectal adenocarcinoma (SCA) patients and 300 controls was analyzed by polymerase chain reaction followed by restriction digestion for the polymorphisms analyses. RESULTS/FINDINGS: The frequencies of MTHFR C677T and A1298C genotypes were similar in patients and controls. Similar overall risks for disease were seen in individuals with the distinct MTHFR genotypes. However, an excess of the MTHFR 677TT and 677CT genotypes was seen in patients under 50 years, compared with patients at an older age (19.2 vs 13.1% and 61.6 vs 39.5%, respectively; P = 0.04). The differences were more prominent when the frequency of the 677TT plus 677CT genotype was seen in both group of patients (80.8 vs 52.6%, respectively; P = 0.01), and in younger patients compared to controls (80.8 vs 52.3%, P < 0.01). Individuals with the combined genotype had 3.82-fold (95% confidence interval, 1.41-10.42) increased risk of developing SCA under 50 years, compared with those harboring the wild-type genotype. INTERPRETATION/CONCLUSION: These results suggest a role for the MTHFR 677TT plus 677CT genotype in increasing SCA diagnosed at a low age in southeastern Brazil, but additional studies with larger sample sizes should be carried out to clarify this issue.

Possible influence of glutathione S-transferase GSTT1 null genotype on age of onset of sporadic colorectal adenocarcinoma.

INTRODUCTION: Glutathione S-transferase enzymes mediate exposure to cytotoxic and genotoxic agents and may be involved in cancer susceptibility. Both glutathione S-transferase mu 1 (GSTM1) and GST theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The association of glutathione S-transferase null genotype and risk of developing colorectal cancer is not yet fully clarified. METHODS: We tested whether the null genotypes for GSTM1 and GSTT1 genes altered the risk for sporadic colorectal adenocarcinoma in Brazilian patients. Genomic DNA from 102 sporadic colorectal adenocarcinoma patients and 300 controls was analyzed by polymerase chain reaction. RESULTS: Frequencies of GSTM1, GSTT1, and null combined genotypes were similar in patients and controls (49.9 vs. 44.6 percent, 16.6 vs. 17.3 percent, and 8.8 vs. 8 percent, respectively). We found a 1.03-fold (95 percent confidence interval, 0.96-1.10) and 1.08-fold (95 percent confidence interval, 0.99-1.18) increased risk associated with GSTM1 and GSTT1 null genotypes, respectively (P = 0.45 and P = 0.08) and a 1.18-fold (95 percent confidence interval, 0.47-2.90) increased risk associated with the combined null genotype (P = 0.74). The GSTT1 null genotype was more common in patients who were diagnosed before the age of 60 years than in those who were diagnosed at an older age (28.8 vs. 4 percent, respectively; P = 0.0008). CONCLUSIONS: The results suggest that inherited absence of this carcinogen detoxification pathway may not be associated with sporadic colorectal adenocarcinoma in the present cases. However, a higher frequency of GSTT1 null genotype in patients diagnosed before the age of 60 years suggests that this genotype could influence the age of disease onset in Brazil.

O emprego da artetia colica media e da arcada vascular do colon direito na irrigaçao de resertvatorios ileais / Lengthening of the mesentery and blood supply to the ileal pouch - Use of the vascular arcade of the right colon

A anastomose do reservatorio ileal ao canal anal pode ocasionalmente ser realizada sob tensao, com serias consequencias. Os autores propoem a preservaçao da arteria colica media e da arcada vascular do colon direito de forma a suplementar a irrigaçao do ileo terminal. Dessa forma, para se evitar que o mesenterio da alça a sr abaixada fique esticado, torna-se possivel a secçao do terço distal da arteria mesenterica superior e de alguns vasos da arcada vascular do mesenterio. Assim, o fluxo sanguineo ao resevatorio ocorreria proximalmente pela arcada dos vasos mesentericos e distalmente pela arcada do colon direito, atraves da arteria colica media. A utilizaçao desta tecnica permite que se aumente o comprimento do mesenterico da alça a ser abaixada em cerca de 9 cm ou mais, tornando a anastomose mais segura e facilmente realizavel