London Protocol under water-perfused HRM in a healthy population, towards novel 3D manometric parameters in an evaluation of anorectal functional disorders.

BACKGROUND/AIM: London Protocol (LP) and Classification allied to high-resolution manometry (HRM) technological evolution has updated and enhanced the diagnostic armamentarium in anorectal disorders. This study aims to evaluate LP reproducibility under water-perfused HRM, provide normal data and new parameters based on 3D and healthy comparison studies under perfusional HRM. METHODS: Fifty healthy (25 F) underwent water-perfused 36 channel HRM based on LP at resting, squeeze, cough, push, and rectal sensory. Additional 3D manometric parameters were: pressure-volume (PV) 104mmHg2.cm (resting, short and long squeeze, cough); highest and lowest pressure asymmetry (resting, short squeeze, and cough). Complementary parameters (CP) were: resting (mean pressure, functional anal canal length); short squeeze (mean and maximum absolute squeeze pressure), endurance (fatigue rate, fatigue rate index, capacity to sustain); cough (anorectal gradient pressure); push (rectum-anal gradient pressure, anal canal relaxation percent); recto-anal inhibitory reflex (anal canal relaxation percent). RESULTS: No difference to genders: resting (LP, CP, and 3D); short squeeze (highest pressure asymmetry); endurance (CP); cough (CP, highest and lowest pressure asymmetry); push (gradient pressure); rectal sensory. Higher pressure in men: short squeeze (maximum incremental, absolute, and mean pressure, PV, lowest pressure asymmetry); long squeeze (PV); cough (anal canal and rectum maximum pressure, anal canal PV); push (anal canal and rectum maximum pressure). Anal canal relaxation was higher in women (push). CONCLUSIONS: LP reproducibility is feasible under water-perfused HRM, and comparative studies could bring similarity to dataset expansion. Novel 3D parameters need further studies with healthy and larger data to be validated and for disease comparisons. KEY POINTS: • London Protocol and Classification allied with the technological evolution of HRM (software and probes) has refined the diagnostic armamentarium in anorectal disorders. • Novel 3D and deepening the analysis of manometric parameters before the London Classification as a contributory diagnostic tool. • Comparison of healthy volunteers according to the London Protocol under a perfusional high-resolution system could establish equivalence points.

Anti-TNF therapy for ulcerative colitis in Brazil: a comparative real-world national retrospective multicentric study from the Brazilian study group of IBD (GEDIIB).

BACKGROUND: Anti-TNF therapy represented a landmark in medical treatment of ulcerative colitis (UC). There is lack of data on the efficacy and safety of these agents in Brazilian patients. The present study aimed to analyze rates of clinical and endoscopic remission comparatively, between adalimumab (ADA) and infliximab (IFX), in Brazilian patients with UC, and evaluate factors associated with clinical and endoscopic remission after 1 year of treatment. METHODS: A national retrospective multicenter study (24 centers) was performed including patients with UC treated with anti-TNF therapy. Outcomes as clinical response and remission, endoscopic remission and secondary loss of response were measured in different time points of the follow-up. Baseline predictive factors of clinical and endoscopic remission at week 52 were evaluated using logistic regression model. Indirect comparisons among groups (ADA and IFX) were performed using Student's t, Pearson χ2 or Fisher's exact test when appropriated, and Kaplan Meier analysis. RESULTS: Overall, 393 patients were included (ADA, n = 111; IFX, n = 282). The mean age was 41.86 ± 13.60 years, 61.58% were female, most patients had extensive colitis (62.40%) and 19.39% had previous exposure to a biological agent. Overall, clinical remission rate was 66.78%, 71.62% and 82.82% at weeks 8, 26 and 52, respectively. Remission rates were higher in the IFX group at weeks 26 (75.12% vs. 62.65%, p < 0.0001) and 52 (65.24% vs. 51.35%, p < 0.0001) when compared to ADA. According to Kaplan-Meier survival curve loss of response was less frequent in the Infliximab compared to Adalimumab group (p = 0.001). Overall, endoscopic remission was observed in 50% of patients at week 26 and in 65.98% at week 52, with no difference between the groups (p = 0.114). Colectomy was performed in 23 patients (5.99%). Age, non-prior exposure to biological therapy, use of IFX and endoscopic remission at week 26 were associated with clinical remission after 52 weeks. Variables associated with endoscopic remission were non-prior exposure to biological therapy, and clinical and endoscopic remission at week 26. CONCLUSIONS: IFX was associated with higher rates of clinical remission after 1 year in comparison to ADA. Non-prior exposure to biological therapy and early response to anti-TNF treatment were associated with higher rates of clinical and endoscopic remission.

Adalimumab and postoperative complications of elective intestinal resections in Crohn's disease: a propensity score case-matched study.

BACKGROUND: data are scarce regarding the effect of preoperative Adalimumab (ADA) in postoperative complications in Crohn's disease (CD) patients. AIM: to compare the rates of postoperative complications after intestinal resections in CD, with and without previous exposure to ADA. METHOD: case-matched retrospective observational study of patients submitted to intestinal resections for CD. The patients were allocated to 2 groups, according to their previous exposure to ADA before surgery. The patients under ADA therapy were matched with controls (patients without previous biologics) with the propensity score method (PSM), according to age at surgery, CD location (Montreal L) and phenotype (Montreal B). Medical and surgical complications were compared. RESULTS: 123 patients were initially considered, 71 with previous biologics (32 under ADA therapy) and 52 without. The PSM selected 25 ADA patients to be matched with 25 controls from the non-biologics group. There was no difference regarding overall surgical complications (40% in the control vs 36% in the ADA group; p = 1.0000) or medical complications (36% vs 12% in the control and ADA groups, respectively; p = 0.095). In univariate analysis, previous ADA was not considered a risk factor for higher postoperative complication rates. Stomas were considered a risk factor for surgical complications, and previous steroids were associated to higher medical complication rates. CONCLUSIONS: preoperative ADA did not influence the rates of medical and surgical complications after elective intestinal resections for CD. This was the first study to include exclusively patients under ADA therapy. This article is protected by copyright. All rights reserved.

Tumor Necrosis Factor Alpha Inhibitors Did Not Influence Postoperative Morbidity After Elective Surgical Resections in Crohn's Disease.

BACKGROUND: The real impact of anti-tumor necrosis alpha (TNF) therapy in postoperative complications after intestinal resections in Crohn's disease (CD) still needs to be determined. AIMS: To compare the postoperative complication rates after elective intestinal resections in CD patients, with or without previous exposure to anti-TNF therapy. METHODS: This was a retrospective and observational study, with elective intestinal resections for CD (emergency procedures were excluded). Patients were allocated in two groups according to preoperative anti-TNF status. Surgical and medical complications were analyzed and subsequently compared between the groups. RESULTS: A total of 123 patients were included (71 with and 52 without preoperative anti-TNF). The groups were considered homogeneous, except for perianal CD, previous azathioprine, and stomas. There was no significant difference between the groups regarding overall surgical complications (32.69% in anti-TNF- vs. 39.44% in anti-TNF+ patients, p = 0.457) or overall medical complications (21.15 vs. 21.13%, respectively, p = 1.000). In univariate analysis, previous steroids, perianal CD, and stomas were considered risk factors for surgical complications, and previous steroids and hypoalbuminemia for medical complications. In multivariate analysis, previous steroids were associated with higher rates of surgical and medical complications, while hypoalbuminemia was associated with higher medical complication rates. CONCLUSIONS: There was no influence of the previous use of anti-TNF agents in postoperative surgical and medical complication rates in elective intestinal resections for CD. Previous steroids and hypoalbuminemia were associated with higher complication rates. This was the first case series of the literature describing outcomes in exclusively elective operations.

INFLUENCE OF NEOADJUVANT THERAPY ON THE RATIO OF LYMPH NODES.

BACKGROUND: To evaluate the relationship between the ratio of affected lymph nodes (LNR) and clinical and anatomopathological variables in patients with rectal adenocarcinoma submitted or not to neoadjuvant chemoradiotherapy. METHODS: The LNR was determined by dividing the number of compromised LNR by the total number of LNR dissected in the surgical specimen. Patients were divided into two groups: with QRT and without QRT. In each group, the relationship between LNR and the following variables was evaluated: degree of cell differentiation, depth of invasion in the rectal wall, angiolymphatic /perineural invasion, degree of tumor regression and occurrence of metastases. The LNR was evaluated in patients with more than 1, LNR (LNR >12) or less (LNR<12) in the surgical specimen with overall survival (OS) and disease-free survival (DFS). The results were expressed as the mean with the respective standard deviation. Qualitative variables were analyzed using Fisher's exact test, while quantitative variables were analyzed using the Kruskal -Wallis and Mann-Whitney tests. The significance level was 5%. RESULTS: We evaluated 282 patients with QRT and 114 without QRT, between 1995-2011. In the QRT Group, LNR showed a significant association with mucinous tumors (P=0.007) and degree of tumor regression (P=0.003). In both groups, LNR was associated with poorly differentiated tumors (P=0.001, P=0.02), presence of angiolymphatic invasion (P<0.0001 and P=0.01), perineural (P=0.0007, P=0.02), degree of rectal wall invasion (T3>T2; P<0.0001, P=0.02); Compromised LNR (P<0.0001, P<0.01), metastases (P<0.0001, P<0.01). In patients with QRT, LNR<12 was associated with DFS (5.889; 95%CI1.935-19.687; P=0.018) and LNR>12 with DFS and OS (17.984; 95%CI5.931-54.351; P<0.001 and 10.286; 95%CI 2.654-39.854; P=0.007, respectively). CONCLUSION: LNR was associated with histological aspects of poor prognosis, regardless of the use of QRT. In the occurrence of less than 12 evaluated LNR, the LNR was associated only with the DFS. BACKGROUND: • Assessment of the lymph nodes during pathological analysis of the surgical specimen is crucial to determine treatment and prognosis. BACKGROUND: • Neoadjuvance therapy reduces the number of lymph nodes, being lower than recommended, therefore the lymph node ratio can be an alternative analysis for a better prognosis.

Pharmacological Therapy in Inflammatory Bowel Diseases: A Narrative Review of the Past 90 Years.

Inflammatory Bowel Diseases had their first peak in incidence in countries in North America, Europe, and Oceania and are currently experiencing a new acceleration in incidence, especially in Latin America and Asia. Despite technological advances, 90 years after the development of the first molecule for the treatment of IBD, we still do not have drugs that promote disease remission in a generalized way. We carried out a narrative review on therapeutic advances in the treatment of IBD, the mechanisms of action, and the challenges facing the therapeutic goals in the treatment of IBD. Salicylates are still used in the treatment of Ulcerative Colitis. Corticosteroids have an indication restricted to the period of therapeutic induction due to frequent adverse events, while technologies with less systemic action have been developed. Most immunomodulators showed a late onset of action, requiring a differentiated initial strategy to control the disease. New therapeutic perspectives emerged with biological therapy, initially with anti-TNF, followed by anti-integrins and anti-interleukins. Despite the different mechanisms of action, there are similarities between the general rates of effectiveness. These similar results were also evidenced in JAK inhibitors and S1p modulators, the last therapeutic classes approved for the treatment of IBD.

Adalimumab Serum Concentrations, Clinical and Endoscopic Disease Activity in Crohn's Disease: A Cross-Sectional Multicentric Latin American Study.

Despite some variability in ideal serum Adalimumab (ADA) concentrations, there is increasing evidence that higher concentrations of anti-TNF-α agents can be associated with sustained efficacy, and low or undetectable levels may lead to loss of response. This study aims to correlate serum ADA concentrations with clinical and endoscopic activity in patients with Crohn's disease (CD). A cross-sectional and multicentric study was performed with patients with CD, who used ADA for at least 24 weeks. Patients were allocated into groups according to the presence of clinical or endoscopic disease activity. Serum ADA concentrations were measured and compared between groups. Overall, 89 patients were included. A total of 27 patients had clinically active CD and 62 were in clinical remission. Forty patients had endoscopic disease activity and 49 were in endoscopic remission. The mean serum ADA concentration was 10.2 µg/mL in patients with clinically active CD and 14.3 µg/mL in patients in clinical remission (p = 0.395). The mean serum ADA concentration in patients with endoscopic activity was 11.3 µg/mL as compared to 14.5 µg/mL in those with endoscopic remission (p = 0.566). There was no difference between serum ADA concentrations regarding clinical or endoscopic activity in CD, as compared to patients in remission.

Association of Fibrinolytic Potential and Risk of Mortality in Cancer Patients.

Cancer is a leading cause of death, and the fibrinolytic system shows cooperative effects that facilitate the growth of tumors and the appearance of metastases. This prospective study aimed to evaluate the fibrinolytic potential in cancer patients and its association with mortality outcomes using the fluorometric method of simultaneous thrombin and plasmin generation. The study included 323 cancer patients and 148 healthy individuals. During the 12-month follow-up, 68 patients died. Compared to the control group, cancer patients showed alterations in thrombin production consistent with a hypercoagulability profile, and an increase in plasmin generation. Mortality risk was associated with two parameters of thrombin in both univariate and multivariable analysis: maximum amplitude (Wald 11.78, p < 0.001) and area under the curve (Wald 8.0, p < 0.005), while such associations were not observed for plasmin. In conclusion, this was the first study able to demonstrate the simultaneous evaluation of thrombin and plasmin generation in newly diagnosed untreated cancer patients. Patients with cancer have been observed to exhibit a hypercoagulable profile. During the study, two parameters linked to thrombin generation, MA and AUC, were identified and found to have a potential association with mortality risk. However, no associations were found with parameters related to plasmin generation.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF ULCERATIVE COLITIS IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel diseases are immune-mediated disorders that include Crohn's disease (CD) and ulcerative colitis (UC). UC is a progressive disease that affects the colorectal mucosa causing debilitating symptoms leading to high morbidity and work disability. As a consequence of chronic colonic inflammation, UC is also associated with an increased risk of colorectal cancer. OBJECTIVE: This consensus aims to provide guidance on the most effective medical management of adult patients with UC. METHODS: A consensus statement was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's Disease and Colitis [GEDIIB]). A systematic review including the most recent evidence was conducted to support the recommendations and statements. All recommendations/statements were endorsed using a modified Delphi Panel by the stakeholders/experts in inflammatory bowel disease with at least 80% or greater consensus. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological) were mapped according to the stage of treatment and severity of the disease onto three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus targeted general practitioners, gastroenterologists and surgeons who manage patients with UC, and supports decision-making processes by health insurance companies, regulatory agencies, health institutional leaders, and administrators.

SECOND BRAZILIAN CONSENSUS ON THE MANAGEMENT OF CROHN'S DISEASE IN ADULTS: A CONSENSUS OF THE BRAZILIAN ORGANIZATION FOR CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Inflammatory bowel disease (IBD) is an immune-mediated disorder that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized by a transmural intestinal involvement from the mouth to the anus with recurrent and remitting symptoms that can lead to progressive bowel damage and disability over time. OBJECTIVE: To guide the safest and effective medical treatments of adults with CD. METHODS: This consensus was developed by stakeholders representing Brazilian gastroenterologists and colorectal surgeons (Brazilian Organization for Crohn's disease and Colitis (GEDIIB)). A systematic review of the most recent evidence was conducted to support the recommendations/statements. All included recommendations and statements were endorsed in a modified Delphi panel by the stakeholders and experts in IBD with an agreement of at least 80% or greater consensus rate. RESULTS AND CONCLUSION: The medical recommendations (pharmacological and non-pharmacological interventions) were mapped according to the stage of treatment and severity of the disease in three domains: management and treatment (drug and surgical interventions), criteria for evaluating the effectiveness of medical treatment, and follow-up/patient monitoring after initial treatment. The consensus is targeted towards general practitioners, gastroenterologists, and surgeons interested in treating and managing adults with CD and supports the decision-making of health insurance companies, regulatory agencies, and health institutional leaders or administrators.

Evaluation of different tools for body composition assessment in colorectal cancer - a systematic review.

BACKGROUND: The nutritional status of patients with colorectal cancer (CRC) impacts on treatment response and morbidity. An effective evaluation of the body composition includes the measurements of fat and visceral fat-free mass and is currently being used in the diagnosis of the nutritional status. The better understanding regarding nutritional tools for body composition evaluation in CRC patients may impact on the outcome. METHODS: Systematic review conducted according to Preferred Items of Reports for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A literature search was performed using the BVS (LILACS), PubMed, Embase, Cochrane, Scopus, and Web of Science databases. RESULTS: For the initial search, 97 studies were selected and 51 duplicate manuscripts were excluded. Thus, 46 were reviewed and seven studies included with a total of 4,549 patients. Among them were one clinical trial, one prospective study (cohort), two retrospective cohort and two cross-sectional studies. All studies included body composition evaluated by computed tomography, one with bioelectrical impedance, one with handgrip strength, and two employed mid-arm muscle circumference and body mass index. CONCLUSION: Current evidence suggests that computed tomography has better accuracy in the diagnosis of sarcopenia, visceral fat, and myopenia among individuals with CRC. Further studies are needed to identify cutoff points for these changes aggravated by CRC.

STUDY OF ANORECTAL PHYSIOLOGY PRE AND POS NEOADJUVANT THERAPY FOR RECTAL CANCER BY ANORECTAL MANOMETRY AND JORGE-WEXNER SCORE.

BACKGROUND: The treatment of distal rectal cancer may be accompanied by evacuation disorders of multifactorial etiology. Neoadjuvant chemoradiotherapy (NCRT) is part of the standard treatment for patients with locally advanced extraperitoneal rectal cancer. The assessment of anorectal function after long-term NCRT in patients with cancer of the extraperitoneal rectum has been poorly evaluated. OBJECTIVE: The aim of the present study was to evaluate the effects of NCRT on anorectal function and continence in patients with extraperitoneal rectal cancer. METHODS: Rectal adenocarcinoma patients undergoing neoadjuvant therapy were submitted to functional evaluation by anorectal manometry and the degree of fecal incontinence using the Jorge-Wexner score, before and eight weeks after NCRT. The manometric parameters evaluated were mean resting anal pressure (ARp), maximum voluntary contraction anal pressure (MaxSp) and average voluntary contraction anal pressure (ASp). All patients underwent the same NCRT protocol based on the application of fluoropyrimidine (5-FU) at a dosage of 350 mg/m2 associated with folic acid at a dosage of 20 mg/m2, intravenously, in the first and last week of treatment, concomitantly with conformational radiotherapy with a total dose of 50.4Gy, divided into 28 daily fractions of 1.8Gy. For statistical analysis of the quantitative variables with normal distribution, the mean, standard deviation, median and interquartile range were calculated. For comparison of two related samples (before and eight weeks after NCRT), Wilcoxon's non-parametric test was used. RESULTS: Forty-eight patients with rectal cancer were included in the study, with a mean age of 62.8 (39-81) years, 36 (75%) of whom were male. The use of NCRT was associated with a decrease in the values of ARp (55.0 mmHg vs 39.1 mmHg, P<0.05) and ASp (161.9 mmHg vs 141.9 mmHg, P<0.05) without changing MaxSp values (185,5 mmHg vs 173 mmHg, P=0.05). There was no worsening of the incontinence score eight weeks after the use of NCRT (3.0 vs 3.3; P>0.05). CONCLUSION: NCRT was associated with a reduction in the values of ARp and the ASp. There was no change in MaxSp, as well as in the degree of fecal continence by the Jorge-Wexner score.

EXPRESSION OF E-CADHERIN AND CLAUDIN-3 IN THE COLONIC EPITHELIUM AFTER THE INFLIXIMAB THERAPY: EXPERIMENTAL MODEL OF DISUSE COLITIS. / EXPRESSÃO DE E-CADERINA E CLAUDINA-3 NO EPITÉLIO CÓLICO APÓS TERAPIA COM INFLIXIMABE: MODELO EXPERIMENTAL DE COLITE DE EXCLUSÃO.

AIM: The etiopathogenesis of disuse colitis (DC) has not yet been fully elucidated. The main theories consider that the disease may be related to an increase in anaerobic bacteria, the lack of short-chain fatty acid (SCFA) supply, and immunological disorders that develop in the colorectal segments devoid of fecal transit. The aim of this study was to verify whether the application of infliximab modifies the tissue content of E-cadherin and claudin-3 proteins in colonic epithelium of rats devoid of intestinal transit. METHODS: A total of 22 rats underwent intestinal transit bypass using Hartmann's procedure. They remained with the shunt for 12 weeks to allow the development of DC. Later, they were divided into three experimental groups: six animals received 2.0 mL saline solution/week, eight received infliximab at a dose of 5 mg/kg/week, and eight received infliximab at a dose of 10 mg/kg/week for 5 consecutive weeks. At the end of this period, the animals were euthanized, and the colonic segments with and without intestinal transit were removed. DC was diagnosed based on the histological changes defined by a previously validated scale. The tissue expression of E-cadherin and claudin-3 was assessed by immunohistochemistry, and the tissue content of both proteins was quantified by computer-aided image analysis. RESULTS: The colonic segments excluded from fecal transit showed a higher degree of inflammation than those exposed to fecal transit. The degree of inflammation was lower in animals treated with infliximab, regardless of the dose used. The levels of E-cadherin and claudin-3 were reduced in the excluded colon. Treating animals with infliximab increased the levels of both proteins in the colonic segments without intestinal transit, especially in animals receiving a dose of 10 mg/kg/week. CONCLUSION: Infliximab therapy reduces inflammation in the colonic segments excluded from intestinal transit and increases the tissue content of E-cadherin and claudin-3 proteins, especially when used at a concentration of 10 mg/kg/week.

OBJETIVO: A etiopatogenia da colite por desuso (DC) ainda não foi totalmente elucidada. As principais teorias consideram que a doença pode estar relacionada ao aumento de bactérias anaeróbias, falta de suprimento de ácidos graxos de cadeia curta (AGCC) e distúrbios imunológicos que se desenvolvem em segmentos colorretais desprovidos de trânsito fecal. Verificar se a aplicação de infliximabe modifica o conteúdo tecidual das proteínas E-caderina e claudina-3 no epitélio cólico de ratos sem trânsito intestinal. MÉTODOS: Vinte dois ratos foram submetidos a derivação do trânsito intestinal pelo procedimento de Hartmann. Eles permaneceram com o ostoma por 12 semanas para permitir o desenvolvimento da colite de exclusão. Em seguida, foram divididos em três grupos experimentais: seis animais receberam 2,0 ml de solução salina/semana, oito infliximabe na dose de 5 mg/Kg/semana e, os demais, infliximabe na dose de 10 mg/Kg/semana por 5 semanas consecutivas. Em seguida, os animais foram eutanasiados e os segmentos cólicos com e sem trânsito intestinal foram removidos. A colite por desuso foi diagnosticada pelas alterações histológicas definidas por uma escala previamente validada. Expressão tecidual de E-caderina e claudina-3 foi avaliada por imuno-histoquímica, e o conteúdo tecidual de ambas as proteínas foi quantificado por análise de imagem assistida por computador. RESULTADOS: Segmentos cólicos exclusos de trânsito fecal apresentaram maior grau de inflamação do que os expostos ao trânsito fecal. Inflamação foi menor nos animais tratados com infliximabe, independente da dose utilizada. Níveis de E-caderina e claudina-3 estavam reduzidos no cólon excluso. O tratamento com infliximabe aumentou os níveis das proteínas em segmentos do cólon sem trânsito intestinal, principalmente nos animais que receberam a dose de 10mg/kg/semana. CONCLUSÃO: Infliximabe reduz inflamação nos segmentos do cólon excluso e aumenta o conteúdo tecidual de E-caderina e claudina-3, especialmente na concentração de 10mg/kg/semana.

Pouchitis: insight into the pathogenesis and clinical aspects.

Ulcerative colitis (UC) is a chronic intestinal inflammatory disease and familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease. Both diseases, despite being different, may require the same surgical procedure: proctocolectomy with ileal pouch-anal anastomosis (IPAA). The main complication after this procedure is pouch inflammation (pouchitis). This inflammatory complication can affect up to 60 percent of patients who receive IPAA for UC, and a very small percentage of the FAP patients. The purpose of this review was to determine the current molecular mechanisms in its pathogenesis and detail the risk factors involved in pouchitis, its diagnosis, and treatment.

Gene polymorphisms involved in folate and methionine metabolism and increased risk of sporadic colorectal adenocarcinoma.

This pilot study has compared the polymorphic genotype frequencies of methylenetetrahydrofolate reductase (MTHFR A1298C and C677T), methionine synthase (MTR A2756G), methionine synthase reductase (MTRR A66G), and thymidylate synthase (TS 2R/3R) in 113 patients with sporadic colorectal adenocarcinoma (SCA) and 188 healthy blood donors, used as matched controls. The aim was to assess the role of these genotypes in the increased risk of SCA among the southeastern Brazilian population. Carriers of genotype MTRR 66GG, or the combined variants MTHFR 1298AC + CC plus 677CT + TT, or MTHFR 677CT + TT plus MTR 2756AG + GG, or MTHFR 1298AC + CC plus 677CT + TT plus MTR 2756AG + GG, or yet, MTHFR 1298AC + CC plus 677CT + TT plus MTRR 66AG + GG, respectively, showed an increased risk of the order of 1.99-, 3.26-, 2.22-, 10.92-, and 14.88-fold of developing SCA when compared with carriers of the other studied polymorphic genotypes, whether in isolation or in combination. In addition, individuals with the MTHFR 677CT + TT or the MTR 2756AG + GG genotypes had a 2.12- and a 1.42-fold increased risks of SCA onset before 50 years of age. African-Brazilians with the MTRR 66GG genotype had a 1.98-fold increased risk of SCA while individuals with the MTR 2756AG + GG and the MTHFR 677CT + TT genotypes showed a 2.11- and a 1.62-fold increased risk of undifferentiated and advanced tumors at diagnosis, respectively. Carriers of genotype MTHFR 1298AC + CC or MTHFR 1298AC + CC plus MTRR 66AG + GG had a 1.42- and a 3.07-fold increased risk of rectal tumor, respectively. Additionally, carriers of MTHFR 677CT + TT or MTHFR 677CT + TT plus TS 2R/3R + 3R/3R had a 1.55- and a 5.39-fold increased risk for colon tumor, respectively, in comparison with carriers of the wild genotypes. These data suggest that all polymorphisms coding for folate and methionine-dependent enzymes, particularly when present in combination with other polymorphisms, have consistent roles in the increased risk of SCA among the southeastern population of Brazil.

Myosteatosis Differentially Affects the Prognosis of Non-Metastatic Colon and Rectal Cancer Patients: An Exploratory Study.

Body composition performed by computed tomography (CT) impacts on cancer patients' prognoses and responses to treatment. Myosteatosis has been related to overall survival (OS) and disease-specific survival in colorectal cancer (CRC); however, the independent impact of the association of myosteatosis with prognosis in colon cancer (CC) and rectal cancer (RC) is still unclear. CT was performed at the L3 level to assess body composition features in 227 patients with CRC. Clinical parameters were collected. Overall survival (OS) was the primary outcome, and the secondary outcome was disease-free survival (DFS). Skeletal muscle attenuation and intramuscular adipose tissue area were associated with DFS (p = 0.003 and p = 0.011, respectively) and OS (p < 0.001 and p < 0.001, respectively) in CC patients but not in RC patients. Only the skeletal muscle area was associated with better prognosis related to OS in RC patients (p = 0.009). When CC and RC were analyzed separately, myosteatosis influenced survival negatively in CC patients, worsening DFS survival (hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.07-6.82; p = 0.035) and OS (HR, 5.76; 95% CI, 1.31-25.40; p = 0.021). By contrast, the presence of myosteatosis did not influence DFS (HR, 1.02; 95% CI, 0.52-2.03; p = 0.944) or OS (HR, 0.76; 95% CI, 0.33-1.77; p = 0.529) in RC patients. Our study revealed the interference of myosteatosis in the therapy and survival of patients with CC but not in those with RC, strengthening the value of grouping the two types of cancer in body composition analyses.

EPIDEMIOLOGICAL PROFILE AND CLINICAL CHARACTERISTICS OF INFLAMMATORY BOWEL DISEASES IN A BRAZILIAN REFERRAL CENTER.

BACKGROUND: The increase in the incidence and prevalence rates of inflammatory bowel disease (IBD) is evident in many newly industrialized countries in Asia, Africa, Eastern Europe, and the American continent. In Brazil, records are still scarce, and further studies on this topic are needed. OBJECTIVE: To evaluate the epidemiological profile and clinical characteristics of patients with IBD who were followed up at a reference service in the state of São Paulo. METHODS: We retrospectively analyzed the medical records of patients with IBD who were followed up in a Brazilian Referral Center. RESULTS: A total of 625 patients was evaluated, 416 with Crohn's disease (CD), 190 with ulcerative colitis (UC), and 19 with indeterminate colitis. The average age of the patients was 31.6 years, with a homogeneous distribution between males and females patients. In patients with CD, the most predominant Montreal classification was A2, L3, and B1, with 44.8% of patients presenting with perianal disease; in UC, it was E2, and S0. The main extraintestinal manifestation was rheumatologic, followed by cutaneous and ophthalmic lesions. The majority of patients (85.4%) used some type of medication, the most frequent being aminosalicylates in patients with UC and biological therapy in patients with CD. Regarding surgeries, in CD, a significant percentage of patients underwent some type of surgical procedure, unlike the UC patients, including fistulotomies and placement of seton, derivative ostomies, enterectomy, ileocecectomy/right colectomy, total or partial colectomy, and strictureplasty. Only 195 (31.2%) patients lived in the city of Campinas, while 443 (70.9%) were from the 7th Regional Health Department (RHD), which corresponds to the macro-region of Campinas. CONCLUSION: In this study, most patients came from the 7th RHD of Campinas; the patients were young, with no predominance of either sex; there was a higher frequency of patients with CD (66.6%). Most of them (85.4%) were undergoing pharmacological treatment, and a significant percentage of CD patients had undergone surgery.

RELATIONSHIP AMONG PSYCHOLOGICAL WELL-BEING, RESILIENCE AND COPING WITH SOCIAL AND CLINICAL FEATURES IN CROHN'S DISEASE PATIENTS.

BACKGROUND: Crohn's disease is chronic, requires prolonged treatment, affects the physical and psychosocial health of patients and may alter their routine, quality of life and well-being. Recent studies recommend monitoring the health of these patients considering physical, psychological and psychosocial aspects, because they are directly related to the disease activity. These studies highlight the relevance of patients' emotional and behavioral conditions and suggest that the identification of the factors that influence the psychological well-being, resilience and Coping in these patients can favor the proper treatment. OBJECTIVE: To relate psychological well-being, resilience and Coping with social and clinical features of Crohn's disease patients. METHODS: Prospective study including 104 patients with Crohn's disease, both genders and mean age of 39 years. Standardized scales were used to assess and to relate psychological well-being, resilience and Coping with social and clinical variables. A questionnaire to characterize the sample and standardized scales in data collection (psychological well-being, resilience pillars and Coping strategies inventory - Folkman & Lazarus) were used. Descriptive analysis of data and statistics for comparison of results were performed. RESULTS: There were significant differences (P<0.05) showing better psychological well-being for male patients, those who without children, were not religious, were employed and were doing complementary activities in addition to clinical treatment. More resilience for the male gender, those who without children, were not religious, divorced, separated or widowed, that received some monthly income; who did not undergo surgery, had the first symptoms after 30 years old and who had complementary activity. There were also significant differences in the use of Coping: usually, women used more developed escape and avoidance strategies; single, married or in stable-union patients used more self-control; not religious used positive revaluation strategy; the ones who were employed showed more self-control and positive reassessment; the ones who had lower family income indicated that they used less the self-control; the ones who had higher family income used more positive re-evaluation; patients who were diagnosed with Crohn's disease between the second decade of life showed to use mores more the positive reassessment strategy than those who were 20 years old or younger. CONCLUSION: Social aspects influenced psychological well-being, resilience and Coping in patients with Crohn's disease more strongly than clinical aspects. It was possible to identify the profiles with better and worse psychological well-being, resilience and Coping of those who need more support, as well as to know the most used Coping strategies in the studied group.