Influência da terapia neoadjuvante na razão de linfonodos / Influence of neoadjuvant therapy on the ratio of lymph nodes

ABSTRACT 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.

RESUMO Contexto: Avaliar a relação entre a razão de linfonodos (RLA) acometidos e variáveis clínicas e anatomopatológicas em portadores de adenocarcinoma de reto submetidos ou não à quimiorradioterapia neoadjuvante. Métodos: A RLA foi determinada dividindo-se o número total de linfonodos (LFNs) dissecados no espécime cirúrgico pelo número de comprometidos. Os doentes foram divididos em dois grupos: com QRT e sem QRT. Em cada grupo foi avaliada a relação entre a RLA e as seguintes variáveis: grau de diferenciação celular, profundidade de invasão na parede retal, invasão angiolinfática/perineural, grau de regressão tumoral e ocorrência de metástases. Avaliou-se a RLA em pacientes com mais do que 12 LFNs (RLA>12) ou menos (RLA<12) na peça cirúrgica com a sobrevida global (SG) e sobrevida livre de doença (SLD). Os resultados foram expressos pela média com o respectivo desvio padrão. As variáveis qualitativas foram analisadas utilizando-se o teste exato de Fisher, enquanto as quantitativas pelos testes de Kruskal-Wallis e Mann-Whitney. O nível de significância foi de 5%. Resultados: Foram avaliados 282 pacientes com QRT e 114 sem QRT, entre 1995-2011. No Grupo QRT, RLA mostrou associação significativa com os tumores mucinosos (P=0,007) e grau de regressão tumoral (P=0,003). Nos dois grupos, a RLA associou-se com tumores pouco diferenciados (P=0,001 e P=0,02), presença de invasão angiolinfática (P<0,0001 e P=0,01), perineural (P=0,0007 e P=0,02), grau de invasão da parede retal (T3>T2; P<0,0001 e P=0,02); LFNs comprometidos (P<0,0001 e P<0,01), metástases (P<0,0001 e P<0,01). Nos pacientes com QRT, a RLA <12 associou-se com a SLD (5,889; IC95%1,935-19,687; P=0,018) e a RLA >12 com SLD e SG (17,984; IC95%5,931-54,351; P<0,001 e 10,286; IC95%2,654-39,854; P=0,007, respectivamente). Conclusão: A RLA associou-se a aspectos histológicos de mau prognóstico, independentemente do emprego de QRT. Na ocorrência de menos de 12 LFNs avaliados, a RLA associou-se apenas com a SLD.

Mucin levels in glands of the colonic mucosa of rats with diversion colitis subjected to enemas containing sucralfate and n-acetylcysteine alone or in combination

ABSTRACT Purpose: To evaluate the tissue content of neutral and acidic mucins, sulfomucins and sialomucins in colonic glands devoid of intestinal transit after enemas containing sucralfate and n-acetylcysteine alone or in combination. Methods: Sixty-four rats underwent intestinal transit bypass. A colonic segment was collected to compose the white group (without intervention). After derivation, the animals were divided into two groups according to whether enemas were performed daily for two or four weeks. Each group was subdivided into four subgroups according to the substance used: control group: saline 0.9%; sucralfate group (SCF): SCF 2 g/kg/day; n-acetylcysteine group (NAC): NAC 100 mg/kg/day; and SCF+NAC group: SCF 2 g/kg/day + NAC 100 mg/kg/day.Neutral and acidic mucins were stained by periodic acid-Schiff and alcian-blue techniques, respectively. The distinction between sulfomucins and sialomucin was made by the high alcian-blue iron diamine technique. The content of mucins in the colonic glands was measured by computerized morphometry. The inflammatory score was assessed using a validated scale. The results between the groups were compared by the Mann-Whitney's test, while the variation according to time by the Kruskal-Wallis' test (Dunn's post-test). A significance level of 5% was adopted. Results: There was reduction in the inflammatory score regardless of the application of isolated or associated substances. Intervention with SCF+NAC increased the content of all mucin subtypes regardless of intervention time. Conclusions: The application of SCF+NAC reduced the inflammatory process of the colonic mucosa and increased the content of different types of mucins in the colonic glands of segments excluded from fecal transit.

Impact of the covid-19 pandemic on the emergency surgical treatment of colorectal cancer / Impacto da pandemia da covid-19 no tratamento cirúrgico emergencial do câncer colorretal

ABSTRACT BACKGROUND: Colorectal cancer (CRC) is the most common malignancy of the gastrointestinal tract and the third most common type of cancer worldwide. The COVID-19 pandemic, during the years 2020 and 2022, increased the difficulties in offering adequate early diagnosis and treatment to CRC patients worldwide. During this period, it was only possible to treat patients who evolved with complications, mainly intestinal obstruction and perforation. AIMS: To assess the impact of the COVID-19 pandemic on the treatment of patients with CRC. METHODS: A review of data from a total of 112 patients undergoing emergency surgical treatment due to complications of CRC was carried out. Of these, 78 patients underwent emergency surgery during the COVID-19 pandemic (2020/2021), and 34 were treated before the pandemic (2018/2019). Ethnic aspects, clinical symptoms, laboratory tests, histopathological variables, intra and postoperative complications, and 90-day postoperative follow-up were compared between the two groups. RESULTS: Between the years 2018 and 2019, 79.4% (27/34) of patients had intestinal obstruction, while 20.6% (7/34) had intestinal perforation. During the period of the COVID-19 pandemic (2020/2021), 1.3% (1/78) of patients underwent surgery due to gastrointestinal bleeding, 6.4% (5/78) due to intestinal perforation, and 92.3% (72/78) due to intestinal obstruction. No statistically significant differences were recorded between the two groups in ethnic aspects, laboratory tests, type of complications, number of lymph nodes resected, compromised lymph nodes, TNM staging, pre or intraoperative complications, length of stay, readmission, or mortality rate. When considering postoperative tumor staging, among patients operated on in 2018/2019, 44.1% were classified as stage III and 38.2% as stage IV, while during the pandemic period, 28.2% presented stage III and 51.3% stage IV, also without a statistically significant difference between the two periods. Patients operated on during the pandemic had higher rates of vascular, lymphatic and perineural invasion. CONCLUSIONS: The COVID-19 pandemic increased the rate of complications related to CRC when comparing patients treated before and during the pandemic. Furthermore, it had a negative impact on histopathological variables, causing worse oncological prognoses in patients undergoing emergency surgery.

RESUMO RACIONAL: O câncer colorretal (CCR) é a doença maligna mais comum do trato gastrointestinal sendo o terceiro tipo de câncer mais comum em todo o mundo. A pandemia de COVID-19 durante os anos de 2020 e 2022 aumentou as dificuldades em se oferecer diagnóstico e tratamento precoce adequado aos pacientes com CCR em todo o mundo. Nesse período, só foi possível tratar os pacientes que evoluíram com complicações representadas, principalmente, pela obstrução e perfuração intestinal. OBJETIVOS: Avaliar o impacto da pandemia de COVID-19 no tratamento de pacientes com CCR. MÉTODOS: Foi realizada uma revisão dos dados de um total de 112 pacientes submetidos ao tratamento cirúrgico de urgência devido complicações do CCR. Destes, 78 pacientes foram submetidos a cirurgia de emergência durante o período da pandemia de COVID-19 (2020/2021), e 34 pacientes foram operados no período anterior à pandemia (2018/2019). Aspectos étnicos, sintomas clínicos, exames laboratoriais, variáveis histopatológicas, complicações intra e pós-operatórias e acompanhamento pós-operatório de 90 dias foram analisados comparando os dois grupos. RESULTADOS: Entre os anos 2018 e 2019, 79,4% (27/34) dos pacientes apresentaram obstrução intestinal enquanto 20,6% (7/34) perfuração intestinal. Durante o período da pandemia de COVID-19 (2020/2021) 1,3% (1/78) dos pacientes foram operados por hemorragia digestiva baixa, 6,4% (5/78) por perfuração intestinal e 92,3% (72/78) por obstrução intestinal. Não foram registradas diferenças estatisticamente significativas entre os dois grupos nos aspectos étnicos, exames laboratoriais, tipo de complicações, número de linfonodos ressecados, linfonodos comprometidos, estadiamento TNM, complicações pré ou intraoperatórias, tempo de internação, readmissão e taxa de mortalidade. Ao considerar o estadiamento tumoral pós-operatório, entre os pacientes operados em 2018/19, 44,1% foram classificados como estágio III e 38,2% como estágio IV, enquanto no período pandêmico, 28,2% apresentaram estágio III e 51,3% estágio IV, também sem diferença estatisticamente significativa entre os dois períodos. Doentes operados durante a pandemia apresentaram maiores índices de invasão vascular, linfática e perineural. CONCLUSÕES: A pandemia de COVID-19 aumentou as taxas de complicações relacionadas ao CCR, comparando pacientes tratados antes e durante a pandemia. Além disso, teve impacto negativo nas variáveis histopatológicas, causando piores prognósticos oncológicos em pacientes submetidos a cirurgias de emergência.

Intra-abdominal desmoid tumors in familial adenomatous polyposis: How much do clinical and surgical variables interfere with their development?

Abstract Objective: Familial Adenomatous Polyposis is a complex hereditary disease that exposes the carrier to a great risk of Colorectal Cancer (CRC). After prophylactic surgery, intra-abdominal desmoid tumors are known to be one the most important cause of death. Therefore, recognition of increased-risk patients and modification of operative strategy may be crucial. Aim: The objective of this study was to estimate the desmoid tumor risk in relation to various surgical and clinical variables. Methods: Patients who had undergone polyposis since 1958 were included in the study. After exclusion criteria were met, those who had developed desmoid tumors were selected to undergo further evaluation. Results: The study revealed that the risk of developing desmoid tumors was associated with various factors such as sex ratio, colectomy, and reoperations. On the other hand, the type of surgery, family history, and surgical approach did not affect the risk of developing desmoid tumors. The data collected from 146 polyposis patients revealed that 16% had desmoid polyps. The sex ratio was 7:1, and the median age at colectomy was 28.6 years. Family history, multiple abdominal operations, and reoperations were some of the characteristics that were common in desmoid patients. Conclusion: Recognition of clinical (female sex) and surgical (timing of surgery and previous reoperations) data as unfavorable variables associated with greater risk may be useful during the decision-making process.

Estudo da fisiologia anorretal pré e pós terapia neoadjuvante para câncer de reto por manometria anorretal e escore de Jorge-Wexner / Study of anorectal physiology pre and pos neoadjuvant therapy for rectal cancer by anorectal manometry and jorge-wexner score

ABSTRACT 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.

RESUMO Contexto: O tratamento do câncer retal distal pode ser acompanhado por distúrbios evacuatórios de etiologia multifatorial. A quimiorradioterapia neoadjuvante faz parte do tratamento padrão para pacientes com câncer retal extraperitoneal localmente avançado. A avaliação da função anorretal após neoadjuvância de longa duração em pacientes com câncer de reto extraperitoneal tem sido pouco estudada. Objetivo: O objetivo do presente estudo foi avaliar os efeitos da neoadjuvância na função anorretal e na incontinência em pacientes com câncer retal extraperitoneal. Métodos: Pacientes com adenocarcinoma de reto candidatos à terapia neoadjuvante foram submetidos a avaliação funcional por manometria anorretal e avaliação do grau de incontinência fecal pelo escore de Jorge-Wexner, pré e oito semanas após a neoadjuvância. Os parâmetros manométricos avaliados foram pressão anal média de repouso, pressão anal de contração voluntária máxima e pressão anal média de contração voluntária. Todos os pacientes foram submetidos ao mesmo protocolo de neoadjuvância baseado na aplicação de fluoropirimidina (5-FU) na dosagem de 350 mg/m2 associada ao ácido fólico na dosagem de 20 mg/m2, por via intravenosa, na primeira e última semana de tratamento, concomitantemente à radioterapia conformacional com dose total de 50,4Gy, dividida em 28 frações diárias de 1,8Gy. Para análise estatística das variáveis quantitativas com distribuição normal, foram calculados a média, desvio padrão, mediana e intervalo interquartil. Para comparação de duas amostras relacionadas (antes e oito semanas após a neoadjuvância, foi utilizado o teste não paramétrico de Wilcoxon. Resultados: Quarenta e oito pacientes com câncer retal foram incluídos no estudo, com média de idade de 62,8 (39-81) anos, sendo 36 (75%) do sexo masculino. O uso de neoadjuvância foi associado à diminuição dos valores de média de pressão de repouso (55,0 mmHg vs 39,1 mmHg, P<0,05) e média de pressão de contração voluntária (161,9 mmHg vs 141,9 mmHg, P<0,05) sem alterar os valores de pressão de contração voluntária máxima ((185,5 mmHg vs 173 mmHg, P=0.05)). Não houve piora do escore de incontinência oito semanas após o uso da quimiorradioterapia neoadjuvante (3,0 vs 3,3; P>0,05). Conclusão: A neoadjuvância associou-se à redução dos valores de média de pressão de repouso e média dos valores contração voluntária. Não houve alteração nos valores de contração voluntária máxima, bem como no grau de continência fecal pelo escore de Jorge-Wexner.

Is it possible to optimize stapled hemorrhoidopexy outcomes by enlarging operative criteria indications? results of a tailored procedure with associated resection in a comparative personal series / é possível otimizar os resultados da hemorroidopexia grampeada pela ampliação dos critérios de indicação operatória? resultados de um procedimento personalizado com ressecção associada em uma série comparativa pessoal

ABSTRACT BACKGROUND: Since its introduction, stapled hemorrhoidopexy has been increasingly indicated in the management of hemorrhoidal disease. AIM: Our primary end point was to evaluate the incidence of recurrent disease requiring another surgical intervention. On a secondary analysis, we also compared pain, complications, and patient's satisfaction after a tailored surgery. METHODS: We retrospectively reviewed 196 patients (103 males and 93 females) with a median age of 47.9 years (range, 17-78) who were undergoing stapled hemorrhoidopexy alone (STG; n=65) or combined surgery (CSG; n=131, stapled hemorrhoidopexy associated with resection). RESULTS: Complications were detected in 11 (5.6%) patients (4.6% for STG vs. 6.1% for CSG; p=0.95). At the same time, symptoms recurrence (13.8% vs. 8.4%; p=034), reoperation rate for complications (3.1% vs. 3.0%; p=1.0), and reoperation rate for recurrence (6.1% vs. 4.6%; p=1.0) were not different among groups. Grade IV patients were more commonly managed with simultaneous stapling and resection (63% vs. 49.5%), but none of them presented symptoms recurrence nor need reoperation due to recurrence. Median pain score during the first week was higher in CSG patients (0.8 vs. 1.7). After a follow-up of 24.9 months, satisfaction scores were similar (8.6; p=0.8). CONCLUSION: Recurrent symptoms were observed in 10% of patients, requiring surgery in approximately half of them. Even though the association of techniques may raise pain scores, a tailored approach based on amplified indication criteria and combined techniques seems to be an effective and safe alternative, with decreased relapse rates in patients suffering from more advanced hemorrhoidal disease. Satisfaction scores after hemorrhoidopexy are high.

RESUMO RACIONAL: Desde sua introdução, a hemorroidopexia por grampeamento tem sido cada vez mais indicada no manuseio da doença hemorroidária. OBJETIVOS: Nosso objetivo primário foi avaliar a incidência de doença recidivada que requeira tratamento cirúrgico. Numa análise secundária, também comparamos dor, complicações e satisfação do paciente após uma operação ajustada a cada caso. MÉTODOS: Foram revistos retrospectivamente 196 pacientes (103 homens e 93 mulheres) com idade média de 47,9 anos (17-78) submetidos a hemorroidopexia mecânica isoladamente (STG; n=65) ou cirurgia combinada (CSG; n=131, hemorroidopexia por grampeamento com ressecção). RESULTADOS: Complicações foram detectadas 11 (5,6%) pacientes (4,6% para STG vs. 6,1% para CSG; p=0,95). Ao mesmo tempo, recidiva de sintomas (13,8% vs. 8,4%; p=034), reoperações por complicações (3,1% vs. 3,0%; p=1,0) ou por recidiva (6,1 vs. 4,6%; p=1,0) não foram diferentes entre os dois grupos. Pacientes com grau IV foram mais comumente manuseados com grampeamento e ressecção simultâneos (63% vs. 49,5%), mas nenhum deles apresentou recidiva ou necessitou reoperação. O escore médio de dor na primeira semana foi maior no grupo CSG (0,8 vs. 1,7). Após seguimento de 24,9 meses, os índices de satisfação foram similares (8,6; p=0,8). CONCLUSÕES: Sintomas de recidiva foram observados em 10%, requerendo cirurgia em aproximadamente metade dos doentes. Embora a associação de técnicas aumente os escores de dor, um procedimento sob medida baseado em critérios ampliados de indicação e técnicas combinadas parece ser uma alternativa efetiva e segura, com menor recidiva em pacientes portadores de doença hemorroidária mais avançada. Os escores de satisfação após hemorroidopexia são altos.

Selective hemorrhoidal dearterialization with high mucopexy in the surgical treatment of hemorrhoidal disease

The doppler-guided transanal hemorrhoidal dearterialization technique associated with mucopexy is a noninvasive surgical option used to treat hemorrhoidal disease (HD). Objective: To compare and analyze the results using a variation of the doppler-guided transanal hemorrhoidal dearterialization technique with the technique of selective hemorrhoidal dearterialization with high mucopexy in the treatment of HD. Method: A total of 292 patients who underwent surgical treatment for grade II, III and IV HD from March 2012 to December 2017 were studied. From this total, 110 (37.6%) patients underwent a conventional doppler-guided transanal hemorrhoidal dearterialization with mucopexy (CD), and 182 (62.3%) underwent selective hemorrhoidal dearterialization with highmucopexy (SHeLF). In the group of patients undergoing CD, 4 patients (3.64%) had grade II HD, 82 (74.55%) grade III, and 24 (21.82%) grade IV. In the group submitted to SHeLF, 18 (9.89%) patients had grade II HD, 86 (47.25%) had grade III, and 65 (35.71%) had grade IV. The same surgeon operated all patients under spinal anesthesia. In patients undergoing CD, six arterial branches have been dearterialized, while in patients undergoing SHeLF, the hemorrhoidary nipples submitted to a dearterialization were selected (from 1 to 5) by intraoperative evaluation followed by high rectal mucopexy. In the postoperative period, the following parameters were evaluated: pain, tenesmus, bleeding, and recurrence. Moderate results to severe pain was a postoperative complaint reported by 13 (11.82%) patients undergoing CD, and by 19 (10.44%) undergoing SHeLF. Intense tenesmus was reported by 26 (23.64%) patients undergoing CD and by 7 (3.85%) undergoing SHeLF. Three patients (2.73%) undergoing CD and 1 (0.55%) undergoing SHeLF evolved with postoperative bleeding. One patient (0.55%) in the group undergoing CD required surgical review of hemostasis. Six patients (5.45%) who underwent CD and 8 (4.39%) who underwent SHeLF were reoperated due to disease recurrence. Conclusion: Comparing statistics, patients undergoing the SHeLF technique have less postoperative pain, tenesmus and postoperative bleeding when compared with CD. (AU)

Sucralfate enemas reduce the oxidative tissue damage and preserves the contents of E-cadherin and Β-catenin in colonic mucosa without fecal stream

ABSTRACT Purpose: To evaluate the effects of sucralfate enemas in tissue contents of E-cadherin and ?-catenin in an experimental diversion colitis. Methods: Thirty-six male Wistar rats were submitted to a proximal colostomy and a distal mucous fistula. They were allocated into three groups: first group received daily saline enemas (2 mL/day) and the two other groups daily enemas with sucralfate at dosage of 1 or 2 g/kg/day, respectively. Six animals of each group were euthanized after two weeks and six animals after four weeks. The inflammation of the excluded mucosa was evaluated by histological analysis. The oxidative damage was quantified by measurement of malondialdehyde tissue levels. The expression of E-cadherin and ?-catenin was identified by immunohistochemistry, and its contents were quantified by computer-assisted image analysis. Results: Sucralfate enemas reduced inflammation in animals subjected to treatment with 2 g/kg/day by four weeks, and the levels of oxidative damage in mucosa without fecal stream irrespective of concentration and time of intervention. E-cadherin and ?-catenin content increased in segments without fecal stream in those animals subjected to treatment with sucralfate. Conclusions: Sucralfate reduces the inflammation and oxidative stress and increases the tissue content of E-cadherin and ?-catenin in colonic mucosa devoid to the fecal stream.

Enema de sulcralfato pode prevenir colite em segmentos colônicos sem trânsito fecal? / Can sucralfate enema prevent colitis in colonic segments without fecal transit?

RESUMO - RACIONAL: O estresse oxidativo é um dos principais mecanismos associados à ruptura dos mecanismos de defesa que formam a barreira epitelial cólica e reduz o conteúdo tecidual das proteínas claudina-3 e ocludina principais constituintes das junções de oclusão intercelulares. O sucralfato, possui atividade antioxidante e tem sido usado para tratar diferentes formas de colite. OBJETIVO: Mensurar o conteúdo tecidual de claudina-3 e ocludina da mucosa do cólon sem trânsito fecal, submetido à intervenção com sucralfato. MÉTODO: Trinta e seis ratos foram submetidos à colostomia do cólon esquerdo e fístula mucosa distal. Os animais foram divididos em dois grupos de acordo com a eutanásia ser realizada duas ou quatro semanas após a intervenção. Cada grupo foi dividido em três subgrupos de acordo com o tipo de intervenção realizada diariamente: solução salina isolada; sucralfato a 1 g/kg/dia ou sucralfato a 2g/kg/dia. A colite foi diagnosticada por análise histológica adotando escala de validação prévia. A expressão tecidual de ambas as proteínas foi identificada por imunoistoquímica. O conteúdo das proteínas foi quantificado por análise de imagem assistida por computador. RESULTADOS: O escore inflamatório foi maior nos segmentos cólicos sem trânsito fecal e os enemas com sucralfato reduziram o escore inflamatório nesses segmentos, principalmente nos animais submetidos à intervenção com sucralfato em maior concentração e por período mais longo de intervenção. Houve aumento no conteúdo tecidual das proteínas claudina-3 e ocludina, relacionado com a concentração de sucralfato. O conteúdo tecidual de ambas as proteínas não se modificou com a duração da intervenção. CONCLUSÃO: Enemas com sucralfato reduzem a inflamação e aumentam o conteúdo tecidual de claudina-3 e ocludina na mucosa cólica sem trânsito intestinal.

ABSTRACT - BACKGROUND: Oxidative stress is one of the main mechanisms associated with the rupture of the defense mechanisms of the colonic epithelial barrier; it reduces the tissue content of the claudin-3 and occludin proteins, which are the main constituents of intercellular tight junctions. Sucralfate (SCF) has antioxidant activity and has been used to treat different forms of colitis. AIM: This study aimed to measure the tissue claudin-3 and occludin content of the colon mucosa without fecal transit, subjected to intervention with SCF. METHODS: Thirty-six rats were subjected to left colon colostomy and distal mucous fistula. They were divided into two groups according to euthanasia that was performed 2 or 4 weeks after the intervention. Each group was divided into three subgroups according to the enema applied daily: saline alone, SCF at 1 g/kg/day, or SCF at 2 g/kg/day. Colitis was diagnosed by the histological analysis adopting the previous validate scale. The tissue expression of both proteins was identified by immunohistochemical technique. The content of proteins was quantified by computer-assisted image analysis. RESULTS: The inflammatory score was high in colonic segments without fecal transit, and enemas with SCF reduced the inflammatory score in these segments, mainly in those animals submitted to intervention with SCF in greater concentration and for a longer period of intervention. There was an increase in tissue content of claudin-3 and occludin, related to SCF concentration. The tissue content of both proteins was not related to the intervention time. CONCLUSION: Enemas with SCF reduced the inflammation and increased the tissue content of claudin-3 and occludin in colonic mucosa without fecal stream.

Expressão de e-caderina e claudina-3 no epitélio cólico após terapia com infliximabe: modelo experimental de colite de exclusão / Expression of e-cadherin and claudin-3 in the colonic epithelium after the infliximab therapy: experimental model of disuse colitis

RESUMO - RACIONAL: 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. OBJETIVO: 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.

ABSTRACT - BACKGROUND: 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. AIM: 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.

Effects of anti-TNF-α in experimental diversion colitis

Abstract Purpose: To evaluate the effects of infliximab on the inflammation of the colonic mucosa devoid from fecal stream. Methods: Twenty-four rats were submitted to a Hartmann's procedure. They remained for 12 weeks with the fecal derivation to development of diversion colitis on excluded colorectal stump. After this period, they were divided into 3 groups: one group received intervention with saline (2.0 mL / week), other group infliximab at doses of 5 mg/kg/week and the other 10 mg/kg/week for five consecutively weeks. Concluded the intervention period, the animals were euthanized to remove colon segments with and without fecal stream. Colitis was diagnosed by histological analysis and the degree of inflammation by validated score. The neutrophilic infiltrate was evaluated by tissue expression of myeloperoxidase identified by immunohistochemical. The tissue content of myeloperoxidase was measured by computer-assisted image analysis. Results: The inflammatory score was high in colonic segments without fecal stream. The intervention with infliximab reduced the inflammatory score in excluded colonic segments. The content of myeloperoxidase was reduced in colonic segments of animals treated with infliximab mainly in high concentrations. Conclusion: Intervention with infliximab reduced the inflammation and the neutrophil infiltrate in colonic segments devoid of the fecal stream.

Internal hernia through mesocolon defect after left laparoscopic colectomy / Hérnia interna pelo defeito mesocólico após colectomia esquerda laparoscópica

ABSTRACT Introduction: The development of internal hernias due to the mesocolon defect after laparoscopic colectomy is a rare complication with only 39 cases described. There are controversies whether the closure of the defect of the mesocolon after resection of the colon could prevent the development of this complication. Objective: To describe a case of intestinal obstruction due to internal hernia through the mesocolon defect after laparoscopic rectosigmoidectomy and to perform a literature review. Case report: A 59-year-old woman was hospitalized for laparoscopic rectosigmoidectomy due to an adenocarcinoma located in the rectosigmoid junction. She underwent a rectosigmoidectomy by laparoscopy, with an extracorporeal mechanical anastomosis, without closure of the mesocolon defect. In the fifth postoperative day the patient presented an intestinal obstruction due to an internal hernia through the mesocolon defect confirmed by computerized tomography. During the exploratory laparotomy approximately 120 cm jejunum was identified through the mesocolon defect. The reduction of herniated small bowel was done without the need of intestinal resection. The mesocolon defect was corrected by continuous suture. After the reoperation, the patient presented a favorable recovery being discharged on the fifth day. Conclusion: Intestinal obstruction due to internal hernia after laparoscopic rectosigmoidectomy is a rare postoperative complication that can be avoided by the adequate closure of the mesocolon defect.

RESUMO Introdução: O desenvolvimento de hérnias internas pelo defeito mesocólico após a realização de colectomia laparoscópica é uma complicação rara com apenas 39 casos descritos. Existem controvérsias se fechamento do defeito após a ressecção do cólon preveniria o desenvolvimento desta complicação. Objetivo: Descrever um caso de obstrução intestinal por hérnia interna pelo defeito mesocólico, após retossigmoidectomia laparoscópica e revisar a literatura relacionada ao tema. Relato do caso: Mulher, 59 anos foi internada para realizar ressecção cirúrgica de adenocarcinoma localizado na junção retossigmoideana. Foi submetida à retossigmoidectomia laparoscópica, com confecção de anastomose mecânica extracorpórea. O defeito mesocólico não foi corrigido no final do procedimento. No quinto dia de pós-operatório, a doente apresentou quadro de obstrução intestinal cuja tomografia computadorizada identificou presença de hérnia interna pelo defeito do mesocólon. Na laparotomia exploradora identificou-se que aproximadamente 120 cm de alças jejunais estavam herniadas através do defeito mesocólico. Realizou-se a redução do intestino delgado herniado sem necessidade de ressecção intestinal. O defeito foi corrigido por sutura contínua. Após a reoperação a doente apresentou evolução favorável recebendo alta no quinto dia. Conclusão: Obstrução intestinal após retossigmoidectomia laparoscópica consequente à formação de hérnia interna é complicação pós-operatória rara, com alta mortalidade, que pode ser evitada pelo fechamento criterioso do defeito do mesocólico.

Postoperative results of 407 patients submitted to Doppler-guided transanal hemorrhoidal dearterialization / Resultados pós-operatórios de 407 doentes submetidos à desarterialização hemorroidária guiada pelo Doppler

ABSTRACT Introduction: The treatment of hemorrhoidal disease by conventional technique is associated with significant morbidity, mainly represented by the postoperative pain and the late return to daily activities. A technique of hemorrhoidal dearterialization associated with rectal mucopexy is a minimal invasive surgical option that has been used to treat the hemorrhoidal disease and reduce its inconveniences. Objective: To analyze the seven-year results of hemorrhoidal dearterialization associated with rectal mucopexy in the treatment of hemorrhoidal disease. Methods: This study analyzed 407 patients with hemorrhoids grade II, III and IV, who underwent the technique of hemorrhoidal dearterialization in the Luzia de Pinho Melo Hospital, during the period between December 2010 and December 2017. Twenty-seven patients (6.6%) had hemorrhoidal disease of the grade II, 240 (59.0%) grade III, and 117 (28.8%) grade IV. In 23 patients (5.7%), the grade was not found. All patients were operated by the same surgeon under spinal anesthesia. The 407 patients underwent dearterialization, with a varying ligation of one to six arterial branches followed by rectal mucopexy by uninterrupted suture. Eighty-two (20.14%) required removal of concomitant perianal piles or external hemorrhoids and/or fibrosed. In the postoperative follow-up the following parameters were evaluated: pain, tenesmus, bleeding, prolapse, thrombosis, and recurrence. Results: The tenesmus was postoperative complaint reported by 93.6% of patients. Forty-three (10.5%) presented intense tenesmus and 44 (22%), moderate to intense pain. Four (0.98%) patients presented more intense bleeding in postoperative follow up; none of the patients required blood transfusions. The prolapse occurred in 18 (4.42%) patients, thrombosis in 11 (2.7%), and there were 19 (4.67%) recurrences that were reoperated in this period. Conclusion: The hemorrhoidal dearterialization technique presents good results, with light and easy-to-resolve complications and little postoperative pain.

RESUMO Introdução: O tratamento da doença hemorroidária pelas técnicas convencionais cursa com significante redução da qualidade de vida do doente, principalmente relacionada à dor pós-operatória e ao considerável tempo de afastamento do trabalho. A técnica de desarterialização hemorroidária associada à mucopexia retal é uma opção cirúrgica pouco invasiva, a qual é utilizada com o objetivo de tratar a doença hemorroidária e reduzir seus inconvenientes. Objetivo: Analisar os resultados encontrados após sete anos de seguimento em doentes submetidos à técnica da desarterialização hemorroidária associada à mucopexia para o tratamento da doença hemorroidária. Método: Foram estudados 407 portadores de doença hemorroidária de graus II, III e IV, submetidos à técnica da desarterialização hemorroidária no Hospital das Clínicas Luzia de Pinho Melo de Mogi das Cruzes, durante o período de Dezembro de 2010 a Dezembro de 2017. Vinte e sete doentes (6,6%) apresentavam doença hemorroidária de grau II, 240 (59,0%) do grau III e 117 (28,8%) do grau IV. Em 23 doentes (5,7%) não foram encontradas a classificação nos prontuários. Todos os doentes foram operados pelo mesmo cirurgião e sob anestesia raquidiana. Os 407 doentes foram submetidos à desarterialização, variando de um até seis ramos arteriais seguidos de mucopexia por sutura contínua. Oitenta e dois (20,14%) necessitaram ressecções associadas por plicomas ou hemorroidas externas. No pós-operatório foram avaliados os seguintes parâmetros: dor, tenesmo, sangramento, prolapso, trombose e recidiva. Resultados: O tenesmo foi a queixa pós-operatória referida por 93,36% dos doentes. Quarenta e três (10,5%) apresentaram tenesmo intenso e 44 (22%) de moderado a intenso. Quatro (0,98%) doentes apresentaram sangramento de maior intensidade no pós-operatório e em 1 (0,5%) houve necessidade de hemostasia cirúrgica, em nenhum deles houve necessidade de reposição sanguínea. O prolapso ocorreu em 18 (4,42%) doentes, trombose em 11 (2,7%) e houve 19 (4,67%) recidivas reoperados durante o período. Conclusão: A desarterialização hemorroidária apresenta bons resultados, complicações leves e de fácil resolução e pouca dor pós-operatória.

EVALUATION OF BONE METASTASIS OF BREAST CANCER TO LONG OR SHORT BONES, ACCORDING TO MOLECULAR SUBTYPES: RETROSPECTIVE STUDY / Avaliação da metástase óssea do câncer de mama em ossos longos ou curtos, segundo os subtipos moleculares: estudo retrospectivo

Bone is the most frequent site for breast cancer metastasis. Identifying the possible preference of bone metastasis, such as long or short bones, according to molecular subtypes, could alter oncologists approach, paying special attention to these particular group of patients reducing the side effects of the bone metastatic process, involving multidisciplinary team with orthopedists, minimizing possible sequelae of this metastatic process. Detecting different metastatic sites to long or short bones, according to the molecular subtypes and their possible correlation. Fifty-eight patients with only bone metastasis were chosen. The study material was obtained from paraffin embedded primary tumors. Statistical analysis of the data was carried out. The luminal A, luminal B, hybrid luminal, HER2 + and triple-negative / basal-like molecular subtypes were identified. The molecular subtypes compared to the age of bone implants, the distribution of bone implants, and the disease free interval were not statistically significant

Acometimento ósseo é o sítio mais comum de metástase do carcinoma de mama. A identificação de possível preferência conforme os subtipos moleculares, na precocidade ou no acometimento de ossos longos ou chatos, poderia alterar a prática médica de oncologistas, dirigindo especial atenção a esses grupos de pacientes e suas possíveis complicações, em atendimento multidisciplinar com ortopedistas, minimizando possíveis sequelas desse processo metastático. Detectar a instalação dos diferentes sítios metastáticos para ossos longos ou chatos (curtos), conforme os subtipos moleculares e sua possível correlação. Foram selecionados 58 casos de pacientes com câncer de mama que apresentaram exclusivamente metástases ósseas. O material de estudo foi obtido dos tumores primários emblocados em parafina. Realizaram-se análises estatísticas dos dados. Foram identificados os subtipos moleculares luminal A, luminal B, luminal híbrido, HER2+ e triplo-negativo/basal like. Os subtipos moleculares comparados com a idade de implantes ósseos, a distribuição de implantes ósseos e o intervalo livre de doença não mostraram significância estatística.

Adoption rates of laparoscopic techniques for colorectal resections among Brazilian surgeons: limiting factors affecting incorporation into daily practice / Adoção de técnicas laparoscópicas em ressecções colorretais entre cirurgiões brasileiros. Fatores limitantes que afetam a incorporação na prática diária

ABSTRACT Routine adoption of laparoscopy in clinical practice and Medical Residency has not been widely evaluated in Brazil so far. Aim: To take an overview on the adoption and limitations concerning the use of laparoscopic techniques among Brazilian colorectal surgeons. Methods: A questionnaire was sent to 1870 SBCP filiated members, containing personal and professional data such as sex, age, length and local of practice, SBCP filliation, number of procedures, treatment of cancer and laparoscopy limitations. Results: 418 members (22.4%) sent their response (80% men and 20% women). 110 members (26.3%) affirmed they don't perform any laparoscopic procedure, while 308 (73.7%) have already adopted laparoscopy as a routine. An average number of 7.6 laparoscopic colorectal procedures were declared to be performed per month (1 to 40 procedures). Laparoscopic adoption rates were favourably influenced by young age members (46% vs. 28%) and affiliation to University hospitals (p = 0.01). Conversely, surgeons from private clinic showed a greater tendency of no adoption. Among the 308 responders, 106 (34.4%) have already surpassed more than 100 laparoscopic cases, and 167 (54.2%) reported an experience of more than 50 operated patients. The group of surgeons not using minimally invasive techniques incriminated lack of training (73.6%) and laparoscopic instruments availability (27.3%) as the main reasons for no adoption. Conclusions: Adoption rate of laparoscopic techniques to treat colorectal diseases is still low (at least 17%). Future efforts should focus on providing supervised training, proctorship during the initial experience and help instrumental acquisition in centers willing to change their routine and perspectives.

RESUMO Durante as últimas décadas, a incorporação de técnicas minimamente invasivas no tratamento de doenças colorretais testemunhou um progresso lento e firme, principalmente após o reconhecimento da segurança oncológica e melhor evolução. A adoção rotineira na prática clínica e na Residência Médica no Brasil ainda não amplamente avaliada até agora. Objetivos: O presente estudo visou avaliar a adoção e as limitações relativas ao uso de técnicas laparoscópicas entre cirurgiões colorretais brasileiros. Métodos: um questionário foi enviado a 1870 membros filiados à Sociedade Brasileira de Coloproctologia (SBCP) em 2006. As questões foram enviadas por email, incluindo dados pessoais (sexo, idade) e profissionais (tempo e local de prática, filiação à SBCP, número mensal de procedimentos laparoscópicos, tratamento de câncer e limitações para realizar laparoscopia na rotina. Resultados: Entre os 1870 membros, 418 (22.4%) mandaram sua resposta, com uma maior participaçãoo de homens (80%) em comparação às mulheres (20%). A idade média foi de 43 (28-80) anos. A distribuição entre membros titulares e não titulares foi semelhantes (48% vs. 52%). As atividades profissionais foram desenvolvidas em clínica privada (84%), hospitais privados (73%), hospitais públicos (50%) e hospitais universitários (53%). Entre os que responderam (418), 110 (26.3%) não realizavam procedimentos laparoscópicos, enquanto 308 (73.7%) já haviam adotado o acesso laparoscópico rotineiramente na prática clínica. Um número médio de 7.6 procedimentos colorretais laparoscópicos são realizados por mês (1-40). Cerca de 13% dos cirurgiões iniciaram sua experiência laparoscópica diretamente com procedimentos colorretais, enquanto a maioria (87%) começaram por outros procedimentos no trato digestivo. A adoção da laparoscopia foi positivamente influenciada pela idade jovem dos membros (46% vs. 28%) e pela filiação a hospitais universitários (p = 0,01). Inversamente, cirurgiões trabalhando na prática privada demonstraram uma menor tendência em adotar o método. A maioria dos cirurgiões (93%) que adoraram a laparoscopia afirmou incluir pacientes com câncer colorretal em suas indicações operatórias. Entre os que responderam 106 (34,4%) já realizaram mais de 100 procedimentos laparoscópicos, e 167 (54,2%) reportaram experiência maior que 50 casos. Dentre aqueles que não adotaram técnicas minimamente invasivas, a falta de treinamento (73,6%) ou a indisponibilidade de instrumental laparoscópico (27,3%) foram incriminadas como os principais fatores limitantes. Conclusões: o índice de adoção de técnicas laparoscópicas no tratamento de doenças intestinais ainda é baixo (pelo menos 17%) entre cirurgiões colorretais brasileiros. Esforços futuros de nossa Sociedade Médica devem focar na provisão de treinamento supervisionado, na criação de oportunidades para preceptoria durante a experiência inicial e na obtenção de instrumental em centros que queiram mudar sua rotina e perspectivas.

Enemas with mesalazine increase the tissue contents of mucins in the colonic mucosa devoid of fecal stream

Abstract Purpose: To evaluate the inflammatory reaction and measure the content of mucins, in the colonic mucosa without fecal stream submit to intervention with mesalazine. Methods: Twenty-four rats were submitted to a left colostomy and a distal mucous fistula and divided into two groups according to euthanasia to be performed two or four weeks. Each group was divided into two subgroups according daily application of enemas containing saline or mesalazine at 1.0 g/kg/day. Colitis was diagnosed by histological analysis and the inflammatory reaction by validated score. Acidic mucins and neutral mucins were determined with the alcian-blue and periodic acid of Schiff techniques, respectively. Sulfomucin and sialomucin were identified by high iron diamine-alcian blue technique. The tissue contents of mucins were quantified by computer-assisted image analysis. Mann-Whitney test was used to analyze the results establishing the level of significance of 5%. Results: Enemas with mesalazine in colonic segments without fecal stream decreased the inflammation score and increased the tissue content of all subtypes of mucins. The increase of tissue content of neutral, acid and sulfomucin was related to the time of intervention. Conclusion: Mesalazine enemas reduce the inflammatory process and preserve the content of mucins in colonic mucosa devoid of fecal stream.

Is the colon mucosa affected by ten days of gastric restriction in an animal model?

Abstract Purpose To identify whether the colon mucosa is affected by ten days of gastric restriction in an animal model. Methods An experimental model of gastric restriction was devised using rats. The animals were submitted to surgical gastrostomy, and a cylindrical loofah was inserted into the stomach. We studied 30 adult male Wistar rats divided into three groups: the stomach restriction group (R10); the sham group (S10), which underwent the same procedure except for the loofah insertion; and the control group (C10). The expression of neutral and acid mucins was evaluated using histochemical techniques. Goblet cells and protein content were compared between groups using generalized estimation equations (GEEs). Bonferroni's multiple comparison was applied to identify differences between the groups. All tests considered a 5% significance level. Results There was an increased expression of neutral mucins, acid mucins and goblet cells in the R10 group. Collagen was also enhanced in the R10 group. Conclusion The colon mucosa is affected by ten days of gastric restriction in an animal model, increasing neutral mucins, acid mucins and collagen content with trophic maintenance.

Evaluation of enemas containing sucralfate in tissue content of muc-2 protein in experimental model of diversion colitis / Avaliação de enemas com sucralfato no conteúdo tecidual da proteina muc-2 em colite de exclusão experimental

ABSTRACT Background: The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. Aim: To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Methods: Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). Results: The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.

RESUMO Racional: Os efeitos da aplicação tópica de sucralfato (SCF) no conteúdo tecidual da proteína mucina-2 (MUC-2) ainda não foram avaliados em modelos experimentais de colite de exclusão. Objetivo: Mensurar o conteúdo tecidual da proteína MUC-2 na mucosa cólica sem trânsito intestinal submetida à intervenção com SCF. Método: Trinta e seis ratos foram submetidos à derivação intestinal por colostomia proximal terminal e fístula mucosa distal. Foram divididos em três grupos segundo recebessem clisteres contendo solução fisiológica (SF), SCF 1 g/kg/dia e SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos, segundo a eutanásia ser realizada após duas ou quatro semanas. O diagnóstico de colite foi estabelecido por estudo histopatológico e a intensidade inflamatória foi avaliada por escala validada. A expressão tecidual da MUC-2 foi identificada por imunoistoquímica e seu conteúdo mensurado por morfometria computadorizada. Resultados: A aplicação de clisteres com SCF na concentração de 2 g/kg/dia reduziu a intensidade inflamatória no cólon sem trânsito fecal. O conteúdo tecidual de MUC-2 no cólon sem trânsito dos animais submetidos à intervenção com SCF, independente do tempo de intervenção e da concentração utilizada, foi maior quando comparado aos animais tratados com SF (p<0,01). O conteúdo de MUC-2 após a intervenção com SCF na concentração de 2 g/kg/dia foi maior quando comparado aos animais submetidos à intervenção com concentração menor (p<0,01). O conteúdo de MUC-2 foi maior após intervenção com SCF na concentração de 2 g/kg/dia por quatro semanas (p<0,01). Conclusão: A aplicação preventiva de clisteres com SCF reduz o grau de inflamação e preserva o conteúdo tecidual de MUC-2, em segmentos desprovidos de trânsito intestinal, mostrando-se uma estratégia terapêutica válida para preservar a camada de muco que recobre o epitélio intestinal.

[retracted article]: evaluation of enemas containing sucralfate in tissue content of muc-2 protein in experimental model of diversion colitis / [artigo retratado]: avaliação de enemas com sucralfato no conteúdo tecidual da proteina muc-2 em colite de exclusão experimental

ABSTRACT Background: The effects of topical application of sucralfate (SCF) on the tissue content of MUC-2 protein have not yet been evaluated in experimental models of diversion colitis. Aim: To measure the tissue content of MUC-2 protein in the colonic mucosa diverted from fecal stream submitted to the SCF intervention. Methods: Thirty-six rats underwent derivation of intestinal transit through proximal colostomy and distal mucous fistula. The animals were divided into three groups which were submitted application of enemas with saline, SCF 1 g/kg/day and SCF 2 g/kg/day. Each group was divided into two subgroups, according to euthanasia was done after two or four weeks. The colitis diagnosis was established by histopathological study and the inflammatory intensity was evaluated by previously validated scale. The MUC-2 protein was identified by immunohistochemistry and the tissue content was measured computerized morphometry). Results: The application of enemas with SCF in the concentration of 2 g/kg/day reduced inflammatory score of the segments that were diverted from fecal stream. The content of MUC-2 in diverted colon of the animals submitted to the intervention with SCF, independently of intervention period and the used concentration, was significantly greater than animals submitted to the application of enemas containing saline (p< 0.01). The content of MUC-2 after the intervention with SCF in the concentration of 2 g/kg/day was significantly higher when compared to the animals submitted to the application containing SCF at concentration of 1.0 g/kg/day (p<0.01). The tissue content of MUC-2 reached the highest values after intervention with SCF in the concentration of 2 g/kg/day for four weeks (p<0.01). Conclusion: The preventive application of enemas containing SCF reduces the inflammatory score and avoids the reduction of tissue content of MUC-2, suggesting that the substance is a valid therapeutic strategy to preserve the mucus layer that covers the intestinal epithelium.

RESUMO Racional: Os efeitos da aplicação tópica de sucralfato (SCF) no conteúdo tecidual da proteína mucina-2 (MUC-2) ainda não foram avaliados em modelos experimentais de colite de exclusão. Objetivo: Mensurar o conteúdo tecidual da proteína MUC-2 na mucosa cólica sem trânsito intestinal submetida à intervenção com SCF. Método: Trinta e seis ratos foram submetidos à derivação intestinal por colostomia proximal terminal e fístula mucosa distal. Foram divididos em três grupos segundo recebessem clisteres contendo solução fisiológica (SF), SCF 1 g/kg/dia e SCF 2 g/kg/dia. Cada grupo foi dividido em dois subgrupos, segundo a eutanásia ser realizada após duas ou quatro semanas. O diagnóstico de colite foi estabelecido por estudo histopatológico e a intensidade inflamatória foi avaliada por escala validada. A expressão tecidual da MUC-2 foi identificada por imunoistoquímica e seu conteúdo mensurado por morfometria computadorizada. Resultados: A aplicação de clisteres com SCF na concentração de 2 g/kg/dia reduziu a intensidade inflamatória no cólon sem trânsito fecal. O conteúdo tecidual de MUC-2 no cólon sem trânsito dos animais submetidos à intervenção com SCF, independente do tempo de intervenção e da concentração utilizada, foi maior quando comparado aos animais tratados com SF (p<0,01). O conteúdo de MUC-2 após a intervenção com SCF na concentração de 2 g/kg/dia foi maior quando comparado aos animais submetidos à intervenção com concentração menor (p<0,01). O conteúdo de MUC-2 foi maior após intervenção com SCF na concentração de 2 g/kg/dia por quatro semanas (p<0,01). Conclusão: A aplicação preventiva de clisteres com SCF reduz o grau de inflamação e preserva o conteúdo tecidual de MUC-2, em segmentos desprovidos de trânsito intestinal, mostrando-se uma estratégia terapêutica válida para preservar a camada de muco que recobre o epitélio intestinal.