SURGICAL MANAGEMENT OF ADULT CROHN'S DISEASE AND ULCERATIVE COLITIS PATIENTS: A CONSENSUS FROM THE BRAZILIAN ORGANIZATION OF CROHN'S DISEASE AND COLITIS (GEDIIB).

BACKGROUND: Despite optimized medical therapy, contemporary risk of surgery in inflammatory bowel diseases (IBD) after 10 years of diagnosis is 9.2% in patients with ulcerative colitis (UC) and 26.2% in Crohn's disease, (CD) in the biological era. OBJECTIVE: This consensus aims to detail guidance to the most appropriate surgical procedures in different IBD scenarios. In addition, it details surgical indications and perioperative management of adult patients with CD and UC. METHODS: Our consensus was developed by colorectal surgeons and gastroenterologists representing the Brazilian Study Group of Inflammatory Bowel Diseases (GEDIIB), with the Rapid Review methodology being conducted to support the recommendations/statements. Surgical recommendations were structured and mapped according to the disease phenotypes, surgical indications, and techniques. After structuring the recommendations/statements, the modified Delphi Panel methodology was used to conduct the voting by experts in IBD surgery and gastroenterology. This consisted of three rounds: two using a personalized and anonymous online voting platform and one face-to-face presential meeting. Whenever participants did not agree with specific statements or recommendations, an option to outline possible reasons was offered to enable free-text responses and provide the opportunity for the experts to elaborate or explain disagreement. The consensus of recommendations/statements in each round was considered to have been reached if there was ≥80% agreement. RESULTS AND CONCLUSION: This consensus addressed the most relevant information to guide the decision-making process for adequate surgical management of CD and UC. It synthesizes recommendations developed from evidence-based statements and state-of-art knowledge. Surgical recommendations were structured and mapped according to the different disease phenotypes, indications for surgery and perioperative management. Specific focus of our consensus was given to elective and emergency surgical procedures, determining when to indicate surgery and which procedures may be the more appropriate. The consensus is targeted to gastroenterologists and surgeons interested in the treatment and management of adult patients with CD or UC and supports decision-making of healthcare payors, institutional leaders, and/or administrators.

Long-term effectiveness and safety of ustekinumab in bio-naïve and bio-experienced anti-tumor necrosis factor patients with Crohn's disease: a real-world multicenter Brazilian study.

BACKGROUND: The effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD) has been demonstrated in the pivotal Phase 3 UNITI 1 and 2 and IM-UNITI studies in both anti-TNF-naïve and anti-TNF-exposed patients. Given the selective nature of pivotal trial designs, real-world effectiveness and safety studies are warranted. We report our experience with UST treatment in a large, real-world multicenter cohort of Brazilian patients with CD. METHODS: We performed a retrospective multicenter study including patients with CD, predominantly biologically refractory CD, who received UST. The primary endpoint was the proportion of patients in clinical remission at weeks 8, 24 and 56. Possible predictors of clinical and biological response/remission and safety outcomes were also assessed. RESULTS: Overall, 245 CD (mean age 39.9 [15-87]) patients were enrolled. Most patients (86.5%) had been previously exposed to biologics. According to nonresponder imputation analysis, the proportions of patients in clinical remission at weeks 8, 24 and 56 were 41.0% (n = 98/239), 64.0% (n = 153/239) and 39.3% (n = 94/239), respectively. A biological response was achieved in 55.4% of patients at week 8, and 59.3% were in steroid-free remission at the end of follow-up. No significant differences in either clinical or biological remission were noted between bio-naïve and bio-experienced patients. Forty-eight patients (19.6%) presented 60 adverse events during the follow-up, of which 8 (13.3%) were considered serious adverse events (3.2% of 245 patients). Overall, a proximal disease location, younger age, perianal involvement, and smoking were associated with lower rates of clinical remission over time. CONCLUSIONS: UST therapy was effective and safe in the long term in this large real-life cohort of Brazilian patients with refractory CD, regardless of previous exposure to other biological agents.

Tratamento cirúrgico de pacientes adultos com doença de Crohn e retocolite ulcerativa: um consenso da Organização Brasileira de Doença de Crohn e Colite (GEDIIB) / Surgical management of adult crohn's disease and ulcerative colitis patients: a consensus from the brazilian organization of crohn's disease and colitis (gediib)

ABSTRACT Background: Despite optimized medical therapy, contemporary risk of surgery in inflammatory bowel diseases (IBD) after 10 years of diagnosis is 9.2% in patients with ulcerative colitis (UC) and 26.2% in Crohn's disease, (CD) in the biological era. Objective: This consensus aims to detail guidance to the most appropriate surgical procedures in different IBD scenarios. In addition, it details surgical indications and perioperative management of adult patients with CD and UC. Methods: Our consensus was developed by colorectal surgeons and gastroenterologists representing the Brazilian Study Group of Inflammatory Bowel Diseases (GEDIIB), with the Rapid Review methodology being conducted to support the recommendations/statements. Surgical recommendations were structured and mapped according to the disease phenotypes, surgical indications, and techniques. After structuring the recommendations/statements, the modified Delphi Panel methodology was used to conduct the voting by experts in IBD surgery and gastroenterology. This consisted of three rounds: two using a personalized and anonymous online voting platform and one face-to-face presential meeting. Whenever participants did not agree with specific statements or recommendations, an option to outline possible reasons was offered to enable free-text responses and provide the opportunity for the experts to elaborate or explain disagreement. The consensus of recommendations/statements in each round was considered to have been reached if there was ≥80% agreement. Results and conclusion: This consensus addressed the most relevant information to guide the decision-making process for adequate surgical management of CD and UC. It synthesizes recommendations developed from evidence-based statements and state-of-art knowledge. Surgical recommendations were structured and mapped according to the different disease phenotypes, indications for surgery and perioperative management. Specific focus of our consensus was given to elective and emergency surgical procedures, determining when to indicate surgery and which procedures may be the more appropriate. The consensus is targeted to gastroenterologists and surgeons interested in the treatment and management of adult patients with CD or UC and supports decision-making of healthcare payors, institutional leaders, and/or administrators.

RESUMO Contexto: Apesar da terapia medicamentosa otimizada, o risco contemporâneo de cirurgia nas doenças inflamatórias intestinais (DII) após 10 anos do diagnóstico é de 9,2% em pacientes com retocolite ulcerativa (RCU) e de 26,2% na doença de Crohn (DC) na era biológica. Objetivo: Este consenso visa detalhar as orientações para os procedimentos cirúrgicos mais adequados em diferentes cenários da DII. Além disso, detalha as indicações cirúrgicas e o manejo perioperatório de pacientes adultos com DC e RCU. Métodos: Nosso consenso foi desenvolvido por cirurgiões colorretais e gastroenterologistas representantes da Organização Brasileira de Doença de Crohn e Colite (GEDIIB), com a metodologia de revisão rápida sendo conduzida para respaldar as recomendações. As recomendações cirúrgicas foram estruturadas e mapeadas de acordo com os fenótipos da doença, indicações cirúrgicas e técnicas. Após a estruturação das recomendações, a metodologia modificada do Painel Delphi foi utilizada para conduzir a votação por especialistas em cirurgia de DII e gastroenterologia. Esta consistiu em três rondas: duas com recurso a uma plataforma de votação online personalizada e anônima e uma reunião presencial. Sempre que os participantes não concordavam com afirmações ou recomendações específicas, era oferecida uma opção de delinear possíveis razões para permitir respostas em texto livre e dar a oportunidade para os especialistas elaborarem ou explicarem a discordância. O consenso de recomendações/declarações em cada rodada foi considerado alcançado se houve concordância ≥80%. Resultados e conclusão Este consenso abordou as informações mais relevantes para orientar o processo de tomada de decisão para o manejo cirúrgico adequado de DC e RCU. Ele sintetiza recomendações desenvolvidas a partir de evidências e conhecimento de alto nível. As recomendações cirúrgicas foram estruturadas e mapeadas de acordo com os diferentes fenótipos da doença, indicações para cirurgia e manejo perioperatório. O foco específico do nosso consenso foi dado aos procedimentos cirúrgicos eletivos e de emergência, determinando quando indicar a cirurgia e quais procedimentos podem ser os mais adequados. O consenso é direcionado a gastroenterologistas e cirurgiões interessados no tratamento e manejo de pacientes adultos com DC ou RCU e apoia a tomada de decisões de pagadores de saúde, líderes institucionais e/ou administradores.

Tissue content of metalloproteinase-9 and collagen in the colon with and without fecal stream after intervention with infliximab in rats subjected to Hartmann's surgery.

PURPOSE: Quantify the tissue content of metalloproteinase-9 (MMP-9) and collagen in colic mucosa with and without intestinal transit after infliximab administration in rats subjected to Hartmann's surgery. METHODS: Twenty-two rats underwent colon diversion by Hartmann's surgery. Animals were maintained with intestinal bypass for 12 weeks to induce development of diversion colitis (DC). Afterwards, animals were divided into three groups: first group received subcutaneous application of saline solution (SS) 0.9%, while the remaining two groups received infliximab subcutaneously at doses of 5 or 10 mg·kg-1·week-1 for five consecutive weeks. After the intervention, animals were sacrificed, removing the segments with and without intestinal transit. Diversion colitis was diagnosed by histological study, and its intensity was determined by a validated inflammatory scale. Tissue expression of MMP-9 was assessed byimmunohistochemistry, while total collagen was assessed by histochemistry. Tissue content of both was measuredby computerized morphometry. RESULTS: Colon segments without intestinal transit had a higher degree of inflammation, which improved in animals treated with infliximab. Collagen content was always lower in those without intestinal transit. There was an increase in the collagen content in the colon without transit in animals treated with infliximab, primarily at a dose of 10 mg·kg-1·week-1. There was an increase in the content of MMP-9 in the colon without fecal transit, and a reduction was observed in animals treated with infliximab, regardless of the dose used. CONCLUSIONS: Application of infliximab reduces inflammation, increases the total collagen content and decreases the content of MMP-9 in the colon without intestinal transit.

Tissue sulfomucin and sialomucin content in colon mucosa without intestinal transit subjected to intervention with Curcuma longa (curcumin)

Abstract Purpose: To measure the tissue sulfomucin and sialomucin content of the colon mucosa without fecal flow, subjected to intervention with curcumin, and the influence of the concentration used and the intervention time. Methods: Thirty-six rats were subjected to proximal right colostomy and distal mucous fistula. They were divided into two groups according to whether sacrifice was performed two or four weeks after the intervention. Each group was divided into three subgroups according to the enema applied daily: saline alone; curcumin at 50 mg/kg/day or curcumin at 200 mg/kg/day. Acid mucins were diagnosed using the Alcian blue technique. The mucin content was quantified by means of computer-assisted image analysis. The significance level of 5% was used throughout (p < 0.05). Results: There were dose-related increases in the quantities of sulfomucins in the animals subjected to interventions with curcumin, both after two weeks (p < 0.00001) and after four weeks (p < 0.00001). There were increases in sialomucin quantity that were concentration-related (p < 0.00001) and time-related (p < 0.00001). Conclusion: Curcumin enemas increase the quantity of acid mucins in the intestinal flow in the excluded colon, with dose and time dependency.

Claudin-3 and occludin content in the glands of colonic mucosa devoid from fecal stream submitted to topical intervention with oil extract of Curcuma longa

Abstract Purpose: To evaluate the inflammatory intensity and measure the tissue content of the proteins claudin-3 and occludin in the colonic mucosa without fecal stream submit to intervention with curcumin. Methods: Thirty-six rats were submitted to a proximal colostomy and a distal mucous fistula and divided into two groups according to sacrifice to be performed two or four weeks. Each group was divided into three subgroups according daily application of enemas containing saline, curcumin at 50 mg/kg/day or 200 mg/kg/day. Colitis was diagnosed by histological analysis. Claudin-3 and occludin were determined by immunohistochemistry. The tissue content of claudin-3 and occludin were quantified by computer-assisted image analysis. Mann-Whitney, Student t and ANOVA tests were used to analyze the results establishing the level of significance of 5% for both (p<0.05). Results: Curcumin at both concentrations reduces the inflammation and preserves the tissue content of the proteins claudin-3 and occludin, which was related to the concentration used and to the time of the intervention. Conclusion: The application of enemas with curcumin reduces inflammation and preserves the tissue content of the proteins claudin-3 and occludin in the colonic mucosa devoid from the fecal stream.

Neoadjuvant radiotherapy in stage I cancer of the lower rectum / Terapia neoadjuvante para tumores de reto baixo estadio I

Introduction: The mortality rate in low rectal cancer is related to pelvic and distant recurrence. For stage I tumors, local excision has being used increasingly, but recent studies show the need for caution with the use of this technique, as they do not consider the possibility of a positive node in stage I rectal tumors. Therefore, preoperative radiotherapy should be considered for early tumors, as an attempt to prevent recurrence. Objetive: Show the effectiveness of neoadjuvant radiotherapy in stage I cancer of the lower rectum of a cohort population. Material and method: A cohort study in a prospective database was made with a total of 538 patients, of which were considered 75 patients with stage I lower rectal cancer. Preoperative radiotherapy was performed and patients were followed up for a minimum period of five years. Results: Stage I/TI group had 27 patients. All of them presented complete response to the treatment and did not need to be operated. During the follow up time of five years, this group showed no recurrence rate. The stage I/TII group had 48 patients. During the follow up, 8 patients had to be operated due to suspicious lesion or scar. They were submitted to full total local excision. After evaluating the pathological specimen, none of them proved to be adenocarcinoma. Conclusion: Preoperative radiation, not only reduced the local recurrence and mortality rate in lower rectal cancer, but also reduced the need for surgery in patients with stage I cancer.

Introdução: O percentual de mortalidade em pacientes com câncer de reto baixo está relacionado a recorrências pélvica e remota. No caso de tumores no estágio I, a excisão local vem sendo utilizada cada vez mais; contudo, estudos recentemente publicados demonstraram a necessidade de se ter cautela com o uso dessa técnica, por não se levar em consideração a possibilidade de um nodo positivo em tumores de reto no estágio I. Portanto, a radioterapia pré-operatória é uma opção viável para os tumores em fase inicial, como uma tentativa de evitar recorrência. Objetivo: Demonstrar a eficácia da radioterapia neoadjuvante em casos de câncer de reto baixo no estágio I em uma coorte da população. Materiais e métodos: Foi realizado um estudo de coorte em um banco de dados prospectivo, com envolvimento, no total, de 538 pacientes, dos quais 75 foram considerados como tendo câncer de reto baixo no estágio I. No pré-operatório, os pacientes foram tratados com radioterapia e seguidos durante um período mínimo de 5 anos. Resultados: O Grupo no estágio I/TI consistia em 27 pacientes. Todos obtiveram resposta completa ao tratamento e não houve necessidade de reoperação. Durante o período de 5 anos de seguimento, não houve recorrências nesse grupo. O grupo no estágio I/TII consistia em 48 pacientes. Durante o seguimento, 8 pacientes tiveram que ser operados, devido à suspeita de lesão, ou cicatriz. Para esses casos, optou-se por excisão local total completa. Após a avaliação dos espécimes patológicos, nenhum deles teve diagnóstico de adenocarcinoma. Conclusão: O uso da radiação pré-operatória não só diminuiu a recorrência local e o percentual de mortalidade em casos de câncer de reto baixo, mas também diminuiu a necessidade de cirurgia em pacientes com câncer no estágio I.

Associação da obesidade à presença de comorbidades decorrentes em trabalhadores do Hospital e Maternidade Celso Pierro / Association of obesity with its resultant comorbidities in workers from Hospital Celso Pierro

Objetivo O estudo buscou determinar a relação entre obesidade e presença de comorbidades em trabalhadores do Hospital e Maternidade Celso Pierro, de Campinas (SP). Métodos Realizou-se um estudo individual, observacional e transversal (tipo inquérito), por meio da análise de 400 prontuários de funcionários do Hospital e Maternidade Celso Pierro, Campinas (SP), escolhidos aleatoriamente dentro do universo de 2.185 trabalhadores da instituição. Foram avaliados indicadores como sexo, peso, altura (permitindo o cálculo do índice de massa corporal) e presença ou não de comorbidades relacionadas pela literatura à obesidade. Resultados O grupo que apresentou maior porcentagem de peso adequado estava ??16 ??30 anos, (67,4%), enquanto o grupo etário >50 ??66 mostrou maior número de indivíduos com sobrepeso (64,0%). Tais dados coincidiram com o fato de as comorbidades também apresentarem predomínio neste último grupo, em que seis das dez patologias estudadas apareceram com maior frequência percentual. Levando- -se em consideração a relação entre sexo e índice de massa corporal, os dados revelaram preponderância do sexo feminino nos grupos com sobrepeso e com obesidade graus I, II e III. Finalmente, quando analisada a relação entre índice de massa corporal e comorbidades, observou-se ampla superioridade destas nos indivíduos com obesidade graus I, II e III. Conclusão O excesso de peso está relacionado ao aumento da frequência de comorbidades, afetando todas as faixas etárias e ambos os sexos, com relativo predomínio no feminino

Objective The present study attempted to determine the relationship between obesity and its comorbidities in workers from Hospital Celso Pierro in Campinas (SP), Brazil. Methods An individual, observational and cross-sectional study of the survey kind analyzed 400 medical records of occupational medicine employees from the Hospital Celso Pierro. They were randomly chosen from a universe of 2185 employees. The following indicators were collected: gender, weight, high (for calculating body mass index) and presence or not of obesity-related comorbidities according to the literature. Results The group aged ??16 ??30 years presented the highest percentage of individuals with normal weight (67.4%) while the group aged >50 ??66 years presented the highest percentage of individuals with excess weight (64.0%). Coincidently, comorbidities prevailed in this older group. They presented the highest rates of six of the ten studied comorbidities. Regarding the relationship between gender and body mass index, the data showed that there were more overweight and obese (grades I, II and III) females than males. Finally, when the relationship between body mass index and comorbidities was assessed, comorbidities were significantly more common in individuals with grades I, II and III obesity. Conclusion Excess weight is related with an increased rate of comorbidities and affects all age groups and both genders, but preferably females