Factors associated with surgical resection in patients with Crohn's disease: long-term evaluation.

PURPOSE: To evaluate patient characteristics and factors associated with surgical resection in patients with Crohn's disease (CD). METHODS: An analysis was performed on data from 295 patients with CD in follow-up from 2001 to 2018. Medical record data comprised age, gender, location, behavior and duration of the CD, smoking, and extraintestinal manifestation. Patients were divided into two groups according to the presence or absence of surgical resection. RESULTS: Out of the 295 patients with CD, 155 underwent surgical resection (53.2% male, mean age: 43.88 ± 14.35 years). The main indications for surgery were stenosis (44.5%), clinical intractability (15.5%), and intra-abdominal fistulas (15.5%). Smoking (p < 0.001), longer CD duration (p < 0.0001), ileo-colonic location (p = 0.003), stenosing behavior (p < 0.0001), and fistulizing behavior (p < 0.0001) were significantly associated with surgical resection. Initial use of biological was significantly more frequent in the group of patients without surgical resection (p < 0.001). CONCLUSIONS: Patients with CD still frequently need surgical treatment. Smoking (current or past), longer disease time, stenosing and fistulizing behavior, and ileo-colonic localization in CD patients were associated with a higher risk of surgery. Awareness about factors associated with unfavorable outcome allows such patients to be treated more appropriately.

Upadacitinib Reduces Crohn's Disease Symptoms Within the First Week of Induction Therapy.

BACKGROUND & AIMS: Upadacitinib (UPA), an oral Janus kinase inhibitor, is approved to treat moderately to severely active Crohn's disease (CD). Because symptomatic response is an important initial treatment goal for patients, we evaluated the rapidity of symptomatic improvement in patients with CD receiving UPA 45 mg once daily (UPA45) induction therapy. METHODS: This post hoc analysis included pooled data from 2 phase 3, multicenter, double-blind, 12-week induction trials (U-EXCEL and U-EXCEED) and 1 maintenance trial (U-ENDURE). Daily diary data for the first 15 days of UPA45 or placebo (PBO) treatment were used to analyze improvement in very soft/liquid stool frequency (SF) and abdominal pain score (APS). Clinical outcomes were evaluated at every study visit. RESULTS: Overall, 1021 patients (n = 674 UPA45; n = 347 PBO) were analyzed. UPA45 demonstrated greater efficacy vs PBO for SF <3 and APS ≤1, providing rapid relief by day 5 or 6, regardless of prior biologic exposure. Mean changes in SF and APS were greater with UPA45 beginning at week 2 (-2.0 and -0.5, respectively; P < .001) and were maintained through week 12 (-3.0 and -1.0, respectively; P < .001) vs PBO. The first achievement of daily SF/APS clinical remission occurred earlier with UPA45 (median, 13 d) vs PBO (median, 32 d), and patients treated with UPA45 showed improved rates of SF/APS clinical remission (21.1% UPA45 vs 8.9% PBO) and clinical response (58.8% UPA45 vs 37.9% PBO) starting at week 2 (both P ≤ .01). CONCLUSIONS: UPA45 provided rapid relief of clinical symptoms within the first week of treatment in patients with CD. CLINICALTRIALS: gov numbers: NCT03345849, NCT03345836, and NCT03345823.

Leukocyte Dysfunction and reduced CTLA-4 Expression are Associated with Perianal Crohn's Disease.

Although perianal Crohn's disease (PCD) is highly associated with the exacerbated inflammation, the molecular basis and immunological signature that distinguish patients who present history of perianal lesions are still unclear. This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for detection of plasma cytokines and LPS. PBMC were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3/anti-CD28 antibodies. Our results show that CD patients had augmented plasma IL-6 and LPS. However, their PBMC was characterized by decreased IL-6 production, while patients with history of PCD produced higher IL-6, IL-8 and IFN-γ, along with decreased TNF. CD patients had augmented FoxP3 and CTLA-4 regulatory markers, though the PCD subjects presented a significant reduction in CTLA-4 expression. CTLA-4, as well as IL-6 and TNF responses were able to distinguish the PCD patients from those who did not present perianal complications. In conclusion, IL-6, TNF, and CTLA-4 exhibit a distinct expression pattern in CD patients with a history of PCD, regardless of disease activity. These findings clarify some mechanisms involved in the development of the perianal manifestations and may have a great impact in the disease management.

Clinical factors associated with severity in patients with inflammatory bowel disease in Brazil based on 2-year national registry data from GEDIIB.

The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) established a national registry of inflammatory bowel disease (IBD). The aim of the study was to identify clinical factors associated with disease severity in IBD patients in Brazil. A population-based risk model aimed at stratifying the severity of IBD based on previous hospitalization, use of biologics, and need for surgery for ulcerative colitis (UC) and Crohn's Disease (CD) and on previous complications for CD. A total of 1179 patients (34.4 ± 14.7y; females 59%) were included: 46.6% with UC, 44.2% with CD, and 0.9% with unclassified IBD (IBD-U). The time from the beginning of the symptoms to diagnosis was 3.85y. In CD, 41.2% of patients presented with ileocolic disease, 32% inflammatory behavior, and 15.5% perianal disease. In UC, 46.3% presented with extensive colitis. Regarding treatment, 68.1%, 67%, and 47.6% received biological therapy, salicylates and immunosuppressors, respectively. Severe disease was associated with the presence of extensive colitis, EIM, male, comorbidities, and familial history of colorectal cancer in patients with UC. The presence of Montreal B2 and B3 behaviors, colonic location, and EIM were associated with CD severity. In conclusion, disease severity was associated with younger age, greater disease extent, and the presence of rheumatic EIM.

Vedolizumab in Mild-to-Moderate Crohn's Disease Patients Naïve to Biological Therapy: A Multicentric Observational Study.

Background: In real-world experience, the number of patients using vedolizumab as first-line biological therapy was low. We aimed to evaluate the effectiveness and safety of vedolizumab in mild-to-moderate Crohn's disease (CD) biologic-naïve patients. Methods: We performed a retrospective multicentric cohort study with patients who had clinical activity scores (Harvey-Bradshaw Index [HBI]) measured at baseline and weeks 12, 26, 52, as well as at the last follow-up. Clinical response was defined as a reduction ≥3 in HBI, whereas clinical remission as HBI ≤4. Mucosal healing was defined as the complete absence of ulcers in control colonoscopies. Kaplan-Meier survival analysis was used to assess the persistence with vedolizumab. Results: From a total of 66 patients, 53% (35/66) reached clinical remission at week 12. This percentage increased to 69.7% (46/66) at week 26, and 78.8% (52/66) at week 52. Mucosal healing was achieved in 62.3% (33/53) of patients. Vedolizumab was well tolerated, and most adverse events were minor. During vedolizumab treatment, 3/66 patients underwent surgery. Conclusions: This study demonstrates the effectiveness and safety of vedolizumab as a first-line biological agent in patients with mild-to-moderate CD.

Efficacy of Early Optimization of Infliximab Guided by Therapeutic Drug Monitoring during Induction-A Prospective Trial.

Therapeutic drug monitoring (TDM) during induction therapy with anti-tumor necrosis factor drugs has emerged as a strategy to optimize response to these biologics and avoid undesired outcomes related to inadequate drug exposure. This study aimed to describe clinical, biological, and endoscopic remission rates at six months in Brazilian inflammatory bowel disease (IBD) patients following a proactive TDM algorithm guided by IFX trough levels (ITL) and antibodies to IFX (ATI) levels during induction, at week six. A total of 111 IBD patients were prospectively enrolled, excluding those previously exposed to the drug. ITL ≥ 10 µg/mL was considered optimal. Patients with suboptimal ITL (<10 µg/mL) were guided according to ATI levels. Those who presented ATI ≤ 200 ng/mL underwent dose intensification in the maintenance phase, and patients with ATI > 200 ng/mL discontinued IFX. In our study, proactive TDM was associated with persistence in the IFX rate at six months of 82.9%. At that time, rates of clinical, biological, and endoscopic remission in patients under IFX treatment were 80.2%, 73.9%, and 48.1%, respectively. Applying a simplified TDM-guided algorithm during induction seems feasible and can help improve patients' outcomes in clinical practice.

Leukocytoclastic Vasculitis Secondary to Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Diseases: A Multicenter Retrospective Cohort Study.

BACKGROUND: Vasculitis is an uncommon complication of biologics used to treat inflammatory bowel disease (IBD). This study describes a case series of vasculitis induced by anti-tumor necrosis factor (TNF) therapy in IBD patients. METHODS: Retrospective assessments were performed using the medical records of adult IBD patients who underwent outpatient clinical follow-ups between January 2010 and December 2019 in order to identify patients with vasculitis caused by anti-TNF therapy. RESULTS: There were 2442 patients altogether. Of these, 862 (35%) took anti-TNF medication. Five patients (0.6% of the overall patients; n = 3 (60%) Crohn's disease; n = 2 (40%), ulcerative colitis) were identified as having leukocytoclastic vasculitis (LCV) due to anti-TNF therapy; these patients were white, female, and non-smokers. The mean age of LCV diagnosis was 32.2 years, and the mean IBD duration was 7.2 years. The mean time between the start of biologic therapy and LCV onset was 30.8 months. Most of the patients were using adalimumab (80%; n = 4). All the patients were in remission at the time of the LCV diagnosis, and the vasculitis affected the skin in all cases. Anti-TNF therapy was discontinued in the five abovementioned patients, and the response of LCV to the oral steroids was significantly positive. Remarkably, all five patients experienced complete remission from LCV within 4-12 weeks after starting prednisone therapy, and none of them had LCV recurrence in the follow-up period (a mean duration of 28 months). CONCLUSIONS: LCV is an unusual complication of anti-TNF therapy in the IBD setting. In this context, clinicians should have a high degree of suspicion of LCV in patients who develop an unexplained cutaneous rash.

Retrospective analysis of surgical and oncological results of laparoscopic surgeries performed by residents of coloproctology.

INTRODUCTION: with the improvement and wide acceptance of laparoscopy in colorectal operations, there was a need for specific training of surgeons in training. There are few studies evaluating the postoperative results of laparoscopic colectomies performed by resident physicians and their impact on patient safety. PURPOSE: to analyze the surgical and oncological results of laparoscopic colectomies performed by coloproctology residents and compare them with data in the literature. METHODS: this is a retrospective analysis of patients undergoing laparoscopic colorectal surgery performed by resident physicians at the Hospital das Clínicas de Ribeirão Preto, between 2014 and 2018. The clinical characteristics of the patients were studied, as well as the main surgical and oncological aspects in a period of one year. RESULTS: we analyzed 191 operations, whose main surgical indication was adenocarcinoma, most of them stage III. The mean duration of surgeries was 210±58 minutes. There was a need for a stoma in 21.5% of the patients, mainly loop colostomy. The conversion rate was 23%, with 79.5% due to technical difficulties, and the main predictors of conversion were obesity and intraoperative accidents. The median length of stay was 6 days. Preoperative anemia was associated with a higher rate of complications (11.5%) and reoperations (12%). Surgical resection margins were compromised in 8.6% of cases. The one-year recurrence rate was 3.2% and the mortality rate was 6.3%. CONCLUSIONS: videolaparoscopic colorectal surgery performed by residents showed efficacy and safety similar to data found in the literature.

Access to High-Cost Biological Agents: Perceptions of Brazilian Patients with Inflammatory Bowel Diseases.

BACKGROUND AND AIMS: Brazilian patients with inflammatory bowel diseases (IBD) requiring therapy with biological agents usually have access to medicines through the National Unified Health Care System (SUS). This study aimed to analyze Brazilian IBD patient perception regarding access (availability and provision quality) to high-cost drugs in the public health care system. METHODS: A questionnaire-based survey was carried out in an IBD referral center in Brazil. All adult patients with an established diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) that use biological therapy were invited to participate. Data were collected on the biological in use, lack of distribution (number of absences, average time to regularization, impairment in patient treatment), and difficulties reported by patients in obtaining the drugs. RESULTS: Overall, 205 patients met the inclusion criteria and answered the questionnaire. Most of the patients had CD (n = 161, 78.5%), nearly half of them (n = 104, 50.7%) were female; 87 patients (42.4%) were unemployed, and of these, 40 patients (19.5%) had government assistance as the main source of income. Regarding the medications used, infliximab (n = 128, 62.5%) was the most used medication, followed by adalimumab (n = 39, 19.0%). Most patients (n = 172, 83.9%) reported at least one failed delivery of biological medicine in the last year, with a single shortage in forty-two patients (24.4%), at least two shortages in forty-seven patients (27.3%), and three or more shortages in seventy-eight patients (45.3%). The average time to regularize the distribution was up to 1 month in 44 cases (25.6%), up to 2 months in 64 cases (37.2%), and more than 3 months in 56 patients (32.6%). Among patients who reported delays, 101 patients (58.7%) felt that it may have impaired their treatment. CONCLUSION: Brazilian IBD patients reported high rates of failure to dispense biological drugs by the national healthcare system within one year. Our data highlight the need for improvement in this system for the correct supply of medication to avoid treatment failure and relapse.

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.

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.

Effectiveness and Safety of Tofacitinib in the Management of Ulcerative Colitis: A Brazilian Observational Multicentric Study.

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease which affects the colorectal mucosa with a relapsing-remitting pattern. The therapeutic options currently available for the medical management of UC include many options. Tofacitinib is an oral small molecule, Janus kinase (JAK) inhibitor, more selective for JAK1 and JAK3, which reduces the inflammatory process involved in the pathogenesis of UC. Methods: Retrospective observational multicentric study of patients with UC who used tofacitinib in any phase of their treatment. Clinical remission and response (according to Mayo score), mucosal healing, primary and secondary loss of response, discontinuation of the drug with possible causes, and the need for dose optimization or switching to biologicals, need for surgery and adverse events were evaluated. Results: From a total of 56 included patients, clinical remission was observed in 43.6% at week 12, 54.5% at week 26, 57.9% at week 52, and 40% at the last follow-up visit. Clinical response was observed in 71.4%, 81.8%, 89.5%, and 61.8% at the same time periods, respectively. Mucosal healing rates were 50% and 17.8% needed colectomy. Conclusions: Tofacitinib was effective in induction and maintenance of clinical response and remission rates, compatible to other international real-word studies and meta-analyses.

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.

Retrospective analysis of surgical and oncological results of laparoscopic surgeries performed by residents of coloproctology / Análise retrospectiva dos resultados cirúrgicos e oncológicos em cirurgias videolaparoscópicas realizadas por residentes de coloproctologia

ABSTRACT Introduction: with the improvement and wide acceptance of laparoscopy in colorectal operations, there was a need for specific training of surgeons in training. There are few studies evaluating the postoperative results of laparoscopic colectomies performed by resident physicians and their impact on patient safety. Purpose: to analyze the surgical and oncological results of laparoscopic colectomies performed by coloproctology residents and compare them with data in the literature. Methods: this is a retrospective analysis of patients undergoing laparoscopic colorectal surgery performed by resident physicians at the Hospital das Clínicas de Ribeirão Preto, between 2014 and 2018. The clinical characteristics of the patients were studied, as well as the main surgical and oncological aspects in a period of one year. Results: we analyzed 191 operations, whose main surgical indication was adenocarcinoma, most of them stage III. The mean duration of surgeries was 210±58 minutes. There was a need for a stoma in 21.5% of the patients, mainly loop colostomy. The conversion rate was 23%, with 79.5% due to technical difficulties, and the main predictors of conversion were obesity and intraoperative accidents. The median length of stay was 6 days. Preoperative anemia was associated with a higher rate of complications (11.5%) and reoperations (12%). Surgical resection margins were compromised in 8.6% of cases. The one-year recurrence rate was 3.2% and the mortality rate was 6.3%. Conclusions: videolaparoscopic colorectal surgery performed by residents showed efficacy and safety similar to data found in the literature.

RESUMO Introdução: com o aperfeiçoamento e a ampla aceitação da laparoscopia nas operações colorretais, houve necessidade de treinamento específico dos cirurgiões em formação. Existem poucos estudos avaliando os resultados pós operatórios das colectomias videolaparoscópicas realizadas por médicos residentes e seu impacto na segurança do paciente. Objetivo: analisar os resultados cirúrgicos e oncológicos das colectomias videolaparoscópicas realizadas por residentes de coloproctologia e comparar com dados da literatura. Métodos: trata-se de uma análise retrospectiva de pacientes submetidos a cirurgias colorretais laparoscópicas, realizadas por médicos residentes do Hospital das Clínicas de Ribeirão Preto, entre 2014 e 2018. Foram estudadas as características clínicas dos pacientes bem como os principais aspectos cirúrgicos e oncológicos em um período de um ano. Resultados: analisou-se 191 operações, cuja principal indicação cirúrgica foi adenocarcinoma, a maioria estadio III. A duração média das cirurgias foi 210±58 minutos. Houve necessidade de estoma em 21,5% dos pacientes, principalmente colostomia em alça. A taxa de conversão foi 23%, sendo 79,5% por dificuldades técnicas, e os principais fatores preditores de conversão foram obesidade e acidentes intra-operatórios. A mediana do tempo de internação foi 6 dias. Anemia pré operatória associou-se a uma maior taxa de complicações (11,5%) e reoperações (12%). Houve comprometimento das margens de ressecção cirúrgica em 8,6% dos casos. A taxa de recidiva em um ano foi de 3,2%, e a taxa de mortalidade, 6,3%. Conclusões: a cirurgia colorretal videolaparoscópica realizada por residentes apresentou eficácia e segurança semelhante aos dados encontrados na literatura.

HEMATOPOIETIC STEM CELL TRANSPLANTATION AND CROHN'S DISEASE: POSITION PAPER FROM THE TRANSPLANTATION COMMITTEE OF THE BRAZILIAN GROUP FOR THE STUDY OF INFLAMMATORY BOWEL DISEASES (GEDIIB).

Crohn's disease (CD) is a relapse-remitting inflammatory bowel disease that can affect any part of the digestive system. This heterogeneous disease has multiple factors that contribute to an abnormal immune response to intestinal microorganisms. Treatment is based on the use of anti-inflammatories, corticosteroids, immunosuppressants and biologic biologic agents either alone or in combination. Surgical treatment is usual and, ten years after diagnosis, more than 80% of patients report having undergone surgical procedures related to the disease. Unfortunately, none of the treatments described offer a cure, and many cases become refractory or without therapeutic options. In this scenario, hematopoietic stem cell transplantation has been suggested because clinical remission was obtained in patients who had CD associated with malignant hematological diseases and an alternative since the first reports in 2010. In this report, the Transplantation Committee of the Brazilian Group for the Study of Inflammatory Bowel Diseases reviews the history and results of the procedure in patients with CD, detailing and discussing the various relevant points that permeate hematopoietic stem cell transplantation and cell therapy in this disease.

Transplante de células tronco hematopoiéticas e doença de Crohn: posição do Comitê de Transplantes do Grupo Brasileiro para estudo das doenças inflamatórias do intestino (GEDIIB) / Hematopoietic stem cell transplantation and crohn's disease: position paper from the transplantation committee of the brazilian group for the study of inflammatory bowel diseases (gediib)

ABSTRACT Crohn's disease (CD) is a relapse-remitting inflammatory bowel disease that can affect any part of the digestive system. This heterogeneous disease has multiple factors that contribute to an abnormal immune response to intestinal microorganisms. Treatment is based on the use of anti-inflammatories, corticosteroids, immunosuppressants and biologic biologic agents either alone or in combination. Surgical treatment is usual and, ten years after diagnosis, more than 80% of patients report having undergone surgical procedures related to the disease. Unfortunately, none of the treatments described offer a cure, and many cases become refractory or without therapeutic options. In this scenario, hematopoietic stem cell transplantation has been suggested because clinical remission was obtained in patients who had CD associated with malignant hematological diseases and an alternative since the first reports in 2010. In this report, the Transplantation Committee of the Brazilian Group for the Study of Inflammatory Bowel Diseases reviews the history and results of the procedure in patients with CD, detailing and discussing the various relevant points that permeate hematopoietic stem cell transplantation and cell therapy in this disease.

RESUMO A doença de Crohn (DC) é uma doença inflamatória intestinal (DII) recidivante recorrente que pode afetar qualquer parte do sistema digestivo. É doença heterogênea e possui múltiplos fatores que contribuem para uma resposta imune anormal aos microrganismos intestinais. O tratamento baseia-se no uso de anti-inflamatórios, corticosteroides e imunossupressores e imunobiológicos que são utilizados isoladamente ou em combinação. O tratamento cirúrgico é frequente e 10 anos após o diagnóstico, mais de 50% dos pacientes relatam terem sido submetidos a procedimentos cirúrgicos relacionados à doença. Infelizmente, nenhum dos tratamentos descritos oferece cura, e inúmeros casos tornam-se refratários ou sem opções terapêuticas. Nesse cenário, o transplante de células-tronco hematopoéticas (TCTH) em decorrência da remissão clínica de pacientes que apresentavam DC associada a doenças hematológicas malignas, passou a ser alternativa desde os primeiros resultados em 2010. Neste relato, a Comissão de Transplantes do Grupo Brasileiro de Estudo das Doenças Inflamatórias Intestinais revisa a história e os resultados do procedimento em pacientes com DC, detalhando e discutindo os diversos pontos relevantes que permeiam o TCTH e a terapia celular no tratamento da moléstia.

Effectiveness and Safety of Ustekinumab for Moderate to Severely Active Crohn's Disease: Results from an Early Access Program in Brazil.

This prospective, observational, open-label study aimed to provide access to ustekinumab prior to market authorization and assess its safety and effectiveness in patients with Crohn's disease (CD) refractory to anti-tumor necrosis factor-α and conventional drugs in Brazil. Patients with a diagnosis of moderate-to-severe active CD for ≥3 months before screening received ustekinumab in a single intravenous induction dose (~6 mg/kg) at week 0, and a 90 mg maintenance dose, subcutaneously, every 8 or 12 weeks, from week 8 through to 80. Serious adverse events (SAE), adverse drug reactions (ADR), clinical response (per CD Activity Index and Harvey Bradshaw Index (HBI) scores), remission (per HBI scores), biomarkers (C-reactive protein (CRP) and fecal calprotectin (FC)) and endoscopic improvement rate over 80 weeks were assessed. Patients with a mean age of 39.9 years were assessed. Discontinuation rate was low (23%) and most adverse events were mild (68.7%). The SAE rate was 21% (mostly infections/infestations or gastrointestinal disorder), and ADR rate was 44%. The CD Activity Index and HBI scores decreased (by 74% and 81%, respectively) with 50% of patients showing normalized CRP and FC, and 63% achieved endoscopic improvement. Ustekinumab was fairly safe, well tolerated and effective in a Brazilian cohort of CD patients.

Postoperative Complications and Stoma Rates After Laparoscopic Resection of Deep Infiltrating Endometriosis with Bowel Involvement / Complicações pós-operatórias e taxas de estomia após ressecção laparoscópica de endometriose infiltrativa profunda com envolvimento intestinal

Abstract Objective The purpose was to assess the rates of postoperative complications and the need of temporary stoma of laparoscopic surgical treatment for bowel endometriosis in a referral center. Methods The surgical indication, type of operation, operative time, length of hospital stay, need for a temporary stoma, rate of conversion to open surgery, postoperative complications were evaluated. Results One-hundred and fifty patients were included. The average duration of surgery was significantly longer for segmental resection (151 minutes) than for disc excision (111.5 minutes, p < 0.001) and shaving (96.8 minutes, p < 0.001). Patients with segmental resection had longer postoperative lengths of hospital stay (1.87 days) compared with patients with disc excision (1.43 days, p < 0.001) and shaving (1.03 days, p < 0.001). A temporary stoma was performed in 2.7% of patients. Grade II and III postoperative complications occurred in 6.7% and 4.7% patients, respectively. Conclusion Laparoscopic intestinal resection has an acceptable postoperative complication rate and a low need for a temporary stoma.

Resumo Objetivo O objetivo foi avaliar as taxas de complicações pós-operatórias e a necessidade de estomia temporária do tratamento cirúrgico laparoscópico para endometriose intestinal em um centro de referência. Métodos Foram avaliados a indicação cirúrgica, tipo de operação, tempo operatório, tempo de internação, necessidade de estomia temporária, taxa de conversão para cirurgia aberta, complicações pós-operatórias. Resultados Cento e cinquenta pacientes foram incluídos. A duração média da cirurgia foi significativamente maior para a ressecção segmentar (151 minutos) do que para a excisão do disco (111,5 minutos, p < 0,001) e shaving (96,8 minutos, p < 0,001). Pacientes com ressecção segmentar tiveram maior tempo de internação pós-operatória (1,87 dias) em comparação com pacientes com excisão de disco (1,43 dias, p < 0,001) e shaving (1,03 dias, p < 0,001). Um estoma temporário foi realizado em 2,7% dos pacientes. Complicações pós-operatórias de grau II e III ocorreram em 6,7% e 4,7% dos pacientes, respectivamente. Conclusão A ressecção intestinal laparoscópica apresenta taxa aceitável de complicações pós-operatórias e baixa necessidade de estomia temporária.

Postoperative Complications and Stoma Rates After Laparoscopic Resection of Deep Infiltrating Endometriosis with Bowel Involvement.

OBJECTIVE: The purpose was to assess the rates of postoperative complications and the need of temporary stoma of laparoscopic surgical treatment for bowel endometriosis in a referral center. METHODS: The surgical indication, type of operation, operative time, length of hospital stay, need for a temporary stoma, rate of conversion to open surgery, postoperative complications were evaluated. RESULTS: One-hundred and fifty patients were included. The average duration of surgery was significantly longer for segmental resection (151 minutes) than for disc excision (111.5 minutes, p < 0.001) and shaving (96.8 minutes, p < 0.001). Patients with segmental resection had longer postoperative lengths of hospital stay (1.87 days) compared with patients with disc excision (1.43 days, p < 0.001) and shaving (1.03 days, p < 0.001). A temporary stoma was performed in 2.7% of patients. Grade II and III postoperative complications occurred in 6.7% and 4.7% patients, respectively. CONCLUSION: Laparoscopic intestinal resection has an acceptable postoperative complication rate and a low need for a temporary stoma.

OBJETIVO: O objetivo foi avaliar as taxas de complicações pós-operatórias e a necessidade de estomia temporária do tratamento cirúrgico laparoscópico para endometriose intestinal em um centro de referência. MéTODOS: Foram avaliados a indicação cirúrgica, tipo de operação, tempo operatório, tempo de internação, necessidade de estomia temporária, taxa de conversão para cirurgia aberta, complicações pós-operatórias. RESULTADOS: Cento e cinquenta pacientes foram incluídos. A duração média da cirurgia foi significativamente maior para a ressecção segmentar (151 minutos) do que para a excisão do disco (111,5 minutos, p < 0,001) e shaving (96,8 minutos, p < 0,001). Pacientes com ressecção segmentar tiveram maior tempo de internação pós-operatória (1,87 dias) em comparação com pacientes com excisão de disco (1,43 dias, p < 0,001) e shaving (1,03 dias, p < 0,001). Um estoma temporário foi realizado em 2,7% dos pacientes. Complicações pós-operatórias de grau II e III ocorreram em 6,7% e 4,7% dos pacientes, respectivamente. CONCLUSãO: A ressecção intestinal laparoscópica apresenta taxa aceitável de complicações pós-operatórias e baixa necessidade de estomia temporária.