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BACKGROUND AND AIMS: Immunological treatment failure of anti-TNF therapy negatively influences treatment persistence of a second anti-TNF in IBD patients. So far it is unknown if this effect is also observed for other monoclonal antibodies. We assessed the influence of immunogenicity to anti-TNFs on treatment persistence of subsequent ustekinumab and vedolizumab therapy. METHODS: IBD patients with and without immunogenicity to anti-TNFs (undetectable trough levels and antibody titers ≥20 ng/mL) and subsequent ustekinumab (UST) and/or vedolizumab (VDZ) therapy were included in this retrospective, single-center study. The Kaplan-Meier method with the log-rank test and Cox proportional hazards were used as statistical methods. RESULTS: One hundred patients (Crohn's disease: 62, Ulcerative colitis: 31, IBD unclassified: 7) with 127 treatment lines (62 with UST, 65 with VDZ) were included in the analysis. Immunogenicity to previous anti-TNFs did not influence treatment persistence of subsequent ustekinumab and vedolizumab therapy (UST: Log rank: p = .95, Immunogenicity: HR for treatment discontinuation: 0.97 [95% CI 0.31-3.04]; VDZ: p = .65, HR: 0.85 [0.41-1.75]; total cohort [UST and VDZ]: p = .62, HR: 0.86 [0.47-1.57]). Azathioprine co-treatment did not lengthen treatment persistence (UST: Log rank: p = .77, azathioprine: HR: 1.20 [0.34-4.27]; VDZ: p = .92, HR: 0.58 [0.17-1.99]; total cohort: p = .79, HR: 1.10 [0.55-2.20]). In this anti-TNF experienced cohort, patients with ustekinumab remained longer on treatment than patients receiving vedolizumab (Log rank: p = .005, UST: HR: 0.43 [0.23-0.79]). CONCLUSIONS: Immunogenicity to anti-TNFs does not influence treatment persistence of subsequent ustekinumab and vedolizumab therapy.
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Doenças Inflamatórias Intestinais , Ustekinumab , Humanos , Ustekinumab/uso terapêutico , Estudos Retrospectivos , Inibidores do Fator de Necrose Tumoral , Fármacos Gastrointestinais/uso terapêutico , Azatioprina/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Resultado do TratamentoRESUMO
BACKGROUND: Anti-TNF antibodies were the first biologic treatment option for patients with inflammatory bowel diseases. AIMS: To assess length of treatment persistence of first anti-TNF therapy and influencing factors used in the standard care of patients with inflammatory bowel diseases. METHODS: Single-centre, retrospective study from a register including patients who received anti-TNF therapy in the last 20 years at the study centre. Kaplan-Meier analysis with log-rank test was used to describe treatment persistence. With multivariable Cox regression analysis, risk factors for treatment failure were investigated. RESULTS: Five hundred thirty-eight patients (CD, Crohn's disease: 367, UC, ulcerative colitis: 147, inflammatory bowel disease unclassified: 24) with a median follow-up of 8.1 years were included. Median (95% confidence interval) treatment persistence in the total cohort was 2.3 years (28 [22, 38] months), and nearly half of patients withdrew from treatment within 2 years. Male patients were treated longer than females (male: 37 [25, 48] months, female: 23 [14, 33] months, P = 0.002). Treatment persistence was longer in CD compared to UC (CD: 39 [30, 50] months, UC: 13 [9, 19] months, P < 0.001), and patients with CD remained longer on adalimumab than on infliximab treatment (adalimumab: 67 [55, 95] months, infliximab: 19 [14, 31] months, P < 0.001). Treatment failure (52%) and side effects (25%) were the most common reasons for withdrawal from therapy; 14% withdrew due to remission. Female sex was identified as independent predictor for treatment failure in UC (hazard ratio [CI]: 1.73 [1.02-2.92], P = 0.04). CONCLUSION: Long-term treatment persistence of first anti-TNF therapy was limited in patients with inflammatory bowel diseases, primarily due to treatment failure and side effects.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Feminino , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Masculino , Estudos RetrospectivosRESUMO
PURPOSE: Approved systemic therapies for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have shown limited capacity to reduce tumor burden and no antitumor activity after progression to targeted agents (TAs). We investigated the efficacy and safety of lenvatinib in patients with previously treated advanced GEP-NETs. PATIENTS AND METHODS: This was a multicenter, single-arm, open-label, phase II trial with two parallel cohorts (ClinicalTrials.gov identifier: NCT02678780) involving 21 institutions in 4 European countries. Eligible patients had histologically confirmed advanced grade 1-2 pancreatic (panNET) or GI (GI-NET) NETs with documented tumor progression after treatment with a TA (panNET) or somatostatin analogs (GI-NET). Patients were treated with lenvatinib 24 mg once daily until disease progression or treatment intolerance. The primary end point was overall response rate by central radiology review. Secondary end points included progression-free survival, overall survival, duration of response, and safety. RESULTS: Between September 2015 and March 2017, a total of 111 patients were enrolled, with 55 (panNET) and 56 (GI-NET) patients in each cohort. The median follow-up was 23 months. The overall response rate was 29.9% (95% CI, 21.6 to 39.6): 44.2% (panNET) and 16.4% (GI-NET). The median (range) duration of response was 19.9 (8.4-30.8) and 33.9 (10.6-38.3) months in the panNET and GI-NET groups, respectively. The median progression-free survival was 15.7 months (95% CI, 14.1 to 19.5). The most common adverse events were fatigue, hypertension, and diarrhea; 93.7% of patients required dose reductions or interruptions. CONCLUSION: We report the highest centrally confirmed response reported to date with a multikinase inhibitor in advanced GEP-NETs, with a particularly strong response in the panNET cohort. This study provides novel evidence for the efficacy of lenvatinib in patients with disease progression following treatment with other TAs, suggesting the potential value of lenvatinib in the treatment of advanced GEP-NETs.
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Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Europa (Continente) , Feminino , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Compostos de Fenilureia/efeitos adversos , Intervalo Livre de Progressão , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas/efeitos adversos , Fatores de TempoRESUMO
INTRODUCTION: Treatment-refractory, acute graft-versus-host disease (GvHD) of the lower gastrointestinal tract (GI) after allogeneic hematopoietic stem cell transplantation is life threatening and lacks effective treatment options. While fecal microbiota transplantation (FMT) was shown to ameliorate GI-GvHD, its mechanisms of action and the factors influencing the treatment response in humans remain unclear.The objective of this study is to assess response to FMT treatment, factors influencing response, and to study the mucosal immune cell composition in treatment-refractory GI-GvHD. METHODS: Consecutive patients with treatment-refractory GI-GvHD were treated with up to six endoscopically applied FMTs. RESULTS: We observed the response to FMT in four out of nine patients with severe, treatment refractory GI-GvHD, associated with a significant survival benefit (p = 0.017). The concomitant use of broad-spectrum antibiotics was the main factor associated with FMT failure (p = 0.048). In addition, antibiotic administration hindered the establishment of donor microbiota after FMT. Unlike in non-responders, the microbiota characteristics (e.g. α- and ß-diversity, abundance of anaerobe butyrate-producers) in responders were more significantly similar to those of FMT donors. During active refractory GI-GvHD, an increased infiltrate of T cells, mainly Th17 and CD8+ T cells, was observed in the ileocolonic mucosa of patients, while the number of immunomodulatory cells such as regulatory T-cells and type 3 innate lymphoid cells decreased. After FMT, a change in immune cell patterns was induced, depending on the clinical response. CONCLUSION: This study increases the knowledge about the crucial effects of antibiotics in patients given FMT for treatment refractory GI-GvHD and defines the characteristic alterations of ileocolonic mucosal immune cells in this setting.
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BACKGROUND: Faecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of faeces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council. OBJECTIVE: Several European and international consensus statements concerning faecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document. METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about faecal microbiota transplantation. RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening. CONCLUSION: The implementation of faecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor faeces preparations for patients.
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Bancos de Espécimes Biológicos/organização & administração , Transplante de Microbiota Fecal , Fezes , Fatores Etários , Bancos de Espécimes Biológicos/normas , Clostridioides difficile , Infecções por Clostridium/imunologia , Infecções por Clostridium/terapia , Contraindicações de Procedimentos , Seleção do Doador , Transplante de Microbiota Fecal/efeitos adversos , Transplante de Microbiota Fecal/métodos , Humanos , Hospedeiro Imunocomprometido , Consentimento Livre e Esclarecido , Garantia da Qualidade dos Cuidados de Saúde , Recidiva , Manejo de EspécimesRESUMO
BACKGROUND: While platinum-based chemotherapy represents the standard treatment for advanced grade 3 (G3) neuroendocrine neoplasms (NENs) according to the European Neuroendocrine Tumor Society guidelines, the role of radical-intended surgery in these patients, as well as the use of adjuvant chemotherapy, are still controversial. The aim of the present work is to describe, in a retrospective series of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) G3, the overall survival (OS) rate and risk factors for death after radical surgery. Secondary aims are the description of median recurrence-free survival (RFS) and of the role of adjuvant chemotherapy. PATIENTS AND METHODS: Multicenter analysis of a series of stage I-III GEP-NEN G3 patients receiving radical surgery (R0/R1) with/without adjuvant chemotherapy was performed. RESULTS: Sixty patients from eight neuroendocrine tumor (NET) referral centers, with median follow-up of 23 months (5-187 months) were evaluated. While 28.6% of cases had NET G3, 71.4% had neuroendocrine carcinoma G3 (NEC G3). The 2-year OS rate after radical surgery was 64.5%, with a statistically significant difference in terms of Ki67 threshold (cut-off 55%, P = 0.03) and tumor differentiation (NEC G3 vs. NET G3, P = 0.03). Median RFS after radical surgery was 14 months, and 2-year RFS rate was 44.9%. Use of adjuvant chemotherapy provided no benefit in terms of either OS or RFS in this series. CONCLUSIONS: Surgery with radical intent might represent a valid option for GEP-NEN G3 patients with locoregional disease, especially with Ki67 value ≤ 55%.
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Procedimentos Cirúrgicos do Sistema Digestório/métodos , Neoplasias Gastrointestinais/cirurgia , Recidiva Local de Neoplasia/epidemiologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/cirurgia , Quimioterapia Adjuvante , Colectomia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Esofagectomia , Feminino , Gastrectomia , Neoplasias Gastrointestinais/patologia , Humanos , Antígeno Ki-67 , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Tumores Neuroendócrinos/patologia , Pancreatectomia , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia , Compostos de Platina/uso terapêutico , Protectomia , Estudos Retrospectivos , Taxa de SobrevidaAssuntos
Amiloidose/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Doença de Crohn/tratamento farmacológico , Adulto , Amiloidose/diagnóstico , Amiloidose/etiologia , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Quimioterapia Combinada , Feminino , Humanos , Nascido Vivo , Gravidez , Indução de Remissão , Resultado do TratamentoRESUMO
Neuroendocrine tumors of the gastrointestinal tract (GI-NET) are rare tumors. Functional tumors with hormonal syndromes (e.âg., insulinoma, gastrinoma) are less common than non-functional tumors, which usually have an indolent course. Therapy for GI-NET is multimodal, including endoscopic or surgical procedures aiming at complete removal of tumor tissue. Patients in later stages may benefit from interventional radiology or medical therapy. This article gives an overview regarding the key aspects of GI-NET therapy in daily gastroenterology practice with emphasis on endoscopic diagnosis and therapy.
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Gastroenterologia , Neoplasias Gastrointestinais/cirurgia , Tumores Neuroendócrinos/cirurgia , Guias de Prática Clínica como Assunto , Endoscopia Gastrointestinal/efeitos adversos , Gastrinoma , Neoplasias Gastrointestinais/patologia , Humanos , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas , Resultado do TratamentoRESUMO
BACKGROUND AND STUDY AIMS: Quality of inspection during colonoscopy is strictly related to the level of cleansing. High-volume (PEG-based) solutions are highly effective and safe, but their high volume affects tolerability and compliance. The aim of this study was to compare a new low-volume PEG with citrate and simethicone solution (PMF 104,Clensia) with a low-volume PEG with ascorbic acid solution (PEG-ASC; Moviprep). PATIENTS AND METHODS: This was a multicenter, randomized, observer-blind, parallel-group, phase 3 clinical trial, where patients were randomized between PMF 104 and PEG-ASC. In both groups, patients were instructed to take a full-dose regimen the evening before if colonoscopy was scheduled before 11 am to 12 pm, or to take a split regimen if colonoscopy was scheduled after 11 am to 12 pm. The primary end-point was an equivalence between PMF104 and PEG-ASC in the rate of adequate level of cleansing (Ottawa scaleâ≤â6), with safety, mucosal visibility, tolerability, acceptance and compliance being also assessed. RESULTS: Of the 403 enrolled, 367 patients (Mean age [SD]: 55.6 (14.4) years; male:166 [45.2â%]) were included in the per protocol (PP) analysis: 184 being randomized in the PMF 104 group and 183 in the PEG-ASC group.âSuccessful bowel cleansing was 78.3â% and 74.3â% in PMF104 and in PEG-ASC, respectively ( P â=â0.37). Both preparations were equally safe (mild adverse events were observed in 9.2â% and 9.3â% of patients in the PMF104 and in the PEG-ASC group, respectively) and acceptable (no or mild distress during the intake in 81.4â% and 80.8â% in the PMF104 in the PEG-ASC, respectively [ P â=â0.74]). CONCLUSION: The new low-volume product Clensia is equivalent to the reference low-volume PEG-ASC in terms of bowel cleansing, safety and acceptance.
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Context: Functional imaging tests (FITs) detecting somatostatin receptor expression [i.e., somatostatin receptor scintigraphy, 68Ga-DOTA positron emission tomography/computed tomography (CT)] have a pivotal role in the diagnosis of neuroendocrine tumors (NETs), although their indication during follow-up still needs to be clarified. Objective: Investigate the role of FITs after diagnosis of metastatic enteropancreatic NETs, identifying patients who might benefit from these exams. Design: Multicenter retrospective analysis of metastatic enteropancreatic NETs. Setting: Analysis of imaging tests performed between January 1995 and December 2015 in Rome, Berlin, Milan, Marburg, or Graz. Subjects: One hundred forty-three patients with metastatic pancreatic NETs and small intestine NETs, at least 2-year follow-up, and positive FITs. Interventions: Patients had received CT every 6 months (unless clinical conditions and tumor behavior required shorter intervals) and FIT every 12 months. Main Outcome Measures: Clinical usefulness of FITs, defined as changes in patient management (indication to biopsy, medical therapy, surgery, or further imaging tests) due only to FITs. Results: FITs affected management in 73.4% of patients, mostly when G2 vs G1 [odds ratio (OR), 2.40; 95% confidence interval (CI), 1.09 to 5.27; P = 0.03]. Changes were observed in a 12-month time frame especially with pancreatic NETs vs small intestine NETs (OR, 2.89; 95% CI, 1.09 - 7.67; P = 0.03) or metastases since diagnosis vs developed during follow-up (OR, 4.00; 95% CI, 1.43 to 11.17; P < 0.01). Conclusions: FITs used in addition to CT in the follow-up of stage IV enteropancreatic NETs improve patient management (especially for G2 tumors). Follow-up program should be tailored according to tumor features.
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Neoplasias Intestinais/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Peritoneais/diagnóstico por imagem , Adulto , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/patologia , Intestino Delgado/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Tumores Neuroendócrinos/secundário , Compostos Organometálicos , Neoplasias Pancreáticas/patologia , Neoplasias Peritoneais/secundário , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
BACKGROUND: Several risk factors predict clinical outcome in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs); however, the impact of their combination has not been investigated so far. PATIENTS AND METHODS: A retrospective analysis of stage IV GEP-NENs was performed. Multivariate analysis for progression of disease (PD) was performed by Cox proportional hazards method to obtain a risk score. Area under the curve obtained by receiver operating characteristic analysis was used to assess the score performance. Progression-free survival analysis was performed by Kaplan-Meier method. RESULTS: Two hundred eighty-three stage IV GEP-NENs were evaluated, including 93 grade 1 neuroendocrine tumors (32.9%), 153 grade 2 neuroendocrine tumors (54%), and 37 grade 3 neuroendocrine carcinomas (13.1%). Independent risk factors for PD were Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The risk score was calculated as follows: (0.025 × Ki67) + [(0 if no liver metastases or liver involvement <25%) OR (0.405 if liver involvement 25%-50%) OR (0.462 if liver involvement >50%)] + [(0 if no extra-abdominal metastases) OR (0.528 if extra-abdominal metastases present)]. The risk score accuracy to predict PD was superior compared with the G grading system (area under the curve: 0.705 and 0.622, respectively). Three subgroups of patients with low, intermediate, and high risk of PD according to risk score were identified, median progression-free survival being 26 months, 19 months, and 12 months, respectively. CONCLUSION: In stage IV GEP-NENs, a risk score able to predict PD was obtained by combining Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The score may help to discriminate patients with different progression risk level to plan tailored therapeutic approaches and follow-up programs. The Oncologist 2017;22:409-415Implications for Practice: Clinical outcome of patients with advanced gastro-entero-pancreatic neuroendocrine neoplasms is affected by several risk factors, including the proliferative index Ki67, extension of liver metastases, and the presence of distant extra-abdominal lesions. A risk score that combines these variables may help physicians dealing with these diseases to plan the optimal therapeutic approach and follow-up program.
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Progressão da Doença , Neoplasias Intestinais/epidemiologia , Neoplasias Intestinais/patologia , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/patologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Intestinais/diagnóstico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Tumores Neuroendócrinos/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Neoplasias Gástricas/diagnósticoAssuntos
Transplante de Microbiota Fecal , Fezes/microbiologia , Gastroenteropatias/etiologia , Gastroenteropatias/terapia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Terapia Combinada , Diarreia/etiologia , Diarreia/terapia , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/fisiopatologia , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/fisiopatologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The antiproliferative treatment options for neuroendocrine tumors (NET)/neuroendocrine carcinomas of the gastrointestinal tract critically depend on the proliferation rate, evaluated by immunohistochemical staining for Ki-67. According to their grading, tumors are treated with somatostatin analogs, mTOR inhibitors, or cytotoxic substances. This case illustrates downgrading of a primarily highly proliferative NET achieved by a variation of cytotoxic chemotherapy regimens, followed by a combination therapy using everolimus together with lanreotide. The latter medication might lead to a good clinical response as far as tumor growth is concerned.
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Fecal microbiota transplantation (FMT) is a novel therapeutic procedure aiming at restoring a normal intestinal microbiota by application of fecal microorganisms from a healthy subject into the gastrointestinal tract of a patient. FMT is the most effective treatment for recurrent Clostridium difficile infections (CDI). These infections also occur in patients with inflammatory bowel diseases (IBDs), where case series demonstrated a successful treatment of CDI by FMT in 83-92% of patients. The effect of FMT on the activity of IBD has mainly been investigated in ulcerative colitis (UC) patients, including 3 randomized controlled trials. So far, 2 randomized controlled trials showed a superiority of FMT compared to placebo in inducing remission in UC, while 1 study found no significant difference to placebo. The variation in response to FMT between these studies as well as in the uncontrolled trials might be explained by many differences in the way of FMT application, patient pretreatment and patient and donor selection. The data for the use of FMT in Crohn's disease and pouchitis are sparse; currently, no conclusion can be drawn regarding the effectiveness of FMT in these indications. It needs to be noted that cases of IBD activation after FMT have been reported. So far, FMT can only be recommended to be used for the treatment of concomitant CDI in IBD in clinical practice. For treating IBD irrespective of CDI, FMT should be only used in clinical trials. Current forms of FMT, especially protocols using repeated application, are very time and personnel consuming. Future trends are the use of defined stable microbiota preparations, in particular oral preparations, which will enable better and larger controlled trails for investigating FMT in IBD.
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Transplante de Microbiota Fecal/tendências , Previsões , Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais/terapia , Infecções por Clostridium/microbiologia , Infecções por Clostridium/terapia , Colite Ulcerativa/microbiologia , Colite Ulcerativa/terapia , Doença de Crohn/microbiologia , Doença de Crohn/terapia , Seleção do Doador , Fezes/microbiologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/microbiologia , Masculino , Seleção de Pacientes , Pouchite/microbiologia , Pouchite/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Resultado do TratamentoRESUMO
Nesidioblastosis is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. Diagnosis is often challenging and therapeutic options are scarce.In 2009, a 46-year-old female patient presented with recurrent severe hypoglycemia and immediate recovery after glucose ingestion. Although 72-h-fasting test was positive, various imaging technologies (sonography, computed tomography, somatostatin receptor scintigraphy, dopamine receptor positron emission tomography [DOPA-PET]) were negative. Endoscopic ultrasound revealed a lesion in the pancreatic corpus, whereas selective arterial calcium stimulation test, portal venous sampling and GLP-1-receptor scintigraphy were indicative of a lesion in the pancreatic tail, which was surgically removed. The histopathologic examination revealed beta cell hyperplasia and microadenomas expressing glucagon. After surgery, the patient was free of symptoms for 6 months, after which hypoglycemic episodes recurred. After unsuccessful treatment with corticosteroids and somatostatin analogs, treatment with pasireotide, a novel somatostatin analog with high affinity to somatostatin receptor 5 and a possible side effect of hyperglycemia, was initiated (0.6âmg BID). To date, our patient has been free of severe hypoglycemic episodes ever since. Yearly repeated imaging procedures have shown no abnormities over the last 3 years.We report for the first time that pasireotide was successfully used in the treatment of adult nesidioblastosis.
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Nesidioblastose/tratamento farmacológico , Somatostatina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Indução de Remissão , Somatostatina/uso terapêutico , Fatores de TempoAssuntos
Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Imageamento por Ressonância Magnética/métodos , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/secundário , Neoplasias Gástricas/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Síndrome do Carcinoide Maligno/diagnósticoRESUMO
BACKGROUND: Alterations in the intestinal microbiota are thought to be involved in the pathogenesis of inflammatory bowel diseases (IBD). Klebsiella oxytoca is an intestinal pathobiont that can produce a cytotoxin (tillivaline). AIM: We aimed to elucidate the pathogenetic relevance of toxin-producing K. oxytoca in patients with IBD flares and investigated the clonal relationship of K. oxytoca isolates from IBD patients using multilocus sequence typing (MLST). METHODS: Fecal samples of 235 adult IBD patients were collected from January 2008 to May 2009 and were tested for K. oxytoca, C. difficile toxin, and other pathogens by standard microbiological methods. Clinical data and disease activity scores were collected. K. oxytoca isolates were tested for toxin production using cell culture assays. A total of 45 K. oxytoca isolates from IBD patients, healthy, asymptomatic carriers and from patients with antibiotic-associated hemorrhagic colitis in part from our strain collection were tested for their clonal relationship using MLST. RESULTS: The prevalence of K. oxytoca in IBD overall was 4.7%. Eleven K. oxytoca isolates were detected. Two of 11 isolates were tested positive for toxin production. There was no significant difference in the distribution of K. oxytoca isolates between the groups (active vs. remission in UC and CD). MLST yielded 33 sequence types. K. oxytoca isolates from IBD did not cluster separately from isolates from asymptomatic carriers. CONCLUSIONS: Our data demonstrate that toxin (tilivalline)-producing K. oxytoca is not associated with IBD flares.
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Colite Ulcerativa/microbiologia , Doença de Crohn/microbiologia , Intestinos/microbiologia , Infecções por Klebsiella/microbiologia , Klebsiella oxytoca/isolamento & purificação , Adulto , Técnicas de Tipagem Bacteriana , Benzodiazepinonas/isolamento & purificação , Estudos de Casos e Controles , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , DNA Bacteriano/genética , Progressão da Doença , Fezes/microbiologia , Feminino , Humanos , Intestinos/patologia , Infecções por Klebsiella/diagnóstico , Klebsiella oxytoca/classificação , Klebsiella oxytoca/genética , Masculino , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Estudos Prospectivos , Fatores de Risco , Adulto JovemRESUMO
The gastrointestinal immune system is involved in the development of several autoimmune-mediated diseases, including inflammatory bowel disease, multiple sclerosis, and type 1 diabetes mellitus. Alterations in T-cell populations, especially regulatory T cells (Tregs), are often evident in patients suffering from these diseases. To be able to detect changes in T-cell populations in diseased tissue, it is crucial to investigate T-cell populations in healthy individuals, and to characterize their variation among different regions of the gastrointestinal (GI) tract. While limited data exist, quantitative data on biopsies systematically drawn from various regions of the GI tract are lacking, particularly in healthy young humans. In this report, we present the first systematic assessment of how T cells--including Tregs--are distributed in the gastrointestinal mucosa throughout the GI tract of healthy young humans by means of multi-parameter FACS analysis. Gastroduodenoscopy and colonoscopy were performed on 16 healthy volunteers aged between 18 and 32. Biopsies were drawn from seven GI regions, and were used to determine the frequencies of CD8(+)-, CD4(+)- and Tregs in the gastrointestinal mucosa by means of multi-parameter FACS analysis. Our data show that there is significant variation in the baseline T-cell landscape along the healthy human gastrointestinal tract, and that mucosal T-cell analyses from a single region should not be taken as representative of the entire gastrointestinal tract. We show that certain T-cell subsets in the gastrointestinal mucosa vary significantly among regions; most notably, that Tregs are enriched in the appendiceal orifice region and the ascending colon, and that CD8(pos) T cells are enriched in the gastric mucosa.