European consensus conference on faecal microbiota transplantation in clinical practice

Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.Peer reviewe

International consensus conference on stool banking for faecal microbiota transplantation in clinical practice

Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres. Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice, Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.Peer reviewe

A standardised model for stool banking for faecal microbiota transplantation : a consensus report from a multidisciplinary UEG working group

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.Peer reviewe

Distribution of CD4(pos) -, CD8(pos) - and regulatory T cells in the upper and lower gastrointestinal tract in healthy young subjects.

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

Downgrading of a G3 Neuroendocrine Tumor to a G2 Tumor: Can First-Line Cytotoxic Chemotherapy Change the Tumor Biology?

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

Successful Medical Treatment of Adult Nesidioblastosis With Pasireotide over 3 Years: A Case Report.

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 (0.6 mg 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

Relative abundance of CD3^pos cells, CD8^pos -, CD4^pos -T cells and Tregs in the intestinal mucosa.

<p>A) T cells are more or less evenly distributed in the gut B) CD8^pos T cells are enriched in the human gastric corpus and antrum. C) CD3^posCD4^pos T cells are predominantly found in the lower intestinal tract. D) The relative abundance of CD4^posCD25^highCD127^low/negFOXP3 cells was highest in the appendiceal orifice region and the ascending colon. The figures represent cumulative flow cytometry data from all study participants (N=16) from all seven biopsy regions including the gastric corpus (GC), gastric antrum (GA), duodenum (DD), terminal ileum (TI), appendiceal orifice (AO), ascending colon (AC) and sigmoid colon (SC). Unless otherwise indicated, differences were not significant. *P<0.05; **P<0.01; ***P<0.001.</p

Representative gating strategy for the FACS analysis of lamina propria CD3+, CD4+, CD8+ and regulatory T-cells from pinch biopsies obtained from the appendiceal orifice region of one healthy subject.

<p>Representative gating strategy for the FACS analysis of lamina propria CD3+, CD4+, CD8+ and regulatory T-cells from pinch biopsies obtained from the appendiceal orifice region of one healthy subject.</p

Functional imaging in the follow-up of enteropancreatic neuroendocrine tumors: Clinical usefulness and indications

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