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Faecal immunochemical testing (FIT) has a high sensitivity for the detection of colorectal cancer (CRC). In a symptomatic population FIT may identify those patients who require colorectal investigation with the highest priority. FIT offers considerable advantages over the use of symptoms alone, as an objective measure of risk with a vastly superior positive predictive value for CRC, while conversely identifying a truly low risk cohort of patients. The aim of this guideline was to provide a clear strategy for the use of FIT in the diagnostic pathway of people with signs or symptoms of a suspected diagnosis of CRC. The guideline was jointly developed by the Association of Coloproctology of Great Britain and Ireland/British Society of Gastroenterology, specifically by a 21-member multidisciplinary guideline development group (GDG). A systematic review of 13 535 publications was undertaken to develop 23 evidence and expert opinion-based recommendations for the triage of people with symptoms of a suspected CRC diagnosis in primary care. In order to achieve consensus among a broad group of key stakeholders, we completed an extended Delphi of the GDG, and also 61 other individuals across the UK and Ireland, including by members of the public, charities and primary and secondary care. Seventeen research recommendations were also prioritised to inform clinical management. [Abstract copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.]

International audience; Fecal microbiota transplantation (FMT) or donor feces infusion is a therapy that aims to restore a perturbed gut microbiota composition and function. FMT is effective for treatment of patients with (multiple) recurrent Clostridioides difficile infections1–3 and recommended by current guidelines.4–6 In the near future, FMT may also become an accepted treatment option for other intestinal or extra-intestinal diseases.7FMT is performed using suspensions made of donor stool from carefully selected and screened healthy individuals.1,7 Donor screening is time consuming and costly. Before the establishment of stool banks, physicians and patients had to find their own donors. This resulted in uncontrolled application of FMT, and the logistical challenge made physicians reluctant to offer FMT to their patients. To overcome these problems, stool banks have been established.8,9 The mission of those stool banks is :to produce ready-to-use donor feces suspensions for treatment of patients,to improve the quality and safety of FMT by centralization and standardization,to increase the cost effectiveness of FMT, andto facilitate research.Stool banks are built in concordance with the model of blood banks and should follow quality standards applied to other transplantation products. Most stool banks are non-profit institutions, operating at a local (institution-based), national or international level. Recently, a UEG-funded working group was initiated to define quality standards for stool banking and FMT, which will result in further standardization of this new treatment approach. The current costs to deliver a ready-to-use stool suspension are €1050–1700 in Europe.9,10 There are also commercial initiatives,11 which may aim for much higher prices.Driven by the needs of patients, stool banks have emerged as new entities in a landscape without existing regulatory boundaries. This lack of guidance and National or European legislation may become a serious threat to providing the treatment for severely ill patients. This is also illustrated by the recent safety alert in the US about the transmission of multi-drug resistant organisms through FMT,12 which underlines the need for standardization, quality assurance, and a regulatory framework supporting the activities of stool banks. Legislation requires classification of stool as a product to treat patients. We strongly believe that stool should be considered a transplant product, or be regarded equivalent in status to blood products used for transplantation or transfusion purposes. The EU Tissue and Cells Directive (2004/23/EC) is best suited to guide FMT. Currently, this Directive does not cover FMT because the mechanism of action is not mediated by human cells. An adjustment to align this directive with the new reality of fecal transplantation is thus urgently needed. Only in the case of modification to the donated feces, other than those necessary for the conservation of the microbial community, does the product made of the donated feces become comparable to a drug and is best covered within the European directive for medicinal products intended for human use (2001/83/EC).Unfortunately, the misclassification of donor feces suspensions as a drug or pharmaceutical product, although difficult to imagine, is still one of the possible outcomes of the current discussion about classification. Currently, stool has already been classified as a drug in countries such as France, Germany, and the United Kingdom. Recently, companies have formed the “Pharmabiotic Research Institute” in Europe and the “Microbiome Therapeutics Innovation Group (MTIG)” in the US. The mission of those groups is “to improve market access,” and to “enhance the regulatory, investment, and commercial environment for microbiome therapeutic drug product development.” Both groups have published statements about the classification of FMT as a drug.13,14 MTIG actively collaborates with the Food and Drug Administration for the evaluation of safety parameters related to microbiota-based therapeutic products. Concern has been raised by the MTIG that the existence and accessibility of material from stool banks limits enrollment into clinical trials for microbiome therapeutics. This illustrates how companies are active to influence the current discussion about classification and regulation of FMT. In fact, this discussion has already been troubled by commercial interest in the US some years ago.15In this regard, it is important to mention the overall major disadvantages of classification as a drug, which will result in time-consuming and costly registration processes, and a sharp and unjustified rise in costs. Most importantly, this will negatively impact availability and innovation, obstructing, for example, the future development of single-donor individualized solutions due to the requirements for standardization of active substances. We postulate that stool treatment defined as drug treatment is counterproductive. Stool is not a standardized product that is produced in a factory, but a highly diverse and donor-specific substance of human origin (SoHO) delivered by healthy, usually unpaid, volunteer donors. Therefore, stool suspensions require suitable guidance of quality and safety measures comparable to guidance of other SoHO (blood, tissues, cells and organs) within the EU.If government authorities seek affordable and quality-assured FMT, a supportive regulatory framework, in combination with appropriate funding or reimbursement, is required for stool banks. This will not only guarantee broad access and safety of FMT, but also enable the future innovation of this new treatment strategy targeting the gut microbiota. If eventually future research results in the replacement of FMT by standardized mixtures of bacteria (or another yet undiscovered stool extract that could theoretically underly the clinical effects of FMT), these should indeed be regulated as a drug or pharmaceutical product.

The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown.We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range-based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore1 [range, 0 to 3] on any of the four Mayo scale components).The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P0.001 for both comparisons). Among patients who had a response to induction therapy with ustekinumab and underwent a second randomization, the percentage of patients who had clinical remission at week 44 was significantly higher among patients assigned to 90 mg of subcutaneous ustekinumab every 12 weeks (38.4%) or every 8 weeks (43.8%) than among those assigned to placebo (24.0%) (P = 0.002 and P0.001, respectively). The incidence of serious adverse events with ustekinumab was similar to that with placebo. Through 52 weeks of exposure, there were two deaths (one each from acute respiratory distress syndrome and hemorrhage from esophageal varices) and seven cases of cancer (one each of prostate, colon, renal papillary, and rectal cancer and three nonmelanoma skin cancers) among 825 patients who received ustekinumab and no deaths and one case of cancer (testicular cancer) among 319 patients who received placebo.Ustekinumab was more effective than placebo for inducing and maintaining remission in patients with moderate-to-severe ulcerative colitis. (Funded by Janssen Research and Development; UNIFI ClinicalTrials.gov number, NCT02407236.).

Objective GO-COLITIS aimed to measure the effectiveness of subcutaneous golimumab in tumour necrosis factor-α antagonist–naive patients with moderate to severe ulcerative colitis (UC) despite conventional treatment.\ud \ud Design GO-COLITIS was an open label, single arm, phase 4 study with a pragmatic design which reflected UK clinical practice. Adult patients were eligible if diagnosed with UC ≥3 months, partial Mayo score (PMS) 4–9. Patients received subcutaneous golimumab induction (200 mg initially and 100 mg at week 2) followed at week 6 by 50 mg or 100 mg (depending on weight) every 4 weeks until week 54 with a 12-week follow-up. Efficacy was measured by PMS at baseline, week 6, 30, 54 and 66. Health-related quality of life (HRQoL; Inflammatory Bowel Disease Questionnaire (IBDQ) and EuroQol Group 5 Dimensions Health Questionnaire (EQ-5D)) was assessed at baseline, week 6 and week 54. All safety adverse events (AEs) were recorded.\ud \ud Results 207 patients were enrolled and 205 received golimumab (full analysis set (FAS)205). At week 6, 68.8% (95% CI 62.0% to 75.1%) and 38.5% (95% CI 31.8% to 45.6%) of patients were in response and remission, respectively, using PMS. At the end of the induction phase, 140/141 patients in clinical response continued into the maintenance phase (Maintenance FAS). Sustained clinical response through week 54 was achieved in 51/205 (24.9%) of the FAS205 population and 51/140 (36.4%) of the Maintenance FAS population. Statistically significant improvements from baseline to week 6 were observed for the IBDQ total score and for each IBDQ domain score (bowel symptoms, emotional function, systemic symptoms and social function), as well as the EQ-5D index score and associated visual analogue scale score (p

Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.