S. P. Costello

Faecal microbiota transplant for recurrent Clostridium difficile infection using long-term frozen stool is effective: clinical efficacy and bacterial viability data

Faecal microbial transplant (FMT) for recurrent Clostridium difficile infection (rCDI) is greatly facilitated by frozen stool banks. However, the effect of frozen storage of stool for greater than 2 months on the viability of stool bacteria is unknown and the efficacy of FMT is not clear.

Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis

Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods.

Establishing a Fecal Microbiota Transplant Service for the Treatment of Clostridium difficile Infection

Recurrent or refractory Clostridium difficile infection (CDI) has become an increasing problem in the past decade. Fecal microbiota transplant (FMT) is a highly efficacious treatment for recurrent CDI; however, a number of technical, logistical, and regulatory issues have hampered the development of an FMT capability at many hospitals. The development of a frozen stool bank of screened donor stool is an important step in the standardization of the procedure. This gives clinicians rapid access to thoroughly screened donor stool when needed, without the ethical and logistical problems associated with patient-selected donors. We describe the practicalities of establishing such a service using a stool bank of prescreened donor stool including detail regarding donor recruitment and screening, stool preparation, and delivery of the FMT.

Role of FDG-PET in surgical management of patients with colorectal liver metastases.

Background:   [ 18F]‐fluorodeoxyglucose positron emission tomography (FDG‐PET) is reported to change the management in 20−56% of patients with recurrent or metastatic colorectal cancer. It is not clear if FDG‐PET has a role in all such patients or only a subgroup. The aim of the present study was to assess the influence of FDG‐PET on the surgical management of patients with known or suspected colorectal liver metastases.

Fecal Microbiota Transplant for Clostridium difficile Colitis–Induced Toxic Megacolon

panied by major systemic disturbance ( 1 ). It occurs as a complication in up to 5% of cases of Clostridium diffi cile (CD)-induced colitis ( 2–4 ). Th e standard treatment for TMC is subtotal colectomy ( 5 ). Here we report the fi rst case of fecal microbiota transplant (FMT) as an eff ective treatment for TMC without surgery. A 69-year-old woman was transferred to our institution from a renal dialysis center with fever, abdominal pain, and 4 days of profuse watery diarrhea. Th ree weeks prior she had received oral vancomycin for a severe episode of CD colitis following a course of oral fl ucloxacillin for cellulitis. Her past medical history included hemodialysis for end-stage renal failure secondary to polycystic kidney disease, polymyalgia rheumatica, cardiomyopathy, hypertension, and the post-polio syndrome. On admission she was febrile and tachycardic. Her abdomen was soft with bowel sounds present, but there was diffuse tenderness over the lower abdomen without guarding. CT abdomen showed marked wall thickening throughout the colon without dilatation. Flexible sigmoidoscopy showed pseudomembranous colitis of the rectum and sigmoid colon ( Figure 1 ). CD toxin was positive by PCR. Despite oral vancomycin (250 mg 6 hourly), her condition deteriorated over the following 3 days with ongoing fever, frequent diarrhea, and diff use abdominal pain. On day 4 her bowels did not open and she developed shock (blood pressure 76/30 mm Hg, pulse 110 b.p.m.). She was disease from irritable bowel syndrome . Eur J Clin Invest 2013 ; 43 : 1147 – 55 . 6. Tursi A , Elisei W , Picchio M et al. Moderate to severe and prolonged left lower-abdominal pain is the best symptom characterizing symptomatic uncomplicated diverticular disease of the colon: a comparison with fecal calprotectin in clinical setting . J Clin Gastroenterol 2014 ; 49 : 218 – 21 . 7. Tursi A , Brandimarte G , Elisei W et al. Faecal calprotectin in colonic diverticular disease: a case-control study . Int J Colorectal Dis 2009 ; 24 : 49 – 55.

Opioidergic effects on enteric and sensory nerves in the lower GI tract: basic mechanisms and clinical implications.

Opioids are one of the most prescribed drug classes for treating acute pain. However, chronic use is often associated with tolerance as well as debilitating side effects, including nausea and dependence, which are mediated by the central nervous system, as well as constipation emerging from effects on the enteric nervous system. These gastrointestinal (GI) side effects limit the usefulness of opioids in treating pain in many patients. Understanding the mechanism(s) of action of opioids on the nervous system that shows clinical benefit as well as those that have unwanted effects is critical for the improvement of opioid drugs. The opioidergic system comprises three classical receptors (μ, δ, κ) and a nonclassical receptor (nociceptin), and each of these receptors is expressed to varying extents by the enteric and intestinal extrinsic sensory afferent nerves. The purpose of this review is to discuss the role that the opioidergic system has on enteric and extrinsic afferent nerves in the lower GI tract in health and diseases of the lower GI tract, particularly inflammatory bowel disease and irritable bowel syndrome, and the implications of opioid treatment on clinical outcomes. Consideration is also given to emerging developments in our understanding of the immune system as a novel source of endogenous opioids and the mechanisms underlying opioid tolerance, including the potential influence of opioid receptor splice variants and heteromeric complexes.

Compassionate access anti-tumour necrosis factor-α therapy for ulcerative colitis in Australia: the benefits to patients

The efficacy of infliximab has been demonstrated in patients with both acute severe and moderate‐severe ulcerative colitis (UC). However, there is a need for ‘real‐life data’ to ensure that conclusions from trial settings are applicable in usual care. We therefore examined the national experience of anti‐tumour necrosis factor‐α (TNF‐α) therapy in UC.

Limited uptake of ulcerative colitis ‘treat to target' recommendations in real-world practice

A “treat‐to‐target” approach has been proposed for ulcerative colitis (UC), with a target of combined clinical and endoscopic remission. The aim of the study was to evaluate the extent to which proposed targets are achieved in real‐world care, along with clinician perceptions and potential challenges.

Dose tailoring of anti-tumour necrosis factor-alpha therapy delivers useful clinical efficacy in Crohn disease patients experiencing loss of response

‘Dose tailoring’ of anti‐tumour necrosis factor alpha (TNF‐α) therapy in Crohn disease (CD), by dose escalation, or shortening of dosing intervals, has been suggested to regain clinical response following a flare in a proportion of patients. However, reported outcome data are sparse and none exists from Australia.

Editorial: untangling symptoms from mucosal healing in UC--a note of caution for patient-reported outcomes.

Treatment in ulcerative colitis (UC) has evolved such that, in the era of biologics, striving for ‘deep remission’ is the aspiration. Emerging ‘treat-to-target’ consensus statements propose measuring remission with both patient-reported outcomes (PROs) and endoscopy. While this may be the ideal, it will pose significant challenges as evidenced by Jharap et al.. As illustrated, clinical symptoms are frequently discordant with objective inflammation. Put simply, endoscopic mucosal healing does not necessarily mean symptomatic relief, nor vice versa. On review of the ULTRA 1 and 2 studies, symptoms and PROs correlated only moderately with mucosal healing. Although most patients (87%) with mucosal healing had no rectal bleeding, turning this around, the positive predictive value of no rectal bleeding for a Mayo endoscopic subscore of 0 or 1 was only 69%, and only 26% for an endoscopic subscore of 0. Of note, stool frequency rarely normalised in patients with mucosal healing – occurring in only 29% with an endoscopic subscore of 0. Furthermore, very few patients (9% at week 8) reported both absent rectal bleeding and normal stool frequency, despite a much higher proportion achieving mucosal healing. This disparity between clinical and objective measures of disease activity is by no means novel. However, the importance now is that the Food and Drug Administration (FDA) is moving towards composite trial endpoints for drug development, incorporating both PRO’s and endoscopic activity. This approach has risks, as there is the potential to impair interpretation of the efficacy of anti-inflammatory drug therapies as, even when mucosal healing is achieved, symptoms are common and may not reflect inflammation. Moreover, incorporating PRO’s due to causes other than inflammation, such as post-inflammatory nerve sensitisation, may lead to otherwise effective therapies failing efficacy outcomes. A key concept is that both symptoms and mucosal inflammation should be assessed as a part of disease activity evaluation in UC. However, these outcomes should not be regarded as tied. Endoscopic healing is certainly an important target in UC, as it associates with better outcomes 6 and histological remission may yield additional benefit. Endoscopic assessment of inflammatory burden is therefore crucial and ‘false’ reassurance from an absence of symptoms may lead to insufficient treatment. Whilst symptoms matter to patients, not all symptoms are due to inflammation. This disconnect should be acknowledged as intensification of anti-inflammatory therapy is not likely to improve symptoms in those with mucosal healing, and may put them at excess risk. Jharap et al. have demonstrated that in patients with mucosal healing, these likely functional (post-inflammatory) symptoms improved over time but had not normalised in the majority by 52 weeks. Therapies targeting functional symptoms should therefore be considered, and expectation matching and awareness of the time lag to symptomatic improvement may also negate the need for additional therapy. Both mucosal healing and PRO’s are important, but distinct, therapeutic outcomes in UC. Some authors propose that overall disease burden be conceptualised into three domains: the impact of the disease on the patient, measureable inflammatory burden, and disease course. This approach better represents the interplay between distinct yet overlapping components of UC, and should lead to better-informed decision-making than