Simon D. McLaughlin

Review article: restorative proctocolectomy, indications, management of complications and follow-up - a guide for gastroenterologists

Background  Restorative proctocolectomy with ileal pouch‐anal anastomosis is the procedure of choice for the majority of patients with ulcerative colitis who require surgery. Over 2500 patients in the UK have undergone restorative proctocolectomy. It is now increasingly being performed in district general hospitals as well as in specialist inflammatory bowel disease units. Gastroenterologists are increasingly involved in the management of patients following restorative proctocolectomy.

The bacteriology of pouchitis: a molecular phylogenetic analysis using 16S rRNA gene cloning and sequencing.

Objective:To identify, compare, and contrast the microbiota in patients with and without pouchitis after restorative proctocolectomy (RPC) for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Summary Background Data:Pouchitis is the most common complication following RPC. An abnormal host-microbial interaction has been implicated. We investigated the pouch microbiota in patients with and without pouchitis undergoing restorative proctocolectomy for UC and FAP. Methods:Mucosal pouch biopsies, taken from 16 UC (pouchitis 8) and 8 FAP (pouchitis 3) patients were analyzed to the species (or phylotype) level by cloning and sequencing of 3184 full-length bacterial 16S rRNA genes. Results:There was a significant increase in Proteobacteria (P = 0.019) and a significant decrease in Bacteroidetes (P = 0.001) and Faecalibacterium prausnitzii (P = 0.029) in the total UC compared with the total FAP cohort, but only limited differences were found between the UC nonpouchitis and pouchitis groups and the FAP pouchitis and nonpouchitis groups. Bacterial diversity in the FAP nonpouchitis group was significantly greater than in UC nonpouchitis (P = 0.019) and significantly greater in UC nonpouchitis compared with UC pouchitis (P = 0.009). No individual species or phylotype specifically associated with either UC or FAP pouchitis was found. Conclusions:UC pouch patients have a different, less diverse, gut microbiota than FAP patients. A further reduction in bacterial diversity but no significant dysbiosis occurs in those with pouchitis. The study suggests that a dysbiosis occurs in the ileal pouch of UC RPC patients which predisposes to, but may not directly cause, pouchitis.

Celiac disease: Management of persistent symptoms in patients on a gluten-free diet

AIM To investigate all patients referred to our center with non-responsive celiac disease (NRCD), to establish a cause for their continued symptoms. METHODS We assessed all patients referred to our center with non-responsive celiac disease over an 18-mo period. These individuals were investigated to establish the eitiology of their continued symptoms. The patients were first seen in clinic where a thorough history and examination were performed with routine blood work including tissue transglutaminase antibody measurement. They were also referred to a specialist gastroenterology dietician to try to identift any lapses in the diet and sources of hidden gluten ingestion. A repeat small intestinal biopsy was also performed and compared to biopsies from the referring hospital where possible. Colonoscopy, lactulose hydrogen breath testing, pancreolauryl testing and computed tomography scan of the abdomen were undertaken if the symptoms persisted. Their clinical progress was followed over a minimum of 2 years. RESULTS One hundred and twelve consecutive patients were referred with NRCD. Twelve were found not to have celiac disease (CD). Of the remaining 100 patients, 45% were not adequately adhering to a strict gluten-free diet, with 24 (53%) found to be inadvertently ingesting gluten, and 21 (47%) admitting non-compliance. Microscopic colitis was diagnosed in 12% and small bowel bacterial overgrowth in 9%. Refractory CD was diagnosed in 9%. Three of these were diagnosed with intestinal lymphoma. After 2 years, 78 patients remained well, eight had continuing symptoms, and four had died. CONCLUSION In individuals with NRCD, a remediable cause can be found in 90%: with continued gluten ingestion as the leading cause. We propose an algorithm for investigation.

Fecal Coliform Testing to Identify Effective Antibiotic Therapies for Patients With Antibiotic-Resistant Pouchitis

BACKGROUND & AIMS Empiric antibiotic therapy (eg, a combination of ciprofloxacin and metronidazole) is effective in treating the majority of patients with inflammation of the ileal reservoir (pouchitis). Unfortunately, up to 20% of patients develop refractory or rapidly relapsing disease. We developed a fecal sensitivity analysis to determine which antibiotics are most likely to be effective in patients who do not respond to empiric antibiotic therapy or have relapsed after long-term therapy. METHODS Fecal samples from 15 patients with active pouchitis (pouch disease activity index [PDAI], > or =7) who failed standard antibiotic treatment were inoculated onto Iso-sensitest agar. Antibiotic testing discs were added, incubated, and sensitivity patterns were recorded. Patients then were treated with antibiotics based on predicted sensitivity; PDAI scores were assessed 4 weeks later. Thirteen patients enrolled in the study had failed to enter remission after treatment with ciprofloxacin and metronidazole and 2 patients had relapsed after maintenance treatment with ciprofloxacin. RESULTS Antibiotic coliform sensitivity testing showed ciprofloxacin resistance in all samples, co-amoxiclav resistance in 4 samples, trimethoprim resistance in 11 samples, and cefixime resistance in 8 samples. All 15 patients were treated with an antibiotic to which their fecal coliforms were sensitive; 12 (80%) achieved clinical remission (PDAI score, 0). CONCLUSIONS Fecal coliform sensitivity analysis can identify effective antibiotic therapies for patients with antibiotic-resistant pouchitis. This targeted antibiotic approach is recommended in all patients who fail to respond to empiric antibiotic treatment or relapse after long-term antibiotic therapy.

Guide to endoscopy of the ileo-anal pouch following restorative proctocolectomy with ileal pouch-anal anastomosis; indications, technique, and management of common findings

&NA; Restorative proctocolectomy (RPC) with ileal pouch–anal anastomosis is the surgical procedure of choice for patients with ulcerative colitis (UC). It is also performed in selected patients with familial adenomatous polyposis (FAP). A significant proportion of patients will develop pouch dysfunction. Flexible pouchoscopy is the most important initial investigation in patients with dysfunction. It is also important in UC and FAP surveillance. The aim is to provide gastroenterologists with a clear understanding of the technique, indications, and diagnostic pitfalls when investigating RPC patients with flexible pouchoscopy. Flexible pouchoscopy for the investigation of RPC patients with pouch dysfunction has a high diagnostic yield, with most causes of pouch dysfunction identifiable during this procedure. The risk of developing dysplasia following RPC is low. Surveillance pouchoscopy is only recommended in those with FAP, those with a previous history of dysplasia or carcinoma, primary sclerosing cholangitis, those with a retained rectal cuff, and those with Type C histological changes. Flexible pouchoscopy is a useful first‐line investigation in patients with pouch dysfunction. It can be performed without sedation and has a high diagnostic yield; it is also important as part of surveillance in FAP and selected UC patients. (Inflamm Bowel Dis 2009)

The bacterial pathogenesis and treatment of pouchitis

Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis is the operation of choice for patients with ulcerative colitis. Pouchitis is the most common cause of pouch dysfunction. Although the pathogenesis of this disease is not well understood, bacteria have been implicated in the disease process. Numerous bacterial studies have been reported over the last 25 years with few unifying findings. In addition, many different treatments for pouchitis have been reported with varying results. Antibiotic treatment remains the most studied and is the mainstay of treatment. In this article we review the aetiology of pouchitis and the evidenced-based treatment options.

An open study of antibiotics for the treatment of pre‐pouch ileitis following restorative proctocolectomy with ileal pouch–anal anastomosis

Background  Pre‐pouch ileitis is a recently described condition which may occur following restorative proctocolectomy. Its aetiology remains unknown and only one study has reported the effect of treatment. We report a series of fourteen patients treated and followed up with repeat pouchoscopy.

Variable alterations of the microbiota, without metabolic or immunological change, following faecal microbiota transplantation in patients with chronic pouchitis

Faecal microbiota transplantation (FMT) is effective in the treatment of Clostridium difficile infection, where efficacy correlates with changes in microbiota diversity and composition. The effects of FMT on recipient microbiota in inflammatory bowel diseases (IBD) remain unclear. We assessed the effects of FMT on microbiota composition and function, mucosal immune response, and clinical outcome in patients with chronic pouchitis. Eight patients with chronic pouchitis (current PDAI ≥7) were treated with FMT via nasogastric administration. Clinical activity was assessed before and four weeks following FMT. Faecal coliform antibiotic sensitivities were analysed, and changes in pouch faecal and mucosal microbiota assessed by 16S rRNA gene pyrosequencing and 1H NMR spectroscopy. Lamina propria dendritic cell phenotype and cytokine profiles were assessed by flow cytometric analysis and multiplex assay. Following FMT, there were variable shifts in faecal and mucosal microbiota composition and, in some patients, changes in proportional abundance of species suggestive of a “healthier” pouch microbiota. However, there were no significant FMT-induced metabolic or immunological changes, or beneficial clinical response. Given the lack of clinical response following FMT via a single nasogastric administration our results suggest that FMT/bacteriotherapy for pouchitis patients requires further optimisation.

Exclusive elemental diet impacts on the gastrointestinal microbiota and improves symptoms in patients with chronic pouchitis.

BACKGROUND Treatment resistant chronic pouchitis causes significant morbidity. Elemental diet is effective treatment for Crohns disease. Since pouchitis shares some similarities to Crohns disease we hypothesised that elemental diet may be an effective treatment. METHOD Seven pouchitis patients (with ulcerative colitis) were studied. All had active pouchitis with a pouch disease activity index (PDAI) ≥7. Exclusion criteria were recent NSAIDs, antibiotics or probiotics. Sufficient elemental diet to achieve energy requirements was provided. Flexible-pouchoscopy was performed, and the Cleveland Global Quality of Life score (CGQoL), Pouch Disease Activity Index (PDAI) and BMI were recorded at baseline and following 28 days of elemental diet. Faecal samples were also collected at these time points and analysed for major bacterial groups using culture independent fluorescence in situ hybridisation. Data were analysed using Wilcoxons signed-rank test. RESULTS Following 28 days of exclusive elemental diet, median stool frequency decreased from 12 to 6 per day (p=0.028), median clinical PDAI decreased from 4 to 1 (p=0.039). There was no significant difference in quality of life scores or PDAI before and following treatment. There was a trend towards an increase in the concentration of Clostridium coccoides-Eubacterium rectale (median 7.9 to 8.5 log₁₀/g, p=0.08) following exclusive elemental diet. CONCLUSION Treatment with four weeks elemental diet appeared to improve the symptoms of chronic pouchitis in some patients but is not an effective strategy for inducing remission. Although a potential symptom modifier, elemental diet cannot be recommended for the routine treatment of active pouchitis.

An open study of maintenance antibiotic therapy for chronic antibiotic-dependent pouchitis: efficacy, complications and outcome

Aim  About 5% of restorative proctocolectomy (RPC) patients develop chronic antibiotic‐dependent pouchitis. These require antibiotic maintenance therapy. We report our experience in managing this patient group.