Normal Ileal Mucus Is Inadequate for Epithelial Protection in Ileal Pouch Mucosa.

BACKGROUND: Clinical, nonspecific pouchitis is common after restorative proctocolectomy for ulcerative colitis, but its cause is unknown. A possible lack of protection for the ileal mucosa in its role as a reservoir for colonic-type bacteria may be the missing piece in defining the causes of pouchitis. OBJECTIVE: The study aimed to review the causes of pouchitis and introduce the hypothesis that inadequate mucus protection in the pouch, combined with a predisposition to abnormal inflammation, is the most common cause of nonspecific pouchitis. DATA SOURCES: Review of PubMed and MEDLINE for articles discussing pouchitis and intestinal mucus. STUDY SELECTION: Studies published from 1960 to 2023. The main search terms were "pouchitis," and "intestinal mucus," whereas Boolean operators were used with multiple other terms to refine the search. Duplicates and case reports were excluded. MAIN OUTCOME MEASURES: Current theories about the cause of pouchitis, descriptions of the role of mucus in the physiology of intestinal protection, and evidence of the effects of lack of mucus on mucosal inflammation. RESULTS: The crossreference of "intestinal mucus" with "pouchitis" produced 9 references, none of which discussed the role of mucus in the development of pouchitis. Crossing "intestinal mucus" with "pouch" resulted in 32 articles, combining "pouchitis" with "barrier function" yielded 37 articles, and "pouchitis" with "permeability" yielded only 8 articles. No article discussed the mucus coat as a barrier to bacterial invasion of the epithelium or mentioned inadequate mucus as a factor in pouchitis. However, an ileal pouch produces a colonic environment in the small bowel, and the ileum lacks the mucus protection needed for this sort of environment. This predisposes pouch mucosa to bacterial invasion and chronic microscopic inflammation that may promote clinical pouchitis in patients prone to an autoimmune response. LIMITATIONS: No prior studies address inadequate mucus protection and the origin of proctitis. There is no objective way of measuring the autoimmune tendency in patients with ulcerative colitis. CONCLUSIONS: Studies of intestinal mucus in the ileal pouch and its association with pouchitis are warranted.

A Systematic Review and Meta-analysis of Randomized Clinical Trials on the Prevention and Treatment of Pouchitis after Ileoanal Pouch Anastomosis.

BACKGROUND: This systematic review explored different medications and methods for prevention and treatment of pouchitis after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS: PubMed, Scopus, and Web of Science were searched for randomized clinical trials that assessed prevention or treatment of pouchitis. The systematic review was reported in line with updated 2020 PRISMA guidelines. Risk of bias in the trials included was assessed using the ROB-2 tool and certainty of evidence was assessed using GRADE. The main outcomes were the incidence of new pouchitis episodes in the preventative studies and resolution or improvement of active pouchitis in the treatment studies. RESULTS: Fifteen randomized trials were included. A meta-analysis of 7 trials on probiotics revealed significantly lower odds of pouchitis with the use of probiotics (RR: 0.26, 95% CI: 0.16-0.42, I2 = 20%, p < 0.001) and similar odds of adverse effects to placebo (RR: 2.43, 95% CI: 0.11-55.9, I2 = 0, p = 0.579). One trial investigated the prophylactic role of allopurinol in preventing pouchitis and found a comparable incidence of pouchitis in the two groups (31% vs 28%; p = 0.73). Seven trials assessed different treatments for active pouchitis. One recorded the resolution of pouchitis in all patients treated with ciprofloxacin versus 67% treated with metronidazole. Both budesonide enema and oral metronidazole were associated with similar significant improvement in pouchitis (58.3% vs 50%, p = 0.67). Rifaximin, adalimumab, fecal microbiota transplantation, and bismuth carbomer foam enema were not effective in treating pouchitis. CONCLUSIONS: Probiotics are effective in preventing pouchitis after IPAA. Antibiotics, including ciprofloxacin and metronidazole, are likely effective in treating active pouchitis.

Systematic review and meta-analysis of randomised controlled trials: Medical therapies for the treatment and prevention of pouchitis.

BACKGROUND AND AIMS: We conducted a systematic review to assess medical therapy for the treatment and prevention of pouchitis. METHODS: Randomised controlled trials (RCTs) of medical therapy in adults with or without pouchitis were searched to March 2022. Primary outcomes included clinical remission/response, maintenance of remission and prevention of pouchitis. RESULTS: Twenty RCTs (N = 830) were included. Acute pouchitis: One study compared ciprofloxacin with metronidazole. At 2 weeks, 100% (7/7) of ciprofloxacin participants achieved remission, compared with 67% (6/9) of metronidazole participants (RR: 1.44, 95% CI: 0.88-2.35, very low certainty evidence). One study compared budesonide enemas with oral metronidazole. Fifty percent (6/12) of budesonide participants achieved remission compared with 43% (6/14) of metronidazole participants (RR: 1.17, 95% CI: 0.51-2.67, low certainty evidence). Chronic pouchitis: Two studies (n = 76) assessed De Simone Formulation. Eighty-five percent (34/40) of De Simone Formulation participants maintained remission at 9-12 months compared with 3% (1/36) placebo participants (RR: 18.50, 95% CI: 3.86-88.56, moderate certainty evidence). One study assessed vedolizumab. Thirty-one percent (16/51) of vedolizumab participants achieved clinical remission at 14 weeks compared with 10% (5/51) of placebo participants (RR: 3.20, 95% CI: 1.27-8.08, moderate certainty evidence). PROPHYLAXIS: Two studies assessed De Simone Formulation. Ninety percent (18/20) of De Simone Formulation participants did not develop pouchitis compared with 60% (12/20) of placebo participants (RR: 1.50, 95% CI: 1.02-2.21, moderate certainty evidence). CONCLUSIONS: Apart from vedolizumab and the De Simone formulation, the effects of other medical interventions for pouchitis are uncertain.

The efficacy of probiotics on the prevention of pouchitis for patients after ileal pouch-anal anastomosis: A meta-analysis.

BACKGROUND: To date, a few studies indicated that probiotics are beneficial to pouchitis, but no meta-analyses summarized the outcomes of probiotics in pouchitis in detail. OBJECTIVE: This meta-analysis discusses probiotics in the prevention of pouchitis for patients after ileal pouch-anal anastomosis (IPAA) and the relationship between probiotics preventive effect and the duration of therapy and history. METHODS: PubMed, EMBASE and Cochrane Library databases were searched from inception until February 2022. Risk ratio (RR), mean difference (MD) and their 95% confidence interval (CI) were analyzed by Review Manager 5.3. The subgroup analysis was also performed to explore the agent for influencing outcomes. RESULTS: A total of 8 studies were included in this meta-analysis. The incidence of pouchitis in probiotics was significantly lower than that in the control (RR = 0.19, 95%CI [0.12, 0.32], P⁢ï⁢»â¢ 0.00001), and the PDAI (pouchitis disease activity index) in probiotics was also significantly lower (MD =-5.65, 95%CI [-9.48, -1.83]). After the subgroup analysis, we found that probiotics work better in the short-term (RR = 0.12, 95%CI [0.04, 0.40], P= 0.0004), but may not achieve the desired effect in the long-term (RR = 1.20, 95%CI [0.40, 3.60], P= 0.75). CONCLUSIONS: Probiotics are beneficial in the prevention of pouchitis after IPAA, especially in the short-term.

Network meta-analysis: efficacy of treatment for acute, chronic, and prevention of pouchitis in ulcerative colitis.

INTRODUCTION: Pouchitis is a clinically significant complication of ileal pouch-anal anastomosis. There is a paucity of head-to-head comparisons between treatments and no data were available about how each treatment rank against each other. A network meta-analysis of the different treatments used for acute, chronic and prevention of pouchitis was conducted. METHODS: Biomedical databases and the Cochrane Central registry were searched between 1978 and 2021 for randomised controlled trials examining treatment for acute, chronic and prevention of pouchitis. A network meta-analysis was performed using the frequentist model with pooled relative risks and P scores used to rank treatments. RESULTS: 18 studies were included from a screen of 4291 abstracts. When compared to placebo, rifaximin was found to be the best antibiotic for acute pouchitis whereas ciprofloxacin ranked highest against metronidazole. For chronic pouchitis, metronidazole followed by probiotics was statistically significant and effective treatments in inducing remission although metronidazole had the highest adverse events. Adalimumab and bismuth were also found to be superior to placebo; however, they did not reach statistical significance. Probiotics proved superior to placebo in the prevention of pouchitis development. CONCLUSIONS: This is the first network meta-analysis which compares the efficacy and tolerability of treatments in the management and prevention of acute and chronic pouchitis. It confirms that antimicrobial therapy remains the mainstay of treatment and adds weight to current guideline recommendations. Our results demonstrate that rifaximin and probiotics may deserve a more prominent role. While biologics are starting to show promise, large-scale head-to-head comparisons are warranted to validate the efficacy of these treatments.

Treatment of pouchitis, Crohn's disease, cuffitis, and other inflammatory disorders of the pouch: consensus guidelines from the International Ileal Pouch Consortium.

Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches.

Review article: the impact of diet on ileoanal pouch function and on the pathogenesis of pouchitis.

BACKGROUND: There is expanding interest in the role that diet plays in ileoanal pouch function and in the pathogenesis of pouchitis. AIMS: To present a narrative review of published literature regarding the relationship of diet with pouch function and the pathogenesis of pouchitis, and to provide potentially beneficial dietary strategies. METHODS: Current relevant literature was summarised and critically examined. RESULTS: Dietary components influence pouch function via their effect on upper gastrointestinal transit, small bowel water content and the structure and fermentative activity of the pouch microbiota. FODMAPs in fruits and vegetables appear to affect pouch function the most, with intake positively associated with increased stool frequency and reduced consistency. Dietary factors that influence the pathogenesis of pouchitis appear different and, at times, opposite to those better for optimising function. For example, risk of pouchitis appears to be inversely associated with intake of fruits. The food components mechanistically responsible for this observation are not known, but a rich supply of fermentable fibres and micronutrients in such foods might play a beneficial role via modulation of microbial community structure (such as increasing diversity and/or changing microbial communities to favour 'protective' over 'pathogenic' bacteria) and function and/or anti-inflammatory effects. CONCLUSION: Available data are weak but suggest tailoring dietary recommendations according to pouch phenotype/behaviour and pouchitis risk might improve outcomes. More sophisticated dietary strategies that utilise the physiological and pathophysiological effects of dietary components on ileoanal pouches have potential to further improve outcomes. Well designed, adequately powered studies are required.

Recommendations of the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on pouchitis in ulcerative colitis. Part 2: Treatment. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre la reservoritis en la colitis ulcerosa. Parte 2: Tratamiento.

Pouchitis treatment is a complex entity that requires a close medical and surgical relationship. The elective treatment for acute pouchitis is antibiotics. After a first episode of pouchitis it is recommended prophylaxis therapy with a probiotic mix, nevertheless it is not clear the use of this formulation for preventing a first episode of pouchitis after surgery. First-line treatment for chronic pouchitis is an antibiotic combination. The next step in treatment should be oral budesonide. Selected cases of severe, chronic refractory pouchitis may benefit from biologic agents, and anti-TNF α should be recommended as the first option, leaving the new biologicals for multi-refractory patients. Permanent ileostomy may be an option in severe refractory cases to medical treatment.

Adherence to the Mediterranean diet is associated with decreased fecal calprotectin in patients with ulcerative colitis after pouch surgery.

BACKGROUND: Mediterranean diet (MED) is associated with health benefits, yet scarce data exist regarding the role of MED in inflammatory bowel diseases (IBD). Herein, we aimed to evaluate the association between MED and inflammatory markers in patients with IBD after pouch surgery. METHODS: Consecutive patients after pouch surgery due to ulcerative colitis (UC) were recruited at a comprehensive pouch clinic. Adherence to MED was calculated according to MED score, ranging from 0 (low adherence) to 9 (high adherence), based on food-frequency questionnaires. Pouch behavior was defined as normal pouch (NP) or pouchitis based on Pouchitis Disease Activity Index (PDAI) and disease activity was defined as active or inactive. C-reactive protein (CRP) and fecal calprotectin were assessed. RESULTS: Overall 153 patients were enrolled (male gender 47%; mean age 46 ± 14 years; mean pouch age 9.5 ± 7 years). MED scores were higher in patients with normal vs. elevated CRP and calprotectin levels (4.6 ± 1.8 vs. 4.4 ± 1.6, p = 0.28; 4.8 ± 1.8 vs. 4.07 ± 1.7, p < 0.05, respectively). In a multivariate regression, MED score was associated with decreased calprotectin levels (OR = 0.74 [0.56-0.99]). Adherence to MED was associated with dietary fiber and antioxidants intake. Finally, in a subgroup of patients with NP followed up for 8 years, higher adherence to MED trended to be inversely associated with the onset of pouchitis (log rank = 0.17). CONCLUSIONS: In patients with UC after pouch surgery, adherence to MED is associated with decreased calprotectin levels. Thus, MED may have a role in modifying intestinal inflammation in IBD.

Prolyl Hydroxylase Inhibition Mitigates Pouchitis.

BACKGROUND: Pouchitis is the most common long-term complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) or familial adenomatous polyposis (FAP), which can eventually progress to pouch failure, necessitating permanent stoma construction. Hypoxia-inducible transcription factor prolyl hydroxylase-containing enzymes (PHD1, PHD2, and PHD3) are molecular oxygen sensors that control adaptive gene expression through hypoxia-inducible factor (HIF). Emerging evidence supports PHDs as being therapeutic targets in intestinal inflammation. However, pharmacological inhibition of PHDs has not been validated as a treatment strategy in pouchitis. METHODS: PHD1-3 mRNA and protein expression were analyzed in mucosal pouch and prepouch ileal patient biopsies. After establishment of a preclinical IPAA model in rats, the impact of the pan-PHD small-molecule inhibitor dimethyloxalylglycine (DMOG) on dextran sulfate sodium (DSS)-induced pouchitis was studied. Clinical and molecular parameters were investigated. RESULTS: PHD1, but not PHD2 or PHD3, was overexpressed in pouchitis in biopsies of patients with IPAA for UC but not FAP. In addition, PHD1 expression correlated with disease activity. DMOG treatment profoundly mitigated DSS-induced pouchitis in a rodent IPAA model. Mechanistically, DMOG restored intestinal epithelial barrier function by induction of tight junction proteins zona occludens-1 and claudin-1 and alleviation of intestinal epithelial cell apoptosis, thus attenuating pouch inflammation. CONCLUSIONS: Together, these results establish a strong therapeutic rationale for targeting PHD1 with small-molecule inhibitors in pouchitis after IPAA for UC.

Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis.

BACKGROUND: Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (UC). OBJECTIVES: The primary objective was to determine the efficacy and safety of medical therapies for prevention or treatment of acute or chronic pouchitis. SEARCH METHODS: We searched MEDLINE, Embase and CENTRAL from inception to 25 July 2018. We also searched references, trials registers, and conference proceedings. SELECTION CRITERIA: Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for UC were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was evaluated using GRADE. The primary outcome was clinical improvement or remission in participants with acute or chronic pouchitis, or the proportion of participants with no episodes of pouchitis after IPAA. Adverse events (AEs) was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. MAIN RESULTS: Fifteen studies (547 participants) were included. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis. Three studies were low risk of bias. Three studies were high risk of bias and the other studies were unclear. Acute pouchitis: All ciprofloxacin participants (7/7) achieved remission at two weeks compared to 33% (3/9) of metronidazole participants (RR 2.68, 95% CI 1.13 to 6.35, very low certainty evidence). No ciprofloxacin participants (0/7) had an AE compared to 33% (3/9) of metronidazole participants (RR 0.18, 95% CI 0.01 to 2.98; very low certainty evidence). AEs included vomiting, dysgeusia or transient peripheral neuropathy. Forty-three per cent (6/14) of metronidazole participants achieved remission at 6 weeks compared to 50% (6/12) of budesonide enema participants (RR 0.86, 95% CI 0.37 to 1.96, very low certainty evidence). Fifty per cent (7/14) of metronidazole participants improved clinically at 6 weeks compared to 58% (7/12) of budesonide enema participants (RR 0.86, 95% CI 0.42 to 1.74, very low certainty evidence). Fifty-seven per cent (8/14) of metronidazole participants had an AE compared to 25% (3/12) of budesonide enema participants (RR 2.29, 95% CI 0.78 to 6.73, very low certainty evidence). AEs included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. Twenty-five per cent (2/8) of rifaximin participants achieved remission at 4 weeks compared to 0% (0/10) of placebo participants (RR 6.11, 95% CI 0.33 to 111.71, very low certainty evidence). Thirty-eight per cent (3/8) of rifaximin participants improved clinically at 4 weeks compared to 30% (3/10) of placebo participants (RR 1.25, 95% CI 0.34 to 4.60, very low certainty evidence). Seventy-five per cent (6/8) of rifaximin participants had an AE compared to 50% (5/10) of placebo participants (RR 1.50, 95% CI 0.72 to 3.14, very low certainty evidence). AEs included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. Ten per cent (1/10) of Lactobacillus GG participants improved clinically at 12 weeks compared to 0% (0/10) of placebo participants (RR 3.00, 95% CI 0.14 to 65.90, very low certainty evidence). Chronic pouchitis: Eighty-five per cent (34/40) of De Simone Formulation (a probiotic formulation) participants maintained remission at 9 to 12 months compared to 3% (1/36) of placebo participants (RR 20.24, 95% CI 4.28 to 95.81, 2 studies; low certainty evidence). Two per cent (1/40) of De Simone Formulation participants had an AE compared to 0% (0/36) of placebo participants (RR 2.43, 95% CI 0.11 to 55.89; low certainty evidence). AEs included abdominal cramps, vomiting and diarrhea. Fifty per cent (3/6) of adalimumab patients achieved clinical improvement at 4 weeks compared to 43% (3/7) of placebo participants (RR, 1.17, 95% CI 0.36 to 3.76, low certainty evidence). Sixty per cent (6/10) of glutamine participants maintained remission at 3 weeks compared to 33% (3/9) of butyrate participants (RR 1.80, 95% CI 0.63 to 5.16, very low certainty evidence). Forty-five per cent (9/20) of patients treated with bismuth carbomer foam enema improved clinically at 3 weeks compared to 45% (9/20) of placebo participants (RR 1.00, 95% CI 0.50 to 1.98, very low certainty evidence). Twenty-five per cent (5/20) of participants in the bismuth carbomer foam enema group had an AE compared to 35% (7/20) of placebo participants (RR 0.71, 95% CI 0.27 to 1.88, very low certainty evidence). Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain. PREVENTION: At 12 months, 90% (18/20) of De Simone Formulation participants had no episodes of acute pouchitis compared to 60% (12/20) of placebo participants (RR 1.50, 95% CI 1.02 to 2.21, low certainty evidence). Another study found 100% (16/16) of De Simone Formulation participants had no episodes of acute pouchitis at 12 months compared to 92% (11/12) of the no treatment control group (RR 1.10, 95% 0.89 to 1.36, very low certainty evidence). Eighty-six per cent (6/7) of Bifidobacterium longum participants had no episodes of acute pouchitis at 6 months compared to 60% (3/5) of placebo participants (RR 1.43, 95% CI 0.66 to 3.11, very low certainty evidence). Eleven per cent (1/9) of Clostridium butyricum MIYAIRI participants had no episodes of acute pouchitis at 24 months compared to 50% (4/8) of placebo participants (RR 0.22, 95% CI 0.03 to 1.60, very low certainty evidence). Forty-six per cent (43/94) of allopurinol participants had no episodes of pouchitis at 24 months compared to 43% (39/90) of placebo participants (RR 1.06, 95% CI 0.76 to 1.46; low certainty evidence). Eighty-one per cent (21/26) of tinidazole participants had no episodes of pouchitis over 12 months compared to 58% (7/12) of placebo participants (RR 1.38, 95% CI 0.83 to 2.31, very low certainty evidence). AUTHORS' CONCLUSIONS: The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.

ANTECEDENTES: La reservoritis ocurre en aproximadamente el 50% de los pacientes después de la anastomosis entre la bolsa ileal y el ano (IPAA, por sus siglas en inglés) para la colitis ulcerosa crónica (CU). OBJETIVOS: El objetivo primario fue determinar la eficacia y la seguridad de los tratamientos médicos para la prevención o el tratamiento de la reservoritis aguda o crónica. MÉTODOS DE BÚSQUEDA: Se hicieron búsquedas en MEDLINE, Embase y en CENTRAL, desde su inicio hasta el 25 julio 2018. También se buscó en las listas de referencias, registros de ensayos en curso y actas de congresos. CRITERIOS DE SELECCIÓN: Se consideraron para inclusión los ensayos controlados aleatorios de prevención o tratamiento de la reservoritis aguda o crónica en adultos a los que se les realiza IPAA para la CU. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos autores de la revisión, de forma independiente, evaluaron la elegibilidad de los estudios, extrajeron los datos y analizaron el riesgo de sesgo. La calidad de la evidencia se evaluó mediante los criterios GRADE. El resultado primario la mejoría clínica o remisión en los pacientes con reservoritis aguda o crónica, o la proporción de pacientes sin episodios de reservoritis después de IPAA. Se incluyeron los eventos adversos como resultado secundario. Se calculó el cociente de riesgos (CR) y el intervalo de confianza (IC) del 95% correspondiente para los resultados dicotómicos. RESULTADOS PRINCIPALES: Se incluyeron 15 estudios (547 participantes). Cuatro estudios evaluaron el tratamiento de la reservoritis aguda. Cinco estudios evaluaron el tratamiento de la reservoritis crónica. Seis estudios evaluaron la prevención de la reservoritis. Tres estudios presentaban bajo de riesgo de sesgo. En tres estudios el riesgo fue alto y en los otros estudios fue poco claro. reservoritis aguda: Todos los pacientes que recibieron ciprofloxacina (7/7) lograron la remisión a las dos semanas en comparación con el 33% (3/9) de los pacientes que recibieron metronidazol (CR 2,68; IC del 95%: 1,13 a 6,35) (evidencia de certeza muy baja). Ninguno de los participantes que recibieron ciprofloxacina (0/7) presentó eventos adversos en comparación con el 33% (3/9) de los participantes que recibieron metronidazol (CR0,18; IC del 95%: 0,01 a 2,98; evidencia de certeza muy baja). Los eventos adversos incluyeron vómitos, disgeusia o neuropatía periférica transitoria. El 40% (6/14) de los participantes que recibieron metronidazol lograron la remisión a las 6 semanas en comparación con el 50% (6/12) de los participantes que recibieron enema de budesonida (CR 0,86; IC del 95%: 0,37 a 1,96; evidencia de certeza muy baja). El 50% (7/14) de los participantes del grupo de metronidazol mejoraron clínicamente a las 6 semanas en comparación con el 58% (7/12) de los participantes que recibieron enema de budesonida (CR 0,86; IC del 95%: 0,42 a 1,74; evidencia de certeza muy baja). El 57% (8/14) de los participantes del grupo de metronidazol presentaron eventos adversos en comparación con el 25% (3/12) de los participantes que recibieron enema de budesonida (CR 2,29; IC del 95%: 0,78 a 6,73; evidencia de certeza muy baja). Los eventos adversos incluyeron anorexia, náuseas, cefalea, astenia, sabor metálico, vómitos, parestesia y depresión. El 25% (2/8) de los participantes que recibieron rifaximina lograron la remisión a las 4semanas en comparación con el 0% (0/10) de los participantes que recibieron placebo (CR 6,11; IC del 95%: 0,33 a 111,71; evidencia de certeza muy baja). El 38% (3/8) de los participantes del grupo de rifaximina mejoraron clínicamente a las 4 semanas en comparación con el 30% (3/10) de los participantes que recibieron placebo (CR 1,25; IC del 95%: 0,34 a 4,60; evidencia de certeza muy baja). El 75% (6/8) de los participantes del grupo de rifaximina presentaron un evento adverso en comparación con el 50% (5/10) de los participantes que recibieron placebo (CR 1,50; IC del 95%: 0,72 a 3,14; evidencia de certeza muy baja). Los eventos adversos incluyeron diarrea, flatulencias, náuseas, proctalgia, vómitos, sed, cándida, infección de las vías respiratorias superiores, aumento de las enzimas hepáticas y cefalea en racimos. El 10% (1/10) de los participantes del grupo de Lactobacillus GGmejoraron clínicamente a las 12 semanas en comparación con el 0% (0/10) de los participantes que recibieron placebo (CR 3,00; IC del 95%: 0,14 a 65,90; evidencia de certeza muy baja). Reservoritis crónica: El 85% (34/40) de los pacientes que recibieron la formulación De Simone mantuvieron la remisión de nueve a 12 meses en comparación con el 3% (1/36) de los participantes que recibieron placebo (CR 20,24; IC del 95%: 4,28 a 95,81; dos estudios; evidencia de certeza baja). El 2% (1/40) de los participantes que recibieron la fórmula De Simone presentaron un evento adverso, en comparación con el 0% (0/36) de los participantes que recibieron placebo (CR 2,43; IC del 95%: 0,11 a 55,89; evidencia de certeza baja). Los efectos secundarios incluyeron cólicos abdominales, vómitos y diarrea. Cuarenta y tres por ciento (3/6) de los pacientes en el grupo de adalimumab lograron una mejoría clínica a las 4 semanas en comparación con un 43 (3/7) de los pacientes del grupo de placebo (CR 1,17, IC del 95%: 0,36 a 3,76; evidencia de certeza baja). El 60% (6/10) de los participantes del grupo de glutamina mantuvieron la remisión a las 3 semanas en comparación con el 33% (3/9) de los participantes que recibieron placebo (CR 1,80; IC del 95%: 0,63 a 5,16; evidencia de certeza muy baja). El 45% (9/20) de los participantes del grupo de enema de espuma de carbómero de bismuto mejoraron clínicamente a las 3 semanas en comparación con el 45% (9/20) de los participantes que recibieron placebo (CR 1,00; IC del 95%: 0,50 a 1,98; evidencia de certeza muy baja). El 25% (5/20) de los participantes del grupo de aceite de cannabis presentaron un evento adverso en comparación con el 35% (7/20) de los participantes que recibieron placebo (CR 0,71; IC del 95%: 0,27 a 1,88; evidencia de certeza muy baja). Los eventos adversos incluyeron diarrea, síntomas de empeoramiento, cólicos, sinusitis y dolor abdominal. Prevención: A los 12 meses, el 90% (18/20) de los pacientes que recibieron la formulación De Simone no presentaron episodios de reservoritis aguda en comparación con el 60% (12/20) de los pacientes que recibieron placebo (CR 1,50: IC del 95%: 1,02 a 2,21; evidencia de certeza baja). Otro estudio halló que el 100% (16/16) de los participantes que recibieron la fórmula De Simone no presentaron episodios de reservoritis aguda a los 12 meses en comparación con el 92% (11/12) de los pacientes del grupo control sin tratamiento (CR 1,10: IC del 95%: 0,89 a 1,36; evidencia de certeza muy baja). El 86% (6/7) de los participantes del grupo de Bifidobacterium longum no presentaron episodios de reservoritis aguda a los 6 meses en comparación con el 60% (3/5) de los participantes que recibieron placebo (CR 1,43; IC del 95%: 0,66 a 3,11; evidencia de certeza muy baja). El 11% (1/9) de los participantes del grupo de Clostridium butyricum MIYAIRI no presentaron episodios de reservoritis aguda a los 24 meses en comparación con el 50% (4/8) de los participantes que recibieron placebo (CR 0,22; IC del 95%: 0,03 a 1,60; evidencia de certeza muy baja). El 46% (43/94) de los participantes del grupo de alopurinol no presentaron episodios de reservoritis a los 24 meses en comparación con el 43% (39/90) de los participantes que recibieron placebo (CR1,06; IC del 95%: 0,76 a 1,46; evidencia de certeza baja). El 81% (21/26) de los participantes del grupo de tinidazol no presentaron episodios de reservoritis a los 12 meses en comparación con el 58% (7/12) de los participantes que recibieron placebo (CR 1,38; IC del 95%: 0,83 a 2,31; evidencia de certeza muy baja). CONCLUSIONES DE LOS AUTORES: No se conocen los efectos de los antibióticos, probióticos y otras intervenciones para el tratamiento y la prevención de la reservoritis. Se necesitan estudios bien diseñados con poder estadístico suficiente para determinar la forma óptima de tratamiento y prevención de la reservoritis.

Prevention and Medical Treatment of Pouchitis In Ulcerative Colitis.

Approximately 50% of patients who have undergone IPAA surgery for Ulcerative Colitis (UC) develop at least 1 episode of pouchitis. Patients with pouchitis have a wide range of symptoms, endoscopic and histologic features, disease course, and prognosis. To date, there are no universally accepted diagnostic criteria in terms of endoscopy and histology; though, semi-objective assessments to diagnose pouchitis in patients with ileal pouch- anal anastomosis (IPAA) have been proposed using composite scores such as the Pouchitis Triad, Heidelberg Pouchitis Activity Score and Pouchitis Disease Activity Index (PDAI). In a systematic review that included four randomized trials evaluating five agents for the treatment of acute pouchitis, ciprofloxacin was more effective at inducing remission as compared with metronidazole. Rifaximin was not more effective than placebo, while budesonide enemas and metronidazole were similarly effective for inducing remission of acute pouchitis. Patients with pouchitis relapsing more than three times per year are advised maintenance therapy, and guidelines recommend ciprofloxacin or the probiotic VSL#3. In patients with antibiotic-refractory pouchitis, secondary factors associated with an antibiotic-refractory course should be sought and treated. In this review, we will discuss the prevention and management of pouchitis in Ulcerative Colitis patients.

Dual arterial blood supply D-pouch in a patient with ulcerative colitis undergoing proctocolectomy and ileal pouch-anal anastomosis: A case report.

INTRODUCTION: Pouchitis is the most common complication in Ulcerative colitis (UC) patients after restorative proctocolectomy with ileal pouch-anal anastomosis (RP-IPAA) and ischemia may be a significant contributing factor. Tension and blood supply are the primary concerns while performing the procedure. A dual arterial blood supply technique is designed to decrease tension while ensuring sufficient blood perfusion. PATIENT CONCERNS: A 61-year-old female patient with 14 years history of UC wanted to seek surgical treatment. DIAGNOSES: Ulcerative colitis. INTERVENTIONS: After physical examination and treatment of parenteral nutrition, the patient underwent a D-pouch with dual arterial blood supply after total proctocoloectomy. OUTCOMES: The patient recovered well and was discharged 10 days after her procedure. Postoperatively dual arterial blood supply to the D-pouch was demonstrated by computed tomography angiography (CTA). CONCLUSION: D-pouch with dual arterial blood supply is feasible and safe in patients with UC undergoing RP-IPAA.

Treatment and prevention of pouchitis after ileal pouch-anal anastomosis for chronic ulcerative colitis.

BACKGROUND: Pouchitis occurs in approximately 50% of patients following ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (UC). OBJECTIVES: The primary objective was to determine the efficacy and safety of medical therapies for prevention or treatment of acute or chronic pouchitis. SEARCH METHODS: We searched MEDLINE, Embase and CENTRAL from inception to 25 July 2018. We also searched references, trials registers, and conference proceedings. SELECTION CRITERIA: Randomized controlled trials of prevention or treatment of acute or chronic pouchitis in adults who underwent IPAA for UC were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for eligibility, extracted data and assessed the risk of bias. The certainty of the evidence was evaluated using GRADE. The primary outcome was clinical improvement or remission in participants with acute or chronic pouchitis, or the proportion of participants with no episodes of pouchitis after IPAA. Adverse events (AEs) was a secondary outcome. We calculated the risk ratio (RR) and corresponding 95% confidence interval (CI) for each dichotomous outcome. MAIN RESULTS: Fifteen studies (547 participants) were included. Four studies assessed treatment of acute pouchitis. Five studies assessed treatment of chronic pouchitis. Six studies assessed prevention of pouchitis. Three studies were low risk of bias. Three studies were high risk of bias and the other studies were unclear.Acute pouchitis: All ciprofloxacin participants (7/7) achieved remission at two weeks compared to 33% (3/9) of metronidazole participants (RR 2.68, 95% CI 1.13 to 6.35, very low certainty evidence). No ciprofloxacin participants (0/7) had an AE compared to 33% (3/9) of metronidazole participants (RR 0.18, 95% CI 0.01 to 2.98; very low certainty evidence). AEs included vomiting, dysgeusia or transient peripheral neuropathy. Forty-three per cent (6/14) of metronidazole participants achieved remission at 6 weeks compared to 50% (6/12) of budesonide enema participants (RR 0.86, 95% CI 0.37 to 1.96, very low certainty evidence). Fifty per cent (7/14) of metronidazole participants improved clinically at 6 weeks compared to 58% (7/12) of budesonide enema participants (RR 0.86, 95% CI 0.42 to 1.74, very low certainty evidence). Fifty-seven per cent (8/14) of metronidazole participants had an AE compared to 25% (3/12) of budesonide enema participants (RR 2.29, 95% CI 0.78 to 6.73, very low certainty evidence). AEs included anorexia, nausea, headache, asthenia, metallic taste, vomiting, paraesthesia, and depression. Twenty-five per cent (2/8) of rifaximin participants achieved remission at 4 weeks compared to 0% (0/10) of placebo participants (RR 6.11, 95% CI 0.33 to 111.71, very low certainty evidence). Thirty-eight per cent (3/8) of rifaximin participants improved clinically at 4 weeks compared to 30% (3/10) of placebo participants (RR 1.25, 95% CI 0.34 to 4.60, very low certainty evidence). Seventy-five per cent (6/8) of rifaximin participants had an AE compared to 50% (5/10) of placebo participants (RR 1.50, 95% CI 0.72 to 3.14, very low certainty evidence). AEs included diarrhea, flatulence, nausea, proctalgia, vomiting, thirst, candida, upper respiratory tract infection, increased hepatic enzyme, and cluster headache. Ten per cent (1/10) of Lactobacillus GG participants improved clinically at 12 weeks compared to 0% (0/10) of placebo participants (RR 3.00, 95% CI 0.14 to 65.90, very low certainty evidence).Chronic pouchitis: Eighty-five per cent (34/40) of De Simone Formulation participants maintained remission at 9 to 12 months compared to 3% (1/36) of placebo participants (RR 20.24, 95% CI 4.28 to 95.81, 2 studies; low certainty evidence). Two per cent (1/40) of De Simone Formulation participants had an AE compared to 0% (0/36) of placebo participants (RR 2.43, 95% CI 0.11 to 55.89; low certainty evidence). AEs included abdominal cramps, vomiting and diarrhea. Fifty per cent (3/6) of adalimumab patients achieved clinical improvement at 4 weeks compared to 43% (3/7) of placebo participants (RR, 1.17, 95% CI 0.36 to 3.76, low certainty evidence). Sixty per cent (6/10) of glutamine participants maintained remission at 3 weeks compared to 33% (3/9) of butyrate participants (RR 1.80, 95% CI 0.63 to 5.16, very low certainty evidence). Forty-five per cent (9/20) of patients treated with bismuth carbomer foam enema improved clinically at 3 weeks compared to 45% (9/20) of placebo participants (RR 1.00, 95% CI 0.50 to 1.98, very low certainty evidence). Twenty-five per cent (5/20) of participants in the bismuth carbomer foam enema group had an AE compared to 35% (7/20) of placebo participants (RR 0.71, 95% CI 0.27 to 1.88, very low certainty evidence). Adverse events included diarrhea, worsening symptoms, cramping, sinusitis, and abdominal pain. PREVENTION: At 12 months, 90% (18/20) of De Simone Formulation participants had no episodes of acute pouchitis compared to 60% (12/20) of placebo participants (RR 1.50, 95% CI 1.02 to 2.21, low certainty evidence). Another study found 100% (16/16) of De Simone Formulation participants had no episodes of acute pouchitis at 12 months compared to 92% (11/12) of the no treatment control group (RR 1.10, 95% 0.89 to 1.36, very low certainty evidence). Eighty-six per cent (6/7) of Bifidobacterium longum participants had no episodes of acute pouchitis at 6 months compared to 60% (3/5) of placebo participants (RR 1.43, 95% CI 0.66 to 3.11, very low certainty evidence). Eleven per cent (1/9) of Clostridium butyricum MIYAIRI participants had no episodes of acute pouchitis at 24 months compared to 50% (4/8) of placebo participants (RR 0.22, 95% CI 0.03 to 1.60, very low certainty evidence). Forty-six per cent (43/94) of allopurinol participants had no episodes of pouchitis at 24 months compared to 43% (39/90) of placebo participants (RR 1.06, 95% CI 0.76 to 1.46; low certainty evidence). Eighty-one per cent (21/26) of tinidazole participants had no episodes of pouchitis over 12 months compared to 58% (7/12) of placebo participants (RR 1.38, 95% CI 0.83 to 2.31, very low certainty evidence). AUTHORS' CONCLUSIONS: The effects of antibiotics, probiotics and other interventions for treating and preventing pouchitis are uncertain. Well designed, adequately powered studies are needed to determine the optimal therapy for the treatment and prevention of pouchitis.

Fruit Consumption is Associated with Alterations in Microbial Composition and Lower Rates of Pouchitis.

BACKGROUND: Patients with ulcerative colitis [UC] who undergo proctocolectomy with an ileal pouch-anal anastomosis commonly develop pouch inflammation [pouchitis]. Pouchitis develops in a previously normal small intestine and may involve environmental factors. We explored whether diet and microbiota alterations contributed to the pathogenesis of pouchitis. METHODS: Patients were recruited and prospectively followed at a comprehensive pouch clinic. Pouch behaviour was clinically defined as a normal pouch [NP] or pouchitis. Patients completed Food Frequency Questionnaires [FFQs]. Faecal samples were analysed for microbial composition [16S rRNA gene pyrosequencing]. RESULTS: Nutritional evaluation was performed in 172 patients [59% females], and of these, faecal microbial analysis was performed in 75 patients (microbiota cohort: NP [n = 22], pouchitis [n = 53]). Of the entire cohort, a subgroup of 39 [22.6%] patients had NP at recruitment [NP cohort]. Of these, 5 [12.8%] developed pouchitis within a year. Patients at the lowest tertile of fruit consumption [<1.45 servings/day] had higher rates of pouchitis compared with those with higher consumption [30.8% vs 3.8%, log rank, p = 0.03]. Fruit consumption was correlated with microbial diversity [r = 0.35, p = 0.002] and with the abundance of several microbial genera, including Faecalibacterium [r = 0.29, p = 0.01], Lachnospira [r = 0.38, p = 0.001], and a previously uncharacterized genus from the Ruminococcaceae family [r = 0.25, p = 0.05]. Reduction in fruit consumption over time was associated with disease recurrence and with reduced microbial diversity [Δ = -0.8 ± 0.3, p = 0.008]. CONCLUSIONS: Fruit consumption is associated with modification of microbial composition, and lower consumption was correlated with the development of pouchitis. Thus, fruit consumption may protect against intestinal inflammation via alteration of microbial composition.

Prevention of Postoperative Recurrence in CD: Tailoring Treatment to Patient Profile.

Crohn's disease (CD) is an immune-mediated condition characterized by the transmural inflammation of the gut tissue, associated with progressive bowel damage often leading to surgical intervention. As operative resection of the damaged segment is not curative, a majority of patients undergoing intestinal resections for complicated CD present disease recurrence within 3 years after the intervention. Postoperative recurrence can be defined as endoscopic, clinical, radiological or surgical. Endoscopic recurrence rates within 1 year exceed 60% and the severity, according to the Rutgeerts' score, is associated with worse prognosis and can predict clinical recurrence (in up to 1/3 of the patients). Most importantly, about 50% of patients will undergo a reoperation after 10 years of their first intestinal resection. Therefore, the prevention of postoperative recurrence in CD remains a challenge in clinical practice and should be properly managed. We aim to summarize the most recent data on the definition, risk factors, assessment and treatment of postoperative CD recurrence.

Adalimumab in the treatment of chronic pouchitis. A randomized double-blind, placebo-controlled trial.

BACKGROUND: Pouchitis is a complication of ileal pouch-anal anastomosis and occurs in up to 50% of patients 10 years after IPAA with 10% developing refractory pouchitis. OBJECTIVE: To evaluate the effect of a TNF-α inhibitor (Adalimumab) in the treatment of refractory pouchitis. MATERIALS AND METHODS: A multicenter, randomized double-blind, placebo-controlled trial includes patients with refractory pouchitis for more than 4 weeks despite antibiotic treatment. Patients were randomized to Adalimumab or placebo for 12 weeks. Primary outcome was reduction in clinical pouchitis disease activity index (PDAI) of ≥2 at any time. Secondary endpoints were remission of pouchitis, endoscopic and histologic effect and quality of life. RESULTS: Thirteen patients were included; six patients received active treatment and seven patients received placebo. Nine patients (5/4, Adalimumab/placebo) completed the 12-week program. Reduction in clinical PDAI ≥ 2 was achieved in three patients in each group (50%/43%, Adalimumab/placebo, p > .5). Total PDAI improved in six patients treated with Adalimumab and two patients on placebo (100%/29%, p = .13). There were no differences in secondary endpoints between the groups. CONCLUSIONS: In this randomized controlled trial of treatment with Adalimumab in patients with refractory pouchitis, we were not able to identify any clinical benefit in the primary or secondary endpoints.

Sulfasalazine in Prevention of Pouchitis After Proctocolectomy with Ileal Pouch-Anal Anastomosis for Ulcerative Colitis.

BACKGROUND: Pouchitis is the most frequent complication after ileal pouch-anal anastomosis for refractory ulcerative colitis. A non-standardized preventative treatment exists. Sulfasalazine has proved effective in acute pouchitis therapy. AIMS: The aim of this study was to retrospectively evaluate the effect of sulfasalazine in primary prophylaxis of pouchitis after proctocolectomy with ileal pouch-anal anastomosis. METHODS: Data files of patients who underwent total proctocolectomy with ileal pouch-anal anastomosis for refractory ulcerative colitis and/or dysplasia from January 2007 to December 2014, with a follow-up until August 2015, were analyzed. After closure of loop ileostomy, on a voluntary basis, patients received a primary prophylaxis of pouchitis with sulfasalazine (2000 mg per day) continually until acute pouchitis flare and/or drop out due to side effects. RESULTS: Follow-up data were available for 51 of the 55 surgical patients. Median follow-up time was 68 months (range 10-104). Thirty postoperative complications occurred in 25 patients. 45% of patients developed pouchitis. Sulfasalazine prophylaxis was administered in 39.2% of patients; 15% of the these developed pouchitis versus 64.5% (20/31) of the non-sulfasalazine patients (p < 0.001). Pouchitis-free survival curves were 90.55 months in sulfasalazine patients and 44.46 in non-sulfasalazine patients (log-rank test p = 0.001, Breslow p = 0.001). CONCLUSION: Sulfasalazine may be potentially administered in pouchitis prophylaxis after proctocolectomy with ileal pouch-anal anastomosis, but large prospectively controlled trials are needed.

The effect of Clostridium butyricum MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis.

PURPOSE: Ulcerative colitis (UC) is a chronic, relapsing, and refractory disorder of the intestine. Total proctocolectomy with ileal pouch anal anastomosis (IPAA) is the preferred and standard surgical procedure for patients' refractory to medical therapy. Pouchitis is one of the most common long-term complications after IPAA. In the present study, the safety and efficacy of Clostridium butyricum MIYAIRI (CBM) as a probiotic were examined. METHODS: A randomized and placebo-controlled study was performed. Seventeen patients were recruited from 2007 to 2013. Nine tablets of MIYA-BM(®) or placebo were orally administered once daily. The cumulative pouchitis-free survival, pouch condition (using the modified pouch disease activity index), and blood parameters were evaluated. A fecal sample analysis was also performed. RESULTS: Subjects were randomly allocated to receive MIYA-BM or placebo (9 and 8 subjects, respectively). One subject in the MIYA-BM group and four subjects in the placebo group developed pouchitis. No side effects occurred in either group. Characteristic intestinal flora was observed in each group. CONCLUSIONS: Our results suggest that probiotic therapy with CBM achieved favorable results with minimal side effects and might be a useful complementary therapy for the prevention of pouchitis in patients with UC who have undergone IPAA.