Pouch Disease Research Articles

Pelvic Radiation Therapy Increases Risk of Pouch Failure in Patients with Inflammatory Bowel Disease and Ileal Pouch.

The effect of radiation on the ileal pouch is less well studied in patients with inflammatory bowel disease (IBD) and ileal pouch-anal anastomosis. This retrospective study investigates the impact of external radiation therapy on the outcomes of ileal pouches. The study included 82 patients with IBD and ileal pouches, of whom 12 received pelvic radiation, 16 abdominal radiation, 14 radiation in other fields, and 40 served as controls with no radiation. Pouch-related outcomes, including pouch failure, worsening of symptoms, pouchitis, and development of strictures, along with changes in Pouch Disease Activity Index (PDAI) scores pre- and post-radiation were assessed. The pelvic radiation group exhibited a significantly higher rate of pouch failure (25%, p < 0.004) and worsening pouch-related symptoms (75%, p = 0.012) compared to other groups. Although not statistically significant, a higher incidence of pouchitis was observed in the pelvic radiation group (45.5%, p = 0.071). Strictures were more common in the pelvic radiation group (25%, p = 0.043). Logistic regression analysis revealed that pelvic radiation significantly increased the odds of pouch-related adverse outcomes (OR 5.66; 95% confidence interval: 1.61-21.5). Pelvic radiation significantly impacts the outcomes of ileal pouches in patients with IBD, increasing the risk of pouch failure, symptom exacerbation, and structural complications. These findings underscore the need for careful consideration of radiation therapy in this patient population and highlight the importance of closely monitoring and managing radiation-induced pouch dysfunction.

MEDICAL, ENDOSCOPIC, AND SURGICAL THERAPIES FOR THE TREATMENT OF RECTAL CUFFITIS IN ULCERATIVE COLITIS PATIENTS WITH AN ILEAL POUCH-ANAL ANASTOMOSIS: A SYSTEMATIC REVIEW

Abstract BACKGROUND Patients who undergo ileal pouch-anal anastomosis (IPAA) without mucosectomy are left with a rectal cuff, which can develop inflammation known as cuffitis. Treatment of cuffitis typically includes mesalamine suppositories or corticosteroids, but individuals with refractory cuffitis may require advanced therapies, endoscopic intervention, or surgical intervention. The aim of this review is to summarize the existing literature regarding treatments options for cuffitis. METHODS A broad search strategy was created by a medical librarian to capture rectal cuffitis in IPAA patients. The following databases were searched: Ovid Medline® ALL, Ovid Embase, Cochrane Central Register of Controlled Trials (Wiley), and 3 indexes in Web of Science from Clarivate: Science Citation Index-Expanded, Conference Proceedings Citation Index, and BIOSIS Citation Index. A total of 1,652 citations were identified, and 836 studies remained after removal of 816 duplicates. Two reviewers screened all 836 abstracts and 241 full-text articles to determine if they were eligible for inclusion in this review. RESULTS A total of 21 studies (10 cohort studies, 9 case-series, 2 open-label clinical trials) met the inclusion criteria. Medical interventions were investigated in 15 studies (Table 1) with mesalamine being the most common (4 studies) followed by corticosteroids (3 studies), ustekinumab (3 studies), vedolizumab (2 studies), tofacitinib (1 study), and infliximab (1 study). Studies investigating mesalamine and corticosteroid use generally had larger sample sizes (ranging 4-120 patients) and showed symptomatic improvement in 51.7-100% of patients and decreases of 1.14-1.8 points in endoscopic disease activity indices. In contrast, studies investigating advanced therapies had small sample sizes (ranging 1-21 patients) and showed variable responses ranging from no clinical (tofacitinib) or endoscopic (ustekinumab, vedolizumab) improvements to clinical (ustekinumab) or endoscopic (vedolizumab) responses in 75% of patients. Endoscopic and surgical approaches were explored in 6 studies (Table 2) and included secondary mucosectomy (2 studies), endoscopic cuff resection, transanal minimally invasive surgery, endoscopic needle-knife therapy, and balloon dilation for cuffitis patients with concomitant outlet strictures (1 study each). These techniques generally resulted in resolution of symptoms but were limited by small sample sizes (ranging 3-16 patients). CONCLUSIONS Most studies evaluating therapies used to treat rectal cuffitis suggest beneficial effects of conventional mesalamine or corticosteroid-based therapies, whereas data regarding the efficacy of advanced therapies and interventional procedures are inconsistent given small sample sizes. Further research is needed to effectively characterize additional management options for this condition. Table 1. Medical therapies used for treatment of cuffitis. Abbreviations – BM: bowel movements, CRP: C-reactive protein, UST: ustekinumab, HBOT: hyperbaric oxygen therapy, mPDAI: modified Pouch Disease Activity Index, 5-ASA: 5-aminosalicylate, ESR: erythrocyte sedimentation rate, PDAI: Pouch Disease Activity Index, CGQOL: Cleveland Global Quality of Life score, IPS: Irritable Pouch Syndrome, CAI: Cuffitis Activity Index. Table 2. Endoscopic and surgical therapies used for treatment of cuffitis. Abbreviations – FISI: Fecal Incontinence Severity Index, CGQOL: Cleveland Global Quality of Life score, PDAI: Pouch Disease Activity Index, BM: bowel movements.

Association between mucosectomy and endoscopic outcomes in patients with ileal pouch-anal anastomosis.

In patients with inflammatory bowel disease (IBD) for whom medical therapy is unsuccessful or who develop colitis-associated neoplasia, restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is often indicated. One consideration for surgeons performing this procedure is whether to create this anastomosis using a stapled technique without mucosectomy or using a hand-sewn technique with mucosectomy. This study tested the association between IPAA anastomosis technique and cuffitis and/or pouchitis, assessed endoscopically. This was a retrospective cohort study. We included consecutive adult patients with IBD who had undergone IPAA and had received index pouchoscopies at Columbia University Irving Medical Center between 2020 and 2022. Patients were then followed up from this index pouchoscopy for ≤12 months to a subsequent pouchoscopy. The primary exposure was mucosectomy vs non-mucosectomy and the primary outcome was cuffitis and/or pouchitis, defined as a Pouch Disease Activity Index endoscopy subscore of ≥1. There were 76 patients who met study criteria including 49 (64%) who had undergone mucosectomy and 27 (36%) who had not. Rates of cuffitis and/or pouchitis were 49% among those with mucosectomy vs 41% among those without mucosectomy (P = 0.49). Time-to-event analysis affirmed these findings (log-rank P = 0.77). Stricture formation was more likely among patients with mucosectomy compared with those without mucosectomy (45% vs 19%, P = 0.02). There was no association between anastomosis technique and cuffitis and/or pouchitis among patients with IBD. These results may support the selection of stapled anastomosis over hand-sewn anastomosis with mucosectomy.

Diagnostic Imaging of Diseases Affecting the Guttural Pouch.

The most common diseases of the guttural pouch are empyema, tympany, mycosis and temporohyoid osteoarthropathy. The challenge in diagnosis of guttural pouch diseases lies in the complex anatomy of the guttural pouch and adjacent associated structures. Diagnostic imaging is a good complement to endoscopy for the diagnosis of some guttural pouch diseases, especially to make a full assessment of the lesions involving the pouch and surrounding structures. This review article describes the value of each diagnostic imaging technique in the diagnosis of guttural pouch disease and the corresponding imaging findings. Radiography is generally used as the first line to complement endoscopic findings, and can give useful additional information although it is limited by superimposition. Ultrasonographic examination of the guttural pouch is of limited value due to the presence of gas in the guttural pouch but can eventually be used to detect fluid within the pouch or can help to evaluate the soft tissues located lateral and ventral to the guttural pouch. Cross-sectional imaging, especially CT, is increasingly available and appears to be the best technique to fully assess the surrounding soft tissues and to precisely identify lesions of the temporohyoid apparatus, temporal bone and skull base that are associated with guttural pouch disease.

Preoperative Use of Multiple Advanced Therapies Is Not Associated With Endoscopic Inflammatory Pouch Diseases.

Patients with an ileal pouch-anal anastomosis (IPAA) can experience pouch inflammation postoperatively. The use of antitumor necrosis factor (anti-TNF) biologics may be associated with pouch inflammation, but limited data exist on the impact of multiple advanced therapies on development of subsequent pouch inflammation. The aim of this study was to assess for an association between preoperative use of multiple advanced therapies and risk of endoscopically detected inflammatory pouch diseases (EIPDs). We performed a retrospective analysis of ulcerative colitis (UC) and indeterminate colitis (IBDU) patients who underwent an IPAA at a quaternary care center from January 2015 to December 2019. Patients were grouped based on number and type of preoperative drug exposures. The primary outcome was EIPD within 5 years of IPAA. Two hundred ninety-eight patients were included in this analysis. Most of these patients had UC (95.0%) and demonstrated pancolonic disease distribution (86.1%). The majority of patients were male (57.4%) and underwent surgery for medically refractory disease (79.2%). The overall median age at surgery was 38.6 years. Preoperatively, 68 patients were biologic/small molecule-naïve, 125 received anti-TNF agents only, and 105 received non-anti-TNF agents only or multiple classes. Ninety-one patients developed EIPD. There was no significant association between type (P = .38) or number (P = .58) of exposures and EIPD, but older individuals had a lower risk of EIPD (P = .001; hazard ratio, 0.972; 95% confidence interval, 0.956-0.989). Development of EIPD was not associated with number or type of preoperative advanced therapies.

P726 Fecal calprotectin and quality of life questionnaires are responsive to change in pouch disease activity following antibiotic therapy—results from a prospective clinical trial

Abstract Background Whether fecal calprotectin (FC) and quality of life (QoL) questionnaires reflect change in disease activity in patients with a J-pouch is unknown. Methods Patients with UC following ileal pouch-anal anastomosis developing acute pouchitis were prospectively recruited to a clinical trial at the Rabin Medical Center in Israel, a major referral center for patients with a J-pouch. Consecutive patients with acute pouchitis were diagnosed clinically by the treating physician in a patient with compatible clinical symptoms. Patients were treated with a 2-week course of antibiotics – either metronidazole and ciprofloxacin or metronidazole and doxycycline. Full PDAI, including clinical, endoscopic, and histologic evaluation, was performed at baseline and following 2 weeks of antibiotic therapy. Patients had comprehensive laboratory tests, including fecal calprotectin (FC) measurements at both time points. Patients also filled out QoL questionnaires (short inflammatory bowel disease questionnaire - SIBDQ, inflammatory bowel disease [IBD] disk) at both time points. Outcomes of interest included the responsiveness of FC and QoL questionnaires to change in pouch disease activity according to the PDAI. Paired analyses were performed to compare results between the 2-time points. Results Twenty patients were enrolled in a prospective clinical trial. At enrollment, the median age was 36 years IQR [27-56], females 12 (60%). The median interval from the ileostomy closure was 7 years IQR [2-17]. Median PDAI score: 9 IQR [8-11.5], median FC: 661 ug/g IQR [425-1261], median C-reactive protein: 1.1 mg/dl IQR [0.5-1.8] and median hemoglobin: 13.2 g/dl IQR [12.1-14.1]. Following 14 days of antibiotic treatment, there was a significant decrease in the total PDAI, which decreased from a median of 9 IQR[8-11.5] to 6 IQR[2.5-7],(p=0.007). This difference was mainly related to a significant reduction in both the clinical (p=0.01) and endoscopic subscores (p=0.001) but not the histologic subscore (p=0.1). FC was responsive to this change in PDAI and correlated with the change in endoscopic findings; it decreased significantly between the 2-time points from a median of 661 ug/g IQR[425-1261] to 294 ug/g IQR[113-418] (p=0.02). Both quality of life questionnaires (SIBDQ, IBD disk) improved significantly following antibiotic therapy: The median SIBDQ increased from 44 to 50 (p=0.02), and the median IBD disk score decreased from 59 to 31 (p=0.01) Figure 2 Panel B and C respectively. Conclusion FC is a sensitive and rapidly responsive biomarker of pouch disease activity, and we encourage its use when managing patients with pouchitis. Likewise, the SIBDQ and IBD disk accurately reflect change in QoL associated with change in disease state in patients with a pouch

P235 Patients with inflammatory ileal pouch anal anastomosis (IPAA) disorders are characterized by a distinct breath volatile organic compounds (VOC) metabolome profile

Abstract Background Following creation of an IPAA in patients with ulcerative colitis (UC), more than 60% of subjects develop inflammatory complications. The current objective assessment for inflammation of the pouch is limited to surrogate stool and blood biomarkers or endoscopy. The development of non-invasive and accurate biomarkers for the assessment of IPAA inflammation is an area of unmet need. Measurement of exhaled breath volatile organic metabolome compounds (VOCs) has shown promise as a biomarker for the diagnosis and monitoring of inflammatory disorders. We here aimed to characterize the pattern of VOCs in the exhaled breath of patients with an IPAA and assess whether VOC analysis is able to discriminate patients with endoscopically active IPAA inflammation from patients without IPAA inflammation. Methods This is a cross-sectional study of patients with an IPAA created for the management of UC. Exhaled breath samples were collected at time of endoscopic evaluation of the pouch and 97 VOC metabolites assessed via selective ion flow tube mass spectrometry (SIFT-MS). The IPAA cohort was dichotomized using the endoscopic pouch disease activity index (PDAI) into endoscopic PDAI of &amp;gt;= 4 (severe inflammation), or endoscopic PDAI score &amp;lt;= 1 (mild or no inflammation). Principle component analysis (PCA) was conducted to reveal the VOCs with the strongest discriminatory capability and principle component regression (PCR) was performed to assess the association of exhaled breath VOC analysis in differentiating the groups. Results Exhaled breath metabolome analysis was performed on 10 subjects with PDAI &amp;gt;=4 and 7 subjects with PDAI &amp;lt;=1. Demographics are provided in Table 1. PCA indicated robust discrimination of the two groups based on breath VOCs (Figure 1). 10 out of 97 VOCs were up-regulated in the PDAI &amp;gt;=4 group compared to control, including ammonia and hydrogen sulfide. Isopropenyltoluene, tetrachloroethylene, and 3-pentanone provided the highest contribution to differentiate between the cohorts (Figure 2). Receiver operative curve (ROC) analysis of the PCR model indicated an area under the curve (AUC) of 0.81 (0.61-99), suggesting a strong association of breath VOCs with inflammation of the pouch (Figure 1). Conclusion VOC exhaled breath metabolome analysis shows a strong ability to discriminate patients with severe endoscopic pouch inflammation from patients with minimal to no endoscopic inflammation. The differences in reported VOCs point toward metabolic differences in bacterial fermentation, lipid and carbohydrate metabolism, and an increase in reactive oxygen species in patients with endoscopic pouch inflammation. Validation studies addressing the role of VOC analysis for non-invasive disease assessment patients with IPAA are ongoing.

Fecal Calprotectin and Quality of Life Questionnaires Are Responsive to Change in Pouch Disease Activity After Antibiotic Therapy: Results From a Prospective Clinical Trial.

Whether fecal calprotectin (FC) and quality of life (QoL) questionnaires reflect change in disease activity in patients with a J-pouch is unknown. Patients with acute pouchitis were prospectively treated with a 2-week course of antibiotics. The full Pouchitis Disease Activity Index, FC, and QoL questionnaires were measured at baseline and after antibiotic therapy. Twenty patients were prospectively enrolled. After 2 weeks of antibiotic treatment, the Pouchitis Disease Activity Index decreased from a median of 9 to 5 ( P = 0.007). FC decreased from a median of 661 ug/g to 294 ug/g ( P = 0.02), and QoL questionnaires improved significantly. FC and QoL questionnaires reflect real-time changes in inflammatory pouch activity.

Clinical outcome of horses with guttural pouch infection following transpharyngeal fenestration.

To report the clinical outcomes of horses with chronic guttural pouch infection characterized by accumulation of mucopurulent material following transpharyngeal diode laser fenestration. 13 client-owned horses. Horses undergoing diode laser fenestration for chronic guttural pouch infection were identified by medical record search. Signalment, disease history, presence of mucopurulent empyema or chondroids, and pre- and postoperative therapy were recorded. Owners were contacted for follow-up information at a minimum of 6 months following surgery. 13 horses underwent laser fenestration for chronic guttural pouch infection. Thirteen had mucopurulent nasal discharge on presentation, and 3 were coughing. At follow-up, 12 horses treated with transpharyngeal diode laser fenestration had complete resolution of nasal discharge and coughing. One horse, despite resolution of guttural pouch infection on endoscopy, continued to have nasal discharge and coughing attributed to concurrent equine asthma syndrome. All owners expressed satisfaction with the surgical procedure and clinical resolution of guttural pouch infection. This surgical technique for transpharyngeal diode laser fenestration of the guttural pouch was uncomplicated to perform and well tolerated in sedated horses and attributed to resolution of clinical signs associated with guttural pouch infection, and owners reported a high satisfaction with the clinical outcome. Implementing this surgical technique could be considered to hasten resolution of chronic guttural pouch disease in horses with few technique-related complications.

P323 The Crohn’s Disease Exclusion Diet (CDED) for pouch inflammation: an interventional pilot study

Abstract Background Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgical treatment of choice for patients with UC. Unfortunately, pouchitis is a common condition, reported in up to, 72% of pouch patients. Pouchitis pathogenesis is not entirely clear and has similarities to that of Crohn’s disease (CD), given the de-novo inflammation of the small intestine, the microbial dysbiosis and the occurrence of a penetrating phenotype. The Crohn’s Disease Exclusion Diet (CDED) has demonstrated its efficacy in improving clinical and biochemical parameters of intestinal inflammation in CD. Therefore, we aimed to examine whether the CDED may be effective for the treatment of active pouchitis. Methods A non-controlled, open-label, interventional pilot trial. Active pouchitis patients were recruited at the comprehensive pouch clinic of the Tel Aviv Medical Center (TLVMC), a tertiary center. Patients were treated with the CDED (phases, 1–3) for, 24 weeks, underwent, 5 clinic visits (weeks, 0, 3, 6, 12 and, 24) which included physician assessment and monitoring [clinical pouch disease activity index (cPDAI) sub score evaluation], dietary evaluation and guidance, inflammatory biomarkers evaluation, and collection of biologic samples. Patients underwent three pouchoscopy procedures (baseline, end of phase, 2 and end of phase, 3) for assessment of endoscopic and histologic disease activity. The primary endpoint of the study was week-6 clinical remission (cPDAI subscore≥2). Results Fifteen patients (mean age, 42.6±11.2, 3 males, mean pouch age, 14.7±10.7 years) with pouchitis were recruited (Crohn’s like disease of the pouch, n=5; chronic pouchitis, n=4; acute pouchitis, n=3; recurrent acute pouchitis, n=3). Nine patients completed the study protocol and were evaluated throughout, 24 weeks, while six patients were withdrawn: four due to exacerbation requiring antibiotics, and two due to bowel obstruction. No other adverse events were noted. Clinical remission was achieved by, 66.7% of the study population at week, 6 by per-protocol analysis, and was maintained by, 60.0% at week, 12. Modified PDAI (mPDAI) decreased at week, 12 compared to baseline (8.0 vs., 5.0, P=0.027), with an improvement in the median number of defecations per day (24h) (12.5 vs., 7.0, P=0.003), and night (2.5 vs., 1.0, P=0.018). CRP and fecal calprotectin decreased compared to baseline (11.1±5.2 vs, 6.0±4.0, P=0.007, and, 697±680 vs, 497±483, P=0.607). Among patients who achieved clinical remission at week, 6, 80% maintained remission at week, 12 (P=0.025). Conclusion This pilot study demonstrates that CDED is a beneficial and safe therapeutic dietary intervention for pouchitis. Larger controlled trials should be performed in this population.

Position of the midline septum of the guttural pouches in horses subjected to computed tomography

Standing computed tomographic (CT) examination of the equine guttural pouch frequently reveals deviation of the midline septum. The significance of deviation is currently unknown. The aims of this retrospective, single-centre study were to determine the prevalence of deviation of the midline septum of the guttural pouch and determine whether there was an association between the presence and degree of deviation of the septum, and guttural pouch disease. Case records were reviewed, identifying 95 horses that had undergone a standing, sedated, head CT and guttural pouch endoscopy. The presence, laterality, subjective degree and angle of deviation of the midline septum on CT was recorded. A total of 69 (72.6%) horses were identified with deviation of the midline septum, with the mean angle of deviation 13.4o and a maximum deviation of 52.6o. No significant association between the presence of deviation of the midline septum (P = .722) or severity of deviation (P = .428) and an endoscopic abnormality within the guttural pouch was found. The laterality of deviation and guttural pouch abnormalities were also not associated (P = .000). Deviation of the midline septum of the guttural pouch is a common finding on CT examination, and does not have clinical significance in this study.

P104 Inflammatory complications of the pouch, and therapetic requirements after colectomy in patients with ulcerative colitis. Results from the RESERVO Study of GETECCU

Abstract Background Pouchitis and other inflammatory pouch diseases (IPD) are frequent in pouch-carrying patients operated for a previous diagnosis of ulcerative colitis. We evaluated characteristics and differences in therapeutic requirements between pouchitis, Crohn′s-like disease of the pouch (CDP) and cuffitis. Methods This is a retrospective and multicentric Spanish cohort of GETECCU (RESERVO Study), including pouch-carrying patients (operated 1995 to 2016) with previous ulcerative colitis, ileostomy closure and subsequent diagnosis of IPD (pouchitis, CDP or cuffitis), following ECCO diagnostic criteria1. Follow up extended to June 2020. Pouchitis was categorized attending current classifications. Use of medical and surgical therapies was collected and differences between pouchitis and CDP were analyzed using descriptive and comparative statistics. Results A total of 338 patients were included. Demographic and clinical characteristics are presented in Table 1. The most frequent IPD was pouchitis (n=258, 76%), followed by CDP (n=55, 16%) and cuffitis (n=25, 7.4%). Pouchitis was diagnosed at a median time of 27 (range 1–342) months. Prevalence according to pouchitis classification is presented in Figure 1. CDP was diagnosed at a median time of 77 (range 5–324) months, around 75% with a previous pouchitis diagnosis. Location of CDP (not mutually excludent) was pouch CDP (91%), 87% pre-pouch ileitis, and 41% perianal disease. Regarding behavior: 26 (47%) were inflammatory, 12 (22%) stricturing and 17 (31%) penetrating (8 rectovaginal fistulas). Cuffitis was diagnosed at a median time of 18 (range 1–219) months. Medical and surgical therapies used are shown in Figure 2. Immunosuppressants (58.2 vs 22.4%, p 0.001), biologics (74.5 vs 34.8%, p 0.0001), and surgery (41.8 vs 21.3%, p 0.003) were more used in CDP than in pouchitis. Conclusion Pouchitis and CDP are heterogeneous inflammatory pouch complications with a wide and high therapeutic requirement. CDP presents a later diagnosis and has higher therapeutic needs than pouchitis. 1. Fernando Magro, Paolo Gionchetti, Rami Eliakim et al, for the European Crohn’s and Colitis Organisation [ECCO], Third European Evidence-based Consensus on Diagnosis and Management of Ulcerative Colitis. Part 1: Definitions, Diagnosis, Extra-intestinal Manifestations, Pregnancy, Cancer Surveillance, Surgery, and Ileo-anal Pouch Disorders, J Crohns Colitis 2017; 11(6): 649–670.

Pyloric gland metaplasia: Potential histologic predictor of severe pouch disease including Crohn’s disease of the pouch in ulcerative colitis

Crohn’s disease of the pouch (CDP) is seen in a subset of ulcerative colitis (UC) patients following ileal pouch-anal anastomosis (IPAA). Histologic or clinical predictors of CDP are unknown. UC patients with subsequent CDP diagnosis were identified. The rationales for the diagnosis, the interval from the initial signs of CDP to the diagnosis, family history and smoking history were reviewed. Archived pathology materials were reviewed for the presence of pyloric gland metaplasia (PGM) and compared with those from UC with similar severity of pouchitis with CDP (matched UC controls), random UC controls, and ileocolectomies from primary CD patients. CDP diagnosis was made in 26 (18.1%) of 144 patients; all of them met commonly used diagnostic criteria for CDP. The diagnosis was rendered on average 15 months after the initial CD-like signs. PGM was found in 58% of CDP, more common than random UC controls but no different from primary CD and matched UC controls. PGM preceded first signs of CD in a subset. Patients with a family history of CD were more likely to develop CDP than those without a family history of any type of inflammatory bowel disease. Smoking status did not affect the likelihood of developing CDP. Finding PGM in proctocolectomy, ileostomy and follow-up biopsies in UC patients post IPAA may warrant close follow up for the potential development of pouchitis. Some of these patients, especially those with family history of CD, may further progress and develop severe disease meeting the clinical diagnostic criteria for CDP.

Pre-pouch Ileitis is Associated with Development of Crohn's Disease-like Complications and Pouch Failure.

It is unclear whether pre-pouch ileitis heralds an aggressive inflammatory pouch disease in patients with ileal pouch-anal anastomosis [IPAA]. We compared outcomes of patients with pouchitis and concomitant pre-pouch ileitis with those with pouchitis alone. Patients undergoing IPAA surgery for inflammatory bowel disease, who subsequently developed pouchitis with concomitant pre-pouch ileitis [pre-pouch ileitis group], were matched by year of IPAA surgery and preoperative diagnosis [ulcerative colitis or inflammatory bowel disease-unclassified] with patients who developed pouchitis alone [pouchitis group]. Primary outcomes were development of Crohn's disease [CD]-like complications [non-anastomotic strictures or perianal disease >6 months after ileostomy closure] and pouch failure. Secondary outcomes were need for surgical/endoscopic interventions and immunosuppressive therapy. Log-rank testing was used to compare outcome-free survival, and Cox regression was performed to identify predictors of outcomes. There were 66 patients in each group. CD-like complications and pouch failure developed in 36.4% and 7.6% patients in the pre-pouch ileitis group and 10.6% and 1.5% in pouchitis group, respectively. CD-like complications-free survival [log-rank p = 0.0002] and pouch failure-free survival [log-rank p = 0.046] were significantly lower in the pre-pouch ileitis group. The pre-pouch ileitis group had a higher risk of requiring surgical/endoscopic interventions [log-rank p = 0.0005] and immunosuppressive therapy [log-rank p <0.0001]. Pre-pouch ileitis was independently associated with an increased risk of CD-like complications (hazard ratio [HR] 3.8; p = 0.0007), need for surgical/endoscopic interventions [HR 4.1; p = 0.002], and immunosuppressive therapy [HR 5.0; p = 0.0002]. Pre-pouch ileitis is associated with a higher risk of complicated disease and pouch failure than pouchitis. It should be considered a feature of CD.

High Abundance of Proteobacteria in Ileo-Anal Pouch Anastomosis and Increased Abundance of Fusobacteria Associated with Increased Pouch Inflammation.

Low diversity intestinal dysbiosis has been associated with inflammatory bowel disease, including patients with ulcerative colitis with an ileo-anal pouch anastomosis. Furthermore, specific Escherichia coli phylogroups have been linked to inflammatory bowel disease. Our aim was to characterize the differences among microbiota and E. coli phylogroups in active and inactive pouchitis. Disease activity was assessed using the modified pouch disease activity index and by fecal calprotectin. Microbiota diversity was assessed by 16S rDNA MiSeq sequencing. E. coli phylogroup was determined after triplex PCR. Twenty patients with ulcerative colitis with an ileo-anal pouch anastomosis were included, 10 of whom had active pouchitis. Ileo-anal pouch anastomosis patients had an increased abundance of Proteobacteria colonization compared to patients with ulcerative colitis or Crohn’s disease and healthy controls, p = 1.4·10−5. No differences in E. coli phylogroup colonization could be determined between cases of active and inactive disease. No significant link was found between α-diversity and pouch inflammation. However, higher levels of Fusobacteria colonization were found in patients with a pouch with a fecal calprotectin level above 500, p = 0.02. In conclusion, patients with a pouch had an increased Proteobacteria abundance, but only Fusobacteria abundance was linked to inflammation.

Evaluation of the effect of laser salpingopharyngostomy on the guttural pouch environment in horses.

Laser salpingopharyngostomy has been used as an adjunct to primary medical therapy allowing for topical debridement, topical treatment or to potentially alter the guttural pouch environment in horses with guttural pouch disease. To evaluate the effect of a laser salpingopharyngostomy on the guttural pouch environment in healthy horses. Experimental study. In six adult Standardbred female horses, under standing sedation a stab incision was made ventral to the sternocephalicus tendon and a customised trocar inserted into the medial guttural pouch compartment. Baseline (day 0) temperature, humidity, oxygen (O2 ) and carbon dioxide (CO2 ) levels were recorded. A laser salpingopharyngostomy was subsequently made into the right guttural pouch. The guttural pouch environment was re-sampled as above on days 7 and 14 to detect differences in the local environment of the guttural pouch caused by the laser salpingopharyngostomy. The guttural pouch environment was altered by the laser salpingopharyngostomy. Baseline recorded values within the guttural pouch were highly constant within each horse. Post laser salpingopharyngostomy there was considerable variation within the guttural pouch between horse and during the period of sampling. Specifically, CO2 levels post laser salpingopharyngostomy appeared to be linked directly to the horse's respiratory pattern with peaks and troughs recorded post laser salpingopharyngostomy. The variation in CO2 was significantly different at days 7 and 14 post laser salpingopharyngostomy compared with baseline levels (day 7=6mmHg, day 14=8.83mmHg). Oxygen levels were also more varied during sampling compared with baseline (day 7=3.4%, day 14=1.83%). There was no change in humidity or temperature during the study. This study was conducted on horses with no evidence of guttural pouch abnormalities or disease. Laser salpingopharyngostomy alters the guttural pouch environment and this may be useful in the treatment of guttural pouch disease where this alteration is desirable.

P844 Higher proportions of genera and species in the Firmicutes phylum are associated with a healthy pouch compared with patients with chronic pouchitis

Abstract Background Studies highlighting changes in bacterial composition in the ileoanal pouch are limited by heterogeneity in analysis techniques and sampling strategies Therefore, caution must be used when interpreting microbiota data. Similar to findings in IBD, a decrease in bacterial diversity and ‘dysbiosis’ are associated with acute and chronic inflammation in the pouch. Changes in Clostridium spp. and E. coli are associated with inflamed pouches and treatment response. This study aimed to compare the bacterial microbiota composition in patients with chronic pouchitis who responded to antibiotics vs. those who did not. Methods Patients with confirmed chronic pouchitis defined by a pouch disease activity score ≥ 7 were treated with antibiotics. If patients were already on antibiotics, they were offered the opportunity to stop. Follow up was at 4 weeks to check clinical status. Patients who came off antibiotics who flared were given the opportunity to restart the antibiotics to prevent deterioration. Patients were analysed as either on antibiotics if they received antibiotics 2 weeks prior to the clinic or off antibiotics if they had stopped all antibiotics 2 weeks prior to follow-up. Stool was collected from patients on follow-up and DNA was extracted from this stool. Sequencing was performed on an Illumina platform. Statistical analysis was performed using STAMP 2.1.3 software with Welch’s two-sided t-test for comparing two groups with false discovery rate correction. Results There were 28 patients in the cohort; 23 patients with chronic pouchitis and 5 healthy controls who had never had pouchitis. Ten patients were female. The median age of the cohort was 47 years (range 26–74 years). A total of 12 samples on antibiotics and 11 off antibiotics. There were 10 responders and 13 non-responders. There were no differences between responders and non-responders and no differences in those taking antibiotics vs. those not taking antibiotics with chronic pouchitis. Healthy controls had significantly higher proportions of clostridium genera (p = 0.01) when compared with patients who fail to respond to antibiotics. Healthy controls had significantly higher proportions of lachnospiraceae species (p = 0.03) when compared with those that responded to antibiotic treatment for chronic pouchitis. Conclusion In a small cohort with chronic pouchitis we were unable to detect any bacterial differences between those that responded to antibiotics vs. those that did not. Despite this a healthy pouch had significantly higher proportions of Firmicutes species and genera which has been supported in other literature.

Vedolizumab for chronic antibiotic-refractory pouchitis.

BackgroundChronic antibiotic-refractory pouchitis (CARP) is a complication of ileal pouch-anal anastomosis (IPAA), which poses a therapeutic challenge. Vedolizumab, a gut-selective monoclonal antibody to the α4β7 of integrin, has been used in such patients, but data on its efficacy are limited. Our aim was to assess the efficacy and safety of vedolizumab as induction therapy in CARP patients.MethodsIn this single-center, historic cohort, patients with CARP who received vedolizumab between January 2015 to June 2017 were identified and analysed. Patients were included if they had active pouchitis with a total of modified pouch disease activity index (mPDAI) score ≥5 or if unavailable clinician diagnosis of active pouchitis. Pre-treatment and at 3-month post-therapy pouchoscopy and clinical visits were used to calculate mPDAI.ResultsA total of 19 patients were included in the study. The mean age was 26.7 ± 12.8 years, with 10 (53%) males. Nine (47%) patients had been treated with anti-tumor necrosis factor (TNF) agents before colectomy and 10 (53%) had anti-TNFs after colectomy and IPAA. Six (32%) patients had improvement in the mPDAI symptom subscores (P = 0.031) and 14 (74%) had improvement in both endoscopic and total mPDAI scores with a median change of –2 units (both P = 0.031). Adverse events were noted only in two (11%) patients and four (21%) required surgery for CARP.ConclusionsOur study suggests that vedolizumab has efficacy and can be safely used for CARP patients. Larger studies with a higher number of patients are required to confirm these findings.

Loss of tolerance to glycoprotein 2 isoforms 1 and 4 is associated with Crohn's disease of the pouch.

Zymogen granule glycoprotein 2 (GP2) is a major autoantigen of Crohn's disease-specific pancreatic autoantibodies. To test a link between loss of tolerance to isoforms of GP2 and pouch disorders in a cross-sectional study in ulcerative colitis patients with ileal pouch-anal anastomosis (IPAA). Serum samples of 117 consecutive ulcerative colitis patients after IPAA were tested for presence of Anti-GP2 isoforms 1 (GP21 ) & 4 (GP24 ) IgG and IgA as well as anti-Saccaromyces cervisiae (ASCA) IgG and IgA antibodies in a blinded fashion via enzyme-linked immunosorbent assay. Pouch disorders were diagnosed based on clinical, endoscopic, histological and radiographic criteria. Crohn's disease of the pouch was defined as involvement of the small bowel mucosa proximal to the ileal pouch with Crohn's disease, development of perianal complications or pouch fistula more than 3months after ileostomy closure. Positivity and level of Anti-GP21 IgG (AUC 0.77; P<0.001 & P=0.02, respectively), Anti-GP24 IgG (AUC 0.74; P<0.001 & P=0.025, respectively) and Anti-GP24 IgA (AUC 0.77; P<0.001 to P=0.018, respectively) were specifically associated with Crohn's disease of the pouch. Anti-GP2 was not associated with endoscopic or histological pouch disease activity index. Neither positivity nor levels of ASCA IgG (AUC 0.63; P=0.12 & P=0.35, respectively) or ASCA IgA (AUC 0.67; P=0.38 & P=0.53) were associated with pouch phenotypes. The novel anti-GP21 and GP24 antibodies are associated with Crohn's disease of the pouch in ulcerative colitis patients after IPAA. Serological anti-GP2 antibodies could aid in diagnosis of Crohn's disease of the pouch.

Guttural pouch diseases in horses: A challenging differential diagnosis

Guttural pouch diseases in horses: A challenging differential diagnosis