Clinical and histological impact of diffuse inflammation at pouchoscopy.

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Kenichiro Toritani, Hideaki Kimura, Koki Goto, Mao Matsubayashi, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3886677/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The anatomical location of inflammation in and around the ileal pouch affects the pouch survival rate, and diffuse inflammation have poor pouch survival rates. Aims We aimed to clarify the symptoms and histological findings of diffuse inflammation of the pouch. Methods We evaluated the symptoms, treatment, and histological findings according to the endoscopic phenotypes of diffuse inflammation, focal inflammation, and normal as the pouch body phenotype, and afferent limb involvement, inlet involvement, cuffitis, and fistula as the peripheral findings. Results Of the 318 pouchoscopies, 47 had diffuse inflammation, 201 had focal inflammation and 70 were normal. Symptomatic patients had diffuse inflammation more frequently (46.8%) than focal inflammation (13.4%) and normal (14.2%), with no difference between focal inflammation and normal. Antibiotics and steroids were higher rate administered in cases of diffuse inflammation, but not in cases of focal inflammation or in normal cases. Histological inflammation, inflammatory bowel disease (IBD)-specific finding, and colonic metaplasia showed severity in the order of diffuse inflammation > focal inflammation > normal. The number of peripheral inflammatory findings overlapped in the following order: diffuse inflammation > focal inflammation > normal. The number of symptomatic patients increased as the number of peripheral inflammatory findings increased. Conclusion Pouches with diffuse inflammation are more symptomatic, have a higher use of therapeutic agents, and have more severe histological inflammation, IBD-specific finding and colonic metaplasia accompanying peripheral inflammatory findings than the other groups. The higher the overlap of inflammatory findings in the surrounding tissues, the more symptomatic the patients will appear. Ulcerative colitis Ileal pouch Pouchitis diffuse inflammation Chicago classification Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Inflammation of the pouch (pouchitis) is a common complication of ileal pouch-anal anastomosis (IPAA). The pouchitis disease activity index (PDAI) and pouchitis activity score (PAS) are widely used in the diagnosis and severity of pouchitis [ 1 , 2 ]; however, the long-term impact and prognosis of pouchitis are not well understood. Recently, the prognosis of ileal pouches has been shown to differ depending on the site of inflammation [ 3 ]. The Chicago classification focuses on the inflammation site of the ileal pouch, and patients with diffuse inflammation in the pouch and patients with overlapping classifications have low pouch survival rate [ 4 ]. Reports based on the Chicago classification have been published in recent years [ 5 , 6 ]. However, the clinical symptoms and histological findings in these patients are not clear, and it is unclear why diffuse inflammation have a poor long-term prognosis. The present study therefore clarified the clinical and histological effects of the endoscopic phenotype of the diffuse inflammation in the pouch. Materials and Methods Study population and material The study population and materials are shown in Fig. 1 . We enrolled 187 consecutive patients who underwent initial surgical resection of ulcerative colitis (UC) at Yokohama City University Medical Center in Japan, a tertiary referral IBD center, from January 2012 to December 2018. The exclusion criteria were as follows: (1) no ileal pouch construction; (2) no postoperative pouchoscopy; and (3) an insufficient assessment or biopsy at pouchoscopy. The indications, technique, and the procedure for surgery were as previously reported [ 7 – 9 ]. In brief, stapled IPAA was performed in patients whose surgical indications were severe or refractory colitis, and proctocolectomy with hand-sewn IPAA was performed in patients whose surgical indications were cancer or dysplasia. A 12 cm-long ileal J-pouch was constructed for all patients. Pouchoscopy was also performed routinely every 2 years as previously reported [ 7 ]. Patients were referred every 3 months or when symptomatic. Pouchitis was diagnosed by the clinician based on symptoms and the recent endoscopic findings, and an antibiotic was prescribed. If the patient was resistant to antibiotics, steroid or inflammatory bowel disease (IBD) drugs were prescribed in agreement with the patient. Probiotics and antidiarrheal medications were prescribed based on the patient's wishes and the defecation condition. A total 187 patients and 318 pouchoscopies (until March 2020) were enrolled. The characteristics of the study population are presented in Supplementary Tables 1 and 2. The postoperative diagnosis were UC in 186 patients and indeterminate colitis in 1 patient. The mean follow-up period was 4.7 (interquartile range: 3.3–6.6) years. No postoperative oncogenesis was observed in any patient during the follow-up period. Pouch failure was experienced in 1 case (0.5%). Pouchitis was observed in 35 cases (18.7%) during the follow-up period, and 59 cases (18.6%) were symptomatic of pouchitis at the time of pouchoscopy. Endoscopic definition of Chicago classification The anatomical lesion at pouchoscopy was evaluated based on the Chicago classification (Figure.2) [ 4 ]. In summary, the oral side of the pouch was defined as the afferent limb (AL), the inflow portion into the pouch as the inlet (IL), and the contralateral side of the AL as the tip of J (Tip). The oral half of the pouch was defined as proximal pouch (PP), the anal half as distal pouch (DP), and the area from the dentate line to the ileal pouch-anal anastomosis as the rectal cuff (RC). Inflammation in these lesions was also evaluated based on the Chicago classification [ 4 ], and endoscopic inflammatory findings (edema, granularity, friability, loss of vascular pattern, mucous exudate, and ulceration) were evaluated according to the PDAI [ 1 ]. Diffuse inflammation was defined as two or more inflammatory findings at all pouch sites (Tip, PP and DP). Normal was defined as no inflammation at any sites of the pouch, and focal inflammation was defined as neither normal nor diffuse inflammation (Figure. 3). Peripheral findings of the pouch were classified as AL involvement if one or more inflammatory findings were found in the AL, IL involvement if one or more inflammatory findings were found in the IL, cuffitis if one or more inflammatory findings were found in the RC, and fistulas if there was fistula at any site six months postoperatively (Figure.4). Based on this definition, pouches were classified as having diffuse inflammation, normal, or focal inflammation, and the peripheral findings around the pouch (AL involvement, IL involvement, cuffitis, and fistula) were considered accompanying findings (peripheral inflammatory findings). Two physicians (H.K. and K.T.) specializing in IBD and with more than 5 years of experience, checked the colonoscopy's report. Clinical and Histopathological evaluation The clinical evaluation was performed using clinical reports. All patients were surveyed for stool frequency, medication status, and clinical symptoms according to the PDAI clinical subscore (PDAI-C) at the time of pouchoscopy [ 1 ]. Biopsies were obtained from the most endoscopically inflamed sites in each segment (AL, PP, and DP). Hematoxylin and eosin-stained histological sections from biopsy specimens of the AL, PP and DP were re-examined. The histopathological evaluation was performed as described in our previous report [ 4 ]. In brief, histological inflammation was evaluated using the PDAI histology subscore (PDAI-H) [ 1 ], IBD-specific findings (basal plasmacytosis, crypt distortion, crypt atrophy, and paneth cell metaplasia) as the IBD Score (S IBD ) [ 10 ], colonic metaplasia (villus atrophy and crypt hyperplasia) as the colonic metaplasia scores (CMS) [ 11 ], and presence of granuloma as one of the characteristics of Crohn’s disease (CD). Statistical analyses Descriptive statistics were reported as the median and interquartile range for continuous variables, and frequencies and percentiles for categorical variables. Differences between continuous variables were tested using the Mann-Whitney U test, and categorical variables were tested using chi-squared test. P-values of < 0.05 were considered statistically significant, but the Bonferroni method was used when multiple comparisons were conducted (3 group comparison, P-values of < 0.017 were considered statistically significant). Statistical analyses were performed using the SPSS software program (version 25.0, SPSS Inc., Chicago, IL, USA). Ethical Considerations Approval of the Research Protocol: The study protocol was approved by the Ethical Advisory Committee of Yokohama City University Graduate School of Medicine and the institutional review board of each participating hospital before the study was initiated (B210400067). Results Symptoms and treatment according to the pouch phenotype Symptoms and treatment between diffuse inflammation, focal inflammation. and the normal are listed in Table 1. The proportion of symptomatic patients with diffuse inflammation was significantly higher (46.8%) than that with focal inflammation (13.4%) and normal (14.2%), but there was no marked difference between the proportions with focal inflammation and those with normal groups. The PDAI-C was also significantly higher in diffuse inflammation than in focal inflammation and normal. Among these symptoms, increased stool frequency and fecal urgency were significantly more common in patients with diffuse inflammation than in others. Regarding medication at pouchoscopy, there were no marked differences in the rates of probiotics, berberine chloride medication, and IBD drugs among the three groups. However, the use of loperamide was significantly lower in normal than in focal inflammation, and the use of antibiotic and steroid was significantly higher in diffuse inflammation than in other groups. The PDAI score was significantly higher in the diffuse inflammation group, following by the focal inflammation group and then the normal group, and the same trend was observed for the positive rate of PDAI and modified PDAI. Symptoms and treatment according to the number of the peripheral inflammatory findings The symptoms and treatment according to the number of peripheral inflammatory findings were shown in Table 2 . Cases with multiple peripheral inflammatory finding were more common in diffuse inflammation and less in normal, whereas cases with no peripheral inflammatory findings were more common in normal and less common in diffuse inflammation. Details of regarding the duplication of the pouch phenotype and peripheral inflammatory findings are shown in Supplementary table 3. The number of symptomatic patients and PDAI-C increased in relation to the number of peripheral inflammatory findings. The frequency of defecation was significantly higher in pouches with multiple peripheral inflammatory findings than in those with no peripheral inflammation. The use of antibiotics was significantly higher in the multiple peripheral inflammatory finding group than in the single and no peripheral inflammatory findings groups. Endoscopic and histological inflammation according to the pouch phenotype Endoscopic and histological inflammation according to pouch phenotype are shown in Fig. 5 and Supplementary Fig. 1. Endoscopic and histological inflammation in the pouch were significantly higher in the diffuse inflammation group, followed by the focal inflammation and then normal group. The S IBD and CMS according to the pouch phenotype were shown in Supplementary Figs. 2 and 3. The IBD score and CMS in the pouch were significantly higher in the diffuse inflammation group, followed by the focal inflammation and then normal group. None of the specimens showed granulomas. Discussion We evaluated 187 patients and 318 pouchoscopies and found that pouches with diffuse inflammation were more symptomatic, with a higher use of therapeutic agents and severe endoscopic and histological inflammation accompanying peripheral inflammatory findings than in the other groups. Diffuse inflammation in the pouch is associated with a high risk of pouch excision [ 4 ], and it cause low Cleveland Global Quality of Life score [ 5 ]. We also found that symptoms characteristic of pouchitis, such as increased stool frequency, stool urgency, and fever, were often observed in patients with diffuse inflammation of the pouch, and the decreased quality of life associated with these symptoms may be linked to pouch failure. Histological inflammation and colonic metaplasia (villus atrophy and crypt hyperplasia) in the pouch were high in cases of diffuse inflammation. Severe inflammation and villus atrophy (type C mucosa) have been reported to be risk factors for carcinogenesis [ 12 ], and carcinogenesis in the pouch leads to pouch failure. However, in a multicenter surveillance pouchoscopy study using the same risk classification, no neoplasia was found at follow-up in the pouch with type C mucosa [ 13 ]. We found many cases of high inflammation with colonic metaplasia, including villous atrophy in diffuse inflammation, but no case of carcinogenesis. In the latest consortium, the relationship between pouch inflammation and carcinogenesis was unclear [ 14 ]. Treatment of asymptomatic patients with diffuse inflammation are controversial. Cases of focal inflammation, i.e. pouches with localized inflammation, had fewer symptoms than cases of diffuse inflammation, but the clinical symptoms did not differ markedly from normal. Focal inflammation may thus not contribute to the clinical symptoms. Loperamide, a powerful antidiarrheal agent, was used more in focal inflammation than in normal cases, and inflammation was more concentrated in the distal pouch than the proximal pouch and tips in focal inflammation. Some focal inflammation may be an adaptive change to fecal stasis [ 15 ]. IBD-specific findings showed that over half of the diffuse inflammation pouch bodies had definite IBD (IBD score ≥ 2), whereas over half of the focal inflammation pouch bodies had unknown or non-IBD (IBD score ≥ 0). Therefore, these groups may be distinguished from those with pouchitis associated with IBD pathogenesis [ 14 ]. Normal cases with no inflammation in the pouch were associated with the highest rate of pouch survival rate [ 4 ]. In our study, 14.2% of cases had some pouchitis symptoms. Surrounding inflammation or structural disease may cause symptoms of pouchitis when the pouch is not inflamed [ 16 ]. If there are no abnormality in these cases, functional pouch disorders such as irritable pouch syndrome, pouchalgia fugax, and neuropathic pain may be considered [ 17 ]. Peripheral inflammatory findings, and inflammatory findings outside of the pouch, were classified in the same category as findings within the pouch in the Chicago classification. We focused on the impact of diffuse inflammation within the pouch; therefore, we categorized the peripheral inflammatory findings as accompanying findings. Peripheral inflammatory findings were more common in diffuse inflammation, the number of symptomatic patients increased in proportion to the number of peripheral inflammatory findings, and the use of antibiotic was higher in patients with multiple peripheral inflammatory findings than in the other patients. Peripheral inflammatory findings were classified as AL involvement, IL involvement, cuffitis, and fistula, as in previous reports. AL and IL involvement are both pre-pouch ileitis, and the symptoms of pre-pouch ileitis are not specific [ 18 ]. Pre-pouch ileitis has been reported in cases diagnosed with CD or CD like pouch, and these cases are resistant to treatment and have poor prognostic factors [ 3 , 18 ]. However, pre-pouch ileitis can also be caused by systemic inflammatory reactions similar to duodenitis and extraintestinal complications, backwash ileitis from diffuse pouchitis, ischemia, use of non-steroidal anti-inflammatory drugs, and structural complications in addition to CD [ 14 ]. In our data, granulomas were not observed in all cases, and about half of the cases were complicated by diffuse inflammation, suggesting that many cases may not have been inflammation due to CD pathology. Cuffitis shows inflammation in the retained rectal mucosa, with symptoms similar to those of pouchitis, such as bleeding, increased stool frequency, and fecal urgency. Although classic cuffitis is secondary to residual UC in rectal tissue, non-classic cuffitis is defined as inflammation from any other cause [ 19 ]. As shown in Supplementary Table 3, cuffitis was more common with diffuse inflammation and focal inflammation than with normal cases. Therefore, inflammation in some cases with a residual rectum may be related to inflammation of the pouch. Hand-sewn IPAA completely removes the rectal mucosa and theoretically cannot cause cuffitis (cuffitis in this study was Stapled IPAA/hand-sewn IPAA: 46.2%/0.0%, data not shown in the results). Because stapled IPAA is a simple procedure and has good anorectal function [ 7 ], the indication for hand-sewn or stapled IPAA should be examined based on its risks and benefits. Fistulas were found in all three groups, and there was no significant difference among them. Late-onset fistula, i.e. all cases except early-onset fistula (anastomosis leakage), which was also excluded from the fistula cases in this study, is considered a suspicious finding for CD pouch and CD-like pouch [ 3 ]. Fistulas due to cryptoglandular infection from the dentate line are more frequently observed than those from the pouch [ 20 ], and this frequency has been found to be higher in UC patients than in healthy controls [ 21 ]. In our experience, over half of fistulas occur from the dentate line, and it should be noted that not all post-IPAA fistulas are associated with CD. Several limitations associated with the present study warrant mention. First, it was a single-center, retrospective study. Because only routine endoscopies are performed for surveillance, endoscopies are not performed when the symptoms are severe. In addition, cases with insufficient assessment, imaging findings, and tissue evaluation were excluded, so cases with structural complications, such as stenosis, may have been among the excluded cases. Second, the short follow-up period led to resection of the pouch in only one case. Long-term follow-up is required to investigate why pouch resection is often performed in patients with diffuse inflammation. Conclusion Pouches with diffuse inflammation are more symptomatic, have a higher use of therapeutic agents, and more severe endoscopic and histological inflammation accompanying peripheral inflammatory findings than the other groups. The greater the overlap of inflammatory findings in the surrounding tissues, the more symptomatic patients will appear. These symptoms, histological findings, and treatment needs may explain the poor prognosis of pouches with diffuse inflammation. Declarations Author contribution: KT and HK contributed to the study design. All of the authors contributed to the data collection and interpretation. HK and KT evaluate endoscopic findings. MO and KT evaluate histopathological findings. All of the authors contributed to the writing or review of the report and approved the final version. Acknowledgment of grant support: This work was supported by no grant support of any kind. Financial disclosures and conflict of interest: This study has no financial disclosures or conflicts of interest. Hideaki Kimura reports receiving lecture fees from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, Janssen Pharmaceutical K.K., Kyorin Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Johnson and Johnson and receiving research funding from Chugai Pharmaceutical Co., Ltd. while conducting the study. Reiko Kunisaki reports receiving research grants or personal fees from AbbVie GK, Janssen Pharmaceutical K.K., JIMRO Co,. Ltd, Kyorin Pharmaceutical Co., Ltd, Kyowa Hakko Kirin Co., Ltd, Nippon Kayaku Co.,Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharma Co Ltd and Zeria Pharmaceutical Co. Ltd while conducting the study. Jun Watanabe reports receiving honoraria for lectures from Johnson and Johnson, Medtronic, Eli Lilly, and Takeda Pharmaceuticals and receiving research funding from Medtronic, AMCO, TERUMO, and Stryker Japan outside the submitted work. Itaru Endo reports receiving personal fees from ASAHI KASEI PHARMA CORPORATION while conducting the study. Kenichiro Toritani, Koki Goto, Mao Matsubayashi, Atsushi Ishibe, and Masako Otani have no financial disclosures or conflicts of interest. Disclosure of financial arrangements: None. Acknowledgments The authors gratefully acknowledge the patients who participated in the study. Data Availability The data underlying this article cannot be shared publicly per the Yokohama City University Medical Center’s Institutional Review Board policy to preserve the privacy of individuals that participated in the study. The data will be shared on reasonable request to the corresponding author. References Sandborn WJ, Tremaine WJ, Batts KP, Pemberton JH, Phillips SF. Pouchitis after ileal pouch-anal anastomosis: a pouchitis disease activity index. Mayo Clin Proc. 1994;69:409–415. Heuschen UA, Autschbach F, Allemeyer EH, et al. Long-term follow-up after ileoanal pouch procedure: algorithm for diagnosis, classification, and management. Dis Colon Rectum. 2001;44(4):487–99. Huguet M, Pereira B, Goutte M, et al. Systematic Review With Meta-Analysis: Anti-TNF Therapy in Refractory Pouchitis and Crohn’s Disease-Like Complications of the Pouch After Ileal Pouch-Anal Anastomosis Following Colectomy for Ulcerative Colitis. 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Tables Table.1 The symptoms and treatment between the phenotypes of the pouch Factors Diffuse inflammation (n=47) Focal inflammation (n=201) Normal (n=70) p value D/ F D/ N F/ N Age at pouchoscopy (year)* 44 (27-57) 39 (27-52) 44 (28-57) 0.360 0.969 0.284 Duration of pouch usage (year)* 1.4(1.2-3.4) 2.3(1.2-3.6) 1.4 (1.3-2.7) 0.079 0.898 0.027 PDAI clinical subscore* PDAI clinical subscore ≥1 Increased stool frequency Bleeding Fecal urgency Fever 0 (0-1) 22 (46.8) 11 (23.4) 4 (8.5) 14 (29.7) 2 (4.2) 0 (0-0) 27 (13.4) 14 (7.0) 12 (5.9) 11 (5.4) 0 (0.0) 0 (0-0) 10 (14.2) 4 (5.7) 2 (2.9) 5 (7.1) 0 (0.0) <0.001 <0.001 0.001 0.529 <0.001 0.003 <0.001 <0.001 0.001 0.180 0.001 0.084 0.912 0.858 0.526 0.317 0.597 n.a Stool frequency* 8 (7-10) 7 (5-10) 7 (5-10) 0.012 0.020 0.956 Medication Probiotics Berberine chloride Loperamide Antibiotic Steroid IBD drugs 34 (72.3) 33 (70.2) 15 (31.9) 7 (14.9) 5(10.6) 1(2.1) 148 (73.6) 137 (68.1) 60 (29.9) 9 (4.5) 3(1.5) 2(1.0) 49(70.0) 42 (60.0) 10 (14.3) 1 (1.4) 1(1.4) 0(0.0) 0.857 0.785 0.781 0.009 <0.001 0.523 0.785 0.259 0.023 0.005 0.027 0.220 0.557 0.214 0.010 0.244 0.970 0.402 PDAI PDAI ≥7 Modified PDAI Modified PDAI≥5 9 (7-11) 38 4 (3-5) 19 5 (4-6) 37 2(2-2) 9 2 (1-3) 0 0 (0-0) 0 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 Values in parentheses are percentages, unless indicated otherwise *Values are median (interquartile range) PDAI, Pouch disease activity index; IBD drugs, inflammatory bowel disease drugs including amino salicylates, immunosuppressor, immunomodulators and biologics. Table 2. The symptoms and treatment between the number of the peripheral inflammatory findings Factors Multiple peripheral inflammation (n=41) Single peripheral inflammation (n=135) No peripheral inflammation (n=142) p value M/ S M/ N S/ N Age at pouchoscopy (year)* 42 (26-49) 42 (26-55) 42 (30-53) 0.609 0.577 0.967 Duration of pouch usage (year)* 1.7 (1.2-3.9) 1.6 (1.2-3.5) 1.5 (1.2-3.4) 0.590 0.537 0.927 Phenotypes of the pouch Normal Focal inflammation Diffuse inflammation 0 (0.0) 13 (31.7) 28 (68.3) 17 (12.6) 101 (74.8) 17 (12.6) 53 (37.3) 87 (61.3) 2 (1.4) <0.001 <0.001 <0.001 PDAI clinical sub-score PDAI clinical sub-score≥1 Increased stool frequency Bleeding Fecal urgency Fever 0 (0-2) 19 (46.3) 13 (31.7) 6 (14.6) 13 (31.7) 1 (2.4) 0 (0-0) 27 (20.0) 8 (5.9) 7 (5.1) 13 (9.6) 1 (0.7) 0 (0-0) 13 (9.2) 7 (4.9) 5 (3.5) 4 (2.8) 0 (0) <0.001 0.001 <0.001 0.043 <0.001 0.369 <0.001 <0.001 <0.001 0.009 <0.001 0.064 0.014 0.010 0.662 0.566 0.020 0.308 Stool frequency 9 (7-10) 7 (6-10) 6 (5-10) 0.051 0.001 0.025 Medication Probiotics Berberine chloride Loperamide Antibiotic Steroid IBD drugs 31 (75.6) 29 (70.7) 15 (36.6) 10 (24.3) 2 (4.9) 1 (2.4) 106 (78.5) 100 (74.1) 40 (29.6) 3 (2.1) 4 (2.9) 2 (1.5) 94 (66.2) 83 (58.5) 30 (21.1) 4 (2.8) 3 (2.1) 0 (0.0) 0.694 0.672 0.400 <0.001 0.554 0.678 0.254 0.155 0.043 <0.001 0.339 0.062 0.022 0.006 0.104 0.753 0.652 0.145 Values in parentheses are percentages, unless indicated otherwise *Values are median (interquartile range) AL, afferent limbs; PP, proximal pouch; DP, distal pouch; PDAI, Pouchitis disease activity index; IBD drugs, inflammatory bowel disease drugs including amino salicylates, immunosuppressor, immunomodulators and biologics; M, Multiple peripheral inflammation; S, Single peripheral inflammation; N, no peripheral inflammation. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3886677","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":268628308,"identity":"c57ea216-1700-47a0-81f0-7b1e7f8f9426","order_by":0,"name":"Kenichiro Toritani","email":"","orcid":"","institution":"Yokohama City University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Kenichiro","middleName":"","lastName":"Toritani","suffix":""},{"id":268628309,"identity":"710c5880-2742-40b3-a2f2-9eecf95ae58a","order_by":1,"name":"Hideaki Kimura","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8UlEQVRIiWNgGAWjYBACAx7GBoYPQJpBAllYApd6qBbGGSRqYWBg5sHQgg+Y8xxu3WzbZmPML938dMMPBrvEBvbDDxgsd+DWYtnb2HY7ty3NTHLOMbObPQzJiQ08aQYMkmfwOOw8I0jLYRuDGwlmN3j/HUhsYMhhYJBsI6DFEqwl/dvNPwxALfxvCGg5C3QYY9thM4MbOWa3eUBaJAjZcuZg282ec2nGkjNyym7LMCQbt0k8MziA1y9n0p/d+FFmY9gvkb7t5hsGO9l+/uSHjyXxhBgYMLIhcUDsw5INBLQw/EE34yNBLaNgFIyCUTCCAACpqVRw5GjnoAAAAABJRU5ErkJggg==","orcid":"","institution":"Yokohama City University Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Hideaki","middleName":"","lastName":"Kimura","suffix":""},{"id":268628310,"identity":"b42c572a-3a7e-4d34-adf0-2162d96e423f","order_by":2,"name":"Koki Goto","email":"","orcid":"","institution":"Yokohama City University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Koki","middleName":"","lastName":"Goto","suffix":""},{"id":268628311,"identity":"b70e1696-19a8-4365-b89a-e69f875f63ee","order_by":3,"name":"Mao Matsubayashi","email":"","orcid":"","institution":"Yokohama City University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Mao","middleName":"","lastName":"Matsubayashi","suffix":""},{"id":268628312,"identity":"c9064c7c-76a7-4065-be1b-029f69f4fca4","order_by":4,"name":"Reiko Kunisaki","email":"","orcid":"","institution":"Yokohama City University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Reiko","middleName":"","lastName":"Kunisaki","suffix":""},{"id":268628313,"identity":"ac484345-cc4d-49d7-841e-3968fe10ea89","order_by":5,"name":"Jun Watanabe","email":"","orcid":"","institution":"Yokohama City University Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Watanabe","suffix":""},{"id":268628314,"identity":"e4bb7454-2b83-4894-922a-06311d796bb7","order_by":6,"name":"Atsushi Ishibe","email":"","orcid":"","institution":"Yokohama City University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Atsushi","middleName":"","lastName":"Ishibe","suffix":""},{"id":268628315,"identity":"41aa681b-49ec-4eea-a70e-6fb1bde3837d","order_by":7,"name":"Masako Otani","email":"","orcid":"","institution":"International University of Health and Welfare Mita Hospital","correspondingAuthor":false,"prefix":"","firstName":"Masako","middleName":"","lastName":"Otani","suffix":""},{"id":268628316,"identity":"a3f6b2ea-771c-4111-982e-707a287e61e3","order_by":8,"name":"Itaru Endo","email":"","orcid":"","institution":"Yokohama City University Graduate School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Itaru","middleName":"","lastName":"Endo","suffix":""}],"badges":[],"createdAt":"2024-01-22 02:29:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3886677/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3886677/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50116719,"identity":"771c4597-c77b-43e9-87a2-3efc0ac52f50","added_by":"auto","created_at":"2024-01-24 18:52:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":210931,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOutline of patient selection.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eUC, Ulcerative colitis; AL, afferent limbs.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-3886677/v1/ed6cc912f071ae9e37f4c4fb.png"},{"id":50117847,"identity":"a4e53c76-e650-40c1-ad00-705c0007fff9","added_by":"auto","created_at":"2024-01-24 19:00:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":280548,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eAnatomical lesion within and around the pouch\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-3886677/v1/5f3aee2e34180d10247d4cc8.png"},{"id":50116724,"identity":"5f9a17ed-d53f-4f2c-9ee4-92269a3b3e4d","added_by":"auto","created_at":"2024-01-24 18:52:21","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1107401,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDefinition of the classification of the pouch findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePP, proximal pouch; DP, distal pouch; PDAI-E, pouchitis disease activity index endoscopic sub-score.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-3886677/v1/1d9a74e0a991cd242e800f41.png"},{"id":50117849,"identity":"9333fd46-06b4-4484-b6e2-3833563764c1","added_by":"auto","created_at":"2024-01-24 19:00:21","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":865741,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eDefinition of the classification of the peripheral findings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAL, afferent limbs; IL, inlet; PDAI-E, pouchitis disease activity index endoscopic sub-score.\u003c/p\u003e","description":"","filename":"image4.png","url":"https://assets-eu.researchsquare.com/files/rs-3886677/v1/6f813b8b74a8099637ca8a67.png"},{"id":50118170,"identity":"7318456d-fb0d-41b9-9777-556efb716adc","added_by":"auto","created_at":"2024-01-24 19:08:21","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":293292,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHistological inflammation according to the pouch phenotype\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHistological inflammation of the pouch body is in the order of diffuse inflammation\u0026gt; focal inflammation\u0026gt; normal. PDAI-H of diffuse inflammation is 1 (1-3) at AL, 4 (3-5) at PP, 4 (3-5) at DP. PDAI-H of focal inflammation is 0 (0-1) at AL, 2 (1-3) at PP, and 2 (1-3) at DP. PDAI-H of normal is 0 (0-1) at AL, 1 (0-2) at PP, and 2 (1-3) at DP.\u003c/p\u003e\n\u003cp\u003ePDAI-H, pouchitis disease activity index histological sub-score; AL, afferent limbs; PP, proximal pouch; DP, distal pouch.\u003c/p\u003e","description":"","filename":"image5.png","url":"https://assets-eu.researchsquare.com/files/rs-3886677/v1/948e78d1c88dac6578bb1c0f.png"},{"id":50658942,"identity":"29db9812-aaff-4851-9ee4-2e8da38c2a16","added_by":"auto","created_at":"2024-02-05 11:12:28","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3192632,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3886677/v1/88c94ede-2fc4-4004-ac5e-d96f1a0384e5.pdf"},{"id":50116723,"identity":"1c7591be-2cd2-466b-9d69-71654b632b60","added_by":"auto","created_at":"2024-01-24 18:52:21","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":328859,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarydata.docx","url":"https://assets-eu.researchsquare.com/files/rs-3886677/v1/7a3d0c8435813794fcd61263.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical and histological impact of diffuse inflammation at pouchoscopy.","fulltext":[{"header":"Introduction","content":"\u003cp\u003eInflammation of the pouch (pouchitis) is a common complication of ileal pouch-anal anastomosis (IPAA). The pouchitis disease activity index (PDAI) and pouchitis activity score (PAS) are widely used in the diagnosis and severity of pouchitis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]; however, the long-term impact and prognosis of pouchitis are not well understood.\u003c/p\u003e \u003cp\u003eRecently, the prognosis of ileal pouches has been shown to differ depending on the site of inflammation [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The Chicago classification focuses on the inflammation site of the ileal pouch, and patients with diffuse inflammation in the pouch and patients with overlapping classifications have low pouch survival rate [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Reports based on the Chicago classification have been published in recent years [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, the clinical symptoms and histological findings in these patients are not clear, and it is unclear why diffuse inflammation have a poor long-term prognosis.\u003c/p\u003e \u003cp\u003eThe present study therefore clarified the clinical and histological effects of the endoscopic phenotype of the diffuse inflammation in the pouch.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and material\u003c/h2\u003e \u003cp\u003eThe study population and materials are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. We enrolled 187 consecutive patients who underwent initial surgical resection of ulcerative colitis (UC) at Yokohama City University Medical Center in Japan, a tertiary referral IBD center, from January 2012 to December 2018. The exclusion criteria were as follows: (1) no ileal pouch construction; (2) no postoperative pouchoscopy; and (3) an insufficient assessment or biopsy at pouchoscopy.\u003c/p\u003e\u003cp\u003eThe indications, technique, and the procedure for surgery were as previously reported [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In brief, stapled IPAA was performed in patients whose surgical indications were severe or refractory colitis, and proctocolectomy with hand-sewn IPAA was performed in patients whose surgical indications were cancer or dysplasia. A 12 cm-long ileal J-pouch was constructed for all patients. Pouchoscopy was also performed routinely every 2 years as previously reported [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Patients were referred every 3 months or when symptomatic. Pouchitis was diagnosed by the clinician based on symptoms and the recent endoscopic findings, and an antibiotic was prescribed. If the patient was resistant to antibiotics, steroid or inflammatory bowel disease (IBD) drugs were prescribed in agreement with the patient. Probiotics and antidiarrheal medications were prescribed based on the patient's wishes and the defecation condition.\u003c/p\u003e \u003cp\u003eA total 187 patients and 318 pouchoscopies (until March 2020) were enrolled. The characteristics of the study population are presented in Supplementary Tables\u0026nbsp;1 and 2. The postoperative diagnosis were UC in 186 patients and indeterminate colitis in 1 patient. The mean follow-up period was 4.7 (interquartile range: 3.3\u0026ndash;6.6) years. No postoperative oncogenesis was observed in any patient during the follow-up period. Pouch failure was experienced in 1 case (0.5%). Pouchitis was observed in 35 cases (18.7%) during the follow-up period, and 59 cases (18.6%) were symptomatic of pouchitis at the time of pouchoscopy.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eEndoscopic definition of Chicago classification\u003c/h2\u003e \u003cp\u003eThe anatomical lesion at pouchoscopy was evaluated based on the Chicago classification (Figure.2) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In summary, the oral side of the pouch was defined as the afferent limb (AL), the inflow portion into the pouch as the inlet (IL), and the contralateral side of the AL as the tip of J (Tip). The oral half of the pouch was defined as proximal pouch (PP), the anal half as distal pouch (DP), and the area from the dentate line to the ileal pouch-anal anastomosis as the rectal cuff (RC). Inflammation in these lesions was also evaluated based on the Chicago classification [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and endoscopic inflammatory findings (edema, granularity, friability, loss of vascular pattern, mucous exudate, and ulceration) were evaluated according to the PDAI [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Diffuse inflammation was defined as two or more inflammatory findings at all pouch sites (Tip, PP and DP). Normal was defined as no inflammation at any sites of the pouch, and focal inflammation was defined as neither normal nor diffuse inflammation (Figure. 3). Peripheral findings of the pouch were classified as AL involvement if one or more inflammatory findings were found in the AL, IL involvement if one or more inflammatory findings were found in the IL, cuffitis if one or more inflammatory findings were found in the RC, and fistulas if there was fistula at any site six months postoperatively (Figure.4). Based on this definition, pouches were classified as having diffuse inflammation, normal, or focal inflammation, and the peripheral findings around the pouch (AL involvement, IL involvement, cuffitis, and fistula) were considered accompanying findings (peripheral inflammatory findings). Two physicians (H.K. and K.T.) specializing in IBD and with more than 5 years of experience, checked the colonoscopy's report.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eClinical and Histopathological evaluation\u003c/h2\u003e \u003cp\u003eThe clinical evaluation was performed using clinical reports. All patients were surveyed for stool frequency, medication status, and clinical symptoms according to the PDAI clinical subscore (PDAI-C) at the time of pouchoscopy [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBiopsies were obtained from the most endoscopically inflamed sites in each segment (AL, PP, and DP). Hematoxylin and eosin-stained histological sections from biopsy specimens of the AL, PP and DP were re-examined. The histopathological evaluation was performed as described in our previous report [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In brief, histological inflammation was evaluated using the PDAI histology subscore (PDAI-H) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], IBD-specific findings (basal plasmacytosis, crypt distortion, crypt atrophy, and paneth cell metaplasia) as the IBD Score (S\u003csub\u003eIBD\u003c/sub\u003e) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], colonic metaplasia (villus atrophy and crypt hyperplasia) as the colonic metaplasia scores (CMS) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and presence of granuloma as one of the characteristics of Crohn\u0026rsquo;s disease (CD).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eDescriptive statistics were reported as the median and interquartile range for continuous variables, and frequencies and percentiles for categorical variables. Differences between continuous variables were tested using the Mann-Whitney \u003cem\u003eU\u003c/em\u003e test, and categorical variables were tested using chi-squared test. P-values of \u0026lt;\u0026thinsp;0.05 were considered statistically significant, but the Bonferroni method was used when multiple comparisons were conducted (3 group comparison, P-values of \u0026lt;\u0026thinsp;0.017 were considered statistically significant). Statistical analyses were performed using the SPSS software program (version 25.0, SPSS Inc., Chicago, IL, USA).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eEthical Considerations\u003c/h2\u003e \u003cp\u003e Approval of the Research Protocol: The study protocol was approved by the Ethical Advisory Committee of Yokohama City University Graduate School of Medicine and the institutional review board of each participating hospital before the study was initiated (B210400067).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003eSymptoms and treatment according to the pouch phenotype\u003c/h2\u003e\n \u003cp\u003eSymptoms and treatment between diffuse inflammation, focal inflammation. and the normal are listed in Table\u0026nbsp;1. The proportion of symptomatic patients with diffuse inflammation was significantly higher (46.8%) than that with focal inflammation (13.4%) and normal (14.2%), but there was no marked difference between the proportions with focal inflammation and those with normal groups. The PDAI-C was also significantly higher in diffuse inflammation than in focal inflammation and normal. Among these symptoms, increased stool frequency and fecal urgency were significantly more common in patients with diffuse inflammation than in others. Regarding medication at pouchoscopy, there were no marked differences in the rates of probiotics, berberine chloride medication, and IBD drugs among the three groups. However, the use of loperamide was significantly lower in normal than in focal inflammation, and the use of antibiotic and steroid was significantly higher in diffuse inflammation than in other groups.\u003c/p\u003e\n \u003cp\u003eThe PDAI score was significantly higher in the diffuse inflammation group, following by the focal inflammation group and then the normal group, and the same trend was observed for the positive rate of PDAI and modified PDAI.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003eSymptoms and treatment according to the number of the peripheral inflammatory findings\u003c/h2\u003e\n \u003cp\u003eThe symptoms and treatment according to the number of peripheral inflammatory findings were shown in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Cases with multiple peripheral inflammatory finding were more common in diffuse inflammation and less in normal, whereas cases with no peripheral inflammatory findings were more common in normal and less common in diffuse inflammation. Details of regarding the duplication of the pouch phenotype and peripheral inflammatory findings are shown in Supplementary table 3. The number of symptomatic patients and PDAI-C increased in relation to the number of peripheral inflammatory findings. The frequency of defecation was significantly higher in pouches with multiple peripheral inflammatory findings than in those with no peripheral inflammation. The use of antibiotics was significantly higher in the multiple peripheral inflammatory finding group than in the single and no peripheral inflammatory findings groups.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eEndoscopic and histological inflammation according to the pouch phenotype\u003c/h2\u003e\n \u003cp\u003eEndoscopic and histological inflammation according to pouch phenotype are shown in Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e and Supplementary Fig. 1. Endoscopic and histological inflammation in the pouch were significantly higher in the diffuse inflammation group, followed by the focal inflammation and then normal group. The S\u003csub\u003eIBD\u003c/sub\u003e and CMS according to the pouch phenotype were shown in Supplementary Figs. 2 and 3. The IBD score and CMS in the pouch were significantly higher in the diffuse inflammation group, followed by the focal inflammation and then normal group. None of the specimens showed granulomas.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eWe evaluated 187 patients and 318 pouchoscopies and found that pouches with diffuse inflammation were more symptomatic, with a higher use of therapeutic agents and severe endoscopic and histological inflammation accompanying peripheral inflammatory findings than in the other groups.\u003c/p\u003e \u003cp\u003eDiffuse inflammation in the pouch is associated with a high risk of pouch excision [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and it cause low Cleveland Global Quality of Life score [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. We also found that symptoms characteristic of pouchitis, such as increased stool frequency, stool urgency, and fever, were often observed in patients with diffuse inflammation of the pouch, and the decreased quality of life associated with these symptoms may be linked to pouch failure. Histological inflammation and colonic metaplasia (villus atrophy and crypt hyperplasia) in the pouch were high in cases of diffuse inflammation. Severe inflammation and villus atrophy (type C mucosa) have been reported to be risk factors for carcinogenesis [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and carcinogenesis in the pouch leads to pouch failure. However, in a multicenter surveillance pouchoscopy study using the same risk classification, no neoplasia was found at follow-up in the pouch with type C mucosa [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. We found many cases of high inflammation with colonic metaplasia, including villous atrophy in diffuse inflammation, but no case of carcinogenesis. In the latest consortium, the relationship between pouch inflammation and carcinogenesis was unclear [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Treatment of asymptomatic patients with diffuse inflammation are controversial.\u003c/p\u003e \u003cp\u003eCases of focal inflammation, i.e. pouches with localized inflammation, had fewer symptoms than cases of diffuse inflammation, but the clinical symptoms did not differ markedly from normal. Focal inflammation may thus not contribute to the clinical symptoms. Loperamide, a powerful antidiarrheal agent, was used more in focal inflammation than in normal cases, and inflammation was more concentrated in the distal pouch than the proximal pouch and tips in focal inflammation. Some focal inflammation may be an adaptive change to fecal stasis [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. IBD-specific findings showed that over half of the diffuse inflammation pouch bodies had definite IBD (IBD score\u0026thinsp;\u0026ge;\u0026thinsp;2), whereas over half of the focal inflammation pouch bodies had unknown or non-IBD (IBD score\u0026thinsp;\u0026ge;\u0026thinsp;0). Therefore, these groups may be distinguished from those with pouchitis associated with IBD pathogenesis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNormal cases with no inflammation in the pouch were associated with the highest rate of pouch survival rate [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In our study, 14.2% of cases had some pouchitis symptoms. Surrounding inflammation or structural disease may cause symptoms of pouchitis when the pouch is not inflamed [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. If there are no abnormality in these cases, functional pouch disorders such as irritable pouch syndrome, pouchalgia fugax, and neuropathic pain may be considered [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePeripheral inflammatory findings, and inflammatory findings outside of the pouch, were classified in the same category as findings within the pouch in the Chicago classification. We focused on the impact of diffuse inflammation within the pouch; therefore, we categorized the peripheral inflammatory findings as accompanying findings. Peripheral inflammatory findings were more common in diffuse inflammation, the number of symptomatic patients increased in proportion to the number of peripheral inflammatory findings, and the use of antibiotic was higher in patients with multiple peripheral inflammatory findings than in the other patients.\u003c/p\u003e \u003cp\u003ePeripheral inflammatory findings were classified as AL involvement, IL involvement, cuffitis, and fistula, as in previous reports. AL and IL involvement are both pre-pouch ileitis, and the symptoms of pre-pouch ileitis are not specific [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Pre-pouch ileitis has been reported in cases diagnosed with CD or CD like pouch, and these cases are resistant to treatment and have poor prognostic factors [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, pre-pouch ileitis can also be caused by systemic inflammatory reactions similar to duodenitis and extraintestinal complications, backwash ileitis from diffuse pouchitis, ischemia, use of non-steroidal anti-inflammatory drugs, and structural complications in addition to CD [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In our data, granulomas were not observed in all cases, and about half of the cases were complicated by diffuse inflammation, suggesting that many cases may not have been inflammation due to CD pathology. Cuffitis shows inflammation in the retained rectal mucosa, with symptoms similar to those of pouchitis, such as bleeding, increased stool frequency, and fecal urgency. Although classic cuffitis is secondary to residual UC in rectal tissue, non-classic cuffitis is defined as inflammation from any other cause [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. As shown in Supplementary Table\u0026nbsp;3, cuffitis was more common with diffuse inflammation and focal inflammation than with normal cases. Therefore, inflammation in some cases with a residual rectum may be related to inflammation of the pouch. Hand-sewn IPAA completely removes the rectal mucosa and theoretically cannot cause cuffitis (cuffitis in this study was Stapled IPAA/hand-sewn IPAA: 46.2%/0.0%, data not shown in the results). Because stapled IPAA is a simple procedure and has good anorectal function [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], the indication for hand-sewn or stapled IPAA should be examined based on its risks and benefits. Fistulas were found in all three groups, and there was no significant difference among them. Late-onset fistula, i.e. all cases except early-onset fistula (anastomosis leakage), which was also excluded from the fistula cases in this study, is considered a suspicious finding for CD pouch and CD-like pouch [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Fistulas due to cryptoglandular infection from the dentate line are more frequently observed than those from the pouch [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], and this frequency has been found to be higher in UC patients than in healthy controls [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. In our experience, over half of fistulas occur from the dentate line, and it should be noted that not all post-IPAA fistulas are associated with CD.\u003c/p\u003e \u003cp\u003eSeveral limitations associated with the present study warrant mention. First, it was a single-center, retrospective study. Because only routine endoscopies are performed for surveillance, endoscopies are not performed when the symptoms are severe. In addition, cases with insufficient assessment, imaging findings, and tissue evaluation were excluded, so cases with structural complications, such as stenosis, may have been among the excluded cases. Second, the short follow-up period led to resection of the pouch in only one case. Long-term follow-up is required to investigate why pouch resection is often performed in patients with diffuse inflammation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePouches with diffuse inflammation are more symptomatic, have a higher use of therapeutic agents, and more severe endoscopic and histological inflammation accompanying peripheral inflammatory findings than the other groups. The greater the overlap of inflammatory findings in the surrounding tissues, the more symptomatic patients will appear. These symptoms, histological findings, and treatment needs may explain the poor prognosis of pouches with diffuse inflammation.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contribution:\u0026nbsp;\u003c/strong\u003eKT and HK contributed to the study design. All of the authors contributed to the data collection and interpretation. HK and KT evaluate endoscopic findings. MO and KT evaluate histopathological findings. All of the authors contributed to the writing or review of the report and approved the final version.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment of grant support:\u0026nbsp;\u003c/strong\u003eThis work was supported by no grant support of any kind.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial disclosures and conflict of interest:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study has no financial disclosures or conflicts of interest.\u003c/p\u003e\n\u003cp\u003eHideaki Kimura reports receiving lecture fees from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, Janssen Pharmaceutical K.K., Kyorin Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Johnson and Johnson and receiving research funding from Chugai Pharmaceutical Co., Ltd. while conducting the study.\u003c/p\u003e\n\u003cp\u003eReiko Kunisaki reports receiving research grants or personal fees from AbbVie GK, Janssen Pharmaceutical K.K.,\u0026nbsp;JIMRO Co,. Ltd, Kyorin Pharmaceutical Co., Ltd, Kyowa Hakko Kirin Co., Ltd, Nippon Kayaku Co.,Ltd, Mitsubishi Tanabe Pharma Corporation, \u0026nbsp; Takeda Pharma Co Ltd and Zeria Pharmaceutical Co. Ltd while conducting the study.\u003c/p\u003e\n\u003cp\u003eJun Watanabe reports receiving honoraria for lectures from Johnson and Johnson, Medtronic, Eli Lilly, and Takeda Pharmaceuticals and receiving research funding from Medtronic, AMCO, TERUMO, and Stryker Japan outside the submitted work.\u003c/p\u003e\n\u003cp\u003eItaru Endo reports receiving personal fees from ASAHI KASEI PHARMA CORPORATION while conducting the study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eKenichiro Toritani, Koki Goto, Mao Matsubayashi, Atsushi Ishibe, and Masako Otani have no financial disclosures or conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDisclosure of financial arrangements:\u0026nbsp;\u003c/strong\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge the patients who participated in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data underlying this article cannot be shared publicly per the Yokohama City University Medical Center\u0026rsquo;s Institutional Review Board policy to preserve the privacy of individuals that participated in the study. The data will be shared on reasonable request to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSandborn WJ, Tremaine WJ, Batts KP, Pemberton JH, Phillips SF. Pouchitis after ileal pouch-anal anastomosis: a pouchitis disease activity index. Mayo Clin Proc. 1994;69:409\u0026ndash;415.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHeuschen UA, Autschbach F, Allemeyer EH, et al. Long-term follow-up after ileoanal pouch procedure: algorithm for diagnosis, classification, and management. Dis Colon Rectum. 2001;44(4):487\u0026ndash;99.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuguet M, Pereira B, Goutte M, et al. Systematic Review With Meta-Analysis: Anti-TNF Therapy in Refractory Pouchitis and Crohn\u0026rsquo;s Disease-Like Complications of the Pouch After Ileal Pouch-Anal Anastomosis Following Colectomy for Ulcerative Colitis. Inflamm Bowel Dis. 2018;24(2):261\u0026ndash;268\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkiyama S, Ollech JE, Rai V, et al. Endoscopic Phenotype of the J Pouch in Patients With Inflammatory Bowel Disease: A New Classification for Pouch Outcomes. Clin Gastroenterol Hepatol. 2022;20(2):293\u0026ndash;302.e9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu W, Wang Y, Hua Z, et al. Risk Factors and Quality of Life in Patients with Diffuse Pouchitis After Ileal Pouch Anal Anastomosis According to the Chicago Classification for J Pouch: a Retrospective Multicenter Cohort Study in China. J Gastrointest Surg. 2023;27(4):766\u0026ndash;776.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAkiyama S, Ollech JE, Traboulsi C, et al. Histopathology of Colectomy Specimens Predicts Endoscopic Pouch Phenotype in Patients with Ulcerative Colitis. Dig Dis Sci. 2022;67(8):4020\u0026ndash;4031.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKuwabara H, Kimura H, Kunisaki R, et al. Postoperative complications, bowel function, and prognosis in restorative proctocolectomy for ulcerative colitis-a single-center observational study of 320 patients. Int J Colorectal Dis. 2021; 2022;37(3):563\u0026ndash;572.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eToritani K, Kimura H, Fukuoka H, et al. Preoperative risk factors of incisional surgical site infection in severe or intractable ulcerative colitis. Surg Today. 2022;52(3):475\u0026ndash;484.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eToritani K, Kimura H, Otani M, et al. Inflammatory bowel disease-specific findings are common morphological changes in the ileal pouch with ulcerative colitis. Sci Rep. 2022;12(1):20361.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTanaka M, Saito S, Fukuda Y, Sasaki Y, Munakata A, Kudo H. Simple Mucosal Biopsy Criteria Differentiating among Crohn Disease, Ulcerative Colitis, and Other Forms of Colitis: Measurement of Validity. Scand J Gastroenterol. 2000;35(3);281\u0026ndash;286.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFurin A, Zammer O, Stuccbi A, O'Brien M, Becker JM. Colonic Metaplasia in the Ileal Pouch Is Associated With Inflammation and Is Not the Result of Long-Term Adaptation. J Gastrointest Surg. 2003;7(2);246\u0026ndash;254.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eB Veress, Reinholt FP, Lindquist K, L\u0026ouml;fberg R, Liljeqvist L. Long-term histomorphological surveillance of the pelvic ileal pouch: dysplasia develops in a subgroup of patients. Gastroenterology. 1995;109(4):1090\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSamaan MA, Forsyth K, Segal JP, et al. Current Practices in Ileal Pouch Surveillance for Patients With Ulcerative Colitis: A Multinational, Retrospective Cohort Study. J Crohns Colitis. 2019;13(6):735\u0026ndash;743.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShen B, Kochhar GS, Kariv R, et al. Diagnosis and classification of ileal pouch disorders: consensus guidelines from the International Ileal Pouch Consortium. Lancet Gastroenterol Hepatol. 2021;6(10):826\u0026ndash;849.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Silva HJ, Millard PR, Kettlewell M, Mortensen NJ, Prince C, Jewell DP. Mucosal characteristics of pelvic ileal pouches. Gut. 1991;32(1):61\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu B, Lian L, Li Y, et al. Clinical course of cuffitis in ulcerative colitis patients with restorative proctocolectomy and ileal pouch-anal anastomoses. Inflamm Bowel Dis. 2013;19(2):404\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShen B, Fazio VW, Remzi FH, et al. Risk factors for diseases of ileal pouch-anal anastomosis after restorative proctocolectomy for ulcerative colitis. Clin Gastroenterol Hepatol. 2006;4(1):81\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRottoli M, Vallicelli C, Bigonzi E et al. Prepouch Ileitis After Ileal Pouch-anal Anastomosis: Patterns of Presentation and Risk Factors for Failure of Treatment. J Crohns Colitis. 2018;12(3):273\u0026ndash;279\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHembree AE, Scherl E. Diagnosis and Management of Cuffitis: A Systematic Review. Dis Colon Rectum. 2022;65(S1):S85-S91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOzuner G, Hull T, Lee P, Fazio VW. What happens to a pelvic pouch when a fistula develops? Dis Colon Rectum. 1997;40(5):543\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSahnan K, Askari A, Adegbola SO, et al. Persistent Fistula After Anorectal Abscess Drainage: Local Experience of 11 Years. Dis Colon Rectum. 2019;62(3):327\u0026ndash;332.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable.1\u003c/strong\u003e \u003cstrong\u003eThe symptoms and treatment between the phenotypes of the pouch\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"643\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.90357698289269%\" rowspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eFactors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\" rowspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiffuse inflammation\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=47)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.774494556765163%\" rowspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eFocal inflammation\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=201)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.618973561430794%\" rowspan=\"2\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eNormal\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=70)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.08398133748056%\" colspan=\"3\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eD/ F\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eD/ N\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"33.333333333333336%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u003cstrong\u003eF/ N\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.95638629283489%\" valign=\"bottom\"\u003e\n \u003cp\u003eAge at pouchoscopy (year)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e44 (27-57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e39 (27-52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e44 (28-57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e0.360\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e0.969\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e0.284\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.95638629283489%\" valign=\"bottom\"\u003e\n \u003cp\u003eDuration of pouch usage (year)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e1.4(1.2-3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e2.3(1.2-3.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e1.4 (1.3-2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e0.079\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e0.898\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e0.027\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.95638629283489%\" valign=\"bottom\"\u003e\n \u003cp\u003ePDAI clinical subscore*\u003c/p\u003e\n \u003cp\u003ePDAI clinical subscore\u0026nbsp;\u0026ge;1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp;Increased stool frequency\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Bleeding\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Fecal urgency\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Fever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e0 (0-1)\u003c/p\u003e\n \u003cp\u003e22 (46.8)\u003c/p\u003e\n \u003cp\u003e11 (23.4)\u003c/p\u003e\n \u003cp\u003e4 (8.5)\u003c/p\u003e\n \u003cp\u003e14 (29.7)\u003c/p\u003e\n \u003cp\u003e2 (4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003cp\u003e27 (13.4)\u003c/p\u003e\n \u003cp\u003e14 (7.0)\u003c/p\u003e\n \u003cp\u003e12 (5.9)\u003c/p\u003e\n \u003cp\u003e11 (5.4)\u003c/p\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003cp\u003e10 (14.2)\u003c/p\u003e\n \u003cp\u003e4 (5.7)\u003c/p\u003e\n \u003cp\u003e2 (2.9)\u003c/p\u003e\n \u003cp\u003e5 (7.1)\u003c/p\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e0.529\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e0.180\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e0.084\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e0.912\u003c/p\u003e\n \u003cp\u003e0.858\u003c/p\u003e\n \u003cp\u003e0.526\u003c/p\u003e\n \u003cp\u003e0.317\u003c/p\u003e\n \u003cp\u003e0.597\u003c/p\u003e\n \u003cp\u003en.a\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.95638629283489%\" valign=\"bottom\"\u003e\n \u003cp\u003eStool frequency*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e8 (7-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e7 (5-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e7 (5-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e0.956\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.95638629283489%\" valign=\"bottom\"\u003e\n \u003cp\u003eMedication\u003c/p\u003e\n \u003cp\u003eProbiotics\u003c/p\u003e\n \u003cp\u003eBerberine chloride\u003c/p\u003e\n \u003cp\u003eLoperamide\u003c/p\u003e\n \u003cp\u003eAntibiotic\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Steroid\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; IBD drugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e34 (72.3)\u003c/p\u003e\n \u003cp\u003e33 (70.2)\u003c/p\u003e\n \u003cp\u003e15 (31.9)\u003c/p\u003e\n \u003cp\u003e7 (14.9)\u003c/p\u003e\n \u003cp\u003e5(10.6)\u003c/p\u003e\n \u003cp\u003e1(2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e148 (73.6)\u003c/p\u003e\n \u003cp\u003e137 (68.1)\u003c/p\u003e\n \u003cp\u003e60 (29.9)\u003c/p\u003e\n \u003cp\u003e9 (4.5)\u003c/p\u003e\n \u003cp\u003e3(1.5)\u003c/p\u003e\n \u003cp\u003e2(1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e49(70.0)\u003c/p\u003e\n \u003cp\u003e42 (60.0)\u003c/p\u003e\n \u003cp\u003e10 (14.3)\u003c/p\u003e\n \u003cp\u003e1 (1.4)\u003c/p\u003e\n \u003cp\u003e1(1.4)\u003c/p\u003e\n \u003cp\u003e0(0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.857\u003c/p\u003e\n \u003cp\u003e0.785\u003c/p\u003e\n \u003cp\u003e0.781\u003c/p\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.523\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\" valign=\"bottom\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.785\u003c/p\u003e\n \u003cp\u003e0.259\u003c/p\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003cp\u003e0.027\u003c/p\u003e\n \u003cp\u003e0.220\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.557\u003c/p\u003e\n \u003cp\u003e0.214\u003c/p\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003cp\u003e0.244\u003c/p\u003e\n \u003cp\u003e0.970\u003c/p\u003e\n \u003cp\u003e0.402\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.95638629283489%\" valign=\"bottom\"\u003e\n \u003cp\u003ePDAI\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; PDAI\u0026nbsp;\u0026ge;7\u003c/p\u003e\n \u003cp\u003eModified PDAI\u003c/p\u003e\n \u003cp\u003eModified PDAI\u0026ge;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e9 (7-11)\u003c/p\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003cp\u003e4 (3-5)\u003c/p\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.797507788161994%\"\u003e\n \u003cp\u003e5 (4-6)\u003c/p\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003cp\u003e2(2-2)\u003c/p\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.641744548286605%\"\u003e\n \u003cp\u003e2 (1-3)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.320872274143302%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues in parentheses are percentages, unless indicated otherwise\u003c/p\u003e\n\u003cp\u003e*Values are median (interquartile range)\u003c/p\u003e\n\u003cp\u003ePDAI, Pouch disease activity index; IBD drugs, inflammatory bowel disease drugs including amino salicylates, immunosuppressor, immunomodulators and biologics.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. The symptoms and treatment between the number of the peripheral inflammatory findings\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"670\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.508196721311474%\" rowspan=\"2\" valign=\"bottom\" style=\"width: 21.6405%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFactors\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.49925484351714%\" rowspan=\"2\" valign=\"bottom\" style=\"width: 13.9616%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultiple peripheral inflammation\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=41)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.157973174366617%\" rowspan=\"2\" valign=\"bottom\" style=\"width: 13.1239%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSingle peripheral inflammation\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=135)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.84053651266766%\" rowspan=\"2\" valign=\"bottom\" style=\"width: 14.6597%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;peripheral inflammation\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=142)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.994038748137108%\" colspan=\"3\" valign=\"bottom\" style=\"width: 24.2653%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.375%\" valign=\"bottom\" style=\"width: 16.1955%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM/ S\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"35.625%\" valign=\"bottom\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eM/ N\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.875%\" valign=\"bottom\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS/ N\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.55223880597015%\" valign=\"bottom\" style=\"width: 21.6405%;\"\u003e\n \u003cp\u003eAge at pouchoscopy (year)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.522388059701493%\" style=\"width: 13.9616%;\"\u003e\n \u003cp\u003e42 (26-49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.17910447761194%\" style=\"width: 13.1239%;\"\u003e\n \u003cp\u003e42 (26-55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.865671641791046%\" style=\"width: 14.6597%;\"\u003e\n \u003cp\u003e\u0026nbsp; 42 (30-53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.014925373134329%\" style=\"width: 16.1955%;\"\u003e\n \u003cp\u003e0.609\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.507462686567164%\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e0.577\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.611940298507463%\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e0.967\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.55223880597015%\" valign=\"bottom\" style=\"width: 21.6405%;\"\u003e\n \u003cp\u003eDuration of pouch usage (year)*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.522388059701493%\" style=\"width: 13.9616%;\"\u003e\n \u003cp\u003e1.7 (1.2-3.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.17910447761194%\" style=\"width: 13.1239%;\"\u003e\n \u003cp\u003e1.6 (1.2-3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.865671641791046%\" style=\"width: 14.6597%;\"\u003e\n \u003cp\u003e1.5 (1.2-3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.014925373134329%\" style=\"width: 16.1955%;\"\u003e\n \u003cp\u003e0.590\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.507462686567164%\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e0.537\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.611940298507463%\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e0.927\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.55223880597015%\" valign=\"bottom\" style=\"width: 21.6405%;\"\u003e\n \u003cp\u003ePhenotypes of the pouch\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Normal\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Focal inflammation\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Diffuse inflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.522388059701493%\" style=\"width: 13.9616%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003cp\u003e13 (31.7)\u003c/p\u003e\n \u003cp\u003e28 (68.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.17910447761194%\" style=\"width: 13.1239%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e17 (12.6)\u003c/p\u003e\n \u003cp\u003e101 (74.8)\u003c/p\u003e\n \u003cp\u003e17 (12.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.865671641791046%\" style=\"width: 14.6597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e53 (37.3)\u003c/p\u003e\n \u003cp\u003e87 (61.3)\u003c/p\u003e\n \u003cp\u003e2 (1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.014925373134329%\" style=\"width: 16.1955%;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.507462686567164%\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.611940298507463%\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.55223880597015%\" valign=\"bottom\" style=\"width: 21.6405%;\"\u003e\n \u003cp\u003ePDAI clinical sub-score\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;PDAI clinical sub-score\u0026ge;1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u0026nbsp;Increased stool frequency\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Bleeding\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Fecal urgency\u003c/p\u003e\n \u003cp\u003e\u0026nbsp; Fever\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.522388059701493%\" style=\"width: 13.9616%;\"\u003e\n \u003cp\u003e\u0026nbsp;0 (0-2)\u003c/p\u003e\n \u003cp\u003e19 (46.3)\u003c/p\u003e\n \u003cp\u003e13 (31.7)\u003c/p\u003e\n \u003cp\u003e6 (14.6)\u003c/p\u003e\n \u003cp\u003e13 (31.7)\u003c/p\u003e\n \u003cp\u003e1 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.17910447761194%\" style=\"width: 13.1239%;\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003cp\u003e27 (20.0)\u003c/p\u003e\n \u003cp\u003e8 (5.9)\u003c/p\u003e\n \u003cp\u003e7 (5.1)\u003c/p\u003e\n \u003cp\u003e13 (9.6)\u003c/p\u003e\n \u003cp\u003e1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.865671641791046%\" style=\"width: 14.6597%;\"\u003e\n \u003cp\u003e0 (0-0)\u003c/p\u003e\n \u003cp\u003e13 (9.2)\u003c/p\u003e\n \u003cp\u003e7 (4.9)\u003c/p\u003e\n \u003cp\u003e5 (3.5)\u003c/p\u003e\n \u003cp\u003e4 (2.8)\u003c/p\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.014925373134329%\" style=\"width: 16.1955%;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.369\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.507462686567164%\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.611940298507463%\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003cp\u003e0.010\u003c/p\u003e\n \u003cp\u003e0.662\u003c/p\u003e\n \u003cp\u003e0.566\u003c/p\u003e\n \u003cp\u003e0.020\u003c/p\u003e\n \u003cp\u003e0.308\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.55223880597015%\" valign=\"bottom\" style=\"width: 21.6405%;\"\u003e\n \u003cp\u003eStool frequency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.522388059701493%\" style=\"width: 13.9616%;\"\u003e\n \u003cp\u003e9 (7-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.17910447761194%\" style=\"width: 13.1239%;\"\u003e\n \u003cp\u003e7 (6-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.865671641791046%\" style=\"width: 14.6597%;\"\u003e\n \u003cp\u003e6 (5-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.014925373134329%\" style=\"width: 16.1955%;\"\u003e\n \u003cp\u003e0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.507462686567164%\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.611940298507463%\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.55223880597015%\" valign=\"bottom\" style=\"width: 21.6405%;\"\u003e\n \u003cp\u003eMedication\u003c/p\u003e\n \u003cp\u003e Probiotics\u003c/p\u003e\n \u003cp\u003e Berberine chloride\u003c/p\u003e\n \u003cp\u003e Loperamide\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Antibiotic\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;Steroid\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;IBD drugs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.522388059701493%\" style=\"width: 13.9616%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31 (75.6)\u003c/p\u003e\n \u003cp\u003e29 (70.7)\u003c/p\u003e\n \u003cp\u003e15 (36.6)\u003c/p\u003e\n \u003cp\u003e10 (24.3)\u003c/p\u003e\n \u003cp\u003e2 (4.9)\u003c/p\u003e\n \u003cp\u003e1 (2.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.17910447761194%\" style=\"width: 13.1239%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e106 (78.5)\u003c/p\u003e\n \u003cp\u003e100 (74.1)\u003c/p\u003e\n \u003cp\u003e40 (29.6)\u003c/p\u003e\n \u003cp\u003e3 (2.1)\u003c/p\u003e\n \u003cp\u003e4 (2.9)\u003c/p\u003e\n \u003cp\u003e2 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.865671641791046%\" style=\"width: 14.6597%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e94 (66.2)\u003c/p\u003e\n \u003cp\u003e83 (58.5)\u003c/p\u003e\n \u003cp\u003e30 (21.1)\u003c/p\u003e\n \u003cp\u003e4 (2.8)\u003c/p\u003e\n \u003cp\u003e3 (2.1)\u003c/p\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.014925373134329%\" style=\"width: 16.1955%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.694\u003c/p\u003e\n \u003cp\u003e0.672\u003c/p\u003e\n \u003cp\u003e0.400\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.554\u003c/p\u003e\n \u003cp\u003e0.678\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"8.507462686567164%\" valign=\"bottom\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.254\u003c/p\u003e\n \u003cp\u003e0.155\u003c/p\u003e\n \u003cp\u003e0.043\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.339\u003c/p\u003e\n \u003cp\u003e0.062\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.611940298507463%\" style=\"width: 6.4223%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003cp\u003e0.104\u003c/p\u003e\n \u003cp\u003e0.753\u003c/p\u003e\n \u003cp\u003e0.652\u003c/p\u003e\n \u003cp\u003e0.145\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eValues in parentheses are percentages, unless indicated otherwise\u003c/p\u003e\n\u003cp\u003e*Values are median (interquartile range)\u003c/p\u003e\n\u003cp\u003eAL, afferent limbs; PP, proximal pouch; DP, distal pouch; PDAI, Pouchitis disease activity index; IBD drugs, inflammatory bowel disease drugs including amino salicylates, immunosuppressor, immunomodulators and biologics; M, Multiple peripheral inflammation; S, Single peripheral inflammation; N, no peripheral inflammation.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Ulcerative colitis, Ileal pouch, Pouchitis, diffuse inflammation, Chicago classification","lastPublishedDoi":"10.21203/rs.3.rs-3886677/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3886677/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe anatomical location of inflammation in and around the ileal pouch affects the pouch survival rate, and diffuse inflammation have poor pouch survival rates.\u003c/p\u003e\u003ch2\u003eAims\u003c/h2\u003e \u003cp\u003eWe aimed to clarify the symptoms and histological findings of diffuse inflammation of the pouch.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe evaluated the symptoms, treatment, and histological findings according to the endoscopic phenotypes of diffuse inflammation, focal inflammation, and normal as the pouch body phenotype, and afferent limb involvement, inlet involvement, cuffitis, and fistula as the peripheral findings.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOf the 318 pouchoscopies, 47 had diffuse inflammation, 201 had focal inflammation and 70 were normal. Symptomatic patients had diffuse inflammation more frequently (46.8%) than focal inflammation (13.4%) and normal (14.2%), with no difference between focal inflammation and normal. Antibiotics and steroids were higher rate administered in cases of diffuse inflammation, but not in cases of focal inflammation or in normal cases. Histological inflammation, inflammatory bowel disease (IBD)-specific finding, and colonic metaplasia showed severity in the order of diffuse inflammation\u0026thinsp;\u0026gt;\u0026thinsp;focal inflammation\u0026thinsp;\u0026gt;\u0026thinsp;normal. The number of peripheral inflammatory findings overlapped in the following order: diffuse inflammation\u0026thinsp;\u0026gt;\u0026thinsp;focal inflammation\u0026thinsp;\u0026gt;\u0026thinsp;normal. The number of symptomatic patients increased as the number of peripheral inflammatory findings increased.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003ePouches with diffuse inflammation are more symptomatic, have a higher use of therapeutic agents, and have more severe histological inflammation, IBD-specific finding and colonic metaplasia accompanying peripheral inflammatory findings than the other groups. The higher the overlap of inflammatory findings in the surrounding tissues, the more symptomatic the patients will appear.\u003c/p\u003e","manuscriptTitle":"Clinical and histological impact of diffuse inflammation at pouchoscopy.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-24 18:52:16","doi":"10.21203/rs.3.rs-3886677/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5e615f12-b92d-4b21-b328-3e2f767bd011","owner":[],"postedDate":"January 24th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-02-05T11:04:20+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-24 18:52:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3886677","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3886677","identity":"rs-3886677","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}