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.