The diameter of the ileal J-pouch-anal anastomosis as an important risk factor of pouchitis – clinical observations

Background

Inflammation of the pouch mucosa is diagnosed in a considerable number of patients after restorative proctocolectomy. The reported incidence of pouchitis varies between 23% and 60% [1–4]. The etiology of pouchitis still remains unclear. The list of postulated contributing factors is long and includes autoimmunological mechanisms, mucosal edema, bile acids, short chain fatty acids, and stasis of ileal contents with subsequent bacterial overgrowth. In some cases, backwash ileitis in the course of the ulcerative colitis can be a potential factor for pouchitis development [5]. In our previous studies on bacterial overgrowth in patients after restorative proctocolectomy, there was no difference between the group with pouchitis and the group without it [6]. However, the stasis of the ileal contents within the pouch may be an independent proinflammatory factor, and may be associated with anastomotic stricture. Narrowing of the anastomotic lumen occurs in the physiological process of healing, as a result of increased activity of the fibroblasts and intensified collagen production at the site of anastomosis. Stricture of the anastomosis is also an important complication of restorative proctocolectomy, which may affect as many as 15% of the patients operated on [7]. The absence of fecal flow through the diverted pouch is also postulated to stimulate anastomotic stricture, but the results of a meta-analysis of 17 studies on 1486 patients proved that the incidence of anastomotic stricture was higher in the patients operated on without temporary loop ileostomy. Therefore, faecal flow is a factor stimulating anastomotic stricture, probably by increasing inflammatory response [8]. It is difficult to clearly define adequate diameter of the ileo-anal anastomosis. Commonly, the anastomosis is constructed with 28–35 mm diameter circular stapling instruments. Due to the aforementioned stricturizing processes, final diameter of the anastomosis should not be less than half of the initial one, which is a mean of 15 mm, with critical value, adopted after Dolinsky, of 8 mm [9]. Normal bowel transit is an important element influencing patient quality of life after restorative proctocolectomy. Any functional impairment may lead to severe disability and long-term complications. The aim of this study was to evaluate the influence of anastomotic stricture on the incidence of pouch mucosa inflammation. The severity of the inflammation has been rated with the pouchitis disease activity index (PDAI), which is widely recognized and applied. The index was introduced by Sandborn et al in 1994; it consists of clinical, endoscopic and histological sections, and allows for the diagnosis of pouchitis when total score equals 7 or higher [10]. However, some publications suggest the possibility of inflammation with scores below 7, which raised some criticism [11]; nevertheless, PDAI remains one of the most important and accepted tools for diagnosing pouchitis [12]. This scale is primarily based on subjective patient symptoms and subjective assessment by the examining physician. Although the PDAI scale is generally accepted, certain co-morbidities or disruptions within the pouch can lead to a false overvaluing of points, which can cause difficulties with final interpretation of the result.

Another relatively new method of determining the activity of pouchitis is evaluation of biochemical activity of fecal markers of inflammation. One of the first markers to be evaluated was pyruvate kinase, whose usefulness in diagnosing pouchitis was reported by Walkowiak et al. in 2005 [13], and confirmed in further studies [14]. Other fecal biochemical markers of pouch inflammation include lactoferrine and calprotectin [15].

Maximum tolerable volume is another parameter measured in anorectal manometry, and it correlates with severity of pouchitis. This parameter has not been used in clinical practice as a marker of inflammation; however, there are encouraging reports indicating low maximum tolerable volume is associated with pouchitis [16]. On the other hand, it is difficult to establish whether low compliance of a pouch may cause pouchitis, or if it is a direct result of inflammation.

Material and Methods

STATISTICAL ANALYSIS:

Statistical analysis was performed with Fisher’s exact test and ANOVA exact test for comparison of age, kinase activity, time of stoma closure, PDAI and maximum tolerable volume in the 3 groups of patients with different anastomosis diameters. The analysis was conducted with StatXact package software (Cytel Co.).

Results

There were no statistically important associations between the diameter of the anastomosis and sex, age, maximum tolerable volume, the time of ileostomy closure or pyruvate kinase activity (Table 1). In 2 parameters, time of ileostomy closure and pyruvate kinase activity, standard deviation values were high. Additionally, there was no association between the diameter of the anastomosis and the reason for restorative proctocolectomy (ulcerative colitis vs familial polyposis coli) (Table 2).

The study revealed statistically important associations between the diameter of the anastomosis and the presence of inflammation (Table 3), between the diameter of the anastomosis and severity of the inflammation (Figure 1), and between the diameter of the anastomosis and villous atrophy in Laumonier’s score (Table 4). The tables below present the results. Patients with narrow anastomosis and grade IV villous atrophy constituted the majority (25.51%). This was statistically significant (p<0.05) in comparison to the groups with wider anastomosis and lower grades of villous atrophy. Patients with grade IV villous atrophy, and belonging to group 1 or 2 regarding the anastomosis diameter, constituted a 2-fold lower percent of the studied population. The number of patients in this group did not significantly differ from the number of the patients with grade III villous atrophy and belonging to group 2 anastomosis diameter (9.68%). However, it was significantly higher than the number of patients with lower grades of villous atrophy and greater anastomosis diameter (Table 4).

Discussion

Despite many publications on pouchitis, its etiology still remains unclear. Differentiation between causes of an inflammatory reaction, which can lead to narrowing of an anastomosis, and an inflammation that is the result of narrowing, is difficult and ambiguous. One of the common theories of pouch mucosa inflammation is that the stasis of ileal contents within the pouch results in alternated ileal bacterial flora, bacterial overgrowth, impaired vascular perfusion and direct proinflammatory reactions. Empirical proof of that theory is the clinical effectiveness of therapy with Metronidazole and Ciprofloxacin in many cases of pouchitis. However, lack of direct evidence of bacterial overgrowth has been reported in some patients with pouchitis [6], and in some patients antibiotics fail in pouchitis therapy. Therefore, it appears that many different factors may be involved in the etiology of pouch inflammation.

Stricture of the ileal pouch-anal anastomosis is one of the potential complications of restorative proctocolectomy. Among the factors that may increase the risk of stricture are the use of the 25mm circular stapling instrument, creation of a diverting ileostomy, anastomotic leak, and inflammation in the pelvis [18]. Opinions on the use of a temporary stoma are very divergent, and there are publications stating that strictures occurred more often in patients without ileostomy [19]. It is recommended that one-step restorative proctocoloctomies without temporary stoma should be performed only in carefully selected patients.

In our study, a significant association between narrow lumen of the anastomosis and signs of pouchitis was found. That association referred to pouchitis assessed with PDAI, and higher PDAI scores were seen in patients with narrower anastomosis. There were no statistically important differences in the diameter of the anastomosis between the patients operated on for ulcerative colitis and the patients operated on for familial adenomatous polyposis coli. In analyzed material, a relatively high percentage of patients operated on because of FAP had an inflammation. This could be due to social and economic situations of these patients – diagnosis of pouchitis, especially chronic, based mainly on symptoms reported by patients, could significantly simplify receiving of permanent social and financial benefits. Hence, it seems that anastomotic stricture is determined by factors other than the primary condition for which the patient has been operated on. That confirms our observation of largely similar postoperative courses in patients after restorative proctocolectomy for ulcerative colitis and familial polyposis coli [20]. In the results of our study, attention should be drawn also to the correlation between villous atrophy assessed with Laumonier’s score and the diameter of the anastomosis. It is assumed that villous atrophy is a response to a chronic inflammation. Although it facilitates adaptive changes of the mucosa, it also increases the risk of dysplasia. The above association confirms the fact that patients with narrow anastomoses are exposed to higher risk of chronic inflammation, which induces the atrophy of ileal villi.

Our study failed to determine any association between pyruvate kinase activity and anastomosis diameter. The activity of fecal pyruvate kinase is a useful marker of pouchitis [13,14]. In our study population we recorded a high value of standard deviation; therefore, it is possible that anastomotic stricture and related fecal stasis may influence the activity of pyruvate kinase. No association between anastomosis stricture and maximum tolerable volume was detected. This may indicate that narrow anastomosis does not influence pouch volume; however, a high value of standard deviation was recorded for this parameter. This may be related to the highly variable time elapsed from stoma closure and the phenomenon of so-called “pouch aging”. The time after stoma closure had no influence on the diameter of the anastomosis, so the potential anastomotic stricture should be considered with the same probability at every step of follow-up, including the period before reversal of the stoma. Stricture of the anastomosis occurring at that time proves to be a factor significantly increasing the risk of pouchitis after stoma closure [1]. Some authors suggest prophylactic use of Ciprofloxacin and Metronidazole in patients with anastomosis stricture [1]. In our department a standard protocol for follow-up after pouch surgery was adopted – pouch enema with Metronidazole solution once a day for 5–7 days after ileal pouch-anal anastomosis, then repeated every 4–6 weeks until stoma closure and digital examination of the anastomosis with dilation in the case of a stricture every 4–6 weeks until the stoma is reversed.

Severe anastomotic stricture with apparent clinical manifestations calls for adequate therapeutic measures. The first recommended step is an endoscopic dilation, which is a safe and effective method [18] that increases the quality of life of patients with anastomosis stricture [21]. In case of failed endoscopic dilation, reoperation may be the only remedy. Remzi et al recently reported that anastomotic stricture constituted 17.6% of all indications for reoperation, and that the results of repeated surgeries were very good [22].

Inflammation of the ileal pouch mucosa is a polymorphic clinical reaction for a number of endogenous and exogenous triggering actors. The mechanism of pouchitis is complex and difficult, if not impossible, to define. It appears that in order to reduce the incidence of pouchitis and refining the functional outcomes of pouch surgery, new clinically significant risk factors of pouchitis should be identified and eliminated. Anastomotic stricture is one of the causes of pouchitis, therefore early detection of a stricture and its dilation, together with adequate prophylaxis of stricture, is of an utmost importance.