Ileal Pouch Mucosa Research Articles

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

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

Long-term outcomes of metachronous neoplasms in the ileal pouch and rectum after surgical treatment in patients with familial adenomatous polyposis.

Background and study aims Restorative proctocolectomy has become the most common surgical option for patients with familial adenomatous polyposis (FAP). However, adenomas and even carcinomas may develop in the ileal pouch over time. The aim of this study was to evaluate the long-term incidence and nature of ileal pouch or distal ileal adenomas and carcinomas in patients with FAP. Patients and methods This was a retrospective study of 47 FAP patients with Kock’s continent ileostomy (Kock) (n = 8), ileorectal anastomosis (IRA) (n = 13), and ileal pouch-anal anastomosis (IPAA) (n = 26). Patients were followed with a standardized protocol including chromoendoscopy and biopsies of visible polyps in the ileal pouch, distal ileum, and rectum every 6 to 12 months. Results Median follow-up was 21.0 years. Overall risk of adenoma development was significantly higher in IRA patients, with incidence rates of 85 % and 100 % at 5 and 10 years’ follow-up, respectively, compared to pouch patients (Kock + IPAA) ( P < 0.001). However, there was also a high frequency of adenomas in the ileal pouch mucosa, with rates of 12 %, 33 %, and 68 %, at 5, 10, and 20 years of follow-up, respectively. Maximum size of ileal pouch adenomas was significantly related to time since surgery ( P = 0.0214). Six cases of advanced adenomas including two cases of adenocarcinomas developed in the ileal pouch mucosa. Conclusions There is a significant incidence of adenoma(s) in the ileal pouch of FAP patients on long-term follow-up. Regular endoscopic surveillance is recommended, not only in IRA patients, but also in pouch patients after proctocolectomy.

SATB2 and Hep Par 1 Immunohistochemistry Is Helpful in Distinguishing Between Inflamed and Architecturally Altered Ileal Pouch and Rectal Cuff Mucosa.

The management of patients with ulcerative colitis after proctocolectomy with ileal pouch-anal anastomosis includes independent histological assessments of inflammation in the ileal pouch and the rectal cuff. However, the distinction between pouchitis and cuffitis can be impeded both endoscopically and histologically by the combined effects of inflammation and regeneration. We investigated the use of 2 markers, hepatocyte paraffin 1 (Hep) and SATB2 (special AT-rich sequence-binding protein 2), which are expressed immunohistochemically in the small and large bowel epithelium, respectively, as ancillary methods to deal with this problem. Immunohistochemical staining was performed retrospectively on 20 consecutive pairs of post-ileal pouch-anal anastomosis biopsies with varying degrees of histological inflammation and architectural distortion, which had each been designated as "ileal pouch" or "rectal cuff" by the referring endoscopists. Expression was graded as focal (10% to 74% stained cells) or diffuse (75% to 100%). Among the ileal pouch biopsies, 20 (100%) expressed Hep either diffusely (75%) or focally (25%), whereas SATB2 staining was either negative in 15 (75%) or focal in 5 (25%), the latter group all expressing Hep diffusely. Among the rectal cuff biopsies, 14 expressed SATB2 diffusely. Of these, Hep was either negative in 11 (79%) or focally positive in 3 (21%), the latter group all expressing SATB2 diffusely. Six ostensibly rectal cuff biopsies (30%) expressed Hep diffusely and were negative for SATB2, suggesting endoscopic misidentification. None of the 40 biopsies expressed both markers diffusely. We conclude that in doubtful cases, diffuse expression of either Hep or SATB2 can be helpful in discriminating between ileal pouch and rectal cuff mucosa, respectively.

Enteral nutrition combined with glutamine promotes recovery after ileal pouch-anal anastomosis in rats.

AIMTo assess the effect of enteral nutrition (EN) supplemented with glutamine on recovery after ileal pouch-anal anastomosis (IPAA) in rats, to provide an experimental basis for nutritional support in patients with ulcerative colitis (UC) after IPAA.METHODSMale Sprague-Dawley (SD) rats were randomly divided into three groups (n = 8) after IPAA operation using a microsurgical technique. From the third postoperative day, rats in the control group, EN group, and immune nutrition (IN) group were fed standard rat chow, short peptide EN, and short peptide EN combined with glutamine ad libitum, respectively. The rats’ general condition was observed throughout the study. Serum levels of total protein (TP), albumin (ALB), prealbumin (PA), and transferrin (TF) were detected on the 30th postoperative day, using an automatic biochemical analyzer. The ileal pouch mucosa was stained with hematoxylin and eosin (HE), and occludin protein levels were detected by immunohistochemistry.RESULTSThe body weight of rats in the EN group (359.20 ± 10.06 g) was significantly higher than that in the control group (344.00 ± 9.66 g) (P < 0.05) and lower than that in the IN group (373.60 ± 9.86 g) (P < 0.05) on the 30th postoperative day. The levels of serum TP, ALB, PA, and TF in the EN group were significantly higher than those in the control group (P < 0.01 for all) and lower than those in the IN group (P < 0.05 for all). Histopathological score (EN: 0.80 ± 0.37; IN: 0.60 ± 0.40; control group: 2.29 ± 0.18) and expression level of occludin protein (EN: 0.182 ± 0.054; IN: 0.188 ± 0.048; control group: 0.127 ± 0.032) were significantly lower in the control group compared with the EN and IN groups (P < 0.05 for all), but there were no significant differences between the latter two groups (P > 0.05 for all).CONCLUSIONEN combined with glutamine may effectively improve nutritional status after IPAA. Our results suggest a benefit of glutamine supplementation in EN for UC patients undergoing IPAA, although human studies are required to confirm this finding.

Ileal Pouch of Ulcerative Colitis Patients Exhibit Impaired Autophagy

BACKGROUND: Total rectocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgery of choice for patients with ulcerative colitis (UC) that are refractory to clinical treatment and for familial adenomatous polyposis (FAP) with many rectal polyps. The main complication after this procedure is the pouch inflammation (pouchitis) that can affect up to 45 percent of patients who are submitted to IPAA for UC, and only five percent of the FAP patients who undergo the same procedure. Previous studies have shown increased pro-inflammatory cytokines in the ileal pouch (IP) mucosa of UC patients, even in the absence of clinical, endoscopic and histological inflammation. Autophagy is an evolutionarily conserved catabolic pathway that consists of selective degradation of cellular components and a homeostatic mechanism that protects cells exposed to stress situations (toxins, starvation), and defects in this pathway have been reported in inflammatory bowel diseases. However, there are no studies on the IP. Therefore, we studied markers for autophagy in the IP mucosa of UC and FAP patients comparing them to controls with a normal distal ileum. METHODS: Sixteen patients with IP in "J" shape, asymptomatic and with endoscopically normal mucosa were evaluated. The control group consisted of eight patients with normal colonoscopy. Gene expression was analyzed by qPCR and protein levels by immunoblotting and immunofluorescence. This study was approved by the Ethics Committee of the University of Campinas and was performed in accordance with the Declaration of Helsinki. All results were reported as means ± SEM. Data were analyzed by non-parametric Test, comparing all groups. The level of significance was set at P<0.05. RESULTS: There was a significant decrease in the transcriptional levels of ATG5, MAP1LC3A and BAX in the FAP group (P<0.05). There was also a decrease in the protein level of Beclin-1 in the UC and FAP compared to the control group (P<0.05). Although the LC3II levels by immunoblot were higher in the UC group, total LC3 and LC3/p62 co-localization were lower in the immunofluorescence analysis in the UC and FAP compared to the control group (P<0.05). Corroborating to these results, there was an increase of p62 by immunoblot in the UC group, compared to controls (P<0.05). CONCLUSION(S): These results indicate impaired macroautophagy mechanism in the IP. In FAP, decreased autophagy may be related to impaired apoptosis, otherwise in UC, may be mainly due to increased Toll-Like Receptors (TLR) activation. These findings may explain the inflammation predisposition, mainly in the IP mucosa of UC patients. Acknowledgments: We thank FAPESP (São Paulo Research Foundation) for financial support. Negreiros LMV (co-author) received scholarship from FAPESP. We are grateful to Prof. Tristan Torriani for English grammar revision. We thank Francesca Ramos and José Diego Botezelli for technical assistance and the staff of the Life Sciences Core Facility (LaCTAD) from State University of Campinas (UNICAMP), for the Cell Biology analysis.

Neoplasia in the colorectal specimens of patients with ulcerative colitis and ileal pouch-anal anastomosis – need for routine surveillance?

Objective. Patients who undergo ileal pouch-anal anastomosis (IPAA) after colectomy for ulcerative colitis (UC) occasionally have neoplasia in the IPAA. Patients with evidence of dysplasia or carcinoma in the colorectal specimen may have an increased risk of such neoplasia. A surveillance program has been suggested. The aims of this study were to evaluate the outcomes of surveillance of a large patient cohort, and to investigate the prevalences of neoplasia in the ileal pouch mucosa and in the anal transitional zone (ATZ). Material and methods. A total of 629 patients underwent IPAA for UC at Sahlgrenska University Hospital, Gothenburg, Sweden. Identified from a register, 73 patients with neoplasia in their specimen considered eligible for the trial were prospectively enrolled, and underwent clinical examination, endoscopy with macroscopic evaluation, and mucosal biopsies from the ileal pouch and the ATZ. The biopsies were independently evaluated by two experienced gastro-pathologists. Results. In all, 56 patients (39 males) with a median follow-up time of 18 (range, 1–29) years were evaluated. One patient (1.8%; 95% CI 0%–5.3%) showed low-grade dysplasia in the pouch, as recorded by one of the two pathologists. The individual pathologists recorded indefinite for dysplasia (IFD) in the pouch for 19 and 20 patients, respectively, and IFD in the ATZ for 2 and 4 patients, respectively. None of the biopsies showed evidence of high-grade dysplasia (HGD) or carcinoma. Conclusions. Neoplasia in the ileal pouch or ATZ after IPAA for UC is rare in the proposed risk group. The necessity for and value of a routine surveillance program should be prospectively evaluated.

Pouch adenomas in Familial Adenomatous Polyposis after restorative proctocolectomy

Introduction: Australian Clinical Practice Guidelines suggest six to twelve-monthly endoscopic pouch surveillance in patients after restorative proctocolectomy for Familial Adenomatous Polyposis (FAP). There are several reports of adenomas and carcinomas forming within the ileum, ileal pouch mucosa or residual rectal mucosa. A retrospective clinical study was performed to audit pouch endoscopic surveillance at a large Sydney tertiary referral Hospital. The aim was to evaluate adenoma development after restorative proctocolectomy for FAP and the adherence rate to published clinical guidelines. Methods: Thirty-nine patients who had restorative proctocolectomy for FAP from 1985 to 2011 were identified. Demographic data, details of surgery, original histopathology and details of follow-up pouch endoscopy and pathology findings were obtained. Results: Of the thirty-nine patients, twenty-seven patients were included in this study. Adenomas were found in twelve of 27 (44%) patients. Mean time to first polyp formation was 88 months and median time was 72 months (range 18–249 months). All polyps were either tubular or tubulovillous in histology. One polyp had high grade dysplasia. The remainder had mild or moderate dysplasia. Polyps were excised either endo-anally or during pouchoscopy. None of the five patients who had a hand-sewn ileal pouch-anal anastomosis (IPAA) developed polyps on follow-up, compared with 12 of the 22 (55%) with a double stapled anastomosis (fishers exact test; p = 0.047 (two-tailed)). Of those who developed pouch adenomas, eight (67%) developed further pouch adenomas on follow-up. Conclusions: This study supports guidelines recommending lifelong pouch surveillance after restorative proctocolectomy for FAP. Those who develop pouch adenomas may be at greater risk of developing further adenomas. Residual rectal mucosa at the pouch-anal anastomosis should be carefully examined.

Risk of ileal pouch neoplasms in patients with familial adenomatous polyposis

Restorative proctocolectomy is the most common surgical option for patients with familial adenomatous polyposis (FAP). However, adenomas may develop in the ileal pouch mucosa over time, and even carcinoma in the pouch has been reported. We therefore reviewed the prevalence, nature, and treatment of adenomas and carcinoma that develop after proctocolectomy in the ileal pouch mucosa in patients with FAP. In 25 reports that were reviewed, the incidence of adenomas in the ileal pouch varied from 6.7% to 73.9%. Several potential factors that favor the development of pouch polyposis have been investigated, but many remain controversial. Nevertheless, it seems certain that the age of the pouch is important. The risk appears to be 7% to 16% after 5 years, 35% to 42% after 10 years, and 75% after 15 years. On the other hand, only 21 cases of ileal pouch carcinoma have been recorded in the literature to date. The diagnosis of pouch carcinoma was made between 3 to 20 years (median, 10 years) after pouch construction. Although the risk of malignant transformation in ileal pouches is probably low, it is not negligible, and the long-term risk cannot presently be well quantified. Regular endoscopic surveillance, especially using chromoendoscopy, is recommended.

Suppurative granulomatous inflammation in the ileo-anal pouch

Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is commonly performed for medically refractory ulcerative colitis (UC), however with multiple possible complications, most notably pouchitis, cuffitis, Crohn's disease of the pouch and irritable pouch syndrome. We present a unique case of suppurative granulomatous inflammation in the ileal pouch mucosa, most likely infective in nature, that is unrelated to recognised causes of such pathology, especially yersiniosis.

Severe and Extensive Enteritis following Colectomy for Ulcerative Colitis

Ulcerative colitis is an inflammatory condition usually confined to the colonic mucosa. However, inflammatory changes have been recorded in the small bowel with ulcerative colitis, specifically in ileal pouch mucosa after colectomy (ie, ‘pouchitis’) or in the terminal ileum with severe pancolitis (ie, ‘backwash ileitis’). There have also been rare previous reports of a more diffuse and distinctive form of diffuse and extensive enteritis following total colectomy that responded to steroids or calcineurin inhibitor use (1–3). Rarely, a fatal form of diffuse enteritis following colectomy has been described (4,5). We report a dramatic presentation of severe steroid-resistant panenteritis in a patient three months after total colectomy for severe ulcerative colitis that responded to tacrolimus.

Innate Immune Environment in Ileal Pouch Mucosa: α5 Defensin Up-regulation as Predictor of Chronic/Relapsing Pouchitis

Defensins are small cationic peptides with antibacterial activity expressed in Paneth cells (α-defensins) or generally in intestinal epithelial cells (β-defensins) that have a profound effect on gut microbiota. Chronic pouchitis, which occurs in 5% of patients after restorative proctocolectomy and can cause pouch failure, is associated to a significant increase of Clostridiaceae spp. The aim of this study was to gain further insight in the pathogenesis of pouch dysbiosis by exploring defensin expression. Thirty-two consecutive patients coming for follow-up endoscopy were recruited. On pouch biopsies, we cultured bacteria adherent to the mucosa and determined α- and β-defensins and toll-like receptor-4 and −2 mRNA by quantitative real-time RT-PCR. Serum and mucosal levels of IL-1β, IL-6 and TNF-α were measured with immunometric assays. Faecal lactoferrin was analysed by quantitative ELISA. After a median follow-up of 23 (IQR 20–24) months, the patients were contacted for a reassessment of current and past disease activity. During the follow-up, chronic/relapsing pouchitis was diagnosed in six patients. The mucosal level of α-5 and α-6 defensins correlated with chronic/relapsing pouchitis onset (τ = 0.30, p = 0.034 and τ = 0.28, p = 0.053, respectively). High levels of α-5 defensin resulted to be predictive of chronic/relapsing pouchitis [AUC = 74% (95% CI = 53–89%), p = 0.052]. Patients with high levels of α-5 and α-6 defensins had earlier pouchitis relapses (p = 0.009 and p = 0.034, respectively). High levels of α-5 defensin were associated to a significant risk of chronic/relapsing pouchitis [OR = 10.6 (95% CI = 1.2–97.6), p = 0.027]. At multivariate analysis, the mucosal levels of α-5 defensin and the number of CFU of mucosa-associated Clostridiaceae spp resulted to be independent predictors of chronic/relapsing pouchitis [β = 0.46 (0.18), p = 0.024 and β = 0.44 (0.18), p = 0.027, respectively]. In conclusion, chronic/relapsing pouchitis is associated to increased expression of mucosal HD-5 and to increased antimicrobial activity against Escherichia coli. In patients with chronic/relapsing pouchitis, HD-5 and TLR-4 over-expression is likely to create a hostile environment against Enterobacteriaceae, thus favouring Clostridiaceae spp by decreasing competing bacteria families.

TLR2 and TLR4 Up-regulation and Colonization of the Ileal Mucosa by Clostridiaceae spp. in Chronic/Relapsing Pouchitis 1,2

Chronic pouchitis, which can lead to pouch failure, occurs in approximately 5% of patients after restorative proctocolectomy for ulcerative colitis (UC). This work examined the interplay between the microbiota adherent to the ileal pouch mucosa and the mucosal immune system in chronic/relapsing pouchitis. Thirty-two consecutive patients attending our surgical gastroenterological department following restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for UC were considered eligible candidates for this study. Biopsy samples of bacteria adherent to the mucosa were collected. TLR4 and TLR2 mucosal expression was measured by Real Time RT-PCR. Serum and mucosal IL-1β, IL-6, and TNF-α levels were assessed using immunometric assays. Fecal lactoferrin concentrations were determined by quantitative ELISA. After a median follow-up of 23 months (IQR 20-24 months) each patient underwent a global assessment of their clinical condition and disease activity status. Six patients were diagnosed with relapsing/chronic pouchitis during the follow-up period. Mucosal TLR2 and TLR4 expression was higher in the chronic/relapsing pouchitis group than in the no or only one episode of pouchitis group (P = 0.036 and P= 0.016, respectively). The number of colony forming units (CFU) of mucosa-associated Clostridiaceae spp. was higher in the former than in the latter group (P= 0.031). Clostridiaceae were associated to a significant risk of chronic/relapsing pouchitis [OR: 14 (95% CI 0.887-224.021), P = 0.045]. Chronic/relapsing pouchitis is associated to higher mucosal TLR2 and TLR4 expression. Mucosal colonization by Clostridiaceae spp seems to play a role in the pathogenesis of chronic/relapsing pouchitis.

Innate Immune Environment in Ileal Pouch Mucosa: α-5 Defensin Up-Regulation as Predictor of Chronic/Relapsing Pouchitis

Innate Immune Environment in Ileal Pouch Mucosa: α-5 Defensin Up-Regulation as Predictor of Chronic/Relapsing Pouchitis

CD10 immunohistochemistry stains enteric mucosa, but negative staining is unreliable in the setting of active enteritis

Ileal pouch–anal anastomosis is the definitive therapy for ulcerative colitis that is refractory to medical treatment or that has developed neoplasia. Patients with this procedure are routinely followed using directed endoscopic biopsies to monitor for dysplasia in the rectal cuff, residual/recurrent ulcerative colitis, and nonspecific acute inflammation of the ileal pouch (pouchitis), which have different clinical management and outcomes. Thus, accurate localization of mucosal biopsies is crucial to a definitive histological diagnosis, but is complicated by overlapping clinical presentations of pouchitis and ulcerative colitis, post-surgical and inflammatory changes to the mucosa, and altered endoscopic anatomy, resulting in difficulty determining whether a mucosal biopsy is ileal or rectal in origin for both the endoscopist and the pathologist. We explored the utility of CD10 immunohistochemistry to aid diagnosis in this clinical setting by highlighting the enteric mucosa, based on previous studies showing its utility in brush border staining and in the diagnosis of microvillous inclusion disease. We found uniformly positive CD10 immunostaining in normal enteric mucosa, but variable loss of expression in the setting of active enteritis. Specifically, CD10 staining was lost in up to 10% of the mucosa in 1/12 ileostomies and 4/13 enteric anastomoses, in 10–80% of the mucosa in 9/10 cases of Crohn's ileitis, in 10–60% of the mucosa in 7/16 ileal pouches, and in 20–90% of the mucosa in 6/8 cases of backwash ileitis, usually in the presence of active inflammation. There was no CD10 expression by normal or diseased colonic mucosa. Therefore, while CD10 immunostaining identifies normal enteric mucosa with 100% specificity, negative staining does not definitively exclude small intestinal mucosa in the setting of active enteritis, a common condition in ileal pouch mucosa.

Ileal pouch adenocarcinoma after proctocolectomy for familial adenomatous polyposis

Dear Editor: Familial adenomatous polyposis (FAP) is an inherited disease characterized by the development of hundreds of colorectal adenomas, leading to a 100% lifetime risk of colorectal cancer. Thus, a prophylatic proctocolectomy is recommended for patients with FAP to prevent colorectal cancer. Four surgical strategies are available for patients with FAP: proctocolectomy with permanent ileostomy, proctocolectomy with Kock’s pouch continent ileostomy (Kock), colectomy with ileorectal anastomosis (IRA), and restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). IRA produces good functional results, and this surgery is associated with less morbidity than the other procedures. However, continuing endoscopic surveillance for adenomas in the rectum is necessary, and there is a 13% to 25% cumulative risk of rectal cancer after 15 to 25 years, despite surveillance. On the other hand, both Kock’s pouch construction and IPAA (pouch patients) theoretically eliminate the risk of colorectal cancer and adenomas, and perhaps the need for further lower gastrointestinal surveillance. However, development of ileal adenomas in patients who undergo Kock or IPAA procedures is becoming evident. In a recent study, Parc et al. showed the risk of adenoma development in the ileal pouch was 7%, 35%, and 75% at 5, 10, and 15 years of follow-up, respectively. Furthermore, there are a few reports of the development of adenocarcinomas in the pouch of FAP patients. Although most of the cancers that develop in the pouch are likely from residual rectal or anal transitional epithelium, there are four reports of cancers arising from the ileal pouch mucosa in patients with FAP. The etiology of these true pouch cancers seem to be different from the cancers arising from residual rectal or anal transitional epithelium, and the risks associated with these true pouch are controversial. Here, we report two patients with adenocarcinoma developing in the ileal pouch mucosa. A 55-year-old female presented in 1989, at age 46 years, with gastric adenoma with high-grade dysplasia. A barium enema was performed as part of preoperative evaluation which showed a rectal tumor with multiple synchronous colorectal polyps, and a diagnosis of FAP was made. Her parents and four siblings were unaffected, and it seems that she had a de novo genetic mutation. Colonoscopy confirmed the presence of a rectal tumor and multiple colorectal polyps. Biopsy from the rectal tumor showed a well-differentiated adenocarcinoma. An IPAA was performed. The resected colon had an estimated 100 polyps, and the rectum had an estimated 150 polyps. Histology of the surgical specimen confirmed many tubular adenomas distributed throughout the colon and rectum, and a moderately differentiated rectal adenocarcinoma of 45 mm size M. Tajika (*) : T. Nakamura Department of Endoscopy, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan e-mail: mtajika@aichi-cc.jp

S1164 Is Maintenance Therapy with Biologics Associated to a Better Quality of Life (QOL) Compared to Conventional Drugs in Non-Active Crohn's Disease (CD) Patients?

G A A b st ra ct s age, 41 years) with pouchitis and in use of antibiotics. Ileal pouch endoscopy was performed, and tissue biopsy samples were collected for histopathological analysis. RESULTS: Colonic metaplasia was found in 15(36,6%) of 41 patients: 5(25%) of group 1, 8(57,1%) of group 2 and 2(28,6%) of group 3. However, no correlation was established between its presencewith pouchitis (p=0,17). No differences existed in mucosal atrophy, chronic or acute inflammation degree between the groups 1, 2 and 3 (p>0,45). No dysplasia or neoplastic changes were observed. Atrophy degree of ileal pouch mucosa correlated well with time of postoperative follow-up (p=0,05). CONCLUSIONS: Atrophic mucosal changes are more prominent in patients with longer time of postoperative follow-up. Therefore, not only fecal stasis and bacteria overgrowth are responsible for mucosal adaptations, and patients with longer followup are at higher risk of development of neoplastic changes. Pouchitis is not associated to colonic metaplasia.

Prevalence of Adenomas and Carcinomas in the Ileal Pouch After Proctocolectomy in Patients with Familial Adenomatous Polyposis

PurposeRestorative proctocolectomy has become the most common surgical option for patients with familial adenomatous polyposis (FAP). However, adenomas may develop in the ileal pouch mucosa over time, and even carcinoma in the pouch has been reported. Our aim was to evaluate the prevalence, nature, and etiology of ileal pouch and nonpouch adenomas and carcinoma in patients with FAP. Patients and methodsThis was a retrospective study of 31 FAP patients with Kock’s continent ileostomy (Kock; n = 8), ileorectal anastomosis (IRA; n = 7), and ileal pouch–anal anastomosis (IPAA) (n = 16). All patients were followed with a standardized protocol including chromoendoscopy and biopsies of visible polyps in the ileal pouch and nonpouch mucosa. ResultsSixteen of 24 pouch patients (Kock and IPAA) developed adenomas in the ileal pouch mucosa, and all patients with IRA developed adenomas in the rectal mucosa. The prevalence of ileal adenomas was significantly higher in pouch patients than in IRA patients (P = 0.002). Only one patient with Kock showed adenoma in the prepouch area. Two cases of adenocarcinomas and one case of advanced adenoma were found in the ileal pouch mucosa. ConclusionOur results show a high frequency of adenomas in the ileal pouch mucosa, with evolution into carcinoma in some patients. Regular endoscopic surveillance of the pouch is recommended at a frequency similar to that for the rectal mucosa after IRA in pouch patients with FAP.

Processo inflamatório em mucosa de reservatórios ileais de doentes assintomáticos

A inflamação inespecífica do reservatório ileal (RI) após retocolectomia total é a complicação pós-operatória mais comum nos doentes operados por retocolite ulcerativa inespecífica (RCUI). Os mecanismos imunológicos envolvidos na etiologia não são totalmente conhecidos. OBJETIVO: Avaliar a ativação de STAT-1 e a expressão da citocina INF-γ em mucosa de RI endoscópica e histologicamente normal, de doentes operados por RCUI e PAF, assintomáticos. CASUISTICA E MÉTODOS: Estudou-se 18 doentes submetidos à retocolectomia total com RI em "J", sendo nove com RCUI e nove com polipose adenomatosa familiar (PAF). Realizou-se biópsias da mucosa dos RI e de íleo terminal. As expressões de INF-γ e a ativação de STAT-1 foram avaliadas por meio de imunoblot de extrato protéico total. RESULTADOS: A ativação de STAT-1 foi maior em mucosa de RI de doentes operados por RCUI, quando comparada aos grupos PAF e Controle (p&lt;0.05). A expressão de INF-γ foi maior no grupo RCUI quando comparada ao grupo Controle (p&lt;0.05), mas não em relação ao grupo PAF (p&gt;0.05). CONCLUSÃO: Estes achados podem justificar a maior susceptibilidade dos doentes com RCUI à inflamação inespecífica do RI quando comparados aos portadores de PAF, sendo a principal via inflamatória similar à verificada na RCUI.

Adenocarcinoma after restorative proctocolectomy for cancer in ulcerative colitis

Dear Editor, Restorative proctocolectomy with creation of an ileal pouch-anal anastomosis is currently the procedure of choice for elective treatment of patients affected by ulcerative colitis with medically refractory disease, dysplasia or cancer. Although dysplastic transformation within the ileal pouch mucosa and in the rectal cuff in patients operated for ulcerative proctocolitis seems to be rare, 22 cases of adenocarcinoma adjacent to the ileo-anal anastomotic site after restorative proctocolectomy for ulcerative colitis have been described in literature so far. We report the case of a 52-year-old woman who was diagnosed with ulcerative colitis in 1980 at the age of 27. After the diagnosis, she required many hospital admissions for severe disease treated with sulphasalazine and steroids with good results. Past medical history also included a posttransfusional HCV infection treated in 2000 with interferon and ribavirin. In 2003, a colonoscopy revealed foci of adenocarcinoma and high-grade dysplasia in the descending and sigmoid colon. Consequently, the patient underwent restorative proctocolectomy with the formation of an ileal J pouch with double-stapled ileo-anal anastomosis. Histology of the surgical specimen revealed well-differentiated adenocarcinoma next to two non-invasive high-grade and low-grade lesions in the ascending colon; another welldifferentiated adenocarcinoma with necrotic areas was found in the transverse colon (G2T2N0M0). The rectum was clear of dysplasia or cancer. The phenotypic characterization of the lesions demonstrated <10% of neoplastic necrosis with no vascular nor perineural neoplastic invasion. No neoplastic lesions were found in the referred biopsy locations in the descending and sigmoid colon. Thirty-two months after the operation, a routine endoscopy showed a polipoid lesion at the anastomotic cuff in the anal transitional zone. Biopsies revealed high-grade dysplasia with foci of invasive adenocarcinoma. The patient underwent an abdominal–perineal resection with excision of the pouch and anus and formation of an end ileostomy. Surgical pathology evidenced a tubular-villous adenoma with predominant villous aspects; diffuse high-grade dysplasia and well-differentiated adenocarcinoma invading the stalk and into the submucosa of the bowel wall were demonstrated in association to a solitary ulcer and active ulcerative colitis (G1T1N0). Six months later the patient is doing well and is disease-free. Restorative proctocolectomy for patients with ulcerative colitis and co-existing colorectal cancer can be performed with a favourable prognosis and function. It is appropriate for curative intent, given that an adequate margin without tumour is obtained. Lee et al. reported three cases of adenocarcinoma after restorative proctocolectomy with a handsewn anastomosis adding to the 16, which had been previously reported. The authors noted that the overall incidence was extremely low and that the evidence to support surveillance was controversial with no clear defined dysplasia and carcinoma sequence. Factors that seemed to be related to the reported cases included a long history of antecedent ulcerative colitis (10–15 years), dysplasia or carcinoma in the original specimen, poor post-operative surveillance or severe or delayed presentation of pouchitis. Anal transitional zone dysplasia after ileal pouch-anal anastomosis is infrequent, usually self-limiting, most common in the first 2 to 3 years post-operatively and may Int J Colorectal Dis (2007) 22:1557–1558 DOI 10.1007/s00384-006-0269-4

Increased epithelial cell proliferation in the ileal pouch mucosa of patients with familial adenomatous polyposis

To eliminate the risk of colorectal cancer in patients with familial adenomatous polyposis (FAP), reconstructive proctocolectomy is performed. Although most colonic mucosa is resected during the ileal pouch anal anastomosis, adenomas and carcinomas may develop in the pouch. This may be caused by altered cell kinetics due to intraluminal changes in the pouch. In 32 patients with FAP, biopsy specimens from the mucosa of the pouch and also of the afferent ileal loop were taken. Tissue sections were immunohistochemically processed with the monoclonal antibodies M30 and MIB-1 to assess apoptotic and proliferative indices, respectively. Cell proliferation was also assessed by a modified sign test. There were no significant differences in apoptotic rates between the mucosa of the pouch and the mucosa of the afferent ileal loop. However, cell proliferation was significantly higher in the mucosa of the pouch vs afferent ileal loop, both by using the quantitative (68.3% vs 61.6%, p = 0.001) and semiquantitative methods (p < 0.05). Our newly developed semiquantitative approach outperformed previously described methods. The higher cell proliferation in the pouch as compared to the afferent ileal loop may contribute to the increased risk for adenomas and carcinomas in the pouch of patients with FAP and emphasizes the need for regular endoscopic surveillance.