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Background: Although dysplasia is thought to be the precursor lesion in the development of colitis-associated colorectal cancer (CRC), a significant proportion of patients with ulcerative colitis (UC) and low-grade (LGD) or indefinite (IND) dysplasia remain cancer-free during endoscopic follow-up. There is a need for biomarkers that predict neoplastic progression. We studied the value of a series of immunohistochemical markers in UC patients with flat LGD or IND with regard to neoplastic progression., Methods: Tissue samples were collected from 12 UC patients (six flat LGD, six IND) without progression and from 10 UC patients (eight flat LGD, two IND) with documented progression to HGD and/or CRC during a median of 25 and 23 months of colonoscopic follow-up, respectively. Immunohistochemistry using monoclonal antibodies was performed for p53, CD44, Ki67, AMACR, β-catenin, cyclin D1, p21, and ALDH. Positive and negative staining patterns were compared for progression to advanced neoplasia., Results: When patients showed coexpression of p53 and AMACR, 6/7 patients (86%) developed advanced neoplasia, compared to 4/15 patients (27%) without p53/AMACR coexpression (P = 0.02). Patients with p53/AMACR coexpression developed advanced neoplasia in a time period of 19 months (median, range 1-101) compared to 80 months (median, range 8-169) in patients without p53/AMACR coexpression (P = 0.14). Interestingly, in three patients with progression and previous dysplasia-negative biopsies, two out of three biopsies were p53-positive a median of 12 months (range 10-14) before the LGD/IND diagnosis., Conclusions: This study suggests a role for p53/AMACR coexpression as a potential marker of neoplastic progression in patients with UC., (Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.)

Background: The natural behavior of flat low-grade (LGD) and indefinite dysplasia (IND) in patients with inflammatory bowel disease (IBD) remains uncertain and seems to be dependent on the interpretation of the pathologist. We studied the progression rate of flat LGD and IND to advanced neoplasia (high-grade dysplasia [HGD] or colorectal cancer [CRC]) before and after histopathological review by a panel of gastrointestinal expert pathologists., Methods: A nationwide pathology database was used to identify IBD patients with dysplasia in six Dutch university medical centers between 1990 and 2006. Medical charts of patients with recorded flat LGD or IND were reviewed. Histological slides from three university medical centers were reviewed by a panel of three expert gastrointestinal pathologists., Results: We identified 113 flat LGD patients and 26 flat IND patients. Advanced neoplasia was found in 18 flat LGD patients (16%) after a median follow-up of 48 months, resulting in a 5-year progression rate of 12%. Five IND patients (19%) developed advanced neoplasia after a median follow-up of 24 months, resulting in a 5-year progression rate of 21%. Review of 1547 histological slides from 87 patients resulted in an increase of the 5-year progression rate of flat LGD to advanced neoplasia to 37%, whereas the progression rate of IND decreased to 5%., Conclusions: A diagnosis of flat LGD that is confirmed by a panel of expert gastrointestinal pathologists is associated with a substantial risk of progression to advanced neoplasia, while confirmed IND is associated with a low risk of progression., (Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.)

Background: Ileo-neorectal anastomosis (INRA), an alternative restorative procedure, was developed to reduce the pouch-related complication rate with an (at least) equal functional result., Methods: For this surgical outcome, data of all INRA patients, including bowel function and complications, were prospectively recorded. The reservoir capacity was determined repeatedly by physiologic tests. The anal sphincter complex was assessed by manometry and ultrasound examination. Evaluation of the neorectal mucosa was performed by endoscopy., Results: An INRA procedure was carried out in 39/53 selected patients (47 ulcerative colitis and 6 familial adenomatous polyposis). Fourteen UC cases were converted to ileal pouch anal anastomosis or proctectomy only, because of impossibility to completely remove the rectal mucosa or short of length of the rectal stump. The median operation time for INRA was 323 min (range 240-518), with 1,400 ml blood loss (400-4,500). The reservoirs were permanently defunctioned in 2 patients--one because of reclassification into Crohn's disease, and one with pouchitis refractory to medical treatment. In 18 out of 37 cases, web-like stenoses occurred at the mucosa-anal level, which were treated by single (9) or repeated (5) dilatation or surgical stenoplasty (2). No pouch-related complications like pelvic sepsis, fistula or sexual dysfunction occurred. Thirteen patients had episodes of 'pouchitis', successfully treated with antibiotics, and 7 other cases, with functioning reservoirs, also had proximal 'non-specific' (i.e. no histological criteria of Crohn's disease found) small bowel inflammation. The median bowel frequency decreased from 15x/24 h initially to 7x/24 h at 2 years. Continence was perfect in 24/37 cases. Twelve out of 37 cases had occasional nocturnal soiling and passive nocturnal fecal incontinence was reported by 2/37 patients. The neorectal compliance volume recovered from 12.5 ml kPa after subtotal colectomy and 11 ml/kPa at 6 months after INRA to a neorectal compliance of 24 ml/kPa at 2 years' follow-up (p < 0.002; Wilcoxon signed rank test)., Conclusion: The INRA procedure shows a low complication rate and reasonable functional results, there was however a considerable conversion rate in these first 53 cases and a high incidence of reclassification to CD., (Copyright 2004 S. Karger AG, Basel.)

Introduction: To reduce pouch related complications after restorative proctocolectomy, an alternative procedure was developed, the ileo neo-rectal anastomosis (INRA). This technique consists of rectal mucosa replacement by ileal mucosa and straight ileorectal anastomosis. Our study provides a detailed description of the functional results after INRA., Patients and Methods: Eleven patients underwent an INRA procedure with a temporary ileostomy. Anorectal function tests were performed two months prior to and six and 12 months after closure of the ileostomy and comprised: anal manometry, ultrasound examination, rectal balloon distension, and transmucosal electrical nerve stimulation (TENS). Function was subsequently related to the histopathology of rectal biopsy samples., Results: Median stool frequency decreased from 15/24 hours (10-25) to 6/24 hours (4-11) at one year. All patients reported full continence. Anal sensibility, and resting and squeeze pressures did not change after INRA. Rectal compliance decreased (2.1 (0.7-2.8) v 1.5 (0.4-2.2) and 1.4 (0.8-3.7) ml/mm Hg (p=0.03)) but the maximum tolerated volume increased (70 (50-118) v 96 (39-176) (NS) and 122 (56-185) ml (p=0.03)). Decreasing rectal sensitivity was found: the maximum tolerated pressure increased (14 (8-24) v 22 (8-34) (NS) and 26 (14-40) (p=0.02)) and the rectal threshold for TENS displayed a similar tendency. All patients displayed a low grade chronic inflammatory infiltrate in neorectal biopsy samples before closure of the ileostomy, with no change during follow up., Conclusions: The technique of INRA provides a safe alternative for restorative surgery. Stool frequency after INRA improves with time and seems to be related to decreasing sensitivity and not to histopathological changes in the neorectum. Furthermore, after the INRA procedure, all patients reported full continence.

Objective: To evaluate a new surgical procedure, ileoneorectal anastomosis (INRA), in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP)., Summary Background Data: Surgical treatment in UC and FAP aims to resect diseased colonic mucosa and restore oroanal continuity. The ileopouch anal anastomosis achieves this but has a 15% to 35% complication rate, a 10% failure rate, and an unpredictable functional outcome. An alternative surgical technique, INRA, has been developed in which the rectal mucosa is replaced by a vascularized ileal mucosa graft., Methods: Eleven patients underwent an INRA procedure with a temporary diverting ileostomy. Clinical history, repeat endoscopy, histologic examination, and rectal compliance measurements were carried out before and after surgery., Results: The INRA procedure was technically successful in all patients. Endoscopy showed ingrowth of ileal mucosa in the neorectum, with 100% coverage after 6 weeks. No patient had pelvic sepsis, neorectal-anal or -vaginal fistula, autonomic nerve damage, or fecal incontinence. Neorectal function improved with time. The median 24-hour defecation frequency decreased from 15 (range 9 to 25) to 7 (range 4 to 10) at 11 months follow-up, and the median maximum tolerated volume increased to 157 (range 130 to 225) ml. Anal manometry and electrosensitivity were not affected by the surgery. Histologic biopsy samples after 1 year showed a normal small intestinal mucous membrane, without inflammation or fibrosis., Conclusion: The combination of a low complication rate and good neorectal function at 1 year is a substantial improvement that justifies extension of the clinical application in patients with UC and FAP.

Reconstructive surgery for ulcerative colitis and familial adenomatous polyposis nowadays usually takes the form of an ileoanal pouch, involving making a reservoir of the terminal portion of the ileum which subsequently is anastomosed to the anal canal. This method results in definite cure in many cases, but is associated with a morbidity of 15-30% and fails in 10%. A new surgical treatment includes complete removal of the affected large bowel mucosa, guaranteeing oroanal intestinal continuity, limiting complications and providing good function of the reservoir or of the new rectum. In creation of an ileoneorectal anastomosis, complete removal of the affected mucous membrane is followed by preparing a functional 'neorectum' by means of pedicle grafting of ileal mucous membrane on to the uncovered muscular wall of the rectum. This operation gave good results in a small-scale clinical trial.