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.

Preoperative treatment with a non-steroidal anti-inflammatory drug (NSAID) increases tumor tissue infiltration of seemingly activated immune cells in colorectal cancer.

This study evaluates HLA gene expression and tumor infiltration by B-cells, macrophages, dendritic cells, T-helper and cytotoxic T-lymphocytes in response to short-term preoperative treatment with cyclooxygenase inhibitors. Patients with colorectal carcinoma were randomized to receive oral NSAID (indomethacin or celebrex) for three days preoperatively; controls received esomeprazol. Peroperative tumor biopsies and normal colon tissue were analyzed by microarray, quantitative PCR and immunohistochemistry. Efficacy of short-term systemic NSAID treatment was confirmed by measurement of PGE2 production in blood monocytes from healthy volunteers. NSAID treatment upregulated genes at the MHC locus on chromosome 6p21 in tumor tissue, but not in normal colon tissue, from the same patient. 23 of the 100 most upregulated genes belonged to MHC class II. HLA-DM, -DO (peptide loading), HLA-DP, -DQ, -DR (antigen presentation), granzyme B, H, perforin and FCGR3A (CD16) (cytotoxicity) displayed increased expression, as did CD8, a marker of cytotoxic T-lymphocytes, while HLA-A and -C expression were not increased by NSAID treatment. MHC II protein (HLA-DP, -DQ, -DR) levels and infiltration by CD4+ T-helper cells of tumor stroma increased upon NSAID treatment, while CD8+ cytotoxic T-lymphocytes increased in both tumor stroma and epithelium. Molecules associated with immunosuppressive T regulatory cells (FOXP3, IL-10) were significantly decreased in indomethacin-exposed tumors. Standard oral administration of NSAID three days preoperatively was enough to increase tumor infiltration by seemingly activated immune cells. These findings agree with previous information that high prostanoid activities in colorectal cancer increase the risk for reduced disease-specific survival following tumor resection.

T- and B-cell immune responses of patients who had undergone colectomies to oral administration of Salmonella enterica serovar Typhi Ty21a vaccine.

The capacity of an oral live attenuated Salmonella enterica serovar Typhi Ty21a vaccine to induce immune responses in patients who had undergone colectomies because of ulcerative colitis was evaluated, and these responses were compared with those of healthy volunteers. Purified CD4(+) and CD8(+) T cells from peripheral blood were stimulated in vitro by using the heat-killed Ty21a vaccine strain, and the proliferation and gamma interferon (IFN-gamma) production were measured before and 7 or 8 days after vaccination. Salmonella-specific immunoglobulin A (IgA) and IgG antibody responses in serum along with IgA antibody responses in ileostomy fluids from the patients who had undergone colectomies were also evaluated. Three doses of vaccine given 2 days apart failed to induce proliferative T-cell responses in all the six patients who had undergone colectomies, and increases in IFN-gamma production were found only among the CD8(+) cells from three of the patients. In contrast, both proliferative responses and increased IFN-gamma production were observed among CD4(+) and CD8(+) T cells from 3 and 6 of 10 healthy volunteers, respectively. Salmonella-specific IgA and/or IgG antibody responses in serum were observed for five (56%) of nine patients who had undergone colectomies and in 15 (88%) of 17 healthy volunteers. In ileostomy fluids, significant anti-Salmonella IgA antibody titer increases were detected in six (67%) of nine patients who had undergone colectomies. The impaired T- and B-cell immune responses found after vaccination in the circulation of patients who have undergone colectomies may be explained by a diminished colonization of the Ty21a vaccine strain due to the lack of a terminal ileum and colon.