Can laparoscopic surgery enhance colorectal cancer spread?

AlO54 SSAT ABSTRACTS

GASTROENTEROLOGY Vol. 118, No.4

2397

2399

TELOMERASE ACTIVITY OF MALIGNANT CELLS CORRELATES WITH DUKES' STAGE IN COLORECTAL CANCER.

ILEOANAL POUCH FUNCTION IS RELATED TO POSTPRAN· DIAL POUCH TONE.

Aqeel Ghori, Bernhard Usselmann, Steve Ferryman, Ian Fraser, Alan Morris, Dept of Surg, Walsgrave Hosp, Coventry, United Kingdom; Dept of Biology Sci, Univ of Warwick, Coventry, United Kingdom; Dept of Pathology, Walsgrave Hosp, Coventry, United Kingdom.

J. Steens, W. A. Bemelman, W. J. Meijerink, G. Griffioen, R. A. Hogezand, C. B. Lamers, A. A. Masclee, Dept of Gastroenterology, LUMC, Leiden, Netherlands; Dept of Surg, Acad Med Ctr, Amsterdam, Netherlands; Dept of Surg, LUMC, Leiden, Netherlands.

Introduction: The ribonucleoprotein telomerase, which is responsible for elongating chromosomal telomeres, has been proposed as a potential prognostic or diagnostic marker for malignancy. Whether telomerase activity of clinical specimens correlates with other clinico-pathological variables, however, remains controversial. In colorectal cancer there is evidence that telomerase activity is higher in advanced cancers, although this has not been demonstrated in all studies. We therefore designed experiments to assay telomerase activity in isolated malignant cells of primary colorectal cancers. This allowed us to correct for the contribution of other cellular components of a cancer and for the presence of telomerase inhibitors in telomerase assays. We were then able to correlate telomerase activity of separated malignant cells with pathological stage of the disease. Methods: Thirty colorectal cancer and 20 corresponding normal mucosa specimens were obtained following surgical resection. Tissues were mechanically disaggregated and digested overnight with collagenase, DNase and hyaluronidase. Debris was removed by filtration and density gradient centrifugation (Lymphoprep). The epithelial cell population was separated using Ber-EP4 pan-epithelial antibody and Magnetic Activated Cell Sorting. Recovered cells of half the cancers were H&E stained to determine purity. Telomerase activity was quantified by the Telomeric Repeat Amplification Protocol (TRAPeze™, Intergen Company) and telomerase activity expressed as Total Product Generated (TPG). Results: Epithelial cells of three of 20 normal mucosa specimens were telomerase positive with weak activity. In the cancer group the vast majority (99%) of the epithelial cells recovered were malignant by cytological critera. These cells were telomerase positive in all the cancers, with a wide range of telomerase activity values (0.19-308 TPGs). Telomerase activity correlated with Dukes' stage (r=0.52, p=O.OO4, Spearman's rank). Conclusions: Pathological stage correlates with telomerase activity of the malignant cell population of the primary tumour in colorectal cancer. This suggests that telomerase activity may increase during the progression of a cancer, possibly through the selection of telomerase rich clones. This has implications for the design or use of anti-telomerase agents as potential adjuvant therapy, suggesting that these agents have increased efficacy in advanced stage malignancy.

Functional impairments are frequently observed in patients with an ileal pouch-anal anastomosis. It has recently been shown that meal ingestion increases pouch tone and motility. Little is known however on the influence of meal stimulated pouch characteristics on pouch function. Aim of this study was to characterize basal and postprandial pouch motor and sensory characteristics in relation to clinical pouch function in patients with an ileoanal pouch using an electronic barostat. Nineteen patients with an ileoanal J-pouch after proctocolectomy for ulcerative colitis were studied after a postoperative follow-up period of 2. I :!: 0.6 yr. None of the patients had fecal incontinence. The groups were divided into those with high stool frequency (>6 per 24 hr, n=8 patients) or an adequate stool frequency (::56 per 24 hr, n= II patients). All patients underwent a pressure distension procedure of the pouch, from which pouch compliance and sensitivity characteristics were calculated. A barostat procedure at operating pressure was performed to assess the influence of a meal on pouch tone and motility. Results: Compliance was not significantly different between the two groups (10:!:2 vs. I I:!: I mI/mmHg), nor were sensitivity characteristics of urge and pain. However, after meal ingestion the pouch volume decreased by 70:!:10% in the group with poor pouch function compared to 29:!:9% in the group with adequate pouch function (p