Metallothionein—An early marker in the carcinogenesis of ulcerative colitis-associated colorectal carcinoma

A1382 AGA ABSTRACTS

GASTROENTEROLOGY Vol. 118, No.4

6283 METALLOTHIONEIN·AN EARLY MARKER IN THE CARCINO· GENESIS OF ULCERATIVE COLITIS·ASSOCIATED COLOREC· TAL CARCINOMA.

useful in the characterization of neoplastic tissue within the gastrointestinal tract.

Matthias Bruewer, Kurt W. Schmid, Norbert Senninger, Guido Schuermann, Westfalian Wilhelms-University, Muenster, Germany; Dept of Pathology, Essen, Germany; Dept of Gen Surg, Muenster, Germany. Introduction Patients with longstanding ulcerative colitis (UC) have an increased risk for colorectal carcinoma (CaC). Metallothioneins (MT) are low-molecular weight-proteins with a high affinity for zinc. Wild-type p53 is not demonstrable by immunohistochemistry (IHC) in contrast to the mutated form. An overexpression of MT has been described at an early premalignant stage in breast carcinoma whereas in CaC MT hasn't been investigated yet. Methods MT expression was semiquantitatively analysed by IHC with a monoclonal antibody (mAb) against MT, the expression of p53 with mAbs (00-7 and 1801) and a polyclonal Ab (CM-I) against p53 on surgical UC specimens of 14 patients with CaC, 23 patients with dysplasia (n=13 high grade dysplasia (HGD), n=1O low grade dysplasia (LGD)), 30 patients with UC (> 10 years) without dysplasia or carcinoma and 10 normal controls (NC). Specimens with positive staining of more than 20% of tumor cells or, in non malignant tissue, epithelial cells were considered as positive. Statistical analysis was performed with Fisher's exact test. Results Positive MT staining was found in the majority of UC and LGD, but only in the minority of HGD (5/13) and CaC (p20%) ofMT and p53 inCaC, UC with and without dysplasia and NC

MT p53 (CM·1) p53 (1801) p53 (00·7)

CaC

UC·HGO

UC·LGO

UC

NC

3114 10114 8114 8114

5113 8113 8113 8113

9110 0110 0110 0110

21130 2130 2130 2130

0110 0110 0110 0110

6284 ULTRASOUND MODULATED LASER TOMOGRAPHY OF CO· LONIC NEOPLASMS. Navtej S. Buttar, Lehong Wang, Krishnawatie K. Krishnadath, Lori S. Lutzke, Marlys A. Anderson, Guillermo Marquez, Kenneth K. Wang, Mayo Clio, Rochester, MN; Texas A&M, College station, TX. A variety of imaging modalities have been developed to determine the characteristics of tumors in the colon. Endoscopic ultrasonography has been applied clinically to stage the depth of invasion of colon cancers and more recently, optical coherence tomography has been developed in the laboratory to increase imaging of the mucosal surface. We have initiated the first application of ultrasound modulated laser tomography to colonic tumors. This technique has the advantage of combining ultrasound and light to characterize tissue. Methods: The principle behind this technique is to use ultrasound waves to modulate laser light passing through a tissue. The modulated laser light can then be detected and amplified to generate a signal that is characteristic of that tissue. The system we used consists of a helium-neon laser to generate a 632-nm beam, which is focused on the tissue. A function generator is used to create a sinusoidal wave at I MHz, which is amplified to drive an ultrasound transducer placed perpendicular to the tissue. The signal is detected by a photodiode, which converts the modulated light to a current, which can be filtered using the current from the function generator. The time domain signal can then be processed and displayed. Results: The following graphs display the signal taken from 8 resected normal colon tissue and colon cancers. The X-axis represent wavelength while the Y-axis represents absorption in AU. The graph on the right represents colon cancer while the graph on the left represents the modulated signal from normal colon. The most prominant difference was noted between two samples at wave length of 350 nm. Conclusions: The signal received from ultrasound modulated optical tomography appears to differentiate between colonic cancer and normal tissue. This tool may be

6285 A POPULATION-BASED STUDY OF GASTRIC CANCER AND BARRETT'S ESOPHAGUS IN A RURAL POPULATION IN COLOMBIA: LACK OF PROTECTION BY H. PYLORI. Hector Cardona, Oscar Gutierrez, 1. Becerra, William Otero, Antonia Sepulveda, David Y. Graham, Univ Nacional de Colombia, Bogota, Colombia; VAMC and Baylor Coli of Medicine, Houston, TX. Background: Gastric cancer (GC ) is the second cause of malignant neoplasia in the world. In Colombia this tumor an endemic behavior specially in some rural areas. In the last three decades it has been described a decrease in the incidence of antral location and an increment in the cases of cardial Gc. Some studies suggest a strong association with GERD and protection with H. pylori infection. Aim: To investigate prospectively the prevalence of cardial GC, its association with GERD, the histological gastric findings and presence of H. pylori in a Colombian rural population at high risk of Gc. Methods: This investigation was done in a village with 62,400 inhabitants. The study was performed based on the 95% CI of an Expected Prevalence of I %. Subjects remitted for an EGO were consecutively studied in a II months period. Prior to endoscopy questions about dyspeptic symptoms were collected. GER was considered abnormal with 3 or more episodes/wk. Biopsies from the body (3), antrum (3) were taken; cardia biopsies were taken when any alteration was observed ( e.g., Barrett's Esophagus =EB). Results: 1029 subjects were studied: 17 cases of GC were confirmed (1.7%) which were compared with an sex and age (avg. 51 y) matched control group (n=34). 53% of the cases of GC were located at the cardial region and 47% in the distal stomach . General prevalence of EB in the studied population was of 4%. H. pylori was present in >95% of both groups. Conclusions: The prevalence of GC in the population is high and similar to other Colombian cities. The distribution was unexpected with an unexpected increase in GC of cardiallocation and in BE. This population based study did not confirm hypothesis generated from studies relying on symptomtic patients often from referal centers. Adenocarcinoma of the gastric cardia and Barrett's esophagus were not prevented by H. pylori infection in this large population in Colombia.

6286 INFLUENCE OF PREOPERATIVE HIGH DOSE RADIOTHERAPY ON POSTOPERATIVE OUTCOME AND COLONIC ANASTO· MOTIC HEALING: AN EXPERIMENTAL STUDY IN THE RAT. Wim P. Ceelen, Mohamed M. EI Malt, Piet Pattyn, Ghent Univ Hosp, Ghent, Belgium. Background: surgical treatment of rectal cancer is followed by local recurrence in up to 50% of cases. Recently, preoperative low dose radiotherapy (RT) has been shown to improve both local recurrence rate and overall survival. Downstaging of locally advanced tumors, however, requires preoperati ve doses of at least 50-60 Gy. Most experimental studies investigating the effect of preoperative RT have made use of a single dose or a limited number of fractions. Moreover, in most studies both limbs of the anastomosis are irradiated, in contrast to clinical practice where one limb of the anastomosis consists of non irradiated bowel. We studied the effect of a clinically relevant scheme of high dose preoperative RT on colonic anastomotic healing in the rat. Animals and methods: in a first experiment. male Wistar rats randomly received 0, 40, 60 or 80 Gy of preoperative RT on one limb of the anastomosis only. In a second experiment, we compared unilateral (only one limb of the anastomosis) with bilateral (both limbs) RT at 40 Gy. RT doses were validated with implanted dosimeters; prior to the start of RT the caecum was fixed inside or outside the radiation field. A clinically employed fractionation scheme of 2 Gy/day during 2-5 weeks was used. The day after RT completion, a side to side colorectal anastomosis was performed. Rats were sacrified 10 days following surgery. The following parameters were determined: presence of abscess or peritonitis, anastomotic complications (stenosis, leak, dehiscence), intestinal obstruction and anastomotic hydroxyproline content. Results: In the first experiment, no significant differences were found in peritonitis rate, anastomotic complications, or hydroxyproline content. Irradiated animals gained weight more slowly than the control group. In the second experiment. a higher rate of anastomotic complications was seen in the