Surgical treatment of distal third rectal carcinoma: Oncologic outcome following rectal excision with coloanal anastomosis versus abdominal perineal resection

GASTROENTEROLOGY Vol. 118, No.4

AI030 SSAT ABSTRACTS

2247 SURGICAL TREATMENT OF DISTAL TffiRD RECTAL CARCINOMA: ONCOLOGIC OUTCOME FOLLOWING RECTAL EXCISION WITH COLOANAL ANASTOMOSIS VERSUS ABDOMINAL PERINEAL RESECTION. Reza A. Gamagami, Sarhang Mohammed, Arnaud Liagre, Franck Lazorthes, UC San Diego, San Diego, CA; Purpan Hosp, Toulouse, France. The standard surgical treatment of patients with distal third rectal cancer has remained abdominal perineal resection (APR). The high pelvic recurrence rate and compromising cure have served as. arguments against sphincter saving resections (SSR). In this prospective case-control study. we compare survival and local recurrence rates for patients with cancers of the lower third of the rectum (4-7cm from the anal verge) treated, by abdominal perineal resection (APR) versus rectal excision with coloanal anastomosis. Between 1977 and 1993,620 rectal excisions were performed for rectal adenocarcinoma. 320 were for distal third rectal adenocarcinomas. In order to eliminate, selection bias two separate periods were identified when either only rectal excision and coloanal anastomosis (sphincter preservation) or abdominal perineal resections were being exclusively performed. The 2 groups were matched for sex, age, stage, and adjuvant therapy. From 1977 to 1983,33 patients were treated by abdominal perineal resection. They were compared to another 34 patients who were treated by curative abdomino trans-sphincteric resection, from 19881993. There was no postoperative death. Patients were followed for a mean of 4.8 years after SSR and 5.5 after APR. At 5 years actuarial local recurrence rates were 6.5% and 15% for SSR and APR respectively. The cancer specific 5 year actuarial rates were 77.4 and 73.5 for APR and SSR respectively. Sphincter saving resection does not seem to compromise local recurrence or survival for patients with tumors located in the distal third of the rectum.

2248 DETECTION OF LYMPH NODE MICROMETASTASES IN ESOPHAGEAL CARCINOMA: PATHOLOGY OF LYMPH NODE INVOLVEMENT. Marcus Feith, Hubert 1. Stein, James Mueller, J. Ruediger Siewert, Tech Universtitaet Muenchen, Munich, Germany; Tech Univ Muenchen, Munich, Germany. Introduction: Lymph node microinvolvement has been identified as prognostic factor in a variety of epithelial tumors. No comperative data is available on adenocarcinoma and squamous cell carcinoma of the esophagus. Material and Methodes: We investigated 73 patients with adenocarcinoma of the distal esophagus and 69 patients with squamous cell carcinoma of the esophagus who were primary RO-resected in our department. 3718 removed lymph nodes were assessed immunhistochemically with the antibody cocktail AEl/AE3 and the antibody Ber-EP4 to identify epithelial tumor cells. Newly identified single tumor cells and tumor cell clusters <0.2mm in diameter with stromal reaction were classified as micrometastases. Results: On standard histopathologic evaluation there was no evidence of lymph node metastases in 41 of 73 patients with adenocarcinoma and 41 of 69 patients with squamous cell carcinoma of the esophagus. Immunhistochemical analysis showed lymph node micrometastases in 9.7% of patients with adenocarcinoma staged as pNO compared to 31.7% of the patients with squamous cell carcinoma (p<0.05). Lymph node micrometastases were found in none of the 28 patients with adenocarcinoma staged pTINO in contrast to 6/24 patients with a pTlNO staged squamous cell carcinoma (p
2249 THE IMMUNOHISTOCHEMICAL SIMILARITY OF CARDIAC MUCOSA, INTESTINAL METAPLASIA OF THE CARDIA, AND BARRETT'S ESOPHAGUS, Steve R. DeMeester, Kumari S. Wickramasinghe, Reginald L. Lord, Adam Friedman, Univ of Southern CA, Los Angeles, CA; USC, Los Angeles, CA. Introduction: Cardiac mucosa is a distinct type of simple columnar epithelium characterized histologically by the presence of mucous cells and the absence of parietal or chief cells. Within cardiac mucosa goblet cells, indicative of intestinal metaplasia (1M), may develop. Controversy surrounds the nature of cardiac mucosa, the etiology of 1M limited to the gastroesophageal junction (ClM), and the relationship of CIM to Barrett's

esophagus. The aim of this study was to further characterize cardiac mucosa and lM on the basis of immunoreactivity to specific antibodies. Methods: Endoscopic and histologic findings were used to select Paraffinembedded, formalin fixed biopsy specimens from 30 patients who had undergone upper endoscopy for reflux symptoms. Ten patients had only cardiac mucosa, 10 had CIM, and 10 patients had Barrett's esophagus. New slides from the original tissue blocks were cut and stained for cytokeratins (CK) 7 and 20, ornithine decarboxylase (ODC), and DAS-l antibody. Each slide was examined in a blinded fashion by two investigators. Sections from a known colon cancer and breast cancer were used for positive controls. Results: The columnar epithelium of cardiac mucosa, CIM, and Barrett's had an identical CK 7/20 staining profile, and differed markedly from both gastric and squamous mucosa. Heavy CK 7 staining of the surface mucous cells with lighter patchy staining of the deeper columnar cells was seen in all cases. In patients with 1M the columnar cells demonstrated immunoreactivity, but goblet cells did not. Staining with CK 20 was similar to CK 7 but less intense in all groups. Immunoreactivity with ODC was none or trace in the cardiac mucosa and CIM sections. In the Barrett's sections it was also minimal unless dysplasia was present, in which case moderate ODC staining was noted. Goblet cells from all patients with 1M demonstrated heavy staining with DAS-l antibody. Cardiac mucosa without lM and the columnar cells surrounding goblet cells in sections with 1M did not demonstrate immunoreactivity with DAS-l antibody. Conclusions: Without goblet cells the histology of elM and Barrett's esophagus would be identical to cardiac mucosa. The shared CK 7/20 profile of these tissues suggests a shared etiology and perhaps common origin. Likewise, the identical staining of ClM and Barrett's with DAS-I antibody, an antibody specific for Barrett's, is further evidence that these two entities are closely linked and may represent two ends of a spectrum.

2250 TELOMERASE ACTIVITY IN BARRETT'S ESOPHAGUS AND ESOPHAGEAL ADENOCARCINOMA. Mark S. Diamond, Ziad Younes, Petra H. Nass, Tsung-Tseh Wu, Parviz Nikoomanesh, Mark D. Duncan, Michael D. Crowell, John W. Harmon, Princeton Univ, Princeton, NJ; Johns Hopkins Univ, Baltimore, MD. Telomerase activity has been detected in the majority of cancer types. There is limited information regarding telomerase activity in either esophageal cancer or the premalignant Barrett's metaplasia or dysplasia. Aims: To compare telomerase activity in tissue samples from the esophagus of 10 controls, 18 patients with Barrett's esophagus (9 without dysplasia and 9 with high-grade dysplasia), and 15 patients with esophageal adenocarcinoma. Methods: Telomerase activit was measured using a semi-quantitative PCRlELISA assay (TRAPeze ,Invitrogen). Protein extracts were incubated in a reaction mix where active telomerase containing samples extended a biotinylated template. The extended products were then amplified via PCR using DNP labeled primers. In a final ELISA step, the PCR products were bound to a streptavidin coated microtiter plate and visualized using a horseradish-peroxidase conjugated anti-DNP antibody. Absorbance was measured at A=450 and mean absorbance values were obtained by subtracting the adjusted (A4 5o - A6 30)values from a heat inactivated control. Absorbance values higher than 0.15 were considered positive for telomerase activity. Results: 30% of the controls, 67% of Barrett's metaplasia (7/9 non-dysplastic, 5/9 dysplasia), and 67% of adenocarcinoma tested positive for telomerase activity. An semi-quantitative analysis of the absorbance values revealed no differences between Barrett's metaplasia, dysplasia, and adenocarcinoma. The mean values in controls were lower than Barrett's and adenocarcinoma with p values of 0.035 and 0.085 respectively. Conclusions: We conclude that telomerase activity is induced in patients with Barrett's metaplasia and esophageal adenocarcinoma. The similarity in activity in non-dysplastic Barrett's and adenocarcinoma suggests that telomerase is involved early in esophageal carcinogenesis. The positivity of telomerase activity in some control samples may limit the clinical usefulness of this assay as a tumor marker in esophageal carcinogenesis.

fM

Positive telomeraae Mean Absorbance

Controls

Barrett's

Dysplasia

Adenocarcinoma

3110 (30%) 0.129±0.048

7/9 (78%) 0.567±o.171.

5/9 (56%) 0.318+0.122..

10/15 (67%) 0.423±0.128'"

Student's ttest, different from control group: 'p=0.035, "p=0.181, "'p=0.085

2251 DUODENOGASTRIC REFLUX AND FOREGUT CARCINOGENESIS: ANALYSIS OF THE DUODENAL JUICE IN THE RODENT CANCER MODEL. Martin Fein, Karl H. Fuchs, Helga Stopper, Dominik Wittmann, Stefanie Diem, Markus Herderich, Dept of Surg, Wuerzburg, Germany; Institute of Toxicology, Wuerzburg, Germany; Institute of Pharmacy and Food Chemistry, Wuerzburg, Germany. Purpose: The incidence of esophageal adenocarcinoma is rapidly increasing. In the rodent cancer model surgically induced duodenoesophageal reflux is carcinogenic. One proposed mechanism of carcinogenesis relies