DNA single strand breaks are more commonly found in superficial gastric epithelial cells
1
April 1998 These data support the evidence for a protective effect of aspirin on colorectal cancer and the further investigation in the use of selective COX2 inhibitors in colonic neoplasia. • G2432 DNA SINGLE STRAND BREAKS ARE MORE COMMONLY FOUND IN SUPERFICIAL GASTRIC EPITHELIAL CELLS. S Everett. K White, C Schorah, Axon ATR. Centre for Digestive Diseases, The General Infirmary at Leeds, UK Introduction: H.pylori infection is associated with a 3-4 fold increased risk of developing gastric carcinoma. Using single cell electrophoresis (comet assay), however, we have demonstrated fewer epithelial cell DNA single strand breaks in H. pylori infected compared with uninfected mucosa. In this study we have examined serial digestions of gastric biopsies for DNA strand breaks to estimate the site of the damaged ceils in the epithelium, and the effect of different rates of cell turnover. Methods: At endoscopy, antral biopsies were taken for histology, Clo test and the comet assay. Biopsies were disaggregated to single epithelial ceils using pronase and collagenase: after 25 minutes the entire cell suspension is removed for the comet assay, and the biopsy remnants resuspended in fresh enzymes. This process was repeated up to 4 times. The comet assay involves high pH electophoresis of lysed single cells. Broken DNA strands migrate in the electric field; cells with DNA strand breaks appear as comets after fluorescent staining, and are counted as a % of the total (comet %). Results: We studied 14 H. pylori positive, and 29 H. pylori negative patients. Median comet % for all patients fell as disaggregation time increased (54.5% at 25 rains n=26; 35% at 50 mins, n=33; 16% at 75 mins, n=lT; 0% at 100 mins, n---5, p<0.001 Kruskall-Wallis test). This pattern was similar both for H. pylori positive and negative patients: H. pylori negative H. pylori positve Time comet % (med) n comet % (med) n p* 25 mins 61 17 38 9 0.001 25 rains 45 23 27 10 0.000 75 mins 19 9 11 8 0.04 100 mins 0 2 0 3 0.8 * Mann Whitney U test Conclusions: Mature, superficial cells from high in the epithelial crypt are more likely to have DNA damage than deeper cells. In the rapidly proliferating epithelium of H. pylori gastritis superficial ceils will be less mature and are thus less likely to have damaged DNA. These non dividing cells are unlikely, however, to have carcinogenic potential, emphasising the need to locate and study stern cells when assessing carcinogenic risk. • G2433 SCREENING FOR GASTRIC CARCINOMA USING H. PYLORI SEROLOGY. S Everett, J Davies, M Wilcox, H Sue-Ling, D Johnston, A Axon. Centre for Digestive Diseases, The General Infirmary at Leeds, UK Introduction: H.pylori infection is associated with a 3-4 fold increased risk of developing gastric carcinoma. Currently, detection of gastric cancer is based on early endoscopy for all patients with dyspepsia. It may, however, be possible to select patients for early endoscopy by serological testing for H. pylori. We wished to examine this by determining the prevalence of H. pylori infection in patients presenting with gastric carcinoma in a University Teaching Hospital in the UK, using two serological kits to maximise sensitivity. Methods: 138 consecutive patients attending the surgical department from October 1990 - 95 with histologically proven gastric carcinoma had 10ml whole blood taken either preoperatively or no later than 2 weeks postoperatively. H. pylori specific IgG assays were performed using both the Pylori Elisa II (Bit Whitaker) and Premier H. pylori (Launch) enzyme linked immunosorbent assay (ELISA) kits. Results: We studied 138 patients with a median age of 70 years. Overall, the Launch kit was positive for H. pylori in 103/138 cases (74.6%), and the BioWhitaker kit was positive in 84/138 cases (60.9%; 10 cases equivocal). Concordance between kits was 81.9%. If either kit was positive, 105/138 were H. pylori positive giving a maximum sensitivity for detection of carcinoma of 76.1%. The prevalence of H. pylori did not increase significantly in younger patients (21/28, 75% patients under 60 years vs 84/110, 76.4% of over 60's, p=0.9), in lower and mid third tumours compared with upper third (42/55, 76%; 19/26, 73%; and 34/43, 79%, respectively, p---0.6) or according to tumour stage (21/26, 80.7% stage I; 9/14, 64.3%, stage II; 38•43, 88.4% stage III; and 37155, 67.3% stage IV, p=0.06). Of the 33 patients that were negative for H. pylori on both kits, 4 had had previous gastric surgery and 1 had family history of gastric cancer, but no other risk factors could be identified. Conclusions: Just under one quarter of our patients with gastric carcinoma were negative for H. pylori using two ELISA kits. This approach is not, therefore, recommended for prioritisation of the investigation of dyspepsia in our population. This research was assisted financially by Launch Diagnostics Ltd. Gastrointestinal Oncology A593 • G2434 UTILITY OF ENDORECTAL ULTRASOUND IN THE MANAGEMENT OF RECTAL CANCER. DO Falgel, PY Lee* Portland VA, Oregon Health Sciences University and *The Colon Rectal Clinic, Portland, OR Endorectal ultrasound (ErUS) provides detailed images of rectal neoplasia allowing for more accurate preoperative staging than with other modalities. Its role in the management of rectal cancer has yet to be defined. Methods: Consecutive patients referred for ErUS of suspected rectal cancer were included. Prior to ErUS, the planned operative procedure (i.e., Local excision (LOC), Low Anterior Resection (LAR), Abdominoperineal Resection (APR)) and plans for preoperative chemo/radiotherapy (C/RT) were recorded. ErUS was then performed unsedated with either the Olympus GFUM20 echoendoscope (Olympus America) scanning at 7.5 and 12 MHz (n=16), or B&K probe (B&K Medical) at 5 and 7 MHz introduced through a rigid proctoscope (n=21). The T and N stages were recorded and compared to the subsequent surgical stages. Patients were followed prospectively through surgery and the planned therapy was compared to the therapy actually received. Results: 37 patients (32M, 5F), mean age 64 years were included. 34 had adenocarcinoma, 3 had villous adenomas. ErUS Tstages were: TI: 12, T2: 13, T3: 12. ErUS T-stage accuracies were: TI: 93% (11/12), T2: 62% (8/13), T3: 75% (9/12), Overall: 76% (28/37). ErUS N-stages were NO: 17, NI: 7, N2: 2, Nx: 1. Surgical N-stage was not available in 16 patients treated with local excision and 1 LAR and ErOS N-stage in 1 with an obstructing tumor. ErUS N-stage accuracy: NO: 90% (9/10), N1 or N2: 56% (5/9). Preoperative C/RT was initially planned in 6 patients; following ErUS an additional 3 received preoperative C/RT (total=9). 11 patients received less invasive operative procedures than planned and 2 more invasive. Of 29 patients planned for LAR or APR, 9 had LOC (31%). Procedure Received LOC I LAR APR Total LOC 7 i0 0 7 APt ii~i:~ii~ii~.:~:~i i~i~iiiiii~:i:i 9 15 Total: 16 10 11 37 Conclusions: 1. ErUS is highly accurate for T1 lesions. 2. ErUS may have a role in selecting patients for preoperative neoadjuvant therapy protocols. 3. ErUS may modify the surgical approach by identifying patients for local excision and should be considered in all patients with rectal cancer. @ G2435 EVALUATION OF THE ANTIPROLIFERATIVE EFFECT OF LANREOTIDE OR INTERFERON-ALPHA OR THE COMBINATION OF BOTH IN THE THERAPY OF METASTATIC NEURO- ENDOCRINE TUMORS. S. Faiss 1, E.-O. Riecken 1, B. Wiadanmann 2 and the Int. Lanreotide and Interferon-alpha study group Departments of Gastroenterology Benjamin Franklin Medical Center, Free University Berlin l and Virchow Medical Center, Humboldt University Berlin2, Germany Somatostatin-analogs and interferon-alpha control hypersecretion syndromes and possess also an antiproliferative effect in patients with metastatic neuroendocrine tumors (NET) of the gastroenteropancreatie system. So far, it is unknown, if a combination of somatostatin-analogs and interferon-alpha is superior to a monotherapy of the two. Therefore, we performed a randomized prospective multicenter study. Material and Methods: 59 patients with progressive histologically proven NET disease (primary localization: foregut n=27, midgut n=21, hindgut n=3, unknown n=8; functionality: functional n=24, non4unctional n=35) were treated either with lanreotide (3xlmg/day s.c.) or interferon-alpha (3x5Mio I.E./week s.c,) or with the combination of both. With the exception of surgery, all patients were not treated previously. During treatment the anttiproliferative effect was examined by transabdominal ultrasound, CT or MRI as well as biochemical madcers (e.g. serum serotonin and chromogranin A, urinary 5-HIAA). Results; 20 patients were treated with lanreotide, 19 patients with interferon- alpha and 20 patients with the combination. Stable disease was observed in 11/20 patients in the lanreotide arm, 10/19 patients in the interferon-alpha arm and 11/20 patients in the combination arm. Within 12 months of therapy, tumor progression was only observed in 3/20 patients in the combination arm, whereas 8/20 patients (lanreotide arm) and 6/19 patients (interferon-alpha arm) had progressive disease. Side-effects leading to an interruption of the therapy were more frequent in the combination group (6/20) and to lesser extent in the monotherapy arms (3/19 interferon-alpha, 1/20 lanreotide). Conclusions. Our results suggest that the combination of lanreotide and interferon-alpha has a higher antiproliferative effect as compared to monotherapy with lanreotide or interferon-alpha in patients with metastatic NET. However, side-effects are more common in the combination arm.
Transcript of DNA single strand breaks are more commonly found in superficial gastric epithelial cells
April 1998
These data support the evidence for a protective effect of aspirin on colorectal cancer and the further investigation in the use of selective COX2 inhibitors in colonic neoplasia.
• G2432
DNA SINGLE STRAND BREAKS ARE MORE COMMONLY FOUND IN SUPERFICIAL GASTRIC EPITHELIAL CELLS. S Everett. K White, C Schorah, Axon ATR. Centre for Digestive Diseases, The General Infirmary at Leeds, UK
Introduction: H.pylori infection is associated with a 3-4 fold increased risk of developing gastric carcinoma. Using single cell electrophoresis (comet assay), however, we have demonstrated fewer epithelial cell DNA single strand breaks in H. pylori infected compared with uninfected mucosa. In this study we have examined serial digestions of gastric biopsies for DNA strand breaks to estimate the site of the damaged ceils in the epithelium, and the effect of different rates of cell turnover. Methods: At endoscopy, antral biopsies were taken for histology, Clo test and the comet assay. Biopsies were disaggregated to single epithelial ceils using pronase and collagenase: after 25 minutes the entire cell suspension is removed for the comet assay, and the biopsy remnants resuspended in fresh enzymes. This process was repeated up to 4 times. The comet assay involves high pH electophoresis of lysed single cells. Broken DNA strands migrate in the electric field; cells with DNA strand breaks appear as comets after fluorescent staining, and are counted as a % of the total (comet %). Results: We studied 14 H. pylori positive, and 29 H. pylori negative patients. Median comet % for all patients fell as disaggregation time increased (54.5% at 25 rains n=26; 35% at 50 mins, n=33; 16% at 75 mins, n=lT; 0% at 100 mins, n---5, p<0.001 Kruskall-Wallis test). This pattern was similar both for H. pylori positive and negative patients:
H. pylori negative H. pylori positve Time comet % (med) n comet % (med) n p* 25 mins 61 17 38 9 0.001 25 rains 45 23 27 10 0.000 75 mins 19 9 11 8 0.04 100 mins 0 2 0 3 0.8 * Mann Whitney U test
Conclusions: Mature, superficial cells from high in the epithelial crypt are more likely to have DNA damage than deeper cells. In the rapidly proliferating epithelium of H. pylori gastritis superficial ceils will be less mature and are thus less likely to have damaged DNA. These non dividing cells are unlikely, however, to have carcinogenic potential, emphasising the need to locate and study stern cells when assessing carcinogenic risk.
• G2433
SCREENING FOR GASTRIC CARCINOMA USING H. PYLORI SEROLOGY. S Everett, J Davies, M Wilcox, H Sue-Ling, D Johnston, A Axon. Centre for Digestive Diseases, The General Infirmary at Leeds, UK
Introduction: H.pylori infection is associated with a 3-4 fold increased risk of developing gastric carcinoma. Currently, detection of gastric cancer is based on early endoscopy for all patients with dyspepsia. It may, however, be possible to select patients for early endoscopy by serological testing for H. pylori. We wished to examine this by determining the prevalence of H. pylori infection in patients presenting with gastric carcinoma in a University Teaching Hospital in the UK, using two serological kits to maximise sensitivity. Methods: 138 consecutive patients attending the surgical department from October 1990 - 95 with histologically proven gastric carcinoma had 10ml whole blood taken either preoperatively or no later than 2 weeks postoperatively. H. pylori specific IgG assays were performed using both the Pylori Elisa II (Bit Whitaker) and Premier H. pylori (Launch) enzyme linked immunosorbent assay (ELISA) kits. Results: We studied 138 patients with a median age of 70 years. Overall, the Launch kit was positive for H. pylori in 103/138 cases (74.6%), and the BioWhitaker kit was positive in 84/138 cases (60.9%; 10 cases equivocal). Concordance between kits was 81.9%. If either kit was positive, 105/138 were H. pylori positive giving a maximum sensitivity for detection of carcinoma of 76.1%. The prevalence of H. pylori did not increase significantly in younger patients (21/28, 75% patients under 60 years vs 84/110, 76.4% of over 60's, p=0.9), in lower and mid third tumours compared with upper third (42/55, 76%; 19/26, 73%; and 34/43, 79%, respectively, p---0.6) or according to tumour stage (21/26, 80.7% stage I; 9/14, 64.3%, stage II; 38•43, 88.4% stage III; and 37155, 67.3% stage IV, p=0.06). Of the 33 patients that were negative for H. pylori on both kits, 4 had had previous gastric surgery and 1 had family history of gastric cancer, but no other risk factors could be identified. Conclusions: Just under one quarter of our patients with gastric carcinoma were negative for H. pylori using two ELISA kits. This approach is not, therefore, recommended for prioritisation of the investigation of dyspepsia in our population. This research was assisted financially by Launch Diagnostics Ltd.
Gastrointestinal Oncology A593
• G2434
UTILITY OF ENDORECTAL ULTRASOUND IN THE MANAGEMENT OF RECTAL CANCER. DO Falgel, PY Lee* Portland VA, Oregon Health Sciences University and *The Colon Rectal Clinic, Portland, OR
Endorectal ultrasound (ErUS) provides detailed images of rectal neoplasia allowing for more accurate preoperative staging than with other modalities. Its role in the management of rectal cancer has yet to be defined. Methods: Consecutive patients referred for ErUS of suspected rectal cancer were included. Prior to ErUS, the planned operative procedure (i.e., Local excision (LOC), Low Anterior Resection (LAR), Abdominoperineal Resection (APR)) and plans for preoperative chemo/radiotherapy (C/RT) were recorded. ErUS was then performed unsedated with either the Olympus GFUM20 echoendoscope (Olympus America) scanning at 7.5 and 12 MHz (n=16), or B&K probe (B&K Medical) at 5 and 7 MHz introduced through a rigid proctoscope (n=21). The T and N stages were recorded and compared to the subsequent surgical stages. Patients were followed prospectively through surgery and the planned therapy was compared to the therapy actually received. Results: 37 patients (32M, 5F), mean age 64 years were included. 34 had adenocarcinoma, 3 had villous adenomas. ErUS Tstages were: TI: 12, T2: 13, T3: 12. ErUS T-stage accuracies were: TI: 93% (11/12), T2: 62% (8/13), T3: 75% (9/12), Overall: 76% (28/37). ErUS N-stages were NO: 17, NI: 7, N2: 2, Nx: 1. Surgical N-stage was not available in 16 patients treated with local excision and 1 LAR and ErOS N-stage in 1 with an obstructing tumor. ErUS N-stage accuracy: NO: 90% (9/10), N1 or N2: 56% (5/9). Preoperative C/RT was initially planned in 6 patients; following ErUS an additional 3 received preoperative C/RT (total=9). 11 patients received less invasive operative procedures than planned and 2 more invasive. Of 29 patients planned for LAR or APR, 9 had LOC (31%).
Procedure Received LOC I LAR APR Total
LOC 7 i0 0 7
APt ii~i:~i i~ii~.:~:~i i~i~iiiiii~:i:i 9 15 Total: 16 10 11 37
Conclusions: 1. ErUS is highly accurate for T1 lesions. 2. ErUS may have a role in selecting patients for preoperative neoadjuvant therapy protocols. 3. ErUS may modify the surgical approach by identifying patients for local excision and should be considered in all patients with rectal cancer.
@ G2435
EVALUATION OF THE ANTIPROLIFERATIVE EFFECT OF LANREOTIDE OR INTERFERON-ALPHA OR THE COMBINATION OF BOTH IN THE THERAPY OF METASTATIC NEURO- ENDOCRINE TUMORS. S. Faiss 1, E.-O. Riecken 1, B. Wiadanmann 2 and the Int. Lanreotide and Interferon-alpha study group Departments of Gastroenterology Benjamin Franklin Medical Center, Free University Berlin l and Virchow Medical Center, Humboldt University Berlin 2, Germany
Somatostatin-analogs and interferon-alpha control hypersecretion syndromes and possess also an antiproliferative effect in patients with metastatic neuroendocrine tumors (NET) of the gastroenteropancreatie system. So far, it is unknown, if a combination of somatostatin-analogs and interferon-alpha is superior to a monotherapy of the two. Therefore, we performed a randomized prospective multicenter study. Material and Methods: 59 patients with progressive histologically proven NET disease (primary localization: foregut n=27, midgut n=21, hindgut n=3, unknown n=8; functionality: functional n=24, non4unctional n=35) were treated either with lanreotide (3xlmg/day s.c.) or interferon-alpha (3x5Mio I.E./week s.c,) or with the combination of both. With the exception of surgery, all patients were not treated previously. During treatment the anttiproliferative effect was examined by transabdominal ultrasound, CT or MRI as well as biochemical madcers (e.g. serum serotonin and chromogranin A, urinary 5-HIAA). Results; 20 patients were treated with lanreotide, 19 patients with interferon- alpha and 20 patients with the combination. Stable disease was observed in 11/20 patients in the lanreotide arm, 10/19 patients in the interferon-alpha arm and 11/20 patients in the combination arm. Within 12 months of therapy, tumor progression was only observed in 3/20 patients in the combination arm, whereas 8/20 patients (lanreotide arm) and 6/19 patients (interferon-alpha arm) had progressive disease. Side-effects leading to an interruption of the therapy were more frequent in the combination group (6/20) and to lesser extent in the monotherapy arms (3/19 interferon-alpha, 1/20 lanreotide). Conclusions. Our results suggest that the combination of lanreotide and interferon-alpha has a higher antiproliferative effect as compared to monotherapy with lanreotide or interferon-alpha in patients with metastatic NET. However, side-effects are more common in the combination arm.
