- Email: [email protected]
A computerized colorectal cancer prevention registry and risk assessment tool
April 1998
mRNA for MMP-2 was detected ill 15/20 carcinomas and 2/20 normal tissue samples, mRNA for MT-MMP-1 was detected in 14/20 carcinomas and 5/20 normal tissue samples, mRNA for MT-MMP-2 was detected in only 3 samples, all tumour mRNA Tumour median Normal median P= MMP-2 7.35 × 10-7 1.0 x 10"g 0.017 MT-MMP-1 6.5 × 10.4 1.0 × 10-s 0.027 MT-MMP-2 3 x 10-4 0 Relative amounts of each enzyme were compared using Wilcoxon statistics. Co-localisation of the mRNA for MMP-2 and its activator MT-MMP-1 has been demonstrated. There is a significant difference between tumour and normal mucosa in the quantity of mRNA for these two enzymes demonstrated using RT-PCR. G2848 A COMPUTERIZED COLORECTAL CANCER PREVENTION REGISTRY AND RISK ASSESSMENT TOOL. Lawrence J. Timm0ns, Elsa C. Carlson, John E. King, Noralane M. Lindor, David A. Ahlquist, Charles E. Treder, William E. Kames, Jr., Colorectal Neoplasia Group, Mayo Clinic, Rochester, MN. Colorectal cancer is the second leading cause of cancer deaths in the United States but is potentially preventable through the development and implementation of cost-effective screening, surveillance and treatment of premalignant adenomas before cancer develops. The anticipated benefits of such interventions are greatest if "high risk" individuals are targeted, educated, and evaluated in an efficient manner. To facilitate achievement of these goals, we developed a Colorectal Neoplasia Prevention Registry based on Microsoft Access 95. The registry performs five primary functions that facilitate clinical and research activities: 1) prospective and uniform collection of data related to known risk factors for colorectal cancer; 2) risk cohort identification based on family and personal history; 3) identification of inherited cancer syndromes; 4) research project-specific data collection; and 5) automated patient contacts for purposes of follow-up, education and surveys of "high risk" probands and kindred members. Risk cohorts are defined by two calculated risk indi¢es, one based on personal history and the other based on family history. The first is an index of personal risk that examines colonoscopic and hist0pathological findings and applies weights to extent of exam, quality of colon preparation, and current and previous colonoscopic findings including neoplasm number, size, histology, and degree of dysplasia. The second is a familial risk index that utilizes SEER data to calculate a ratio of the observed vs. the expected number of colorectal cancers (and associated cancers) within a kindred based on age distributions. Based on its demonstrated utility and ease of use in our practice we believe this registry may benefit other clinics with special interests in colorectal neoplasia prevention, inherited colorectal cancer syndromes, epidemiological studies, outcomes research, and prospective evaluations of novel screening, surveillance or chemopreventative modalities. Importantly, the registry provides a rigorous mechanism to identify and educate a subset of the population at high risk for colorectal cancer. Funded by the Mayo Foundation. G2849 TRANS-ANAL ULTRASOUND GUIDED INTERSTITIAL IMPLANT FOR TREATING ANAL CARCINOMA. Lok Tio, Anita Reddy and Michael Kuettel, Division of Gastroenterology and Dept. of Radiation Medicine, Georgetown University Hospital, Washington, D.C., 20007
Back~,round: The treatment of anal carcinoma has been radically modified over the last decade. Since irradiation (RT) and chemotherapy results in a high degree of curability, abdominal-perineal resection (APR) is generally no longer considered appropriate as initial treatment and is reserved for oneologic or functional failures. Sphincter-sparing approaches have provided a high local control rate but have also been associated with a risk of major chronic complications that may significantly impair the patient's quality of life. Increasing the RT dose has resulted in a higher local control but also greater complications. In order to permit higher RT doses to the tumor without excessively treating normal tissue (reducing complications), we have developed a trans-anal ultrasound guided interstitial implant procedure for treating anal carcinoma. Case; A 44 year old man with biopsy proven squamous carcinoma of the anal canal was referred for RT. The initial treatment was started one month after the diagnosis. Following the initial extemal beam RT to the pelvis with concomitant chemotherapy, a low dose rate interstitial 192Ir implant is performed 2-4 weeks later. The number of needles implanted, the active length of the 192Ir wires and the dose applied is patient dependent. A custom designed perineal template was used to permit an echoendoscope (Olympus UM-20) passing through. The tip of the echoendoscope was inserted into the rectum and then gradually withdrawn until the target was clearly seen. The needles were inserted via the template Under US guidance into the target of interest. The patient was still disease free during the follow up of two years. Conclusion: Residual tumor burden visualized by US permits a customized implant. This technique limits the high doses of RT to the initial gross tumor
Gastrointestinal Oncology A689
reducing the risk of major complications and optimizing the therapeutic ratio. We believe that EUS is very helpful in guiding the placement of 192Ir implant. G2850 GASTRIC MALT LYMPI-IOMA: PATHOGENETIC ROLE OF HEPATITIS C VIRUS, EM Tkoub (1), M Levy (1), C Haionn (2), JM Pawlotsky (3), D Dhumeaux (1), JC Delchier (1). Services d'H6patogastroent~rologie (1), d'H~matologie (2), de Virologie (3), H6pital Henri Mondor, Cr&eil, France.
Non-Hodgkin lymphomas (NHL) have been reported in patients chronically infected with hepatitis C virus (HCV). Lymphomas of the MALT type are due to monoclonal proliferation of B -cells showing characteristic histopathological features of mucosa-associated lymphoid tissue (MALT). A high prevalence of HCV infection in patients with low-grade MALT lymphoma has been reported in Italy. The aim of the present study was to compare the prevalence of HCV infection in patients with gastric MALT lymphoma to that observed in two control groups, one with Helicobacter pylori (Hp)-associated gastroduodenal disease, the other with nongastroduodenal B-eall NHL. Methods: Of the 47 patients, 30 had a low-grade lymphoma (male-to-female ratio (M/F): 13117, mean age 50 years) and 17 had a high-grade lymphoma (M/F: 10/7, 54 years). Hp infection was demonstrated by serological and/or histological tests. One hundred and sixty-five patients with gastroduodeoal disease (gastroduodenal ulcer: 103, non ulcer dyspepsia: 62) and 104 patients with non-gastroduodenal B-eaU NHL were recruited to compose the control groups. Both groups were comparable in terms of age, prevalence of Hp and risk factors for HCV infection (previous parenteral exposure to blood products, intravenous drug misuse, nosocomial exposure). Diagnosis of gastric MALT lymphoma was based on gastric biopsy specimens evaluated according to Isaacson's classification. Anti-HCV antibodies were determined by third-generation ELISA and confirmed by third-generation RIBA in all patients. Results: There was no significant difference between the prevalence of HCV infection in the MALT lymphoma group and control groups: among the patients with gastric MALT lymphoma, only 1 had anti-HCV antibodies (2.2%), as compared to 4 of the 165 patients with gastroduodenal disease (2.3%) and 2 of the 104 patients with B-cell NHL (1.9%). Conclusion: Prevalence of HCV infection was not found higher in patients with gastric MALT lymphoma than in patients from both control groups. These results indicate that there is no link between HCV infection and gastric MALT lymphoma in France. • G2851
HELICOBACTER PYLORI AND GASTRIC MALT LYMPHOMA: ROLE OF THE CagA PROTEIN. E M Tkoub (1), L Deforges (2), M Levy (1), D Lamarque (1), A Lepicard (1), C Haioun (3), J C Delchier (1). Services d'H~patologie et de Gastro-Ent~rologie (1), de bact~riologie (2), d'h6matologie (3), H6pital Henri Mondor, Cr&eil. Gastric MALT lymphoma (GML) is closely related to Helicobacter pylori (Hp) infection. In vitro studies have demonstrated Hp-induced B-cell proliferation to be strain-dependent. CagA protein is a virulence factor strongly related to peptic ulcer disease. The prevalence of CagA protein was recently estimated by Eck et al. (Gastroenterology 1997; 112:1482) to be of 95% in GML. The aim of the present study was to evaluate both the prevalence of Hp infection and that of CagA protein in a series of 41 patients with GML in comparison with that observed in infected patients with benign gastroduodenal disease. Methods: Of the 41 patients, 29 had a low grade GML (12 males, 17 females, mean age 50 years) and 12 had a high grade GML (6 males, 6 females, mean age 53 years). Among the 162 subjects of the control group, 103 had gastroduodenal ulcer (GDU) and 54 non ulcer dyspepsia (NUD). Both groups were comparable in terms of age. Diagnosis of GML was based on gastric biopsy specimens evaluated according to Isaacson's classification. Anti-Hp antibodies were assayed by third-generation ELISA (Enzygnost®) and Western Blot assay (Helico Blot 2.0 ®) was used to detect antibodies against eight antigens with different molecular weight including CagA protein (116 kDa). Results: Of the 41 GML patients, 33 had a positive ELISA test (80%), 17 of whom (51.5%) had anti-CagA antibodies. In comparison, anti-CagA antibodies were found in 87 / 103 (84.4%) GDU patients (P< 0.01) and in 20/54 (37%) NUD patients (NS). Conclusion:Our results confirm a high prevalence of Hp infection in GML patients, even if all were not infected. On the other hand, the prevalence of CagA in lip infected GML is not statistically different from that observed in NUD and is significantly lower than that observed in GDU. It appears that, at least in France, CagA is not clearly involved in the pathogenesis of GML.
mRNA for MMP-2 was detected ill 15/20 carcinomas and 2/20 normal tissue samples, mRNA for MT-MMP-1 was detected in 14/20 carcinomas and 5/20 normal tissue samples, mRNA for MT-MMP-2 was detected in only 3 samples, all tumour mRNA Tumour median Normal median P= MMP-2 7.35 × 10-7 1.0 x 10"g 0.017 MT-MMP-1 6.5 × 10.4 1.0 × 10-s 0.027 MT-MMP-2 3 x 10-4 0 Relative amounts of each enzyme were compared using Wilcoxon statistics. Co-localisation of the mRNA for MMP-2 and its activator MT-MMP-1 has been demonstrated. There is a significant difference between tumour and normal mucosa in the quantity of mRNA for these two enzymes demonstrated using RT-PCR. G2848 A COMPUTERIZED COLORECTAL CANCER PREVENTION REGISTRY AND RISK ASSESSMENT TOOL. Lawrence J. Timm0ns, Elsa C. Carlson, John E. King, Noralane M. Lindor, David A. Ahlquist, Charles E. Treder, William E. Kames, Jr., Colorectal Neoplasia Group, Mayo Clinic, Rochester, MN. Colorectal cancer is the second leading cause of cancer deaths in the United States but is potentially preventable through the development and implementation of cost-effective screening, surveillance and treatment of premalignant adenomas before cancer develops. The anticipated benefits of such interventions are greatest if "high risk" individuals are targeted, educated, and evaluated in an efficient manner. To facilitate achievement of these goals, we developed a Colorectal Neoplasia Prevention Registry based on Microsoft Access 95. The registry performs five primary functions that facilitate clinical and research activities: 1) prospective and uniform collection of data related to known risk factors for colorectal cancer; 2) risk cohort identification based on family and personal history; 3) identification of inherited cancer syndromes; 4) research project-specific data collection; and 5) automated patient contacts for purposes of follow-up, education and surveys of "high risk" probands and kindred members. Risk cohorts are defined by two calculated risk indi¢es, one based on personal history and the other based on family history. The first is an index of personal risk that examines colonoscopic and hist0pathological findings and applies weights to extent of exam, quality of colon preparation, and current and previous colonoscopic findings including neoplasm number, size, histology, and degree of dysplasia. The second is a familial risk index that utilizes SEER data to calculate a ratio of the observed vs. the expected number of colorectal cancers (and associated cancers) within a kindred based on age distributions. Based on its demonstrated utility and ease of use in our practice we believe this registry may benefit other clinics with special interests in colorectal neoplasia prevention, inherited colorectal cancer syndromes, epidemiological studies, outcomes research, and prospective evaluations of novel screening, surveillance or chemopreventative modalities. Importantly, the registry provides a rigorous mechanism to identify and educate a subset of the population at high risk for colorectal cancer. Funded by the Mayo Foundation. G2849 TRANS-ANAL ULTRASOUND GUIDED INTERSTITIAL IMPLANT FOR TREATING ANAL CARCINOMA. Lok Tio, Anita Reddy and Michael Kuettel, Division of Gastroenterology and Dept. of Radiation Medicine, Georgetown University Hospital, Washington, D.C., 20007
Back~,round: The treatment of anal carcinoma has been radically modified over the last decade. Since irradiation (RT) and chemotherapy results in a high degree of curability, abdominal-perineal resection (APR) is generally no longer considered appropriate as initial treatment and is reserved for oneologic or functional failures. Sphincter-sparing approaches have provided a high local control rate but have also been associated with a risk of major chronic complications that may significantly impair the patient's quality of life. Increasing the RT dose has resulted in a higher local control but also greater complications. In order to permit higher RT doses to the tumor without excessively treating normal tissue (reducing complications), we have developed a trans-anal ultrasound guided interstitial implant procedure for treating anal carcinoma. Case; A 44 year old man with biopsy proven squamous carcinoma of the anal canal was referred for RT. The initial treatment was started one month after the diagnosis. Following the initial extemal beam RT to the pelvis with concomitant chemotherapy, a low dose rate interstitial 192Ir implant is performed 2-4 weeks later. The number of needles implanted, the active length of the 192Ir wires and the dose applied is patient dependent. A custom designed perineal template was used to permit an echoendoscope (Olympus UM-20) passing through. The tip of the echoendoscope was inserted into the rectum and then gradually withdrawn until the target was clearly seen. The needles were inserted via the template Under US guidance into the target of interest. The patient was still disease free during the follow up of two years. Conclusion: Residual tumor burden visualized by US permits a customized implant. This technique limits the high doses of RT to the initial gross tumor
Gastrointestinal Oncology A689
reducing the risk of major complications and optimizing the therapeutic ratio. We believe that EUS is very helpful in guiding the placement of 192Ir implant. G2850 GASTRIC MALT LYMPI-IOMA: PATHOGENETIC ROLE OF HEPATITIS C VIRUS, EM Tkoub (1), M Levy (1), C Haionn (2), JM Pawlotsky (3), D Dhumeaux (1), JC Delchier (1). Services d'H6patogastroent~rologie (1), d'H~matologie (2), de Virologie (3), H6pital Henri Mondor, Cr&eil, France.
Non-Hodgkin lymphomas (NHL) have been reported in patients chronically infected with hepatitis C virus (HCV). Lymphomas of the MALT type are due to monoclonal proliferation of B -cells showing characteristic histopathological features of mucosa-associated lymphoid tissue (MALT). A high prevalence of HCV infection in patients with low-grade MALT lymphoma has been reported in Italy. The aim of the present study was to compare the prevalence of HCV infection in patients with gastric MALT lymphoma to that observed in two control groups, one with Helicobacter pylori (Hp)-associated gastroduodenal disease, the other with nongastroduodenal B-eall NHL. Methods: Of the 47 patients, 30 had a low-grade lymphoma (male-to-female ratio (M/F): 13117, mean age 50 years) and 17 had a high-grade lymphoma (M/F: 10/7, 54 years). Hp infection was demonstrated by serological and/or histological tests. One hundred and sixty-five patients with gastroduodeoal disease (gastroduodenal ulcer: 103, non ulcer dyspepsia: 62) and 104 patients with non-gastroduodenal B-eaU NHL were recruited to compose the control groups. Both groups were comparable in terms of age, prevalence of Hp and risk factors for HCV infection (previous parenteral exposure to blood products, intravenous drug misuse, nosocomial exposure). Diagnosis of gastric MALT lymphoma was based on gastric biopsy specimens evaluated according to Isaacson's classification. Anti-HCV antibodies were determined by third-generation ELISA and confirmed by third-generation RIBA in all patients. Results: There was no significant difference between the prevalence of HCV infection in the MALT lymphoma group and control groups: among the patients with gastric MALT lymphoma, only 1 had anti-HCV antibodies (2.2%), as compared to 4 of the 165 patients with gastroduodenal disease (2.3%) and 2 of the 104 patients with B-cell NHL (1.9%). Conclusion: Prevalence of HCV infection was not found higher in patients with gastric MALT lymphoma than in patients from both control groups. These results indicate that there is no link between HCV infection and gastric MALT lymphoma in France. • G2851
HELICOBACTER PYLORI AND GASTRIC MALT LYMPHOMA: ROLE OF THE CagA PROTEIN. E M Tkoub (1), L Deforges (2), M Levy (1), D Lamarque (1), A Lepicard (1), C Haioun (3), J C Delchier (1). Services d'H~patologie et de Gastro-Ent~rologie (1), de bact~riologie (2), d'h6matologie (3), H6pital Henri Mondor, Cr&eil. Gastric MALT lymphoma (GML) is closely related to Helicobacter pylori (Hp) infection. In vitro studies have demonstrated Hp-induced B-cell proliferation to be strain-dependent. CagA protein is a virulence factor strongly related to peptic ulcer disease. The prevalence of CagA protein was recently estimated by Eck et al. (Gastroenterology 1997; 112:1482) to be of 95% in GML. The aim of the present study was to evaluate both the prevalence of Hp infection and that of CagA protein in a series of 41 patients with GML in comparison with that observed in infected patients with benign gastroduodenal disease. Methods: Of the 41 patients, 29 had a low grade GML (12 males, 17 females, mean age 50 years) and 12 had a high grade GML (6 males, 6 females, mean age 53 years). Among the 162 subjects of the control group, 103 had gastroduodenal ulcer (GDU) and 54 non ulcer dyspepsia (NUD). Both groups were comparable in terms of age. Diagnosis of GML was based on gastric biopsy specimens evaluated according to Isaacson's classification. Anti-Hp antibodies were assayed by third-generation ELISA (Enzygnost®) and Western Blot assay (Helico Blot 2.0 ®) was used to detect antibodies against eight antigens with different molecular weight including CagA protein (116 kDa). Results: Of the 41 GML patients, 33 had a positive ELISA test (80%), 17 of whom (51.5%) had anti-CagA antibodies. In comparison, anti-CagA antibodies were found in 87 / 103 (84.4%) GDU patients (P< 0.01) and in 20/54 (37%) NUD patients (NS). Conclusion:Our results confirm a high prevalence of Hp infection in GML patients, even if all were not infected. On the other hand, the prevalence of CagA in lip infected GML is not statistically different from that observed in NUD and is significantly lower than that observed in GDU. It appears that, at least in France, CagA is not clearly involved in the pathogenesis of GML.