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Gastric MALT-lymphoma: The clinical and endoscopic spectrum of t(11;18) positive and negative cases
tested positive for the t(11;18)(9%), and B-cell monoclonality was found in 10/16 patients tested (62.5%). So far, 19 patients underwent at least the first control examination, 14 of those achieved CR after a median of 115 days (73.6%), 4 patients showed partial remission (21%) after 9 months awaiting the 12-momhs control, and 1 patient showed no change after 1 year being t( 11;18)-positive, initially. This patient will be included into the HELYX II protocol. Another patient being t(1 l:18)-positive achieved CR after eradication therapy, and will be fallowed-up The patient included in HELYX II reached CR after radiation, and remains in CCR for 12 months. Conclusion: Eradication therapy remains the first line therapy in H. pylori-positive gastric low-grade MALT lymphoma. CR can occur even in patients being positive for t(11;18), however, follow-up will have to exclude later relapse. Radiation therapy is a stomach-conserving salvage therapy for all patients that do not achieve CR after antibiotic therapy. Patients being H. pylori-negative should primarily receive radiation therapy.
$1674
Molecular Cytogenetic Analysis of Formalin-Fixed, Paraffin-Embedded Malt/Malt Lymphoma Tissue by Comparative Genomic Hybridization After Universal DnaAmplification Hala M. E1-Zimaity, James W Luea, Hiroyoshi Ota, Massimo Ruggae, David Y. Graham, Maha M T. fil-Zimaity, Tsutomu Katsuyama Background: Mucosa-associated lymphoid tissue (MALT) lymphoma is a subset of nonHodgkin's lymphoma that arises from lymphoid aggregates in the lamina propria of the stomach primarily following H. pylori infection. The cytogenetic abnormalities of are only partially known. Karyotyping has been difficult in MALT lymphoma in part because conventional cytogenetic studies depend on the availability of fresh tissue that is rarely available in MALT lymphoma particularly early cases. The current system of diagnosis is only partially predictive o f outcome as diagnosis remains primarily based on morphologic criteria. Methods: We performed comparative genomic hybridization following universal DNA-amplification on formalin fixed paraffin embedded tissue of MALT/MALT lympboma. Results: We performed comparative genomic hybridization on 10 cases with low-grade MALT lympboma, 10 cases with high-grade primary gastric lymphoma, and 8 cases with reactive gastritis. CGH analysis was possible in all cases. A total of 9 DNA copy number changes were detected in low grade MALT lymphoma (median 2, range 0-9) as compared to 10 DNA copy number changes in high-grade pnmary gastric lymphoma (median 5, range 0-10) and 7 DNA copy number changes in chronic gastritis (median 2, range 0-7). In low grade MALT lymphoma, the most frequem gains involved Ypl and Yql (50% of cases), and 21pl and 21q2(30% of cases); the most frequent losses were X - - p 2 (30% of cases). In high-grade primary gastric lymphoma, the most frequent gains involved X--p2 (40% of cases), and 16ql (30% of cases); the most frequent losses were lp3 (30% of cases). In chronic gastritis, the most frequent gains involved 20pl (10% of cases), and 12ql (5 % of cases); the most frequent losses were 4q3 and 4q3 (5% of cases). Conclusion: Our data demonstrate the feasibility of this method to visualize complete and partial chromosome gains and losses and gene amplification in archived tumor samples. Findings suggest frequent gains/losses on chromosome X in both low grade and high grade MALT lympboma.
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Features of Intestinal Lymphoma m Capsule Endoscopy Dimitri Flieger, Rail Keller, Wolfgang Fischbach
Background: In contrast to gastric lymphomas detected by endoscopy, intestinal lymphomas are usually diagnosed by explorative laparotomy and small bowel resection. However, there is evidence that intestinal lymphoma can he successfully treated by combined radiochemotherapy Capsule endoscopy (CE) offers for the first time imaging of the entire small bowel. We here report our first experience with CE in gastrointestinal lymphoma patients focusing on morphological features revealed by this new technology. Methods: Commercially available capsule video endoscopes (Given M2A, Given Imaging Ltd.) were given to five patients with known or suspected gastrointestinal lymphoma. One patient was investigated twice within a 6 months interval. Results: Case 1:60 year old female with multifocal (duodenum, jejunum, ileum) manifestation of follicular lymphoma grade I histologically verified by endoscopic biopsies from the duodenum. CE showed multiple ulcerations throughout the small intestine. Case 2:53 )'ear old man with a diagnosis of follicular lymphoma grade I diagnosed from biopsies of the duodenum and terminal ileum, CE revealed a singular nodulus in the ileum. Case 3:59 year old male patient with a gastric marginalzone-B-cell lymphoma of MALTtype. Multiple noduli throughout the ileum and areas of focal atrophic mucosa were seen in CE, Case 4:63 year old man diagnosed to have histologically proven gastric marginalzoneB-cell lymphoma of MALT-type and follicular lymphoma of the duodenum and terminal ileum. While the MALT-lymphoma was successfully treated by H. pylori eradication therapy with complete remission for more than 5 years, follicular lymphoma was unchanged. CE detected disseminated noduli of up to 4 mm in the small intestine. Case 5: The 59 year old man underwent surgery with the diagnosis of intestinal low grade B-cell lymphoma, Postoperative CE revealed nodular and ulcerative loci as well as dyscolork mucosa and focal atrophy in the ileum These findings progressed in the second CE performed after 6 months compared to the initial findings Conclusions: Capsule endoscopy offers a new diagnostic tool in patients wltb gastrointestinal lymphoma. We focus our current activities on two possible indications: (1) Evaluation of the small bowel in patients with histologically proven gastric lymphoma. Considering locafisation and stage of lymphoma as major prognostic factors, CE would influence management of these patients. (2) Prospective assessment of CE for diagnosis o[ intestinal T-cen lymphoma in patients with refractory sprue
$1675
Yield of Repeat Wireless Video Capsule Endoscopy (CE) in Patients with Obscure GI Bleeding (OGIB) Bradford H. Jones, Virender K. Sharma, Jonathan A. Leighton, Russell I. Heigh, Ray F. Keate, David E. Fleischer Purpose: CE is a new technology that allows visualization of the entire small intestine. CE has been useful for patients with OGIB. It is not known if repeating CE improves diagnostic yield or changes patient management in patients with recurrent bleeding or in whom the initial CE was not definitive. The aims of the study are (1) to understand the reasons for repeat CE (2) to determine the diagnostic yield of repeat CE. Methods: CE was performed using a standard protocol that includes an eight hour fast prior to capsule ingestion and no routine bowel preparation. Between August, 2001 and December, 2002 we performed 229 capsule studies. Of these, ten patients have undergone repeat CE for obscure GI bleed. Each CE was read by a trained gastroenterologist who was not blinded to the results of the initial CE. We retrospectively reviewed the charts of these ten patients. Results: In all patients the indication for the initial CE was obscure GI bleeding. The reasons for repeat CE were: recurrent GI bleeding (5); limited v~sualization on first exam (3) (poor prep in two; active bleed in one); confirmation of ulcer healing (1); unsuccessful study (i) (capsule impaction at cricopharyngeus). 5/10 repeat CE showed additional findings (2 angioectasia, 1 ulcer resolution, 1 blood, 1 mass). Repeat CE findings led to changes in patient management in 3 cases. 5/10 repeat CE were nondiagnostic. In two of the patients who underwent a third CE for recurrent bleeding the studies were nondiagnostic. Conclusions: Indications for repeat CE vary widely but most commonly include recurrent GI bleeding and limited visualization on initial study, in half of the patients repeat CE found lesions not seen on the initial study Re'~eat CE should be considered when the initial study is nondiagnostic or incomplete
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Gastric MALT-Lymphoma: The Clinical and Endoscopic Spectrum of t(ll;18) Positive and Negative Cases Henk Boot, Berthe Aleman, Lucy Boerrigter, Jan Paul De Boer, Babs Taal, Daphne De Jong Introduction: Chronic H.pylori infection is the main cause of LG gastric MALT-lymphoma. Antibiotic treatment leads to histological remission in 70% of patients. Factors predictive of response: stage I, no increased number o f blasts, absence of translocation t( 11 ;18). T( 11 ;18) is the most frequent single chromosomal abnormality in LG (gastric) MALT lymphomas. There is no information of clinical presentation and endoscopy in t(11;18) positive vs t(11;18) negative cases. Aim of study and methods: Review of clinical, endoscopic and staging data in consecutive series of 58 patients with low-grade MALT lymphomas at the Netherlands Cancer Institute between 1994-2002. The diagnosis gastnc MALT-lymphoma was according to the WHO-classification. T(11;18) was determined with multiplex RT-PCR on fresh frozen or formalin-fixed samples Results: 58 patients with low-grade gastric MALT-NHL were seen. In 8 the t(11;18) status is not yet known, There were 30 males and 20 females, median age 59 yr (26-85yr), T(ll;18) was positive in 24 (males 60%, females 40%), negative in 26 patients. They presented with dyspepsia-50%, weight loss-20% without difference between t(11;18) pos. and neg. cases. Bleeding in 25% vs. 12% in pos. vs. neg. and perforation in 1 t(11;18) pos. case. Stage and endoscopic findings are described in the table. There were no significant differences between males and females or t(11; 18) pos. and neg. cases, t(11;18) St St St Hpyl Endosopy I II1 IV +vs.- Gastritis-Ulcer-Diffuse-Tumor Pos (n=24) 18 4 2 21-3 8 12 0 4 Neg (n=26) 21 2 3 25-1 9 15 1 1 Histological transformation occurred in 2 t(11;18) pos. patients during follow-up: 1 patient presented with a HG MALT lymphoma of the gastric stump, 12 years after a partial gastrectomy for gastric ulcer, in retrospect a low-grade MALT lymphoma. The other patient developed HG tonsillar lymphoma 15 months after H.pylori eradication Despite the loss of t(ll;18) in the tonsillar lymphoma, it was clonally related to the original gastric MALT-NHL. Conclusion: On clinical and endoscopic grounds no significant differences could be demonstrated between t(11;18) positive and negative gastric MALT-lymphomas, Staging revealed no significant differences between these patient groups The presence or absence of t(ll;18) could not be predicted on clinical, endoscopic or staging features The risk of histological transformation in gastric MALT lymphoma, including t(11;18) positive cases, is low at 4%.
AGA Abstracts
$1676
Videocapsule Endoscopy Renders Obscure Gastrointestinal Bleeding No Longer Obscure Alan Buchman, Anita Walfin Hemorrhage arising from endoscopically inaccessible areas of the gastrointestinal tract has long been an enigma in gastroenterology. The advent ot the Given M2A video capsule endoscope now permits direct visualization of small bowel mucosa The purpose of this study was to compare the diagnostic yield of the Given M2A video capsule endoscope to conventional push enteroscopy. 20 consecutively referred patients (9 M aged 54.8-+21.7 yrs; 11 F aged 65.6-+ 16.6 yrs who had previously 1.6 + 0.8 (range: 1-3)EGDs, and 1.6 -+0.8 (range:l-3) colonoscopies, Meckela scans (6), nudear bleeding scans (5), enterodysls (1), and abd/pelvic CT 1. Subjects had been hospitalized 1.4 -+ 1.3 (range 0-4) times previous to the study. 13 patients had blood transfusions (6.2 -+ 3.9 units) prior to tile study. Vldeocapsule endoscopy was successful in determining a bleeding source in 12/20 (60%) patients. Diagnoses included vascular ectasias (8), Crohns disease (2), bamartoma (1), NSAID ulcer (1). An incidental polyp was observed in one subject. 7 studies were normal, and 1 patient bad a poor prep. Vtdeocapsule endoscopy lead to successful surgical resection in 3 patients. The bleeding source was found at enteroscopy in 2/13 (15%) of subjects; both were vascular ectasias which were treated successfully with bipolar electrocautery. Using the McNemara Chi Square test for paired data, p=O.02 for the change in diagnosis from that obtained during the videocapsule endoscopy versus push enteroscopy. Videocapsule found a bleeding source in 9/13 subjects who had enteroscopy. Of the patients that refused enteroscopy 4 had normal videocapsule studies, 1 had vascular ectasias, 1 had an NSAID-related ulcer, and 1 had an incondustve study. Our clinical experience (through 11/25/02) has now included an additional 17 studies in 16 patients for obscure GI bleeding. These included
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Molecular Cytogenetic Analysis of Formalin-Fixed, Paraffin-Embedded Malt/Malt Lymphoma Tissue by Comparative Genomic Hybridization After Universal DnaAmplification Hala M. E1-Zimaity, James W Luea, Hiroyoshi Ota, Massimo Ruggae, David Y. Graham, Maha M T. fil-Zimaity, Tsutomu Katsuyama Background: Mucosa-associated lymphoid tissue (MALT) lymphoma is a subset of nonHodgkin's lymphoma that arises from lymphoid aggregates in the lamina propria of the stomach primarily following H. pylori infection. The cytogenetic abnormalities of are only partially known. Karyotyping has been difficult in MALT lymphoma in part because conventional cytogenetic studies depend on the availability of fresh tissue that is rarely available in MALT lymphoma particularly early cases. The current system of diagnosis is only partially predictive o f outcome as diagnosis remains primarily based on morphologic criteria. Methods: We performed comparative genomic hybridization following universal DNA-amplification on formalin fixed paraffin embedded tissue of MALT/MALT lympboma. Results: We performed comparative genomic hybridization on 10 cases with low-grade MALT lympboma, 10 cases with high-grade primary gastric lymphoma, and 8 cases with reactive gastritis. CGH analysis was possible in all cases. A total of 9 DNA copy number changes were detected in low grade MALT lymphoma (median 2, range 0-9) as compared to 10 DNA copy number changes in high-grade pnmary gastric lymphoma (median 5, range 0-10) and 7 DNA copy number changes in chronic gastritis (median 2, range 0-7). In low grade MALT lymphoma, the most frequem gains involved Ypl and Yql (50% of cases), and 21pl and 21q2(30% of cases); the most frequent losses were X - - p 2 (30% of cases). In high-grade primary gastric lymphoma, the most frequent gains involved X--p2 (40% of cases), and 16ql (30% of cases); the most frequent losses were lp3 (30% of cases). In chronic gastritis, the most frequent gains involved 20pl (10% of cases), and 12ql (5 % of cases); the most frequent losses were 4q3 and 4q3 (5% of cases). Conclusion: Our data demonstrate the feasibility of this method to visualize complete and partial chromosome gains and losses and gene amplification in archived tumor samples. Findings suggest frequent gains/losses on chromosome X in both low grade and high grade MALT lympboma.
S1672
Features of Intestinal Lymphoma m Capsule Endoscopy Dimitri Flieger, Rail Keller, Wolfgang Fischbach
Background: In contrast to gastric lymphomas detected by endoscopy, intestinal lymphomas are usually diagnosed by explorative laparotomy and small bowel resection. However, there is evidence that intestinal lymphoma can he successfully treated by combined radiochemotherapy Capsule endoscopy (CE) offers for the first time imaging of the entire small bowel. We here report our first experience with CE in gastrointestinal lymphoma patients focusing on morphological features revealed by this new technology. Methods: Commercially available capsule video endoscopes (Given M2A, Given Imaging Ltd.) were given to five patients with known or suspected gastrointestinal lymphoma. One patient was investigated twice within a 6 months interval. Results: Case 1:60 year old female with multifocal (duodenum, jejunum, ileum) manifestation of follicular lymphoma grade I histologically verified by endoscopic biopsies from the duodenum. CE showed multiple ulcerations throughout the small intestine. Case 2:53 )'ear old man with a diagnosis of follicular lymphoma grade I diagnosed from biopsies of the duodenum and terminal ileum, CE revealed a singular nodulus in the ileum. Case 3:59 year old male patient with a gastric marginalzone-B-cell lymphoma of MALTtype. Multiple noduli throughout the ileum and areas of focal atrophic mucosa were seen in CE, Case 4:63 year old man diagnosed to have histologically proven gastric marginalzoneB-cell lymphoma of MALT-type and follicular lymphoma of the duodenum and terminal ileum. While the MALT-lymphoma was successfully treated by H. pylori eradication therapy with complete remission for more than 5 years, follicular lymphoma was unchanged. CE detected disseminated noduli of up to 4 mm in the small intestine. Case 5: The 59 year old man underwent surgery with the diagnosis of intestinal low grade B-cell lymphoma, Postoperative CE revealed nodular and ulcerative loci as well as dyscolork mucosa and focal atrophy in the ileum These findings progressed in the second CE performed after 6 months compared to the initial findings Conclusions: Capsule endoscopy offers a new diagnostic tool in patients wltb gastrointestinal lymphoma. We focus our current activities on two possible indications: (1) Evaluation of the small bowel in patients with histologically proven gastric lymphoma. Considering locafisation and stage of lymphoma as major prognostic factors, CE would influence management of these patients. (2) Prospective assessment of CE for diagnosis o[ intestinal T-cen lymphoma in patients with refractory sprue
$1675
Yield of Repeat Wireless Video Capsule Endoscopy (CE) in Patients with Obscure GI Bleeding (OGIB) Bradford H. Jones, Virender K. Sharma, Jonathan A. Leighton, Russell I. Heigh, Ray F. Keate, David E. Fleischer Purpose: CE is a new technology that allows visualization of the entire small intestine. CE has been useful for patients with OGIB. It is not known if repeating CE improves diagnostic yield or changes patient management in patients with recurrent bleeding or in whom the initial CE was not definitive. The aims of the study are (1) to understand the reasons for repeat CE (2) to determine the diagnostic yield of repeat CE. Methods: CE was performed using a standard protocol that includes an eight hour fast prior to capsule ingestion and no routine bowel preparation. Between August, 2001 and December, 2002 we performed 229 capsule studies. Of these, ten patients have undergone repeat CE for obscure GI bleed. Each CE was read by a trained gastroenterologist who was not blinded to the results of the initial CE. We retrospectively reviewed the charts of these ten patients. Results: In all patients the indication for the initial CE was obscure GI bleeding. The reasons for repeat CE were: recurrent GI bleeding (5); limited v~sualization on first exam (3) (poor prep in two; active bleed in one); confirmation of ulcer healing (1); unsuccessful study (i) (capsule impaction at cricopharyngeus). 5/10 repeat CE showed additional findings (2 angioectasia, 1 ulcer resolution, 1 blood, 1 mass). Repeat CE findings led to changes in patient management in 3 cases. 5/10 repeat CE were nondiagnostic. In two of the patients who underwent a third CE for recurrent bleeding the studies were nondiagnostic. Conclusions: Indications for repeat CE vary widely but most commonly include recurrent GI bleeding and limited visualization on initial study, in half of the patients repeat CE found lesions not seen on the initial study Re'~eat CE should be considered when the initial study is nondiagnostic or incomplete
S1673
Gastric MALT-Lymphoma: The Clinical and Endoscopic Spectrum of t(ll;18) Positive and Negative Cases Henk Boot, Berthe Aleman, Lucy Boerrigter, Jan Paul De Boer, Babs Taal, Daphne De Jong Introduction: Chronic H.pylori infection is the main cause of LG gastric MALT-lymphoma. Antibiotic treatment leads to histological remission in 70% of patients. Factors predictive of response: stage I, no increased number o f blasts, absence of translocation t( 11 ;18). T( 11 ;18) is the most frequent single chromosomal abnormality in LG (gastric) MALT lymphomas. There is no information of clinical presentation and endoscopy in t(11;18) positive vs t(11;18) negative cases. Aim of study and methods: Review of clinical, endoscopic and staging data in consecutive series of 58 patients with low-grade MALT lymphomas at the Netherlands Cancer Institute between 1994-2002. The diagnosis gastnc MALT-lymphoma was according to the WHO-classification. T(11;18) was determined with multiplex RT-PCR on fresh frozen or formalin-fixed samples Results: 58 patients with low-grade gastric MALT-NHL were seen. In 8 the t(11;18) status is not yet known, There were 30 males and 20 females, median age 59 yr (26-85yr), T(ll;18) was positive in 24 (males 60%, females 40%), negative in 26 patients. They presented with dyspepsia-50%, weight loss-20% without difference between t(11;18) pos. and neg. cases. Bleeding in 25% vs. 12% in pos. vs. neg. and perforation in 1 t(11;18) pos. case. Stage and endoscopic findings are described in the table. There were no significant differences between males and females or t(11; 18) pos. and neg. cases, t(11;18) St St St Hpyl Endosopy I II1 IV +vs.- Gastritis-Ulcer-Diffuse-Tumor Pos (n=24) 18 4 2 21-3 8 12 0 4 Neg (n=26) 21 2 3 25-1 9 15 1 1 Histological transformation occurred in 2 t(11;18) pos. patients during follow-up: 1 patient presented with a HG MALT lymphoma of the gastric stump, 12 years after a partial gastrectomy for gastric ulcer, in retrospect a low-grade MALT lymphoma. The other patient developed HG tonsillar lymphoma 15 months after H.pylori eradication Despite the loss of t(ll;18) in the tonsillar lymphoma, it was clonally related to the original gastric MALT-NHL. Conclusion: On clinical and endoscopic grounds no significant differences could be demonstrated between t(11;18) positive and negative gastric MALT-lymphomas, Staging revealed no significant differences between these patient groups The presence or absence of t(ll;18) could not be predicted on clinical, endoscopic or staging features The risk of histological transformation in gastric MALT lymphoma, including t(11;18) positive cases, is low at 4%.
AGA Abstracts
$1676
Videocapsule Endoscopy Renders Obscure Gastrointestinal Bleeding No Longer Obscure Alan Buchman, Anita Walfin Hemorrhage arising from endoscopically inaccessible areas of the gastrointestinal tract has long been an enigma in gastroenterology. The advent ot the Given M2A video capsule endoscope now permits direct visualization of small bowel mucosa The purpose of this study was to compare the diagnostic yield of the Given M2A video capsule endoscope to conventional push enteroscopy. 20 consecutively referred patients (9 M aged 54.8-+21.7 yrs; 11 F aged 65.6-+ 16.6 yrs who had previously 1.6 + 0.8 (range: 1-3)EGDs, and 1.6 -+0.8 (range:l-3) colonoscopies, Meckela scans (6), nudear bleeding scans (5), enterodysls (1), and abd/pelvic CT 1. Subjects had been hospitalized 1.4 -+ 1.3 (range 0-4) times previous to the study. 13 patients had blood transfusions (6.2 -+ 3.9 units) prior to tile study. Vldeocapsule endoscopy was successful in determining a bleeding source in 12/20 (60%) patients. Diagnoses included vascular ectasias (8), Crohns disease (2), bamartoma (1), NSAID ulcer (1). An incidental polyp was observed in one subject. 7 studies were normal, and 1 patient bad a poor prep. Vtdeocapsule endoscopy lead to successful surgical resection in 3 patients. The bleeding source was found at enteroscopy in 2/13 (15%) of subjects; both were vascular ectasias which were treated successfully with bipolar electrocautery. Using the McNemara Chi Square test for paired data, p=O.02 for the change in diagnosis from that obtained during the videocapsule endoscopy versus push enteroscopy. Videocapsule found a bleeding source in 9/13 subjects who had enteroscopy. Of the patients that refused enteroscopy 4 had normal videocapsule studies, 1 had vascular ectasias, 1 had an NSAID-related ulcer, and 1 had an incondustve study. Our clinical experience (through 11/25/02) has now included an additional 17 studies in 16 patients for obscure GI bleeding. These included
A-244