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Gastrointestinal Lymphomas

Gastrointestinal Lymphomas. „Extranodal Lymphomas“. Definition: „....presenting with the main disease bulk at an extranodal site....“ Incidence: 24 – 48% of all lymphomas Considerable geographic variation. Extranodal Lymphomas: Incidence. USA: 24% Canada: 27% Hong Kong: 29%

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Gastrointestinal Lymphomas

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  1. Gastrointestinal Lymphomas

  2. „Extranodal Lymphomas“ Definition: „....presenting with the main disease bulk at an extranodal site....“ Incidence: • 24 – 48% of all lymphomas • Considerable geographic variation

  3. Extranodal Lymphomas: Incidence • USA: 24% • Canada: 27% • Hong Kong: 29% • Israel: 36% • Denmark: 37% • Holland: 41% • Lebanon: 44% • Italy: 48% Zucca et al, Ann Oncol 1997

  4. MALT:Mucosa Associated Lymphoid Tissue • GALT: Gut associated...... a priori: Peyer’s patches • BALT: Bronchus associated • Salivary glands, thyroid gland, skin

  5. Histological Classification • B-Cell: Mucosa associated lymphoid tissue Diffuse large B-cell lymphoma (+/- MALT-component) Mantle cell lymphoma (Lymphomatous polyposis) Burkitt‘s lymphoma Other types corresponding to nodal equivalents (follicular, lymphocytic) Immunodeficiency related lymphomas • T – Cell: Enteropathy type T-cell lymphoma Other types not associated with enteropathy

  6. Frequency of gastric lymphoma:Vienna Lymphoma Registry 1997 – 9/2002 • Initial diagnosis: MALT lymphoma: n = 100 Diffuse large B-cell lymphoma: n = 113 (18)

  7. Predominant sites of MALT-lymphoma • Stomach • GI-Tract • Lung • Salivary Glands • Ocular Adnexa • Skin

  8. Standardized staging: Ophthalmologic investigation Ear, nose and throat (incl Sono/MR) Endosonography + Gastroscopy (multiple biopsies) Enteroklysma (-CT) Colonoskopy CT-Thorax + Abdomen Bone marrow biopsy (?)

  9. Gastric Lymphoma • Resected patients:n = 1609 Perioperative deaths: n = 75 (4.7 %) • Unresected patients:n = 587 Major complications: n = 27 (4.6 %) Gobbi et al; Haematologica 2000

  10. Conservative management plus surgery vs conservative alone Koch et al, J Clin Oncol 2001

  11. Warren JR, Marshall B.Unidentified curved bacilli on gastric epithelium in active chronic gastritis.Lancet 1983; 1: 1273-5

  12. Factors associated with acquired MALT • Helicobacter pylori • Helicobacter Heilmanii • Chronic infection / inflammation • Borrelia Burgdorferi • Autoimmune conditions: Sjögren’s Syndrome Hashimoto’s Thyroiditis ........................................

  13. Time to Remission after HP-Eradication • Isaacson et al.: 4 weeks – 14 months • Sackmann et al.: 6 – 14 months • Neubauer et al.: 4 – 18 months • Montalban et al.: 2 – 7 months „The cases of late remission encourage us to wait for at least one year after eradication of H. pylori.“ A. Savio, Recent Results Cancer Res 2000

  14. Factors predicitive of response • Staging / Endosonographic assessment: Stage EI1 vs more advanced stages Probability of complete response stage EI1 (n=22): 6 mos 60% 12 mos 79% 14 mos 100% Sackmann et al, Gastroenteroloy 1997

  15. t(11;18) (q21;q21) • Characteristic translocation for MALT-lymphomas  found in up to 50% of gastric MALT-lymphomas • Not detected in other MZBL and extranodal DLBCL • Fusion of the apoptosis inhibitor gene API2 (11q21) and the novel MALT1 gene (18q21) • Fusion product inhibits apoptosis by caspase pathways

  16. t(11;18) translocation in gastric MALT-lymphoma • Number of patients: 111 • Response to eradication:48 • t(11;18) positive:2 / 48 responders 42 / 63 non-responders Liu et al, Gastroenterology 2002

  17. Helicobacter eradication: Facts ..... • HP is a major factor in the development of MALT-lymphoma. • Eradication leads to durable remissions in about 80% of selected patients. • t(11;18)+ patients seem to be unresponsive to HP eradication. • Relapse triggered by re-infection with HP remains sensitive to eradication. • A high percentage of patients (-50%) remain PCR-positive even in case of pathological complete remission.

  18. ................ and speculations • Role of HP-eradication following extragastric spread of the lymphoma? • Benefit of additional therapy following eradication? • Does underlying autoimmune disease impair response to HP-eradication? • Is persisting positive PCR an indicator for relapse? • Regression of DLCL following eradication?

  19. Non-surgical management of gastric lymphoma • Radiotherapy (stage I – II1): „Low grade“: – 100% CR 5-year-survival: > 90% „High grade“: 80% CR 5-year-survival: > 60% • Chemotherapy (stages II2 – IV): „Low grade“: - 75% CR 5-year-survival: > 80% „High grade“: - 80% CR 5-year-survival: 40 – 93%

  20. Treatment for gastric lymphoma: MALT-type • Stage I1: HP-eradication • Stage I2 – II2: HP eradication + radiation? HP-eradication + chemotherapy? • Stage III/IV:HP-eradication + chemotherapy • Chemotherapeutic options: Cyclophosphamide, Chlorambucil, 2 CdA, MCP Surgery as an emergency procedure (bleeding, perforation)

  21. Treatment for gastric lymphoma: Difuse large cell lymphoma • Stage I - IV: HP-eradication + chemotherapy • Stage I – II2: HP eradication + chemotherapy (+ radiation?) • Chemotherapeutic options: CHOP, R-CHOP, ......?

  22. “...for all gastric lymphomas, surgery probably belongs to the history of medicine...” E. Roggero et al. J Natl Cancer Inst 1997; 89:1328-30

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