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Gastric lymphoma: changing role of surgery

Gastric lymphoma: changing role of surgery. Joint Hospital Surgical Grand Round Dr Bonita HK Mark RHTSK. Gastric lymphoma. What is gastric lymphoma? Why do we need to know about it? What is the evidence in literature ? How to treat? When to operate / not to operate?. Lymphoma

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Gastric lymphoma: changing role of surgery

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  1. Gastric lymphoma: changing role of surgery Joint Hospital Surgical Grand Round Dr Bonita HK Mark RHTSK

  2. Gastric lymphoma • What is gastric lymphoma? • Why do we need to know about it? • What is the evidence in literature? • How to treat? • Whento operate / not to operate?

  3. Lymphoma Hodgkin’s Non-Hodgkin’s Extranodal Nodal MALT Splenic GI Tract Others

  4. Working formulation (NCI 1982)

  5. B-cell lymphoma Lymphoblastic Small lymphocytic Lymphoplasmacytoid Mantle-cell Follicular center (follicular, diffuse, small) Marginal-zone (nodal, extranodal, splenic) Diffuse large B-cell Burkitt’s / Burkitt-like T cell lymphoma Lymphoblastic Mycosis fungoides/ sezary syndrome Peripheral T-cell Revised European-American Lymphoma (REAL) (WHO 1993)

  6. MALT lymphoma • MALT (mucosa associated lymphoid tissue) lymphoma • First described in 1983 • Extra-nodal marginal zone B-cell lymphoma • Indolent (low grade) • Most common in GI tract (50%) • Stomach mostly involved (50-70% of GI MALT) • 4% primary gastric tumours • 40-50% primary gastric lymphomas

  7. MALT lymphoma

  8. MALT lymphoma – clinical features

  9. MALT lymphoma - diagnosis • Upper endoscopy • Biopsy of suspicious area • Ulceration • Nodular mass • Diffuse infiltration • Antral biopsy for H pylori • Endoscopic ultrasound • Depth of tumour invasion • Perigastric LN enlargement • CT chest, abdomen and pelvis/ PET scan • Bone marrow biopsy

  10. MALT lymphoma - endoscopy

  11. MALT lymphoma - endoscopy

  12. MALT lymphoma – endoscopic US Serosal involvement Superficial (submucosal) involvement

  13. MALT lymphoma – endoscopic US Perigastric LN enlargement

  14. Musshoff’s modification of Ann Arbor system MALT lymphoma - staging

  15. H pylori eradication therapy • Low grade MALT lymphoma: stage I or II disease with slow progression • H pylori in 90% gastric MALT lymphoma • 2/3 lymphoma regresses after eradication • Prognosis good: 10-year survival 80-90%

  16. H pylori eradication therapy Annals of Surgery, Vol 240(1), July 2004, p28-37

  17. Predictive factors for poor response to H pylori eradication therapy • Perigastric LN involvement (stage II₁) • 0% with stage II vs. 79% with stage I (Multicentre French study, Gut 2001; 48:297-303) • 33% LN +ve vs. 76% LN –ve (Am J Gastroenterology 2002; 97:292-297) • A t (11:18) chromosomal translocation • review of 111 patients by Liu et al: 73% vs. 4% (Gastroenterology 2002; 122: 1286-1294) • H pylori -ve

  18. What is the best Rx modality?

  19. Implications to surgeons

  20. Low grade vs high grade

  21. Early vs advanced disease

  22. Literature review

  23. Surgery for gastric lymphoma • Brands et al reviewed 100 papers analyzing 3157 patients with all stages of gastric lymphoma • Treated from 1974 to 1995 • The overall survival during that time period ↑from 37% to 87%.

  24. Rev Esp Enferm Dig 2006; 98:180-188

  25. Review article Ann Surg 2004; 240:28-37

  26. Survival rate? Perforation? Haemorrhage? Recurrence?

  27. Chemotherapy/RT without surgery • Aviles et al in 1991 • 52 patients with stage I or II gastriclymphoma • Prospectivelyrandomized • Chemo vs. surgery + chemo • Relapse-free survival and overall survival were equivalent • Five-year overall survival75% in both groups • Milan series by Ferreri et al in 1999 • 83patients with stage I or II high-grade gastric lymphoma • Reviewed retrospectively • Chemo/ chemo + RT vs. surgery +/- adjuvant • No difference in survival • 5-year survival of 82%, 10-year survival of 64% (non-surgical)

  28. Chemotherapy/RT without surgery • GermanMulticenter Study Group by Koch et al in 2001 • Prospectivenonrandomized study • 185 patients with stage I or II • 1992 -1996 • Surgery (gastrectomy + RT or + chemo+RT) :106 • Non-surgery (RT or chemo +RT): 79 • No significant difference in survival (overall 5-year survival rate: 82% vs. 84%)

  29. Chemotherapy/RT without surgery • Aviles et al • Noperforation • Bleeding: 3 (non-surgical) vs. 2 (surgical) • GermanMulticenter Study Group by Koch et al • Perforation: 1 (non-surgical) vs. none (surgical) • No bleeding

  30. Chemotherapy/RT without surgery • GermanMulticenter Study Group by Koch et al • 6 recurred after surgical Rx: 3 systemically, 3 loco-regionally • 7 recurred after non-surgical Rx: all locally • Ferreri et al • 17/62 recurred after surgical Rx: 2 locally and 15 systemically • 4/19 complete responders recurred: 2 locally and 2systemically • Recurrence patterns may differ: • Surgical: tend to recursystemically • Non-surgical: more localrecurrence

  31. Retrospective review J Formos Med Assoc 2006; 105(3): 194-202

  32. Retrospective review • Objective: • To evaluate the outcome of PGL (except MALT lymphoma) treated with chemo alone or surgery followed by chemo • Methods: • 1986-2003 • 55 PGL patients (MALT lymphoma excluded) • Localized 32 (IE 15 + IIE 17) • Advanced 23 • Chemo alone vs. Combination (surgery + chemo)

  33. Retrospective review • Results: • Complete remission no sig. difference: • Chemo: 84.2% • Combination: 92.3% • 5-year overall survival no sig. difference: • Chemo: 73.4% • Combination: 87.5% • 5-year disease-free survival no sig. difference: • Chemo: 68.4% • Combination: 84.6%

  34. Retrospective review • Post-chemo life-threatening haemorrhage: • 5/32 (15.6%) in localized group (stage IE/IIE1) • 4 chemo + 1 combination • 9/23 in advanced group • 6 chemo + 3 combination • 5 of them developed perforation and died • Grade 3-4 neutropenia: • Chemo: 13.2 • Combination: 17.6% • Thrombocytopenia: • Chemo: 2.6% • Combination: 5.9%

  35. Retrospective review - conclusion • Clinical outcome of localized PGL treated by chemo alone is comparable to that treated by combination therapy • In terms of : tumour response, disease-free survival and overall survival • Bulky tumours: tumour bleeding/perforation • Debulking surgery followed by chemo can offer better tumour control / ↓complication

  36. In summary

  37. Gastric lymphoma Rx • MALT lymphoma • H pylori eradication therapy • High-grade (non-MALT) • Chemo +/-RT • Surgery • For bulky tumourto prevent bleeding/perforation • For local residual disease post chemo/RT • For palliation of symptoms like obstruction

  38. THANK YOU!

  39. Some additional information For discussion

  40. Gastric lymphoma grading

  41. International prognostic index • Age: <60 years vs. >60 years • Serum LDH: normal vs. elevated • Performance status:0 or 1 vs. 2-4 • Stage: stage I / II vs. stage III / IV • Extranodal site involvement: 0 or 1 vs. 2-4

  42. Performance status

  43. Time interval for response • 4 weeks to 12 months • Subgroup with high success rate (confined to gastric wall, no translocation, no LN): await for 12 months • Subgroup with low success rate: consider other therapy earlier e.g. 3-6 months

  44. Retrospective study

  45. Retrospective study • Objective: • To assess whether surgical excision is still a valid therapeutic option • Patients and method: • A retrospective study • 1974 - 1999 • 69 consecutive patients stage IE-IIE • 65 (94.2%) gastrectomy • Mean age: 62.6 years (28-85)

  46. Retrospective study 5-year survivalprobability (SP): 87.93% Rev Esp Enferm Dig 2006; 98(3): 180-188

  47. Retrospective study • Statisticalanalysis: • Ann Arbor stage: • Gastric wall invasion, H. pylori , margin: • Histological type: borderline significance (p = 0.056)

  48. Retrospective study Rev Esp Enferm Dig 2006; 98(3): 180-188

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