gastric lymphoma: changing role of surgery joint hospital surgical grand round dr bonita hk mark...

Gastric lymphoma: Gastric lymphoma: changing role of surgerychanging role of surgery

Joint Hospital Surgical Grand RoundJoint Hospital Surgical Grand Round

Dr Bonita HK MarkDr Bonita HK MarkRHTSKRHTSK

Gastric lymphomaGastric lymphoma

WhatWhat is gastric lymphoma? is gastric lymphoma?

WhyWhy do we need to know about it? do we need to know about it?

WhatWhat is the evidence in is the evidence in literatureliterature? ?

HowHow to treat? to treat?

WhenWhen to operate /to operate / not not to operate? to operate?

Lymphoma Lymphoma

Hodgkin’s Non-Hodgkin’s Hodgkin’s Non-Hodgkin’s

Extranodal NodalExtranodal Nodal

MALTMALT Splenic Splenic

GI Tract OthersGI Tract Others

Working formulation (NCI 1982)Working formulation (NCI 1982)

Low grade Intermediate grade

High grade Miscellaneous

Small Small lymphocyticlymphocytic

Follicular Follicular large celllarge cell

Diffuse large Diffuse large cell cell

immunoblasticimmunoblastic

CompositeComposite

Follicular Follicular small cellsmall cell

Diffuse small Diffuse small cleaved cellcleaved cell

LymphoblasticLymphoblastic Mycosis Mycosis fungoidesfungoides

Follicular Follicular mixed small & mixed small &

largelarge

Diffuse mixed Diffuse mixed small & largesmall & large

Small cell Small cell (Burkitt’s or (Burkitt’s or

non-Burkitt’s)non-Burkitt’s)

OthersOthers

Diffuse large Diffuse large cellcell

Revised European-American Revised European-American Lymphoma (REAL) (WHO 1993)Lymphoma (REAL) (WHO 1993)B-cell lymphomaB-cell lymphoma– Lymphoblastic Lymphoblastic – Small lymphocytic Small lymphocytic – Lymphoplasmacytoid Lymphoplasmacytoid – Mantle-cell Mantle-cell – Follicular center Follicular center

(follicular, diffuse, (follicular, diffuse, small)small)

– Marginal-zone Marginal-zone (nodal, (nodal, extranodalextranodal, splenic), splenic)

– Diffuse large B-cellDiffuse large B-cell

Burkitt’s / Burkitt-likeBurkitt’s / Burkitt-likeT cell lymphomaT cell lymphoma– LymphoblasticLymphoblastic– Mycosis fungoides/ Mycosis fungoides/

sezary syndromesezary syndrome– Peripheral T-cellPeripheral T-cell

MALT lymphomaMALT lymphoma

MALT (mucosa associated lymphoid tissue) MALT (mucosa associated lymphoid tissue) lymphoma lymphoma First described in 1983First described in 1983Extra-nodal marginal zone B-cell lymphomaExtra-nodal marginal zone B-cell lymphomaIndolent (low grade)Indolent (low grade)Most common in GI tract (50%)Most common in GI tract (50%)Stomach mostly involved (50-70% of GI MALT)Stomach mostly involved (50-70% of GI MALT)4% primary gastric tumours4% primary gastric tumours40-50% primary gastric lymphomas40-50% primary gastric lymphomas

MALT lymphomaMALT lymphoma

MALT lymphoma – clinical featuresMALT lymphoma – clinical featuresBrooks et al Brooks et al

(n=56)(n=56)Rackner et al Rackner et al

(n=33)(n=33)Hockey et al Hockey et al

(n=153)(n=153)

PainPain 78%78% 67%67% 70%70%

Weight lossWeight loss 40%40% 39%39% 15%15%

NauseaNausea 14%14% 12%12%

VomitingVomiting 32%32% 14.4%14.4%

FatigueFatigue 4%4% 21%21% 3.3%3.3%

Night sweatNight sweat 2%2%

DysphagiaDysphagia 9%9% 4.6%4.6%

BleedingBleeding 20%20% 24%24% 8.5%8.5%

ObstructionObstruction 0%0%

AnorexiaAnorexia 10%10% 6.5%6.5%

PerforationPerforation 3%3%

MassMass 20%20% 0.7%0.7%

LymphadenopathyLymphadenopathy 12%12%

MALT lymphoma - diagnosisMALT lymphoma - diagnosis

Upper endoscopyUpper endoscopyBiopsy of suspicious areaBiopsy of suspicious area UlcerationUlceration Nodular massNodular mass Diffuse infiltrationDiffuse infiltration

Antral biopsy for H pyloriAntral biopsy for H pyloriEndoscopic ultrasoundEndoscopic ultrasound Depth of tumour invasionDepth of tumour invasion Perigastric LN enlargementPerigastric LN enlargement

CT chest, abdomen and pelvis/ PET scanCT chest, abdomen and pelvis/ PET scanBone marrow biopsyBone marrow biopsy

MALT lymphoma - endoscopyMALT lymphoma - endoscopy

MALT lymphoma – endoscopic USMALT lymphoma – endoscopic US

Superficial (submucosal) involvement

Serosal involvement

MALT lymphoma – endoscopic USMALT lymphoma – endoscopic US

Perigastric LN enlargement

MALT lymphoma - stagingMALT lymphoma - stagingMusshoff’s modification of Ann Arbor systemMusshoff’s modification of Ann Arbor system

StageStage DefinitionDefinition

IEIE Lymphoma limited to the stomachLymphoma limited to the stomach

IIEIIE₁₁ Involvement of stomach and contiguous LNInvolvement of stomach and contiguous LN

IIEIIE₂₂ Involvement of stomach and noncontiguous Involvement of stomach and noncontiguous subdiaphragmatic LNsubdiaphragmatic LN

IIIIII Involvement of stomach and LN on both Involvement of stomach and LN on both sides of diaphragmsides of diaphragm

IVIV HHaaematogenous spread (stomach and one or ematogenous spread (stomach and one or more extra-lymphatic organs or tissues)more extra-lymphatic organs or tissues)

H pylori eradication therapyH pylori eradication therapy

Low grade MALT lymphoma: stage I or II disLow grade MALT lymphoma: stage I or II disease with slow progressionease with slow progression

H pylori H pylori in 90% gastric MALT lymphomain 90% gastric MALT lymphoma

2/3 lymphoma regresses after eradication2/3 lymphoma regresses after eradication

Prognosis good: 10-year survival 80-90%Prognosis good: 10-year survival 80-90%

H pylori eradication therapyH pylori eradication therapy

Annals of Surgery, Vol 240(1), July 2004, p28-37

Predictive factors for poor response Predictive factors for poor response to H pylori eradication therapyto H pylori eradication therapy

Perigastric LN involvement (stage Perigastric LN involvement (stage IIII₁)₁)– 0% with stage II vs. 79% with stage I 0% with stage II vs. 79% with stage I (Multicentre French study, Gut 2001; 48:297-303)(Multicentre French study, Gut 2001; 48:297-303)– 33% LN +ve vs. 76% LN –ve 33% LN +ve vs. 76% LN –ve (Am J Gastroenterology 2002; 97:292-297(Am J Gastroenterology 2002; 97:292-297))

A t (11:18) chromosomal translocation A t (11:18) chromosomal translocation – review of 111 patients by Liu et al: 73% vs. 4% review of 111 patients by Liu et al: 73% vs. 4%

(Gastroenterology 2002; 122: 1286-1294)(Gastroenterology 2002; 122: 1286-1294)

H pylori -veH pylori -ve

What is the best Rx modality?What is the best Rx modality?

Implications to surgeonsImplications to surgeons

Low grade vs high gradeLow grade vs high grade

Early vs advanced diseaseEarly vs advanced disease

Surgery for gastric lymphomaSurgery for gastric lymphoma

Brands et al reviewed Brands et al reviewed 100 papers100 papers analyzing analyzing 31573157 patients with all stages of gastric lymphoma patients with all stages of gastric lymphoma

Treated from Treated from 1974 to 19951974 to 1995

The overall survival during that time period The overall survival during that time period ↑↑from from 37% to 87%. 37% to 87%.

Rev Esp Enferm Dig 2006; 98:180-188

Review articleReview article

Ann Surg 2004; 240:28-37

Chemotherapy/RT without surgeryChemotherapy/RT without surgery

Aviles et al in 1991Aviles et al in 1991– 52 patients with stage I or II gastric lymphoma52 patients with stage I or II gastric lymphoma– Prospectively randomized Prospectively randomized – Chemo vs. surgery + chemoChemo vs. surgery + chemo– Relapse-free survival and overall survival were equivalentRelapse-free survival and overall survival were equivalent– Five-year overall survival 75% in both groupsFive-year overall survival 75% in both groups

Milan series by Ferreri et al in 1999Milan series by Ferreri et al in 1999– 83 patients with stage I or II high-grade gastric lymphoma83 patients with stage I or II high-grade gastric lymphoma– Reviewed retrospectivelyReviewed retrospectively– Chemo/ chemo + RT vs. surgery +/- adjuvantChemo/ chemo + RT vs. surgery +/- adjuvant– No difference in survival No difference in survival – 5-year survival of 82%, 10-year survival of 64% (non-surgical) 5-year survival of 82%, 10-year survival of 64% (non-surgical)


German Multicenter Study Group by Koch et German Multicenter Study Group by Koch et al in 2001al in 2001– Prospective nonrandomized study Prospective nonrandomized study – 185 patients with stage185 patients with stage I or II I or II– 1992 1992 --19961996– Surgery (gastrectomy Surgery (gastrectomy + + RT or RT or + + chemochemo +RT) :106+RT) :106– Non-surgery (RT or chemo +RT): 79 Non-surgery (RT or chemo +RT): 79 – No significant difference in survival (overall 5-year No significant difference in survival (overall 5-year

survival rate: 82% vs. 84%) survival rate: 82% vs. 84%)


Aviles et alAviles et al– No perforation No perforation – Bleeding: 3 (non-surgical) vs. 2 (surgical)Bleeding: 3 (non-surgical) vs. 2 (surgical)

German Multicenter Study Group by Koch et al German Multicenter Study Group by Koch et al – Perforation: 1 (non-surgical) vs. none (surgical)Perforation: 1 (non-surgical) vs. none (surgical)– No bleedingNo bleeding


German Multicenter Study Group by Koch et alGerman Multicenter Study Group by Koch et al– 6 recurred after surgical Rx: 3 systemically, 3 loco-regionally6 recurred after surgical Rx: 3 systemically, 3 loco-regionally– 7 recurred after non-surgical Rx: all locally7 recurred after non-surgical Rx: all locally

Ferreri et al Ferreri et al – 17/62 recurred after surgical Rx: 2 locally and 15 systemically17/62 recurred after surgical Rx: 2 locally and 15 systemically– 4/19 complete responders recurred: 2 locally and 2 systemically 4/19 complete responders recurred: 2 locally and 2 systemically

Recurrence patterns may differ:Recurrence patterns may differ:– Surgical: tend to recur systemicallySurgical: tend to recur systemically– Non-surgical: more local recurrenceNon-surgical: more local recurrence

Retrospective reviewRetrospective review

J Formos Med Assoc 2006; 105(3): 194-202


Objective:Objective:– To evaluate the outcome of PGL (except MALT To evaluate the outcome of PGL (except MALT

lymphoma) treated with chemo alone or surgery lymphoma) treated with chemo alone or surgery followed by chemofollowed by chemo

Methods:Methods:– 1986-20031986-2003– 55 PGL patients (MALT lymphoma excluded)55 PGL patients (MALT lymphoma excluded)– Localized 32 (IE 15 + IIE 17) Localized 32 (IE 15 + IIE 17) – Advanced 23Advanced 23– Chemo alone vs. Combination (surgery + chemo)Chemo alone vs. Combination (surgery + chemo)


Results:Results:– Complete remission no sig. difference:Complete remission no sig. difference:

Chemo: 84.2% Chemo: 84.2% Combination: 92.3%Combination: 92.3%

– 5-year overall survival no sig. difference:5-year overall survival no sig. difference:Chemo: 73.4%Chemo: 73.4%Combination: 87.5%Combination: 87.5%

– 5-year disease-free survival no sig. difference:5-year disease-free survival no sig. difference:Chemo: 68.4%Chemo: 68.4%Combination: 84.6%Combination: 84.6%


– Post-chemo life-threatening haemorrhage:Post-chemo life-threatening haemorrhage:5/32 (15.6%) in localized group (stage IE/IIE1)5/32 (15.6%) in localized group (stage IE/IIE1)4 chemo + 1 combination4 chemo + 1 combination9/23 in advanced group9/23 in advanced group6 chemo + 3 combination6 chemo + 3 combination5 of them developed perforation and died5 of them developed perforation and died

– Grade 3-4 neutropenia:Grade 3-4 neutropenia:Chemo: 13.2Chemo: 13.2Combination: 17.6%Combination: 17.6%

– Thrombocytopenia:Thrombocytopenia:Chemo: 2.6%Chemo: 2.6%Combination: 5.9%Combination: 5.9%

Retrospective review - conclusionRetrospective review - conclusion

Clinical outcome of localized PGL treated by Clinical outcome of localized PGL treated by chemo alonechemo alone is is comparable comparable to that treated by to that treated by combination therapycombination therapy

In terms of : In terms of : tumour response, disease-free tumour response, disease-free survival and overall survivalsurvival and overall survival

Bulky tumours: tumour bleeding/perforationBulky tumours: tumour bleeding/perforation

Debulking Debulking surgerysurgery followed by chemo can offer followed by chemo can offer better tumour control / better tumour control / ↓complication↓complication

Gastric lymphoma RxGastric lymphoma Rx

MALT lymphomaMALT lymphoma– H pylori eradication therapyH pylori eradication therapy

High-grade (non-MALT)High-grade (non-MALT)– Chemo +/-RTChemo +/-RT– Surgery Surgery

FFor bulky tumouror bulky tumour to prevent bleeding/perforationto prevent bleeding/perforation

For local residual disease post chemo/RTFor local residual disease post chemo/RT

For palliation of symptoms like obstructionFor palliation of symptoms like obstruction

Some additional informationSome additional information

For discussionFor discussion

Gastric lymphoma gradingGastric lymphoma grading

International prognostic indexInternational prognostic index

1)1) Age: <60 years vsAge: <60 years vs.. >60 years >60 years

2)2) Serum LDH: normal vsSerum LDH: normal vs.. elevated elevated

3)3) Performance status:Performance status: 0 or 1 vs0 or 1 vs.. 2-4 2-4

4)4) Stage: stage I Stage: stage I / / II vsII vs.. stage III stage III / / IV IV

5)5) Extranodal site involvement: 0 or 1 vsExtranodal site involvement: 0 or 1 vs.. 2-4 2-4

Performance statusPerformance statusGradeGrade DescriptionDescription

00 Fully active, able to carry on all pre-disease performance Fully active, able to carry on all pre-disease performance without restriction without restriction

11 Restricted in physically strenuous activity but ambulatory Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, and able to carry out work of a light or sedentary nature,

e.g., light house work, office work e.g., light house work, office work

22 Ambulatory and capable of all selfAmbulatory and capable of all self--care but unable to carry care but unable to carry out any work activities. Up and about more than 50% of wout any work activities. Up and about more than 50% of w

aking hours aking hours

33 Capable of only limited selfCapable of only limited self--care, confined to bed or chair care, confined to bed or chair more than 50% of waking hours more than 50% of waking hours

44 Completely disabled. Cannot carry on any self-care. Completely disabled. Cannot carry on any self-care.

Totally confined to bed or chairTotally confined to bed or chair 55 Dead Dead

Time interval for responseTime interval for response

4 weeks to 12 months4 weeks to 12 months

Subgroup with high success Subgroup with high success rate (confined to gastric rate (confined to gastric wall, no translocation, no wall, no translocation, no LN): await for 12 monthsLN): await for 12 months

Subgroup with low success Subgroup with low success rate: consider other therapy rate: consider other therapy earlier e.g. 3-6 monthsearlier e.g. 3-6 months

Retrospective studyRetrospective study


Objective: Objective: – To assess whether surgical excision is still a vTo assess whether surgical excision is still a v

alid therapeutic optionalid therapeutic optionPatients and method: Patients and method: – A retrospective studyA retrospective study– 1974 - 19991974 - 1999– 69 consecutive patients stage IE-IIE 69 consecutive patients stage IE-IIE – 65 65 (94.2%) (94.2%) gastrectomygastrectomy– Mean age: 62.6 years (28-85)Mean age: 62.6 years (28-85)


5-year survival probability (SP): 87.93%5-year survival probability (SP): 87.93%

Rev Esp Enferm Dig 2006; 98(3): 180-188Rev Esp Enferm Dig 2006; 98(3): 180-188


Statistical analysis:Statistical analysis:– Ann Arbor stage: Ann Arbor stage:

– Gastric wall invasion, Gastric wall invasion, H. pylori ,H. pylori , margin: margin:

– Histological type: borderline significance Histological type: borderline significance

(p = 0.056)(p = 0.056)


Rev Esp Enferm Dig 2006; 98(3): 180-188

Retrospective study - conclusionRetrospective study - conclusion

Good long-term survival (> 87% after 5 years)Good long-term survival (> 87% after 5 years)

No prognostic value in surgical margin No prognostic value in surgical margin involvement. involvement.

Radical excision (R0), according to the criteria Radical excision (R0), according to the criteria used in carcinomas, was not associated with a used in carcinomas, was not associated with a significantly longer survival than excisions significantly longer survival than excisions leaving microscopic residual tumor (R1). leaving microscopic residual tumor (R1).

gastric lymphoma: changing role of surgery joint hospital surgical grand round dr bonita hk mark...

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