Dr. CC ChanKwong Wah Hospital

Role of Surgeon in Management of Gastric

Lymphoma

Introduction Primary gastric lymphoma

◦ Uncommon disease◦ 5% of all gastric malignancy◦ 10% of all malignant lymphoma

Stomach is by far the most common site of extra-nodal non-Hodgkin lymphoma (NHL)◦ Accounting for 60% of cases

Revised European-American Lymphoma (REAL) (WHO 1993)• B-cell lymphoma– Diffuse Large B-cell– Marginal-zone

(Extranodal, Nodal, splenic)

– Lymphoblastic – Small lymphocytic – Lymphoplasmacytoi

d – Mantle-cell – Follicular center

(follicular, diffuse, small)

• T cell lymphoma– Lymphoblastic–Mycosis

fungoides/ sezary syndrome

– Peripheral T-cell• Burkitt’s /

Burkitt-like

Two histological subtypes accounted for over 90% of cases:◦ Diffuse large B-cell (DLBC) Lymphoma◦ Marginal zone B-cell lymphoma

Low-grade (Indolent NHL)◦ Derived from Mucosa Associated lymphoid tissue

(MALT)◦ Remained localized for extended period of time

High-grade (Aggressive NHL)◦ One third contained low-grade component

Progress from low grade lesion◦ Includes diffuse large B cell lymphoma (DLBCL)◦ Disseminate more rapidly

Presenting symptoms are non-specific◦ Abdominal pain (80%)◦ Weight loss (40%)◦ Gastrointestinal bleeding (36%)◦ Vomiting (32%)

Delay in diagnosis◦ Median time from onset of symptoms to diagnosis

is about 3 months

Historically, laparotomy and biopsy is required for diagnosis and accurate staging of the disease

Upper endoscopy ◦ Three main patterns: ulcerative, diffuse infiltrative,

polypoid mass◦ Multiple biopsies from macroscopic lesions ◦ Antrum biopsy

Assess for H. pylori infection◦ Achieved 90% efficacy in diagnosing gastric

lymphoma

Gastroenterology Research • 2009;2(5):253-258

Musshoffs modification of Ann Arbor system

Stage Definition

IE Lymphoma limited to the stomach

IIE₁ Involvement of stomach and contiguous LN

IIE₂ Involvement of stomach and non-contiguous sub-diaphragmatic LN

III Involvement of stomach and LN on both sides of diaphragm

IV Hematogenous spread (stomach and one or more extra-lymphatic organs or

tissues)

Endoscopic ultrasound◦ Determine depth of tumor invasion◦ Detect any enlarged peri-gastric lymph nodes◦ Sensitivity

T staging: 80–92% N staging: 77–90%

Ann Oncol 1993;4(10):839-846., Endoscopy 1993;25(8):531-533

Look for distant spread of disease◦ Bone marrow biopsy◦ CT scan of thorax, abdomen and pelvis◦ Positron emission tomography (PET) scan

Diagnostic value only for DLBCLs but controversial for MALT lymphomas

Low-grade MALT lymphoma◦ Presented as stage I or II disease with slow

progression◦ Helicobacter pylori identified in 90% of cases

Systematic review in 2010 of 32 studies including 1408 patients◦ Remission rate after HP eradication up to 77.5%

Prognosis◦ 10-year survival 80-90%

Gastroenterol Hepatol 2010;8:105e10.

Complete remission◦ Within 6 to12 months from eradication

Follow-up (EGILS consensus report 2011)◦ First endoscopy 3-6 months after triple therapy

Check for H pylori status◦ Subsequent follow-up endoscopy every 4-6

months until complete remission

Stage III & IV disease◦ Primary treatment with chemotherapy and

monoclonal antibody (R-CHOP)

Surgery indicated in:◦ Patient with localized residual disease in stomach

alone after chemoRT◦ To Palliate symptoms of bleeding and obstruction

that do not resolve with non-operative therapies

Ann Surg 2004;240: 28–37

Optimal Treatment for Early Stage High Grade Gastric Lymphoma

Radicality of Gastrectomy

Management of Complications◦ Bleeding & Perforation during Chemotherapy◦ Obstruction

Journal of Cancer Therapy, 2013, 4, 145-152

Brands et al reviewed 100 papers analyzing over 3000 patients of gastric lymphoma treated from 1974 to 1995

For early stage disease◦ 80% of studies recommended treatment with

surgery

Eur J Surg. 1997;163:803–813

Results of combined modality (Surgery + chemotherapy) and chemotherapy compared◦ No significant difference in survival rate in both groups

5 year survival rate ranged from 75% to 84%

Aviles et al in 1991German Multicenter Study Group by Koch et al in 2001

Aveiles et al in Ann Surg 2004 Prospective Randomized Control Study 589 patients of Stage I & II Diffuse Large B cell

Lymphoma Four groups:

◦ Surgery alone◦ Surgery + Radiotherapy ◦ Surgery + Chemotherapy ◦ Chemotherapy (CHOP: Cyclophamide, vincristine,

doxorubicin, prednisolone)

Ann Surg 2004;240:44–50.

Overall Survival Rate at 10 years◦ Surgery alone: 52% [46% to 64%]◦ Surgery + Radiotherapy: 53% [45% to 65%]◦ Surgery + Chemotherapy: 91% [85% to 99%] ◦ Chemotherapy: 96% [90% to 100%]

No difference observed between chemotherapy alone & Surgery + Chemotherapy

Surgical resection before chemotherapy◦ Not affect complete response rate, survival rate and

disease free survival

Ann Surg 2004;240:44–50.

American Journal of Medicine, Vol. 90, No. 1, 1991, pp. 77-84.

Annals of Oncology, Vol. 14, No. 12, 2003, pp. 1751-1757.

Risk of Gastrectomy◦ Mortality: 5%◦ Complication Rate: 30%

Better Quality of Life in patient with gastric preservation◦ Dumping syndrome◦ Nutrition malabsorption

Chemotherapy recommended as first line treatment for early stage high grade gastric lymphoma

Better outcome in radical resection compared with incomplete resection or biopsy alone

More recent studies◦ Positive margin has no impact on outcome◦ ? Related to lower tumor burden which allow

complete resection

Role of Chemotherapy

Rev Esp Enferm Dig 2006; 98(3): 180-188Gastroenterology Research 2009;2(5):253-258

J Surg Oncol 1997;64(3):237-241, J Clin Oncol 2001;19(18):3874-3883.

Risk of perforation◦ Low: 1.7% without surgery

Risk of bleeding◦ 2.1% (without surgery) vs 2.2% (with surgery)◦ Not significant different

Obstruction◦ High dose steroid◦ Non-responder: Surgical resection

Ann Surg 2004;240: 28–37

Management of primary gastric lymphoma should involve a multidisciplinary approach

Treatment for primary gastric lymphoma◦ For low-grade MALToma: HP eradication therapy ◦ Chemotherapy for early stage high grade lymphoma

and advanced disease Controversy still exists in the radicality of surgery Risk of bleeding and perforation during chemotherapy

is extremely low Surgeons still play a role in diagnosing and accurate

staging of gastric lymphoma as well as management of complication

Thank you