Joint Hospital Surgical Grand Round

25 July 2009Dr. David KW Leung

Tseung Kwan O Hospital

Outline

Introduction Lymphadenectomy

PrincipleDefinition and extentLiterature review

Conclusion

Introduction

One of the most common cancers in the world

Highest incidences in Eastern Asia (Japan and Korea) (70 per 100,000), Southern & Central America, Eastern Europe (40 per 100,000)

Incidence of Gastric Cancer in HK

HK Cancer Registry

Treatment - SurgeryAdequate surgical resection offers best

chance of cure or long term survival

PrinciplesResection with adequate tumor-free margin

(~5cm) Subtotal/ total gastrectomy

Regional lymph node clearance corresponding to the location of the primary tumor

Safe and well-functioning anastomosis

Lymphadenectomy - principles

Lymph node metastasis is the commonest mode of spread

Gastric cancer with regional LN involvement considered as localized disease in the absence of haematogenous spread

Adequate lymphadenectomy can be curative

Lymphadenectomy –Definition and extentThe Japanese introduced the concept of tiers

of regional lymphadenectomy

Regional LNs groups into 3 tiersN1: perigastric nodes closest to the primary

lesionN2: distant perigastric nodes and the nodes

along the main arteries supplying the stomachN3: Nodes outside the normal lymphatic

pathways of the stomachJapanese Classification of Gastric Carcinoma – 2nd English Ed. Japanese Gastric Cancer Association

Japanese Classification of Gastric Carcinoma – 2nd English Ed. Japanese Gastric Cancer Association

Lymphadenectomy - Nomenclature

D1: Limited lymphadenectomyAll N1 nodes removed en bloc with the

stomachD2: Systematic lymphadenectomy

All N1 and N2 nodes are removed en bloc with the stomach

D3: Extended lymphadenectomyAll three tiers nodes are removed en bloc

Lymphadenectomy - JapanThe conventional treatment is D2 systematic

lymphadenectomy in JapanSuggests a lower recurrence rate and increased

survival ratesBased on retrospective reports

It forms the basis of two large multicentre randomized controlled trials in Europe in 1990s

Noguchi et al. Radical Surgery for gastric cancer: A review of the Japanese Experience. Cancer 1989;64:2053-62.Maruyama et al. Progress in Gastric Cancer Surgery in Japan and its Limits of Radicality. World J Surg 1987;6:215-25.

MRC/ Dutch trialMRC trial Medical Research Council (MRC) Gastric Cancer

Surgical Trial (ST01)Cuschieri et al. Postoperative morbidity and mortality after

D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. Lancet 1996;347:995-99.

Cuschieri et al. Patient survival after D1 and D2 resections for gastric cancer: long term results of the MRC randomised surgical trial. Br J Cancer 1999;79:1522-30

Dutch trialBonenkamp et al. Randomised comparison of morbidity

after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet 1995;345:745-48.

Bonenkamp et al. Extended lymph-node dissection for gastric cancer. NEJM 1999;340:908-14.

MRC/ Dutch trialMulticenter randomized controlled trials400 (MRC) and 711 (Dutch) patients were

studied

Comparing D1 and D2 lymphadenectomyDutch trial

Definition according to Japanese Research Society for the Study of Gastric Cancer (JRSGC)

D1: removal of perigastric nodes D2: additional removal of LN in N2 tier

MRC/ Dutch trialMRC trial

D1: removal of LN within 3.0cm of the tumor (N1 in old TNM staging)

D2: additional removal of omental bursa, hepatoduodenal and retroduodenal LN, splenic artery/ splenic hilar and retropancreatic LN

For proximal tumor, resection of spleen and distal pancreas were done for clearance of N2 lymph nodes

Morbidity and mortality

Bonenkamp et al. Randomised comparison of morbidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients. Lancet 1995;345:745-48.

Cuschieri et al. Postoperative morbidity and mortality after D1 and D2 resections for gastric cancer: preliminary results of the MRC randomised controlled surgical trial. Lancet 1996;347:995-99.

5-year survival

Cuschieri et al. Patient survival after D1 and D2 resections for gastric cancer: long term results of the MRC randomised surgical trial. Br J Cancer 1999;79:1522-30

Bonenkamp et al. Extended lymph-node dissection for gastric cancer. NEJM 1999;340:908-14.

D1: 35%D2: 33%

D1: 45%D2: 47%

MRC/ Dutch trials - critics

Inadequate pre-trial training

Failure to deliver the intended treatmentContamination and non-compliance

Associated morbidity and mortality in pancreatico-splenectomy

McCulloch et al. Extended versus limited lymph node dissection technique for adenocarcinoma of the stomach (review). Cochrane Database of Systematic Reviews 2003, Issue 4.

Cuschieri et al. Patient survival after D1 and D2 resections for gastric cancer: long term results of the MRC randomised surgical trial. Br J Cancer 1999;79:1522-30

“the possibility that D2 resection without pancreatico- splenectomy may be better than standard D1 resection cannot be dismissed”

Newer evidenceD2 total gastrectomy without splenectomy

Csendes et al. A prospective randomized study comparing D2 total gastrectomy versus D2 total gastrectomy plus splenectomy in 187 patients with gastric carcinoma. Surgery 2002;131:401-7.

Yu et al. Randomized clinical trials of splenectomy versus splenic preservation in patients with proximal gastric cancer. Br J Surg 2006;93:559-563.

D1 gastrectomy vs. D2 gastrectomy without pancreatico-splenectomy Degiuli et al. Morbidity and mortality after D1 and D2

gastrectomy for cancer: Interim analysis of the Italian Gastric cancer Study Group (IGCSG) randomised surgical trial. Eur J Surg Onco 2004;30:303-8.

D2 total gastrectomy without splenectomy

Randomised controlled trialsTotal 187 (Csendes et al.) and 207 (Yu et al.)

patients are included

Csendes et al. A prospective randomized study comparing D2 total gastrectomy versus D2 total gastrectomy plus splenectomy in 187 patients with gastric carcinoma. Surgery 2002;131:401-7.

Yu et al. Randomized clinical trials of splenectomy versus splenic preservation in patients with proximal gastric cancer. Br J Surg 2006;93:559-563.

D2 total gastrectomy without splenectomyCompare D2 total gastrectomy with or without

splenectomy in proximal gastric cancers

In spleen preservation group, the lymph nodes along the splenic artery (station 11) and at the hilum of spleen (station 10) are dissected without sacrificing the spleen and splenic vessels

In splenectomy group, distal pancreas are not resected

Mortality

With splenectomy

Without splenectomy

P values

Csendes et al. 2002

4/90 (4.4%) 3/97 (3.1%) > 0.7

Yu et al. 2006 2/104 (1.9%) 1/103 (1%) 1.000

Morbidity

Yu et al. Br J Surg 2006;93:559-563.

Csendes et al. Surgery 2002;131:401-7.TG: total gastrectomyTGS: total gastrectomy with spelenectomy

5-year survival

With splenectomy

Without splenectomy

P values

Csendes et al. 2002

42% 36% > 0.5

Yu et al. 2006 59/104 (56.7%)

52/103 (50.4%)

0.503

D1 vs. D2 gastrectomy without pancreatico-splenectomy – IGCSG trialProspective randomised trialComparing D1 with D2 gastrectomy

according to the JRSGC rulesD2: during total gastrectomy

Pancreas was removed only when it is suspected to be involved by the tumor

Splenectomy was performed with pancreas preservation technique when required (T>1 on the greater curvature of the proximal/ middle thirds of stomach)

Degiuli et al. Morbidity and mortality after D1 and D2 gastrectomy for cancer: Interim analysis of the Italian Gastric cancer Study Group (IGCSG) randomised surgical trial. Eur J Surg Onco 2004;30:303-8.

D1 vs. D2 gastrectomy without pancreatico-splenectomy – IGCSG trialQuality control

Restricted to 5 centers at which more than 25 D2 dissections had been performed during earlier studies

A minimum number of 25 retrieved nodes were required

162 patients (76 in D1) and (86 in D2) are included

Splenectomy performed in 16 patientsDistal pancreatectomy was done in 4 patients

Results

Long term results (5-year survival) is pending

P<0.29

ConclusionEvidence from RCT that D1 and D2 resection

confers no difference in survival

Distal pancreatectomy and splenectomy is associated with higher morbidity and mortality but offers no survival benefit

D2 gastrectomy should be performed by surgeons with experience of this type of radical surgery