3. INTRODUCTION
Gastric cancer is the second leading worldwide cause of cancer death
and the fourth most common cancer .
The high mortality rate - advanced disease at presentation and
relatively aggressive biology.
Early lesions - asymptomatic and infrequently detected
Prognosis has improved, attributable to advances in surgical treatment,
postoperative care, and multimodality therapy.
4. In all cases surgery is the standard of care for all resectable tumours:
radical gastrectomy with regional lymphadenectomy
(Surgical treatment of gastric cancer: 15-year follow-up results of the randomised
nationwide Dutch D1D2 trial.Songun I et al Lancet Oncol. 2010 May; 11(5):439-49)
Nodal involvement - most important prognostic factor.
Hence the importance to lymphadenectomy and its extension.
6. TIMELINE OF EARLY TRENDS
1950s
Failure of limited surgery to control disease loco-regionally by Gordon
McNeer.
>20% cancer recurrence in the non-resected perigastric nodes or the
gastric bed
1960s
the Japanese Society suggested removal of the appropriate number of
tiers would increase the chance of negative “lymphadenectomy
margins”
7. INTRODUCTION
The lymph node stations - precisely defined by the Japanese Gastric
Cancer Association (JGCA),
formerly known as the Japanese Research Society for Gastric Cancer
Aim of Japanese classification a common language for the clinico-
pathological description of gastric cancer.
Previously the JGCA divided these stations into four levels (N1 through
N4)
8.
9. DEFINITIONS OF DIFFERENT LEVELS OF LYMPH NODE
DISSECTION
For total gastrectomy
1. D1 lymphadenectomy are stations from No.1 to 7;
2. D1+ includes D1 stations plus stations No.8a, 9, and 11p, and
3. D2 includes D1 stations plus stations No.8a, 9, 10, 11p, 11d, and 12a.
For tumors invading the esophagus,
1. D1+ includes N0. 110 and
2. D2 includes Nos. 19,20,110 and 111.
10. For distal gastrectomy,
1. D1 lymphadenectomy includes stations No.1, 3, 4sb, 4d, 5, 6 and 7;
2. D1+ includes D1 stations plus stations No.8a, and 9, and
3. D2 includes D1 stations plus stations No.8a, 9, 11p, and 12a.
11. D1 Gastrectomy
Early forms not suitable for endoscopic treatment -> a D1 or D1 plus
lymphadenectomy in cases with clinically negative nodes.
(Japanese gastric cancer treatment guidelines 2010 (ver. 3) 2011 Jun; 14(2):113-23)
D1 lymphadenectomy along with
1. proximal gastrectomy and
2. pylorus preserving gastrectomy
only recommended for T1N0 disease.
When lymph nodes are clinically positive, a D2 dissection
1. removal of stations 12a and 11p in subtotal gastrectomy, and
2. stations 12a, 11d and 10 in total gastrectomy
12. D2 Gastrectomy
Systematic (D2) Lymphadenectomy
Resection of the perigastric lymph nodes and those along the feeding
vessels (N2) with the gastrectomy specimen.
will vary according to the position of the primary tumour
13. D2 Gastrectomy
Indication
Curative Treatment for Resectable cancer of stomach
(Results are best in patients with stage II and IIIa disease)
Contraindication
Stage IV disease
14. D2 Lymphadenectomy –
An ACCEPTED STANDARD procedure
for gastric cancer
Why ?
CURRENT EVIDENCE
15. Rationale for D2 resections
LN metastasis – a significant prognostic factor
Occult metastasis in N2 nodes of JRSGC in EGC(2-17%)
Decreased incidence of recurrence in gastric bed & perigastric
lymphatics
Appropriate staging & standardisation of results
Absence of a truly effective adjuvant therapy
16. Japanese and Korean experience
5yr survival rates by Pathologic stage
Stage 1st period
1963-66
2ndperiod
1969-73
3rdperiod
1974-78
4th period
1979-90
I 94.4% 96.4% 96.6% 100%
II 56.1% 71.8% 72% 81.2%
III 30.1% 43.8% 44.8% 61%
IV 9.3% 13.1% 7.7% 14%
• D2 - accepted in Far East as the standard treatment for both
(EGC) and (AGC) for many decades.(mostly based on observational
and retrospective studies)
17. 5yr survival rates by LN dissection
Stage 1st period
1963-66
2ndperiod
1969-73
3rdperiod
1974-78
4th period
1979-90
D0 26% 20.5% 18.4% 32.5%
D1 42.4% 46% 49.8% 62.1%
D2/D3 48.1% 61.6% 64.2% 76.9%
Japanese experience
18. Western experience
Surgeons from the West have conventionally preferred the D1 approach
because of
(a) lower incidence of gastric cancer and therefore scant opportunities
(b) lack of training in performing D2 resection compared with their
Japanese counterpart
(c) technical demands with unproven benefits based on a number of RCTs
(d) fear of increased risk of complications and even deaths
19. Initial Western experience
Results of prospective randomized trials
Name Study
period
No of pts Post op
morbid
Post
opMort
5yr
survival
South
Africa
(Dent et al)
1982-
1986
D1 D2 D1 D2 D1 D2 D1 D2
22 21 15 30 0 0 0.69 0.67
Dutch
Gastric
cancer trial
1983-
1993
380 331 25 43 4 10 42 47
MRC
trial,UK
1986-
1993
200 200 28 46 6.5 13 35 33
•MRC, Dutch and Italian RCTs - conducted to show a survival benefit of
D2 over D1.
•Both the MRC and the Dutch trials failed to show a survival benefit
20. Only 15 years after the conclusion of accrual, Dutch trial reported
significant decrease of recurrence after D2 procedure.
Italian RCT could demonstrate a benefit for patients treated with D2
gastrectomy without splenopancreatectomy.
It has been suggested in several national guidelines including NCCN as
the recommended procedure for patients with AGC.
22. South African Trial
Dent et al in South Africa randomized 43patients.
Major findings were that blood transfusion requirements, operating
time and hospital stay were longer with extended lymphadenectomy.
At a median follow-up of 3.1 years no benefit regarding survival was
seen.
23. Hong Kong Trial
Robetson et al randomized 55 patients in Hong Kong
Operating time, transfusion requirements and hospital stay, all
increased with extended lymphadenectomy.
Contrary to the expectations overall survival was significantly worse
and this was attributed to the impact of increased blood transfusion.
24. UK MRC Trial
In hospital mortality was high in both groups compared to high volume
Asian centers, and significantly higher in the D2 versus D1 arm (13 vs.
6.5%)
No significant difference in overall survival at 5 years (D1 35%; D2
33%; P = 0.43).
Cons
The authors found - additional mortality in the D2 group could be
attributed to the performance of distal pancreatectomy and
splenectomy
25. Dutch Trial
Patients in the D2 group had
1. significantly higher rates of complications (43 vs. 25%; P < 0.001)
2. post-operative death (10 vs. 4% P = 0.004).
Overall survival at 5 years was not statistically different (45% for D1;
47% for D2).
26. 15 year-follow up of the Dutch study
[Surgical treatment of gastric cancer: 15-year follow-up results of the randomised
nationwide Dutch D1D2 trial. Songun et al Lancet Oncol. 2010 May; 11(5):439-49]
1. Loco-regional recurrence rate is significantly lower in patients
treated with D2 lymphadenectomy vs D1.
2. Survival benefit with the enlarged dissection.
27. Studies recently demonstrated that even in Europe trained surgeons
could safely perform D2 with spleen and pancreas preservation and
More favourable recurrence pattern and cancer-related survival,
D2 seemed to be the recommended treatment for patients
with resectable gastric cancer .
[Extended lymph node dissection without routine spleno-pancreatectomy for treatment
of gastric cancer: low morbidity and mortality rates in a single center series of 250
patients.Biffi R et al J Surg Oncol. 2006 Apr 1; 93(5):394-400]
28. Limitations
-- outcome of multivariate analysis was not reported
-- protocol deviations
1. noncompliance (ie, performance of less dissection than specified)
2. contamination (ie, performance of more extensive dissection than
specified)
29. Italian Trial
Italian Research Group for Gastric Cancer (GIRCG) database
1. Proximal tumors and diffuse-mixed type show a relative increase
2. Endoscopic resections, are much less adopted in the West.
3. The GIRCG guidelines advice a D2 lymphadenectomy in clinically
early forms not suitable for endoscopic treatment
(The SIC-GIRCG 2013 Consensus Conference on Gastric Cancer.De Manzoni G et al
Updates Surg. 2014 Mar; 66(1):1-6.)
30. D2 dissection - limited risk of complications and mortality in the West, when
performed in specialized centers and avoiding spleno-pancreatectomy
[RCT comparing survival after D1 or D2 gastrectomy for gastric cancer.Degiuli M et al
Italian Gastric Cancer Study Group. Br J Surg. 2014 Jan; 101(2):23-31].
Only in selected cases more limited procedures (D1 plus) are adviced by
the GIRCG group.
1. high-risk patients (age > 70 yrs)
2. early forms with favourable pathological characteristics.
31. Limitations
1. Poor accrual
2. Closed after 8 years with a low statistical power as only 267 patients
were randomized.
32. Taiwanese Trial
Wu et al , 211 patients
Extended lymphadenectomy increased operating times, blood loss,
transfusion and hospital stay.
Morbidity was increased mostly due to abdominal sepsis but mortality
did not differ.
Extended lymphadenectomy led to significantly higher 5-year Overall
Survival but no difference in the Recurrence Rates was seen in the cases
with R0 resection.
36. Role of Splenectomy and Pancreatectomy
The overall consensus is that routine splenectomy and distal
pancreatectomy during D2 dissection has no long-term survival benefit
and may even be counter productive.
However it may be performed for selected patients with
1. T3 tumors or
2. direct invasion or
3. metastasis at the splenopancreatic hilum.
Meta-Analysis of D1 Versus D2 Gastrectomy for Gastric Adenocarcinoma. Annals of
surgery · March 2011 DOI: 10.1097
37. Concept of Stage Migration
For stages I–III, stage for stage overall survival is 14–30% lower for
SEER database patients.
At MSKCC (80% of patients receive a D2 ), stage for stage overall
survival is intermediate between SEER database patients and
NCC/SNUH patients
Reason
1. Routine D2 lymphadenectomy, greater number of nodes are
examined.
2. Shifted nearly a third of patients from N1 to N2 disease.
38. Conclusion
EGC --- D1 /D1+ surgery is only to patients not fitted for less invasive
treatment.
AGC --- debate on the extent of nodal dissection open for many decades.
While D2 gastrectomy - standard procedure in eastern countries, mostly based
on observational and retrospective studies,
Japanese D2 with pancreas preservation – a safe radical treatment for gastric
cancer in selected western patients treated in experienced centers.
West meets the East
39. D2 is an accepted minimal standard procedure
D2 lymphadenectomy with spleen and pancreas preservation can be
performed safely with excellent survival outcomes.
Significant improvement in overall survival is observed with D2
lymphadenectomy, without increased surgical morbidity and mortality.
Minimally invasive surgery for gastric cancer including D2 Gastrectomy
is the way of the future.
