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Lymphadenectomy for Gastric Adenocarcinoma: Should West

Meet East?SAM S. YOON,a HAN-KWANG YANGb

aDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts,

USA; bDepartment of Surgery, Seoul National University Hospital, Seoul University College of Medicine,

Seoul, South Korea

Key Words. Gastric cancer Surgery Lymphadenectomy Outcomes Review

Disclosures: Sam S. Yoon: None; Han-Kwang Yang: None.Section editors Richard M. Goldberg, Patrick G. Johnston, and Peter J. ODwyer have disclosed no financial

relationships relevant to the content of this article.The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free

from commercial bias.

LEARNING OBJECTIVES

After completing this course, the reader will be able to:

1. Calculate the lymph node drainage patterns of gastric adenocarcinoma based on the location of the tumor.

2. Differentiate and explain the extent of lymphadenectomies performed in different countries.

3. Analyze the risks and benefits of performing more extensive lymphadenectomies for gastric adenocarcinoma.

This article is available for continuing medical education credit at CME.TheOncologist.com.CMECME

ABSTRACT

The extent of lymphadenectomy that should be performed

for gastric adenocarcinoma has been a topic of persistent

debate. In countries such as Japan and Korea, where the

incidence of gastric adenocarcinoma is high, more exten-

sive (e.g., D2) lymphadenectomies are routinely per-

formed, usually by experienced surgeons with low

morbidity and mortality. In western countries such as the

U.S., where the incidenceof gastric adenocarcinoma is ten-fold lower, the performance of more extensive lymphade-

nectomies is generally limited to specialized centers, and

quite possibly the majority of patients are treated at non-

referral centers with less than a D1 lymphadenectomy.

There is little disagreement among gastric cancer experts

that the minimum lymphadenectomy that should be per-

formed for gastric adenocarcinoma shouldbe at least a D1

lymphadenectomy. Two large, prospective randomized

trials performed in the United Kingdom and the Nether-

lands failed to demonstrate a survival benefit of D2 over

D1 lymphadenectomy, but these trials have been criticized

for high surgical morbidity and mortality rates in the D2

group. More recent studies have demonstrated that west-

ern surgeons can be trained to perform D2 lymphadenec-

tomies on western patients with low morbidity andmortality. Retrospective analyses and one prospective,

randomized trial suggest that there may be some benefits

to more extensive lymphadenectomies when performed

safely, but this assertion requires further validation. This

article provides an update on the current literature re-

garding the extent of lymphadenectomy for gastric adeno-

carcinoma. The Oncologist 2009;14:871882

Correspondence: Sam S. Yoon, M.D., Division of Surgical Oncology, Department of Surgery, Massachusetts General Hospital, Yawkey7B-7926, 55 Fruit Street, Boston, MA 02114, USA. Telephone: 617-726-4241; Fax: 617-724-895; e-mail: [email protected] Received April 6, 2009; accepted for publication August 6, 2009; first published online in The Oncologist Express onSeptember 8, 2009. AlphaMed Press 1083-7159/2009/$30.00/0 doi: 10.1634/theoncologist.2009-0070

TheOncologistThe Oncologist CME Program is located online at http://cme.theoncologist.com/.

To take the CME activity related to this article, you must be a registered user.

GastrointestinalCancer

The Oncologist 2009;14:871 882 www.TheOncologist.com

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INTRODUCTION

Gastric cancer is one of the leading worldwide causes of

cancer death, with about 803,000 deaths each year [1]. The

incidence of gastric adenocarcinoma varies tremendouslythroughout the world, with the highest incidence occurring

in South Korea at 66.572.5 per 100,000 males and 19.5

30.4 per 100,000 females [2]. The incidence of gastric can-

cer in the U.S. is only one tenth that of South Korea. The

estimated number of new gastric cancer cases in the U.S. in

2008 was 21,500, and the estimated number of deaths was

10,880 [3].

Gastric adenocarcinoma frequently metastasizes to re-

gional lymph nodes. For T1 lesions invading the submu-

cosa, lymph node involvement is found in about 19% of

patients [4]. For T2 lesions (invading the muscularis pro-pria or submucosa), the lymph node metastasis rate in-

creases to 50%. There is also significant evidence that

some patients with lymph node metastases beyond the im-

mediate perigastric lymph nodes can be cured with surgical

resection alone [5]. Whether this group of patients repre-

sents a significant percentage of patients with resectable

gastric cancer is a matter of debate, and thus the optimal ex-

tent of lymphadenectomy for adenocarcinoma of the stom-

ach continues to be controversial.

There are significant differences in the extent of lymph-

adenectomy performed by surgeons in different countries.To broadly generalize, surgeons in Japan and Korea rou-

tinely perform more extensive lymphadenectomies (D2

lymphadenectomy or greater) whereas most surgeons in the

U.S. and many other western countries perform more lim-

ited lymphadenectomies (D1 lymphadenectomy or less).

Two large, prospective randomized trials performed in The

Netherlands and the United Kingdom found no survival

benefit for D2 over D1 lymphadenectomy [6, 7]. However,

there were significant problems with these studies, includ-

ing a high morbidity and mortality rate in the D2 group,

which was associated with inadequate surgical training, and

with the frequent performance of a distal pancreatectomy

and splenectomy in the D2 group, which is now considered

unnecessary [8, 9].

Several studies since these randomized trials have sug-

gested that more extensive lymphadenectomies may be

beneficial in certain patients with gastric adenocarcinoma.

These studies have demonstrated that: (a) D2 lymphadenec-

tomies can be performed in specialized western centers

without distal pancreatectomy or splenectomy and with low

morbidity and mortality [1, 10, 11], (b) there may be a sur-

vival benefit for D2 lymphadenectomy if performed with

low morbidity and mortality [12], and (c) there may be a

survival benefit if lymph node stations that are predicted to

have metastatic disease preoperatively are removed [13,

14].

This article examines important historical trials andcontemporary studies regarding lymphadenectomy for gas-

tric adenocarcinoma. Regional differences in the extent of

lymphadenectomy are reviewed. Hypothetical advantages

of more extensive lymphadenectomies are discussed fol-

lowed by an analysis of the available studies supporting or

disclaiming these potential advantages. Barriers to the per-

formance of more extended lymphadenectomies in western

countries are also examined, followed by a discussion of

how these barriers may be overcome.

NODAL STATION ANDLYMPHADENECTOMY DEFINITIONS

Prior to a discussion of lymph node dissections for gastric

adenocarcinoma, one must define the terms to be used. The

lymph node stations surrounding the stomach have been

precisely defined by the Japanese Research Society for

Gastric Cancer (JRSGC) [15] (Fig. 1, Table 1). The JRSGC

defines four levels of lymph node stations, N1N4. The

designation of N1N4 nodes varies according to the site of

the primary tumor (i.e., upper, middle, or lower third of the

stomach). The D level of lymphadenectomy (formerly

known as the R level of lymphadenectomy) is based on theJRSGC definitions of lymph node station level [16]. A D1

lymphadenectomy is defined as removal of all N1 level

nodes, and a D2 dissection is defined as removal of all N1

and N2 level nodes. Table 2 shows the lymph node stations

that should be removed for a D1 and D2 lymphadenectomy

(based on the location of the primary tumor) as recom-

mended by the Japanese Gastric Cancer Association.

REGIONAL DIFFERENCES IN LYMPHADENECTOMY

FOR GASTRIC ADENOCARCINOMA

As noted earlier, South Korea has the highest incidence of

gastric adenocarcinoma in the world. Despite the high inci-

dence of gastric adenocarcinoma in Korea, patients are of-

ten referred to tertiary care centers for treatment. Two thirds

of all gastric cancer surgeries in South Korea are performed

at 16 high-volume institutions, which perform at least 200

gastric cancer surgeries per year. Thus, gastric cancer sur-

geons at high-volume institutions in Korea gain tremendous

experience in the surgical management of gastric cancer.

The minimum lymphadenectomy performed by Korean

surgeons for gastric adenocarcinoma is generally a D2

lymphadenectomy. Despite performing extensive lymph-

adenectomies, the morbidity and mortality rates are quite

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low. For example, Seoul National University Hospital,

which performs almost 1,000 gastric cancer operations per

year, recently reported a morbidity rate of 18% and mortal-

ity rate of 0.5% [17]. Japanese patients with gastric cancer

are also frequently treated at high-volume institutions with

low complication rates. In a prospective, randomized trial

from 24 Japanese institutions of D2 versus extended para-

aortic lymphadenectomy, the morbidity rate was 20.9%

28.1%, and the mortality rate was 0.8% [18].

Unlike in Korea and Japan, the majority of gastric can-

cer surgeries in the U.S. are performed at nonreferral cen-

ters, and thus a high-volume institution in the U.S. has

been reported in some studies to be centers with only 1520

or more cases per year [19, 20]. Birkmeyer et al. [19] re-

viewed a database of Medicare patients and found that hos-

pitals that performed 20 gastrectomies per year had

significantly lower mortality rates, yet 80% of patients

were operated on at centers that performed 20 gastrecto-

mies per year. Given that most U.S. general surgeons see

few gastric cancer patients, these surgeons likely err on the

side of more limited lymphadenectomies in order to avoid

excess morbidity and mortality. The American College of

Surgeons performed a survey study in 1993 of18,000 pa-

tients treated at 700 institutions [21]. Of the 77% of pa-

tients that underwent gastric resection, perigastric lymph

nodes were resected in 50% of patients. The overall sur-

vival rate in resected patients at 5 years was 19%, and the

first site of recurrence was local or regional in 41% of pa-

tients that recurred. In the Intergroup 0116 trial, in which

patients were randomized after gastric cancer surgery to no

further therapy or chemoradiation, 50% of patients en-

rolled received less than a D1 lymphadenectomy [22, 23].

Most gastric cancer experts in both the east and west would

agree that a D1 lymphadenectomy is the minimum lymph-

Figure 1. Locations of lymph node stations. Adapted from Japanese Gastric Cancer Association. Japanese classification of gas-tric carcinoma2nd English editionresponse assessment of chemotherapy and radiotherapy for gastric carcinoma: Clinicalcriteria. Gastric Cancer 2001;4:18, with permission.

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adenectomy that should be performed for gastric adenocar-

cinoma beyond an early T1 lesion [24].

Despite the performance of less extensive lymphade-

nectomies in the U.S., surgical morbidity and mortality

rates for gastric adenocarcinoma are generally much higher

in the U.S. than in South Korea and Japan. A recent analysis

of the Nationwide Inpatient Sample from 19982003 of

50,000 patents with gastric cancer found that the overallmortality rate following gastric surgery was 6% [25]. Sin-

gle-institution series have reported morbidity rates follow-

ing gastrectomy of up to 40% [26]. Certain factors in

Japanese and Korean patients, such as less advanced gastric

cancer and fewer comorbidities such as cardiovascular dis-

ease and obesity, allow for lower morbidity and mortality

rates, but almost certainly the surgical expertise and better

perioperative care that comes with a higher volume play a

significant role. Thus, in order for western surgeons to con-

sider performing more extended lymphadenectomies with

low morbidity and mortality, volume at referral centersneeds to be increased and some additional surgical training

is likely needed. The learning curve for training general sur-

geons for D2 lymphadenectomy has been estimated to be at

least 23 cases [27]. Following adequate training, D2 lymph-

adenectomies can be performed by western surgeons on

western patients with low morbidity and mortality rates

similar to high-volume centers in the east [10, 11].

POTENTIAL BENEFITS OF MORE

EXTENSIVE LYMPHADENECTOMIES

Lymphadenectomy for cancer can serve three primary pur-

poses: staging of disease, prevention of locoregional recur-

Table 1. Regional lymph nodes of the stomach

Number Description

1 Right paracardial

2 Left paracardial

3 Lesser curvature

4 Greater curvature

sa Along short gastric vessels

sb Along left gastroepiploic vessels

d Along right gastroepiploic vessels

5 Suprapyloric

6 Infrapyloric

7 Along left gastric artery

8 Along common hepatic artery

a Anterosuperior group

p Posterior group

9 Around celiac artery

10 Splenic hilum

11 Along splenic artery

p Along proximal splenic artery

d Along distal splenic artery

12 Hepatoduodenal ligament

a Along hepatic artery

b Along bile duct

p Along portal vein

13 Posterior surface of pancreatic head

14 Along superior mesenteric vesselsv Along superior mesenteric vein

a Along superior mesenteric artery

15 Along middle colic vessels

16

a1 Aortic hiatus

a2 Abdominal aorta (from upper margin of celiactrunk to lower margin left renal vein)

b1 Abdominal aorta (from lower margin leftrenal vein to upper margin inferior mesentericartery)

b2 Abdominal aorta (from upper margin inferior

mesenteric artery to aortic bifurcation)17 On anterior surface of pancreatic head

18 Along inferior margin of pancreas

19 Infradiaphragmatic

20 In esophageal hiatus of diaphragm

110 Paraesophageal in lower thorax

111 Supradiaphragmatic

112 Posterior mediastinal

Table 2. Extent of lymphadenectomy

Location D1 dissection D2 dissection

LMU 16 7, 8a, 9, 10, 11p, 11d,12a, 14v

LD/L 3, 4d, 5, 6 1, 7, 8a, 9, 11p, 12a,14v

LM, M, ML 1, 3, 4sb, 4d, 5, 6 7, 8a, 9, 11p, 12a

MU, UM 16 7, 8a, 9, 10, 11p, 11d,12a

U 1, 2, 3, 4sa, 4sb 4d, 7, 8a, 9, 10, 11p,11d

When the tumor involves only one of the three portions ofthe stomach, this is expressed by U, M, or L.If the lesions involves more than one of the three portionsof the stomach, this is expressed by listing the primarilyinvolved portion first followed by the less involvedportion(s).

Abbreviations: D, duodenum; L, lower; M, middle; U,upper.Adapted from Japanese Gastric Cancer Association.Japanese classification of gastric carcinoma2nd Englisheditionresponse assessment of chemotherapy andradiotherapy for gastric carcinoma: Clinical criteria.Gastric Cancer 2001;4:1 8.




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rence, and improvement in overall survival. There is little

doubt that more extensive lymphadenectomies for gastric

adenocarcinoma lead to better staging of disease. The 2002

Sixth Edition of the American Joint Committee on Cancer

Staging Manual for gastric adenocarcinoma recommends

that at least 15 lymph nodes be examined for correct assess-

ment of the N category [28]. An analysis of6,000 gastric

cancer patients treated at 691 U.S. hospitals found that

40% of patients undergoing surgical resection had the

requisite 15 lymph nodes examined [29]. Using the Surveil-

lance, Epidemiology, and End Results database, Coburn et

al. [30] found that only 29% of 10,807 resected gastric can-

cer patients had 15 lymph nodes examined. In a study

from the United Kingdom analyzing 18 hospitals, only 31%

of the 699 surgical resections resulted in15 lymph nodes

analyzed [31]. Thus, many western patients are understaged

following surgical resection of their gastric cancers becauseof inadequate lymph node sampling.

Significant variability in the extent of lymphadenec-

tomy and number of lymph nodes examined pathologically

leads to difficulty in comparing the outcomes of patients

from different regions based on stage of disease as well as

stage migration. It is difficult to be confident that a tumor is

truly node negative when 10 lymph nodes are examined

[32, 33], and N1 tumors can be upstaged to N2 or even N3

tumors as more lymph nodes are harvested [33, 34]. Fur-

thermore, it is impossible to be categorized as N3 if15

lymph nodes are harvested. Several studies have demon-strated that examination of even more than 15 lymph nodes

improves the ability to predict prognosis in patients with

gastric adenocarcinoma [33, 35]. Shen et al. [35] found that

increasing the total lymph nodes examined to 30 im-

proved the accuracy of staging for patients with T3 disease.

Several authors have found that the ratio of involved lymph

nodes to resected lymph nodes may be a better predictor of

prognosis than the absolute number of positive lymph

nodes. In one study of 9,058 patients who underwent resec-

tion for gastric cancer, the ratio of involved lymph nodes to

resected lymph nodes was a more precise predictor of prog-

nosis than the absolute number of positive lymph nodes

[36]. Similar findings were reported by the German Gastric

Cancer Study [37] and the Italian Research Group for Gas-

tric Cancer [38]. Thus, there is little debate that more exten-

sive lymphadenectomies improve staging for patients with

gastric adenocarcinoma.

One must also recognize that, even if a surgeon per-

forms an extensive lymphadenectomy, the pathologist is

usually the one who finds and examines the dissected

lymph nodes. Thus, a coordinated effort is required be-

tween the surgeon and pathologist if more extensive lymph-

adenectomies are to result in better staging of patients. In

Japan and Korea, following the en bloc dissection of the

stomach and lymph nodes, the surgeon dissects out the in-

dividual nodal stations from the surgical specimen, allow-

ing the pathologist to examine and report the number of

positive and negative lymph nodes for each nodal station.

At Massachusetts General Hospital, where one author has

been routinely been performing D2 lymphadenectomies,

the institution of a protocol of dissecting out the individual

nodal stations from the resected surgical specimen has in-

creased the average number of lymph nodes examined per

specimen from 35 to 42.

There is some indirect evidence that more extensive

lymphadenectomies result in lower rates of locoregional re-

currence. Locoregional recurrence after potentially cura-

tive surgery for gastric adenocarcinoma can be quite high.

In a 1982 series from the University of Minnesota, 107 pa-

tients with gastric adenocarcinoma underwent second-looklaparotomy, and 80% had a recurrence [39]. Of these recur-

rences, 88% were locoregional, 54% were peritoneal, and

29% were distant. More recently, in the U.S. Intergroup

0116 trial, 177 of 275 patients (64%) in the surgery-only

group developed recurrent disease [22]. In terms of the site

of first relapse, 29% had local recurrence, 72% had regional

recurrence, and only 18% had distant recurrence. Rates of

locoregional recurrence are generally lower in reports from

both western and Asian institutions that perform more ex-

tensive lymphadenectomies. In a series of 367 patients with

recurrent gastric adenocarcinoma from Memorial Sloan-Kettering Cancer Center over 15 years, 81% of patients had

a D2 or greater lymphadenectomy, and the median number

of lymph nodes removed was 22 [40]. Of patients who re-

curred, locoregional recurrence was the initial and only site

of recurrence in 26% of patients and was a component of

initial recurrence in 54% of patients. Yoo et al. [41] exam-

ined 508 patients who developed recurrent disease after

curative gastrectomy at Yonsei University in South Korea.

Nineteen percent of patients had locoregional recurrence

only as the first site of recurrence, and 32.5% of patients had

locoregional recurrence combined with peritoneal or dis-

tant recurrence as the initial site of recurrent disease. In the

patients with only locoregional disease as the site of first

recurrence, the anastamosis was the most common location

of recurrence, followed by the lymph nodes. In a Japanese

prospective randomized trial of adjuvant S-1 chemother-

apy, 188 (35.5%) of 530 patients treated with surgery suf-

fered a recurrence [42]. The site of first recurrence in those

188 patients was local in 7.9% and in lymph nodes in

24.5%.

The effect of more extensive lymphadenectomies on

overall survival for gastric cancer is still quite controver-

sial. The majority of gastric surgeons in Korea and Japan

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its 1,024 patient accrual goal. A D2 lymphadenectomy is

required for that trial, and survival results are pending.

SPLEEN, PANCREAS, AND

D2 LYMPHADENECTOMIES

Tumors of the upper and middle stomach are known to me-

tastasize to the splenic artery (station 11) and splenic hilar

(station 10) lymph nodes, and distal pancreatectomy and

splenectomy were historically routinely performed to clear

these nodal stations [52]. Pancreatic fistula rates were high,

thus significantly increasing the morbidity of the D2

lymphadenectomy procedure. Maruyama et al. [47] de-

scribed a pancreas-preserving D2 lymphadenectomy that

resected the spleen and splenic artery along with the station

10 and 11 lymph nodes. A retrospective study from Japan of

nearly 400 patients found that there was no survival benefit

in patients undergoing total gastrectomy combined withdistal pancreatectomy and splenectomy over patients un-

dergoing total gastrectomy with splenectomy only [53].

Distal pancreatectomy is now generally considered to be

unwarranted in the routine performance of a D2 lymphad-

enectomy until there is direct extension of the tumor. A ret-

rospective Japanese study of 224 patients with proximal

gastric cancer found no survival benefit in patients who

received pancreaticosplenectomy or splenectomy over

pancreas and spleen preservation, but morbidity was signif-

icantly greater in the pancreaticosplenectomy group [54].

As shown in Table 3, Sasako et al.[55]estimatedthe benefitof dissecting the station 10 and 11 lymph nodes for a prox-

imal gastric cancer at 5.6%. Hartgrink et al. [56] analyzed

the patients in the Dutch Gastric Cancer Trial who had

lymph node metastases at stations 10 and 11. Of the 18 pa-

tients with station 10 metastases, the 11-year survival rate

was 11%. Of the 24 patients with station 11 metastases, the

11-year survival rate was 8%. The authors concluded that

the relevance of the dissection of these nodes has to be

questioned as the survival benefit is small and morbidity

and hospital mortality are significantly increased.

Although most expert gastric cancer surgeons no longer

resect the distal pancreas as part of a D2 lymphadenectomy

unless there is direct tumor extension, the resection of the

spleen continues to be controversial. Two prospective ran-

domized trials of total gastrectomy and lymphadenectomy

with or without splenectomy have been performed in Chile

and South Korea [57, 58]. Both studies found no difference

in overall survival, and the Chilean study found a signifi-

cantly higher rate of infectious complications in the sple-

nectomy group. However, the number of patients in these

studies was 187207, and thus the power of these studies to

determine a modest improvement in survival for splenec-

tomy is limited. A multicenter randomized trial to evaluate

the role of splenectomy for proximal gastric cancers is cur-

rently under way in Japan [59].

Taking lymph node stations beyond those incorporatedin a D2 lymphadenectomy (D2 lymphadenectomy) likely

does not improve survival, given that disease at such distant

nodal stations is unlikely to be cured by surgical therapy

alone. Based on data from the National Cancer Center

(NCC) in Japan, the station 13 lymph nodes posterior to the

head of the pancreas are rarely involved, and their involve-

ment predicts a 5-year survival rate close to 0% [52]. Add-

ing dissection of station 16 para-aortic nodes to a D2

lymphadenectomy was studied in a multicenter, prospec-

tive randomized trial in Japan. In that study, 523 patients

were randomized to D2 lymphadenectomy or D2 lymphad-

enectomy plus additional para-aortic lymph node dissection

(D2) [18]. The surgical morbidity rate was slightly higher

in the D2 group (28.1% versus 24.5%), but the mortality

rate was only 0.8% in both groups. The 5-year overall

survival rate was 69%70% in both groups [60]. Thus,

performing lymphadenectomies beyond a D2 lymphade-

nectomy is not warranted.

CAN WESTERN SURGEONS PERFORM MORE

EXTENSIVE LYMPHADENECTOMIES SAFELY?

Dr. Maurizio Degiuli and colleagues in Turin, Italy, ap-

proached the issue of western surgeons performing more

Table 3. Estimated benefit from lymph node dissectionat each nodal station, according to tumor location (%)

StationLowerthird

Middlethird

Upperthird

Entirestomach

1 1.6b

7.9a

12.0a

3.7a

2 0.0c 0.9b 5.1a 1.5a

3 17.3a 26.3a 17.1a 11.7a

4 14.5a 13.0a 3.0a 10.1a

5 3.9a 0.8a 0.0b 2.7a

6 21.3a 3.9a 0.4b 7.0a

7 8.2b 10.5b 5.3b 8.2b

8 7.5b 4.6b 2.0b 5.9b

9 3.9b 5.2b 3.3b 3.8b

10 0.0c 4.0b 3.8b 1.6b

11 1.0c 1.3b 1.8b 0.8b

12 2.7c

0.5c

0.0c

0.0c

13 0.0c 0.0c 0.0c 0.0c

14 2.1c 0.0c 0.0c 0.0c

16 2.4d 0.0d 0.0d 2.9d

aFirst level (N1).bSecond level (N2).cThird level (N3).dFourth level (N4).

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extensive lymphadenectomies in western patients in a se-

ries of two prospective clinical trials [10]. Dr. Degiuli

learned the D2 lymphadenectomy method at the NCC Hos-

pital in Tokyo, Japan, from Dr. Mitsuru Sasako, a well-known Japanese gastric surgeon. He was also given

didactic videos and manuscripts. Dr. Degiuli then orga-

nized meetings for 16 surgeons from eight university or

general hospitals in northern Italy (Italian Gastric Cancer

Study Group). At those meetings, the terminology was ex-

plained and indications and technique were agreed upon for

the trials. At least one of the two surgeons from each center

attended the first 10 procedures of the trial, which were per-

formed at Dr. Degiulis hospital. Dr. Degiuli then attended

the first three operations performed at each of the remaining

seven centers. Following this advanced training of surgeons

in gastric surgery, a phase II trial of D2 lymphadenectomy

was instituted. At each institution, all surgeries were per-

formed by the same two attending surgeons. Of the 191 pa-

tients enrolled in the study, 106 (55%) were ultimately

found to be ineligible, usually as a result of more extensive

disease. The mean number of lymph nodes removed was 39

(range, 2293). The overall postoperative morbidity and

mortality rates were impressively low, at 20.9% and 3.1%,

respectively. Subsequent to this study, the surgeons from

the five highest volume centers performed a randomized

trial of D1 versus D2 lymphadenectomy [11]. Of 296 pa-

tients registered, 134 patients (45%) were ineligible, with

the most common causes of ineligibility being N2 or N3

nodal spread (25.2%), peritoneal disease (19.3%), and T4

disease (18.4%). Of 162 randomized patients, the total mor-

bidity rate was 10.5% in the D1 group and 16.3% in the D2group. Only one postoperative death occurred, and that pa-

tient received a D1 dissection. Survival results are pending.

The experience of the Italian Gastric Cancer Study Group

clearly demonstrates that, following a period of fairly rig-

orous training, western surgeons can perform D2 lymphad-

enectomies on western patients with morbidity and

mortality results similar to those of high-volume centers in

Korea and Japan.

LOW MARUYAMA INDEX SURGERY

Many centers in Japan and Korea have been performing ex-

tended lymphadenectomies for gastric cancer for decades.

At the NCC in Japan, gastric cancer surgeons routinely per-

form D2 or greater lymphadenectomies and meticulously

dissect out and label each station of lymph nodes following

removal of the surgical specimen. NCC pathologists then

examine each nodal station separately and document posi-

tive and negative nodes in each nodal station. Using a large

database of patients treated with D2 or greater lymphade-

nectomy, Maruyama et al. [61] calculated the riskfor lymph

node metastasis in each lymph node station by location of

the primary tumor (Table 4). In 1989, the NCC database of

3,843 cases was used to create the Maruyama computer

Table 4. Incidence of lymph node metastasis and 5-year survival rates of those having nodal metastasis in each station,according to tumor location

Station

Lower third Middle third Upper third Entire stomach

Incidence

5-yr

survival Incidence

5-yr

survival Incidence

5-yr

survival Incidence

5-yr

survival

1 6.2 25.0 15.0 52.6 38.0 31.7 32.7 11.3

2 7.1 0.0 3.4 25.0 22.0 23.2 18.2 8.0

3 40.9 42.2 44.8 58.7 45.1 37.9 66.0 17.8

4 34.2 42.3 26.8 48.4 14.5 20.5 53.1 19.0

5 10.5 37.5 2.4 33.3 3.0 0.0 14.2 18.8

6 46.3 46.0 14.6 26.8 6.8 6.3 37.7 18.7

7 23.4 34.9 22.6 46.5 26.9 19.7 44.4 18.5

8 24.5 30.6 11.0 41.5 10.2 20.0 30.6 19.2

9 12.8 30.4 11.0 47.5 16.0 20.5 18.5 20.7

10 3.8 0.0 11.9 33.3 17.4 21.6 21.6 7.4

11 6.7 15.4 6.3 21.4 16.1 11.4 20.6 3.7

12 9.0 29.6 1.6 33.3 2.5 0.0 4.4 0.0

13 8.3 0.0 0.0 0.0 2.5 0.0 5.6 0.0

14 14.6 14.3 8.7 0.0 10.0 0.0 4.5 0.0

16 13.1 18.2 7.4 0.0 12.1 0.0 26.5 11.1




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program [62]. This program estimates the risk for lymph

node metastasis for each lymph node station based on the

input of eight variables: sex, age, endoscopic or Bormanns

classification, depth of invasion, maximal diameter, loca-

tion (upper, middle, or lower third), position (lesser or

greater curvature, anterior or posterior wall, or circumfer-

ential), and World Health Organization histological classi-

fication. The Maruyama computer program was later

expanded to include 4,302 cases (WinEstimate 2.5) [63].

By matching input variables to this large database of pa-

tients, the program gives a percent likelihood of disease in

each of the 16 lymph node stations defined by the JRSGC.

The accuracy of this program was analyzed in 222 patients

treated at the Technical University in Munich, Germany.

The accuracies for lymph node stations 16, 712, and

1316 were 82%, 89%, and 96%, respectively [64]. Guad-

agni et al. [65] subsequently analyzed 282 Italian patientswith gastric cancer who underwent at least a D2 lymphad-

enectomy and found the Maruyama program to be 83% ac-

curate for stations 16, 82% accurate for stations 712, and

72% accurate for stations 1316. Moreover, if an absolute

cutoff point of 0% was used to direct the subsequent har-

vesting of lymph nodes, only six patients (3.4%) would

have had lymph node metastases left undissected.

Using the NCC database, Sasako et al. [52] were able to

not only determine the incidence of lymph node metastasis

in each nodal station based on location but to also determine

the 5-year survival rate of patients who had lymph node me-tastasis to any given stationstratifiedby tumor location (Ta-

ble 4). Using these data, the estimated benefit from lymph

node dissection of each nodal station was calculated strati-

fied by tumor location (Table 3). When one compares the

likelihood of involvement of lymph node stations (Table 4)

with the nodal stations resected in a D1 versus D2 lymph-

adenectomy (Table 2), one can see that there is a significant

risk of leaving involved lymph nodes undissected when

performing a D1 dissection for a tumor in any stomach lo-

cation. Performing less than a D1 lymphadenectomy leaves

even more positive lymph nodes behind. Hundahl et al. [66]

went on to define the Maruyama Index (MI) of unresected

disease as the sum of the regional nodal disease (stations

112) percentages, as estimated by the Maruyama program,

not removed by the surgeon. That study calculated the MI

for 553 patients who enrolled in the Intergroup 0116 pro-

spective, randomized trial of 5-FUbased chemoradiation

versus surgery alone. Only 10% of patients in that study un-

derwent the recommended D2 lymphadenectomy. Thus,

the median MI for 553 analyzed patients was 70, and MI

proved to be an independent prognostic factor for overall

survival (p .005) and recurrence-free survival (p .002).

The authors concluded that surgical undertreatment of pa-

tients in this study clearly underminedsurvival. Peeters et

al. [14] calculated the MI for 648 patients enrolled in the

Dutch trial and found the median MI to be 26. MI5 was

found to be an independent predictor of longer overall and

recurrence-free survival times on univariate and multivari-

ate analysis. Moreover, a doseresponse relationship was

demonstrated, with longer survival times as the MI de-

creased. The authors concluded that MI was a quantitative

yardstick for assessing the adequacy of lymphadenectomy

in gastric cancer.

Performing less than a D2 lymphadenectomy can result

in leaving positive lymph nodes behind. The Maruyama

computer program thus allows one to prospectively know

with fairly high accuracy which nodal stations have any

likelihood of harboring metastatic disease. Retrospective

analyses suggest that removal of all nodal stations that are

predicted to harbor metastases results in superior survival,but a prospective trial of this approach is needed to confirm

any validity.

BARRIERS TO PERFORMANCE OF MORE EXTENSIVE

LYMPHADENECTOMIES IN WESTERN COUNTRIES

Several tertiary referral centers in western countries rou-

tinely perform D2 lymphadenectomies for gastric cancer

[40], but as noted earlier, lymphadenectomies for gastric

cancer in western countries are limited and often do not

even reach the D1 threshold. There are several reasons why

more extensive lymphadenectomies are not more com-monly performed. First and foremost is the lack of a proven

benefit in terms of overall survival for D2 over D1 lymph-

adenectomy based on the Dutch and United Kingdom trials.

Unfortunately, many western surgeons have interpreted the

results of these trials to mean any lymphadenectomy does

not improve overall survival. Certainly some patients with

lymph node positivedisease are cured by surgical resec-

tion alone, and these patients would undoubtedly not have

been cured if diseased lymph nodes were left undissected

without additional therapy. Another significant obstacle to

the performance of more extensive lymphadenectomies is

the relative paucity of gastric adenocarcinomas seen at any

given institution. In order for more extensive lymphadenec-

tomies to benefit gastric cancer patients, they must be per-

formed without excess morbidity and mortality, and this

can be achieved only with adequate surgical training and

adequate case volume. Contributing to the lack of high-

volume centers for gastric cancer surgery is a significant re-

luctance of general surgeons to refer gastric cancer patients

to tertiary referral centers, given that gastric surgery has

historically been the realm of the general surgeon [67]. Fi-

nally, there are geographical and language barriers between

different countries that make dissemination of information

879Yoon, Yang




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and techniques on the surgical treatment of gastric cancer

difficult.

SUMMARY

The Dutch and United Kingdom trials of D1 versus D2

lymphadenectomy demonstrated that when D2 lymphad-

enectomy is performed with excess morbidity and

mortality there is no survival benefit over D1 lymphad-

enectomy. What have we learned since these trials?

Many, and perhaps the majority, of patients in the U.S.

receive an inadequate lymphadenectomy (i.e., less than a

D1 lymphadenectomy). Distal pancreatectomy is not re-

quired to perform an adequate D2 lymphadenectomy and

likely should be performed only when there is direct tu-

mor invasion. Splenectomy is not required for distal tu-

mors, but the role of splenectomy for mid or proximal

tumors is currently being investigated in a prospective,

randomized trial in Japan. D2 lymphadenectomy can be

taught to western surgeons such that the procedure can be

performed on western patients with low morbidity and

mortality [10]. When a more extensive lymphadenec-

tomy is performed, there is clearly a benefit in terms of

staging, and possibly in terms of less locoregional recur-

rence. If D2 lymphadenectomy is performed with low

morbidity and mortality, there also may be a benefit in

terms of overall survival [12], but this potential benefit

needs to be demonstrated by prospective, randomized tri-

als in western patients. D1 lymphadenectomies incor-

porating only lymph node stations beyond the N1 level

that are predicted to harbor metastatic disease by the Ma-

ruyama computer program may optimize resection of

disease and minimize complications, but this has not

been proven. There exist several barriers to the perfor-

mance of more extensive lymphadenectomies in western

countries. Future collaborations and clinical trials will

hopefully answer whether west should meet east, east

should meet west, or there exists some utopian Shan-

gri-La in between.

AUTHOR CONTRIBUTIONSConception/Design: Sam S. Yoon, Han-Kwang YangAdministrative support: Sam S. YoonProvision of study materials: Sam S. Yoon, Han-Kwang YangCollection/assembly of data: Sam S. Yoon, Han-Kwang YangData analysis: Sam S. Yoon, Han-Kwang YangManuscript writing: Sam S. Yoon, Han-Kwang YangFinal approval of manuscript: Sam S. Yoon, Han-Kwang Yang

REFERENCES

1 World Health Organization Cancer. World Health Organization Fact Sheet

No. 297. February 2009. Available at http://www.who.int/mediacentre/

factsheets/fs297/en/index.html, accessed September 1, 2009.

2 Lee J, Demissie K, Lu SE et al.Cancer incidenceamong Korean-American

immigrants in theUnited Statesand nativeKoreans in South Korea.Cancer

Control 2007;14:78 85.

3 Jemal A, Siegel R, Ward E et al. Cancer statistics, 2008. CA Cancer J Clin

2008;58:7196.

4 Gotoda T, Yanagisawa A, Sasako M et al. Incidence of lymph node metas-

tasis from early gastric cancer: Estimation with a large number of cases at

two large centers. Gastric Cancer 2000;3:219225.

5 Jansen EP, Boot H, Verheij M et al. Optimal locoregional treatment in gas-

tric cancer. J Clin Oncol 2005;23:45094517.

6 Cuschieri A, Fayers P, Fielding J et al. Postoperative morbidity and mor-

tality after D1 and D2 resections for gastric cancer: Preliminary results ofthe MRC randomised controlled surgical trial. The Surgical Cooperative

Group. Lancet 1996;347:995999.

7 BonenkampJJ, SongunI, Hermans J et al.Randomised comparison of mor-

bidity after D1 and D2 dissection for gastric cancer in 996 Dutch patients.

Lancet 1995;345:745748.

8 Uyama I, Ogiwara H, Takahara T et al. Spleen- and pancreas-preserving

total gastrectomy with superextended lymphadenectomy including dissec-

tion of the para-aortic lymph nodes for gastric cancer. J Surg Oncol 1996;

63:268270.

9 Biffi R, Chiappa A, Luca F et al. Extended lymph node dissection without

routine spleno-pancreatectomy for treatment of gastric cancer: Low mor-

bidity and mortality rates in a single center series of 250 patients. J Surg

Oncol 2006;93:394 400.

10 Degiuli M, Sasako M, Ponti A et al. Morbidity and mortality after D2 gas-

trectomy for gastric cancer: Results of the Italian Gastric Cancer Study

Group prospective multicenter surgical study. J Clin Oncol 1998;16:1490

1493.

11 Degiuli M, Sasako M, Calgaro M et al. Morbidity and mortality after D1

and D2 gastrectomy for cancer: Interim analysis of the Italian Gastric Can-

cer Study Group (IGCSG) randomised surgical trial. Eur J Surg Oncol

2004;30:303308.

12 Wu CW, Hsiung CA, Lo SS et al. Nodal dissection for patients with gas-

tric cancer: A randomised controlled trial. Lancet Oncol 2006;7:309

315.

13 Hundahl SA, Macdonald JS, Benedetti J et al. Surgical treatment variation

in a prospective, randomized trial of chemoradiotherapy in gastric cancer:

The effect of undertreatment. Ann Surg Oncol 2002;9:278286.

14 Peeters KC, Hundahl SA, Kranenbarg EK et al. Low Maruyama index sur-

gery for gastric cancer: Blinded reanalysis of theDutchD1D2trial.World

J Surg 2005;29:15761584.15 Japanese Research Society for Gastric Cancer. The general rules for the

gastric cancer study in surgery. Jpn J Surg 1973;3:6171.

16 Japanese Gastric Cancer Association. Japanese classification of gastric car-

cinoma2nd English edition. Gastric Cancer 1998;1:1024.

17 Park DJ, Lee HJ, Kim HH et al. Predictors of operative morbidity and mor-

tality in gastric cancer surgery. Br J Surg 2005;92:10991102.

18 Sano T, Sasako M, Yamamoto S et al. Gastric cancer surgery: Morbidity

and mortality results from a prospective randomized controlled trial com-

paring D2 and extended para-aortic lymphadenectomyJapan Clinical

Oncology Group study 9501. J Clin Oncol 2004;22:27672773.

19 Birkmeyer JD, Siewers AE, Finlayson EV et al. Hospital volume and

surgical mortality in the United States. N Engl J Med 2002;346:1128

1137.




Downloadedfrom


11/13

20 Smith DL, Elting LS, Learn PA et al. Factors influencing the volume-

outcome relationship in gastrectomies: A population-based study. Ann

Surg Oncol 2007;14:18461852.

21 Wanebo HJ, Kennedy BJ, Chmiel J et al. Cancer of the stomach. A patient

care study by the American College of Surgeons. Ann Surg 1993;218:583

592.

22 MacdonaldJS, Smalley SR,Benedetti J et al.Chemoradiotherapyafter sur-

gery compared with surgery alone for adenocarcinoma of the stomach or

gastroesophageal junction. N Engl J Med 2001;345:725730.

23 American Joint Committee on Cancer. AJCC Cancer Staging Manual,

Sixth Edition. New York: Springer, 2002:199.

24 Sano T. Tailoring treatments for curable gastric cancer. Br J Surg 2007;94:

263264.

25 Smith JK, McPhee JT, Hill JS et al. National outcomes after gastric resec-

tion for neoplasm. Arch Surg 2007;142:387393.

26 Marcus SG, Cohen D, Lin K et al. Complications of gastrectomy following

CPT-11-based neoadjuvantchemotherapy for gastric cancer. J Gastrointest

Surg 2003;7:10151022; discussion 1023.

27 Lee JH, Ryu KW, Lee JH et al. Learning curve for total gastrectomy with

D2 lymph node dissection: Cumulative sum analysis for qualified surgery.

Ann Surg Oncol 2006;13:11751181.

28 Stomach. In: American Joint Committee on Cancer. AJCC Cancer Staging

Manual, Sixth Edition. New York: Springer, 2002:99106.

29 Reid-Lombardo KM, Gay G, Patel-Parekh L et al. Treatment of gastric ad-

enocarcinomamay differamonghospitaltypesin theUnited States, a report

from the National Cancer Data Base. J Gastrointest Surg 2007;11:410

419; discussion 419 420.

30 Coburn NG, Swallow CJ, Kiss A et al. Significant regional variation in ad-

equacy of lymph node assessment and survival in gastric cancer. Cancer

2006;107:21432151.

31 Mullaney PJ, Wadley MS, Hyde C et al. Appraisal of compliance with theUICC/AJCC staging system in the staging of gastric cancer. Union Inter-

nacional Contra la Cancrum/American Joint Committee on Cancer. Br J

Surg 2002;89:14051408.

32 Bouvier AM, Haas O, Piard F et al. How many nodes must be examined to

accurately stage gastric carcinomas? Results from a population based

study. Cancer 2002;94:28622866.

33 Smith DD, Schwarz RR, Schwarz RE. Impact of total lymph node count on

staging and survival after gastrectomy for gastric cancer: Data from a large

US-population database. J Clin Oncol 2005;23:71147124.

34 Estes NC, Macdonald JS, Touijer K et al. Inadequate documentation and

resection for gastric cancer in the United States: A preliminary report. Am

Surg 1998;64:680 685.

35 Shen JY,Kim S,Cheong JHet al.The impactof total retrievedlymphnodes

on staging and survival of patients with pT3 gastric cancer. Cancer 2007;

110:745751.

36 Kim JP, Lee JH, Kim SJ et al. Clinicopathologic characteristics and prog-

nostic factors in 10 783 patients with gastric cancer. Gastric Cancer 1998;

1:125133.

37 Siewert JR,Bttcher K,SteinHJ etal. Relevant prognostic factors ingastric

cancer: Ten-year results of the German Gastric Cancer Study. Ann Surg

1998;228:449461.

38 Marchet A, Mocellin S, Ambrosi A et al. The ratio between metastatic

and examined lymph nodes (N ratio) is an independent prognostic factor

in gastric cancer regardless of the type of lymphadenectomy: Results

from an Italian multicentric study in 1853 patients. Ann Surg 2007;245:

543552.

39 Gunderson LL, Sosin H. Adenocarcinoma of the stomach: Areas of failure

in a re-operation series (second or symptomatic look) clinicopathologic

correlation and implications for adjuvant therapy. Int J Radiat Oncol Biol

Phys 1982;8:111.

40 DAngelica M,GonenM, Brennan MF et al.Patternsof initial recurrence in

completely resected gastric adenocarcinoma. Ann Surg 2004;240:808

816.

41 Yoo CH, Noh SH, Shin DW et al. Recurrence following curative resection

for gastric carcinoma. Br J Surg 2000;87:236242.

42 Sakuramoto S, Sasako M, Yamaguchi T et al. Adjuvant chemotherapy for

gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med 2007;357:

18101820.

43 Lee HK, Yang HK, Kim WH et al. Influence of the number of lymph

nodes examined on staging of gastric cancer. Br J Surg 2001;88:1408

1412.

44 Siewert JR, Bttcher K, Roder JD et al. Prognostic relevance of systematic

lymph node dissection in gastric carcinoma. German Gastric Carcinoma

Study Group. Br J Surg 1993;80:10151018.

45 Yildirim E, Celen O, Berberoglu U. The Turkish experience with curativegastrectomies for gastric carcinoma: Is D2 dissection worthwhile? J Am

Coll Surg 2001;192:2537.

46 Karpeh MS, Leon L, Klimstra D et al. Lymph node staging in gastric can-

cer: Is location moreimportant than number? An analysis of 1,038 patients.

Ann Surg 2000;232:362371.

47 Maruyama K, Sasako M, Kinoshita T et al. Pancreas-preserving total gas-

trectomy for proximal gastric cancer. World J Surg 1995;19:532536.

48 Roggin KK, Posner MC. D3 or not D3. . . that is not the question. Lancet

Oncol 2006;7:279280.

49 Lordick F, Siewert JR.Recent advancesin multimodal treatmentfor gastric

cancer: A review. Gastric Cancer 2005;8:7885.

50 KimS, LimDH, LeeJ et al.An observational study suggesting clinical ben-efit for adjuvant postoperative chemoradiation in a population of over 500

cases after gastric resection with D2 nodal dissection for adenocarcinoma

of the stomach. Int J Radiat Oncol Biol Phys 2005;63:12791285.

51 Cunningham D,Allum WH,StenningSP et al.Perioperative chemotherapy

versus surgery alone for resectable gastroesophageal cancer. N Engl J Med

2006;355:1120.

52 Sasako M, Sano T, Katai H et al. Radical surgery. In: Sugimura T, Sasako

M. Gastric Cancer. Oxford: Oxford University Press, 1997:223249.

53 Kitamura K, Nishida S, Ichikawa D et al. No survival benefit from com-

binedpancreaticosplenectomy and totalgastrectomy for gastric cancer. Br J

Surg 1999;86:119122.

54 KoderaY, Yamamura Y, Shimizu Y et al.Lackof benefit of combined pan-

creaticosplenectomy in D2 resection for proximal-third gastric carcinoma.World J Surg 1997;21:622627; discussion 627628.

55 Sasako M, McCulloch P, Kinoshita T et al. New method to evaluate the

therapeutic value of lymph node dissection for gastric cancer. Br J Surg

1995;82:346351.

56 Hartgrink HH, van de Velde CJ, Putter H et al. Extended lymph node dis-

section for gastric cancer: Who may benefit? Final results of the random-

ized Dutch gastric cancer group trial. J Clin Oncol 2004;22:20692077.

57 Csendes A, Burdiles P, Rojas J et al. A prospective randomized study com-

paring D2 total gastrectomy versus D2 total gastrectomy plus splenectomy

in 187 patients with gastric carcinoma. Surgery 2002;131:401407.

58 Yu W, Choi GS, Chung HY. Randomized clinical trial of splenectomy ver-

sus splenic preservation in patients with proximal gastric cancer. Br J Surg

2006;93:559563.

881Yoon, Yang




Downloadedfrom


12/13

59 Sano T, Yamamoto S, Sasako M. Randomized controlled trial to evaluate

splenectomy in total gastrectomy for proximal gastric carcinoma: Japan

Clinical Oncology Group study JCOG 0110-MF. Jpn J Clin Oncol 2002;

32:363364.

60 Sasako M, Sano T, Yamamoto S et al. D2 lymphadenectomy alone or with

para-aortic nodal dissection for gastric cancer. N Engl J Med 2008;359:

453462.

61 Maruyama K, Okabayashi K, Kinoshita T. Progress in gastric cancer

surgery in Japan and its limits of radicality. World J Surg 1987;11:418

425.

62 Kampscher GH,Maruyama K,van deVeldeCJ etal. Computeranalysis in

making preoperative decisions: A rational approach to lymph node dissec-

tion in gastric cancer patients. Br J Surg 1989;76:905908.

63 Siewert JR, Kelsen D, Hoelscher AH. Gastric Cancer Diagnosis and Treat-

mentAn Interactive Training Program. Berlin: Springer Electronic Me-

dia, 2000.

64 Bollschweiler E, Boettcher K, Hoelscher AH et al. Preoperativeassessment

of lymph node metastases in patients with gastric cancer: Evaluation of the

Maruyama computer program. Br J Surg 1992;79:156160.

65 Guadagni S, de Manzoni G, Catarci M et al. Evaluation of the Maruyama

computer program accuracy for preoperative estimation of lymph node

metastases from gastric cancer. World J Surg 2000;24:15501558.

66 Hundahl SA, Peeters KC, Kranenbarg EK et al. Improved regional control

and survival with low Maruyama Index surgery in gastric cancer: Au-

topsy findings from the Dutch D1D2 Trial. Gastric Cancer 2007;10:84

86.

67 Karpeh MS Jr. Should gastric cancer surgery be performed in community

hospitals? Semin Oncol 2005;32(suppl 9):S94S96.

68 Japanese Gastric Cancer Association. Japanese classification of gastric car-

cinoma2nd English editionresponse assessment of chemotherapy and

radiotherapy for gastric carcinoma: Clinical criteria. Gastric Cancer 2001;

4:18.




Downloadedfrom


13/13

DOI: 10.1634/theoncologist.2009-00702009;14;871-882; originally published online September 8, 2009;The Oncologist

Sam S. Yoon and Han-Kwang YangLymphadenectomy for Gastric Adenocarcinoma: Should West Meet East?

This information is current as of October 13, 2011

& ServicesUpdated Information

http://theoncologist.alphamedpress.org/content/14/9/871including high-resolution figures, can be found at:



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