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Annals of Surgical Oncology 9:401-405 (2002)
© 2002 Society of Surgical Oncology

ORIGINAL ARTICLES

Is D2 Lymph Node Dissection Necessary for Early Gastric Cancer?

Takaki Yoshikawa, MD, PhD, Akira Tsuburaya, MD, DMedSc, Osamu Kobayashi, MD, DMedSc, Motonori Sairenji, MD, DMedSc, Hisahiko Motohashi, MD, DMedSc and Yoshikazu Noguchi, MD, DMedSc

From the Department of Gastrointestinal Surgery (TY, AT, OK, MS, HM), Kanagawa Cancer Center Hospital, Yokohama, Japan; and Department of Surgery (YN), Yokohama Kowan Hospital, Yokohama, Japan.

Correspondence: Address correspondence and reprint requests to: Takaki Yoshikawa, MD, PhD, Department of Gastrointestinal Surgery, Kanagawa Cancer Center, 1-1-2 Nakao, Asahi-Ku, Yokohama 241, Japan; Fax: 81-45-361-4692; E-mail: yoshika{at}yc5.so-net.ne.jp


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: The objective of this study was to clarify a survival benefit of D2 lymphadenectomy in patients with early gastric carcinoma (GC).

Methods: A retrospective study was conducted to examine the incidence of metastasis to level 2 lymph nodes, the causes of postoperative death, and the mode of recurrence in 1041 patients who had early GC and underwent D2 lymphadenectomy with curative intent.

Results: Postoperative mortality occurred in 129 (12.4%) of 1041 patients, 6 patients (.6%) died of surgical complications, 108 (10.2%) died of diseases other than cancer, and 16 (1.5%) died of recurrence. Hematogenous metastasis was the major mode of recurrence (56.3% of recurrences). The incidence of metastasis to level 2 nodes was 2.5% (26 of 1041 patients, 18 of whom were alive). Thus, the estimated survival benefit of radical lymphadenectomy for patients with early GC was calculated to be 1.7% (18 of 1041 patients).

Conclusions: D2 lymphadenectomy in patients with early GC had little survival benefit because (1) metastasis to level 2 nodes was rare, (2) most causes of death were not related to the tumor, and (3) more than half the recurrences were hematogenous. Use of radical lymphadenectomy for early GC should be limited.

Key Words: Gastric carcinoma • Lymph node dissection • Prognosis • Survival


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Early gastric carcinoma (GC) is defined as GC in which invasion is confined to either the mucosa or submucosa, regardless of the presence or absence of regional lymph node metastasis.1 As a result of increased diagnostic accuracy and the wider application of mass surveys, the proportion of early GC among resected gastric cancers has steadily increased, not only in Japan, but also in some Western countries.2,3 A survival rate of >90% in patients with early GC treated with radical surgery has been repeatedly documented.4–8

The most widely applied treatment for early GC in Japan and in some European countries has been total or subtotal gastrectomy with D2 lymphadenectomy. Gastrectomy with node dissection up to N2 nodes was defined in Japan in the 1960s as the standard treatment for GC and has been practiced uniformly, irrespective of the stage of the disease.9–11 This applies equally to cases of early GC. Such extended surgery has been gradually accepted in some Western countries,2,12 but because of the higher morbidity and mortality, it has never been accepted as a standard treatment.13 Recently, two prospective, randomized, controlled trials in Europe failed to demonstrate any survival benefit of D2 node dissection compared with D1 lymphadenectomy.14–17 Despite the absence of randomized, controlled trials that show a survival advantage for D2 lymph node dissection, Japanese surgeons still recommend D2 lymphadenectomy, on the basis of retrospective analyses of the incidence of lymph node metastasis and survival of certain patients with lymph node metastases. However, a new trend in Japan is to customize surgery for GC on the basis of the stage of disease. This is particularly applicable to early GC, because early GC metastasizes to level 2 lymph nodes less frequently than does advanced GC.7,10,11,18–32 In this study we attempted to determine whether there was any survival benefit to D2 lymphadenectomy in patients with early GC by analyzing a large database containing >1000 cases of resected early GC at a single institution.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
From 1975 to 1995, 1041 patients underwent curative gastrectomy with D2 lymph node dissection for primary early GC at the Department of Gastric Surgery, Kanagawa Cancer Center Hospital. Resected specimens were examined, and findings were recorded according to the general rules for GC study.1 The outcomes of postoperative gastrectomy patients were obtained through routine clinical appointments at the outpatient clinic or by telephone contact. This report is based on a review of data collected up to August 2000. The observation period ranged from 56.0 to 310.8 months, with a median of 155.8 months. The cause of death was determined for each patient who died on the basis of autopsy or clinical findings, including computed tomography, ultrasonography, endoscopy, and cytologies. Survival was analyzed with the Kaplan-Meier method.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
The clinicopathologic characteristics of patients included in the study are listed in Table 1, and their status as of the last follow-up is given in Table 2. At last follow-up, 912 (87.6%) of the 1041 patients were alive, and 129 (12.4%) had died. Six patients (.6%) died of surgical complications, 108 (10.2%) died of diseases other than the primary GC, including secondary cancers and cardiopulmonary disease, and 15 (1.4%) died of recurrence. Overall survival rates were 94.0% at 5 years and 88.7% at 10 years (Fig. 1). Disease-free rates were 99.2% at 5 years and 97.6% at 10 years (Fig. 2).


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  		TABLE 1. Clinicopathologic characteristics of patients with early gastric cancer
 

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  		TABLE 2. Status at last follow-up
 


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  		FIG. 1. Overall survival of 1041 patients with early gastric cancer who underwent D2 lymphadenectomy. The observation period ranged from 56.0 to 310.8 months, with a median of 155.8 months. Five- and 10-year survival rates were 94.0% and 88.7%, respectively.

 


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  		FIG. 2. Disease-specific survival of 1041 patients with early gastric cancer who underwent D2 lymphadenectomy. Five- and 10-year disease-free survival rates were 99.2% and 97.6%, respectively.

 
In addition to the 15 patients who died of recurrence, 1 of the 912 surviving patients was alive with recurrence. The overall recurrence rate was 1.5% (16 of 1041 patients). The most common mode of recurrence was hematogenous (9 of 16 patients; 56.3%), followed by peritoneal dissemination and local recurrence in 3 patients each (18.8%) and lymph node metastases in 1 patient (6.3%).

The incidence of metastasis to level 2 lymph nodes was 2.5%, including in .4% of mucosal tumors (2 of 552 and 4.9% of submucosal tumors (24 of 489 cases). Among these 26 patients with distant or N2 lymph node metastasis, 1 of the 2 patients with a mucosal tumor and 7 of the 24 patients with a submucosal tumor were dead at the last follow-up. Five of these patients (19.2%) died from other disease, and three (11.5%) died from hematogenous recurrence of GC. Only 18 of the 26 patients with distant lymph node metastasis were alive, out of 1041 who underwent curative D2 lymph node dissection for early GC. The estimated survival benefit of D2 lymphadenectomy was 1.7% (18 of 1041 patients). The estimated survival benefit in patients with mucosal tumors was .2% (1 of 552 patients), and in those with submucosal tumors it was 3.5% (17 of 489 patients).


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Gastrectomy and D2 lymph node dissection with curative intent has been recommended and practiced for the treatment of early GC,9–11 resulting in an excellent prognosis for patients with early GC in Japan.4–8 The prognostic significance of lymph node metastasis in early GC has been discussed.32–36 Most reports have concluded that radical lymphadenectomy is necessary because early GC does metastasize to level 2 lymph nodes.32–36 However, does the low incidence of metastasis to distant nodes in early GC justify a uniform practice of D2 lymph node dissection?

Despite the strong belief in D2 lymphadenectomy among Japanese surgeons, no randomized controlled trials have been performed in Japan that prove it advantageous. All studies investigating this issue conducted in Europe and South Africa have been negative. Even the recent prospective, randomized, controlled trial in Holland clearly demonstrated that D2 lymphadenectomy resulted in a higher mortality when compared with D1 lymphadenectomy and that there was no survival benefit.14–17

Lymph node metastasis has been documented as a prognostic factor in early GC by many Japanese surgeons.32–36 However, its actual degree of importance is unknown. We attempted to determine how many patients with early GC were saved by radical lymph node dissection and how effective the procedure was by examining the incidence of metastasis to the level 2 nodes and the causes of death among a large number of patients. We demonstrated that metastasis of early GC to level 2 lymph nodes was rare, occurring in only .4% of mucosal tumors and in 4.9% of submucosal tumors; these results were in accord with data reported by others (Table 3). 11,18–32


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  		TABLE 3. Incidence of distant lymph node metastasis in patients with early gastric cancer
 
In patients with early GC who underwent radical surgery for cure, the causes of death were more frequently not related to the tumor than related to it.37–41 During the study follow-up period, 84% of the deaths were for reasons other than GC. This might be a reflection of an older patient population and an improved rate of cure for the disease. The recurrence rate was only 1.5%. In addition, the major mode of this recurrence was hematogenous, and all recurrences in patients with N2-positive disease were hematogenous. Sano et al.40 also reported that the most frequent mode of recurrence for early GC was hematogenous, regardless of nodal status. Isozaki et al.41 documented an even higher rate of hematogenous recurrence (81.8%). These results suggest that in patients with early GC, treatment failure was not due to local or lymph node metastasis but to the systemic spread of the tumor.

Does radical lymphadenectomy provide a therapeutic effect against recurrence? The main purpose of D2 dissection is to remove N2 nodes. Of the 26 N2-positive patients, 18 were saved by this surgery. Thus, D2 dissection did have a therapeutic effect against recurrence, but in only 1.7% of the patient population (18 of 1041 patients). The therapeutic effect was less clear in mucosal tumors, in which only .2% (1 of 552) of patients were saved.

The rationale for any specific surgical management of disease should be based on a balance between the survival benefit and the operative mortality. Operative mortality in this data set was .6%, which was slightly lower than in previous reports from Japan.7,10,11,18,19 However, in Western countries, published estimates of mortality due to the operation range14–17,42,43 from 1% to 10%. Recent randomized, controlled trials in Holland indicate that mortality for D1 lymphadenectomy was 4% to 6% and for D2 lymphadenectomy was as high14–17 as 13%. Although radical surgery is a safe procedure in Japan, it may be a highly morbid procedure in other countries. A small survival benefit from radical surgery for early GC might be insufficient to justify a D2 procedure even with the lowest operative mortality.

The rate of early GC was reported to be increasing in the United States as well as in Europe.2,3 Furthermore, several articles clearly documented that early GC in North America had an excellent prognosis, similar to that in Japan.2,44 Although there are some differences between the pathologic diagnoses of in situ carcinoma and dysplasia,45 these data would be applicable to Western surgical practice.

One concern of abandoning radical lymph node dissection in early GC is the accuracy of current methodology in detecting small metastatic foci in the nodes. In examining the microinvolvement of lymph nodes, Siewert et al.46 found that in 62 patients previously staged as node negative, 56 (90%) had at least 1 node with microinvolvement. Other groups have also reported that the number of nodes containing metastatic deposits was nearly doubled when more sensitive immunostaining methods were used in addition to routine hematoxylin and eosin staining.47 These reports may suggest that detailed examinations increase the rate of positivity at level 2 nodes as well. However, to date, there are few studies that address the clinical significance of micrometastasis in N2 nodes in early GC. Even taking this into consideration, the survival benefit of D2 dissection for early GC seems to be limited. Results of this retrospective study suggest that uniform nodal dissection of N2 nodes in early GC should be carefully re-evaluated.

Received for publication July 18, 2001. Accepted for publication January 17, 2002.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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