ARTICLES

Introduction

Early gastric cancer (EGG) is a unique form of gastric carcinoma confined to mucosa and submucosa (irrespective of the involvement of lymph nodes) with an excellent prognosis. Earlier, this tumor was most commonly diagnosed in Japan secondary to aggressive screening practices, [1, 2] but, now it is increasingly being recognized and diagnosed worldwide;[3-6] with an excellent prognosis (5 year survival>90%), similar to that in Japan. [7]

Controversy in the management of early gastric cancer

The extent of lymph node dissection remains a controversial issue in the management of early gastric cancer. A recent trend in the surgical treatment of early gastric carcinoma has been to limit surgery so that a complete cure is achieved and the patient's quality of life is optimized. [8, 9] The treatment of these tumors in Japan is becoming less aggressive as "good prognostic factors" are increasingly recognized. [7] Although regional lymph node metastasis from early gastric carcinoma (EGG) is less common, it is very impol1ant to clarify the characteristics of patients having lymph nodal metastases in order to determine appropriate therapy, [10] as the protocol of surgical treatment most appropriate for the treatment of early gastric cancer with lymph node metastasis is still evolving. [8, 9]

Survival in early gastric cancer

Many studies have shown that node-positive patients with early gastric cancer had a significantly poorer survival rate than node-negative patients (p<O.O5). [7, 8, 11, 12] In fact, it has been even suggested that the definition of EGG should be modified to "gastric carcinoma confined to mucosa and submucosa without the involvement of lymph nodes". [13, 14]

Patients with five or more positive nodes and positive nodes distant from the common hepatic artery have an extremely poor prognosis. [12, 15]

Incidence of lymph node metastasis in early gastric

cancer

The overall incidence of metastasis reported in cases of EGG is 5.7% to 13%. [8,9, 16, 17]The reported rate of node metastasis for mucosal carcinoma is 1.2% to 2.6%, and that for submucosal carcinoma is 16.5% to 23.8%. [9, 13, 17, 18] with a significant (p < 0.001) difference of nodal involvement between the two.

Factors affecting lymph node metastasis in early gastric cancer

Basically, 5 factors affect !ymph node metastasis in cases of EGG [7-10.12,16.11.19] :

Factors affecting lymph node metastasis in early gastric cancer

Basically, 5 factors affect lymph node metastasis in cases of EGG [7-10, 12, 16, 11,19] :

1. Tumor size :

The incidence of undifferentiated carcinomas increases with tumor diameter, irrespective of whether they are mucosal or submucosal carcinomas, and they are significantly (p < 0.001 for mucosal carcinomas and p<0.05 for submucosal ones) more node-positive than are differentiated carcinomas. [9, 20]

2. Depth of cancer invasion :

Patients with mucosal tumors show no relation between metastatic rate and tumor size, whereas those with submucosal tumors show an increasing metastatic rate with tumor size. [16] Research workers at the Memorial Sloan Kettering Cancer Center, New York, found that those tumors that were limited to the mucosa and less than 4.5 cm in size had a 4% rate of positive nodes. In contrast, those tumors that were 4.5 cm and larger and had penetrated into the submucosa had a 56% chance of positive nodes. [7] Patients with both slight invasion into the submucosa and less than 5 mm of horizontal expansion in the submucosa are often negative for lymph node involvement.[21 ] Submucosal carcinomas has been classified in-to three categories according to the depth of invasion by dividing the submucosal layer (sm) into three equal parts, sm1 , sm2 and sm3; [13, 20] and found that the incidence of lymph node metastasis increases from 2% to 12% and 20% respectively. [20]

3. Macroscopic appearance :

The macroscopically elevated or compound-type carcinomas, 10 mm or less in diameter are all node- negative, whereas some depressed-type carcinomas are node-positive. Gross appearance of Type I, IIc + III or Ila + IIc are more likely to be node-positive. [19]

4. Histological growth pattern :

   The undifferentiated carcinomas are significantly (p<0.001 for mucosal carcinomas and. p<0.05 for submucosal ones) more node-positive than are differentiated carcinomas. [9] The occurrence of metastasis is highest tor lesi.ons of the macroscopically mixed type, microscopically diffuse type' and with histologic ulceration of the tumor. [17]

5. Lymphatic invasion :

   Involvement of lymph nodes depends on the severity of vessel invasion. [19] Lymph vessel invasion is significantly more common in node positive cancers than in node negative cancers. [8, 15, 20]

Yamao et al. from the National Cancer Center, Tokyo, from the univariate analysis of their data, showed that younger age « 57 years), macroscopic depressed type, 1arger tumor size (> or = 30 mm), undifferentiated histologic type, histologic ulceration of the carcinoma, and lymphatic vessel invasion had a significant association with regional lymph node metastasis. Their multivariate analysis revealed that lymphatic vessel invasion, histologic ulceration of the tumor, and larger size (>or = 30 mm) were independent risk factors for regional lymph node metastasis. The incidence of lymph node metastasis from intramuco'sal EGC negative for these 3 risk factors was only 0.36% (1 in 277 patients). [10]

Lymph Nodes involved in early gastric cancer

The distribution of involved nodes for early gastric carcinoma is similar to that for advanced carcinoma, [17] and rarely Group 2 and 3 nodes are affected [12, 22]; metastases mostly being confined to lymph node stations defined as Group 1 locations. [16]

Decision making vis-a-vis conventional surgery or limited surgery

The carcinomas satisfying the following criteria are node-negative and eligible for limited (endoscopic mucosal resection or laparoscopic local resection) surgery:

( 1 ) mucosal carcinoma; (2) elevated or flat lesion <10 mm in diameter; (3) differentiated adenocarcinoma; and (4) no ulcer or ulcer scar. The other carcinomas are potentially node-positive and standard surgery is recommended. [9, 16, 17] Yokota et at. [8] suggest 2 cms and Hochwald et al. [7] suggest 4.5 cms as the upper margin of the size of EGG (mucosal; elevated or flat type), which can be subjected to limited surgery. Most authors agree that there is no role of limited surgery for the submucosal carcinomas and these carcinomas should be subjected to standard surgery with gastrectomy and combined dissection of lymph nodes.[17, 23]

Some compelling arguments against limited resections are that :

1. Majority of noncurative resections have cancer cells at the resectioil margin, caused by inadequate resection. [18]

2. Operative mortality from extensive lymphadenectomy is almost the same as from simple gastrectomy. [1' ]

3. Since pre-operative and intra-operative assessment of the stage for gastric cancer is not always accurate, surgical intervention must be carried out in an oncological sense. [23] Preoperative endoscopic ultrasonography has a 55% diagnostic acturacy in determining tumor depth and only 15% sensitivity in diagnosing lymph node metastases.[16] About one fifth cases with macroscopic Stage 1 gastric cancer are understaged, hence it is suggested that whenever there is doubt regarding the accurate staging of EGG, gastrectomy plus radical lymphadenectomy (at least 02) should be the treatment

of choice. [24]

4. Extensive nodal dissection appears to prevent

recurrence and to significantly (p <,0.005) improve the cancer-specific survival in EGG patients with nodal metastasis. [11]

Based on retrospective discriminant analysis of their clinico-pathological data, researct-1 workers have at- tempted to predict the lymph node metastasis in cases of EGG, which then serves as a guideline for the need for the lymphadenectomy.[19] Now useful algorithms, helpful in such a decision making, are increasingly available. [16, 25] (Table I)

Surgical management of EGG is the balance between maximum locoregional control and acceptable quality of life in patients who undergo an aggressive lymph nodes dissection. [8] Keeping this in mind, Miwa et al. have developed a vagus nerve-saving technique of 02 lymphadenectomy (VS-02). This procedure constitutes 02 and saving of hepatic and celiac branches of the vagus nerve, whereas conventional 02 consists of 02 and pre- serving hepatic branches alone of the vagus nerve. They found lower occurrence rate of postoperative diarrhoea (p < 0.01 ), postoperative incomplete weight regain (p = 0.08) and the incidence of formation of gallstones (3% versus 13%) in patients with VS-02 than that in patients with conventional 02. [26]

Summary

Early gastric cancer is a unique form of gastric carcinoma confined to mucosa and submucosa (irrespective of the involvement of lymph nodes) with an excellent prognosis. The treatment of these tumors is becoming less aggressive as "good prognostic factors" are increasingly recognized, but the extent of lymph node dissection remains a controversial issue. Node-positive patients with early gastric cancer have a significantly poorer survival rate than node-negative patients. The overall incidence otmetastasis reported in cases of EGG is 5.7% to 13%, with the reported rate of node metastasis for mucosal carcinoma at 1.2% to 2.6%, and that for submucosal carcinoma at 16.5% to 23.8%. Factors affecting lymph node metastasis in cases of EGG are tumor size. depth of cancer invasion, macroscopic appearance, histological growth pattern and lymphatic invasion. The small differentiated mucosal carcinomas are node-negative and eligible for limited surgery. Proponents of lymphadenectomy for every cas~ of EGG argue that since pre-operative and intra-operative assessment of the stage for gastric cancer is not always accurate, and operative mortality from oxtensive lymphadenectomy is almost the same as from simple gastrectomy, surgical intervention must be carried out in an oncological sense.

References

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