For patients with EGC without nodal metastasis, the generally agreed-on action is minimally invasive surgery. For patients with EGC with possible lymph node metastasis, however, is it appropriate to limit the extent of lymph node dissection?
Kikuchi et al. showed that treatment results using radical surgery for node-positive EGC patients were excellent in patients whose lymph node metastasis was limited to perigastric lymph nodes. They concluded that the lack of a sufficiently precise diagnostic tool that could predict lymph node metastasis in most patients suggested that radical gastrectomy combined with lymphadenectomy was necessary when minimally invasive treatments were not indicated. Extended lymphadenectomy improved postoperative survival in patients with N0 submucosal cancer. The significance of these findings has been argued for a long time. The clinical effects of prophylactic lymphadenectomy might be explained, however, by the recent, improved understanding of micrometastasis including 1) metastasis limited to the perinodal sinus, 2) the correlation between lymphatic involvement and lymph node metastases and 3) the occurrence of skip metastases, which has reportedly occurred in 7% of EGC cases.
On the other hand, some investigators suggest changing the extent of lymph node dissection in cases of EGC, because 75% of node-positive submucosal tumors are limited to the N1 group
(1,
2 ).
Takaki Yoshikawa et al. conducted a retrospective study 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.
They concluded that 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
( 3 ).
Shinya Shimada et al. propose a practical treatment protocol for early gastric cancer on the basis of the clinicopathologic and prognostic data of 1051 patients with early gastric cancer. The pathologic analysis of specimens from endoscopic mucosal resection is the major determinant of the need for further treatment in this protocol. Because macroscopic examinations sometimes fail to diagnose the difference between M and SM or the presence of ulceration or ulceration scar, endoscopic mucosal resection should be used initially to allow options for the best surgical treatment for the patients with early gastric cancer.
All mucosal lesions without ulceration or ulceration scar should be treated by endoscopic mucosal resection. Those tumors out of reach for endoscopic mucosal resection should be treated by laparoscopic local resection. If histologic examination of the endoscopic mucosal resection specimen reveals complete resection, the treatment is complete and the patient only needs follow-up. If histologic examination reveals an incomplete resection, laparoscopic local resection is required. For a mucosal tumor with ulceration or ulceration scar, or an SM1a tumor, laparoscopy-assisted gastrectomy with D1 is indicated. SM1b tumors require gastrectomy with D2 lymph node dissection. Tumors macroscopically diagnosed as M with ulceration or ulceration scar should be treated by laparoscopy-assisted gastrectomy with D1. All macroscopic SM cancer should be treated by gastrectomy with D2
( 4 ).
In the Kunisaki et al study, univariate and multivariate analyses demonstrated that depth of invasion independently predicted lymph node metastasis in patients with early gastric cancer. In patients with mucosal cancer, tumor diameter proved to be an independent predictor of lymph node metastases.
Their results suggest strongly that dissection of regional lymph nodes in patients with mucosal cancer measuring less than 30 mm is unnecessary. The value of 30 mm was obtained as a safety value from the following formula: Mean diameter - Standard deviation of tumor with metastatic lymph nodes.
Mucosal cancers measuring 30 mm or greater should be locally resected with dissection of the perigastric lymph nodes nearest the tumor. When they locally resect a tumor, they suggest at least a 2-cm margin of normal stomach tissue in early gastric cancer. Thus, taking the deformity of the resected stomach into consideration, the area of resected tissue depends on the location of the tumor . Moreover, if the tumor diameter is 50 mm or greater, local resection could also result in a deformed remnant stomach, and so local resection should be avoided.
In mucosal cancer, lymph node dissection to the group 2 station (D2 resection) appears to be an excessively aggressive procedure except in rare situations. Even routine lymph node dissection of all group 1 nodes (D1 resection) may be excessive. Thus, individual lymph node dissection procedures should be selected on the basis of the clinicopathologic features diagnosed preoperatively and intraoperatively.
The intraoperative practice of immediate pathologic diagnosis of resected lymph nodes is very effective. If metastatic lymph nodes are detected in an intraoperative pathologic examination, the dissection field can be expanded, so that, for example, D1 or D2 resection would be possible after partial dissection of the perigastric lymph nodes. If the tumor is palpable intraoperatively, which suggests that it has invaded as far as or deeper than the submucosal layer, these limited operative procedures should not be carried out in preference to a standard gastrectomy with D2 resection.
In patients with submucosal cancer, it was not possible to predict lymph node metastasis by any pathologic variables or to differentiate between the pathologic characteristics in patients with group 1 or group 2 nodal metastases. It is thus difficult to suggest minimizing the dissection field in patients with submucosal cancer. However, when the sites of lymph node metastases are considered, less invasive surgery is possible in each tumor site.
In the lower third of the stomach, distal gastrectomy with a D1 resection should be accompanied with dissection of the lymph nodes along the left gastric artery, anterosuperior common hepatic artery, celiac artery and proximal portion of the splenic artery.
When an early gastric cancer invading the submucosa is in the middle third of the stomach, lymph node dissection similar to that for the lower third of the stomach seems to be indicated.
In contrast, for tumors in the upper third of the stomach, fundectomy with D1 and dissection of lymph nodes along the left gastric artery, anterosuperior common hepatic artery, celiac artery and the proximal part of the splenic artery appear appropriate.
Because the incidence of group 2 lymph node metastases was low, even in submucosal cancer, dissection of group 2 lymph nodes can be omitted in compromised hosts or older patients.
The reduction of the area of the stomach resected and the area of lymph node dissection, while maintaining curability, should improve the patient's quality of life by avoiding some postgastrectomy complications.
In Japan, it is generally agreed that endoscopic mucosal resection is indicated in mucosal cancer patients with protruding (measuring 20 mm or less) or depressed (measuring 10 mm or less) type tumors. Furthermore, these cases should be histologically confined to the differentiated type
( 5 ).
In the Shimoyama study patterns and sites of nodal involvement were retrospectively investigated in 294 patients with solitary submucosal gastric cancer in association with other clinicopathologic characteristics, including pre- and intraoperative evaluations of cancer depth (cT) and nodal involvement (cN).
Among the early (cT1) and node-negative (cN0) cancer, intestinal (<= 1.5 cm) and diffuse types (<= 1.0 cm) of submucosal cancer showed low incidences of nodal involvement (3%) confined to the first tier. When the cancer exceeded these cutoff diameters, positive nodes of the second tier were confined to three priority stations (left gastric, common hepatic, and celiac arteries) at an incidence of 2.3%. Perigastric and preferential dissection of these three node stations (modified D2 dissection) showed survival benefits identical to those of a conventional D2 dissection.
Therefore when submucosal cancer is evaluated as cT1cN0, a virtually sufficient minimized scope of lymphadenectomy is a D1 dissection for that within the cutoff diameter and a modified D2 dissection for that exceeding the cutoff diameter. These two types of dissection can even cover the infrequently observed node-positive stations and can realize no residual disease at surgery
( 6 ).
According to the Takeno study it seems difficult to predict the progression of EGC with SM invasion from the data currently obtained by preoperative endoscopic examination. It was suggested that less invasive surgery could be scheduled only for simple protuberance type cases that were <2 cm in diameter. Radical gastrectomy and D2 lymph node dissection is required, in open surgery or laparoscopic surgery, for any other type of EGC with SM invasion.
However, when lymphatic vessel invasion is observed pathologically after local resection without lymphadenectomy, strict follow-up with a short interval or a second surgery with D2 lymphadenectomy should be required because of the high risk of lymph node recurrence
( 11 ).
Seto et al affirm that limited surgery, in particular local resection, should be employed for EGC without lymph node metastasis, whereas additional extended lymphadenectomy is necessary when nodal involvement is observed intraoperatively or on histological examination of the resected specimen. However, most patients who have a diagnosis of M- cancer and N0 can benefit from local resection.
N0 and M- cancers, m-cancers less than 4 cm in diameter, and sm-cancers no larger than 1 cm in diameter may be appropriate indications for limited surgery
( 17 ).
Based on their large series of cases ( 5265 patients ), Gotoda et al. have been able to clarify the risks associated with EGC and to propose expansion of the criteria for local treatment. However, accurate histological evaluation of the resected specimen is essential to avoid recurrence for such EGCs that should be cured.
None of the 1230 well differentiated intramucosal cancers of less than 30mm diameter regardless of ulceration findings, were associated with metastases. None of the 929 lesions without ulceration were associated with nodal metastases regardless of tumor size. Similarly to findings for intramucosal cancers, for submucosal lesions, there was a significant correlation between tumor size larger than 30 mm and lymphatic-vascular involvement with an increased risk of LNM. None of the 145 differentiated adenocarcinomas of less than 30 mm diameter without lymphatic or venous permeation were associated with LNM, provided that the lesion had invaded less than 500 micronm into te submucosa ( 19 ).
Yamaguchi et al. studied 45 patients with node-positive mucosal gastric cancer who underwent gastrectomy with lymphadenectomy at the National Cancer Center Hospital, Tokyo. The majority of patients ( 87% ) were treated with D2 lymphadenectomy. The metastasis was confined to the perigastric nodes ( pN1 by the Japanese classification ) in 30 patients ( 67% ). The number of positive nodes was less than seven ( pN1 by TNM ) in 42 patients ( 93% ). Two patients had para-aortic nodal metastasis. The median follow up period was 11 years. Four patients died of definite or possible recurrent disease and the disease specific 5 and 10 year survival rates were 95 and 89% respectively ( 20 ).
Higashi et al in a retrospective study analyze the distribution of lymph node metastases, including micrometastases, according to the location of the gastric cancer with submucosal invasion.
The distribution of lymph node metastasis for tumors at upper or middle portions of the stomach was mainly found along the left gastric artery. The distribution of lymph node metastasis for tumors in the lower and lesser curvature varied. Immunohistochemical analysis found that 15 of 23 patients with lymph node metastasis found by histologic examination had micrometastases. The presence of two or more lymph node micrometastases was found in these 15 patients, and they were distributed in another stations, including distant nodes. The incidence of micrometastasis was
24.2% (23/95) in pN0 patients. Lymph node micrometastases were confined to regional nodes near the primary tumor.
In the present study, the incidence of micrometastasis in the lymph nodes was quite high, even when routine histologic examination did not reveal lymph node metastases. The authors recommend that a patient found to have lymph node metastasis by preoperative imaging methods or histologic diagnosis of intraoperative frozen sections should undergo a sufficient lymphadenectomy (e.g., D2
lymph node dissection) because there is a distinct possibility that micrometastases are present in another region. On the other hand, lymph node metastasis in this study was limited to the area near the primary tumor in patients with micrometastasis alone. If sentinel node navigation surgery is introduced in gastric cancer surgery, lymph node micrometastasis should be sought intraoperatively by immunohistochemical examination of a frozen section. If micrometastasis cannot be detected by such a method, they suggest that a reduced form of lymphadenectomy is likely to be adequate for
such patients ( 21 ).
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