腹腔镜胃癌手术的根治性

Laparoscopic gastrectomy was applied in the surgical management of gastric cancer in recent decades[1], its application is being propagated progressively. Especially in Asian countries such as Japan and Korea, it has become a standard therapy for early stage gastric cancer[2,3]. But there are still controversies about the feasibility of laparoscopic radical gastrectomy for cancer of the stomach, and one of the most concerned questions is about the curability of laparoscopic gastrectomy. Since 1998, laparoscopic gastrectomy was performed in our institution for gastric cancer. So we would like to give an analysis about our 10-year experience about it, and make a comparison with open surgery in some aspects, so to evaluate its curability and feasibility for gastric cancer.

Materials and methods

Patients and operative procedures

All the gastric cancer patients treated with laparoscopic surgery from Jan, 1998 to Dec, 2007 were enrolled. Patients who received only laparoscopic exploration and the cases with conversion to laparotomy were excluded.

All the patient received operation under general anesthesia on a supine position with legs apart. The operation was performed with five-ports technique. The pressure of CO2 pneumoperitoneum was 8-10mmHg. Mobilization of the stomach and dissection of perigastric lymph node were performed following the Japanese Gastric Cancer Association (JGCA) gastric cancer treatment guidelines[4]. The range of gastric resection and extent of lymphatic dissection were determined according to the location of the primary lesion and clinical stage. The type of gastric resection included mucosectomy, wedge resection, segmental gastrectomy, laparoscopic (assisted) pyloric preserving gastrectomy (LPPG), laparoscopic (assisted) distal gastrectomy (LDG), laparoscopic (assisted) proximal gastrectomy (LPG) and laparoscopic (assisted) total gastrectomy (LTG). The lymphatic dissection included D0, which means no lymphatic dissection or incomplete dissection of group1 lymph nodes; D1, dissection of group 1 lymph nodes; D1+α, dissection of group 1 lymph nodes plus No. 7 and No. 8a lymph nodes if the primary focus located in the lower third of the stomach; D1+β, dissection of group 1 lymph nodes plus No. 7, No. 8a and No. 9 lymph nodes; and D2, which refers to the dissection of all the group 1 and 2 lymph nodes. In some cases, the lymphadenectomy with extent between D1 and D2 was defined as selective D2(sD2). For each operation, a self-evaluation about the curative potential was performed by the operator as Resection A, B or C according to the Japanese Classification of Gastric Carcinoma of JGCA[5].

Variables

General and clinicopathological data of eligible patients were retrieved from the medical reports and reviewed retrospectively. The variables included gender, age, pathological stage according to the Japanese Classification of Gastric Carcinoma[5], operative procedures and the extent of lymphatic dissection, the number of dissected lymph nodes and those with metastasis, the status of specimen margin and the distances from the lesion to the proximal and distal margin (proximal distance and distal distance). In cases after endoscopic mucosal resection (EMR), the distance was measured from the margin of scar following EMR.

Evaluation of curability

According to the Japanese Classification of Gastric Carcinoma of JGCA and Gastric Cancer Clinical Practice Guidelines of the National Comprehensive Cancer Network(NCCN), the criteria for the extent of a possibly curable gastric cancer operation included: no involvement of the proximal and distal margins with no less than 10 mm proximal and distal distances, enough lymph node dissection with no less than 15 lymph node dissected[6]. All the eligible patients were evaluated with this criteria. The curability related variables were compared among different operative procedures and lymph node dissections.

Comparison of curability between laparoscopic and open radical gastrectomy with D2 dissection

To compare the curability of operation between laparoscopic and open radical gastrectomy, procedures with D2 dissection were evaluated. All cases of laparoscopic gastrectomy with D2 dissection were enrolled. Cases of open radical gastrectomy (Resection A or B) with D2 dissection in recent 2 years were selected as the control group, with an exclusion of patients with combined splenectomy. The number of dissected lymph nodes, the proximal and distal distances were compared.

Statistics

All the continuous variables were expressed as mean±SD. Student’s t test, one-way ANOVA (analysis of variance) and Dunnett’s C test were used for comparison and post hoc multiple comparison of means. χ² test (Pearson Chi-Square test) was used for analysis of categorical variables.

P<0.05 was considered to be statistically significant and all the statistical analysis was performed with SPSS13.0 software.

The planned sample size for the comparison of D2 dissection between laparoscopic operation and open control group was 31. It was calculated on the basis that averagely 30.7±11.1 lymph nodes were dissected by D2 dissection with open surgery in recent two years, the hypothesis of about 25% reduction (8 lymph nodes, which mainly refereed to incomplete or no dissection of stations No. 11p, 12a and 14v) in the number of lymph nodes dissected laparoscopically, and a statistical power of 80% for two-tailed type I error of 5%.

RESULTS

Description of patients demographics

From Jan, 1998 to Dec, 2007, 404 patients with gastric cancer were treated with laparoscopic surgery in our institution. The average age was 63.3±10.6 years (ranged 32-92 years), among them there were 271 male patients (67.1%) and 133 (32.9%) females. Conversion to open surgery occurred in 13 cases and they were excluded for evaluation of curability. For the remaining 391 patients, the composition of pathological stage, procedure of operation and lymph node dissection were shown in Table 1. Most of the patients were stage I. LDG was the most popular procedure. More than 80 percent of the patients received sub-D2 dissection(D1+α, D1+β or sD2). The 18 operations with D0 dissection were all local resection except for 1 case of segmental resection. Except for 2 cases of Resection C and 8 cases of Resection B operation, the remaining 381(97.5%) cases were all classified as Resection A.

During the 1 to 113-month follow up period(median 40 months), no port-site recurrence was observed. There are 4 cases whose cancers relapsed postoperatively. Among them, peritoneal metastasis occurred in 3 cases and liver metastasis in 1 patients. .

Comparison of margin distances among procedures

The mean proximal and distal distance were 3.73±2.11cm (ranged from 0 to 14.0cm) and 5.31±3.26cm (ranged from 0.2 to 19.0cm) respectively. In 10 patients, the proximal distance was less than 1.0cm. Among these patients, 5 were wedge resection(5 among 22 cases of wedge resection, 5/22), the other 5 cases included the 2 patients with mucosectomy(2/2), 1 case of LPPG(1/129) and 2 cases of LDG(2/170). The case of 0cm proximal distance was a LDG following EMR and the resection line was just located on the margin of scar of endoscopic resection. All the specimens with proximal distance less than 1cm were negative in pathological examination. In only one case, the proximal margin after PPG was positive in spite of a 2.3cm proximal distance, and for this reason, a total gastrectomy was performed later on. All the distal margins were negative on pathological examination. Only in 5 cases the distal distance was less than 1.0cm, one was mucosectomy(1/2) and the others were all wedge resection(4/22). The differences among percentages of distance less than 1cm of each kind of procedures were statistically significant(P<0.001 for both proximal distance and distal distance). Among the 391cases, a further intraoperative resection to get a negative margin was performed in 12 cases, and 9 cases of them were done because of an insufficient proximal distance.

The differences among proximal and distal distances of different procedures were statistically significant (F=10.385 and 16.360 for proximal and distal distance respectively, P<0.001). The results of post hoc multiple comparisons were shown in Figure 1.

Comparison among different lymph node dissections

In each operation, about 22 lymph nodes were dissected averagely (21.7±12.1, ranged from 0 to 84). Lymphatic metastasis occurred in 33 patients (33/391, 8.4%), and in most cases(29/33, 87.9%) the number of affected lymph nodes was less than 6. Only in one patient, metastasis was detected in more than 15 lymph nodes (18 among 68 retrieved lymph nodes). In about 1/4 patients(100/391, 25.6%), the number of lymph nodes harvested was less than 15. Among these patients, lymphatic metastasis was detected in 11 lymph nodes of 6 patients. For each of these 6 patients, more than 10 lymph nodes were dissected and the ratio of cancer affected nodes were less than 20%.

The difference among numbers of retrieved lymph nodes of different lymph node dissection was statistically significant (F=26.499, P<0.001) and the results of post hoc multiple comparisons were shown in Figure 2.

Comparison between open and laparoscopic D2 dissection

To compare the curability related variables between open and laparoscopic D2 dissection, all the 43 cases of laparoscopic D2 dissection were selected. The control group was composed of all the 57 cases of open radical gastrectomy with D2 dissection performed in year 2006 and 2007, with exclusion of procedures with combined splenectomy. The two groups were mainly composed of distal gastrectomy (38/43 vs 50/57, P=0.921) and were homogenous except for the pathological stage of disease as most patients of the control group were affected with advanced cancer. For the extent of gastric resection, the proximal distance in open surgery was about 1cm longer than that of laparoscopic gastrectomy(open vs laparoscopic, 4.994±2.5943cm vs 4.058±1.8677cm, P=0.038), while the difference between distal distances was not significant(6.940±3.5151cm vs 7.237±4.6389cm, P=0.187). The numbers of dissected lymph nodes were similar in two groups(open vs laparoscopic, 30.70±11.094 vs 33.18±15.028, P=0.156), but the mean number of cancer affected lymph nodes was significantly higher in open surgery group (2.89±3.549 vs 0.86±2.976, P=0.04).

Discussion

The application of laparoscopic techniques in the management of gastric cancer propagated significantly in recent years. In some Asia countries like Japan and Korea, laparoscopic gastrectomy has become the standard therapy for early stage gastric cancer[2,3]. But there are still controversies about the feasibility of laparoscopic radical gastrectomy for cancer of the stomach. Due to some shortcomings such as lack of direct palpation of the primary lesion and the difficulties in meticulous dissection, the curability of laparoscopic operation for gastric cancer is an often considered problem, especially for the relatively complicated clinical anatomy of radical gastectomy. For this reason, the extent of gastric resection and lymphatic dissection were key indices for evaluating curability and oncologic feasibility of laparoscopic gastrectomy for gastric cancer.

Of course there have been some studies about the curability of laparoscopic gastrectomy and comparison between it and open surgery[7-18]. Most of these studies verified the feasibility of laparoscopic resection of gastric cancer, mainly in terms of number of lymph nodes retrieved, and distances between primary lesion and specimen margins in some cases. But on the other hand, maybe due to the limited application and immature techniques of laparoscopic gastrectomy in the early period, the sample size of most of these studies were small or even insufficient, and usually only a given kind of procedure was evaluated. During the past ten years since year 1998, more than 400 cases of laparoscopic gastrectomy were performed in our institution. Based on this data, we made an overview of our 10-year’s experience, performed comparisons among different procedures and between open and laparoscopic D2 lymphatic dissection, so to make a systematic insight about the curability of laparoscopic gastrectomy for treatment of gastric cancer.

The difficulty in determining the exact location of the primary lesion of early gastric cancer is well known, due to lack of direct palpation and the small and superficial lesion. So it is important to mark the tumor with pigmentation or clips endoscopically before operation. At the time of resection, the relationship between mark and lesion, and the distance from resection line to mark should be checked carefully, especially in the cases of the proximal resection of LDG or LPPG. In our series, the mean distances to both the distal and proximal margins were sufficient according to the JGCA gastric cancer treatment guidelines and were comparable to those reported by other authors[17,19,20], but there were still 15 patients(3.8%) in which the proximal or distal distances were less than 1cm. Furthermore, an additional resection was performed in 12 patients to get a negative or sufficient distance. When compared with open surgery, the proximal distance of laparoscopic gastrectomy was also significantly shorter. Although the statistically significant 1cm difference between 4cm and 5cm did not have so much practical meaning in early gastric cancer, such a tendency of a shorter proximal distance should be noticed and enough attention should be paid for a safe margin, especially for the proximal resection line[13]. And as most of the insufficient distances occurred in mucosectomy and wedge resection, more attention should be paid to the selection of candidate of these two procedures and to keep sufficient extent of resection.

About the lymphatic dissection, in about 1/4 patients the number of lymph nodes retrieved was less than 15, which was thought not enough for the evaluation of lymph node status according to the criteria of NCCN[6]. But as there were only very few cases with lymphatic metastasis and the ratio of affected lymph nodes was quite lower, we think that even in these cases, the lymphatic dissection was sufficient for either therapy or staging. When the lymph nodes number of different extents of lymphatic dissection were compared, significant differences were revealed among D0-D1, subD2(D1+α, D1+β, SD2) and D2 dissection. These confirmed the exact differences among different dissections. And maybe the 3 kinds of sub D2 dissection share the same role in staging for early gastric cancer as the numbers of dissected lymph nodes were not significantly different.

When compared with open surgery, it is relatively difficult to perform a standard D2 lymphadenectomy laparoscopically, mainly due to difficulties in dissection of the stations No. 11p, 12a and 14v. So although results of many studies confirmed the curability of laparoscopic surgery in terms of dissected lymph nodes number[8-12,14-18], a stratified analysis revealed that the lymph nodes retrieved by laparoscopic D2 dissection was significant less than that of open surgery, while the numbers of lymph nodes retrieved by D1+α or D1+β lymphadenectomy were same with open surgery[13]. But we think this difference was not a symbol of insufficiency of laparoscopic D2 lymphadenectomy but a result of immature operative techniques, due to the fact that the numbers of lymph nodes dissected by D1+β or D2 were almost the same in their study. The result of our series showed that the lymph nodes number harvested by laparoscopic D2 lymphadenectomy was not statistically different from that of open D2 lymphadenectomy. On the other hand, the number was significantly higher than those of other laparoscopic lymphadenectomies. Based on this result, we would like to say that laparoscopic operation possess the same capacity with open surgery in terms of lymph node dissection, at least in the extent of no more than D2 dissection.

Based on the abovementioned results, we think that laparoscopic operation is an oncologically safe procedure for the management of gastric cancer, at least for stage I and II diseases. Although now it is earlier to get a endpoint index such as survival rate, according to these curability related variables, a satisfied survival of gastric cancer patients treated laparoscopically was prospected in a not far future.