Comparison efficacy and safety of total laparoscopic gastrectomy and laparoscopically assisted total gastrectomy in treatment of gastric cancer

Abstract

BACKGROUND

The development of laparoscopic technology has provided a new choice for surgery of gastric cancer (GC), but the advantages and disadvantages of laparoscopic total gastrectomy (LTG) and laparoscopic-assisted total gastrectomy (LATG) in treatment effect and safety are still controversial. The purpose of this study is to compare the efficacy and safety of the two methods in the treatment of GC, and to provide a basis for clinical decision-making.

AIM

To compare the efficacy of totally LTG (TLTG) and LATG in the context of radical gastrectomy for GC. Additionally, we investigated the safety and feasibility of the total laparoscopic esophagojejunostomy technique.

METHODS

Literature on comparative studies of the above two surgical methods for GC (TLTG group and LATG group) published before September 2022 were searched in the PubMed, Web of Science, Wanfang Database, CNKI, and other Chinese and English databases. In addition, the following search keywords were used: Gastric cancer, total gastrectomy, total laparoscopy, laparoscopy-assisted, esophagojejunal anastomosis, gastric/stomach cancer, total gastrectomy, totally/completely laparoscopic, laparoscopic assisted/laparoscopy assisted/laparoscopically assisted, and esophagojejunostomy/esophagojejunal anastomosis. Review Manager 5.3 software was used for the meta-analysis after two researchers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies.

RESULTS

After layer-by-layer screening, 258 pieces of literature were recovered, and 11 of those pieces were eventually included. This resulted in a sample size of 2421 instances, with 1115 cases falling into the TLTG group and 1306 cases into the LATG group. Age or sex differences between the two groups were not statistically significant, according to the meta-analysis, however the average body mass index of the TLTG group was considerably higher than that of the LATG group (P = 0.01). Compared with those in the LATG group, the incision length in the TLTG group was significantly shorter (P < 0.001), the amount of intraoperative blood loss was significantly lower (P = 0.003), the number of lymph nodes removed was significantly greater (P = 0.04), and the time of first postoperative feeding and postoperative hospitalization were also significantly shorter (P = 0.03 and 0.02, respectively). There were no significant differences in tumor size, length of proximal incisal margin, total operation time, anastomotic time, postoperative pain score, postoperative anal exhaust time, postoperative anastomosis-related complications (including anastomotic fistula, anastomotic stenosis, and anastomotic hemorrhage), or overall postoperative complication rate (P > 0.05).

CONCLUSION

TLTG and esophagojejunostomy are safe and feasible. Compared with LATG, TLTG has the advantages of less trauma, less bleeding, easier access to lymph nodes, and faster postoperative recovery, and TLTG is also suitable for obese patients.

Key Words: Total laparoscopic gastrectomy; Laparoscopically assisted total gastrectomy; Gastric cancer; Meta-analysis

Core Tip: This study used a systematic review and meta-analysis to determine how well and safely laparoscopic total gastrectomy and laparoscopically assisted total gastrectomy can treat gastric cancer (GC). Clinical trial data from relevant literature were collected and analyzed to evaluate the differences between the two surgical methods in terms of surgical effect, postoperative complications, and postoperative quality of life. Through the systematic synthesis of the results, an objective evaluation of the advantages and disadvantages of these two surgical methods is provided, which provides a scientific basis for clinicians to optimize the treatment of GC patients.

INTRODUCTION

Surgery has been used for more advanced cases of gastric cancer (GC) as well as earlier cases of the disease[1]. Additionally, surgical methods have changed from laparoscopic-assisted radical gastrectomy to total laparoscopic radical gastrectomy[2]. However, reconstructing the digestive tract through total laparoscopic surgery is difficult. This is especially true for totally laparoscopic total gastrectomy (TLTG) and esophagojejunostomy, which require advanced endoscopic techniques and are not sure how well they work. There is also debate about whether they are safe and possible[3].

This study will conduct a meta-analysis of published comparative studies on TLTG and laparoscopic-assisted total gastrectomy (LATG) in the treatment of GC, aiming to observe the difference in efficacy of the two surgical methods in the treatment of GC and discuss the safety and feasibility of TLTG for GC and esophagojejunostomy. The aim is to obtain the best evidence to guide clinical practice.

MATERIALS AND METHODS

Literature retrieval strategy

The subject of this study was a controlled clinical study of TLTG and LATG for GC published before September 2023. The search databases used were PubMed, Web of Science, Wanfang Database, CNKI, and other Chinese and English databases. Keywords in the Chinese search were GC, total gastrectomy, total laparoscopy, and laparoscopy-assisted esophagojejunostomy. The key words in English were gastric/stomach cancer, total gastrectomy, totally/completely laparoscopic, laparoscopic assisted/laparoscopic assisted/laparoscopic assisted, and esophagojejunostomy/esophagojejunal anastomosis. The literature was reviewed by hand.

Inclusion criteria

All patients were confirmed by pathological examination to have GC; (2) all studies involved the comparison of the efficacy of TLTG and LATG in GC; (3) accurate and important clinical data should be provided, especially the incidence of postoperative anastomosis-related complications; (4) original statistical data should be provided, such as the mean and standard deviation of continuous variables and specific values of binary variables; and (5) for the literature of the same unit, recently published literature with higher quality statistics should be selected.

Exclusion criteria

(1) Patients with cancers other than those of the stomach; (2) patients who underwent distal gastrectomy, proximal gastrectomy, or palliative total gastrectomy; (3) patients who received neoadjuvant chemotherapy before surgery; and (4) patients whose clinical data, such as the rate of anastomosis-related complications, were not available.

Data extraction and quality evaluation

Using a unified data collection table, two system evaluators independently extracted the following data from the included literature: first author, data source (country), publication time, number of cases, patient age, sex, body mass index (BMI), length of surgical incision, total surgical time, anastomosis time, intraoperative blood loss, number of lymph node removals, tumor size, length of proximal incisal margin, postoperative pain score (visual analog scale), postoperative anal exhaust time, postoperative eating time, postoperative hospital stay, postoperative surgery overall complication rate, postoperative anastomosis-related complication rate, and other indicators. Disagreements were resolved after discussion with a third researcher.

The Newcastle-Ottawa Scale (NOS) was used to score the quality of the included studies. The evaluation content included three main aspects: research selection, research comparison, and interesting research results. The maximum possible score was 9 points, and an overall score > 6 was considered to indicate high-quality research.

Statistical analysis

The Cochrane Collaboration provided RevMan 5.3 software for statistical analysis. The odds ratio of binary data was calculated as the combined statistic, and the weighted mean difference (WMD) of continuous variable data was calculated as the combined statistic. The results were expressed with a 95%CI, and the test level was α = 0.05. The incidence of postoperative anastomosis-related complications was measured by a funnel plot to determine publication bias. A heterogeneity test was conducted for all included studies. An I² ≤ 50% indicated that there was no significant heterogeneity among all studies. A fixed effects model (F model) was used for combined analysis; otherwise, a random effects model (R model) was used. To avoid the influence of different surgical operators and surgical methods on the results, the R model was adopted for the analysis of clinical data related to surgery.

RESULTS

Literature retrieval results and included research characteristics

Based on the inclusion and exclusion criteria (Figure 1), 11 papers[4-14] about clinical control studies of TLTG and LATG in GC were ultimately included. These were all nonrandomized controlled studies. There were 2421 clinical cases, including 1115 in the TLTG group and 1306 in the LATG group, mainly from China, South Korea, and Japan. According to the NOS quality score, nine studies[4-12] were considered to be of high quality, all of which compared the two groups by age and sex. Seven of them[4-6,8-11] also compared the body mass indices of the two groups, and the results showed that there was no significant difference in age or sex between the two groups (P = 0.60 and 0.61, respectively), while the average BMI of the TLTG group was significantly greater than that of the LATG group (P = 0.01). The basic information and quality evaluation of the included studies are shown in Table 1.

Figure 1 Flow chart of literature retrieval and screening.

Table 1 Basic information of included literature.

Ref.	Countries	Sample size		Age (yr, mean ± SD)		Body mass index (kg/m²), mean ± SD)		NOS score
		TLTG group	LATG group	TLTG group	LATG group	TLTG group	LATG group
Kim et al[4], 2013	South Korea	90	23	58.0 ± 10.8	56.8 ± 14.2	23.2 ± 2.9	22.2 ± 1.8	7
Kim et al[5], 2016	South Korea	27	29	60.8 ± 9.1	59.3 ± 13.1	24.0 ± 2.9	23.3 ± 3.2	7
Chen et al[6]	China	108	145	59.4 ± 11.1	57.3 ± 12.5	23.5 ± 3.5	23.1 ± 4.2	8
Gong et al[7], 2017	South Korea	421	266	57.78 ± 11.2	55.69 ± 11.96	/	/	7
Huang et al[8], 2017	China	51	456	55.5 ± 12.1	61.6 ± 11.2	22.5 ± 13.1	22.3 ± 13.5	7
Lu et al[9], 2016	China	25	25	59+8.9	58.4 ± 7.7	22.5 ± 2.5	22.9 ± 3.7	8
Cui et al[10]	China	16	47	61.3 ± 13.	67.6+13	22.8 ± 1.2	23.2+1.3	8
Hong et al[11], 2017	China	183	190	58 ± 11	60 ± 10	23 ± 3	22 ± 3	8
Hua et al[12], 2017	China	47	47	48.51 ± 2.47	48.67 ± 2.51		/	7
Xiao et al[13], 2015	China	30	32	/	/		/	6
Ito et al[14], 2014	Japan	117	46			/	/	6

TLTG: Totally laparoscopic total gastrectomy; LATG: Laparoscopic-assisted total gastrectomy; NOS: Newcastle-Ottawa Scale.

Meta-analysis results

The meta-analysis results of this study showed that, compared with those in the LATG group, the length of surgical incisions in the TLTG group was significantly shorter (P < 0.001), the amount of intraoperative blood loss was significantly less (P = 0.003), and the number of lymph nodes removed was significantly greater (P = 0.04). The time of first feeding and hospital stay were also significantly shorter (P = 0.03 and 0.02, respectively), but there were no significant differences in tumor size, length of proximal incisal margin, operation time, postoperative pain score, postoperative anal exhaust time, or postoperative complication rate (P > 0.05). Table 2 summarizes the intraoperative and postoperative information of the 11 studies included in this paper.

Table 2 Intraoperative and postoperative clinical data and analysis results included in the literature.

Observation indicators	References	Sample size (examples)		Heterogeneity	Effect model	Comprehensive effect value	95%CI	P value
		TLTG group	LATG group
Operative time	9	664	1008	< 0.001, 83%	R	WMD = 7.62	-4.35-19.59	0.21
Match time	3	165	206	< 0.001, 86%	R	WMD = 6.40	-2.28-15.08	0.15
Tumor size	7	905	1134	0.02, 61%	R	WMD = -0.29	-0.65-0.17	0.12
Proximal edge distance	5	597	512	< 0.001, 84%	R	WMD = -0.22	-0.86-0.41	0.49
Intraoperative bleeding volume	9	604	1017	< 0.001, 84%	R	WMD = -26.29	-43.70 to -8.88	0.003
Number of lymph node removals	9	973	1235	0.02, 57%	R	WMD = 1.78	0.06-3.50	0.04
Postoperative pain score
On the first day after surgery (8:00 am)	2	511	289	0.91, 0%	R	WMD = 0.03	-0.20-0.27	0.78
On the 3rd day after surgery (8:00 am)	2	511	289	0.46, 0%	R	WMD = 0.08	-0.13-0.28	0.45
Postoperative peak pain	2	511	289	0.09, 66%	R	WMD = 0.17	-0.71-1.05	0.70
Postoperative anal exhaust time	8	547	962	< 0.001, 89%	R	WMD = -0.22	-0.56-0.13	0.22
Postoperative feeding time	8	547	962	< 0.001, 86%	R	WMD = -0.56	-1.07 to -0.06	0.03
Postoperative hospitalization time	9	577	994	< 0.001, 93%	R	WMD = -1.53	-2.83 to -0.23	0.02
The incidence of anastomotic complications	11	1115	1306	0.74, 0%	R	OR = 0.71	0.47-1.06	0.09
Anastomotic fistula	11	1115	1306	0.53, 0%	R	OR = 0.70	0.42-1.18	0.18
Anastomotic stenosis	11	1115	1306	0.85, 0%	R	OR = 0.84	0.41-1.71	0.63
Anastomotic bleeding	8	439	817	0.93, 0%	R	OR = 0.86	0.34-2.15	0.74
Overall incidence of complications	9	947	804	0.81, 0%	R	OR = 0.93	0.71-1.21	0.58

TLTG: Totally laparoscopic total gastrectomy; LATG: Laparoscopic-assisted total gastrectomy; WMD: Weighted mean difference.

Intraoperative data comparison

Four of the eleven studies in this paper[10-13] examined the length of surgical incisions. The incisions in the TLTG group were significantly shorter than those in the LATG group (WMD = -4.21, 95%CI: -5.51 to -2.91, P < 0.001; Figure 2A). The total operation time was compared in nine studies[4-6,8-12,14]. There was no statistically significant difference in the total operation time between the two groups (WMD = 7.62, 95%CI: -4.35–19.59, P = 0.21; Figure 2B). Three studies[5,6,13] compared surgical anastomosis time, and the results indicated that there was no statistically significant difference in the anastomosis time between the TLTG group and the LATG group (WMD = 6.40, 95%CI: -2.28-15.08, P = 0.15; Figure 2C). Nine studies[5,6,8-14] compared the amount of blood loss during surgery. Much less blood was lost in the TLTG group than in the LATG group (WMD = -26.29, 95%CI: -43.70 to -8.88, P = 0.003; Figure 2D).

Figure 2 Meta-analysis of efficacy and safety of totally laparoscopic total gastrectomy and laparoscopic-assisted total gastrectomy in the treatment of gastric cancer. A: Surgical incision length; B: Operative time; C: Surgical anastomosis time; D: Intraoperative blood loss; E: The number of lymph nodes removed; F: Tumor size; G: Proximal incisal margin length; H: Postoperative anal exhaust time; I: Postoperative eating time; J: Postoperative hospital stay meta-analysis. TLTG: Totally laparoscopic total gastrectomy; LATG: Laparoscopic-assisted total gastrectomy.

In nine studies[4-8,10-13], the number of lymph nodes removed during surgery was compared. More lymph nodes were removed in the TLTG group than in the LATG group (WMD = 1.78, 95%CI: 0.06-3.50; P = 0.04; Figure 2E). Seven studies[4-9,11] examined the sizes of tumors that had been removed. The results showed that there was no statistically significant difference in the sizes of the tumors between the two groups (WMD = -0.29, 95%CI: -0.65-0.07, P = 0.12; Figure 2F). Five studies[5-7,9,10] compared the length of the proximal incisal margin, and the results indicated that there was no statistically significant difference in the length of the proximal incisal margin between the TLTG group and the LATG group (WMD = -0.22, 95%CI: -0.86-0.41, P = 0.49; Figure 2G).

Postoperative data comparison

Two studies[4,7] compared postoperative pain scores, and the results indicated that there was no statistically significant difference in postoperative pain peak values or pain scores at the 1st and 3rd days after surgery between the TLTG group and the LATG group (P = 0.70, P = 0.78, and P = 0.45, respectively). In 8 studies[4-6,8-12], the postoperative anal exhaust time was compared. There was no significant difference between the two groups (WMD = -0.22, 95%CI: -0.56-0.13, P = 0.22; Figure 2H). Eight studies[4-6,8-12] compared the first feeding after surgery. The first feeding in the TLTG group occurred significantly earlier than that in the LATG group (WMD = -0.56, 95%CI: -1.07 to -0.06, P = 0.03; Figure 2I).

A total of nine studies[4-6,8-13] compared the length of hospital stay after surgery. The TLTG group had a significantly shorter length of hospital stay than did the LATG group (WMD = -1.53, 95%CI: -2.83 to -0.23, P = 0.02; Figure 2J). The 11 studies included in this study all compared the incidence of postoperative anastomosis-related complications, and the results indicated that there was no significant difference between the two groups (OR = 0.71, 95%CI: 0.47-1.06, P = 0.09; Figure 3 and Table 2). The incidence of anastomotic fistula in the TLTG and LATG groups was 2.51% and 3.98%, respectively (OR = 0.70, 95%CI: 0.42-1.18, P = 0.18); the incidence of anastomotic stenosis was 1.43% and 1.45%, respectively (OR = 0.84, 95%CI: 0.41-1.71, P = 0.63); and the incidence of anastomotic hemorrhage was 1.59% and 1.22%, respectively (OR = 0.86, 95%CI: 0.34-2.15, P = 0.74; Figure 4). Nine studies[4-7,9-13] examined the overall rate of complications after surgery. The results showed that there was no statistically significant difference between the two groups in this rate (OR = 0.93, 95%CI: 0.71-1.21; P = 0.58). In all the studies included in this study, no surgery-related deaths occurred in either group, and no second surgery was reported.

Figure 3 Literature quality evaluation chart.

Figure 4 Funnel plot of literature publication bias. A: Funnel plot of publication bias in surgical incision length; B: Funnel plot of publication bias in operative time; C: Funnel plot of publication bias in surgical anastomosis time; D: Funnel plot of publication bias in intraoperative blood loss; E: Funnel plot of publication bias in the number of lymph nodes removed; F: Funnel plot of publication bias in tumor size.

Sensitivity analysis

The incidence of postoperative anastomosis-related complications is an important index for evaluating surgical efficacy, and it is also the focus of this study. Since low-quality research data may affect the overall research results[15], when the two studies of lower quality[13,14] were removed, the incidence data of postoperative anastomosis-related complications from nine high-quality studies[4-12] were pooled and analyzed. The number of complications related to the anastomosis after surgery did not differ significantly between the TLTG and LATG groups (OR = 0.72, 95%CI: 0.47-1.09, P = 0.12), which suggests that the addition of two lower-quality studies did not change the initial results.

This study focused on the safety and feasibility of in vivo esophagojejunostomy. Different anastomosis methods or anastomosis instruments may have affected the final results of the study. Among the 11 studies included in this paper[4-14], 9 items[4,5,7-13] were reconstructed by Roux-en-Y anastomosis. Among them, 8 items[4,5,7-10,12,13] were all esophagojejunostomies using linear staplers. Huang et al[8] reported a new anastomosis method (the isometric retrocut and overlap method of the jejunum). Ito et al[14] used circular staplers for anastomosis, and the other two[6,11] used various anastomosis methods. Therefore, the last four studies[6,8,11,14] were removed from further sensitivity analysis. When the four studies were removed, there was no significant change in the results of any of the studies (Figure 3).

Publication bias

In this paper, funnel plots were drawn for the incidence of postoperative anastomosis-related complications in the TLTG group and the LATG group. The results of the plots showed basic symmetry, suggesting no clear publication bias (Figure 4). Egger linear regression analysis further confirmed that there was no significant publication bias in the included literature (P > 0.05).

DISCUSSION

Laparoscopic-assisted radical gastrectomy has become the most commonly used surgical method for treating GC[15]. With the improvement of endoscopy technology, the surgical path for treating GC has gradually moved toward full laparoscopy. However, due to the late development of total laparoscopic radical gastrectomy, high technical requirements, and difficulty, most medical units do not regard it as the preferred method for GC surgery[16]. Digestive tract reconstruction is the focus and difficulty of laparoscopic radical gastrectomy for treating GC. In total laparoscopic radical gastrectomy for GC, esophagojejunal anastomosis is very difficult due to its "anatomical particularity" (high anastomosis site, narrow operating space, etc.), and it is also the key to successful surgery. Therefore, the safety and feasibility of TLTG and esophagojejunostomy are of great concern.

There are many ways to reconstruct the digestive tract after laparoscopic total gastrectomy[17]. Roux-en-Y anastomosis, which is currently the main surgical method for reconstruction, can effectively reduce reflux esophagitis and maintain good nutritional status[18]. In previous studies, two methods of in vivo esophagojejunostomy were introduced, including manual suturing and mechanical suturing (linear stapling and circular stapling)[19]. Using linear staplers for reconstruction inside the body during endoscopy can make tension-free anastomosis possible, preventing damage to nearby structures[20]. Unlike circular staplers, linear staplers can be inserted into the abdominal cavity through a cannula hole (Tocar) to complete digestive tract reconstruction without the need for an auxiliary incision. Gong et al[7] suggested that TLTG with a linear stapler was more suitable for endoscopic surgery than LATG with a circular stapler and recommended it for the treatment of upper GC. Nine of the eleven studies in this paper[4,5,7-13] used Roux-en-Y anastomosis to reconstruct the digestive tract. Huang et al[8] reported a new anastomosis method called the isometric retroincision and overlapping jejunum method. Eight studies[4,5,7-10,12,13] used linear staplers to connect the esophagus and jejunum. Ito et al[14] used circular staplers, and two studies[6,11] used more than one method of anastomosis. The results of this meta-analysis showed that the incidence of postoperative anastomosis-related complications (including anastomotic fistula, anastomotic stenosis, and anastomotic hemorrhage) was lower in the TLTG group than in the LATG group (4.39% and 6.20%, respectively), and there was no statistically significant difference between the two groups (P = 0.09). Some studies[6,8,11,14] that used different anastomosis methods or devices were removed from the sensitivity analysis in this paper. The results of these studies did not change significantly. Therefore, in vivo digestive tract reconstruction is safe and feasible. To confirm the effectiveness of different anastomotic methods, further long-term and large-scale randomized controlled trials are needed.

Studies[21-25] have shown that total laparoscopic radical gastrectomy and esophagojejunostomy for GC can increase the duration of surgery and even cause much more blood to be lost during surgery. The results of this meta-analysis showed that there were no statistically significant differences in the total operation time or anastomotic time between the TLTG group and the LATG group, and the intraoperative blood loss in the TLTG group was significantly less than that in the LATG group[26-28]. The reasons for the low blood loss in the TLTG group were as follows: (1) there was no auxiliary abdominal incision in the TLTG, and the intraperitoneal wound was small; (2) TLTG can reduce excessive tissue traction and reduce the risk of bleeding; and (3) laparoscopic surgical techniques may affect intraoperative blood loss, and operators differ between the TLTG and LATG groups. According to relevant studies, TLTG will take much less time after the surgeon learns and practices total laparoscopic distal gastrectomy (residual stomach and duodenal anastomosis). Therefore, this may be related to the operator's proficiency in endoscopic surgery.

The main difference between complete laparoscopic and laparoscopic-assisted radical gastrectomy for GC lies in the different paths of digestive tract reconstruction[29]. The former is completed under laparoscopy (in vivo), while the latter requires an auxiliary incision in vitro. However, for obese patients, total gastrectomy and esophagojejunal anastomosis in vitro with the aid of an abdominal incision are very difficult to perform, and the surgical incision must be prolonged, which ultimately extends the operation time and even increases the surgical risk and postoperative pain of patients[30-33]. The results of this meta-analysis showed that the average BMI of the TLTG group was significantly greater than that of the LATG group, and the length of surgical incision was significantly shorter than that of the LATG group; however, there were no statistically significant differences in the total operation time, anastomotic time, or postoperative pain score between the two groups. In conclusion, complete LGT and esophagojejunostomy in obese patients are still safe, feasible, and even more advantageous.

Most of the studies[34-38] included in this paper only compared the short-term efficacy of TLTG and LATG, and the results showed that the postoperative feeding time and postoperative hospital stay in the TLTG group were significantly shorter than those in the LATG group, while there were no significant differences in the postoperative anal venting time, postoperative anastomosis-related complications, or overall complications between the two groups[39-41]. Therefore, compared with patients in the LATG group, patients in the TLTG group achieved faster postoperative recovery.

This study has several limitations. First, we focused on the safety and feasibility of in vivo esophagojejunostomy, but laparoscopic surgical skills may affect surgical outcomes, and surgical operators differ between the TLTG and LATG groups. Second, most of the studies that were examined did not report or evaluate the long-term effectiveness of total laparoscopic radical gastrectomy for GC. This means that the differences in long-term effectiveness between TLTG and LATG need to be studied further. In addition, all the included studies were retrospective studies and did not include blinded or randomized controlled trials, and the sample size may not be sufficient; therefore, a large-scale randomized care trial study of the two groups is needed in the future.

CONCLUSION

TLTG under full laparoscopy is technically safe and feasible, and it is equally suitable or even more beneficial for obese patients. Compared with LATG, TLTG has the advantages of less trauma, less bleeding, easier access to lymph nodes, faster postoperative recovery, etc. Total laparoscopic radical gastrectomy is likely to be a future direction for the treatment of GC.