AIM: To systematically review the surgical outcomes of totally laparoscopic gastrectomy (TLG) vs open gastrectomy (OG) for gastric cancer.

METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was conducted. All original studies comparing TLG with OG were included for critical appraisal. Data synthesis and statistical analysis were carried out using RevMan 5.1 software.

RESULTS: One RCT and 13 observational studies involving 1532 patients were included (721 TLG and 811 OG). TLG was associated with longer operation time [weighted mean difference (WMD) = 58.04 min, 95%CI: 37.77-78.32, P < 0.001], less blood loss [WMD = -167.57 min, 95%CI: -208.79-(-126.34), P < 0.001], shorter hospital stay [WMD = -3.75 d, 95%CI: -4.88-(-2.63), P < 0.001] and fewer postoperative complications (RR = 0.71, 95%CI: 0.58-0.86, P < 0.001). The number of harvested lymph nodes, surgical margin, mortality and cancer recurrence rate were similar between the two groups.

CONCLUSION: TLG may be a technically safe, feasible and favorable approach in terms of better cosmesis, less blood loss and faster recovery compared with OG.

Laparoscopy-assisted gastrectomy (LAG) for gastric cancer was first reported in 1994[1], and has undergone rapid development and gained popularity in the past few decades. Laparoscopic surgery has multiple benefits compared with open gastrectomy (OG) such as minimal invasiveness, the possibility of practical maneuvers based on anatomic understanding through a good visual field and magnification, earlier patient recovery after surgery and better postoperative quality of life[2-5]. During LAG, lymph node dissection is performed laparoscopically. However, a mini-laparotomy is performed in the epigastrium, through which the anastomosis is performed under direct vision. Totally laparoscopic gastrectomy (TLG) preserves the integrity of the abdominal wall, which is considered to be incisionless, except for the trocar wounds[6], and is a laparoscopic approach for intracorporeal anastomosis without auxiliary incision and contact with the tumor. TLG represents the evolution of LAG. However, there are some technical difficulties when performing intracorporeal anastomosis, thus LAG is still a common approach in laparoscopic surgery[7]. The safety and efficacy of LAG has been demonstrated in large retrospective studies and randomized controlled trials (RCTs)[2,3,8-11]. In addition, several meta-analyses and systematic reviews have been published on LAG[12-15]. Similar studies have not been conducted to assess the potential benefits and disadvantages of TLG. The aim of this study was to compare TLG with OG with respect to surgical outcomes, morbidity, mortality and functional recovery. Long-term outcomes after TLG and OG in patients with any stage of gastric cancer were also evaluated in a systematic review of the literature and meta-analyses were performed.

The TLG technique was first conceptualized by Goh et al[39] in 1992, who reported two TLGs for the treatment of peptic ulcers. In 1996, Ballesta-Lopez first used this surgical technique for the treatment of gastric cancer and documented its feasibility and efficacy[40]. Although TLG has been in use for over 20 years, its development has been limited as successful reconstruction of the digestive tract has been difficult to achieve laparoscopically. However, continuous improvement and technical advances (in equipment as well as training) have made the application of TLG techniques in oncologic surgery for gastric cancer possible. Although RCTs are ideal for a meta-analysis, it is difficult to conduct a high-quality RCT to evaluate a new surgical intervention due to obstacles such as learning curve effects, ethical and cultural resistance, and urgent or unexpected events during surgery. For these reasons, the inclusion of non-RCTs is an appropriate strategy to extend the source of evidence. Therefore, our meta-analysis included existing observational studies with strict inclusion and exclusion criteria to evaluate the safety and efficacy of TLG.

Postoperative morbidity is usually used to estimate the feasibility and safety of a procedure. Morbidity was significantly lower in the TLG group than in the OG group, regardless of surgical or medical complications. Fewer surgical complications were primarily attributed to reduced wound complications (infections, dehiscence, etc.) in the TLG group. The scattered trocar incisions and contractible sample-extracting incision may explain the reduced wound infection seen in the TLG group. However, other surgical complications (such as leakage and intra-abdominal abscess) were not reduced in the TLG group. This is not surprising as the laparoscopic technique, although less invasive, results in the same organ and lymphatic resection as the open procedure. The significantly reduced medical complications could be explained by the reduced invasiveness of the laparoscopic technique and less postoperative pain. Postoperative pain was less serious in the TLG group than in the OG group as seen by the lower dosage or shorter duration of analgesic use. We also found that pulmonary complications occurred less often in the TLG group than in the OG group. One plausible hypothesis might be that the pain caused by a large incision as well as the use of tension sutures and abdominal bandages after laparotomy can make patients loath to cough, expectorate and perform exercise breathing effectively, thus the patients are prone to complications such as pulmonary infection. Our pooled analysis demonstrated that the postoperative hospital stay was 3.75 d shorter for TLG patients. The reduced use of analgesic drugs, shortened time of abdominal cavity exposure, less bowel manipulation, reduced inflammatory reactions, and earlier postoperative activities are considered to be the main reasons for earlier gastrointestinal recovery from laparoscopic surgery. However, the considerably longer postoperative stay may also have been related to local preferences and different health care systems, and some current series from referral centers report a median stay of more than 14 d after OG, which was considerably longer than that after TLG[25,26,36,37]. The current median length of stay at our hospital after TLG is 10 d, which is similar to most of the included studies[41]. Theoretically, decreased postoperative complication rates and faster recovery have the potential to allow eligible patients to receive postoperative chemotherapy in a timely manner, and therefore, possibly contribute to an improved oncologic outcome. However, these theoretical advantages are unproven.

Operative blood loss and the need for transfusions were lower in TLG cases shown in the pooled analysis. The reduced length of the incision wound and the application of energy-dividing devices, such as the Harmonic Scalpel and Ligasure, contributed to the reduction in blood loss. Another reason is that laparoscopy allows a magnified view of small vessels, particularly during dissection of the plane between the pancreas envelope and some major vessels such as the left gastric artery, common hepatic artery, coeliac trunk and splenic vessels. The most consistent finding in this meta-analysis was the longer operation time for TLG. The learning curve which is related to the surgeon’s experience, familiarity with instruments, and assistant compliance, can influence some of the outcomes studied, such as operation time and lymph node retrieval[42]. It has been suggested that experienced laparoscopic surgeons reach a plateau in operation time after about 40 operations[42,43]. As most of the studies in the present analysis did not explicitly describe the surgeon’s level of proficiency, a subgroup analysis was carried out by selecting studies in which the surgeon had performed more than 40 TLG operations as a surrogate marker of proficiency. This analysis demonstrated a moderate reduction in TLG operation time. Another reason for the prolonged operation time for TLG may be related to the reconstruction step, which is more difficult to complete during laparoscopy. To overcome these potential problems, various modified techniques have been reported. The most representative methods for distal gastrectomy are a delta-shaped anastomosis to perform a Billroth-I gastroduodenostomy and a linear stapler method to perform a side-to-side Billroth II gastrojejunostomy[41,44]. Two other intracorporeal reconstruction methods used in total gastrectomy are also representative; one using a transorally inserted anvil (OrVil™; Covidien) to perform an end-to-side esophagojejunostomy[45], the other using linear staplers to perform a side-to-side anastomosis[46]. These methods help to simplify the procedure of reconstruction and shorten the operation time.

Oncological outcome is a critical measure of success in laparoscopic surgery for malignant tumors. The number of retrieved lymph nodes and surgical resection margin are the major indicators of oncological surgical quality. The present meta-analysis showed that the number of retrieved lymph nodes with TLG was similar to that for OG, and significantly more than the 15 lymph nodes advocated by the Union for International Cancer Control (UICC). To reduce heterogeneity, a subgroup analysis of the extent of modified D₂ lymphadenectomy was performed[26,28-30,32,33,37,38], which confirmed that similar numbers of lymph nodes were harvested. With regard to the length of the resection margin, only a limited number of studies reported on the proximal margin. There were no significant differences between the two groups overall. However, our previous meta-analysis demonstrated a reduced proximal margin in the LAG group compared with the OG group[4,15]. We argued that such a result may relate to the nature of LAG, where the specimen is resected and reconstruction is performed through a mini-laparotomy; and it is difficult to pull the proximal stomach using a narrow incision, which may influence the distance of the proximal margin. TLG avoids such difficulties and a longer proximal margin may be expected. The length of the distal resection margin was also similar between the two groups. Both proximal and distal margin lengths demonstrated that TLG is oncologically acceptable for proximal or distal located tumors. Cancer recurrence and long-term survival rate are two visually effective outcomes for evaluating surgical interventions in oncological therapy. The majority of recurrences occur during the first two years after surgery[47], therefore, we used two years as the qualification for NOS to assess the adequate follow-up period of each study. Based on these data, postoperative cancer recurrence and long-term survival rate in the TLG group were similar to those in the OG group. We extracted OS and DFS from data in all available articles. However, we did not analyze this due to the lack of survival data. Therefore, more studies of long-term outcomes are still required to assess the oncological adequacy of TLG.

This analysis has some limitations: (1) most of the studies included were non-randomized and retrospective in nature. Hence, these results are only an estimate of the true benefit of TLG for gastric cancer. We would like to emphasize the importance of RCTs for evaluating the potential short- and long-term benefits of TLG; (2) the laparoscopic cohorts from most, if not all of these institutions, represented initial experiences, and most of the studies had small sample sizes with fewer than 50 TLG procedures, which could have introduced a bias against the outcomes of TLG, because surgical parameters might be influenced by the surgeon’s learning curve; (3) the homogeneity test for the continuous variables showed the existence of significant heterogeneity among the included studies. Therefore, we used a random effects model to evaluate these parameters; and (4) some studies reported that TLG could further reduce trauma compared to LAG, especially in obese patients[48,49]. However, none of the included studies evaluated the effectiveness of TLG for very obese patients, which could undermine the strength of the analysis to some extent.

In conclusion, TLG is a safe, feasible approach for patients with gastric cancer. The results of TLG were favorable in terms of better cosmesis, less blood loss and faster recovery. However, more methodologically high-quality comparative studies are required to adequately evaluate the status of TLG.