Jeong Ho Song,Sang-Uk Han

Department of Surgery,Ajou University School of Medicine,Suwon 16499,Republic of Korea

Abstract Gastrectomy is the main treatment option for gastric cancer patients.Laparoscopic approach has become popular as an alternative to open method during the last decades,and clinical trials have revealed safety and feasibility in the short-and long-term outcomes of laparoscopic gastrectomy.The aim of this review is to summarize the results of prospective clinical trials and propose future perspectives for laparoscopic gastrectomy.

Keywords: Gastric cancer;laparoscopic gastrectomy;minimally-invasive surgery

Introduction

Since the first laparoscopic gastric cancer surgery was performed in 1991,laparoscopic gastrectomy has progressed a lot over the past few decades (1).Laparoscopic gastrectomy was initially performed for patients with early gastric cancer,but the scope of the operation was gradually expanded to patients with advanced gastric cancer.Even recently,reduced-port gastrectomy is performed to decrease postoperative pain and increase patient’s cosmetic satisfaction.Advances of the laparoscopic gastrectomy were mainly driven by Asian countries.Later,Western surgeons have introduced laparoscopic gastrectomy and have worked to prove the efficacy of laparoscopic approach in Western patients.In this review,we summarize pivotal multicenter trials,including randomized controlled trial (RCT),and propose future perspectives for laparoscopic gastrectomy.

Laparoscopic gastrectomy for early gastric cancer

The rate of early gastric cancer has been increasing in East Asia as a result of national cancer screening program (2-4).According to several Asian gastric cancer treatment guidelines,D1+lymph node dissection is recommended for early gastric cancer patients (5-7).For early gastric cancer located in the distal to middle portion of the stomach,laparoscopic distal gastrectomy was established as a standard procedure of choice through the prospective multi-institutional RCTs from Korea and Japan,KLASS-01 and JCOG0912 (8-11). Short-term postoperative outcomes of laparoscopic gastrectomy showed less intraoperative blood loss,but the rates of complications,reoperation,and mortality were comparable to those of open gastrectomy.Long-term oncologic outcomes of laparoscopic gastrectomy were not inferior to those of open gastrectomy.These results were in line with the outcomes of several meta-analyses (12-14).

For early gastric cancer located in the proximal portion of the stomach,there is one prospective multi-institutional RCT of laparoscopic total gastrectomy compared to the open surgery.The CLASS-02 multicenter RCT from China identified that overall morbidity and mortality rates of patients who underwent laparoscopic total gastrectomy were not significantly different from those who underwent open total gastrectomy [rate difference -1.1% [95%confidence interval (95% CI),-11.8%-9.6%) for morbidity,and rate difference 1.0% (95% CI,-2.5%-5.2%) for mortality] (15).The single-arm prospective multicenter studies from Korea and Japan,KLASS-03 and JCOG1401,showed safety of laparoscopic gastrectomy in patients with early gastric cancer located in the upper body of the stomach.The KLASS-03 study demonstrated acceptable postoperative complications[33/160 (20.6%) for overall complications and 15/160(9.4%) for Clavien-Dindo grade III or higher complications] and mortality rates [1/160 (0.6%)] in patients who underwent laparoscopic total gastrectomy(16).The JCOG1401 study confirmed the safety of laparoscopic-assisted total or proximal gastrectomy in terms of the incidence of esophagojejunal anastomotic leakage [6/244 (2.5%)] (17).The long-term benefit of laparoscopic gastrectomy for early gastric cancer has not yet been confirmed.However,considering the rare recurrences of stage I gastric cancer,similar oncologic outcomes were anticipated between laparoscopic and open gastrectomy.

Function-preserving gastrectomy,such as pyloruspreserving gastrectomy and proximal gastrectomy,is the limited surgery for gastric cancer.Compared to the distal or total gastrectomy,function-preserving gastrectomy has the limited extent of lymph node dissection and similar difficulty of anastomosis.Although few studies focused on the laparoscopic feasibility,no differences in surgeryrelated complications were found in a study as expected using propensity-score matching between laparoscopic and open pylorus-preserving gastrectomy (8.9% for laparoscopic groupvs.11.1% for open group) (18).

Laparoscopic gastrectomy for advanced gastric cancer

Subtotal or total gastrectomy with D2 lymph node dissection is a standard surgery for advanced gastric cancer patients according to the several Asian gastric cancer treatment guidelines (5-7). Laparoscopic subtotal gastrectomy is recommended through the recently published prospective multi-institutional RCTs from China and Korea,CLASS-01 and KLASS-02,for advanced gastric cancer located in the distal to middle portion of the stomach (19-24).Laparoscopic gastrectomy showed lower morbidity rate,lower patients’ pain score,earlier first flatus,and shorter hospital stays compared with the open gastrectomy. Oncologic outcomes of laparoscopic gastrectomy were comparable with those of open gastrectomy.However,caution is required in interpreting these trials.A large portion of patients enrolled in these trials had pathologic stage I (CLASS-01 29.2% and KLASS-02 35.2%),and patients with far-advanced diseases such as clinical T4b,tumors larger than 3 cm,or bulky lymph nodes were excluded.

Safety study on the short-and long-term outcomes of laparoscopic total gastrectomy for advanced gastric cancer patients is ongoing in Korea and China in the form of multi-institutional RCTs (KLASS-06 and CLASS-07).Total gastrectomy including splenic hilar lymph node dissection and esophagojejunostomy is considered technically more challenging procedure than distal gastrectomy.However,the safety of laparoscopic esophagojejunostomy was already verified in the aforementioned RCT (CLASS-02) and single-arm prospective multicenter studies KLASS-03 and JCOG1401.To overcome the difficulties in dissecting lymph nodes around splenic hilar area,several novel surgical techniques were suggested,such as SHINY maneuver (25),Huang three-step maneuver (26),and fluorescent lymphography(27).Although we wait for the results of KLASS-06 and CLASS-07,it is expected that laparoscopic total gastrectomy for patients with advanced gastric cancer in the proximal stomach will become a safe and standard surgical method.

The efficacy of laparoscopic gastrectomy after chemotherapy is lacking in prospective multi-institutional RCTs and is still controversial.A recent single-institutional RCT in China reported short-term outcomes in patients who underwent laparoscopic distal gastrectomy after neoadjuvant chemotherapy compared with those who underwent open distal gastrectomy (28).Laparoscopic group showed lower morbidity rates,lower postoperative visual analog scale scores for pain,and better adjuvant chemotherapy completion rates than open group.The long-term oncologic outcomes of the study will be published soon.Korean researchers are preparing another prospective multi-institutional RCT on this topic(KLASS-08).

Reduced-port laparoscopic gastrectomy

Laparoscopic gastrectomy is usually performed with multiple ports.With the development of new laparoscopic instruments and advancement of surgical skills,some experienced surgeons introduced reduced-port or singleport gastrectomy.Despite technical difficulties caused by the limited surgical support from assistants and collision between instruments,several retrospective studies documented less blood loss and less pain scores in reducedport surgery group than conventional-port surgery group(29-31).According to the recently published RCT in Japan,single-port group showed less postoperative pain score,shorter operating time,and comparable postoperative complications rates compared to the multi-port group (32).Korean researchers are recruiting patients for multiinstitutional RCT comparing postoperative complications of reduced-port and conventional laparoscopic distal gastrectomy in early gastric cancer patients (KLASS-12).The safety of reduced-port distal gastrectomy is expected to be established,and the next study will be on the feasibility of reduced-port distal gastrectomy in patients with advanced gastric cancer.

Laparoscopic gastrectomy in Western countries

Advances in minimally invasive surgery for gastric cancer have been mainly demonstrated in the Eastern countries.Due to the lower incidence of gastric cancer and the diagnosis of the disease at an advanced stage,few RCTs were published in Westerns countries.Actually,a singlecenter RCT was published in 2005 showing the feasibility and safety of laparoscopic subtotal gastrectomy compared to open approach (33).Although limited numbers of participating patients (total 59 patients),laparoscopic approach offered an alternative to laparotomy.Then,results of first Western multi-institutional RCT comparing laparoscopicvs.open gastrectomy for gastric cancer,LOGICA trial,was announced in 2021 (34).Laparoscopic group had less blood loss and longer operating time than the open group. The rates of the postoperative complications,mortality,and readmission as well as 1-year survival outcomes were similar between the groups.The results were in line with the findings of studies in the East.

Neoadjuvant or perioperative chemotherapy with gastrectomy is the standard choice of procedure for patients with advanced gastric cancer according to the Western gastric cancer guidelines (35,36).STOMACH trial verified the non-inferior outcomes of laparoscopic surgery compared to the open surgery regarding perioperative and long-term oncologic outcomes (37).Despite the small sample size of the studies (a total of 227 patients for the LOGICA trial and 96 patients for the STOMACH trial),laparoscopic gastrectomy is expected to become the standard treatment in Westerns countries.

Recent laparoscopic gastrectomy studies on quality of life

Researchers in Eastern countries,where the rate of early gastric cancer patients is high,are looking the quality of life beyond the survival rates of patients.Studies to prevent long-term complications after gastrectomy such as dumping syndrome,gallstone formation and vitamin B12 deficiency are ongoing.One such promising tool is sentinel node navigation surgery.Since the stomach has a relatively complex lymphatic flow,mapping the sentinel node is not easy.However,multicenter prospective trial in Japan showed a sentinel node detection rate of 97.5%,an accuracy of nodal evaluation for metastasis of 99%,and a very low rate of false-negative sentinel node (38).A recent multicenter RCT in Korea demonstrated that laparoscopic sentinel lymph node surgery group showed comparable postoperative complication rates and non-inferior 3-year disease-free survival rates to laparoscopic standard gastrectomy group (39,40). However,better physical function,less gastrectomy-related symptoms,and improved nutritional parameters were documented in the sentinel lymph node surgery group than the standard gastrectomy group.

Korean researchers are conducting several clinical studies for quality of life in gastric cancer patients.An RCT in Korea for comparing changes in hemoglobin levels and amount of vitamin B12 supplementation between laparoscopic proximal gastrectomy with double-tract reconstruction and laparoscopic total gastrectomy for early gastric cancer in upper stomach will be published in the near future (KLASS-05) (41).In diabetic gastric cancer patients,a study comparing the improvement or remission of diabetes between long-limbs and conventional bypass reconstruction after subtotal gastrectomy is recruiting patients (KLASS-09).

Robotic gastrectomy

Despite higher cost compared to laparoscopic gastrectomy,early paper of robotic gastrectomy did not show superior perioperative outcomes. In a Korean multicenter prospective comparative study in 2016,the benefits of robotic gastrectomy were unremarkable in terms of complication rates,estimated blood loss,and length of hospital stay (42).As robotic surgical technique is upgraded over time and spread around the world,advantages of robot,such as articulated devices,steady camera and tremor filtration,have been demonstrated in terms of perioperative results.In a Japanese multi-institutional prospective study in 2019,robotic gastrectomy showed significant reduction of morbidity than laparoscopic approach (43).In a single-center RCT in China,robotic distal gastrectomy demonstrated reduced morbidity and more numbers of harvested extra-perigastric lymph nodes than laparoscopic approach (44).However,there are no large-scale studies showing superior long-term oncologic outcomes of robotic surgery to laparoscopic surgery to date(45).Considering the high cost of robot platforms,the importance of laparoscopic gastrectomy will continue until the survival advantage of robots is established.

Conclusions and future perspectives

Laparoscopic subtotal gastrectomy has been established as a standard procedure alternative to open surgery.For patients with advanced proximal gastric cancer,laparoscopic total gastrectomy is under active research and is expected to yield promising short-and long-term outcomes.The indication of reduced-port laparoscopic gastrectomy is expanding to total gastrectomy or D2 lymph node dissection,and further research is need to confirm safety.These advancements were mainly based on surgeries performed by experienced Asian surgeons,and further research is needed to confirm whether they can be applied to Western countries with a low incidence of gastric cancer.Finally,laparoscopic gastrectomy will play a pivotal role in gastric cancer surgery without the cost saving or survival benefits of robotic systems.

Acknowledgements

None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.