Robot‐assisted minimally invasive esophagectomy for esophageal cancer: Meticulous surgery minimizing postoperative complications

Abstract Minimally invasive esophagectomy (MIE) has been reported to reduce postoperative complications especially pulmonary complications and have equivalent long‐term survival outcomes as compared to open esophagectomy. Robot‐assisted minimally invasive esophagectomy (RAMIE) using da Vinci surgical system (Intuitive Surgical, Sunnyvale, USA) is rapidly gaining attention because it helps surgeons to perform meticulous surgical procedures. McKeown RAMIE has been preferably performed in East Asia where squamous cell carcinoma which lies in more proximal esophagus than adenocarcinoma is a predominant histological type of esophageal cancer. On the other hand, Ivor Lewis RAMIE has been preferably performed in the Western countries where adenocarcinoma including Barrett esophageal cancer is the most frequent histology. Average rates of postoperative complications have been reported to be lower in Ivor Lewis RAMIE than those in McKeown RAMIE. Ivor Lewis RAMIE may get more attention for thoracic esophageal cancer. The studies comparing RAMIE and MIE where recurrent nerve lymphadenectomy was thoroughly performed reported that the rate of recurrent nerve injury is lower in RAMIE than in MIE. Recurrent nerve injury leads to serious complications such as aspiration pneumonia. It seems highly probable that RAMIE is beneficial in performing recurrent nerve lymphadenectomy. Surgery for esophageal cancer will probably be more centralized in hospitals with surgical robots, which enable accurate lymph node dissection with less complications, leading to improved outcomes for patients with esophageal cancer. RAMIE might occupy an important position in surgery for esophageal cancer.


| INTRODUC TI ON
Worldwide, 445 800 new esophageal cancer cases occurred, while 400 200 deaths occurred in 2012. 1 Curative treatment for intrathoracic esophageal cancer comprises preoperative chemotherapy 2,3 or chemoradiotherapy 4,5 followed by surgical resection, which is the most invasive procedure in gastroenterological surgery resulting in 40% of the morbidity rate with a mortality rate of 3%, according to the National Clinical Database in Japan. 6 Subtotal esophagectomy with extensive mediastinal lymphadenectomy remains a critical element in the treatment of esophageal cancer. Minimally invasive esophagectomy (MIE), which uses thoracoscope or laparoscope to minimize the surgical trauma to the thoracic or abdominal wall, has been introduced to reduce the operative stress in the area of esophageal surgery especially in high-volume centers. Randomized controlled trials and meta-analyses have revealed that MIE reduces postoperative complications, especially pulmonary complications, and has equivalent longterm survival outcomes as compared to open esophagectomy. [7][8][9] However, traditional thoracoscopic esophagectomy requires such high skill that only limited expert surgeons can perform this surgery. Some of the reasons that make this surgery so difficult are: limited range of movement of the instrument tip caused by narrow intercostal space; proximity of important organs such as trachea, main bronchi, and thoracic aorta, lymph node dissection around the recurrent nerves; and narrow upper mediastinum surgical space.
In 2000, da Vinci was approved in the Food and Drug Administration (FDA) as the first computerized telesurgical device in the United States. 10 Initially, robot-assisted surgery was widespread in the field of pelvic surgery, including prostate surgery and gynecological surgery. The da Vinci surgical system provides surgeons with a three-dimensional camera, instruments with 7° freedom of movement, tremor filtration, and motion scaling, which enable surgeons to overcome the difficulty encountered in conventional MIE and to perform extremely delicate procedures needed for esophageal cancer surgery more easily and precisely.
In this article, we aim to highlight the development and current status of robot-assisted minimally invasive esophagectomy (RAMIE) and compare it with conventional MIE, reviewing the pertinent literature.

| S TUDY S ELEC TI ON
A manual search using PubMed and Embase was conducted for references related to studies on RAMIE published until 30 March 2020. The following search terms were used: "Esophagus" and "robot." A total of 49 out of 815 studies were selected that: (a) included more than 10 patients; (b) in which the RAMIE technique used was clearly described; Comparison not to convenƟonal minimally invasive esophagectomy: n = 13 Cohort described in other arƟcle: n = 11 Full text not available: n = 9 RAMIE technique or complicaƟons not clearly described: n = 21 and (c) in which the complications were adequately described. For manuscripts from the same institution, new reports were adopted if they were considered to contain the same cases ( Figure 1).

| CL A SS IFI C ATI ON OF R AMIE
RAMIE is thought to be classified into three categories; transthoracic thoracoscopic esophagectomy with cervical anastomosis (McKeown RAMIE), transthoracic thoracoscopic esophagectomy with intrathoracic anastomosis (Ivor Lewis RAMIE), and transhiatal esophagectomy (transhiatal RAMIE).

| IVOR LE WIS R AMIE
On the other hand, Ivor Lewis RAMIE, which was first reported by

| COMPARISON OF S HORT-TERM OUTCOME S B E T WEEN R AMIE AND MIE
One systematic review with meta-analysis of retrospective studies comparing short-term outcomes between RAMIE and MIE has been reported. 49 However, no prospective randomized controlled trial comparing RAMIE and MIE has been reported yet.

| D ISS EC TI ON OF RECURRENT NERVE LYMPH NODE S
The extent and quality of recurrent nerve lymph node dissection substantially vary among different regions. In the Western countries, where predominant histological type of esophageal cancer is adenocarcinoma and preoperative chemoradiotherapy followed by surgical resection is the standard of care for esophageal cancer, recurrent nerve lymph node dissection may be quite different from that performed in Japan. Therefore, comparison of recurrent nerve injury rate between the studies does not directly translate into the comparison of the quality of esophageal surgery. There have been four studies which compared RAMIE and MIE where the methods of recurrent nerve dissection were described in detail and the number of harvested recurrent nerve lymph nodes was five or more. 14,55,60,61 All these studies reported that the rate of recurrent nerve injury is lower in RAMIE than in MIE. Recurrent laryngeal nerve injury leads to serious complications such as aspiration pneumonia. It is highly probable that RAMIE is beneficial in performing extended upper mediastinal lymph node dissection.
One of the keys to successful lymph node dissection around the recurrent nerves is how to avoid tractional damage to the nerves. with that in the successful recurrent nerve lymph node dissection in RAMIE.

| FUTURE D IREC TI ON
In April 2018, robot-assisted thoracoscopic esophagectomy was covered by the national insurance in Japan. Subsequently, robotassisted mediastinoscopic esophagectomy was also covered by the national insurance in Japan in April 2020. Japan has been far be- were better in high-volume centers than those in low-volume centers. [63][64][65] Though not as many as in other countries, surgical robots have been installed in the majority of leading high-volume centers in Japan but might not be installed in many other centers. This may be because only high-volume centers can afford to buy and maintain running these robots, as there is a large financial burden associated with the da Vinci surgical system. Surgery for esophageal cancer will probably be more centralized in hospitals with surgical robots, leading to improved outcomes for esophageal cancer surgery.
There are two ongoing multicenter prospective randomized controlled trials comparing RAMIE and MIE which are called "REVATE" trial 66 and "RAMIE" trial. 67 "REVATE" trial is designed to demonstrate the superiority of RAMIE regarding recurrent nerve lymph node dissection. The primary endpoint is set to be the rate of unsuccessful recurrent nerve lymph node dissection defined as failure to remove lymph nodes along the left recurrent nerve or occurrence of permanent left recurrent nerve injury. "RAMIE" trial is designed to demonstrate non-inferiority of RAMIE in overall survival. These trials will provide important evidence of usefulness of RAMIE compared to MIE.

| CON CLUS ION
RAMIE is one of the operations that can maximize the advantages of surgical robots. Most of the studies reported so far dealt with the initial experience of RAMIE. According to these results, the safety and feasibility of RAMIE during the learning period were confirmed.
In the surgical resection for esophageal squamous carcinoma, which is a predominant histological type of esophageal cancer in East Asia including Japan, lymph node dissection around recurrent nerve is the most important point. This recurrent nerve lymph node dissection is where the robotic surgery can be most beneficial through precise movement of robotic instrument. Esophageal cancer surgery including RAMIE will be centralized more and more. Although the entire field of RAMIE is still so immature that further studies are needed to demonstrate the superiority of RAMIE to the other surgical methods, RAMIE might occupy an important position in surgery for esophageal cancer.

CO N FLI C T O F I NTE R E S T S
Authors declare no conflict of interests for this article.