Surgical Techniques and Related Perioperative Outcomes After Robot-assisted Minimally Invasive Gastrectomy (RAMIG)

Objective: To gain insight into the global practice of robot-assisted minimally invasive gastrectomy (RAMIG) and evaluate perioperative outcomes using an international registry. Background: The techniques and perioperative outcomes of RAMIG for gastric cancer vary substantially in the literature. Methods: Prospectively registered RAMIG cases for gastric cancer (≥10 per center) were extracted from 25 centers in Europe, Asia, and South-America. Techniques for resection, reconstruction, anastomosis, and lymphadenectomy were analyzed and related to perioperative surgical and oncological outcomes. Complications were uniformly defined by the Gastrectomy Complications Consensus Group. Results: Between 2020 and 2023, 759 patients underwent total (n=272), distal (n=465), or proximal (n=22) gastrectomy (RAMIG). After total gastrectomy with Roux-en-Y-reconstruction, anastomotic leakage rates were 8% with hand-sewn (n=9/111) and 6% with linear stapled anastomoses (n=6/100). After distal gastrectomy with Roux-en-Y (67%) or Billroth-II-reconstruction (31%), anastomotic leakage rates were 3% with linear stapled (n=11/433) and 0% with hand-sewn anastomoses (n=0/26). Extent of lymphadenectomy consisted of D1+ (28%), D2 (59%), or D2+ (12%). Median nodal harvest yielded 31 nodes (interquartile range: 21–47) after total and 34 nodes (interquartile range: 24–47) after distal gastrectomy. R0 resection rates were 93% after total and 96% distal gastrectomy. The hospital stay was 9 days after total and distal gastrectomy, and was median 3 days shorter without perianastomotic drains versus routine drain placement. Postoperative 30-day mortality was 1%. Conclusions: This large multicenter study provided a worldwide overview of current RAMIG techniques and their respective perioperative outcomes. These outcomes demonstrated high surgical quality, set a quality standard for RAMIG, and can be considered an international reference for surgical standardization.


Upper-GI International Robotic Association
Since the founding of UGIRA in 2017, UGIRA aims to guide the implementation of robotic techniques in upper-gastrointestinal surgery by effective training pathways, perform international research, and establish standardized procedure guidelines.The establishment of the UGIRA Esophageal Registry in 2018 motivated an increasing number of robotic uppergastrointestinal surgeons to join UGIRA, resulting in several scientific papers using the registry. 37,38After establishing the UGIRA Gastric Registry in 2020, prospective RAMIG cases were registered until the present day.The current study is the first research based on the UGIRA Gastric Registry.

Design
All RAMIG cases with histologic confirmation of resectable gastric cancer were included until February 2023.Centers with <10 cases were considered not eligible for participation and were excluded.Other exclusion criteria consisted of squamous cell carcinoma, benign indications or other histology (eg, gastrointestinal stromal tumors or neuroendocrine differentiation), wedge resections or (palliative) surgery without surgical resection of the primary tumor, and previous gastric surgery.In total, 25 centers from Europe, Asia, and South-America participated in this study, as listed in Supplementary Methods, Supplemental Digital Content 1, http://links.lww.com/SLA/E936 and Supplementary Figure 1, Supplemental Digital Content 1, http://links.lww.com/SLA/E936.Participating surgeons were considered proficient in open and minimally invasive gastrectomy and had surgical experience varying between 10 and 110 RAMIG cases.Central ethics approval was obtained in UMC Utrecht, waiving informed consent (20/134), and institutional review board approval was acquired in each participating center.All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions.

Prospective Data Collection
The proposed items for the data collection were determined in a consensus meeting by the UGIRA Collaborative Group.All data were collected prospectively.RAMIG cases were registered consecutively and in chronological order.The registry was hosted by Castor EDC, a secure online data-capturing platform that meets international privacy, ethical, and regulatory requirements. 39Baseline data consisted of patient demographics including age, sex, body mass index (BMI), weight loss, American Society of Anesthesiologists (ASA) classification, comorbidities, previous surgery, disease stage according to the 8th edition of TNM staging by the American Joint Committee on Cancer, and neoadjuvant therapy. 40Intraoperative data consisted of operating time, blood loss, conversion, complications, and RAMIG techniques for the surgical resection, reconstruction, anastomosis, and lymphadenectomy.Histopathologic data consisted of tumor histology, lymph node yield, and resection margin status.Nodal stations were based on the 5th guidelines of the Japanese Gastric Cancer Association (JGCA). 41Complications were uniformly defined according to the Gastrectomy Complications Consensus Group (GCCG) and graded using the Clavien-Dindo classification. 34,42For postoperative recovery, hospital and intensive care unit stay, reoperations, application of Enhanced Recovery After Surgery (ERAS) guidelines, re-admission within 30 days after discharge, and 30-day mortality were recorded. 43o identifiable patient data were registered to safeguard patient privacy.Therefore, cases were registered at once after the 30-day follow-up period.To ensure data quality and minimize registration error, automated built-in data verification steps were implemented; missing items were highlighted in color automatically, and an audit trail registered all adjustments.The registry coordinator (C.d.J.) instructed centers individually for the data entry and performed additional data cleaning to verify registered data and check the completeness of data entry.

Outcomes
The main outcomes included techniques used for resection, reconstruction, anastomosis, and lymphadenectomy.These technical factors were analyzed and related to perioperative surgical and oncological outcomes.Furthermore, textbook outcome was assessed, which was defined as a composite measure including R0 resection, nodal yield ≥ 15 nodes, no intraoperative complications, no severe postoperative complications ( ≥ 3b Clavien-Dindo grading), no reoperations, no ICU admission, hospitalization <21 days, and no 30-day mortality.

Statistical Analysis
Patients were categorized according to the extent of gastrectomy (total, distal, or proximal gastrectomy) and outcomes were descriptively reported for these 3 subgroups.Depending on data distribution, continuous variables were presented as means with SD or medians with range or interquartile range (IQR).Categorical variables were displayed as frequencies with percentages (%).Analyses were performed using IBM SPSS Statistics version 27.0 (SPSS Inc., Chicago, IL).

Intraoperative Drain Placement
Surgical drains were often placed during total (80%) and distal gastrectomy (90%).Most centers (n = 21) placed intraoperative drains as part of routine practice to detect and drain a potential leakage or for bleeding control, whereas 4 centers did not.These 21 centers routinely inserted a drain near the esophagojejunal/gastrojejunal anastomosis, and several centers (n = 4) standardly placed a second drain near the duodenal stump or in the perihepatic region.Median hospital stay without routine perianastomotic drains was 3 days shorter than observed after standard intraoperative drain placement (Table 6).Without  intraoperative drain insertion during total gastrectomy or with standard drain placement, comparable complication severity, and rates of complications (42% and 42%), anastomotic leakage (11% and 10%), reoperations (7% and 9%), and additional postoperative drain placement (18% and 16%) were observed.Distal gastrectomy showed similar results (Table 6).

DISCUSSION
This worldwide multicenter study presents an international cohort of currently applied RAMIG techniques with its associated perioperative surgical outcomes and short-term oncological findings.The observed perioperative outcomes demonstrated high surgical quality of RAMIG.Differences in  18) 102 ( 22) 10 ( 45) Definition of the D-levels for lymphadenectomy were based on the 5th edition of the Japanese Gastric Cancer Association (JGCA), and consisted for D1 of stations 1 to 7, for D1+ stations 8, 9 and 11p were added to D1, for D2 stations 11d and 12a were added to D1+, and D2+ consisted of lymphadenectomy beyond D2 (stations 10 or 13-16).
Percentages may not add up to 100% due to rounding.
]31,[48][49][50][51] Furthermore, a previous retrospective study was conducted using the multicenter IMIGASTRIC registry after propensity score matching to compare outcomes after for open, laparoscopic, and robot-assisted gastrectomy. 30This registry-based research also reported similar surgical and oncological outcomes to our findings, although textbook outcome was not assessed.Importantly, higher textbook outcome rates were found for RAMIG after total (64%) and distal gastrectomy (74%) in the current study than the 22% to 55% textbook outcome after mostly laparoscopic and open gastrectomy that was reported in 4 population-based studies from different Western countries. 46,47,52,53Only one of these nationwide studies included robotic gastrectomies, showing 52% textbook outcome in the entire American population, or up to 60% when only including high-volume centers. 475][56] Indeed, one previous study (highvolume, single center) found 73% textbook outcome after RAMIG. 32Although RAMIG is not yet applied on large scale internationally, these perioperative surgical and oncological outcomes are concordant with previous results from high-volume expert centers, set a quality standard for RAMIG, and can be used as international reference standard in gastric cancer surgery.
In general, most centers adhere to one particular anastomotic technique per gastrectomy type and then optimize their technique as much as possible to achieve their best outcomes, especially regarding anastomotic leakage rates.The observed anastomotic leakage rates varied per technique.Low leakage rates were found for linear stapled (6%) and hand-sewn (8%) anastomosis, whereas circular stapling frequently showed leakage (21%).This variation in leakage rates likely reflects a learning curve for circular stapling, and may be secondary due to differences in patient factors, disease stage, and surgical experience per center.The higher leakage rate after circular stapling might also result from the technique itself.A previous meta-analysis (n = 2983) showed significantly more anastomotic leakage and complications after circular compared with linear stapling. 57][59] Although firm conclusions based on the current study cannot be made as patients were not specifically matched and surgeon experience was not corrected for, our results certainly warrant further prospective studies to determine whether linear stapled and hand-sewn anastomoses may be superior to circular stapling.
‡According to the 5the definitions of the Japanese Gastric Cancer Association (JGCA) classification.
Western patients had higher age, BMI, ASA classification, and comorbidities than Eastern patients, which is well known from literature. 72Furthermore, total gastrectomy was frequently performed, reflecting advanced disease stages, and proximal gastrectomy was mainly performed in the Asian population, as previously established. 72Future cross-continental studies with larger sample size should further evaluate intercontinental differences in RAMIG techniques and outcomes in-depth.
Since the participating centers registered all their RAMIG cases, also including the very first cases within their learning curve, our findings should be interpreted within this context.[21][22][73][74][75] A shorter RAMIG proficiency gain curve probably underlies technical advantages of robotic surgery, including improved dexterity and magnified 3-dimensional visualization.The benefit of robot-assisted surgery is most evident for technical steps including the anastomosis and lymphadenectomy, and in challenging cases such as salvage surgery.Although our results already showed high surgical quality, including learning curve cases implies that the reported perioperative outcomes after RAMIG in the present study are not yet optimal and could be further improved.
This study has limitations.Although expert centers use RAMIG as standard approach for all gastrectomies, centers in the early phase of their learning curve may carefully select their first few patients for RAMIG.This might translate into lower risk of surgery and relatively good perioperative outcomes for this small subgroup of patients, but on the contrary might also translate into slightly higher risk of surgery by performing RAMIG during a surgeon's learning curve.However, in order to present a realistic overview of the current stance of RAMIG, we consider it a strength to also retrieve data from centers in their RAMIG learning curve.Second, despite that all data were collected prospectively and uniform definitions (GCCG) were used, differences between centers could exist in reporting their complications, possibly introducing hospital reporting bias.Last, to guarantee anonymous data collection and facilitate patient privacy, the registry has limited follow-up, therefore impeding survival and quality of life analyses.Nonetheless, this study is based on an international population with prospective data from high-volume robotic centers, and is currently the largest published RAMIG cohort.Although not all known RAMIG centers contributed in this registry, the overview can be considered representative for worldwide practice of RAMIG.Furthermore, the UGIRA Gastric Registry facilitates international comparison as uniform definitions were used and stimulates standardization for gastric cancer surgery and RAMIG.
In conclusion, this worldwide multicenter study presents an overview of the currently applied surgical techniques with their respective perioperative outcomes after RAMIG.These findings from the UGIRA Gastric Registry demonstrated high surgical quality, set a quality standard for RAMIG and can be used as international reference standard.The optimal RAMIG techniques in terms of appropriate perioperative surgical outcomes and shortterm oncological results should be further explored.

TABLE 2 .
Surgical Techniques and Intraoperative Details for all RAMIG Procedures (n = 759)

TABLE 4 .
Anastomotic Leakage Rates According to Different Anastomotic Techniques After RAMIG *There were 11 missing (1%) for anastomotic technique or leakage.

TABLE 5 .
Overview of the Lymphadenectomy Types During RAMIG, Stratified Per Clinical Disease Stage