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Minimally Invasive and Open Gastrectomy for Gastric Cancer: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials

Minimally Invasive and Open Gastrectomy for Gastric Cancer: A Systematic Review and Network... Ann Surg Oncol https://doi.org/10.1245/s10434-023-13654-6 REVIEW ARTICLE – GASTROINTESTINAL ONCOLOGY Minimally Invasive and Open Gastrectomy for Gastric Cancer: A Systematic Review and Network Meta‑Analysis of Randomized Clinical Trials 1 2 3 Matthew G. Davey, MCh, MRCSI, PhD , Hugo C. Temperley, MB, BCh , Niall J. O’Sullivan, MB, BCh , 4 4 1,4 1,5 Vianka Marcelino , Odhrán K. Ryan, MB, BCh , Éanna J. Ryan, MD, MRCSI , Noel E. Donlon, MRCSI, PhD , 6 5 Sean M. Johnston, FRCSI(Gen) , and William B. Robb, FRCSI(Gen) 1 2 Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Republic of Ireland; Department of Surgery, Trinity St. James’s Cancer Institute, Trinity, St. James’s Hospital, Trinity College Dublin, Dublin, Republic of Ireland; 3 4 Department of Surgery, Tallaght University Hospital, Dublin, Republic of Ireland; Department of Surgery, St. Vincent’s University Hospital, Dublin, Republic of Ireland; Department of Upper Gastrointestinal Surgery, Beaumont Hospital, Dublin 9, Co Dublin, Republic of Ireland; Department of Surgery, Midlands University Hospital, Tullamore, Co. Offaly, Republic of Ireland ABSTRACT no differences in OS in meta-analysis (OR 1.02, 95% CI Background and Objectives. Optimal surgical manage- 0.77–1.52). Importantly, patients undergoing LAG experi- ment for gastric cancer remains controversial. We aimed enced reduced intraoperative blood loss, surgical incisions, to perform a network meta-analysis (NMA) of randomized distance from proximal margins, postoperative hospital clinical trials (RCTs) comparing outcomes after open gas- stays, and morbidity post-resection. trectomy (OG), laparoscopic-assisted gastrectomy (LAG), Conclusions. LAG was associated with non-inferior onco- and robotic gastrectomy (RG) for gastric cancer. logical and surgical outcomes compared with OG. Surgi- Methods. A systematic search of electronic databases was cal outcomes following LAG and RG superseded OG, with undertaken. An NMA was performed as per the Preferred similar outcomes observed for both LAG and RG. Given Reporting Items for Systematic Reviews and Meta-Analyses these findings, minimally invasive approaches should be (PRISMA)-NMA guidelines. Statistical analysis was per- considered for the resection of local gastric cancer, once formed using R and Shiny. surgeon and institutional expertise allows. Results. Twenty-two RCTs including 6890 patients were included. Overall, 49.6% of patients underwent LAG Keywords Gastric cancer · Gastrectomy · Minimally (3420/6890), 46.6% underwent OG (3212/6890), and 3.7% invasive surgery · Surgical oncology · Oncological underwent RG (258/6890). At NMA, there was a no sig- outcomes nificant difference in recurrence rates following LAG (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.77–1.49) compared with OG. Similarly, overall survival (OS) out- Gastric cancer is the fifth most common cancer world- comes were identical following OG and LAG (OS: OG, wide and third leading cause of cancer-related mortality. Its 87.0% [1652/1898] vs. LAG: OG, 87.0% [1650/1896]), with management paradigm has evolved with the advent of multi- modal therapeutic strategies, including novel combinations 2 3 of chemotherapeutic agents, radiotherapies, and immu- © The Author(s) 2023 nomodulatory drugs, all of which may be tailored in accord- ance with patient and tumour factors to improve oncologic First Received: 3 January 2023 Accepted: 4 May 2023 outcomes. This personalized approach is conducted with the intention of minimizing treatment-related toxicities, while simultaneously achieving the best pathological responses M. G. Davey, MCh, MRCSI, PhD 5,6 to conventional therapeutic strategies. Despite these e-mail: matthewdavey21@rcsi.com Vol.:(0123456789) M. G. Davey et al. advances, high-quality radical en bloc surgical resection of and RG relative to OG is yet to be determined. Importantly, 7,8 the tumour remains the cornerstone of management, Tra- two recent RCTs have reported short-term postoperative 38,39 ditionally, gastrectomy was performed as an open procedure and survival outcomes following RG, and anticipation (OG), although more recently, minimally invasive surgical among gastroesophageal surgeons is that such minimally (MIS) approaches have undergone widespread adoption, invasive approaches should enhance patient outcomes. including laparoscopic-assisted gastrectomy (LAG) and Therefore, application of the network meta-analysis (NMA) 9,10 robotic-assisted gastrectomy (RG). Advocates of MIS methodology here is timely to allow simultaneous compari- hold this approach to be advantageous for several reasons, son (direct and indirect) of minimally invasive approaches 41,42 particularly reduced morbidity, and enhanced recovery and to gastrectomy with OG using RCT data only. 11,12 cosmesis. Nevertheless, OG remains the approach of choice for certain cases, as surgical approach is dependent METHODS on an array of patient, pathological, and societal parameters, as well as surgeon and institutional expertise. A systematic review was performed in accordance with The first LAG was performed for gastric cancer in 1994, the Preferred Reporting Items for Systematic Reviews and and this approach has subsequently been developed and Meta-Analyses (PRISMA) extension statement for report- refined. Several studies, including multicentre, prospec- ing of systematic reviews incorporating NMAs of healthcare tive, randomized clinical trials (RCTs), have illustrated interventions. This study was registered with the Interna- the non-inferiority of long-term oncological and survival tional Prospective Register of Systematic Reviews (PROS- outcomes following LAG and OG. Consequently, LAG is PERO, CRD42022330440). a well-established surgical approach in the management of 16–19 early gastric carcinoma. Increasingly, LAG is currently Search Strategy emerging as feasible, safe and effective for radical resection 20,21 of locally advanced distal gastric cancer. Nevertheless, A formal systematic search of four electronic databases there remains debate surrounding the differences in postop- was performed in March 2022 for relevant titles. Details in erative and oncological outcomes following LAG, as well as relation to the search strategy can be found in Appendix 1 in the considerable technical aspects and learning curve associ- the electronic supplementary material (ESM). Study-specific 22–26 ated with the laparoscopic approach. definitions and the research question determined using the Robot-assisted surgery has been proposed as a potential Population, Intervention, Comparison, Outcomes (PICO) platform to overcome some of the limitations of conven- framework are outlined in detail in ESM Appendices 2 tional laparoscopy and has recently undergone widespread and 3. adoption by many specialists and surgical oncology units for the management of many solid organ cancers. This is Eligibility Criteria principally due to the reported advantages of three-dimen- sional vision, enhanced skill acquisition (due to a shorter All published RCTs with full-text manuscripts comparing learning curve relative to laparoscopic surgery), increased the outcomes of two or more methods of surgical interven- operator dexterity, improved mobility in narrow areas that tion for gastric cancer (i.e., OG, LAG or RG) were included. have restricted access, and improved ergonomics for the The inclusion criteria for studies were (1) compared post- 27,28 operating surgeon. However, while the first RG was operative surgical outcomes (e.g., complications, estimated performed in Japan 20 years ago by Hashizume et al., the blood loss, lymph node yield [LNY], etc.) or long-term uptake of robotic surgery in upper gastrointestinal surgery oncological and survival outcomes (e.g., disease recurrence, has lagged considerably behind other surgical specialties. overall survival [OS], etc.); (2) were of a prospective, rand- At present, data available in relation to robotic surgery is omized design; (3) recruited patients aged 18 years or older primarily obtained from studies of a retrospective design, undergoing surgery for known primary gastric cancer; and typically involving outcomes regarding single-centre or (4) studies had to have full-text manuscripts available. Note single-surgeon experiences of using robotics for gastric that when overlapping trial data were reported from two dif- cancer resections, with limited long-term oncological out- ferent sources, the source with the longest patient follow-up comes being reported. Therefore, there is a paucity of high- or largest sample size was included. quality data evaluating the role of RG for resection of gastric The exclusion criteria were (1) studies failing to fulfil the 31–33 tumours. above inclusion criteria; (2) studies that only have results 32,34–37 Several RCTs and standard pairwise meta-analyses published in abstract form or from conference proceedings; have attempted to determine the optimal surgical approaches (3) studies not published in the English language; or (4) used for the resection of gastric carcinoma, however consen- studies in which the primary indication for the gastrectomy sus in relation to the oncological and surgical safety of LAG Minimally Invasive and Open Gastrectomy …        was not for gastric cancer (e.g., bariatric sleeve gastrectomy, Risk‑of‑Bias Assessment etc.). Assessment of potential biases within the included RCTs was assessed using the Cochrane Collaboration tool (for Statistical Analysis RCTs). This assessment tool grades the risk of bias in each study as being high risk (marked in red), low risk (marked in Descriptive statistics were used to outline the characteris- tics of the included trials. Data pertaining to recurrence, OS, green), or uncertain risk (marked in yellow) of bias across six categories. The critical appraisal was independently morbidity, complications and readmission were expressed as dichotomous or binary outcomes, reported as odds ratios completed by two reviewers (HCT and MGD), and in the case of discrepancies in opinion, a third reviewer (NED) (ORs) with 95% confidence intervals (CIs). ORs were cal - culated using crude event RCT data, to compare interven- was asked to arbitrate. tions using per-protocol data, where applicable. Continuous data were calculated using mean values, standard deviations RESULTS (SDs) and pooled mean variance, with differences expressed as weighted mean differences (WMDs). OG was the prin- Literature Search cipal comparator for all analyses. Bayesian NMAs were 45 46 conducted using netameta and Shiny packages for R. In total, 7385 articles were identified and 4220 duplicate Point estimates of effect sizes were described with a 95% articles were excluded. Thereafter, study titles and abstracts CI. Results were considered statistically significant at the were screened, resulting in 53 studies being eligible for full- p < 0.050 level if the 95% CI did not include a value of 1. text review. Of these, 22 RCTs met the eligibility criteria 22–26,39,51–66 Estimates of mean and SDs were calculated using standard and were included. The PRISMA flow chart is 47,48 statistical methods, where applicable. Rank probabilities illustrated in Fig. 1. were plotted against the possible ranks for all competing treatments. The confidence in estimates of the outcome was Study Characteristics assessed using the Confidence in Network Meta-Analysis (CINeMA) tool. Overall, 6890 patients with gastric cancer were included, of whom 3212 patients underwent OG (46.6%, 3212/6890), 3420 patients underwent LAG (49.6%, 3420/6890) and 258 FIG. 1 PRISMA flowchart outlining the systematic search process. PRISMA Preferred Records identified from data-base Reporting Items for Systematic searching: (n = 7385) Duplicate records removed Reviews and Meta-Analyses, RCTs randomized controlled (n = 4220) Databases (n = 4) trials Records excluded Records screened (n = 3114) (n = 7385) Reports excluded (n = 21) Reports assessed for eligibility - 8 incomplete study design - 5 incomplete outcomes (n = 53) - 5 conference abstracts - 3 incomplete RCTs Studies included in review - RCT n = 22 Included Screening Identification M. G. Davey et al. patients underwent RG (3.7%, 258/6890). The mean age Compared with OG, there was a significant reduction in at surgery was 60.9 years (range 54.5–72.0 years). Over- IBL for those who underwent LAG (OR − 79.4, 95% CI all, 15/22 studies included distal gastrectomy (DG) only − 108.0 to − 52.3) and the robotic group (OR − 87.2, 95% CI (68.2%), with 6/22 (27.3%) and 4/22 (18.2%) also includ- − 173.0 to − 2.75) (Fig. 3b and ESM Appendix 3b). Further- ing total gastrectomy (TG) and partial gastrectomy (PG), more, there was a non-significant reduction in IBL in those respectively. Overall, 40.9% reported outcomes for early undergoing RG compared with those undergoing LAG (OR gastric cancer (9/22), 18.2% for locally advanced gastric − 7.83, 95% CI − 88.83 to 73.02). cancer (4/22), 9.1% for advanced gastric cancer (2/22), and Overall, 50.0% of included studies reported on the num- 31.8% for resectable gastric cancer (7/22). The characteris- ber of LNs harvested (11/22). Compared with OG, LAG tics of the trials included in this meta-analysis are shown in showed a significantly decreased LN yield (OR − 1.52, 95% Table 1. All ranking tables illustrating the data are presented CI − 2.75 to − 0.45), whereas there was a non-significant in Table 2. difference in LNs harvested for those who underwent RG (OR − 1.95, 95% CI − 5.77 to 1.25) (Fig.  3c and ESM Primary Outcome Measures Appendix 3c). In total, 31.8% of the included studies reported on the Disease Recurrence distance from the proximal margin (7/22). This distance Overall, 27.3% of studies reported outcomes with respect from the proximal margin was significantly lower in those to disease recurrence (6/22). The mean follow-up was 56.4 undergoing LAG compared with OG (OR − 0.310, 95% months (range 22.1–99.8 months), and the overall recurrence CI − 0.565 to − 0.0992) (Fig. 3d and ESM Appendix 3d). rate was 9.1% (435/4775). LAG had the highest recurrence The rank probability was highest in those undergoing LAG rate (9.5%, 226/2,373), followed by OG (8.7%, 209/2402). (0.99), indicating a decreased distance from the proximal Of note, recurrence was not reported in any of the studies margin in those undergoing LAG (Table 2). reporting outcomes following RG. When compared with an In total, 27.3% of the included studies reported on the OG, the risk of disease recurrence was similar for those who distance from the distal margin (6/22). The distance from underwent LAG (OR 1.09, 95% CI 0.77–1.49) (Fig. 2a) and distal margin was similar to those who underwent LAG and ESM Appendix 2a]. OG (OR − 0.220, 95% CI − 0.530 to 0.0617) (Fig. 3e and ESM Appendix 3e). The rank probability was highest in Overall Survival those undergoing LAG (0.95), indicating a decreased dis- Overall, 31.8% of included studies reported outcomes tance from the distal margin associated with LAG (Table 2). for analysis in relation to OS (7/22). The mean follow-up In total, 36.4% of the included studies reported on the was 56.4 months (range 22.1–99.8 months). For the overall length of surgical incision (8/22). This was significantly patient cohort, 87.0% of patients were alive at follow-up shorter in those undergoing LAG compared with OG (OR (3302/3794). Of note, OS rates were identical for both OG − 11.7, 95% CI − 14.5 to − 8.91) (Fig. 3f and ESM Appen- and LAG (OS: OG, 87.0% [1652/1898] vs. LAG: OG, 87.0% dix 3f). The rank probability was highest in those undergo- [1650/1896]). OS was not reported in the RG groups. When ing LAG (0.99), indicating a decreased length of surgical compared with OG, OS was similar for those who under- incision associated with LAG (Table 2). went LAG (OR 1.02, 95% CI 0.765–1.52) (Fig. 2b and ESM Appendix 2b]. Postoperative Outcomes Overall, 95.5% of included studies reported outcomes Secondary Outcome Measures in relation to overall morbidity (21/22). Compared with OG, there was a significant reduction in morbidity in those Intraoperative Outcomes undergoing LAG (OR 0.80, 95% CI 0.67–0.95) and RG (OR All 22 RCTs reported outcomes on intraoperative time. 0.35, 95% CI 0.19–0.62), respectively. Compared with LAG, LAG (OR 64.3, 95% CI 51.0–78.7) and RG (OR 99.3, 95% those undergoing RG had a significant reduction in overall CI 55.1–145.0) were associated with significantly longer morbidity (OR 0.43, 95% CI 0.25–0.76) [ESM Appendices intraoperative duration than OG. Compared with LAG, intra- 4 and 5]. operative time was not significantly different to those who In total, 59.1% of included studies reported outcomes in underwent RG (OR 34.96, 95% CI − 7.53 to 77.84) (Fig. 3a relation to major morbidity (13/22). Compared with OG, and ESM Appendix 3a). Of note, the rank probability was there was similar major morbidity in those undergoing LAG highest in the OG group (0.999), indicating the lowest intra- (OR 1.15, 95% CI 0.79–1.65) and RG (OR 0.43, 95% CI operative time associated with OG (Table 2). 0.16–1.17). Compared with LAG, there was a significant In total, 95.5% (21/22) of the included studies reported reduction in major morbidity in those undergoing RG (OR outcomes in relation to intraoperative blood loss (IBL). 0.38, 95% CI 0.14–0.99) [ESM Appendices 4 and 5]. Minimally Invasive and Open Gastrectomy …        TABLE 1 Characteristics of trials included in the meta-analysis Author, year Country Study period Multicentre Surgery No. of patients Age M/F Gastrectomy type Cancer stage Tumour size Staging Kitano Japan 1998–2001 No OG 14 60 ± 3 8/6 DG EGC 2.3 ± 0.3 JCGC LAG 14 63 ± 3 9/5 2.3 ± 0.3 Huscher Italy 1992–1996 No OG 29 63.6 ± 13 21/8 DG GC NA AJCC 5th LAG 30 63.2 ± 12 18/12 NA Lee Korea 2001–2003 No OG 23 59.5 ± 11 15/8 DG EGC 1.8 ± 1.6 AJCC 5th LAG 24 56.6 ± 11 11/13 1.4 ± 0.8 Hayashi Japan 1999–2001 No OG 14 62 ± 6.5 13/1 DG EGC NA NA LAG 14 56 ± 5.7 9/7 NA Cai China 2008–2009 Yes OG 47 60.2 ± 10.2 37/10 PG, DG, TG GC 4.3 ± 1.8 JCGC 13th LAG 49 60.2 ± 9.8 39/10 4.2 ± 2.0 Chen Hu China 2009–2011 No OG 20 64.5 ± 6.5 12/8 DG GC NA JCGC 13th LAG 22 62.5 ± 6.7 10/12 NA Takiguchi Japan 2003–2006 No OG 20 62.5 ± 3 13/7 DG EGC 2.4 ± 0.2 NA LAG 20 61.5 ± 4.3 12/8 2.2 ± 0.5 Kim Korea 2003–2005 No OG 82 54.5 ± 8.3 47/35 DG EGC 3.4 ± 2.1 AJCC 6th LAG 82 56.7 ± 7.5 47/35 3.4 ± 1.8 Yamashita Japan 2005–2008 No OG 32 61 ± 7.6 25/7 DG EGC 3.6 ± 2.4 AJCC 5th LAG 31 58 ± 9.6 17/14 3.9 ± 2.0 Cu China 2010–2012 No OG 142 57.5 ± 11.2 98/44 PG, DG, TG GC NA AJCC 7th LAG 128 60.1 ± 12.6 88/40 NA Aoyama Japan 2011 NA OG 13 63.8 ± 8.9 7/6 DG EGC NA JCGC 14th LAG 13 60.3 ± 11.8 7/6 NA Sh China 2010–2012 No OG 160 NA NA PG, DG, TG AGC NA JCGC 13th LAG 162 NA NA NA Kata Japan 2010–2013 Yes OG 459 64 ± 2.1 275/184 DG, PG ECG 2.5 ± 0.1 JCGC 13th LAG 462 63 ± 1.8 275/184 2.7 ± 0.3 Wang China 2014–2017 Yes OG 220 60.6 ± 10 133/87 DG, TG LAGC 3.9 ± 2.2 AJCC 7th LAG 222 59.4 ± 12 144/78 3.6 ± 1.8 Park Korea 2010–2011 Yes OG 96 60.1 ± 8.2 65/31 DG AGC NA AJCC 7th LAG 100 58.6 ± 8.9 69/31 NA Yu China 2012–2014 Yes OG 520 55.8 ± 11 346/174 DG LAGC 4.0 ± 2 AJCC 7th LAG 519 56.5 ± 10 380/139 4.0 ± 2 Kim Korea 2006–2010 Yes OG 611 57.8 ± 11 412/200 DG EGC NA AJCC 7th LAG 644 56.8 ± 11 425/219 NA Li China 2015–2017 No OG 50 61 ± 2.2 34/16 DG LAGC 2.5 ± 0.5 AJCC 7th LAG 45 59 ± 3.2 32/13 2.5 ± 0.4 Hyung Korea 2011–2015 Yes OG 498 59.6 ± 11 346/152 DG LAGC NA AJCC 7th LAG 513 59.8 ± 11 370/143 NA Vanderveen Netherlands 2015–2018 Yes OG 112 66.9 ± 12.1 72/40 DG, TG GC NA AJCC 8th LAG 115 67.9 ± 11.4 68/37 NA M. G. Davey et al. TABLE 2 SUCRA scores for the outcomes measures. Parameter OG LAG RG Overall recurrence 0.732 (1st) 0.268 (2nd) NR Overall survival 0.563 (1st) 0.437 (2nd) NR Operative time 0.999 (1st) 0.001 (2nd) 0.000 (3rd) Intraoperative blood loss 0.000 (3rd) 0.420 (2nd) 0.580 (1st) Lymph node harvest 0.001 (3rd) 0.391 (2nd) 0.608 (1st) Distance from proximal 0.006 (2nd) 0.996 (1st) NR margin Distance from distal margin 0.050 (2nd) 0.950 (1st) NR Length of incision 0.001 (2nd) 0.999 (1st) NR Wound complications 0.047 (2nd) 0.634 (1st) 0.319 Anastomotic leak 0.281 (2nd) 0.073 (3rd) 0.646 (1st) Length of stay 0.000 (3rd) 0.274 (2nd) 0.725 (1st) Days until sips 0.012 (3rd) 0.220 (2nd) 0.768 (1st) Days until solids 0.099 (3rd) 0.679 (1st) 0.222 (2nd) Days until flatus passed 0.000 (3rd) 0.257 (2nd) 0.743 (1st) Days until ambulation 0.136 (3rd) 0.217 (2nd) 0.647 (1st) Cost 0.646 (1st) 0.331 (2nd) 0.023 (3rd) Tumour size 0.034 (3rd) 0.296 (2nd) 0.670 (1st) OG open gastrectomy, LAG laparoscopic-assisted gastrectomy, RG robotic gastrectomy, NR not reported In total, 68.2% of included studies reported outcomes in relation to perioperative mortality (15/22). Compared with OG, there was similar perioperative mortality in those undergoing LAG (OR 0.90, 95% CI 0.43–1.89) and RG (OR 0.91, 95% CI 0.05–16.18). Compared with LAG, periopera- tive morality was similar for those who underwent RG (OR 0.99, 95% CI 0.06–15.88) [ESM Appendices 4 and 5]. Complications Overall, 50.0% of RCTs reported on wound complica- tions (11/22). Compared with OG, there were similar wound complications for undergoing LAG (OR 0.628, 95% CI 0.30–1.18) and RG (OR 1.03, 95% CI 0.11–10.70). Com- pared with LAG, wound complications were similar for those who underwent RG (OR 1.65, 95% CI 0.20–15.91) [ESM Appendices 4 and 5]. In total, 40.9% of included studies reported on cardiac complications (9/22). Compared with OG, cardiac complica- tions were similar for those who underwent LAG (OR 1.47, 95% CI 0.68–3.17) and RG (OR 8.1, 95% CI 0.96–68.2). Compared with LAG, cardiac complications were similar for those who underwent RG (OR 0.18 95% CI 0.02–1.29). Of note, however, one of the two RCTs evaluating RG illus- trated a significant increase in cardiac complications (OR 33.5, 95% CI 1.97–568.6) [ESM Appendices 4 and 5]. In total, 81.8% of included studies reported on respira- tory complications (18/22). Compared with OG, there was Table 1 (continued) Author, year Country Study period Multicentre Surgery No. of patients Age M/F Gastrectomy type Cancer stage Tumour size Staging Jun Lu China 2017–2020 No LAG 142 59.3 ± 11 90/52 DG GC 3.9 ± 1.9 AJCC 8th RG 141 59.4 ± 10 94/47 3.5 ± 1.8 Ojima Japan 2018–2020 Yes LADG 119 72 ± 8.3 77/42 DG, TG GC 3.2 ± 1.9 AJCC 8th RG 117 71 ± 9.3 73/44 3.5 ± 2.4 OG open gastrectomy, LAG laparoscopic-assisted gastrectomy, RG robotic gastrectomy, M male, F female, DG distal gastrectomy, PG proximal gastrectomy, TG total gastrectomy, NA not avail- able, JCGC Japanese Classification of Gastric Carcinoma, AJCC American Joint Committee on Cancer, EGC early gastric cancer, GC gastric cancer, LAGC locally advanced gastric cancer, AGC advanced gastric cancer Minimally Invasive and Open Gastrectomy …        Outcome Forrest Plot Network plot Network plot of all studies (a) Open Odds Ratio (95% Crl) Compared with Open 1.09 (0.768, 1.49) Laparoscopic 0.1 15 Laparoscopic Network plot of all studies (b) Open Odds Ratio (95% Crl) Compared with Open 1.02 (0.765, 1.52) Laparoscopic 0.1 1 5 Laparoscopic FIG. 2 Forest and network plots with respect to (a) disease recurrence and (b) overall survival a similar rate of respiratory complications for those who 0.00–4.03). Compared with LAG, the risk of anastomotic underwent LAG (OR 0.85, 95% CI 0.62–1.17) and RG (OR stenosis was similar for those who underwent RG (OR 0.17, 0.65, 95% CI 0.29–1.46). Compared with LAG, the risk of 95% CI 0.01–3.39) [ESM Appendices 4 and 5]. respiratory complications was similar for those who under- went RG (OR 0.76, 95% CI 0.36–1.61) [ESM Appendices Recovery 4 and 5]. Overall, 45.5% of included studies reported outcomes on In total, 59.1% of included studies reported on pancreatic length of hospital stay, in days (10/22). When compared with complications (13/22). Compared with OG, the risk of pan- an OG, there was a significant reduction in length of hos- creatic complications was similar for those who underwent pital stay for those who underwent LAG (OR − 1.18, 95% LAG (OR 0.72, 95% CI 0.34–1.51) and RG (OR 0.20, 95% CI − 2.01 to − 0.48). Compared with OG, length of hospital CI 0.01–4.32). Compared with LAG, the risk of pancreatic stay was similar for patients who underwent RG (OR − 1.78, complications was similar for those who underwent RG (OR 95% CI − 4.15 to 0.419). Compared with LAG, length of 0.14, 95% CI 0.01–2.82) [ESM Appendices 4 and 5]. hospital stay was similar for patients who underwent RG (OR In total, 18.2% of included studies reported on VTE 0.60, 95% CI − 1.54 to 2.78) [ESM Appendices 6 and 7]. (4/22). Compared with OG, the risk of VTE was similar for In total, 40.9% of included studies reported on the num- those who underwent LAG (OR 0.90, 95% CI 0.43–1.89) ber of days until a patient could ingest sips of fluids (9/22). and RG (OR 0.91, 95% CI 0.05–16.18). Similarly, the risk Compared with an OG, there was a non-significant reduction of VTE was comparable between LAG and RG (OR 0.99, in the number of days until a patient could ingest sips of flu- 95% CI 0.06–15.88) [ESM Appendices 4 and 5]. ids for those undergoing LAG (OR − 0.416, 95% CI − 0.826 Overall, 72.7% of included studies reported on anasto- to 0.0227) and RG (OR − 0.679, 95% CI − 1.53 to 0.245). motic leak (16/22). Compared with OG, the risk of anas- Compared with LAG, the number of days until a patient tomotic leak was similar for those who underwent LAG could ingest sips of fluids was comparable for those who (OR 1.17, 95% CI 0.69–1.96) and RG (OR 0.70, 95% CI underwent RG (OR − 0.26, 95% CI − 1.02 to 0.54) [ESM 0.12–3.67). Compared with LAG, the risk of anastomotic Appendices 6 and 7]. leak was similar for those who underwent RG (OR 0.61, 95% In total, 31.8% of included studies reported on the num- CI 0.11–2.80) [ESM Appendices 4 and 5]. ber of days until a patient could ingest solid food (7/22). In total, 22.7% of included studies reported on anasto- Compared with OG, the number of days until a patient could motic stenosis (5/22). Compared with OG, the risk of anas- ingest solid food was similar for those who underwent LAG tomotic stenosis was similar for those who underwent LAG (OR − 0.620, 95% CI − 1.81 to 0.55) and RG (OR 0.379, (OR 0.84, 95% CI 0.19–3.71) and RG (OR 0.14, 95% CI 95% CI − 2.79 to 3.54). Compared with LAG, the number M. G. Davey et al. OutcomeForrest Plot Network plot Network plot of all studies (a) Compared with Open Open Laparoscopic 64.3 (51.0, 78.7) Robotic 99.3 (55.1, 145.) 0 200 Laparoscopic Robotic Network plot of all studies (b) Compared with Open Open Laparoscopic –79.4 (–108., –52.3) Robotic –87.2 (–173., –2.75) Laparoscopic –200 0 Robotic Network plot of all studies (c) Compared with Open Open –1.52 (–2.75, –0.450) Laparoscopic Robotic –1.95 (–5.77, 1.25) –10 0 10 Laparoscopic Robotic (d) Open Mean Difference (95% Crl) Compared with Open Laparoscopic –0.310 (–0.565, –0.0992) –1 0 1 Laparoscopic (e) Open Mean Difference (95% Crl) Compared with Open Laparoscopic –0.220 (–0.530, –0.0617) –1 0 1 Laparoscopic (f) Open Mean Difference (95% Crl) Compared with Open –11.7 (–14.5, –8.91) Laparoscopic –20 0 Laparoscopic Minimally Invasive and Open Gastrectomy …        ◂FIG. 3 Forest and network plots with respect to intraoperative data. risk-of-bias assessment for RCTs. In brief, three of the (a) Intraoperative time; (b) intraoperative blood loss; (c) lymph node included RCTs had ‘low’ risk of bias, 12 RCTs had ‘some’ harvest; (d) distance from the proximal margin; (e) distance from the risk of bias, and 7 RCTs illustrated evidence of ‘high’ risk of distal margin; and (f) length of incision bias. Comprehensive summaries of the risk-of-bias assess- ment are outlined in ESM Appendix 10. of days until a patient could ingest solid food was similar for those who underwent RG (OR 1.00, 95% CI − 1.95 to 3.95) DISCUSSION [ESM Appendices 6 and 7]. In total, 77.3% of included studies reported on the num- The management paradigm for gastric carcinoma has ber of days until a patient could first pass flatus (17/22). evolved such that multimodal therapeutic strategies are Compared with OG, there was a significant reduction in now pragmatically tailored to each patient, which has trans- the number of days until a patient could first pass flatus for lated into enhanced oncological and survival outcomes. those undergoing both LAG (OR − 0.455, 95% CI − 0.650 In addition, the inclusion of quality-of-life (QoL) outcome to − 0.259) and RG (OR − 0.61, 95% CI − 1.13 to − 0.080). measures is now routinely utilized to establish the impact Compared with LAG, there was a non-significant reduction of both local and systemic therapies on host (or biological) in the number of days until a patient could first pass flatus function, to determine whether the oncological benefit of for those undergoing RG (OR − 0.15, 95% CI − 0.64 to 0.34) such treatments os ff et their associated toxicities and morbid - [ESM Appendices 6 and 7]. ity. This NMA was performed to establish the oncologi- In total, 36.4% of included studies reported on days till cal and surgical safety of MIS gastrectomy compared with first ambulation (8/22). Compared with OG, there was a conventional OG, including data from 6890 patients treated similar number of days to first ambulation for those who for primary gastric carcinoma in 22 independent RCTs. This underwent LAG (OR − 0.15, 95% CI − 0.81 to 0.50) and RG analysis illustrated the non-inferiority of LAG compared (OR − 0.40, 95% CI − 1.69 to 0.89). Compared with LAG, with OG with respect to survival, while highlighting the days to ambulation were similar for those who underwent improved surgical and recovery outcomes associated with RG (OR − 0.25, 95% CI − 1.36 to 0.87) [ESM Appendices 6 the MIS approaches, supporting their use where possible. and 7]. Consequently, LAG should be considered for patients with Overall, 18.2% of included studies reported on readmis- primary resectable gastric cancer, providing that surgeon sion (4/22). Compared with OG, the rates of readmission and institutional expertise allows, echoing the previous com- were similar to those who underwent LAG (OR 0.91, 95% prehensive results of a standard pairwise meta-analysis of CI 0.53−1.56) or RG (OR 0.92, 95% CI 0.12–7.10) [ESM RCTs performed by Lou et al. in 2022, albeit limited by Appendices 6 and 7]. Compared with LAG, the rate of read- the inclusion of studies performed three decades previously. mission was similar for those who underwent RG (OR 0.99, Traditionally, extensive locoregional resection using OG 95% CI 0.14–7.15). was the standard of care for resection of gastric carcinoma, which has since been surpassed by the adoption of both lapa- 70,71 roscopic and robotic approaches as routine. Importantly, Tumour Size this study illustrated the non-inferiority of LAG relative to Overall, 68.2% of included studies reported tumour size OG with respect to long-term oncological and survival out- (15/22). Compared with OG, tumour size was similar to comes, despite reduced nodal yields harvested and closer those who underwent LAG (OR − 0.13, 95% CI − 0.32 to distances to specimen margins with LAG. OS was identi- 0.06) and RG (OR − 0.24, 95% CI − 0.75 to 0.30). Compared cal for both OG and LAG (both 87.0%) at approximately with LAG, tumour size was similar to those who underwent 5 years’ follow-up, with similar recurrence observed for RG (OR − 0.11, 95% CI − 0.59 to 0.40) [ESM Appendices 8 both (9.5% vs. 8.7%), which likely represents a significant and 9]. proportion of patients with early-stage disease, limiting the translatability of these results into the locally advanced set- Cost Effectiveness ting. However, notably, disease recurrence and OS outcomes Overall, 13.6% of included studies reported on cost are as yet unavailable for patients undergoing RG compared (3/22). RG was significantly more expensive than LAG (OR with the other modalities. Therefore, while this study com- 3258.00, 95% CI 3204–59,3311.41) [ESM Appendices 8 and prehensively establishes the non-inferiority of LAG versus 9]. OG for disease recurrence and OS, the absence of RCT data for RG limits the synthesis of any similar level 1 conclusions Risk of Bias regarding the oncologic efficacy of RG. In a previous meta- All 22 of the included studies were ‘low’ risk of bias analysis of 19 non-randomized, observational studies includ- for most categories, using the Cochrane Collaboration ing 7275 patients, Ma et al. reported similar OS (hazard M. G. Davey et al. ratio [HR] 0.95, 95% CI 0.76–1.18), recurrence-free sur- Therefore, this study highlights the premise for LAG to be vival (HR 0.91, 95% CI 0.69–1.21) and disease recurrence utilized for primary gastric resection where feasible, should (HR 0.90, 95% CI 0.67–1.21) for patients undergoing RG institutional expertise allow, with further evaluation of RG versus LAG. Furthermore, a previous propensity-matched approaches required to determine what benefit, if any, this analysis performed by Obama et al. demonstrated the non- approach may have over LAG. inferiority of RG relative to LAG for disease recurrence Despite the absence of survival data, this study does pro- (6.7% vs. 5.0%) and OS (8.9% vs. 11.6%). Interestingly, vide preliminary data in support of RG, which was associ- however, there was an increase in locoregional recurrence ated with reduced morbidity, major morbidity, and similar rates following RG relative to LAG (42.9% vs. 30.8%). In the cardiorespiratory, pancreatic and other significant postop- absence of RCT data, the results from studies such as that by erative complications in this study compared with OG and Obama et al. are important to highlight the potential risks LAG. Moreover, when compared with LAG, patients under- and fundamental challenges to introducing and implement- going RG had a significant reduction in overall morbidity ing new surgical techniques, albeit being limited due to its (OR 0.43, 95% CI 0.25–0.76), further potentiating RG as a single-centre, retrospective design. However, it is important pragmatic minimally invasive approach to gastrectomy in that further rigorous scientific evaluation of RG with pro- patients with early gastric cancer. These are important find- spective, randomized studies are conducted to ensure patient ings that strengthen the perceived benefit associated with safety and to avoid the unexpected issues that have arose RG, particularly when the application of robotic technology during the early adoption of other new surgical techniques is an attractive addition to the surgeons’ armamentarium, 74,75 for cancer, while remaining cognizant of the fact that due to the theoretical advantages over conventional lapa- premature adoption, inadequate proctoring and suboptimal roscopy, including improved dexterity, enhanced visualiza- execution, rather than any issue with the technique itself, tion, and superior ergonomics. Shortcomings of robotic may be to blame. surgery include the longer operative time and increased While the survival outcomes for LAG and OG are equivo- expense associated with this approach, as well as purchasing cal, it is imperative that the other results in this NMA are and maintaining equipment and training operators, a steep considered when selecting the optimal technique for per- learning curve, and poorer cost effectiveness in low-volume 80–83 forming gastrectomy for gastric cancer, particularly in terms centres. While the data suggest reasonable equipoise of the enhanced patient recovery and reduced complication between RG and LAG surgery in terms of morbidity and rate associated with the MIS approaches, which coincide recovery, the argument that robotic instrumentation may with the robust implementation of enhanced recovery after allow for improved mobility in narrow areas with restricted surgery (ERAS) protocols in contemporary surgical oncol- access, for example, at the diaphragmatic hiatus and when 77 84 ogy. Patients undergoing LAG experienced a reduction in performing anastomoses, seems plausible. Another exam- IBL, shorter surgical incisions, reduced distance from proxi- ple is lymphadenectomy, where the removal of the D2 nodes mal margins, shorter postoperative hospital stays, and, most is considered the standard surgical procedure for the major- importantly, reduced morbidity post-resection. When inter- ity of patients with resectable gastric carcinoma. Con- pretating these data, these important findings tip this study in troversary remains in relation to resection beyond D2 for favour of minimally invasive techniques, particularly when cases of advanced disease, for several reasons, including the these data support the comparability of LAG and OG regard- reduced operative freedom, the signic fi ant dic ffi ulty control - ing long-term follow-up. MIS is advantageous as patients ling haemorrhage, and the relative ease of trauma to local tend to be subject to less physiological stress, immunologic structures. The results of the present NMA show a sig- burden, faster recovery times, lower complication rates, nificant reduction in LNY following LAG, with similar out- and less immediate and long-term burden on healthcare comes observed following OG and RG, indicating that RG resources. Therefore, MIS techniques may prove advan- may offer an advantage over LAG for technically difficult tageous in improving cost effectiveness in the long-term, manoeuvres such as extensive lymphatic resection during despite the greater direct cost associated with such surgical ‘D2 plus’ lymphadenectomy for advanced gastric cancer. approaches as described in the current analysis. Accord- The current analysis is subject to limitations. First, as ingly, this study further validates the current paradigm shift described in detail, none of the two included RCTs reported towards adopting MIS techniques where possible, as these survival outcomes following RG, limiting the conclusions approaches are associated with longer operative duration rel- that may be drawn from the current study. Second, the stud- ative to OG, as well as RG being significantly more expen- ies included in this review failed to provide survivorship data sive than LAG in the current NMA, coupled with emerg- that may inform the psychosocial impact of OG, LAG, and ing evidence suggesting an increased risk of cardiovascular RG on patients’ QoL following resection. Third, there are complications, rendering patient selection imperative if RG several competing factors that may confound the data pre- is being contemplated during multidisciplinary discussion. sented in this study; these include the prescription of (neo) Minimally Invasive and Open Gastrectomy …        FUNDING Open Access funding provided by the IReL Consortium. adjuvant chemo-, radio-, or immunotherapeutic agents to No funding was received for this study. improve survival outcomes, as well as the impact of surgi- cal approach in the context of early, locally advanced, or DATA AVAILABILITY Data can be made available upon reason- advanced gastric carcinoma. Unfortunately, attempts to per- able request from the corresponding author. form analyses allowing for correction of such factors have DISCLOSURE been futile, thus limiting these results. Finally, evaluation of surgeon-specific proficiency and the influence of the cen- Matthew G. Davey, Hugo C. Temperley, Niall J. O’Sullivan, Vianka Marcelino, Odhrán K. Ryan, Éanna J. Ryan, Noel E. Donlon, Sean M. tralisation of gastric cancer treatment to high-volume cen- Johnston, and William B. Robb have no conflicts of interest to declare. tres was not evaluated to determine their impact on clinical outcomes. Therefore, those responsible for the provision of ETHICAL APPROVAL Not applicable as this is a review of previ- the next generation of prospective, randomized gastrectomy ously published studies. trials should consider these confounding factors at the time of trial design to ensure the optimisation of data outcomes. OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adap- tation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, CONCLUSION provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are This analysis demonstrates the non-inferiority of onco- included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in logical and surgical outcomes for OG and LAG in patients the article’s Creative Commons licence and your intended use is not being treated predominantly for early gastric cancer follow- permitted by statutory regulation or exceeds the permitted use, you will ing 5 years of follow-up. Moreover, surgical outcomes fol- need to obtain permission directly from the copyright holder. To view a lowing minimally invasive gastrectomy superseded those copy of this licence, visit http://cr eativ ecommons. or g/licen ses/ b y/4.0/ . following OG, with enhanced outcomes observed for both LAG and RG. This highlights the oncological and surgical safety of LAG relative to OG, while also illustrating that REFERENCES the short-term surgical, morbidity and recovery outcomes 1. Sung H, Ferlay J, Siegel RL, et  al. Global cancer statistics following RG are comparable with LAG. Given these find- 2020: GLOBOCAN estimates of incidence and mortality ings, LAG may be considered for patients with primary worldwide for 36 cancers in 185 countries. CA Cancer J Clin. resectable gastric cancer, providing that surgeon and insti- 2021;71(3):209–49. tutional expertise allows, however further RCTs are war- 2. Wagner AD, Syn NL, Moehler M, et  al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. ranted before definitive conclusions may be drawn in the 2017;8:4CD004064. setting of advanced disease. However, given the challenges 3. Ng SP, Leong T. Role of radiation therapy in gastric cancer. Ann in adopting high-quality LAG for all cases, evaluation of Surg Oncol. 2021;28(8):4151–7. new techniques that might make the procedure easier and 4. Donlon NE, Davern M, Hayes C, et al. The immune response to major gastrointestinal cancer surgery and potential implica- thereby reduce the incidence of poor oncological and func- tions for adjuvant immunotherapy. Crit Rev Oncol Hematol. tional outcome are warranted. The concept of utilizing RG in 2022;175:103729. these circumstances offers a number of theoretical but as yet 5. Smyth EC, Verheij M, Allum W, et al. Gastric cancer: ESMO unproven advantages, apart from LNY as was demonstrated clinical practice guidelines for diagnosis, treatment and follow- up. Ann Oncol. 2016;27(Suppl 5):v38–49. in this analysis. In time, as more institutions employ an RG 6. Banks M, Graham D, Jansen M, Gotoda T, Coda S, di Pietro approach, it is likely that surgical and institutional expertise M, et al. British society of gastroenterology guidelines on the will facilitate further evaluation of the MIS techniques to diagnosis and management of patients at risk of gastric adeno- determine the relative advantages and disadvantages of both carcinoma. Gut. 2019;68(9):1545–75. https:// doi.or g/ 10. 1136/ gutjnl- 2018- 318126. techniques, which have not been extensive explored in this 7. Jin T, Liu HD, Yang K, Chen ZH, Zhang YX, Hu JK. Effec- study. In the interim, technique selection should be based on tiveness and safety of robotic gastrectomy versus laparoscopic individual tumour characteristics and patient expectations, gastrectomy for gastric cancer: a meta-analysis of 12,401 gastric as well as surgeon and institutional expertise. cancer patients. Updates Surg. 2022;74(1):267–81. 8. Japanese Gastric Cancer A. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer. 2017;20(1):1-19. SUPPLEMENTARY INFORMATION The online version con- 9. Caruso S, Giudicissi R, Mariatti M, Cantafio S, Paroli GM, Sca- tains supplementary material available at https:// doi. or g/ 10. 1245/ tizzi M. Laparoscopic vs. open gastrectomy for locally advanced s10434- 023- 13654-6. gastric cancer: a propensity score-matched retrospective case- control study. Curr Oncol. 2022;29(3):1840–65. ACKNOWLEDGEMENT The authors would like to thank Dr. Amirhossein Jalali, School of Medicine, University of Limerick, Lim- erick, Ireland, for his expertise and assistance with the study. M. G. Davey et al. 10. Chen K, Pan Y, Zhang B, Maher H, Wang XF, Cai XJ. Robotic 27. Ashrafian H, Clancy O, Grover V, Darzi A. The evolution of versus laparoscopic gastrectomy for gastric cancer: a systematic robotic surgery: surgical and anaesthetic aspects. Br J Anaesth. review and updated meta-analysis. BMC Surg. 2017;17(1):93. 2017;119(Suppl 1):i72–84. 11. Kodera Y, Fujiwara M, Ohashi N, et al. Laparoscopic surgery for 28. Kang BH, Xuan Y, Hur H, Ahn CW, Cho YK, Han SU. Com- gastric cancer: a collective review with meta-analysis of rand- parison of surgical outcomes between robotic and laparoscopic omized trials. J Am Coll Surg. 2010;211(5):677–86. gastrectomy for gastric cancer: the learning curve of robotic sur- 12. Bobo Z, Xin W, Jiang L, et al. Robotic gastrectomy versus lapa- gery. J Gastric Cancer. 2012;12(3):156–63. https://d oi. org/ 10. roscopic gastrectomy for gastric cancer: meta-analysis and trial 5230/ jgc. 2012. 12.3. 156. sequential analysis of prospective observational studies. Surg 29. Hashizume M, Shimada M, Tomikawa M, et al. Early experi- Endosc. 2019;33(4):1033–48. ences of endoscopic procedures in general surgery assisted 13. Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, by a computer-enhanced surgical system. Surg Endosc . Arnold D. Gastric cancer: ESMO clinical practice guidelines for 2002;16(8):1187–91. diagnosis, treatment and follow-up. Ann Oncol. 2016;27:v38–49. 30. Alhossaini RM, Altamran AA, Seo WJ, Hyung WJ. Robotic gas- 14. Kitano S, Iso Y, Moriyama M, Sugimachi K. Laparoscopy- trectomy for gastric cancer: current evidence. Ann Gastroenterol assisted Billroth I gastrectomy. Surg Laparosc Endosc. Surg. 2017;1(2):82–9. 1994;4(2):146–8. 31. Li Z, Li J, Li B, et  al. Robotic versus laparoscopic gastrec- 15. Antonakis PT, Ashrafian H, Isla AM. Laparoscopic gastric sur - tomy with D2 lymph node dissection for advanced gastric can- gery for cancer: where do we stand? World J Gastroenterol. cer: a propensity score-matched analysis. Cancer Manag Res. 2014;20(39):14280–91. 2018;10:705–14. https:// doi. org/ 10. 2147/ CMAR. S1610 07. 16. Claassen YHM, van Amelsfoort RM, Hartgrink HH, et al. Effect 32. Ma J, Li X, Zhao S, Zhang R, Yang D. Robotic versus laparo- of hospital volume with respect to performing gastric cancer scopic gastrectomy for gastric cancer: a systematic review and resection on recurrence and survival: results from the CRITICS meta-analysis. World J Surg Oncol. 2020;18(1):306. trial. Ann Surg. 2019;270(6):1096–102. 33. Kassab P, Castro OAP. Distal gastrectomy: the evidence—a nar- 17. Kim HH, Han SU, Kim MC, et al. Effect of laparoscopic distal rative overview. Ann Laparosc Endosc Surg. 2022;7:7. gastrectomy vs open distal gastrectomy on long-term survival 34. Muaddi H, Hafid ME, Choi WJ, et  al. Clinical outcomes of among patients with stage I gastric cancer: the KLASS-01 rand- robotic surgery compared to conventional surgical approaches omized clinical trial. JAMA Oncol. 2019;5(4):506–13. (laparoscopic or open): a systematic overview of reviews. Ann 18. Katai H, Mizusawa J, Katayama H, et  al. Survival outcomes Surg. 2021;273(3):467–73. after laparoscopy-assisted distal gastrectomy versus open distal 35. Chen X, Feng X, Wang M, Yao X. Laparoscopic versus open gastrectomy with nodal dissection for clinical stage IA or IB distal gastrectomy for advanced gastric cancer: a meta-analysis gastric cancer (JCOG0912): a multicentre, non-inferiority, phase of randomized controlled trials and high-quality nonrandomized 3 randomised controlled trial. Lancet Gastroenterol Hepatol. comparative studies. Eur J Surg Oncol. 2020;46(11):1998–2010. 2020;5(2):142–51. 36. Best LM, Mughal M, Gurusamy KS. Laparoscopic versus open 19. Hyung WJ, Yang HK, Han SU, et al. A feasibility study of lapa- gastrectomy for gastric cancer. Cochrane Database Syst Rev. roscopic total gastrectomy for clinical stage I gastric cancer: a 2016;3:CD011389. prospective multi-center phase II clinical trial, KLASS 03. Gas‑ 37. Aiolfi A, Lombardo F, Matsushima K, et al. Systematic review tric Cancer. 2019;22(1):214–22. and updated network meta-analysis of randomized controlled 20. Yu J, Huang C, Sun Y, et al. Effect of laparoscopic vs open dis- trials comparing open, laparoscopic-assisted, and robotic distal tal gastrectomy on 3-year disease-free survival in patients with gastrectomy for early and locally advanced gastric cancer. Sur‑ locally advanced gastric cancer: the CLASS-01 randomized gery. 2021;170(3):942–51. clinical trial. JAMA. 2019;321(20):1983–92. 38. Woo Y, Hyung WJ, Pak KH, et al. Robotic gastrectomy as an 21. Hyung WJ, Yang HK, Park YK, et al. Long-term outcomes of oncologically sound alternative to laparoscopic resections laparoscopic distal gastrectomy for locally advanced gastric can- for the treatment of early-stage gastric cancers. Arch Surg. cer: the KLASS-02-RCT randomized clinical trial. J Clin Oncol. 2011;146:1086–9. 2020;38(28):3304–13. 39. Lu J, Zheng CH, Xu BB, et al. Assessment of robotic versus 22. Park YK, Yoon HM, Kim YW, et al. Laparoscopy-assisted versus laparoscopic distal gastrectomy for gastric cancer: a randomized open D2 distal gastrectomy for advanced gastric cancer: results controlled trial. Ann Surg. 2021;273(5):858–67. from a randomized phase II multicenter clinical trial (COACT 40. Lee S, Kim HH. Minimally invasive surgery in advanced gastric 1001). Ann Surg. 2018;267(4):638–45. cancer. Ann Gastroenterol Surg. 2022;6(3):336–43. 23. Lee HJ, Hyung WJ, Yang HK, et al. Short-term outcomes of a 41. Jansen JP, Naci H. Is network meta-analysis as valid as stand- multicenter randomized controlled trial comparing laparoscopic ard pairwise meta-analysis? It all depends on the distribution of distal gastrectomy with D2 lymphadenectomy to open distal gas- effect modifiers. BMC Med. 2013;11:159. trectomy for locally advanced gastric cancer (KLASS-02-RCT). 42. Mills EJ, Ioannidis JP, Thorlund K, Schunemann HJ, Puhan MA, Ann Surg. 2019;270(6):983–91. Guyatt GH. How to use an article reporting a multiple treatment 24. Hu Y, Huang C, Sun Y, et  al. Morbidity and mortality of comparison meta- analysis. JAMA. 2012;308(12):1246e53. laparoscopic versus open D2 distal gastrectomy for advanced 43. Hutton B, Salanti G, Caldwell DM, et al. The PRISMA exten- gastric cancer: a randomized controlled trial. J Clin Oncol. sion statement for reporting of systematic reviews incorporating 2016;34(12):1350–7. network meta-analyses of health care interventions: checklist and 25. Li Z, Shan F, Ying X, et al. Assessment of laparoscopic dis- explanations. Ann Intern Med. 2015;162(11):777–84. tal gastrectomy after neoadjuvant chemotherapy for locally 44. Armstrong EC. The well-built clinical question: the key to find- advanced gastric cancer: a randomized clinical trial. JAMA Surg. ing the best evidence efficiently. WMJ. 1999;98(2):25–8. 2019;154(12):1093–101. 45. Rücker G, Krahn U, König J, Efthimiou O, Schwarzer G. Net- 26. Wang Z, Xing J, Cai J, et al. Short-term surgical outcomes of meta: network meta-analysis using frequentist methods. R pack‑ laparoscopy-assisted versus open D2 distal gastrectomy for age version. 2019;1. locally advanced gastric cancer in North China: a multicenter randomized controlled trial. Surg Endosc. 2019;33(1):33–45. Minimally Invasive and Open Gastrectomy …        46. Chang W, Cheng J, Allaire J, Xie Y, McPherson J. Shiny: web 64. Kim W, Kim HH, Han SU, et al. Decreased morbidity of lapa- application framework for R. R package version. 2017;1(5). roscopic distal gastrectomy compared with open distal gastrec- 47. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and vari- tomy for stage I gastric cancer: short-term outcomes from a ance from the median, range, and the size of a sample. BMC Med multicenter randomized controlled trial (KLASS-01). Ann Surg. Res Methodol. 2005;5(1):13. 2016;263(1):28–35. 48. Luo D, et al. Optimally estimating the sample mean from the 65. Katai H, Mizusawa J, Katayama H, et al. Short-term surgical out- sample size, median, mid-range, and/or mid-quartile range. Stat comes from a phase III study of laparoscopy-assisted versus open Methods Med Res. 2018;27(6):1785–805. distal gastrectomy with nodal dissection for clinical stage IA/IB 49. Wan X, et al. Estimating the sample mean and standard deviation gastric cancer: Japan clinical oncology group study JCOG0912. from the sample size, median, range and/or interquartile range. Gastric Cancer. 2017;20(4):699–708. BMC Med Res Methodol. 2014;14(1):135. 66. Ojima T, Nakamura M, Hayata K, et al. Short-term outcomes 50. Higgins JPT, Altman DG, Gotsche PC, et al. The Cochrane Col- of robotic gastrectomy vs laparoscopic gastrectomy for patients laboration’s tool for assessing risk of bias in randomised con- with gastric cancer: a randomized clinical trial. JAMA Surg. trolled trials. BMJ. 2011;343:d5928. 2021;156(10):954–63. 51. Kim HY. Statistical notes for clinical researchers: chi-squared 67. Joshi SS, Badgwell BD. Current treatment and recent progress test and Fisher’s exact test. Restor Dent Endod. 2017;42(2):152– in gastric cancer. CA Cancer J Clin. 2021;71(3):264–79. 5. https:// doi. org/ 10. 5395/ rde. 2017. 42.2. 152. 68. Heneghan HM, Zaborowski A, Fanning M, et al. Prospective 52. Huscher CG, Mingoli A, Sgarzini G, et al. Laparoscopic ver- study of malabsorption and malnutrition after esophageal and sus open subtotal gastrectomy for distal gastric cancer: five- gastric cancer surgery. Ann Surg. 2015;262(5):803–7. year results of a randomized prospective trial. Ann Surg. 69. Lou S, Yin X, Wang Y, Zhang Y, Xue Y. Laparoscopic ver- 2005;241(2):232–7. sus open gastrectomy for gastric cancer: a systematic review 53. Lee JH, Han HS, Lee JH. A prospective randomized study com- and meta-analysis of randomized controlled trials. Int J Surg. paring open vs laparoscopy-assisted distal gastrectomy in early 2022;102:106678. gastric cancer: early results. Surg Endosc. 2005;19(2):168–73. 70. Park SH, Kim JM, Park SS. Current status and trends of mini- 54. Hayashi H, Ochiai T, Shimada H, Gunji Y. Prospective rand- mally invasive gastrectomy in Korea. Medicina (Kaunas). omized study of open versus laparoscopy-assisted distal gas- 2021;57(11):1195. trectomy with extraperigastric lymph node dissection for early 71. Scarritt T, Hsu CH, Maegawa FB, Ayala AE, Mobily M, Ghaderi gastric cancer. Surg Endosc. 2005;19(9):1172–6. I. Trends in utilization and perioperative outcomes in robotic- 55. Takiguchi S, Fujiwara Y, Yamasaki M, et  al. Laparoscopy- assisted bariatric surgery using the MBSAQIP database: a 4-year assisted distal gastrectomy versus open distal gastrectomy. analysis. Obes Surg. 2021;31(2):854–61. A prospective randomized single-blind study. World J Surg. 72. Ma J, Li X, Zhao S, Zhang R, Yang D. Robotic versus laparo- 2013;37(10):2379–86. scopic gastrectomy for gastric cancer: a systematic review and 56. Aoyama T, Yoshikawa T, Hayashi T, et al. Randomized compari- meta-analysis. World J Surg Oncol. 2020;18(1):306. son of surgical stress and the nutritional status between laparos- 73. Obama K, Kim Y-M, Kang DR, et al. Long-term oncologic out- copy-assisted and open distal gastrectomy for gastric cancer. Ann comes of robotic gastrectomy for gastric cancer compared with Surg Oncol. 2014;21(6):1983–90. laparoscopic gastrectomy. Gastric Cancer. 2018;21(2):285–95. 57. Shi Y, Xu X, Zhao Y, et al. Short-term surgical outcomes of a 74. Larsen SG, Pfeffer F, Kørner H. Norwegian morato - randomized controlled trial comparing laparoscopic versus open rium on transanal total mesorectal excision. Br J Surg. gastrectomy with D2 lymph node dissection for advanced gastric 2019;106(9):1120–1. cancer. Surg Endosc. 2018;32(5):2427–33. 75. van Oostendorp SE, Belgers HJ, Bootsma BT, et al. Locoregional 58. Cai J, Wei D, Gao CF, Zhang CS, Zhang H, Zhao T. A pro- recurrences after transanal total mesorectal excision of rectal spective randomized study comparing open versus laparoscopy- cancer during implementation. Br J Surg. 2020;107(9):1211–20. assisted D2 radical gastrectomy in advanced gastric cancer. Dig 76. Soomro NA, Hashimoto DA, Porteous AJ, et  al. Systematic Surg. 2011;28(5–6):331–7. review of learning curves in robot-assisted surgery. BJS Open. 59. Chen HuJ, Xin Jiang L, Cai L, et  al. Preliminary experience 2020;4(1):27–44. of fast-track surgery combined with laparoscopy-assisted radi- 77. Desiderio J, Trastulli S, D’Andrea V, Parisi A. Enhanced recov- cal distal gastrectomy for gastric cancer. J Gastrointest Surg. ery after surgery for gastric cancer (ERAS-GC): optimizing 2012;16(10):1830–9. patient outcome. Transl Gastroenterol Hepatol. 2020;5:11. 60. Cui M, Li Z, Xing J, et al. A prospective randomized clinical trial 78. Cooper MA, Hutfless S, Segev DL, Ibrahim A, Lyu H, Makary comparing D2 dissection in laparoscopic and open gastrectomy MA. Hospital level under-utilization of minimally inva- for gastric cancer. Med Oncol. 2015;32(10):241. sive surgery in the United States: retrospective review. BMJ. 61. van der Veen A, Brenkman HJF, Seesing MFJ, et  al. Lapa- 2014;349:g4198. roscopic versus open gastrectomy for gastric cancer (LOG- 79. Woo Y, Hyung WJ, Pak KH, et al. Robotic gastrectomy as an ICA): a multicenter randomized clinical trial. J Clin Oncol. oncologically sound alternative to laparoscopic resections 2021;39(9):978–89. for the treatment of early-stage gastric cancers. Arch Surg. 62. Kim YW, Baik YH, Yun YH, et al. Improved quality of life out- 2011;146(9):1086–92. comes after laparoscopy-assisted distal gastrectomy for early 80. Nomine-Criqui C, Germain A, Ayav A, Bresler L, Brunaud gastric cancer: results of a prospective randomized clinical trial. L. Robot-assisted adrenalectomy: indications and drawbacks. Ann Surg. 2008;248(5):721–7. Updates Surg. 2017;69(2):127–33. 63. Sakuramoto S, Yamashita K, Kikuchi S, et al. Laparoscopy ver- 81. Pineda-Solís K, Medina-Franco H, Heslin MJ. Robotic versus sus open distal gastrectomy by expert surgeons for early gastric laparoscopic adrenalectomy: a comparative study in a high-vol- cancer in Japanese patients: short-term clinical outcomes of a ume center. Surg Endosc. 2013;27(2):599–602. randomized clinical trial. Surg Endosc. 2013;27(5):1695–705. 82. Owen RK, Bradbury N, Xin Y, Cooper N, Sutton A. MetaInsight: an interactive web-based tool for analyzing, interrogating, and M. G. Davey et al. visualizing network meta-analyses using R-shiny and netmeta. gastrectomy for early gastric cancer: result of a randomized con- Res Synth Methods. 2019;10(4):569–81. trolled trial (COACT 0301). Surg Endosc. 2013;27(11):4267–76. 83. Hyams ES, Mullins JK, Pierorazio PM, Partin AW, Allaf 88. Yamashita K, Sakuramoto S, Kikuchi S, Futawatari N, Katada ME, Matlaga BR. Impact of robotic technique and surgi- N, Hosoda K, et al. Laparoscopic versus open distal gastrectomy cal volume on the cost of radical prostatectomy. J Endourol. for early gastric cancer in Japan: long-term clinical outcomes of 2013;27(3):298–303. a randomized clinical trial. Surg Today. 2016;46(6):741–9. 84. Kostakis ID, Sran H, Uwechue R, et al. Comparison between 89. van der Veen A, Brenkman HJF, Seesing MFJ, Haverkamp L, robotic and laparoscopic or open anastomoses: a systematic Luyer MDP, Nieuwenhuijzen GAP, et al. Laparoscopic versus review and meta-analysis. Robot Surg. 2019;6:27–40. open gastrectomy for gastric cancer (LOGICA): a multicenter 85. Li JQ, He D, Liang YX. Current status of extended “D2 plus” randomized clinical trial. J Clin Oncol. 2021;39(9):978–89. lymphadenectomy in advanced gastric cancer. Oncol Lett. 2021;21(6):467. Publisher’s Note Springer Nature remains neutral with regard to 86. Lee HJ, Hyung WJ, Yang HK, et al. Short-term outcomes of a jurisdictional claims in published maps and institutional affiliations. multicenter randomized controlled trial comparing laparoscopic distal gastrectomy with D2 lymphadenectomy to open distal gas- trectomy for locally advanced gastric cancer (KLASS-02-RCT). Ann Surg. 2019;270(6):983–91. 87. Kim YW, Yoon HM, Yun YH, Nam BH, Eom BW, Baik YH, et  al. Long-term outcomes of laparoscopy-assisted distal http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Surgical Oncology Springer Journals

Minimally Invasive and Open Gastrectomy for Gastric Cancer: A Systematic Review and Network Meta-Analysis of Randomized Clinical Trials

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Abstract

Ann Surg Oncol https://doi.org/10.1245/s10434-023-13654-6 REVIEW ARTICLE – GASTROINTESTINAL ONCOLOGY Minimally Invasive and Open Gastrectomy for Gastric Cancer: A Systematic Review and Network Meta‑Analysis of Randomized Clinical Trials 1 2 3 Matthew G. Davey, MCh, MRCSI, PhD , Hugo C. Temperley, MB, BCh , Niall J. O’Sullivan, MB, BCh , 4 4 1,4 1,5 Vianka Marcelino , Odhrán K. Ryan, MB, BCh , Éanna J. Ryan, MD, MRCSI , Noel E. Donlon, MRCSI, PhD , 6 5 Sean M. Johnston, FRCSI(Gen) , and William B. Robb, FRCSI(Gen) 1 2 Department of Surgery, Royal College of Surgeons in Ireland, Dublin 2, Republic of Ireland; Department of Surgery, Trinity St. James’s Cancer Institute, Trinity, St. James’s Hospital, Trinity College Dublin, Dublin, Republic of Ireland; 3 4 Department of Surgery, Tallaght University Hospital, Dublin, Republic of Ireland; Department of Surgery, St. Vincent’s University Hospital, Dublin, Republic of Ireland; Department of Upper Gastrointestinal Surgery, Beaumont Hospital, Dublin 9, Co Dublin, Republic of Ireland; Department of Surgery, Midlands University Hospital, Tullamore, Co. Offaly, Republic of Ireland ABSTRACT no differences in OS in meta-analysis (OR 1.02, 95% CI Background and Objectives. Optimal surgical manage- 0.77–1.52). Importantly, patients undergoing LAG experi- ment for gastric cancer remains controversial. We aimed enced reduced intraoperative blood loss, surgical incisions, to perform a network meta-analysis (NMA) of randomized distance from proximal margins, postoperative hospital clinical trials (RCTs) comparing outcomes after open gas- stays, and morbidity post-resection. trectomy (OG), laparoscopic-assisted gastrectomy (LAG), Conclusions. LAG was associated with non-inferior onco- and robotic gastrectomy (RG) for gastric cancer. logical and surgical outcomes compared with OG. Surgi- Methods. A systematic search of electronic databases was cal outcomes following LAG and RG superseded OG, with undertaken. An NMA was performed as per the Preferred similar outcomes observed for both LAG and RG. Given Reporting Items for Systematic Reviews and Meta-Analyses these findings, minimally invasive approaches should be (PRISMA)-NMA guidelines. Statistical analysis was per- considered for the resection of local gastric cancer, once formed using R and Shiny. surgeon and institutional expertise allows. Results. Twenty-two RCTs including 6890 patients were included. Overall, 49.6% of patients underwent LAG Keywords Gastric cancer · Gastrectomy · Minimally (3420/6890), 46.6% underwent OG (3212/6890), and 3.7% invasive surgery · Surgical oncology · Oncological underwent RG (258/6890). At NMA, there was a no sig- outcomes nificant difference in recurrence rates following LAG (odds ratio [OR] 1.09, 95% confidence interval [CI] 0.77–1.49) compared with OG. Similarly, overall survival (OS) out- Gastric cancer is the fifth most common cancer world- comes were identical following OG and LAG (OS: OG, wide and third leading cause of cancer-related mortality. Its 87.0% [1652/1898] vs. LAG: OG, 87.0% [1650/1896]), with management paradigm has evolved with the advent of multi- modal therapeutic strategies, including novel combinations 2 3 of chemotherapeutic agents, radiotherapies, and immu- © The Author(s) 2023 nomodulatory drugs, all of which may be tailored in accord- ance with patient and tumour factors to improve oncologic First Received: 3 January 2023 Accepted: 4 May 2023 outcomes. This personalized approach is conducted with the intention of minimizing treatment-related toxicities, while simultaneously achieving the best pathological responses M. G. Davey, MCh, MRCSI, PhD 5,6 to conventional therapeutic strategies. Despite these e-mail: matthewdavey21@rcsi.com Vol.:(0123456789) M. G. Davey et al. advances, high-quality radical en bloc surgical resection of and RG relative to OG is yet to be determined. Importantly, 7,8 the tumour remains the cornerstone of management, Tra- two recent RCTs have reported short-term postoperative 38,39 ditionally, gastrectomy was performed as an open procedure and survival outcomes following RG, and anticipation (OG), although more recently, minimally invasive surgical among gastroesophageal surgeons is that such minimally (MIS) approaches have undergone widespread adoption, invasive approaches should enhance patient outcomes. including laparoscopic-assisted gastrectomy (LAG) and Therefore, application of the network meta-analysis (NMA) 9,10 robotic-assisted gastrectomy (RG). Advocates of MIS methodology here is timely to allow simultaneous compari- hold this approach to be advantageous for several reasons, son (direct and indirect) of minimally invasive approaches 41,42 particularly reduced morbidity, and enhanced recovery and to gastrectomy with OG using RCT data only. 11,12 cosmesis. Nevertheless, OG remains the approach of choice for certain cases, as surgical approach is dependent METHODS on an array of patient, pathological, and societal parameters, as well as surgeon and institutional expertise. A systematic review was performed in accordance with The first LAG was performed for gastric cancer in 1994, the Preferred Reporting Items for Systematic Reviews and and this approach has subsequently been developed and Meta-Analyses (PRISMA) extension statement for report- refined. Several studies, including multicentre, prospec- ing of systematic reviews incorporating NMAs of healthcare tive, randomized clinical trials (RCTs), have illustrated interventions. This study was registered with the Interna- the non-inferiority of long-term oncological and survival tional Prospective Register of Systematic Reviews (PROS- outcomes following LAG and OG. Consequently, LAG is PERO, CRD42022330440). a well-established surgical approach in the management of 16–19 early gastric carcinoma. Increasingly, LAG is currently Search Strategy emerging as feasible, safe and effective for radical resection 20,21 of locally advanced distal gastric cancer. Nevertheless, A formal systematic search of four electronic databases there remains debate surrounding the differences in postop- was performed in March 2022 for relevant titles. Details in erative and oncological outcomes following LAG, as well as relation to the search strategy can be found in Appendix 1 in the considerable technical aspects and learning curve associ- the electronic supplementary material (ESM). Study-specific 22–26 ated with the laparoscopic approach. definitions and the research question determined using the Robot-assisted surgery has been proposed as a potential Population, Intervention, Comparison, Outcomes (PICO) platform to overcome some of the limitations of conven- framework are outlined in detail in ESM Appendices 2 tional laparoscopy and has recently undergone widespread and 3. adoption by many specialists and surgical oncology units for the management of many solid organ cancers. This is Eligibility Criteria principally due to the reported advantages of three-dimen- sional vision, enhanced skill acquisition (due to a shorter All published RCTs with full-text manuscripts comparing learning curve relative to laparoscopic surgery), increased the outcomes of two or more methods of surgical interven- operator dexterity, improved mobility in narrow areas that tion for gastric cancer (i.e., OG, LAG or RG) were included. have restricted access, and improved ergonomics for the The inclusion criteria for studies were (1) compared post- 27,28 operating surgeon. However, while the first RG was operative surgical outcomes (e.g., complications, estimated performed in Japan 20 years ago by Hashizume et al., the blood loss, lymph node yield [LNY], etc.) or long-term uptake of robotic surgery in upper gastrointestinal surgery oncological and survival outcomes (e.g., disease recurrence, has lagged considerably behind other surgical specialties. overall survival [OS], etc.); (2) were of a prospective, rand- At present, data available in relation to robotic surgery is omized design; (3) recruited patients aged 18 years or older primarily obtained from studies of a retrospective design, undergoing surgery for known primary gastric cancer; and typically involving outcomes regarding single-centre or (4) studies had to have full-text manuscripts available. Note single-surgeon experiences of using robotics for gastric that when overlapping trial data were reported from two dif- cancer resections, with limited long-term oncological out- ferent sources, the source with the longest patient follow-up comes being reported. Therefore, there is a paucity of high- or largest sample size was included. quality data evaluating the role of RG for resection of gastric The exclusion criteria were (1) studies failing to fulfil the 31–33 tumours. above inclusion criteria; (2) studies that only have results 32,34–37 Several RCTs and standard pairwise meta-analyses published in abstract form or from conference proceedings; have attempted to determine the optimal surgical approaches (3) studies not published in the English language; or (4) used for the resection of gastric carcinoma, however consen- studies in which the primary indication for the gastrectomy sus in relation to the oncological and surgical safety of LAG Minimally Invasive and Open Gastrectomy …        was not for gastric cancer (e.g., bariatric sleeve gastrectomy, Risk‑of‑Bias Assessment etc.). Assessment of potential biases within the included RCTs was assessed using the Cochrane Collaboration tool (for Statistical Analysis RCTs). This assessment tool grades the risk of bias in each study as being high risk (marked in red), low risk (marked in Descriptive statistics were used to outline the characteris- tics of the included trials. Data pertaining to recurrence, OS, green), or uncertain risk (marked in yellow) of bias across six categories. The critical appraisal was independently morbidity, complications and readmission were expressed as dichotomous or binary outcomes, reported as odds ratios completed by two reviewers (HCT and MGD), and in the case of discrepancies in opinion, a third reviewer (NED) (ORs) with 95% confidence intervals (CIs). ORs were cal - culated using crude event RCT data, to compare interven- was asked to arbitrate. tions using per-protocol data, where applicable. Continuous data were calculated using mean values, standard deviations RESULTS (SDs) and pooled mean variance, with differences expressed as weighted mean differences (WMDs). OG was the prin- Literature Search cipal comparator for all analyses. Bayesian NMAs were 45 46 conducted using netameta and Shiny packages for R. In total, 7385 articles were identified and 4220 duplicate Point estimates of effect sizes were described with a 95% articles were excluded. Thereafter, study titles and abstracts CI. Results were considered statistically significant at the were screened, resulting in 53 studies being eligible for full- p < 0.050 level if the 95% CI did not include a value of 1. text review. Of these, 22 RCTs met the eligibility criteria 22–26,39,51–66 Estimates of mean and SDs were calculated using standard and were included. The PRISMA flow chart is 47,48 statistical methods, where applicable. Rank probabilities illustrated in Fig. 1. were plotted against the possible ranks for all competing treatments. The confidence in estimates of the outcome was Study Characteristics assessed using the Confidence in Network Meta-Analysis (CINeMA) tool. Overall, 6890 patients with gastric cancer were included, of whom 3212 patients underwent OG (46.6%, 3212/6890), 3420 patients underwent LAG (49.6%, 3420/6890) and 258 FIG. 1 PRISMA flowchart outlining the systematic search process. PRISMA Preferred Records identified from data-base Reporting Items for Systematic searching: (n = 7385) Duplicate records removed Reviews and Meta-Analyses, RCTs randomized controlled (n = 4220) Databases (n = 4) trials Records excluded Records screened (n = 3114) (n = 7385) Reports excluded (n = 21) Reports assessed for eligibility - 8 incomplete study design - 5 incomplete outcomes (n = 53) - 5 conference abstracts - 3 incomplete RCTs Studies included in review - RCT n = 22 Included Screening Identification M. G. Davey et al. patients underwent RG (3.7%, 258/6890). The mean age Compared with OG, there was a significant reduction in at surgery was 60.9 years (range 54.5–72.0 years). Over- IBL for those who underwent LAG (OR − 79.4, 95% CI all, 15/22 studies included distal gastrectomy (DG) only − 108.0 to − 52.3) and the robotic group (OR − 87.2, 95% CI (68.2%), with 6/22 (27.3%) and 4/22 (18.2%) also includ- − 173.0 to − 2.75) (Fig. 3b and ESM Appendix 3b). Further- ing total gastrectomy (TG) and partial gastrectomy (PG), more, there was a non-significant reduction in IBL in those respectively. Overall, 40.9% reported outcomes for early undergoing RG compared with those undergoing LAG (OR gastric cancer (9/22), 18.2% for locally advanced gastric − 7.83, 95% CI − 88.83 to 73.02). cancer (4/22), 9.1% for advanced gastric cancer (2/22), and Overall, 50.0% of included studies reported on the num- 31.8% for resectable gastric cancer (7/22). The characteris- ber of LNs harvested (11/22). Compared with OG, LAG tics of the trials included in this meta-analysis are shown in showed a significantly decreased LN yield (OR − 1.52, 95% Table 1. All ranking tables illustrating the data are presented CI − 2.75 to − 0.45), whereas there was a non-significant in Table 2. difference in LNs harvested for those who underwent RG (OR − 1.95, 95% CI − 5.77 to 1.25) (Fig.  3c and ESM Primary Outcome Measures Appendix 3c). In total, 31.8% of the included studies reported on the Disease Recurrence distance from the proximal margin (7/22). This distance Overall, 27.3% of studies reported outcomes with respect from the proximal margin was significantly lower in those to disease recurrence (6/22). The mean follow-up was 56.4 undergoing LAG compared with OG (OR − 0.310, 95% months (range 22.1–99.8 months), and the overall recurrence CI − 0.565 to − 0.0992) (Fig. 3d and ESM Appendix 3d). rate was 9.1% (435/4775). LAG had the highest recurrence The rank probability was highest in those undergoing LAG rate (9.5%, 226/2,373), followed by OG (8.7%, 209/2402). (0.99), indicating a decreased distance from the proximal Of note, recurrence was not reported in any of the studies margin in those undergoing LAG (Table 2). reporting outcomes following RG. When compared with an In total, 27.3% of the included studies reported on the OG, the risk of disease recurrence was similar for those who distance from the distal margin (6/22). The distance from underwent LAG (OR 1.09, 95% CI 0.77–1.49) (Fig. 2a) and distal margin was similar to those who underwent LAG and ESM Appendix 2a]. OG (OR − 0.220, 95% CI − 0.530 to 0.0617) (Fig. 3e and ESM Appendix 3e). The rank probability was highest in Overall Survival those undergoing LAG (0.95), indicating a decreased dis- Overall, 31.8% of included studies reported outcomes tance from the distal margin associated with LAG (Table 2). for analysis in relation to OS (7/22). The mean follow-up In total, 36.4% of the included studies reported on the was 56.4 months (range 22.1–99.8 months). For the overall length of surgical incision (8/22). This was significantly patient cohort, 87.0% of patients were alive at follow-up shorter in those undergoing LAG compared with OG (OR (3302/3794). Of note, OS rates were identical for both OG − 11.7, 95% CI − 14.5 to − 8.91) (Fig. 3f and ESM Appen- and LAG (OS: OG, 87.0% [1652/1898] vs. LAG: OG, 87.0% dix 3f). The rank probability was highest in those undergo- [1650/1896]). OS was not reported in the RG groups. When ing LAG (0.99), indicating a decreased length of surgical compared with OG, OS was similar for those who under- incision associated with LAG (Table 2). went LAG (OR 1.02, 95% CI 0.765–1.52) (Fig. 2b and ESM Appendix 2b]. Postoperative Outcomes Overall, 95.5% of included studies reported outcomes Secondary Outcome Measures in relation to overall morbidity (21/22). Compared with OG, there was a significant reduction in morbidity in those Intraoperative Outcomes undergoing LAG (OR 0.80, 95% CI 0.67–0.95) and RG (OR All 22 RCTs reported outcomes on intraoperative time. 0.35, 95% CI 0.19–0.62), respectively. Compared with LAG, LAG (OR 64.3, 95% CI 51.0–78.7) and RG (OR 99.3, 95% those undergoing RG had a significant reduction in overall CI 55.1–145.0) were associated with significantly longer morbidity (OR 0.43, 95% CI 0.25–0.76) [ESM Appendices intraoperative duration than OG. Compared with LAG, intra- 4 and 5]. operative time was not significantly different to those who In total, 59.1% of included studies reported outcomes in underwent RG (OR 34.96, 95% CI − 7.53 to 77.84) (Fig. 3a relation to major morbidity (13/22). Compared with OG, and ESM Appendix 3a). Of note, the rank probability was there was similar major morbidity in those undergoing LAG highest in the OG group (0.999), indicating the lowest intra- (OR 1.15, 95% CI 0.79–1.65) and RG (OR 0.43, 95% CI operative time associated with OG (Table 2). 0.16–1.17). Compared with LAG, there was a significant In total, 95.5% (21/22) of the included studies reported reduction in major morbidity in those undergoing RG (OR outcomes in relation to intraoperative blood loss (IBL). 0.38, 95% CI 0.14–0.99) [ESM Appendices 4 and 5]. Minimally Invasive and Open Gastrectomy …        TABLE 1 Characteristics of trials included in the meta-analysis Author, year Country Study period Multicentre Surgery No. of patients Age M/F Gastrectomy type Cancer stage Tumour size Staging Kitano Japan 1998–2001 No OG 14 60 ± 3 8/6 DG EGC 2.3 ± 0.3 JCGC LAG 14 63 ± 3 9/5 2.3 ± 0.3 Huscher Italy 1992–1996 No OG 29 63.6 ± 13 21/8 DG GC NA AJCC 5th LAG 30 63.2 ± 12 18/12 NA Lee Korea 2001–2003 No OG 23 59.5 ± 11 15/8 DG EGC 1.8 ± 1.6 AJCC 5th LAG 24 56.6 ± 11 11/13 1.4 ± 0.8 Hayashi Japan 1999–2001 No OG 14 62 ± 6.5 13/1 DG EGC NA NA LAG 14 56 ± 5.7 9/7 NA Cai China 2008–2009 Yes OG 47 60.2 ± 10.2 37/10 PG, DG, TG GC 4.3 ± 1.8 JCGC 13th LAG 49 60.2 ± 9.8 39/10 4.2 ± 2.0 Chen Hu China 2009–2011 No OG 20 64.5 ± 6.5 12/8 DG GC NA JCGC 13th LAG 22 62.5 ± 6.7 10/12 NA Takiguchi Japan 2003–2006 No OG 20 62.5 ± 3 13/7 DG EGC 2.4 ± 0.2 NA LAG 20 61.5 ± 4.3 12/8 2.2 ± 0.5 Kim Korea 2003–2005 No OG 82 54.5 ± 8.3 47/35 DG EGC 3.4 ± 2.1 AJCC 6th LAG 82 56.7 ± 7.5 47/35 3.4 ± 1.8 Yamashita Japan 2005–2008 No OG 32 61 ± 7.6 25/7 DG EGC 3.6 ± 2.4 AJCC 5th LAG 31 58 ± 9.6 17/14 3.9 ± 2.0 Cu China 2010–2012 No OG 142 57.5 ± 11.2 98/44 PG, DG, TG GC NA AJCC 7th LAG 128 60.1 ± 12.6 88/40 NA Aoyama Japan 2011 NA OG 13 63.8 ± 8.9 7/6 DG EGC NA JCGC 14th LAG 13 60.3 ± 11.8 7/6 NA Sh China 2010–2012 No OG 160 NA NA PG, DG, TG AGC NA JCGC 13th LAG 162 NA NA NA Kata Japan 2010–2013 Yes OG 459 64 ± 2.1 275/184 DG, PG ECG 2.5 ± 0.1 JCGC 13th LAG 462 63 ± 1.8 275/184 2.7 ± 0.3 Wang China 2014–2017 Yes OG 220 60.6 ± 10 133/87 DG, TG LAGC 3.9 ± 2.2 AJCC 7th LAG 222 59.4 ± 12 144/78 3.6 ± 1.8 Park Korea 2010–2011 Yes OG 96 60.1 ± 8.2 65/31 DG AGC NA AJCC 7th LAG 100 58.6 ± 8.9 69/31 NA Yu China 2012–2014 Yes OG 520 55.8 ± 11 346/174 DG LAGC 4.0 ± 2 AJCC 7th LAG 519 56.5 ± 10 380/139 4.0 ± 2 Kim Korea 2006–2010 Yes OG 611 57.8 ± 11 412/200 DG EGC NA AJCC 7th LAG 644 56.8 ± 11 425/219 NA Li China 2015–2017 No OG 50 61 ± 2.2 34/16 DG LAGC 2.5 ± 0.5 AJCC 7th LAG 45 59 ± 3.2 32/13 2.5 ± 0.4 Hyung Korea 2011–2015 Yes OG 498 59.6 ± 11 346/152 DG LAGC NA AJCC 7th LAG 513 59.8 ± 11 370/143 NA Vanderveen Netherlands 2015–2018 Yes OG 112 66.9 ± 12.1 72/40 DG, TG GC NA AJCC 8th LAG 115 67.9 ± 11.4 68/37 NA M. G. Davey et al. TABLE 2 SUCRA scores for the outcomes measures. Parameter OG LAG RG Overall recurrence 0.732 (1st) 0.268 (2nd) NR Overall survival 0.563 (1st) 0.437 (2nd) NR Operative time 0.999 (1st) 0.001 (2nd) 0.000 (3rd) Intraoperative blood loss 0.000 (3rd) 0.420 (2nd) 0.580 (1st) Lymph node harvest 0.001 (3rd) 0.391 (2nd) 0.608 (1st) Distance from proximal 0.006 (2nd) 0.996 (1st) NR margin Distance from distal margin 0.050 (2nd) 0.950 (1st) NR Length of incision 0.001 (2nd) 0.999 (1st) NR Wound complications 0.047 (2nd) 0.634 (1st) 0.319 Anastomotic leak 0.281 (2nd) 0.073 (3rd) 0.646 (1st) Length of stay 0.000 (3rd) 0.274 (2nd) 0.725 (1st) Days until sips 0.012 (3rd) 0.220 (2nd) 0.768 (1st) Days until solids 0.099 (3rd) 0.679 (1st) 0.222 (2nd) Days until flatus passed 0.000 (3rd) 0.257 (2nd) 0.743 (1st) Days until ambulation 0.136 (3rd) 0.217 (2nd) 0.647 (1st) Cost 0.646 (1st) 0.331 (2nd) 0.023 (3rd) Tumour size 0.034 (3rd) 0.296 (2nd) 0.670 (1st) OG open gastrectomy, LAG laparoscopic-assisted gastrectomy, RG robotic gastrectomy, NR not reported In total, 68.2% of included studies reported outcomes in relation to perioperative mortality (15/22). Compared with OG, there was similar perioperative mortality in those undergoing LAG (OR 0.90, 95% CI 0.43–1.89) and RG (OR 0.91, 95% CI 0.05–16.18). Compared with LAG, periopera- tive morality was similar for those who underwent RG (OR 0.99, 95% CI 0.06–15.88) [ESM Appendices 4 and 5]. Complications Overall, 50.0% of RCTs reported on wound complica- tions (11/22). Compared with OG, there were similar wound complications for undergoing LAG (OR 0.628, 95% CI 0.30–1.18) and RG (OR 1.03, 95% CI 0.11–10.70). Com- pared with LAG, wound complications were similar for those who underwent RG (OR 1.65, 95% CI 0.20–15.91) [ESM Appendices 4 and 5]. In total, 40.9% of included studies reported on cardiac complications (9/22). Compared with OG, cardiac complica- tions were similar for those who underwent LAG (OR 1.47, 95% CI 0.68–3.17) and RG (OR 8.1, 95% CI 0.96–68.2). Compared with LAG, cardiac complications were similar for those who underwent RG (OR 0.18 95% CI 0.02–1.29). Of note, however, one of the two RCTs evaluating RG illus- trated a significant increase in cardiac complications (OR 33.5, 95% CI 1.97–568.6) [ESM Appendices 4 and 5]. In total, 81.8% of included studies reported on respira- tory complications (18/22). Compared with OG, there was Table 1 (continued) Author, year Country Study period Multicentre Surgery No. of patients Age M/F Gastrectomy type Cancer stage Tumour size Staging Jun Lu China 2017–2020 No LAG 142 59.3 ± 11 90/52 DG GC 3.9 ± 1.9 AJCC 8th RG 141 59.4 ± 10 94/47 3.5 ± 1.8 Ojima Japan 2018–2020 Yes LADG 119 72 ± 8.3 77/42 DG, TG GC 3.2 ± 1.9 AJCC 8th RG 117 71 ± 9.3 73/44 3.5 ± 2.4 OG open gastrectomy, LAG laparoscopic-assisted gastrectomy, RG robotic gastrectomy, M male, F female, DG distal gastrectomy, PG proximal gastrectomy, TG total gastrectomy, NA not avail- able, JCGC Japanese Classification of Gastric Carcinoma, AJCC American Joint Committee on Cancer, EGC early gastric cancer, GC gastric cancer, LAGC locally advanced gastric cancer, AGC advanced gastric cancer Minimally Invasive and Open Gastrectomy …        Outcome Forrest Plot Network plot Network plot of all studies (a) Open Odds Ratio (95% Crl) Compared with Open 1.09 (0.768, 1.49) Laparoscopic 0.1 15 Laparoscopic Network plot of all studies (b) Open Odds Ratio (95% Crl) Compared with Open 1.02 (0.765, 1.52) Laparoscopic 0.1 1 5 Laparoscopic FIG. 2 Forest and network plots with respect to (a) disease recurrence and (b) overall survival a similar rate of respiratory complications for those who 0.00–4.03). Compared with LAG, the risk of anastomotic underwent LAG (OR 0.85, 95% CI 0.62–1.17) and RG (OR stenosis was similar for those who underwent RG (OR 0.17, 0.65, 95% CI 0.29–1.46). Compared with LAG, the risk of 95% CI 0.01–3.39) [ESM Appendices 4 and 5]. respiratory complications was similar for those who under- went RG (OR 0.76, 95% CI 0.36–1.61) [ESM Appendices Recovery 4 and 5]. Overall, 45.5% of included studies reported outcomes on In total, 59.1% of included studies reported on pancreatic length of hospital stay, in days (10/22). When compared with complications (13/22). Compared with OG, the risk of pan- an OG, there was a significant reduction in length of hos- creatic complications was similar for those who underwent pital stay for those who underwent LAG (OR − 1.18, 95% LAG (OR 0.72, 95% CI 0.34–1.51) and RG (OR 0.20, 95% CI − 2.01 to − 0.48). Compared with OG, length of hospital CI 0.01–4.32). Compared with LAG, the risk of pancreatic stay was similar for patients who underwent RG (OR − 1.78, complications was similar for those who underwent RG (OR 95% CI − 4.15 to 0.419). Compared with LAG, length of 0.14, 95% CI 0.01–2.82) [ESM Appendices 4 and 5]. hospital stay was similar for patients who underwent RG (OR In total, 18.2% of included studies reported on VTE 0.60, 95% CI − 1.54 to 2.78) [ESM Appendices 6 and 7]. (4/22). Compared with OG, the risk of VTE was similar for In total, 40.9% of included studies reported on the num- those who underwent LAG (OR 0.90, 95% CI 0.43–1.89) ber of days until a patient could ingest sips of fluids (9/22). and RG (OR 0.91, 95% CI 0.05–16.18). Similarly, the risk Compared with an OG, there was a non-significant reduction of VTE was comparable between LAG and RG (OR 0.99, in the number of days until a patient could ingest sips of flu- 95% CI 0.06–15.88) [ESM Appendices 4 and 5]. ids for those undergoing LAG (OR − 0.416, 95% CI − 0.826 Overall, 72.7% of included studies reported on anasto- to 0.0227) and RG (OR − 0.679, 95% CI − 1.53 to 0.245). motic leak (16/22). Compared with OG, the risk of anas- Compared with LAG, the number of days until a patient tomotic leak was similar for those who underwent LAG could ingest sips of fluids was comparable for those who (OR 1.17, 95% CI 0.69–1.96) and RG (OR 0.70, 95% CI underwent RG (OR − 0.26, 95% CI − 1.02 to 0.54) [ESM 0.12–3.67). Compared with LAG, the risk of anastomotic Appendices 6 and 7]. leak was similar for those who underwent RG (OR 0.61, 95% In total, 31.8% of included studies reported on the num- CI 0.11–2.80) [ESM Appendices 4 and 5]. ber of days until a patient could ingest solid food (7/22). In total, 22.7% of included studies reported on anasto- Compared with OG, the number of days until a patient could motic stenosis (5/22). Compared with OG, the risk of anas- ingest solid food was similar for those who underwent LAG tomotic stenosis was similar for those who underwent LAG (OR − 0.620, 95% CI − 1.81 to 0.55) and RG (OR 0.379, (OR 0.84, 95% CI 0.19–3.71) and RG (OR 0.14, 95% CI 95% CI − 2.79 to 3.54). Compared with LAG, the number M. G. Davey et al. OutcomeForrest Plot Network plot Network plot of all studies (a) Compared with Open Open Laparoscopic 64.3 (51.0, 78.7) Robotic 99.3 (55.1, 145.) 0 200 Laparoscopic Robotic Network plot of all studies (b) Compared with Open Open Laparoscopic –79.4 (–108., –52.3) Robotic –87.2 (–173., –2.75) Laparoscopic –200 0 Robotic Network plot of all studies (c) Compared with Open Open –1.52 (–2.75, –0.450) Laparoscopic Robotic –1.95 (–5.77, 1.25) –10 0 10 Laparoscopic Robotic (d) Open Mean Difference (95% Crl) Compared with Open Laparoscopic –0.310 (–0.565, –0.0992) –1 0 1 Laparoscopic (e) Open Mean Difference (95% Crl) Compared with Open Laparoscopic –0.220 (–0.530, –0.0617) –1 0 1 Laparoscopic (f) Open Mean Difference (95% Crl) Compared with Open –11.7 (–14.5, –8.91) Laparoscopic –20 0 Laparoscopic Minimally Invasive and Open Gastrectomy …        ◂FIG. 3 Forest and network plots with respect to intraoperative data. risk-of-bias assessment for RCTs. In brief, three of the (a) Intraoperative time; (b) intraoperative blood loss; (c) lymph node included RCTs had ‘low’ risk of bias, 12 RCTs had ‘some’ harvest; (d) distance from the proximal margin; (e) distance from the risk of bias, and 7 RCTs illustrated evidence of ‘high’ risk of distal margin; and (f) length of incision bias. Comprehensive summaries of the risk-of-bias assess- ment are outlined in ESM Appendix 10. of days until a patient could ingest solid food was similar for those who underwent RG (OR 1.00, 95% CI − 1.95 to 3.95) DISCUSSION [ESM Appendices 6 and 7]. In total, 77.3% of included studies reported on the num- The management paradigm for gastric carcinoma has ber of days until a patient could first pass flatus (17/22). evolved such that multimodal therapeutic strategies are Compared with OG, there was a significant reduction in now pragmatically tailored to each patient, which has trans- the number of days until a patient could first pass flatus for lated into enhanced oncological and survival outcomes. those undergoing both LAG (OR − 0.455, 95% CI − 0.650 In addition, the inclusion of quality-of-life (QoL) outcome to − 0.259) and RG (OR − 0.61, 95% CI − 1.13 to − 0.080). measures is now routinely utilized to establish the impact Compared with LAG, there was a non-significant reduction of both local and systemic therapies on host (or biological) in the number of days until a patient could first pass flatus function, to determine whether the oncological benefit of for those undergoing RG (OR − 0.15, 95% CI − 0.64 to 0.34) such treatments os ff et their associated toxicities and morbid - [ESM Appendices 6 and 7]. ity. This NMA was performed to establish the oncologi- In total, 36.4% of included studies reported on days till cal and surgical safety of MIS gastrectomy compared with first ambulation (8/22). Compared with OG, there was a conventional OG, including data from 6890 patients treated similar number of days to first ambulation for those who for primary gastric carcinoma in 22 independent RCTs. This underwent LAG (OR − 0.15, 95% CI − 0.81 to 0.50) and RG analysis illustrated the non-inferiority of LAG compared (OR − 0.40, 95% CI − 1.69 to 0.89). Compared with LAG, with OG with respect to survival, while highlighting the days to ambulation were similar for those who underwent improved surgical and recovery outcomes associated with RG (OR − 0.25, 95% CI − 1.36 to 0.87) [ESM Appendices 6 the MIS approaches, supporting their use where possible. and 7]. Consequently, LAG should be considered for patients with Overall, 18.2% of included studies reported on readmis- primary resectable gastric cancer, providing that surgeon sion (4/22). Compared with OG, the rates of readmission and institutional expertise allows, echoing the previous com- were similar to those who underwent LAG (OR 0.91, 95% prehensive results of a standard pairwise meta-analysis of CI 0.53−1.56) or RG (OR 0.92, 95% CI 0.12–7.10) [ESM RCTs performed by Lou et al. in 2022, albeit limited by Appendices 6 and 7]. Compared with LAG, the rate of read- the inclusion of studies performed three decades previously. mission was similar for those who underwent RG (OR 0.99, Traditionally, extensive locoregional resection using OG 95% CI 0.14–7.15). was the standard of care for resection of gastric carcinoma, which has since been surpassed by the adoption of both lapa- 70,71 roscopic and robotic approaches as routine. Importantly, Tumour Size this study illustrated the non-inferiority of LAG relative to Overall, 68.2% of included studies reported tumour size OG with respect to long-term oncological and survival out- (15/22). Compared with OG, tumour size was similar to comes, despite reduced nodal yields harvested and closer those who underwent LAG (OR − 0.13, 95% CI − 0.32 to distances to specimen margins with LAG. OS was identi- 0.06) and RG (OR − 0.24, 95% CI − 0.75 to 0.30). Compared cal for both OG and LAG (both 87.0%) at approximately with LAG, tumour size was similar to those who underwent 5 years’ follow-up, with similar recurrence observed for RG (OR − 0.11, 95% CI − 0.59 to 0.40) [ESM Appendices 8 both (9.5% vs. 8.7%), which likely represents a significant and 9]. proportion of patients with early-stage disease, limiting the translatability of these results into the locally advanced set- Cost Effectiveness ting. However, notably, disease recurrence and OS outcomes Overall, 13.6% of included studies reported on cost are as yet unavailable for patients undergoing RG compared (3/22). RG was significantly more expensive than LAG (OR with the other modalities. Therefore, while this study com- 3258.00, 95% CI 3204–59,3311.41) [ESM Appendices 8 and prehensively establishes the non-inferiority of LAG versus 9]. OG for disease recurrence and OS, the absence of RCT data for RG limits the synthesis of any similar level 1 conclusions Risk of Bias regarding the oncologic efficacy of RG. In a previous meta- All 22 of the included studies were ‘low’ risk of bias analysis of 19 non-randomized, observational studies includ- for most categories, using the Cochrane Collaboration ing 7275 patients, Ma et al. reported similar OS (hazard M. G. Davey et al. ratio [HR] 0.95, 95% CI 0.76–1.18), recurrence-free sur- Therefore, this study highlights the premise for LAG to be vival (HR 0.91, 95% CI 0.69–1.21) and disease recurrence utilized for primary gastric resection where feasible, should (HR 0.90, 95% CI 0.67–1.21) for patients undergoing RG institutional expertise allow, with further evaluation of RG versus LAG. Furthermore, a previous propensity-matched approaches required to determine what benefit, if any, this analysis performed by Obama et al. demonstrated the non- approach may have over LAG. inferiority of RG relative to LAG for disease recurrence Despite the absence of survival data, this study does pro- (6.7% vs. 5.0%) and OS (8.9% vs. 11.6%). Interestingly, vide preliminary data in support of RG, which was associ- however, there was an increase in locoregional recurrence ated with reduced morbidity, major morbidity, and similar rates following RG relative to LAG (42.9% vs. 30.8%). In the cardiorespiratory, pancreatic and other significant postop- absence of RCT data, the results from studies such as that by erative complications in this study compared with OG and Obama et al. are important to highlight the potential risks LAG. Moreover, when compared with LAG, patients under- and fundamental challenges to introducing and implement- going RG had a significant reduction in overall morbidity ing new surgical techniques, albeit being limited due to its (OR 0.43, 95% CI 0.25–0.76), further potentiating RG as a single-centre, retrospective design. However, it is important pragmatic minimally invasive approach to gastrectomy in that further rigorous scientific evaluation of RG with pro- patients with early gastric cancer. These are important find- spective, randomized studies are conducted to ensure patient ings that strengthen the perceived benefit associated with safety and to avoid the unexpected issues that have arose RG, particularly when the application of robotic technology during the early adoption of other new surgical techniques is an attractive addition to the surgeons’ armamentarium, 74,75 for cancer, while remaining cognizant of the fact that due to the theoretical advantages over conventional lapa- premature adoption, inadequate proctoring and suboptimal roscopy, including improved dexterity, enhanced visualiza- execution, rather than any issue with the technique itself, tion, and superior ergonomics. Shortcomings of robotic may be to blame. surgery include the longer operative time and increased While the survival outcomes for LAG and OG are equivo- expense associated with this approach, as well as purchasing cal, it is imperative that the other results in this NMA are and maintaining equipment and training operators, a steep considered when selecting the optimal technique for per- learning curve, and poorer cost effectiveness in low-volume 80–83 forming gastrectomy for gastric cancer, particularly in terms centres. While the data suggest reasonable equipoise of the enhanced patient recovery and reduced complication between RG and LAG surgery in terms of morbidity and rate associated with the MIS approaches, which coincide recovery, the argument that robotic instrumentation may with the robust implementation of enhanced recovery after allow for improved mobility in narrow areas with restricted surgery (ERAS) protocols in contemporary surgical oncol- access, for example, at the diaphragmatic hiatus and when 77 84 ogy. Patients undergoing LAG experienced a reduction in performing anastomoses, seems plausible. Another exam- IBL, shorter surgical incisions, reduced distance from proxi- ple is lymphadenectomy, where the removal of the D2 nodes mal margins, shorter postoperative hospital stays, and, most is considered the standard surgical procedure for the major- importantly, reduced morbidity post-resection. When inter- ity of patients with resectable gastric carcinoma. Con- pretating these data, these important findings tip this study in troversary remains in relation to resection beyond D2 for favour of minimally invasive techniques, particularly when cases of advanced disease, for several reasons, including the these data support the comparability of LAG and OG regard- reduced operative freedom, the signic fi ant dic ffi ulty control - ing long-term follow-up. MIS is advantageous as patients ling haemorrhage, and the relative ease of trauma to local tend to be subject to less physiological stress, immunologic structures. The results of the present NMA show a sig- burden, faster recovery times, lower complication rates, nificant reduction in LNY following LAG, with similar out- and less immediate and long-term burden on healthcare comes observed following OG and RG, indicating that RG resources. Therefore, MIS techniques may prove advan- may offer an advantage over LAG for technically difficult tageous in improving cost effectiveness in the long-term, manoeuvres such as extensive lymphatic resection during despite the greater direct cost associated with such surgical ‘D2 plus’ lymphadenectomy for advanced gastric cancer. approaches as described in the current analysis. Accord- The current analysis is subject to limitations. First, as ingly, this study further validates the current paradigm shift described in detail, none of the two included RCTs reported towards adopting MIS techniques where possible, as these survival outcomes following RG, limiting the conclusions approaches are associated with longer operative duration rel- that may be drawn from the current study. Second, the stud- ative to OG, as well as RG being significantly more expen- ies included in this review failed to provide survivorship data sive than LAG in the current NMA, coupled with emerg- that may inform the psychosocial impact of OG, LAG, and ing evidence suggesting an increased risk of cardiovascular RG on patients’ QoL following resection. Third, there are complications, rendering patient selection imperative if RG several competing factors that may confound the data pre- is being contemplated during multidisciplinary discussion. sented in this study; these include the prescription of (neo) Minimally Invasive and Open Gastrectomy …        FUNDING Open Access funding provided by the IReL Consortium. adjuvant chemo-, radio-, or immunotherapeutic agents to No funding was received for this study. improve survival outcomes, as well as the impact of surgi- cal approach in the context of early, locally advanced, or DATA AVAILABILITY Data can be made available upon reason- advanced gastric carcinoma. Unfortunately, attempts to per- able request from the corresponding author. form analyses allowing for correction of such factors have DISCLOSURE been futile, thus limiting these results. Finally, evaluation of surgeon-specific proficiency and the influence of the cen- Matthew G. Davey, Hugo C. Temperley, Niall J. O’Sullivan, Vianka Marcelino, Odhrán K. Ryan, Éanna J. Ryan, Noel E. Donlon, Sean M. tralisation of gastric cancer treatment to high-volume cen- Johnston, and William B. Robb have no conflicts of interest to declare. tres was not evaluated to determine their impact on clinical outcomes. Therefore, those responsible for the provision of ETHICAL APPROVAL Not applicable as this is a review of previ- the next generation of prospective, randomized gastrectomy ously published studies. trials should consider these confounding factors at the time of trial design to ensure the optimisation of data outcomes. OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adap- tation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, CONCLUSION provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are This analysis demonstrates the non-inferiority of onco- included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in logical and surgical outcomes for OG and LAG in patients the article’s Creative Commons licence and your intended use is not being treated predominantly for early gastric cancer follow- permitted by statutory regulation or exceeds the permitted use, you will ing 5 years of follow-up. Moreover, surgical outcomes fol- need to obtain permission directly from the copyright holder. To view a lowing minimally invasive gastrectomy superseded those copy of this licence, visit http://cr eativ ecommons. or g/licen ses/ b y/4.0/ . following OG, with enhanced outcomes observed for both LAG and RG. This highlights the oncological and surgical safety of LAG relative to OG, while also illustrating that REFERENCES the short-term surgical, morbidity and recovery outcomes 1. Sung H, Ferlay J, Siegel RL, et  al. Global cancer statistics following RG are comparable with LAG. Given these find- 2020: GLOBOCAN estimates of incidence and mortality ings, LAG may be considered for patients with primary worldwide for 36 cancers in 185 countries. CA Cancer J Clin. resectable gastric cancer, providing that surgeon and insti- 2021;71(3):209–49. tutional expertise allows, however further RCTs are war- 2. Wagner AD, Syn NL, Moehler M, et  al. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. ranted before definitive conclusions may be drawn in the 2017;8:4CD004064. setting of advanced disease. However, given the challenges 3. Ng SP, Leong T. Role of radiation therapy in gastric cancer. Ann in adopting high-quality LAG for all cases, evaluation of Surg Oncol. 2021;28(8):4151–7. new techniques that might make the procedure easier and 4. Donlon NE, Davern M, Hayes C, et al. The immune response to major gastrointestinal cancer surgery and potential implica- thereby reduce the incidence of poor oncological and func- tions for adjuvant immunotherapy. Crit Rev Oncol Hematol. tional outcome are warranted. The concept of utilizing RG in 2022;175:103729. these circumstances offers a number of theoretical but as yet 5. Smyth EC, Verheij M, Allum W, et al. Gastric cancer: ESMO unproven advantages, apart from LNY as was demonstrated clinical practice guidelines for diagnosis, treatment and follow- up. Ann Oncol. 2016;27(Suppl 5):v38–49. in this analysis. In time, as more institutions employ an RG 6. Banks M, Graham D, Jansen M, Gotoda T, Coda S, di Pietro approach, it is likely that surgical and institutional expertise M, et al. British society of gastroenterology guidelines on the will facilitate further evaluation of the MIS techniques to diagnosis and management of patients at risk of gastric adeno- determine the relative advantages and disadvantages of both carcinoma. Gut. 2019;68(9):1545–75. https:// doi.or g/ 10. 1136/ gutjnl- 2018- 318126. techniques, which have not been extensive explored in this 7. Jin T, Liu HD, Yang K, Chen ZH, Zhang YX, Hu JK. Effec- study. In the interim, technique selection should be based on tiveness and safety of robotic gastrectomy versus laparoscopic individual tumour characteristics and patient expectations, gastrectomy for gastric cancer: a meta-analysis of 12,401 gastric as well as surgeon and institutional expertise. cancer patients. Updates Surg. 2022;74(1):267–81. 8. Japanese Gastric Cancer A. Japanese gastric cancer treatment guidelines 2014 (ver. 4). Gastric Cancer. 2017;20(1):1-19. SUPPLEMENTARY INFORMATION The online version con- 9. Caruso S, Giudicissi R, Mariatti M, Cantafio S, Paroli GM, Sca- tains supplementary material available at https:// doi. or g/ 10. 1245/ tizzi M. Laparoscopic vs. open gastrectomy for locally advanced s10434- 023- 13654-6. gastric cancer: a propensity score-matched retrospective case- control study. Curr Oncol. 2022;29(3):1840–65. ACKNOWLEDGEMENT The authors would like to thank Dr. Amirhossein Jalali, School of Medicine, University of Limerick, Lim- erick, Ireland, for his expertise and assistance with the study. M. G. Davey et al. 10. Chen K, Pan Y, Zhang B, Maher H, Wang XF, Cai XJ. Robotic 27. Ashrafian H, Clancy O, Grover V, Darzi A. The evolution of versus laparoscopic gastrectomy for gastric cancer: a systematic robotic surgery: surgical and anaesthetic aspects. Br J Anaesth. review and updated meta-analysis. BMC Surg. 2017;17(1):93. 2017;119(Suppl 1):i72–84. 11. Kodera Y, Fujiwara M, Ohashi N, et al. Laparoscopic surgery for 28. Kang BH, Xuan Y, Hur H, Ahn CW, Cho YK, Han SU. Com- gastric cancer: a collective review with meta-analysis of rand- parison of surgical outcomes between robotic and laparoscopic omized trials. J Am Coll Surg. 2010;211(5):677–86. gastrectomy for gastric cancer: the learning curve of robotic sur- 12. Bobo Z, Xin W, Jiang L, et al. Robotic gastrectomy versus lapa- gery. J Gastric Cancer. 2012;12(3):156–63. https://d oi. org/ 10. roscopic gastrectomy for gastric cancer: meta-analysis and trial 5230/ jgc. 2012. 12.3. 156. sequential analysis of prospective observational studies. Surg 29. Hashizume M, Shimada M, Tomikawa M, et al. Early experi- Endosc. 2019;33(4):1033–48. ences of endoscopic procedures in general surgery assisted 13. Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, by a computer-enhanced surgical system. Surg Endosc . Arnold D. Gastric cancer: ESMO clinical practice guidelines for 2002;16(8):1187–91. diagnosis, treatment and follow-up. Ann Oncol. 2016;27:v38–49. 30. Alhossaini RM, Altamran AA, Seo WJ, Hyung WJ. Robotic gas- 14. Kitano S, Iso Y, Moriyama M, Sugimachi K. Laparoscopy- trectomy for gastric cancer: current evidence. Ann Gastroenterol assisted Billroth I gastrectomy. Surg Laparosc Endosc. Surg. 2017;1(2):82–9. 1994;4(2):146–8. 31. Li Z, Li J, Li B, et  al. Robotic versus laparoscopic gastrec- 15. Antonakis PT, Ashrafian H, Isla AM. Laparoscopic gastric sur - tomy with D2 lymph node dissection for advanced gastric can- gery for cancer: where do we stand? World J Gastroenterol. cer: a propensity score-matched analysis. Cancer Manag Res. 2014;20(39):14280–91. 2018;10:705–14. https:// doi. org/ 10. 2147/ CMAR. S1610 07. 16. Claassen YHM, van Amelsfoort RM, Hartgrink HH, et al. Effect 32. Ma J, Li X, Zhao S, Zhang R, Yang D. Robotic versus laparo- of hospital volume with respect to performing gastric cancer scopic gastrectomy for gastric cancer: a systematic review and resection on recurrence and survival: results from the CRITICS meta-analysis. World J Surg Oncol. 2020;18(1):306. trial. Ann Surg. 2019;270(6):1096–102. 33. Kassab P, Castro OAP. Distal gastrectomy: the evidence—a nar- 17. Kim HH, Han SU, Kim MC, et al. Effect of laparoscopic distal rative overview. Ann Laparosc Endosc Surg. 2022;7:7. gastrectomy vs open distal gastrectomy on long-term survival 34. Muaddi H, Hafid ME, Choi WJ, et  al. Clinical outcomes of among patients with stage I gastric cancer: the KLASS-01 rand- robotic surgery compared to conventional surgical approaches omized clinical trial. JAMA Oncol. 2019;5(4):506–13. (laparoscopic or open): a systematic overview of reviews. Ann 18. Katai H, Mizusawa J, Katayama H, et  al. Survival outcomes Surg. 2021;273(3):467–73. after laparoscopy-assisted distal gastrectomy versus open distal 35. Chen X, Feng X, Wang M, Yao X. Laparoscopic versus open gastrectomy with nodal dissection for clinical stage IA or IB distal gastrectomy for advanced gastric cancer: a meta-analysis gastric cancer (JCOG0912): a multicentre, non-inferiority, phase of randomized controlled trials and high-quality nonrandomized 3 randomised controlled trial. Lancet Gastroenterol Hepatol. comparative studies. Eur J Surg Oncol. 2020;46(11):1998–2010. 2020;5(2):142–51. 36. Best LM, Mughal M, Gurusamy KS. Laparoscopic versus open 19. Hyung WJ, Yang HK, Han SU, et al. A feasibility study of lapa- gastrectomy for gastric cancer. Cochrane Database Syst Rev. roscopic total gastrectomy for clinical stage I gastric cancer: a 2016;3:CD011389. prospective multi-center phase II clinical trial, KLASS 03. Gas‑ 37. Aiolfi A, Lombardo F, Matsushima K, et al. Systematic review tric Cancer. 2019;22(1):214–22. and updated network meta-analysis of randomized controlled 20. Yu J, Huang C, Sun Y, et al. Effect of laparoscopic vs open dis- trials comparing open, laparoscopic-assisted, and robotic distal tal gastrectomy on 3-year disease-free survival in patients with gastrectomy for early and locally advanced gastric cancer. Sur‑ locally advanced gastric cancer: the CLASS-01 randomized gery. 2021;170(3):942–51. clinical trial. JAMA. 2019;321(20):1983–92. 38. Woo Y, Hyung WJ, Pak KH, et al. Robotic gastrectomy as an 21. Hyung WJ, Yang HK, Park YK, et al. Long-term outcomes of oncologically sound alternative to laparoscopic resections laparoscopic distal gastrectomy for locally advanced gastric can- for the treatment of early-stage gastric cancers. Arch Surg. cer: the KLASS-02-RCT randomized clinical trial. J Clin Oncol. 2011;146:1086–9. 2020;38(28):3304–13. 39. Lu J, Zheng CH, Xu BB, et al. Assessment of robotic versus 22. Park YK, Yoon HM, Kim YW, et al. Laparoscopy-assisted versus laparoscopic distal gastrectomy for gastric cancer: a randomized open D2 distal gastrectomy for advanced gastric cancer: results controlled trial. Ann Surg. 2021;273(5):858–67. from a randomized phase II multicenter clinical trial (COACT 40. Lee S, Kim HH. Minimally invasive surgery in advanced gastric 1001). Ann Surg. 2018;267(4):638–45. cancer. Ann Gastroenterol Surg. 2022;6(3):336–43. 23. Lee HJ, Hyung WJ, Yang HK, et al. Short-term outcomes of a 41. Jansen JP, Naci H. Is network meta-analysis as valid as stand- multicenter randomized controlled trial comparing laparoscopic ard pairwise meta-analysis? It all depends on the distribution of distal gastrectomy with D2 lymphadenectomy to open distal gas- effect modifiers. BMC Med. 2013;11:159. trectomy for locally advanced gastric cancer (KLASS-02-RCT). 42. Mills EJ, Ioannidis JP, Thorlund K, Schunemann HJ, Puhan MA, Ann Surg. 2019;270(6):983–91. Guyatt GH. How to use an article reporting a multiple treatment 24. Hu Y, Huang C, Sun Y, et  al. Morbidity and mortality of comparison meta- analysis. JAMA. 2012;308(12):1246e53. laparoscopic versus open D2 distal gastrectomy for advanced 43. Hutton B, Salanti G, Caldwell DM, et al. The PRISMA exten- gastric cancer: a randomized controlled trial. J Clin Oncol. sion statement for reporting of systematic reviews incorporating 2016;34(12):1350–7. network meta-analyses of health care interventions: checklist and 25. Li Z, Shan F, Ying X, et al. Assessment of laparoscopic dis- explanations. Ann Intern Med. 2015;162(11):777–84. tal gastrectomy after neoadjuvant chemotherapy for locally 44. Armstrong EC. The well-built clinical question: the key to find- advanced gastric cancer: a randomized clinical trial. JAMA Surg. ing the best evidence efficiently. WMJ. 1999;98(2):25–8. 2019;154(12):1093–101. 45. Rücker G, Krahn U, König J, Efthimiou O, Schwarzer G. Net- 26. Wang Z, Xing J, Cai J, et al. Short-term surgical outcomes of meta: network meta-analysis using frequentist methods. R pack‑ laparoscopy-assisted versus open D2 distal gastrectomy for age version. 2019;1. locally advanced gastric cancer in North China: a multicenter randomized controlled trial. Surg Endosc. 2019;33(1):33–45. Minimally Invasive and Open Gastrectomy …        46. Chang W, Cheng J, Allaire J, Xie Y, McPherson J. Shiny: web 64. Kim W, Kim HH, Han SU, et al. Decreased morbidity of lapa- application framework for R. R package version. 2017;1(5). roscopic distal gastrectomy compared with open distal gastrec- 47. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and vari- tomy for stage I gastric cancer: short-term outcomes from a ance from the median, range, and the size of a sample. BMC Med multicenter randomized controlled trial (KLASS-01). Ann Surg. Res Methodol. 2005;5(1):13. 2016;263(1):28–35. 48. Luo D, et al. Optimally estimating the sample mean from the 65. Katai H, Mizusawa J, Katayama H, et al. Short-term surgical out- sample size, median, mid-range, and/or mid-quartile range. Stat comes from a phase III study of laparoscopy-assisted versus open Methods Med Res. 2018;27(6):1785–805. distal gastrectomy with nodal dissection for clinical stage IA/IB 49. Wan X, et al. Estimating the sample mean and standard deviation gastric cancer: Japan clinical oncology group study JCOG0912. from the sample size, median, range and/or interquartile range. Gastric Cancer. 2017;20(4):699–708. BMC Med Res Methodol. 2014;14(1):135. 66. Ojima T, Nakamura M, Hayata K, et al. Short-term outcomes 50. Higgins JPT, Altman DG, Gotsche PC, et al. The Cochrane Col- of robotic gastrectomy vs laparoscopic gastrectomy for patients laboration’s tool for assessing risk of bias in randomised con- with gastric cancer: a randomized clinical trial. JAMA Surg. trolled trials. BMJ. 2011;343:d5928. 2021;156(10):954–63. 51. Kim HY. Statistical notes for clinical researchers: chi-squared 67. Joshi SS, Badgwell BD. Current treatment and recent progress test and Fisher’s exact test. Restor Dent Endod. 2017;42(2):152– in gastric cancer. CA Cancer J Clin. 2021;71(3):264–79. 5. https:// doi. org/ 10. 5395/ rde. 2017. 42.2. 152. 68. Heneghan HM, Zaborowski A, Fanning M, et al. Prospective 52. Huscher CG, Mingoli A, Sgarzini G, et al. Laparoscopic ver- study of malabsorption and malnutrition after esophageal and sus open subtotal gastrectomy for distal gastric cancer: five- gastric cancer surgery. Ann Surg. 2015;262(5):803–7. year results of a randomized prospective trial. Ann Surg. 69. Lou S, Yin X, Wang Y, Zhang Y, Xue Y. Laparoscopic ver- 2005;241(2):232–7. sus open gastrectomy for gastric cancer: a systematic review 53. Lee JH, Han HS, Lee JH. A prospective randomized study com- and meta-analysis of randomized controlled trials. Int J Surg. paring open vs laparoscopy-assisted distal gastrectomy in early 2022;102:106678. gastric cancer: early results. Surg Endosc. 2005;19(2):168–73. 70. Park SH, Kim JM, Park SS. Current status and trends of mini- 54. Hayashi H, Ochiai T, Shimada H, Gunji Y. Prospective rand- mally invasive gastrectomy in Korea. Medicina (Kaunas). omized study of open versus laparoscopy-assisted distal gas- 2021;57(11):1195. trectomy with extraperigastric lymph node dissection for early 71. Scarritt T, Hsu CH, Maegawa FB, Ayala AE, Mobily M, Ghaderi gastric cancer. Surg Endosc. 2005;19(9):1172–6. I. Trends in utilization and perioperative outcomes in robotic- 55. Takiguchi S, Fujiwara Y, Yamasaki M, et  al. Laparoscopy- assisted bariatric surgery using the MBSAQIP database: a 4-year assisted distal gastrectomy versus open distal gastrectomy. analysis. Obes Surg. 2021;31(2):854–61. A prospective randomized single-blind study. World J Surg. 72. Ma J, Li X, Zhao S, Zhang R, Yang D. Robotic versus laparo- 2013;37(10):2379–86. scopic gastrectomy for gastric cancer: a systematic review and 56. Aoyama T, Yoshikawa T, Hayashi T, et al. Randomized compari- meta-analysis. World J Surg Oncol. 2020;18(1):306. son of surgical stress and the nutritional status between laparos- 73. Obama K, Kim Y-M, Kang DR, et al. Long-term oncologic out- copy-assisted and open distal gastrectomy for gastric cancer. Ann comes of robotic gastrectomy for gastric cancer compared with Surg Oncol. 2014;21(6):1983–90. laparoscopic gastrectomy. Gastric Cancer. 2018;21(2):285–95. 57. Shi Y, Xu X, Zhao Y, et al. Short-term surgical outcomes of a 74. Larsen SG, Pfeffer F, Kørner H. Norwegian morato - randomized controlled trial comparing laparoscopic versus open rium on transanal total mesorectal excision. Br J Surg. gastrectomy with D2 lymph node dissection for advanced gastric 2019;106(9):1120–1. cancer. Surg Endosc. 2018;32(5):2427–33. 75. van Oostendorp SE, Belgers HJ, Bootsma BT, et al. Locoregional 58. Cai J, Wei D, Gao CF, Zhang CS, Zhang H, Zhao T. A pro- recurrences after transanal total mesorectal excision of rectal spective randomized study comparing open versus laparoscopy- cancer during implementation. Br J Surg. 2020;107(9):1211–20. assisted D2 radical gastrectomy in advanced gastric cancer. Dig 76. Soomro NA, Hashimoto DA, Porteous AJ, et  al. Systematic Surg. 2011;28(5–6):331–7. review of learning curves in robot-assisted surgery. BJS Open. 59. Chen HuJ, Xin Jiang L, Cai L, et  al. Preliminary experience 2020;4(1):27–44. of fast-track surgery combined with laparoscopy-assisted radi- 77. Desiderio J, Trastulli S, D’Andrea V, Parisi A. Enhanced recov- cal distal gastrectomy for gastric cancer. J Gastrointest Surg. ery after surgery for gastric cancer (ERAS-GC): optimizing 2012;16(10):1830–9. patient outcome. Transl Gastroenterol Hepatol. 2020;5:11. 60. Cui M, Li Z, Xing J, et al. A prospective randomized clinical trial 78. Cooper MA, Hutfless S, Segev DL, Ibrahim A, Lyu H, Makary comparing D2 dissection in laparoscopic and open gastrectomy MA. Hospital level under-utilization of minimally inva- for gastric cancer. Med Oncol. 2015;32(10):241. sive surgery in the United States: retrospective review. BMJ. 61. van der Veen A, Brenkman HJF, Seesing MFJ, et  al. Lapa- 2014;349:g4198. roscopic versus open gastrectomy for gastric cancer (LOG- 79. Woo Y, Hyung WJ, Pak KH, et al. Robotic gastrectomy as an ICA): a multicenter randomized clinical trial. J Clin Oncol. oncologically sound alternative to laparoscopic resections 2021;39(9):978–89. for the treatment of early-stage gastric cancers. Arch Surg. 62. Kim YW, Baik YH, Yun YH, et al. Improved quality of life out- 2011;146(9):1086–92. comes after laparoscopy-assisted distal gastrectomy for early 80. Nomine-Criqui C, Germain A, Ayav A, Bresler L, Brunaud gastric cancer: results of a prospective randomized clinical trial. L. Robot-assisted adrenalectomy: indications and drawbacks. Ann Surg. 2008;248(5):721–7. Updates Surg. 2017;69(2):127–33. 63. Sakuramoto S, Yamashita K, Kikuchi S, et al. Laparoscopy ver- 81. Pineda-Solís K, Medina-Franco H, Heslin MJ. Robotic versus sus open distal gastrectomy by expert surgeons for early gastric laparoscopic adrenalectomy: a comparative study in a high-vol- cancer in Japanese patients: short-term clinical outcomes of a ume center. Surg Endosc. 2013;27(2):599–602. randomized clinical trial. Surg Endosc. 2013;27(5):1695–705. 82. Owen RK, Bradbury N, Xin Y, Cooper N, Sutton A. MetaInsight: an interactive web-based tool for analyzing, interrogating, and M. G. Davey et al. visualizing network meta-analyses using R-shiny and netmeta. gastrectomy for early gastric cancer: result of a randomized con- Res Synth Methods. 2019;10(4):569–81. trolled trial (COACT 0301). Surg Endosc. 2013;27(11):4267–76. 83. Hyams ES, Mullins JK, Pierorazio PM, Partin AW, Allaf 88. Yamashita K, Sakuramoto S, Kikuchi S, Futawatari N, Katada ME, Matlaga BR. Impact of robotic technique and surgi- N, Hosoda K, et al. Laparoscopic versus open distal gastrectomy cal volume on the cost of radical prostatectomy. J Endourol. for early gastric cancer in Japan: long-term clinical outcomes of 2013;27(3):298–303. a randomized clinical trial. Surg Today. 2016;46(6):741–9. 84. Kostakis ID, Sran H, Uwechue R, et al. Comparison between 89. van der Veen A, Brenkman HJF, Seesing MFJ, Haverkamp L, robotic and laparoscopic or open anastomoses: a systematic Luyer MDP, Nieuwenhuijzen GAP, et al. Laparoscopic versus review and meta-analysis. Robot Surg. 2019;6:27–40. open gastrectomy for gastric cancer (LOGICA): a multicenter 85. Li JQ, He D, Liang YX. Current status of extended “D2 plus” randomized clinical trial. J Clin Oncol. 2021;39(9):978–89. lymphadenectomy in advanced gastric cancer. Oncol Lett. 2021;21(6):467. Publisher’s Note Springer Nature remains neutral with regard to 86. Lee HJ, Hyung WJ, Yang HK, et al. Short-term outcomes of a jurisdictional claims in published maps and institutional affiliations. multicenter randomized controlled trial comparing laparoscopic distal gastrectomy with D2 lymphadenectomy to open distal gas- trectomy for locally advanced gastric cancer (KLASS-02-RCT). Ann Surg. 2019;270(6):983–91. 87. Kim YW, Yoon HM, Yun YH, Nam BH, Eom BW, Baik YH, et  al. Long-term outcomes of laparoscopy-assisted distal

Journal

Annals of Surgical OncologySpringer Journals

Published: Sep 1, 2023

Keywords: Gastric cancer; Gastrectomy; Minimally invasive surgery; Surgical oncology; Oncological outcomes

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