MD Alexandre Challine

MD, PhD Thibault Voron

MD, PhD Bertrand Dousset

MD Ben Creavin

MD, PhD Sandrine Katsahian

MD, PhD Yann Parc

MD, PhD Andrea Lazzati

Professor Jérémie H Lefèvre
email: jeremie.lefevre@aphp.fr

Postoperative outcomes after laparoscopic or open gastrectomy. A national cohort study of 10,343 patients

Background: Laparoscopy for gastric cancer has not been as popular compared with other digestive surgeries, with conflicting reports on outcomes. The aim of this study focuses on the surgical technics comparing open and laparoscopy by assessing the morbi-mortality and long-term complications after gastrectomy.

Methods: A retrospective study (2013)(2014)(2015)(2016)(2017)(2018) was performed on a prospective national cohort (PMSI). All patients undergoing resection for gastric cancer with a partial gastrectomy (PG) or total gastrectomy (TG) were included. Overall morbidity at 90 post-operative days and long-term results were the main outcomes. The groups (open and laparoscopy) were compared using a propensity score and volume activity matching after stratification on resection type (TG or PG).

Results: A total of 10,343 patients were included. The overall 90-day mortality and morbidity were 7% and 45%, with reintervention required in 9.1%. High centre volume was associated with improved outcomes. There was no difference in population characteristics between groups after matching. An overall benefit for a laparoscopic approach after PG was found for morbidity (Open=39.4% vs. Laparoscopy=32.6%, p=0.01), length of stay (Open=14[10-21] vs.

Laparoscopy=11[8-17] days, p<0.0001). For TG, increased reintervention rate (Open=10.8% vs.

Laparoscopy=14.5%, p=0.04) and increased oesophageal stricture rate (HR=2. 54[1.67-3.85], p<0.001) were encountered after a laparoscopic approach. No benefit on mortality was found for laparoscopic approach in both type of resections after adjusted analysis.

Conclusions:

Laparoscopy is feasible for PG with a substantial benefit on morbidity and length of stay, however, laparoscopic TG should be performed with caution, with of higher rates of reintervention and oesophageal stricture.

INTRODUCTION

Minimally invasive surgery has become the preferred choice in a number of specialties including colorectal, bariatric, oesophageal and hepatic surgery. [START_REF] Study | A comparison of laparoscopically assisted and open colectomy for colon cancer[END_REF][START_REF] Weller | Comparing outcomes of laparoscopic versus open bariatric surgery[END_REF][START_REF] Mariette | Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer[END_REF][START_REF] Nguyen | World review of laparoscopic liver resection-2,804 patients[END_REF] However, a laparoscopic approach for gastric cancer has not been as popular, with conflicting reports on outcomes seen in the literature.

A recent randomized clinical trial (RCT) KLASS-01 [START_REF] Kim | Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer: Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01)[END_REF] comparing laparoscopic and open partial gastrectomy (PG) in stage I gastric cancer reported an advantage for laparoscopy on overall morbidity rate, although, major abdominal complications were similar. Oncological outcomes were not compromised and showed the safety of the laparoscopic approach, with no difference observed in 5-year cancer specific survival rates between the open and laparoscopic group. [START_REF] Kim | Effect of Laparoscopic Distal Gastrectomy vs Open Distal Gastrectomy on Long-term Survival Among Patients With Stage I Gastric Cancer: The KLASS-01 Randomized Clinical Trial[END_REF] Similar results were encountered in the Klass-02 RCT [START_REF] Lee | Short-term Outcomes of a Multicenter Randomized Controlled Trial Comparing Laparoscopic Distal Gastrectomy With D2 Lymphadenectomy to Open Distal Gastrectomy for Locally Advanced Gastric Cancer (KLASS-02-RCT)[END_REF] with a significantly reduced morbidity seen in the laparoscopic group, while the oncologic result of CLASS-01 showed no difference between laparoscopic or open resection for locally advanced cancer. [START_REF] Yu | Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric Cancer: The CLASS-01 Randomized Clinical Trial[END_REF] However, Rod et al. reported increased severe morbidity in terms of post-operative bleeding and reinterventions after laparoscopic gastrectomy. Conflicting reports have also been reported after laparoscopic total gastrectomy (TG). [START_REF] Rod | Comparison between open and laparoscopic gastrectomy for gastric cancer: A monocentric retrospective study from a western country[END_REF] A recent large retrospective study showed some benefit for the laparoscopic approach in terms of hemostasis and quicker return to normal physiological function, however, the authors did observe higher leakage and anastomotic stricture rates. [START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF] The latest meta-analysis of retrospective studies has reported equivalent safety to the open approach with similar five-year overall survival. [START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF] Due to the conflicting reports in the literature, the present study aimed at analysing large nationwide cohort of patients undergoing gastrectomy in order to report a pragmatic real-life morbidity rate and assess the potential benefit of the laparoscopic approach. Because of the lack of oncological staging in this database, the present study focused on results of surgical procedures by assessing postoperative complications.

PATIENTS AND METHODS

Study design and participants

A retrospective review of a prospectively maintained national database named PMSI "programme de médicalisation des systèmes d'informations" was realized. [START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF] Mandatory routine data collection on all in-hospital admissions is performed in both private and general hospitals in France.

The purpose of this database is to set the financial budget of French hospitals based on the number of patients and type of procedures performed. All details regarding a patient hospitalization was recorded in individual centres. The validity of this database has been tested by cross referencing it with other cohort databases. [START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF] Information in the database includes the hospital identifier, length of stay, diagnostic codes and a national procedures classification (Classification Commune des Actes Médicaux [CCAM]) which describes surgical, endoscopic and radiological procedures.

All patients undergoing resection for gastric cancer (C16 in ICD-10 classification) as defined by the table in appendix 1, between January 2013 to December 2018, were included.

Patients with subtotal distal gastrectomy and total gastrectomy without Billroth 1 reconstruction or atypical gastric resection were included. Two groups were created: Laparoscopic and open groups (appendix 1). Patients in the laparoscopic group who underwent a conversion to open were attached in the laparoscopic group in an intention-to-treat analysis. Patients with metastatic disease or enlarged resection for locally advanced tumour requiring combined resection of adjacent organs (colon, hepatic, pancreatic) and those with peritoneal carcinomatosis (peritoneal resection or hyperthermic intraperitoneal chemotherapy), defined by CCAM codes from Appendix 1 were excluded. Patients undergoing simultaneous splenectomy or cholecystectomy during a gastrectomy were included in the study cohort.

Covariates

Patient characteristics and demographics extracted from the database included age, gender and hospital site. Nutritional status (malnutrition "E43 E44 E46" and obesity "E66") and Charlson comorbidity index [START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF] were constructed as reported in the appendix 2. Data on type of surgical resection and chemotherapy use were also collected. One chemotherapy session was defined as one hospital attendance for chemotherapy, with subsequent chemotherapy session not counted. This last variable was used as a proxy in order to take into account the lack of oncological staging.

Outcomes

Postoperative outcomes were examined. The early in-hospital mortality rate and short-term outcomes were defined as a complication or death occurring within 90 postoperative days (POD).

Complications were defined as follow: leakage or deep abscess, bleeding, thrombo-embolic disease, pulmonary complications or renal insufficiency according to ICD 10 described in Appendix 3. Algorithm of complications was adapted to upper-gastro-intestinal surgery from our previous publications. [START_REF] Challine | Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis[END_REF][START_REF] Challine | Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery: A Nation-wide Cohort Study[END_REF][START_REF] Lazzati | Readmissions After Bariatric Surgery in France, 2013-2016: a Nationwide Study on Administrative Data[END_REF] The occurrence of any one of these complications contributed to the overall morbidity at 90 POD. The impact of these complications on patients was assessed by the need for surgical reintervention as outlined in Appendix 4.

Long-term outcomes were defined as the occurrence of an incisional hernia, bowel obstruction or oesophageal stricture during follow-up. The ICD 10 codes for these complications are reported in Appendix 3. All hospital stays for each patient were recorded until December 2019.

Statistical analysis

Descriptive statistics were reported in percentage for categorical variables, with median and interquartile range for continuous variable. All analysis was stratified by type of surgery (TG or PG). Univariate analysis was performed with t-test and Chi-Square-test for respectively continuous and categorical outcomes. The impact of volume was studied with regression curves used on the main outcomes by the activity of centre per years using general linear model for binary outcomes and linear model for quantitative outcomes.

A propensity score on the probability of a laparoscopic approach was calculated for each patient using several variables: age, gender, Charlson comorbidity index, malnutrition, obesity, preoperative chemotherapy, cholecystectomy, preoperative laparoscopy and year of resection. A matching between open and laparoscopy using the nearest neighbour method for propensity score and the exact method on the volume of activity was performed with a ratio 1/1. The R-package (MatchIt) was used. [START_REF] Ho | MatchIt : Nonparametric Preprocessing for Parametric Causal Inference[END_REF] An univariate analysis after matching was performed for 90-day outcomes and the Kaplan Meier method, log rank test and hazard ratio with 95% confidence of cox model for long term outcomes. A p value of <0.05 was considered significant. In order to avoid bias of centre selection and learning curve, a sensitivity analysis was realized using a matching on centre identifier and propensity score with the same methods as previously explained. Analysis was done with R software. [START_REF] Team | R: A language and environment for statistical computing[END_REF]

RESULTS

Characteristics of population

A total of 13,819 gastric cancer surgeries were performed in 661 centres between January 1, 2013 and December 31, 2018. The patient's flowchart is presented in appendix 5. After exclusion of metastatic patients (n=1,541) and patients with associated procedures (n=1,935), 10,343 were included in the final analysis. Characteristics of these patients are summarized in table 1. The median age was 70 [61-79] years with 3,996 (39%) females. 1,342 patients (13%) had diabetes, 1,226 patients (12%) were obese and 4,116 (40%) presented with substantial malnutrition.

Preoperative chemotherapy was given to 4,309 patients (42%), with chemotherapy being more frequently administered prior to total gastrectomy (TG: 54% vs. PG: 30% p<0.001). Most patients had less than four chemotherapy sessions (≤4: 68%, >4: 32%). TG was the most common procedure performed (5,782, 56%), including 745 (13%) laparoscopic TG. Laparoscopic PG was done for 664 (15%) patients. A concomitant cholecystectomy or splenectomy was more commonly performed in the open group (Laparoscopy: 13.6% vs. Open: 20.6%, p<0.001; Laparoscopy: 0.01% vs. Open: 3.0%, p<0.001 respectively). Laparoscopic resection rate significantly increased over the years (2013-2014: 8.2%, 2015-2016: 13.0%, 2017-2018: 20.1%; p<0.001). The table of general characteristics of the population after adjustment is given in appendix 6.

Short term outcomes

90-POD mortality and morbidity rates were 6.9% (n=714) and 45.4% (n=4,693) (Table 2). The most frequent complications were anastomotic leakage or deep abscess (22.5%, n=2,330). The overall reintervention rate was 9.1% (n=945). The overall median length of stay was 15 [START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF][START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF][START_REF] Challine | Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis[END_REF][START_REF] Challine | Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery: A Nation-wide Cohort Study[END_REF][START_REF] Lazzati | Readmissions After Bariatric Surgery in France, 2013-2016: a Nationwide Study on Administrative Data[END_REF][START_REF] Ho | MatchIt : Nonparametric Preprocessing for Parametric Causal Inference[END_REF][START_REF] Team | R: A language and environment for statistical computing[END_REF] days. Tables 2 and3 summarized the short-term outcomes before and after matching.

For TG, in univariate analysis, the mortality rate and length of stay were shorter in the laparoscopy group (Open=7.5% vs. Laparoscopy=5.2%, p=0.03; Open=15 [START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF][START_REF] Challine | Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis[END_REF][START_REF] Challine | Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery: A Nation-wide Cohort Study[END_REF][START_REF] Lazzati | Readmissions After Bariatric Surgery in France, 2013-2016: a Nationwide Study on Administrative Data[END_REF][START_REF] Ho | MatchIt : Nonparametric Preprocessing for Parametric Causal Inference[END_REF][START_REF] Team | R: A language and environment for statistical computing[END_REF][START_REF] Park | Predictors of operative morbidity and mortality in gastric cancer surgery[END_REF] vs. laparoscopy=14 [START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF][START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF][START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF][START_REF] Challine | Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis[END_REF][START_REF] Challine | Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery: A Nation-wide Cohort Study[END_REF][START_REF] Lazzati | Readmissions After Bariatric Surgery in France, 2013-2016: a Nationwide Study on Administrative Data[END_REF][START_REF] Ho | MatchIt : Nonparametric Preprocessing for Parametric Causal Inference[END_REF] days, p<0.0001, respectively). The laparoscopic approach was associated with increased bleeding (Open=7.6% vs. Laparoscopy=10.1%; p=0.03) and surgical reintervention rate (Open=11.5% vs.

Laparoscopy=14.5%; p=0.02). After matching, a significantly higher reintervention rate was observed in the laparoscopic group (Open=10.8% vs. Laparoscopy=14.5%, p=0.04). However, a significant decrease of hospital stay was reported in the laparoscopy group (Open=14 [START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF][START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF][START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF][START_REF] Challine | Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis[END_REF][START_REF] Challine | Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery: A Nation-wide Cohort Study[END_REF][START_REF] Lazzati | Readmissions After Bariatric Surgery in France, 2013-2016: a Nationwide Study on Administrative Data[END_REF][START_REF] Ho | MatchIt : Nonparametric Preprocessing for Parametric Causal Inference[END_REF] vs.

Laparoscopy=11 [START_REF] Yu | Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric Cancer: The CLASS-01 Randomized Clinical Trial[END_REF][START_REF] Rod | Comparison between open and laparoscopic gastrectomy for gastric cancer: A monocentric retrospective study from a western country[END_REF][START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF][START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF][START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF] days, p<0.0001).

For PG, in univariate analysis, mortality rate, overall morbidity rate and length of stay were lower in the laparoscopic group (Open=7.0% vs. Laparoscopy=3.5%, p<0.001; Open=40.2% vs.

Laparoscopy=32.7%, p<0.001; Open=15 [START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF][START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF][START_REF] Challine | Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis[END_REF][START_REF] Challine | Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery: A Nation-wide Cohort Study[END_REF][START_REF] Lazzati | Readmissions After Bariatric Surgery in France, 2013-2016: a Nationwide Study on Administrative Data[END_REF][START_REF] Ho | MatchIt : Nonparametric Preprocessing for Parametric Causal Inference[END_REF][START_REF] Team | R: A language and environment for statistical computing[END_REF] vs. Laparoscopy=11 [START_REF] Yu | Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric Cancer: The CLASS-01 Randomized Clinical Trial[END_REF][START_REF] Rod | Comparison between open and laparoscopic gastrectomy for gastric cancer: A monocentric retrospective study from a western country[END_REF][START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF][START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF][START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF] days, p<0.001, respectively). However, the surgical reintervention rate was higher in the laparoscopic group (Open=5.3% vs. Laparoscopy=7.5%, p=0.026). After matching, the benefit on morbidity and length of stay were confirmed: a laparoscopic approach significantly decreased overall morbidity rateat 90 days (Open=39.4% vs. Laparoscopy=32.6%, p=0.01) and length of stay (Open=14 [START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF][START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF][START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF][START_REF] Challine | Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis[END_REF][START_REF] Challine | Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery: A Nation-wide Cohort Study[END_REF][START_REF] Lazzati | Readmissions After Bariatric Surgery in France, 2013-2016: a Nationwide Study on Administrative Data[END_REF][START_REF] Ho | MatchIt : Nonparametric Preprocessing for Parametric Causal Inference[END_REF] vs. Laparoscopy=11 [START_REF] Yu | Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric Cancer: The CLASS-01 Randomized Clinical Trial[END_REF][START_REF] Rod | Comparison between open and laparoscopic gastrectomy for gastric cancer: A monocentric retrospective study from a western country[END_REF][START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF][START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF][START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF] days, p<0.0001).

Long term outcomes

Long term outcomes are presented in figure 1. For TG, more oesophageal strictures were observed after a laparoscopic approach before and after adjustment (HR=2.54[1.67-3.85], p<0.001). No differences between groups were found on incisional hernia or bowel obstruction (p=0.08, p=0.33) (Figure 1). For PG, no benefit for the laparoscopic approach were observed for incisional hernia or bowel obstruction (p=0.37, p=0.09).

Impact of center volume on outcomes

The 10,343 gastrectomies were performed in 661 centers with a median of 2 (1-3) patients per year. 86% of patients (n=8852) had been operated in a center with an activity < 12 gastrectomies per year. Figure 2 reported the regression curves in function of activity per year per center. All curves showed a benefit on outcomes with increased volume except for mortality and reintervention rates after laparoscopic PG. The increased prevalence of esophageal stricture (HR=2.42 [1.32-4.40], p<0.001) and reduced length of stay (Open=15 [START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF][START_REF] Challine | Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis[END_REF][START_REF] Challine | Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery: A Nation-wide Cohort Study[END_REF][START_REF] Lazzati | Readmissions After Bariatric Surgery in France, 2013-2016: a Nationwide Study on Administrative Data[END_REF][START_REF] Ho | MatchIt : Nonparametric Preprocessing for Parametric Causal Inference[END_REF][START_REF] Team | R: A language and environment for statistical computing[END_REF] vs. Laparoscopy=14 [START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF][START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF][START_REF] Challine | Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis[END_REF][START_REF] Challine | Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery: A Nation-wide Cohort Study[END_REF][START_REF] Lazzati | Readmissions After Bariatric Surgery in France, 2013-2016: a Nationwide Study on Administrative Data[END_REF][START_REF] Ho | MatchIt : Nonparametric Preprocessing for Parametric Causal Inference[END_REF][START_REF] Team | R: A language and environment for statistical computing[END_REF] days, p=0.04) was confirmed for TG after laparoscopy. The benefit of laparoscopy on overall morbidity and length of stay for PG was in line with previous results as reported in table 4 (Open=40.9% vs. Laparoscopy=32.6%, p=0.052 and Open=14 [START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF][START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF][START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF][START_REF] Charlson | A new method of classifying prognostic comorbidity in longitudinal studies: development and validation[END_REF][START_REF] Challine | Impact of coronavirus disease 2019 (COVID-19) lockdown on in-hospital mortality and surgical activity in elective digestive resections: A nationwide cohort analysis[END_REF][START_REF] Challine | Impact of Oral Immunonutrition on Postoperative Morbidity in Digestive Oncologic Surgery: A Nation-wide Cohort Study[END_REF][START_REF] Lazzati | Readmissions After Bariatric Surgery in France, 2013-2016: a Nationwide Study on Administrative Data[END_REF][START_REF] Ho | MatchIt : Nonparametric Preprocessing for Parametric Causal Inference[END_REF] vs. Laparoscopy=11 [START_REF] Yu | Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric Cancer: The CLASS-01 Randomized Clinical Trial[END_REF][START_REF] Rod | Comparison between open and laparoscopic gastrectomy for gastric cancer: A monocentric retrospective study from a western country[END_REF][START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF][START_REF] Oh | Laparoscopic total gastrectomy as a valid procedure to treat gastric cancer option both in early and advanced stage: A systematic review and meta-analysis[END_REF][START_REF] Domin | Le Programme de médicalisation des systèmes d'information (PMSI): De l'indicateur de comptabilité hospitalière au mode de tarification (1982-2012)[END_REF][START_REF] Quantin | Qualité des données périnatales issues du PMSI : comparaison avec l'état civil et l'enquête nationale périnatale 2010[END_REF][START_REF] Quantin | Estimation of National Colorectal-Cancer Incidence Using Claims Databases[END_REF][START_REF] Pierron | Évaluation de la qualité métrologique des données du programme de médicalisation du système d'information (PMSI) en périnatalité : étude pilote réalisée dans 3 CHU[END_REF][START_REF] Charlson | The Charlson Comorbidity Index Can Be Used Prospectively to Identify Patients Who Will Incur High Future Costs[END_REF] days, p<0.0001).

Sensitivity analysis

DISCUSSION

This study reports the postoperative outcomes of more than 10,000 gastric cancer resections in a French nationwide cohort between 2013 and 2018. The overall 90-day morbidity was roughly 45%, made up mainly of leakage or deep abscess (22.5%), pulmonary complications (17.4%) and bleeding (7%). After matching, a laparoscopic PG was associated with reduced morbidity rate.

Significant higher oesophageal stricture and reintervention rates were observed after TG. A benefit of length of stay was reported in both groups after laparoscopy.

Patient characteristics differed significantly between the two groups in the present study. The laparoscopic group included younger patients, with less malnutrition, less preoperative chemotherapy and more frequently operated in low volume centres. This may have influenced the post-operative morbidity rate in the laparoscopic group as age [START_REF] Park | Predictors of operative morbidity and mortality in gastric cancer surgery[END_REF], malnutrition [START_REF] Arends | ESPEN guidelines on nutrition in cancer patients[END_REF] and centre volume [START_REF] El Amrani | Specificity of Procedure volume and its Association With Postoperative Mortality in Digestive Cancer Surgery: A Nationwide Study of 225,752 Patients[END_REF] are recognized as independent risk factors of post-operative morbidity. Additionally, concomitant cholecystectomy or splenectomy, which were more frequently performed in the open group, could have also influenced differences observed in morbidity between groups. To limit this selection bias, an adjusted analysis using a matching on propensity score and volume of activity was performed. After adjustment, the two groups were comparable as reported in appendix 6.

The overall morbidity in the present study was in line with a previous French retrospective series (47-54%), [START_REF] Rod | Comparison between open and laparoscopic gastrectomy for gastric cancer: A monocentric retrospective study from a western country[END_REF] with similar 90-day mortality rates to previous French nationwide cohort studies (~7%) [START_REF] El Amrani | Specificity of Procedure volume and its Association With Postoperative Mortality in Digestive Cancer Surgery: A Nationwide Study of 225,752 Patients[END_REF]. Our results are also consistent with a recent European observational study including 27 expert centers. [START_REF] Baiocchi | Incidence and Grading of Complications After Gastrectomy for Cancer Using the GASTRODATA Registry: A European Retrospective Observational Study[END_REF][START_REF] Baiocchi | International consensus on a complications list after gastrectomy for cancer[END_REF] Complication rate was 30% and mortality rate was 5%. [START_REF] Baiocchi | Incidence and Grading of Complications After Gastrectomy for Cancer Using the GASTRODATA Registry: A European Retrospective Observational Study[END_REF] The morbidity reported in the present study was higher than that reported in previous studies (13-30%). [START_REF] Kim | Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer: Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01)[END_REF][START_REF] Lee | Short-term Outcomes of a Multicenter Randomized Controlled Trial Comparing Laparoscopic Distal Gastrectomy With D2 Lymphadenectomy to Open Distal Gastrectomy for Locally Advanced Gastric Cancer (KLASS-02-RCT)[END_REF][START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF][START_REF] Baiocchi | Incidence and Grading of Complications After Gastrectomy for Cancer Using the GASTRODATA Registry: A European Retrospective Observational Study[END_REF][START_REF] Best | Laparoscopic versus open gastrectomy for gastric cancer[END_REF][START_REF] Wang | Severity and incidence of complications assessed by the Clavien-Dindo classification following robotic and laparoscopic gastrectomy for advanced gastric cancer: a retrospective and propensity score-matched study[END_REF] All codes for complications including minor complications are recorded in the database in order to recover optimal funding for the hospitals. This may lead to an overreporting of minor complications during the patient's hospital stay. Moreover, significantly higher rates of chemotherapy use (41%), malnutrition (42%) for open TG were observed in the present study, when compared to previous reports. [START_REF] Kim | Effect of Laparoscopic Distal Gastrectomy vs Open Distal Gastrectomy on Long-term Survival Among Patients With Stage I Gastric Cancer: The KLASS-01 Randomized Clinical Trial[END_REF][START_REF] Lee | Short-term Outcomes of a Multicenter Randomized Controlled Trial Comparing Laparoscopic Distal Gastrectomy With D2 Lymphadenectomy to Open Distal Gastrectomy for Locally Advanced Gastric Cancer (KLASS-02-RCT)[END_REF][START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF][START_REF] Hu | Morbidity and Mortality of Laparoscopic Versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: A Randomized Controlled Trial[END_REF] Most prospective studies only included PG without preoperative chemotherapy. [START_REF] Kim | Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer: Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01)[END_REF][START_REF] Yu | Effect of Laparoscopic vs Open Distal Gastrectomy on 3-Year Disease-Free Survival in Patients With Locally Advanced Gastric Cancer: The CLASS-01 Randomized Clinical Trial[END_REF] The present study furthermore included both highand low-volume centres, with some centres having little laparoscopic experience, all of which might have a detrimental impact on morbidity. [START_REF] El Amrani | Specificity of Procedure volume and its Association With Postoperative Mortality in Digestive Cancer Surgery: A Nationwide Study of 225,752 Patients[END_REF][START_REF] Yoo | Short-term outcomes of laparoscopic-assisted distal gastrectomy for gastric cancer during a surgeon's learning curve period[END_REF] At least, previous studies only reported 30-day morbidity, whereas the present study reported on 90-day morbidity. [START_REF] Kim | Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer: Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01)[END_REF][START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF][START_REF] Hu | Morbidity and Mortality of Laparoscopic Versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: A Randomized Controlled Trial[END_REF] Adjusted analysis reported a benefit on morbidity and length of stay after laparoscopic PG. The results on morbidity and LOS were in line with several randomized trials on this topic. [START_REF] Kim | Decreased Morbidity of Laparoscopic Distal Gastrectomy Compared With Open Distal Gastrectomy for Stage I Gastric Cancer: Short-term Outcomes From a Multicenter Randomized Controlled Trial (KLASS-01)[END_REF][START_REF] Lee | Short-term Outcomes of a Multicenter Randomized Controlled Trial Comparing Laparoscopic Distal Gastrectomy With D2 Lymphadenectomy to Open Distal Gastrectomy for Locally Advanced Gastric Cancer (KLASS-02-RCT)[END_REF][START_REF] Hu | Morbidity and Mortality of Laparoscopic Versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: A Randomized Controlled Trial[END_REF].

This may have been influenced by national guidelines stating that a laparoscopic approach should be preferentially used for early node negative gastric cancers. [START_REF] Zaanan | Gastric cancer: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO)[END_REF][START_REF] Smyth | Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[END_REF] Adjusting for the volume of a centre could reduce disparity between groups, especially for mortality which has previously been demonstrated in oesophageal resections. [START_REF] Markar | Pattern of Postoperative Mortality After Esophageal Cancer Resection According to Center Volume: Results from a Large European Multicenter Study[END_REF] The present study again demonstrated that laparoscopic PG was safe and feasible.

The role of laparoscopic TG remains unclear. The higher surgical reintervention rate in the laparoscopic group was probably due to the increased prevalence of post-operative bleeding observed in this cohort (10.1%). Meticulous dissection and haemostasis is therefore a major issue for laparoscopic TG to reduce postoperative bleeding. [START_REF] Rod | Comparison between open and laparoscopic gastrectomy for gastric cancer: A monocentric retrospective study from a western country[END_REF] Oesophageal stricture was also more frequently reported after laparoscopic TG, as reported by others. [START_REF] Sakamoto | Short-Term Outcomes of Laparoscopic and Open Total Gastrectomy for Gastric Cancer: A Nationwide Retrospective Cohort Analysis[END_REF] The performance of a laparoscopic circular anastomosis between the oesophagus and jejunum is difficult and can lead to a higher anastomotic leakage rate, which was not observed in the present study. The lack of data concerning the technique used for anastomosis in the present study limits our explanations for oesophageal stricture rate. Moreover, the lack of oncological data concerning tumour location and R-status of the oesophageal section could also bias the long-term oesophageal stricture analysis. However, large randomized trials examining the anastomotic technique and its influence on longterm morbidity are warranted to truly improve our understanding.

The impact of centre volume on post-operative outcome is very important. As showed in the regression curves, morbi-mortality and length of stay were correlated to centre volume. In our database, the median number of procedures per centre per year was very low. The same results were observed in restorative proctocolectomy with ileal pouch anal anastomosis in France (mean:

1.65 procedure/year/center). [START_REF] Parc | Restorative Proctocolectomy and Ileal Pouch-anal Anastomosis[END_REF] This could be explained by the low threshold in France to treat gastro-intestinal cancers (30 cancers per years). There are currently no national guidelines for a specific cut-off allowing gastric surgery for cancer. High volume centers are associated with better outcomes and with multidisciplinary team input which ultimately improves the quality of care. [START_REF] Richardson | The effect of multidisciplinary teams for rectal cancer on delivery of care and patient outcome: has the use of multidisciplinary teams for rectal cancer affected the utilization of available resources, proportion of patients meeting the standard of care, and does this translate into changes in patient outcome?[END_REF] El Amrani et al. showed that a cut-off of 16 gastrectomies per year was associated with a lower mortality. [START_REF] El Amrani | Specificity of Procedure volume and its Association With Postoperative Mortality in Digestive Cancer Surgery: A Nationwide Study of 225,752 Patients[END_REF] This observation raises the need for centralization of gastric surgery for cancer in France to high-volume centers as already proposed by several authors. [START_REF] Vonlanthen | Toward a Consensus on Centralization in Surgery[END_REF] In order to take into account this bias, the analysis integrates the volume per center and the sensitivity analysis used a perfect matching for center. This database used for high-volume cohort studies is often criticized, since the mandatory input of data is collected for economical purposes and legal requirements, which may lead to over-reporting of complications. In return, the overstatement of complications is similarly reported, whatever the surgical approach used, and the strength of such studies relies on a "true-life" analysis of surgical practice and their large sample size. The lack of precise data concerning pathological reports, number of retrieved lymph nodes, tumour location, and TNM status might also bias the analysis, especially for quality of laparoscopic gastric resection. The analysis was therefore adjusted on neoadjuvant chemotherapy and excluded patients with locally advanced or metastatic tumours. A possible imbalance between on preoperative chemotherapy response, type of lymphadenectomy could bias the analysis of morbidity after propensity score matching. Nevertheless, national guidelines actually advocate the open approach as the standard for advanced gastric cancer for total gastrectomy. [START_REF] Zaanan | Gastric cancer: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO)[END_REF] This recommendation could disfavour the Open group. This study was therefore only focused on surgical procedures and post-operative complications limiting risk of oncological interpretation.

Conclusion

On a national scale, including a series of over 10,000 gastrectomies, laparoscopic PG demonstrated a significant benefit on overall morbidity and length of stay. Laparoscopic TG should be performed with caution, in view of higher rates of surgical reintervention and oesophageal stricture. This is in line with national and international guidelines, emphasizing the need for randomized trials and results of long-term oncological outcomes.

  After matching on center and propensity score, 346 laparoscopic TG were matched with 346 open TG and 301 laparoscopic PG with 301 open PG.

Figure 1 .Figure 2 .

 12 Figure 1. Long term outcomes for total gastrectomy and partial gastrectomy after matching.

Table 1 .

 1 Patient characteristics and 90-day post-operative outcomes (n=10,343).

			Total gastrectomy n= 5,782	Partial gastrectomy n=4,561
	Characteristics		Open (n=5,037)	Laparoscopy (n=745)	p	Open (n=3,897)	Laparoscopy (n=664)	p
	Age		68 [58-76]	64 [54-74]	< 0.0001	75 [65-82]	73 [63-81]	0.0001
	Female		1784 (35.4%)	283 (38.0%)	0.185	1652 (42.4%)	277 (41.7%)	0.777
		2	2.885 (57.3%)	437 (58.7%)		2.099 (53.9%)	376 (56.6%)
	Charlson score categorization	3-4 5-6	1372 (27.2%) 230 (4.6%)	215 (28.9%) 34 (4.6%)	0.094	1195 (30.7%) 267 (6.9%)	194 (29.2%) 38 (5.7%)	0.513
		≥7	550 (10.9%)	59 (7.9%)		336 (8.6%)	56 (8.4%)
	Diabetes		626 (12.4%)	85 (11.4%)	0.465	557 (14.3%)	74 (11.1%)	0.035
	Severe diabetes		149 (3.0%)	21 (2.8%)	0.925	148 (3.8%)	21 (3.2%)	0.490
	Congestive heart failure	152 (3.0%)	18 (2.4%)	0.429	201 (5.2%)	34 (5.1%)	1.0
	Myocardial infarction	229 (4.5%)	28 (3.8%)	0.380	229 (5.9%)	41 (6.2%)	0.832
	Distal vascular disease	253 (5.0%)	22 (3.0%)	0.017	213 (5.5%)	34 (5.1%)	0.787
	Cerebral vascular disease	250 (5.0%)	42 (5.6%)	0.487	244 (6.3%)	38 (5.7%)	0.656
	Obesity		584 (11.6%)	97 (13.0%)	0.286	467 (12.0%)	78 (11.7%)	0.913
	Malnutrition		2115 (42.0%)	282 (37.9%)	0.0358	1557 (40.0%)	212 (31.9%)	0.0001
	Enteral nutrition prior surgery	209 (4.1%)	20 (2.7%)	0.0699	59 (1.5%)	4 (0.6%)	0.093
	Laparoscopic exploration prior surgery	469 (9.3%)	87 (11.7%)	0.0478	157 (4.0%)	42 (6.3%)	0.010
	Hospitalization for chemotherapy before surgery	0 1-3 4 5-8 ≥9	2.455 (48.7%) 855 (17.0%) 888 (17.6%) 757 (15.0%) 82 (1.6%)	336 (45.1%) 102 (13.7%) 180 (24.2%) 117 (15.7%) 10 (1.3%)	0.0002	2.783 (71.4%) 402 (10.3%) 363 (9.3%) 314 (8.1%) 35 (0.9%)	460 (69.3%) 51 (7.7%) 82 (12.3%) 66 (9.9%) 5 (0.8%)	0.016
	Cholecystectomy		1192 (23.7%)	124 (16.6%)	< 0.0001	647 (16.6%)	67 (10.1%)	< 0.0001
	Splenectomy		243 (4.8%)	12 (1.6%)	< 0.0001	28 (0.7%)	2 (0.3%)	0.332
		<3	1,669 (33.1%)	191 (25.6%)		1,745 (44.8%)	225 (33.9%)
		3-5	1229 (24.4%)	189 (25.4%)		894 (22.9%)	162 (24.4%)
	Volume of	6-12	1314 (26.1%)	230 (30.9%)		818 (21.0%)	186 (28.0%)
	surgical centre	13-18	563 (11.2%)	114 (15.3%)		315 (8.1%)	75 (11.3%)
		19-24	163 (3.2%)	13 (1.7%)		65 (1.7%)	6 (0.9%)
		>24	99 (2.0%)	8 (1.1%)	< 0.0001	60 (1.5%)	10 (1.5%)	< 0.0001
	Teaching Centre		1671 (33.2%)	210 (28.2%)	0.0076	1019 (26.1%)	195 (29.4%)	0.092
		2013	942 (18.7%)	65 (8.7%)		758 (19.5%)	66 (9.9%)
		2014	859 (17.1%)	73 (9.8%)		719 (18.5%)	87 (13.1%)
	Years of resection	2015 2016	851 (16.9%) 854 (17.0%)	98 (13.2%) 126 (16.9%)	< 0.0001	671 (17.2%) 613 (15.7%)	105 (15.8%) 116 (17.5%)	< 0.0001
		2017	771 (15.3%)	186 (25.0%)		599 (15.4%)	128 (19.3%)
		2018	760 (15.1%)	197 (26.4%)		537 (13.8%)	162 (24.4%)
	Continuous variables are represented as median and interquartile range.

Table 2 .

 2 Univariate analysis of short-term outcomes.

		Total gastrectomy n= 5,782	Partial gastrectomy n=4,561
	Outcomes	Open (n=5,037)	Laparoscopy (n=745)	p	Open (n=3,897)	Laparoscopy (n=664)	p
	Death at 90 POD	379 (7.5%)	39 (5.2%)	0.030	273 (7.0%)	23 (3.5%)	0.0008
	Global morbidity at 90 POD	2541 (50.4%)	367 (49.3%)	0.572	1568 (40.2%)	217 (32.7%)	0.0003
	Leakage	1377 (27.3%)	212 (28.5%)	0.552	649 (16.7%)	92 (13.9%)	0.080
	Bleeding	385 (7.6%)	75 (10.1%)	0.027	218 (5.6%)	48 (7.2%)	0.116
	Thromboembolic disease	285 (5.7%)	33 (4.4%)	0.198	184 (4.7%)	27 (4.1%)	0.520
	Pulmonary complication	1045 (20.7%)	171 (23.0%)	0.183	520 (13.3%)	65 (9.8%)	0.013
	Renal insufficiency	469 (9.3%)	75 (10.1%)	0.553	281 (7.2%)	34 (5.1%)	0.060
	Surgical reintervention	581 (11.5%)	108 (14.5%)	0.023	206 (5.3%)	50 (7.5%)	0.026
	Length of stay	15 [12-23]	14 [10-21]	< 0.0001	15 [11-22]	11 [8-17]	<0.0001
	Length of stay > 15 days	2784 (55.3%)	342 (45.9%)	< 0.0001	1942 (49.8%)	451 (67.9%)	<0.0001

POD: Post-operative days; continuous variables are represented as median and interquartile range.

Table 3 .

 3 Adjusted analysis of peri-operative outcomes at 90 post-operative days for total and partial gastrectomy after matching on propensity score and volume activity

			TG			PG
	Outcomes	Open n=743	Laparoscopy n=743	p	Open n=662	Laparoscopy n=662	p
	Death at 90 POD	38 (5.1%)	39 (5.2%)	1.00	30 (4.5%)	23 (3.5%)	0.40
	Global morbidity at 90 POD	340 (45.8%)	365 (49.1%)	0.21	261 (39.4%)	216 (32.6%)	0.01
	Surgical reintervention	80 (10.8%)	108 (14.5%)	0.04	33 (5.0%)	50 (7.6%)	0.07
	Length of stay median [iqr]	[12, 22]	14 [10, 21]	<0.0001	14 [10, 21]	11 [ 8.0, 16.8] <0.0001

POD: Post-operative days; ICU: intensive care unit; OR: Odd ratio; 95% CI: 95% confidence interval

Table 4 .

 4 Sensitive analysis with matching on propensity score and centers

			TG			PG
	Outcomes	Open n=346	Laparoscopy n=346	p	Open n=301	Laparoscopy n=301	p
	Death at 90 POD 27 (7.8%)	20 (5.8%)	0.36	19 (6.3%)	11 (3.7%)	0.19
	Global morbidity at 90 POD	185 (53.5%)	170 (49.1%)	0.29	123 (40.9%)	99 (32.9%)	0.052
	Surgical reintervention	39 (11.3%)	53 (15.3%)	0.15	21 (7.0%)	27 (9.0%)	0.45
	Length of stay median [iqr]	15 [12, 22]	14 [11, 22]	0.04	14 [10, 21]	11 [ 8, 16]	<0.0001

POD: Post-operative days; continuous variables are represented as median and interquartile range.

Acknowledgment: No conflict of interest to report.

Manuscript words count: 2638

F010, F0100, F01000, F01001, F01002, F0101, F01010, F01011, F01012, F0102, F01020, F01021, F01022, F0103, F01030, F01031, F01032, F0104, F01040, F01041, F01042, F011, F0110, F01100, F01101, F01102, F0111, F01110, F01111, F01112, F0112, F01120, F01121, F01122, F0113, F01130, F01131, F01132, F0114, F01140, F01141, F01142, F012, F0120, F01200, F01201, F01202, F0121, F01210, F01211, F01212, F0122, F01220, F01221, F01222, F0123, F01230, F01231, F01232, F0124, F01240, F01241, F01242, F013, F0130, F01300, F01301, F01302, F0131, F01310, F01311, F01312, F0132, F01320, F01321, F01322, F0133, F01330, F01331, F01332, F0134, F01340, F01341, F01342, F018, F0180, F01800, F01801, F01802, F0181, F01810, F01811, F01812, F0182, F01820, F01821, F01822, F0183, F01830, F01831, F01832, F0184, F01840, F01841, F01842, F019, F0190, F01900, F01901, F01902, F0191, F01910, F01911, F01912, F0192, F01920, F01921, F01922, F0193, F01930, F01931, F01932, F0194, F01940, F01941, F01942, F02, F020, F0200, F02000, F02001, F02002, F0201, F02010, F02011, F02012, F0202, F02020, F02021, F02022, F0203, F02030, F02031, F02032, F0204, F02040, F02041, F02042, F021, F0210, F02100, F02101, F02102, F0211, F02110, F02111, F02112, F0212, F02120, F02121, F02122, F0213, F02130, F02131, F02132, F0214, F02140, F02141, F02142, F022, F0220, F02200, F02201, F02202, F0221, F02210, F02211, F02212, F0222, F02220, F02221, F02222, F0223, F02230, F02231, F02232, F0224, F02240, F02241, F02242, F023, F0230, F02300, F02301, F02302, F0231, F02310, F02311, F02312, F0232, F02320, F02321, F02322, F0233, F02330, F02331, F02332, F0234, F02340, F02341, F02342, F024, F0240, F02400, F02401, F02402, F0241, F02410, F02411, F02412, F0242, F02420, F02421, F02422, F0243, F02430, F02431, F02432, F0244, F02440, F02441, F02442, F028, F0280, F02800, F02801, F02802, F0281, F02810, F02811, F02812, F0282, F02820, F02821, F02822, F0283, F02830, F02831, F02832, F0284, F02840, F02841, F02842, F03, F03+0, F03+00, F03+01, F03+02, F03+1, F03+10, F03+11, F03+12, F03+2, F03+20, F03+21, F03+22, F03+3, F03+30, F03+31, F03+32, F03+4,

G45, G450, G451, G452, G453, G454, G458, G459, G46, G460, G461, G462, G463, G464, G465, G466, G467, G468, H340, I60, I600, I601, I602, I603, I604, I605, I606, I607, I608, I609, I61, I610, I611, I612, I613, I614, I615, I616, I618, I619, I62I, 620, I621, I629, I63, I630, I631, I632, I633, I634, I635, I636, I638, I639, I64, I65, I650, I651, I652, I653, I658, I659, I66, I660, I661, I662, I663, I664, I668, I669, I67, I670, I671, I672, I673, I674, I675, I676, I677, I678, I679, I68, I680, I681, I682, I688, I69, I690, I691, I692, I693, I694, I698 Dementia 1 F00, F000, F0000, F00000, F00001, F00002, F0001, F00010, F00011, F00012, F0002, F00020, F00021, F00022, F0003, F00030, F00031, F00032, F0004, F00040, F00041, F00042, F001, F0010, F00100, F00101, F00102, F0011, F00110, F00111, F00112, F0012, F00120, F00121, F00122, F0013, F00130, F00131, F00132, F0014, F00140, F00141, F00142, F002, F0020, F00200, F00201, F00202, F0021, F00210, F00211, F00212, F0022, F00220, F00221, F00222, F0023, F00230, F00231, F00232, F0024, F00240, F00241, F00242, F009, F0090, F00900, F00901, F00902, F0091, F00910, F00911, F00912, F0092, F00920, F00921, F00922, F0093, F00930, F00931, F00932, F0094, F00940, F00941, F00942, F01, F03+40, F03+41, F03+42, F051, G30, G300, G301, G308, G309, G311 Chronic pulmonary disease 1 ( I278, I279, J40, J41, J410, J411, J418, J42, J43, J430, J431, J432, J438, J439, J44, J440, J441, J448, J449, J45, J450, J451, J458, J459, J46, J47, J60, J61, J62, J620, J628, J63, J630, J631, J632, J633, J634, J635, J638, J64, J65, J66, J660, J661, J662, J668, J67, J670, J671, J672, J673, J674, J675, J676, J677, J678, J679, J684, J701, J703 G041, G114, G801, G802, G81, G810, G8100, G8101, G8108, G811, G819, G82, G820, G821, G822, G823, G824, G825, G830, G831, G832, G833, G834, G839 Moderate or severe renal disease 2 I120, I131, N032, N033, N0330, N0339, N034, N035, N036, N037, N052, N053, N054, N055, N056, N057, N18, N180, N181, N182, N183, N184, N185, N188, N189, N19, N250, Z490, Z491, Z492, Z940, Z992, Z992+0, Z992+1, Z992+8 Diabetes with end organ damage

Appendix 3. Definition of complications as per ICD classification