Minimally Invasive Oncologic Upper Gastrointestinal Surgery can be Performed Safely on all Weekdays: A Nationwide Cohort Study

Background Existing literature suggests deteriorating surgical outcome of esophagogastric surgery as the week progresses. However, these studies were conducted in the pre-centralization and pre-minimally invasive era. In addition, they failed to correct for fixed weekdays of esophagogastric cancer surgery among hospitals. This study aimed to describe the impact of weekday of minimally invasive upper gastrointestinal surgery on short-term surgical outcomes. Methods All patients registered in the Dutch Upper Gastrointestinal Cancer Audit who underwent curative minimally invasive esophageal or gastric carcinoma surgery in 2015–2019, were included in this nationwide cohort study. Using multilevel multivariable logistic regression, the impact of weekday of surgery on 14 short-term surgical outcomes was investigated. To correct for interhospital variance in fixed weekday(s) of surgery multilevel analyses was used. Results were adjusted for patient, tumor, and treatment characteristics using multivariable logistic regression analyses. Results This study included 4,102 patients undergoing minimally invasive upper gastrointestinal surgery (2,968 esophageal cancer and 1,134 gastric cancer patients). Weekday of surgery did not impact postoperative complications, severe postoperative complications, surgical/technical complications, medical complications, anastomotic leakage, complicated postoperative course, failure to rescue, surgical radicality, lymph node yield, 30-day/in-hospital mortality, reinterventions, length of ICU stay, 30-day readmission, and textbook outcome after neither esophageal cancer nor gastric cancer surgery. Conclusions Minimally invasive esophagogastric surgery can be performed safely on all weekdays with respect to short-term surgical outcomes, which is important information for operation room scheduling. Supplementary Information The online version contains supplementary material available at 10.1007/s00268-021-06160-x.


Introduction
Gastric and esophageal carcinoma are the third and sixth leading causes of cancer-related mortality worldwide [1]. Surgical resection combined with (neo)adjuvant chemo(radio)therapy is the cornerstone of curative treatment [2][3][4]. Upper gastrointestinal resections are invasive procedures with overall complication rates around 65% and 42% after esophagectomy and gastrectomy, respectively [5]. These technically complex procedures require specialized knowledge and skill, experience and concentration. A Swedish nationwide study hypothesized that surgical team precision deteriorates as the week progresses since they found worse overall survival after esophagectomy on Wednesday-Friday compared to Monday-Tuesday [6]. The study suggested that this weekday effect was aggravated by centralization as high-volume surgeons perform several exhaustive esophagectomies per week. Another explanation might be reduced staffing or less experienced surgeons on-call during the weekends. However, a Dutch study group found no association between weekday of surgery and surgical outcomes after esophagogastric surgery [7,8]. Therefore, results on the weekday effect of esophagogastric cancer surgery are inconclusive. It is, however, important information for operation room scheduling.
The studies referred to above were conducted largely in the pre-centralization and pre-minimally invasive era. Minimally invasive surgery might require even more concentration and surgical team precision than its open equivalent. Additionally, none of these studies [6][7][8] accounted for differences in day of the week on which hospitals routinely perform upper gastrointestinal surgery. This is vital as significant hospital variation in outcomes after upper gastrointestinal surgery exists [9]. In addition, we believe short-term outcomes (like surgical/technical complications) are better proxies for surgeon accuracy and the quality of early postoperative care (e.g., failure to rescue; a proxy for early identification; and treatment of postoperative complications) than long-term survival which is multifactorial.
Therefore, this study aimed to describe the impact of weekday of surgery, corrected for interhospital variance in fixed weekday(s) of surgery, on short-term surgical outcomes after minimally invasive esophagectomy and gastrectomy.

Study design
This population-based cohort study used data from the Dutch Upper Gastrointestinal Cancer Audit (DUCA). Since 2011, this compulsory audit registers all esophagogastric cancer patients undergoing surgery with the intention of resection in the Netherlands [10]. In previous verification, completeness was estimated at 99.2% and outcome measure accuracy at 95.3-100% [11]. This study's protocol received approval from the DUCA scientific committee. Dutch law did not require ethical review or informed consent.

Patient selection
All patients undergoing curative, minimally invasive, esophagogastric cancer surgery between Jan 1, 2015, and Dec 31, 2019, were considered for inclusion. This timeframe was chosen to minimize selection bias; from 2015 onward the majority of both gastric and esophageal resections was performed on a minimally invasive basis [12]. In addition, hospital volumes stabilized in recent years as a result of centralization of upper gastrointestinal surgery in the Netherlands [13]. Converted procedures were included on an intention-to-treat basis. Patients undergoing emergency surgery or surgery during the weekend, were excluded. In addition, to review the current Dutch situation, patients were excluded when undergoing surgery in hospitals that stopped performing esophagogastric cancer surgery before 2019.

Secondary outcome measures
The following secondary outcome measures were investigated: (1) postoperative complications (any Clavien-Dindo) [14], (2)  , and type of resection (esophageal: transthoracic (includes both McKeown and Ivor-Lewis procedures), transhiatal; gastric: total, partial gastrectomy). The following variables were added for esophageal carcinoma only: histology (adenocarcinoma, squamous cell carcinoma, other), anastomotic location (intrathoracic, cervical, other), and salvage surgery (no, yes). In the DUCA, salvage surgery is defined as surgery after previous definitive chemoradiotherapy without initial intent of surgical resection. There are no restrictions as to what definitive scheme is used or the length of the interval between definitive chemoradiotherapy and surgery.

Ancillary support
In the Netherlands, esophagectomy and gastrectomy patients are generally extubated immediately after surgery. After esophagectomy, protocol length of postoperative ICU stay varies from 0 to 2 days among Dutch hospitals [19]. Standard procedure after gastrectomy is not to admit patients to the ICU. In general, physiotherapists and dieticians are part of the treatment team in the early postoperative phase of all esophagectomy and gastrectomy patients.

Statistical analyses
All analyses were performed separately for esophageal cancer (including gastro-esophageal junction) and gastric cancer. Baseline characteristics were compared between patients undergoing surgery on each weekday using descriptive statistics. Multilevel multivariable logistic regression analyses investigated the impact of weekday of surgery, categorized in the four ways described above, on the 3 primary and 11 secondary outcomes. The two-level random effect accounted for differences in (fixed) days of the week on which hospitals routinely perform esophagogastric surgery. All baseline characteristics described above were added to the multivariable model. In case the degrees of freedom were insufficient for the entire correction model (i.e., \ 10 (non)-events per category in the model), only relevant confounders were added. Factors changing any of the ORs of the weekday variable by 10% or more were considered relevant confounders [20,21]. The relevance of the random effect was assessed using the likelihood ratio test.
A two-tailed p value \ 0.05 was considered statistically significant. Missing items were analyzed in separate groups if exceeding 5%. Multicollinearity was assessed in all multivariable analyses by calculating the variance inflation factor (VIF). A VIF C 2.5 was considered indicative of multicollinearity. All statistical analyses were performed using R-studio version 3.5.1, The R Foundation for Statistical Computing [22].

Sensitivity analyses
To validate if exclusion of patients undergoing open surgery did not bias results, sensitivity analyses were performed including only patients undergoing open and hybrid surgery. These analyses investigated the impact of the dichotomized weekday (Monday-Tuesday versus Wednesday-Friday) on the above-mentioned outcome measures. The dichotomization was applied because of the low number of open resections and subsequent small group sizes on separate weekdays.

Results
A total of 2,968 esophageal cancer patients from 16 hospitals and 1,134 gastric cancer patients from 15 hospitals were included (Online Resource Fig. 1). Annual esophagectomy hospital volumes ranged from 17 to 100, and annual gastrectomy volumes ranged from 4 to 44. Baseline characteristics of patients undergoing surgery for esophageal or gastric cancer on each weekday are depicted in Tables 1 and 2, respectively. Esophageal surgery was most frequently performed on Monday and Tuesday. Tumor location, histology, cT and cN stage, type of esophagectomy, anastomotic location, and hospital volume differed significantly between the weekdays (Table 1). Gastric cancer surgery was also most frequently performed on Monday and Tuesday. Except for cN-stage there were no baseline differences between weekdays.

Short-term outcomes after esophageal and gastric cancer surgery
The incidence of each of the 14 short-term surgical outcomes after esophageal and gastric cancer surgery is presented in Table 3. Severe complications, short-term mortality and textbook outcome rates after esophagectomy were 31%, 2.6% and 47%, respectively, and 19%, 3.3% and 54% after gastrectomy.

The impact of weekday of surgery on outcomes
When analyzing all weekdays separately, there were no statistically significant differences in severe complications, short-term mortality and textbook outcome after esophageal nor gastric cancer surgery (Table 4). There were also no significant differences between the separate days of the week in terms of complications, technical complications, medical complications, anastomotic leakage, complicated postoperative course, failure to rescue, surgical radicality, lymph node yield, reinterventions, length of ICU stay, and 30-day readmissions (Online Resource Table 1).
Also when analyzing Monday and Friday separately, no statistically significant differences in both primary and secondary outcomes were identified (Tables 5 and 6, Online Resource Tables 2&3).

Additional analyses
For esophageal cancer, there were no significant differences between surgery on Monday-Tuesday and Wednesday-Friday in any of the 14 investigated outcome measures (Online Resource Table 4). For gastric cancer, 30-day readmission rates were higher after surgery on Wednesday-Friday compared to surgery early in the week (OR 1.43, 95%CI [1.01-2.04]).

Sensitivity analyses
In total, 840 and 620 patients underwent open/hybrid esophagectomy and gastrectomy, respectively. In these cohorts of patients, outcomes did not differ after surgery on Monday-Tuesday or on Wednesday-Friday (Online Resource Table 5).

Discussion
This nationwide cohort study is the first to investigate the impact of weekday of surgery on short-term outcomes of minimally invasive esophagogastric cancer surgery after statistical correction for differing fixed weekdays of surgery among hospitals. Weekday of surgery did not impact postoperative complications, severe postoperative complications, surgical/technical complications, medical complications, complicated postoperative course, failure to rescue, surgical radicality, 30-day/in-hospital mortality, lymph node yield, reinterventions, length of ICU stay, 30-day readmission, and textbook outcome after neither esophageal nor gastric cancer surgery. However, readmission rates were higher after gastric cancer surgery on Wednesday-Friday compared to Monday-Tuesday.

Gastric cancer
Another Swedish study (including a largely overlapping cohort with the study described above) [6] found survival benefit for surgery performed early in the week among 6,124 patients with esophagogastric cancer [26]. Subgroup analyses for gastric cancer patients found similar results. A 2018 German single-center study found contradictory results [27]. It included 460 gastric cancer patients and found no association between weekday of surgery and long-term survival, radicality, lymph node yield, or shortterm mortality. A nationwide Dutch study including 3,776 gastric cancer patients between 2006 and 2014 also found no association between long-term survival and weekday of gastrectomy [8]. It did, however, find lower lymph node yield after surgery later in the week. The current study did not find significant differences in short-term outcomes between weekdays of gastrectomy. Nor could it conform the results by the previous Dutch study that lymph node  (7) 255 (93) 20 (7) 121 (98) 3 (2) 208 (90 23 (10) 180 (93) 13 (7) 1053 (93) 81 (7) 0.137  (17) 57 (18) 56 (18) 71 (23) 74 (24) 43 (16) 60 (22) 55 (20) 61 (22) 56 (20) 17 (14) 18 (15) 24 (19) 35 (28) 30 (24) 39 (17) 36 (16) 45 (20) 48 (21) 63 (27) 16 (8) 40 (21) 33 (17) 54 (28) 50 (26) 168 (15) 211 (19) 213 (19) 269 (24) 273 ( yield is lower after surgery late in the week. The current study did display significantly higher 30-day readmission rates after gastrectomy later in the week. A previous DUCA study showed higher readmission rates after weekend discharge [28]. This might explain the higher readmission rates after surgery later in the week as median length of hospital stay after gastrectomy approximates 8 days [5]. This hypothesis could currently not be verified as noise was added to date of discharge to ensure anonymity of the dataset. Some argue that complex surgery should be performed early in the week since postoperative complications usually emerge after one to three days and healthcare services are downscaled in the weekend [29][30][31]. The current study showed that failure to rescue, which is a proxy for early identification, recognition and treatment of complications, did not diminish during the week for neither  Patients undergoing a radical, curative resection with at least 15 resected lymph nodes, without intraoperative complication, severe postoperative complication a , reintervention, readmission (to the ICU), mortality, and a length of hospital stay shorter than 21 days esophagectomy nor gastrectomy. One might argue that no association between failure to rescue and weekday could be found since a large part of patients undergoing surgery late in the week will be on the ICU during the weekend. On the ICU, health-care provision is ordinarily continued during the weekend. However, in 51% of esophagectomy patients length of ICU admission was only 0 or 1 days. This was 88% for gastrectomy patients. Additionally, length of ICU stay was similar when undergoing surgery early or later in the week. Many factors might play a confounding role when comparing surgical outcomes between weekdays. Not only do hospitals have fixed weekdays of esophagogastric surgery, surgeons might also have fixed surgery days. Variation in operation room personnel, residents, and ICU staff might also confound results. In addition, call schedules and associated fatigue might play a role. Unfortunately, as the DUCA does not register data at individual physician level, these factors could not be accounted for in the current study. However, this is the only study that corrected for fixed weekdays of surgery at hospital level. Existing literature failed to correct for hospital difference in day of surgery. Additionally, given the large number of inclusions, we feel that these possible confounders might level out at a population level. Therefore, current study's results refute previous literature on the subject and suggest that esophagogastric cancer surgery can be performed safely on all days of the week. This is important information that is helpful in operation room planning.
This study excludes open surgery which might have introduced selection bias. Since minimally invasive surgery is the gold standard in the Netherlands, open surgery might be reserved for anticipated difficult surgery. However, by only including minimally invasive surgery results are more uniform and weekdays can be compared fairly. In addition, the sensitivity analyses (including only patients undergoing open surgery) confirmed the absence of a weekday effect in upper gastrointestinal surgery. Another limitation is that a significant proportion of patients is excluded from analyses due to non-curative surgery (e.g., open-close). However, augmented numbers of non-curative surgery might also reflect inferior surgical quality.

Conclusions
This Dutch nationwide study conducted in the era of centralization, shows surgical precision of minimally invasive esophagogastric cancer surgery does not deteriorate as the week progresses. In addition, there are no signs of inferior early postoperative care late in the week or during the weekend. Therefore, in the Netherlands, upper gastrointestinal surgery can be conducted safely on all weekdays.