Abstract
Background: The aim of this study was to retrospectively investigate the impact of intersphincteric resection (ISR) and Enhanced Recovery After Surgery (ERAS) protocols for rectal cancer. Patients and Methods: Since we implemented rectal ERAS protocol and ISR in 2016, we retrospectively assessed and compared clinical, pathological and survival outcomes of two groups of patients: group 1, treated 2000-2015 (n=242); and group 2, treated 2016-2020 (n=108). Propensity score matching using nearest-neighbor method was used to match each patient of group 1 to a patient of group 2. Results: Before and after matching, the American Society of Anesthesiology score for patients in group 1 was significantly lower than in group 2 (score of 3: 9.9% vs. 25.9%, p<0.0001) as were grade I-II complications (27.7% vs. 45.4% p<0.001). Before and after matching, the quality of the mesorectum excision was significantly lower in group 1 (complete in 31% vs. 59.2% p<0.0001). After matching, 3-year overall survival for groups 1 and 2 were similar (88.2% vs. 92.6%; p=0.988). Conclusion: ERAS and ISR had no negative impact on the oncological outcome of our patients and increased the preservation of bowel continuity.
- Low rectal cancer
- neoadjuvant chemoradiotherapy
- rectal surgery
- intersphincteric resection
- enhanced recovery after surgery
- ERAS
- clinical outcome
Colorectal carcinoma (CRC) is the third most common cancer in France and accounts for approximately 20% of all cancer (1, 2). Clinical outcomes in rectal cancer therapy improved significantly when Heald et al. introduced total mesorectal excision (TME). This new surgical approach resulted in a significant reduction in the local recurrence rate (3, 4). In parallel with TME, radiotherapy (RT) and chemotherapy (CTx) were introduced, especially for locally advanced rectal cancer (5). Later, the laparoscopic approach contributed to further optimizing the treatment of these patients. Laparoscopic surgery resulted in shortened hospital stay, reduced use of analgesics and faster postoperative recovery, all with oncologically equal outcomes compared with conventional open rectal surgery (6). This multifaceted optimization of CRC treatment has led to a paradigm shift, as removal of a tumor is no longer the only goal. In addition to this, preservation of bowel continuity and faster postoperative recovery of patients are other crucial goals. Since the 1990s, intersphincteric resection (ISR) has helped to further achieve these goals. The technique of ISR dates to the initial experience of Schiessel et al. in 1994 (7). It allows removal of very low rectal tumors that would otherwise have required abdominoperineal resection (APR). This technique has increased the number of patients in whom bowel continuity can be preserved. Several studies have demonstrated the safety of ISR in terms of short- and long-term outcomes, with equivalent oncological outcomes for laparoscopic and open procedures (8–10). Fast-track surgery, later referred to as Enhanced Recovery After Surgery (ERAS), was introduced in the 1990s by Kehlet et al. (11). The concept of ERAS includes perioperative patient management, which has been shown in several studies to reduce morbidity and shorten hospital stays, leading to faster recovery, lower hospital costs, and better oncological outcomes (12–15). ERAS protocols follow the guidelines published by the ERAS Society (16), but so far seem to be efficient in rectal surgery (17, 18). In our tertiary referral center, ERAS protocols and ISR were introduced in 2016.
The aim of this study was to investigate the clinical impact of ISR and ERAS protocols at our center on the clinical outcome. Therefore, we compared the surgical and oncologic outcomes of rectal cancer during two time periods, from 2000 to 2015 (group 1) and 2016 to 2020 (group 1). Primary endpoints were the length of hospital stay, complication rates, and survival. Factors affecting complication rates were explored by multivariate analysis.
Patients and Methods
Legal background and study population. The French law does not require any institutional review board statement or approval for retrospective studies. This study was approved by the local Committee of Informatics and Liberty (CIL) (no. 2020-067) According to the French law (Code de la santé publique, Article R1121-1 Modifié par Décret n°2017-884 du 9 mai 2017 - art.2). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from all individual participants included in the study. Of all patients operated on for colorectal cancer at Tours University Hospital between January 2000 and December 2020, 350 had rectal cancer. Patients with distant metastases and patients who underwent emergency surgery or other concomitant surgical procedures were excluded. Data were retrospectively collected from our center’s database. Preoperative investigations included clinical examination (digital pelvic examination, anoscopy) and paraclinical examinations [complete colonoscopy with biopsies, rectal endoscopic ultrasound, magnetic resonance imaging (MRI) of the pelvis, thoracoabdominal computed tomography (CT)]. Evaluation of T-stage was through endoscopic ultrasonography (EUS) according to Hildebrandt et al. (19) and preoperative MRI. These examinations confirmed the location of rectal cancer (lower: 0 to 5 cm from the anal verge; mid: 5 to 10 cm; upper: 10 to 15 cm) and helped to assess lymph node involvement. Upper rectal tumors were treated with partial or complete TME. Mid rectal tumors were treated with complete TME. Low rectal tumors were treated according to the period and location of the tumor. Complete TME was performed when the tumor was high enough and anastomosis was possible, with partial ISR for tumors <1 cm from the anorectal junction (upper part of the anal sphincter), and complete ISR for tumors infiltrating the internal anal sphincter. APR was performed for tumors infiltrating the external sphincter after neoadjuvant treatment. Both ERAS protocol and partial/complete ISR were routinely implemented from January 2016.
Neoadjuvant and adjuvant treatment. Two hundred and twenty-nine patients with lower/middle rectal T3/4 tumors and lymph node involvement received long-term neoadjuvant RCTx. It consisted of 5-fluorouracil- or capecitabine-based CTx combined with external pelvic RT of 50 Gy administered in 25 fractions delivered over 5 weeks. In 36 patients, short-term RT was chosen for age or personal reasons to achieve a close sequence of therapy sessions. Four patients did not undergo RT and the others received only CTx or had no neoadjuvant treatment. All patients underwent clinical follow-up (digital examination, anoscopy, or occasionally anal examination under general anesthesia) six weeks after completion of neoadjuvant therapy. The EUS examination was performed by the same team as the initial examination. The development of T and N staging before the treatment was assessed by MRI scan compared with the EUS T and N staging according to the version 1.1 of the RECIST criteria (20). Adjuvant CTx was performed in patients with incomplete resection and lymph node involvement. It consisted in 5-fluorouracil, capecitabine, or oxaliplatin based CTx.
ERAS protocol. In January 2016, an ERAS protocol was implemented with a multidisciplinary team of anesthesiologists, surgeon, nurses, physical and respiratory therapists. The ERAS protocol was implemented on top of standard perioperative care protocols. The details of the ERAS ERAS protocol and conventional perioperative management protocols are summarized in Table I. We considered a patient to have been treated according to the ERAS protocol when at least 75% of the predefined points of the ERAS protocol were fulfilled.
ERAS protocol items and comparison with management prior to ERAS implementation.
Surgical procedures. Patients received mechanical bowel preparation one day preoperatively and antibiotic prophylaxis immediately before surgery. After 2016, all patients received mechanical preparation and antibiotic prophylaxis with metronidazole five days before surgery. The laparoscopic approach was the standard approach, except for T4 tumors, in which an open approach was preferred (21). The medial-lateral approach was the technique of choice. A diverting stoma (ileostomy) was routinely created for patients with middle and lower rectal tumors. Complete and partial TME were performed as follows: The inferior mesenteric vein was ligated at the inferior border of the pancreas, followed by mobilization of the left colon, splenic flexure (the extent of mobilization was at the surgeon’s discretion), and ligation of the inferior mesenteric artery. When possible, the left colonic artery (LCA) was preserved. The rectum was transected using the double staple technique. The proximal colon was transected approximately 10 cm above the tumor top. The specimen was removed from the abdominal cavity through a small abdominal incision (21). Either mechanical colorectal or manual colo-anal anastomosis (side-to-end or end-to-end) was performed depending on the tumor height. After 2016, complete or partial ISR was performed as follows: Intra-abdominal steps were similar to TME. Perineal dissection involved the use of a Lone Star® retractor to completely expose the anal canal. The incision was based on tumor height, with a full-thickness circular incision made 1 cm below the tumor. In partial ISR, an incision was made at the dentate line and one-third or one-half of the internal anal sphincter was removed. In full-thickness ISR, an incision was made 1 or 2 cm below the dentate line, and two-thirds or all the internal anal sphincter was removed. The rectum was closed after transection, and the perineal dissection was connected to the abdominal dissection. The specimen was removed through an abdominal incision or through the anus. A manual coloanal anastomosis was then performed. Finally, APR was performed as follows: The intra-abdominal steps were similar to those of TME. Perineal dissection was initiated by a circular incision around the anus, which was previously closed by suturing. Dissection was carried into an ascending path, removing the anal canal, rectum and sphincters until the TME performed beforehand was met. The perineal area was then filled with an omental plug and closed with separate sutures. A definitive colostomy completed the operation.
Postoperative short-term outcomes. Anastomotic leakage (AL) was defined according to the International Study Group of Rectal Cancer guidelines (22). Any clinical (sepsis, peritonitis, gas, pus, or fecal leakage from the pelvic drain, purulent discharge from the anus, or rectovaginal fistula) or biological suspicion of AL led to early CT scan evaluation. Symptomatic treatment included antibiotics, radiological or transanal drainage, and/or early redo abdominal surgery (23). Postoperative 30-day complications were recorded according to the Clavien–Dindo classification (24).
Pathology reports. Primary tumors were analyzed according to a standardized protocol (25). Tumors were graded according to the eighth edition of the American Joint Committee of Cancer TNM classification (26). Resection margins were defined as positive (R+) when they were less than 1 mm circumferentially (lateral distance between fascia recti and the closest tumoral nodule or node in the mesorectum near the fascia recti) or to 1 cm distally (the bottom edge of tumor and the distal rectal section). Complete or partial mesorectal excision, degree of colloid component, degree of differentiation, presence of vascular and lymphatic, or peri- nervous emboli were included and documented accordingly.
Long-term outcomes. Recurrence, disease-free (DFS) and overall (OS) survival were analyzed. Recurrence was defined as tumor on clinical, radiological or endoscopic findings in follow-up. DFS was defined as the time between the primary procedure and the first evidence of tumor recurrence. OS was defined as the time between primary surgery and death or study end. Patients were followed-up until death or study end (September 2021). Postoperative follow-up included clinical, biochemical, and radiological examinations every 3 months during the first postoperative year. Subsequently, every 6 months thereafter until 5 years postoperatively, and every year thereafter until a follow-up period of 10 years. Surviving patients were evaluated for disease recurrence and its location. Follow-up data were obtained from medical records and direct patient or family doctor interviews.
Statistical analysis. We analyzed postoperative morbidity and mortality, survival and oncological outcomes, comparing two periods: 2000 to 2015 (group 1 patients) and 2016 to 2020 (group 2 patients). Propensity score matching (PSM) using nearest-neighbor method was used to match each patient treated between 2000 to 2015 to a patient treated between 2016 to 2020 period. The PSM model was generated using tumor location (namely upper, middle, or lower rectum) and tumor extent (i.e., T-stage) as matching covariate. Qualitative variables are presented in percentages and were compared using chi-squared test with Bonferroni correction whenever necessary. Quantitative variables are presented as medians and interquartile range and were compared using Student or Wilcoxon test. The Kaplan–Meier method was used to estimate DFS and OS which were compared using the log-rank test. Continuous variables were compared using analysis of variance or nonparametric analysis of variance tests, accordingly. This study is in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines (27).
Results
Demographic and preoperative characteristics. Three hundred and fifty patients with a mean age of 69 (60-76) years underwent surgery for rectal cancer in the years 2000 to 2020. Of these, 242 patients (69%) were treated between 2000 and 2015 (group 1) while another 108 (31%) patients were treated between 2016 and 2020 (group 2). Demographic and preoperative characteristics of the whole patient’s cohort are shown in Table II. Most tumors were located in the mid (40%) or lower rectum (39.4%). Before PSM, more low rectal cancers tended to be observed in group 1 than group 2 (48.2% vs. 35.5%, p=0.234). Neoadjuvant treatment with prolonged RT with CTx was given to 65.4% of the study population, with no difference between the two groups. The main difference between the two groups was related to medical history, with American Society of Anesthesiology (ASA) scores being significantly higher in group 2 compared to group 1, at 49.1% with ASA 2 versus 41.0% and 25.9% with ASA 3 versus 9.9%, respectively (p<0.0001). After PSM, a statistical difference was still observed in terms of higher ASA levels in patients in group 2 versus group 1.
Demographic and preoperative characteristics of the 350 patients with rectal cancer treated between 2000 and 2020. Patients of group 1 were treated in 2000-2015 and those of group 2 in 2016-2020.
Intraoperative parameters. Operative details of the whole cohort are given in Table III. Overall, 88.3% of patients underwent laparoscopic surgery. The conversion rate was comparable in both groups at 21.1%. After 2016, 41.7% of patients completed ERAS protocol. The rate of complete TME was 73.4% and was significantly higher in group 2 than in group 1 (80.6% vs. 71.5%; p=0.022). ISR and transanal mesorectal excision rates were significantly higher after 2016 (16.7% vs. 0.8% and 18.5% vs. 0%, respectively p<0.0001). The overall rate of APR was 19.4% and was significantly lower in group 2 (12.03% vs. 20.2%; p=0.010). Anastomotic technique also changed over time, with more termino-terminal rectal anastomoses performed in group 2 than in group 1 (62.8% vs. 42.1%, p=0.004). There were more manual colo-anal anastomoses in group 2, at 22.2% vs. 9.5% in group 1 (p=0.002). After PSM, APR rate was significantly lower in group 2 (12.6 vs. 24.3%; p<0.0472). Likewise, the transanal TME rate was higher in group 2 (19.4% vs. 0; p<0.0001) and there were more termino-terminal anastomoses in group 2 (62.8 vs. 43.6; p=0.0005).
Operative details of the 350 patients with rectal cancer treated between 2000 and 2020. Patients of group 1 were treated in 2000-2015 and those of group 2 in 2016-2020.
Early post-operative outcomes. Early postoperative outcomes are given in Table IV. Overall morbidity was 47.7%. AL occurred in 44 patients (12.6%), postoperative fluid collection in 44 patients (12.6%), and anastomotic stenosis in 10 patients (2.9%). Repeat emergency surgery was required in 38 (10.9%) patients. Conservative treatment (antibiotics only) and CT-guided drainage was required in 102 (29.1%) and three (0.9%) patients, respectively. The median hospital stay was 13 (9–18) days and the median time to stoma reversal was 98 (75-193) days, with no difference between the two groups.
Early postoperative outcomes of the 350 patients with rectal cancer treated between 2000 and 2020. Patients of group 1 were treated in 2000-2015 and those of group 2 in 2016-2020.
Significantly more complications occurred in group 2 (56.5% vs. 43.8%; p=0.04) due to a higher rate of Clavien I/II complications (41.7% vs. 23.6%; p=0.002). However, the rate of AL, anastomotic stenosis, fluid collection, peritonitis, perineal wound-healing disorders, or emergency repeat surgery were similar in the two groups. In contrast, the need for surgical drainage of abdominal fluid collection was significantly higher in group 1 (7.9% vs. 0.93%; p=0.035). After PSM, complication rates were similar for the two time periods. In univariate analysis, the study period, higher body mass index (BMI), ASA score 3, complete TME, APR, and total ISR were associated with higher morbidity. In multivariate analysis, higher BMI [odds ratio (OR)=1.005, 95% confidence interval (CI)=1.002-1.008; p=0.003], APR (OR=8.018, 95% CI=1.529-49.6; p=0.017) and total ISR (OR=8.8, 95% CI=1.238-182; p=0.05) were associated with higher morbidity. In contrast, preservation of the left colic artery (OR=0.471, 95%, CI=0.285-0.768; p=0.003) was found to be associated with lower morbidity. Data regarding univariate and multivariate analyses of factors associated with the occurrence of complications are summarized in Table V.
Univariate and multivariate analysis of factors associated with the occurrence of postoperative complications in the 350 patients with rectal cancer treated between 2000 and 2020.
Pathological results. Overall, rectal tumors were mostly at stage T2 (25.1%) and T3 (42%), and lymph node metastases occurred in 27.1% of cases, with no significant difference between the two groups (Table VI). The median number of lymph nodes harvested was higher in group 2 (27 vs. 17; p<0.0001). Furthermore, circumferential margins were more frequently <1 mm (16.7% vs. 5.4%; p=0.0007) and likewise distal margins were more frequently <1 cm (8.3% vs. 0.8%; p=0.0016) in group 2. Complete mesorectal excision was more frequent in group 2 (61.3% vs. 29.3%; p<0.0001). After PSM, there was no difference between the two groups regarding the circumferential and distal margins - specifically for low rectal cancer. However, matching showed that the rate of complete mesorectal excision (59.2% vs. 31.1%; p<0.0001), as well as the median number of harvested lymph nodes (26 vs. 16; p<0.0001), were significantly higher in group 2.
Pathology results of the 350 patients with rectal cancer and treated between 2000 and 2020. Patients of group 1 were treated in 2000-2015 and those of group 2 in 2016-2020.
Late postoperative outcomes and survival rates. Overall, adjuvant CTx was required in 23.4% of patients. The recurrence rate was similar in both groups at 20.6%. The median follow-up time was longer for group 1 at 43 months vs. 17 months for group 2 (p<0.0001). The rate of late stenosis was 8.6% and the fecal incontinence rate was 9.7% – similar in both groups. OS and DFS at 3 and 5 years were also similar for both groups. After PSM, for groups 1 and 2, 3-year OS (88.2% vs. 92.6%, respectively; p=0.988), and 3-year DFS (77.9% vs. 65%, respectively; p=0.311) were comparable. Data regarding survival analyses are summarized in Figure 1. In subgroup analysis, survival rates did not differ between study periods, regardless of lymph node status (Figure 2) and margin involvement (Figure 3). In multivariate analysis, BRAF mutation (OR=9.371, 95% CI=2.213-39.68, p=0.002) and T4 stage (OR=6.684, 95% CI=1.456-30.69, p=0.015) were the strongest predictors of poor OS, while neoadjuvant CTx (OR=0.283, 95% CI=0.127-0.628, p=0.001) was the strongest predictor of better OS. The strongest predictors of poor DFS were lymph node metastasis (hazard ratio=2.9, 95% CI=1.23-7.29, p=0.016) and T4 stage (hazard ratio=4.2, 95% CI=1.06-16.4, p=0.041). Data regarding univariate and multivariate analyses of survival predictors are summarized in Table VII and Table VIII.
Overall (A) and disease-free (B) survival according to year of treatment of 350 patients with rectal cancer. Group 1: Treated 2000-2015; group 2: treated 2016-2020.
Overall (A) and disease-free (B) survival according to year of treatment of 350 patients with rectal cancer with lymph node metastases (N+) and without (N−). Group 1: Treated 2000-2015; group 2: treated 2016-2020.
Overall (A) and disease-free (B) survival according to year of treatment of 350 patients with rectal cancer with positive (R1/2) and negative (R0) margins. Group 1: Treated 2000-2015; group 2: treated 2016-2020.
Late postoperative outcome of the 350 patients with rectal cancer and treated between 2000 and 2020. Patients of group 1 were treated in 2000-2015 and those of group 2 in 2016-2020.
Univariate and multivariate analyses of factors associated with overall survival of the 350 patients with rectal cancer and treated between 2000 and 2020.
Discussion
The aim of this monocentric retrospective study was to evaluate the outcomes of rectal cancer treatment since the introduction of ISR and ERAS in our institution. Using PSM, there was no difference in overall morbidity between groups 1 and 2 (44.7% vs. 56.3%, p=0.125). However, Clavien–Dindo grade I/II complications were significantly more frequent at 41.7% in group 2 compared to 23.6% in group 1 (p=0.002). The mean length of hospital stay was similar for the two-time frames studied. Furthermore, using PSM there was no difference in terms of circumferential and distal resection margins between the two groups. On the other hand, it seems the quality of mesorectal excision improved with 59.2% (n=61) complete mesorectum specimens in group 2 vs. 31.1% (n=32) in group 1 (p<0.0001). There was also a higher median number of harvested lymph nodes. Oncological outcomes in terms of tumor recurrence and survival were similar for both groups.
ERAS and ISR are part of the arsenal of modern rectal cancer surgery and optimization of perioperative management. Previous studies have shown that when consistently implemented, ERAS protocols can improve perioperative outcomes in rectal surgery (16–18). Our data support these evidences. Implementing ERAS protocols, we did not observe a higher overall postoperative complication rate in group 2 patients, nor a higher mortality rate. However, Clavien–Dindo grade I/II complications were higher in group 2. This apparent contradiction can be explained by the fact that patients in group 2 had higher ASA scores (ASA-3: 25.9%) than in previous reports (ASA-3: 9.9%; p<0.0001). Indeed, multivariate analysis revealed that an ASA score >2, especially in rectal surgery was an independent prognostic factor for increased postoperative complications (28). Even though there were more Clavien–Dindo grade I/II complications, hospital stay was similar for both groups and reinterventions in group 2 were not more frequent, implying no supplementary health cost. However, our findings are only of limited validity in drawing final conclusions about the role of the ERAS protocol implementation by our Department. Indeed, we found that only 41.7% of our patients were treated according to the ERAS guidelines. As well as its retrospective design, this is certainly a clear limitation of this study, with a more fragile patient population and a low rate of patients treated according to the ERAS protocol. The high number of patients whose management deviated from the ERAS protocol is similar to earlier data which showed that management of patients with an ASA score >2 deviated more frequently from the ERAS protocol (29). Finally, another important reason is certainly that in our Department, only one physician and one nurse were responsible for the implementation of the ERAS protocol. The lack of qualified healthcare workers has been reported as a risk factor for a higher number of ERAS protocol violations (30). Thus, our study reflects current daily clinical practice with a shortage of specialists in the public health system and the increasingly aging and more fragile patient population in Western countries.
From 2016, the surgical practice in our Department changed. After matching, the proportions of TME and partial mesorectal excision were similar for groups 1 and 2: 75.7% vs. 81.6% for TME, and 24.3% vs. 18.4% for partial mesorectal excision (p=0.241). Partial mesorectal excision is controversial in the treatment of upper rectal cancer. Kanso et al. did not find any difference in terms of morbidity or oncological results between the two procedures (31). Another change was that more termino-terminal stapled anastomoses were performed from 2016 to 2020 (62.8% vs. 43.6%, p=0.0005) with a decrease in latero-terminal anastomoses accordingly. After matching, we observed that manual anastomoses tended to be more frequently realized in group 2 (23.3% vs. 12.6%, p=0.069). Data from previous studies showed that manual anastomosis for ISR is associated with a higher rate of AL (32). However, ISR should be at least as safe and practicable as APR and rectal anterior resection for very low rectal tumors (8–10), mostly T1/2 carcinomas without preoperative functional impairments (33, 34). In comparison, we found an increased AL rate after ISR in our patient collective. The reasons for this remain unclear. When we introduced ISR, a learning curve may have played a certain role. In the literature, however, the learning curve of ISR does not seem to explain our observed higher morbidity completely, since experience does not change the complication rate (33, 35). We therefore have to critically question whether our patient selection for ISR can be refined and optimized. Besides ISR, endoscopic transanal proctectomy was also implemented after 2016 and it was recently shown that that this procedure leads to more positive circumferential margins and local recurrences (36).
Furthermore, in our multivariate analysis we found increased BMI, APR and complete ISR to be independent predictors for increased rates of complications. An increased BMI or obesity are already known predictors for complications in rectal cancer surgery (37) and ISR (38). Since the introduction of ISR, APR has only been used more frequently for locally more advanced tumors (34), which may have also led to more complications in this study. However, the preservation of the LCA was found to be a protective factor in our study. This finding is in line with data of a recent meta-analysis (39), which revealed that preservation of the LCA was protective against AL while there was no effect on the pathological or oncological results. In summary, the current evidence favors preserving the LCA whenever technically feasible. Finally, the multivariate analysis did not reveal the study period (2000-2015 vs. 2016-2020) to be a risk factor for complications. In other words, implementation of ERAS protocols and ISR did not increase morbidity. Some authors have experienced worse functional results with ISR compared to TME (40, 41). The fact that we had the same functional outcomes is important to consider when it comes to fulfilling the patients’ wishes of restoring bowel continuity whenever possible.
In conclusion, after the implementation of ISR and ERAS, the results of our PSM analysis did not find an increased overall morbidity, with the exceptions of Clavien–Dindo grade I/II complications that were more frequent but did not increase the length of stay. Moreover, the rate of complete mesorectal excision and the median number of lymph nodes harvested increased, leading to comparable survival and oncological outcomes being achieved in patients in group 2 that were in worse general condition (higher proportion of ASA 3). ERAS and ISR had no negative impact on the oncological outcomes of our patients. However, the low compliance with ERAS protocols is a limitation to the validity of our results. Validation by other series and prospective cohort is necessary.
Acknowledgements
The Authors are deeply grateful to Guillaume Proutheau for his invaluable secretarial assistance.
Footnotes
↵* These Authors contributed equally to this study and should be considered first authors.
Authors’ Contributions
Study concept and design: M. Ouaissi. Acquisition of data: M. Ouaissi and R. Sindayigaya. Analysis and interpretation: M. Ouaissi and E. Karam. Drafting of the article: M. Ouaissi, U. Giger-Pabst and E. Karam. Critical review of the article: M. Ouaissi, E. Karam, R. Sindayigaya, N. MIchot, L. Courtot, N. Tabchouri, D. Moussata, T. Lecomte, S. Chapet, G. Callais, P. Bourlier, E. Salamé and M Gabriel. Statistical analysis: M. Ouaissi, R. Sindayigaya. Administrative, technical, and material support: M. Ouaissi. Study supervision: M. Ouaissi and U. Giger Pabst.
Conflicts of Interest
All Authors have no conflicts of interest.
- Received December 25, 2021.
- Revision received January 27, 2022.
- Accepted February 16, 2022.
- Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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