ERAS has been implemented clinically for many years and accepted by a large number of surgeons, including urological, gastrointestinal, and gynecological surgeons.11–13 There is only a limited amount of research about the implementation of ERAS for esophageal cancer patients at present. Particularly, there is no discussion about the feasibility of ERAS implemented in esophageal cancer patients who underwent NACT. In this retrospective study, our data proved that ERAS for NACT group patients are safe and feasible, although preoperative PNI and cTNM stage were significantly worse in the NACT group.
NACT followed by esophagectomy for treatment of ESCC has been widely accepted. Although chemotherapy may have some side effects such as leukopenia, previous studies have shown that NACT followed by esophagectomy is a feasible and safe, and there was no increase in postoperative complications and hospital length of stay after surgery.7,8 However, NACT may lead to necrosis and fibrosis, which can increase the surgical duration and intraoperative blood loss.6 This was a little different from our study. In our study, NACT group patients had a longer operating time, yet there were no significant differences in intraoperative bleeding compared with the non-NACT group. The number of lymph nodes harvested was also similar for the two group. Meanwhile, Nomoto, D. et al.7 showed that NACT followed by esophagectomy did not increase the operation time and intraoperative blood loss.
Previous studies had suggested that the implementation of ERAS protocol in minimally invasive McKeown esophagectomy was safe and feasible.8 In a randomized controlled trial about locally advanced gastric cancer, the author demonstrated that patients who received NACT can benefit from ERAS similarly to patients who were not administered NACT.14 Our study showed that there were no significant differences between the two groups in postoperative complications or readmission, and that the hospital LOS after surgery was also similar between the two group.
The overall complication rate was similar between the NACT group and non-NACT group in our study (22.1% vs. 21.0%). This was similar to a previous study,6 where they had demonstrated that NACT did not increase postoperative complications. However, we seem to have a lower postoperative complication rate compared with Ma S et al. study (22.1% vs. 31.6%, 21.0% vs. 29.9%, respectively).6 In addition, the severity grade of complications was also similar in the two groups. Frequency of complications analysis showed that the NACT group had a higher rate in vocal cord paralysis, which may be explained by the fact that most patients in the NACT group had a locally advanced stage(c TNM stage ≥ III) ESCC. There was no significant difference in LOS and the time of chest tube removal between the two groups. We demonstrated that ERAS for patients with NACT was also feasible and safe.
EOF is likely a crucial element of ERAS protocols for esophagectomy and an important contributor to the decrease in the postoperative LOS. Berkelmans et al.15 showed EOF promotes recovery of gastrointestinal function without increasing the incidence and severity of postoperative complications. In Sun’s study,16 patients who underwent esophagectomy were allowed to eat a regular diet on POD1. They demonstrated that patients in the EOF group had a quicker recovery of bowel function and improved short-term quality of life without increased postoperative complications. However, some studies had shown that direct oral feeding following esophagectomy may increase the rate of anastomotic leakage and aspiration pneumonia.17,18 In our study, we adopted a more conservative feeding time. All patients included in this study received EOF and it was allowed on POD2 or POD3. Our results demonstrated that EOF for patients who received NACT were also safe, which did not increase the rate of anastomotic leakage and aspiration pneumonia. Meanwhile, it is worth considering whether we can implement a more aggressive EOF time.
The major purpose of NACT is to increase the rate of R0 resection through tumor down-staging for locally advanced cancer patients. In our study, there was no significant difference in R0 resection rate between the two groups, which is consistent with a previous study.8 However, the NACT group had significantly more patients in the latter stages than the non-NACT group (P < 0.001, Table 3). In this case, it is reasonable to assume that NACT could lead to tumor down-staging.
Currently, there are two main strategies to perform esophageal cancer lymphadenectomy: three-field dissection (3D) and 2D. For thoracic esophageal cancer, there have been several controversies for many years about the best way to perform lymphadenectomy. Some studies have shown that for thoracic esophageal cancer patients, 3D should be a priority, especially for those with positive lymph nodes, but other studies showed different results.19 Koterazawa et al.20 had shown that 3D approach did not improve long-term prognosis but increased postoperative complications. Moreover, in the study by Wang et al.,21 a 2D method was recommended as the first-choice surgical treatment for ESCC. In our institution, we have introduced two types of lymph node dissection method, 2D + and 2D.
A trend showed that NACT group may have had a high number of lymph nodes harvested compared with non-NACT group, especially in thoracic lymph nodes dissection. However, there was no statistical difference (P > 0.05), which was different from previous studies.6–8 A previous study showed that the location of lymph nodes might play a more important role than the number of lymph nodes harvested in esophagectomy, especially in the dissection of bilateral recurrent laryngeal nerve lymph nodes.22
This study had some limitations. This was a retrospective study, and the disadvantages of such a study is that the patients enrolled were not randomly assigned and selection bias was unavoidable. Although, a considerable number of patients with locally advanced stage refused neoadjuvant therapy and requested surgical treatment, the NACT group still contained more advanced cases than the non- NACT group. The sample size of the study was small, and it was a single-center study. Thus, further validation is necessary with multi-institution studies, which should include high-volume institutions. In addition, our study only included the patients who underwent neoadjuvant chemotherapy. Patients who underwent neoadjuvant radiotherapy and immunotherapy were not included. Therefore, the safety and feasibility of ERAS implemented in these patients remains to be further studied.
Neoadjuvant therapy plays an increasingly important role in patients with esophageal cancer, and ERAS will be accepted by more surgeons.23 There will also be a trend to implement ERAS protocols for patients receiving neoadjuvant therapy. ERAS is not a specific standard nor invariable, thus ERAS protocols should be improved constantly with the development of new approaches, methods, materials, technology, and equipment.