Oesophageal cancer is the seventh most common malignant tumour and the sixth leading cause of cancer-related deaths globally (1). The long-term survival for patients with oesophageal cancer remains poor despite therapeutic improvements (2). The primary treatment for patients with resectable oesophageal cancer remains surgical resection. Ivor Lewis oesophagectomy is a common surgical approach for patients with cancers in the middle or lower third of the oesophagus. Hybrid minimally invasive Ivor Lewis oesophagectomy (HILO) is widely used in clinical practice, not only for radical resection but also in terms of safety in anastomosis (3). With the application of enhanced recovery after surgery among patients undergoing oesophagectomy, totally minimally invasive Ivor Lewis oesophagectomy (TILO) has gained popularity in recent years because it greatly reduces trauma to patients (4).

TILO appears superior to open thoracotomy and laparotomy, with a significant reduction in postoperative complications (5). Similarly, the MIRO trial has shown that minimally invasive oesophagectomy might improve patients’ health-related quality of life mediated by reductions in postoperative complications compared with open oesophagectomy (6). Moreover, Gottlieb-Vedi et al. have found that the long-term survival after minimally invasive oesophagectomy compares well with open procedures and might even be better (7). However, considering the choice between TILO and HILO, no consensus has been reached, with only two retrospective studies with small sample sizes concluding that there was no difference in short-term outcomes between the two groups (8, 9). There is also limited evidence on long-term patient survival for these procedures.

The aim of this study is to compare short- and long-term outcomes of TILO versus HILO for patients with cancers in the middle or lower third of the oesophagus.

The patient selection flow diagram is shown in Figure 1 . A total of 324 consecutive patients were screened. We excluded 30 patients ( Figure 1 ). Finally, 294 patients were included in the analysis.

In this study using PSM analysis, we found that the TILO approach was associated with a lower risk of postoperative major complications including pneumonia, and pleural effusion, while the estimated blood loss and chest drainage were also reduced in this group. While the difference arrived at statistical significance in estimated blood loss, we cannot state clinical significance. The 3-year overall survival and disease-free survival rate of patients in the TILO group were similar to those in the HILO group.

Here we found that the TILO procedure was associated with a 12.5% lower incidence of postoperative pneumonia than HILO. This effect was most probably because it reduces physiological trauma and can achieve better control of postoperative pain (16, 17). A recent randomized controlled trial (16) showed that HILO resulted in a lower incidence of postoperative pulmonary complications compared with open oesophagectomy, consistent with our results. However, our study constitutes a further step toward a comprehensive understanding of how TILO can improve early postoperative outcomes in patients with oesophageal cancers. Our results are also consistent with those presented by Souche et al. (9), in which the major postoperative pulmonary complications were significantly lower in the minimally invasive oesophagectomy group compared with a hybrid surgery group. However, we had a sample size of approximately twice as many patients. Although a few studies have reported on the short-term outcomes after TILO compared with HILO, those results remain controversial (8, 9, 18, 19). Most of them reported the initial experience and aimed to prove the technique’s safety. Other studies showed no difference in postoperative pneumonia between the two procedures, which could have arisen from the limited sample size (fewer than 15 patients who underwent minimally invasive oesophagectomy) and might be explained by the surgeons’ learning curve (19). Moreover, Fumagalli et al. compared the two groups indirectly without showing the baseline data (8).

The main challenge for TILO might be the difficulties in performing intrathoracic anastomosis. However, several such techniques and experiences have been reported, including thoracoscopic hand-sewn, intrathoracic circular stapled, and robot-assisted anastomoses (20–22). In our study, no significant differences were observed between the two groups with respect to anastomotic leak. A possible reason might be that the surgeons have already passed the learning curve. TILO has been initially performed in our institution since 2011. All the surgeons were experienced in performing minimally invasive oesophagectomy including both TILO and HILO before this study conducted since 2014.

Adequate lymph node yield among node-positive patients is critical for accurate assessment of tumour staging and for improving the long-term survival in patients with oesophageal cancer (23). No statistical difference was found in the total numbers of harvested lymph nodes between the two groups in our study, but there were significantly more lymph nodes harvested in the superior mediastinum in the TILO than in the HILO groups. In our experience, thoracoscopic-assisted or robot-assisted surgery provides a high-definition field and increased spatial precision during surgery compared with conventional thoracotomy, which might be the reason for the difference.

Evidence for the long-term survival benefit of minimally invasive oesophagectomy seems limited and contradictory. Thus, Gottlieb-Vedi et al. reported long-term survival benefits after minimally invasive oesophagectomy compared with open oesophagectomy (7). However, Mariette et al. (16) concluded that there was no difference in long-term survival between patients subjected to hybrid or open oesophagectomy in a randomized controlled trial. Evidence for long-term survival comparing TILO with HILO is still deficient. In the PSM analysis, we found a trend but no significant prognostic benefit after TILO compared with HILO. Moreover, when we performed a subgroup analysis based on pathological tumour stage, no significant effects were observed in 3-year overall survival and disease-free survival rate between the two groups. The duration of follow-up time and the heterogeneity of the oesophagogastrostomy technique might weaken the significance of the survival analysis in our study.

This study has been the first to investigate whether the choice between TILO and HILO influences the long-term survival in patients with oesophageal cancers. We performed a PSM analysis in a relatively large sample size to minimize confounding bias. As a result, the study population was more homogeneous. The study by Souche et al. had a long time span of over 5 years with a smaller sample size (9). However, our study also had a relatively short time span to ensure homogeneity of surgical technique and postoperative administration. There were also some limitations in our study. First, it was retrospective and observational, with inherent flaws. Second, several studies have found evidence that anastomotic techniques might have a significant correlation with subsequent leakage (24, 25). Because of the absence of standardized intrathoracic oesophagogastrostomy approaches (26), various anastomotic techniques were used in this study, potentially increasing the bias. However, multiple factors including blood supply, anastomotic tension and diabetes, have been proposed to influence anastomotic healing. Further multicentre prospective, randomized controlled clinical trials are needed.

In conclusion, TILO resulted in improved short-term outcomes, especially less pulmonary complications, than HILO for patients with cancers of the middle or lower third of the oesophagus, with similar survival outcomes.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by the Ethics Committee of West China Hospital of Sichuan University. The patients/participants provided their written informed consent to participate in this study.

L-QC and W-PW conceptualized the study, revised the manuscript and supervised the study. Y-MG and H-LZ collected the data, drafted the manuscript and made the figures. Y-SY, YY, YH and G-WC revised the manuscript. All authors read and approved the final manuscript.

This research was supported by Excellence Surgery Grant of Bethune Charitable Foundation (Grant No. HZB-20181119-52).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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