Surgical intervention after neoadjuvant therapy in esophageal cancer: a narrative review

Introduction

Esophageal cancer (EC) is a malignant tumor originating from the esophageal epithelium, and most cases are classified as either esophageal squamous cell carcinoma (ESCC) or esophageal adenocarcinoma cancer (EAC). Esophageal cancer is the seventh most common cancer and the sixth leading cause of cancer death worldwide (1,2). According to the report “Global Cancer Statistics 2020”, there are about 604,000 new cases and about 544,000 deaths from EC worldwide each year, and the five-year survival rate is less than 20% (3). China has a high incidence of EC, and more than half of EC cases worldwide are diagnosed in China. Epidemiological data show that the new cases and deaths of EC in China account for 53.70% and 55.35% of the global total, respectively (4,5). At present, EC is a major threat endangering national health. Active prevention and treatment of EC is very important for reducing the mortality rate and improving the quality of life of patients. Currently, commonly used clinical treatment options for EC include radiotherapy, chemotherapy, and surgery. Clinically, about 50% of patients with esophageal cancer are at an advanced stage when diagnosed, resulting in a missed opportunity for optimal early surgical intervention (6). At this time, even if surgical intervention is adopted, it is difficult to obtain a good prognosis, with the 5-year survival rate after surgery ranging from 20–35% (7). The 2022 Chinese guidelines for the diagnosis and treatment of EC recommend neoadjuvant therapy for patients with cTis-2N1-3M0 or cT3-4aN0-3M0. In recent years, clinical studies have shown that preoperative neoadjuvant therapy can significantly improve overall survival (OS) of patients with locally advanced resectable EC, mainly by reducing the risk of locoregional recurrence and distant metastasis (8-10). Compared with traditional chemoradiotherapy, neoadjuvant therapy can improve the survival rate of advanced stage patients and increase the possibility of surgery to a certain extent (11). The application prospect of surgical intervention for EC after neoadjuvant therapy is good and worthy of clinical attention (12,13). We present the following article in accordance with the Narrative Review reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-420/rc).

Methods

To complete this narrative review, we searched PubMed, Google Scholar, and Cochrane Library to identify relevant articles. The following combination of search terms was used: esophageal cancer, neoadjuvant therapy, neoadjuvant chemotherapy, chemoradiotherapy, immunotherapy, targeting, surgery, complications. Two authors conducted a full-text review of relevant literature (Table 1). Because our study was designed as a narrative review, the meta-analysis cited in this study did not use standard methodological methods or statistical analysis.

Definition and progress of neoadjuvant therapy for esophageal cancer

Neoadjuvant therapy for EC refers to treatment options, such as chemoradiotherapy, before surgery is performed for EC. Neoadjuvant therapy before esophagectomy is the standard treatment for locally advanced and operable EC (7). At present, neoadjuvant therapy for EC mainly includes neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy (nCT), and emerging immunotherapy combined with chemotherapy radiation therapy (CRT) (14).

nCT

The study of nCT in EC first began in the 1980s. At that time, commonly used chemotherapy regimens were double- or triple-drug regimens based on cisplatin [cisplatin + 5-fluorouracil (5-FU)/methotrexate/vincristine/bleomycin, among others]. Clinical studies have shown that nCT plays a small role in the treatment of esophageal cancer, because nCT does not significantly improve the survival of patients (15,16). However, study also found that the survival of patients with better pathologic complete response (PCR) was significantly longer, and the survival rate was double compared with that of patients with surgery alone (16). The advantage of preoperative systemic chemotherapy over surgery was also demonstrated in a major trial (17) and as a result, the exploration of nCT continues. nCT regimens vary. In a previous study involving 162 patients with ESCC and up to 5 years of follow-up, Sugimura et al. (18) reported that compared with patients treated with cisplatin + fluorouracil + doxorubicin, recurrence free survival (RFS) and 5-year OS of the cisplatin + fluorouracil + docetaxel group were significantly longer, and locoregional and distant recurrence rates were significantly lower in the subgroup of patients with advanced clinical tumor (T) and lymph node (N) stages. In addition, in a three-arm study of stages II and III locally advanced esophageal squamous cell carcinoma, the JCOG1109 NExT study, we found that preoperative DCF significantly prolonged overall survival compared with preoperative CF (19). As a result, cisplatin + fluorouracil + docetaxel regimen is a candidate for neoadjuvant treatment of resectable ESCC. In 2022, Chidambaram et al. (20) conducted a meta-analysis of 22 clinical studies on the use of nCT in patients with locally advanced EC, involving a total of 2,666 patients. The results showed that compared with the docetaxel + cisplatin + 5-FU treatment regimen, the fluorouracil + leucovorin + oxaliplatin + docetaxel treatment regimen could improve the PCR of patients to a certain extent, but there was no significant difference between the two regimens [P=0.148, 95% confidence interval (CI): 0.080–0.259]. Therefore, comparison between different treatment regimens of nCT requires further exploration. In terms of the duration of nCT, Shiraishi et al. (21) conducted a multicenter phase II clinical trial in 2021 involving 180 patients with EC. The results showed that 3 courses of nCT resulted in a better response than 2 courses, and there was no significant increase in adverse events.

nCRT

nCRT refers to the chemoradiotherapy performed before the implementation of local treatment, which is suitable for locally advanced EC (clinical stage above T3, positive circumferential resection margin, and lymph node metastasis). The decade-long CROSS trial (22), which randomized 366 patients to 5 weekly cycles of preoperative carboplatin and paclitaxel plus concurrent radiotherapy or surgery alone, confirmed better OS in patients who received preoperative nCRT, with a significant 13% improvement in 10-year OS (38% vs. 25%). Li et al. (23) found that nCRT had advantages in PCR, R0 resection rate, and OS, and had lower postoperative adverse reactions than nCT. A previous study has shown that with the continuous innovation and development in the field of modern cancer treatment. The 5-year survival rate for esophageal cancer has increased from 19% in 1970 to 47% today. A significant improvement in survival depends on the widespread use of nCRT in advanced esophageal cancer (14). However, in two previous randomized trials in the United States and Europe, we found no significant increase in survival with nCRT as compared with nCT (24,25). But, in a phase II trial, we considered preoperative chemoradiotherapy as an option in esophageal adenocarcinoma with regard to margin involvement, although there was no difference in survival (26). The meta-analysis by Han et al. (27) included a total of 4,529 patients (nCT: 2,035; nCRT: 2,494). The 3-year survival rate, R0 resection rate, and PCR rate of nCRT were significantly higher than those of nCT, and the rates of local recurrence and distant metastasis were significantly lower than those of nCT. Postoperative complications have always been an area of concern in EC. Jin et al. (28) found in a meta-analysis that nCRT and neoadjuvant radiotherapy (NRT) did not significantly increase the risk of postoperative anastomotic leak in EC patients. nCRT has attracted a great deal of attention. The results of a meta-analysis of 31 clinical studies (29) showed that taxane regimens were equally effective as cisplatin plus 5-FU regimens in ESCC patients, but the OS of taxane regimens (P=0.03) was superior to cisplatin plus 5-FU regimens. In addition, the vinorelbine plus cisplatin regimen (30) has also been well tolerated and effective in Chinese ESCC patients. In addition to the above dual therapies, triple therapy has also attracted clinical attention in recent years. The results of a phase II clinical trial (31) showed that the overall response rate of docetaxel, nedaplatin, and 5-FU combination chemotherapy was 87.0%. Another triple regimen (paclitaxel, cisplatin, and capecitabine) has resulted in excellent PCR rates with a low incidence of adverse effects in patients with locally advanced ESCC (32). The application prospect of nCRT in the field of EC is highly anticipated. The use of nCT and nCRT and the results of different treatment regimens are summarized in Table 2.

Neoadjuvant immunotherapy

Immunotherapy has evolved as a promising new treatment modality across cancer types (33). An available study (34) indicates that immune check-point inhibitors (ICIs) such as pembrolizumab and nivolumab can be used as a first-line treatment for patients with locally advanced EC. In 2020, Kojima et al. (35) randomized 628 patients with advanced EC to pembrolizumab or chemotherapy. Patients were identified in a phase 3 trial, with a positive score ≥10 had significantly higher 12-month OS with pembrolizumab versus chemotherapy (43% vs. 20%) and significantly lower rates of adverse events with treatment (18.2% vs. 40.9%). In 2019, a multicenter phase III trial (34) involving 419 patients randomized to nivolumab or chemotherapy showed a median follow-up for OS of 10.5 months in the nivolumab group and 8.0 months in the chemotherapy group. At a minimum follow-up of 17.6 months, OS was significantly improved with nivolumab versus chemotherapy (10.9 vs. 8.4 months, P=0.019). To evaluate atezolizumab’s stability after definitive chemoradiotherapy in locally advanced ESCC patients, the TENERGY trial (36) involved 50 patients with advanced EC. Blood samples were obtained at 3 time points (before CRT, after CRT, and 4 weeks after initiation of atezolizumab) for exploratory biomarkers. The study results have not yet been published and were ultimately found to require further attention. A study (37) has also shown that the combination of immunotherapy and chemotherapy in neoadjuvant therapy may have more advantages in terms of pathological response in patients with locally advanced resectable EC. In order to verify the effect of neoadjuvant immunotherapy combined with chemotherapy followed by surgery, Hong et al. (38) enrolled 76 patients and divided them into a surgery alone group and immunotherapy combined with chemotherapy followed by surgery group. The results showed that the complications of the 2 groups were similar, and there were no significant differences in intraoperative blood loss, intensive care unit (ICU) stay time, postoperative stay time, and hospitalization cost. Rates of 30-day mortality, 30-day readmissions, and ICU readmissions were also similar between the concurrent immunotherapy and chemotherapy group and surgery group. The emergence of neoadjuvant immunotherapy may provide a new treatment option for locally advanced EC. In a previous study by Huang et al. (39), 54 patients with advanced EC were randomly divided into immunotherapy group and chemotherapy group, and all received radical surgery after treatment. Compared with the chemotherapy alone group, the PCR rate and objective response rate of the chemotherapeutic combination group were significantly higher (30.4% vs. 9.7%, P=0.048; 86.9% vs. 95.7%, P=0.017), as was the tumor regression grade ≥2 (80.7% vs. 50.0%, P=0.013). Compared with traditional therapy, immunotherapy has been shown to have obvious advantages in many malignant tumors and may become the mainstream drug treatment for unresectable and progressive or metastatic EC. Neoadjuvant immunotherapy has been shown to be safe and effective. A large number of prospective clinical studies and more data support are also needed. Table 3 shows the results of studies with neoadjuvant immune checkpoint inhibitors in patients with EC.

Neoadjuvant targeted therapy

Targeted therapy is a new treatment technology, which plays an important role in the treatment of esophageal cancer. Drugs included cetuximab and bevacizumab, which act on epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), respectively. Drugs targeting surface antigens and other signaling pathways are in development (40). The results of a phase III trial by Ruhstaller et al. (41) found that in patients with resectable ESCC, cetuximab combined with other therapies (radiotherapy, chemotherapy, and surgery) significantly controlled the development of regional ESCC and improved progression-free survival (PFS) and overall survival (OS), without an increase in toxicity and adverse events. In order to verify the clinical effect of nimotuzumab combined with chemotherapy, Han et al. (42) conducted a five-year study involving 21 patients with EC, and the results showed that the objective response rate was 38.1% and the disease control rate was 81%. The mean PFS was 7 months, and the 18-month OS was 10%, and no drug-related toxicities were noted during long-term follow-up. Regarding the EGFR pathway, in addition to the above 2 drugs, gefitinib (43) and icotinib (44) are also expected to be effective, but their therapeutic effects still need to be supported by more clinical trial data. Trastuzumab, a commonly used drug targeting the human epidermal growth factor receptor 2 (HER2) pathway, has a good effect in the treatment of most tumors but has little effect in EC. A phase II study by Makiyama et al. (45), which included 91 patients randomly assigned to paclitaxel or trastuzumab, confirmed that the median PFS was 3.2 months and 3.7 months in the paclitaxel and trastuzumab groups, respectively, and the median OS was 10 months and 10.2 months in the 2 groups, respectively. Overall response rates were 32% and 33%, respectively, and no biomarkers were found to correlate with response in the trastuzumab group. In contrast, a phase III study by Hecht et al. (46) involving 545 patients assigned 1:1 to placebo or lapatinib showed a median OS of 12.2 months and 10.5 months, and a median PFS of 6.0 months and 5.4 months, respectively, in the lapatinib and placebo groups. The response rate was significantly higher with lapatinib (53% vs. 39%). For gastrointestinal cancers, VEGFR inhibitors appear to be more commonly used (47). However, there are still many problems in the safety of EC treatment. Cunningham et al. (48) conducted a multicenter phase II and III trial involving 1063 patients with EAC who were divided into bevacizumab plus chemotherapy (experimental group) and chemotherapy alone (control group). The results showed that the 3-year OS rate was 50.3% in the control group and 48.1% in the experimental group. The incidence of postoperative anastomotic leakage was higher in the experimental group (24% vs. 10%). In the RAINBOW-Asia trial, Xu et al. (49) randomly assigned 440 patients to a ramucirumab group and the paclitaxel group. The results showed that the median PFS was 4.14 months in the ramucirumab group and 3.15 months in the paclitaxel group (P=0.0184). The median OS was 8.71 months with ramucirumab and 7.92 months with paclitaxel. At present, ramucirumab is one of the most commonly used second-line treatment options for EC in China. Althougha previous study (50) has found that crizotinib has some antitumor activity in EAC patients, it still needs to be further verified by large-scale clinical studies. With the continuous discovery of new targets, more and more targeted therapeutic drugs will be developed in the future.

Summary

Neoadjuvant therapy includes nCT, nCRT, immunotherapy and targeted therapy, etc. There is no effective evidence on which treatment method is the most beneficial for patients. At present, radiotherapy and chemotherapy are still the preferred clinical treatment for the vast majority of patients with esophageal cancer. Immunotherapy and targeted therapy have benefited limited specific patient groups, but the overall clinical application is still limited, and more trials are needed to verify their safety and efficacy. Common neoadjuvant targeted therapies are summarized in Table 4.

Timing of surgery after neoadjuvant therapy for esophageal cancer

In clinical practice, the timing of surgery after neoadjuvant therapy has a great impact on the clinical prognosis of patients, although specific optimal surgical timing remains unclear. Traditionally, the best time for surgery is 4–6 weeks after completing nCRT (51), but some scholars have suggested otherwise. Qin et al. (52) included 15,086 patients in a meta-analysis showing that compared with patients with an interval of fewer than 7–8 weeks after nCRT, the PCR rate was significantly improved in the group with a gap of 7–8 weeks (P=0.001), although both 2-year OS (P=0.002) and 5-year OS (P=0.0009) were significantly reduced for the longer period. Xiao et al. (53) randomized a total of 224 patients into group A (≤10 weeks) and group B (>10 weeks) in a 4-year study based on the timing of surgical treatment after nCRT. The results showed that among patients who achieved PCR after surgery, there was no significant difference in survival benefit between the A and B groups (P=0.618). However, in patients who did not achieve PCR, increasing the operation time reduced the survival rate (P=0.035) and accelerated cancer progression (P=0.036). The study by Roh et al. (54) included 348 EC patients divided into 3 groups (no nCRT before surgery, surgery within 35 days of nCRT, and surgery more than 35 days after nCRT). The incidence of anastomotic fistula of the no nCRT group, ≤35 days after nCRT group, and the >35 days after nCRT group was 14.7%, 7.3%, and 20.0%, respectively, and the difference between the groups was statistically significant (P=0.020). These results suggested radical esophagectomy within 35 days of NCRT could significantly reduce the incidence of anastomotic fistula. Current studies have shown that patients who achieve PCR after nCRT have significantly longer OS than those who achieve a pathologically partial response or no response (55,56). However, whether delays in surgery after nCRT lead to increased likelihood of PCR and improved survival remains debatable. The study by Singla et al. (57) included a total of 226 EC patients divided into an early group (≤50 days) and advanced group (>50 days). The results showed that age, sex, comorbidities, Eastern Cooperative Oncology Group (ECOG) status, location, grade, and tumor histology were similar, and the difference in PCR rate between the early and late groups was not statistically significant (26.9% vs. 19.0%, P=0.24). A total of 8,489 patients were included in the study by Levinsky et al. (58). The patients were divided into a timely esophagectomy group (<90 days) and delayed esophagectomy group, and the results showed that the delayed esophagectomy group had a higher PCR rate (22.2% vs. 18.6%, P=0.043) and 90-day mortality (10.4% vs. 7.8%, P<0.01). In multivariate analysis, delayed esophagectomy was not independently associated with OS reduction. The optimal time for surgery is uncertain and needs further study and discussion.

Summary: The optimal timing of surgery is of great significance for the survival and prognosis of EC patients and the reduction of postoperative complications. However, the optimal timing for surgery after neoadjuvant therapy is still unclear, and the current clinical practice is to perform surgery for patients after 4–8 weeks before the emergence of new evidence, and the survival rate of patients will decrease after 10 weeks. Under the premise of ensuring clinical efficacy, surgery should be performed as soon as possible. We found that the timing of surgery had different effects on the survival prognosis of patients (Table 5).

Selection of surgical methods for esophageal cancer after neoadjuvant therapy

Neoadjuvant therapy combined with surgery is an effective strategy for the treatment of patients with advanced EC (59), but the choice of surgical method varies for individual patients. Currently available surgical techniques include Ivor Lewis esophagectomy (abdominal and right thoracic incision), McKeown esophagectomy (abdominal, right thoracic, and neck incision), the Sweet procedure (left unilateral thoracotomy), abdominal left thoracotomy, and transesophageal resection, among others (60). In 2022, a retrospective study published by Ising et al. (61) involving 7,163 patients divided into a conventional thoracotomy group and minimally invasive esophagectomy group confirmed that patients in the minimally invasive group had significantly more harvested lymph nodes than those in the open thoracotomy group. The R0 resection rate was 96.1% vs. 94.3% (P=0.053), postoperative hospital stay was 9 vs. 10 days (P=0.001), and postoperative survival rate was significantly higher for the minimally invasive group (P<0.001). Transthoracic and transabdominal approaches are common techniques for radical resection of EC. In a 2020 meta-analysis involving 2,331 patients, Wu et al. (62) found that patients in the transthoracic approach (TH) group had reduced intraoperative blood loss, shorter hospital stay, and lower incidence of pulmonary complications. The TH method may be more suitable for Siewert type II adenocarcinoma of the esophagogastric junction (AEG), especially for esophageal invasion ≤4 cm. However, the operation mode for Siewert type II AEG is still controversial. The prospective study of Huang et al. (63) included 10 patients with Siewert type II AEG who underwent total laparoscopic radical resection through the left diaphragm and left thoracic auxiliary hole, and the results showed it was a good surgical option for patients with esophageal tumors that have invaded <3 cm. A retrospective data study by Hu et al. (64) included 41 patients with AEG. The 3-year survival rate, upper resection margin, postoperative complications, and estimated benefit index of lymph node dissection were analyzed. Finally, it was confirmed that total gastrectomy through the abdominal cavity access approach may be the best surgical technique for advanced Siewert type II AEG. However, a multicenter study broke this conclusion and concluded that total gastrectomy and para-aortic lymph node dissection were not necessary. When the lesion involves the esophagus exceeds at 4.0 cm, subtotal esophagectomy plus superior mediastinum 106recR (right recurrent laryngeal nerve) resection is recommended. When it exceeds 2.0 cm, 110 stations of the lower mediastinum (paraesophageal) should be dissected (65). At the same time, study has found that the transcervical approach can completely remove the lymphatic chain along the recurrent laryngeal nerve at the cervicothoracic junction, which is helpful to improve the cure rate of surgery in patients with Siewert type II tumors (66). In terms of different surgical positions, Chen et al. (67) used the prone position, and the results showed that the R0 resection rate was 93.4%, and the negative circumferential resection margin rate was 96.7%. The median total lymph node dissection rate was 21%, and the thoracic lymph node dissection rate was 13%. The positive rates of lower mediastinal lymph nodes in upper, middle, and lower tumors were 1.1%, 3.5%, and 2.4%, respectively. As a more traditional position, the lateral position is still widely used in clinical practice. In a study of 200 patients, Miura et al. (68) showed that the mean thoracic surgery time in the lateral position group was shorter than that in the prone position group (228.9 vs. 299.1 minutes, P<0.001), but the mean chest blood loss was significantly higher in the lateral position group (186.9 vs. 76.5 mL, P<0.001), the mean number of harvested thoracic lymph nodes was lower in the lateral position group than in the prone position group (23.5 vs. 26.9, P<0.05), and the incidence of pulmonary complications was significantly higher (30.8% vs. 15.4%, P<0.05). There was no significant difference in the 5-year OS rate and PFS rate between the 2 positions. For middle thoracic EC, Shi et al. (69) showed that the operation time of the Ivor Lewis group was significantly shorter than that of the McKeown group, and the incidence of anastomotic leakage, anastomotic stenosis, and pulmonary infection was significantly lower than that of McKeown group. With application of Da Vinci robotic-assisted thoracic surgery, new treatment options have emerged. Robotic surgery is an extension and progress of traditional minimally invasive surgery. due to better survival outcomes and a significantly reduced incidence of pulmonary complications (70). A previous meta-analysis by Angeramo et al. (71), which included 6,249 patients, showed that compared with conventional surgery, robotic esophagectomy resulted in less intraoperative blood loss and postoperative pneumonia [odds ratio (OR): 0.46, P<0.001] and lower overall morbidity (OR: 0.67, P<0.001), while achieving a higher R0 resection rate (OR: 2.84, P<0.001). In the study by Motoyama et al. (72), a total of 121 EC patients were randomly divided into conventional video-assisted thoracoscopic surgery (VATS) group and robot-assisted VATS group. The overall local recurrence rate in the surgical field was significantly higher in the conventional VATS group than in the robot-assisted VATS group (9% vs. 0%, P=0.039). At present, there are various surgical treatment methods for EC after neoadjuvant therapy. The choice of surgical methods should be based on the characteristics of the disease.

Summary: With the continuous progress and innovation of modern medical technology, surgical methods for EC after neoadjuvant therapy are gradually diversifying. The main surgical options include traditional thoracotomy, minimally invasive surgery, and robot-assisted surgery, among others. There is increasing evidence that the application rate of minimally invasive surgery has reached a high level, and robotic surgery is an emerging method that may replace minimally invasive surgery in the future. In the table, we document in more detail the current surgical procedures that are commonly used (Table 6).

Postoperative complications and management of esophageal cancer after neoadjuvant therapy

Postoperative complications of EC directly determine the quality of life and survival time of patients, and the prevention and appropriate treatment of complications are key. Although great progress has been made in the multimodal treatment of EC, the occurrence of postoperative complications continues to impact the prognosis and long-term survival rate of patients (73). In 2015, the Esophagectomy Complications Consensus Group (ECCG) reported that the most common complications after esophagectomy included pneumonia (14.6%), arrhythmia (14.5%), anastomotic leakage (11.4%), chylothorax (4.7%), recurrent laryngeal nerve palsy (4.2%), and tube necrosis (1.3%) (74). Pneumonia after esophageal surgery has a high incidence and significantly increases mortality and length of hospital stay (75). Therefore, in order to reduce the incidence of pneumonia, minimally invasive surgery is often performed instead of open surgery. In a single-center randomized controlled trial involving 118 patients who underwent open transthoracic esophagectomy (OTE group) or robot-assisted minimally invasive thoracoscopic esophagectomy (RAMIE group), van der Sluis et al. (76) showed that compared with the OTE group, overall procedural-related postoperative complications were significantly lower in the RAMIE group (59% vs. 80%, P=0.02), and intraoperative blood loss was significantly reduced (400 vs. 568 mL, P<0.001). In addition, the incidence of pulmonary complications was significantly lower in the RAMIE group (P=0.005), and the RAMIE group had better functional recovery at 14 days after operation (P=0.038). Because the esophagus is close to the left atrium, the occurrence of postoperative atrial fibrillation (AF) is sometimes unavoidable. The incidence of postoperative adverse events in patients with EC complicated with AF is significantly higher than that in patients without AF (OR =5.50), including 30-day mortality (OR =2.49), anastomotic leakage (OR =2.65), and pneumonia (OR =3.42) (77). A randomized clinical trial by Ojima et al. (77) involved 100 patients randomly assigned 1:1 to receive landiolol or placebo and confirmed a significantly lower incidence of AF after EC surgery (10% vs. 30%, P=0.012) and a significantly lower overall incidence of postoperative complications (P=0.046) in patients receiving landiolol. As one of the most serious postoperative complications, anastomotic leakage has attracted the attention of clinicians, but the best treatment is still unknown. A previous 10-year retrospective study by Plum et al. (78), which included 70 patients who received self-expanding metal stents (SEMS) for the treatment of anastomotic leakage after esophagectomy, found that 71.4% of the patients underwent successful esophageal stenting and the mortality rate was less than 20%. Postoperative chylothorax in patients with EC is caused by damage to the thoracic duct or its branches. At present, surgery is still the preferred intervention for the treatment of chylothorax, and no research results provide support for preoperative prophylactic ligation of the thoracic duct to reduce the incidence of postoperative chylothorax (79). In a study by Lin et al. (80), a total of 296 patients with EC were divided into conventional group (group A) and selective group (group B). The results confirmed that the incidence of postoperative chylothorax and chylothorax-related reoperation in group A was significantly higher than that in group B (9.1% vs. 0%, P<0.01) and (3.6% vs. 0%, P<0.01). The detection rate of chylous fistula (chylothorax and chylous ascites) in group B was significantly higher than that in group A (9.5% vs. 0%, P<0.01). In addition, study has shown that surgery after nCRT causes more adverse events (81). The reduction of complications is key to the success of surgery. With the emergence of new technologies, the incidence of postoperative complications is believed to be lower, but whether other complications will derive from the new technology is still unknown.

In summary, there are many postoperative complications of EC, among which the most common complication is pulmonary infection, followed by AF, chylothorax, and anastomotic leakage, among others. Preoperative prevention and active postoperative intervention are important measures to reduce the incidence of complications and poor prognosis. However, the emergence of new technology will generate new complications. In addition to improving our surgical techniques, the proper arrangement of the whole perioperative period should not be ignored. Through the clinical studies described above, we found that active management of complications is particularly important (Table 7).

Deficiencies and prospects of surgical intervention after neoadjuvant therapy for esophageal cancer

EC is one of the most common malignant tumors in China. Surgical intervention after neoadjuvant therapy is one of the most common treatment methods for clinical patients. However, the current research on surgery after neoadjuvant therapy at home and abroad has the following shortcomings. First, although there are many options, individual responses of patients to different surgical methods vary. Therefore, actively exploring an individualized surgical plan suitable for different populations is important. Secondly, the optimal timing of surgery after neoadjuvant therapy is still unclear and needs further investigation. Finally, the effective prevention of surgical complications after neoadjuvant therapy is the focus of the clinical perioperative period and further research based on a large number of clinical trials is needed. This review briefly summarized the research progress for EC after neoadjuvant therapy, but the effect of different surgical methods on the prognosis of patients and effective measures for reducing postoperative complications need further analysis and summary. Our goal was to verify the stability of surgical intervention after neoadjuvant therapy by reviewing the important clinical trials related to the subject of this article. However, we found that this is not imminent 1 and requires a larger sample size and multicenter collaboration to obtain accurate data.

Conclusions

Esophageal adenocarcinoma is more common in Western developed countries, and more than half of the cases worldwide are esophageal squamous cell carcinoma. EC is a malignant tumor with high morbidity and mortality in China. Surgical intervention after neoadjuvant therapy is the first choice for reducing mortality and improving the prognosis of patients. However, the surgical method, optimal time of treatment, and postoperative complications are still the areas of clinical concern. Therefore, to improve the prognosis of patients and reduce postoperative complications, individualized surgical treatment at the optimal time after neoadjuvant therapy based on the specific situation of individual patients is important and worthy of clinical attention and ongoing exploration. At present, the efficacy of neoadjuvant therapy still needs to be proved by a large number of trials, and neoadjuvant multimodal combination therapy may become a new direction in the future. On the basis of minimally invasive surgery, esophageal surgery can choose the most favorable way according to individual differences after different surgical approaches, fundamentally reduce the incidence of complications and further improve the survival rate of patients.

Acknowledgments

Funding: This work was supported by the Science and Technology Special Fund of Maoming City (No. 2020S003) and the Science and Technology Innovation Strategy Special Fund of Guangdong Province (“Big Project + Task List”) project (No. 2021S006).

Footnote

Reporting Checklist: The authors have completed the Narrative Review reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-420/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-420/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-420/coif). All authors report that this work was supported by the Science and Technology Special Fund of Maoming City (No. 2020S003) and the Science and Technology Innovation Strategy Special Fund of Guangdong Province (“Big Project + Task List”) project (No. 2021S006). The authors have no other conflicts of interest to declare.

Ethical Statement:The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Fernández-Montes A, Alcaide J, Alsina M, et al. SEOM-GEMCAD-TTD Clinical Guideline for the diagnosis and treatment of esophageal cancer (2021). Clin Transl Oncol 2022;24:658-69. [Crossref] [PubMed]
2. Li J, Xu J, Zheng Y, et al. Esophageal cancer: Epidemiology, risk factors and screening. Chin J Cancer Res 2021;33:535-47. [Crossref] [PubMed]
3. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin 2021;71:209-49. [Crossref] [PubMed]
4. Health Commission Of The People's Republic Of China N. National guidelines for diagnosis and treatment of esophageal carcinoma 2022 in China (English version). Chin J Cancer Res 2022;34:309-34. [Crossref] [PubMed]
5. Cao W, Chen HD, Yu YW, et al. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl) 2021;134:783-91. [Crossref] [PubMed]
6. Miller KD, Nogueira L, Devasia T, et al. Cancer treatment and survivorship statistics, 2022. CA Cancer J Clin 2022;72:409-36. [Crossref] [PubMed]
7. Kelly RJ. Emerging Multimodality Approaches to Treat Localized Esophageal Cancer. J Natl Compr Canc Netw 2019;17:1009-14. [Crossref] [PubMed]
8. Bu Q, Huang JX. Application of neoadjuvant therapy in the treatment of esophageal cancer. Int J Oncol 2020;47:244-8.
9. Kelly RJ, Ajani JA, Kuzdzal J, et al. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med 2021;384:1191-203. [Crossref] [PubMed]
10. Takahashi T, Kaneoka Y, Maeda A, et al. Neoadjuvant chemotherapy with S-1 plus cisplatin for esophageal squamous cell carcinoma. Updates Surg 2022;74:675-83. [Crossref] [PubMed]
11. Zhang T, Guo Z, Chen X, et al. A retrospective study comparing definitive chemoradiotherapy vs. chemoradiotherapy followed by surgery in T4 esophageal squamous cell carcinoma patients who were downstaged after neochemoradiotherapy. Radiat Oncol 2022;17:148. [Crossref] [PubMed]
12. Wang Q, Sun Z, Xu X, et al. The Evaluation of a SEER-Based Nomogram in Predicting the Survival of Patients Treated with Neoadjuvant Therapy Followed by Esophagectomy. Front Surg 2022;9:853093. [Crossref] [PubMed]
13. Chow R, Murdy K, Vaska M, et al. Definitive chemoradiotherapy versus neoadjuvant chemoradiotherapy and esophagectomy for the treatment of esophageal and gastroesophageal carcinoma - A systematic review and meta-analysis. Radiother Oncol 2021;165:37-43. [Crossref] [PubMed]
14. Li J, Ma S. History and current situation of neoadjuvant treatment for locally advanced esophageal cancer. Thorac Cancer 2021;12:2293-9. [Crossref] [PubMed]
15. Apinop C, Puttisak P, Preecha N. A prospective study of combined therapy in esophageal cancer. Hepatogastroenterology 1994;41:391-3. [PubMed]
16. Wang H, Tang H, Fang Y, et al. Morbidity and Mortality of Patients Who Underwent Minimally Invasive Esophagectomy After Neoadjuvant Chemoradiotherapy vs Neoadjuvant Chemotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Randomized Clinical Trial. JAMA Surg 2021;156:444-51. [Crossref] [PubMed]
17. Reynolds JV, Preston SR, O'Neill B, et al. ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS). BMC Cancer 2017;17:401. [Crossref] [PubMed]
18. Sugimura K, Yamasaki M, Yasuda T, et al. Long-term results of a randomized controlled trial comparing neoadjuvant Adriamycin, cisplatin, and 5-fluorouracil vs docetaxel, cisplatin, and 5-fluorouracil followed by surgery for esophageal cancer (OGSG1003). Ann Gastroenterol Surg 2021;5:75-82. [Crossref] [PubMed]
19. Kato K, Ito Y, Daiko H, et al. A randomized controlled phase III trial comparing two chemotherapy regimens and chemoradiotherapy regimens as neoadjuvant treatment for locally advanced esophageal cancer, JCOG1109 NExT study. J Clin Oncol 2022;40:238. [Crossref]
20. Chidambaram S, Sounderajah V, Maynard N, et al. Evaluation of tumor regression by neoadjuvant chemotherapy regimens for esophageal adenocarcinoma: a systematic review and meta-analysis. Dis Esophagus 2023;36:doac058. [Crossref] [PubMed]
21. Shiraishi O, Makino T, Yamasaki M, et al. Two versus three courses of preoperative cisplatin and fluorouracil plus docetaxel for treating locally advanced esophageal cancer: short-term outcomes of a multicenter randomized phase II trial. Esophagus 2021;18:825-34. [Crossref] [PubMed]
22. Eyck BM, van Lanschot JJB, Hulshof MCCM, et al. Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial. J Clin Oncol 2021;39:1995-2004. [Crossref] [PubMed]
23. Li X, Yu X, Zhang J, et al. To compare the efficacy and safety of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Chongqing Med 2021;50:5.
24. Stahl M, Walz MK, Riera-Knorrenschild J, et al. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): Long-term results of a controlled randomised trial. Eur J Cancer 2017;81:183-90. [Crossref] [PubMed]
25. Burmeister BH, Thomas JM, Burmeister EA, et al. Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial. Eur J Cancer 2011;47:354-60. [Crossref] [PubMed]
26. von Döbeln GA, Klevebro F, Jacobsen AB, et al. Neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the esophagus or gastroesophageal junction: long-term results of a randomized clinical trial. Dis Esophagus 2019; [Crossref] [PubMed]
27. Han J, Wang Z, Liu C. Survival and complications after neoadjuvant chemotherapy or chemoradiotherapy for esophageal cancer: a meta-analysis. Future Oncol 2021;17:2257-74. [Crossref] [PubMed]
28. Jin Z, Zhang J, Chen D, et al. Neoadjuvant chemoradiotherapy, chemotherapy, and radiotherapy do not significantly increase the incidence of anastomotic leakage after esophageal cancer surgery: a meta-analysis. Dis Esophagus 2022;35:doab089. [Crossref] [PubMed]
29. Wang T, Yu J, Liu M, et al. The benefit of taxane-based therapies over fluoropyrimidine plus platinum (FP) in the treatment of esophageal cancer: a meta-analysis of clinical studies. Drug Des Devel Ther 2019;13:539-53. [Crossref] [PubMed]
30. Yang H, Liu H, Chen Y, et al. Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial. J Clin Oncol 2018;36:2796-803. [Crossref] [PubMed]
31. Ohnuma H, Sato Y, Hayasaka N, et al. Neoadjuvant chemotherapy with docetaxel, nedaplatin, and fluorouracil for resectable esophageal cancer: A phase II study. Cancer Sci 2018;109:3554-63. [Crossref] [PubMed]
32. Zhang W, Li Y, Xue L, et al. Encouraging Pathological Complete Response Rate from Neoadjuvant Chemotherapy with Albumin-Bound Paclitaxel Plus Cisplatin and Capecitabine for Locally Advanced Esophageal Squamous Carcinoma: Preliminary Outcome of a Retrospective Study. Cancer Manag Res 2021;13:2163-70. [Crossref] [PubMed]
33. Turgeman I, Ben-Aharon I. Evolving treatment paradigms in esophageal cancer. Ann Transl Med 2021;9:903. [Crossref] [PubMed]
34. Paydary K, Reizine N, Catenacci DVT. Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging Evidence. Cancers (Basel) 2021;13:5929. [Crossref] [PubMed]
35. Kojima T, Shah MA, Muro K, et al. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol 2020;38:4138-48. [Crossref] [PubMed]
36. Bando H, Kotani D, Tsushima T, et al. TENERGY: multicenter phase II study of Atezolizumab monotherapy following definitive Chemoradiotherapy with 5-FU plus Cisplatin in patients with unresectable locally advanced esophageal squamous cell carcinoma. BMC Cancer 2020;20:336. [Crossref] [PubMed]
37. Jing SW, Zhai C, Zhang W, et al. Comparison of neoadjuvant immunotherapy plus chemotherapy versus chemotherapy alone for patients with locally advanced esophageal squamous cell carcinoma: A propensity score matching. Front Immunol 2022;13:970534. [Crossref] [PubMed]
38. Hong ZN, Weng K, Peng K, et al. Neoadjuvant Immunotherapy Combined Chemotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Study. Front Oncol 2021;11:797426. [Crossref] [PubMed]
39. Huang B, Shi H, Gong X, et al. Comparison of efficacy and safety between pembrolizumab combined with chemotherapy and simple chemotherapy in neoadjuvant therapy for esophageal squamous cell carcinoma. J Gastrointest Oncol 2021;12:2013-21. [Crossref] [PubMed]
40. Yang YM, Hong P, Xu WW, et al. Advances in targeted therapy for esophageal cancer. Signal Transduct Target Ther 2020;5:229. [Crossref] [PubMed]
41. Ruhstaller T, Thuss-Patience P, Hayoz S, et al. Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08). Ann Oncol 2018;29:1386-93. [Crossref] [PubMed]
42. Han X, Lu N, Pan Y, et al. Nimotuzumab Combined with Chemotherapy is a Promising Treatment for Locally Advanced and Metastatic Esophageal Cancer. Med Sci Monit 2017;23:412-8. [Crossref] [PubMed]
43. Petty RD, Dahle-Smith A, Stevenson DAJ, et al. Gefitinib and EGFR Gene Copy Number Aberrations in Esophageal Cancer. J Clin Oncol 2017;35:2279-87. [Crossref] [PubMed]
44. Huang J, Fan Q, Lu P, et al. Icotinib in Patients with Pretreated Advanced Esophageal Squamous Cell Carcinoma with EGFR Overexpression or EGFR Gene Amplification: A Single-Arm, Multicenter Phase 2 Study. J Thorac Oncol 2016;11:910-7. [Crossref] [PubMed]
45. Makiyama A, Sukawa Y, Kashiwada T, et al. Randomized, Phase II Study of Trastuzumab Beyond Progression in Patients With HER2-Positive Advanced Gastric or Gastroesophageal Junction Cancer: WJOG7112G (T-ACT Study). J Clin Oncol 2020;38:1919-27. [Crossref] [PubMed]
46. Hecht JR, Bang YJ, Qin SK, et al. Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC--A Randomized Phase III Trial. J Clin Oncol 2016;34:443-51. [Crossref] [PubMed]
47. Rajabi M, Mousa SA. The Role of Angiogenesis in Cancer Treatment. Biomedicines 2017;5:34. [Crossref] [PubMed]
48. Cunningham D, Stenning SP, Smyth EC, et al. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol 2017;18:357-70. [Crossref] [PubMed]
49. Xu RH, Zhang Y, Pan H, et al. Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol 2021;6:1015-24. [Crossref] [PubMed]
50. Yang Y, Wu N, Shen J, et al. MET overexpression and amplification define a distinct molecular subgroup for targeted therapies in gastric cancer. Gastric Cancer 2016;19:778-88. [Crossref] [PubMed]
51. Nilsson K, Klevebro F, Rouvelas I, et al. Surgical Morbidity and Mortality From the Multicenter Randomized Controlled NeoRes II Trial: Standard Versus Prolonged Time to Surgery After Neoadjuvant Chemoradiotherapy for Esophageal Cancer. Ann Surg 2020;272:684-9. [Crossref] [PubMed]
52. Qin Q, Xu H, Liu J, et al. Does timing of esophagectomy following neoadjuvant chemoradiation affect outcomes? A meta-analysis. Int J Surg 2018;59:11-8. [Crossref] [PubMed]
53. Xiao X, Cheng C, Cheng L, et al. Longer Time Interval from Neoadjuvant Chemoradiation to Surgery is Associated with Poor Survival for Patients Without Clinical Complete Response in Oesophageal Cancer. Ann Surg Oncol 2023;30:886-96. [Crossref] [PubMed]
54. Roh S, Iannettoni MD, Keech J, et al. Timing of Esophagectomy after Neoadjuvant Chemoradiation Therapy Affects the Incidence of Anastomotic Leaks. Korean J Thorac Cardiovasc Surg 2019;52:1-8. [Crossref] [PubMed]
55. Donahue JM, Nichols FC, Li Z, et al. Complete pathologic response after neoadjuvant chemoradiotherapy for esophageal cancer is associated with enhanced survival. Ann Thorac Surg 2009;87:392-8; discussion 398-9. [Crossref] [PubMed]
56. Alnaji RM, Du W, Gabriel E, et al. Pathologic Complete Response Is an Independent Predictor of Improved Survival Following Neoadjuvant Chemoradiation for Esophageal Adenocarcinoma. J Gastrointest Surg 2016;20:1541-6. [Crossref] [PubMed]
57. Singla S, Gabriel E, Alnaji R, et al. Complete pathologic response is independent of the timing of esophagectomy following neoadjuvant chemoradiation for esophageal cancer. J Gastrointest Oncol 2018;9:73-9. [Crossref] [PubMed]
58. Levinsky NC, Wima K, Morris MC, et al. Outcome of delayed versus timely esophagectomy after chemoradiation for esophageal adenocarcinoma. J Thorac Cardiovasc Surg 2020;159:2555-66. [Crossref] [PubMed]
59. Hirohata R, Hamai Y, Hihara J, et al. Evaluation of Neoadjuvant Chemoradiotherapy Followed by Surgery for Borderline Resectable Esophageal Squamous Cell Carcinoma. World J Surg 2022;46:1934-43. [Crossref] [PubMed]
60. Chevallay M, Jung M, Chon SH, et al. Esophageal cancer surgery: review of complications and their management. Ann N Y Acad Sci 2020;1482:146-62. [Crossref] [PubMed]
61. Ising MS, Smith SA, Trivedi JR, et al. Minimally Invasive Esophagectomy Is Associated with Superior Survival Compared to Open Surgery. Am Surg 2022; Epub ahead of print. [Crossref] [PubMed]
62. Wu H, Shang L, Du F, et al. Transhiatal versus transthoracic surgical approach for Siewert type II adenocarcinoma of the esophagogastric junction: a meta-analysis. Expert Rev Gastroenterol Hepatol 2020;14:1107-17. [Crossref] [PubMed]
63. Huang Y, Liu G, Wang X, et al. Safety and feasibility of total laparoscopic radical resection of Siewert type II gastroesophageal junction adenocarcinoma through the left diaphragm and left thoracic auxiliary hole. World J Surg Oncol 2021;19:73. [Crossref] [PubMed]
64. Hu C, Zhu HT, Xu ZY, et al. Novel abdominal approach for dissection of advanced type II/III adenocarcinoma of the esophagogastric junction: a new surgical option. J Int Med Res 2019;47:398-410. [Crossref] [PubMed]
65. Kurokawa Y, Takeuchi H, Doki Y, et al. Mapping of Lymph Node Metastasis From Esophagogastric Junction Tumors: A Prospective Nationwide Multicenter Study. Ann Surg 2021;274:120-7. [Crossref] [PubMed]
66. Okamura A, Watanabe M, Imamura Y, et al. Cervicothoracoscopic Approach in Esophagectomy. Ann Surg Oncol 2018;25:333. [Crossref] [PubMed]
67. Chen C, Ding C, He Y, et al. Prone position thoracoscopic-assisted total mesoesophageal excision: initial experiences and benefits of lymph node dissection. Surg Endosc 2023;37:2379-87. [Crossref] [PubMed]
68. Miura S, Nakamura T, Miura Y, et al. Long-Term Outcomes of Thoracoscopic Esophagectomy in the Prone versus Lateral Position: A Propensity Score-Matched Analysis. Ann Surg Oncol 2019;26:3736-44. [Crossref] [PubMed]
69. Shi Y, Wang A, Yu S, et al. Thoracoscopic-laparoscopic Ivor-Lewis surgery vs. McKeown surgery in the treatment of thoracic middle-lower segment esophageal cancer. J BUON 2021;26:1062-9. [PubMed]
70. Tsunoda S, Obama K, Hisamori S, et al. Lower Incidence of Postoperative Pulmonary Complications Following Robot-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer: Propensity Score-Matched Comparison to Conventional Minimally Invasive Esophagectomy. Ann Surg Oncol 2021;28:639-47. [Crossref] [PubMed]
71. Angeramo CA, Bras Harriott C, Casas MA, et al. Minimally invasive Ivor Lewis esophagectomy: Robot-assisted versus laparoscopic-thoracoscopic technique. Systematic review and meta-analysis. Surgery 2021;170:1692-701. [Crossref] [PubMed]
72. Motoyama S, Sato Y, Wakita A, et al. Lower local recurrence rate after robot-assisted thoracoscopic esophagectomy than conventional thoracoscopic surgery for esophageal cancer. Sci Rep 2021;11:6774. [Crossref] [PubMed]
73. Rasmussen SR, Nielsen RV, Fenger AS, et al. Postoperative complications and survival after surgical resection of esophageal squamous cell carcinoma. J Thorac Dis 2018;10:4052-60. [Crossref] [PubMed]
74. Fabian T. Management of Postoperative Complications After Esophageal Resection. Surg Clin North Am 2021;101:525-39. [Crossref] [PubMed]
75. Low DE, Alderson D, Cecconello I, et al. International Consensus on Standardization of Data Collection for Complications Associated With Esophagectomy: Esophagectomy Complications Consensus Group (ECCG). Ann Surg 2015;262:286-94. [Crossref] [PubMed]
76. van der Sluis PC, van der Horst S, May AM, et al. Robot-assisted Minimally Invasive Thoracolaparoscopic Esophagectomy Versus Open Transthoracic Esophagectomy for Resectable Esophageal Cancer: A Randomized Controlled Trial. Ann Surg 2019;269:621-30. [Crossref] [PubMed]
77. Ojima T, Nakamori M, Nakamura M, et al. Randomized clinical trial of landiolol hydrochloride for the prevention of atrial fibrillation and postoperative complications after oesophagectomy for cancer. Br J Surg 2017;104:1003-9. [Crossref] [PubMed]
78. Plum PS, Herbold T, Berlth F, et al. Outcome of Self-Expanding Metal Stents in the Treatment of Anastomotic Leaks After Ivor Lewis Esophagectomy. World J Surg 2019;43:862-9. [Crossref] [PubMed]
79. Jínek T, Adamčík L, Duda M, et al. Prophylactic ligation of the thoracic duct in the prevention of chylothorax after esophagectomy. Rozhl Chir 2018;97:328-34. [PubMed]
80. Lin Y, Li Z, Li G, et al. Selective En Masse Ligation of the Thoracic Duct to Prevent Chyle Leak After Esophagectomy. Ann Thorac Surg 2017;103:1802-7. [Crossref] [PubMed]
81. Klevebro F, Johnsen G, Johnson E, et al. Morbidity and mortality after surgery for cancer of the oesophagus and gastro-oesophageal junction: A randomized clinical trial of neoadjuvant chemotherapy vs. neoadjuvant chemoradiation. Eur J Surg Oncol 2015;41:920-6. [Crossref] [PubMed]

(English Language Editor: A. Muijlwijk)