Respiratory complications following minimally invasive esophagectomy: associated factors and predictive value of lung age

Abstract

Background:

Postoperative complications following esophageal surgery are severe, with respiratory complications being the most common. This study aims to evaluate the rate of respiratory complications and related factors post-esophagectomy and lymph node dissection for esophageal squamous cell carcinoma (ESCC).

Subjects and methods:

A prospective cross-sectional study was conducted from October 2022 to March 2024 on ESCC who underwent minimally invasive esophagectomy and extended two-field lymph node dissection.

Results:

Pneumonia was observed in 18 cases (25.7%), with 15 cases recorded as Clavien-Dindo grade II, 2 cases as grade III, and 1 case as grade IV. There were no deaths within 120 days postoperative. Factors significantly affected the respiratory complications, including recurrent laryngeal nerve (RLN) palsy (P = 0.02), lung age (P = 0.04), lung-age and real-age (L—R) difference—L—R (P = 0.03), FEV1 (P = 0.045), and the obstructive/restrictive lung disease (P = 0.015). The average intensive care unit stay and hospital stay were longer in the group with respiratory complications (P = 0.000 and P = 0.001, respectively). Lung age and the L-R difference were more predictive of respiratory complications than FEV1, FEV1%, and Tiffeneau index (P < 0.05, AUC > 0.5). Thresholds of ≥23.7 years for L–R difference and ≥76.4 years for lung age were identified as predictive.

Conclusion:

Respiratory complications are common following esophageal cancer surgery, with a rate of 25.7%. Factors affecting the incidence of respiratory complications include RLN palsy, pulmonary age, L-R difference, FEV1, and the obstructive/restrictive lung disease. Lung age and the L-R difference were more predictive of respiratory complications than FEV1, FEV1%, and Tiffeneau index.

Background

Esophageal cancer is a poor prognosis cancer among gastrointestinal malignancies. According to GLOBOCAN 2022^[1], esophageal cancer ranks 11th in terms of the number of new cases and 7th in terms of the number of deaths; with a 5-year survival rate of less than 20%.

Surgical treatment for esophageal cancer presents many challenges, with postoperative complications being a serious issue affecting patient survival. Among these complications, respiratory complications—primarily pneumonia—are the most common post-esophagectomy and can occur in up to 40%^[2]. In major gastrointestinal surgeries, the incidence of pneumonia is highest in patients who have undergone esophageal surgery, 2.5 times greater than in those who have had gastric surgery^[3]. Postoperative respiratory complications in esophageal surgery include pneumonia, mediastinitis, pleuritis, pleural effusion, atelectasis, chylothorax, pulmonary embolism, and respiratory failure, all of which significantly impact recovery and outcomes. Understanding the severity and frequency of respiratory complications is crucial for improving surgical techniques and postoperative care in the treatment of esophageal cancer.

HIGHLIGHTS

• Respiratory complications occurred in a significant proportion of patients after minimally invasive esophagectomy.

• Lung age and lung age–real age difference (L–R difference) were significant predictors of postoperative complications.

• Recurrent laryngeal nerve palsy and reduced pulmonary function were strongly associated with respiratory complications.

In Asia, squamous cell carcinoma accounts for about 90% of esophageal cancers. The Japanese Esophageal Society guidelines recommend extended two-field lymph node dissection (including lymph nodes around the RLN) for ESCC. However, dissection of this group presents significant challenges due to the difficult site and the potential for severe complications, particularly respiratory issues such as aspiration risk, decreased cough reflex, and airway obstruction.

This study aims to evaluate the incidence and risk factors associated with respiratory complications following minimally invasive esophagectomy with extended two-field lymph node dissection for the treatment of esophageal cancer.

Subjects and methods

A cross-sectional study was conducted from October 2022 to March 2024. 70 patients were selected for the study. These cases were all definitively diagnosed with thoracic esophageal squamous cell carcinoma. They underwent 3D thoraco- laparoscopic esophagectomy with extended two-field lymph node dissection according to Matsuda’s classification^[4], including bilateral RLN lymph node dissection. The decision for upfront surgery or neoadjuvant chemoradiotherapy was based on the National Comprehensive Cancer Network (NCCN) guidelines^[5].

Surgical procedure

All patients underwent respiratory preparation as part of the Enhanced Recovery After Surgery (ERAS) program. This included preoperative counseling, avoiding alcohol and smoking. preoperative pulmonary function test, respiratory physiotherapy (such as spiroball exercises), and respiratory muscle training for at least 2 weeks prior to surgery.

Surgical Procedure: All patients underwent 3D thoraco-laparoscopic esophagectomy with extended two-field lymph node dissection. The McKeown approach was chosen, with the anastomosis performed in the neck. The initial approach involved thoracoscopic surgery with the patient in either the left lateral or prone position, allowing for esophagectomy and dissection of all lymph node groups as recommended by the Japan Esophageal Society for ESCC.

The abdominal phase was also performed laparoscopically, including lymph node dissection and gastric tube reconstruction. The anastomosis was conducted in the neck using either hand-sewn or circular stapler techniques. Postoperative, patients were extubated within 1-2 hours and managed in the surgical ICU. Respiratory complications were diagnosed and graded according to the classification system of the Japanese Clinical Oncology Group, which is based on the extended Clavien-Dindo classification^[6], that included pleural effusion, pneumonia, mediastinitis, pleuritis, atelectasis, chylothorax, pulmonary embolism, and respiratory failure

We calculated the following specific indices in this study

• Tiffeneau Index =FEV1/FVC (where FVC = Forced vital capacity; FEV1 = Forced Expiratory Volume in 1 second).

• Lung Age Index is calculated using the formula provided by the Japanese Respiratory Society (JRS)^[7]. “Lung age” has been shown to be related to the incidence, severity, and onset duration of postoperative pneumonia following esophagectomy.

Male: $Lungage=\frac{0,036\times height\left(cm\right)-1,178-FEV1\left(L\right)}{0,028}$

Female: $Lungage=\frac{0,022\times height\left(cm\right)-0,005-FEV1\left(L\right)}{0,022}$

• L-R difference (lung age—real age): The difference between the lung age and the real age of the patient.

Statistical analysis

Data collection and analysis were conducted using the SPSS software (version 20, SPSS Inc., Chicago, IL, USA). Risk factors for respiratory complications were assessed using the Chi-square or Fisher’s exact test. A P-value < 0.05 with a 95% confidence interval was considered statistically significant. We used area under the curve (AUC) to evaluate the prediction ability and Youden’s Index for estimate the threshold for respiratory complications.

This prospective, cross-sectional study has been reported in line with the Strengthening the Reporting of Cohort, Cross-sectional and case-control studies in Surgery (STROCSS) guideline^[8].

Results

With 70 patients who underwent esophagectomy and extended two-field lymph node dissection from September 2022 to March 2024, we obtained the results: Respiratory complications were observed in 18 cases (25.7%), including 12 cases of pleural effusion (Table 1). According to the Clavien-Dindo classification, 2 cases were classified as Grade III (requiring tracheostomy), and 1 case was classified as Grade IV (with multiple organ failure). There were no deaths within 120 days post-operative (Table 1). Factors significantly affecting the incidence of respiratory complications include: RLN palsy (P = 0.02), lung age (P = 0.04), lung age difference (P = 0.03), FEV1 (P = 0.045), and obstructive/restrictive lung disease (P = 0.015) (Table 2). The average ICU stay and the average hospital stay were statistical significance longer in the group with respiratory complications compared to the group without complications (P = 0.000 and P = 0.001, respectively) (Table 2).

Table 1.

Characteristics of respiratory complications

Characteristics	N	%
Complications	70
Pneumonia	18	25.7
Pleural effusion	12	17.1
Atelectasis	4	5.7
Respiratory failure	3	4.3
Clavien-Dindo Classification
II	15	83.3
III	2	11.1
IV	1	5.6
Treatment methods
Medical treatment	18	100
Tracheostomy	2	11.1
120-day mortality
No	18	100
Yes	0	0

Table 2.

Factors associated with respiratory complications

Characteristics	Respiratory complications (n = 18)	No respiratory complications (n = 52)	P value
Age (year)	56.9 ± 5.5	56.6 ± 7.0	0.86
Mean ± Standard deviation
Diabetes/cardiovascular disease:			0.53
Yes	6 (33.3%)	12 (66.6%)
No	12 (23.1%)	40 (76.9%)
Smoking			0.26
Yes	11 (22%)	39 (78%)
No	7 (35%)	13 (65%)
Body mass index (kg/m2)	20.5 ± 2.4	21.2 ± 2.5	0.32
Tumor location			0.1
Middle	5 (16.1%)	26 (83.9%)
Lower	13 (33.3%)	26 (66.7%)
T stage			0.61
T1	11 (26.8%)	30 (73.2%)
T2 + T3 + T4	6 (33.3%)	12 (66.7%)
N stage			0.25
N0	9 (20.9%)	34 (79.1%)
N(+)	9 (33.3%)	18 (66.7%)
Chemoradiotherapy			0.42
Yes	5 (20%)	20 (80%)
No	13 (28.9%)	32 (71.1%)
RLN palsy			0.02
Yes	8 (50%)	8 (50%)
No	10 (18.5%)	44 (81.5%)
Mean ICU stay (days)	10.2 ± 10.0	4.5 ± 2.1	0.000
Mean hospital stay (days)	18.6 ± 12.0	11.7 ± 4.7	0.001
Mean lung age (year)	78.6 ± 14.8	69.0 ± 17.7	0.04
Mean lung age difference (L—R)	21.7 ± 15.8	12.4 ± 15.4	0.03
Mean FEV1 (L)	2.6 ± 0.4	2.8 ± 0.5	0.045
Mean FEV1%	88.6 ± 12.6	95.4 ± 14.5	0.08
Tiffeneau	77.6 ± 7.6	78.2 ± 6.3	0.73
Restrictive/obstructive lung disease			0.015
Yes	6 (60%)	4 (40%)
No	12 (20%)	48 (80%)

The bold value indicates a statistically significant difference between the two groups.

Using the AUC Curve to evaluate the value of preoperative respiratory indices: Lung age and the L-R difference had higher predictive value for respiratory complications postoperative compared to FEV1, FEV1%, and the Tiffeneau index (P < 0.05, AUC > 0.5) (Fig. 1). With the Youden’s Index, we determined that the threshold for L-R = 23.7 was found to be predictive of postoperative respiratory complications, with a sensitivity of 55.6% and a specificity of 80.8% (J = 0.363). Lung age = 76.4 was predictive of postoperative pneumonia, with a sensitivity of 66.7% and a specificity of 67.3% (J = 0.340) (Table 3).

Figure 1.

Comparison of the area under the curve (AUC) for the following indices: L-R (difference in lung age and real age), lung age, FEV1, % FEV1, and Tiffeneau index in relation to the occurrence of respiratory complications.

Table 3.

Area under the curve (AUC) corresponding to preoperative respiratory indices

Index	Area under the curve	P value	95% confidence interval
L–R difference	0.681	0.023	0.532–0.831
Lung age	0.664	0.039	0.515–0.813
FEV1	0.355	0.069	0.205–0.505
FEV1%	0.349	0.058	0.210–0.489
Tiffeneau index	0.490	0.904	0.318–0.662

Discussion

With 70 case of esophageal squamous cell carcinoma who underwent esophagectomy and extended two-field lymph node dissection, we observed a respiratory complication rate of 25.7%. All cases involved pneumonia, with 66% also experiencing pleural effusion. The incidence of respiratory complications following esophageal cancer surgery varies globally, ranging from 20% to 40%. However, most studies emphasize that respiratory complications are the most common following esophagectomy^[2,9].

Respiratory complications often have relatively severe consequences for both short-term and long-term outcomes. Our study found that the average ICU stay and hospital stay were significantly prolonged, extending by an average of 5.7 days in the ICU and 6.9 days in the hospital. This extended stays due to respiratory complications lead to various consequences, such as increased hospital-acquired infections, pressure ulcers, tracheal injuries, and higher economic costs. In terms of long-term prognosis, a meta-analysis of 674 patients by Manara et al (2024) revealed that patients with respiratory complications had an average overall survival time and disease-free survival time that were 5.4 and 8.5 months shorter, respectively, compared to those without respiratory complications^[10].

Factors significantly associated with the incidence of respiratory complications identified in our study include: RLN palsy (P = 0.02), lung age (P = 0.04), L-R difference (P = 0.03), FEV1 (P = 0.045), and obstructive/restrictive lung disease (P = 0.015). Specifically, the incidence of respiratory complications was 50% in patients with RLN palsy, compared to 18.5% in those without such injury. The recurrent laryngeal nerve controls all intrinsic laryngeal muscles (except the cricothyroid muscle, which is innervated by the superior laryngeal nerve), thus facilitating vocal cord movement. Injury to this nerve can lead to vocal cord paralysis, hoarseness, and aspiration due to incomplete closure of the vocal cords, increasing the risk of aspiration pneumonia. Severe bilateral nerve palsy can result in significant airway obstruction, necessitating emergency tracheostomy to ensure adequate ventilation. Notably, in our study, the two patients who required tracheostomy did not have RLN palsy.

Identifying high-risk esophageal cancer patients for respiratory complications is pivotal. Historically, preoperative spirometry has been used to assess lung function and is widely employed as a routine preoperative test for various thoracic surgeries^[11]. Previously, a Tiffeneau index >70% was considered acceptable for preoperative lung function assessment^[12]. An FEV1/FVC ratio <70% has been associated with increased risk of overall postoperative complications, including cardiovascular issues, atrial fibrillation, pulmonary complications, and pneumonia^[13]. Our study found that the difference between “lung age” and “real age” (L-R), as well as the lung age itself, were more valuable indicators than FEV1, %FEV1, and the Tiffeneau index for predicting the risk of postoperative respiratory complications. This outcome is similar with the findings of Hong et al (2022), who divided 625 esophageal cancer patients undergoing minimally invasive esophagectomy into three groups based on L-R values: Group A (L–R ≤ 0), Group B (0 < L–R ≤ 15), and Group C (L–R ≥ 15). The study found significant differences in hospital stay duration, postoperative stay, and hospital costs among the three groups, with Group C having the longest durations. Furthermore, overall survival differed between Group A and the other groups.

Conclusion

Respiratory complications are common follow esophageal cancer surgery, with a rate of 25.7%. Factors affecting the incidence of respiratory complications include RLN palsy, lung age, L-R difference, FEV1, and the obstructive/restrictive lung disease. Lung age and the L-R difference are more predictive of postoperative respiratory complications than FEV1, FEV1%, and the Tiffeneau index.

Ethical approval

This study was conducted with the informed consent of patient and received the requisite ethical approval from the Scientific Council of Vietnam National Cancer Hospital. The council comprises expert representatives from relevant specialties, including gastrointestinal surgeons, radiologists, oncologists, gastroenterologists, and pathologists. Their comprehensive review and endorsement ensured adherence to the highest ethical standards throughout the research process. Our procedures adhered to the Declaration of Helsinki.

Consent

Written informed consent was obtained from the patients for publication and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request. Informed consent. Informed consent was obtained from the study patients.

Sources of funding

This is a nonfunded study.

Author contributions

B.V.P.: Surgeon, study design, data collection, data statistics, data interpretation, preparation of manuscript, literature analysis/search, resources, supervision; DDN: Surgeon, study design, data collection, data statistics, data interpretation, preparation of manuscript, literature analysis/search, resources, supervision; A.D.T.: Surgeon, study design, data collection, data statistics, data interpretation, preparation of manuscript, literature analysis/search; M.D.T.: Surgeon, data collection; T.D.N.: Surgeon, data collection, B.T.N.: Surgeon, data collection.

Conflicts of interest disclosure

The authors declare that they have no financial conflict of interest with regard to the content of this report.

Guarantor

Binh Van Pham, Duy Duc Nguyen, and An Duc Thai accept full responsibility for the work and the conduct of the study, had access to the data, and controlled the decision to publish.

Research registration unique identifying number (UIN)

None applicable.

Data availability statement

Data are available upon reasonable request.

Provenance and peer review

Not commissioned, externally peer-reviewed.