Association between preoperative diaphragm thickening fraction and postoperative pulmonary complications in patients undergoing thoracoscopic esophagectomy for esophageal cancer

doi:10.21203/rs.3.rs-5076364/v1

Objective:

This study aimed to investigate the association between preoperative diaphragm thickening assessed using ultrasound imaging and postoperative pulmonary complications (PPCs) in patients undergoing thoracoscopic esophagectomy for esophageal cancer.

Methods:

This single-center, prospective, cohort study enrolled patients with esophageal cancer who were scheduled to undergo thoracoscopic esophagectomy between June 2021 and May 2024. The diaphragm thickening fraction (DTF) was measured using ultrasound imaging preoperatively and at 1 and 2 weeks postoperatively. Our primary outcome comprised overall PPCs. We investigated the longitudinal change in the DTF and the relationship between the DTF and PPCs. We also examined the optimal cutoff value for the ability of the DTF to predict PPCs.

Results:

This study enrolled 73 patients. PPCs occurred in 21 (29%) patients, 10 (14%) of whom had pneumonia. The estimated difference between the preoperative and 1-week postoperative least squares means of the DTF was − 56.3% (95% credible interval [CrI]: −65.4, − 47.2) and − 36.5% (95%CrI: −43.7, − 29.2) between the preoperative and 2-week postoperative values. The mean odds ratio of preoperative DTF to PPCs was 0.82 per 10% increase (95%CrI: 0.66, 0.97), after adjusting for potential confounders. According to the receiver operating characteristic curve, the optimal cutoff value predicting PPCs was 123.6%.

Conclusion:

DTF is decreased at 1 and 2 weeks after thoracoscopic esophagectomy in patients with esophageal cancer. The higher the preoperative DTF, the lower the odds of occurrence of PPCs.

Surgery

Cardiothoracic Surgery

Gastrointestinal Surgery

Physical Medicine & Rehab

Diaphragm

Ultrasonography

Postoperative pulmonary complication

Perioperative rehabilitation

Esophagectomy

Esophageal cancer

Esophagectomy is an important albeit highly invasive treatment for esophageal cancer. Although advances in surgery and perioperative management have reduced the operative mortality rate after esophagectomy, the postoperative complication rate remains high ¹. Postoperative pulmonary complications (PPCs) remain the most common complication after esophagectomy, causing postoperative mortality and long-term deterioration in the health-related quality of life ^2–4. Therefore, it is necessary to assess the risks of PPCs and develop methods to mitigate them.

The risk factors for PPCs after esophagectomy include smoking status, nutritional status, respiratory function, advanced cancer stage, neoadjuvant therapy, sarcopenia, and exercise tolerance ^3,5–11. Moreover, we previously reported that preoperative low inspiratory mouth pressure was associated with the incidence of PPCs in patients undergoing esophagectomy ¹². Non-invasive ultrasonography-based functional assessment of the diaphragm, a primary inspiratory muscle, has recently found widespread application. The function of the diaphragm is reportedly associated with the development of PPCs in cardiac, lung resection, and abdominal surgeries ^13–15. Esophagectomy entails thoracic and upper abdominal procedures, resulting in impaired diaphragmatic contractility; thus, preoperative diaphragmatic function may be related to postoperative sputum expectoration ability and the occurrence of PPCs ^16,17.

Therefore, this study aimed to investigate the association between preoperative diaphragm thickening assessed using ultrasound imaging and PPCs in patients with esophageal cancer undergoing esophagectomy. Elucidating these associations could aid in the perioperative management of patients with esophageal cancer since diaphragmatic function can be improved preoperatively.

Study design and ethics

This study incorporated a single-center, prospective, cohort design. All participants underwent ultrasound imaging of the diaphragm preoperatively and at 1 and 2 weeks postoperatively, in addition to routine evaluation. This study was approved by the Institutional Review Board of Akita University Graduate School of Medicine (approval number: 2692) and conducted in accordance with the Declaration of Helsinki. The objective and content of the study were explained to the participants orally, as well as in written documents. Written informed consent was obtained after the participants were informed that they could participate based on their own free will and that their privacy would be reasonably protected.

Participants

Patients with esophageal cancer who were scheduled to undergo thoracoscopic esophagectomy at Akita University Hospital between June 2021 and May 2024 and received pre- and postoperative rehabilitation were enrolled. The exclusion criteria were as follows: salvage esophagectomy, open thoracic esophagectomy, transhiatal esophagectomy, laryngopharyngeal esophagectomy, two-stage surgery, scheduled to undergo tracheostomy, diagnosis of hemiplegia owing to cerebrovascular disease, diagnosis of dementia, and need for assistance with daily living.

Measurements

Ultrasound imaging of the diaphragm

We assessed the diaphragm thickening fraction (DTF) using ultrasound imaging ¹⁸. Diaphragm thickness (DT) was measured (with the patient in the supine position) using B-mode ultrasonography with a 10–5 MHz linear transducer (iViz air, FUJIFILM SonoSite, Inc.) at the zone of apposition between the eighth or ninth right intercostal space at the anterior axillary and midaxillary line. In this area, the diaphragm appears as a three-layered structure, viz. a non-echogenic central layer bordered by two echogenic layers, i.e., the peritoneum and diaphragmatic pleurae. DT at rest (DT_RE), end of the maximal inspiration (DT_EI), and end of maximal expiration (DT_EE) was measured as the distance from the deep edge of the peritoneum to the superficial edge of the diaphragmatic pleura (Fig. 1) using an electronic caliper to the nearest 0.1 mm. The values of three subsequent measurements were averaged. The DTF was calculated using the following formula:

DTF = (DT_EI – DT_EE) / DT_EE × 100.

Measurements were performed preoperatively, and 1 (7 to 9 postoperative days) and 2 weeks postoperatively (14 to 16 postoperative days). One investigator with more than 10 years’ experience in ultrasonography of the diaphragm performed the measurements.

Outcomes

The primary outcome was all PPCs, including atelectasis/sputum expectoration difficulty (e.g., need for bronchoscopy), pneumonia, or reintubation for respiratory failure. Postoperative pneumonia was defined as the presence of new or progressive infiltrates on chest radiography or computed tomography and the presence of at least one of the following parameters per the revised Uniform Pneumonia Score: temperature ≥ 38°C or ≤ 36°C and white blood cell count ≤ 4,000 or ≥ 10,000/µL ¹⁹. Other patients with closely approximated above criteria and who were diagnosed as pneumonia by a physician were also included. All PPCs were classified as grade II or higher according to the Clavien–Dindo classification ²⁰.

Collection of clinical and confounding data

Demographic data (sex, age, height, weight, body mass index, smoking and alcohol status, comorbidities, blood test results, nutritional status, and pulmonary function), tumor-specific data (cancer histology, tumor location, clinical staging according to the Union for International Cancer Control 8th edition tumor–node–metastasis classification ²¹, and neoadjuvant therapy), operative details (surgical procedure, surgical time, blood loss volume, and reconstruction route), postoperative complications, and postoperative length of hospital stay were collated from the patient medical records.

Smoking status was assessed using the Brinkman index. Comorbidity status was assessed using the Charlson Comorbidity Index (CCI). Data on comorbidities including hypertension, diabetes mellitus, and chronic respiratory disease (chronic obstructive pulmonary disease, asthma, or interstitial lung disease) were collected. Hemoglobin, serum albumin and serum C-reactive protein levels were obtained from the hematological data. Malnutrition was assessed using the Global Leadership Initiative on Malnutrition (GLIM) criteria. Data on pulmonary function, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁), and forced expiratory volume % in one second (FEV₁/FVC), were collected and the percentage of the predicted value was calculated. Anastomotic leakage, recurrent laryngeal nerve palsy (RLNP), arrhythmia, and surgical site infection were designated as major postoperative complications of esophagectomy and designated as Clavien-Dindo grade ≥ 2. The exception was RLNP, which was recorded as grade 1 or higher.

Surgical procedure

Our standard surgical procedure consisted of right thoracoscopic (including robot-assisted surgery) esophagectomy with two-field or extended three-field lymphadenectomy, including the bilateral cervical, mediastinal, and abdominal lymph nodes. Standard reconstruction was performed with a gastric tube (or pedicled colon) through an open laparotomy via the retrosternal or posterior mediastinal route ^12,22. Almost all of the patients were extubated in the operating room and admitted to the intensive care unit. Intraoperative ventilation was performed with one-lung ventilation using bronchial blockers and is regulated by the anesthesiologist according to lung protection strategies. The tidal volume was set ≤ 6–8 mL/kg with reference to ideal body weight. Peak inspiratory pressure was set ≤ 30 cmH2O whenever possible to minimize driving pressure. A reasonable level of positive end-expiratory pressure of 5–10 cmH2O was used, also considering the surgical visualization. Mild hypercapnia (partial pressure of carbon dioxide < 60 torr) was accepted, and the fraction of inspired oxygen was set as low as possible to maintain oxygen saturation ≥ 95%. Lung recruiting maneuvers were not routinely performed but were used as needed to relieve hypoxemia. Patients were extubated in the operating room and admitted to the intensive care unit.

Perioperative rehabilitation program

All patients underwent a similar perioperative rehabilitation program ¹², which was conducted for 1–3 sessions before surgery and consisted of breathing exercises mainly for diaphragmatic breathing, sputum expectoration exercises (e.g., active cycle breathing technique), and orientation to postoperative rehabilitation, especially early mobilization. The postoperative rehabilitation program was initiated on the day after surgery and out-of-bed mobilization performed as early as possible. Positioning and sputum expectoration assistance were provided in the early postoperative period. Patients were typically discharged from the intensive care unit 5 days after surgery. Thereafter, aerobic exercise, such as with a bicycle ergometer, was commenced as soon as possible (approximately 7–10 days after surgery) and continued until hospital discharge.

Statistical analysis

All analyses were performed within a Bayesian framework with Markov chain Monte Carlo (MCMC) methods to calculate the posterior distributions of the outcomes. Posterior distributions were summarized using mean values as point estimates and percentile-based 95% credibility intervals (CrIs). We also extracted the probabilities of different effects from the posterior distributions. The MCMC estimation in each model was performed with 5,000 iterations, using the initial 2,500 iterations as a burn-in and four chains with random initial chain values. Convergence was confirmed visually using trace plots and the Gelman–Rubin convergence diagnostic (Rhat) < 1.1 for each variable. To accommodate missing data, a complete case analysis was planned if data were missing in less than 5% of all participants. If data were missing in more than 5% of all participants, multiple imputation methods were used.

First, we examined the longitudinal changes in the DTF using linear mixed models. The fixed effect included the measurement time point (preoperatively and 1 and 2 weeks postoperatively). The random effect consisted of the random intercept, allowing individual differences to be reflected at baseline. The prior distribution of the change in the DTF was assumed to be normal with mean of 0 and variance of 10000 as a weakly informative prior distribution.

Second, we examined the relationship between the DTF and PPCs using a logistic regression model. The dependent variable for the model was the PPC, and the independent variable DTF. We calculated the generalized propensity score for the degree of the DTF using a general linear model to estimate balancing weights. In this generalized propensity score model, a response variable was DTF and explanatory variables were the following characteristics that were selected as potential confounders for DTF and PPCs based on previous studies: age, smoking status (Brinkman index), comorbidity status (CCI), malnutrition (GLIM criteria), pulmonary function (FEV₁/FVC), advanced cancer stage (clinical stage ≥ II) and postoperative RLNP. Stabilized inverse probability weights calculated using the generalized propensity score were used for the balancing weights. The Spearman’s correlation coefficient was used to assess the balance after weighting for covariates; the correlation coefficient < 0.1 was considered well-balanced ²³. We conducted two logistic regression models, which were unweighted and weighted, to calculate the odds ratios (OR). The prior distribution of the coefficients of DTF was assumed to be normal with a mean of 0 and a variance of 100 as a weakly informative prior distribution.

Finally, a receiver operating characteristic (ROC) curve was plotted to validate the optimal cutoff of the DTF to predict PPCs. The prediction accuracy of PPCs was analyzed using the area under curve (AUC). The 95% confidence interval (CI) for the AUC were calculated with 2000 stratified bootstrap sampling. Additionally, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated using the standard formula. We selected the optimal cutoff values, based on the Youden’s index (sensitivity + specificity -1), and the threshold where the specificity was the highest in the range where the sensitivity (recall) > 80% for coverage.

All analyses were performed using R version 4.2.2 with the Tidyverse, the WeightIt, the brms, and the pROC packages.

Patient characteristics

Ninety-four patients underwent esophagectomy during the study period. Twenty-one patients were excluded owing to salvage esophagectomy (n = 5), open thoracic esophagectomy (n = 5), transhiatal esophagectomy (n = 6), diagnosis of hemiplegia owing to cerebrovascular disease (n = 2), not receiving preoperative rehabilitation (n = 2), and their decline to participate (n = 1). Consequently, 73 patients were included in this study (Fig. 2). There were no missing data in the baseline; we selected a complete case analysis.

Table 1 presents the patients preoperative characteristics. Overall, 80% of patients were men and > 80% had a history of smoking or alcohol consumption. Fourteen (19%) patients had a CCI of 2 or greater. Squamous cell carcinoma was the predominant histological type in 88% of patients. Approximately 70% of patients had advanced stage cancer and > 60% of patients received neoadjuvant therapy. Malnutrition was observed in 19 (26%) patients. Table 2 summarizes the intraoperative and postoperative variables. Sixty percent of patients underwent robot-assisted thoracoscopic esophagectomy. Major complications, such as anastomotic leakage and RLNP, occurred in 5 (7%) and 27 (37%) patients, respectively. PPCs occurred in 21 patients (29%), 10 (14%) of whom had pneumonia.

Table 1

Preoperative characteristics of patients with and without PPCs
		Overall	PPCs (+)	PPCs (−)
Variables		n = 73	n = 21	n = 52
Sex (male)	n	59 (81%)	20 (95%)	39 (75%)
Age	years	67 (8)	68 (8)	67 (8)
BMI	kg/m²	20.8 (2.8)	20.4 (3.3)	21.0 (2.5)
History of alcohol intake	n	65 (89%)	20 (95%)	45 (87%)
History of smoking	n	62 (85%)	20 (95%)	42 (81%)
Brinkman index		600 (300, 920)	900 (600, 1060)	470 (200, 803)
Comorbidity
Hypertension	n	38 (52%)	14 (67%)	24 (46%)
Diabetes mellitus	n	7 (10%)	4 (19%)	3 (6%)
Chronic respiratory disease	n	2 (3%)	1 (5%)	1 (2%)
Charlson comorbidity index		0 (0, 1)	1 (0, 2)	0 (0, 1)
≥ 2	n	14 (19%)	6 (29%)	8 (15%)
Cancer histology
Squamous cell carcinoma	n	64 (88%)	19 (90%)	45 (87%)
Adenocarcinoma	n	9 (12%)	2 (10%)	7 (13%)
Tumor location
Upper thoracic	n	8 (11%)	3 (14%)	5 (10%)
Middle thoracic	n	37 (51%)	10 (48%)	27 (52%)
Lower thoracic	n	17 (23%)	5 (24%)	12 (23%)
Gastric–esophagus	n	11 (15%)	3 (14%)	8 (15%)
Clinical stage
I	n	21 (29%)	8 (38%)	13 (25%)
II	n	13 (18%)	2 (10%)	11 (21%)
III	n	35 (48%)	10 (48%)	25 (48%)
IV	n	4 (5%)	1 (5%)	3 (6%)
Neoadjuvant therapy	n	46 (64%)	11 (52%)	35 (67%)
Chemotherapy	n	23 (32%)	3 (14%)	20 (38%)
Chemoradiation therapy	n	23 (32%)	8 (38%)	15 (29%)
Hemoglobin	g/dL	11.5 (1.4)	11.5 (1.6)	11.5 (1.3)
Albumin	mg/dL	3.7 (0.5)	3.6 (0.5)	3.8 (0.5)
CRP	mg/dL	0.07 (0.04, 0.23)	0.21 (0.05, 0.78)	0.05 (0.03, 0.10)
Malnutrition (GLIM criteria)	n	19 (26%)	8 (38%)	11 (21%)
FVC	%predicted	104.3 (16.3)	100.1 (13.2)	106.0 (17.2)
FEV₁	%predicted	99.3 (14.3)	92.5 (13.2)	102.1 (13.9)
FEV₁/FVC	%	76.7 (7.0)	75.0 (7.3)	77.3 (6.8)
DT_RE	mm	1.6 (0.3)	1.6 (0.3)	1.6 (0.3)
DT_EE	mm	1.5 (0.2)	1.5 (0.2)	1.5 (0.2)
DT_EI	mm	3.4 (0.7)	3.1 (0.6)	3.5 (0.6)
DTF	%	123.3 (32.1)	108.3 (20.9)	129.3 (34.0)
Statistics: n (%), mean (standard deviation), median (1st quartile, 3rd quartile) PPCs, postoperative pulmonary complications; BMI, body mass index; CRP, C-reactive protein; GLIM, Global Leadership Initiative on Malnutrition; FVC, forced vital capacity; FEV₁, forced expiratory volume in one second; FVC, forced vital capacity; DT_RE, diaphragm thickness at the rest; DT_EE, diaphragm thickness at end of maximal expiration; DT_EI, diaphragm thickness at end of maximal inspiration; DTF, diaphragm thickening fraction

Table 2

Intraoperative and postoperative variables of patients with and without PPCs
		Overall	PPCs (+)	PPCs (−)
Variables		n = 73	n = 21	n = 52
Surgical procedure
Robot-assisted thoracoscopic	n	44 (60%)	13 (62%)	31 (60%)
Thoracoscopic	n	29 (40%)	8 (38%)	21 (40%)
Lymphadenectomy
Two-field	n	20 (27%)	5 (24%)	15 (29%)
Three-field	n	53 (73%)	16 (76%)	37 (71%)
Reconstructive route
Retrosternal	n	55 (75%)	16 (76%)	39 (75%)
Posterior mediastinal	n	13 (18%)	3 (14%)	10 (19%)
Other	n	5 (7%)	2 (10%)	3 (6%)
Surgery time	min	670 (618, 740)	699 (664, 813)	663 (594, 736)
Blood loss	mL	311 (219, 451)	307 (237, 454)	333 (214, 447)
Postoperative complications
Anastomotic leakage	n	5 (7%)	1 (5%)	4 (8%)
RLNP	n	27 (37%)	12 (57%)	15 (29%)
Surgical site infection	n	5 (7%)	2 (10%)	3 (6%)
Arrhythmia	n	11 (15%)	6 (29%)	5 (10%)
Postoperative pulmonary complications	n	21 (29%)	-	-
ARDS	n	1 (1%)	1 (5%)	-
Pneumonia	n	10 (14%)	10 (48%)	-
Atelectasis/sputum expectoration difficulty	n	20 (26%)	19 (90%)	-
Postoperative length of hospital stays	days	23 (18, 32)	23 (18, 26)	29 (20, 51)
Statistics: n (%); median (1st quartile, 3rd quartile) PPCs, postoperative pulmonary complications, RLNP, recurrent laryngeal nerve palsy; ARDS, acute respiratory distress syndrome

Changes in the DTF

The mean preoperative DTF was 123.3% (standard deviation [SD]: 32.1%) (Table 1). The difference in the least squares means of the DTF between the preoperative and 1-week postoperative time points estimated by the linear mixed model was − 56.3% (95%CrI: −65.4, − 47.2), and the difference between the preoperative and 2-week postoperative time points was − 36.5% (95%CrI: −43.7, − 29.2). The posterior distribution of the model revealed > 99.9% probability of a 40% decrease in the DTF at 1 week postoperatively and an 91.4% probability of a 50% decrease. Moreover, there was > 99.9% probability of a 20% decrease in the DTF at 2 weeks postoperatively and 95.8% probability of a 30% decrease in the DTF at 2 weeks postoperatively (Figure S1). In all models, the values of Rhat for the independent variables were equal to 1.0, indicating convergence across the four chains. The trace plots for each model are shown in Figure S2.

Relationships between preoperative DTF and PPCs

The preoperative DTF in patients with PPCs was 108.3% (SD: 20.9%) compared to 129.3% (SD: 34.0%) in those without PPCs (Table 1). The mean OR of the preoperative DTF to PPCs was 0.75 per 10% increase (95%CrI: 0.59, 0.92) in the unweighted model (Table 3). The mean OR of preoperative DTF was 0.82 per 10% increase (95%CrI: 0.66, 0.97) in the weighted model. The Spearman’s correlation coefficients between the DTF and covariates after weighting were all 0.1 or less, indicating that the covariates were well balanced (Figure S3). In the posterior distribution of each model, the probability that the OR of the DTF per 10% increase would be < 1 was 99.9% and 98.7% in the unweighted and weighted models, respectively. Figure 3 depicts the density plots of the posterior distributions of the OR of DTF per 10% increase for each model. In both models, the values of Rhat for the independent variable were equal to 1.0, indicating convergence across the four chains. The trace plots for each model are shown in Figure S2.

Table 3

Summary of posterior distributions of coefficients and odds ratios of DTF estimated using logistic regression model with the MCMC method
	Coefficient				Odds ratio
	Mean	SD	2.5%	97.5%	Mean	SD	2.5%	97.5%
Model 1	-0.29	0.11	-0.52	-0.08	0.75	0.08	0.59	0.92
Model 2	-0.21	0.10	-0.42	-0.03	0.82	0.08	0.66	0.97
The dependent variable in all models is PPCs, and the independent variable is DTF with 10% as a unit. Model 1 is an unweighted model. Model 2 is a weighted model adjusted for potential confounders (age, smoking status, comorbidity status, malnutrition, pulmonary function, advanced cancer stage, and recurrent laryngeal nerve palsy). DTF, diaphragm thickening fraction; MCMC, Markov chain Monte Carlo; SD, standard deviation; PPCs, postoperative pulmonary complications

Optimal cutoff value of DTF to predict PPCs

Figure 4 depicts the ROC curves of DTF for predicting PPCs. The AUC for the ability of the DTF to predict the PPCs was 0.711 (95%CI: 0.584, 0.827). The cutoff value for DTF with the Youden’s index was 123.6% with a sensitivity of 81%, specificity of 54%, PPV of 41%, and NPV of 88%. Seventeen of the 41 patients (41%) with DTF < 123.6% developed PPCs.

We measured DTF preoperatively and postoperatively and investigated its changes and relationship with PPCs in patients with esophageal cancer undergoing esophagectomy. The DTF was lower at 1 week postoperatively than preoperatively and even lower at 2 weeks postoperatively. According to the logistic regression model, preoperative DTF was associated with PPCs in patients with esophageal cancer who underwent esophagectomy. This association remained evident even after adjusting for preoperative factors and RLNP. Furthermore, the optimal cutoff for the DTF for a coverage-based prediction of PPCs was 124%.

Several studies have evidenced diaphragmatic function impairment after thoracic surgery. Welvaart et al. performed muscle biopsies and demonstrated that the force-generating capacity of the diaphragm’s muscle fibers was reduced 2 h after thoracic surgery ¹⁶. Spadaro et al. reported a decrease in diaphragmatic excursion on ultrasonography in the early postoperative period after lung resection ¹⁴. Cardiac and abdominal surgeries have also validated diaphragmatic dysfunction assessed by DTFs and similarly reported a decrease in DTFs after surgery ^13,15. Thus, the ability to measure diaphragmatic function non-invasively using ultrasound imaging has led to reports of diaphragmatic dysfunction after various types of surgery. This study re-assessed DTF at 1 and 2 weeks postoperatively, making the follow-up longer than that in previous studies. At 1 week postoperatively, there was a greater than 90% probability that DTF would decrease by 40% or more compared to the preoperative levels in our cohort. Similarly, studies using maximal inspiratory pressure (MIP) as a measure of inspiratory muscle strength have reported a decrease in MIP at 1 week postoperatively after esophagectomy ^24,25; therefore, the current results support previous findings. Moreover, at 2 weeks postoperatively, there was a greater than 90% probability that the DTF would decrease by 20% or more compared to the preoperative value. The inspiratory muscles, primarily the diaphragm, must counteract decreased respiratory compliance for various reasons postoperatively. Thus, postoperative diaphragmatic dysfunction leads to poor lung re-expansion and airway clearance, which may be associated with pneumonia.

A novel finding of this study is that preoperative DTF is associated with PPCs such as atelectasis, sputum expectoration difficulty, and pneumonia after esophagectomy. As mentioned above, DTF decreases significantly postoperatively; hence, patients with low DTF preoperatively will have a lower DTF postoperatively. In other words, the demand exceeds the capacity of the diaphragm, and the risk of PPCs is deemed to be higher. Thus, preoperative assessment of diaphragmatic function can help identify patients who require more intensive preoperative and postoperative rehabilitation (e.g., more frequent physiotherapy) ^26–28. Furthermore, the results of this study suggest that improving diaphragmatic function preoperatively may contribute to preventing PPCs. A reasonable target value for DTF may be 123.6%. However, although several studies have reported the effects of preoperative inspiratory muscle training (IMT) in patients with esophageal cancer, the results were inconclusive ^24,25,29. One suggestion is that IMT may effectively prevent PPC in patients with reduced diaphragmatic function, warranting further validation.

Some limitations of this study must be acknowledged. First, it is a single-center study with a small sample size. Although its results are less generalizable than those of large-cohort multicenter studies, it is informative for patients undergoing esophagectomy. Second, our basic technique comprised thoracoscopic esophagectomy and gastric tube reconstruction via open laparotomy. These findings may not be applicable to open thoracotomy because PPCs are reportedly more common in this method than thoracoscopic esophagectomy ³⁰. However, it may be helpful in thoracoscopic-laparoscopic esophagectomy, since one study reported no difference in PPCs between open and laparoscopic procedures ³¹. Finally, there are study-wise and institution-wise differences in the definition of PPCs. Although pneumonia is difficult to define using only the Clavien–Dindo classification, this study used this classification in combination with other criteria to minimize differences in decision-making among physicians.

Diaphragmatic function assessed using DTF was decreased at 1 and 2 weeks after thoracoscopic esophagectomy in patients with esophageal cancer. Preoperative diaphragmatic function was associated with PPCs, and higher preoperative DTF with lower the odds of PPCs.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Funding statement

This study was supported by JSPS KAKENHI Grant Number JP21K21245.

Conflict of interest disclosure

The authors have no conflicts of interest to declare.

Ethics approval statement

This study was approved by the Institutional Review Board of Akita University Graduate School of Medicine (approval number: 2692) and conducted in accordance with the Declaration of Helsinki.

Patient consent statement

The objective and content of the study were explained to the participants orally, as well as in written documents. Written informed consent was obtained after the participants were informed that they could participate based on their own free will and that their privacy would be reasonably protected.

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Valkenet K, Trappenburg JCA, Ruurda JP et al (2018) Multicentre randomized clinical trial of inspiratory muscle training versus usual care before surgery for oesophageal cancer. Br J Surg 105:502–511
Tukanova KH, Chidambaram S, Guidozzi N et al (2022) Physiotherapy Regimens in Esophagectomy and Gastrectomy: a Systematic Review and Meta-Analysis. Ann Surg Oncol 29:3148–3167
Zhong J, Zhang S, Li C et al (2022) Active cycle of breathing technique may reduce pulmonary complications after esophagectomy: A randomized clinical trial. Thorac Cancer 13:76–83
Wang W, Liu Q, Yu Y et al (2020) Hand-assisted sputum excretion can effectively reduce postoperative pulmonary complications of esophageal cancer. Ann Palliat Med 9:3721–3730
van Adrichem EJ, Meulenbroek RL, Plukker JTM et al (2014) Comparison of two preoperative inspiratory muscle training programs to prevent pulmonary complications in patients undergoing esophagectomy: a randomized controlled pilot study. Ann Surg Oncol 21:2353–2360
Murakami K, Yoshida M, Uesato M et al (2021) Does thoracoscopic esophagectomy really reduce post-operative pneumonia in all cases? Esophagus 18:724–733
Takeuchi M, Endo H, Kawakubo H et al (2024) No difference in the incidence of postoperative pulmonary complications between abdominal laparoscopy and laparotomy for minimally invasive thoracoscopic esophagectomy: a retrospective cohort study using a nationwide Japanese database. Esophagus 21:11–21

The authors declare no competing interests.

240903Suppl.docx
Supplement materials

Association between preoperative diaphragm thickening fraction and postoperative pulmonary complications in patients undergoing thoracoscopic esophagectomy for esophageal cancer

Status:

Version 1

Abstract

Objective:

Methods:

Results:

Conclusion:

Figures

INTRODUCTION

MATERIAL and METHODS

Study design and ethics

Participants

Measurements

Ultrasound imaging of the diaphragm

Outcomes

Collection of clinical and confounding data

Surgical procedure

Perioperative rehabilitation program

Statistical analysis

RESULTS

Patient characteristics

Changes in the DTF

Relationships between preoperative DTF and PPCs

Optimal cutoff value of DTF to predict PPCs

DISCUSSION

CONCLUSION

Declarations

References

Additional Declarations

Supplementary Files

Status:

Version 1