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Changes in exercise capacity, muscle strength, and health-related quality of life in esophageal cancer patients undergoing esophagectomy

  • Takayuki Inoue1,
  • Satoru Ito1, 2Email author,
  • Masahiko Ando3,
  • Motoki Nagaya1,
  • Hiromichi Aso2,
  • Yota Mizuno1,
  • Keiko Hattori1,
  • Hiroki Nakajima1,
  • Yoshihiro Nishida1,
  • Yukiko Niwa4,
  • Yasuhiro Kodera4,
  • Masahiko Koike4 and
  • Yoshinori Hasegawa2
Contributed equally
BMC Sports Science, Medicine and RehabilitationBMC series – open, inclusive and trusted20168:34

DOI: 10.1186/s13102-016-0060-y

Received: 12 May 2016

Accepted: 25 October 2016

Published: 3 November 2016

Abstract

Background

Surgery for cancer of the thoracic esophagus is a challenging procedure associated with high morbidity and mortality. Perioperative rehabilitation has been introduced to promote early mobilization of the patients and to prevent postoperative pulmonary complications. The purpose of the present study was to characterize the preoperative functional exercise capacity, muscle strength, anxiety, depression, and health-related quality of life (QOL) in patients with esophageal cancer, and to evaluate the impact of radical esophagectomy on these parameters.

Methods

We performed a retrospective review of 34 consecutive patients with newly diagnosed resectable esophageal cancer who underwent esophagectomy followed by postoperative rehabilitation from January to December 2014. Patients were tested for 6-min walk distance (6MWD), knee-extensor muscle strength, hand grip strength, the Hospital Anxiety and Depression Scale (HADS), and the chronic obstructive pulmonary disease (COPD) assessment test (CAT) before and two weeks after the surgery. Before surgery, the pulmonary function test, and components of the MOS 36-item Short-Form Health Survey (SF-36) Questionnaire for general health were assessed.

Results

The mean age was 67.3 ± 8.1 years. The patients were predominantly male (76.4 %), had high rates of smoking history (91.2 %), and squamous cell carcinoma (97.1 %). The predicted value for forced expiratory volume in 1 s was 94.0 ± 15.9 %, and 12 patients (35.3 %) had COPD. The clinical stage was 0-I in 12 patients, II in 4 patients, III in 16 patients, and IV in 2 patients. Thirty-one patients (91.2 %) underwent open surgery. At the baseline, components of the SF-36 scores significantly correlated with CAT and HADS scores, and the physical status was significantly poorer in patients with COPD than those without. Comparisons between the preoperative and postoperative values revealed significant decreases in 6MWD, hand grip strength, isometric knee extensor muscle strength, and a significant increase in CAT scores but not in HADS scores after surgery. In multiple regression analysis, decreases in 6MWD after the surgery significantly correlated with the preoperative physical component summary of SF-36.

Conclusions

Our results indicate that surgery remained detrimental to health outcomes at two weeks. Further research should investigate whether prehabilitation would improve the postoperative outcomes, QOL, and physical fitness.

Keywords

Esophagectomy COPD assessment test Health-related quality of life Pulmonary rehabilitation Six-minute walk test

Background

Esophagectomy is the standard therapy for patients with localized esophageal cancer, but it is a highly invasive procedure and associated with serious postoperative complications such as pulmonary complications, anastomotic leaks, and sepsis [1]. Major pulmonary complications after esophagectomy have been implicated in prolonged hospital stays and postoperative mortality [2, 3]. The preoperative health status is important because advanced age, preoperative chemoradiotherapy, and comorbidity of chronic obstructive pulmonary disease (COPD) are associated with the increased risk of postoperative complications and mortality [4, 5]. Moreover, it has been reported that a lack of preoperative physical activity and the loss of maximum oxygen uptake are risk factors for pulmonary or cardiopulmonary complications [68].

Perioperative rehabilitation has been expected to improve physical fitness, promote early mobilization, and reduce postoperative pulmonary complications in patients with esophageal cancer [9, 10]. In order to manage the rehabilitation program, it is important to adequately assess the status of functional exercise capacity and health-related quality of life (QOL) before surgery. Moreover, esophagectomy itself worsens health-related QOL and physical fitness [1113]. A prospective study by Reynolds et al. demonstrated that esophageal resection had a negative impact on health-related QOL as assessed by the 30-item European Organization for the Research and Treatment of Cancer (EORTC) QOL Core Questionnaires (QLQ) (EORTC QLQ-C30) [14] and esophageal cancer-specific EORTC QLQ (EORTC QLQ-OES24) [15] 3 months after surgery [12]. Moreover, Teoh et al. reported that esophagectomy was associated with worsened physical functioning and fatigue symptoms as assessed by EORTC QLQ-C30 and QLQ-OES24 up to 6 months after treatment [11]. Tatematsu et al. reported that 6MWD and knee-extensor muscle strength were significantly decreased approximately 3 weeks after esophagectomy [13]. However, the pre- and postoperative physical fitness, health-related QOL, psychological aspects, and their relationships have not been fully evaluated in patients with esophageal cancer who have undergone esophagectomy.

The purpose of the present study was to characterize the preoperative functional exercise capacity, muscle strength, anxiety, depression, and health-related QOL in patients with esophageal cancer, and to evaluate the impact of radical esophagectomy on these parameters 2 weeks after the surgery.

Methods

Patients

Records of 43 consecutive patients with esophageal cancer who underwent scheduled radical esophagectomy in the Department of Gastroenterological Surgery II, Nagoya University Hospital from January to December 2014 were retrospectively reviewed. Patients who underwent emergency surgery were not included. At our institution, perioperative pulmonary rehabilitation is routinely performed on patients who underwent esophagectomy. In addition, physical, mental, and QOL status are routinely assessed before and after surgery as the perioperative rehabilitation program according to previous reports and guidelines [2, 10, 13, 1619]. Patients are allowed to refuse the assessment if they do not wish. A flow chart describing the inclusion process is shown in Fig. 1. Thirty-four patients who underwent pre- and postoperative physical assessment were evaluated. Nine patients were excluded because they were discharged within 14 days after surgery (n = 3), were unable to walk without assistance due to invasive pharyngolaryngectomy (n = 2), were postoperatively admitted to the Intensive Care Unit (n = 2), and had atrial fibrillation (n = 1), and physiological status was evaluated 3 weeks after surgery (n = 1). The tumors were staged according to the seventh edition of the Union for International Cancer Control TNM staging system, and the tumor grades were classified according to the WHO classification of histological differentiation. The severity of postoperative complications was classified using the Clavien-Dindo classification [20]. Information about patients was collected through a review of electronic medical records.
Fig. 1

Flow of participants

Pulmonary function tests

Preoperative pulmonary functions were routinely measured using computerized equipment (Fudak77, Fukuda Sangyo, Tokyo, Japan) at the clinical laboratory within 30 days before the operation. As spirometric parameters, vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1) were measured. COPD was defined as an FEV1/FVC ratio <70 % without any other respiratory diseases. The predicted values for spirometry and lung volumes were calculated according to the method of the Japanese Respiratory Society [21].

Measurements of physical fitness

The 6-min walk distance (6MWD) was measured by the 6-min walk test (6MWT) according to guidelines of the American Thoracic Society [22]. During the 6MWT, oxygen saturation of a peripheral artery (SpO2) was measured using a pulse oximeter (Pulsox-Me300; Teijin Pharma Co., Tokyo, Japan) without supplemental oxygen. Desaturation was defined as a fall in SpO2 ≥ 4 % or SpO2 < 90 % during the 6MWT [23]. Isometric knee extensor muscle strength was assessed using a hand-held dynamometer (Mutus F-100; Anima Co., Tokyo, Japan). Hand grip strength was measured using a digital dynamometer (Grip-D, Takei Co., Niigata, Japan).

Assessment of anxiety, depression, and health-related QOL

Anxiety and depression were measured using the validated Japanese version of the Hospital Anxiety and Depression Scale (HADS) [24]. The scores range from 0 to 21 for each subscale, with a score ≥8 denoting a probable case. A higher score represents a higher level of anxiety or depression. Health-related QOL was assessed by the validated Japanese version of the MOS 36-item Short-Form Health Survey (SF-36) version 2, which has eight subscales and three component summary scores: a physical component summary (PCS), mental component summary (MCS), and role/social component summary (RCS) [25]. A higher SF-36 score represents a better health-related QOL. Respiratory health-related QOL was assessed by a validated Japanese version of the COPD assessment test (CAT), an eight-item questionnaire including cough, phlegm, chest tightness, breathlessness, activity limitation, confidence to leave home, sleep, and energy [26]. A higher CAT score represents a poorer respiratory health-related QOL.

Rehabilitation program

Pre- and postoperative rehabilitation was performed by specialized physical therapists (T.I., M.N, Y.M., K.H., and H.N.). The preoperative pulmonary rehabilitation protocol included (1) measurements of 6MWD, knee extensor muscle strength, and hand grip strength, (2) assessment of HADS, SF-36, and CAT, and (3) orientation to the postoperative rehabilitation program and encouragement of early mobilization. Preoperative measurements were assessed 1 to 10 days before the surgery. All patients performed the postoperative pulmonary rehabilitation, which consisted of positioning, stretching of respiratory muscles and thoracic cage, deep diaphragmatic breathing, coughing and huffing, and early mobilization from the first postoperative day. When possible, 6MWD, muscle strength, HADS, and CAT were re-evaluated 14 days after the operation.

Statistical analysis

Data were expressed as means ± SD or median (range). The paired t-test or Fisher’s exact test was used to evaluate statistical significance. When data failed a normality test, the Mann-Whitney U test was performed. Correlations between variables were analyzed using Spearman’s rank correlation coefficient. Regression analysis was used for univariate analysis and multiple regression analysis (forced entry method) was used for multivariate analysis. All analyses were conducted using SPSS ver. 19 (SPSS Inc., Tokyo, Japan). P < 0.05 was considered statistically significant.

Results

Clinical characteristics

The characteristics and results of preoperative pulmonary function and laboratory tests of the 34 patients are shown in Table 1. The patients were predominantly male (76.4 %), had a high rate of smoking history (91.2 %), and squamous cell carcinoma (97.1 %). COPD was present in 12 patients (35.3 %). The preoperative clinical stage was 0-I in 12 patients, II in 4 patients, III in 16 patients, and IV in 2 patients. Twenty-two patients (64.7 %) received some sort of induction therapy (chemotherapy or chemoradiotherapy). Thirty-one patients (91.2 %) underwent open surgery. Three (8.8 %) patients experienced postoperative pulmonary complications. Two patients developed pneumonia (Clavien-Dindo Grade II) and one patient pneumothorax (Grade I). There was no in-hospital death or reoperation after esophagectomy.
Table 1

Clinical characteristics of 34 subjects

Variable

 

Sex, male/female

N = 26/8

Age, years (range)

67.3 ± 8.1 (50–84)

Height, cm

163.2 ± 7.9

Weight, kg

54.9 ± 7.6

Body mass index

20.6 ± 2.2

Smoking history

N = 31

Squamous cell carcinoma/adenocarcinoma

N = 33/1

Clinical stage, 0-I/II/III/IV

N = 12/4/16/2

Lymphadenectomy, 1/2/3 fields

N = 1/24/9

Preoperative adjuvant therapy

N = 22

COPD

N = 12

%VC

101.5 ± 14.1

%FEV1

94.0 ± 15.9

FEV1/FVC, %

73.0 ± 7.9

Open surgery/video-assisted thoracic surgery

N = 31/3

Operation time, min

520 ± 90

Blood loss during surgery, ml

719 ± 456

Intensive Care Unit stay, days

1.3 ± 0.6

Timing of extubation, 0/1/2 postoperative days

N = 23/9/2

Hospital stay after surgery, days

21.2 ± 15.0

Walking with support, postoperative days

1.9 ± 1.8

Values are numbers (N) or mean ± SD. Total numbers of subjects are 34. COPD chronic obstructive pulmonary disease, VC vital capacity, FEV 1 forced expiratory volume in one second, FVC forced vital capacity

Correlations between preoperative parameters

Correlations between various parameters before the surgery are shown in Table 2. The preoperative 6MWD significantly correlated with hand grip strength (right: r = 0.562, P = 0.001, left: r = 0.511, P = 0.002), isometric knee extensor muscle strength (right: r = 0.482, P = 0.006, left: r = 0.535, P = 0.002), and SF-36 components, physical functioning (r = 0.454, P = 0.013), general health (r = 0.465, P = 0.011), mental health (r = 0.382, P = 0.045), and MCS (r = 0.497, P = 0.010). CAT scores showed significant inverse correlation with hand grip strength (right: r = -0.490, P = 0.005, left: r = -0.406, P = 0.002) and isometric knee extensor muscle strength (right: r = -0.491, P = 0.008, left: r = -0.565, P = 0.002). Correlations between QOL parameters or 6MWD and pulmonary functions before surgery are shown in Table 3. Correlations between SF-36 scores and CAT or HADS before surgery are shown in Table 4. Total CAT scores showed significant inverse correlation with most SF-36 components: physical functioning (r = -0.384, P = 0.040), general health (r = -0.432, P = 0.019), social functioning (r = -0.658, P < 0.001), vitality (r = -0.503, P = 0.005), role emotional (r = -0.381, P = 0.041), mental health (r = -0.510, P = 0.006), MCS (r = -0.584, P = 0.002), and RCS (r = -0.433, P = 0.027). HADS anxiety and depression significantly correlated with most SF-36 components. In contrast, HADS anxiety and depression did not significantly correlate with CAT scores.
Table 2

Correlation between preoperative parameters

Parameters

 

6MWD

Hand grip strength

Isometric knee extensor muscle strength

Right

Left

Right

Left

6MWD

r

1

0.562

0.511

0.482

0.535

P value

0

0.001 (n = 34)

0.002 (n = 34)

0.006 (n = 31)

0.002 (n = 31)

CAT scores

r

−0.332

−0.490

−0.406

−0.491

−0.565

P value

0.068 (n = 31)

0.005 (n = 31)

0.024 (n = 31)

0.008 (n = 28)

0.002 (n = 28)

SF-36 component

 Physical functioning

r

0.454

0.137

0.258

0.350

0.365

P value

0.013 (n = 29)

0.478 (n = 29)

0.177 (n = 29)

0.080 (n = 26)

0.067 (n = 26)

 Role physical

r

0.334

0.413

0.490

0.589

0.473

P value

0.076 (n = 29)

0.026 (n = 29)

0.007 (n = 29)

0.002 (n = 26)

0.015 (n = 26)

 Bodily pain

r

0.126

0.123

0.166

0.172

0.125

P value

0.516 (n = 29)

0.525 (n = 29)

0.389 (n = 29)

0.401 (n = 26)

0.542 (n = 26)

 General health

r

0.465

0.382

0.367

0.478

0.376

P value

0.011 (n = 29)

0.041 (n = 29)

0.050 (n = 29)

0.014 (n = 26)

0.058 (n = 26)

 Social functioning

r

0.334

0.221

0.221

0.370

0.306

P value

0.077 (n = 29)

0.249 (n = 29)

0.248 (n = 29)

0.063 (n = 26)

0.128 (n = 26)

 Vitality

r

0.287

0.356

0.398

0.433

0.283

P value

0.131 (n = 29)

0.058 (n = 29)

0.034 (n = 29)

0.027 (n = 26)

0.161 (n = 26)

 Role emotional

r

0.243

0.197

0.317

0.515

0.385

P value

0.204 (n = 29)

0.305 (n = 29)

0.093 (n = 29)

0.007 (n = 26)

0.052 (n = 26)

 Mental health

r

0.382

0.124

0.317

0.355

0.310

P value

0.045 (n = 28)

0.529 (n = 28)

0.093 (n = 28)

0.081 (n = 25)

0.131 (n = 25)

 PCS

r

0.159

0.345

0.346

0.284

0.228

P value

0.436 (n = 26)

0.084 (n = 26)

0.083 (n = 26)

0.189 (n = 23)

0.296 (n = 23)

 MCS

r

0.497

0.220

0.180

0.354

0.349

P value

0.010 (n = 26)

0.281 (n = 26)

0.379 (n = 26)

0.097 (n = 23)

0.103 (n = 23)

 RCS

r

0.292

0.225

0.345

0.587

0.435

P value

0.148 (n = 26)

0.269 (n = 26)

0.084 (n = 26)

0.003 (n = 23)

0.038 (n = 23)

Spearman’s rank correlation coefficient was used for the analysis. 6MWD 6-min walk distance, CAT COPD assessment test, SF-36 the MOS 36-item Short-Form Health Survey Questionnaire, PCS physical component summary, MCS mental component summary, RCS, role/social component summary

Table 3

Correlation between preoperative parameters and pulmonary functions

Parameters

 

VC

%VC

FEV1

%FEV1

FEV1/FVC

6MWD (n = 34)

r

0.502

0.098

0.579

0.015

0.291

P value

0.002

0.581

<0.001

0.934

0.095

CAT scores (n = 31)

r

− 0.418

− 0.334

− 0.415

− 0.269

− 0.265

P value

0.019

0.066

0.020

0.143

0.149

SF-36 component

 Physical functioning (n = 29)

r

0.367

0.310

0.423

0.184

0.184

P value

0.050

0.102

0.022

0.339

0.340

 Role physical (n = 29)

r

0.403

0.009

0.197

− 0.315

− 0.236

P value

0.030

0.964

0.305

0.096

0.218

 Bodily pain (n = 29)

r

− 0.001

− 0.050

− 0.027

− 0.246

− 0.220

P value

0.997

0.798

0.891

0.199

0.251

 General health (n = 29)

r

0.174

− 0.079

0.142

− 0.223

− 0.070

P value

0.367

0.684

0.462

0.244

0.717

 Social functioning (n = 29)

r

0.177

0.275

0.210

0.180

0.106

P value

0.358

0.149

0.275

0.350

0.585

 Vitality (n = 29)

r

0.329

0.112

0.255

− 0.122

− 0.099

P value

0.081

0.562

0.182

0.527

0.611

 Role emotional (n = 29)

r

0.268

0.007

0.150

− 0.186

− 0.197

P value

0.160

0.973

0.437

0.335

0.307

 Mental health (n = 28)

r

0.334

0.310

0.368

0.245

0.212

P value

0.082

0.108

0.054

0.208

0.279

 PCS (n = 26)

r

0.095

− 0.136

0.022

− 0.426

− 0.276

P value

0.645

0.508

0.916

0.030

0.173

 MCS (n = 28)

r

0.217

0.284

0.291

0.200

0.157

P value

0.286

0.159

0.149

0.327

0.443

 RCS (n = 26)

r

0.435

0.075

0.290

− 0.165

− 0.121

P value

0.026

0.717

0.150

0.420

0.556

Spearman’s rank correlation coefficient was used for the analysis. VC vital capacity, %VC % of the predicted value for VC, FEV 1 forced expiratory volume in 1 s, %FEV 1 % of the predicted value for FEV1, FVC forced vital capacity

Table 4

Correlation between SF-36 and CAT or HADS before surgery

SF-36 component

 

CAT

HADS anxiety

HADS depression

Physical functioning

r

−0.384

−0.339

−0.500

P value

0.040

0.072

0.006

Role physical

r

−0.323

−0.745

−0.557

P value

0.088

<0.001

0.002

Bodily pain

r

−0.167

−0.368

−0.252

P value

0.385

0.049

0.187

General health

r

−0.432

−0.543

−0.321

P value

0.019

0.002

0.090

Social functioning

r

−0.658

−0.464

−0.403

P value

<0.001

0.011

0.030

Vitality

r

−0.503

−0.448

−0.554

P value

0.005

0.015

0.002

Role emotional

r

−0.381

−0.593

−0.470

P value

0.041

0.001

0.010

Mental health (n = 28)

r

−0.510

−0.379

−0.563

P value

0.006

0.047

0.002

PCS (n = 26)

r

−0.245

−0.364

−0.266

P value

0.228

0.067

0.188

MCS (n = 26)

r

−0.584

−0.361

−0.317

P value

0.002

0.070

0.115

RCS (n = 26)

r

−0.433

−0.653

−0.648

P value

0.027

<0.001

<0.001

Spearman’s rank correlation coefficient was used for the analysis. N = 29, otherwise indicated. HADS the Hospital Anxiety and Depression Scale

Correlations between postoperative parameters

Correlations between various parameters after the surgery are shown in Table 5. The postoperative 6MWD significantly correlated with postoperative left isometric knee muscle extensor strength (r = 0.526, P = 0.003).
Table 5

Correlation between postoperative parameters

Parameters

 

6MWD

Hand grip strength

Isometric knee extensor muscle strength

Right

Left

Right

Left

6MWD

r

1

0.159

0.071

0.325

0.526

P value

0

0.394 (n = 31)

0.704 (n = 31)

0.085 (n = 29)

0.003* (n = 29)

CAT scores

r

−0.053

−0.020

0.014

−0.421

−0.383

P value

0.816 (n = 22)

0.927 (n = 23)

0.948 (n = 23)

0.058 (n = 21)

0.086 (n = 21)

Spearman’s rank correlation coefficient was used for the analysis. *P < 0.05

Comparison between pre- and postoperative measurements

Next, the effects of esophagectomy on physical and psychological status were examined. Comparisons and changes of 6MWD, desaturation during the 6MWT, muscle strength, HADS, and CAT before and after surgery are shown in Table 6. The post-operative 6MWD (409 ± 108 m) was significantly shorter than the pre-operative value (496 ± 76 m, P < 0.001). Muscle strength results showed that both right and left hand grip strengths were significantly decreased after the operation (P = 0.01). Left side isometric knee extensor muscle strength was significantly decreased after the operation (P = 0.02). That of the right side was also decreased after the operation, but the difference was not statistically significant level (P = 0.08). The number of patients whose HADS anxiety score was ≥8 increased from 4 to 8 after surgery, although the difference did not reach a statistically significant level by Fisher’s exact test (P = 0.31). CAT scores significantly increased after surgery (P = 0.02).
Table 6

Comparison of 6MWD, muscle strength, and HADS before and after surgery

 

Before

After surgery

P value

Changes

6MWD, m (n = 32)

494 ± 76

409 ± 108

0.001 > *

−85 ± 88

Desaturation during 6MWTa

N = 5

N = 5

1

 

Hand grip strength, kgf (n = 33)

 Right

30.6 ± 9.1

28.7 ± 8.6

0.01*

−1.9 ± 3.9

 Left

28.8 ± 8.6

27.5 ± 7.7

0.01*

−1.3 ± 2.8

Isometric knee extensor muscle strength, kgf (n = 31)

 Right

26.0 ± 8.5

24.7 ± 8.2

0.08

−1.3 ± 3.8

 Left

25.2 ± 9.4

22.9 ± 7.8

0.02*

−2.3 ± 4.9

 HADS anxiety (n = 23)

5.4 ± 2.9

5.1 ± 4.0

0.76

−0.3 ± 4.0

  Scores ≥ 8

N = 4

N = 8

0.31

 

 HADS depression (n = 23)

5.7 ± 3.7

5.4 ± 3.8

0.54

−0.3 ± 2.3

  Scores ≥ 8

N = 6

N = 7

1

 

 CAT (n = 24)

10.4 ± 5.6

15.9 ± 7.3

0.02*

5.5 ± 7.5

Values are mean ± SD and compared by paired t-test or Fisher’s exact test. aDesaturation was defined as a fall in SpO2 ≥ 4 % or SpO2 < 90 % during the 6MWT. *P <0.05

Two different surgical techniques, open surgery for 31 patients and video-assisted thoracic (closed) surgery for three patients, were performed (Table 1). Demographics and data of pre- and postoperative measurements of three patients who underwent video-assisted thoracic surgery are shown in Additional file 1: Table S1. The mean values of postoperative 6MWD and changes of 6MWD after the surgery were 364 m and −60 m. The mean changes of right and left hand grip strengths and right isometric knee extensor muscle strength were −3.8 kgf, −2.5 kgf, and −2.3 kgf, respectively. Left isometric knee extensor muscle strength was increased in two patients, and the mean changes were 1.0 kgf.

Effects of COPD and preoperative chemoradiotherapy

The effects of comorbidity of COPD on physical and QOL parameters were examined. The parameters of patients with and without COPD are compared in Table 7. Preoperative %FEV1 (P < 0.001), FEV1/FVC (P < 0.001), postoperative 6MWD (P = 0.034), and preoperative left isometric knee extensor muscle strength (P = 0.018) were significantly lower in patients with COPD than those without COPD. There was no significant difference in preoperative SF-36 components between the groups.
Table 7

Comparison of data with and without COPD

 

Non-COPD (n = 22)

COPD (n = 12)

P value

Pre %FEV1

101.3 ± 12.7

75.2 ± 21.1

<0.001*

Pre FEV1/FVC, %

77.3 ± 5.7

60.5 ± 16.3

<0.001*

Pre 6MWD, m

509 ± 80

466 ± 60

0.127

Desaturation during 6MWTa

N = 3

N = 2

0.580

Post 6MWD, m

438 ± 100 (n = 21)

351 ± 105 (n = 11)

0.034*

Desaturation during 6MWTa

N = 2

N = 3

0.290

Changes in 6MWD, m

−70 ± 83 (n = 21)

−114 ± 98 (n = 11)

0.123

Pre hand grip strength, kgf

 Right

32.4 ± 8.4

28.4 ± 10.5

0.204

 Left

30.7 ± 8.8

27.0 ± 9.4

0.204

Post hand grip strength, kgf

 Right

29.6 ± 7.9 (n = 21)

26.6 ± 9.7

0.152

 Left

28.7 ± 7.3 (n = 21)

25.8 ± 8.0

0.242

Pre isometric knee extensor muscle strength, kgf

 Right

26.7 ± 8.2 (n = 20)

24.7 ± 9.4 (n = 11)

0.502

 Left

27.6 ± 8.9 (n = 20)

20.1 ± 9.1 (n = 11)

0.018*

Post isometric knee extensor muscle strength, kgf

 Right

25.8 ± 8.3 (n = 20)

22.8 ± 8.0 (n = 11)

0.183

 Left

24.9 ± 7.7 (n = 20)

19.3 ± 6.9 (n = 11)

0.020*

 Pre HADS anxiety

6.1 ± 2.8 (n = 21)

4.5 ± 3.2 (n = 10)

0.135

  Scores ≥ 8

N = 5

N = 2

1

 Pre HADS depression

5.6 ± 3.2 (n = 21)

5.5 ± 4.1 (n = 10)

0.852

  Scores ≥ 8

N = 5

N = 4

0.781

 Post HADS anxiety

4.8 ± 3.3 (n = 15)

5.6 ± 5.4 (n = 8)

0.925

  Scores ≥ 8

N = 4

N = 4

0.676

 Post HADS depression

5.7 ± 3.8 (n = 15)

4.9 ± 4.1 (n = 8)

0.681

  Scores ≥ 8

N = 5

N = 2

1

 Pre CAT (n = 31)

8.1 ± 5.5 (n = 21)

14.2 ± 5.5 (n = 10)

0.008*

 Post CAT (n = 24)

14.1 ± 5.3 (n = 16)

19.6 ± 9.6 (n = 8)

0.136

Pre SF-36 component

 Physical functioning

49.5 ± 15.1 (n = 19)

40.9 ± 15.5 (n = 10)

0.308

 Role physical

37.6 ± 19.3 (n = 19)

38.1 ± 21.6 (n = 10)

0.456

 Bodily pain

44.8 ± 12.9 (n = 19)

41.4 ± 24.5 (n = 10)

0.804

 General health

45.3 ± 9.5 (n = 19)

45.4 ± 11.4 (n = 10)

0.946

 Vitality

43.2 ± 17.6 (n = 19)

39.0 ± 18.4 (n = 10)

0.804

 Social functioning

49.0 ± 11.2 (n = 19)

38.8 ± 17.3 (n = 10)

0.069

 Role emotional

41.3 ± 18.2 (n = 19)

40.7 ± 17.0 (n = 10)

0.604

 Mental health

49.3 ± 14.3 (n = 19)

38.4 ± 12.7 (n = 9)

0.061

 PCS

46.7 ± 5.8 (n = 19)

52.5 ± 9.7 (n = 7)

0.209

 MCS

51.2 ± 10.1 (n = 19)

45.5 ± 9.6 (n = 7)

0.073

 RCS

38.1 ± 12.4 (n = 19)

36.3 ± 23.3 (n = 7)

0.955

Values are mean ± SD and compared by paired t-test, Mann-Whitney U test or Fisher’s exact test. *P < 0.05. aDesaturation was defined as a fall in SpO2 ≥ 4 % or SpO2 < 90 %. The HADS score ≥8 denotes a probable case. Pre preoperative, Post postoperative

We also compared the results of physical and QOL parameters of patients with and without preoperative chemotherapy or radiotherapy (Table 8). Among preoperative SF-36 components, role emotional and PCS scores of patients undergoing chemoradiotherapy were significantly lower than those without (P = 0.019). There was no significant difference in other parameters between the groups.
Table 8

Comparison of data with and without chemoradiotherapy

 

Without (n = 12)

Chemotherapy and/or radiotherapy (n = 22)

P value

%FEV1

93.3 ± 20.4

94.5 ± 13.9

0.466

FEV1/FVC, %

69.8 ± 7.7

74.8 ± 7.8

0.136

Pre 6MWD, m

485 ± 59

499 ± 82

0.790

Desaturation during 6MWTa

N = 4

N = 1

1

Post 6MWD, m

389 ± 109

421 ± 109 (n = 20)

0.654

Desaturation during 6MWTa

N = 0

N = 5

0.155

Changes in 6MWD, m

−97 ± 61

−78 ± 104 (n = 20)

0.158

Pre hand grip strength, kgf

 Right

33.0 ± 12.0

29.9 ± 7.4

0.327

 Left

31.8 ± 11.0

28.1 ± 7.8

0.261

Post hand grip strength, kgf

 Right

30.8 ± 11.3 (n = 11)

27.7 ± 7.0

0.560

 Left

28.4 ± 8.9 (n = 11)

27.1 ± 7.2

0.693

Pre isometric knee extensor muscle strength, kgf

 Right

30.0 ± 9.4

23.4 ± 7.0 (n = 20)

0.059

 Left

28.8 ± 11.6

23.0 ± 7.2 (n = 20)

0.269

Post isometric knee extensor muscle strength, kgf

 Right

28.3 ± 9.0

22.5 ± 7.0 (n = 20)

0.120

 Left

25.4 ± 8.8

21.3 ± 6.8 (n = 20)

0.287

 Pre HADS anxiety

4.9 ± 3.5

6.0 ± 2.6 (n = 19)

0.367

  Scores ≥8

N = 3

N = 4

1

 Pre HADS depression

4.5 ± 2.9

6.2 ± 3.7 (n = 19)

0.287

  Scores ≥8

N = 3

N = 5

1

 Post HADS anxiety

5.3 ± 4.8 (n = 7)

5.0 ± 3.8 (n = 16)

1

  Scores ≥8

N = 2

N = 6

1

 Post HADS depression

3.3 ± 2.6 (n = 7)

6.3 ± 4.0 (n = 16)

0.103

  Scores ≥8

N = 2

N = 9

0.682

 Pre CAT (n = 31)

9.3 ± 6.4

10.6 ± 6.1 (n = 19)

0.509

 Post CAT (n = 24)

13.7 ± 8.6 (n = 6)

16.7 ± 6.9 (n = 18)

0.343

Pre SF-36 component

 Physical functioning

51.7 ± 20.1 (n = 11)

43.4 ± 11.6 (n = 18)

0.146

 Role physical

46.2 ± 25.3 (n = 11)

32.6 ± 13.8 (n = 18)

0.084

 Bodily pain

38.7 ± 21.0 (n = 11)

46.7 ± 14.6 (n = 18)

0.387

 General health

49.2 ± 7.9 (n = 11)

42.9 ± 10.6 (n = 18)

0.055

 Vitality

48.1 ± 19.0 (n = 11)

37.9 ± 16.1 (n = 18)

0.188

 Social functioning

45.0 ± 18.1 (n = 11)

45.7 ± 11.7 (n = 18)

0.580

 Role emotional

50.2 ± 19.7 (n = 11)

35.5 ± 13.7 (n = 18)

0.049*

 Mental health

47.1 ± 17.4 (n = 10)

45.1 ± 13.2 (n = 18)

1.000

 PCS

53.2 ± 6.6 (n = 8)

46.0 ± 6.6 (n = 18)

0.019*

 MCS

48.9 ± 8.5 (n = 8)

50.0 ± 10.8 (n = 18)

0.807

 RCS

44.3 ± 11.3 (n = 8)

32.5 ± 16.0 (n = 18)

0.090

Values are mean ± SD and compared by paired t-test, Mann-Whitney U test or Fisher’s exact test. aDesaturation was defined as a fall in SpO2 ≥ 4 % or SpO2 < 90 %

Factors affecting postoperative 6MWD

Next, we aimed to identify pre- and intraoperative factors affecting the postoperative loss of exercise capacity. Changes in 6MWD before and after surgery were chosen because the 6MWT is a validated method to assess functional exercise capacity and efficacy of pulmonary rehabilitation [27]. Results of the univariate regression analysis showed that the preoperative PCS, a component of SF-36, significantly correlated with decrease of 6MWD (r = 0.437, P = 0.033) (Table 9). On the other hand, preoperative 6MWD, pulmonary functions, muscle strength, COPD comorbidity, chemoradiotherapy, blood loss during surgery, and operation time did not predict changes in 6MWD (Table 9). Multiple regression analysis including all relevant variables with P values <0.10 in univariate analysis showed that only PCS significantly correlated with changes in 6MWD (r = 0.488, P = 0.027) (Table 9). There was a trend toward a greater risk of loss of 6MWD as preoperative %VC decreased (P = 0.077).
Table 9

Correlations between changes in 6MWD after esophagectomy and other parameters

Parameters

Univariate analysis

Multivariate analysis

Standardized partial regression coefficient

P value

Standardized partial regression coefficient

P value

Preoperative parameters

 Body mass index

−0.056

0.760

ND

ND

 %VC

−0.327

0.068

−0.573 (n = 23)

0.077

 %FEV1

−0.302

0.093

0.369 (n = 23)

0.273

 6MWD

0.153

0.403

ND

ND

Hand grip strength

 Right

0.273

0.130

ND

ND

 Left

0.254

0.162

ND

ND

Isometric knee extensor muscle strength

 Right (n = 29)

0.028

0.885

ND

ND

 Left (n = 29)

−0.101

0.601

ND

ND

 CAT (n = 29)

0.220

0.251

ND

ND

SF-36 component

 Physical functioning (n = 27)

−0.186

0.353

ND

ND

 Role physical (n = 27)

−0.008

0.968

ND

ND

 Bodily pain (n = 27)

0.283

0.153

ND

ND

 General health (n = 27)

0.049

0.809

ND

ND

 Social functioning (n = 27)

−0.217

0.276

ND

ND

 Vitality (n = 27)

0.210

0.293

ND

ND

 Role emotional (n = 27)

0.028

0.891

ND

ND

 Mental health (n = 26)

−0.145

0.480

ND

ND

 PCS (n = 24)

0.437

0.033*

0.488 (n = 23)

0.027*

 MCS (n = 24)

−0.073

0.734

ND

ND

 RCS (n = 24)

0.115

0.593

ND

ND

 With-without COPD

0.241

0.184

ND

ND

 With-without chemo-radio therapy

−0.103

0.575

ND

ND

Intraoperative parameters

 Blood loss during surgery

0.145

0.428

ND

ND

 Operation time

0.145

0.430

ND

ND

Postoperative parameters

 Postoperative hospital stays

0.046

0.802

ND

ND

Changes in hand grip strength

 Right (n = 31)

0.153

0.412

ND

ND

 Left (n = 31)

0.143

0.442

ND

ND

Changes in isometric knee extensor muscle strength

 Right (n = 29)

0.045

0.815

ND

ND

 Left (n = 29)

0.089

0.646

ND

ND

 Changes in CAT scores (n = 23)

−0.219

0.315

ND

ND

The multivariate analysis includes relevant variables with P values <0.10 in univariate analysis (preoperative %VC and %FEV1, and PCS). ND not done. *P < 0.05. N = 32 otherwise indicated

Discussion

The main findings of the present study of patients with esophageal cancer who underwent esophagectomy with perioperative pulmonary rehabilitation were: 1) 6MWD and skeletal muscle strength had significantly decreased and CAT scores had increased 2 weeks after surgery, 2) PCS, a component of SF-36, significantly correlated with the decrease of 6MWD, and 3) comorbidity of COPD had a significant impact on health-related QOL, muscle strength, and 6MWD. To our knowledge, this is the first study to characterize the status of physical fitness, exercise capacity, health-related QOL, anxiety, and depression in patients with esophageal cancer before and after the surgery.

The 6MWT is a simple but well validated method to assess functional exercise capacity in patients with pulmonary and cardiovascular diseases [22] and the efficacy of pulmonary rehabilitation [27]. In the present study, preoperative 6MWD positively correlated with hand grip and isometric knee extensor muscle strength. It is expected that postoperative pulmonary rehabilitation helped maintain and recover the physical status of patients. However, the postoperative 6MWD and muscle strength were significantly lower than the preoperative values. Importantly, a mean decrease in the 6MWD of 85 m exceeded the clinically important distance of 54 m [28], demonstrating the significant short-term impact of esophagectomy on exercise capacity. Even in the three patients who underwent video-assisted thoracic surgery, the mean decrease in 6MWD was 60 m, above the clinically important value. Our results were consistent with the previous report by Tatematsu et al. that 6MWD and knee-extensor muscle strength, which were measured on the day of hospital discharge (median 21 days after surgery), were significantly decreased after esophagectomy [13]. Tatematsu et al. also reported that the change in the physical functional score on EORTC QLQ-C30 was significantly affected by that in the 6MWD by multiple regression analysis [13]. In our study, results of multiple and univariate regression analysis show that the loss of 6MWD was significantly affected by the preoperative SF-36 physical component PCS. In contrast, comorbidity of COPD, preoperative adjuvant therapy, pulmonary function test results, operation duration, or blood loss during surgery did not affect the change in 6MWD, consistent with the results of Tatematsu et al. These findings indicate that the 6MWT is a convenient and useful tool to assess the physical status in order to plan a perioperative rehabilitation program for patients with esophageal cancer.

Long-term cigarette smoking is an important risk factor for developing COPD as well as squamous cell carcinoma of the esophagus. It has been reported that COPD is one of the predictors of postoperative mortality after esophagectomy [5]. In our study, 91.2 % of patients were smokers, and the prevalence of COPD was relatively high (35.3 %). Moreover, both physical and QOL parameters were affected by comorbidity with COPD. The CAT is a validated questionnaire designed to assess and quantify the impact of COPD symptoms on health-related QOL [26]. The CAT scores strongly correlate with scores on the St. George Respiratory Questionnaire, a tool to evaluate the respiratory-related QOL [26]. Significant correlations between scores of total CAT and SF-36, a measure of the general health-related QOL, were found in our cohort, consistent with findings in COPD patients [29]. Preoperative CAT scores were significantly higher and postoperative 6MWD and left hand grip strength were significantly lower in patients with COPD than those without. In addition, postoperative CAT scores were significantly higher than preoperative scores, suggesting the impact of esophagectomy on respiratory-related QOL. Although the use of CAT for assessment of the respiratory-related QOL after surgery such as esophagectomy has not been validated yet, CAT was used before and after the surgery for the following reasons. First, almost all the patients in our cohort were smokers with a high prevalence of COPD. Second, pulmonary rehabilitation was the main objective of our perioperative rehabilitation program in order to prevent pulmonary complications after esophagectomy. Third, a recent study demonstrated that the CAT is beneficial to assess respiratory symptom and complications even in smokers without COPD [30]. Future studies are required to validate the use of CAT to assess respiratory-related QOL in patients who receive perioperative pulmonary rehabilitation. It would also be useful to evaluate the correlation between scores of CAT and QOL questionnaires specific for cancer and esophageal diseases such as the EORTC QLQ-C30 [14] and EORTC QLQ-OES24 [15].

The long-term impacts of esophagectomy on physical, QOL, or mental status after discharge have been investigated by other groups [11, 15, 31, 32]. In contrast, there is little information on postoperative physical and QOL status before discharge. The major purpose of our study was to evaluate how the physical, mental, and QOL parameters have recovered 2 weeks after esophagectomy during the hospital stay. Severer cases were excluded from the analysis because of gait disturbance 2 weeks after the surgery (Fig. 1). The incidence of pulmonary complications (8.8 %) was lower than that in previous reports (15–36 %) [4, 33, 34]. Thus, our patients reflect a relatively good clinical course shortly after the esophagectomy.

This study has several limitations. The data were collected retrospectively from patients who underwent esophagectomy. We did not aim to determine the factors that predict postoperative complications or examine the effectiveness of perioperative pulmonary rehabilitation either. It is impossible to clarify whether the rehabilitation was beneficial for health outcomes after the esophagectomy from the present study design. A previous study demonstrated that intensive prehabilitation reduced postoperative pulmonary complications after esophagectomy [10], indicating that improvement of physical fitness before the surgery may lead to better clinical outcomes after esophagectomy. Our findings demonstrated both the physical and QOL status of in-hospital patients two weeks after esophagectomy with perioperative rehabilitation. Further improvements, both from the viewpoint of minimally invasive surgery and perioperative management, are warranted. Prospective studies with a larger number of subjects including patients both with and without pulmonary rehabilitation are necessary to characterize the risk factors of postoperative complications and to improve the perioperative rehabilitation programs.

Conclusion

Our results indicate that esophagectomy is detrimental to health-related QOL and physical fitness at two weeks after surgery. Further investigation is required to establish a strategy for perioperative rehabilitation to improve postoperative outcomes.

Abbreviations

6MWD: 

6-min walk distance

6MWT: 

6-min walk test

CAT: 

COPD assessment test

COPD: 

Chronic obstructive pulmonary disease

EORTC QLQ: 

European Organization for the Research and Treatment of Cancer QOL Core Questionnaire

FEV1

Forced expiratory volume in one second

FVC: 

Forced vital capacity

HADS: 

Hospital Anxiety and Depression Scale

MCS: 

Mental component summary

PCS: 

Physical component summary

QOL: 

Quality of life

RCS: 

Role/social component summary

SF-36: 

The MOS 36-item Short-Form Health Survey version 2

SpO2

Oxygen saturation of a peripheral artery

VC: 

Vital capacity

Declarations

Acknowledgements

The authors thank Ms. Katherine Ono for providing language help.

Funding

This work was supported by Grant in Aid (No. 16 K21081 to T. Inoue) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Availability of data and material

The dataset supporting the conclusions of this article is available in Additional file 2: Table S2.

Authors’ contributions

SI was responsible for the present study’s concept and design, as well as for data acquisition, analysis, interpretation, and drafting of the manuscript. TI, MN, HA, YM, KH, HN, and YNiwa undertook the measurements and analyses of data. TI, MK, and YK analyzed the data and wrote the manuscript. MA was responsible for the statistical analysis. YK, YNis and YH supervised the research work. All the authors have approved the submission of the manuscript.

Competing interests

The authors declare they have no competing interests.

Consent for publication

The study information was disclosed to website of Nagoya University Hospital. The patients are able to access to the study information through internet so that they retain the right to refuse to have their data included in the analysis.

Ethics approval and consent to participate

This retrospective study was approved by the local ethics committee of Nagoya University Hospital (approval No. 2015-0413). No patient identifiers were included. Informed consent to participate and publish was not required for this retrospective analysis.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Department of Rehabilitation, Nagoya University School of Medicine
(2)
Department of Respiratory Medicine, Nagoya University School of Medicine
(3)
Center for Advanced Medicine and Clinical Research, Nagoya University School of Medicine
(4)
Gastroenterological Surgery II, Nagoya University School of Medicine

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