Definition of the psychological distress
The definition of the psychological distress is negative emotional state characterized by physical and/or emotional discomfort, pain, or anguish. In other words, it is psychological discomfort that interferes with your activities of daily living. The definition of “psychological distress” and the definition of “Anxiety and depression” are not the same concepts. However, psychological distress can result in negative views of the environment, others, and the self. Sadness, anxiety, distraction, and symptoms of mental illness are manifestations of psychological distress [10, 11].
Several screening scales have been developed for the early detection of patients' psychological distress. The HADS score was developed by Zigmond and Snaith [12] and is well accepted to screen for psychiatric problems in medically ill patients. Genellary, cancer patients whose psychological distress is mainly characterized by anxiety and depression can benefit from using HADS to detect this distress. And also, Kugaya et al. [9] proved the reliability and validity of the Japanese version of HADS, and the scale appeared to be a simple, sensitive and specific scales for screening for psychological distress in Japanese cancer patients. Therefore, we use the HADS scales for screening for psychological distress in the present study.
Study Design and Endpoints
Participants comprised 152 consecutive patients who attended the outpatient clinic at the Department of Gastrointestinal Surgery at Toranomon Hospital between April 2017 and April 2019 were assessed for trial eligibility. Among these 152 patients, 102 patients who met the eligibility criteria participated in this study. The inclusion criteria were as follows: esophageal cancer including Siewert type I/II tumors of esophagogastric junction; scheduled for subtotal esophagectomy; age 20 years to 85 years; performance status 0 to 2; ability to provide informed consent; with previous oncological therapies for cancer; with previous surgical treatment for other diseases. We included patients with 20-85 years-old. The reason is because patients may have senile dementia. Generally, about 3 % of people between the ages of 65-74 have dementia, 19 % between 75 and 84, and nearly half of those over 85 years of age [13]. Therefore, we selected the patients with 20-85 years old.
The following exclusion criteria were applied: informed consent has not been obtained; on treatment for mental disorder; unsuitability for participation in the study because of psychological or physical stress in the opinion of the medical stuff; refusal to undergo surgery; and requested nonsurgical treatment. The flow diagram of this study is shown in Figure 1. Questionnaires were administered at 5 time points as follows: at the time of outpatient consultation before definitive diagnosis (time 1); at the time of determination of clinical stage before treatment; both of surgery and neoadjuvant therapy (time 2); about 2 weeks after surgery before final staging (time 3); at the time of determination of final staging (time 4); and at 3 months after surgery (time 5). The questionnaires were administered in a fixed waiting room at our institution because we would like to perform the survey acquisition under the stable condition as much as possible. We selected three questionnaires; the Japanese version of HADS, MAC scale, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30/ the oesophageal cancer-specific module (EORTC QLQ-C30/OES18). The questionnaires (HADS/EORTC QLQ-C30/OES18) were administered at all 5 time points, and MAC scale was administered once, at time 1. From the trends of HADS scores on each points of the treatment, we selected two groups: “persistent high HADS scores” and “persistent low HADS scores”. Of 102 patients who met the eligibility criteria participated in this study, 21 patients were allocated to the “persistent high (H-) group”, and 38 patients were allocated to the “persistent low (L-) group”(Figure 2). We investigated the characteristics of H-group compared with L-group especially from standpoints of personal coping styles and HRQOL. Esophageal cancer staging (Clinical (c-)/ pathological(p-) stage) is defined by the UICC TNM grading system, 7th edition;.the sub-classifications based on the depth of invasion of the primary tumor (c-/ p-T factors), lymph node involvement (c-/ p-N factors), and extent of metastatic disease (c-/ p-M factors) [14]. T factors classified the following; Tis: high-grade dysplasia, T1: invasion into the lamina propria, muscularis mucosae, or submucosa, T2: invasion into muscularis propria, T3: invasion into adventitia, T4a: invades resectable adjacent structures (pleura, pericardium, diaphragm), and T4b: invades unresectable adjacent structures (aorta, vertebral body, trachea). Similary, N factors classified the following; N0: no regional lymph node metastases, N1: 1 to 2 positive regional lymph nodes, N2: 3 to 6 positive regional lymph nodes, and N3: 7 or more positive regional lymph nodes. M factors classified the following; M0: no distant metastases and M1: distant metastases[14]. All postoperative complications were graded using the Clavien-Dindo classification [15]; events more severe than grade ≥ III were recorded as complications. We chose this cut-off value on the basis of the Japanese version of HADS, which has been validated for Japanese patients with cancer [12]; a cut-off HADS total score ≥ 11 has been recommended for identifying patients with potential adjustment disorder and major depression [12]. We defined a total score ≥ 11 as indicating psychological distress. The study protocol was approved by the institutional review boards of the Graduate School of Medical and Dental Sciences (approval number M2016-241) and Toranomon Hospital (approval number 1312) and registered with the UMIN Clinical Trials Registry (UMIN-CTR, R000033229). All procedures were conducted in accordance with the ethical standards of the Helsinki Declaration of 1975. Informed consent was obtained from all study participants at the time of the first outpatient appointment.
Measures
Mental Adjustment to Cancer scale
This scale (MAC scale) assesses the extent to which patients respond and adjust to their diagnosis of cancer and its treatment [16, 17]. It was developed as a self-rating questionnaire that would be patient-friendly and could be administered easily at busy oncology clinics. The scale includes five subscales that measure five types of response: fighting spirit(“I firmly believe that I will get better”, 16 items); helpless/hopelessness (‘I feel that life is hopeless”, 6 items); anxious preoccupation (“I suffer great anxiety about it”, 9 items); fatalism (“I’ve left it all to my doctors”, 8 items); and avoidance (“I don’t really believe I have cancer”, 1 item). Each item is scored on a 4-point Likert scale (1, “definitely does not apply to me”; 4, “definitely applies to me”). Scores for the subscales are calculated by summing the answers for the assigned items. Generally, the coping skills does not greatly change in the short time, therefore we didn’t measure the MAC scale at each time point [18, 19]. This questionnaire was administered once, at time 1, in this study.
Hospital Anxiety and Depression Scale
This scale (HADS) is a 14 item self-report questionnaire comprising of two subscales measuring symptoms of depression (HADS-D) and symptoms of anxiety (HADS-A) over the last week. Each subscale contains 7 items with scores ranging from 0 to 21 [11]. A total score of ≥ 11 on either subscale indicates a definitive case. The Japanese version of HADS was back-translated by Kitamura [20] and its reliability and validity were confirmed by Kugaya et al. [9]. The questionnaire was administered at all 5 time points in this study.
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30
This questionnaire (EORTC QLQ-C30) is one of the most frequently used questionnaires to measure health-related quality of life in patients with cancer [21-23]. Its 30 question items have been validated in several studies in various types of cancer. This score is a 30-items questionnaire divided into five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and neusea/ vomiting), six single-item questions (financial impact and various physical symptoms such as dyspnea, insomnia, anorexia, constipation, and diarrhea), and a global health status/quality of life. The items on the functional subscales are rated on a 4-point Likert scale (1, “not at all”; 4, “very much”). The raw subscale scores are transformed into a scale of 0–100 (0, poor QOL; 100, excellent QOL). The questionnaire was administered at all 5 time points in this study.
EORTC QLQ-OES18 questionnaire
The EORTC QLQ-OES18 is a self-reported 18-item questionnaire designed to assess health-related quality of life in patients undergoing a single treatment or a combination of treatments for esophageal cancer (i.e., esophagectomy, chemotherapy, radiotherapy, and/or chemo-radiotherapy). It includes 12 items grouped into 4 symptom scales (dysphagia; 3 items, eating; 4 items, reflux; 2 items, and pain; 3 items) and 6 single items (trouble with swallowing saliva, choking, dry mouth, taste, cough, and speech). The time frame is “during the past week”. All items are scored using a 4-point Likert scale (1, “not at all”; 4, “very much”) and responses to the questionnaires were transformed into a 0-100 scale using EORTC guidelines [24]. The questionnaire was administered at all 5 time points in this study.
Operative procedure for esophagectomy
We perform esophagectomy with two-field or three-field lymphadenectomy depending on the degree of disease progression and the surgical risk involved. The operative thoracic approach entails video-assisted thoracoscopic surgery or thoracotomy and the abdominal approach involves hand-assisted laparoscopic surgery or open laparotomy depending on the individual case. We generally preserve the thoracic duct in patients with clinical stage I disease but resect it in those with clinical stage ≥II disease for the purpose of lymphadenectomy [13]. However, we resected the thoracic duct even if the patient has clinical stage I disease when we suspect lymph node metastasis or have confirmed a metastasis in the lymph nodes along the bilateral recurrent laryngeal nerves on intraoperative pathologic analysis. However, we try to preserve the thoracic duct in patients at high risk of impaired hepatic or pulmonary function. A manually sutured esophagogastric or esophagoileal anastomosis in the neck is fashioned for all patients [25-29].
Statistical analysis
Differences between the two groups (H-group/ L-group) were tested for statistical significance using Fisher’s exact test, the unpaired Student’s t-test, the Mann-Whitney U test, and Pearson’s chi-squared test as appropriate.
Risk factors for psychological distress (H-group) were assessed by bivariate logistic regression analysis (Backward stepwise selection). The variables with a p-value less than 0.05 in univariate analysis were entered into bivariate logistic analysis. Odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated. A p-value less than 0.05 was considered statistically significant in bivariate logistic analysis. The correlations between MAC scale and HRQOL status were assessed using Spearman’s correlation coefficient and statistical significance was tested using Spearman’s rank-sum test. The internal consistency (reliability) of each scale was estimated by Cronbach's alpha coeffcient [30]. A value of 0.70 or greater was considered acceptable for group comparison. All analysis was performed using SPSS for Windows software (version 19.0J; IBM Corp., Armonk, NY).