This prospective, single-arm, nonrandomized pilot study was conducted at the First Affiliated Hospital of Sun Yat-sen University in Guangzhou, China, which has 2850 beds serving 4.9 million patients each year. The Department of Thoracic Surgery cares for more than 300 patients with esophageal cancer each year. The study was registered at the Chinese Clinical Trial Registry (ChiCTR-IPR-1800019900) and was approved by the ethics committee of the First Affiliated Hospital of Sun Yat-sen University according to the Declaration of Helsinki.

Patients diagnosed with esophageal cancer and scheduled for esophageal radical resection were referred by thoracic oncologists in the inpatient department of the hospital from December 2018 to October 2019. Those who met the eligibility criteria were invited to join the study. The inclusion criteria of the study were a diagnosis of esophageal cancer, suitability for the modified McKeown procedure (thoracoscopic esophageal mobilization three-incision esophagectomy) [27] and jejunostomy before surgery, age between 18 and 75 years with an expected survival of 12 months or longer, normal preoperative gastrointestinal function, Karnofsky performance scores of ≥90 before surgery, ability to walk continuously for 6 minutes or longer before surgery, own WeChat account or an account among family members, cognitive capability to understand Chinese and the study procedures, and ability to provide written informed consent. Individuals were excluded if they had esophageal carcinoma with distant metastases, were unable to engage in physical exercise owing to medical comorbidities, were HIV seropositive, were pregnant or lactating, were unable to finish the questionnaire owing to mental problems or other reasons, did not undergo R₀ resection, failed to have a jejunostomy feeding tube fitted, or had other serious medical, psychiatric, or cognitive illnesses that would interfere with their participation. Interested participants had appointments with trained research staff to receive further information about the study, signed the informed consent form, and completed the baseline assessment.

Figure 1 depicts the flow chart of the study. Of 38 patients diagnosed with esophageal cancer and scheduled for resection with the modified McKeown surgical approach, 10 did not meet the inclusion criteria and 8 declined to take part in the study. Personal reasons for rejection included concerns for patient privacy from family members and patients’ unstable postoperative condition. Thus, the final sample included 20 patients. The overall response rate was 52.6% (20/38). Of the 20 patients enrolled, 16 (80%) completed the study and 4 (20%) dropped out at the 3-month follow-up owing to disease exacerbation, unwillingness to continue, or missing routine assessments.

A 3-month CIMmH program was delivered to participants after surgery by specialists in the hospital (offline) and through the enhanced WeChat platform (online). The program included general guidelines on postsurgery recovery, strategies to cope with postoperative complications, nutrition guidelines, physical exercise promotion, and psychological support courses. Details of the CIMmH are provided in Table 1. The components of the CIMmH are presented below.

The participants were assessed at the following three time points: baseline (about 1 week before surgery) and 1 month and 3 months after surgery. The assessments were conducted in the hospital with the use of tablets and were assisted by trained research staff. Sociodemographic characteristics were collected, and they included age, gender, marital status, education, employment, and income. For measuring patient QOL, the European Organization for Research and Treatment of Cancer-Quality of life Question-Core (EORTC-QLQ-C30, version 3.0) and Oesophageal Cancer Module (EORTC-QLQ-OES-18) questionnaires [38] were used. EORTC-QLQ-C30 is a 30-item measure that includes an overall QOL scale, five functional scales (physical, role, emotional, cognitive, and social), three symptom subscales (fatigue, nausea & vomiting, and pain), and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The scores of EORTC-QLQ-C30 range from 0 to 100, with higher scores indicating a higher QOL. The Chinese version of the scale has been used in Chinese patients with cancer and has high validity and reliability [39].

EORTC-QLQ-OES-18 is a supplement of the disease-specific module for patients with esophageal cancer [40]. It consists of four symptom subscales (dysphagia, difficulty with eating, reflux, and pain) and six single items (trouble swallowing saliva, choking at swallowing, dry mouth, trouble with tasting, coughing, and talking). The Chinese version of the scale is reliable and acceptable to measure the health-related QOL of patients with esophageal cancer in China [41]. In addition to QOL, the patients’ body weight and physical fitness measured by the 6MWD were assessed by medical doctors. Psychological status was measured using the Chinese versions of Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms, General Anxiety Disorder-7 (GAD-7) for anxiety, and Perceived Stress Scale-10 (PSS-10) for stress. All these measures have high validity and reliability in Chinese populations [42-44].

Descriptive analyses of the sociodemographic characteristics and health outcomes were conducted. Means and SDs were used to describe normally distributed continuous variables, while medians and IQRs were used for continuous variables that were not normally distributed, and proportions were used for categorical variables. Pre-post comparisons of outcomes between baseline and the 1-month follow-up and between baseline and the 3-month follow-up were conducted. Paired Student t tests were used for normally distributed continuous variables, Wilcoxon signed-rank tests were used for nonnormally distributed variables, and chi-square tests were used for categorical variables. The rates of depressive symptoms and anxiety in the participants were calculated using the cutoff scores of at least 10 and 7 for PHQ-9 and GAD-7, respectively [45,46]. The analyses were performed using SAS version 9.4 (SAS Institute, Inc).

In total, 95% (19/20) of the participants used the online program. Moreover, participants used the online program for an average of 71 minutes in total during the study period. Participants viewed on average 84% (3.38/4) of the online video intervention content and completed on average 14% (3.20/23) and 34% (9.44/28) of the online audio and article content, respectively. Participants completed on average 63% (5.01/8), 100.00% (1/1), and 24% (10.89/46) of the online nutrition, physical exercise, and psychological intervention content, respectively. There was no serious adverse event in any of the participants.

Participants’ sociodemographic and clinical characteristics are summarized in Table 2. The mean age of the participants was 62.2 years (SD 7.1 years). The majority (18/20, 90%) of the participants were male, and more than half lived in rural regions (12/20, 60%) and did not complete high school (11/20, 55%). Most participants (13/20, 65%) had not received neoadjuvant chemotherapy or radiotherapy, and half (10/20, 50%) had a tumor in the middle thoracic area.

Table 3 presents the scores of all outcome variables at baseline, the 1-month follow-up, and the 3-month follow-up.

At the end of the study, participants were asked about their experiences of the intervention through the WeChat platform. Of the 20 participants, 18 (90%) reported that they were satisfied with the intervention program. Some suggested that the intervention interface and content could be designed in a more interesting and attractive way. One patient suggested that more intervention programs should be delivered in video format. Eight patients reported that they would like to receive more information about effective strategies to cope with postoperative complications.

To the best of our knowledge, this prospective pilot study is the first attempt to develop and test the feasibility of an mHealth-based comprehensive intervention with nutrition, exercise, and psychological support through an online platform to help promote the ERAS program for patients with esophageal cancer.

For patients with cancer, ERAS is critical and challenging, as they experience both physical and mental complications. Tailor-made comprehensive interventions are needed for patients with specific cancers, as different types of cancers have different needs. Patients with esophageal cancer, for example, need special attention for nutrition intake and rehabilitation of respiratory movement after esophagectomy. The CIMmH is a comprehensive intervention addressing poor nutrition, physical inactivity, and intensified mental health symptoms within a single program for patients with esophageal cancer after surgery. The findings from this study indicate that the CIMmH is feasible and safe with no serious adverse effects for patients. The relevant decrease in overall QOL and increases in symptoms like fatigue, pain, dyspnea, difficulty with eating, trouble with coughing, trouble with talking, and reflux at the 1-month follow-up were expected, as patients were still in the recovery period after the surgery and were using feeding tubes. The results indicated that at the 3-month follow-up, except for pain, difficulty with eating, dry mouth, and trouble with talking, most of the QOL measures returned to the levels at the preoperative stage, indicating that recovery in these dimensions occurred 3 months after surgery. Compared with this study, previous studies that used traditional postoperative rehabilitation programs reported greater decreases in most functional dimensions of QOL and more serious deterioration of symptoms at 1 month and 3 months after surgery [47-49]. The CIMmH facilitated more comprehensive recovery for patients undergoing esophagectomy by restoring their declining functions faster and easing the symptoms caused by surgical injury. Nevertheless, patients still reported more problems with talking, coughing, and eating at 3 months after the surgery compared with the preoperative stage. These issues might stem from neurological injury during surgery, requiring a longer recovery time. These findings therefore highlight the need for routine evaluation and assessment of the postoperative functional status in patients. Careful consideration of the effects of possible complications on functional outcomes after surgery is thus needed when providing counseling services to patients before they make their decisions to undergo surgery and to plan rehabilitation.

As surgical injury often worsens the nutritional status of patients with esophagectomy, decreases in body weight and BMI are expected and have been well documented [8,50]. However, the drop in BMI was smaller in this study (1.0 and 1.5 at the 1- and 3-month follow-ups, respectively) than in a previous report (1.9 and 2.3 at the 1- and 3-month follow-ups, respectively) [50]. The minor drop in nutritional measures in this study indicates improved nutritional outcomes compared with the previous study [50].

Results of the 6MWD test at the 3-month follow-up demonstrated physical status comparable to that at baseline, indicating the effects of the CIMmH with regard to buffering the deterioration of physical fitness in patients after esophagectomy. Previous studies involving traditional postoperative rehabilitation showed a greater decrease in the 6MWD in the third month after surgery when compared with the finding in this study [51,52]. Lastly, with respect to psychological outcomes, depressive symptoms greatly increased at the 1-month follow-up, while anxiety and stress did not change greatly across all time points. Increased scores for depressive symptoms were expected as patients were greatly affected by surgical injuries at 1 month and were experiencing difficulties in eating, speaking, and even breathing in some cases. Nevertheless, the rates of depressive symptoms and anxiety in the present sample at 3 months after surgery were 6% (1/16) and 12% (2/16), respectively, whereas in a previous study, more than 40% of patients had depressive symptoms and anxiety after surgery [53], showing the potential of the CIMmH to support patients in coping with their conditions.

In this study, the mHealth system yielded a unique opportunity to provide much needed postsurgical care for the included patients. The functions of automatic monitoring, timely interventions, and feedback through the online mHealth system helped improve intervention adherence, as 80% (16/20) of participants completed the intervention. Although no formal qualitative data were collected in this study, some participants reported that they liked the video talks given by the medical doctors on how to take care of themselves and found the information on nutrition, exercise, and symptom management useful and helpful. In addition, professionals in the hospital reflected that the comprehensive intervention model of combining online (mHealth) and offline (face-to-face) services in this study was cost-effective and easier to incorporate into existing clinical practice and health care services, as less professional time was required and patients could receive tailor-made and timely interventions at home [54]. Given the large number of patients with esophageal cancer in low- and middle-income countries, the CIMmH has the potential to be a feasible cost-effective therapeutic option for improving postsurgery recovery in patients with esophageal cancer after esophagectomy.

Patient engagement data indicated that online intervention content in video format was more popular than audio or written materials. One possible reason might be that most participants in this study were elderly people who might have found it easier to understand vivid videos compared with audio content and articles. Future interventions may consider using more intervention materials in video format. Moreover, the completed proportions of the online nutrition and exercise intervention content were much higher than the completed proportion of the psychological intervention content. One possible explanation could be that the mental health status of the participants at baseline was better than that during follow-ups, so it was very likely that participants paid more attention to coping with postoperative complications than mental health–related issues. Another reason might be that there was insufficient emphasis on the importance of mental health at the beginning of the program. Mental health is an important problem in patients with esophageal cancer, as many of these patients experience depressive symptoms and anxiety after surgery [53,55]. Future interventions should emphasize the importance of mental health issues and educate patients to pay attention to their mental wellness after surgery.

The CIMmH has yielded a unique opportunity to provide much needed postsurgical care in patients with esophageal cancer for the likely improvement of postoperative nutrition and the physical and mental status. This pilot study has shown that the CIMmH approach is a feasible and well-received option for ERAS in patients with esophageal cancer. Experiences of the CIMmH pilot study may help future development of a large randomized controlled trial or similar programs for patients with esophageal cancer or other cancers, especially those who are not able to visit the hospital frequently or who reside in rural areas. For example, patient adherence to the program needs to be enhanced in future interventions for better treatment effects, especially in the component of psychological intervention. More intervention programs should be delivered in video format, as video talks by medical doctors on patient self-care are particularly well received by patients.

Despite the positive outcomes, there were several limitations in this study. First, the sample size was small and there was no comparison group; thus, caution is needed to avoid over interpreting the findings. Second, some outcome data were missing owing to the drop-out of several patients at follow-up assessments. Third, effects of the CIMmH might be influenced by adherence and complications after surgery, which differ from patient to patient. Future studies should adopt a larger sample size and preferably use a randomized controlled trial design. The subjective experience of the participants should also be explored by collecting qualitative feedback throughout the study.

The CIMmH is the first mHealth-based comprehensive intervention developed and tested in patients with esophageal cancer after esophagectomy. Our results show that the CIMmH is usable, feasible, and safe among patients with esophageal cancer after surgery in China. Future studies with a more rigorous design and larger samples are needed to establish efficacy in patients with esophageal cancer and those with other types of cancers.

6MWD

6-minute walk distance