Effect of direct oral feeding following minimally invasive esophagectomy on costs and quality of life

Abstract

Aims

Following (minimally invasive) esophagectomy, patients often rely on tube feeding, since oral intake is often delayed. Consequently, additional support by a dietician and home care is needed until oral intake is commenced. In this study, the effects of direct start of oral feeding compared with tube feeding following an esophagectomy was evaluated on treatment costs and health-related quality of life (QoL).

Methods

Patients undergoing a minimally invasive esophagectomy were randomized in the NUTRIENT II study between controls (nil-per-mouth during 5 days and subsequent tube feeding) and a group in whom oral feeding was started directly postoperatively. Total hospital costs (including readmission and outpatient costs) and home care data for a period of 6 months after surgery were analyzed. QoL (measured using EORTC-QLQ-C30 and EORTC OG-25) was assessed preoperatively and 6 weeks, 12 weeks, and 6 months postoperatively.

Results

A total 132 patients were included (n = 65 direct oral feeding group and n = 67 control group). Mean patient hospital costs were €26,014 in the intervention group over a 6-month period compared to €26,989 in the control group (p = .825). Furthermore, people with direct oral feeding required significantly less home care assistance; i.e. 23 (48.9%) intervention patients versus 37 (77.1%) control patients (p = .004). Also, QoL in patients with direct oral feeding progressed more quickly when compared to the control group.

Limitations

Hospital costs were derived from a single hospital unit whereas costs from all the participating units may be a better reflection of the cost deviation. Availability of homecare data was limited, leading to difficulty in detecting differences in costs.

Conclusion

This study suggests that direct oral feeding leads to similar total costs and a significantly reduced need for home care assistance. Furthermore, QoL in intervention group increased more quickly when compared to the control group.

Keywords:

• Direct oral feeding
• esophagectomy
• hospital costs
• home care
• quality of life

JEL CLASSIFICATION CODES:

• I10
• I15

Introduction

Esophageal cancer is the sixth leading cause of cancer-related mortality and the eighth most common cancer worldwide¹. The incidence of esophageal cancer in the Netherlands and other Western countries is increasing rapidly^2–4. In the Netherlands, this is growing at a rate of roughly 400% in the recent years from 684 diagnoses in 1989 to 2,500 in 2018^5,6. A total of 2,536 new cases were identified in 2019⁷. This is due to the increasing prevalence of known risk factors such as obesity, gastroesophageal reflux disease and smoking^8,9. The Dutch healthcare costs for esophageal cancer care are expected to increase in the future with the increasing incidence and the improved neoadjuvant and surgical treatment¹⁰. Esophagectomy remains the cornerstone in esophageal cancer treatment. Postoperative complications following an esophagectomy are substantial and associated with a prolonged hospital stay, increased resource use and a reduced quality of life (QoL) ^11,12.

Enhanced recovery after surgery (ERAS) protocols that aim to improve postoperative recovery after an esophagectomy and thereby reducing the cost burden, are more frequently implemented¹³. Although early start of nutrition is an essential part of ERAS, oral intake is often delayed for at least five days in patients undergoing an esophagectomy because of fear of increased complications. Recently it was demonstrated that direct oral feeding was well tolerated and resulted in a similar functional recovery and complication rate compared to standard of care¹⁴. Patients in the intervention group directly started an oral diet whereas patients in standard of care received nil-by-mouth for the first 5 days after surgery and tube feeding.

The aim of the current study is to assess treatment costs (including need for home care) and QoL in patients that started oral feeding directly following minimally invasive esophagectomy (MIE) compared to patients receiving standard of care.

Methods

For this study, we used data of patients participating in the NUTritional Route In Esophageal Resection Trial (NUTRIENT) II study¹⁴. The NUTRIENT II study was approved by the Medical Ethics Committee United (MEC-U) and registered at ClinicalTrials.gov with the registration number NCT02378948 and at the Dutch trial registry with registration number NTR4972. The NUTRIENT II study was a multicenter prospective open-label randomized controlled trial performed at two hospital units in the Netherlands and one hospital in Sweden between 1 October 2015, and 14 May 2018. The trial was designed to investigate the effects of direct oral feeding versus standard of care on functional recovery following esophagectomy. Inclusion criteria were patients aged 18 or older, undergoing elective minimally invasive esophagectomy for cancer with intrathoracic anastomosis. Exclusion criteria were inability for oral intake (congenital or traumatic anatomical abnormalities), inability to place a feeding jejunostomy, inability to provide written consent, swallowing disorder, achalasia, Karnofsky Performance Status <80 and malnutrition.

Patients in the direct oral feeding group received a liquid/purified diet directly postoperatively with a daily inclining volume¹⁴. On postoperative day (POD) 20, a solid diet was started. In these patients a jejunostomy was inserted and used only when oral intake was neither possible nor sufficient. Patients in the control group received tube feeding via jejunostomy and were only allowed sips of water up to 250 cc for the first 4 days and then gradually expanded their oral intake similarly to the intervention cohort.

All patients provided written informed consent. Data on hospital costs, home care usage and costs, and health-related QoL of patients were analyzed. Quality of life data was obtained using questionnaires (patient reported) whereas cost data for each patient was obtained using electronic hospital system (i.e. individual data separately recorded for each patient in the clinical trial; patient level). In the original trial, a total of 132 patients were included of which 65 patients in the direct oral feeding group and 67 patients in the standard of care group. In order to adequately analyze the costs in this study, data was only gathered for the Dutch centers (direct oral feeding, n = 47 versus control, n = 48) Hospital cost analysis, home care usage and cost analysis were based on patients from one hospital and region (the Catharina Hospital from Eindhoven (n = 95).

Hospital costs

Hospital costs were determined by retrospectively extracting financial data from the electronic hospital system. Hospital costs were defined as all costs made during the initial admission (i.e. surgery costs and admission costs) as well as readmission and costs at the outpatient clinic. Surgery costs were based on the operating room costs (depicted by the duration of surgery and a fixed starting rate) and operating room personnel costs. Admission costs included costs made for surgical ward and/or intensive care unit stay, charges for parenteral and tube feeding, and postoperative diagnostic procedure. Costs of readmission within 6 months after surgery due to complications related to the primary operation were also collected. Outpatient costs consisted out of costs made for outpatient visits and additional diagnostic procedures within the 6 months after surgery. Monetary units are expressed in Euros (€).

Home care

Routine home care after an esophagectomy consisted of cleaning of the jejunostomy, flushing of the jejunostomy tube and connection of the jejunostomy tube to the feeding pump. Since, tube feeding is the main denominator for patients requiring home care after esophagectomy, data regarding tube feeding, home care assistance and costs for a period of 6 months following surgery were requested from the home care organizations. Patients requiring additional care (rehabilitation including home care) after discharge were scored as needing home care assistance, but excluded from home care cost analysis due to lack of availability of data. Data was gathered from home care organizations regarding the number of days receiving home care and corresponding home care costs. Based on the available home care costs, average costs of home care per day and total costs per patient were calculated. The average home care costs per patient were extrapolated to all patients receiving home care.

Health-related QoL

Health-related QoL was assessed pre- and postoperatively using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire(QLQ)-C30 (version 3.0), a validated questionnaire to measure the QoL in patients with cancer¹⁵. Additionally, the EORTC QLQ-OG25 supplements the EORTC QLQ-C30 when assessing health-related QoL in patients with esophageal, junctional or gastric cancer. Questionnaires were administrated at baseline (up to two weeks prior to surgery), 6 weeks, 12 weeks and 6 months postoperatively. Missing data were imputed according to the EORTC guidelines¹⁶.

EORTC QLQ-C30 questionnaire is composed of 5 functional scales (physical, role, social, emotional and functional) and 3 symptom scales (fatigue, nausea/vomiting, and pain) and a global health status/QoL scale. Furthermore, it contains 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The QLQ-OG25 has a functional scale (Body image) and symptom scales (dysphagia, eating, reflux, odynophagia, pain, anxiety, eating with others, dry mouth, trouble with taste and swallowing saliva, choked when swallowing, trouble with coughing, weight loss and hair loss). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale, represents a high level of functioning, a high score for the global health status represents a high QoL, but a high score for a symptom scale/item represents a high level of symptomology/problems.

Statistical analysis

All statistical analyses were performed using IBM SPSS Statistic Version 24 for Windows (IBM corp., Armonk, NY, USA). Normally distributed data are presented as mean with standard deviation and tested using an independent T-test. Nonparametric data are presented as median with interquartile range and were tested using the Mann–Whitney U test. All initial analyses were performed using an intention-to-treat approach. Also, a per-protocol analysis on hospital costs was performed to explain the effect of complications after esophagectomy. In short, only patients adhering to any nutritional protocol (i.e. either direct oral feeding or control group) were compared to patients deviating from any nutritional protocol¹⁴. Cost data were presented as mean, median and 95% confidence interval (CI). Cost differences were checked with nonparametric bootstrapping based on 5,000 replications. Mean and median cost data were compared using the unpaired T-test and Mann–Whitney U test.

Results

Clinical outcomes

Clinical outcomes of the NUTRIENT study have been previously published¹⁴. Median age was 65 years, predominantly male with an adenocarcinoma (77/95) of the distal esophagus (58/95). Functional recovery was comparable for both groups (7 in the intervention versus 8 days in the control group). Furthermore, the total postoperative complication rate was similar between groups (43.1% in intervention group versus 50.7% in control group).

Hospital costs

Total mean costs after an esophagectomy were €26,014 in direct oral feeding group and €26,989 in the control group (p = .825) and mostly determined by initial admission costs; see Table 1 for hospital costs in the 6 months following surgery.

Table 1. Hospital cost analysis for a period of 6 months after surgery, comparing the direct oral feeding group with the standard of care group.

	Direct oral feeding N = 47			Standard of care N = 48			p Value
	Mean	Median	95% CI	Mean	Median	95% CI	T-test	MWU
Admission costs	18,081	11,058	[13,119 − 24,781]	17,035	13,675	[13,730 − 20,790]	.769	.457
Surgery costs	4,095	4,059	[3,961 − 4,233]	4,089	3,987	[3,936 − 4,251]	.961	.777
Readmission costs	2,156	0	[936 − 3,855]	4,159	0	[1,698 − 7,676]	.336	.153
Outpatient costs	1,680	973	[1,069 − 2,573]	1,704	1,101	[1,278 − 2,202]	.958	.164
Total costs	26,014	17,182	[20,397 − 32,881]	26,989	20,442	[22,055 − 33,075]	.825	.240

All costs are presented in €.

Abbreviations. CI, confidence interval; MWU, Mann–Whitney U.

Patients who adhered to any nutritional protocol (i.e. direct oral feeding or standard of care) to patients who deviated from any nutritional protocol, had significantly lower admission (€10,767 versus €30,913; p < .001), readmission (€2,697 versus €4,097; p = .525) and total hospital costs (€19,258 versus €40,777; p < .001). Surgery (€4,096 versus €4,084; p = .914) and outpatient costs (€1,697 versus €1,682; p = .976) were similar in the intervention and control group.

Home care

Tube feeding at hospital and home was required in 18 out of 47 intervention patients (38.3%) and in all patients receiving the standard of care. The median number of the days patients receiving tube feeding was significantly shorter in the intervention group (0 days [IQR 0–41]) when compared to the control group (28 days [IQR 21–50], p < .001).

The need for home care assistance was significantly lower in the intervention group; 23 patients (48.9%) compared to 37 patients (77.1%) in the control group (p = .004). One patient in the intervention group and two patients in the control group required additional care after discharge, thus were excluded from home care cost analysis. Data regarding the length of home care assistance was only available in 32 (53.3%) patients and home care costs were known for 14 (23.3%) patients. Average home care cost was estimated on €37.34 per day and €1,310.31 per patient. Home care costs in the intervention group were estimated €28,826.39 (€1310.31 × 22) and €45,860.16 (€1310.31 × 35) in the control group respectively (Table 2).

Table 2. Tube feeding and home care analysis of patients in the direct oral feeding compared to the standard of care group for a period of 6 months after surgery.

	Direct oral feeding N = 47			Standard of care N = 48			p Value
	N	%	Median [IQR]	N	%	Median [IQR]	Chi^2	MWU
Tube feeding, days	18	38.3	0 [0 − 41]	48	100	28 [21–50]	<.001	<.001
Home care assistance, total costs^a	23	48.9	28,826.39	37	77.1	45,860.16	.004

Costs are presented in €.

^aOne patient in the intervention and two patients in the control group received institutional home care, so data was excluded in the cost analysis: 22 and 35 respectively.

Abbreviations. Chi², Chi-square; MWU, Mann–Whitney U; IQR, interquartile range.

Health-related QoL

In total, 126 (95%) patients completed the preoperative baseline QoL questionnaire, 110 (83%) patients completed the questionnaire at 6 weeks, 113 (85%) patients at 12 weeks and 100 (75%) patients at 6 months postoperatively. As a result, a total of 118 patients completed the questionnaires at two or more time points (56 patients in the direct oral feeding group and 62 patients in the standard of care group).

QoL in the direct oral feeding increased quicker in time compared with QoL of patients in the control group (Figure 1). Both groups had a score of 83 at 6 months postoperative. Global QoL score did not significantly differ between the intervention and control group for the 4 perioperative measurements (Supplementary Table 1).

Figure 1. Global quality of life for patients receiving direct oral feeding (intervention) and standard of care (nil-by-mouth for 5 days and tube feeding, control). Baseline measurement was up to 2 weeks prior to surgery. Median with Interquartile range: Baseline direct oral feeding (DOF) 62[50–75], standard of care (SOC) 66[50–75]; 6 weeks DOF 66[50–75], SOC 66[50–75]; 12 weeks DOF 75[66–83], SOC 66[66–83]; 6 months DOF 83[75–83], SOC 83[66–83].

Insomnia score at 12 weeks postoperative showed a significantly lower median in the intervention group (p = .041). At six months postoperative, significantly less patients from the direct oral feeding group experienced diarrhea (p = .024). Also nausea/vomiting (p = .033), odynophagia (p = .046) and trouble with taste (p = .028) showed a significant difference while the median scores were similar. No other significant differences were observed between the groups. Complete health-related QoL scores are shown in Supplementary Table 1 (QLQ-C30) and Supplementary Table 2 (QLQ-OG25).

Discussion

This study suggests that patients starting with oral intake directly following esophagectomy had lower home care costs and progressed more quickly to a higher QoL than patients with nil-by-mouth for five days and tube feeding. Also, it was shown that total costs following esophagectomy are high and mainly determined by initial admission period and admission related costs.

To our knowledge, no other studies have compared direct oral feeding with tube feeding and nil-by-mouth directly after (minimally invasive) esophagectomy in terms of costs and quality of life. In the current trial, all patients were operated upon with a minimally invasive approach. Previous studies comparing MIE with open surgery have shown increased surgical costs, but lower postoperative costs in the MIE group, resulting in conflicting conclusions. Total costs¹⁷ and surgical costs^11,18 for MIE in the current trial were lower than the costs for the open or combined open and minimally invasive approach in other studies. Differences between studies could be explained by effective implementation of an ERAS protocol leading to an optimized postoperative care pathway and an acceptable complication rate that is reduced following a learning curve^13,18–20. Compared to the current results, Weindelmayer et al.¹⁷ – only including open Ivor Lewis esophagectomies – found higher surgical costs (in contrast with previous studies stating surgical costs are higher in the MIE setting) while admission costs were lower. Hospital costs in this study were slightly lower compared to a randomized trial by Hulscher et al.²¹ of adenocarcinoma patients undergoing an open esophagectomy between 1994 and 2000. A more recent study by Goense et al., found average hospital costs of €37,571 from esophagectomy until 90 days after discharge. This is higher than in the current trial, in which the study period includes hospital costs from esophagectomy until 6 months postoperative¹¹. In multivariable analysis they found an increase in costs for female patients, age >70 year and several postoperative complications (anastomotic leakage, cardiac complications, chyle leakage and postoperative bleeding). Since the cohort of Goense et al. consisted of more female patients with a higher age, and both the AL and chyle leakage rates were 10% higher, this could explain the difference found between studies. Noteworthy, the significantly reduced chyle leakage rate found in the direct oral feeding group of NUTRIENT II trial¹⁴ and the succeeding analysis²² implies direct oral feeding could further reduce costs in these patients. Importantly, the learning curve was surpassed, thereby reducing the complication rate and complication-related costs.

In line, hospital costs for patients deviating from their nutritional protocol – which can be regarded as a proxy for a (severely) complicated postoperative course¹⁴ – were significantly higher compared to patients abiding to their nutritional protocol in this study. This was despite the presence of (minor) complications not prohibiting intake according to protocol.

The current standard of care is tube feeding via jejunostomy to ensure sufficient intake after esophagectomy. However, weight loss following esophagectomy occurs once tube feeding is stopped²³ regardless of the postoperative feeding regimen (oral vs. enteral)²⁴. Moreover, the need for prolonged routine feeding jejunostomy for enteral nutrition is being questioned^25–27 due to the frequent occurrence of jejunostomy-related complications^23,27, For example, bowel obstruction which is a severe jejunostomy-related complication has been found to be significantly higher in patients that received enteral feeding via a jejunostomy^25,28. Furthermore, a randomized pilot study for 6 weeks home enteral nutrition found no clear cost-effectiveness of prolonged enteral feeding²⁹.

In this study, total home care costs were based on data obtained for a smaller cohort and extrapolated to all patients needing home care assistance. Retrieval of home care data was challenging due privacy guidelines of home care facilities to share data, which resulted in the need for additional consent from all patients that participated in the trial. Despite the lack of a formal trial-based economic evaluation, the higher amount of patients receiving tube feeding and the longer period of tube feeding in the control group implies that this relative cost-effectiveness in absolute cost might be different, but always indicate superiority of the intervention group.

Hospital and home care cost analyses in this study imply that routine implementation of direct oral feeding after surgery could lead to a substantial reduction of costs and patient burden of home care organizations without compromising long-term outcomes on weight and even improving QoL.

QoL persistently improved after surgery in the direct oral feeding group whereas this improvement was not observed until six months after surgery in the control group. A possible explanation for this phenomenon could be that patients received tube feeding for a shorter period, or not at all. To our knowledge, only one other trial studying QoL in patients with early oral feeding after upper GI surgery by Sun et al.³⁰ reported a significantly improved global QoL for patients with early oral feeding after a McKeown esophagectomy. Two reasons could explain the difference with the current study: [1] patients in the control group received a naso-enteral feeding tube on POD 1, potentially leading to a diminished QoL caused by the discomfort of these feeding tubes which were not inserted in the intervention group, and [2] the first (global) QoL measurement was at 2 weeks postoperative. The significantly higher global QoL found by Sun et al. at 2 and 4 weeks postoperative equalized between their intervention and control group at 8 weeks postoperative, and since the 8 weeks values are comparable with the global QoL found in the current study, this suggests our measurement of QoL at 6 weeks postoperative was too late to find a significant difference.

When comparing global QoL with other studies, the population in this study performed better at 6 months postoperative. Kauppila et al.³¹ showed a global QoL score of 63 (95% CI 57–69) at 6 months postoperative. Akkerman et al.³² studied patients alive without disease recurrence at 1 year or more after surgery (median 36 months, range 12–75) and found a global QoL comparable with their used Dutch background population (mean 76 [SD 19] vs. mean 78 [SD 17]), but lower than the population at final study follow-up in this study. In disease-free patients, QoL is expected to restore within 6 months after surgery³³. The expectation is that the QoL in this cohort would further improve over time, since symptoms like fatigue, pain and coughing problems can persist for at least a year after surgery³⁴.

Few symptoms were significantly different at long-term follow-up. Nausea/vomiting and diarrhea at 6 months in the current trial were comparable with Kauppila et al.³¹ Diarrhea at 6 months in the intervention group was already comparable with the symptom level of patients at 36 m after surgery measured by Akkerman et al.^31,32

An important strength of this study was that patient level data was collected as a part of randomized controlled trial. However, this study also has some limitations. First, hospital costs were derived from a single hospital unit whereas costs from all the participating units may be a better reflection of the cost deviation. Second, limited availability of homecare data which leads to difficulty to detecting differences in the costs. Lastly, the study was conducted based on a single center data which may limit the generalizability of the results³⁵. Further studies with a full economic evaluation comparing costs from a societal or health insurance perspective and using QALY as outcome would be needed to confirm the cost-effectiveness of the intervention.

In conclusion, implementation of direct start of oral feeding lead to a significant reduction of patients requiring home care assistance and related costs, and a quicker increase in quality of life while hospital costs were similar between groups. Since direct start of oral feeding resulted in a similar postoperative complication rate in multicenter international setting and significantly reduced complications in a center with a stable and acceptable postoperative complication rate, it may also reduce costs after adopting of a safe and feasible direct oral feeding protocol.

Transparency

Declaration of funding

The randomized NUTRIENT II trial was supported by the KWF Kankerbestrijding (Dutch Cancer Society) under project number 10495; and Medtronic.

Declarations of financial/other relationships

The authors declare no conflict of interest.

A peer reviewer on this manuscript has disclosed that they are an employee of Bristol Myers Squibb, and stock owner of Bristol Myers Squibb. The peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

ML, MH and SE conceived the study; MP, LF, ML, MH, SE participated in its design; MP, LF and AD contributed to data collection. MP and LF performed the analysis and drafted the manuscript. ML, MH and SE helped drafting the manuscript. All authors reviewed and approved the final manuscript.

Acknowledgements

None reported.