Gastroesophageal Reflux after Mckeown Esophagectomy with Embedded or Non- embedded Anastomosis: a Propensity Score Matched Cohort Study

doi:10.21203/rs.3.rs-4872194/v1

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Research Article

Gastroesophageal Reflux after Mckeown Esophagectomy with Embedded or Non- embedded Anastomosis: a Propensity Score Matched Cohort Study

https://doi.org/10.21203/rs.3.rs-4872194/v1

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Backgrounds: Gastroesophageal reflux lowers the quality of life (QoL) in patients with esophageal cancer after esophagectomy with gastric conduits. This study aimed to investigate the incidence of gastroesophageal reflux, dysphagia, and QoL among patients with esophageal cancer undergoing embedded and non-embedded anastomosis during Mckeown esophagectomy.

Materials and methods: Data from patients who underwent Mckeown esophagectomy for esophageal cancer from March 2022 to December 2022 were retrospectively analyzed. The incidence of gastroesophageal reflux, dysphagia, and QoL were measured. We included 218 patients, including 155 patients undergoing non-embedded anastomosis (NA group) and 63 patients undergoing embedded anastomosis (EA group). Propensity score matching was used to provide a balanced cohort consisting of 63 paired cases. Patients’ demographics and clinical data were compared between the two arms.

Results: Before propensity score matching, there were no significant differences between the two arms in terms of sex, age, body mass index, or comorbidities. Neoadjuvant therapy was the only unbalanced variable. After propensity matching, baseline characteristics were all comparable between the two arms. Anastomotic leakage occurred in 1 (1.6%) patient in the embedded anastomosis arm and in 2 patients (3.2%) in the non-embedded anastomosis arm (P = 1.000). Forty-one (65.1%) patients in the non-embedded anastomosis arm and fifty-one (81%) patients in the embedded anastomosis arm slept in the supine position without reflux (P = 0.045). Multivariable logistic regression analysis in the matched cohorts [OR (95% CI): 2.539 (1.084, 5.949), P = 0.032] showed that embedded anastomosis was the only protective factor against gastroesophageal reflux. Evaluation of quality of life showed embedded anastomosis was superior to non-embedded anastomosis in the pain domain (P = 0.036) of EORTC QLQ-OES18. No significant difference was observed in dysphagia severity, measured by Mellow-Pinkas Scale, or dysphagia subscale of QoL.

Conclusion: Embedded anastomosis achieved sufficient control of gastroesophageal reflux without causing dysphagia. It also improved QoL compared with non-embedded anastomosis.

Esophageal cancer surgery

Esophagogastric anastomosis

Gastroesophageal reflux

Quality of life

Propensity score matching (PSM)

We conducted a study to investigate the incidence of gastroesophageal reflux among patients undergoing two types of anastomoses. After propensity score matching, forty-one (65.1%) patients in the non-embedded anastomosis arm and 51 (81%) patients in the embedded anastomosis arm slept in the supine position without reflux (P=0.045).

Gastroesophageal reflux impairs the quality of life of patients with esophageal cancer who undergo esophagectomy.

The cross-bedded anti-reflux anastomosis was proven to be feasible and favorably controlled gastroesophageal reflux and dysphagia.

What is the implication, and what should change now?

The cross-bedded anti-reflux anastomosis can be widely used to prevent the incidence of gastroesophageal reflux and dysphagia.

Esophageal cancer ranks eighth in terms of incidence and sixth in terms of mortality among malignancies[1]. Squamous cell carcinoma and adenocarcinoma are the most common types of esophageal cancer [2]. Surgery remains the main modality of treatment for resectable esophageal cancer, and the stomach is the most widely used substitution for esophagus [3]. Due to the destruction of anti-reflux structures in Mckeown esophagectomy, gastroesophageal reflux is very common after esophagectomy, and most patients experience reflux after lying flat when they are full. The incidence rate is still 30% -80% after extending the interval between meals and lying flat and sleeping in a sloping position [4–9]. The quality of life (QoL) will also be affected. The anastomosis technique is decisive for reconstructing the alimentary tract and preventing complications. Various techniques of anastomosis have been adopted; however, the optimal one is yet to be determined [10–13]. An optimal anastomosis technique should prevent postoperative leakage, allow early and unlimited oral feeding, and effectively alleviate digestive symptoms [14].

Due to the devascularization effect of radiotherapy, it can impair the healing process of anastomosis stoma. Some studies showed that neoadjuvant radiation therapy can increase the risk of anastomotic leakage in the future anastomosis site [15, 16]. Embedded anastomosis is a common technique that can decrease the tension at the anastomosis site and promote anastomotic healing after gastrointestinal reconstruction [17–19]. The end-to-end intussusception anastomosis was found to be safe even after neoadjuvant radiation therapy for local tumors [20]. The intussuscepted tissue functioning as a unidirectional valve also showed certain reflux-preventing effects. Nevertheless, dysphagia was reported frequently. Reduction of the intussuscepted structure was assumed to be the key to eliminating the obstruction and preventing anastomotic leakage and gastroesophageal reflux. The authors successfully accomplished anastomosis in patients with megaesophagus who underwent Mckeown esophagectomy [21]. This anastomosis technique was named cross-bedded anti-reflux (CAR) anastomosis and was applied to patients with esophageal cancer. Figure 1 shows its coronary view. We reviewed the clinical and follow-up data of patients who underwent minimally invasive Mckeown esophagectomy for esophageal cancer to investigate whether mucosal intussusception is enough to maintain the anti-reflux effect and prevent dysphagia in larger groups. We also compared postoperative obstruction, gastroesophageal reflux, and QoL between the CAR anastomosis arm and the non-intussuscepted anastomosis arm.

Patients

We included patients who underwent minimally invasive Mckeown esophagectomy for esophageal cancer in West China Hospital of Sichuan University between March 2022 and December 2022, regardless of histological subtype. Individualized neoadjuvant therapy was given to patients with locally advanced lesions. Patients with a history of malignancy within the last 5 years, those who did not receive stomach as a substitution for esophagus, and those lacking complete clinical and six-month follow-up information were excluded. Patients who received CAR anastomosis were classified as the embedded anastomosis (EA) arm. Other patients undergoing non-embedded anastomosis were included in the non-embedded anastomosis (NA) arm.

Operation Procedures

Minimally invasive Mckeown esophagectomy involving cervical, thoracic, and abdominal procedures was regularly performed. After thoracoscopic mobilization of the thoracic esophagus and laparoscopic mobilization of the stomach, a 5 cm incision was made below the xiphoid process to extract the stomach. Pyloromytomy was routinely performed for patients in both groups. We then stapled the stomach into a 3–5 cm gastric tube and transported its tip to the neck incision through the esophageal bed.

The anastomosis technique was chosen based on surgeons’ preference. Non-embedded anastomosis was defined as all anastomosis techniques lacking reconstructed anti-reflux structures. In our institution, they include handsewn end-to-end anastomosis (layered or not) and mechanical end-to-side anastomosis.

Figure 2 illustrates the specific procedures of CAR anastomosis, which was described in a previous study [22]. Briefly, using a three-leaf clamp, the esophagus and gastric tube were aligned at the cervical incision where the diameter of the stomach was slightly larger than that of the esophagus. The seromuscular layer of the stomach exceeding the clamp 0.5 cm was carefully peeled off the alimentary mucosa. We then

exposed the posterior walls of the esophagus and stomach. A row of interrupted sutures was placed between the posterior cutting edge of the seromuscular layer of the stomach and the muscular layer of the esophagus at the same level to form the posterior outer layer of the anastomosis. The redundant gastric mucosa and esophageal wall exceeding the clamp by more than 2.5 cm were resected. In addition, 2 cm of the gastric mucosa and the whole layer of the esophagus were left above the sutures. We continuously sutured the remaining gastric mucosa and the whole layer of the esophagus to form the inner layer of anastomosis. This is where the “cross-bedded” comes from. This layer was then inserted into the gastric lumen after removing the three-leaf clamp. Finally, the anterior part of the outer layer of the anastomosis was formed by suturing the anterior esophageal wall to the seromuscular layer of the stomach using interrupted 4 − 0 Vicryl sutures.

Outcome Measurements

Demographic and perioperative data of patients were recorded. Demographic characteristics included age, sex, and body mass index. Comorbidities included diabetes, and dysfunction of pulmonary, renal, cardiovascular, and hepatic systems. Tumor characteristics included tumor location, histological subtype and differentiation, and clinical T and N stages. Whether neoadjuvant therapy was applied and the specific regimens of neoadjuvant therapy were also clarified. Operative data included operation time, blood loss, and conversion to thoracotomy. Postoperative complications, such as anastomotic leakage, pneumothorax and hydrothorax requiring thoracocentesis, chylothorax, pulmonary infection, cerebral infarction, and recurrent laryngeal nerve injury were specified. Surgical margins were classified as R0 if no microscopic residue was found, R1 with microscopic residue or R2 with macroscopic residue. Neurological and/or lymphatic invasion were also recorded. Tumor regression grade was assessed for lesions undergoing neoadjuvant therapy.

Before discharge, patients in the database were educated that raising the pillow can reduce the risk of gastroesophageal reflux. The final sleeping position was determined by their own exploration. Using a standardized questionnaire during outpatient and telephone follow-up, gastroesophageal reflux, dysphagia, nutritional status, and QoL were routinely assessed six months after the surgery. The evaluation was postponed to two weeks after adjuvant therapy if there was one. Reflux frequency was classified as none, once or twice a month, once a week, and twice a week or more. The overall severity of regurgitation and heartburn was assessed using a visual analog scale, and scores ranged from 0 to 10. The questionnaire also evaluated gastroesophageal reflux severity within the last month combining posture and dietary factors [23]. The reflux scenarios were divided into no reflux in the supine position, fasting reflux in the supine position, postprandial reflux in the supine position, fasting reflux in the slope position, or postprandial reflux in the slope position. The fasting state was defined as 3 hours of not eating after the last meal. We also recorded the height of the pillow to specify the difference in slope. In addition, the incidence of other reflux-related symptoms, such as cough, and aspiration pneumonia was recorded. If the gastroesophageal reflux was still severe enough to bother patients after behavioral adjustment, a proton pump inhibitor was administered and the usage was recorded. Dysphagia was rated using the Mellow-Pinkas scale, which is based on the texture of food they were able to swallow [24]. Food intake during each meal was quantified as 200 grams, 400 grams, or 600 grams or more. Belching difficulty, postprandial fullness frequency, abdominal pain, and time taken to relieve were also measured. Postoperative weight loss was calculated as weight six months after the surgery minus the preoperative weight to estimate nutritional status. EORTC QLQ-C30 and EORTC QLQ-OES18 scales were also included in the questionnaire to assess the quality of life [25, 26].

Ethics Approval

The Institutional Review Board of West China Hospital of Sichuan University approved the protocol of this study. Patients’ informed consent was waived due to the retrospective nature of this study. The IRB number and date of approval are as follows: 95, January 16, 2024. We also followed the ethics standards defined by the Helsinki Declaration to conduct this study.

Statistical Analysis

Means ± standard deviation or median and upper and lower quartiles were used to describe continuous variables, and frequency was used for categorical variables. Differences in continuous variables between the NA and CA arms were compared using student’s t-tests or Mann-Whitney U test. Differences in categorical variables were analyzed using Pearson’s chi-square, Fisher’s exact test, or Mann-Whitney U test.

Propensity score-matching (PSM) with the nearest neighbor matching method was used to select patients from the control arm who matched patients in the experimental arm. Age, sex, body mass index (BMI), absence or presence of comorbidities, tumor location at upper/middle/lower thoracic cavity, clinical T stage ≥ 3 or not before treatment, and neoadjuvant treatment (Yes/No) were used for matching. Logistic regression analysis was performed to identify independent risk factors for the incidence of gastroesophageal reflux. P-value of 2-sided test < 0.05 was considered significant. All statistical analyses were performed using SPSS 27.0 software (IBM Corp, Armonk, NY) and R version 4.2.3.

Patients’ Characteristics

Figure 3 presents the flow chart of patients’ selection. After searching the database, 256 patients meeting the inclusion criteria were identified for further assessment. Four patients with jejunum as a substitution for esophagus, 7 patients with malignancy history within the last 5 years, and 27 patients lacking 6-month follow-up data were excluded. Finally, 218 patients were included, consisting of 155 patients in the NA arm and 63 patients in the EA arm. In the unmatched cohort, 79.4% of patients in the NA arm and 84.1% of patients in the EA arm were male. Participants’ age was 63.43 ± 7.53 years in the NA arm and 62.16 ± 9.56 years in the EA arm. The proportion of patients receiving neoadjuvant therapy was 46.5% in the NA arm and 74.6% in the EA arm. All baseline characteristics except for neoadjuvant therapy were comparable between the arms. The complete baseline characteristics of participants are shown in Supplementary table 1. As mentioned above, a fully matched cohort was designed using PSM with 63 patients in each arm. The matching quality is shown in Table 1.

Table 1

Propensity score matching details
		Unmatched cohorts				Matched cohorts
		Non-embedded anastomosis	Embedded anastomosis	P-value	test SMD	Non-embedded anastomosis	Embedded anastomosis	P-value	test SMD
n		155	63			63	63
Sex (%)	Male	32 (20.6)	10 (15.9)	0.535	0.124	9 (14.3)	10 (15.9)	1	0.044
	Female	123 (79.4)	53 (84.1)			54 (85.7)	53 (84.1)
Age (mean (SD))		63.43 (7.52)	62.16 (9.56)	0.297	0.148	63.16 (7.41)	62.16 (9.56)	0.513	0.117
BMI (mean (SD))		22.74 (2.81)	22.75 (3.19)	0.972	0.005	22.82 (2.86)	22.75 (3.19)	0.904	0.022
Neoadjuvant therapy	No	83 (53.5)	16 (25.4)	<0.001	0.601	16 (25.4)	16 (25.4)	1	<0.001
	Yes
Clinical T stage ≥ 3	No	70 (45.2)	24 (38.1)	0.421	0.144	23 (36.5)	24 (38.1)	1	0.033
	Yes	85 (54.8)	39 (61.9)			40 (63.5)	39 (61.9)
Comorbidities (%)	No	86 (55.5)	37 (58.7)	0.774	0.066	37 (58.7)	37 (58.7)	1	<0.001
	Yes	69 (44.5)	26 (41.3)			26 (41.3)	26 (41.3)
Tumer location (%)		10 (6.5)	7 (11.1)	0.242	0.247	7 (11.1)	7 (11.1)	0.981	0.035
		106 (68.4)	36 (57.1)			37 (58.7)	36 (57.1)
		39 (25.2)	20 (31.7)			19 (30.2)	20 (31.7)
BMI: body mass index

Perioperative Events and Pathological Findings

Before PSM, surgical time or blood loss was comparable between the two arms. The most common complication was pulmonary infection, occurring in 49 (31.6%) of patients in the NA arm and in 16 (25.4%) of patients in the EA arm (P = 0.36). Patients in the two arms had no difference in terms of other complications. Table 2 shows that after PSM, EA did not increase the average duration of surgery or the volume of blood loss (278.14 ± 49.37 minutes vs. 270.41 ± 46.36 minutes (P = 0.37); 51.11 ± 22.66 mL vs. 46.67 ± 20.40 mL (P = 0.249) in the NA arm and the EA arm, respectively). In the matched cohort, the incidence of postoperative complications, return to intensive care unit (ICU) rate, and hospital stay after surgery were also comparable between the two arms. Tumor residues observed under the naked eye or microscope were found in only one patient in the EA arm.

Table 2

Perioperative data of patients undergoing Mckeown esophagectomy after propensity score matching.
		Non-embedded anastomosis n = 63	Embedded anastomosis n = 63	P-value
Operation time, min Mean ± SD		278.14 ± 49.37	270.41 ± 46.36	0.37
Blood loss, ml Mean ± SD		51.11 ± 22.655	46.67 ± 20.40	0.249
Conversion to open		0(0%)	0(0%)
Complication
	Anastomotic leakage	2(3.2%)	1(1.6%)	1
	Pneumothorax requiring thoracocentesis	(0%)	0(0%)
	Hydrothorax requiring thoracocentesis	4(6.3%)	3(4.8%)	1
	Pulmonary Infection	20(31.7%)	16(25.4%)	0.43
	Cerebral Infarction	0(0%)	0(0%)
	Recurrent laryngeal nerve injury	0(0%)	1(1.6%)	1
	Other	3(4.8%)	3(4.8%)	1
Hospital stay after surgery		9(8,13)	8(7,12)	0.628
Back to ICU		4(6.3%)	4(6.3%)	1
Radicality				1
	R0	63(100%)	62(98.4%)
	R1	0(0%)	1(1.6%)
	R2	1(0%)	0(0%)
Tumor regression grade				0.64
	0	19(30.2%)	13(20.6%)
	1	7(11.1%)	8(12.7%)
	2	14(22.2%)	14(22.2%)
	3	7(11.1%)	12(19%)
	No neoadjuvant therapy	16(25.4%)	16(25.4%)
Local invasion				0.632
	None	48(76.2%)	44(69.8%)
	Neurologic	9(14.3%)	9(14.3%)
	Lymphatic vascular	3(4.8%)	3(4.8%)
	Both	3(4.8%)	7(11.1%)
PSM: Propensity score matching; ICU: intensive care unit.

Anastomotic Leakage

In the unmatched cohort, 1 (1.6%) patient in the EA arm and 8 (5.2%) patients in the NA arm developed anastomotic leakage (P = 0.408). All patients with anastomotic leakage were treated with conservative treatments, such as total parenteral nutrition and antibiotics. After PSM, 2 (3.2%) patients in the NA arm experienced anastomotic leakage (P = 1).

Gastroesophageal Reflux

Before PSM, embedded anastomosis was superior to non-embedded anastomosis in terms of reflux frequency (P = 0.013). Extra complaints in the NA arm focused on regurgitation. There was no significant difference regarding PPI usage (used by 11 (7.1%) patients in the NA arm and 5 (7.9%) patients in the EA arm). 41(65.1%) patients in the non-embedded anastomosis arm and 51 (81%) patients in the embedded anastomosis arm slept in the supine position without reflux (P = 0.045). Participants in the EA arm had a flatter sleeping posture (P < 0.001), and 95.2% of participants in the EA arm and 69% of participants in the NA arm retained normal pillow height. The follow-up data of cohorts after PSM are shown in Table 3. The proportion of reflux-free participants in the NA arm increased to 68.3%, without a significant difference. Other differences remained significant. Especially, orty-one (65.1%) patients in the non-embedded anastomosis arm and fifty-one (81%) patients in the embedded anastomosis arm slept in the supine position without reflux (P = 0.045). As is shown in Table 4, the multivariable logistic regression analyses before/after PSM both showed that non-embedded anastomosis was an independent risk factor [OR (95%CI) before PSM: 2.517(1.212,5.227), P = 0.013; after PSM: 2.539(1.084,5.949), P = 0.032] for gastroesophageal reflux (Yes/No).

Table 3

Follow-up data of patients undergoing Mckeown esophagectomy after propensity score matching.
			Non-embedded anastomosis n = 63	Embedded anastomosis n = 63	P-value
Reflux frequency, n(%)					0.390
	None		43(68.3%)	51(81%)
	Once or twice a month		16(25.4%)	9(14.3%)
	Once a week		2(3.2%)	2(3.2%)
	Two times a week or more		2(3.2%)	1(1.6%)
VAS-regurgitation			0(0,2)	0(0,0)	0.009 ^e
VAS-heartburn			0(0,0)	0(0,0)	0.981
Cough, n(%)			4(6.3%)	0(0%)	0.127
Aspiration pneumonia, n(%)			2(3.2%)	2(3.2%)	1.000
PPI usage, n(%)			3(4.8%)	5(7.9%)	0.715
Scenarios where reflux occurs, n(%)					<0.001 ^e
	No reflux in the supine position		41(65.1%)	51(81%)
	Fasting reflux in the supine position		0(0%)	9(14.3%)
	Postprandial reflux in the supine position		1(1.6%)	0(0%)
	Fasting reflux in the slope position		21(33.3%)	3(4.8%)
	Postprandial reflux in the slope position		0(0%)	0(0%)
Head alleviation during sleep, n(%)					<0.001 ^e
	1 pillow		44(69.8%)	60(95.2%)
	2 pillows		12(19%)	1(1.6%)
	3 pillows		6(9.5%)	1(1.6%)
	4 pillows or more		1(1.6%)	1(1.6%)
Burping difficulty, n(%)			1(1.6%)	0(0%)	1.000
Postprandial fullness frequency, n(%)					0.115
	None		57(90.5%)	62(98.4%)
	Once or twice a month		5(7.9%)	1(1.6%)
	Once a week		1(1.6%)	0(0%)
	Two or three times a week or more		0(0%)	0(0%)
Time for fullness to relieve, n(%)					0.120
	no fullness		57(90.5%)	62(98.4%)
	1 hour		6(9.5%)	1(1.6%)
	2 hours		0(0%)	0(0%)
	3 hours or more		0(0%)	0(0%)
		0.073
	no fullness		57(90.5%)	62(98.4%)
	yes		4(6.3%)	0(0%)
	no		2(3.2%)	1(1.6%)
Mellow-Pinkas score					1.000
	Able to eat normal diet/no dysphagia		47(74.6%)	47(74.6%)
	Able to swallow some solid foods		15(23.8%)	14(22.2%)
	Able to swallow only semisolid foods		0(0%)	1(1.6%)
	Able to swallow liquids only		1(1.6%)	1(1.6%)
	Unable to swallow anything/total dysphagia		0(0%)	0(0%)
Food intake, n(%)					1.000
	200 grams		61(96.8%)	62(98.4%)
	400 grams		2(3.2%)	1(1.6%)
	600 grams or more		0(0%)	0(0%)
Weight loss compared with baseline			2(1, 6)	4(1,7)	0.331
PSM: Propensity score matching; VAS: visual analogue scale; ^e statistically significant (P < 0.05).

Table 4

Multivariable analyses in cohorts after propensity score matching to investigate potential factors influencing the gastroesophageal reflux incidence.
		OR (95% CI)	P value
Anastomosis		2.539(1.084,5.949)	0.032 ^e
Sex		2.622(0.886,7.758)	0.082
Age		0.962(0.909,1.018)	0.182
BMI		0.997(0.865,1.148)	0.962
Neoadjuvant therapy		1.988(0.698,5.659)	0.198
Clinical T stage ≥ 3		0.558(0.218,1.432)	0.225
Commorbidity		0.817(0.323,2.062)	0.668
Tumer location	Lower thoracic
	Middle thoracic	0.901(0.184,4.425)	0.898
	Upper thoracic	1.038(0.396,2.719)	0.939
BMI: body mass index; ^e statistically significant (P < 0.05).

Dysphagia and Nutritional Status

Before PSM, the Mellow-Pinks scores were comparable between the NA arm and the EA arm, and 69.7% and 74.6% of patients could eat solid food in the NA and EA arms, respectively (P = 0.471). Food intake was not significantly different between the two groups. Compared with baseline, median weight loss and the lower and upper quartiles were 3 (2,7) and 4 (1,7) kilograms. There was no significant difference regarding dysphagia and nutritional status after PSM.

Quality of life

In the unmatched cohort, the mean diarrhea score was higher in the EA arm than in the NA arm [10.32 ± 23.89 vs. 18.52 ± 30.40, P = 0.036]. Similar findings were observed in the matched cohort [6.88 ± 19.08 vs 18.52 ± 30.4. P = 0.011]. Table 5 shows the results of QoL analysis after PSM. Although none of the domains of OES-18 was significantly different between the two arms before PSM, a significant difference was presented in the pain domain after PSM (6.35 ± 12.58 vs 2.65 ± 5.89, P = 0.036).

Table 5

Quality of life of patients undergoing Mckeown esophagectomy after propensity score matching.
	Non-embedded anastomosis n = 63	Embedded anastomosis n = 63	P-value
EORTC QLQ-C30
Functional scales
Physical functioning	94.07 ± 20.08	96.72 ± 13.16	0.383
Role functioning	93.65 ± 22.29	95.77 ± 18.44	0.563
Emotional functioning	94.58 ± 9.37	94.44 ± 9.23	0.936
Cognitive functioning	97.89 ± 6.34	94.97 ± 21.72	0.309
Social functioning	95.50 ± 13.78	98.94 ± 5.07	0.065
Symptom Scales
Fatigue	9.00 ± 23.00	7.23 ± 17.07	0.626
Nausea and vomiting	5.82 ± 19.67	8.73 ± 23.92	0.457
Pain	9.79 ± 21.30	6.61 ± 15.99	0.346
Dyspnoea	10.05 ± 24.42	4.23 ± 11.19	0.089
Insomnia	14.29 ± 32.08	10.05 ± 25.84	0.416
Appetite Loss	5.82 ± 20.34	5.29 ± 16.07	0.872
Constipation	3.17 ± 14.31	1.59 ± 12.6	0.51
Diarrhoea	6.88 ± 19.08	18.52 ± 30.4	0.011 ^e
Financial Difficulties	4.23 ± 11.19	1.59 ± 7.16	0.117
Global health status	80.29 ± 15.58	78.97 ± 14.81	0.626
EORTC QLQ-OES18
OESDYS	3.36 ± 9.28	2.12 ± 7.16	0.405
OESEAT	7.80 ± 10.46	3.24 ± 10.99	1
OESRFX	9.26 ± 17.90	14.29 ± 22.37	0.166
OESPA	6.35 ± 12.58	2.65 ± 5.89	0.036 ^e
OESSV	0 ± 0	0.53 ± 4.2	0.319
OESCH	4.23 ± 11.19	6.88 ± 17.1	0.306
OESDM	3.17 ± 14.31	6.35 ± 16.78	0.255
OESTA	5.29 ± 17.15	3.7 ± 14.8	0.579
OESCO	0 ± 0	0 ± 0
OESSP	0.53 ± 4.20	0 ± 0	0.319
^e statistically significant (P < 0.05).

Surgical margin is undoubtedly associated with the survival of patients after surgery [6]. In the present study, CAR anastomosis showed overall non-inferiority in terms of negative cutting edge at both esophageal and gastric ends, although the extra length of the esophageal stump is needed. For tumors located in the lower cervical or upper thoracic esophageal region, the upper end of the esophagus should reach the lower end of the pharynx to guarantee a tumor-free cutting edge for anastomosis. If necessary, the length of the inserted mucosa and esophagus can be reduced to ensure a clean cutting edge. The shortest length was 1.2 cm in this study. CAR anastomosis has another limitation. Handsewn anastomosis can hardly be applied in Ivor-Lewis esophagectomy.

Anastomotic leakage is one of the most devastating postoperative complications. It can be influenced by many factors, such as nutritional status, blood supply of the tubularized stomach, adjuvant treatment, anastomotic technique, etc [20, 27]. These factors may also interact with each other. Even though the sample size limited the power to distinguish the difference between CAR anastomosis and traditional anastomosis, the low incidence of anastomotic leakage was sufficient to consider CAR anastomosis as a safe anastomosis technique.

The diameter of the stoma should be meticulously controlled to prevent both gastroesophageal reflux and dysphagia. Dysphagia can annoy patients by making them uncomfortable after traditional anastomosis, even after mitigating reflux [19]. It may also limit nutrient intake when food intake is confined to liquids. The poor nutritional status can also influence survival [12, 28]. The wider diameter of the gastric tube and slimmer intussuscepted tissue may determine the patency of CAR anastomosis. In addition, the valve formed by the intussuscepted tissue keeps the flow direction of gastric contents downward [21].

QoL assessment plays a pivotal role in the symptomatic management of diseases like gastroesophageal reflux. Lifestyle modification, including lifting the head up during sleeping and leaving intervals between meals and lying, is the primary measure to deal with regurgitation and heartburn. Proton pump inhibitors should be considered if the symptoms remain unbearable after dietary and behavioral modifications [29, 30]. The reflux domain of the EORTC QLQ-OES18 was used to distinguish the effect of the two anastomoses in this study because the accuracy of the brief assessment can be affected by behavioral factors. The clarification of detailed behavioral factors may help understand the true severity of gastroesophageal reflux.

There were a few limitations to the present study. Firstly, the retrospective nature of this study increased the risk of biases and confounding factors even after using PSM. Secondly, the follow-up interval was short and did not allow us to analyze the survival benefits. Thirdly, more objective assessments, such as 24-h PH surveillance and gastroscopy, can help more effectively measure the reflux-preventing effects. Nevertheless, subjective symptoms remain the gold standard for diagnosing gastroesophageal reflux, and invasive objective assessment tools are not acceptable for most patients [31].

Cross-bedded anti-reflux anastomosis can be applied in esophagectomy for esophageal cancer with a lower risk of anastomotic leakage and dysphagia, better gastroesophageal reflux control, and improved QoL compared with non-intussuscepted anastomosis.

BMI

body mass index

CAR

Cross-bedded Anti-reflux Anastomosis

Embedded anastomosis

ICU

intensive care unit

Non-embedded anastomosis

PSM

Propensity score matching

QoL

Quality of life

Ethics approval and consent to participate

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Funding

Not applicable.

Author Contribution

(I) Conceptualization and design: Yang Hu; (II) Administrative support: Yang Hu; (III) Provision of study materials or patients: Yong Yuan, Longqi Chen, Wenping Wang; (IV) Collection of data: Na Wu, Lei Wang, Yu Zeng, Yutian Lai, Qi Xia, Dong Tian, Zheng Liu, Xiaolong Zhang, Wei-peng Hu, Pei-song Yuan, Xianyu Wu, Wen Yang; (V) Data analysis and interpretation: Na Wu, Lei Wang; (VI) Manuscript writing: Na Wu, Lei Wang; (VII) Final approval of manuscript: All authors. Na Wu and Lei Wang contributed to this article equally and should be considered as co-first authors. The images in this article were created by Bohai Yu. The authors would like to express our gratitude to Editsprings (http://editsprings.cn) for the expert linguistic services provided.

Acknowledgement

Na Wu and Lei Wang contributed to this article equally and should be considered as co-first authors. The images in this article were created by Bohai Yu. The authors would like to express our gratitude to Editsprings (http://editsprings.cn) for the expert linguistic services provided.

Data Availability

The datasets used and analyzed for the current study will be available from the corresponding author upon proper request.

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Gastroesophageal Reflux after Mckeown Esophagectomy with Embedded or Non- embedded Anastomosis: a Propensity Score Matched Cohort Study

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