Vascular calcification does not predict anastomotic leak or conduit necrosis following oesophagectomy

Table 1 Details of how calcification scores were allocated to each vessel

Site	Score 1 (Minor calcification)	Score 2 (Major calcification)
Proximal aorta	Nine or fewer foci and Three or fewer foci extending over three or more sections	More than nine foci or More than three foci extending over three or more sections
Coeliac trunk	Calcifications extending over 3 or fewer sections and Maximal cross- sectional diameter of a single focus less than 10mm	Calcifications extending over three or more sections and maximal cross sectional diameter of a single focus greater than 10mm or Calcifications involving both the proximal and distal parts
Right post	One or more calcifications	NA
Coeliac arteries
Left post	One or more calcifications	NA
Coeliac arteries
Distal aorta	Nine or fewer foci and Three or fewer foci extending over three or more sections	More than nine foci or More than three foci extending over three or more sections or Subjectively assessed as having heavy calcifications
Aortic bifurcation	Calcifications affecting less than 40% of the circumference of the vessel	Calcifications affecting more than 40% of the circumference of the vessel

For each site, a score of zero was assigned in cases where there were no calcifications. A focus refers to a distinct area of calcification. Section refers to a single computed tomography image in the axial plane

Table 2 Patient demographics and comorbidities

	n	Statistic
Age at surgery (yr)	413	64.8 ± 9.5
Gender	413
Female		87 (21.1)
Male		326 (78.9)
BMI (kg/m2)	402	26.8 ± 4.9
ASA	397
1		78 (19.6)
2		222 (55.9)
3		89 (22.4)
4		8 (2.0)
ECOG status	324
0		146 (45.1)
1		142 (43.8)
2		36 (11.1)
Ischemic heart disease	412
No		360 (87.4)
Yes		52 (12.6)
Renal impairment	412
No		408 (99.0)
Yes		4 (1.0)
Diabetes	412
No		364 (88.3)
Yes		48 (11.7)
COPD	412
No		381 (92.5)
Yes		31 (7.5)
Previous cancer	412
No		393 (95.4)
Yes		19 (4.6)
Significant smoking history	412
No		354 (85.9)
Yes		58 (14.1)
Alcohol misuse/ heavy drinker	412
No		404 (98.1)
Yes		8 (1.9)

Data are reported as n (%), mean ± SD, or as median (IQR), as applicable. BMI: Body mass index; ASA: American Society of Anaesthesiologists grade; ECOG: Eastern Cooperative Oncology Group Performance Status; COPD: Chronic obstructive pulmonary disease.

Table 3 Disease and treatment-related factors

	n	Statistic
Neoadjuvant chemotherapy	413
No		69 (16.7)
Yes		344 (83.3)
Mandard score	387
Mandard 1 (Complete)		20 (5.2)
Mandard 2		26 (6.7)
Mandard 3		69 (17.8)
Mandard 4		115 (29.7)
Mandard 5 (None)		88 (22.7)
No Chemo		69 (17.8)
Operation stages	413
Two-stage		379 (91.8)
Three-stage		34 (8.2)
Operation type	413
Hybrid		224 (54.2)
MIO		103 (24.9)
Open		86 (20.8)
Type of Tumour	409
Adenocarcinoma		322 (78.7)
Adenosquamous		8 (2.0)
Squamous		65 (15.9)
Other		14 (3.4)
T-stage	410
T0		17 (4.1)
T1		43 (10.5)
T2		51 (12.4)
T3		274 (66.8)
T4		25 (6.1)
N-stage	412
N0		154 (37.4)
N1		171 (41.5)
N2		54 (13.1)
N3		33 (8.0)
M-stage	405
M0		396 (97.8)
M1		9 (2.2)
R-status	407
R0		255 (62.7)
R1		141 (34.6)
R2		11 (2.7)
Peri-neural invasion	314
No		207 (65.9)
Yes		107 (34.1)
Lymph nodes total	412	30.3 ± 10.8
Lymph nodes involved	412	1 (0-4)

Data are reported as n (%), mean ± SD, or as median (IQR), as applicable. Mandard Score is a measure of tumour regression due to chemotherapy, with a score of 1 being complete regression, and 5 being no regression. MIO: Minimally invasive oesophagectomies.

Table 4 Predictive accuracy of calcification scores

		Anastomotic leak			Conduit necrosis
	Distributio nof scores	n/n(%)	AUROC (SE)	P Value	n/n (%)	AUROC (SE)	P value
Proximal	n = 4121		0.518 (0.039)	0.652		0.559 (0.067)	0.454
0	159 (38.6)	24/159 (15.1)			3/159 (1.9)
1	199 (48.3)	31/197 (15.7)			10/197 (5.1)
2	54 (13.1%)	10/54 (18.5)			1/54 (1.9)
Coeliac	n = 4131		0.514 (0.039)	0.714		0.570 (0.083)	0.374
0	316 (76.5)	48/315 (15.2)			9/315 (2.9)
1	91 (22.0)	17/90 (18.9)			4/90 (4.4)
2	6 (1.5)	0/6 (0.0)			1/6 (16.7)
R Post Coeliac	n = 4131		0.502 (0.039)	0.951		0.486 (0.077)	0.860
0	401 (97.1)	63/400 (15.8)			14/400 (3.5)
1	12 (2.9)	2/11 (18.2)			0/11 (0.0)
L Post Coeliac	n = 4131		0.492 (0.039)	0.840		0.443 (0.072)	0.465
0	337 (81.6)	54/336 (16.1)			13/336 (3.9)
1	76 (18.4)	11/75 (14.7)			1/75 (1.3)
Distal	n = 3801		0.499 (0.040)	0.990		0.582 (0.076)	0.297
0	50 (13.2)	6/50 (12.0)			1/50 (2.0)
1	191 (50.3)	33/191 (17.3)			6/191 (3.1)
2	139 (36.6)	20/137 (14.6)			7/137 (5.1)
Bifurcation	n = 3801		0.545 (0.040)	0.275		0.492 (0.077)	0.921
0	108 (28.4)	13/108 (12.0)			4/108 (3.7)
1	182 (47.9)	30/181 (16.6)			7/181 (3.9)
2	90 (23.7)	16/89 (18.0)			3/89 (3.4)

¹The number of patients for whom the score was recorded. P-values are from the ROC curve analyses. AUROC: Area under the ROC curve. Analyses of outcomes exclude n = 2 patients for whom complication data were not available.

Table 5 Predictive accuracy of calcification scores with respect to composite outcomes

	n	Anastomotic leak or conduit necrosis			Anastomotic leak and conduit necrosis
		n (%)	AUROC (SE)	P value	n (%)	AUROC (SE)	P value
Proximal			0.518 (0.038)	0.634		0.574 (0.079)	0.426
0	159	25 (15.7)			2 (1.3)
1	197	34 (17.3)			7 (3.6)
2	54	10 (18.5)			1 (1.9)
Coeliac			0.525 (0.039)	0.517		0.532 (0.094)	0.731
0	315	50 (15.9)			7 (2.2)
1	90	18 (20.0)			3 (3.3)
2	6	1 (16.7)			0 (0.0)
R Post			0.501 (0.038)	0.972		0.486 (0.090)	0.882
0	400	67 (16.8)			10 (2.5)
1	11	2 (18.2)			0 (0.0)
L Post			0.486 (0.038)	0.716		0.458 (0.087)	0.648
0	336	58 (17.3)			9 (2.7)
1	75	11 (14.7)			1 (1.3)
Distal			0.501 (0.039)	0.976		0.605 (0.081)	0.259
0	50	7 (14.0)			0 (0.0)
1	191	34 (17.8)			5 (2.6)
2	137	22 (16.1)			5 (3.6)
Bifurcation			0.544 (0.039)	0.272		0.481 (0.091)	0.841
0	108	14 (13.0)			3 (2.8)
1	181	32 (17.7)			5 (2.8)
2	89	17 (19.1)			2 (2.2)

P values are from the ROC curve analyses. AUROC: Area under the ROC curve.

Table 6 Summary of existing literature

Author (Year)	Type of Oesophagecto-my	n1	Anastomotic leak rate	Conduit ischaemia rate	Arterial vessels assessed	Association with anastomotic leakage or gastric conduit necrosis	Definition of anastomotic leak
van Rossum et al[7], 2015	3-stage	246	24%	NA	Aorta, coeliac trunk, right and left post-coeliac arteries	Aorta and right post coeliac calcification associated with leakage	Defined by either extravasation of water-soluble contrast material during a contrast material swallow study or CT scan, visualization of anastomotic dehiscence or fistulae during endoscopy, or visible loss of saliva through the cervical wound
Zhao et al[8], 2016	3-stage	709	17.20%	NA	Aorta, coeliac trunk, right and left post-coeliac arteries	Aorta and coeliac artery calcifications associated with leakage	Anastomotic leakage was clinically suspected, a CT scan, water-soluble contrast swallow study or endoscopy was performed
Goense et al[9], 2016	2-stage	167	24%	NA	Aorta, coeliac trunk, right and left post-coeliac arteries	Aortic calcification associated with leakage	Clinical signs of leakage from a thoracic drain, radiologic signs of leakage, including contrast leakage or fluid and air levels surrounding the anastomosis, or signs of anastomotic dehiscence during endoscopy or reoperation
Lainas et al[12], 2017	2-Stage	481	NA	2.10%	Coeliac Trunk	Extrinsic and intrinsic stenosis of the coeliac artery associated with gastric conduit necrosis	NA
Chang et al[10], 2018	2-stage	164	8.50%	NA	Aorta, coeliac trunk, right and left post-coeliac arteries	Calcification showed no association with leakage, coeliac trunk stenosis was associated with leakage	Anastomotic dehiscence confirmed during endoscopy or operation
Borggreve et al[11], 2018	3-stage	406	25.60%	NA	Coronary, supra-aortic, thoracic aorta, coeliac axis, abdominal arota, common iliac external iliac arteries; aortic valve	Calcification of coronary arteries, supra-aortic arteries, and thoracic aorta associated with leakage	Visible loss of saliva through the cervical wound, extravasation of water-soluble contrast material during a contrast swallow study or CT scan, or visualization of anastomotic dehiscence or fistulae during endoscopy or surgical re-intervention

¹Number of patients included in the study. CT: Computed tomography; NA: Not reported.