Barrett’s esophagus with high grade dysplasia is associated with non-esophageal cancer

Table 1 Demographic, endoscopic and histologic characteristics of the study population

Patient data	All sample (n = 386)	HGD (n = 12)	Non-HGD (n = 367)
Age at study inclusion	60.0 (13.1) [61.1, 18.4-89.6]	66.3 (12.8) [66.6, 42.4-85.8]	59.8 (13.2) [60.6, 18.4-89.6]
Gender - male	268 (69.43)	9 (75)	253 (68.94)
Number of endoscopies per patient	2.5 (2.0) [2, 1-17]	6.6 (2.6) [7, 3-11]	2.4 (1.7) [2, 1-10]b
Patients with multiple endoscopies	245 (63.47%)	12 (100)	227 (61.9)a
Circumferential extent of BE (cm)	3.3 (3.3) [2, 0-19]	4.5 (2.92) [4.5, 1-11]	3.2 (3.23) [2, 0-19]
Maximal extent of BE (cm)	4.4 (3.2) [3, 0.2-20]	6.0 (3.22) [6, 2-14]	4.25 (3.17) [3, 0.2-20]a
Presence of endoscopic abnormalities	56 (14.51)	8 (66.67)	44 (11.99)b
Ultra-short BE segment (BE < 1 cm)	28 (7.43)	0 (0)	28 (7.8)
Short BE segment (1 cm ≤ BE < 3 cm)	124 (32.89)	2 (18.18)	122 (33.98)
Long BE segment (BE ≥ 3 cm)	225 (59.68)	9 (81.82)	209 (58.22)
Worst degree of dysplasia
Esophageal adenocarcinoma	6 (1.6)
Intramucosal carcinoma	1 (0.3)
High grade dysplasia	12 (3.1)
Low grade dysplasia	19 (4.9)

Continuous variables were presented as mean (SD) and [median, range]. Categorical variables are presented as n (%). Statistical difference refers to the HGD and non-HGD groups.

^aP < 0.01;

^bP < 0.001. BE: Barrett’s esophagus; HGD: High grade dysplasia; Non-HGD: Low grade or without dysplasia.

Table 2 Overall cancer cases, stratified to pre-study and incident cases n (%)

	Pre-study cancers	Incident cancers	Lifetime cancers
Esophagus	2 (0.5)2	4 (1)	6 (1.6)
Cardia	2 (0.5)	3 (0.8)	5 (1.3)
Stomach	3 (0.8)	0 (0)	3 (0.8)
Colorectal cancer	9 (2.3)	1 (0.3)	10 (2.6)
Small intestine	1 (0.3)	0 (0)	1 (0.3)
Cholangiocarcinoma	1 (0.3)	0 (0)	1 (0.3)
Pancreas	0 (0)	2 (0.5)	2 (0.5)
Bladder	5 (1.3)	4 (1)	9 (2.3)
Prostate	11 (2.8)	0 (0)	11 (2.8)
Kidney	2 (0.5)	2 (0.5)	4 (1)
Hematologic cancer	8 (2.07)	4 (1)	12 (3.1)
Skin	4 (1)	2 (0.5)	6 (1.6)
Breast	4 (1)	2 (0.5)	6 (1.6)
Thyroid	3 (0.8)	0 (0)	3 (0.8)
Lung	0 (0)	2 (0.5)	2 (0.5)
Kaposi	0 (0)	1 (0.3)	1 (0.3)
Laryngeal	3 (0.8)	0 (0)	3 (0.8)
Cervical	1 (0.3)	0 (0)	1 (0.3)
Any type of cancer	59 (15.3)	27 (7)	86 in 75 (19.4) patients1
BE cancer	3 (0.8)	7 (1.8)	10 in 10 (2.6) patients
Non-BE cancers	56 (14.5)	20 (5.2)	76 in 65 (16.8) patients

¹There were 9 patients with 2 lifetime cancers, and one with 3 cancer cases;

²One patient had a pre-study diagnosis of esophageal squamous cell carcinoma (thus, not counted as BE related and not included in the outcome analysis for non-BE cancer free survival). BE: Barrett’s esophagus.

Table 3 Univariate and multivariable Cox regression for the prediction of non- Barrett’s esophagus cancers

n = 379 (excluding EAC and IMC)	HR (95%CI)	Adjusted HR (95%CI)
Age at study inclusion1	1.11 (0.99-1.24)	1.07 (0.95-1.21)
Gender - male	2.19 (0.63-7.55)
Number of endoscopies per patient	0.82 (0.59-1.12)	0.72 (0.50-1.03)
Presence of endoscopic abnormalities	1.19 (0.34-4.09)
Circumferential extent of BE (cm)	0.99 (0.79-1.26)
Maximal extent of BE (cm)	1.06 (0.92-1.23)
Ultra-short segment (BE < 1 cm)	1
Short segment (1 cm ≤ BE < 3 cm)	0.96 (0.11-8.24)
Long segment (BE ≥ 3 cm)	0.99 (0.13-7.85)
Pre-study cancer history	2.58 (0.92-7.25)	2.12 (0.73-6.17)
HGD vs non-HGD	3.40 (0.78-14.84)	8.32 (1.35-51.33)a

^aP < 0.05;

¹For a 3-year increase. BE: Barrett’s esophagus; HGD: High grade dysplasia; Non-HGD: Low grade or without dysplasia; EAC: Esophageal adenocarcinoma; IMC: Intramucosal carcinoma.

Table 4 Univariate and multivariable Cox regression for the prediction of any cancer

n = 386 (including EAC and IMC)	HR (95%CI)	Adjusted HR (95%CI)
Age at study inclusion1	1.09 (0.99-1.20)	1.08 (0.97-1.21)
Gender - male	2.29 (0.79-6.67)
Number of endoscopies per patient	1.11 (0.96-1.29)	0.99 (0.82-1.21)
Presence of endoscopic abnormalities	2.27 (0.95-5.44)
Circumferential extent of BE (cm)	1.10 (0.96-1.26)
Maximal extent of BE (cm)	1.12 (1.008-1.24)a	1.13 (1.000-1.27)
Ultra-short segment (BE < 1cm)	1
Short segment (1 cm ≤ BE < 3 cm)	0.97 (0.11-8.30)
Long segment (BE ≥ 3 cm)	1.77 (0.23-13.34)
Pre-study cancer history	2.15 (0.86-5.39)
HGD vs non-HGD	6.33 (2.37-16.91)b	4.28 (1.17-15.76)a

^aP < 0.05,

^bP < 0.01.

¹For a 3-year increase. BE: Barrett’s esophagus; EAC: Esophageal adenocarcinoma; IMC: Intramucosal carcinoma; HGD: High grade dysplasia; Non-HGD: Low grade or without dysplasia.