Identification of breath volatile organic compounds to distinguish pancreatic adenocarcinoma, pancreatic cystic neoplasm, and patients without pancreatic lesions

Table 1 Comparison of baseline characteristics between pancreatic adenocarcinoma, intraductal papillary mucinous neoplasm, and the control group

Variables	PDAC, n = 54	IPMN, n = 42	Normal pancreas, n = 60	P value
Age, mean ± SD	64.8 ± 10.4	63.2 ± 10.3	60.0 ± 10.6	0.057
Male, n (%)	25 (46.3)	20 (47.6)	24 (40.0)	0.695
Smoking, n (%)	7 (13.0)	5 (11.9)	8 (13.6)	0.970
Alcohol consumption, n (%)	16 (29.6)	14 (33.3)	16 (26.7)	0.768
Participants’ comorbidity, n (%)
HBV	1 (1.9)	4 (9.5)	4 (6.8)	0.258
HCV	0 (0.0)	0 (0.0)	2 (3.3)	0.198
NAFLD	1 (1.9)	3 (7.1)	8 (13.3)	0.071
CAD	2 (3.7)	2 (4.8)	5 (9.3)	0.441
ESRD	0 (0.0)	1 (2.4)	0 (0.0)	0.255
DM	3 (5.6)	4 (9.5)	0 (0.0)	0.066
HT	2 (3.7)	3 (7.1)	0 (0.0)	0.127
Old CVA	2 (3.8)	3 (7.1)	0 (0.0)	0.128
Laboratory results, mean ± SD
Albumin in g/dL	3.7 ± 0.7	3.8 ± 1.1	4.2 ± 0.3	0.002
Total bilirubin in mg/dL	5.7 ± 9.7	1.8 ± 4.6	0.7 ± 0.3	0.009
Aspartate aminotransferase in U/L	73.4 ± 115.1	26.0 ± 18.0	23.0 ± 7.4	0.001
Alanine aminotransferase in U/L	86.9 ± 156.1	23.4 ± 11.9	25.9 ± 14.8	< 0.001
Alkaline phosphatase in U/L	279.8± 412.6	95.2 ± 91.3	73.5 ± 22.5	< 0.001
INR	1.2 ± 0.2	1.2 ± 0.6	1.0 ± 0.1	0.009
Amylase	120.8 ± 160.0	82.0 ± 52.2	74.1 ± 16.3	0.879

CAD: Coronary artery diseases; CVA: Cerebrovascular disease; DM: Diabetes mellitus; ESRD: End-stage renal disease; HBV: Chronic hepatitis B virus infection; HCV: Chronic hepatitis C virus infection; HT: Hypertension; INR: International normalized ratio; IPMN: Intraductal papillary mucinous neoplasm; NAFLD: Non-alcoholic fatty liver disease; PDAC: Pancreatic ductal adenocarcinoma; SD: Standard deviation.

Table 2 Comparison of exhaled breath volatile organic compound levels between three groups¹

Variable	PDAC, n = 54	IPMN, n = 42	Normal pancreas, n = 60	P value2
1,4-pentadiene	0.34 ± 0.34	0.32 ± 0.28	0.32 ± 0.21	0.626
Acetone dimer	5.19 ± 0.74	4.49 ± 0.81	3.95 ± 0.86	< 0.001
Acetone monomer	3.99 ± 0.79	4.21 ± 0.59	4.07 ± 0.69	0.411
Acetonitrile	0.13 ± 0.05	0.14 ± 0.10	0.13 ± 0.06	0.544
Benzene	0.20 ± 0.15	0.19 ± 0.11	0.25 ± 0.19	0.336
Dimethyl sulfide	0.94 ± 0.40	0.74 ± 0.38	0.73 ± 0.40	0.008
Ethanol	0.25 ± 0.06	0.26 ± 0.05	0.26 ± 0.07	0.726
Isopropyl alcohol	0.31 ± 0.45	0.19 ± 0.23	0.20 ± 0.27	0.731
Toluene	0.56 ± 0.42	0.57 ± 0.52	0.50 ± 0.37	0.655

¹Volatile organic compounds levels are expressed as mean ± standard deviation in arbitrary unit;

²P value adjusted for multiple comparisons. IPMN: Intraductal papillary mucinous neoplasm; PDAC: Pancreatic ductal adenocarcinom.

Table 3 Comparison of exhaled breath volatile organic compound level between metastasis pancreatic adenocarcinoma and non-metastasis pancreatic adenocarcinoma¹

Variable	Metastasis, n = 30	Non-metastasis, n = 24	P value2
1,4-pentadiene	0.36 ± 0.24	0.31 ± 0.47	0.741
Acetone dimer	5.10 ± 0.92	5.26 ± 0.57	0.403
Acetone monomer	3.90 ± 0.82	4.08 ± 0.75	0.497
Acetonitrile	0.14 ± 0.05	0.12 ± 0.05	0.315
Benzene	0.19 ± 0.09	0.22 ± 0.20	0.932
Dimethyl sulfide	0.96 ± 0.41	0.92 ± 0.38	0.016
Ethanol	0.24 ± 0.05	0.26 ± 0.08	0.321
Isopropyl alcohol	0.39 ± 0.56	0.19 ± 0.18	0.308
Toluene	0.56 ± 0.45	0.57 ± 0.39	0.676

¹Volatile organic compounds levels are expressed as mean ± standard deviation in arbitrary unit;

²P value adjusted for multiple comparisons.

Table 4 Performance for pancreatic adenocarcinoma diagnosis of acetone dimer, CA19-9, and combination of acetone dimer and CA19-9

Biomarker	AUC	Cut off	Sensitivity, %	Specificity, %	Accuracy, %	NPV, %	PPV, %	P value1
CA19-9	0.796	28.75	76.7	88.4	85.3	83.3	88.4	-
Dimethyl sulfide	0.671	0.78	68.5	59.8	62.8	78.2	47.4	0.115
Dimethyl sulfide + CA19-9	0.823	0.31	80	76.7	57.0	84.6	70.6	0.555
Acetone dimer	0.910	4.97	87.0	92.2	90.4	93.1	85.5	0.116
Acetone dimer + CA19-9	0.936	0.29	96.7	86.0	90.4	97.4	82.9	0.020

¹P value when compared to the area under the receiver operating characteristic curve of CA19-9. NPV: Negative predictive value; PPV: Positive predictive value.