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

BACKGROUND: Volatile organic compounds (VOCs) are a promising potential biomarker that may be able to identify the presence of cancers. AIM: To identify exhaled breath VOCs that distinguish pancreatic ductal adenocarcinoma (PDAC) from intraductal papillary mucinous neoplasm (IPMN) and healthy volunteers. METHODS: We collected exhaled breath from histologically proven PDAC patients, radiological diagnosis IPMN, and healthy volunteers using the ReCIVA® device between 10/2021-11/2022. VOCs were identified by thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry and compared between groups. RESULTS: A total of 156 participants (44% male, mean age 62.6 ± 10.6) were enrolled (54 PDAC, 42 IPMN, and 60 controls). Among the nine VOCs identified, two VOCs that showed differences between groups were dimethyl sulfide [0.73 vs 0.74 vs 0.94 arbitrary units (AU), respectively; P = 0.008] and acetone dimers (3.95 vs 4.49 vs 5.19 AU, respectively; P < 0.001). After adjusting for the imbalance parameters, PDAC showed higher dimethyl sulfide levels than the control and IPMN groups, with adjusted odds ratio (aOR) of 6.98 (95%CI: 1.15-42.17) and 4.56 (1.03-20.20), respectively (P < 0.05 both). Acetone dimer levels were also higher in PDAC compared to controls and IPMN (aOR: 5.12 (1.80-14.57) and aOR: 3.35 (1.47-7.63), respectively (P < 0.05 both). Acetone dimer, but not dimethyl sulfide, performed better than CA19-9 in PDAC diagnosis (AUROC 0.910 vs 0.796). The AUROC of acetone dimer increased to 0.936 when combined with CA19-9, which was better than CA19-9 alone (P < 0.05). CONCLUSION: Dimethyl sulfide and acetone dimer are VOCs that potentially distinguish PDAC from IPMN and healthy participants. Additional prospective studies are required to validate these findings.

Volatile organic compounds for diagnosis of early hepatocellular carcinoma in at-risk patients.

BACKGROUND: Volatile organic compounds (VOCs) have been shown as promising biomarkers for hepatocellular carcinoma (HCC) diagnosis. We aimed to investigate the performance of VOCs for diagnosing early-stage HCC in patients at-risk for HCC. METHODS: VOCs were identified in exhaled breath samples collected from 87 early-stage HCC patients, 90 cirrhotic patients, and 72 HBV-infected patients using thermal desorption-gas chromatography/field-asymmetric ion mobility spectrometry. The VOC levels were compared between the three groups. An association between VOCs and HCC was determined using logistic regression analysis. Diagnostic performance of VOCs was estimated using the AUROC and compared to serum alpha-fetoprotein (AFP). RESULTS: The levels of acetone monomer, dimethyl sulfide, 1,4-pentadiene, isopropyl alcohol, and acetone dimer were significantly different between the three groups. After adjusting for liver function test and AFP, acetone dimer was significantly associated with HCC. Acetone dimer significantly outperformed AFP with 86.2 % vs. 61.2 % sensitivity, 87.6 % vs. 66.2 % specificity, 86.9 % vs. 63.5 % for accuracy, and AUROC of 0.908 vs. 0.665, p = 0.007, <0.001, <0.001, and 0.001, respectively, for differentiating between HCC and cirrhosis. CONCLUSION: Acetone showed a better performance than AFP for diagnosing early HCC in at-risk patients. Further studies to validate the utility of VOCs as an HCC surveillance tool are needed.

VOCs from Exhaled Breath for the Diagnosis of Hepatocellular Carcinoma.

BACKGROUND: Volatile organic compound (VOC) profiles as biomarkers for hepatocellular carcinoma (HCC) are understudied. We aimed to identify VOCs from the exhaled breath for HCC diagnosis and compare the performance of VOCs to alpha-fetoprotein (AFP). The performance of VOCs for predicting treatment response and the association between VOCs level and survival of HCC patients were also determined. METHODS: VOCs from 124 HCC patients and 219 controls were identified using the XGBoost algorithm. ROC analysis was used to determine VOCs performance in differentiating HCC patients from controls and in discriminating treatment responders from non-responders. The association between VOCs and the survival of HCC patients was analyzed using Cox proportional hazard analysis. RESULTS: The combination of 9 VOCs yielded 70.0% sensitivity, 88.6% specificity, and 75.0% accuracy for HCC diagnosis. When differentiating early HCC from cirrhotic patients, acetone dimer had a significantly higher AUC than AFP, i.e., 0.775 vs. 0.714, respectively, p = 0.001. Acetone dimer classified HCC patients into treatment responders and non-responders, with 95.7% sensitivity, 73.3% specificity, and 86.8% accuracy. Isopropyl alcohol was independently associated with the survival of HCC patients, with an adjusted hazard ratio of 7.23 (95%CI: 1.36-38.54), p = 0.020. CONCLUSIONS: Analysis of VOCs is a feasible noninvasive test for diagnosing and monitoring HCC treatment response.

Exhaled volatile organic compounds for diagnosis of hepatocellular carcinoma.

Volatile organic compounds (VOCs) profile for diagnosis and monitoring therapeutic response of hepatocellular carcinoma (HCC) has not been well studied. We determined VOCs profile in exhaled breath of 97 HCC patients and 111 controls using gas chromatography-mass spectrometry and Support Vector Machine algorithm. The combination of acetone, 1,4-pentadiene, methylene chloride, benzene, phenol and allyl methyl sulfide provided the highest accuracy of 79.6%, with 76.5% sensitivity and 82.7% specificity in the training set; and 55.4% accuracy, 44.0% sensitivity, and 75.0% specificity in the test set. This combination was correlated with the HCC stages demonstrating by the increased distance from the classification boundary when the stage advanced. For early HCC detection, d-limonene provided a 62.8% sensitivity, 51.8% specificity and 54.9% accuracy. The levels of acetone, butane and dimethyl sulfide were significantly altered after treatment. Patients with complete response had a greater decreased acetone level than those with remaining tumor post-treatment (73.38 ± 56.76 vs. 17.11 ± 58.86 (× 106 AU, p = 0.006). Using a cutoff of 35.9 × 106 AU, the reduction in acetone level predicted treatment response with 77.3% sensitivity, 83.3% specificity, 79.4%, accuracy, and AUC of 0.784. This study demonstrates the feasibility of exhaled VOCs as a non-invasive tool for diagnosis, monitoring of HCC progression and treatment response.