This study evaluated the feasibility and clinical utility of liquid-based cytology (LBC) specimens via endoscopic ultrasound–guided fine-needle biopsy (EUS-FNB) for next-generation sequencing (NGS) of pancreatic cancer (PC). We prospectively evaluated the performance of DNA extraction and NGS using EUS-FNB samples obtained from PC. Thirty-three consecutive patients with PC who underwent EUS-FNB at our hospital were enrolled. DNA samples were obtained from 96.8% of the patients. When stratified with a variant allele frequency (VAF) > 10% tumor burden, the NGS success rate was 76.7% (n = 23) in formalin-fixed paraffin-embedded (FFPE), 83.3% (n = 25) in LBC, and 76.7% (n = 23) in frozen samples. The overall NGS success rate was 86.7% (n = 26) using FFPE, LBC, or frozen samples. The detection rates for the main mutated genes were as follows: 86.7% for KRAS, 73.3% for TP53, 66.7% for CDKN2A, 36.7% for SMAD4, and 16.7% for ARID1A. LBC had the highest median value of VAF (23.5%) for KRAS and TP53. PC mutation analysis using NGS was successfully performed using LBC compared with FFPE and frozen samples. This approach provides an alternative and affordable source of molecular testing materials.

Background/Objectives: Aldehyde dehydrogenase 2 (ALDH2) detoxifies acetaldehyde, and impaired ALDH2 activity has been implicated in carcinogenesis. The acetaldehyde breath test (ABT) enables noninvasive functional assessment of ALDH2 activity, but its association with pancreatic disease remains unclear. We examined associations between ABT-assessed ALDH2 activity and pancreatic disease outcomes. Methods: This case–control study included 287 health checkup participants, 131 patients with benign pancreatic disease, and 65 patients with pancreatic cancer. Participants underwent ABT, and the acetaldehyde-to-ethanol (A/E) ratio was calculated. The ALDH2 inactive phenotype was defined as an A/E ratio ≥ 23.3. Multinomial logistic regression used health checkup participants as the reference. Results: The median A/E ratio was higher in patients with benign pancreatic disease and pancreatic cancer than in health checkup participants (21.7 and 24.2 vs. 13.6; p < 0.001). The ALDH2 inactive phenotype was associated with benign pancreatic disease (relative risk ratio [RRR], 3.55; 95% confidence interval [CI], 1.85–6.83) and pancreatic cancer (RRR, 4.82; 95% CI, 2.13–10.88). The highest A/E ratio category was also associated with benign pancreatic disease (RRR, 8.77; 95% CI, 3.59–21.39) and pancreatic cancer (RRR, 12.79; 95% CI, 4.41–37.09). Exploratory spline analyses showed associations between higher A/E ratios and pancreatic disease outcomes without clear evidence of nonlinearity. Conclusions: A higher ABT-derived A/E ratio was associated with benign pancreatic disease and pancreatic cancer in this selected case–control study. Prospective studies are needed to determine whether functional assessment of aldehyde metabolism provides clinically useful information for pancreatic disease risk assessment. Trial registration number: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000052609; registered 1 November 2023.

Takehiko Koga, Yusuke Ishida, Akihisa Ohno, Ryota Sagami, Yoshitaka Nakamura, Makoto Hinokuchi, Kosuke Takahashi, Hidefumi Nishikori, Nao Fujimori, Yasuhisa Hiroshima, Hiroki Taguchi, Shinichi Hashimoto, Eisuke Ozawa, Hiroaki Tsuji, Naoaki Tsuchiya, Takanori Kitaguchi, Keisuke Matsumoto, Makoto Fukuyama, Tatsuro Nii, Fumihito Hirai. Gut and Liver -0001;0:. https://doi.org/10.5009/gnl260042