Yusuke Kamikihara

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.

Background/Objectives: Several reports have shown that the hypoattenuation pattern of contrast-enhanced computed tomography (CECT) in pancreatic neuroendocrine tumors (PanNETs) is associated with poor overall survival (OS). However, these studies also included neuroendocrine carcinoma. Therefore, this study retrospectively investigated the relationship between attenuation patterns and OS, specifically in PanNETs. Methods: Between July 2005 and August 2022, 80 consecutive patients (median age, 64 years; 39 males and 41 females) with pathologically confirmed PanNETs were enrolled. Pretreatment factors associated with PanNET prognosis were evaluated. Results: The median tumor diameter was 18 mm (range, 6–150 mm). The PanNET grades were G1 in 45 patients (56%), G2 in 31 (39%), and G3 in 4 (5%). Hyperattenuation and hypoattenuation patterns were observed in 64 (80%) and 16 (20%) patients, respectively. Surgery was performed on 63 patients (79%), and 18 (23%) had distant metastases. Multivariate analysis identified the hypoattenuation pattern on pretreatment CECT as a factor significantly associated with OS in all participants (p < 0.001; hazard ratio [HR], 9.45) and in patients with PanNET G2 (p = 0.007; HR, 9.13). Median OS was longer in the hyperattenuation group than in the hypoattenuation group among all participants (hyperattenuation, not reached; hypoattenuation, 40.1 months; p < 0.001) and among patients with PanNET G2 (hyperattenuation, not reached; hypoattenuation, 36.3 months; p = 0.001). Conclusions: PanNETs with a hypoattenuation pattern on CECT had a worse prognosis than those with hyperattenuation, even among tumors of the same pathological grade (G2).