Impact of metabolic dysfunction-associated fatty liver disease on the incidence of Helicobacter pylori-negative gastric cancer.

AIM: The incidence of Helicobacter pylori-negative gastric cancer (HPNGC) is increasing worldwide. Recently, metabolic dysfunction-associated fatty liver disease (MAFLD) has been reported to be associated with various cancers, but its association with HPNGC has not been reported. We aimed to identify important independent factors associated with HPNGC, including MAFLD. METHODS: This multicenter observational cohort study enrolled patients with gastric cancer (n = 1078) and health checkup examinees (n = 17 408). We analyzed patients with HPNGC (n = 26) and healthy participants with no H. pylori infection or any abnormal findings on upper gastrointestinal endoscopy (n = 1130). A logistic regression model was used to identify independent factors associated with HPNGC. The priority of the factors associated with HPNGC was evaluated using a decision-tree algorithm and random forest analysis. RESULTS: Among all patients with gastric cancer, 2.4% (26/1078) were diagnosed with HPNGC (mean age, 64 years; male/female, 13/13). In the logistic regression analysis, age, smoking, and MAFLD (odds ratio, 6.5359; 95% confidence interval, 2.5451-16.7841; p < 0.0001) were identified as independent factors associated with HPNGC. Metabolic dysfunction-associated fatty liver disease was also identified as the most important classifier for the presence of HPNGC in decision-tree analyses. Helicobacter pylori-negative gastric cancer was observed in 5.2% of patients with MAFLD and 0.8% of patients without MAFLD. In the random forest analysis of the HPNGC, MAFLD was identified as the distinguishing factor with the highest variable importance (0.32). CONCLUSIONS: Metabolic dysfunction-associated fatty liver disease was the most influential independent factor associated with HPNGC. These findings suggest that fatty liver and metabolic dysfunction could be involved in the pathogenesis of HPNGC.

Nanoliposomal irinotecan with fluorouracil and folinic acid, FOLFIRINOX, and S-1 as second-line treatment for unresectable pancreatic cancer after gemcitabine/nab-paclitaxel.

This study aimed to compare second-line treatment outcomes for patients with unresectable pancreatic cancer previously treated with gemcitabine plus nab-paclitaxel (GnP) therapy. We conducted an integrated analysis of two retrospective studies included 318 patients receiving nanoliposomal irinotecan + 5-fluorouracil/folinic acid (NFF) (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment. Median overall survival (OS) in the NFF group was 9.08 months, significantly better than S-1 (4.90 months, P = 0.002). FOLFIRINOX had a median OS of 4.77 months, not statistically different from NFF. Subgroup analyses of OS indicated NFF was generally superior, however, a statistical interaction was observed between the treatment regimen in serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). Median progression-free survival (PFS) was 2.93 months for NFF, significantly better than S-1 (2.53 months, P = 0.024), while FOLFIRINOX had a comparable PFS (3.04 months, P = 0.948). Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors for OS. This study concludes that second-line NFF therapy demonstrated a more favorable OS compared to S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment.

A multicenter retrospective observational NAPOLEON2 study of nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable pancreatic cancer.

Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2). The results of the retrospective part were reported herein. In this retrospective study, we evaluated 161 consecutive patients who received NFF as second-or-later-line regimen. The main endpoint was overall survival (OS), and the other endpoints were response rate, disease control rate, progression-free survival (PFS), dose intensity, and adverse events (AEs). The median age was 67 years (range, 38-85 years). The median OS and PFS were 8.1 and 3.4 months, respectively. The objective response and disease control rates were 5% and 52%, respectively. The median relative dose intensity was 81.6% for nanoliposomal irinotecan and 82.9% for fluorouracil. Grade 3 or 4 hematological and nonhematological AEs occurred in 47 and 42 patients, respectively. Common grade 3 or 4 AEs included neutropenia (24%), anorexia (12%), and leukocytopenia (12%). Subanalysis of patients treated with second-line and third-or-later-line demonstrated no statistical significant difference in OS (7.6 months vs. 9.1 months, respectively; hazard ratio, 0.92; 95% confidence interval, 0.64-1.35; p = 0.68). In conclusion, NFF has acceptable efficacy and safety profile even in real-world clinical settings. The prospective study is in progress to validate these findings.