Objectives: The oral–gut axis is believed to play a role in the pathogenesis of colorectal cancer (CRC). Previous studies have demonstrated the transmission of oral microbiota to the gut, disrupting gut microbial balance and creating a protumorigenic microenvironment conducive to CRC progression. Fusobacterium nucleatum is a putative periodontal pathogen recognized as a specific bacterium that promotes CRC development. However, the possible involvement of other periodontal pathogens in CRC is poorly understood. This study aimed to explore the effects of ingested periodontal pathogens on experimental CRC in mice and elucidate the underlying mechanisms. Methods: In this study, experimental colitis-induced CRC mouse models were used. The mice were orally administered periodontal pathogens (Porphyromonas gingivalis and Prevotella intermedia) three times a week during the experimental period. The CRC severity between the P. gingivalis-treated and P. intermedia-treated groups was compared. Lumen-associated microbiota (LAM) and mucosa-associated microbiota (MAM) were analyzed in both mouse and human samples. In vitro studies were conducted using intestinal epithelial cells to explore the possible mechanisms by which the periodontal pathogens affect the CRC development. Results: The P. gingivalis-treated group exhibited significantly increased CRC severity compared to the other groups among azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse models. The LAM and MAM exhibited distinct bacterial compositions, and P. gingivalis was enriched more in MAM than in LAM. In vitro adhesion assays revealed that P. gingivalis had higher adhesive capacity to intestinal epithelial cells than P. intermedia and indicated the possible involvement of gingipains in such a capacity. Conclusion: P. gingivalis is enriched in MAM, and its subsequent adhesion to intestinal epithelial cells is potentially involved in the progression of CRC.

Background: Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early gastric cancer (GC); however, post‐ESD bleeding remains a serious and unpredictable complication. This study aimed to develop machine‐learning (ML) models to predict post‐ESD bleeding and identify associated risk factors, ensuring accurate and interpretable predictions.Methods: A retrospective, multicenter clinical database was constructed for patients who underwent ESD for early GC. An ML model was developed using patient characteristics and perioperative findings to predict bleeding within 28 days post‐ESD. Its performance was compared with that of a logistic regression–based non‐ML model. Feature importance analysis was performed to aid interpretation.Results: Among 1084 patients (median age: 75 years), post‐ESD bleeding occurred in 63 (5.8%). The area under the curve of the ML model was better than that of the non‐ML model (0.80 vs. 0.71, p = 0.03). Furthermore, the ML model demonstrated a trend toward higher sensitivity compared with the non‐ML model (0.74 vs. 0.58, p = 0.58). When stratified by ML‐estimated bleeding probability, observed bleeding rates were 2.3%, 8.8%, and 28.6% in the low‐ (< 50%), intermediate‐ (50%–80%), and high‐probability (≥ 80%) groups, respectively. The odds of bleeding were significantly higher in the intermediate‐ (OR 4.03, p = 0.03) and high‐probability (OR 16.7, p < 0.01) groups compared to the low‐probability group. Anticoagulant use with atrial fibrillation emerged as a key predictor.Conclusions: The ML model effectively rules out post‐ESD bleeding and identifies clinically meaningful risk factors, supporting its use in personalized prophylactic strategies.

Triamcinolone acetonide (TA), a steroid, is often used clinically to prevent dysfunctions associated with fibrosis. The objective of this study was to examine whether TA can be suspended in a gelatin sheet for tissue engineering using a mouse skin wound model. TA was suspended in biodegradable gelatin and freeze-dried in a sheet form. The sheet was analyzed for homogeneity and controlled release of TA by high-performance liquid chromatography. We made two skin wounds on the dorsal side of mice. Gelatin sheets with TA (TA sheet) and without TA (control sheet) were attached to each skin wound. To determine the efficacy of the prepared TA sheet on the skin wounds, TA-sheet versus TA-injection experiments were conducted. Hematoxylin and eosin staining was performed to assess the grade of epithelialization and alpha smooth muscle actin (α-SMA) immunohistochemical staining was conducted to evaluate myofibroblast infiltration. In the TA-release test in vitro, 7.7 ± 2.3% of TA was released from the sheet by 24 h. After replacing the initial phosphate-buffered saline (PBS) with collagenase PBS, the amount of released TA increased over time. The wound area/original skin wound area after 15 days with the TA sheet was significantly larger than that with the control sheet (26.9 ± 5.5% vs 10.7 ± 2.6%, p = 0.023). The α-SMA positive area/whole area with the TA sheet was significantly lower than that with the control sheet (4.65 ± 0.66% vs 7.24 ± 0.7%, p = 0.023). Furthermore, the α-SMA positive area/whole area with the TA sheet was significantly lower than that with TA injection (5.32 ± 0.45% vs 7.93 ± 0.75%, p = 0.013). We developed a TA sheet and confirmed both the homogeneity of the suspended TA and controlled-release of the TA in the presence of collagenase in vitro. The TA sheet caused less myofibroblast infiltration into the tissue than the control sheet or TA injection did.

Sato C, et al. J Gastric Cancer. 2022 Sep;22:e30. https://doi.org/10.5230/jgc.2022.22.e30