Satoru Kikuchi

Esophageal cancer remains a highly aggressive malignancy with a poor prognosis, despite ongoing advancements in treatments such as immunotherapy. The tumor microenvironment, particularly cancer-associated fibroblasts (CAF), plays a crucial role in driving the aggressiveness of esophageal cancer. In a previous study utilizing human-derived xenograft models, we successfully developed a novel cancer treatment that targeted CAFs with near-infrared photoimmunotherapy (NIR-PIT), as an adjuvant therapy. In this study, we sought to translate our findings toward clinical practice by employing patient-derived xenograft (PDX) models and utilizing humanized mAbs, specifically sibrotuzumab, which is an antihuman fibroblast activation protein (FAP) Ab and already being investigated in clinical trials as monotherapy. PDX models derived from patients with esophageal cancer were effectively established, preserving the expression of key biomarkers such as EGFR and FAP, as observed in primary tumors. The application of FAP-targeted NIR-PIT using sibrotuzumab, conjugated with the photosensitizer IR700DX, exhibited precise binding and selective elimination of FAP-expressing fibroblasts in vitro. Notably, in our in vivo investigations using both cell line–derived xenograft and PDX models, FAP-targeted NIR-PIT led to significant inhibition of tumor progression compared with control groups, all without inducing adverse events such as weight loss. Immunohistologic assessments revealed a substantial reduction in CAFs exclusively within the tumor microenvironment of both models, further supporting the efficacy of our approach. Thus, our study demonstrates the potential of CAF-targeted NIR-PIT employing sibrotuzumab as a promising therapeutic avenue for the clinical treatment of patients with esophageal cancer.

Background and aim: Recently, several studies have demonstrated the safety and feasibility of laparoscopic and endoscopic cooperative surgery for duodenal tumors (D-LECS). However, the standard procedure for D-LECS has not been established. Herein, we introduce the feasibility and safety of a surgical strategy based on tumor characteristics and location in D-LECS. Methods: This retrospective single-center study included 17 consecutive patients with duodenal tumors who underwent D-LECS between October 2017 and November 2023. Results: Two, 13 and 2 tumors were located in the first, second and third portions of the duodenum, respectively. Three tumors were protruded type and 14 were superficial type. The median tumor size was 25 (6–45) mm. Supracolic, mesenteric and inferior approaches were employed in 14, 2 and 1 case, respectively, during D-LECS. Laparoscopic reinforcement after endoscopic submucosal dissection (ESD) (D-LECS with ESD), laparoscopic suturing after full-thickness resection (FTR) (D-LECS with FTR) and Closed-LECS were performed in 13, 2 and 2 cases, respectively. The median operation time and blood loss were 237 (159–420) min and 0 (0–75) ml, respectively. En-bloc pathological curative resection was achieved in all cases. Two patients had paralytic ileus and delayed gastric emptying as postoperative complications. The median duration of postoperative hospital stay was 10 (6–22) days. One local recurrence was observed in a case of adenocarcinoma in situ during the median follow-up of 13 (2–71) months. Conclusions: The feasibility and safety of our surgical strategy based on the tumor characteristics and location were demonstrated in D-LECS.