小西 孝宜

INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is commonly performed for enteral nutrition in patients with various diseases. However, there are few reports on abdominal surgeries for patients after PEG, and the tips for these procedures have not been established. Specifically, in laparoscopic surgeries of the upper abdomen, a gastrostomy can interfere with the surgical field. In addition, perioperative management of concomitant diseases that require PEG placement, including neuromuscular disorders, is required. CASE PRESENTATION: A 64-year-old man with a PEG due to malnutrition from myotonic dystrophy was diagnosed with acute cholangitis and choledocholithiasis. After lithotomy during endoscopic retrograde cholangiopancreatography, the patient was scheduled for laparoscopic cholecystectomy for the cholelithiasis. Although the patient had myotonic dystrophy and limited respiratory function, his general condition was deemed acceptable for surgery. Given the potential risk of gastrostomy injury and the need to ensure sufficient working space, the location of the gastrostomy tube was preoperatively confirmed via a computed tomography scan, and precautions were taken to prevent injuries caused by port insertion, forceps manipulation, and pneumoperitoneum during the procedure. Ultimately, the gastrostomy did not interfere with manipulation around the gallbladder, and the surgery was completed without any complications. To manage myotonic dystrophy, general intravenous anesthesia with propofol was administered, with minimal use of muscle relaxants during surgery. Postoperatively, the patient was managed with high nasal flow to reduce respiratory workload, epidural anesthesia to prevent respiratory depression due to pain, and early initiation of aggressive physical therapy. The patient was discharged on postoperative day 4 without complications. CONCLUSIONS: Using appropriate surgical strategies, laparoscopic cholecystectomy may be safely performed for patients with myotonic dystrophy after PEG.

Pancreatic ductal adenocarcinoma (PDAC) is a progressive cancer with a poor prognosis. It contains a complex tumor microenvironment (TME) that includes various stromal cell types. Comprehending cellular communications within the TME is difficult due to a lack of research models that can recapitulate human PDAC-TME. Previously, we recapitulated, in part, the PDAC-TME containing a diversity of cancer-associated fibroblasts (CAFs) in vitro. This was done by establishing a PDAC organoid by co-culturing patient-derived cancer cells with human induced pluripotent stem cell (hiPSC)-derived mesenchymal and endothelial cells, which was designated the fused pancreatic cancer organoid (FPCO). We further incorporated macrophages derived from the THP-1 cell line, which are the source of tumor-associated macrophages (TAMs), a major TME component, into FPCO, which was designated M0-FPCO. Bulk RNA sequencing (RNAseq) analysis revealed that macrophages in M0-FPCO (FPCO-Mac) lost their pro-inflammatory features but acquired pro-angiogenic features. Consistently, the formation of an endothelial cell network was enhanced in M0-FPCO. Single-cell RNA-seq (scRNA-seq) analysis revealed that M0-FPCO contained five TAM subpopulations similar to the corresponding TAM in human PDAC tissue in the integrated analysis, including SPP1⁺-TAM, which has been correlated with tumor angiogenesis and cell proliferation. Focusing on PDAC cells, we found that they could survive longer within the organoid in the presence of TAM. Consistent with the prolonged proliferation and survival of PDAC cells, PDAC subclusters were characterized by proliferative features, such as increased M0-FPCO. Therefore, by establishing a PDAC organoid with macrophages, we recapitulated the diversity of TAMs and identified the role of TAM in endothelial network formation as well as in the modulation of PDAC cell properties. SIGNIFICANCE: PDAC organoids, including macrophages using hiPSC, showed that PDAC-TAM has angiogenic features and contributes to PDAC cell survival.