Pancreatic ductal adenocarcinoma has a particularly poor prognosis as it is often detected at an advanced stage and acquires resistance to chemotherapy early during its course. Stress adaptations by mitochondria, such as metabolic plasticity and regulation of apoptosis, promote cancer cell survival; however, the relationship between mitochondrial dynamics and chemoresistance in pancreatic ductal adenocarcinoma remains unclear. We here established human pancreatic cancer cell lines resistant to gemcitabine from MIA PaCa‐2 and Panc1 cells. We compared the cells before and after the acquisition of gemcitabine resistance to investigate the mitochondrial dynamics and protein expression that contribute to this resistance. The mitochondrial number increased in gemcitabine‐resistant cells after resistance acquisition, accompanied by a decrease in mitochondrial fission 1 protein, which induces peripheral mitosis, leading to mitophagy. An increase in the number of mitochondria promoted oxidative phosphorylation and increased anti‐apoptotic protein expression. Additionally, enhanced oxidative phosphorylation decreased the AMP/ATP ratio and suppressed AMPK activity, resulting in the activation of the HSF1–heat shock protein pathway, which is required for environmental stress tolerance. Synergistic effects observed with BCL2 family or HSF1 inhibition in combination with gemcitabine suggested that the upregulated expression of apoptosis‐related proteins caused by the mitochondrial increase may contribute to gemcitabine resistance. The combination of gemcitabine with BCL2 or HSF1 inhibitors may represent a new therapeutic strategy for the treatment of acquired gemcitabine resistance in pancreatic ductal adenocarcinoma.

To prevent chylothorax after esophageal cancer surgery, it is important to recognize morphological patterns of the thoracic duct intraoperatively. The present study aimed to evaluate the safety and usefulness of near‐infrared (NIR) fluorescence imaging with subcutaneous inguinal injection of indocyanine green (SII‐ICG) to detect the thoracic duct during thoracoscopic esophagectomy for esophageal cancer. Patients (n = 16) who underwent thoracoscopic esophagectomy in the prone position with SII‐ICG at Shinshu University Hospital between June 2020 and January 2022 were enrolled in the present study and retrospectively reviewed. Immediately prior to thoracoscopic esophagectomy, we injected 0.2–0.5 mg/kg ICG into the subcutaneous tissue in the bilateral inguinal region. The identification rate of the thoracic duct was 93.8% (n = 15), and the success rate of fluorescence using SII‐ICG was 87.5% (n = 14). The visible thoracic ducts had four patterns: a typical pattern in 50% (n = 8), duplication pattern in 18.8% (n = 3), branching pattern in 12.5% (n = 2), and plexiform pattern in 12.5% (n = 2). In all cases, ICG fluorescence did not disappear and was visible during the thoracic surgery. No SII‐ICG‐related complications were observed. Intraoperative NIR fluorescence imaging of the thoracic duct using SII‐ICG is a simple and safe method with very high detection sensitivity. This method can be a powerful tool for avoiding thoracic duct injuries during esophageal cancer surgery.