Lipid Peroxidation Regulators GPX4 and FSP1 as Prognostic Markers and Therapeutic Targets in Advanced Gastric Cancer.

Gastric cancer is one of the most common cancers worldwide, and new therapeutic strategies are urgently needed. Ferroptosis is an intracellular iron-dependent cell death induced by the accumulation of lipid peroxidation, a mechanism different from conventional apoptosis and necrosis. Therefore, induction of ferroptosis is expected to be a new therapeutic strategy. Glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) have been identified as the major inhibitors of ferroptosis. Herein, we performed immunohistochemistry for GPX4, FSP1, and 4-HNE using tissues from patients with gastric cancer and investigated the relationship between these factors and prognosis. Patients with high GPX4 expression or high GPX4 expression and low 4-HNE accumulation tended to have a poor prognosis (p = 0.036, 0.023), whereas those with low FSP1 expression and high 4-HNE accumulation had a good prognosis (p = 0.033). The synergistic induction of cell death by inhibiting GPX4 and FSP1 in vitro was also observed, indicating that the cell death was non-apoptotic. Our results indicate that the expression and accumulation of lipid peroxidation-related factors play an important role in the clinicopathological significance of gastric cancer and that novel therapeutic strategies targeting GPX4 and FSP1 may be effective in treating patients with gastric cancer who have poor prognosis.

Novel reconstruction using pedicled ileocolic interposition with intrathoracic esophago-ileal anastomosis after distal esophagectomy for esophagogastric junction cancer: A report of two cases.

There is no optimal reconstruction after radical distal esophagectomy for cancers of the esophagogastric junction. We designed a novel reconstruction technique using pedicled ileocolic interposition with intrathoracic anastomosis between the esophagus and the elevated ileum. Two patients underwent the surgery. Case 1 was a 70-year-old man with esophagogastric junction adenocarcinoma with 3 cm of esophageal invasion. Case 2 was a 70-year-old man with squamous cell carcinoma of the esophagogastric junction; the epicenter of which was located just at the junction. These two patients underwent radical distal esophagectomy and pedicled ileocolic interposition with intrathoracic anastomosis. They were discharged on postoperative days 17 and 14, respectively, with no major complication. Pedicled ileocolic interposition is characterized by sufficient elevation and perfusion of the ileum, which is fed by the ileocolic artery and vein. As a result, we can generally adapt this reconstruction method to most curable esophagogastric junction cancers.

Left thoracoscopic approach in the supine position for torsion of the residual esophagus after esophagectomy: a case report.

BACKGROUND: Anastomotic stenosis can occur after esophagectomy and gastric tube reconstruction. The effective surgical treatment for refractory anastomotic stenosis, which seems difficult to resolve with endoscopic treatment, has not been established. We report a case of refractory stenosis due to esophageal torsion in which reconstructive surgery was possible using a left thoracoscopic approach in the supine position. CASE PRESENTATION: A 72-year-old man who underwent thoracoscopic subtotal esophagectomy and retrosternal gastric tube reconstruction for esophageal cancer 6 months previously presented to us. Postoperative endoscopy revealed that the residual esophagus was twisted approximately 360°, just above the anastomotic site. Conservative endoscopic treatment failed to improve the condition due to severe passage obstruction, and reconstructive surgery was repeated. Surgery was performed in the supine position using a left thoracoscopic approach. The entire circumferences of the gastric tube and residual esophagus were dissected from the inferior mediastinum to the top of the sternum, with focus on preserving the right gastroepiploic vein and gastric-tube wall. Subsequently, laparoscopic surgery was performed to remove the gastric tube from the thoracoabdominal junction. After separating the esophagus on the oral side of the torsion from the left cervical wound, the abdomen was opened, the gastric tube was pulled out through the abdominal wound, and adhesions in the abdominal cavity were peeled off to raise the gastric tube cranially via the retrosternal route. An end-to-side anastomosis was performed using a circular stapler, and the esophageal torsion and previous anastomosis were resected. Oral intake was resumed on the 7th postoperative day, and the patient was discharged on the 38th day. CONCLUSIONS: After subtotal esophagectomy and retrosternal gastric tube reconstruction, the left thoracoscopic approach is one of the most minimally invasive approaches and is especially useful for preserving the right gastroepiploic artery and veins and for mobilizing the gastric tube wall.