A Case of Unresectable Advanced Esophageal Cancer with Recurrent Pneumatosis Intestinalis and Portal Venous Gas...

Esophageal squamous cell carcinoma is an aggressive malignancy often diagnosed at an advanced stage. Immune checkpoint inhibitors (ICIs), such as pembrolizumab, have shown promising outcomes for improving survival. Although rare, immune-related adverse events (irAEs) associated with ICI therapy, such as pneumatosis intestinalis (PI) and portal venous gas (PVG), can be fatal.

A 60-year-old man with unresectable advanced esophageal squamous cell carcinoma received cisplatin, 5-fluorouracil (FP), and pembrolizumab. Three days after treatment initiation, the patient experienced abdominal pain and hypotension. Imaging revealed extensive PI and PVG, with no signs of bowel ischemia. Emergency laparotomy confirmed PI involving the entire length of the small intestine, with no visible perforations. Symptoms resolved with conservative management. After benefits and potential adverse events of the current chemotherapy regimen were explained, the patient chose to continue pembrolizumab-based chemotherapy. In the second and third courses, the doses of cisplatin and 5-FU were reduced to 75% (cisplatin 60 mg/m², 5-FU 600 mg/m²), while the dose of pembrolizumab was maintained (200 mg). No major adverse events occurred, and follow-up CT scans showed shrinkage of the primary lesion, and PI did not recur during this period. However, 26 days after the 3rd treatment course, the patient developed sudden-onset abdominal pain, shock, more severe PI, and PVG. Despite receiving intensive care, the patient died the following day. Autopsy revealed diffuse intestinal erosion with a CD8-positive lymphocytic infiltration and histologically confirmed pneumatosis intestinalis extensively involving the small intestine and colon.

The patient experienced two episodes of PI and PVG with distinct clinical courses. Although the exact cause of the first episode remains unclear, the fatal recurrence suggests that rechallenging with suspected causative agents carries a significant risk, even after dose reduction. While ICI-based chemotherapy for esophageal cancer was highly effective, this case highlights the importance of continuously reassessing the risk-benefit balance during treatment. Discontinuation of ICIs should be considered when serious irAE are suspected.