Case Presentation: A 59-year-old male with past medical history of Stage IV esophageal squamous cell carcinoma (ESCC) with metastasis to the adrenal glands and brain, undergoing chemotherapy with docetaxel and whole brain radiation, presented to the emergency department for chest pain. The patient was hypoxic, with an O2 saturation of 88 on room air, and hypotensive. Lab work demonstrated leukocytosis of 65,000 and broad-spectrum antibiotics of Cefepime, Vancomycin, and Metronidazole were initiated. CT imaging revealed lymph node enlargement and a large loculated right pleural effusion. The patient was started on vasopressors and admitted to the stepdown unit. A chest tube was placed which yielded 1660 mL of fluid notable for elevated leukocytes and mixed gram positive and negative bacteria. An esophagram revealed an esophagopleural fistula (EPF) contributing to the continued effusion- a progression of disease despite continued chemotherapy in the outpatient setting. With worsening leukocytosis and hypotension, diflucan was initiated on top of the existing regimen and patient was started on midodrine. With continued deterioration, goals of care were addressed with family, and the patient was ultimately enrolled in inpatient hospice with comfort measures.
Discussion: We demonstrate the progression of ESCC with EPF formation despite guideline directed therapy. This patient completed systemic treatments including initial FOLFOX with pembrolizumab, and later docetaxel. Despite intensive management, the patient developed adrenal and multifocal brain metastases revealing limitations to modern therapy once the disease becomes refractory. Furthermore, EPF is a rare but serious complication of ESCC. Risk factors attributing to the occurrence of EPF includes tumor invasion, local tissue inflammation, and necrosis [1]. Malignant EPFs are associated with poor prognosis and increase morbidity and mortality in these patients. Patients may present with chest pain, cough, shortness of breath, or pleural effusions [1]. Given the nonspecific and vague symptoms, diagnosis can be challenging. Management includes drainage of pleural fluid along with broad-spectrum antibiotics. ESCC with brain metastasis is rare and carries a poor prognosis [2]. Although WBRT can reduce peritumoral edema and delay neurological decline [5], patient deterioration often continues as seen in this case. Adrenal metastasis also is a part of widespread metastasis of ESCC and can be a marker of systemic involvement [6]. This can reveal reduced responsiveness to goal-directed therapy. This case underscores the ethical importance of beneficence and the recognition of treatment-related burdens in advanced ESCC care. Complications such as EPF, neurological symptoms from brain involvement, and worsening functional decline can limit additional therapeutic approaches.
Conclusions: ESCC is an aggressive malignancy often with early metastasis. Clinicians should maintain a high index of suspicion for fistula formation in patients with recurrent or loculated pleural effusions. Early recognition, pleural drainage, and surgical intervention when feasible is essential in preventing further complications. While there are current trials for ESCC, further research is needed to evaluate more customized therapies for these patients aiming to prevent and treat distant metastasis, while minimizing toxicities and functional decline.