Preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for locally advanced esophageal carcinosarcoma: a case report and review of the literature

Abstract Background Esophageal carcinosarcoma is a relatively rare malignant neoplasm composed of both epithelial carcinomatous and mesenchymal sarcomatous elements. There is no recommended clinical treatment for esophageal carcinosarcoma because of the rarity of the disease. This report describes a case of esophageal carcinosarcoma that was effectively treated with docetaxel, cisplatin, and 5-fluorouracil as preoperative chemotherapy. Case presentation A 73-year-old man had a chief complaint of dysphagia with epigastric pain. Esophagogastroduodenoscopy (EGD) revealed a polypoid neoplasm combined with an infiltrative ulcer that exhibited a mixture of squamous cell carcinoma and spindle cell sarcoma histologically. Computed tomography findings showed swollen lymph nodes in the mediastinum and around the cardia. We diagnosed esophageal carcinosarcoma cT3N1M0 cStage III. After preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil, the patient underwent thoracoscopic esophagectomy with three-field lymph node dissection. Histological findings revealed that the sarcomatous component had completely disappeared and the carcinomatous component was only confined by the basement membrane with scar formation of the muscularis propria. Mural fibrotic lesions were observed in several resected regional lymph nodes. Hence, immediately after preoperative therapy, the esophageal carcinosarcoma was diagnosed as ypTisN0M0 fStage I. The patient remained alive without tumor recurrence at 12 months after the operation. Conclusions A review of the literature revealed that there is still no established therapeutic strategy for locally advanced esophageal carcinosarcoma, especially against the sarcomatous component. We herein provide the first report in which the sarcomatous component showed a complete response to preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil. Preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by esophagectomy with extended lymphadenectomy may achieve definitive treatment for locally advanced esophageal carcinosarcoma

The apoptotic initiator Caspase-8: its functional ubiquity and genetic diversity during animal evolution

The caspases, a family of cysteine proteases, play multiple roles in apoptosis, inflammation, and cellular differentiation. Caspase-8 (Casp8), which was first identified in humans, functions as an initiator caspase in the apoptotic signaling mediated by cell-surface death receptors. To understand the evolution of function in the Casp8 protein family, casp8 orthologs were identified from a comprehensive range of vertebrates and invertebrates, including sponges and cnidarians, and characterized at both the gene and protein levels. Some introns have been conserved from cnidarians to mammals, but both losses and gains have also occurred; a new intron arose during teleost evolution, whereas in the ascidian Ciona intestinalis, the casp8 gene is intronless and is organized in an operon with a neighboring gene. Casp8 activities are near ubiquitous throughout the animal kingdom. Exogenous expression of a representative range of nonmammalian Casp8 proteins in cultured mammalian cells induced cell death, implying that these proteins possess proapoptotic activity. The cnidarian Casp8 proteins differ considerably from their bilaterian counterparts in terms of amino acid residues in the catalytic pocket, but display the same substrate specificity as human CASP8, highlighting the complexity of spatial structural interactions involved in enzymatic activity. Finally, it was confirmed that the interaction with an adaptor molecule, Fas-associated death domain protein, is also evolutionarily ancient. Thus, despite structural diversity and cooption to a variety of new functions, the ancient origins and near ubiquitous distribution of this activity across the animal kingdom emphasize the importance and utility of Casp8 as a central component of the metazoan molecular toolkit