ABSTRACT
BACKGROUND: Oesophageal cancer is the seventh most prevalent malignancy globally, and the sixth most common cause of cancer-related death. Oesophageal cancer is also one of the most costly cancers to treat. The aim of this study was to assess the financial impact of post-operative morbidity and hospital readmissions following oesophagectomy for oesophageal cancer. METHODS: A retrospective analysis was performed on a prospectively maintained database of patients with oesophageal cancer who underwent an oesophagectomy at a single centre between July 2014 and June 2019 (N = 56). Readmission costs were also assessed in this cohort for 12 months post-operatively. RESULTS: The total median cost for oesophagectomy in this cohort was AU$57 250. Major complications occurred in 40% of patients, with a median total admission cost of AU$74 606, significantly higher than patients with either minor or no complications (median admission cost of AU$52 713, P < 0.001). Patients whose operation was complicated by an anastomotic leak had a higher median admission cost than those without a leak (AU$104 328 and AU$54 972 respectively, P < 0.001). Cost centres representing the greatest proportion of costs were theatre resources and surgical ward care (medical and nursing). A total of 110 readmissions in 25 patients were recorded in the 12 months post-operatively, the majority for gastroscopy and dilatation of anastomotic stricture. CONCLUSION: Post-oesophagectomy morbidity greatly increases cost of care. In addition to the clinical benefits, interventions to minimize post-operative complications are likely to result in substantial cost savings.
Subject(s)
Esophageal Neoplasms , Patient Readmission , Humans , Retrospective Studies , Financial Stress , Esophagectomy/adverse effects , Esophageal Neoplasms/surgery , Postoperative Complications/etiologyABSTRACT
Inflammasomes are key regulators of innate immunity in chronic inflammatory disorders and autoimmune diseases, but their role in inflammation-associated tumorigenesis remains ill-defined. Here we reveal a protumorigenic role in gastric cancer for the key inflammasome adaptor apoptosis-related speck-like protein containing a CARD (ASC) and its effector cytokine IL18. Genetic ablation of ASC in the gp130F/F spontaneous mouse model of intestinal-type gastric cancer suppressed tumorigenesis by augmenting caspase-8-like apoptosis in the gastric epithelium, independently from effects on myeloid cells and mucosal inflammation. This phenotype was characterized by reduced activation of caspase-1 and NF-κB activation and reduced expression of mature IL18, but not IL1ß, in gastric tumors. Genetic ablation of IL18 in the same model also suppressed gastric tumorigenesis, whereas blockade of IL1ß and IL1α activity upon genetic ablation of the IL1 receptor had no effect. The specific protumorigenic role for IL18 was associated with high IL18 gene expression in the gastric tumor epithelium compared with IL1ß, which was preferentially expressed in immune cells. Supporting an epithelial-specific role for IL18, we found it to be highly secreted from human gastric cancer cell lines. Moreover, IL18 blockade either by a neutralizing anti-IL18 antibody or by CRISPR/Cas9-driven deletion of ASC augmented apoptosis in human gastric cancer cells. In clinical specimens of human gastric cancer tumors, we observed a significant positive correlation between elevated mature IL18 protein and ASC mRNA levels. Collectively, our findings reveal the ASC/IL18 signaling axis as a candidate therapeutic target in gastric cancer.Significance: Inflammasome activation that elevates IL18 helps drive gastric cancer by protecting cancer cells against apoptosis, with potential implications for new therapeutic strategies in this setting. Cancer Res; 78(5); 1293-307. ©2017 AACR.
