Anastomotic Leak after Esophagectomy: The role of Pre- and Postoperative Blood-based Biomarkers - A Prospective Observational Cohort Study.

Introduction: Esophageal cancer, according to GLOBOCAN 2022, currently ranks as the eleventh most common cancer and the seventh leading cause of death due to cancer worldwide. In India, it ranks fifth with regard to both the annual incidence and the cancer-related death. The standard approach to most esophageal cancer would include a comprehensive management, i.e., establishing diagnosis on endoscopy along with biopsy confirmation, staging the extent of the disease with Computed tomography (CT) scan, and post that planning on neoadjuvant therapy (chemoradiation or chemotherapy), finally culminating in definitive surgery. Esophagectomy is the mainstay of treatment for esophageal cancer, and the surgery has always been a formidable one to perform due to the anatomical challenges and diminished physiological reserves of the patients. According to the OesophagoGastric Anastomosis Audit (OGAA) Group, the anastomotic leak (AL) is one of the major complications post esophagectomy, which has remained a challenge to date. Despite efforts to prehabilitate patients to improve their nutrition and respiratory reserve, anastomotic leak (AL) rates have not improved. This suggests that other factors may be contributing. Traditionally, the anastomotic site is infiltrated by neutrophils on post-operative day (POD) 0-4, followed by macrophages (POD 1-4), and is replaced by lymphocytes and fibroblasts by POD 4-14. In patients with colorectal anastomosis, it has been noted that there is increased macrophage activity in patients who develop a leak. There are currently lacking studies that show a similar association in esophageal cancer-associated AL. Through this study, we thus look into the blood-based biomarkers predictive of AL post-esophagectomy.

Methodology: Patients diagnosed with esophageal cancer and undergoing curative surgery will be prospectively enrolled in the study. Complete blood counts, including differential count, will be recorded at four time points: pre-operative (within 7 days from the date of surgery), POD1, POD3, and POD5. This is the standard of care for all major oncological surgeries, including esophagectomies. The blood sample will be collected as part of the routine investigations. The patients will be followed up to discharge and 30 days post-discharge to document any evidence of AL. Definition of AL: As defined by the Esophagectomy Complications Consensus Group (ECCG) - “Full thickness GI defect involving esophagus, anastomosis, staple line, or conduit irrespective of presentation or method of identification”. Patient demographic data such as age, gender, co-morbidity, body mass index, histology of cancer, upper gastrointestinal endoscopy findings, computed tomography findings, neoadjuvant therapy, and surgical findings will also be collected.

Conclusion: The changes in the blood counts in the immediate peri-operative period play a key role in the anastomotic healing, especially the monocyte count. These simple blood-based biomarkers can thus act as a harbinger of AL and predict the occurrence of AL. Altering the biomarkers with anti-inflammatory measures can help in decreasing AL rates.