Analysis of Pleural Biomarkers in Intrathoracic Anastomotic Leakage After Esophagectomy for Cancer: Preliminary Results of the Plan-a Study

Background Anastomotic leakage (AL) is a relatively frequent complication that occurs in 10–15% of patients after esophagectomy. Despite its common occurrence, little is known about the pleural processes that accompany this complication in patients with intrathoracic anastomosis. In search of new, pleural biomarkers for early detection of AL, pleural fluid after esophagectomy was prospectively sampled in context of the PLAN-A study for as long as a pleural drain was present. As part of the preliminary analyses of this study, an in-depth analysis was performed of patients that underwent esophagectomy for cancer through left thoraco-abdominal incision with intrathoracic anastomosis, and experienced AL. Methods Pleural analyses of amylase, lactate, glucose and LDH of three patients with intrathoracic AL were compared to medians of 22 patients with intrathoracic anastomosis without AL. Only implicated sides were considered during analysis. Baselines mentioned are left-sided median values with interquartile range (IQR) on postoperative day (POD) 1 in the no-leak group. Discrepancy was defined as falling outside the IQR of the no-leak group. The diagnoses of AL were made according to ECCG criteria with computed tomography (CT) or endoscopy. Results In 2 out of 3 patients, pleural changes were bilateral. Baseline no-leak lactate decreased to plateau around 2.5 mmol/L on POD4, but increased in the AL-group on POD2–4. POD4 AL-lactate was 6.7–12.5 mmol/L (left-sided) and 9.3–14.3 mmol/L (right-sided). Glucose in the no-leak group decreased from 127.0 mg/dl(101.0–142.5 mg/dl) to plateau around 90 mg/dl on days 3–5, and afterwards returned to baseline. AL-glucose plateaued on <45 mg/dl on days 4–5. No-leak-LDH decreased to plateau at <500 U/L on POD4. AL-LDH decreased slower or increased again. POD5 AL-LDH was 644-3505 U/L (left-sided) and 1303-1750 U/L (right-sided). All markers displayed discrepancy 6–8 (median:8) days before AL-diagnosis on POD9–12. Conclusion This in-depth analysis of intrathoracic AL after esophagectomy of cancer, demonstrated that in 2 out of 3 patients the pleural spaces on both sides were involved in the process. Besides the known biomarker amylase, also pleural lactate, LDH, and glucose all showed signs of AL in the pleural space up to 8 days before diagnosis of the AL. These analyses present as possible biomarkers for early detection of AL after esophagectomy.