High surgical stress and a high incidence of postoperative arrhythmia are associated with esophagectomy. All organs may be affected and the secretion of numerous proinflammatory and antiinflammatory substances may increase as a result of the numerous local or systemic inflammatory reactions it can set off. The immune system's delicate equilibrium is disturbed by cancer surgery. Significant surgical trauma may lower the survival rate of cancer patients and increase preoperative adverse responses(11).
Recent research has revealed a link between systemic indicators of inflammation and a poor prognosis for esophageal cancer. For instance, in esophageal cancer patients, the level of C-reactive protein indicates prognosis(12). However, not all hospitals frequently conduct C-reactive protein testing. The information regarding red blood cells, white blood cells, and platelets is available through a complete blood count, which is simple to administer, less expensive, and easily accessible. Platelets release pro-inflammatory mediators such as desmoplasticization and cytokines. Platelet activation plays an important role in coronary artery disease (CAD) and cardiovascular disease (CVD) (13,14). A strong predictor of death in patients with acute myocardial infarction is a high baseline platelet count(15). A common indicator of inflammation in CVD is the WBC count. Abdelhadi RH et al. showed that there was a strong correlation between elevated white blood cells after coronary artery bypass grafting or heart valve surgery and the occurrence of atrial fibrillation after cardiac surgery, supporting a role in the mechanism of atrial fibrillation after cardiac surgery (16). Lymphocytes are involved in the long-term response of the immune system, and the cell-mediated immune response is largely dependent on lymphocytes; large numbers of infiltrating lymphocytes are associated with a favorable prognosis, whereas lymphopenia is considered to be a predictor of a poor prognosis (17). After major surgery, lymphocyte numbers and function are known to continuously drop (18). By preventing lymphocyte-mediated cytolysis, neutrophils can provide a tumor-friendly environment. One of the most significant innate immune system mediators, the neutrophils are abnormally overactivated by a number of inflammatory cytokines and chemokines produced by cancer cells, which can enhance cell arrest within capillaries and lead to the destruction of healthy host tissues (19). Increased neutrophil counts indicate a higher risk of negative outcomes in percutaneous coronary intervention (PCI) patients (20). Similar to this, alterations in inflammatory markers roughly coincide with the time course of atrial fibrillation following heart surgery (21).
Numerous systemic indicators of inflammation have been identified to aid in the diagnosis and development of numerous illnesses, including inflammatory diseases. Integration of various immune pathways, including NLR, dNLR, PLR, LMR, and SII, which are interdependent and play a significant role in prognosis, in COVID-19(22), preterm labor(23), acute pancreatitis(24), rheumatic diseases(25), and coronary artery disease(14,26–28). These indices gather various complete blood count values and are more prone to react to inflammation in afflicted people. Since chronic rather than acute inflammation is largely mediated by monocytes, which are monocyte-derived macrophages, and lymphocytes, LMR has been employed as a marker of the chronic systemic inflammatory response. Increased neutrophil and platelet counts are characteristic changes in acute systemic inflammatory responses. NLR, dNLR, and PLR have been reported to be associated with the development of cardiovascular disease, and several studies have demonstrated that high NLR and high mean platelet volume (MPV) are independent predictors of long-term major adverse cardiovascular events (MACE) after PCI, especially in acute coronary syndrome (ACS)(26). Other studies have also shown that PLR at admission is significantly associated with the severity and complexity of coronary atherosclerosis in patients with ACS (13,28). In this study, systemic inflammatory indices such WBC, NE, NE%, NLR, dNLR, LMR, and SII on the first post-esophagectomy day were considerably greater in patients with PA than in patients with non-PA, and LMR was significantly lower than that in non-PA. Among of all the inflammatory indices, SII and NLR exhibited the highest area under the curve (AUC = 0.661). LMR showed the best specificity (95.5%), however it also had a low sensitivity. With a sensitivity of 86.0%, SII had the highest level, but it was not extremely sensitive.
In recent years, the systemic immune inflammation index (SII), SII = ANC×APC/ALC, which incorporates three different types of inflammatory cells and is based on platelet count and NLR, has been established. It considers the inflammatory and immune condition of the patient. SII is a comprehensive measure of inflammation that is highly predictive of cardiovascular disease. High SII readings have been shown to negatively and independently affect the advancement of coronary atherosclerotic plaque, unfavorable progression such as congestive heart failure, hospitalization, and the long-term course of severe coronary syndromes(27,29,30). In another study conducted by Erdoğan et al., it has been found that SII can be a strong predictor of coronary artery occlusion compared to PLR and NLR, which is considered to be hemodynamically significant and can be used as an independent predictor of coronary artery occlusion, which may lead to heart attack (31). A different study found that SII had a higher level of predictive accuracy than PLR and NLR and could independently predict the presence of left ventricular hypertrophy (LVH) (32). Additionally, SII may support the differential diagnosis of venous thrombosis patients. It is more accurate than PLR and NLR for estimating venous thrombosis in patients (33). In addition, on the fifth post-esophagectomy day, some systemic inflammatory indices in our study remained greater in PA patients than in non-PA patients. The recovery of PA patients was slower in terms of systemic nutritional markers.
Surgery-related trauma and the inflammatory reactions that follow are crucial in the etiology of PA. A recent study found that postoperative triggers operating on the delicate atrial substrate created by preoperative, medically induced, and postoperative remodeling processes are what cause atrial fibrillation (AF). The addition of transient surgically induced AF-promoting changes to prior atrial remodeling (preexisting substrate) exceeds the threshold vulnerability, allowing autonomic nervous system (ANS)-promoted triggering, inflammation, and oxidative stress to initiate postoperative AF (3). Research is being done on the pathophysiological pathways that involve oxidative stress and inflammation. Given that arrhythmia may contribute to the development of inflammation and that inflammation may cause arrhythmia. As a result, the two could create a dangerous vicious circle (4). Along with the intrusiveness of the surgery itself, cytokines that promote inflammation are also known to be released as a result of postoperative infectious complications (PIC) (34). Recent research has demonstrated that PIC following esophagectomy negatively affects patient survival (35).
According to a study by David Amar and colleagues, taking statins prior to major thoracic surgery was linked to a lower incidence of atrial fibrillation following the procedure (36). Additionally, James et al. demonstrated that prophylactic intravenous amiodarone was linked to postoperative hypotension, bradycardia, and a longer QTc interval in addition to a lower incidence of AF after esophagectomy (37). A substantial association between PA patients and other postoperative problems was found in our study. PA may have been viewed thus far as an early warning indication of other (infectious) issues rather than as the cause of these complications, however, this may be owing to uncertainty in this relatively small study. The prevention of PA may merely serve to conceal early clinical indications of additional surgical problems and to postpone treatment. Because PA is rather simple to cure and typically goes away quickly after the start of medication, the need for prophylaxis of the condition is still debatable. The discovery of risk variables, however, might signal the emergence of more severe issues. Therefore, in order to avoid postoperative arrhythmia surgeons should carefully consider the use of pertinent drugs.
The clinical implications of this study are significant. It is possible to identify early patients who are at high risk of developing PA after esophageal surgery by performing a simple and cost-effective peripheral blood test, which may be easily brought to the attention of surgeons in the perioperative phase. This study has certain limitations. To start, it can be challenging to prove causality and generalization and control for bias and confounding factors because it is based on a single institution. Second, because this was a clinical study, it was unable to explore the molecular biological pathways by which inflammatory variables affect the arrhythmia that was being examined.