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Thoracotomy Procedures Effect Cytokine Levels After Thoracoabdominal Esophagectomy

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Thoracotomy Procedures Effect Cytokine Levels After Thoracoabdominal Esophagectomy 258 ONCOLOGY REPORTS 27: 258-264, 2012 Thoracotomy procedures effect cytokine levels after thoracoabdominal esophagectomy VILMA OLIVEIRA FRICK1, CHRISTOPH JUSTINGER1, CLAUDIA RUBIE1, STEFAN GRAEBER2, MARTIN K. SCHILLING1 and WERNER LINDEMANN3 1Department of General, Visceral, Vascular and Pediatric Surgery, University of the Saarland; 2Institute of Medical Biometrics, Epidemiology, and Medical Informatics (IMBEI), University of the Saarland, 66421 Homburg/Saar; 3Department of Visceral, Vascular and Thoracic Surgery, Ortenau Klinikum Lahr-Ettenheim, 77931 Lahr, Germany Received July 5, 2011; Accepted August 26, 2011 DOI: 10.3892/or.2011.1493 Abstract. Pulmonary complications together with surgical resultant cytokine levels may contribute to the occurrence complications are the most frequent causes for morbidity of postoperative pulmonary complications and may have an and mortality after thoracoabdominal esophagectomy. The impact on the extent and severity of the surgical stress. con tinuous improvement of surgical techniques has led to a decrease in surgical complications, whereas up to 30% of the Introduction patients develop postoperative pulmonary complications such as acute lung injury (ALI) or even the more severe acute respi- Cytokines act as messengers both within the immune system ratory distress syndrome (ARDS), which are characterized by and between the immune system and other systems of the an acute inflammation in the lung parenchyma and the airspace. body, forming an integrated network that is highly evolved Evidence from several studies indicates that a complex network in the regulation of immune responses. After elective surgery of inflammatory cytokines and mediators play a key role in an acute phase response is often observed which commonly mediation, amplification, and perpetuation of the process of results in an activation of the cytokine network as an important lung injury and that the thoracotomy itself is a risk factor for part of this response. In particular, IL6 has been shown to play developing ALI or ARDS. In this trial, the cytokine levels of a pivotal role of in the acute phase response after surgery (1-3), IL6, IL8 and IL10 were measured and compared in 30 patients resulting in increased plasma levels which correlate with the who had undergone an extended radical thoracoabdominal extent and severity of the surgical stress (1,3). esophagectomy for esophageal cancer, via anterolateral thora- Acute lung injury (ALI) and a more severe form, the acute cotomy (n=17) or posterolateral thoracotomy (n=13). Patients of respiratory distress syndrome (ARDS), are characterised by both groups were similar in terms of age, sex and preoperative a diffuse inflammation and an increased alveolar-capillary pulmonary function as well as in the anesthetic procedures they membrane permeability that causes diffuse interstitial and have undergone. All patients displayed significantly increased alveolar oedema and persistent refractory hypoxemia (4). serum levels of IL6 and IL8 after thoracoabdominal esophagec- Evidence from several studies indicates that a complex network tomy. However, patients who were subjected to an anterolateral of inflammatory cytokines and chemokines has a leading role thoracotomy were reported with significantly higher serum in mediation, amplification and perpetuation of the process of levels of IL6 and IL8 compared to patients who had received a lung injury (5). posterolateral thoracotomy. Thus, the choice of the thoracotomy ARDS is one of the primary contributors to mortality in ICU method during the thoracoabdominal esophagectomy and the patients. A wide variety of clinical conditions such as sepsis, burns, trauma and major surgery and esophageal resection in particular, constitute a predisposition for the development of ARDS (6-8). The prognosis of esophageal cancer is generally poor because Correspondence to: Dr Vilma Oliveira Frick, Department of General, Visceral, Vascular and Pediatric Surgery, University of the of its biological aggressiveness and anatomical character istics. Saarlands, 66421 Homburg/Saar, Germany In order to improve the prognosis, an extended radical esopha- E-mail: [email protected] gectomy with radical lymphadenectomy is often performed. However, transthoracic esophagectomy with lymphadenectomy Key words: cytokines, acute lung injury, acute respiratory distress is well known as one of the most stressful gastrointenstinal syndrome, thoracoabdominal esophagectomy, esophageal cancer operations, which considerably increases the amount of surgical stress (9,10). As a result, the operative morbidity rate is still high, despite recent improvements in the peri-operative management (11). Moreover, it has been reported that elevated plasma FRICK et al: CYTOKINE LEVELS AFTER THORACOABDOMINAL ESOPHAGECTOMY 259 cytokine levels correlate with postoperative morbidity and padded sand bag below the buttocks and back. The ipsilateral mortality rates (12,13). Sakamoto et al reported that plasma arm was placed on an elevated armrest. The skin incision levels of IL6 after thoracic surgery, such as pneumonectomy followed the submammary fold and extends from the sternum and esophagectomy, were much higher than levels after anteriorly to the midaxillary line. The chest cavity was entered abdominal surgery, such as pancreaticoduodenectomy and in the fourth or fifth intercostal space. Dissecting the dorsal colorectal resection (14). mediastinum the lung was obtructed via spatula. Among the postoperative complications after thoraco- Posterolateral thoracotomy. To enter the chest cavity abdominal esophagectomy, pulmonary complications as well via posterolateral thoracotomy, the patient was placed in the as anastomotic leakage tend to be the most critical (15,16). For appropriate complete lateral decubitus position. The incision instance, up to 30% of the patients after thoracoabdominal followed the course of the underlying ribs, and extends from esophagectomy develop pulmonary complications such as ALI a point located ~8 cm from the mid-spinal line to the anterior or even ARDS (17). Although a variety of insults may lead to axillary line, thus passing below the tip of the scapula. ALI and ARDS, a common pathway may probably result in lung damage (18-20). Excluding criteria. Patients with chronic inflammatory diseases A complex series of inflammatory events have been and patients with chronic viral infections such as hepatitis and recognized during the development of ARDS, but the exact HIV were not included. sequence of the events remains unclear. Leukocyte activation and free radical release, proteases, arachidonic acid meta- Blood sampling and processing. Peripheral blood samples were bolites, inflammatory and anti-inflammatory cytokines result collected in sterile heparinized tubes under sterile con ditions. in the increased alveolar-capillary membrane permeability The samples were centrifuged at 1500 x g for 5 min and the (21-24). plasma was stored at -80˚C until ELISA assays were performed. The activation of the cytokine network is crucial for the development of e.g. ALI or ARDS (4,6,25) and plasma Enzyme-linked immunosorbent assay of IL6, IL8 and IL10. cytokine levels are known to correlate with postoperative Human IL6, IL8 and IL10 concentrations in the plasma were morbidity and mortality rates (12,13). To address this issue, we measured in duplicate using commercially available ELISA investigated the impact of the thoracic approach in thoraco- kits (Biosource Europe, Nivelles, Belgium) following the abdominal esophagectomy on plasma cytokine levels. To our manufacturer's guidelines. knowledge, anterolateral thoracotomy has not been compared to posterolateral thoracotomy with respect to trauma-related Statistical analysis. All cytokine concentrations are presented changes in the metabolism and immune response as measured as mean and SEM (standard of the mean). All statistical calcula- in terms of cytokine production. tions were done with the MedCalc software package (MedCalc Thus, the present study was designed to quantify differences Software, Mariakerke, Belgium) (26). The parametric Student's in surgical trauma between anterolateral and posterolateral t-test was applied, if normal distribution was given, otherwise, thoracotomy during thoracoabdominal esophagectomy by the Wilcoxon's rank sum test was used. p<0.05 at an α<0.05 measuring concomitant levels of IL6, IL8 and IL10 production. was considered significant. Materials and methods Results Patients. Approval for this investigation was gained from Patients characteristics, perioperative cytokine levels and the ethics committee of the University of the Saarland. After comparison of background factors. Prior to the thoraco- informed consent was obtained, thirty consecutive patients abdominal esophagectomy, 30 patients were enrolled in this undergoing esophagectomy for esophageal malignancies were study over a 45-month period. Tables I and II summarize the included in this prospective trial between February 2002 and biographic and operative data. Male (25, 83.3%) and female October 2005. According to the respective approach to the (5, 16.7%) patients were included in the study with a median chest cavity patients were allocated into two groups. Group I age of 61 years (42-77). The interleukin expression was evalu- consisted of 17 patients who had an anterolateral thoracotomy ated in all patients before surgery. There was a great variation and group II included 13 patients who had a posterolateral in the serum levels of the analysed
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