This study was a retrospective, single-center, two-arm cohort study performed between 2016 and 2018 at the National Cancer Center Hospital East, Japan. Eligible patients were assigned to receive skin disinfection with either 1.5% olanexidine gluconate (Olanedine™; Otsuka Yakuhin Kogyo, Tokyo, Japan) or 1.0% chlorhexidine-alcohol (Sterichlone™; Kenei Seiyaku, Tokyo, Japan) 30 min before surgery, and 372 consecutive patients were analyzed. Written informed consent was obtained from all patients. The study was approved by the Committee for ethics of the National Cancer Center (Japan) (approval number #2018-332). Also, this study confirms to the provisions of the Declaration of Helsinki (as revised in Tokyo 2004).
Patients who underwent thoracic esophagectomy for esophageal cancer at the National Cancer Center Hospital East, Japan, were investigated. Preoperative diagnoses were based on imaging studies, including upper gastrointestinal studies, endoscopy, and conventional cross-sectional imaging (computed tomography). Histological evaluation of endoscope-guided biopsy specimens was performed in all cases. Data on the preoperative stage of the disease, histopathological findings, surgical procedures performed, and outcomes were collected from the patient medical records, as described previously .
In all cases, thoracic esophagectomy was performed under the direction of the regular attending surgeon. For transthoracic esophagectomy, subtotal resection of the esophagus was performed with three-field regional lymph node dissection, regardless of the tumor stage. In the thoracoscopic approach, we preserved the azygos arch and the right bronchial artery. In contrast, the azygos arch was transected in all patients who underwent the thoracotomy approach. The laparoscopic approach was principally used, except in cases with bulky lymph node metastasis or previous history of abdominal surgery via laparotomy. The esophagus was usually reconstructed with a gastric tube via the retrosternal route; right hemi-colic reconstruction was performed via the posterior sternal route when gastrectomy of the remnant stomach was required, as described previously .
Anesthesia and intraoperative management during thoracic esophagectomy
The standard institutional anesthetic practice for thoracic esophagectomy was modified to enable the development of intraoperative core hypothermia in the present study. In brief, upon patient arrival in the operating room, routine monitoring was applied, which included electrocardiography, noninvasive blood pressure monitoring, pulse oximetry, and capnography. Before the induction of anesthesia, an epidural catheter was inserted at the fifth to sixth thoracic interspace, and placed 5 cm beyond the introducing needle tip, as described previously .
Anesthesia was induced with 1.5–2.5 mg/kg propofol, 1–2 μg/kg fentanyl, and 0.1 mg/kg vecuronium. Anesthesia was maintained with 3% end-tidal sevoflurane in oxygen until tracheal intubation. Anesthesia was then maintained with 2% end-tidal sevoflurane at 40% oxygen (air/oxygen mixture at 4 L/min) supplemented with doses of fentanyl and vecuronium. A heat- and moisture-exchanging filter was positioned between the endotracheal tube and the breathing circuit, as described previously .
Definition of surgical complications
SSI was judged in accordance with the definition established by the Surgical Wound Infection Task Force 1, and included infections at the incision site or organ/space manipulated during operative intervention. Remote infections were not included in the definition of an SSI, with the exception of bloodstream infections related to a SSI. Symptomatic remote infections were also included in the analysis. Among the remote infections, respiratory infection was defined as the presence of new or progressive infiltrates on chest radiographs, plus at least two of the following signs of respiratory tract infection: temperature > 38 °C, purulent sputum, leukocytosis of > 1 × 104/mm3 or leukopenia of < 4 × 103/mm3, and signs of inflammation on auscultation, as described previously .
Perioperative management was performed with the same clinical management pathway (CMP) for all patients, regardless of the type of abdominal approach, as described previously . All patients received enteral nutrition through a nasal feeding tube until the start of oral intake on postoperative day (POD) 6. In brief, fluid balance was achieved through a peripheral line, with additional enteral feeding on POD 1. Enteral nutrition was discontinued after the absence of anastomotic leakage was confirmed on POD 6. Perioperative antimicrobials are used only the surgery Cefmetazole sodium.
Perioperative management was performed by the same clinical staff in the same environment using the ICU and subsequent ward-based facilities. The same principles of care were applied to both groups. The CMP was applied in both the ICU (POD 1 and 2) and the surgical ward (POD 3 and later). In brief, the endotracheal tube was removed from all patients in the operating room or immediately upon arrival in the ICU. Patients remained in the ICU for 1 day after surgery. On POD 6, a radiographic contrast agent swallow examination was performed to evaluate the anastomosis and any passage problems. If this examination showed no leakage or obstruction, the nasogastric tube was removed and oral intake was initiated in accordance with the postoperative diet program. In the absence of any complications, the patient was enrolled in the postoperative rehabilitation program and discharged on POD 12–20, as described previously .
If there were any abnormal clinical findings such as hypoxia, leukocytosis, or abnormal pleural drainage during the course of the postoperative CMP, computed tomography and radiographic examinations were performed to diagnose and optimally manage the abnormality as soon as possible as described previously .
Propensity score matching was used to assemble two comparable groups. The covariates were preoperative treatment, thoracic surgical approach, abdominal surgical approach, clinical stage, ASA Grade, and type of antibiotics. Each patient in the olanexidine gluconate group was matched to a patient in the chlorhexidine-alcohol group who had the closest propensity score using simple 1:1 matching without replacement. To prevent poor matches, a caliper of 0.20 of the standard deviation of the logit of the propensity score was used. Intergroup differences were analyzed using the Chi-squared test and the Mann–Whitney U-test. A p value < 0.05 was considered to indicate a statistically significant difference. All statistical analysis were performed using R calculation software.