Patients
The medical records of consecutive patients who underwent radical esophagectomy (subtotal esophagectomy with two/three-field lymph node dissection) for ESCC at the Okayama University Hospital (Okayama, Japan) from January 2010 to February 2015 were retrospectively reviewed. A total of 273 ESCC cases without evidence of distant metastases underwent radical esophagectomy. To investigate advanced resectable ESCC, cases with clinical stage over II were selected, excluding those with T4b and supraclavicular lymph node metastasis and other organ metastasis at the time of treatment initiation. Four patients after definitive chemoradiotherapy were excluded. Nine patients with unresectable or residual cancer (R1/2) at operation were also excluded. To eliminate differences in surgical invasiveness, the operative procedure was limited to radical esophagectomy with gastric tube reconstruction; other procedures (two-stage operation, reconstruction with jejunum/colon) were excluded. Cases that underwent combined resection of other organs with cancer were also excluded. Finally, 30 cases were excluded because of insufficient CT data. Thus, 72 cases were eligible for this study (Figure 1).
Surgical Procedures
Esophagectomy with two/three-field lymph node dissection was performed. The operations were performed by open esophagectomy (OE) with right thoracotomy in 17 cases and thoracoscopic esophagectomy in the prone position (TEPP) as minimally invasive surgery (MIS) in 55 cases. Subsequently, abdominal lymphadenectomy and gastric conduit reconstruction were performed under laparotomy or hand-assisted laparoscopic surgery (HALS). Details of the surgical techniques of radical esophagectomy have been reported (15). Data of the surgical procedure, operative time, amount of blood loss, and infusion volume were recorded as operative factors.
Postoperative Management
During this period, there was no change in postoperative care, including drugs administered (methylprednisolone, antibiotics, proton pump inhibitors, catecholamine). The patients were admitted to the intensive care unit (ICU) on mechanical ventilation after radical esophagectomy. The patients were extubated on POD 1 if they had no problems on chest X-ray, blood examinations, and bronchoscopy. On POD 3, CT was performed to detect postoperative acute complications. If there were no serious findings on CT, and the patient’s course was good, the patient could be discharged from the ICU.
CT analysis
The preoperative baseline CT examination was taken with in 1 week before surgery (at the time admission for surgery) for the cases with preoperative therapy or preoperative sarcopenia and taken within 1 month before surgery for the cases without both preoperative therapy and preoperative sarcopenia. The original purpose of the CT examination in the postoperative acute phase (POD 3) was to detect postoperative complications such as pneumonia, anastomotic leakage, and venous thrombosis for all patients who underwent ESCC surgery. Therefore, the changes in skeletal muscle mass could be analyzed using the CT images of the postoperative acute phase and preoperative baseline images before surgery. Following previously published reports about sarcopenia, skeletal muscle mass was measured at the level of the third lumbar vertebra (L3) with CT images. Although there are many reports using total skeletal muscle mass at the L3 level (11, 13, 16-20), only the psoas muscle was measured to as much as possible exclude the effects of edema in the postoperative acute phase (6). The images were evaluated using a CT image analysis system (Synapse Vincent, Fujifilm Medical, Tokyo, Japan). The iliopsoas area was measured using Hounsfield units (HU) of -29 to +150 (Fig. 2). The quantity of skeletal muscle was evaluated with the total psoas major muscle mass index (TPI). The TPI was defined by normalizing the cross-sectional areas of the bilateral psoas major muscles for height (cm2/m2). The change in the SML from the preoperative state to the postoperative acute phase was analyzed using the change of TPI. The TPI decrease rate was calculated using the formula (postoperative TPI-preoperative TPI) / preoperative TPI × 100, and it was defined as the psoas muscle loss index (PMLI, %). Furthermore, the median PMLI cutoff value (-4.4%) was used as the cutoff value to divide patients into the PMLI mild group and the PMLI severe group.
Analyzed Parameters
Using the PMLI, SML in the acute phase after ESCC surgery was retrospectively analyzed. The preoperative factors (age, blood data, etc.) and intraoperative factors (surgical procedure, blood loss, operative time, etc.) concerned with SML in the acute phase after ESCC surgery were investigated. Furthermore, the relationship between SML in the acute phase after ESCC surgery and long-term prognosis was investigated together with other clinicopathological parameters.
Statistical Analysis
Clinicopathological factors were noted according to the Union for International Cancer Control (UICC) Tumor Nodes Metastasis (TNM) Classification of Malignant Tumors, 8th edition (21). To evaluate the differences between the two groups, continuous variables were assessed using the Wilcoxon rank-sum test, and categorical variables were evaluated using Fisher’s exact test. Differences were considered significant when the P value was <0.05. Kaplan-Meier analyses were also used to estimate the cumulative survival of patients. To identify the preoperative prognostic factors for three-year survival, all variables with P < 0.05 on the univariate analysis were included in the multivariate logistic regression model. All analyses were performed using JMP version 14 statistical analysis software (SAS Institute, Cary, NC, USA).