Patients and Study Protocol
This retrospective study was initiated by reviewing the medical records of patients who underwent a surgical tumor resection due to histologically proven colon cancer in the Hanyang University Hospital Medical Center between 2003 and 2008. Detailed information was obtained from the computerized clinical information system, including demographic information, height and weight, laboratory findings, pathological findings, and semi-automated assessment of the subcutaneous and visceral fat compartments on multi-detector computed tomography (MDCT). A total of 278 patients with colon cancer underwent surgical tumor resection with regional lymphadenectomy, which is dissection of at least the group 1 LNs. In 186 patients with colon cancer, fat measurement was evaluated with preoperative MDCT and these patients were included in the study. Based on our exclusion criteria, patients with limited and palliative resections or those with emergency surgery for tumor-related complications (hemorrhage, ileus, perforation) were not considered for this subgroup. Furthermore, patients who were diagnosed with histologic subtypes other than adenocarcinoma (e.g., small cell carcinoma or neuroendocrine tumor) were excluded.
BMI was calculated as weight divided by height squared. Patients were divided into four groups based on the National Institute of Health (NIH) classification for obesity: normal weight (18.5 ≤ BMI <25), underweight (BMI <18.5), overweight (25 ≤ BMI <30) and obese (30 ≤ BMI). Semi-automated assessment of subcutaneous and visceral fat compartments was performed using a dedicated software package (Fat Assessment Tool, EBW version 4.5, Philips Healthcare). The transverse cross section at the umbilical level was used to derive all abdominal fat measurements, as previously described and validated.9,10 The vendor-default histogram method was used, which determines the average attenuation value (in Hounsfield units) and standard deviation (SD) obtained from a range of −400 to 0 HU on a selected slice. Fat regions are then defined as the area enclosed under the fat histogram curve. Subcutaneous fat is defined as fat that is superficial to the abdominal wall musculature, whereas visceral fat is deep in the muscular wall and includes the mesenteric, subperitoneal, and retroperitoneal components. After the boundaries for subcutaneous and visceral compartments had been adjusted at the umbilical level, automated fat segmentation was performed, which can be further manipulated by the user to include or exclude focal regions if needed. The program then derives the subcutaneous fat area (SFA), the visceral fat area (VFA), total fat area (TFA = SFA + VFA), and the percentage of visceral fat to total fat area (V/T = VFA/TFA × 100). V/T was calculated to provide a single measure of abdominal fat, as published previously.11,12 Elevated V/T indicated higher visceral fat compared with subcutaneous fat, and a threshold was set at V/T = 29 % to define visceral obesity (V/T ≤ 29 % indicated subcutaneous obesity (VFs) and V/T > 29 % indicated visceral obesity (VFv)).12,13
Individual pathologic data were collected including maximum tumor diameter (mm), pathologic tumor stage (including T and N stage), tumor location, degree of tumor differentiation, and presence of lympho-vascular invasion or peri-neural invasion. In addition, the number of examined LNs, the number of metastatic LNs, and the metastatic LN ratio (MLR; number of metastatic LNs/number of examined LNs) was determined for each patient. LNs were recovered by routine mesenteric dissection by the pathologist and LN metastases were determined from subsequent pathologic reports. All pathologic results including MLR were interpreted by an independent pathologist who had no knowledge of the fat measurement data or clinical information. Furthermore, the pT and pN categories were based on the 2002 International Union Against Cancer and American Joint Committee on Cancer pTNM classification (i.e., pT category: pT1 [mucosa or submucosa infiltration] vs pT2 [muscularis propria] vs pT3 [subserosa or beyond without other organs involvement] vs pT4 [extension to other structures or perforates the visceral peritoneum], pN category: pN0 [no metastasis] vs pN1 [1 to 3 metastatic LNs] vs pN2 [4 or more metastatic LNs]).14 Right-sided colon cancers were defined as those arising from the cecum to the transverse colon. Left-sided colon cancers were defined as those arising from the splenic flexure down to and including the recto-sigmoid junction.15,16
Patient follow-up was conducted until death or the last contact date. Patient follow-up ended on June 30, 2010 and the mean follow-up was 45 months. During the follow-up period, 50 patients died of recurrence or metastasis, and survival time ranged from 4 to 89 months.
MLR is defined as the number of involved LNs divided by the number of dissected LNs. The MLR cutoff was designated at 18 %. Thus, MLR was categorized as MLR = 0 %, MLR < 18 % and MLR ≥ 18 %.17,18 Adjuvant therapy was administered according to pathologic stage and physician recommendation.
Descriptive statistics were provided for binary and continuous variables using incidence frequency (%) and mean ± standard deviation. The chi-square test was used to compare binary variables, and two-sample t test was used to compare continuous variables. Multivariate logistic regression analysis adjusted by confounding factors was used to assess inter-group differences in MLR. The Kaplan-Meier model with log-rank test was used to assess the impact of different characteristics on survival. Hazard ratios were calculated using the Cox proportional hazard regression model to assess potential predictors of survival. All statistical analyses were performed using SPSS software for windows, version 17 (SPSS Inc. Chicago, IL, USA).
The study described in this report was approved by the Ethics Committee of Hanyang University School of Medicine, Seoul, Korea, in accordance with the Declaration of Helsinki.