3.1. Patients
This retrospective study was approved by our institutional review board and written informed consent was waived. Between January 2010 and December 2013, 94 patients with rectal cancer underwent MR imaging for preoperative tumor staging. Thirty-three of the 94 patients were excluded because of status post neoadjuvant chemotherapy (n = 17), biopsy-only diagnosis with no confirmatory surgical specimens (n = 8), status post radiation therapy (n = 4), preoperative distant metastases (n = 3), and image quality severely degraded by artifacts (n = 1). Thus, the remaining 61 patients (mean age, 64.5 ± 12.1 years; age range, 32 - 86 years), consisting of 41 men (mean age, 65.1 ± 12.5 years; age range, 32 - 86 years) and 20 women (mean age, 63.2 ± 11.5 years; age range, 47 - 83 years) were included in our study cohort.
The interval between the preoperative MR imaging and surgery ranged from 2 to 82 days, with the mean of 19 days. The type of surgery was a low anterior resection in 46 patients, abdominoperineal resection in 13 patients, and local transanal resection in two patients. A total of 62 lesions in 61 patients were histopathologically confirmed as rectal cancer. One patient had synchronous tumors in the rectum. The types of rectal cancer were adenocarcinoma in 60 lesions and squamous cell carcinoma in two.
3.2. MR Imaging Protocol
Pelvic MR imaging was performed using a 3-T MR system (Intera Achieva Quasar Dual; Philips Medical Systems, Netherlands) and a SENSE-Torso coil. The MR protocol included the following sequences: two-dimensional fat-suppressed axial T1-weighted turbo spin-echo imaging (repetition time (TR)/echo time (TE), 759/15 msec; matrix, 464 × 232; field of view, 26 × 26 cm; parallel imaging factor, 1.9; 5-mm section thickness with a 2-mm intersection gap; acquisition time for 20 sections, 2 minute 39 seconds); two-dimensional sagittal T1-weighted turbo spin-echo imaging (TR/ TE, 714/17 msec; matrix, 480 × 240; field of view, 28 × 28 cm; parallel imaging factor, 1.5; 5-mm section thickness with a 2-mm intersection gap; acquisition time for 20 sections, 3 minute 23 seconds); two-dimensional axial T2-weighted turbo spin-echo imaging (TR/TE, 5,894/90 msec; matrix, 512 × 256; field of view, 26 × 26 cm; parallel imaging factor, 1.5; 5-mm section thickness with a 2-mm intersection gap; acquisition time for 20 sections, 3 minute 13 seconds); two-dimensional sagittal T2-weighted turbo spin-echo imaging (TR/TE, 5,625/90 msec; matrix, 512 × 256; field of view, 28 × 28 cm; parallel imaging factor, 1.5; 5-mm section thickness with a 2-mm intersection gap; acquisition time for 20 sections, 3 minute 11 seconds); and two-dimensional axial diffusion-weighted imaging with a single-shot echo-planar sequence (TR/TE, 4,997/60 msec; matrix, 112 × 90; field of view, 28 × 28 cm; parallel imaging factor, 2.3; b factors, 0 and 1,000 sec/mm2; 5-mm section thickness with a 2-mm intersection gap; acquisition time for 20 sections, 1 minute 44 seconds).
3.3. ADC Value Measurement
Two experienced radiologists with 6 and 5 years of post-training experience interpreting MR images, who had no knowledge of patient clinical information, measured the ADC value of rectal cancer in consensus. For the ADC value measurement, mean ADC value was obtained by placing a circular region-of-interest (ROI) cursor (37 - 837 mm2). A ROI was drawn to encompass the entire tumor at the image presenting the largest cross-section area of the tumor (Figure 1).
Figure 1.
A 74-year-old woman with rectal adenocarcinoma who was diagnosed with lung metastasis 6 months after surgery. A, Axial T2-weighted image shows an ill-defined mass located in the rectosigmoid portion (white arrow). B, Diffusion-weighted image (reversed black-and-white image) and C, Apparent diffusion coefficient (ADC) map show a low ADC value (0.721 × 10-3 mm2/sec) in the mass (circle in part C).
3.4. Prognostic Factors
Various tumor markers and clinical-pathologic risk factors were recorded from the hospital information system at the time of cancer diagnosis. The tumor markers and clinical factors were plasmatic CEA, carbohydrate antigen (CA) 19-9 level, and the presence or absence of postoperative local recurrence or distant metastases. The histological risk factors were pathological T stage (T1, T2, T3, and T4), pathological N stage (N0, N1, and N2), TNM stage (I, II, III, and IV), tumor differentiation grade (1 = well differentiated; 2 = moderately differentiated; and 3 = poorly differentiated), lymphatic (ly0, ly1, ly2, and ly3), and microvascular invasion (v0, v1, v2, and v3). The lymphatic and microvascular invasion were as follow: ly/v0 = no or slight invasion; ly/v1 = mild invasion; ly/v2 = moderate invasion; and ly/v3 = severe invasion.
3.5. Statistical Analysis
Statistical analyses were performed using MedCalc Software for Windows (version 15.8). Fisher’s exact test was conducted to evaluate differences in patient clinical-pathologic risk factors between the patients with and without postoperative local recurrence or distant metastases. An optimal cutoff value that yielded the maximal sensitivity and specificity for the prediction of tumors with postoperative local recurrence or distant metastases was determined using the receiver operating characteristic (ROC) curve. The patients were classified into two groups according to this cutoff value. For each observer measurement, the intraclass correlation coefficient was calculated to evaluate interobserver differences for significance. Other parameters and the cutoff values that we used in the analysis were age (60 years old), plasmatic CEA (5 ng/mL), and CA19-9 (37 U/mL). These plasmatic CEA and CA19-9 cutoff values are based on our institutional standard.
The primary outcome was the disease-free survival, i.e., the length of time from the surgery to the development of postoperative local recurrence or distant metastases. Univariate analysis was performed using the Kaplan-Meier method and log-rank test. Risk factors statistically significant (P < 0.2) from the univariate analysis were reassessed in multivariate analysis that used the Cox proportional hazards regression model. For the subgroup of patients with postoperative local recurrence or distant metastases, disease-free survival was compared between patients below and above the ADC cutoff. A P value less than 0.05 was considered as significant.
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