Institutional Review Board approval was obtained from the Sun Yat-sen Memorial Hospital, Sun Yat-sen University (Guangzhou, China). Patients with BCa who underwent radical cystectomy between July 2007 and March 2017 at Sun Yat-sen Memorial Hospital were included. The exclusion criteria were as follows: (1) patients who underwent neoadjuvant chemotherapy before surgery; (2) patients who underwent laparoscopic radical cystectomy without standard pelvic lymphadenectomy; (3) patients who underwent imaging in other hospitals; (4) CT or MRI performed more than 10 days before surgery; (5) patients with MRI artifacts. All patients met the following selection criteria were included: (1) a contrast-enhanced pelvic CT or MRI performed before surgery in our hospital, with clear images; (2) the lymph nodes resected were recorded and marked group by group; and (3) the bladder tumors and the metastatic lymph nodes were confirmed by pathologic examinations.
Multidetector spiral CT
All patients underwent contrast-enhanced pelvic CT using a 64-detector row CT scanner (Somatom sensation 64, Siemens Medical Systems, Erlangen, Germany). The CT scanning parameters included a tube voltage of 120 kV, 200 effective mAs, a pitch of 0.8, a gantry rotation time of 0.5 s, and a matrix size of 512 × 512. After unenhanced CT scanning, dynamic contrast-enhanced CT scanning was performed after intravenous administration of 80–100 mL nonionic contrast material (iopamidol, 370 mg I/mL, Bracco, Milan, Italy) using a bolus-tracking technique at a rate of 4 mL/s and a flush using 20 mL saline. Arterial phase, vein phase, and delayed phase scans were obtained at 25, 60 s, and 3–5 min, respectively. The slice thickness used to reconstruct images for retrospective review was 1.0 mm.
MRI examinations were performed with 3.0T superconducting scanner (Philips Achieva, Philips Medical System, Best, the Netherlands) using a phased-array coil. T2-weighted MRI sequence (repetition time/echo time = 2497–3500/70–90 ms; slice thickness, 4.0 mm; number of acquisitions, 2–4) and T1-weighted MRI sequence (repetition time/echo time = 272–497/6–14 ms; section thickness, 3.0 mm; number of acquisitions, 2 or 3) were used. All patients underwent contrast-enhanced scanning after administration of gadopentetate dimeglumine (Magnevist; Guangzhou Schering, Guangzhou, China) at a dosage of 0.1 mmol/kg. Pelvic transverse diffusion-weighted (DW) imaging was performed when necessary. The imaging parameters for DW imaging were as follows: repetition time/echo time/inversion time = 2103/60/180 ms; b values, 0 and 800 s/mm2; slice thickness, 4.0 mm without gap; sense reduction factor, 2; number of average, 8; echo train length, 31; flip angle, 90°; fast imaging mode, echo-planar imaging; shot mode, single-shot; fat-suppressed mode, spectral presaturation inversion recovery.
Image analysis and data measurement
Two radiologists with more than 10 years of experience in reading pelvic images reviewed all images without the knowledge of pathologic results. Images were reviewed on Picture Archiving and Communication System (PACS), and determinations were made jointly by consensus. The pelvic lymph nodes were divided into groups according to the drainage region: (1) the perivesical lymph nodes; (2) the bilateral internal iliac, external iliac, and obturator lymph nodes; (3) the presacral, presciatic, and common iliac lymph nodes; and (4) the para-aortic and paracaval lymph nodes. The parameters observed on CT included (1) the size (because the lymph node with maximum short-axis diameter < 3.0 mm couldn’t be identified or measured precisely, we just evaluated the lymph nodes with maximum short-axis diameter ≥ 3.0 mm) and morphologic characteristics (including the presence of the fatty hilum of lymph nodes, the ratio of short/long-axis diameter of lymph nodes, and the margin) of the lymph nodes; (2) the enhancement degree of lymph nodes (CT attenuation value increased 10–40 Hu after enhancement indicates mild-moderate enhancement, and an increase of more than 40 Hu indicates remarkable enhancement); and (3) the presence of necrosis inside lymph nodes. Correspondingly, we observed the following characteristics of MR images: (1) the size (only the lymph nodes with maximum short-axis diameter ≥ 3.0 mm were evaluated) and morphology of lymph nodes; (2) whether the diffusion of the LNs was limited in DW MRI (we did not get a quantitative apparent diffusion coefficient map because many lymph nodes were too small to measure the region of interest); and (3) the enhancement degree of lymph nodes (an enhancement degree similar to that of the bladder muscle layer indicates remarkable enhancement and a lower degree indicates mild-moderate enhancement) and necrosis in lymph nodes.
The resected tumors and lymph nodes were sampled for conventional hematoxylin–eosin (HE) staining and immunohistological staining for cytokeratin 7 (CK7), cytokeratin 20 (CK20), epithelial membrane antigen (EMA), P63, P53, Vimentin, prostate-specific antigen (PSA), the Ki-67 labeling index, and GATA-binding protein-3 (GATA-3).
The data of CT and MRI were compared with those of pathologic examination. Non-numerical data was analyzed with Kruskal–Wallis test, and categorical data were compared using χ 2 test. Differences were considered significant when the P values were less than 0.05. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the optimal cutoff value of lymph node size for diagnosing metastasis. The area under the ROC curve (AUC) was evaluated for diagnostic ability. All statistical tests were performed by using the SPSS software (version 20.0; SPSS, Chicago, IL, USA).