From March 2017 to April 2018, consecutive 23 patients undergoing laparoscopic surgery for the rectal cancer for Union for International Cancer Control (UICC) stage I-III rectal adenocarcinoma in Kansai Medical University Hospital were recruited for this trial. All tumors diagnosed within 15cm from the anal verge by the flexible endoscopy were eligible for this study. Initial staging of T and N categories in all but 2 cases of cT2, were diagnosed by 1.5-3.0T MRI. These 2 cases of cT2 underwent only CT scan. Thirteen cases with cT1-2, cT3 (in-vivoCRM≧1mm, cN0-1) and extramural venous invasion (EMVI) (-) and tumor deposits (TD) (-) underwent primary surgery (low anterior reaction (LAR) with TME), and 10 cases with cT4 or cT3 (in-vivoCRM<1mm, ≧cN2, EMVI (+), TD (+)) underwent neoadjuvant chemo-radio therapy (CRT: 45-50.4 Gy; 1.8 Gy x 25-28 + TS1®: TAIHO PHARMACEUTICAL CO., LTD. Tokyo, Japan) followed by surgery after 6 weeks later. In CRT cases, the operative procedure was selected according to the status of post CRT in-vivoCRM after restaging with MRI. The LAR with TME was selected for 5 cases with post CRT in-vivoCRM≧1mm. In these 16 cases of LAR with TME the in-vivoCRM and smrCRM values were obtained by one radiologist and compared with the pCRM.
In the other 5 cases whose post CRT in-vivoCRM were <1mm, total pelvic exenteration (n=1), abdominoperineal resection (n=2), LAR with combined resection of bilateral seminal vehicle and prostate shaving (n=1) were performed for the pCRM negative surgery. One case with pathological complete response (pCR) underwent LAR with TME and it was excluded in the CRM examination. In all cases (n=23), specimen MRI was performed according to our procedures as describe below and compared mesorectal nodules with pathological results to know the diagnostic accuracy of the specimen MRI for detecting malignancy in these nodules (Fig 1). The patient characteristics are summarized in Table 1. The male to female ratio was 18: 5. The median age was 67 years (range: 45-79 years). Median tumor distance from the anal verge was 8.0 cm (range: 0-13 cm). Pre-operative long-course chemoradiotherapy was administered in 10 patients. Pathological TNM, T stages were pTx:1, pT1:1 , pT2:3, pT3:18, and the N stages were pN0:12, pN1a:5, pN1b:2, pN1c:3, pN2b:1. pStages were X:1, I:3, IIA:8, IIIA:1, IIIB:9, IIIC:1. Sixteen cases of them underwent LAR with TME according to the preoperative CRM evaluation (in-vivoCRM >1mm). Their data of CRMs were used to know the diagnostic accuracy of smrCRM.
Preparation of specimen for MRI of the resected specimen (smr) (Fig 2)
Surgical specimen of the rectum was inked on the TME dissection plane with a poster marker (2-A). After stuffing gauze into the specimen, a plastic rod was inserted into the lumen of the specimen, which was then placed in a semi-cylindrical tray made of moldable plastic (2-B). Three to four sutures were placed at each end of it and tied to the edges of the plastic tray to minimize shrinkage. The specimen in the plastic tray was subsequently inserted into a plastic tube before MRI examination (2-C).
MRI of resected specimen (smr) and Formalin Fixation and Slicing (Fig 3)
The images are T2-weighted and taken as fat-suppression images（Signa excite-HD）with a head coil. GE 3·0T: FOV (mm) 250x250, Read matrix 512x512. Contiguous images (3 mm thick) of the specimen were obtained from the distal end along the length of the mesorectum. The specimens were then immersed in 10% neutral buffered formalin and fixed for at least 48 h. The most important site of the CRM to analyze was determined based on the distance from the distal end of the specimen according to smr findings and sliced transversely in order to provide coronal sections through the rectum and mesorectum. After obtaining 6 mm thick sections, pictures of these sections were taken and documented.
Correlation coefficient between in-vivoCRM, smrCRM and pCRM values
In order to measure the CRM microscopically, made a section including most CRM threatening tumor lesion that include not only primary tumor lesion but also any suspicious malignant nodules and EMVI affecting CRM under image navigation of smr. Practically, we made a first section, that include the tumor lesion threatening CRM. In these 16 cases of LAR with TME, in-vivoCRM and smrCRM values were obtained by one radiologist and compared with the pCRM.
Diagnostic accuracy of smr for the mesorectal nodules
With reference to the Mercury study II , Taylor of MRI staging , based on the following diagnostic criteria, the nodule was diagnosed as malignant: irregular outlines or internal signal heterogeneity, tumor signal intensity expanding a vessel. A total of 96 pathologically diagnosed nodules, that could affect the CRM status in smr, were selected in the mesorectum of 23 cases of surgical specimens. These nodules were indicated on the pictures of the specimen sections and assessed by two radiologists who were blinded to the pathological findings on smr.
Descriptive statistics were used to summarize the variables. Because variables were nonparametric distribution, we used the statistical method below. In order to know the correlations between in-vivoCRM, smrCRM and pCRM, the single regression analysis and Spearman’s rank correlation coefficient were used. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of our criteria for malignant nodules were computed and reported with 95% CIs. All statistical analyses were performed with software (Statflex ver.6; Artec Co., Ltd. Osaka, Japan)