Oncology Review article High-Resolution MRI in Rectal Cancer

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1 Oncology Review article High-Resolution MRI in Rectal Cancer Adriana Dieguez Department Of Magnetic Resonance And Computed Tomography In Oncologic Diseases, Diagnóstico Médico Junín 1023, C1113AAE. Buenos Aires, Argentina. ( Abstract High-resolution MRI is the best method of assessing the relation of the rectal tumor with the potential circumferential resection margin (CRM). Therefore it is currently considered the method of choice for local staging of rectal cancer. The primary surgery of rectal cancer is total mesorectal excision (TME), which plane of dissection is formed by the mesorectal fascia surrounding mesorectal fat and rectum. This fascia will determine the circumferential margin of resection. At the same time, high resolution MRI allows adequate pre-operative identification of important prognostic risk factors, improving the selection and indication of therapy for each patient. This information includes, besides the circumferential margin of resection, tumor and lymph node staging, extramural vascular invasion and the description of lower rectal tumors. All these should be described in detail in the report, being part of the discussion in the multidisciplinary team, the place where the decisions involving the patient with rectal cancer will take place. The aim of this study is to provide the information necessary to understand the use of high resolution MRI in the identification of prognostic risk factors in rectal cancer. The technical requirements and standardized report for this study will be describe, as well as the anatomical landmarks of importance for the total mesorectal excision (TME), as we have said is the surgery of choice for rectal cancer. Key Words: Rectal cancer; High - resolution magnetic resonance imaging; Circumferential resection margin; Multidisciplinary team; Prognostic risk factors Introduction Colorectal cancer ranks third amongst the most frequently diagnosed tumors in the world, after lung cancer and breast cancer (1). It ranks third in women and fourth in men (1,2). Currently, rectal cancer is handled by a multidisciplinary team (MDT), thus allowing the best diagnosis and treatment options to the patient. It is here where radiologists are confronted with a big challenge, which lies in the importance that our support has within the MDT, since the adequate staging allows proper treatment selection. Active participation in these meetings offers the possibility of continuous exchange between colleagues (oncologists, surgeons, radiotherapists, gastroenterologists, etc.), who will audit our work. We should stress that diagnostic and therapeutic success are directly related with obtaining free margins in histopathology, the so-called circumferential resection margin. High-resolution MRI is the best method of assessing the relation of the tumor to the potential circumferential resection margin: the mesorectal fascia (3). Total mesorectal excision (TME) is the primary surgery for rectal cancer. The dissection plane is formed by the mesorectal fascia that surrounds the mesorectal fat and rectum (4).

2 This fascia determines the circumferential resection margin (Fig.1). The presence of tumor at 1 mm or less from the fascia is directly related with local recurrence and a poor survival rate. While TME cures early stages of the disease, preoperative radiotherapy or chemoradiotherapy provide tumor size and staging reduction in most extensive disease, increasing the possibility of attaining free margins in surgery. Traditionally, surgeons evaluated rectal cancer patients using digital examination, endorectal ultrasound and, in some cases, computed tomography. These methods do not provide the information necessary concerning the relation of the tumor with the circumferential resection margin, which we can access today through high-resolution MRI. As principal benefits, adequate staging by high-resolution MRI avoids unnecessary preoperative treatments, provides an objective staging system for future clinical trials and allows the selection of the best possible preoperative therapy for the patients that need it (3). Technique The high spatial resolution sequences permit a better morphological analysis of the images, a fundamental characteristic for the evaluation of the different prognostic risk factors that we must identify. As with all diagnostic studies that use images, this one is supported by two fundamental pillars: the proper technique and the correct interpretation, which in this case requires trained radiologists. Sometimes intestinal peristalsis degrades the quality of the high-resolution images, impeding an adequate interpretation. For this reason we have implemented in our center a preparation the patient must accomplish before the exam: 1) two days before the exam: 2 pills of simethicone 200mg after each meal (8 pills a day); 2) during those 2 days: avoid meals that contain flour and green-leaf vegetables; 3) the day of the exam: 2 pills of simethicone 200mg 2 hours before the MRI; 4) 8 hours of fasting The exploration time is prolonged, which should be communicated to the patient. A phased-array coil is used, thus improving the signal and providing greater exploration surface for the ETM when compared to the endorectal coil, which is already in disuse for rectal cancer local staging. The images shown in this paper were made using 1.5T equipment (Signa Horizon LX, GE Medical System, Milwaukee, Wisconsin, USA). The rectal cancer staging protocol consists of T2 weighted images (Table 1), in the 3 planes (Fig. 2): sagittal (following the inferior rectal axis and anal canal of the locator), axial (perpendicular to the rectum at the site of the tumor in the high-resolution sagittal images obtained in first place) and, in tumors in the inferior rectum, concluding with the coronal plane (parallel to the anal canal in the high-resolution sagittal images). The study of the pelvis is completed with the evaluation of the retroperitoneal space (to evaluate ascendant and lateral lymphatic dissemination) and of the hepatic gland (to determine the presence of metastasis and the possibility of resection) (Tables 2 and 3). We complete the rectal cancer staging with a helical computed tomography of the chest without endovenous contrast, for the identification of secondary lesions of the lungs.

3 Preoperative Staging of Rectal Cancer As we have already mentioned, rectal cancer is a disease addressed by a multidisciplinary team compromised of, amongst others, surgeons, oncologists, radiotherapists, radiologists and pathologists. Discussion within the multidisciplinary team of the findings of the high-resolution MRI and of the preoperative therapeutic strategy is fundamental given that it significantly reduces the positive circumferential resection margin in rectal cancer patients (5). Within this multidisciplinary task, the fundamental contribution of the radiologist lies in determining if the circumferential resection margin is free or compromised, this way acquiring, through the high-resolution MRI, an important role and, therefore, a great responsibility in the handling of the rectal cancer patient. As Dr. Nagtegaal and Dr. Quirke (6) conclude: In the current era, when evidence-based medicine and quality control are keywords, we believe that the best practice demands the reporting of circumferential resection margin by radiologists and pathologists alike. Therefore, this information should always be present in the high-resolution MRI report, keeping in mind that therapeutic success is directly related with the achievement of free margins in the histopathology. Patients with involved circumferential resection margin should be identified prior to surgery, as they will be selected to receive neoadjuvant therapy. A radiologist trained in the interpretation of high-resolution MRI of rectal cancer patients must be conscious of the responsibility this medical procedure entails. Over-staging implies performing unnecessary therapies, while under-staging requires postoperative combined treatment, generally accompanied with worse functional results, greater toxicity and less local control. In prognostic terms, patients with positive circumferential resection margin show local recurrence at 5 years in approximately 23.7% of cases and disease-free survival at 5 years in approximately 44.5% of cases. In contrast, patients with negative circumferential resection margin have a rate of local recurrence at 5 years of approximately 8.9% and disease-free survival at 5 years at a rate of 66.7% (7). Once the study is finished, we must identify the prognostic risk factors in rectal cancer, knowing that they will be taking into account for the correct choice of treatment. Consequently, we should state with precision the following information: 1) depth of extramural spread in T3 tumors; 2) peritoneal involvement; 3) increasing percentage of nodal disease; 4) extramural vascular invasion; 5) Full thickness T2 or more at the level of puborectal muscle. 1) Tumor Staging The principal purpose of the high-resolution MRI in rectal cancer tumor staging is to determine the extramural extension in T3 tumors and the involvement of neighboring organs in T4. For superficial tumors, endorectal ultrasound has higher accuracy in the evaluation of parietal involvement (8). The seventh edition of the TNM classification of rectal cancer, effective as of January 2010, has presented changes in tumor staging (T), specifically in T4 (9) (Table 4). In T3, the tumor invades the subserosa through the muscularis propria. We assign the term extramural depth of tumor invasion to the distance between the lateral border of the longitudinal muscular layer of the muscularis propria and the lateral border of the tumor (Fig. 3). The measurement of the extramural depth of the tumor by high-resolution MRI is equivalent to the corresponding measurement in the histological analysis (10). In accordance with the extramural depth of the tumors, the T3 is divided into: T3a (<1mm), T3b (1.01-5mm), T3c ( mm) and T3d (>15mm) (10,11). This

4 distance is important for a proper therapeutic choice. Five years survival rate after surgery for patients with extramural depth greater than 5 mm is 54%, while for those patients with a maximum depth less than 5 mm it is 85% (10). In the tumors of the upper-third and upper-half it is of the utmost importance to seek the relation with the peritoneal reflection and its possible compromise, in which case we are speaking of T4a staging (Fig. 4). Involvement of the bladder and uterus must also be ruled out in high tumors. In middle third tumors and below in men, an invasion of the prostate and seminal vesicles may occur, or of the cervix and uterine body in women. Lateral extension may compromise the pelvic wall and the posterior the sacrum. When the tumor invades other organs and structures in the high-resolution MRI images, we speak of T4b staging, having this worse diagnosis. 2) Lymph Node Staging The lymphatic dissemination of rectal cancer can follow an ascendant path, a lateral (uni- or bilateral) path, or a combination of the two. Ascending path presents pararectal dissemination along the superior rectal and inferior mesenteric arteries. The lateral dissemination occurs towards the middle rectal, obturator, external iliac and internal iliac arteries. It is necessary to analyze in detail the probable paths of dissemination keeping in mind that low rectal tumors have a greater tendency to disseminate laterally. Just like in tumor staging, lymph node staging presents modifications in the latest TNM classification (Table 5), subdividing the N1 and N2. It is worth noting that the N3 stopped being used in the previous edition (the sixth), in effect from the year 2002 to december 2009, due to being recategorized. With respect to the criteria employed to evaluate lymph node involvement in rectal cancer, it has been shown that the size of the positive and negative lymph nodes in the mesorectum is similar, with 50% of the positive lymph nodes reaching a diameter less than 5mm. Therefore, if size is considered as sole parameter, the percentage of false positives increases. Gina Brown (12) evaluated lymph node size, the morphology and signal intensity, improving the predictive value of the high-resolution MRI. The border of the evaluated lymph nodes were classified as regular and well-defined or irregular and poorly-defined. In the high-resolution MRI, the lymph nodes with irregular and poorly-defined borders suggest metastatic involvement with a sensibility of 75% and a specificity of 98% (Fig. 5A). The discovery of lymph nodes with mixedsignal intensity (foci of different signal intensity within the lymph node) presents a specificity of 98% in determining metastatic involvement (Fig. 5B). The mixed signal intensity by high-resolution MRI in the lymph nodes correlates with tumor deposits, areas of necrosis or extracellular mucin in the histopathological analysis. Currently USPIO (Ultrasmall Superparamagnetic Iron Oxide Particles) agents are being evaluated to determine lymph node involvement in rectal cancer patients. After administration of the contrast in non-metastatic lymph nodes, central or homogeneous hypointensity is observed. The discovery of lymph nodes with homogeneous or peripheral hyperintensity suggests tumor involvement (13,14). The importance of the information provided by the high-resolution MRI translates for oncologists and radiotherapists into the determination of the type and extension of the neoadjuvant therapy. For surgeons it provides information in relation to the extension of surgical resection. We must keep in mind that the majority of the mesorectal lymph nodes are located in the dorsolateral region, without significant differences in regards to the distribution among positives and negatives. With respect to the height of the tumor, the majority of the positive lymph nodes are found at the same level as the tumor or proximal to the tumor. Positive lymph nodes distal to the tumor are rare, being found in patients with greater numbers of proximal metastases (15). Extramesorectal positive lymph

5 nodes occur with greater frequency in the low rectal cancer, with lymph node involvement in the mesorectum. 3) Extramural Vascular Invasion The term extramural vascular invasion is applied to the presence of tumor cells within blood vessels located outside the intestinal wall, being found in % of colorectal cancer patients (16). High-resolution MRI is useful in the preoperative detection of extramural vascular invasion (Fig. 6). Patients with positive identification by high-resolution MRI have a 3-year disease-free survival of 35%, versus 74% for those with negative identification by high-resolution MRI. It is important to take into consideration that the scoring system of extramural vascular invasion by high-resolution MRI is equivalent to the histology in the prediction of disease-free survival (17) (Fig. 7). Histological extramural vascular invasion is recognized as an independent predictive factor of local and distant recurrence and poorer overall survival (16-18). Classification of extramural vascular invasion by high-resolution MRI is important for the correct preoperative treatment choice and also determines the postoperative surveillance; at the same time, it provides additional staging information, showing vascular invasion that is not recognized in the histopathology. The depth of the tumor invasion indicates the potential of the extramural vascular invasion, being associated with greater pt, pn and, generally, positive circumferential resection margin (16,17). 4) Circumferential Resection Margin When the circumferential resection margin is evaluated by high-resolution MRI, the minimum distance between the tumor and the mesorectal fascia must be measured. It is called involvement of the margin when the tumor is located at a distance of less than 1 mm, is in direct contact, or extends through the mesorectal fascia (11,19) ; the distance between the fascia and the involved lymph nodes also should be included, as well as tumor deposits and extramural vascular invasion. At the present time, the work of the MDT is focused on obtaining free circumferential resection margin, with the goal of avoiding local recurrence (20). We have stated that diagnostic and therapeutic success is directly related with obtaining free margins in the histopathology. Therefore radiologists must identify in the high-resolution MRI images the patients with an involved circumferential resection margin in order to provide them with preoperative treatment. We must not forget that the larger the distance of the tumor from the circumferential resection margin is, the better the prognosis (6,21). In a publication from the Mercury group (3), the specificity of the high-resolution MRI in determining the free circumferential resection margin was 92%. The free circumferential resection margin implies a lower local recurrence rate and greater overall survival (7). 5) Low Rectal Tumors Low rectal tumors are located in the area of the rectum and mesorectum, under the origin of the levator complex, where the mesorectum thins, generally 6 cm from the anal margin. They make up a third of rectal tumors. Due to their anatomical characteristics, rectal tumors at this location are associated with a greater risk of involvement of the circumferential resection margin and anal sphincter. For this reason they imply a therapeutic challenge for the MDT, with the objectives being local control and the preservation of the sphincter. Recent publications incorporated a new staging by highresolution MRI for low rectal tumors, useful in the handling of these patients that differ from those cases of superior and middle localization (Table 6) (11). In these patients it is important to describe the relationship of the tumor with the muscular layer, the levator muscle and the external anal sphincter (Fig. 8). We should also look for the possible extension towards the prostate, the seminal vesicles, the

6 vagina, the sacrum and the coccyx. The high-resolution MRI offers essential information for determining the relationship of the tumor with the anal sphincter and is, at the same time, useful in defining free margins, both distal and circumferential, allowing adequate selection of treatment and surgical technique (22,23). Post Neoadjuvant High-Resolution Magnetic Resonance The high-resolution MRI presents difficulties in differentiating fibrous tissue with or without tumor cells in patients that were treated with chemoradiotherapy (Fig. 9). Consequently, the technique is not capable of differentiating residual microscopic tumor from complete pathological response in a single test, thus requiring a series of high-resolution MRIs for confirmation. Patients that have received neoadjuvant treatment are evaluated using the degree of tumoral regression from Dworak and collaborators (24), adapted to the images (Table 7) (11). The analysis of the degree of regression is a better predictor of outcome after treatment than T stage. High-resolution MRI shows the presence of fibrosis as well as mucin lakes. According to recent publications, specific findings can predict with great precision the invasion or absence of tumor in mesorectal fascia (25). O'Neil and collaborators (26) began a pilot study that researches non-surgical treatment on patients with complete response using modern techniques for identification, including high-resolution MRI. According to the authors, it is the first prospective study in the world with these characteristics. About 25% of the patients present complete pathological response after the neoadjuvant treatment. Considering these findings, the researchers propose, in an adequately-selected group of patients, to avoid surgery, especially in those patients that need definitive colostomy. High-resolution MRI performed 4 and 6 weeks after chemoradiotherapy being finished rarely is normal, even in patients with complete pathological response. Patients with optimal response at high-resolution MRI present scar tissue at the tumor site; nevertheless, cellular composition cannot be determined. Therefore, a single high-resolution MRI cannot diagnose complete response and monitoring with serial studies is required. The authors perform a high-resolution MRI 4 weeks after neoadjuvant treatment has finished, and another after 8 weeks for patients with at least a partial response. With proper patient selection, they implemented a program of control every 3 months with high-resolution MRI, clinical examination and rectosigmoidoscopy during the first year. If desired results are achieved, this will permit large-scale tests, thus establishing the capability of the high-resolution MRI in predicting complete response after neoadjuvant treatment. The Dr. Regina Beets-Tan group (27,28) evaluated the utility of the high-resolution MRI in the restaging of the patient after neoadjuvant treatment, with the objective of predicting tumor confined to the rectal wall, which permits a more personalized therapeutic plan. The results showed a high positive predictive value (91%) of high-resolution MRI for the prediction of tumor circumscribed to the rectal wall (ypt0-t2) after chemoradiotherapy (27). Therefore, restaging with high-resolution MRI following preoperative treatment can be a useful tool in the identification of residual tumor limited to the rectal wall, allowing consideration of transanal local excision for the patients with good response with less morbidity and mortality rates in relation to conventional surgery. It could also be useful in identifying those patients without lymph node involvement, with a positive predictive value of % (28).

7 Radiologist s contribution to the Multidisciplinary Team The MDT will analyze the particular situation of every patient with rectal cancer. With this aim the accomplished examinations will be taken into consideration to determine local staging and probable distant involvement. The findings from digital examination, colonoscopy, endorectal ultrasound and high-resolution MRI will be evaluated. To determine distant involvement, a helical computed tomography of the chest is indicated and for the examination of the abdomen a computed tomography or MRI is used. In accordance with the prognostic risk factors evaluated by the high-resolution MRI and taking into account the clinical case of each particular patient, the correct treatment will be selected, which, according to what has been previously confirmed, could be primary surgery or neoadjuvant treatment, the latter depending on the extramural extension of the tumor, the number of involved lymph nodes, the presence of extramural vascular invasion and the involvement of the circumferential resection margin. As previously explained, low rectal tumors require a detailed analysis to achieve balance between a safe decision in terms of resection margins and quality of life for the patient trying to avoid a permanent colostomy. Therefore, the information that high-resolution MRI offers is of great importance within the MDT and, consequently, the report must be detailed (10,11) (see Table 8. Standardized Report). As a result, it is crucial to conduct a technically correct study, since an extensive and detailed report, in which millimetric differences will be evaluated and considered in the decision of the adequate therapy of each patient, will be needed. The formation of a work team within the MRI service will help the examination be carried out correctly and the training of the technician who performs the exploration and of the radiologist who directs it is fundamental. The presence of the radiologist during the exam is very important in order to be able to accomplish additional sequences, if necessary, this way avoiding a new visit to the MRI room by the patient, with the burden of stress and anguish that usually accompany the oncological patient. The trained radiologist is responsible for the quality of the exploration and should perform the detailed information analysis to later present it to the MDT. From what has been shown here, we can confirm that the time factor is fundamental: time to perform the exam and time for the analysis of the images. Conclusion The ability of high-resolution MRI for showing with precision the mesorectal anatomy has converted this method into a useful tool in rectal cancer staging. It allows identification of prognostic risk factors that will determine the selection of adequate treatment for each patient. Performing a technically optimal study, that respects the parameters of high-resolution and the presence of technicians trained in its procedures and radiologists that supervise the study, are fundamental for an adequate interpretation of the images. Just as important is a detailed report written by dedicated and trained radiologists that participate at the same time in multidisciplinary groups. Teamwork allows exchange of enriching information, of utmost value for the evaluation of the images. Radiologists occupy a very important space within the group, given that the decisions are made based in part on the information that high-resolution MRI offers. On the other hand, it is also a way to audit our work, allowing the correction of errors and the improvement of the quality of our contribution.

8 Fig.1. A. Patient with rectal cancer, 50 year-old man. T2-weighted high-resolution image, axial plane, showing the mesorectal fascia (arrowheads). B. Patient with rectal cancer, 52 year-old man. T2- weighted high-resolution image, axial plane. Involvement of the circumferential resection margin (dotted line) by extension of the primary tumor towards the mesorectal fascia (Hour 4 to Hour 11). Table 1. High-resolution pelvis MRI parameters. T2 FRFSE SAGITAL AXIAL CORONAL TR TE ETL BANDWITH FREQ PHASE FOV 20cm 20cm 20cm SLICE THICKNESS SPACING NEX FREQ DIR A/P A/P S/I AUTO CENTER FREQ WATER WATER WATER SLICE TIME 8:40 13:05 5:38 AUTOSHIM PULSE SEQ FRFSE-XL FRFSE-XL FRFSE-XL IMAGING OPTIONS NPW, SCIC, TRF, FAST, ZIP512 NPW, SCIC, TRF, FAST, ZIP512 NPW, SCIC, TRF, FAST, ZIP512 MODE 2D 2D 2D ADDITIONAL PARAMETERS SATURATION BANDS (SI) SATURATION BANDS (SI) SATURATION BANDS (SI)

9 A B D F C E G Fig. 2. Patient with low rectal cancer, 64 year-old man. In the initial localization images (A and B) the sagittal plane is programmed for viewing the pelvis from the sacral promontory to the anal margin (C). D and E: In the T2-weighted high resolution images obtained in the sagittal plane, the axial plane is programmed, perpendicular to the major axis of the rectum, at the site of the tumor, from the sacral promontory to the anal margin for the viewing of the mesorectum and iliac chains. F and G: Low rectal tumors are completed with the coronal plane, perpendicular to the anal canal, for the evaluation of the sphincter.

10 Table 2. Hepatic evaluation. AX T2 FRFSE RESP COMP FAT SAT AXIAL TE 90 ECHO TRAIN 17 BANDWITH FOV 38 SLICE THICKNESS 4.0 SPACING 0.0 FREQ 256 PHASE 160 NEX 3.00 PHASE FOV 0.75 FREQ DIR R/L AUTO CENTER FREQ WATER FLOW COMP DIRECTION SLICE PLANE OBLIQUE PULSE SEQ FRFSE XL MODE 2D TIME 4:30 IMAGING OPTIONS FLOW COMPENSATION, TAILORED RF, SURFACE COIL INTENSITY CORRECTION, FAST, RESPIRATORY GAITING / TRIGGERING, ZIP 512

11 Table 3. Retroperitoneal evaluation. AX T2 FRFSE BH AXIAL TR TE 90.O ECHO TRAIN 22 BANDWITH FOV 40 SLICE THICKNESS 6.0 SPACING 0.0 FREQ 320 PHASE 192 NEX 1.00 PHASE FOV 0.75 FREQ DIR R/L AUTO CENTER FREQ WATER FLOW COMP DIRECTION FREQ AUTOSHIM PHASE CORRECT PLANE OBLIQUE PULSE SEQ FRFSE XL MODE 2D TIME 1:42 / 0:20 IMAGING OPTIONS FC, VBw, SCIC, TRF, FAST IMAGEN INFERIOR DE ESTA SECUENCIA = IMAGEN SUPERIOR DE AXIAL DE ALTA RESOLUCIÓN Table 4. Seventh edition TNM classification (2010) Primary tumor (T) (9) TX primary tumor cannot be assessed TO no evidence of primary tumor Tis carcinoma in situ: intraepithelial or invasion of lamina propria T1 the tumor invades submucosa T2 the tumor invades muscularis propria T3 tumor invades through the muscularis propia into pericolorectal tissue T4a the tumor penetrates to the surface of the visceral peritoneum T4b the tumor directly invades or is adherent to other organs or structures

12 Fig. 3. Patient with rectal cancer, 62 year-old woman. The extramural depth of the tumor (arrow) determines the T3 subdivision. The arrow indicates the distance between the lateral border of the muscularis propria and the lateral border of the tumor in the T2-weighted high resolution image, axial plane. Fig 4. Rectal cancer patient, 52 year-old man. T2-weighted high resolution image, sagittal plane, shows tumor extension into the peritoneal reflection. It corresponds to T4a tumor staging of the new TNM classification.

13 Table 5. Seventh edition TNM classification (2010) Regional Lymph Nodes (N) (9) NX N0 N1 N1a N1b N1c N2 N2a N2b Regional lymph nodes cannot be assessed No regional lymph node metastasis Metastasis in 1 3 regional lymph nodes Metastasis in one regional lymph node Metastasis in 2 3 regional lymph nodes Tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues without regional nodal metastasis Metastasis in four or more regional lymph nodes Metastasis in 4 6 regional lymph nodes Metastasis in seven or more regional lymph nodes Fig. 5. A. Rectal cancer patient, 87 year-old woman. T2-weighted high resolution image, axial plane, showing lymph nodes with irregular borders and mixed signal intensity (arrows). B. Rectal cancer patient, 57 year-old man. T2-weighted high resolution image, axial plane. The arrow indicates a lymph node of mixed signal intensity.

14 Fig. 6. A. Rectal cancer patient, 68 year-old man. The T2-weighted high resolution image, axial plane, displays the presence of extramural vascular invasion. The arrows indicate dilated mesorectal vessels with intermediate signal inside due to tumor extension. B. Rectal cancer patient, 33 year-old man. T2weighted high resolution image, sagittal plane. In this patient the image shows extramural vascular invasion engaging the superior rectal vein by extension of the mucinous tumor.

15 Negative Extramural Vascular Invasion by High-Resolution MRI Scoring 0 Smooth tumor border There are no vessels adjacent to the penetration of the tumor Scoring 1 Lightly-nodular tumor border Without adjacent vessels Scoring 2 Tumor border extends into proximity with vessels, but the vessels are of normal caliber and there is no tumor signal within the vessels.

16 Positive Extramural Vascular Invasion by High-Resolution MRI Scoring 3 Intermediate signal in the vessels, with the vascular edge and caliber mildly dilated Scoring 4 Irregular vessel edge or nodular dilation by tumor signal inside Fig. 7. High-Resolution MRI classification of extramural vascular invasion. Scoring 0-4 (Modified of 16) Table 6. Low rectal tumor staging evaluated by high-resolution MRI (11). 1. Tumor limited to rectal wall without full thickness extension, external muscular layer intact 2. Tumor replacing the muscular layer without extension towards the intersphincteric plane 3. Tumor invading intersphincteric plane or located within 1 mm of levator muscle 4. Tumor invading external sphincter and located within 1 mm and beyond levators with or without adjacent organ involvement

17 Fig. 8. A and B. Patient with low rectal tumor, 54 year-old woman. T2-weighted high resolution MRI images, axial plane, showing involvement of the left anal levator muscle (arrows). Table7. Degree of tumoral regression adapted to the images (11) Complete radiological response: No evidence of treated tumor. Good response (dense fibrosis, tumor not visible: minimal or absent residual disease) Moderate response (>50% fibrosis or mucin and visible intermediate signal) Slight response (small areas of fibrosis or mucin, predominating tumor's presence) No response: intermediate signal intensity, same appearance as original tumor A B Fig. 9. A and B. Rectal cancer patient, 58 year-old man. T2-weighted high resolution MRI images, axial plane, of patient with complete pathological response after neoadyuvant treatment (ypt0n0), showing fibrosis in the rectal wall with extension to the mesorectum. The dense fibrosis results in a significant decrease of rectal lumen.

18 Table 8. High-resolution MRI report for local staging of rectal cancer. Is this the 1 st MRI?: (yes/no) Is post-treatment MRI?: (yes/no) Liver: Retroperitoneum: T Staging: mucinous tumor: (yes/no) extramural depth of tumor invasion: tumor invasion site and morphology: (regular / nodular infiltrate) maximum tumor thickness: tumor dimensions and morphology: polypoidal concentric (annular) stenotic eccentric rectal lumen stenosis: Tumor location and relation with neighbors structures: tumor location in axial plane (hourly signal relation): hour to hour relation with peritoneal reflection: distance to sphincter (upper portion): distance to anal margin: N staging: number, size, lymph node location and relation with the tumor: Mesorectal: positives: negatives: Lateral lymphatic dissemination: positives: negatives: Satellite deposits: Evidence of extramural vascular invasion: (yes/no) scoring (0-4) Circumferential resection margin: free involved Distance to mesorectal fascia: Distance to circumferential resection margin: primary tumor: lymph nodes involved: satellite deposits: extramural vascular invasion: Lower-third tumors: level with or below the distal levator insertion muscularis propia involved: (yes/no) levators: free contact infiltration external sphincter: free contact infiltration MRI staging for low rectal tumors: stage Tumor limited to rectal wall without full thickness extension, external muscular layer intact 2. Tumor replacing the muscular layer without extension towards the intersphincteric plane 3. Tumor invading intersphincteric plane or located within 1 mm of levator muscle 4. Tumor invading external sphincter and located within 1 mm and beyond levators with or without adjacent organ involvement Post-chemoradiotherapy response: grade No response: intermediate signal intensity, same appearance as original tumor 4. Slight response (small areas of fibrosis or mucin, predominating tumor's presence) 3. Moderate response (>50% fibrosis or mucin and visible intermediate signal) 2. Good response (dense fibrosis, tumor not visible: minimal or absent residual disease) 1. Complete radiological response: no evidence of treated tumor. Conclusion: final staging