Andrea Laghi, MD

In rectal cancer, mortality rates are high and prognoses are generally poor, owing to the strong risk of metastases and local recurrence. The standard surgical treatment for cancer located in the middle and lower sections of the rectum is total mesorectal excision; that is, resection of the tumor together with the surrounding mesorectal fat.

 This procedure is associated with a recurrence rate of less than 10% when used on its own.

 Although local recurrence has a small effect on survival rate, it has a profound influence on a patient's quality of life, given that rectal cancer is difficult to treat and causes disabling symptoms.

Accurate preoperative imaging can improve the quality of care for patients with rectal cancer. Accurate tumor staging is central to prognosis and preoperative treatment planning, but clinical examination is insufficient.

 Radiological assessment for local tumor staging has consequently assumed a prominent role in the management of patients with rectal neoplasia.

Presurgical staging is aimed at assessing the resectability of neoplasms, while minimizing the risk of local recurrence. Preoperative staging techniques should also identify patients with extrarectal spread, who might benefit from preoperative radiotherapy, and patients with minimal or no sphincter involvement, who might be suitable for sphincter-sparing surgery.

It is essential to stratify patients clinically into those with tumors that can be locally excised (usually reserved for T1 cancers) and those with deeper tumors that will need total mesorectal excision.

 Some patients will also need a long course of preoperative radiation therapy in an attempt to downstage T4 tumors.

Transrectal ultrasound has been used to stage rectal cancer for many years, thanks to its ability to visualize the different layers of the rectal wall with high spatial resolution. The modality can crucially define superficial tumors confined within mucosa and submucosa that are potentially suitable for cure by local excision. The small field-of-view, however, means that it offers limited evaluation of stenosing lesions and tumors located at the rectosigmoid junction. Neither can it identify mesorectal fascia and lymph nodes far from the rectal wall. Transrectal ultrasound is thus not useful for staging advanced rectal cancer.

The accuracy of CT for local staging of rectal cancer is still likely to be poor, despite the advent of multislice technology. This is due to low contrast resolution and the inability to reliably depict tumor parietal infiltration.

MRI is emerging as a problem-solving technique that can define therapeutic planning of rectal carcinoma. Imaging is conducted with either an endorectal coil or a phased-array surface coil. Protocols for patient preparation, pulse sequences, and plane acquisition are independent of coil type.

Studies comparing endorectal MRI and transrectal ultrasound for staging superficial tumors have shown the two techniques to have comparable accuracy.

 Endorectal MRI provides high-resolution images that depict bowel wall layers fully, although clear differentiation between mucosa and submucosa is still difficult. Evaluation of stenosing carcinomas can be tricky, however. Coil insertion can be problematic, painful, and sometimes impossible in cases of high-grade strictures, leading to insertion failure rates as high as 40%.

 Reports have also mentioned poor resolution of pelvic structures surrounding the rectum, such as mesorectal fat, mesorectal fascia, and lymph nodes outside the field-of-view.

Use of a phased-array coil provides images with high spatial resolution over a large field-of-view. Stenosing lesions and tumors at the rectosigmoid junction can be evaluated in all cases, and mesorectal fat and the mesorectal fascia can be visualized. Patient discomfort is reduced considerably.

An imaging protocol for MR-based staging of rectal cancer should yield high-resolution T2-weighted images in three orthogonal planes. These can be obtained with a non-breath-hold turbo spin-echo sequence with the following parameters: 4300 msec TR; 132 msec effective TE; 33 echo train length; 420 x 512 matrix; 28 cm field-of-view; 3 mm section thickness; 0.54 mm x 0.54 mm in-plane resolution. Fat-suppressed T2-weighted imaging has been advocated to improve visualization of tumor spread within perirectal fat. The use of contrast-enhanced T1-weighted sequences (spin-echo or gradient-echo) is still being debated.

Three different layers of the rectal wall can be recognized on T2-weighted MRI. These are an inner hyperintense layer representing mucosa and submucosa (no differentiation is possible between these two anatomic entities), a hypointense intermediate layer representing the muscularis propria, and an external hyperintense layer representing perirectal fat tissue. The mesorectal fascia can also be identified as a fine low-intensity structure enveloping the mesorectum and surrounding perirectal fat tissue. The mesorectal fascia is clearly visible on the lateral and posterior views, but it is difficult to differentiate from Denonvillier's fascia in the anterior view.

Local staging of rectal cancer is determined by the tumor's relationship to the rectal wall (assessed by T-stage classification) and to mesorectal fascia (assessed by the circumferential resection margin). TNM (tumor, nodes, metastases) staging remains an important method of predicting survival. The presence of poor prognostic indicators within each TNM stage means that patient subgroups of differing risk can be identified and treated accordingly.

The real aim of presurgical staging is to identify patients who will be suitable for additional treatment and may consequently have a better outcome. The circumferential resection margin (CRM) is one of the strongest predictors of surgical failure and a marker of the quality of surgical resection. While CRM is not yet included in current TNM staging, there is strong evidence that the neoplastic involvement of CRM is strictly related to a high recurrence rate after surgical treatment.

MRI performed with a phased-array coil consistently permits accurate assessment of the depth of extramural tumor spread and determination of mesorectum involvement. It can also reveal any infiltration of perirectal fat, show whether the lateral resection margin can be predicted, and indicate the extent of any sphincteral involvement.

The feature that helps most in clinical decision-making is the prediction of tumor margin relative to mesorectal fascia. Both T3 lesions and T2 lesions (Figure 1) require total mesorectal excision on surgery. MRI with a phased-array coil can predict the lateral resection margin with great accuracy. This enables appropriate selection of patients for preoperative radiotherapy and avoids unnecessary treatment of patients with a wide tumor-free lateral resection margin (Figures 2 and 3).

Information about sphincter involvement is one of the most important features influencing treatment selection. Such involvement can be predicted with a high degree of certainty using phased-array MRI. The technique provides excellent visualization of the sphincteral complex on coronal images (Figure 4). It is also a valuable tool to exclude or prove external and internal sphincteral infiltration. Phased-array MRI can additionally identify tumors involving adjacent organs. Such tumors will be candidates for preoperative radiotherapy as a downstaging strategy prior to radical tumor resection.

Identification of nodal disease continues to be a problem for radiologists. Lymph nodes measuring just 2 to 3 mm can be identified on images with high spatial resolution. But nodal metastases are not always reliably detected. Characterization and size criteria for enlarged lymph nodes also lack consensus. Some authors report any detectable lymph node, while others just report nodes larger than 3 mm, 5 mm, or 10 mm.

 The problems for morphologic imaging are to distinguish between enlarged reactive and metastatic nodes, and to detect micrometastases.

Ultrasmall superparamagnetic iron-oxide particles (USPIO) promise to make a real improvement in lymph node characterization. These particles are selectively taken up by reticuloendothelial cells of normal lymph nodes, presenting as a dark signal on proton- density and T2-weighted MRI. Pathologic lymph nodes, where reticuloendothelial cells are replaced by neoplastic cells, will not take up the USPIO contrast and present with relatively bright signal. Preliminary results using such agents are promising.

 Further larger studies are now needed to assess their real diagnostic value.

Between 60% and 84% of all tumor recurrences are detected within 24 months of major resection, and 90% to 93% within 48 months.

 Risk factors for local recurrence include tumor stage, tumor grade, distance from anal verge, presence of lymphovascular invasion, anastomotic leak, and tumor perforation during resection. The presence of tumor at the circumferential resection margin is another major risk factor.

A crucial challenge in the follow-up of patients with suspected local recurrence from rectal cancer is differentiation between early tumor recurrences and post-therapeutic alterations. CT has a reported specificity of 69% to 72% and a sensitivity of 82% to 91% for the detection of local pelvic recurrence. MRI has limitations similar to those of CT in the detection of local pelvic recurrence, predominantly based on morphological changes. It was initially thought that increased signal intensity on T2-weighted MRI would help differentiate fibrosis from recurrent tumor. High T2 signal, however, may persist for up to two years after surgery, making interpretation difficult. Conventional contrast-enhanced imaging is also limited in this regard. Benign fibrotic scarring, malignant local tumor recurrence, and inflammation can all enhance following gadolinium administration.

MRI appears to be superior to CT for the detection of local tumor recurrence.

 Sensitivity is between 80% and 90%, and specificity can be as high as 100%. Dynamic enhancement techniques have also generated some interest, given that local tumor recurrence enhances earlier than benign disease.

MRI with a phased-array coil allows excellent visualization of the pelvic structures and will also evaluate the spatial distribution of rectal cancer well. It can predict involvement of both perirectal tissue and anal sphincters reliably, enabling appropriate selection of patients for pre-operative radiotherapy or sphincter-saving surgery.

DR. IAFRATE is a radiologist and research fellow, and DR. LAGHI is an associate professor and director of the CT and MR unit, both in the department of radiological sciences at the University of Rome La Sapienza in Italy.

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Articles

In rectal cancer, mortality rates are high and prognoses are generally poor, owing to the strong risk of metastases and local recurrence. 

MR imaging strides ahead in rectal cancer staging

Colorectal carcinoma is believed to be the third most common malignancy and the third leading cause of cancer-related deaths for men and women in Western countries.

 It is curable if detected at an early stage and preventable if precursor adenomatous polyps are detected and removed promptly.

Diagnosis is traditionally based on conventional colonoscopy and/or double-contrast barium enema. Neither technique can assess the depth of bowel wall invasion, however, and both methods are severely limited in identifying lesions synchronous to the primary tumor.

Several studies in the past decade that investigated the potential roles of CT and MR in the assessment of patients with colorectal carcinoma produced conflicting results.

 But these reports were limited by the use of past-generation scanners (nonspiral CT technology) and inadequate patient preparation (the colon was neither cleansed nor distended prior to examination).

The ideal colorectal cancer diagnostic test should have high sensitivity, high specificity, local staging capabilities (evaluation of the depth of invasion of primary neoplastic mass), distant staging capabilities (assessment of lymphadenopathies and/or metastases), and full colonic evaluation even for obstructive lesions. No preoperative examination meets all of these criteria.

Increasing interest has therefore focused on CT colonography (also known as virtual colonoscopy) as a potential tool for diagnosis and staging of colorectal carcinoma. This technique is based on the acquisition of spiral CT data sets of an air-distended cleansed colon. The data are subsequently postprocessed on dedicated workstations to generate 2D and 3D endoscopic-like images of the colon.

Numerous studies of CT colonography have demonstrated excellent results in lesion detection,

 One study has also shown CT colonography to be suitable as a screening tool for colorectal neoplasia.

CT colonography is similar to a standard abdominal/pelvic CT scan, although several important factors differentiate the two examinations. Patients undergoing CT colonography must ingest a cathartic preparation such as polyethylene glycol, Fosfosoda, or magnesium citrate the day before the examination. These preparations are also used for standard colonoscopy and double-contrast barium enema examinations. Inadequate bowel cleansing can lead to false-negative results on CT colonography if lesions are obscured by fecal matter or false-positive results if waste products simulate lesions.

This onerous bowel preparation restricts the use of CT colonography considerably, and several strategies have been proposed to avoid this step.

 CT colonography is unlikely to demonstrate sufficiently high patient compliance for use in screening unless the need for cathartic preparation is eliminated.

The colon has to be distended prior to CT colonography to prevent collapsed bowel segments from obscuring underlying disease. Distention is often achieved by insertion of a small rubber catheter into the rectum, through which air or carbon dioxide is administered. Insufflation must be performed carefully by a nurse or radiologist until maximum patient tolerance is reached. Colonic distention is reportedly one of the worst parts of the examination for patients,

 but no major complications related to insufflation have been reported in the literature.

A further distinctive feature of CT colonography is intravenous administration of antiperistaltic drugs, either hyoscine butylbromide or glucagon hydrochloride, prior to examination. The use of an antiperistaltic agent minimizes bowel spasm, thus reducing the incidence of bowel collapse and increasing the quality of CT colonography results. The drugs should also theoretically reduce discomfort associated with colonic distention.

Radiologists have yet to reach agreement on the routine use of antiperistaltic drugs with CT colonography. We have found that neither hyoscine butylbromide nor glucagon hydrochloride improves colonic distension, though administration of either reduces patient discomfort substantially.

 We now use hyoscine butylbromide prior to CT colonography at our hospital, unless it is contraindicated.

CT colonography is performed in both the prone and supine positions, unlike standard abdominal and pelvic CT scans. Double acquisition is crucial to differentiating real lesions (polyps or carcinomas) from residual fecal material and thus to improving specificity.

 A lesion's position remains unchanged when the patient is turned, whereas fecal matter moves during repositioning. Moving a patient from the prone to the supine decubitus also allows redistribution of insufflated air within the colon, and poorly distended segments are often better visualized during the second acquisition.

Routine use of double acquisition has raised concerns about the ionizing radiation burden associated with CT colonography. This issue is of paramount importance if the test is proposed for screening. A number of radiation dose reduction strategies have already been investigated.

 All screening CT colonography examinations at our hospital are performed with an optimized low-dose technique that delivers a total radiation exposure of 1.8 mSv for men and 2.4 mSv for women. This is substantially lower than the radiation dose from a barium enema, which ranges from 3 to 7 mSv. Radiation concerns are clearly less important when a patient with known or strongly suspected colorectal carcinoma is referred for CT colonography. The purpose of CT colonography in such patients is to produce images of the highest diagnostic quality to assess precisely the presence of local and distant disease.

We use a high-resolution protocol when performing nonscreening CT colonography on a Siemens Somatom Plus 4 Volume Zoom machine (1-mm slice collimation, 1-mm slice thickness, 1-mm reconstruction interval, 8-mm/sec table speed, 120 kVp, 80 mAs for prone acquisition, 165 mAs for supine). Contrast material is not used routinely in our hospital. For the purposes of local and distant tumor staging, however, IV contrast is administered to all patients referred for colorectal carcinoma and in all cases in which a mass is identified on transverse CT images obtained after the prone acquisition. IV administration during supine acquisition comprises 120 to 150 mL nonionic iodinated contrast, with an infusion rate of 3 mL/sec.

We transfer CT colonography data sets to a dedicated workstation for postprocessing. Image analysis is performed using a software package with volume rendering capabilities (Vitrea 2, Vital Images). Readers first analyze 2D axial images, moving to 2D multiplanar reconstructions and 3D images only when a suspected abnormality is detected. These additional views are used to confirm the suspicious finding and increase diagnostic confidence.

MSCT has several advantages for colorectal carcinoma diagnosis and staging. The combination of prone and supine images provides a complete colonic evaluation in virtually all patients, even when an obstructive neoplasm is present.

 CT colonography not only can detect the primary carcinoma, but it also depicts synchronous lesions, whether carcinomas or coexisting polyps (Figure 1). This feature is of paramount importance because the presence of a synchronous lesion can alter the surgical approach. 

CT colonography offers a more precise description of lesion location than other diagnostic tests, especially conventional colonoscopy (Figure 2). Multiplanar reconstructions are especially helpful in depicting a tumor's location and extent of invasion. Contrast-enhanced CT colonography studies also permit assessment of tumor bowel wall invasion (local staging), and the presence of extracolonic disease such as lymphadenopathies and/or metastases (distant staging) (Figure 3). CT colonography provides a complete preoperative evaluation of patients affected by colorectal carcinoma.

But the technique still has several limitations. CT is not sufficiently sensitive to detect microscopic extramural tumor extension into fat surrounding the colon. This may lead to understaging, especially in the case of T3 tumors. A CT colonography scan is also incapable of distinguishing different layers of the bowel wall, making it extremely difficult to differentiate a T1 from a T2 tumor.

MSCT has further problems in differentiating stenosis due to diverticulitis from obstructive colorectal carcinoma. Imaging features used to differentiate these conditions include the presence of pericolic fat stranding to indicate inflammation or edema, and satellite lymphadenopathies that are highly consistent with malignancy.

 In many cases, however, radiologists find overlapping CT features; histological samples may then be required to reach definitive diagnosis.

Lymph node characterization is another limitation of CT colonography. Benign nodes may be enlarged, whereas subcentimeter nodes may contain metastatic tumor.

Despite these drawbacks, we consider MSCT colonography an excellent tool for detection and staging of colorectal carcinoma. Considering the current limitations of other available techniques, MSCT colonography can be proposed as a first-line diagnostic test for a complete evaluation of patients with colorectal carcinoma.

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DR. IANNACCONE and DR. LAGHI are radiologists, and PROF. PASSARIELLO is head of the department of radiological sciences, at University of Rome La Sapienza. Assisting in the preparation of this article were CARLO CATALANO, FILIPPO MANGIAPANE, and DANIELE MARIN.

Colorectal carcinoma is believed to be the third most common malignancy and the third leading cause of cancer-related deaths for men and women in Western countries. It is curable if detected at an early stage and preventable if precursor adenomatous polyps are detected and removed promptly.

Andrea Laghi, MD

Articles

MR imaging strides ahead in rectal cancer staging

MSCT provides first- line colon assessment