Endoscopic Ultrasound For Rectal Cancer

Gregory G. Ginsberg, M.D.
Nuzhat Ahmad, M.D.

Keywords

EUS, rectal cancer

Introduction

Colorectal cancer is among the most common cancer affecting adult men and women. There are nearly 38,000 new rectal cancers diagnosed each year in the United States. While part of a functional continuum, rectal cancers are distinguished from colon cancers based on some very real anatomic, prognostic, and practical differences. These differences command staging and therapies unique to rectal lesions. Stage-based therapy for rectal cancer has achieved broad acceptance and is considered the standard of care. This submission reviews the role of EUS for the evaluation and management of rectal cancers.

Case/Body

RECTAL ANATOMY

The rectum originates beneath the peritoneal reflection, extending 15 cm to 20 cm from the anal verge. The rectum is contained within the narrow pelvis, confined by the pubic bones anteriorly and the lumbosacral spine and coccyx posteriorly, and surrounded by structures vital to urinary and sexual function. Using trans-rectal EUS, the urinary bladder, seminal vesicles, prostate and urethra are well seen in the male (Figure 1A and 1B). The urinary bladder, uterus, and vagina are less well appreciated in women (Figure 2).

Figure 1A	Figure 1B	Figure 2	Figure 3

The anatomy of the anorectum is specifically designed for storage and controlled evacuation of the fecal bolus. Defecation and continence require the coordinated interaction of several muscular structures in and surrounding the anorectum. The circular muscle of the anus forms a prominent internal anal sphincter, which provides tonic closure of the anus. Specialized skeletal muscles descending from the levator ani apparatus provide a muscular sling and terminate to form the external anal sphincter. When viewed with a radial scanning echoendoscope at the level of the anal verge, the internal and external anal sphincters can be viewed as two distinct rings (Figure 3) (1). The lymphatic drainage of the rectum follows the route of its venous drainage along the inferior, middle, and superior hemorrhoidal veins to the inferior mesenteric veins and along the iliac veins and onto the portal vein.

RECTAL CANCER

The prognosis for rectal cancer correlates with the pathologic stage at the time of diagnosis. So too, management is predicated on tumor stage at diagnosis and response to induction therapy. A wide variety of surgical techniques have been developed for rectal neoplasms in consideration of the anatomic constraints, preservation of function, and intent to achieve cure (2). These are associated with disparate rates of postoperative morbidity. Cancer containing superficial villous adenomas can be cured with endoscopic mucosal resection (EMR). Lesions confined to the wall may be resected by transanal excision or low anterior resection. Lesion involving, or in close proximity to, the anus may warrant abdominoperineal resection preserving anal sphincter function. Patients with locoregionally-advanced lesions (extension onto the perirectal fat and/or perirectal or pelvic adenopathy) should be considered for neoadjuvant chemoradiotherapy. Neoadjuvant therapy has been demonstrated to reduce local recurrence and permit increased likelihood of a sphincter-sparing operation with less toxicity when compared to post-operative regimes (3). Thus, unlike more proximal colon cancer, the optimal method of management for rectal carcinoma is critically dependent on the accurate preoperative staging of the disease as shown in Table 1 (4).

Table 1: EUS tumor stage and lesion location determines treatment options for rectal cancers
High = > 2cm from dentate line; Low = < 2cm from dentate line; EMR = endoscopic mucosal resection; TAEX = transanal excision; LAR = low anterior resection; APR = abdominoperineal resection; NAT = neoadjuvant therapy.

EQUIPMENT AND TECHNIQUE

Figure 4A

Figure 4B

Figure 5

Figure 6A

Figure 6B

Endorectal Ultrasound (ERUS) can be performed either with blind, rigid probes or with flexible echoendoscopes. This discussion will focus on the use of flexible echoendoscopes. The Olympus GF-UM series of echoendoscope is the standard instrument for staging. This is an oblique-viewing (fiber optic or electronic video image) instrument. The tip contains a miniature ultrasound transducer that provides a 360-degree radial image perpendicular to the long axis of the scope at ultrasound frequencies of 5.0 MHz, 7.5 MHz, 12 MHz, or 20 MHz. Piezoelectric curvilinear array scopes are used for EUS-guided fine needle aspiration of extraluminal lymph nodes.

ERUS is an ambulatory procedure. Patients prepare the rectum with two Fleets® enemas in advance. Intravenous sedation is optional. With the patient in the left-lateral-decubitus position, digital rectal exam (DRE) should be performed. DRE should allow assessment of sphincter tone and palpation of the lesion. If palpable, the lesion should be described in terms of location, distance from the anal verge, and fixation or mobility. Forward viewing sigmoidoscopy should be performed to image the lesion both in the forward and retroflexed scope positions (Figure 4). This allows familiarity with the anatomic configuration of the patient’s rectum and the location and distribution of the tumor.

The echoendoscope is inserted and advanced beyond the lesion, under direct vision, to the rectosigmoid junction. ERUS imaging should begin at 5-7.5 MHz during withdrawal of the scope. The lumen is deflated of air and the water-fill balloon adjusted for acoustic coupling. Tip deflection should be passive allowing the transducer to find the right axis to the lumen. During this phase of the exam, surrounding adenopathy is the quarry. Any lymph nodes seen should be interrogated for size, shape, and echo-qualities (Figure 5). The scope is withdrawn to the level of the anal verge.

Next, the tumor itself should be targeted to determine depth of penetration into or through the rectal wall. The choice of frequency is dependent on the lesion size but 7.5 and 12 MHz frequencies are most commonly employed for T-staging. The degree of tip deflection and water-balloon fill should be adjusted to avoid false-findings owing to tumor compression, tangential imaging, and air artifact. Water-filling the lumen through the accessory channel is often necessary to achieve optimal imaging (Figure 6). The echoendoscope is advanced and withdrawn over the lesion to achieve satisfactory imaging over the length of the lesion. Lastly, the scope is withdrawn to the anal verge to interrogate anal sphincters for tumor invasion. Sphincter interrogation is an active process and should incorporate voluntary squeezing and relaxation of the muscles during imaging.

ERUS STAGING OF RECTAL CANCER

The American Joint Committee of Cancer has identified the TNM classification as the preferred staging system (5). This system is based on the determination of depth of tumor invasion (T-classification), the presence of regional lymph node metastases (N-classification), and the presence of distant metastases (M-classification). The individual classifications are combined to provide an overall stage.

EUS Tumor Stage
Endosonographically, the rectal wall is seen as five alternating hyper- and hypoechoic layers (Figure 7). The histologic correlation of the echolayers is as follows:

	First layer (hyperechoic) - interface between water or water-filled balloon and the superficial mucosa. Second layer (hypoechoic) - represents the deep mucosa and the muscularis mucosa. Third layer (hyperechoic) - represents the submucosa and its interfaces. Fourth layer (hypoechoic) - represents the muscularis propria. Fifth layer (hyperechoic) -interface between the serosa and perirectal fat.
Figure 7

Rectal cancer appears as homogeneous hypoechoic soft tissue. Invasion appears as disruption of the normal wall echolayer pattern. A tumor that by EUS appears to be limited to the mucosa or the submucosa (first three echo layers) is classified as a T1 lesion (Figure 8A-8E). A tumor that invades into the muscularis propria (the hypoechoic fourth EUS layer) is a T2 lesion (Figure 9). A T3 lesion penetrates through the rectal wall, extending beyond the five echo layers and into the surrounding perirectal fat (Figure 10). A T4 lesion displays direct invasion into an adjacent organ such as the prostate gland, sacrum, vagina, and bladder (Figure 11).

Figure 8A	Figure 8B	Figure 8C	Figure 8D	Figure 8E

Figure 9	Figure 10	Figure 11

EUS Lymph Node Staging
Endosonographically, lymph nodes appear as round or oval structures, which are hypoechoic compared to the surrounding perirectal fat (Figures 5 and 11). Endosonographic criteria applied to perilesional adenopathy in other regions of the digestive tract for the determination of malignancy versus benignity may not be so well applied in rectal cancer. Data obtained primarily in patients with esophageal carcinoma so have identified four sonographic criteria predictive of malignancy: large size (>1cm), hypoechoic echodensity, sharply demarcated borders, and round (rather than ovoid or flat) shape (6). These criteria may not apply so well to rectal carcinoma in that up to 50% of metastatic lymph nodes associated with rectal cancers are smaller than 5mm (7). While EUS guided fine needle aspiration (FNA) of an individual lymph node might confirm accuracy, it is only rarely called upon for this purpose in initial staging.


ACCURACY OF EUS IN STAGING RECTAL CANCER

Accuracy of tumor and nodal staging is dependent on the experience and expertise of the endosonographer (8). The overall accuracy of T- staging for rectal cancer varies between 70% to 90% (9-17). When EUS is incorrect for T-stage, it is typically due to overstaging rather than under-staging. EUS tends to overstage cancers because high-resolution ultrasound can detect, but not separate inflammation adjacent to the malignancy from the tumor itself. Under-staging is attributed to undetected microscopic invasion of cancer cells beyond that observed by EUS Accuracy is generally lowest for lesions classified as T2 by EUS, which may be overstaged as T3 lesions. Overstaging is apt to occur when imaging tumors located on a haustral fold, due to artifact induced by tangential imaging. Water-filling the rectal vault will improve technical results and likely enhances T-stage accuracy.

The overall accuracy of N-staging by EUS is 73% to 83% (9-16). Lower nodal staging accuracy is attributed to the observation that up to 50% of malignant nodes are less than 5 mm in diameter and EUS detection rates of these nodes may be as low as 20% (7).

Nonetheless, ERUS has been reported to be equal to or superior to computed tomography (CT) for T and N staging. Among several comparative studies, EUS has a greater accuracy than CT scan for staging of rectal cancer: 67% to 93% versus 53% to 86% for T-stage, and 80%- 87% versus 57% to 72% for N-stage (19-21). Magnetic resonance imaging (MRI) with endorectal surface coils has compares similarly but not better that EUS in accuracy (22-26). MR imaging is more expensive than transanal ultrasound and endorectal MRI is not widely available.

While there is little published experience for EUS-FNA for rectal cancer, experience extrapolated from other malignancies has suggested that the performance of fine needle aspiration cytology can markedly increase the accuracy and specificity of EUS nodal classification. Management may be altered when nodal metastasis is identified in a patient in whom T-classification would otherwise suggest the possibility of local endoscopic or transanal resection as a curative option. This applies to the 10% of patients with T1 lesions that have positive lymph nodes.

Figure 12A

Figure 12B

Figure 12C

Figure 13A

Figure 13B

RESTAGING AFTER NEOADJUVANT THERAPY

Pre-operative neoadjuvant chemoradiotherapy is commonly used to down-stage rectal cancers. In addition to improving long-term survival and local recurrence, this approach allows sphincter preserving LAR in many patients who would require APR based on findings at initial presentation. Neoadjuvant therapy of rectal cancer results in tumor regression/necrosis and inflammatory and fibrotic changes in the rectal wall (Figure 12). These changes may be sonographically indistinguishable from viable tumor. As such, accuracy of T and N - staging after chemoradiation therapy is considerably compromised (27). Therefore, we do not apply TNM staging when inspecting lesions for response to preoperative chemoradiatherapy. Rather we assess evidence for tumor regression from surrounding organs, in particular the anal sphincters, vagina, and prostate. In this way EUS can direct therapy in patients who have undergone neoadjuvant therapy as a prelude to possible sphincter-sparing surgery (28).

EUS FOR LOCAL RECURRENCE OF COLORECTAL CARCINOMA

Local recurrence of rectal cancer after presumed curative resection occurs in 10-15% of cases, usually within the first two years after surgery. It is hypothesized that early detection of recurrent local tumor prompting early re-treatment would improve survival. While this notion may be logical, it remains unproved. EUS may be useful in the detection of suspected local recurrence when no mucosal lesions are seen during surveillance sigmoidoscopy. Preliminary data obtained using blind/rigid ultrasound probes suggested that transrectal ultrasound was highly sensitive for the detection of anastamotic recurrence (29, 30). A more recent study using a radial scanning echoendoscope reported EUS as highly sensitive (>90%) in the detection of local rectal tumor recurrence (31). However, the sonographic changes of local tumor recurrence are not specific. Post-operative and post-radiation inflammatory/fibrotic changes have similar appearances (32). EUS should be used to complement sigmoidoscopy when local recurrence is suspected. In these instances, extraluminal local recurrence suspected by EUS can be confirmed by EUS-guided fine needle aspiration (Figure 13).

Discussion/Summary Statement

EUS is the most accurate tool for local staging of rectal carcinoma. In addition to providing accurate T- and N- stage, EUS allows assessment of the internal and external anal sphincters. Accurate endosonographic staging directs the optimal method of management of rectal carcinoma, type of resection, and candidacy for neoadjuvant therapy. Repeat sigmoidoscopic and endosonographic imaging may be considered in selected patients following neoadjuvant therapy. EUS guided FNA can be used to detect suspected local recurrence.

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Editor:
John C. Deutsch, M.D.
Duluth, MN

Editorial Board:
Manoop S. Bhutani, M.D.
Galveston, TX
William R. Brugge, M.D.
Boston, MA
Peter R. McNally, D.O.
Denver, CO
Iqbal S. Sandhu, M.D.
Salt Lake City, UT
Thomas J. Savides, M.D.
San Diego, CA