5 Staging of

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Staging of

Gastrointestinal Cancers 5

A basic understanding of the spread of cancers of the gastrointestinal tract relies upon the depth of mural penetration. Originating in the epithelial layer, the cancer’s invasion of the wall may variously extend into the lamina propria, muscularis mucosae, submucosa, muscularis propria, and subserosal connective tissue or through the serosa with or without direct invasion of adjacent structures. This determination forms the basis of the univer- sally adopted TNM staging classification,^1–3 encompass- ing all three prognostic factors of tumoral mural penetration (T), nodal involvement (N), and distant metastatic spread (M) in one staging system.

Staging is the process by which the anatomic extent of a tumor is defined at a certain point of time. Onco- radiology has had a major influence on the TNM staging system, which has incorporated changes to accommo- date the information available by the widening spectrum of diagnostic and interventional imaging and endosonography.⁴ Depth of tumor invasion (T) is the main criterion for clinical classification, replacing factors such as tumor size, circumferential extent of involvement, and gross morphology. In carcinoma of the esophagus and stomach, depth of invasion as the major determinant of prognosis was clearly established in Japanese studies of more than 3000 cases⁵ and 15,000 cases,⁶ respectively.

This was achieved because of developments in endosonography (EUS) and CT. Similarly, the current TNM classification for colorectal carcinomas is based on the accuracy of cross-sectional images. Developments in sectional imaging contribute significantly to the earlier detection of disease, to determine the stage of a malig- nancy, to substantiate criteria for resectability and non- resectability of a cancer, to monitor posttreatment tumor response, and to evaluate residual or recurrent disease.

Fundamental to the staging system is the concept of pos- sible independence of the TNM states. Because lymph node involvement (N) is designated as a separate cate- gory, there is no assumption that the full thickness of the gut wall must be penetrated before lymph node involvement occurs, as is the assumption behind the Dukes classification of rectal carcinoma.⁷ The concept of the stages of a cancer does not imply a regular pro- gression from stage I to stage IV.

Importance of Staging

Carcinoma of the Esophagus

Patients with esophageal carcinoma should be stratified to determine whether palliative treatment or attemptive curative therapy is appropriate. The importance of the staging of esophageal cancer (Table 5–1) lies in judging the resectability of the tumor and evaluating the prognosis of the patient. The stage of the disease has a direct effect on survival.^8–11

Lymph node metastases are seldom present with a T1 mucosal (T1m) tumor, whereas the incidence with a T1 submucosal (T1sm) tumor is approximately 33%¹² to 45%.^13,14 Submucosal invasion by esophageal carcinoma is a decidedly advanced lesion, compared, for example, to a similar depth of penetration in gastric carcinoma.

For patients with mucosal-type cancers, endoscopic resection or laser ablation is being used in many centers, particularly in Japan. In the United States and Europe, esophageal carcinomas are generally far advanced at the time of presentation.

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Carcinoma of the Stomach

In the TNM classification of gastric cancer^1–3 (Table 5–

2), depth of invasion is the main criterion, as in esophageal carcinoma. The current T staging system is illustrated in Figure 5–1.

The classification presents some limitations. The T1 designation does not distinguish mucosal and submucosal invasion. In the definition of a T2 cancer, no distinction is made as to whether the muscularis propria is

merely invaded or there is extension to involve the subserosa. Invasion of the serosa is the main criterion of a T3 cancer.

The Japanese Research Society for Gastric Cancer has used a detailed classification based on meticulous surgical and pathologic findings,¹⁵ mostly translatable to the TNM system, providing an anatomic basis for systematic lymph node dissection in the surgical treatment of gastric cancer.

There is a distinct correlation between the T stage

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Importance of Staging 267

and the number and sites of invaded lymph nodes.¹⁶ In- creases in either the number of positive nodes or the extent of nodal involvement adversely influence survival.¹⁷

Early Gastric Cancer

As a result of advances in diagnostic procedures, there are increasing numbers of reports concerning the detection of early-stage gastric cancer, particularly in Japan

with the application of mass gastric screening,^18–20 where almost one-half of all gastric cancer diagnoses refer to early lesions.

Early gastric cancer is defined as a tumor confined to the mucosa and submucosa, regardless of the presence or absence of perigastric lymph node metastasis.

Depth of invasion is the most important prognostic factor in early gastric carcinoma. Patients with lesions confined to the mucosa have a <5% chance of having nodal metastases and a nearly 100% 5-year survival. This

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Fig. 5–2. T stages of colonic mural penetration.

(Reproduced from Fielding LP: Staging systems. In Cancer of the Colon, Rectum and Anus. Edited by AM Cohen, SJ Winawer. McGraw-Hill, New York, 1995, p 210.)

Fig. 5–1. TNM classification of gastric cancer.

Increasing T stages correlate with depth of penetration of wall of stomach.

(a) T1 cancers (early gastric can- cer) may be limited to the mucosa or may also invade the submucosa.

(b) T2 cancers may be limited to the muscularis propria or may also invade the subserosa.

(c) T3 cancers penetrate the se- rosa.

(d) T4 lesions further invade ad- jacent structures.

(Reproduced from Spiessel et al.²)

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Importance of Staging 269

outstanding survival is related to the fact that the stomach has a paucity of lymphatic channels in the lamina propria, in contrast to the esophagus and small intestine.

These early carcinomas may be treated by endoscopic mucosectomy^21–23 or by endoscopic laser treatment.²⁴ Invasion through the muscularis mucosae into the submucosa is associated with a 10–20% likelihood of nodal metastases and a 90–95% 5-year survival.

Colorectal Carcinoma

Few investigators have applied imaging methods to staging of suprarectal colonic carcinomas.^25–28 The vast ma- jority of clinical studies have been directed to the di-

agnosis, staging, and management of carcinomas of the rectum.

The TNM classification for colorectal cancer (Table 5–3 and Fig. 5–2) of the American Joint Committee on Cancer (AJCC) and the Union Internationale Contra le Cancer (UICC)^1,3 is compatible with the Dukes classification.

The most important independent pathologic factor for survival or recurrence after potentially curative surgery is the depth of the cancer’s penetration through the bowel wall and the presence and number of positive lymph nodes.^29–31 The status of the cancer in relation to the muscularis propria demarcates T2 and T3 tumors.

The classification stratifies regional nodal involvement by one to three compared with four or more positive nodes, a dichotomy of prognostic significance, with a 5- year survival rate of 66% and 37%, respectively.³²

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Delineation of Normal Mural Components by Sectional Imaging

Five discrete layers of the wall are shown by conven- tional endoscopic ultrasonography. The first hyperechoic and second hypoechoic layers represent the mucosa, the third hyperechoic layer represents the submucosa, the fourth hypoechoic layer is the muscularis propria, and the fifth hyperechoic layer reflects the subserosa and serosa (Figs. 5–3 and 5–4). In the esophagus, lacking a serosa, the latter represents adventitia.

With the development of small 15–20 MHz ultrasonic probes, nine distinct layers of the normal esophageal and gastric wall may be clearly visualized,^33,34 permitting delineation of the lamina propria and muscularis mucosae in addition to a three-layered muscularis propria (Fig.

5–5).

Recent investigations have advanced the accuracy of CT in the detection and staging of gastric cancer. Min- ami et al.³⁵ and Cho et al.³⁶ refined a protocol in which the normal gastric wall showed a two- or three-layered structure: an inner mucosal layer with marked enhancement, an outer submucosal layer with lower attenuation, and another outer muscular-serosal layer with moderate enhancement. Improving the protocol further with the use of dual-phase spiral CT with narrow collimation and close interscan spacing may increase the accuracy of CT.

In dynamic multiphasic MR imaging of the stomach, a decisive feature is a low-signal-intensity band that

Fig. 5–4. Normal gastric wall demonstrated by EUS with a 20-MHz transducer showing the layered structure of the gastrointestinal wall.

shows irregularity in an area of extraserosal invasion by an advanced carcinoma (Fig. 5–6). This band is not a morphologic structure but rather a chemical shift mis- registration artifact and a phase-cancellation artifact between fat and water.³⁷

Identification of the layers of the circumference of the rectal wall is accomplished by plain and contrast- enhanced MR imaging with the endorectal surface coil³⁸ (Fig. 5–7).

Fig. 5–3. Diagram showing the normal layers of the colon.

m = mucosa; sm = submucosa; pm = muscularis propria; ss ~ s = subserosa ~ serosa.

(Reproduced from Hirata et al: Endoscopic ultrasonography in the assessment of colonic wall invasion by adjacent diseases. Abdom Imaging 1994; 19:21–26.)

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Delineation of Normal Mural Components by Sectional Imaging 271

Fig. 5–5. Nine distinct layers of the normal esophageal wall demonstrated in a patient with a small 20-MHz ultrasonic probe.

The mucosa consists of four layers: the first and sec- ond layers (m1 and m2) represent the epithelium, the third layer (m3) the lamina propria, and the fourth layer (m4) the muscularis mucosae. The submucosa (s) is seen as the hyperechoic fifth layer. The muscularis propria is imaged as three layers: the sixth layer (p1) is the circular muscle, the seventh layer (p2) is an inter- face of connective tissue, and the eighth layer (p3) is the longitudinal muscle. The adventitia (a) is repre- sented by the hyperechoic ninth layer.

(Reproduced from Murata et al.³³)

Fig. 5–6. T staging of gastric cancer by MR imaging.

T1 = Lesion is undetectable since there is no abnormal enhancement. T2 = A clear, smooth low-intensity band surrounds the enhanced lesion. T3 = The low-intensity band is interrupted. T4 = The low-intensity band has disappeared, and there is contiguous extension of the enhanced lesion to adjacent organs.

(Reproduced from Oi et al.³⁷)

Fig. 5–7. Endorectal MR image of the normal rectal wall.

Multiple layers are visualized: high-signal-intensity mucus within the rectal lumen (thin white arrows), low-signal- intensity mucosal layer (mucosa and muscularis mucosae) (small white arrowheads), high-signal-intensity submucosal layer (large white arrowheads), low-signal-intensity muscularis propria (small white arrows), and high-signal-intensity perirectal fat (black arrowheads).

(Reproduced from Pegios et al.³⁸)

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T Staging

In the diagnosis and staging of esophageal cancer, CT is highly accurate for detecting distant metastases, espe- cially to the liver, and for determining advanced local spread involving vital mediastinal structures. It cannot, however, distinguish tumors that invade only the mucosa or submucosa (T1) from tumors that invade the muscularis propria (T2). Consequently, CT is much more reliable for classifying stage III and stage IV lesions than stage I and stage II lesions. In contrast, EUS is very accurate for diagnosing stage I and stage II lesions, often good for stage III lesions, and of limited accuracy for stage IV lesions.

T1 Stage

In the esophagus, the distinction of cancer involving only the mucosa (T1m) (Fig. 5–8) from cancer invading the submucosa (T1sm) (Figs. 5–9 and 5–10) may guide the application of endoscopic resection.³³

Early gastric cancer may be defined on contrast- enhanced dynamic CT as an enhancing lesion with an intact low-density stripe at its base (Fig. 5–11).

Figure 5–12 illustrates a thickening limited to the mucosal layer of the rectum with a normal muscularis mucosae representing a sessile adenoma, shown by endorectal MRI. In contrast, Figure 5–13 shows mucosal thickening secondary to carcinoma with preservation of the submucosal layer but with a small regional metastatic lymph node.

Fig. 5–8. Esophageal cancer limited to the lamina propria shown with a small 20-MHz EUS probe.

(a) The white arrowhead indicates cancer invading the lamina pro- pria. The outlined black arrow demonstrates an intact muscularis mucosae.

(b) The endoscopic mucosal re- section specimen.

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T Staging 273

Fig. 5–9. Esophageal cancer invading the muscularis mucosae shown with a small 20-MHz EUS probe.

(a) The outlined black arrow indicates the muscularis mucosae and the white arrowhead designates the point at which the m4 layer is destroyed by tumor infiltration.

(b) The resected specimen. The black arrowhead shows the point of cancerous destruction of the muscularis mucosae.

Fig. 5–10. T1sm esophageal cancer.

EUS reveals a hypoechoic tumor (T) limited to the mucosa (M) and submucosa (SM). A portion of the submucosa beyond the tumor is still intact (arrowheads).

MP = muscularis propria.

(Reproduced from Tio TL.³⁹)

Fig. 5–11. Early gastric cancer (T1).

Early phase of bolus-enhanced dynamic CT of water- distended stomach shows a small, well-defined, elevated lesion (arrowheads) with moderate enhancement in the posterior wall of gastric antrum. Low-attenuation stripe of the submucosa (arrows) is clearly seen at base of tumor.

(Reproduced from Cho et al.³⁶)

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Fig. 5–12. Sessile tubulovil- lous adenoma of the rectum.

Endorectal T1-weighted contrast-enhanced MR image demonstrates the tumor. The differ- ent layers of the rectal wall can be identified. From lateral to medial: the high signal intensity of the perirectal fat tissue (white arrowheads), the low signal inten- sity of the muscularis propria (black arrowheads), a layer of high signal intensity representing the submucosal core (small white ar- rowheads), and the low signal in- tensity of the muscularis muco- sae (thin white arrows). Note the high signal intensity of the thickened mucosal layer (large white arrows).

Fig. 5–13. T1N1 rectal carci- noma.

Endorectal T2-weighted MRI demonstrates a sessile lesion of the rectum showing focal mucosal thickening with a high-signal-intensity submucosal core (black arrowheads). The muscularis propria (small white arrowheads) layer has not been involved.

One small, 3-mm-diameter perirectal lymph node is completely replaced by soft tissue (large white arrowhead).

(Reproduced from Pegios W, et al: MRI diagnosis and staging of rectal carcinoma. Abdom Imag- ing 21:211–218, 1996.)

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T Staging 275

T2 Stage

Extension into the muscularis propria establishes a carcinoma as stage T2 (Figs. 5–14 through 5–16).

T3 Stage

In esophageal carcinoma, the hallmark of a T3 lesion is penetration into the adventitia (Figs. 5–17 and 5–18).

In the stomach, T3 tumors show a reticular or an irregular outer border of thickened gastric wall and/or a blurred fat plane around the lesion (Figs. 5–19 through 5–22).

T3 rectal cancers invade through the muscularis propria to extend into the perirectal fat (Fig. 5–23).

T4 Stage

In esophageal carcinoma, direct invasion of mediastinal structures can be predicted using criteria of mass effect or localized loss of fat planes^39,42–47 (Figs. 5–24 through 5–30). Actual unresectability, however, remains difficult to predict with CT or MRI.^47-52 In the assessment of unresectability by EUS, criteria include tumor invasion into the left atrium, the wall of the descending aorta,

Fig. 5–15. T2 rectal carcinoma.

EUS demonstrates a hypoechoic tumor deeply invading the muscularis propria layer (arrow).

the pulmonary vein and/or artery, the tracheobronchial system, and a vertebral body.³⁹

T4 gastric cancers show obliteration of the fat plane between the gastric tumor and the adjacent organ (Figs.

5–31 and 5–32).

text continues on page 283

Fig. 5–14. T2 gastric cancer demonstrated by dynamic MR imaging.

(a) Early-phase (25 sec) and (b) late-phase (120 sec) images show the gastric cancer in the subcardia (arrow) as a highly enhanced thickened wall. A low-intensity band is observed around the stomach, and that of the lesion remains clear and smooth.

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Fig. 5–16. T2 rectal cancer demonstrated by endorectal MR image.

(a) Dynamic turbo FLASH se- quence after Gd-DTPA administration demonstrates a depressed lesion and complete disruption of the submucosa with an involved but not disrupted muscu- laris propria (white arrowheads).

(b) Histopathology demonstrates tumor invading into but not through the muscularis propria (black arrowheads) (hematoxylin- eosin stain, ×20).

Fig. 5–17. T3 esophageal cancer.

EUS obtained from the midesophagus approximately at the level of the carina reveals a hypoechoic semicircular tumor (T) with penetration into the adventita (AD). The border between the tumor and the aortic wall (AO) is still intact.

LA = left atrium.

(Reproduced from Tio.³⁹)

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T Staging 277

Fig. 5–18. T3 carcinoma of the lower esophagus.

On CT, the slightly irregular outlines of the tumor are due to invasion of the periesophageal fat.

(Reproduced from van Overhagen and Becker.⁴⁰)

Fig. 5–19. T3 carcinoma of the gastric antrum.

CT demonstrates focal nodular thickening of the posterior wall with mild irregularity of the outer contour (arrows), indicating direct extension of tumor into the perigastric fat.

(Reproduced from Yee and Halvorsen.⁴¹)

Fig. 5–20. T3 gastric cancer.

Early phase of bolus-enhanced dynamic CT of water- distended stomach shows a well defined, protruding lesion (solid arrows), with destruction of the multilayered pattern and marked enhancement at lesser curvature of upper body of stomach. The lesion has a reticular outer margin in contrast to the normal three-layered pattern of uninvolved gastric wall (open arrows) at cardia.

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Fig. 5–21. T3 gastric carcinoma.

T1-weighted gradient-echo MR image following intrave- nous administration of Gd-DTPA shows marked enhancement of the thickened antral wall with evidence of irregularity and blurring of the low-signal band along the posterior border of the stomach (arrow). This reflects tumor infiltration through all layers of the gastric wall as well as extraserosal extension.

(Reproduced from Yee and Halvorsen.⁴¹)

Fig. 5–22. T3 gastric cancer demonstrated by dynamic MR imaging.

(a) Late phase image shows that the low-intensity band at the base of the enhancing tumor is interrupted (arrow).

(b) Sagittal image during delayed phase (10 min) shows the enhanced elevated lesion in the posterior wall of the gastric body.

(c) Microscopic section of this interrupted-band lesion reveals extraserosal invasion by the gastric cancer. M = muscularis propria. (hematoxylin-eosin stain, × ^400.)

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T Staging 279

Fig. 5–23. T3 polypoid carcinoma of the rectum.

(a) Endorectal T1-weighted MR image after Gd-DTPA administration demonstrates the inhomogeneous mucosal thickening of a rectal cancer that completely disrupts the submucosa (white arrowheads) and the muscularis propria (black arrowheads). Additionally, one 5-mm-diameter perirectal lymph node (white arrow) was positive for carcinoma at pathologic examination.

(b) Resected specimen shows tumor invading completely through the muscularis propria with focal strands extending into perirectal fat (hematoxylin-eosin stain, × 30).

Fig. 5–24. T4 esophageal carcinoma.

(a) Sagittal and (b) coronal MR views at the level of the cervicothoracic junction reveal direct invasion of an esophageal neoplasm into the lumen of the trachea (arrow).

(Reproduced from Balzarini et al.⁴²)

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Fig. 5–25. Unresectable squamous cell carcinoma of the upper thoracic esophagus with indentation of the posterior wall of the trachea indicating neoplastic invasion (T4).

Note the enlarged periesophageal lymph node adjacent to the tumor (arrow).

Fig. 5–26. Squamous cell carcinoma of the middle thoracic esophagus.

A large esophageal mass (T4) indents the posterior wall of the left mainstem bronchus. Tracheobronchial invasion and resectability were confirmed at surgery.

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T Staging 281

Fig. 5–27. T4 esophageal carcinoma with invasion of mediastinal structures.

Axial MR images at the level of the tracheal bifurcation (a) and subcarinal space (b).

(a) Extraluminal extension of the tumor mass has obliterated the fat adjacent to the wall of the main bronchi (arrowheads).

(b) With neoplastic invasion of the subcarinal space, the left main bronchus is displaced anteriorly and compressed (arrowhead). The angle of contact between the tumor and aorta is approximately 100°

(white arrows). The triangular fat plane between the esophagus, spine, and aorta has been obliterated.

All criteria of aortic invasion are present.

(Reproduced from Balzarini et al.⁴²)

EUS at the level of the carina shows a transmural hypoechoic tumor (T) with deep penetration into and beyond (arrows) the posterior wall of the trachea (TR).

AO = aorta.

EUS obtained from the level of the distal esophagus reveals a circular hypoechoic tumor (T) with deep infiltration (arrowheads) into the aortic wall (AO).

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Fig. 5–30. T4 esophageal cancer demonstrated with catheter echoprobe.

EUS obtained with 7.5-MHz miniature catheter echoprobe reveals a transmural hypoechoic tumor (T) with multiple invasion into the aortic wall (AO) at 7 o’clock (arrows) and into the right bronchus (BR) and the bifurcation

(arrowheads) of the bronchus seen as hyperechoic (white) lines between the esophagus and the left atrium.

Fig. 5–31. T4 gastric carcinoma.

CT demonstrates loss of the normal fat plane between the diffuse thickening of the wall of the antrum and the body of the pancreas (small arrow), indicating pancreatic invasion.

Metastatic perigastric adenopathy is present (large arrow), (Reproduced from Yee and Halvorsen.⁴¹)

Fig. 5–32. T4 gastric cancer.

Bolus-enhanced dynamic CT in early phase shows diffuse wall thickening and destruction of multilayered pattern involving antrum and body of stomach (S) with strong heterogeneous enhancement. Focal obliteration of the fat plane (arrowheads) between thickened gastric wall and pancreatic body, indicating pancreatic invasion, as well as an enlarged metastatic subpyloric lymph node (arrow) are clearly identified.

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Lymph Node Metastases 283

Lymph Node Metastases

Detection of lymphadenopathy is difficult by sectional imaging. Normal-sized lymph nodes may harbor micrometastases (Fig. 5–33), and some enlarged nodes are due to benign reactive hyperplasia.

The original EUS criteria of distinguishing between benign reactive and metastatic lymph nodes on the basis of echo texture, size, and margination (Fig. 5–34) is now undergoing intense doubt.^53–56

Fig. 5–33. Micrometastases in lymph node.

Histologic section demonstrates that metastatic cells in a small zone of a lymph node (arrows) would be undetectable by sectional imaging.

(Courtesy of Clive Bartram, M.D., St. Mark’s Hospital, Northwick Park, England.)

In the past, the diagnosis of lymph node abnormali- ties on CT scans has been based on size criteria, with the upper limits of normal in the upper abdomen re- ported as varying from 6 mm to 11 mm.^57,58 However, accuracy is limited by the presence of micrometastases and reactive nodal hyperplasia. A recent report of im- proved detection using thin-sector contrast enhanced helical CT offers additional criteria to size alone in diagnosing metastatic lymph nodes, based on attenuation and configuration.⁵⁹ The nodal pathways in gastrointestinal cancers are documented in Chapter 6.

Fig. 5–34. Metastatic lymph node shown by EUS.

Enlarged, spherical hypoechoic, sharply marginated node (N) in a case of esophageal carcinoma fulfills the original criteria. (Courtesy of Paul Fockens, M.D., Academic Medical Center, Amsterdam, The Netherlands.)

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