Endoscopic Ultrasonography G. N. J. TYTGAT & P. FOCKENS Academic Medical Centre, Dept. of Gastroenterology-Hepatology, Amsterdam, The Netherlands
Tytgat GNJ, Fockens P. Endoscopic ultrasonography. Scand J Gastroenterol 1992;27 Suppl 192230-87. Endoscopic ultrasonography (ES) enables accurate imaging of the layering structures of the gastrointestinal tract. The equipment is still evolving but has already reached a high degree of sophistication. The most relevant clinical indications are the analysis of submucosal tumors, the imaging of intestinal vascular anomalies, and, especially, the staging of gastrointestinal and biliopancreatic malignancy and the monitoring of the therapeutic efficacy of surgery, Nd:Yag laser photodestruction,and radiotherapy. Scand J Gastroenterol Downloaded from informahealthcare.com by Mcgill University on 11/03/14 For personal use only.
Key words: Endoscopic ultrasonography; gastrointestinal malignancy; submucosal tumors; vascular
disorders Prof. Dr. Guido N . J . Tytgat, M. D . , Academic Medical Centre, Dept. of Gastroenterology-Hepatology, Meibergdreef 9, NL-1105 A Z Amsterdam, The Netherlands
Endoscopic ultrasonography (ES) is a new imaging technique that during the past decade has developed into an important extension of diagnostic endoscopy. At present there is no other diagnostic modality to image the intestinal wall in such detail as can be obtained by ES. The greater the ultrasound frequency, the greater the resolution, but the less the depth of penetration and the more limited the field of view. Since ES places the transducer close to the target organ(s), the frequencies used may be higher than those used in standard external ultrasonography. The usual frequency range for ES is 7.5 to 12 MHz, enabling high-resolution real-time ultrasound images. EQUIPMENT The only mechanical radial scanning ultrasonographic imaging system currently in widespread use for the gastrointestinal tract is that made by Olympus. This consists of a display unit and an echoendoscope. The optical system may be oblique (GF/JF-UM20) or forward-viewing (CF-UM20) (Table I). Systems with a frequency of 7.5MHz (CFUM20) or a switchable frequency of 7.5MHz and 12 MHz (GF/JF-UM20) are currently available. The crystal and acoustic mirror is mechanically rotated at 10 cycles/sec by a motor drive encased in the shaft of the endoscope. The signal from the transducer is transferred electronically down the shaft of the endoscope to a digital scan converter, and a real-time grey-scale radial or sector image is displayed. The display unit (EU-M20) provides a real-time image that is a 360" radial or a 180" sector scan, perpendicular to the axis of the echoendoscope. Images may be recorded by various methods including Polaroid photography, videotape, videoprinter, or laser disk. There is a freeze-frame function for better photographic documentation and for measuring the distances from point to point. The distal tip of the insertion
tube (13mm in diameter) that houses the transducer is relatively long (4.2 cm) and rigid. The penetration depth of 7.5 MHz is approximately 10 cm with an axial resolution of 0.2 mm. The values for 12 MHz are respectively 3 cm and 0.12 mm. In the presence of considerable luminal narrowing, a small-calibre instrument may be used. Recently, a mechanical radial scanner catheter echoprobe (UM-1W) with an outer diameter of 3 mm, which can be introduced through the biopsy channel of a largecalibre forward-viewing gastroscope, became available (1). ENDOSONOGRAPHY EXAMINATION OF THE UPPER INTESTINAL TRACT The endoscopic ultrasound examination is carried out in a manner similar to standard upper gastrointestinal endoscopy after pharyngeal anaesthesia and intravenous sedation with, for example, midazolam (necessary because of discomfort during the insertion of the 4.2-cm long rigid tip of the instrument and filling of the balloon with water). Usually the patient is placed in the left lateral position. In the absence of stenosis, the echoendoscope is inserted past the lesion and introduced into the stomach to visualize any lymph nodes at the level of the coeliac axis, in the paracardial area and along the lesser curvature of the stomach. Ultrasonography requires close contact with the structures to be imaged, without interposed material or structures. In the gastrointestinal tract this means that there must be no gas between the transducer and the target organ. Therefore the transducer is kept in close contact with the intestinal wall. Filling the balloon that covers the transducer with water creates an acoustic window providing clear ultrasonic images. In addition, the target area-for example, the stomachmay be filled with 200 to 500 ml of deaerated water to provide
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Table I. Technical data of the current echoendoscopes
Echoendoscope Endoscope Echoprobe
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Diameter of echoprobe Working length Frequency Depth of penetration Axial resolution ES-guided puncture/biopsy Forcers elevator
GF-UM20
JF-UM20
45" oblique viewing Mechanical
45" oblique viewing Mechanical
radial
radial
scanning (180" or 360")
scanning (180" or
13.2 mm
360") 12.5 mm
1055 m m 7.5 MHz/ 12 MHz' 10 cm/3 cm
7.5 MHz/ 12 MHz* 10 cm/3 cm
0.2mm/
CF-UM20
Catheter echoprobe UM-1W
Forward-
GIF-ITlO/IT20
viewing Radial
Radial
scanning (300")
scanning (360")
17.4 mm
3 mm
1325 mm 7.5 MHz
2500 mm 7.5 MHz
10 cm
3 cm
0.2mm/
0.2 mm
0.2-0.3 mm
Yes
0.12 mm Yes
Yes
No
Yes
Yes
No
No
0.12 mm
1250 mm
* Switchable frequency.
a proper interface for ultrasonography. After the transducer is advanced to the desired position, a full two-dimensional image enables identification of landmarks such as the liver, pancreas, spleen, kidneys, and large blood vessels. The use of the freeze-control facilitates the recording of highresolution sonograms. Standardized images comparable to cross-sectional positions of computed tomography (CT) are obtained. Longitudinal and oblique sections can be made by manouvering the echoprobe, using the thoracic descending aorta or the liver and spleen as major landmarks. In the distal esophagus, the aorta is positioned in the 5 to 6 o'clock position. Posterior appears at the bottom and anterior at the top of the picture-left and right are reversed as if facing a supine patient. Areas of interest are located by advancing the instrument to the level previously identified on standard endoscopy. Important landmarks for oesophageal examination are the heart, aorta, aortic arch, inferior and superior vena cava, and the azygous and hemiazygous veins. The azygous vein progresses in a cephalad direction from posterior to anterior along the right side of the esophagus to enter the superior caval vein. The characteristic total reflection of ultrasound due to the trachea, carina, and bronchi and the visualisation of the left atrium are also important landmarks for staging. The entire pancreas can be examined by a combination of transduodenal and transgastric scanning. It is therefore necessary to insert the instrument fully and to utilize the duodenal scanning position to visualize the head of the pancreas, the biliary system, and other retroperitoneal structures. For visualisation of the body and tail of the pancreas, the endoscope is pulled back into the stomach.
ENDOSONOGRAPHY EXAMINATION OF THE LOWER INTESTINAL TRACT Insertion of the colonscope is done in the usual manner. While withdrawing the instrument, endoscopic inspection of the colonic wall and transmural ultrasound is performed concomitantly. For optimal endosonographic visualisation, the bowel segment to be scanned is filled with 200-300ml deaerated water through the instrumentation channel. Adding some dimethicone emulsion may prevent bubble formation. The 300" ultrasonographic view can easily be completed to 360" by torquing the instrument. The use of a water-filled balloon is helpful, especially in the rectum. Usually, both luminal water filling and balloon water filling are necessary for optimal visualization of the lesions and of the colonic wall.
NORMAL ULTRASONOGRAPHIC WALL LAYERING STRUCTURES Most authors recognize five sonographic layers within the intestinal tract (2-6): 1) an innermost hyperechoic (echodense) layer, corresponding to the boundary echo, and the surface (glandular) layer; 2) an inner hypoechoic (echopoor) layer, corresponding to the deeper glandular layer of the mucosa. It is not entirely clear whether the muscularis mucosae belongs to the second layer or to the third layer; 3) a middle hyperechoic or echogenic layer, corresponding at large to the border echo and the submucosa with loose connective tissue, rich in fat, blood vessels, and lymphatics; 4) an outer hypoechoic layer, corresponding mainly to the
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muscularis propria; and 5) an outermost hyperechoic layer, corresponding to the adventitia (oesophagus) or subserosa and serosa together with peri-intestinal adipose tissue (stomach). According to Kimmey et al. ( 5 ) the five layers correspond to: 1) superficial mucosa; 2) deep mucosa; 3) submucosa plus the acoustic interface between the submucosa and muscularis propria; 4) muscularis propria minus the acoustic interface between submucosa and muscularis propria; and 5) serosa and subserosal fat. Thus this interpretation takes into consideration the echos produced by the tissue layers and the echos produced by the interfaces between different layers. This ideal five-layer structure is sometimes not well visualized in the esophagus owing to focusing problems with currently available equipment (7). Often only a three-layer pattern is seen in the oesophagus. The first hyperechoic layer corresponds to the balloonmucosa-submucosa and submucosa-muscularis propria interface together; the second, hypoechoic, layer corresponds to the muscularis propria; and the third, hyperechoic, layer is the outer border echo. The diameter of the layers and particularly of the muscularis propria is quite variable and relates to the degree of stretching by the balloon and the age of the patient.
adjacent lymph node structures is pathognomonic for metastasis. Lymph nodes at a distance of 10 cm or more from the intestinal lumen cannot be seen adequately with ES. ENDOSONOGRAPHY IN SUBMUCOSAL TUMOURS AND EXTRAINTESTINAL LESIONS
ES is useful in the investigation of intramural lesions or lesions that produce extrinsic deformity of the wall (12-15). Submucosal lesions may be localized within the various sonographic layers of the gut wall, a finding that may be used to suggest a diagnosis based on the tissue of origin. Furthermore, submucosal lesions may be separated into cystic or solid, discrete or infiltrative. A leiomyoma is the commonest benign oesophageal tumour. A leiomyoma is usually seen as a bulging mass covered with smooth intact mucosa. The hypoechoic mass usually has smooth margins that are contiguous to the muscularis propria layer. Occasionally, a central ulcer and hypoechoic foci can be found in the case of extensive leiomyoma, owing to inadequate blood supply. Endoscopic forceps biopsy is rarely helpful in ascertaining the diagnosis and/ or in ruling out malignancy. In contrast, a special guillotine needle biopsy device (Flexi-Temno) may enable a correct histologic diagnosis (16). With ES, a leiomyoma appears as a PATHOLOGIC ULTRASONOGRAPHIC FINDINGS sharply demarcated lesion with a homogeneous echo pattern Pathologic disorders of the intestinal wall cause disruption covered with sonographically normal-appearing mucosa. or destruction of the ES layers which may be either focal or Occasionally, local thickening of the muscularis propria may diffuse. Although the histologic correlate of the sonographic be seen. A leiomyoma compresses but does not infiltrate layers of the gastrointestinal wall is still not fully established, into surrounding tissues. Lipoma, ectopic pancreas, and all investigators agree that the layering pattern is disrupted contiguous variceal structures can be distinguished from by disease processes. The thickness of various layers may be leiomyoma on the basis of the echo pattern, the site of altered, or one or more layers may be obliterated ( 2 , 3 , 7 , 8 ) . origin, and the configuration (13). In general, lipomas have Neoplasms are detected as a disruption in the continuity of a more echogenic texture and do not seem to take off from an ultrasound layer or by diffuse layer thickening. A change the muscularis propria. A submucosal tumour mass with in the echogenicity of an ultrasound layer is another sign of an inhomogeneous echo pattern and poorly demarcated or tissue abnormality. Neoplasms are usually of low or inter- irregularly defined borders is strongly indicative of either a mediate echogenicity: less echogenic than the third echo- leiomyoblastoma or a leiomyosarcoma. It should be stressed genic layer but more echogenic than the second and fourth that differentiation between a benign and a malignant lesion layers. often remains difficult. The presence of suspicious lymph Round or ellipsoid sonographic structures are frequently nodes may be helpful in distinguishing the potentially maligimaged adjacent to the gastrointestinal wall. They cor- nant character of the lesion. Follow-up examination may respond to lymph nodes and can readily be distinguished also help in elucidating the nature of the lesion. from vascular structures. Whether lymph nodes have specific ES is of major help in differentiating extramural from sonographic features that may be used for differential diag- intramural lesions. ES may readily detect the extraintestinal nosis is not entirely clear. In general, a nodal echo pattern origin of a malignancy. This is of importance in difthat is homogeneous and more echo-dense than that of a ferentiating genuine achalasia from pseudoachalasia due to primary lesion and that reveals somewhat indistinct borders invading malignancy. Yasuda et al. (17) showed a 100% is usually considered indicative of benign inflammatory specificity in distinguishing submucosal lesions from extrinsic change. Malignant nodal involvement is usually charac- compression in a series of 83 patients. terized by spherical shape, distinct sharply demarcated borders, and a non-homogeneous echographic pattern that VASCULAR ANOMALIES either resembles the pattern of the primary lesion or is even more hypoechoic or by the presence of heterogeneous echo ES is important for the detection and staging of gastrospots ( S l l ) . Direct extension of the primary lesion into oesophageal varices (18). Especially in the stomach, variceal
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Endoscopic Ultrasonography
structures may be readily identified which are not suspected endoscopically. Varices are displayed by ES as anechoic serpentine duct-like structures with low echos and localized in the mucosa, submucosa, or outside the intestinal wall. Limitation in ES variceal detection may be attributable to problems with focusing the ultrasound display and to compression of the varices by the water-filled balloon. The azygous vein is seen as a rounded echo-free structure between the oesophagus, aorta, and spine. At the level of the fourth thoracic vertebra this vein arches in a forward and slightly lateral direction to enter the superior caval vein. The diameter of the azygos vein is greater in cirrhotics than in controls, and the diameter increases gradually from distal to proximal. The deeper peri-oesophageal collateral veins may be much larger than the submucosal varices. Communication with a further collateral circuit below the diaphragm can be seen in approximately 25% of cases. After endoscopic sclerotherapy, thickening of the oesophageal wall and a thrombus mass of high echogenicity may be observed, demonstrating variceal obstruction. Thereafter the echogenic thrombus changes to a uniform hypoechoic thrombus, indicative of organization (19). In patients with congestive gastropathy, ES shows small round echo-free structures around and within the gastric wall, corresponding to dilated tributaries of the gastric veins which are readily distinguishable from isolated fundal varices (209). ENDOSONOGRAPHY IN RUGAL HYPERPLASIA Both benign and malignant disease may lead to rugal hyperplasia, especially in the stomach. Not uncommonly, standard forceps biopsy specimens fail to provide the correct histopathologic diagnosis. ES is of major importance in this differential diagnosis. In rugal hyperplastic gastropathy, usually Menetrier’s disease, ES demonstrates enlargement of the first and second layer of the gastric wall corresponding to the mucosa. The mucosa may be thickened to 2 or 3 mm, whereas the normal gastric mucosa is about 0.7 to 0.8 mm thick (21; T. L. Tio, J. J. Maas, E. M. Colin, et al. Unpublished observations). Frank gastric rugae may also be produced by infiltrating adenocarcinoma (linitis plastica or scirrhous-type malignancy) or gastric lymphoma. In linitis plastica there is irregular hypoechoic enlargement of the third layer, corresponding to the submucosa, and of the fourth layer, corresponding to the muscularis propria, reflecting cancerous infiltration. In the case of lymphoma, there is usually diffuse transmural thickening of the wall, with abolition of the normal gastric layering. ENDOSONOGRAPHY IN PEDUNCULATED OR SESSILE POLYPOID LESIONS Benign polypoid adenomatous proliferations do not disrupt the third echogenic layer of the intestinal wall. Whenever
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the third layer is abnormal or interrupted, there is a suspicion of focal malignancy. The sensitivity of endosonography in detecting focal malignancy in large villous adenomas is controversial. Some investigators feel that this is impossible (22,23), whereas others are of the opinion that focal malignancy can be detected with a reasonable accuracy provided no prior laser or electrofulguration has been carried out (2427; F. J. Hulsmans, T. L. Tio, E. M. H. Mathus-Vliegen. Unpublished observations). With the currently available, albeit high-frequency ultrasonographic technology, it is not possible to visualize the thin muscularis mucosae, and early invasion through the muscularis mucosae may remain undetected. Excessive compression of polypoid lesions with the water-filled balloon is to be avoided because the subsequent wall identation by the polypoid tissue mass may erroneously suggest malignant infiltration. Difficulties also arise when a polyp is situated close to the anal canal. Examination of this area is difficult because of the inability to keep the scan plane perpendicular. Oblique scanning of a lesion may lead to blurring of the outer margin and hence erroneously suggest tissue infiltration. ENDOSONOGRAPHY IN MALIGNANT TUMOURS The endosonographic classification of the depth of tumour infiltration and for assessing regional lymphnode metastasis is usually made according to the TNM staging system (28). Early carcinoma is visualized as a hypoechoic lesion localized in the mucosa and/or submucosa without penetration into the muscularis propria. There is no evidence of adjacent lymph node involvement. In some cases a benign inflammatory reaction secondary to ulcerative changes within the early cancerous lesion may simulate a more deeply infiltrating malignant lesion. The depth of penetration of early tumours can usually be determined with an accuracy of more than 80%. Advanced cancer is diagnosed when the lesion spreads into or beyond the muscularis propria. The exent of advanced cancer invasion can also be correctly determined in more than 80%. In the evaluation of regional lymph nodes, ES is generally more accurate for diagnosing metastatic involvement than for non-metastatic inflammation. False-positive diagnoses or false-negative diagnoses, however, do occur. The node size by itself is not reliable in defining whether it is malignant. Enlarged nodes may be benign owing to inflammation, and small nodes may already show micrometastatic involvement.
Oesophageal malignancy The overall accuracy of ES in staging oesophageal cancer, especially those malignancies limited to the wall, is satisfactory (29-33). Several studies testify to the high accuracy in T-staging and good accuracy in the detection of malignant nodes. Murata (32) obtained operative confirmation in 139 oeso-
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phageal cancers, staged with ES. The tumours were correctly staged in 84% of cases. The sensitivity in predicting the depth of invasion was impressive: submucosa, 75%; muscularis propria, 64%; adventitia, 94%; and adjacent organs, 100%. Nodal involvement was correctly predicted in 89%. In cases of extensive deep penetration into or through the adjacent tracheobronchial tree, differentiation between an oesophageal and a bronchial or tracheal carcinoma becomes difficult. Bronchoscopy may be helpful in ascertaining the correct diagnosis. Lymph node metastasis at the coeliac axis is to be considered a distant metastasis. It is therefore of paramount importance to examine first the coeliac axis and the lesser curve of the stomach. Suggestive coeliac nodes in oesophageal carcinoma require that an exploratory laparotomy rather than a thoracotomy be performed first for confirmation of the diagnosis by histology. If positive results are obtained, thoracotomy will be superfluous because of the poor ultimate prognosis of the disease once the coeliac nodes are involved. A question often asked concerns the accuracy of ES versus CT in staging oesophageal malignancy (34). This was prospectively studied by Tio et al. (29). For T-staging, ES accuracy was 89%, compared with 59% for CT. Overall accuracy in staging regional lymph nodes was 80% for ES, compared with 51% for CT. ES was superior to CT in the evaluation of tumour infiltration, especially in the early stages and in non-resectable carcinoma. EUS was also more accurate in the assessment of regional lymph nodes metastasis. A limiting factor for ES was severe stenosis in 26% of the patients. Comparable figures were obtained in an American study (7). In T-staging, ES accuracy was 92% compared with CT at 60%. For regional lymph nodes, ES accuracy was 88% compared with 74% for CT.In a recent German study ES accuracy was 89% for staging and 69% for N staging, compared with 51% and 51%, respectively, for CT (35). From these studies it is obvious that ES is superior to CT, especially for the early stages of oesophageal cancer. ES findings of the degree of wall invasion are superior to (JT. ES understages the depth of tumour infiltration in patients with severe stenosis. In those patients CT can be more accurate. ES understaging can also occur in patients with aortic, pericardial, or diaphragmatic involvement, but still the overall accuracy of ES in the evaluation of T4 tumours is higher than that of CT. As overstaging is the most important factor to avoid if patients are not to be denied appropriate surgical intervention, it is encouraging that overstaging rarely occurs with ES. ES is superior for the diagnosis of recurrent cancer at the surgical anastomosis. An accurate diagnosis of recurrent perianastomotic cancer is of essential importance in the selection of appropriate patient management. In a recent study the sensitivity of ES for diagnosing recurrent cancer was 95% and the specificity 80% (36). The role of CT is
limited after resection because of differences in anastomotic morphology and artefacts created by movement, retained metallic clips, and staples. CT is more effective in diagnosing distant metastasis. Finally, ES is useful for monitoring the effects of combined external and intraluminal radiotherapy (T. L. Tio. Unpublished observations). Radiation efficacy is characterized by a reduction in tumour thickness or disappearance of the mural abnormality and reduction in lymph node abnormalities. Radiation effects are visualized as hyperechoic alterations surrounding the hypoechoic cancerous lesion. Gastric malignancy Early gastric adenocarcinoma is visualized as a hypoechoic abnormality, localized in layers 1 to 3 (mucosa 2 submucosa) without penetration into layer 4 (muscularis propria) and with or without immediately adjacent lymph node abnormalities. In contrast, advanced gastric cancer is visualized as a hypoechoic lesion with penetration into or through the muscularis propria, often associated with lymph node abnormalities (29,37,38). Again, accuracy of T-staging is more than 80% and detection of lymph nodes metastasis more than 80% with an overall accuracy of ES superior to CT scanning. Early gastric cancer is readily diagnosed if the size of the tumour is at least 1 cm. Early mucosal cancer presenting as a shallow ulcer is difficult to diagnose by ES alone. Also, differentiation of the extent of carcinomatous tissue infiltration from inflammatory changes that often accompany ulceration is problematic. In scirrhous-type gastric carcinoma there is diffuse infiltration of every layer of the stomach by tumour cells, but especially of the 3rd layer, resulting in gastric wall thickening and destruction of the normal architecture (21). In the early stages of scirrhous carcinoma mural thickening can occur in the absence of stiffening of the gastric wall. In these circumstances the endoscopic appearance may be almost normal, but the endosonographic appearance readily suggests malignancy. Gastric lymphoma is increasingly recognized and can be diagnosed successfully by ES. Often major problems are encountered in staging such lesions. ES may visualize gastric lymphoma as a polypoid, ulcerative, polypoid-ulcerative and/or diffuse transmural hypoechoic abnormality together with suspicious perigastric lymph node abnormalities (39, 40). Especially stages I and I1 of the Ann Arbor classification can only be distinguished accurately with ES. Difficulties arise when giant folds surround gastric ulcers, which readily mimic lymphoma because of similarities in the transmural hypoechoic echo pattern. ES is also accurate at follow-up after surgery, radiotherapy and/or chemotherapy. Thus, ES is a sensitive diagnostic modality for the preoperative staging and follow-up of primary gastric lymphoma. Biliary and pancreatic malignancy The transduodenal and transgastric approach provides
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Endoscopic Ultrasonography
clear visualization of the pancreas and its surrounding structures. Furthermore, certain structures that are affected by pancreatic disease, such as the bile duct, gallbladder, portal vein, splenic artery, and the intestinal wall, are also readily imaged from the intraduodenal and intragastric position. Pancreatic carcinoma is visualized as a hypoechoic inhomogeneous sharply or irregularly demarcated, sometimes polycyclic, parenchymal lesion, which often appears more hypoechoic than the surrounding tissues (4145). The parenchymal and ductular abnormalities together with the peripancreatic lymph nodes can readily be seen. Supplementary findings such as compression of the pancreatic duct, bile duct, or both, with prestenotic dilatation corresponding to the endoscopic retrograde pancreatography (ERCP) findings of the double duct lesion are also helpful when the lesion is suspected of being malignant. In general, sensitivity and specificity in pancreatic tumour diagnosis are significantly higher for ES (>90%) than for standard ultrasonography and CT scanning. Especially for the detection of small lesions and for assessing the extent of local regional tumour spread, ES is currently the most accurate imaging method. However, differentiation between cancer and pseudotumours of inflammatory origin is occasionally a problem (46). A periampullary tumour is seen as a hypoechoic intramural lesion, immediately adjacent to the common bile duct and/or pancreatic duct. Differentiation between adenomyomatosis and early carcinoma is difficult, if not impossible, especially when evidence of penetration into or through the mucularis propria is lacking. In advanced periampullary cancer, invasion into the adjacent pancreatic parenchyma makes the differentiation between primary pancreatic cancer and periampullary carcinoma more difficult. Malignancy in the distal common bile duct is usually visualized as a polypoid hypoechoic structure originating from the bile duct wall and protruding into the dilated lumen. An endoprosthesis is sometimes a useful guide for localizing the main lesions and does not prohibit accurate visualization of the lesion. An inserted biliary endoprosthesis is seen as a double hyperechoic line. The more proximal biliary tree can be recognized after slowly withdrawing the instrument from the area of the papilla of Vater and using the typical localization of the common bile duct immediately adjacent to the duodenal wall as a landmark. From the apical bulbar scanning position, the liver hilum and the gallbladder can be visualized. The confluence of the hepatic duct in the porta hepatis is usually readily recognized. Malignancy is seen as a hypoechoic intraductular lesion localized immediately adjacent to the bifurcation of the bile duct, often associated with dilatation of the intrahepatic ducts in the presence of a normal-calibre distal common bile duct. Carcinoma of the gallbladder is visualized as a hypoechoic polypoid structure, originating from the wall or protruding
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into the cavity of the gallbladder. In an advanced stage tumour extension along the hepatic duct into the hepatobiliary bifurcation is usually seen. In such cases differentiation between a Klatskin tumour and a primary gallbladder carcinoma may be difficult. Colorectal malignancy Rectal EUS may be carried out with a rigid optical instrument or with a flexible endoscopic instrument. The prostate and sacral bone can easily be used for anatomic orientation. Furthermore, the pelvic muscles are readily recognized as hypoechoic spindle-shaped structures encircling the rectal lumen. The echo pattern of rectal carcinoma is more hypoechoic than that of the surrounding tissues. The transition between normal and pathologic wall structure can usually readily be seen. Early malignancy is diagnosed when the hypoechoic lesion does not penetrate and destroy the fourth layer (muscularis propria). Advanced rectal carcinoma is visualized as an irregular hypoechoic intramural structure penetrating into or through the muscularis propria with or without evidence of adjacent lymph node involvement. Many studies have highlighted the accuracy of ES in staging colorectal cancer (22,28,49). Lymph node metastasis can be detected with a sensitivity and specificity of over 70% to 80%, respectively (49; F. J. Hulsmans, T. L. Tio, E. M. H. MathusVliegen. Unpublished observations). Transrectal US is accurate in the follow-up of patients after surgery or laser therapy because of the ability to visualize clearly the intestinal wall structure and adjacent lymph node abnormalities. Recurrent or residual malignancy is visualized as a hypoechoic intramural lesion with or without local regional lymph node involvement.
ENDOSONOGRAPHY IN PERIRECTAL ABSCESS AND FISTULA In patients with Crohn’s disease ES can readily visualize perirectal abscesses or fistula as anechoic or hypoechoic irregular ductular-like lesions adjacent to the lumen with or without communication with the intestinal wall (50; 0. B. Wijers, T. L. Tio, G . N. J. Tytgat. Unpublished observations). The extent of the lesion can clearly be recognized, including the presence or absence of any destruction of the pelvic muscles, which is important for planning surgical strategy. ES is preferred to fistulography in the detection and staging of perirectal fistula because there is improved patient tolerance, more precise imaging, and no risk of spread of infection (50; 0. B. Wijers, T. L. Tio, G. N. J. Tytgat. Unpublished observations). LIMITATIONS O F ENDOSONOGRAPHY Inability to pass a stenotic cancer, usually in the esophagus or at the cardia, with current ES instruments with a diameter
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of 13 mm is a definite limitation. Because of an inability to pass the tumour, ES staging of the tumour and of the nodes, especially of coeliac axis lymph nodes, may be limited. In the Amsterdam study (29) E S accuracy was 68%, compared with 82% for CT scanning in staging coeliac axis lymph nodes. Recently, a mechanical radial scanning catheter echoprobe became available, which can be introduced through the biopsy channel of a large-calibre gastroscope into a tight stenotic oesophageal carcinoma. Experience with this prototype in stenosing oesophageal cancer is still limited but encouraging (1). COMPLICATIONS OF ENDOSONOGRAPHY A potential complication of ES examination is rnucosal tearing because of overstretching by the distending balloon. Balloon decompression may be needed when withdrawing the transducer through the cardia into the esophagus, when passing the aortic arch, and to avoid compression of the trachea. Another complication relates t o perforation when trying to force the instrument through a narrow segment because the oblique or side-viewing optics d o not enable adequate visualization of the esophagus. After prior radiotherapy the wall of the oesophagus may have lost elasticity and is made vulnerable to passage of the balloon covered with a rigid tip. A rare but alarming complication is inversion of the instrument in a widened oesophagus proximal to an irregular malignancy. Attempts to withdraw the inverted instrument may readily damage the oesophageal wall. Using constant fluoroscopic monitoring, careful straightening of the instrument should be carried out first, before instrument withdrawal is attempted.
FUTURE DEVELOPMENTS Although currently available instruments produce suberb images, further developements are likely if not necessary. There is an urgent need for a small-diameter forward-viewing ES instrument to facilitate passage of stenotic areas. Adequate facilities for constantly US-guided cytologic puncture are mandatory. The selection of ultrasound frequencies needs to be expanded and to include the use of very high frequencies for improved tissue characterization. ColorDoppler imaging facilities will further characterize vascular structures and the direction of blood flow. Computer-assisted endoscopic sonography will enable three-dimensional modelling (51). Finally, miniature probes will be developed with different sizes, frequencies, lengths, and so forth, for the insertion into the common bile duct and pancreatic duct. Endosonography is a useful procedure in the evaluation of a variety of both benign and malignant, intrinsic and extrinsic lesions of the gastrointestinal and hepatopancreatic tract. E S provides accurate information about the size and location of such lesions in relation to the gastrointestinal
wall. Although a histopathologic diagnosis is not possible by ES, the procedure demonstrates whether the lesion is cystic, solid, or vascular. E S can localize a lesion intrinsic to the gastrointestinal wall to one or more of the histologic layers, so that it is frequently possible t o infer a correct diagnosis. Further improvements in the manoeuverability and optics of ES instruments and the further refinements of guided tissue sampling will enhance the future utility of ES. Now that many hospitals are faced with major financial constraints there is considerable reluctance in deciding if and when this expensive equipment should be bought. There can be no doubt that the development costs of endosonography instruments were huge. Nevertheless, we hope that the prices will come down to enable more units to apply this important new and clinically applicable development in imaging technology. REFERENCES 1. Rosch T. Classen M. A new ultrasonic Drobe for endosonographic imaging of the upper GI (ract. Endoscopy 1990;22:41-6. 2. TioTL, Tytgat GNJ, Endoscopicultrasonography of normal and pathologic upper gastrointestinal wall structure. Comparison of studies in vivo and in vitro with histology. Scand J Gastroenterol 1986;21 SUPPI123:27-33. 3. Takemoto T, Aibe T, Fuji T, et al. Endoscopic ultrasonography. Clin Gastroenterol 1986;15:305-19. 4. Aibe T, Fuji T, Okita K, et al. A fundamental study of normal layer structure of the gastrointestinal wall visualized by endoscopic ultrasonography. Scand J Gastroenterol 1986;21 Suppl 123:615. 5. Kimmey MB, Martin RW,Haggitt RC, et al. Histological correlates of gastrointestinal ultrasound images. Gastroenterology 1989;96:433-1. 6. Tytgat GNJ. Transintestinal ultrasonography. Present and future. Endoscopy 1987;19:241-2. 7. Lightdale CJ, Botet JF. Esophageal carcinoma: pre-operative staging and evaluation of anastomotic recurrence. Gastrointest Endosc 1990;36:114. 8. Tio TL, Coene PPLO, Luiken GJHM, et al. Endosonography in the clinicalstagingof esophagogastriccarcinoma. Gastrointest Endosc 1990;36:2-10. 9. Aibe T, Ito T, Yoshida T, et al. Endoscopic ultrasonography of lymph nodes surrounding the upper GI tract. Scand J Gastroenterol 1986;21 Suppl 123:164-9. 10. Tio TL, Tytgat GNJ. Endoscopic ultrasonography in analysing pen-intestinal lymph node abnormality. Preliminary results of studies in vitro and in vivo. Scand J Gastroenterol 1986;21 Suppl 123:158-63. 1. Tio TL, den Hartog Jager FCA, Tytgat GNJ. The role of endoscopic ultrasonography in assessing local resectability of oesophagogastric malignancies. Accuracy, pitfalls, and predictability. Scand J Gastroenterol 1986;21 Suppl 123:78-86. 2. Heyder N. Endoscopic ultrasonography of tumours of the oesophagus and the stomach. Surg Endosc 1987;l:17-23. 3. Tio TL, Tytgat GNJ, Den Hartog Jager FCA. Endoscopic ultrasonography for the evaluation of smooth muscle tumors in the upper gastrointestinal tract: an experience in 42 cases. Gastrointest. Endosc 1990;36:342-50. 14. Caletti G, Zani L, Bolondi L. Endoscopic ultrasonography in the diagnosis of gastric submucosal tumor. Gastrointest Endosc 1989;35:413-8. 15. Boyce GA, Sivak MV, Rosch T. Evaluation of submucosal upper gastrointestinal tract lesions by endoscopic ultrasound. Gastrointest Endosc 1991;37:44%54. 16. Caletti GC, Brocchi E, Ferrari. Guillotine needle biopsy as
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Endoscopic Ultrasonography a supplement to endosonography in the diagnosis of gastric submucosal tumors. Endoscopy 1991;23:251-4. 17. Yasuda K, Cho E, Nakajima M, et al. Diagnosis of submucosal lesions of the upper gastrointestinal tract by endoscopic ultrasonography. Gastrointest Endosc 1990;36:S17-S20. 18. Caletti G, Brocchi E, Baraldini M, et al. Assessment of portal hypertension by endoscopic ultrasonography. Gastrointest Endosc 1990;36:21-7. 19. Ziegler K, Gregor M, Zeitz M, et al. Evaluation of endosonography in sclerotherapy of esophageal varices. Endoscopy 1991;23:247-50. 20. Caletti G, Brocchi E, Zani L, et al. The important role of EUS in the assessment of patients with portal hypertension. Gastrointest Endosc 1988;34:154-5. 21. Fujishima H, MisawaT, Chijiiwa Y. Scirrhous carcinoma of the stomach versus hypertrophic gastritis: findings at endoscopic US. Radiology 1991;181:197-200. 22. Shimizu S, Tada M, Kawai K. Use of endoscopic ultrasonography for the diagnosis of colorectal tumors. Endoscopy 1990;22:31-34. 23. Hildebrandt U, Feifel G, Ecker KW. Rectal endosonography. Baillieres Clin Gastroenterol 1989;3:531-41. 24. Glaser F, Schlag P, Herfarth C. Endorectal ultrasonography for the assessment of invasion of rectal tumours and lymph node involvement. Br J Surg 1990;77:883-7. 25. Heintz A, Buess G, Frank K, Kuntz C, Strunck H, Junginger T. Endoluminal ultrasonic examination of sessile polyps and early carcinomas of the rectum. Surg Endosc 1989;3:92-5. 26. Rosch T, Lorenz R, Suchy R. Colonic endoscopic ultrasonography: first results of a new technique. Gastrointest Endosc 199O;36:382-6. 27. Mosnier H, Guivarc’h M, Meduri B, Fritsch J, Outters F. Endorectal sonography in the management of rectal villous tumours. Int J Colorectal Dis 1990;5:90-3. 28. Hermanek P, Sobin LH, editors. TNM classification of malignant tumours. 4th ed. Heidelberg: Springer Verlag, 1987. 29. Tio TL, Coene PPLO, Schouwink MH, Tytgat GNJ. Esophagogastric carcinoma: preoperative TNM classification with endosonography. Radiology 1989;173:411-7. 30. Ti0 TL, Cohen P, Coene PPLO, et al. Endosonography and computed tomography of esophageal carcinoma. Preoperative classification compared to the new (1987) TNM system. Gastroenterology 1989;96:1478-86. 31. Tio TL, Coene PPLO, Den Hartog Jager FCA, Tytgat GNJ. Preoperative TNM classification of esophageal carcinoma by endosonography. Hepatogastroenterology 1990;37:376-81. 32. Murata Y, Muroi M, Yoshida M, et al. Endoscopic ultrasonography in the diagnosis of esophageal carcinoma. Surg Endosc 1987;l:11-6. 33. Takemoto T, Ito T, Aibe T, et al. Endoscopic ultrasonography in the diagnosis of esophageal carcinoma with particular regard to staging it for operability. Endoscopy 1986;18 Suppl 3:22-5.
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34. Tytgat GNJ, Ti0 TL. Techniques for staging oesophageal cancer. Gullet 1990;1:4-9. 35. Ziegler K, Sanft C, Zeitz M, et al. Evaluation of endosonography in TN staging of oesophageal cancer. Gut 1991; 32: 16-20. 36. Lightdale CJ, Botet JF, Kelsen DP, et al. Diagnosis of recurrent upper gastrointestinal cancer at the surgical anastomosis by endoscopic ultrasound. Gastrointest Endosc 1989;35:407-12. 37. Akohoshi K, Misawa T, Fujishima H, et al. Preoperative evaluation of gastric cancer by endoscopic ultrasound. Gut 1991;32:47%82. 38. Okai T, Yamakawa 0, Matsuda H, et al. Analysis of gastric carcinoma growth by endoscopic ultrasonography. Endoscopy 1991;23:121-5. 39. Tio TL, Den Hartog Jager FCA, Tytgat GNJ. Endoscopic ultrasonography of non-Hodgkin lymphoma of the stomach. Gastroenterology 1986;91:401-8. 40. Fujishima H, Misawa T, Maruoka A, et al. Staging and followup of primary gastric lymphoma by endoscopic ultrasonography. Am J Gastroenterol 1991;86:719-24. 41. Yasuda K, Mukai H, Rryimoto S, Nakagima M, Kawai K. The diagnosis of pancreatic cancer by endoscopic ultrasonography. Gastrointest Endosc 1988;34:1-8. 42. Ti0 TL, Tytgat GNJ, Cirot RJLM, Houthoff HJ, Sars PRA. Ampullopancreaticcarcinoma: preoperative TNM classification with endosonography. Radiology 1990;175:455-61. 43. Grimm H, Maydeo A, Soehendra N. Endoluminal ultrasound for the diagnosis and staging of pancreatic cancer. Clin Gastroenterol 1990;4:869-88. 44.Rosch T, Lorenz R, Braig C, et al. Endoscopic ultrasound in pancreatic tumor diagnosis. Gastrointest Endosc 1991;37:34752. 45. Ti0 TL, Tytgat GNJ, Cikot RJLM, et al. Preoperative TNMclassification of pancreatic and ampullary carcinoma by endoscopic ultrasonography. Hepatogastroenterol 1989;36:51-6. 46. Tio TL, Luiken JHM, Tytgat GNJ. Endosonography of groove pancreatitis. Endoscopy 1991;23:291-3. 47. Tio TL, Tytgat GNJ. Comparison of blind transrectal ultrasonography with endoscopic transrectal ultrasonography in assessing rectal and perirectal diseases. Scand J Gastroenterol 1961;21 Suppl 123:104-11. 48. Hildebrandt U, Feifel G, Ecker KW. Rectal endosonography. 49. Hildebrandt U, Klein T, Feifel G. Endosonography of pararectal lymph nodes. Dis Col Rect 1990;33:863-8. 50. Ti0 TL, Mulder CJJ, Wijers OB, Sars PRA, Tytgat GNJ. Endosonography of pen- and pen-adenorectal fistula and/or abscess in Crohn’s disease. Gastrointest Endosc 1990;36:331-6. 51. Hashimoto H , Yokoyama S, Nakao K. The capability of three dimensional display during endoscopic ultrasonography. Dig Endosc 1991;3:194-8.
Tytgat GNJ, Fockens P. Endoscopic ultrasonography. Scand J Gastroenterol 1992;27 Suppl 192230-87. Endoscopic ultrasonography (ES) enables accurate imaging of the layering structures of the gastrointestinal tract. The equipment is still evolving but has already reached a high degree of sophistication. The most relevant clinical indications are the analysis of submucosal tumors, the imaging of intestinal vascular anomalies, and, especially, the staging of gastrointestinal and biliopancreatic malignancy and the monitoring of the therapeutic efficacy of surgery, Nd:Yag laser photodestruction,and radiotherapy. Scand J Gastroenterol Downloaded from informahealthcare.com by Mcgill University on 11/03/14 For personal use only.
Key words: Endoscopic ultrasonography; gastrointestinal malignancy; submucosal tumors; vascular
disorders Prof. Dr. Guido N . J . Tytgat, M. D . , Academic Medical Centre, Dept. of Gastroenterology-Hepatology, Meibergdreef 9, NL-1105 A Z Amsterdam, The Netherlands
Endoscopic ultrasonography (ES) is a new imaging technique that during the past decade has developed into an important extension of diagnostic endoscopy. At present there is no other diagnostic modality to image the intestinal wall in such detail as can be obtained by ES. The greater the ultrasound frequency, the greater the resolution, but the less the depth of penetration and the more limited the field of view. Since ES places the transducer close to the target organ(s), the frequencies used may be higher than those used in standard external ultrasonography. The usual frequency range for ES is 7.5 to 12 MHz, enabling high-resolution real-time ultrasound images. EQUIPMENT The only mechanical radial scanning ultrasonographic imaging system currently in widespread use for the gastrointestinal tract is that made by Olympus. This consists of a display unit and an echoendoscope. The optical system may be oblique (GF/JF-UM20) or forward-viewing (CF-UM20) (Table I). Systems with a frequency of 7.5MHz (CFUM20) or a switchable frequency of 7.5MHz and 12 MHz (GF/JF-UM20) are currently available. The crystal and acoustic mirror is mechanically rotated at 10 cycles/sec by a motor drive encased in the shaft of the endoscope. The signal from the transducer is transferred electronically down the shaft of the endoscope to a digital scan converter, and a real-time grey-scale radial or sector image is displayed. The display unit (EU-M20) provides a real-time image that is a 360" radial or a 180" sector scan, perpendicular to the axis of the echoendoscope. Images may be recorded by various methods including Polaroid photography, videotape, videoprinter, or laser disk. There is a freeze-frame function for better photographic documentation and for measuring the distances from point to point. The distal tip of the insertion
tube (13mm in diameter) that houses the transducer is relatively long (4.2 cm) and rigid. The penetration depth of 7.5 MHz is approximately 10 cm with an axial resolution of 0.2 mm. The values for 12 MHz are respectively 3 cm and 0.12 mm. In the presence of considerable luminal narrowing, a small-calibre instrument may be used. Recently, a mechanical radial scanner catheter echoprobe (UM-1W) with an outer diameter of 3 mm, which can be introduced through the biopsy channel of a largecalibre forward-viewing gastroscope, became available (1). ENDOSONOGRAPHY EXAMINATION OF THE UPPER INTESTINAL TRACT The endoscopic ultrasound examination is carried out in a manner similar to standard upper gastrointestinal endoscopy after pharyngeal anaesthesia and intravenous sedation with, for example, midazolam (necessary because of discomfort during the insertion of the 4.2-cm long rigid tip of the instrument and filling of the balloon with water). Usually the patient is placed in the left lateral position. In the absence of stenosis, the echoendoscope is inserted past the lesion and introduced into the stomach to visualize any lymph nodes at the level of the coeliac axis, in the paracardial area and along the lesser curvature of the stomach. Ultrasonography requires close contact with the structures to be imaged, without interposed material or structures. In the gastrointestinal tract this means that there must be no gas between the transducer and the target organ. Therefore the transducer is kept in close contact with the intestinal wall. Filling the balloon that covers the transducer with water creates an acoustic window providing clear ultrasonic images. In addition, the target area-for example, the stomachmay be filled with 200 to 500 ml of deaerated water to provide
Endoscopic Ultrasonography
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Table I. Technical data of the current echoendoscopes
Echoendoscope Endoscope Echoprobe
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Diameter of echoprobe Working length Frequency Depth of penetration Axial resolution ES-guided puncture/biopsy Forcers elevator
GF-UM20
JF-UM20
45" oblique viewing Mechanical
45" oblique viewing Mechanical
radial
radial
scanning (180" or 360")
scanning (180" or
13.2 mm
360") 12.5 mm
1055 m m 7.5 MHz/ 12 MHz' 10 cm/3 cm
7.5 MHz/ 12 MHz* 10 cm/3 cm
0.2mm/
CF-UM20
Catheter echoprobe UM-1W
Forward-
GIF-ITlO/IT20
viewing Radial
Radial
scanning (300")
scanning (360")
17.4 mm
3 mm
1325 mm 7.5 MHz
2500 mm 7.5 MHz
10 cm
3 cm
0.2mm/
0.2 mm
0.2-0.3 mm
Yes
0.12 mm Yes
Yes
No
Yes
Yes
No
No
0.12 mm
1250 mm
* Switchable frequency.
a proper interface for ultrasonography. After the transducer is advanced to the desired position, a full two-dimensional image enables identification of landmarks such as the liver, pancreas, spleen, kidneys, and large blood vessels. The use of the freeze-control facilitates the recording of highresolution sonograms. Standardized images comparable to cross-sectional positions of computed tomography (CT) are obtained. Longitudinal and oblique sections can be made by manouvering the echoprobe, using the thoracic descending aorta or the liver and spleen as major landmarks. In the distal esophagus, the aorta is positioned in the 5 to 6 o'clock position. Posterior appears at the bottom and anterior at the top of the picture-left and right are reversed as if facing a supine patient. Areas of interest are located by advancing the instrument to the level previously identified on standard endoscopy. Important landmarks for oesophageal examination are the heart, aorta, aortic arch, inferior and superior vena cava, and the azygous and hemiazygous veins. The azygous vein progresses in a cephalad direction from posterior to anterior along the right side of the esophagus to enter the superior caval vein. The characteristic total reflection of ultrasound due to the trachea, carina, and bronchi and the visualisation of the left atrium are also important landmarks for staging. The entire pancreas can be examined by a combination of transduodenal and transgastric scanning. It is therefore necessary to insert the instrument fully and to utilize the duodenal scanning position to visualize the head of the pancreas, the biliary system, and other retroperitoneal structures. For visualisation of the body and tail of the pancreas, the endoscope is pulled back into the stomach.
ENDOSONOGRAPHY EXAMINATION OF THE LOWER INTESTINAL TRACT Insertion of the colonscope is done in the usual manner. While withdrawing the instrument, endoscopic inspection of the colonic wall and transmural ultrasound is performed concomitantly. For optimal endosonographic visualisation, the bowel segment to be scanned is filled with 200-300ml deaerated water through the instrumentation channel. Adding some dimethicone emulsion may prevent bubble formation. The 300" ultrasonographic view can easily be completed to 360" by torquing the instrument. The use of a water-filled balloon is helpful, especially in the rectum. Usually, both luminal water filling and balloon water filling are necessary for optimal visualization of the lesions and of the colonic wall.
NORMAL ULTRASONOGRAPHIC WALL LAYERING STRUCTURES Most authors recognize five sonographic layers within the intestinal tract (2-6): 1) an innermost hyperechoic (echodense) layer, corresponding to the boundary echo, and the surface (glandular) layer; 2) an inner hypoechoic (echopoor) layer, corresponding to the deeper glandular layer of the mucosa. It is not entirely clear whether the muscularis mucosae belongs to the second layer or to the third layer; 3) a middle hyperechoic or echogenic layer, corresponding at large to the border echo and the submucosa with loose connective tissue, rich in fat, blood vessels, and lymphatics; 4) an outer hypoechoic layer, corresponding mainly to the
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G.N. J . Tytgat & P. Fockens
muscularis propria; and 5) an outermost hyperechoic layer, corresponding to the adventitia (oesophagus) or subserosa and serosa together with peri-intestinal adipose tissue (stomach). According to Kimmey et al. ( 5 ) the five layers correspond to: 1) superficial mucosa; 2) deep mucosa; 3) submucosa plus the acoustic interface between the submucosa and muscularis propria; 4) muscularis propria minus the acoustic interface between submucosa and muscularis propria; and 5) serosa and subserosal fat. Thus this interpretation takes into consideration the echos produced by the tissue layers and the echos produced by the interfaces between different layers. This ideal five-layer structure is sometimes not well visualized in the esophagus owing to focusing problems with currently available equipment (7). Often only a three-layer pattern is seen in the oesophagus. The first hyperechoic layer corresponds to the balloonmucosa-submucosa and submucosa-muscularis propria interface together; the second, hypoechoic, layer corresponds to the muscularis propria; and the third, hyperechoic, layer is the outer border echo. The diameter of the layers and particularly of the muscularis propria is quite variable and relates to the degree of stretching by the balloon and the age of the patient.
adjacent lymph node structures is pathognomonic for metastasis. Lymph nodes at a distance of 10 cm or more from the intestinal lumen cannot be seen adequately with ES. ENDOSONOGRAPHY IN SUBMUCOSAL TUMOURS AND EXTRAINTESTINAL LESIONS
ES is useful in the investigation of intramural lesions or lesions that produce extrinsic deformity of the wall (12-15). Submucosal lesions may be localized within the various sonographic layers of the gut wall, a finding that may be used to suggest a diagnosis based on the tissue of origin. Furthermore, submucosal lesions may be separated into cystic or solid, discrete or infiltrative. A leiomyoma is the commonest benign oesophageal tumour. A leiomyoma is usually seen as a bulging mass covered with smooth intact mucosa. The hypoechoic mass usually has smooth margins that are contiguous to the muscularis propria layer. Occasionally, a central ulcer and hypoechoic foci can be found in the case of extensive leiomyoma, owing to inadequate blood supply. Endoscopic forceps biopsy is rarely helpful in ascertaining the diagnosis and/ or in ruling out malignancy. In contrast, a special guillotine needle biopsy device (Flexi-Temno) may enable a correct histologic diagnosis (16). With ES, a leiomyoma appears as a PATHOLOGIC ULTRASONOGRAPHIC FINDINGS sharply demarcated lesion with a homogeneous echo pattern Pathologic disorders of the intestinal wall cause disruption covered with sonographically normal-appearing mucosa. or destruction of the ES layers which may be either focal or Occasionally, local thickening of the muscularis propria may diffuse. Although the histologic correlate of the sonographic be seen. A leiomyoma compresses but does not infiltrate layers of the gastrointestinal wall is still not fully established, into surrounding tissues. Lipoma, ectopic pancreas, and all investigators agree that the layering pattern is disrupted contiguous variceal structures can be distinguished from by disease processes. The thickness of various layers may be leiomyoma on the basis of the echo pattern, the site of altered, or one or more layers may be obliterated ( 2 , 3 , 7 , 8 ) . origin, and the configuration (13). In general, lipomas have Neoplasms are detected as a disruption in the continuity of a more echogenic texture and do not seem to take off from an ultrasound layer or by diffuse layer thickening. A change the muscularis propria. A submucosal tumour mass with in the echogenicity of an ultrasound layer is another sign of an inhomogeneous echo pattern and poorly demarcated or tissue abnormality. Neoplasms are usually of low or inter- irregularly defined borders is strongly indicative of either a mediate echogenicity: less echogenic than the third echo- leiomyoblastoma or a leiomyosarcoma. It should be stressed genic layer but more echogenic than the second and fourth that differentiation between a benign and a malignant lesion layers. often remains difficult. The presence of suspicious lymph Round or ellipsoid sonographic structures are frequently nodes may be helpful in distinguishing the potentially maligimaged adjacent to the gastrointestinal wall. They cor- nant character of the lesion. Follow-up examination may respond to lymph nodes and can readily be distinguished also help in elucidating the nature of the lesion. from vascular structures. Whether lymph nodes have specific ES is of major help in differentiating extramural from sonographic features that may be used for differential diag- intramural lesions. ES may readily detect the extraintestinal nosis is not entirely clear. In general, a nodal echo pattern origin of a malignancy. This is of importance in difthat is homogeneous and more echo-dense than that of a ferentiating genuine achalasia from pseudoachalasia due to primary lesion and that reveals somewhat indistinct borders invading malignancy. Yasuda et al. (17) showed a 100% is usually considered indicative of benign inflammatory specificity in distinguishing submucosal lesions from extrinsic change. Malignant nodal involvement is usually charac- compression in a series of 83 patients. terized by spherical shape, distinct sharply demarcated borders, and a non-homogeneous echographic pattern that VASCULAR ANOMALIES either resembles the pattern of the primary lesion or is even more hypoechoic or by the presence of heterogeneous echo ES is important for the detection and staging of gastrospots ( S l l ) . Direct extension of the primary lesion into oesophageal varices (18). Especially in the stomach, variceal
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Endoscopic Ultrasonography
structures may be readily identified which are not suspected endoscopically. Varices are displayed by ES as anechoic serpentine duct-like structures with low echos and localized in the mucosa, submucosa, or outside the intestinal wall. Limitation in ES variceal detection may be attributable to problems with focusing the ultrasound display and to compression of the varices by the water-filled balloon. The azygous vein is seen as a rounded echo-free structure between the oesophagus, aorta, and spine. At the level of the fourth thoracic vertebra this vein arches in a forward and slightly lateral direction to enter the superior caval vein. The diameter of the azygos vein is greater in cirrhotics than in controls, and the diameter increases gradually from distal to proximal. The deeper peri-oesophageal collateral veins may be much larger than the submucosal varices. Communication with a further collateral circuit below the diaphragm can be seen in approximately 25% of cases. After endoscopic sclerotherapy, thickening of the oesophageal wall and a thrombus mass of high echogenicity may be observed, demonstrating variceal obstruction. Thereafter the echogenic thrombus changes to a uniform hypoechoic thrombus, indicative of organization (19). In patients with congestive gastropathy, ES shows small round echo-free structures around and within the gastric wall, corresponding to dilated tributaries of the gastric veins which are readily distinguishable from isolated fundal varices (209). ENDOSONOGRAPHY IN RUGAL HYPERPLASIA Both benign and malignant disease may lead to rugal hyperplasia, especially in the stomach. Not uncommonly, standard forceps biopsy specimens fail to provide the correct histopathologic diagnosis. ES is of major importance in this differential diagnosis. In rugal hyperplastic gastropathy, usually Menetrier’s disease, ES demonstrates enlargement of the first and second layer of the gastric wall corresponding to the mucosa. The mucosa may be thickened to 2 or 3 mm, whereas the normal gastric mucosa is about 0.7 to 0.8 mm thick (21; T. L. Tio, J. J. Maas, E. M. Colin, et al. Unpublished observations). Frank gastric rugae may also be produced by infiltrating adenocarcinoma (linitis plastica or scirrhous-type malignancy) or gastric lymphoma. In linitis plastica there is irregular hypoechoic enlargement of the third layer, corresponding to the submucosa, and of the fourth layer, corresponding to the muscularis propria, reflecting cancerous infiltration. In the case of lymphoma, there is usually diffuse transmural thickening of the wall, with abolition of the normal gastric layering. ENDOSONOGRAPHY IN PEDUNCULATED OR SESSILE POLYPOID LESIONS Benign polypoid adenomatous proliferations do not disrupt the third echogenic layer of the intestinal wall. Whenever
83
the third layer is abnormal or interrupted, there is a suspicion of focal malignancy. The sensitivity of endosonography in detecting focal malignancy in large villous adenomas is controversial. Some investigators feel that this is impossible (22,23), whereas others are of the opinion that focal malignancy can be detected with a reasonable accuracy provided no prior laser or electrofulguration has been carried out (2427; F. J. Hulsmans, T. L. Tio, E. M. H. Mathus-Vliegen. Unpublished observations). With the currently available, albeit high-frequency ultrasonographic technology, it is not possible to visualize the thin muscularis mucosae, and early invasion through the muscularis mucosae may remain undetected. Excessive compression of polypoid lesions with the water-filled balloon is to be avoided because the subsequent wall identation by the polypoid tissue mass may erroneously suggest malignant infiltration. Difficulties also arise when a polyp is situated close to the anal canal. Examination of this area is difficult because of the inability to keep the scan plane perpendicular. Oblique scanning of a lesion may lead to blurring of the outer margin and hence erroneously suggest tissue infiltration. ENDOSONOGRAPHY IN MALIGNANT TUMOURS The endosonographic classification of the depth of tumour infiltration and for assessing regional lymphnode metastasis is usually made according to the TNM staging system (28). Early carcinoma is visualized as a hypoechoic lesion localized in the mucosa and/or submucosa without penetration into the muscularis propria. There is no evidence of adjacent lymph node involvement. In some cases a benign inflammatory reaction secondary to ulcerative changes within the early cancerous lesion may simulate a more deeply infiltrating malignant lesion. The depth of penetration of early tumours can usually be determined with an accuracy of more than 80%. Advanced cancer is diagnosed when the lesion spreads into or beyond the muscularis propria. The exent of advanced cancer invasion can also be correctly determined in more than 80%. In the evaluation of regional lymph nodes, ES is generally more accurate for diagnosing metastatic involvement than for non-metastatic inflammation. False-positive diagnoses or false-negative diagnoses, however, do occur. The node size by itself is not reliable in defining whether it is malignant. Enlarged nodes may be benign owing to inflammation, and small nodes may already show micrometastatic involvement.
Oesophageal malignancy The overall accuracy of ES in staging oesophageal cancer, especially those malignancies limited to the wall, is satisfactory (29-33). Several studies testify to the high accuracy in T-staging and good accuracy in the detection of malignant nodes. Murata (32) obtained operative confirmation in 139 oeso-
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G . N. J . Tytgat 9 P . Fockem
phageal cancers, staged with ES. The tumours were correctly staged in 84% of cases. The sensitivity in predicting the depth of invasion was impressive: submucosa, 75%; muscularis propria, 64%; adventitia, 94%; and adjacent organs, 100%. Nodal involvement was correctly predicted in 89%. In cases of extensive deep penetration into or through the adjacent tracheobronchial tree, differentiation between an oesophageal and a bronchial or tracheal carcinoma becomes difficult. Bronchoscopy may be helpful in ascertaining the correct diagnosis. Lymph node metastasis at the coeliac axis is to be considered a distant metastasis. It is therefore of paramount importance to examine first the coeliac axis and the lesser curve of the stomach. Suggestive coeliac nodes in oesophageal carcinoma require that an exploratory laparotomy rather than a thoracotomy be performed first for confirmation of the diagnosis by histology. If positive results are obtained, thoracotomy will be superfluous because of the poor ultimate prognosis of the disease once the coeliac nodes are involved. A question often asked concerns the accuracy of ES versus CT in staging oesophageal malignancy (34). This was prospectively studied by Tio et al. (29). For T-staging, ES accuracy was 89%, compared with 59% for CT. Overall accuracy in staging regional lymph nodes was 80% for ES, compared with 51% for CT. ES was superior to CT in the evaluation of tumour infiltration, especially in the early stages and in non-resectable carcinoma. EUS was also more accurate in the assessment of regional lymph nodes metastasis. A limiting factor for ES was severe stenosis in 26% of the patients. Comparable figures were obtained in an American study (7). In T-staging, ES accuracy was 92% compared with CT at 60%. For regional lymph nodes, ES accuracy was 88% compared with 74% for CT.In a recent German study ES accuracy was 89% for staging and 69% for N staging, compared with 51% and 51%, respectively, for CT (35). From these studies it is obvious that ES is superior to CT, especially for the early stages of oesophageal cancer. ES findings of the degree of wall invasion are superior to (JT. ES understages the depth of tumour infiltration in patients with severe stenosis. In those patients CT can be more accurate. ES understaging can also occur in patients with aortic, pericardial, or diaphragmatic involvement, but still the overall accuracy of ES in the evaluation of T4 tumours is higher than that of CT. As overstaging is the most important factor to avoid if patients are not to be denied appropriate surgical intervention, it is encouraging that overstaging rarely occurs with ES. ES is superior for the diagnosis of recurrent cancer at the surgical anastomosis. An accurate diagnosis of recurrent perianastomotic cancer is of essential importance in the selection of appropriate patient management. In a recent study the sensitivity of ES for diagnosing recurrent cancer was 95% and the specificity 80% (36). The role of CT is
limited after resection because of differences in anastomotic morphology and artefacts created by movement, retained metallic clips, and staples. CT is more effective in diagnosing distant metastasis. Finally, ES is useful for monitoring the effects of combined external and intraluminal radiotherapy (T. L. Tio. Unpublished observations). Radiation efficacy is characterized by a reduction in tumour thickness or disappearance of the mural abnormality and reduction in lymph node abnormalities. Radiation effects are visualized as hyperechoic alterations surrounding the hypoechoic cancerous lesion. Gastric malignancy Early gastric adenocarcinoma is visualized as a hypoechoic abnormality, localized in layers 1 to 3 (mucosa 2 submucosa) without penetration into layer 4 (muscularis propria) and with or without immediately adjacent lymph node abnormalities. In contrast, advanced gastric cancer is visualized as a hypoechoic lesion with penetration into or through the muscularis propria, often associated with lymph node abnormalities (29,37,38). Again, accuracy of T-staging is more than 80% and detection of lymph nodes metastasis more than 80% with an overall accuracy of ES superior to CT scanning. Early gastric cancer is readily diagnosed if the size of the tumour is at least 1 cm. Early mucosal cancer presenting as a shallow ulcer is difficult to diagnose by ES alone. Also, differentiation of the extent of carcinomatous tissue infiltration from inflammatory changes that often accompany ulceration is problematic. In scirrhous-type gastric carcinoma there is diffuse infiltration of every layer of the stomach by tumour cells, but especially of the 3rd layer, resulting in gastric wall thickening and destruction of the normal architecture (21). In the early stages of scirrhous carcinoma mural thickening can occur in the absence of stiffening of the gastric wall. In these circumstances the endoscopic appearance may be almost normal, but the endosonographic appearance readily suggests malignancy. Gastric lymphoma is increasingly recognized and can be diagnosed successfully by ES. Often major problems are encountered in staging such lesions. ES may visualize gastric lymphoma as a polypoid, ulcerative, polypoid-ulcerative and/or diffuse transmural hypoechoic abnormality together with suspicious perigastric lymph node abnormalities (39, 40). Especially stages I and I1 of the Ann Arbor classification can only be distinguished accurately with ES. Difficulties arise when giant folds surround gastric ulcers, which readily mimic lymphoma because of similarities in the transmural hypoechoic echo pattern. ES is also accurate at follow-up after surgery, radiotherapy and/or chemotherapy. Thus, ES is a sensitive diagnostic modality for the preoperative staging and follow-up of primary gastric lymphoma. Biliary and pancreatic malignancy The transduodenal and transgastric approach provides
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Endoscopic Ultrasonography
clear visualization of the pancreas and its surrounding structures. Furthermore, certain structures that are affected by pancreatic disease, such as the bile duct, gallbladder, portal vein, splenic artery, and the intestinal wall, are also readily imaged from the intraduodenal and intragastric position. Pancreatic carcinoma is visualized as a hypoechoic inhomogeneous sharply or irregularly demarcated, sometimes polycyclic, parenchymal lesion, which often appears more hypoechoic than the surrounding tissues (4145). The parenchymal and ductular abnormalities together with the peripancreatic lymph nodes can readily be seen. Supplementary findings such as compression of the pancreatic duct, bile duct, or both, with prestenotic dilatation corresponding to the endoscopic retrograde pancreatography (ERCP) findings of the double duct lesion are also helpful when the lesion is suspected of being malignant. In general, sensitivity and specificity in pancreatic tumour diagnosis are significantly higher for ES (>90%) than for standard ultrasonography and CT scanning. Especially for the detection of small lesions and for assessing the extent of local regional tumour spread, ES is currently the most accurate imaging method. However, differentiation between cancer and pseudotumours of inflammatory origin is occasionally a problem (46). A periampullary tumour is seen as a hypoechoic intramural lesion, immediately adjacent to the common bile duct and/or pancreatic duct. Differentiation between adenomyomatosis and early carcinoma is difficult, if not impossible, especially when evidence of penetration into or through the mucularis propria is lacking. In advanced periampullary cancer, invasion into the adjacent pancreatic parenchyma makes the differentiation between primary pancreatic cancer and periampullary carcinoma more difficult. Malignancy in the distal common bile duct is usually visualized as a polypoid hypoechoic structure originating from the bile duct wall and protruding into the dilated lumen. An endoprosthesis is sometimes a useful guide for localizing the main lesions and does not prohibit accurate visualization of the lesion. An inserted biliary endoprosthesis is seen as a double hyperechoic line. The more proximal biliary tree can be recognized after slowly withdrawing the instrument from the area of the papilla of Vater and using the typical localization of the common bile duct immediately adjacent to the duodenal wall as a landmark. From the apical bulbar scanning position, the liver hilum and the gallbladder can be visualized. The confluence of the hepatic duct in the porta hepatis is usually readily recognized. Malignancy is seen as a hypoechoic intraductular lesion localized immediately adjacent to the bifurcation of the bile duct, often associated with dilatation of the intrahepatic ducts in the presence of a normal-calibre distal common bile duct. Carcinoma of the gallbladder is visualized as a hypoechoic polypoid structure, originating from the wall or protruding
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into the cavity of the gallbladder. In an advanced stage tumour extension along the hepatic duct into the hepatobiliary bifurcation is usually seen. In such cases differentiation between a Klatskin tumour and a primary gallbladder carcinoma may be difficult. Colorectal malignancy Rectal EUS may be carried out with a rigid optical instrument or with a flexible endoscopic instrument. The prostate and sacral bone can easily be used for anatomic orientation. Furthermore, the pelvic muscles are readily recognized as hypoechoic spindle-shaped structures encircling the rectal lumen. The echo pattern of rectal carcinoma is more hypoechoic than that of the surrounding tissues. The transition between normal and pathologic wall structure can usually readily be seen. Early malignancy is diagnosed when the hypoechoic lesion does not penetrate and destroy the fourth layer (muscularis propria). Advanced rectal carcinoma is visualized as an irregular hypoechoic intramural structure penetrating into or through the muscularis propria with or without evidence of adjacent lymph node involvement. Many studies have highlighted the accuracy of ES in staging colorectal cancer (22,28,49). Lymph node metastasis can be detected with a sensitivity and specificity of over 70% to 80%, respectively (49; F. J. Hulsmans, T. L. Tio, E. M. H. MathusVliegen. Unpublished observations). Transrectal US is accurate in the follow-up of patients after surgery or laser therapy because of the ability to visualize clearly the intestinal wall structure and adjacent lymph node abnormalities. Recurrent or residual malignancy is visualized as a hypoechoic intramural lesion with or without local regional lymph node involvement.
ENDOSONOGRAPHY IN PERIRECTAL ABSCESS AND FISTULA In patients with Crohn’s disease ES can readily visualize perirectal abscesses or fistula as anechoic or hypoechoic irregular ductular-like lesions adjacent to the lumen with or without communication with the intestinal wall (50; 0. B. Wijers, T. L. Tio, G . N. J. Tytgat. Unpublished observations). The extent of the lesion can clearly be recognized, including the presence or absence of any destruction of the pelvic muscles, which is important for planning surgical strategy. ES is preferred to fistulography in the detection and staging of perirectal fistula because there is improved patient tolerance, more precise imaging, and no risk of spread of infection (50; 0. B. Wijers, T. L. Tio, G. N. J. Tytgat. Unpublished observations). LIMITATIONS O F ENDOSONOGRAPHY Inability to pass a stenotic cancer, usually in the esophagus or at the cardia, with current ES instruments with a diameter
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of 13 mm is a definite limitation. Because of an inability to pass the tumour, ES staging of the tumour and of the nodes, especially of coeliac axis lymph nodes, may be limited. In the Amsterdam study (29) E S accuracy was 68%, compared with 82% for CT scanning in staging coeliac axis lymph nodes. Recently, a mechanical radial scanning catheter echoprobe became available, which can be introduced through the biopsy channel of a large-calibre gastroscope into a tight stenotic oesophageal carcinoma. Experience with this prototype in stenosing oesophageal cancer is still limited but encouraging (1). COMPLICATIONS OF ENDOSONOGRAPHY A potential complication of ES examination is rnucosal tearing because of overstretching by the distending balloon. Balloon decompression may be needed when withdrawing the transducer through the cardia into the esophagus, when passing the aortic arch, and to avoid compression of the trachea. Another complication relates t o perforation when trying to force the instrument through a narrow segment because the oblique or side-viewing optics d o not enable adequate visualization of the esophagus. After prior radiotherapy the wall of the oesophagus may have lost elasticity and is made vulnerable to passage of the balloon covered with a rigid tip. A rare but alarming complication is inversion of the instrument in a widened oesophagus proximal to an irregular malignancy. Attempts to withdraw the inverted instrument may readily damage the oesophageal wall. Using constant fluoroscopic monitoring, careful straightening of the instrument should be carried out first, before instrument withdrawal is attempted.
FUTURE DEVELOPMENTS Although currently available instruments produce suberb images, further developements are likely if not necessary. There is an urgent need for a small-diameter forward-viewing ES instrument to facilitate passage of stenotic areas. Adequate facilities for constantly US-guided cytologic puncture are mandatory. The selection of ultrasound frequencies needs to be expanded and to include the use of very high frequencies for improved tissue characterization. ColorDoppler imaging facilities will further characterize vascular structures and the direction of blood flow. Computer-assisted endoscopic sonography will enable three-dimensional modelling (51). Finally, miniature probes will be developed with different sizes, frequencies, lengths, and so forth, for the insertion into the common bile duct and pancreatic duct. Endosonography is a useful procedure in the evaluation of a variety of both benign and malignant, intrinsic and extrinsic lesions of the gastrointestinal and hepatopancreatic tract. E S provides accurate information about the size and location of such lesions in relation to the gastrointestinal
wall. Although a histopathologic diagnosis is not possible by ES, the procedure demonstrates whether the lesion is cystic, solid, or vascular. E S can localize a lesion intrinsic to the gastrointestinal wall to one or more of the histologic layers, so that it is frequently possible t o infer a correct diagnosis. Further improvements in the manoeuverability and optics of ES instruments and the further refinements of guided tissue sampling will enhance the future utility of ES. Now that many hospitals are faced with major financial constraints there is considerable reluctance in deciding if and when this expensive equipment should be bought. There can be no doubt that the development costs of endosonography instruments were huge. Nevertheless, we hope that the prices will come down to enable more units to apply this important new and clinically applicable development in imaging technology. REFERENCES 1. Rosch T. Classen M. A new ultrasonic Drobe for endosonographic imaging of the upper GI (ract. Endoscopy 1990;22:41-6. 2. TioTL, Tytgat GNJ, Endoscopicultrasonography of normal and pathologic upper gastrointestinal wall structure. Comparison of studies in vivo and in vitro with histology. Scand J Gastroenterol 1986;21 SUPPI123:27-33. 3. Takemoto T, Aibe T, Fuji T, et al. Endoscopic ultrasonography. Clin Gastroenterol 1986;15:305-19. 4. Aibe T, Fuji T, Okita K, et al. A fundamental study of normal layer structure of the gastrointestinal wall visualized by endoscopic ultrasonography. Scand J Gastroenterol 1986;21 Suppl 123:615. 5. Kimmey MB, Martin RW,Haggitt RC, et al. Histological correlates of gastrointestinal ultrasound images. Gastroenterology 1989;96:433-1. 6. Tytgat GNJ. Transintestinal ultrasonography. Present and future. Endoscopy 1987;19:241-2. 7. Lightdale CJ, Botet JF. Esophageal carcinoma: pre-operative staging and evaluation of anastomotic recurrence. Gastrointest Endosc 1990;36:114. 8. Tio TL, Coene PPLO, Luiken GJHM, et al. Endosonography in the clinicalstagingof esophagogastriccarcinoma. Gastrointest Endosc 1990;36:2-10. 9. Aibe T, Ito T, Yoshida T, et al. Endoscopic ultrasonography of lymph nodes surrounding the upper GI tract. Scand J Gastroenterol 1986;21 Suppl 123:164-9. 10. Tio TL, Tytgat GNJ. Endoscopic ultrasonography in analysing pen-intestinal lymph node abnormality. Preliminary results of studies in vitro and in vivo. Scand J Gastroenterol 1986;21 Suppl 123:158-63. 1. Tio TL, den Hartog Jager FCA, Tytgat GNJ. The role of endoscopic ultrasonography in assessing local resectability of oesophagogastric malignancies. Accuracy, pitfalls, and predictability. Scand J Gastroenterol 1986;21 Suppl 123:78-86. 2. Heyder N. Endoscopic ultrasonography of tumours of the oesophagus and the stomach. Surg Endosc 1987;l:17-23. 3. Tio TL, Tytgat GNJ, Den Hartog Jager FCA. Endoscopic ultrasonography for the evaluation of smooth muscle tumors in the upper gastrointestinal tract: an experience in 42 cases. Gastrointest. Endosc 1990;36:342-50. 14. Caletti G, Zani L, Bolondi L. Endoscopic ultrasonography in the diagnosis of gastric submucosal tumor. Gastrointest Endosc 1989;35:413-8. 15. Boyce GA, Sivak MV, Rosch T. Evaluation of submucosal upper gastrointestinal tract lesions by endoscopic ultrasound. Gastrointest Endosc 1991;37:44%54. 16. Caletti GC, Brocchi E, Ferrari. Guillotine needle biopsy as
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34. Tytgat GNJ, Ti0 TL. Techniques for staging oesophageal cancer. Gullet 1990;1:4-9. 35. Ziegler K, Sanft C, Zeitz M, et al. Evaluation of endosonography in TN staging of oesophageal cancer. Gut 1991; 32: 16-20. 36. Lightdale CJ, Botet JF, Kelsen DP, et al. Diagnosis of recurrent upper gastrointestinal cancer at the surgical anastomosis by endoscopic ultrasound. Gastrointest Endosc 1989;35:407-12. 37. Akohoshi K, Misawa T, Fujishima H, et al. Preoperative evaluation of gastric cancer by endoscopic ultrasound. Gut 1991;32:47%82. 38. Okai T, Yamakawa 0, Matsuda H, et al. Analysis of gastric carcinoma growth by endoscopic ultrasonography. Endoscopy 1991;23:121-5. 39. Tio TL, Den Hartog Jager FCA, Tytgat GNJ. Endoscopic ultrasonography of non-Hodgkin lymphoma of the stomach. Gastroenterology 1986;91:401-8. 40. Fujishima H, Misawa T, Maruoka A, et al. Staging and followup of primary gastric lymphoma by endoscopic ultrasonography. Am J Gastroenterol 1991;86:719-24. 41. Yasuda K, Mukai H, Rryimoto S, Nakagima M, Kawai K. The diagnosis of pancreatic cancer by endoscopic ultrasonography. Gastrointest Endosc 1988;34:1-8. 42. Ti0 TL, Tytgat GNJ, Cirot RJLM, Houthoff HJ, Sars PRA. Ampullopancreaticcarcinoma: preoperative TNM classification with endosonography. Radiology 1990;175:455-61. 43. Grimm H, Maydeo A, Soehendra N. Endoluminal ultrasound for the diagnosis and staging of pancreatic cancer. Clin Gastroenterol 1990;4:869-88. 44.Rosch T, Lorenz R, Braig C, et al. Endoscopic ultrasound in pancreatic tumor diagnosis. Gastrointest Endosc 1991;37:34752. 45. Ti0 TL, Tytgat GNJ, Cikot RJLM, et al. Preoperative TNMclassification of pancreatic and ampullary carcinoma by endoscopic ultrasonography. Hepatogastroenterol 1989;36:51-6. 46. Tio TL, Luiken JHM, Tytgat GNJ. Endosonography of groove pancreatitis. Endoscopy 1991;23:291-3. 47. Tio TL, Tytgat GNJ. Comparison of blind transrectal ultrasonography with endoscopic transrectal ultrasonography in assessing rectal and perirectal diseases. Scand J Gastroenterol 1961;21 Suppl 123:104-11. 48. Hildebrandt U, Feifel G, Ecker KW. Rectal endosonography. 49. Hildebrandt U, Klein T, Feifel G. Endosonography of pararectal lymph nodes. Dis Col Rect 1990;33:863-8. 50. Ti0 TL, Mulder CJJ, Wijers OB, Sars PRA, Tytgat GNJ. Endosonography of pen- and pen-adenorectal fistula and/or abscess in Crohn’s disease. Gastrointest Endosc 1990;36:331-6. 51. Hashimoto H , Yokoyama S, Nakao K. The capability of three dimensional display during endoscopic ultrasonography. Dig Endosc 1991;3:194-8.
