2.1 Introduction

The resolving power of an ultrasound probe is directly proportional to the frequency emitted: with a frequency of 7.5 MHz, widely used in EUS, the spatial resolution is in the order of 1 mm. On the other hand, the depth of field that can be analyzed is inversely proportional to the frequency used (Table 1).

Table 1 EUS transducer frequency and depth of field

In recent years, equipment manufacturers have increased the range of frequencies that can be used on the same endoscope by adding relatively low frequencies (5 and 6 MHz), which allow accurate analysis to a depth of 6–8 cm, thus achieving better management of some pancreatic disorders.

2.2 Equipment

Two types of ultrasound technique are used in endoscopic ultrasound.

2.2.1 Radial imaging

Radial imaging provides 360° ultrasound images perpendicular to the axis of the endoscope.

This technique has many advantages, namely:

• Excellent image quality, allowing real-time study of the circumference of the digestive tract through 360° (Fig. 1), making the examination easier overall for all types of gut pathology, particularly for assessing locoregional involvement of cancers and their surveillance or other indications related to diseases of the gastrointestinal wall

• The ability to visualize constantly the major vascular landmarks, facilitating localization of pathology regardless of the oblique optics of the ultrasound image obtained, thus allowing precise evaluation of the structures and organs around the intestinal lumen, particularly the pancreaticobiliary region.

Figure 1 Normal gastric wall with five layers. Electronic radial scope. (1) interface between the gastric lumen and the epithelium, (2) mucosa including muscularis mucosae, (3) submucosa, (4) muscularis propria, (5) serosa and interface with the perigastric fat.

Its main drawback is that it is impossible to carry out EUS-FNA as the path of the needle passes through the plane of the ultrasound image and cannot therefore be monitored in real-time.

Because radial imaging is long-established and relatively easy to perform, it currently remains the most widely used EUS technique. Three types of apparatus have been developed as a result:

• Video-EUS (Fig. 2) for the study of the esophagus, stomach, duodenum, pancreaticobiliary region, anal canal, rectum and colon, with the option of simultaneously visualizing the ultrasound image and the endoscopic image. There are two types of radial video-EUS:

Rotating mechanical: this is the oldest type (developed in the early 1980s). It is used increasingly rarely and Doppler studies are not possible.

Electronic in B-mode. The three companies that manufacture echoendoscopes supply this type of apparatus. The endoscopic view is either end-viewing (Pentax, Fig. 2A, or Fujinon, Fig. 2B), or oblique-forward (Olympus, Fig. 2C). The instruments produce several frequencies (5–12 MHz) and thus allow Doppler studies and power Doppler sonography. The latest instruments, which are connected to very sophisticated ultrasound consoles, allow contrast harmonic ultrasound after intravenous injection of ultrasound contrast agents.

• Rigid probes are designed for examination of the anal canal and its sphincters and the lower and mid-rectum. Both rotating mechanical or electronic transducers are available.

• Miniprobes (Fig. 3) can be introduced into the operating channel of conventional endoscopes, and are particularly suited to the use of very high frequencies (20 and 30 MHz). They were developed in the mid-1990s, and are used before curative endoscopic treatment of superficial flat cancers of the digestive tract (0–IIa, b, c) and high-grade dysplasia; these very high frequency miniprobes allow accurate patient selection for curative endoscopic treatment of superficial cancers whether for endoscopic mucosectomy, submucosal dissection, photodynamic therapy or radiofrequency ablation.

• Mid-way between the miniprobe and the echoendoscope, is the ‘blind’ probe (Fig. 4; Box 1), a flexible instrument with a small diameter (7.8 mm) and lacking endoscopic optics, with a miniature transducer at its end; it uses the rotating mechanical radial technique, emitting at 7.5 MHz, and is tapered at its end (3 mm). The blind probe can be passed over a guidewire previously positioned under endoscopic control. It is intended for the examination of stenotic esophageal or rectal lesions.

Figure 2 (A) Pentax EUS scopes, radial and linear. (B) Fujinon EUS scopes, radial and linear. (C) Olympus EUS scopes, radial and linear.

Figure 3 Olympus high frequency (mechanical radial) miniprobe (30 MHz) used through a standard gastroscope.

Figure 4 Olympus blind probe MH 908 (mechanical radial 7.5 MHz).

Box 1 Blind probe (Olympus GIF-MH908)

For the esophagus, use a transnasal or pediatric gastroscope, which can pass through the stenosis without previous dilation. Aspirate the air present in the gastric lumen, position a 0.035 inch guidewire in the stomach, withdraw the endoscope, slide the blind probe onto the guidewire and insert, under ultrasound control, into the stenosis, moderately inflating the balloon to facilitate its passage. Then advance the probe into the stomach (celiac region). The examination is performed by withdrawing the probe under ultrasound control as far as the cervical esophagus.

2.2.2 Curved linear array (Fig. 2)

The ultrasound image obtained in electronic B mode is a sagittal image (Figs 5, 6) provided by an electronic transducer. The plane of the image is parallel to the axis of the endoscope.

Figure 5 Aorta. 3–5 cm under the cardia seen in longitudinal view with celiac and superior mesenteric artery (SMA) take-off. Olympus linear scope coupled with Aloka α10 console.

Figure 6 Pancreatic cancer located within uncinate process, invading the posterior side of the SMV. IVC, inferior vena cava. Electronic linear scope.

The main advantage of this technique is the ability to carry out intra- or transmural EUS-guided FNA (Fig. 7) as the path of the needle to the target can be followed in real time on the ultrasound image.

Figure 7 (A) EUS-guided FNA of a malignant (15 mm in diameter) lymph node located along the liver under the cardia. (B) Pancreatic adenocarcinoma located within the body with involvement of the celiac axis (left) with EUS-guided FNA (right) using a Pentax linear scope coupled with a Hitachi console. (C) EUS-guided FNA of a pancreatic cystic lesion (left) and a malignant lymph node (right), using a Fujinon scope coupled with a Toshiba console.

As a result of this option, therapeutic EUS uses echoendoscopes with a large operating channel.

The drawback of this type of equipment is the nature of the sagittal images as these are inappropriate for studying the circumference of the GI tract and thus assessing locoregional involvement prior to treatment or surveying cancers of the GI tract.

Two types of instrument use this technique: video-echoendoscopes and rigid probes.

• Video-echoendoscopes can be used to study the esophagus, stomach, duodenum, pancreaticobiliary region, anal canal, rectum, and colon. They are less suited to examining the esophagus, common bile duct, anal canal and rectum than instruments using the radial technique, because of the nature of the images obtained. They are also more difficult to use for the stomach and duodenum. On the other hand, they allow very satisfactory examination of the pancreas and the peripancreatic region, particularly its vascular aspect, and the posterior mediastinum.

• Rigid probes are designed for examination of the anal canal and rectum. Although the image obtained is not very practical for studying the anal sphincters and the pre-treatment assessment of rectal and anal cancers, it nevertheless allows an accurate measurement of the distance between the lower margin of a rectal cancer, the pelvic floor and the internal anal sphincter, thus providing valuable information on whether intersphincteric resection is indicated for low rectal cancers. Rigid probes are also very well suited to dynamic studies in patients with pelvic floor disorders since they allow the simultaneous examination of the lower part of the anterior rectal wall, the anal sphincters, the urethra and bladder, and the rectovaginal septum. Hitachi consoles can provide a useful three-dimensional evaluation of the mesorectal region.

2.3 Sedation analgesia and general anesthesia

EUS, even if performed without FNA sampling, usually requires intravenous sedation or light general anesthesia because the procedures can be prolonged and require the patient to remain completely still. The use of a benzodiazepine (Midazolam) may be sufficient for examination of the esophagus, stomach and mediastinum. Combining this with an opiate or Propofol, to produce short-term general anesthesia may be necessary for pancreaticobiliary examination or for any EUS-FNA, depending on local custom. This means that EUS needs to be performed at centers with appropriate outpatient facilities.

In contrast, endorectal or endoanal ultrasound without FNA may be performed without sedation (except for painful cancer of the anal canal, or perianal abscess or fistula).

2.4 How to position the patient, doctor, and console

2.4.1 Patient position

• For gastroesophageal or duodenal examination, the left lateral decubitus position is usual. The patient’s head and chest may be raised if water is instilled into the stomach or duodenum.

• For pancreaticobiliary examination, left lateral decubitus, tilted forwards by 30°–45°, is the best position (Fig. 8A). The left shoulder should therefore be moved back and the right leg brought to the front. If the patient is very thin, it is often useful to have him/her lie almost prone, to examine the common bile duct and pancreatic head.

• For anorectal examination, supine is the simplest position. Instilled water pools at the most dependent point and therefore indicates the posterior wall of the lower and mid-rectum at the bottom of the screen, and the anterior wall at the top of the screen, the right wall to the right of the screen and the left wall to the left of the screen.

Figure 8 (A) Position of the patient for pancreaticobiliary examination. (B) The neutral position of the echoendoscope handle: the front of the handle is facing the patient. (C) The open position of the echoendoscope handle. (D) The closed position of the echoendoscope handle. (E) The extreme closed position of the echoendoscope handle. (F) The open position facing the console located at the patient’s feet is used for the examination of the posterior mediastinum.

2.4.3 Position of the echoendoscope handle

Definitions concerning the position of the echoendoscope handle:

• The neutral position (Figs 8B, 9) is where the front of the handle is facing the patient.

• The open position (Figs 8C, 9) is where the front of the handle is facing the patient’s feet. It is reached by turning anti-clockwise through 90° from the neutral position.

• The closed position (Figs 8D, 9) is the opposite of the open position. It is reached by turning clockwise through 90° from the neutral position.

• The extreme closed position (Figs 8E, 9) is reached by continuing to turn the handle clockwise through a further 90° by shoulder rotation, bringing the handle opposite the neutral position.

• The neutral and open positions account for at least 75% of the positions used for pancreaticobiliary and rectal examination.

• The closed position is used to examine the pancreatic tail and is one of the three positions used to examine the uncinate process of the pancreas.

• The extreme closed position is used for pancreatic tail biopsy and is one of the three positions used to biopsy the uncinate process of the pancreas.

• When the ultrasound console is at the patient’s head (Fig. 10), the closed position of the handle (facing the console) is used for examination of the posterior mediastinum: the spine and the aorta (posterior) being at the bottom of the screen and the left atrium (anterior) at the top of the screen; the right side of the screen then corresponds to the left of the posterior mediastinum and the left side of the screen to the right of the posterior mediastinum.

• When the console is at the patient’s feet, the open position (Fig. 11) of the handle (which is facing the console) is used (Fig. 8F) for examination of the posterior mediastinum: the spine and aorta (the back) are at the top of the screen and the left atrium (the front) is at the bottom of the screen; the right side of the screen then corresponds to the right side of the posterior mediastinum and the left side of the screen to the left of the posterior mediastinum.

Figure 9 Position of the echoendoscope handle for EUS.

Figure 10 Console adjacent to the patient’s head. The closed position (3) is the most natural. The extreme closed position (4) is easy to obtain. The neutral position (1) is easy to obtain. The open position (2) is very difficult to sustain for any length of time. Passing from the neutral to the open position has to be very precise. This position is used when biopsying the tail or neck of pancreas.

Figure 11 Console adjacent to the patient’s legs. The open position (2) is the natural position. The neutral position (1) is very easy to obtain. The closed position (3) is easy to obtain. The extreme closed position (4) is very difficult to sustain for any length of time. Passing from the closed (3) to the extreme closed position (4) has to be very precise. This position of the console is used for 90% of EUS procedures.

2.4.4 Console position

• The console position is unimportant if there is a second monitor positioned behind the patient’s back. If not, you can choose between the top and bottom of the patient.

• The majority of endosonographers place the console (and therefore the screen) at the patient’s head (Fig. 10), i.e. to the right of the examiner when he/she is facing the patient. As such, the most natural position of the handle is facing the screen, which corresponds to the closed position described. For the handle to face the patient, i.e. in the neutral position, it must be turned anti-clockwise through 90° from the most natural position and this is not problematic. On the other hand, it is difficult to continue to turn the handle anti-clockwise through a further 90° to reach what is described as the open position because the screen is then 180° opposite this position.

It is because the neutral position and the open position account for three-quarters of the positions that are useful for pancreaticobiliary and rectal examination that this console position has not been considered.

• It is advisable to place the console alongside the patient’s legs (Fig. 11). The open position of the handle (Fig. 8C,F) is therefore the natural position, because the examiner is then positioned at an angle of 45° in relation to the screen. The neutral position (Fig. 8B) is easy because the examiner is then facing the patient. The closed position (Fig. 8D) is easy because the left hand, which is holding the endoscope handle, is up against the examiner’s right clavicle and you are facing the patient. Only one handle position is uncomfortable for the examiner when the console is placed at the patient’s feet: this is the extreme closed position (Fig. 8E), i.e. with the handle opposite the patient. It is then difficult to see the screen positioned along the patient’s legs, while maintaining this extreme closed position for any length of time. This handle position is useful only for biopsying certain tumors of the uncinate process and pancreatic tail. In these two situations, it is advisable to change the position of the console and place it at the patient’s head.

• In summary:

It is best to have a second monitor positioned behind the patient’s back

Otherwise, it is best to position the console beside the patient’s legs, since this facilitates pancreaticobiliary and rectal examination (Fig. 12) in which the extreme closed position is rarely used and since this does not complicate esophageal or mediastinal examination; on the contrary, the right side of the screen corresponds well to the right part of the patient’s mediastinum and the left side of the screen to the left part of the patient’s mediastinum.

Figure 12 Examination of the rectum and anus. Patient in supine position. Console next to the patient’s abdomen, alongside their right arm. The positions of the handle that are used are the neutral (1) and the open positions (2). (3) closed position of the handle, is used to pass the scope through the junction sigmoid rectum.

3.1 General technique

EUS examination uses two different methods that are sometimes combined to obtain a satisfactory acoustic window between the transducer and the gut wall, as well as the surrounding region. The first is the balloon method, and the second is the instillation of water through the operating channel of the echoendoscope.

3.2 Examination technique using miniprobes

The miniprobes are introduced into the endoscope operating channel and slid in endoscopic view over the lesion to be studied:

4.1 Indications and contraindications

There is a broad range of indications for EUS-FNA and these are outlined in Box 2.

These indications will continue to evolve, especially with advances in oncology, e.g. restaging after neoadjuvant therapy or to provide tissue for molecular genetic analysis to guide treatment and/or prognosis.

4.2 General aspects

EUS-FNA requires adequate sedation or general anesthesia and patient monitoring for at least 4–6 h afterwards. Many factors influence the success of EUS-FNA (Box 5).

The lesions can be located using either radial or linear EUS. The linear scope is then used to perform EUS-FNA. A balloon is not useful in this setting.

Upwards deflection of the scope tip keeps the transducer tip pressed against the wall and creates a shallow exit angle for the needle. The needle is advanced from its sheath and applied against the gut wall at an exit angle pre-determined by the endoscope being used. The path of the needle towards the target must take account of this predetermined angle making pre-positioning of the echoendoscope in relation to the target essential. Once pre-positioned against the wall, it may be necessary (depending on the needle type) to retract the small central stylet by 5 mm (if there is a blunt end) in order to be able to pass through the wall, especially with 19-gauge needles.

The latest generation Olympus and Pentax echoendoscopes have an elevator and are therefore easier to handle than older echoendoscopes, because the angle of passage through the digestive wall to the target can be adjusted. This is particularly useful for lesions that are difficult to access, notably those of the uncinate process, for lesions remote from the digestive wall (more than 15 mm away), or for very small lesions (≤1 cm in diameter). The Fujinon echoendoscope has a virtual target line (Fig. 7C) that shows the operator the path the needle will take. The exit angle of the needle is very shallow and is comparable, without an elevator, to that provided by Olympus and Pentax instruments when used with their elevators.

4.3 Antibiotic prophylaxis

The value of intravenous antibiotic prophylaxis is debatable for solid lesions unless indicated for prevention of infective endocarditis. Antibiotic prophylaxis is essential for biopsy of a cystic lesion, whether of the pancreas or digestive wall. It is also required if the patient is using gastric antisecretory drugs (PPI) since this type of product encourages gastroduodenal microbial overgrowth. Antibiotic prophylaxis is also required for transrectal FNA. The antibiotic therapy must be continued orally for 3 to 5 days.

4.4 Pancreatic cancer biopsy

A 22 G needle is advanced under ultrasound control into the tumor. Once in position, the stylet, if it has been partially retracted, is pushed back into the needle so that any fragment of the digestive wall present at the tip of the needle will not obstruct it; the stylet is then removed completely and a 10–20 cc syringe, preferably with a continuous negative pressure instrument, is fitted to the needle. Once continuous negative pressure has been obtained, the needle should be moved slowly to and fro several (about 20) times in the lesion without hurrying, without removing the needle from the lesion, and trying, if possible, to change the angle of penetration of the lesion; this is helped by having an elevator, if the target is small and close to the lesion or if the lesion is soft, which is rare in cancer of the pancreas; if, as is more common in pancreatic cancer, the lesion is large, far from the probe or hard, angulation of the endoscope should be adjusted (from up to down angulation) to change the path of the needle in the lesion.

The needle must always be monitored in real time on the screen, during these movements, to avoid vascular or organ injury. To be sure that the needle is correctly centered in the lesion during aspiration, make small clockwise and anti-clockwise movements of the handle. Avoid penetrating any vascular and particularly arterial structures which may be present between the digestive wall and the target. Power Doppler imaging should be used for this purpose. On the other hand, unexpected passage through intramural or adjacent collateral venous circulation does not usually cause any significant complications if the vein is <3 mm in diameter. As little healthy pancreatic tissue should be traversed as possible, in order to limit the risk of acute pancreatitis. It is also advisable to avoid penetrating the common bile duct and main pancreatic duct, particularly if the latter is dilated upstream of a tumor, since the risk of acute pancreatitis is then increased. Do not puncture the gallbladder or the common bile duct above the pancreas owing to the risk of biliary leakage. Once the biopsy has been completed, release the negative pressure otherwise tumor cells may be deposited in the needle tract as it is withdrawn. Once negative pressure has been released, the needle is withdrawn into its protective sheath and the EUS-FNA needle is removed from the operating channel of the echoendoscope, which is left in position over the lesion. The biopsy sample is then checked. It is ideal to have a cytologist present in the biopsy room since he/she can immediately assess the quality of the sample. If there is no cytologist available, several biopsy passes (two to three on average) should be made in the tumor. The sample should preferably be placed in a tube containing formaldehyde or formalin so that histology can be performed on a cell block preparation. For this purpose, the stylet is advanced through the needle, gradually expelling the sample. Once a sufficient sample has been obtained for histological study, the remainder is divided, giving preference to smears (two to three slides should be prepared), and the rest is placed in CytoLyt medium for liquid-based cytology. This is particularly useful if the sample is poor or liquid, as in cystic tumors of the pancreas. Liquid-based cytology involves the automated concentration of the cells and produces a slide that is easy to process with a thin, even layer of cells. Liquid-based cytology can also be used for immunohistochemistry, unlike slide smears. Once the three types of sample have been obtained, the stylet should be withdrawn and the needle purged, using a 10 cc syringe filled with air, onto slides, yielding a further 1–3. The inside of the needle should be purged with 30 cc of physiological saline between biopsies. If the same patient with pancreatic cancer has several targets, the procedure should start with a biopsy of a hepatic metastasis, then a lymph node biopsy and finally the tumor itself. For lymph node biopsies, start with the lymph node least likely to be involved by tumor and end with the most suspicious.

The biopsy procedure must be stopped if blood is aspirated into the syringe.

If the pancreatic cancer is very hard and the sample is very poor (just some serous fluid) and there is no cytologist available in the examination room, a 50 cc or 60 cc suction syringe should be used. For cancer of the pancreatic body or tail, the needle can also be changed for a 19 G needle combined with a 50 cc or 60 cc suction syringe.

4.5 Biopsy of a cystic lesion

For a cystic lesion biopsy, puncture only once to avoid introducing infection. A cystic lesion should be punctured boldly and cleanly by quick, firm pressure so as not to tear the wall (this can happen if you push in the needle slowly while the patient’s respiratory movement causes the lesion to move). After withdrawing the stylet, attach a 10 or 20 cc suction syringe, according to the volume to be aspirated. If no fluid is visible after a few seconds, check that the needle is positioned correctly. If it is, wait because this means that the fluid is viscous (IPMN or mucinous cystadenoma).

Where possible, i.e. if the cystic lesion is not too large, it should be drained completely, in particular if it is a cystic lesion of the pancreas. Cystic lesions of the mediastinum, esophagus or rectum should not be punctured since several cases of abscess formation and in particular mediastinitis have been reported in the literature. The same applies to infected necrosis following acute pancreatitis.

4.6 Lymph node biopsy

For lymph node biopsy, adjust the needle and sampling technique according to the suspected nature of the lymph node and its size.

4.7 Difficult biopsies

Some lesions are difficult to biopsy, for example some benign or malignant pancreatic tumors, either because they are hard (or very fibrotic) or because they are very small (usually endocrine tumors), because they are far from the gut wall, or because they are in areas where the needle has little penetration force.

4.8 Renal cancer metastases and endocrine tumor

The biopsy technique for a pancreatic mass suspected of being an endocrine tumor or a renal cancer metastasis must be different as regards the suction force exerted. Make several back and forth movements without suction, then lightly aspirate using a 2 cc syringe for 1–2 s. Cells from this type of cancer, which are very fragile, thus remain analyzable. This also lowers the risk of post-biopsy hematoma (see Fig. 138) associated with these hypervascular tumors.

4.9 Complications of EUS-FNA

To summarize, EUS-FNA is an invasive technique with low morbidity but it is nevertheless associated with a small number of severe complications.

The indication for performing EUS-FNA should thus be considered carefully and based on an assessment of the risk-benefit ratio – the patient should be fully informed of this.

5.1 General points

After upper endoscopy (EGD) to identify the location of the tumor (distance from the incisors, length, circumferential involvement, degree of stenosis and ulceration), EUS begins in the stomach, 45–50 cm from the incisors, over the posterior side of the lesser curve, at the junction between the upper and middle thirds of the lesser curve. The echoendoscope must be pressed (by up angulation) against the lesser curve, between the liver (segment II) and the junction between the pancreatic neck and body. The air present in the stomach must have been completely aspirated beforehand, especially if EGD has been carried out previously.

The celiac region and the subcardial and left gastric artery lymph node areas are examined by progressively withdrawing the echoendoscope, keeping the transducer pressed against the wall by up angulation of the scope tip.

The anterior subcardial lymph node areas between the anterior surface of the upper part of the stomach and the apex of the left lobe of the liver should also be examined. The splenic hilum should also be examined; this can be a drainage region, in the event of subcardial involvement by esophageal cancer, following the splenic artery and vein to the spleen. If a suspicious lymph node is discovered in the celiac region, the examination should be continued as far as the second part of the duodenum, to examine the retroduodenopancreatic and lumbar aortic lymph node areas and the hepatic pedicle, which may be affected.

By withdrawing the instrument into the posterior mediastinum, the esophagus and peri-esophageal region can be visualized:

Figure 13 (A) Radial examination of the esophagus in the cervical region with visualization of the cricoid cartilage (white arrow), with the console positioned beside the patient’s feet using the open position of the echoendoscope handle. (B) Radial examination of the esophagus in the cervical region with visualization of the thyroid lobes and the common carotid arteries on both sides of the trachea. (C) Small metastatic lymph node (M1a) in the upper thorax in the left tracheo-esophageal angle in a patient with an esophageal cancer at 35 cm arising in Barrett’s esophagus. (D) Small metastatic lymph node in the aorto-pulmonary window in a patient with squamous lung cancer. (E) Subcarinal lymph node. Note the triangular shape and the central area (white arrow) highly suggestive of benign appearance.

Generally speaking, the lymph node drainage areas of esophageal cancers are often ipsilateral (right or left) to the predominant spread of the cancer on one or other of the lateral walls.

Five major regions should be examined very closely for metastatic adenopathy. They are, from the top down:

Tumor stenoses are impassable in only a few cases if a gastroscope has passed through beforehand. If a stenosis is impassable, a blind probe, capable of passing through almost 95% of malignant stenoses, should preferably be used. If a blind probe is unavailable, cautious dilation can be considered. Dilation up to a diameter of 13 mm is usually sufficient to allow the latest generation echoendoscopes to pass through. This type of dilatation is usually safe. The use of a 7.5 or 12 MHz miniprobe is a less satisfactory alternative to a blind probe.

5.2 Special features of radial examination

While studying an esophageal tumor using a radial echoendoscope fitted with a balloon, the balloon should be inflated moderately so that the endoscope can be advanced and retracted without creating an oblique image. The endoscope should be kept angulated so that the transducer remains perpendicular to the lesion examined. This means making sure that the muscle layer is visible through 360° around the lesion examined. For a small lesion, the inflated balloon should be positioned between the lesion and the transducer, with the aid of sufficient angulation so that it is not pressed against the lesion.

5.3 Special features of linear examination

5.3.3 Examination of the posterior mediastinum with linear instruments

The lymph node areas of the posterior mediastinum and the celiac and mesenteric region should be examined in patients with cancer of the esophagus and cardia, when assessing bronchogenic cancer or in patients with benign or malignant mediastinal masses.

The examination always begins in the stomach over the celiac region. The left adrenal gland, readily located by turning the endoscope handle clockwise from the celiac trunk, should then be examined. The left lobe of the liver is easy to locate by turning the handle anti-clockwise from the celiac trunk.

The endoscope is then brought up to the cardia (40 cm from the incisors), following the aorta longitudinally. At this point the suprahepatic venous confluence at the inferior vena cava (Fig. 14A) and the dome of the liver, which is located around it, can be observed by turning the handle clockwise and anti-clockwise, then climbing along the inferior vena cava as far as the right atrium (Fig. 14B). When the right atrium disappears on withdrawal of the endoscope (35 cm from the incisors), the left atrium (Fig. 14C) can be examined by making small clockwise or anti-clockwise turns of the handle, and the endoscope is brought up along the central part of the left atrium (the largest part) as far as its upper margin (28–30 cm from the incisors). On withdrawal, the subcarinal region then appears and the screen shows, below the transducer, from top to bottom, the air present in the trachea and carina, the subcarinal region, the right pulmonary artery in cross-section (Fig. 14D) and the upper part of the left atrium. Turning the handle clockwise and anti-clockwise then allows all the subcarinal lymph nodes (Fig. 14E) to be examined (the right group, which is close to the large azygos vein, the central group between the esophagus and the right pulmonary artery, and the left group near the descending aorta).

Figure 14 (A) Suprahepatic venous confluence seen with a linear scope. (B) Right atrium seen with a linear scope. (C) Right atrium and left atrium seen with linear scope. (D) Subcarinal region with the left atrium, the right pulmonary artery (RPA) and the superior vena cava (SVC) seen with linear scope.(E) Central subcarinal lymph node below the carina in front of the right pulmonary artery (RPA) above the left atrium (LA) seen with linear scope. (F) Aorto-pulmonary window (AP window) between the aortic arch (AO arch) and the left pulmonary artery (LPA) seen with a linear scope. (G) Left common carotid artery (LC) branching from the aortic arch (AO) seen with a linear scope. (H) Left subclavian artery (LSCA) branching from the aortic arch (AO) seen with a linear scope.

With maximum up angulation, withdrawing the endoscope 1–2 cm and turning the handle anti-clockwise, the aortopulmonary window (region IVL) will become visible between the aortic arch, round in section, at the top of the screen, and the left pulmonary artery, round in section, at the bottom of the screen (Fig. 14F).

Continuing withdrawal of the endoscope reveals the supraaortic (left paratracheal and para-esophageal) region with the left common carotid artery (Fig. 14G) and the left subclavian artery (Fig. 14H), then the origin of the left vertebral artery and the left retroclavicular lymph node region, finally, above the left thyroid lobe.

If the handle is turned clockwise from the aortic arch, the trachea, then the supra-azygos region (above the arch of the azygos vein), and if the endoscope is retracted keeping the same image plane, the brachiocephalic trunk will appear followed by its bifurcation into the right subclavian and right carotid artery, the origin of the right vertebral artery, then the right thyroid lobe.

6.1 Introduction

It is advisable to almost always start with a radial instrument. It is far easier and more comprehensive. The linear instrument can be used first only if the examiner has to biopsy a large submucosal tumor suspected of being a GIST. By contrast with conventional teaching, it is advisable to instil water into the stomach only very rarely, because it is usually ineffective and may cause pulmonary aspiration.

6.2 Examination of the stomach with a radial instrument

For malignant or suspected malignant tumor disease, the examination begins in the duodenum, as for pancreaticobiliary examination, looking for retropancreatic and interaortocaval metastatic adenopathy, particularly at the base of the posterior segment of the hepatic pedicle. Returning into the bulb allows examination of the preportal (pyloric) hepatic chain. Moving into the stomach allows examination of the left gastric, celiac and cardiac lymph node regions. Each part of the stomach should be examined systematically, the antrum, body and fundus, to be sure you have examined the lymph node areas adjacent to these regions. The liver is the key landmark anteriorly, the pancreas is the key landmark posteriorly, the spleen for the greater curve, and the lesser curve can be readily located at the junction between the posterior and anterior walls (Fig. 15).

Figure 15 (A) Radial examination of the lesser curve (1), between the posterior side (2), the anterior side (3), in front of the greater curve (4) between the left lobe of the liver (6) and the body of the pancreas (5). (B) Radial examination of the gastric antrum. The scope being pushed immediately upstream the pylorus maintaining maximum up angulation. The lesser curve (1) is between the anterior side of the antrum which is facing the gallbladder (5) and the liver (6). (4) posterior side and the antrum. (2) greater curve of the antrum.

The key to success when performing EUS of the gastric wall is to try to obtain a study of the layers of the wall so that they are perpendicular to the ultrasonic beam (Fig. 1). EUS is not possible across the whole circumference of the stomach simultaneously. In other words, once the anomaly to be examined has been located roughly on one wall of the stomach, focus on this anomaly so that the layers of the wall over and below the anomaly, but also at its edges, are clearly individualized. It is only by proceeding in this manner that you can be sure that the EUS abnormalities are real and not due to an ‘oblique image’ which may be misinterpreted (overlapping of several structures creating false images that suggest serosal involvement of a tumor or wrongly attributing the anomaly to a layer other than the one in which it is actually located). Examination of the fundus is sometimes difficult when the lesion in question is small. It is sometimes easier to perform the examination without instillation of water, after aspirating all the air present. It is sometimes necessary to work with the echoendoscope in retroflexion to visualize the anomaly if it is small. Examination of the body of the stomach is easy, and examination of the antrum is equally easy for the horizontal portion. On the other hand, examination of the incisura is more problematic. The best solution is to inflate the balloon immediately upstream of the pylorus, maintaining maximum up angulation, to check that the gallbladder is facing the anterior side, which means that the lesser curve is then at the bottom of the screen and the greater curve at the top. Once this has been confirmed, withdrawal of the echoendoscope, with the balloon inflated and up angulation, usually means that it can remain perpendicular to the lesser curve, whether in the horizontal portion, the incisura itself or the vertical portion immediately above the incisura. Examination of an immediate prepyloric lesion is difficult because it is often impossible to avoid oblique images of the pylorus itself which will give the impression that there is a submucosal tumor in the muscle layer. This is a frequent cause of false positive results for stromal tumors. This type of error obviously occurs only with small tumors, since large tumors are usually clearly visible, regardless of the image plane used.

6.3 Examination of the stomach with a linear instrument

It is advisable to use a linear instrument only to biopsy a submucosal tumor whose exact location has already been determined by UGIE or by a radial examination performed immediately beforehand.

7.1 Essential anatomic knowledge for correctly performing a pancreaticobiliary examination

Familiarity with the celiac and mesenteric anatomy is required:

7.2 Radial EUS pancreaticobiliary examination

The vascular structures are the anatomical landmarks for the examination of the pancreaticobiliary region (Fig. 16).

Figure 16 General view: The numbers in the graphic refer to the various positions of the head of the radial endoscope for an examination of the pancreaticobiliary region.

7.2.1 Examination of the pancreatic head and the common bile duct

There are three ways of examining the head of the pancreas and the common bile duct:

• Start in the duodenal bulb, with the handle in the neutral position, and advance the echoendoscope under ultrasound control, turning the handle clockwise (which brings it to the closed position). Proceed from the duodenal bulb to the superior duodenal angle and then add up angulation to bring the echoendoscope in front of the ampulla of Vater. The gallbladder can then be visualized above the bulb, then the common bile duct, the portal vein and the mesenteric-portal vein confluence, followed by the superior mesenteric vein, the posterior segment of the pancreatic head, the main pancreatic duct parallel to the common bile duct and finally the ampulla of Vater, between 9 and 8 o’clock on the duodenal circumference.

• Start over the aorta and inferior vena cava viewed in transverse section, in the ‘long’ position (Fig. 17), i.e. with the tip of the echoendoscope pushed immediately below the ampulla of Vater region, with up angulation, and the handle in the neutral position (Fig. 18A). The spine (Fig. 18B) is to the rear (top of the screen), and the right kidney may be visible to the right of the inferior vena cava (right of the screen). The liver is sometimes to the front (bottom of the screen) if it overlaps extensively. The gallbladder, which is distended in obstructive jaundice, can also be visualized to the front (bottom of the screen) in this plane. A pancreatic segment is sometimes visible in this image, at the bottom left of the screen. This is the lower anterior segment of the pancreatic head and uncinate process. In this transverse section (Fig. 18B), the top of the screen corresponds to the back, the bottom corresponds to the front, and the right and left correspond to the right periduodenal and left periduodenal regions, respectively. The mesenteric vessels are often visible (arteries and veins) in a transverse image, to the left of the duodenum.

Figure 17 Transducer being advanced to D2 with the bending section of the endoscope all the way up.

Figure 18 (A) The echoendoscope is pushed into the long position in D2 (90 cm from the incisors), the tip of the scope is positioned at the level of the ampulla of Vater, with the echoendoscope handle in neutral position, with up angulation. (B) EUS scope in D2 in front of the ampulla of Vater, neutral position, up angulation of the handle. (1) aorta, (2) inferior vena cava, (3) spine, (4) superior mesenteric vein, (5) superior mesenteric artery, (6) uncinate process.

By withdrawal of the instrument (Fig. 19), with maximum up angulation, and turning the handle anti-clockwise, which advances the tip into the inferior duodenal angle bringing it upright (Fig. 20), you can see in succession at the top of the screen or the top and right: the aorta (Fig. 21), in a longitudinal image, then the superior mesenteric artery, also in a longitudinal image (to the left on the screen), and the left renal vein in a transverse image between the aorta to the rear and the superior mesenteric artery over and to the front. By withdrawing the echoendoscope a little more, turning anti-clockwise, with up angulation, this image is replaced by a image through the inferior vena cava (Fig. 22), which, like the aorta, occupies the top right of the screen, above the duodenum, the superior mesenteric artery being replaced by the superior mesenteric vein and the mesenteric-portal vein confluence. The segment of the pancreatic head adjacent to the duodenum, between the duodenum, inferior vena cava and superior mesenteric vein, corresponds to the uncinate process of the pancreas then to the posterior segment of the pancreatic head when the echoendoscope is retracted above the ampulla of Vater region. This region is located by the termination of the bile and pancreatic ducts but also by the junction between the two echogenically different regions of the pancreatic head (Fig. 23), present in 75% of patients. These are the hypoechoic right posterior juxta-duodenal area corresponding to the ventral pancreas, and the more echogenic left anterior juxta-mesenteric region corresponding to the dorsal pancreas.

Figure 19 Withdrawal of the scope, maximum up angulation, turning the handle anti-clockwise.

Figure 20 Withdrawal of the transducer (tip deflected fully up) with the handle rotated anti-clockwise in order to image the inferior neck of pancreas vertically.

Figure 21 Because of the withdrawal of the scope, the tip is now at the ‘inferior genu’ (6), allowing imaging the SMA in long section (2) branching of the aorta (1), the left renal vein (3). The celiac axis take-off is visible (4).

Figure 22 (1) portal vein (PV), (2) hepatic artery (HA), (3) SMV, (4) IVC, (5) uncinate process.

Figure 23 (1) HA, (2) PV, (3) portal vein confluence, (4) SMV, (5) IVC, (6) ventral segment of the head, (7) dorsal segment of the head.

The secret of pancreaticobiliary examination is, while continuing to withdraw the endoscope, to obtain a long view of the mesenteric-portal vein confluence and the common bile duct (Figs 24, 25), which is the non-vascular ductal structure located closest to the duodenal wall. If you obtain an image lengthwise through the common bile duct and the mesenteric-portal vein confluence, what appears on the left of the screen is in fact at the front left, what is on the right of the screen is at the back left, what is at the top corresponds to the hepatic hilum and the liver, and what is at the bottom corresponds to the ampulla of Vater region. The segment of the pancreas between the duodenum and the superior mesenteric vein and the mesenteric-portal vein confluence is the posterior segment of the head.

Figure 24 Transducer at the inferior neck (the image is verticalized).

Figure 25 (1) CBD, (2) common hepatic duct (CHD), (3) HA, (4) portal vein confluence, (5) SMV, (6) posterior segment of the head.

The ampulla of Vater region can be examined in several ways: the simplest is to push the endoscope gently, following the common bile duct, once it has been brought into vertical view during the initial withdrawal of the instrument (Fig. 26). When trying to follow the common bile duct, turn the echoendoscope handle gently clockwise from the open position to the neutral position while pushing the instrument. Once you can see the bile duct close to the duodenal wall (Figs 27, 28) slight up angulation should be added which causes the bile duct to disappear and the terminal main pancreatic duct to appear (Fig. 29). The ampulla of Vater is then visible between 8 and 9 o’clock in contact with the balloon (Figs 28, 30, 31). An important point to note is that the ampulla is not satisfactorily visible until the bile duct disappears into the duodenal wall.

Figure 26 (1) HA, (2) PV, (3) SMV, (4) CBD, (5) posterior segment of the head.

Figure 27 (A), (1) HA, (2) PV, (3) portal vein confluence, (4) SMV, (5) CBD, (6) main pancreatic duct (MPD). (B) Pancreatico-biliary confluence. CBD, common bile duct; MPD, main pancreatic duct.

Figure 28 Transducer adjacent to the ampulla of Vater (tip deflected up).

Figure 29 Transducer opposite the ampulla with the endoscope’s tip deflected upward.

Figure 30 (1) Ampulla of Vater, (2) D2.

Figure 31 (A) Ampulla of Vater, with the radial scope in the long position in D2, handle in neutral position with up angulation. (B) Ampulla of Vater, the scope and handle position are the same: oval, hypoechogenic small nodule visualized in the submucosa of the internal (left) side of D2.

There is another way of visualizing the ampulla of Vater, but it is fairly difficult because the echoendoscope tends to withdraw rather too quickly during the maneuver. It involves starting from the long position with the handle in the neutral position and withdrawing the echoendoscope with up angulation, turning the handle anti-clockwise, or angulation to the left, which amounts to the same. After visualizing the superior mesenteric vessels in longitudinal section, at the point when the mesenteric vein appears on the screen (Fig. 22), the termination of the main pancreatic duct is usually visible in contact with the duodenal wall (Fig. 29), which means that the ampulla of Vater is exactly over the transducer. Stop withdrawing and advance again slightly so that you can see the last cm of the pancreatic duct along with its penetration point in the duodenal wall, which is then an indication of the presence of the ampulla of Vater between 8 and 9 o’clock on the duodenal circumference (Figs 30, 31).

• The third way of examining the pancreatic head and the common bile duct is by specific withdrawal. Unlike the withdrawal described previously (classic withdrawal), specific withdrawal starts from the long position, with maximum up angulation of the echoendoscope and above all maximum angulation to the right, turning the echoendoscope handle clockwise towards the closed position, i.e. by pressing the endoscope against the top right part (Fig. 32A) of the examiner’s chest, withdrawing the echoendoscope in this way will place it in the short position. This is the same maneuver that is carried out with a duodenoscope to place it in the short position, but in this case the maneuver is started from a long position. You will see the aorta first of all, followed by the inferior vena cava at the bottom left of the screen, then the junction between the two echogenically different regions of the pancreatic head (ventral and dorsal) between 5 and 6 o’clock and the main pancreatic duct (Fig. 32B) at about 6 o’clock, which means that the ampulla of Vater is visible at this point, if you stop withdrawal and push the echoendoscope again slightly. The ampulla of Vater appears as a small swelling (Fig. 32C) in the duodenal wall, surrounded on all sides by a little submucosa and separated from the pancreatic head by a hypoechoic border corresponding to the muscle layer of the ampulla of Vater (Fig. 32D). This is the best way of examining tumors of the ampulla of Vater and determining whether the submucosa has been infiltrated. This is also the best way of examining the uncinate process of the pancreas and the last 2 cm of the common bile duct and the main pancreatic duct.

• Examination of the gallbladder. The gallbladder can be examined after entering the bulb by inflating the balloon and pushing the transducer towards the superior duodenal angle, handle in the neutral position. The gallbladder is then visible above the balloon (Fig. 33); it disappears as you press on the apex of the bulb and the neck is the last part of the gallbladder visible. If you continue pushing, the bile duct and portal vein then become visible in the left half of the screen (Fig. 34).

Figure 32 (A) Withdrawal of the scope, starting in long position in D2 in front of the ampulla, EUS scope handle in closed position, up angulation. (B) Junction of the ventral hypoechogenic segment of the head and the dorsal hyperechogenic segment of the head and the duodenal wall. The area of the ampulla is identified by the visualization of the end of the MPD at 6 o’clock. (C) The ampulla within the submucosa of the duodenal wall is visualized by slightly pushing the scope when the image 32B is seen. (D) Cross-section of the ampulla of Vater with visualization of the muscularis propria (white arrow), seen on the entire circumference of the duodenum (which means that the ultrasonic beam is perpendicular to the ampulla. This section allows you to accurately stage a small ampullary tumor (T1 vs T2 tumor).

Figure 33 The gallbladder (1) seen through the duodenal bulb. The gallbladder is kept at the top of the screen after intubating the pylorus, while pushing the scope slowly.

Figure 34 (1) CBD, (2) portal vein confluence, (3) posterior segment of the head, (4) right kidney, (5) segment IV of the liver.

If the superior duodenal angle is compliant (rarely the case in slim patients under 40, or in very thin patients of any age), the bile duct can be followed (Fig. 35) to the ampulla of Vater, advancing the endoscope by turning the handle clockwise, with neutral angulation then adding up angulation.

• Large diverticula in the medial duodenal wall hinder the examination of the pancreatic head, the ampulla of Vater region and the terminal common bile duct. Instillation of water into the second part of the duodenum usually allows the diverticulum to be filled temporarily and its presence confirmed. If there is no fluid in the diverticulum, it appears as hyperechoic harmonic air gap between the transducer and the pancreatic head, over the region where the pancreatic duct and the common bile duct terminate.

• Pneumobilia also hinders the examination of the common bile duct. If it is related to previous endoscopic sphincterotomy, it is usually possible to visualize the bile duct termination by instilling water into the second part of the duodenum, over the ampulla of Vater region. This procedure is brief but usually allows a distinction to be made between residual stones and air in the lower common bile duct. Air remains pressed against the duodenal side of the common bile duct, whereas stones tend to sink against the opposite or pancreatic side of the common bile duct. The common bile duct is usually invisible in the hepatic pedicle in patients with choledochoduodenal anastomosis, despite the instillation of water through the anastomosis.

• Examination of the common hepatic duct. The upper part of the common bile duct, i.e. the common hepatic duct and the biliary confluence, can be examined if the diameter of the duct is 5 mm or more. There are two complementary ways, which means that they are rarely both effective in the same patient and depend on his/her specific anatomy.

The simplest way is to start from a neutral handle position, in the duodenal bulb, and advance the echoendoscope, keeping the gallbladder or liver above the balloon and observing the appearance of the common bile duct. At this point, rather than turning the handle clockwise to advance to the second part of the duodenum, turn the handle anti-clockwise to the open position and push the instrument against the superior duodenal angle. You can then see the bile duct running toward the liver: this is the common hepatic duct (Fig. 36) and the superior biliary confluence, often intersected at this point by the right hepatic artery.

If this method is ineffective, you can push the echoendoscope to the long position in the second part of the duodenum and carry out specific withdrawal (Fig. 32). Once the ampulla of Vater has been visualized at 6 o’clock, release right angulation and partially release up angulation, and continue withdrawal of the echoendoscope, with the handle in the closed position.

Figure 35 (1) Portal vein, (2) CBD, (3) posterior segment of the head.

Figure 36 CHD, common hepatic duct; LHD, left hepatic duct; RHD, right hepatic duct; RHA, right hepatic artery; GB, gallbladder; MPD, main pancreatic duct.

The common bile duct appears horizontal under the duodenum (Figs 37A, 37B). The cystic duct joins the common bile duct from below if you continue withdrawal very gently by adjusting the path of the common hepatic duct, keeping it horizontal by means of up angulation under the duodenum, aiming at the liver which is on the left of the screen. The vessel in this image, which is parallel to the common bile duct visible below it, is the inferior vena cava.

Figure 37 (A) Transducer in the duodenal bulb with the endoscope’s bending section up, while the endoscope is being withdrawn. (B) CH: common bile duct, cyst: cystic duct, VBP: CBD, calcul: CBD stone.

This also allows examination of the gallbladder (Fig. 38), which is to the left of the screen between the liver and the duodenum, turning the handle anti-clockwise from the neutral position and adding up angulation. The gallbladder fundus is at the top of the screen in this image, and the neck level with the balloon with its characteristic hook shape. The cystic duct can be followed from the gallbladder neck to the hepatic duct.

• Examination of the anterior side of the pancreatic head and neck. The following image, continuing to withdraw the instrument, reveals the portal vein in a transverse plane in the place of the common bile duct, under the balloon, with the hepatic artery in a transverse image extending in front and above it, almost in contact with the bulb wall (Fig. 39).

Figure 38 Gallbladder visualized through the bulb, withdrawing the scope turning the handle anti-clockwise with up angulation.

Figure 39 (1) Hepatic artery, (2) portal vein, (3) SMA, (4) IVC, (5) anterior segment of the head.

This view, which visualizes the portal vein below the transducer (Fig. 39), shows the anterior and superior segment of the pancreatic head between the bulb wall and the anterior side of the splenoportal vein confluence. At this point there is usually a bifurcation between the hepatic artery and the gastroduodenal artery, which can be followed to the rear of the bulb wall (i.e. below the bulb wall on the screen) by making back and forth movements advancing then withdrawing the endoscope, with up angulation, handle in the closed position (Figs 40, 41).

Figure 40 Transducer in the duodenal bulb under traction with the balloon inflated and the bending section up.

Figure 41 (1) Portal vein, (2) IVC, (3) gastroduodenal artery, (4) anterior segment of the head.

7.2.2 Examination of the pancreatic neck and body

If you continue progressive withdrawal of the echoendoscope, with the balloon very inflated, into the bulb, inverting the pylorus, you will see the pancreatic neck between the pylorus and the anterior side of the splenoportal confluence, below and to the right of the balloon. The landmark which indicates that you are opposite the neck is the superior mesenteric artery which is then visualized below the mesenteric-portal vein confluence (Figs 42, 43), in a transverse image. The main pancreatic duct in the neck is visible between the duodenal wall and the portal confluence.

Figure 42 (1) Dorsal segment of the anterior part of the head, (2) ventral segment of the head, (3) neck of the pancreas, (4) portal vein confluence, (5) SMA, (6) IVC, (7) CBD, (8) gallbladder, (9) left renal vein, (10) aorta, (11) body of the pancreas.

Figure 43 (1) SMA, (2) aorta, (3) right hepatic artery, (4) portal vein confluence, (5) hepatic artery, (6) left renal vein, (7) IVC.

Entering the stomach, continuing to retract the instrument, with the handle in the neutral position and up angulation, usually positions the instrument in the middle of the gastric body (between 45 and 50 cm from the incisors), over the pancreatic body (Figs 44, 45), with the handle in the neutral position. If you angulate to the right and slightly down, the echoendoscope is pressed against the posterior side of the stomach, which usually allows the left portion of the pancreatic body and tail to be examined, along with the splenic vein (Fig. 46). If you angulate up, this usually places the echoendoscope along the vertical part of the lesser curve, and this allows the right part of the pancreatic body to be examined at its junction with the neck (Fig. 47).

Figure 44 Transducer between 45 and 55 cm from the incisors and pressed against the posterior side of the stomach.

Figure 45 (A) Neutral position for the examination of the body and the tail of the pancreas. (B) Conf, portal vein confluence; SMA, superior mesenteric artery; W, Wirsung duct.

Figure 46 AO, aorta; LAG, left adrenal gland.

Figure 47 (1) Left lobe of the liver, (2) neck of the pancreas, (3) body of the pancreas, (4) tail of the pancreas, (5) left kidney, (6) portal vein confluence, (7) SMA, (8) splenic vein.

Changing from one of these positions to the other is usually done by slightly withdrawing the echoendoscope 1–2 cm to examine the left side of the pancreatic body and tail (Figs 48, 49A,B) and slightly advancing the endoscope 2 cm to visualize the right segment of the pancreatic body and neck (Fig. 49C). Apply slight up or neutral angulation when descending to the neck, and neutral or slight down and right angulation when withdrawing the echoendoscope to examine the pancreatic tail.

Figure 48 Transducer 45 cm from the incisors, pressed against the greater curvature.

Figure 49 (A) LK, left kidney; AS, accessory spleen. (B) LK, left kidney. (C) W, Wirsung duct; LC, lesser curve; GC, greater curvature; SMA, superior mesenteric artery; conf, portal vein confluence.

An important point is that it is as easy to examine the whole of the neck, body and tail, including the angle of the main pancreatic duct (Fig. 49C), through the stomach in women (shorter stomach) as it is difficult to visualize the neck and the junction between the neck and the head through the stomach in men. The junction between the neck and the head can thus be visualized (50 cm from the incisors) under the transducer through the bulb (Fig. 42), with the balloon very inflated pulling on the pylorus, with maximum up angulation, and with the handle in the closed position.

The celiac region can be examined immediately above the neck by withdrawing the instrument 1 cm, with maximum up angulation, and the handle in the neutral position (Fig 50A,B). An alternative method of examining the celiac region is to follow the aorta from the cardia, descending along the lesser gastric curve (Fig. 50C).

Figure 50 (A), (1) hepatic artery, (2) splenic artery, (3) celiac axis. (B), (1) hepatic artery, (2) splenic artery, (3) celiac axis. (C), (1) celiac axis, (2) aorta, (3) left adrenal gland, (4) left kidney.

7.3 Linear EUS pancreaticobiliary examination

7.3.2 Examination of the neck and body-tail segment of the pancreas

This examination is carried out through the stomach. Examining the pancreatic and retroperitoneal anatomy is less routine with a linear instrument than with a radial instrument. It is even more crucial with this technique to follow the main vascular and duct landmarks in order to locate the various segments of the pancreatic gland. It is possible to study almost the entire pancreas through the stomach with the linear instrument, not just the neck, body and tail. Only the ampullary and periampullary region, the juxta-duodenal segment of the head and uncinate process cannot be examined by the transgastric route.

There are two approaches to pancreaticobiliary examination through the stomach:

• Follow the aorta from the cardia region to the celiac trunk. Locate the aorta at the cardia, then position it in a longitudinal plane and advance the endoscope following the aorta lengthwise. While following it, locate the origin of the celiac trunk (Fig. 5) and immediately below it the origin of the superior mesenteric artery (Fig. 51). The celiac trunk can be followed longitudinally downwards, allowing visualization of the bifurcation into the splenic and hepatic arteries after observing the takeoff of the left gastric artery (Fig. 52) which climbs to the right of the screen. The pancreatic body appears below the bifurcation of the splenic artery and the hepatic artery (Fig. 53). If the endoscope handle is turned clockwise, the pancreatic gland can be followed towards the tail. If the handle is turned anti-clockwise, the right segment of the pancreatic body is visualized; descending a little, the pancreatic neck and the junction between the neck and the anterior segment of the pancreatic head become visible (Fig. 54). The pancreatic duct can be followed at the genu and it can then be seen descending to the bottom of the screen to the right, then to the posterior segment of the pancreatic head. The origin of the duct of Santorini can sometimes be seen, descending to the left of the screen, extending towards the duodenum, located by air present in the duodenal lumen. By turning the endoscope handle clockwise, withdrawing the instrument slightly upwards, the pancreas can be followed to the left segment of the pancreatic body (Fig. 55A), then the pancreatic tail (Fig. 55B), thus arriving at the splenic hilum (Fig. 55C). It is often necessary to add clockwise torque to the endoscope shaft to increase the clockwise rotation, which is often insufficient when applied only to the endoscope handle.

• Alternatively, begin the examination by following the left lobe of the liver with the endoscope handle in the open position (anti-clockwise); the left lobe of the liver appears in the bottom half of the screen and you will see the left portal branch in the left lobe. You can then advance the endoscope and follow this left portal branch to the hilum of the liver where it receives the right portal branch to form the portal vein. By advancing the endoscope and following the portal vein, the superior mesenteric vein appears (Fig. 56) by turning the endoscope handle clockwise (moving it from the open position to the neutral position). Once you have found the superior mesenteric vein, which has a horizontal path on the screen, the uncinate process and the posterior segment of the pancreatic head can be visualized below the superior mesenteric vein. By withdrawing the echoendoscope and turning the handle anti-clockwise, you can return to the portal vein then to the hepatic hilum, whereas if you retract the endoscope, while turning clockwise, you can follow the splenic vein (Fig. 57) to the splenic hilum. The superior mesenteric artery is easy to find from the aorta located at the cardia. Once the origin of the superior mesenteric artery has been observed, you can follow its longitudinal path by advancing the endoscope and maintaining suitable angulation, until you arrive over the uncinate process. It is then easy to find the superior mesenteric vein (Fig. 58), which runs parallel to the superior mesenteric artery, by applying anti-clockwise rotation. The hepatic artery can also be followed from the bifurcation of the celiac trunk, usually by advancing the endoscope with anti-clockwise rotation, whereas the splenic artery can usually be followed by straightening the endoscope into the up position and applying clockwise rotation.

Figure 51 Ca, celiac axis; sma, superior mesenteric artery.

Figure 52 SMA, superior mesenteric artery; LGA, left gastric artery.

Figure 53 CA, celiac axis; SA, splenic artery; HA, hepatic artery.

Figure 54 MPD, main pancreatic duct; UP, uncinate process; IVC, inferior vena cava; conf, portal vein confluence.

Figure 55 (A) MPD, main pancreatic duct; SV, splenic vein. (B) SA, splenic artery. (C) LK, left kidney.

Figure 56 HA, hepatic artery; IVC: inferior vena cava.

Figure 57 SMV, superior mesenteric vein; SV, splenic vein; IVC, inferior vena cava.

Figure 58 SMV, superior mesenteric vein; SMA, superior mesenteric artery.

7.3.3 Transduodenal examination of the pancreaticobiliary region

The gallbladder (Fig. 59) is easy to observe through the duodenal bulb by turning the endoscope handle anti-clockwise. Once it has been visualized, the common bile duct can be located by advancing the endoscope slightly into the duodenal bulb and applying clockwise rotation. The common bile duct then appears between the duodenum and the right hepatic artery and the mesenteric-portal vein confluence (Fig. 60). If you continue to advance the endoscope, maintaining clockwise rotation, you will follow the common bile duct to the rear of the pancreatic head (Fig. 61) then see it enter the pancreatic head (Figs 62, 63) and terminate at the ampulla of Vater in the duodenum (Fig. 64). The appearance of the main pancreatic duct (Fig. 62) will have been observed in parallel, and can be followed in the same movement (Fig. 63) to its termination at the ampulla (Fig. 64). The reverse maneuver from the ampullary region, i.e. withdrawing the endoscope gently with anti-clockwise rotation, is sufficient to follow the bile duct as far as the hilum (Fig. 65). An alternative method of examining the common bile duct is to put the endoscope in the long position over the ampulla of Vater, then retract it progressively, maintaining maximum up angulation, pressed against the ampullary region and turning the handle clockwise. In this way the uncinate process can be seen located within the angle between the inferior vena cava and the superior mesenteric vein, below and behind the end of the main pancreatic duct and CBD (Fig. 66A). When the endoscope has reached the short position, you will see the termination of the pancreatic duct appear first (Fig. 66B), then the termination of the common bile duct, which can be followed for 2 or 3 cm (Fig. 67), i.e. along its intrapancreatic path.

Figure 59 (1) Gallbladder, (2) duodenal bulb.

Figure 60 (1) Right hepatic artery, (2) common hepatic duct, (3) portal vein.

Figure 61 (1) Inferior vena cava, (2) CBD.

Figure 62 (1) CBD, (2) MPD.

Figure 63 (1) CBD, (2) MPD.

Figure 64 (1) Ampulla.

Figure 65 (A), (1) Cystic duct, (2) CBD, (3) IVC, (4) portal vein confluence. (B) AH, right hepatic artery; (1) common hepatic duct, (2) right hepatic duct, (3) left hepatic duct.

Figure 66 (A), IVC, inferior vena cava; CBD, common bile duct; MPD, main pancreatic duct; SMV, superior mesenteric vein. (B), (1) MPD.

Figure 67 (1) CBD.

8.1 Anatomy

The patient is examined either supine or in left lateral decubitus. It is advisable to position the US console near the patient’s head so the examiner is therefore standing alongside the patient’s right thigh (Fig. 12).

The urogenital organs are the preferred landmarks for examination of the anorectal region for the lower and middle rectum, if the endoscope handle is held in the open position facing the console screen. The prostate (Fig. 68) and the seminal vesicles (Fig. 69) on the one hand, and the vagina (Fig. 70), cervix uteri and uterus on the other, are usually positioned at the top right of the screen, while the sacrum and coccyx are at the bottom left.

Figure 68 Lower rectum in a male.

Figure 69 Mid-rectum in a male.

Figure 70 Lower rectum in a female.

The seminal vesicles are usually located between 7 and 9 cm from the anal verge and constitute the limit between the lower and middle rectum. The line of reflection of the rectovesical pouch is located immediately above the seminal vesicles. It can thus be determined whether a cancer of the anterior wall of the rectum in a man is subperitoneal or above the rectovesical pouch.

In a woman, the rectovaginal septum separates the vagina from the anterior wall of the lower rectum; it continues upwards between the posterior vaginal fornix, which is behind the cervix uteri, and the lower part of the middle rectum, then upwards between the uterus (Fig. 71), also called the neck of the uterus, and the upper part of the middle rectum. The recto-uterine pouch, which is located to the rear of the uterus, begins above the rectovaginal septum.

Figure 71 Mid-rectum in a female.

8.2 Anorectal examination

Examination of the lymph nodes in cancer of the rectum or anal canal should begin at the rectosigmoid junction, which should be reached while avoiding viewing the rectum endoscopically. To achieve this, about 100 cc of water should be instilled into the rectum to flatten the upper part of the rectum and advance the echoendoscope, moving progressively from the open position to the closed position, following the rectal curve revealed. Examination of the lymph nodes therefore begins over the sacral promontory where the spine is visualized at the front along with the vascular structures (Fig. 72), which bifurcate and continue along the withdrawal path of the instrument to the lower rectum, advancing and withdrawing again whenever a round hypoechoic structure appears so as to clearly differentiate a lymph node from a vascular structure: the latter can be followed for a short distance and has a Doppler signal.

Figure 72 Cross-section of the promontory. (1) Left iliac artery, (2) right iliac artery, (3) left iliac vein, (4) right iliac vein.

The instrument is therefore retracted progressively with anti-clockwise rotation moving from the closed to the open handle position on the way down from the upper rectum to the middle and lower rectum. The mesorectum and its external margin (the fascia recti) is clearly visible in patients when it is sufficiently fatty (Fig. 73).

Figure 73 Mesorectum all around the upper part of the mid-rectum: white arrows: fascia recti (outer margin of the mesorectum).

The internal sphincter consists of a clearly visible, circular, hypoechoic band at least 2–3 mm thick (Fig. 74), in the anal canal. The striated external sphincter is less visible; over the anorectal junction and the lower part of the rectum, there is a longitudinal strip which surrounds the anorectal junction from the rear and extends anteriorly along both sides of the anorectal junction (Fig. 74). This is the puborectalis portion of the levator ani and forms a circular sling around the internal sphincter (Fig. 75A). The sphincter anatomy is easy to locate in men (Fig. 75B) and more difficult in women, since the anterior side of the circular striated sphincter is usually fairly short.

Figure 74 (1) Internal sphincter, (2) elevator ani (horizontal segment of the pubo-rectalis muscle).

Figure 75 (A), (1) Internal sphincter, (2) circumferential segment of the external sphincter. (B) Anatomy of the male anal sphincter. (1) Internal sphincter, (2) circular striated sphincter.

9.1 Structure of the digestive wall and basis for interpretation in digestive oncology

At a frequency of 5, 7.5 or 12 MHz, endosonography shows that the wall of the esophagus, stomach, duodenum, rectum and colon consists of five layers (alternately hyper- and hypoechoic) (Fig. 1). Seven layers can sometimes be visualized, particularly in the rectum but also sometimes in the stomach and proximal esophagus in normal individuals (Fig. 76), or in the lower esophagus, particularly in those with a primary motor disorder such as achalasia. The significance of these layers has been determined by in vivo but mainly in ex-vivo studies and is now clearly established.

Figure 76 (A) Stomach wall with 5 layers. (1) interface between the gastric lumen and the epithelium, (2) mucosa including muscularis mucosae, (3)submucosa, (4) muscularis propria, (5) serosa. (B) Esophageal wall: seven layers are visualized with 10 MHz, electronic radial scope. (1) Balloon and epithelium, (2) mucosa including muscularis mucosae, (3) submucosa, (4) internal (circular) layer of the muscularis propria, (5) interface, (6) external (longitudinal) layer of the muscularis propria, (7) adventitia.

9.1.3 Wall with nine layers

By using (Fig. 77) very high frequency miniprobes (20 and especially 30 MHz) and the zoom on electronic radial 10 MHz instrument (Fig. 78), nine concentric layers can be visualized in the gut wall in the esophagus, but also the stomach.

• The first layer is an echogenic layer, corresponding to the interface between the digestive lumen and the epithelium.

• The second layer is hypoechoic and corresponds to the epithelium.

• The third layer is echogenic and corresponds to the interface between the epithelium and the lamina propria, as well as the lamina propria itself.

• The fourth layer, which is hypoechoic, corresponds to the muscularis mucosae.

• The fifth layer, which is echogenic, corresponds to the submucosa.

• The sixth layer, which is hypoechoic, corresponds to the inner circular muscle layer.

• The seventh layer, which is echogenic, corresponds to the interface between the two layers of the muscularis propria.

• The eighth layer, which is hypoechoic, corresponds to the outer longitudinal muscle layer.

• The ninth layer, which is echogenic, corresponds to the interface between the muscularis propria and the peridigestive fat, and is equivalent to serosa or adventitia.

Figure 77 Esophageal wall: nine layers are visualized with the 30 MHz Olympus mechanical radial high frequency miniprobe covered with the Olympus balloon. Muscularis mucosae is visible (arrows) within the mucosa.

Figure 78 Esophageal wall: nine layers are visualized with a 10 MHz electronic radial scope using the zoom. (1) Interface between the digestive lumen and the epithelium. (2) Epithelium. (3) Interface between the epithelium and the lamina propria, as well as the lamina propria. (4) Muscularis mucosae. (5) Submucosa. (6) Inner circular muscle. (7) Interface between the two layers of the muscularis propria. (8) Outer longitudinal muscle layer. (9) Serosa or adventitia.

9.2 Tumor terminology

The endosonographic classification of GI tract cancers is based on the TNM classification. The cancer usually appears as a hypoechoic mass. The involvement of the wall will be determined based on the persistence or disruption of the echogenic layers, i.e. the echogenic middle third layer which corresponds (in a wall with five or seven layers) to the submucosa, and the echogenic outer-fifth layer, which corresponds, or is equivalent, in a five-layer wall, to serosa or adventitia (this also applies to the echogenic peripheral seventh layer of a seven-layer wall).

9.3 T1 tumor

A tumor that leaves all or part of the echogenic middle third layer intact (in a five- or seven-layer wall) is a T1 tumor (Fig. 79), i.e. a superficial tumor. With the frequencies currently in use (5–12 MHz), it is impossible to distinguish within the T1 category between a tumor located in the mucosa (T1m), which has a generally very low risk of lymph node involvement regardless of the organ affected, and a T1 tumor which has already invaded the submucosa (T1sm). These have a distinctly poorer prognosis as there is a significant risk of lymph node involvement, which varies depending on the tumor site (Table 2), degree of differentiation and the presence of lymphovascular invasion.

Figure 79 Nodular UT1 squamous esophageal cancer. (1) Submucosa, (2) interface, (3) external (longitudinal) layer of the muscularis propria.

By using very high frequency miniprobes (20–30 MHz), it is possible to stage these lesions more accurately and select those that may benefit from endoscopic resection or ablation.

From an endosonographic perspective, with regard to the esophagus and stomach, tumors eligible for curative endoscopic treatment are conventionally those that have not infiltrated the muscularis mucosae (hypoechoic fourth layer), if it has been correctly located in the nine layers visualized using a very high frequency miniprobe (preferably 30 MHz) (Figs 77, 80).

Figure 80 Nodular (O-Is) uT1 m3 squamous esophageal cancer.

9.4 T2 tumor

In a wall with five or seven layers, a cancer accompanied by the disappearance of the echogenic middle third layer but leaving the echogenic peripheral fifth layer (or the echogenic peripheral seventh layer in a wall with seven layers) intact theoretically corresponds to a T2 cancer (a cancer that has invaded the muscularis propria) (Figs 81, 82). In 10% of cases, a cancer accompanied by the disappearance of the echogenic middle third layer (submucosa) is overstaged as T2 when it is really a T1 cancer because the submucosa can be entirely invaded by the tumor, without the muscle layer being involved (sm3).

Figure 81 Small UT2 squamous esophageal cancer. (1) Submucosa, (2) Interface between the circular and the longitudinal part of the muscularis propria, (3) External (longitudinal) layer of the muscularis propria.

Figure 82 Large UT2 esophageal adenocarcinoma arising in Barrett’s esophagus.

9.5 T3 and T4 tumor

In a wall with five or seven layers, the disappearance of the fifth or the seventh layer corresponds to a T3 tumor (Fig. 83). In such cases T2 tumors are overstaged as T3 in 5–10% of cases. A tumor is staged T4 when the cancer is invading a neighboring organ.

Figure 83 UT3 esophageal adenocarcinoma arising in Barrett’s esophagus.

9.6 Regional lymph nodes

9.6.1 Lymph node appearances

Metastatic lymph nodes usually appear as round, hypoechoic, finely heterogeneous, spherical structures, i.e. round in all planes and with a well-defined border (Fig. 84). They are sometimes more echogenic (Fig. 85), but this is observed only if the tumor itself is relatively echogenic, since the echostructure of the metastatic lymph node is comparable with that of the primary tumor. They are sometimes very hypoechoic and even anechoic, but in this case their echostructure is also comparable with that of the primary tumor. The presence of readily identifiable lymph nodes in areas that are usually unaffected is an important indicator of malignancy in these lymph nodes, particularly if the lymph node area in question drains directly from the primary tumor (usually on the same side, particularly in the mediastinum). Silicosis (as regards the posterior mediastinum) and some lymph node diseases such as sarcoidosis, histoplasmosis, lymph node tuberculosis or malignant non-Hodgkin’s lymphomas may be accompanied by lymph node anomalies affecting numerous subdiaphragmatic or posterior mediastinal areas, thus mimicking massive lymph node involvement where associated with esophageal, stomach or lung cancer. It is very rare for a digestive tract or lung cancer to coexist with a lymph node disease causing massive enlargement of the peridigestive lymph nodes, but the possibility should not be disregarded.

Figure 84 Typical small (9 mm) metastatic lymph node (LN), spherical, hypoechogenic, well demarcated, with smaller diameter >5 mm.

Figure 85 Small (7 mm) metastatic hyperechogenic lymph node.

9.6.2 Lymph node size

Lymph node size is a criterion of malignant or benign disease. Having a maximum diameter greater than or equal to 1 cm for an oval or round, spherical lymph node (i.e. as large in height as in transverse section) is a very good criterion of malignancy. Having a minimum diameter ≥5 mm for an oval or round, spherical lymph node is also a very good criterion of malignancy.

Very small non-metastatic lymph nodes (reactive or physiological) may be either very hypoechoic, homogeneous, with a distinct border, but are flat (not spherical). They are usually relatively hyperechoic, oval, but not spherical (flat) or triangular, and they are more echogenic than the primary tumor. The presence of calcification, particularly in the subcarinal region and hepatic pedicle, is a sign of benign disease, when the calcifications remain central and are not disorganized. The presence of a linear hyperechoic band (known as a lymph node sinus) in the middle of the lymph node (Fig. 13E) or apparently aiming towards the center of the lymph node (Fig. 86) from its periphery is also a sign of benign disease when a lymph node is enlarged. The interpretation of this phenomenon is that the cause of the enlargement has not had the effect of disrupting the lymph node architecture as an invasive tumor would do. This obviously does not exclude the presence of micrometastasis.

Figure 86 Large (25 mm) benign subcarinal lymph node. Triangular shape and hyperechogenic center (arrow).

9.7 EUS-FNA

The advent of fine-needle biopsy and EUS-FNA (Fig. 87) has totally altered the debate concerning the specificity of endosonographic appearances of lymph nodes for a diagnosis of malignancy, regardless of whether they are peri-esophageal posterior mediastinal or perigastric and in particular celiac or perirectal lymph nodes. The diagnostic accuracy of EUS-FNA of accessible lymph nodes is 90%, which is clearly higher than that obtained by analysis of the EUS morphological features, which varies from 60% to 75% depending on the cancer examined. This improvement in the diagnostic accuracy is related to an improvement in specificity, which is close to 100%. The positive predictive value of malignancy is therefore close to 100%. On the other hand, the sensitivity of EUS-FNA depends on the diameter of the lymph node examined. It is approximately 70% for lymph nodes measuring less than 10 mm in short axis, whereas it is more than 90% for lymph nodes measuring ≥10 mm. This lack of sensitivity explains the negative predictive value for malignancy (ability of the method to strictly exclude a malignant diagnosis) which is approximately 75% (50% when the short axis diameter is <10 mm, 80% when it is ≥10 mm). In other words, when EUS-FNA of a lymph node measuring <10 mm does not yield any evidence of malignancy, there is a 50% chance that this is true, whereas when it yields evidence of malignancy, this is almost always the case. In some locations, the sensitivity and specificity of the EUS image of a spherical hypoechoic lymph node measuring >1 cm and with a distinct border, are greater for a diagnosis of malignancy than the result of EUS-guided FNA; this applies mainly to lymph nodes in the celiac region when they are associated with esophageal cancer.

Figure 87 Small (7 mm) left paraesophageal metastatic lymph node, radial and linear examination and EUS-guided FNA. Squamous cancer on pathological examination obtained with 22 G needle.

10.1 Introduction

Gastrointestinal endosonography has two roles in the diagnosis of cancer of the digestive tract: linitis plastica (where the endosonographic appearance is characteristic) and in assessing the etiology of rectal or esophageal strictures where pathology has been non-diagnostic. In these cases identification of an intraparietal mass by endosonography confirms that these strictures are malignant in origin.

With these exceptions, EUS is not used to diagnose digestive cancers, as the diagnosis of malignancy relies exclusively on histological analysis of biopsies obtained at conventional endoscopy.

10.2 Assessment of GI cancers prior to neoadjuvant therapy or surgery

An imaging technique such as endosonography is useful for assessing locoregional involvement of accessible gastrointestinal cancers prior to treatment only in patients for whom a therapeutic option exists and in whom an accurate assessment of locoregional involvement will influence management.

In contrast, EUS is not useful for assessing pre treatment locoregional involvement of these cancers when it will not alter management (e.g. in colon cancer where surgery is indicated immediately, regardless of locoregional involvement – Dukes A–C), where there is only one curative option or when, for one reason or another (advanced age, co-morbidity, obvious metastatic involvement, etc.) palliative treatment or supportive therapy is more appropriate.

Endosonography is not equally useful for all tumors and its role can be separated into two parts:

10.3 Esophageal cancer

It has been acknowledged for more than 10 years, that endosonography is superior to all the imaging techniques available for assessment of locoregional (parietal and lymph node) involvement in esophageal cancers, when the instrument can pass through the tumor. The endosonographic TNM stage correlates better with the prognosis in particular with 5-year survival than the stage determined by CT, and correlates very well with the pTNM stage.

10.3.1 Performance

Overall, the diagnostic accuracy of endosonography for parietal involvement is 85% (Figs 79, 81–83, 88), whereas the diagnostic accuracy for lymph node involvement is 80%. The diagnostic accuracy is comparable from one T stage to another, although it is not quite as good for stage T2.

Figure 88 (A) Large squamous esophageal cancer with invasion of the anterior side of the descending aorta (ao). (B) Large squamous esophageal cancer with a large nodule invading (arrows) the descending aorta.

The role of endosonography in relation to CT of the chest and abdomen is now well established. CT scanning is used to assess for any hepatic and pulmonary metastases, while endosonography is used for assessment of locoregional involvement if there is no evidence of distant metastases. The role of positron emission tomography (PET scan) is not yet clear, however, owing to its cost and accessibility and to the results of studies of its advantages compared with helical CT and EUS, it makes sense to limit its use to prospective trials or cases in which it is impossible to carry out a full assessment by EUS (Fig. 89).

Figure 89 Staging and management algorithm for esophageal cancer.

10.3.2 Squamous HGD and early esophageal squamous cell cancers

Curative endoscopic treatment of early squamous cell cancer of the esophagus applies to tumors with a very low risk of lymph node involvement, which have not spread to the muscularis mucosae.

Owing to the advent of very high frequency miniprobes, the muscularis mucosae can now be visualized in a high percentage of significant cases. If this technique is applied to a squamous cell cancer with an endoscopic appearance of a flat tumor, it yields a diagnostic accuracy of 85% for detecting infiltration confined to the mucosa, accessible to curative endoscopic mucosal resection (0–3% of metastatic lymph node involvement in this type of cancer). Diagnostic errors are almost always overestimates (demonstration of involvement of the submucosa when the muscularis mucosae has not been infiltrated), related to peritumoral inflammation. Standard EUS should be performed routinely to confirm that the tumor is T1 (the submucosa has not been infiltrated) and N0 (with no apparently metastatic lymph nodes in the peridigestive region). If the patient is operable, he or she may be referred to a practitioner with experience of very high frequency miniprobes once the tumor has been classified as usT1N0 using a standard echoendoscope, so that only usT1mN0 patients are offered endoscopic mucosal resection (EMR) or endoscopic mucosal dissection (ESD) (Figs 90–92), since these techniques are not without significant complications. The use of very high frequency miniprobes is clearly essential before the use of photodynamic therapy and radiofrequency ablation for the treatment of high-grade dysplasia and intramucosal carcinoma with visible lesions, since these destructive techniques do not yield histological confirmation (as after EMR or ESD) of the effectiveness of the treatment. Figures 93 and 94 show the indications of EUS for early squamous cell cancers.

Figure 90 Early flat slightly elevated (O–IIa), squamous esophageal cancer, uT1m2 visualized with 30 MHz Olympus high frequency miniprobe.

Figure 91 Early uT1m3 squamous esophageal cancer visualized with the Olympus 30 MHz miniprobe. mm: muscularis mucosae.

Figure 92 Early uT1sm1 squamous esophageal cancer visualized with the Olympus 30 MHz miniprobe.

Figure 93 Staging and management of early esophageal squamous carcinoma in patients fit for surgery.

Figure 94 Staging and management of early esophageal squamous carcinoma in patients not fit for surgery.

10.3.3 Early Barrett’s cancer

The role of EUS is summarized in Figures 95 and 96.

Figure 95 Staging and management of early esophageal adenocarcinoma in patients fit for surgery.

Figure 96 Staging and management of early esophageal adenocarcinoma in patients not fit for surgery.

10.4 Gastric cancer

Until recently, preoperative endosonographic assessment of locoregional involvement of gastric cancer was not routinely considered, as it was for esophageal cancer, because unlike esophageal cancer, gastric cancer was considered above all a surgical cancer and as such an EUS assessment was indicated only if the information obtained was likely to alter the therapeutic strategy, i.e.:

Figure 97 Early flat slightly elevated (Paris classification O–IIa) gastric adenocarcinoma.

Figure 98 Same patient as Figure 79. Early uT1m2 gastric cancer visualized with the 30 MHz Olympus high frequency miniprobe. mm: muscularis mucosae.

Figure 99 Gastric cancer with peritoneal carcinomatosis located within the lesser sac.

Figure 100 Advanced gastric cancer with invasion of the pancreatic body.

Since the advent of preoperative neoadjuvant therapy, the use of EUS after CT is far commoner (Figs 101, 102) in order to select patients who may be immediately operable (usT2N0M0) and those who should receive neoadjuvant treatment (Fig. 93) (us T >T2 or any T N+).

Figure 101 Stage-directed management of advanced gastric cancer.

Figure 102 Stage-directed management of early gastric cancer.

Overall, the diagnostic accuracy of endosonography is 80% for parietal T involvement and 70% for lymph node involvement. Errors involve overstaging T1 tumors as T2 and T2 tumors as T3. This occurs in gastric cancers owing to the frequency of ulcerating cancers which are responsible for particularly extensive peritumoral fibrous and inflammation, leading to over-estimation of the depth of the tumor involvement.

10.4.2 Linitis plastica

Linitis plastica is often difficult to diagnose (>50% of cases are missed) with endoscopy and biopsies. The entirely characteristic endosonographic appearance of this disease makes EUS the best diagnostic technique (Figs 103, 104). Besides its role in the differential diagnosis of benign hypertrophic gastritis (Figs 105, 106) and linitis plastica, gastric endosonography is capable of detecting minimal ascites which indicates peritoneal carcinosis, undetected by other imaging techniques (Fig. 104). It is also useful for demonstrating infiltration of adjacent organs, in particular the corporeo-caudal region of the pancreas (usually between 45 and 50 cm from the incisors facing the posterior side), or the transverse mesocolon (under the pancreatic body facing the horizontal greater antral curve). The same applies for detecting submucosal involvement upwards to the esophagus or downwards to the duodenal bulb. The results of EUS FNA for the diagnosis of linitis plastica are poor (sensitivity <30%).

Figure 103 Linitis plastica uT3.

Figure 104 Typical linitis plastica. Marked thickening of the wall layers. m, Mucosa; sm, submucosa; mp, muscularis propria. Small amount of ascitis highly suggestive of peritoneal carcinomatosis (white arrow).

Figure 105 Giant folds gastritis. Ménétrier’s disease.

Figure 106 Ménétrier’s disease. Typical aspect of this benign disease with giant gastric folds: huge thickening of the mucosa with normal submucosa.

10.4.3 Gastric lymphomas (Figs 107, 108)

There are several EUS features (Figs 109–111) of gastric lymphomas: flat, large folds, nodular or polypoid, or infiltrated pseudolinitis. None of these features are specific for the diagnosis, despite what was initially described. The diagnosis of lymphoma is a histological diagnosis obtained easily from biopsies performed during endoscopy. The main benefit of endosonography is thus in assessing locoregional involvement. Endosonography is very effective for this purpose with a diagnostic accuracy in the order of 90% for T staging and 80% for N staging. In low-malignancy MALT lymphoma, endosonography is the most reliable predictor of a response to Helicobacter pylori eradication. In addition to the efficacy of antibiotic treatment on H. pylori eradication, two pre-therapeutic endosonographic criteria are highly predictive of a good response, and these are infiltration confined to the mucosa or the superficial part of the submucosa (tumor thickness <5 mm) and the absence of lymph node involvement detectable by EUS. If both these criteria are met, the response rate (complete remission) 18 months after successful H. pylori eradication is 70–80%.

Figure 107 Management of high-grade gastric lymphoma.

Figure 108 Staging and management of low-grade gastric lymphoma (MALToma).

Figure 109 Low-grade malignancy arising in a MALT lymphoma of the fundus. Endoscopic view of giant gastric folds. Hypoechogenic thickening well confined to the mucosa.

Figure 110 Low-grade malignancy arising in a MALT lymphoma. Hypoechogenic thickening of the inner part of the submucosa.

Figure 111 High-grade malignancy arising in a gastric lymphoma. Considerable thickening of the different wall layers which are still visible. M, mucosa; SM, submucosa; MP, muscularis propria.

10.5 Rectal cancer

10.5.1 Parietal involvement

The diagnostic accuracy of endosonography for the parietal involvement of rectal cancers according to the TNM classification varies from 75–95%. It is in the order of 95% for T1 tumors (Figs 112, 113), 75% for T2 tumors (Fig. 114), 90% for T3 tumors (Fig. 115) and 95% for T4 tumors. The distinction between a T1 tumor and greater involvement (T2 to T4) is 95%. The distinction between a tumor located in the wall (T1, T2) and a tumor that has reached the fat or an adjacent organ (T3, T4) is 90%.

Figure 112 uT1 Rectal cancer confined to the mucosa. Submucosa is intact (white arrows).

Figure 113 T1 rectal cancer confined to the mucosa. Muscularis mucosae is well visualized (black arrows), but not invaded.

Figure 114 T2 rectal cancer.

Figure 115 T3 Rectal cancer.

10.5.2 Lymph node involvement

Lymph node involvement is correctly predicted in 70% of cases (Fig. 116). Round (splenical) shape, hypoechogenic, well demarcated, >5 mm in smaller diameter are criteria suggesting malignancy.

Figure 116 Small malignant perirectal lymph node.

10.5.3 In summary

Endosonography is significantly superior to clinical examination and CT for assessing parietal and lymph node involvement. Comparisons have also shown that endosonography is superior to MRI for assessing the spread of localized tumors to the wall, equivalent for assessing the spread of advanced tumors (T3)), and equally sensitive for assessing lymph node involvement. Furthermore, EUS FNA can be carried out if necessary (which improves the specificity of the method). MRI seems to be more accurate than EUS in case of T4 cancer of the upper rectum. The management of early rectal cancer is summarized in Figure 117. Actually, since the last 2 years, the management of advanced rectal cancer has changed because of the better efficacy of the neo-adjuvant chemoradiation therapy in comparison with radiotherapy alone. The indications of neoadjuvant chemo-radiation therapy have dramatically increased. Any rectal cancer which is staged by EUS or MRI as T >T2 receives neoadjuvant chemoradiation therapy whatever the circumferential margin is more or less than 1 mm. Moreover, any lymph node visualized by EUS or MRI leads to chemoradiation therapy. Thus, the specific indications of MRI (i.e. to determine the circumferential margins of the rectal cancer staged as T3 using EUS) have now disappeared.

Figure 117 Role of local treatment for early rectal cancer: recommendations for clinical practice.

Given the very significant difference in the cost of these two methods, rectal endosonography remains the method of choice for the pre-therapeutic assessment of both early tumors and advanced cancers and MRI is mandatory to stage very fixed cancer of the lower and mid rectum with suspicion of T4 lesions at EUS and advanced stenotic cancer of the upper rectum.

10.6 Anal cancer

The depth of the involvement of the anal canal and the rectal wall and the presence of metastatic lymph nodes around the rectum are major prognostic factors as regards the response to radiotherapy or radiochemotherapy. Anorectal endosonography should be considered essential for the treatment of patients with squamous cell cancer of the anal canal (Figs 118, 119); it has, in fact, been shown that endosonographic staging (T1 no invasion of the rectal muscle layer or the internal sphincter, T2 invasion of the rectal muscle layer or the internal sphincter, T3 invasion of the peri-rectal fat or the striated sphincter, T4 invasion of the vagina or rectovaginal septum, invasion of the prostate) is a significantly better predictor of response to treatment than the use of the clinical TNM classification. EUS is particularly useful for cT1 or cT2 tumors in the clinical UICC classification as 20–30% of these tumors are classified uT3 by endosonography. Furthermore, the sensitivity of endosonography for detecting N1 invaded lymph nodes (perirectal) is significantly superior to clinical examination (UICC classification). Finally, EUS FNA can easily be performed if necessary (in contrast with CT, MRI and PET scans).

Figure 118 Small uT1 squamous anal cancer confined to the mucosa and the submucosa.

Figure 119 Large uT4 squamous anal canal cancer invading the anovaginal septum (black arrows).

10.7 Post-therapeutic monitoring of digestive cancers

Post-therapeutic monitoring has been shown to be clearly advantageous in rectal cancer after surgery and probably advantageous for cancers which have not been treated surgically (anal canal or lymphoma). Its value is debatable after neoadjuvant treatment of esophageal cancers. Generally speaking, the post-therapeutic monitoring of digestive cancers treated medically is far more difficult than pre-therapeutic assessment or the post-therapeutic monitoring of cancers after surgery, since residual parietal and peridigestive anomalies detected by EUS are common and they are particularly difficult to interpret (scar or recurrence) (Fig. 120). This underlines the importance of sending these patients to referral centers with experience in this form of monitoring.

Figure 120 Small nodular recurrence located within the internal sphincter 1 year following completion of treatment for anal canal cancer.

11.1 Introduction

The two main reasons why transabdominal ultrasound is less effective in assessing the pancreas and bile ducts than it is in the liver and gallbladder can be overcome by using an echoendoscope in the stomach and duodenum. The distance separating the transducer from the target structure is reduced to a few millimeters, and the result is not subject to disturbance by peridigestive fat and intradigestive air, regardless of the morphology of the patient examined. The use of high frequencies (6–10 MHz) yields images with unequalled spatial resolution, despite major progress made since the mid-1990s and above all the mid-2000s in external image imaging, whether by CT or high-definition MRI, including MRCP. For example, the detection threshold for EUS for common bile duct or gallbladder stones is 0.5 mm, whereas it is 2–3 mm for solid intrapancreatic tumors (as has been demonstrated in patients with multiple endocrine neoplasia type I).

In pancreatic disease, particularly tumors (solid or cystic), there is now no doubt that conventional diagnostic EUS is strongly rivalled by CT and MRCP. However, the advent of EUS FNA toward the end of the 1990s and the development of therapeutic EUS during the 2000s have once again made EUS a key tool in the diagnostic and therapeutic management of pancreatic diseases.

11.2 Diagnosis and assessment of locorectional involvement in pancreatic cancer

11.2.1 How does EUS perform in the diagnosis of pancreatic cancers?

EUS can be used to examine the whole of the pancreatic gland from the uncinate process to the tail in almost all patients, regardless of their morphology. The head cannot be completely examined in patients with impassable duodenal stenosis, or gastrectomy with Billroth II anastomosis. A history of endoscopic sphincterotomy or the presence of a metal stent may hinder the examination of the pancreatic head. Generally speaking, EUS should be performed if possible, whether for diagnostic or histological purposes, before inserting a stent in the common bile duct, if the examination is to be as effective as the best results published in the literature. Examination of the caudal pancreas is unsatisfactory or incomplete in 10% of cases, in my experience, when the radial technique is used because the distance between the greater curve of the stomach and the pancreatic tail is too great. It is then necessary to change to an electronic linear echoendoscope.

The sensitivity of EUS in the diagnosis of pancreatic cancers exceeds 95%, even for small cancers (Fig. 121) with a diameter of 2 cm or less (these cancers are rare but unfortunately represent the vast majority of cancers curable by surgical resection). These small cancers are not detectable by MDCT in 30% of cases because they remain isodense after the injection of contrast medium.

Figure 121 Small (12 mm) uT1 adenocarcinoma (A), (T) of the pancreatic head with slight dilatation (4 mm) of the main pancreatic duct (MPD) revealed by an episode of acute pancreatitis. This small cancer was not demonstrated by MDCT or MRI and was suggested but not visualized by MRCP.

EUS remains superior in terms of diagnostic performance to the best imaging techniques including MDCT and MRI. Its sensitivity, close to 100% for the diagnosis of small cancers, and a resulting negative predictive value of more than 95% mean that EUS remains the reference examination for the detection of a focal lesion of the pancreas when it has not been conclusively identified by modern imaging. Furthermore, a normal EUS examination of the pancreas almost certainly rules out a diagnosis of pancreatic cancer, which is impossible with MDCT and MRI.

Nevertheless, subject to the results of current studies on the use of contrast media (Box 13) and elastography (Box 14), two new methods of tissue characterization whose results are promising, none of the EUS characteristics of pancreatic masses has a sufficient positive or negative predictive value for satisfactorily discriminating between a malignant tumor and an area of pancreatitis. It has, moreover, been shown that in the case of chronic advanced pancreatitis or after a recent episode of severe acute pancreatitis, EUS may miss a pancreatic cancer.

Box 13 Contrast-enhanced EUS

• Requires specific contrast enhancement harmonic (CEH-EUS) software.

• Uses different US contrast agents (UCA).

• In Europe, the most widely used UCA is Sonovue (sulphur hexafluoride).

In CEH-EUS

• Ductal adenocarcinomas of the pancreas are very hypovascular compared to the parenchyma, in the various injection phases (Fig. 122).

• Endocrine tumors of the pancreas are hyper- (Fig. 123) or isovascular (Fig. 124) with a hypervascular rim in relation to the adjacent parenchyma, in the arterial phase (8–20 seconds after the injection).

• Focal pancreatitis is slightly less vascularized or as vascularized as the adjacent parenchyma (Figs 125, 126), during the arterial and the venous phase. It is more vascularized than adenocarcinoma and less vascularized than endocrine tumor.

• Adenoma (mural nodule in the case of IPMN or a tumor of the ampulla of Vater) is isovascular in relation to the adjacent parenchyma.

Figure 122 Contrast-enhanced EUS of a small (17 mm) adenocarcinoma (right image) of the head of the pancreas. Typical aspect of a hypovascular, nodular lesion in the various injection phases.

Figure 123 Contrast-enhanced EUS of a small (8 mm) insulinoma of the body of the pancreas. Typical aspect of a hypervascular (right image) nodular lesion in the arterial phase.

Figure 124 Contrast-enhanced EUS of an insulinoma (14 mm) of the tail of the pancreas. Isovascular (right image) compared to the adjacent parenchyma in the arterial phase, well circumscribed by the hypervascular ring (white arrows). This insulinoma was isoechogenic to the adjacent parenchyma using EUS (left image), and was not visible on MDCT or MRI.

Figure 125 Contrast-enhanced EUS of a pseudotumor in a patient with auto-immune pancreatitis of the tail of the pancreas. First second after injection: the focal mass (right image) is hypoechogenic compared to the normal parenchyma.

Figure 126 Same patient as Figure 125. The pseudotumor (right image) is isovascular to the adjacent parenchyma 6 seconds after injection.

Box 14 EUS elastography

Elastography is a means of measuring tissue stiffness. Malignant tissue is harder than benign tissue and elastography may be able to differentiate between both. The technology is based on the detection of small structure deformations within the B-mode image caused by compression, so that the strain is smaller in hard tissue than in soft tissue. The degree of deformation is used as an indicator of the stiffness of the tissue. Different elasticity values (on a scale of 1–255) are shown as different colors. The system is set up to use a hue color map (red-green-blue), in which hard tissue areas are shown in dark blue, medium-hard tissue areas in cyan, intermediate hardness tissue areas in green, medium-soft tissue areas in yellow, and soft tissue areas in red.

EUS-elastography has been used for the diagnosis of pancreatic cancer and malignant lymphadenopathy with variable sensitivity, specificity, and accuracy in different studies. More recently, specially designed software has been available for computerized analysis of EUS-elastography images and videos. This has allowed quantification of tissue hardness by calculating hue histograms of each individual elastographic image, rather than qualitative analysis of the EUS images.

Elastography may allow differentiation of focal chronic pancreatitis (CP) from pancreatic cancer or, when the latter occurs on a background of CP, it may allow accurate targeting of the best area for FNA biopsy. Results of further studies are awaited.

EUS-FNA has, according to the latest studies, a sensitivity of between 85 and 95% and a specificity in the order of 100% for the diagnosis of malignant pancreatic tumors. Nevertheless, the negative predictive value never exceeds 80%, which means that a negative biopsy does not rule out a diagnosis of cancer. If malignancy is strongly suspected, based on biochemical or morphological clinical criteria, do not hesitate to carry out a second EUS-FNA of a focal pancreatic image, so as not to miss the opportunity for surgical resection which remains the only method likely to cure a patient with pancreatic cancer.

In summary, EUS, combined if necessary with FNA, is essential for the diagnosis of pancreatic cancer when imaging methods (MDCT and MRI) do not provide any certainty (see Fig. 132).

11.2.2 How does EUS perform in the assessment of locoregional involvement in pancreatic cancers?

Definition

• Pancreatic cancer is considered unresectable if there are metastases to organs (liver, peritoneum or lung) or to the left supraclavicular lymph nodes or if the tumor is locally advanced.

• Pancreatic cancer is considered locally advanced if unresectable vascular involvement is present. This is defined as:

Involvement of the superior mesenteric vein, the mesenteric-portal vein confluence and the portal vein, if a thrombosis with or without a cavernoma is present (see below)

Involvement of the hepatic artery, superior mesenteric artery or celiac trunk

This is also the case if there are lymph node metastases remote from the tumor (in the lumbar aortic, superior mesenteric, pyloric, celiac or posterior mediastinal location).

At diagnosis, almost 50% of pancreatic cancers have hepatic or peritoneal metastases, 30% are locally advanced, and 15% to 20% are resectable. Surgical resection is currently the only treatment that can cure a small percentage of patients: approximately 20% of patients with pancreatic cancers, who have undergone curative surgery (R0 resection), are still alive 5 years later, which means that there are 5% survivors at 5 years after a diagnosis of pancreatic cancer. The incidence, i.e. the number of new cases annually of this cancer, is equal to its prevalence, i.e. the total number of surviving patients affected, which means that almost all patients die within a year of diagnosis. The few patients who survive are those who had no lymph node involvement in the resection tissue (N0 patients). It has recently been demonstrated that moderate involvement, affecting the portal vein, the superior mesenteric vein or the mesenteric-portal vein confluence, could undergo curative R0 surgical resection (at the cost of a vascular procedure, and thus greater morbidity) without worsening the prognosis, in other words obtaining approximately 20% survivors at 5 years as if there had been no vascular involvement, however this percentage was obtained only if there was no lymph node involvement in the resection tissue (N0). It has also been shown that even in the absence of recovery, R0 surgical resection is the most effective palliative method in terms of survival and quality of life. It has finally been demonstrated that owing to progress in chemotherapy and endoscopic drainage, the palliative non-surgical management of patients with locally advanced cancer improved the duration and quality of their survival, and that 10% of these patients became eligible for curative surgical resection.

Several studies and teams have, in recent years, proposed laparoscopy as the final stage in diagnosing the resectability of pancreatic head cancers, before curative pancreaticoduodenectomy. The success rate of laparoscopy in these studies after performing a preoperative imaging assessment to diagnose resectability ranged from 20% to 75%, depending on the quality of the preoperative assessment. A recent study has shown that when the assessment of resectability of a cephalic adenocarcinoma included thin section pancreatic MDCT and high-quality EUS, the benefit of routine laparoscopy barely exceeded 10%, confirming that this benefit was inversely proportional to the quality of the preoperative assessment.

Between 1990 and 1997, EUS was regarded as the reference examination for assessing the lymph node and vascular involvement of pancreatic cancers, superior to both CT and angiography. Thin section MDCT centered on the pancreas currently has a diagnostic sensitivity of 80% for venous invasion and 90% for arterial invasion. The specificity of this examination for the diagnosis of vascular non-resectability is close to 100% (excluding malignant IPMN). Combined with the fact that the diagnosis of hepatic metastases is correct in almost 90% of cases, this means that thin section MDCT is sufficient to optimally determine the management of almost 70% of patients with pancreatic cancer. The sensitivity of thin section MDCT for the diagnosis of moderate disease of the superior mesenteric vein, the mesenteric-portal vein confluence or the portal vein is, nevertheless, unsatisfactory, while its sensitivity for the diagnosis of lymph node involvement remains poor and has not improved. Small subcapsular metastases, which are one of the features of pancreatic cancers, remain difficult to detect and peritoneal carcinosis remains undetectable in the majority of cases. These limitations of thin section MDCT are residual indications of EUS for the assessment of locoregional involvement. The method should therefore be used only in patients who have been filtered by thin section MDCT.

In summary

• The sensitivity of EUS for the diagnosis of moderate involvement of the mesenteric-portal vein confluence in patients with pancreatic cancer with a diameter ≤3 cm is close to 100% (Figs 127, 128)

• The sensitivity of EUS for the diagnosis of remote metastatic lymph nodes (N2) is close to 80% (Fig. 129), and it allows EUS FNA which provides histological confirmation of metastasis

• EUS is capable of detecting and confirming by biopsy small subcapsular metastases of segment II and segment I that are invisible or cannot be biopsied during MDCT (Fig. 130)

• EUS is the most sensitive method of detecting slight ascites suggesting peritoneal carcinosis, allowing a cytological study by FNA (Fig. 131).

Figure 127 3 cm uT3 adenocarcinoma of the uncinate process, slightly invading the posterior side of the superior mesenteric vein (SMV).

Figure 128 14 mm, uT3, adenocarcinoma of the upper and posterior part of the head of the pancreas, slightly invading the posterior and right side of the portal vein confluence (white arrows). HA, hepatic artery; CBD, common bile duct.

Figure 129 EUS-guided FNA (22 G needle) of a small (1 cm) malignant lymph node (upper left image), close to the hepatic artery (this is an N2 node if the primary is in the pancreatic head). Cytology (upper right image) was positive for adenocarcinoma. EUS-guided FNA (22 G needle) of a small (12 mm) lumbar aortic malignant lymph node (lower left image) in front of the inferior vena cava (IVC). Cytology (lower right image) was positive for adenocarcinoma.

Figure 130 EUS-guided FNA (22 G needle) of a small (12 mm) subcapsular liver metastasis in segment II.

Figure 131 EUS-guided FNA (22 G needle) of ascitis in a patient with pancreatic body cancer. Positive liquid phase cytology for adenocarcinoma.

After carrying out a thin section pancreatic MDCT, EUS currently remains essential for the optimal management of a large proportion of patients with pancreatic cancer:

• Patients in whom the diagnosis has not been confirmed by MDCT or MRI (Fig. 132)

• Patients without hepatic metastases, considered eligible for resection after MDCT (Fig. 133)

• Patients in whom a histological diagnosis is essential and who have no hepatic metastases accessible to percutaneous biopsy (Figs 134, 135).

Figure 132 No pancreatic mass at MDCT.

Figure 133 Resectable cancer at MDCT.

Figure 134 Unresectable cancer at MDCT without liver metastasis.

Figure 135 Pancreatic cancer with liver metastasis at MDCT.

11.2.3 Indications and results of EUS-FNA of solid pancreatic masses

EUS is the only method of biopsying all parts of the pancreatic gland, including the uncinate process and the tail. Any pancreatic mass with a minimum diameter ≥5 mm can be biopsied. Owing to improvements in echoendoscopes and techniques for cytology and histology (use of immunohistochemistry, P53, Ki67, K ras, etc.), their sensitivity for the diagnosis of malignant pancreatic tumors exceeds 90% and their specificity is close to 100%, whether for adenocarcinoma or a tumor with a less common histology and a better prognosis, such as pancreatic metastases, neuroendocrine cancers or lymphomas.

The rate of complications is low, comprising mainly acute pancreatitis which occurs almost exclusively when benign tumors are biopsied through healthy pancreatic tissue. The risk of peritoneal or parietal spread along the biopsy path is lower than with the percutaneous route, owing to the proximity between the echoendoscope and the tumor (which rarely exceeds a few mm). Furthermore, for a transduodenal biopsy of a potentially resectable tumor (diagnosis of a small cephalic pancreas tumor carried out exclusively by EUS), there is no risk of spread because the biopsy path is removed during pancreaticoduodenectomy. A study has shown that the risk of peritoneal carcinomatosis caused by EUS-FNA was very significantly lower than after CT-guided percutaneous FNA. One explanation for this difference, apart from the length of the biopsy path, is the use of a different needle diameter in each of the two methods: a 22-gauge or 25-gauge needle is sufficient to diagnose malignant disease in more than 90% of cases using an echoendoscope, whereas a 19-gauge needle is necessary to obtain 90% sensitivity by the percutaneous route (the percutaneous use of a 22-gauge needle rarely achieves a sensitivity of >70%).

The validated indications of EUS-FNA are:

• The cytohistological diagnosis of pancreatic masses invisible to MDCT or MRI, detected only by EUS (Fig. 136)

• A differential diagnosis between pancreatic adenocarcinoma and a pancreatitis nodule, in particular in patients with chronic calcifying pancreatitis or a clinical and biochemical picture compatible with pseudotumoral pancreatitis (autoimmune pancreatitis) (Fig. 137)

• A differential diagnosis between pancreatic adenocarcinoma and a pancreatic metastasis of a synchronous or metachronous cancer (in order of frequency: kidney, breast, lung, colon, etc.) (Fig. 138)

• The cytohistological diagnosis of unresectable non-metastatic locally advanced cancers (Figs 134, 139–143) or cancers with hepatic metastases not accessible percutaneously (Fig. 135). A biopsy is essential in these cases before palliative treatment is started, because pancreatic adenocarcinomas account for only 85–90% of pancreatic cancers, with 5–10% being neuroendocrine cancer, 5% a metastasis, and 1–2% lymphoma

• The cytohistological diagnosis of the adenocarcinomatous nature of a resectable tumor before its inclusion in a preoperative chemotherapy protocol for neoadjuvant therapy (Fig. 133)

• The diagnosis of an asymptomatic solid tumor (Figs 144–148) discovered by chance.

Figure 136 Radial EUS and EUS-guided FNA (22 G needle) of a small (11 mm) uT1 pancreatic cancer of the uncinate process only visualized by EUS in a patient with hereditary pancreatic cancer. The histology was positive for adenocarcinoma.

Figure 137 A pseudotumor in a patient with autoimmune pancreatitis (AIP) who presented with jaundice. The main pancreatic duct with a hyperechogenic wall (W) is well seen within the mass. EUS-guided FNA with 22 G needle. Cell block histology revealed an inflammatory process with numerous IgG 4 plasmocytes, compatible with type I AIP.

Figure 138 3 cm pancreatic head mass, invading the gastroduodenal artery (A). EUS-guided FNA (22 G needle) of the mass (B) which was complicated by a hematoma (white arrows) due to the hypervascular nature of the mass. Histology was positive for renal cell cancer metastases on cell block (C).

Figure 139 Locally advanced, unresectable uT4 pancreatic cancer invading the celiac axis (1), left gastric artery (2), superior mesenteric artery (3) and aorta (4).

Figure 140 Small (20 mm), locally advanced, unresectable uT4 pancreatic head cancer invading the portal vein confluence with partial thrombosis of the portal vein.

Figure 141 Same patient as Figure 140. TH, portal vein thrombosis, T, tumor, MPD, main pancreatic duct.

Figure 142 Same patient as Figure 140 seen with linear scope.

Figure 143 Same patient as Figure 140 seen with linear scope. Note the tumor (T) involving the main pancreatic duct (MPD) and portal vein (PV) with portal vein thrombosis (TH).

Figure 144 Pseudosolid serous cystadenoma (T) of the pancreatic neck. (A) Radial examination. (B) Note that the tumor is encorbelled by vessels. (C) EUS-guided FNA with 22 G needle. (D) Histological aspect of serous cystadenoma.

Figure 145 Small (9 mm) solid incidentaloma of the pancreatic head.

Figure 146 Same patient as Figure 145, with EUS-guided FNA (22 G needle).

Figure 147 Same patient as in Figures 145 and 146. The cell block demonstrated positive immunohistochemical staining with chromogranin A (upper image) consistent with a neuroendocrine tumor. Immunohistochemical quantification of the proliferation marker KI 67 evaluated at 20% on liquid phase cytology suggesting a small malignant endocrine cancer (lower image), which was confirmed on histology of the resected specimen.

Figure 148 Small incidentaloma (11 mm) of the uncinate process in a young male. EUS-guided FNA (22 G needle) demonstrated a solid pseudo-papillary tumor.

The commonest of all these indications is of course the cytohistological diagnosis of locally advanced unresectable pancreatic cancers before palliative treatment. In view of the excellent results obtained with very low morbidity, EUS-FNA promises to replace percutaneous biopsy for solid pancreatic masses. Finally, it is important to note that biopsy of a solid pancreatic mass is not indicated when surgical resection is clearly indicated (no doubt about its tumoral nature or resectability).

11.3 Pancreatic neuroendocrine tumors

Ever since the 1980s, EUS has been the reference examination for determining the preoperative location of secretory endocrine tumors potentially of pancreatic or duodenal origin, and in particular the two commonest forms, insulinoma and gastrinoma. When the method is performed by an experienced EUS operator, the diagnostic accuracy of the method for locating pancreatic gastrinomas or insulinomas exceeds 90%, whereas in combination with somatostatin receptor scintigraphy, its sensitivity is 90% for duodenal gastrinomas (Figs 149–157).

Figure 149 Typical aspect of a pancreatic endocrine tumor located within the tail of the pancreas. Thin hypoechogenic ring (white arrow) with peripheral signal enhancement (black arrows).

Figure 150 Small (6 mm) pancreatic endocrine tumor. On the right image vessels can be seen surrounding the tumor.

Figure 151 Pancreatic endocrine tumor with peripheral signal enhancement with vessels which surround and penetrate the tumor.

Figure 152 Isoechogenic pancreatic insulinoma seen only with EUS. The tumor is visualized because of the more homogeneous echostructure compared to the adjacent parenchyma, thin hypoechoic ring and peripheral signal enhancement.

Figure 153 Isoechogenic insulinoma of the tail of the pancreas only seen with EUS. The tumor is visualized because of the more homogeneous echostructure compared to the adjacent parenchyma and the peripheral signal enhancement.

Figure 154 Same tumor as Figure 124.

Figure 155 Same tumor as Figure 124 with the vessels surrounding it.

Figure 156 Small (2.5 mm) duodenal gastrinoma in a patient with Zollinger–Ellison syndrome.

Figure 157 Cystic endocrine tumor of the pancreas.

The detection threshold of a pancreatic endocrine tumor by EUS is approximately 2 mm. EUS is capable of locating almost 80% of pancreatic endocrine tumors in patients with multiple endocrine neoplasia type I. An endocrine tumor is typically round or oval with a distinct boundary, hypoechoic, very homogeneous, surrounded by a very thin hypoechoic ring (Fig. 149). It yields peripheral signal enhancement, indicating hypervascularization. In Doppler energy imaging, it is laced with small vessels that penetrate it (Figs 150, 151); it is a very pretty tumor. It is sometimes isoechoic (Fig. 152) with the parenchyma, and difficult to locate. Its echostructure is more homogeneous than the adjacent parenchyma and it can then be located by peripheral signal enhancement (Fig. 153) or by peripheral vascularization (Figs 154, 155). It is sometimes heterogeneous, with partial attenuation of the ultrasound beam indicating areas of fibrosis. There are sometimes small calcifications. Sometimes it is cystic. If it is large, multiple rather central small cystic areas are fairly common. If it is small and cystic, the antral cystic area accounts for the majority of the tumor volume, the tumor being confined to the wall of the cyst which is fleshy, homogeneous (Figs 157, 158), and covered with small vessels on Doppler energy imaging.

Figure 158 Cystic endocrine tumor of the pancreas.

EUS FNA is very effective, with a sensitivity close to 100% using immunohistochemistry. It is the standard examination for confirming a diagnosis of non-functional endocrine tumor when it has been discovered by chance and in the absence of somatostatin receptor scintigraphy. The histoprognosis based on EUS-FNA correlates well with that obtained by resection. The opportunity for immunohistochemical quantification of the proliferation marker Ki67 and the mitotic index is very helpful when decision-making is difficult. The role of EUS and EUS FNA in the management of pancreatic endocrine tumors is summarized in Figures 159–161.

Figure 159 Clinical and biological features of functional NET without localization of the tumor by MDCT, MRI, and SRS.

Figure 160 Staging and management of non-functional pancreatic neuroendocrine tumors (NET).

Figure 161 Management of pancreatic neuroendocrine tumors discovered coincidentally at EUS.

11.4 Cystic pancreatic tumors

EUS is very useful for examining cystic lesions of the pancreas when their nature has not been clarified by a combination of percutaneous ultrasound and spiral CT or MRI with MRCP. It facilitates the diagnosis of serous cystadenomas (Fig. 162) if it reveals microcysts in an apparently solid tumor (Fig. 163) or in a predominantly macrocystic tumor (these are macrocystic serous cystadenomas (Fig. 164), the frequency of which is probably greatly underestimated). EUS facilitates the diagnosis of mucinous cystadenoma if it detects parietal thickening and thick septa (Fig. 165), or eggshell calcifications (Figs 166, 167A), the presence of a solid component or a mural nodule (Fig. 167B,C) developed from the wall or septal thickening, or if the cyst contents are thick (Fig. 168) or have a fluid-fluid level (Figs 166, 167). It confirms the diagnosis of cystadenocarcinoma if it detects invasion of the adjacent parenchyma from a tumoral solid component or a tumoral thickening of the cyst wall (Fig. 169). It is very effective in the diagnosis of intraductal papillary-mucinous neoplasia of the pancreas, whether it is the form located in the main duct where diagnosis is fairly easy (Figs 170–173) or the form located in the secondary ducts when it shows several fluid images (Fig. 174A–D), distributed through all or part of the pancreatic gland, adjacent to the pancreatic duct, duct-shaped (much longer than it is wide), with or without clearly visible communication with the pancreatic duct with or without dependent droplets of mucus (Fig. 174E). The diagnosis is confirmed when mucus is identified emerging from the major or accessory papilla (Figs 175, 176).

Figure 162 Typical aspect of serous cystadenoma: central star with septa originating from it and microcysts within it.

Figure 163 Other typical aspect of serous cystadenoma: large (8 cm) ovale mass of the head of the pancreas. Hyperechoic mass with numerous microcysts (white arrows) and peripheral minicysts (black arrows).

Figure 164 Macrocystic serous cystadenoma. (A) peripheral thin septa; (B) some microcysts within a peripheral star; (C) EUS-guided FNA for CEA level; (D) after EUS-FNA and aspiration, the typical appearance of a serous cystadenoma can be seen with a central star and microcysts within it.

Figure 165 (A) Typical aspect of a mucinous cystadenoma: round cystic lesion with thick wall and septa. (B) Typical aspect of a mucinous cystadenoma of the tail of the pancreas with thick septa.

Figure 166 Typical small (2.5 cm) mucinous cystadenoma with eggshell calcifications (black arrow) and thick dependent content (white arrows).

Figure 167 (A) Typical mucinous cystadenoma with thick dependent content, and eggshell calcifications. (B) Typical mucinous cystadenoma with solid component (mural nodule) and droplet of mucus. (C) Same patient, with vessels in the stalk of the polypoid mural nodule.

Figure 168 (A) Mucinous cystadenoma with thick visible content. (B) Mucinous cystadenoma with thick septa and visible thick content.

Figure 169 Mucinous cystadenoma with solid component with invasion of the adjacent pancreatic parenchyma (T).

Figure 170 Main duct type IPMN of the head of the pancreas with tumour involving (T) the wall (<3 mm) of the main pancreatic duct (mpd) and mucus within the lumen.

Figure 171 Main duct type IPMN with the presence of a mural nodule, with height >5 mm, indicating at least borderline tumor and more often severe dysplasia.

Figure 172 Main duct type IPMN with thickened wall >3 mm indicating at least borderline tumor and more often severe dysplasia.

Figure 173 Mixed type IPMN of the head of the pancreas with thick mucus within the lumen (thin white arrow) and mural nodule (thick white arrow).

Figure 174 (A–D) Side branch type IPMN with or without communication with the main pancreatic duct. (E) Side branch type IPMN with several dependent droplets of mucus (white arrow).

Figure 175 Endoscopic view of the patulous papilla with mucus.

Figure 176 Same patient: EUS image of the patulous papilla and the dilated main pancreatic duct (w).

When diagnostic uncertainty persists as regards the mucinous or non-mucinous nature of a cystic tumor, or when diagnostic doubt persists between a mucinous cystadenoma and a pseudocyst, it is then useful to carry out FNA of the cystic fluid, with a very low risk of spread along the path, to allow a biochemical analysis (Table 3) (amylase and lipase) and a study of tumor markers (CEA is the most discriminating, while CA 19–9 and CA 72–4 are less effective).

Cytology is helpful in 40–50% of cases, and more effective if liquid phase cytology is used, particularly if there is a nodule to biopsy (sensitivity >80%). The combination of the EUS appearance and the information yielded by biochemical study, cytology and tumor markers can predict the nature of the cystic lesion in 90% of cases. In the specific case of intraductal papillary-mucinous neoplasia of the pancreas, besides its diagnostic contribution which is now rivalled very effectively by MRI with MRCP, EUS is essential for the management of these patients since it has been demonstrated that it is by combining all these imaging techniques that a real picture can be obtained of the longitudinal spread of the disease to guide resection, and of the degree of malignancy. The degree of malignancy is correlated with the extent of parietal thickening in the main duct (Figs 170, 172) or in the secondary ducts and with the presence of a mural nodule (Figs 171, 173, 177), two components that are detected better by EUS than by MDCT and MRI. An MPD diameter >10 mm, parietal thickening >3 mm and a mural nodule height >5 mm are highly predictive of severe dysplasia (Figs 172, 173, 177). In the branch duct type, a diameter <3 cm and the absence of parietal thickening and a mural nodule are highly predictive of low-grade dysplasia. Obviously, the presence of a mass is highly suggestive of invasive carcinoma (Fig. 178).

Figure 177 Mural nodule (height >5 mm) in a side branch IPMN.

Figure 178 (A) Mixed type IPMN. Presence of a mass highly suggestive of invasive carcinoma. (B) Management of intraductal papillary mucinous neoplasia (IPMN).

Given the frequency of totally asymptomatic IPMN located in the secondary ducts, distributed throughout the gland, found in particular in the female population over the age of 60, and discovered by chance (due to progress in non-invasive imaging), and given the low risk of degeneration of this type of IPMN (<10% at 5 years), if there are no predictive signs of malignancy, close monitoring is now the recommended method of treatment. This is based on annual MRI with MRCP, with EUS at intervals of not more than 3 years, since this is the only examination capable of the early detection of changes in the aspect of the secondary ducts in terms of parietal thickening or small mural nodules. Such changes then constitute a convincing argument for prophylactic surgical resection. A significant change in the diameter of a branch duct during the follow-up is also an indication for surgery in a patient who is fit for surgery.

11.5 Chronic pancreatitis (alcoholic or hereditary)

Although ultrasound and CT scanning has long been used routinely to diagnose chronic calcifying pancreatitis, ERCP remained until recently the gold standard for the diagnosis of early chronic pancreatitis (non-calcifying), using a classification of main duct and secondary duct anomalies (Cambridge classification). Several studies in the 1990s showed that EUS, by virtue of its resolving power on pancreatic parenchyma and the pancreatic ducts, correlated well with pancreatographic anomalies to diagnose the absence of chronic pancreatitis and to diagnose moderate to severe chronic pancreatitis (Fig. 179). On the other hand, correlation was poor for the diagnosis of minor chronic pancreatitis and uncertainty concerning the specificity of minor EUS anomalies (fewer than five criteria) was normal for almost 10 years.

Figure 179 (A) EUS image of the tail of the pancreas suggestive of early alcoholic chronic pancreatitis: lobularity with honeycombing (major criteria B), strands, non-shadowing hyperechoic foci, hyperechoic pancreatic duct wall (three minor features), using Rosemont classification. (B) EUS image of the body of the pancreas consistent with early alcoholic chronic pancreatitis: shadowing hyperechoic foci (major criteria A) lobularity with honeycombing (major criteria B), strands and hyperechoic duct wall, using Rosemont classification.

EUS (Box 15) is, in fact, more sensitive than ERCP since almost 70% of chronic alcoholic patients with symptoms of pancreatic disease and who had minor EUS anomalies and normal retrograde pancreatography, eventually had a definite pancreatographic diagnosis of chronic pancreatitis (after 3–5 years). The EUS criteria for a diagnosis of chronic pancreatitis are summarized in Box 15. An alternative method of defining chronic pancreatitis is to use the Rosemont criteria. These criteria were developed by an international consensus panel which was convened in Rosemont, Illinois (Box 16).

Although EUS is not advantageous for the diagnosis of chronic pancreatitis where there is already calcification, it is useful in the management of several of the complications associated with chronic pancreatitis.

In patients with duodenal stenosis, EUS is the standard examination for diagnosing cystic dystrophy of the duodenal wall developed on aberrant pancreas (Fig. 180), which is the leading cause of symptomatic duodenal stenosis in alcoholic chronic pancreatitis. This complication, which often goes unrecognized because it is incorrectly interpreted in cross sectional imaging, is observed in 5–10% of cases of alcoholic chronic pancreatitis and is more frequent with a clinical picture of severe pancreatitis in terms of pain, weight loss and vomiting. EUS is also useful if retrograde pancreatography shows a filling limit in a duct downstream of an area of segmental acute pancreatitis, when it can detect a stone that is not yet calcified, invisible to MDCT, at the junction between the normal pancreatic duct and the diseased area (Fig. 181).

Figure 180 Cystic dystrophy of the duodenal wall developed on an aberrant pancreas in the descending duodenum. Thickening of the duodenal wall (black arrows) and small cyst within the submucosa and the muscularis propria (white arrows).

Figure 181 Non-calcified intraductal pancreatic stone (black arrows), non-visible on MDCT and MRCP and misdiagnosed as a tumoral stenosis on ERCP.

11.6 Acute pancreatitis

Although it is probably very sensitive, EUS has never been validated in the diagnosis of acute pancreatitis which relies on a combination of clinical signs, laboratory tests and characteristic CT features. EUS has also never been validated for assessing the severity of acute pancreatitis, although its ability to detect minimal peripancreatic areas of inflammation is excellent. It has, however, now been clearly demonstrated that EUS is very useful when it has not been possible to determine the origin of acute pancreatitis from questioning the patient, the usual morphological examinations such as ultrasound and MDCT, and specialized laboratory tests.

11.6.1 Acute biliary pancreatitis

EUS has clearly been established as the most accurate technique for identifying an unrecognized biliary cause, which accounts for almost half of all acute cases of pancreatitis of indeterminate origin at the initial assessment. Its sensitivity for the diagnosis of gallbladder microlithiasis in the absence of stones detectable on ultrasound exceeds 90% (Fig. 182) and it is significantly superior to the microscopic study of bile collected by duodenal intubation after cholecystokinin stimulation. EUS is also, as we shall see in the chapter on biliary disease, the standard method for the diagnosis of stones in the common bile duct which are known to be present in one-quarter of all cases after acute biliary pancreatitis (Fig. 182C). EUS is therefore particularly useful before laparoscopic cholecystectomy after mild or moderate acute biliary pancreatitis to ensure the common bile duct is unobstructed. To detect gallbladder microlithiasis, EUS should be performed if possible within 48 h of acute pancreatitis so that fasting will not distort the interpretation of any sludge visualized in the gallbadder. If the examination is performed some time after the episode of acute pancreatitis, it is better to wait for about 2 weeks after resuming eating so that interpretation of the images of the gallbladder are really informative.

Figure 182 Microlithiasis. (A) Microstone (1 mm in size) within the gallbladder; (B) microstone (white arrow) within biliary sludge; (C) microstone (white arrow) within the CBD.

11.7 Autoimmune pancreatitis

Finally, EUS strongly suggests a diagnosis of autoimmune pancreatitis when it shows a diffuse, very great increase in the volume (’sausage shaped’)of the pancreatic gland, which usually has a hypoechoic (Fig. 183A) or heterogeneous hypoechoic ‘salt and pepper’ (Fig. 183B) echostructure, along with a pancreatic duct that is invisible or visible only in places; this aspect is known as ductitis, with hypoechoic (Fig. 183C) or hyperechoic (Fig. 183A) thickening of the wall in the areas where it is invisible or at the junction between an area where it is visible and one where it is invisible, and this is probably specific to this disease. Hypoechoic peripheral rim (Fig. 183D) when observed is also specific. Significant hypoechoic thickening of the bile duct wall (Fig. 183A), particularly in its distal section, is further evidence of an autoimmune origin, given the frequency of an association between autoimmune pancreatitis and autoimmune cholangitis in Mayo Clinic type I AIP. EUS FNA can yield additional support for the autoimmune nature of the disease. EUS FNA is essential if the autoimmune pancreatitis is localized to the pancreatic head, causing a picture of pseudotumoral pancreatitis with obstructive jaundice and a large cephalic mass (Fig. 137). Generally speaking, Mayo Clinic type II AIP is not well classified using HISORt classification, because of the lack of increased level of IgG 4 in the serum, absence of IgG4 plasmocytes in the biopsy specimen of the pancreas and of the papilla and difficulty to obtain typical histology of AIP using 19 G Tru-Cut EUS-guided biopsy. Typical EUS features of AIP including ductitis could be an additional criterion helpful for the diagnosis of Mayo Clinic type II AIP.

Figure 183 (A) Mayo Clinic type I autoimmune pancreatitis (AIP) with hypoechoic ‘sausage shaped’, aspect of the gland, ductitis (white arrow), i.e. main pancreatic duct (MPD) narrowing with hyperechoic thickening of the MPD wall, and autoimmune cholangitis (black arrows), i.e. diffuse thickening of the CBD wall. (B) Mayo Clinic type I AIP with heterogeneous hypoechoic ‘pepper and salt’ ‘sausage shaped’ aspect of gland. (C) Mayo Clinic type II AIP with hypoechoic ‘sausage shaped’ aspect of the gland and ductitis, i.e. hypoechoic thickening of the MPD wall. (D) Hypoechoic peripheral rim (white arrows) around the pancreatic body in AIP. (E) Mayo Clinic type I AIP in a young (15 years old) female with stenosis of the MPD (black arrows) and autoimmune cholangitis of the distal CBD (white arrows).

11.8 Embryological anomalies

Finally, EUS is very effective for the diagnosis of congenital pancreaticobiliary anomalies, whether for choledochocele (Fig. 184), pancreas divisum (Fig. 185), as EUS is equivalent to MRI with MRCP, or rarer anomalies such as an anomalous junction of the pancreatobiliary duct (Fig. 186) or an annular pancreas (Fig. 187).

Figure 184 (A) Choledochocele. D, duodenal lumen filled of water; CBD, common bile duct. (B) Other aspect of a choledochocele.

Figure 185 Pancreas divisum with Santorinicele (white arrow) within the minor papilla and the distal part of the Santorini duct (S) within the dorsal part (bright echostructure) of the head of the pancreas. GDA, gastroduodenal artery.

Figure 186 Anomalous junction of the biliary duct (cbd) and pancreatic duct (Wirsung).

Figure 187 Annular pancreas (white arrows) imaged in the first part of the descending duodenum. IVC, inferior vena cava.

In conclusion, EUS is essential to assess the etiology of acute pancreatitis of indeterminate origin. It can be carried out early to determine whether the etiology is biliary, tumoral or inflammatory. It is useful in severe acute pancreatitis only at a very early stage, to detect stones in the gallbladder and common bile duct.