ENETS Consensus Guidelines for the Standards of Care in ...ic resonance imaging (MRI), ultrasonography (US), con-trast-enhanced US (CEUS), endoscopic US (EUS) and intraoperative US

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ENETS Guidelines

Neuroendocrinology 2009;90:167–183 DOI: 10.1159/000184855

ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Radiological Examinations

Anders Sundin a Marie-Pierre Vullierme b Gregory Kaltsas c

Ursula Plöckinger d and all other Mallorca Consensus Conference participants

a Department of Radiology, Uppsala University Hospital, Uppsala, Sweden; b Service de Gastroentérologie, Hôpital Beaujon, Clichy, France; c G. Genimatas Hospital, Athens, Greece; d Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin , Germany

These distinct features in tumor growth, secretory ca-pacity and localisation are consequently reflected in the wide variation in clinical presentation of different NETs. Moreover, a number of NETs may be found incidentally when patients undergo surgery for unrelated reasons or may be an unexpected finding in the histopathological specimen as with appendiceal carcinoids. Accordingly, the need for diagnostic procedures and the choice of im-aging methods varies considerably depending on the pa-tient’s tumor status at presentation.

The various aspects to consider in the choice of imag-ing methods are related to primary tumor detection, evaluation of its local extent and relation to adjacent an-atomical structures, staging of the tumor concerning re-gional and distant metastases, evaluation of tumor so-matostatin receptor density, therapy monitoring and de-tection of recurrent disease. In this review, the various applications of current radiological modalities are de-scribed, including computed tomography (CT), magnet-ic resonance imaging (MRI), ultrasonography (US), con-trast-enhanced US (CEUS), endoscopic US (EUS) and intraoperative US (IOUS). The corresponding applica-tions of nuclear medicine procedures are presented sepa-rately.

Introduction

In contrast to other common types of malignant tu-mors, the vast majority of gastroenteropancreatic [endo-crine pancreatic (EPTs) and carcinoid] neuroendocrine tumors (NETs) are well differentiated and slowly growing with only a minority showing an aggressive behavior. NETs can produce a variety of metabolically active sub-stances (hormones and amines) leading to distinct clini-cal syndromes (functioning tumors). However, the ma-jority are non-functioning and present either with local-ly advanced disease giving rise to site-specific symptoms or distant metastases mainly to the liver. Patients with midgut carcinoid tumors and liver metastases may expe-rience symptoms of the carcinoid syndrome (flushing and diarrhoea), and develop carcinoid heart disease. In such patients, mesenteric involvement may lead to isch-aemia and/or intestinal obstruction due to a surrounding desmoplastic reaction with kinking of the bowel and vas-cular encasement. Approximately 30–40% of these pa-tients may require emergency surgery and are diagnosed at a relatively early stage before liver metastases have oc-curred.

Received: August 27, 2008 Accepted after revision: October 24, 2008 Published online: August 28, 2009

Anders Sundin Department of RadiologyKarolinska University Hospital SE–171 76 Stockholm (Sweden) Tel. +46 707 999 621, E-Mail [email protected]

© 2009 S. Karger AG, Basel0028–3835/09/0902–0167$26.00/0

Accessible online at:www.karger.com/nen

Sundin /Vullierme /Kaltsas /Plöckinger

Neuroendocrinology 2009;90:167–183 168

Materials and Methods

The participants of the consensus meeting considered the use of various radiological methods for the different imaging applica-tions in relation to documented available figures on sensitivity and specificity together with the expertise of the participants; availability of the various modalities was also taken into account. Further aspects considered were patient preparation and infor-mation, clinical information communicated to the radiologist for optimisation of the examination procedure and imaging inter-pretation, imaging protocols, reporting of results and radiation dose administered to the patient. The use of intravenous (i.v.) con-trast media (CM) for CT in patients with impaired renal function and in subjects with previous experience of side effects by i.v. CM was also addressed.

In general, data from the literature regarding the sensitivity and specificity of the various radiological modalities used for the diagnosis of NETs suffer from the small number of patients in-cluded and the absence of a reliable gold standard for verification of the imaging results. Quite frequently, detection rate is reported instead of sensitivity and specificity. Results are sometimes based on a patient-by-patient analysis and in other reports the results are also, or instead, lesion-by-lesion based. The detection rate merely states the proportion of patients with disease that is de-tected by the imaging method out of all examined subjects. The sensitivity is instead calculated with reference to a gold standard and equals the proportion of patients with the disease detected by the imaging method out of all patients with the disease according to the gold standard [sensitivity = true positive observations/(true positive observations + false negative observations)]. This review includes imaging data on sensitivity and specificity on a patient-by-patient basis. Detection rates are instead based on lesion-by-lesion analyses and report the proportion positive imaging results in patients with biochemically/clinically evident NETs. Also, the studies that were considered used current standards of imaging. Thus, studies in which incremental CT was performed, those without adequate contrast enhancement, and studies that utilised low field strength MRI ( ! 0.5 T) were excluded.

The current presentation, on radiological imaging of NETs, was adapted to the layout of the template for the whole consensus document and is divided into paragraphs according to the various radiological imaging techniques.

Results

Computed Tomography Modern spiral or helical CT, generally multidetector

CT (MDCT) scanners are available in most radiology de-partments and CT has currently replaced several imag-ing applications for which earlier other imaging modali-ties were employed, such as plain film radiography and angiography. By utilising several parallel detector rows, in recent generations of CT scanners at least 64 detector rows and with a tube rotation time of 0.3–0.5 s, hundreds or more of 1-mm or sub-millimetre transaxial images are acquired per second and the whole abdomen and thorax

may be examined during one breath hold. These thin, detailed images may be reformatted in any chosen ana-tomical plane, usually in coronal and sagittal views. The images allow reconstruction in three-dimensional (3D) volumes and can be rotated to better appreciate anatomy and pathological findings. Importantly, as opposed to previous incremental CT scanning, the development of the fast MDCT technique allows considerably better use of i.v. CM and CT imaging can now be performed in sev-eral contrast-enhancement phases, i.e. early arterial (or CT angiography), the late arterial (or portal-venous in-flow) and the venous contrast-enhancement phase. MDCT has therefore developed as one of the basic tech-niques for oncological imaging including NETs.

Sensitivity, Specificity and Detection Rate The CT-acquired sensitivity, specificity and detection

rate (mean and range based on the number of patients and studies) for various NETs is presented in table 1 .

In 5 studies on 162 patients, CT showed a mean 73% (range 63–82%) sensitivity and 96% (range 83–100%) specificity for diagnosing an EPT [1–5] . The mean detec-tion rate for EPTs of a further 6 studies including 178 pa-tients was 73% (range 39–94%) [6–11] . Based on these 11 studies that included 343 EPT patients the mean sensitiv-ity and detection rate for an EPT was 73%, although with a considerably wide variation (39–94%), but a generally high specificity (mean 96%).

In 4 studies reporting on the detection of NET liver metastases in 135 patients the mean sensitivity was 82% (range 78–100%) whereas the mean specificity was 92% range (83–100%) [12–15] . In a single study including 21 patients, the detection rate was 81% [11] . Four studies evaluating the presence of extrahepatic soft tissue metas-tases in 77 patients showed a 75% mean sensitivity (range 63–90%) and 99% specificity (98–100%) [12–15] . Another similar study on 21 patients reported 81% detection rate [15] . Three reports on imaging of various NET metastases in the abdomen and thorax included 164 patients and showed a mean sensitivity of 83% (range 61–100%) and specificity of 76% (range 71–80%) [13, 16, 17] . The detec-tion rate in a similar study including 25 patients was 76% [11] .

CT enteroclysis showed a 50% sensitivity and 25% specificity in 8 patients with NETs compared to capsule endoscopy where the corresponding figures were 38 and 100%, respectively [18] . In 219 patients with small bowel tumors, CT enteroclysis showed a sensitivity and speci-ficity of 85 and 97%, respectively, and 19 of these tumors were carcinoids [19] .

Radiological Examinations in Patients with Neuroendocrine Tumors


Hard- and Software Requirements For CT of the abdomen, thorax and neck, the CT scan-

ner should allow spiral examinations, optimally by MDCT, and should be able to reconstruct at a minimum ̂ 3-mm and optimally ̂ 1-mm images. The high spatial resolution of the thin slices is needed for optimal exami-nation especially of the pancreas, liver and neck. A high temporal resolution is also needed in order to perform examinations during contrast enhancement for abdomi-nal CT angiography, and the various contrast-enhance-ment phases required for proper examination of the liver and pancreas.

The software needed for image reconstruction and image reformats for multiplanar reconstructed images and maximum intensity projections are generally sup-plied with the CT scanner but specialised image refor-matting with volume rendering technique and virtual en-doscopy may need additional software programs.

Patient Information For better patient cooperation and examination re-

sults, the patient should be well informed and properly prepared. Patients should receive information according-ly; the examination generally takes ! 15 min. For abdom-inal CT, patients need to arrive at the department 2 h in advance for filling of the bowel by drinking up to 800 ml of fluid (generally tap water). Then patients are placed on the examination bed and moved into a short tunnel, i.e. the CT gantry, where claustrophobic patients may be-come symptomatic and should be adequately prepared

with diazepam. When CM administration is required via an i.v. catheter, this may lead to a feeling of warmth. The presence of a previous history of renal impairment and i.v. CM-related adverse reactions, whether this was sys-temic or localised, should be checked. In the presence of previous adverse effects the contrast material responsible should be investigated since side effects experienced with older ionic high-osmolar preparations are rare with mod-ern non-ionic and low-osmolar CM.

Fluids but no solid food are recommended during12 h before the examination. In patients with impaired renal function it is of particular importance to inform the patient that he or she needs to be well-hydrated before the examination in order to reduce the risk of CM-related renal adverse effects.

Information on the radiation dose is generally not nec-essary for the patient. It should be documented on the im-aging report, according to local regulatory authorities.

Patient Preparation Patients who have experienced a severe CM-related re-

action by modern non-ionic and low-osmolar CM are pretreated with oral antihistaminic drugs and glucocor-ticoids according to local expertise. Medications should start 13–16 h before the contrast-enhanced CT examina-tion; for urgent procedures the i.v. route is preferred.

Also, the type of CM responsible for a previous or cur-rent CM-related reaction should, if this information is available, be documented in the radiological report. Fur-ther use of this particular CM may then be avoided since

Table 1. CT diagnosis of NETs

Type of NET Sensitivitymean (range)

Specificitymean (range)

Detection ratemean (range)

Number ofpatients/studies

Reference

Endocrine pancreatic tumor 73% (63–82) 96% (83–100) 162/5 1–573% (39–94) 178/6 6–11

Liver metastases 82% (78–100) 92% (83–100) 135/4 12–1581% 21/1 11

Extrahepatic abdominal soft tissue metastases 75% (63–90) 99% (98–100) 77/4 12–1581% 21/1 15

Various NET lesions in abdomen and thorax 83% (61–100) 76% (71–80) 164/3 13, 16, 1776% 25/1 11

Small bowel NET at CT enteroclysis 50% 25% 8/1 1885% 97% 219a/1 19

Data in the literature on the sensitivity, specificity and detection rate for NET diagnosis by CT.a Out of 219 patients included in the study there were 19 subjects with carcinoids.



the CM-related side effect is related to the specific CM molecule, and not to iodine in general.

Diabetic patients treated with metformin should stop the drug the day before, or at the latest, the same day as the CM administration and have serum creatinine checked before restarting metformin. Although serum creatinine is routinely used, it should be interpreted with caution in the elderly and smaller patients; in such cases creatinine clearance can be used instead (normally 1 40 ml/min). A serum creatinine 6 130 � mol/l puts patients at risk for renal impairment; in such cases hydration with at least 1 litre of fluid before and after CM is adminis-trated. When serum creatinine is 1 180 � mol/l, CT ex-amination is generally performed without i.v. contrast enhancement.

As an aid, various computer software is available to make an estimation of the creatinine clearance by using the patient’s serum creatinine, weight, age and sex as in-put parameters according to the formula:

Estimated creatinine clearance = {k � [(140 – age) � weight in kg]/serum creatinine in � mol/l} ,

where k is a constant which is 1.23 for men and 1.04 for women [20] .

Data on the possible benefits of i.v. iodixanol as a CM in patients with renal impairment is still not convincing.

For filling of the bowel, patients generally drink 800 ml of tap water during 2 h before the CT examination of the abdomen. About 20 ml of CM (300–400 mg/ml) may be added to the tap water. However, for CT examination of the pancreas or when duodenal disease is suspected, the duodenum needs to be filled with water without ad-dition of CM. This is best achieved when the patient drinks the last 150–200 ml of water a few minutes before CT examination. It is usually sufficient to start filling of the bowel an hour before CT of the upper abdomen and the water volume may be reduced to 400 ml. Administra-tion of an anticholinergic agent (e.g. butylscopolamine 20 mg i.v.) to reduce bowel motility is optional.

For abdominal CT of the small bowel, CT enteroclysis, the filling of the bowel requires a larger volume, approx-imately 1.5 litres of water. The patient can drink the water during 1 h before the examination or it can be adminis-tered through a naso-gastro-jejunal tube. By using a ded-icated (150 ml/min rate) power injector, optimal filling of the whole small bowel may be achieved during enterocly-sis. CT enteroclysis can also be performed during i.v. con-trast enhancement.

CT of the colon requires i.v. contrast enhancement and is performed after cleaning the bowel and insufflating air

or CO 2 as for CT examination for suspected colonic car-cinoma.

Information Is Provided by the Clinician In order to perform a proper CT examination and to

decrease potential risks, it is necessary that the clinician provide adequate information. This includes the precise diagnosis, current medical therapy, previous surgery, and information regarding the presence of diabetes, renal im-pairment and previous CM-related adverse reactions. The results of previous imaging examinations are man-datory.

Imaging Technique The imaging protocols used for CT of the abdomen,

including the liver and pancreas, thorax and neck vary according to the local experience and routines. Given that the previously recommended hardware require-ments are taken into consideration and that bolus-track-ing technique is available, various examination protocols usually result in equally good examinations. Conse-quently, this consensus document is focused on basic ex-amination parameters, instead of detailed protocols, and important general imaging aspects are discussed.

Currently, MDCT of the abdomen, thorax and neck is performed using 4 ! 2.5- to 64 ! 0.6-mm detectors in 4- and 64-channel MDCT scanners, respectively. A pitch of 1.25–1.5 is recommended. The pitch is the table move-ment per tube rotation divided by the width of the total number of the detectors used. The resulting 1- to 3-mm transaxial images should preferably be reformatted in 2- to 3-mm multiplanar reconstructed images, the coronal and the sagittal planes using a 1/3 to 1/2 overlap to fa-cilitate reading and especially image presentation at clin-ical conferences.

Intravenous CM is administered given that the pa-tient’s renal function is considered. For i.v. contrast en-hancement of the abdomen, 1.5–2 ml/kg body weight (maximum 180 ml) 300–350 mg/ml non-ionic low- or iso-osmolar contrast material should be used at 3–5 ml/s injection rate, using a power injector. The use of a dual syringe injector is recommended by which a 40-ml injec-tion of physiological saline can be administered immedi-ately after the CM injection. This assures that the whole CM volume is utilised for contrast-enhancement purpos-es and it decreases the otherwise undesirably high CM concentration in the brachiocephalic vein and the supe-rior vena cava.

CT angiography and examination of the liver and pan-creas is preferably performed using bolus-tracking tech-



nique. When this is not available, the approximate ex-amination start for CT angiography is 15–25 s, portal-ve-nous inflow phase (also called the late arterial phase) 25–30 s and venous phase (also called portal, or portal-venous phase) 70–90 s after CM injection start. CT angi-ography may be needed in the preoperative setting, but usually the examination in the portal-venous inflow phase is sufficient to evaluate the anatomy of the arteries and their relation to the tumors. Also, the portal-venous inflow phase is in most cases sufficient for EPT diagnosis, and examination in the so-called pancreatic phase (at ap-proximately 40 s after CM injection start), which is advo-cated for CT of ductal pancreatic carcinoma, is generally not as advantageous for EPT imaging.

For proper examination of the liver, a sufficient amount of iodine must be injected in order to achieve adequate enhancement of the normal liver in the venous contrast-enhancement phase to optimise delineation of the poorly vascularised metastases. A high CM injection rate, at least 3–5 ml/s, results in proper enhancement of the aor-ta and the larger arteries for CT angiography. A similarly high i.v. CM influx is needed for enhancement of well-vascularised liver metastases in the portal-venous inflow phase and to achieve adequate enhancement of the pan-creas and renal parenchyma. Also, a high CM injection rate allows a better separation over time between the var-ious contrast-enhancement phases.

For CT enteroclysis, a naso-jejunal tube is placed downstream to the Treitz ligament, and 2 litres of warmed tap water are administered preferably by using a pump at 150–200 ml/min. Intravenous glucagon or anticholiner-gic drug is recommended and CT scanning is then per-formed during i.v. contrast enhancement 50 s after injec-tion of 120–150 ml at 3 ml/s. Because small lesions are anticipated, reconstruction of thin, approximately 2 mm, sections are recommended and viewing using multipla-nar reconstructions and cineloop is mandatory.

When the thorax and/or the neck is examined togeth-er with the abdomen, the amount of CM and the injection rates are adjusted to what is required to perform a proper CT of the abdomen. When the thorax and/or the neck, by contrast, are examined separately, the amount of CM in-jected and the injection rate can be decreased. MDCT of the neck also requires a somewhat lower CM injection rate: approximately 1.5–2 ml/kg body weight of CM is recommended to be injected at 2.5 ml/s and using a 40-s scanning delay. For CT examination of the thorax, even less CM and a lower injection rate can be used. Approxi-mately 1–1.5 ml/kg body weight of CM is administered at about 1.5 ml/s and a scanning delay of 60 s is preferable.

For CT of the liver, a so-called three-phasic examina-tion is required. This involves examination before (non-enhanced, native) and during i.v. contrast enhancement in the portal-venous inflow and in the venous phase. For follow-up of NET liver metastases, some restrict CT ex-amination to the venous contrast-enhancement phase and only when the initial imaging work-up has shown better delineation of the liver metastases in the non-en-hanced examination and/or in the portal-venous inflow phase one or both of these phases are added. This routine is, however, insufficient since there is a risk that new well-vascularised metastases may escape detection. Also, fatty infiltration of the liver, which may be initiated by medical therapy, can significantly change the imaging prerequi-sites. Liver metastases initially diagnosed during the ve-nous phase may no longer be visible at follow-up, but show up in the non-enhanced examination and/or the portal-venous contrast-enhancement phase. The risk of misinterpreting areas of normal parenchyma in a fatty infiltrated liver as metastases is also reduced by using three-phasic CT examination. Moreover, characterisa-tion of an adrenal incidentaloma may be performed when a pre-contrast examination is also included.

Coordination of CT scanning in relation to the CM injection is best controlled by using the ‘bolus-tracking’ technique, for which computer software is regularly sup-plied together with the CT scanner. This allows monitor-ing of the aortic enhancement during contrast medium administration in order to determine the optimum time point for the examination start. Various routines also ex-ist in the use of the bolus-tracking technique. For CT angiography and examination in the portal-venous contrast-enhancement phase a fixed attenuation value (around 150 Hounsfield units, HU) in the abdominal aorta may be used to initiate the scanning start. As an alternative, a lower value (around 100 HU) may be used to trigger the examination start but needs to be followed by a 10–15-s scan delay. In combined CT examinations of the abdomen and thorax, including three-phasic CT of the liver, the order that scanning of these body regions is performed depends on how the bolus-tracking technique is applied. Initially non-enhanced scanning of the liver is generally performed. Then the liver is examined in the portal-venous inflow phase and thereafter the thorax and abdomen in the venous phase. Alternatively, an examina-tion of the thorax early after CM injection start is favored and coordinated so that the subsequent scanning of the liver is performed in the portal-venous inflow phase, and thereafter the whole abdomen is examined in the venous phase.



Radiation Dose The radiation dose administered to the patient varies

with the examination protocol and the type of CT scan-ner. A high tube voltage and tube current, a long tube ro-tation time and a low pitch increases the dose. In order to maintain a proper image quality in large-size patients, the tube current is increased. This may be decreased in small-size patients. This results in a higher radiation dose to large- compared to small-size patients. With a MDCT scanner with few channels, the relatively narrow package of detectors needs to be rotated more times in order to scan the patient than in an MDCT scanner with addition-al channels and a wider detector package. With each tube rotation, the so-called penumbra zone of radiation at the cranial and caudal edges of the detector package adds to the radiation dose, consequently resulting in a higher dose to the patient in the former case.

An examination in a 16-channel MDCT scanner 16 ! 1 mm (‘one run’) of a patient of 70 kg results in an ap-proximate radiation dose of 6 mSv for the whole abdomen and 4 mSv for the upper abdomen (liver) from the dia-phragm to the iliac crest. An optimal MDCT examina-tion of the abdomen comprising three-phasic CT of the liver and examination of the pelvis in this 70-kg patient thus results in a 14-mSv radiation dose. Corresponding figures for MDCT of the thorax is 3.5 mSv and of the neck 4.5 mSv. By comparison, the resulting radiation dose is approximately 1/4 higher when using a 4-channel MDCT scanner (4 ! 2.5 mm).

Image Findings Gastric, duodenal, rectal and colonic NETs are diag-

nosed by endoscopy. The role of CT in these cases is to detect regional and distant metastases for staging of the disease.

For type 1 and type 2 gastric carcinoids, CT is not re-quired except for large ( 1 2 cm) and invasive tumors de-tected by EUS. Type 1 tumors are predominantly located in the fundus and body of the stomach and are typically multicentric, ! 1 cm in diameter, rounded with sharp margin and contrast-enhancing. Type 2 gastric carcinoids are usually multiple and located within the stomach wall which is thickened secondary to gastrin hypersecretion.

Type 3 gastric carcinoids are solitary, large lesions, with a more irregular and more diffusely delineated mar-gin that may ulcerate. These tumors can also extend into the fat surrounding the stomach ( fig. 1 ).

Duodenal NETs are usually small contrast-enhancing tumors and in the case of gastrinomas may be multiple. For CT diagnosis of the primary tumor it is important to

distend the duodenum with water and to perform the ex-amination during i.v. contrast enhancement since this will facilitate detection of the usually markedly contrast-enhancing tumor which is depicted against the low at-tenuating water in the bowel lumen.

Functional EPTs are typically small, sharply delineat-ed and can be multiple in patients with the MEN-1 syn-drome. These tumors tend to be best visualised as evenly contrast-enhancing tumors in the portal-venous inflow phase (at approximately 30 s) rather than in the pancre-atic contrast-enhancement phase (at approximately 40 s after CM injection start). In the venous contrast-en-hancement phase, EPTs usually exhibit higher attenua-tion than the surrounding normal pancreas.

Non-functioning EPTs are usually larger and may have calcifications that are best depicted in the non-con-trast-enhanced examination. Larger EPTs are usually not as well vascularised and may comprise areas of necrosis; contrast enhancement is not as pronounced and usually shows an irregular pattern. CT also delineates the posi-tion of the tumor in relation to the pancreatic and com-mon bile duct, evaluates possible vascular encasement and stages the disease with respect to regional lymph node involvement and presence of distant metastases, mainly to the liver. Larger EPTs can be confused with ductal pancreatic cancers. However, with a usually slow-ly growing EPT occluding the pancreatic duct, this is di-lated proximal to the occlusion and the surrounding pan-

Fig. 1. Transaxial CT image of a large gastric carcinoid type III extending from the stomach into the surrounding fat. Orally ad-ministered contrast medium is seen in the antrum of the stomach (arrow).



creatic parenchyma is severely atrophic and appears like a thin brim surrounding the dilated duct.

The small bowel carcinoids are mostly found in the ileum rather than in the jejunum and are usually small and occasionally multiple. Consequently, these small tumors are difficult to diagnose as filling defects at CT enteroclysis ( fig. 2 ). With the use of a positive (e.g., di-luted barium sulphate solution) oral CM the usually high attenuating carcinoid is more likely to escape de-tection than when the lesion is surrounded by a low at-tenuating oral CM such as water, similarly to what was previously discussed regarding diagnosis of duodenal tumors.

Frequently, midgut carcinoids present as mesenteric metastasis ( fig. 2 ). These can induce an intense desmo-plastic reaction causing contraction and tethering of the adjacent bowel loop resulting in partial or complete in-testinal obstruction. Vascular encasement of the superior mesenteric artery and vein may compromise bowel cir-culation. At CT, this is reflected as an irregular soft tissue mass, typically with one or several areas of calcifications, surrounded by radiating streaks in the mesenteric fat re-sembling spokes in a wheel. The superior mesenteric ar-tery and/or vein or branches/tributaries of these vessels may be encased by the tumor.

For NETs of the colon and the rectum, the role of CT is not to detect the primary tumor or to appreciate its in-vasion of the rectal wall, the surrounding mesorectum

and adjacent organs which instead is most likely better performed by MRI or US. Colonic NETs are generally di-agnosed by colonoscopy and fluoroscopy, and CT is therefore utilised to stage rectal and colonic NETs by de-tecting regional and distant metastases.

CT cannot differentiate liver metastases due to NETs from any other malignant tumors. Generally, NET liver metastases are well vascularised and best depicted during i.v. contrast enhancement in the portal-venous inflow phase where they show up as high attenuating lesions in the non-enhanced normal liver ( fig. 3 ). Poorly vascular-ised NET liver metastases are, however, also frequent. These are best depicted in the venous contrast-enhance-ment phase as low attenuating areas relative to the normal contrast-enhanced high attenuating liver parenchyma. Larger metastases are fairly often visible in the pre-con-trast images in which occasional areas of calcification are best seen. Peripheral contrast enhancement and central necroses in larger NET liver metastases are often seen.

Viewing of the CT examination should always be per-formed using window settings optimised for image read-ing of soft tissues, lung and bone, respectively. For liver and pancreas it is necessary to adjust the window setting and decrease the window width and to increase the win-dow centre (level) in the contrast-enhanced images to op-timise lesion detection.

The CT appearance of NET lymph node metastases is similar to those from other malignant tumors, although a marked contrast enhancement is frequent. However, some particular anatomical sites should be kept in mind during image reading. Besides in the mesentery and in the retroperitoneum, lymph node metastases from mid-gut carcinoids can often be found ventrally in the lower thorax adjacent to the thoracic wall and to the heart ( fig. 4 ). Also, retrocrural lymph node metastases are not infrequent ( fig. 5 ) as well as subcutaneous and breast me-tastases ( fig. 6 ) from midgut carcinoids. When evaluat-ing the CT examination for lymph node metastases, in anatomical regions where these may be surrounded by fat, it is often helpful to adjust the window setting by in-creasing the window width to facilitate lesion detection. Also, the use of multiplanar reconstructed images is ad-vantageous for depiction of small lymph node metasta-ses. Peritoneal carcinosis is occasionally seen, most often in the ventral aspect of the abdomen ( fig. 7 ).

Lung metastases from NETs, similarly to those from other malignant tumors, appear as rounded, usually mul-tiple and generally well-delineated soft tissue opacities. NET bone metastases are often sclerotic (blastic), but can be osteolytic and sometimes show a mixed appearance.

Fig. 2. CT enteroclysis of a contrast-enhancing carcinoid tumor in a small bowel loop (thick arrow). Adjacent to the tumor there are two small contrast-enhancing mesenteric metastases (thin ar-rows).



Documentation and Reporting of Results For research, the RECIST (Response Evaluation Crite-

ria in Solid Tumours) criteria are regularly used as the reference standard by which tumor response to treatment is reported and these criteria are therefore advantageous when comparing the results of different trials. However, in the daily clinical routine, the WHO (World Health Or-ganisation) criteria are usually applied. Measurable le-sions should exceed 1 cm largest diameter. Necrotic or confluent lesions should not be measured. Bone metasta-ses, pleural fluid, ascites, peritoneal carcinosis and lepto-

meningeal disease are non-measurable lesions. Except for the quantitative description of the measurable lesion siz-es and the sum of products or lengths, according to the WHO and RECIST criteria, respectively, also a qualita-tive description of the tumors regarding treatment re-sponse, e.g. necrosis, should be reported. The contrast-enhancement phase in which the lesions are best depicted should be reported. In order to accurately communicate the diagnostic information, liaison between radiologists and clinicians is essential.

Fig. 3. a Transaxial CT image during i.v. contrast enhancement in the portal-ve-nous inflow phase of several well-vascu-larised midgut carcinoid liver metastases. b In the venous phase the metastases are no longer discernible.

Fig. 4. Transaxial CT image during i.v. contrast enhancement in the venous phase of two retrocrural midgut carcinoid lymph node metastases (arrows).

Fig. 5. Transaxial CT image during i.v. contrast enhancement in the venous phase of two metastases in the right thorax in front of and behind the inferior vena cava, respectively (arrows).



Magnetic Resonance Imaging

Sensitivity, Specificity and Detection Rates The number of studies on MRI in NET patients is even

smaller compared to CT. The MRI-acquired sensitivity, specificity and detection rate (mean and range based on the number of patients and studies) for NETs at various anatomical sites is presented in table 2 .

In 2 studies on MRI for detection of EPT, a fairly large number of 54 patients were included and a mean 93% (85–100%) sensitivity and 88% (75–100%) specificity was

obtained [21, 22] . An even larger number of 192 patients were included in 5 studies showing a mean 73% (range 50–94%) detection rate for EPT [6, 9, 11, 23, 24] .

Diagnosis of NET liver metastases was evaluated in 3 trials including 74 patients resulting in an overall mean 82% (range 80–85%) detection rate [11, 15, 23] . In a direct comparison of MRI with somatostatin receptor scintig-raphy and CT in 64 patients, MRI detected 95% of liver metastases [25] .

Extrahepatic abdominal soft tissue metastases were evaluated in 34 patients showing a sensitivity and speci-

Fig. 6. Transaxial CT image during i.v. contrast enhancement in the venous phase of a metastasis in the left breast from a lung car-cinoid.

Fig. 7. Transaxial CT image during i.v. contrast enhancement in the venous phase of a patient with midgut carcinoid who has de-veloped peritoneal carcinosis. Tumor lesions are seen ventrally adjacent to the abdominal wall both on the right and left side (ar-rows).

Table 2. MRI diagnosis of NETs

Type of NET Sensitivitymean (range)




Reference

Endocrine pancreatic tumor 93% (85–100) 88% (75–100) 54/2 21, 2273% (50–94) 192/5 6, 9, 11, 23, 24

Liver metastases 82% (80–85) 74/3 11, 15, 2395% 64/1 25

Extrahepatic abdominal soft tissue metastases 89% 100% 34/1 1568% (55–81) 58/2 11, 23

Data in the literature on the sensitivity, specificity and detection rate for NET diagnosis by MRI.



ficity of 89 and 100%, respectively [15] . In 2 studies on 58 patients a mean detection rate of 68% (range 55–81%) was obtained [11, 23] .

Hard- and Software Requirements The development of MRI over the last few years has

resulted in increased field strengths; with current stan-dards an MR scanner with a field strength of 1.5 T or higher should be used. The use of a phased array torso coil is recommended.

The scanner should allow examination with at least3 mm and not more than 5 mm thick sections. The ability to use fast acquisitions in 3D during one breath hold is rec-ommended to decrease or eliminate respiratory image ar-tefacts and facilitate the use of i.v. CM. Fat-suppressed se-quences are recommended to increase tissue contrast. The image quality for various MRI sequences may, however, vary between scanners from different vendors and with the field strength. For MRI of the pancreas, MR cholan-giopancreatography (MRCP) should be available to visu-alise the pancreatic duct and detect any duct obstruction.

Patient Information and Preparation In general, the presence of magnetic metal implants

and pacemakers is considered a contraindication for per-forming MRI. Patients should be asked about any previ-ous metal implant procedures so that the material can be checked against a list of procedures, available at MRI de-partments, that precludes an MRI examination.

The problem with claustrophobia is more pronounced with MRI than CT and the patient should be informed that during the examination he or she will be placed in a long tunnel and will have to remain still during the ap-proximately 30 min of the examination. If the patient is claustrophobic, administration of diazepam may be nec-essary. During the examination there will be a loud crack-ing sound in the scanner that will require earplugs. When CM needs to be administrated, i.v. access is obtained and before some examinations, e.g. of the small bowel, the patient needs to be at the department an hour in advance for filling of the bowel. Before MRI of the pancreas, fill-ing of the stomach and duodenum with paramagnetic fluid is advantageous to decrease image artefacts that may impair the image quality, especially of MRCP.

The patient’s history should be checked for diabetes and renal impairment, and the risk for nephrogenic sys-temic fibrosis, which may be associated with the use of gadolinium (Gd) CM in patients with chronic renal fail-ure, should be observed when Gd-contrast enhancement is considered.

Information Provided by the Clinician In order to optimise the MRI performance and de-

crease the risks from the examination procedure, the re-ferring physician needs to provide information regarding patient’s diagnosis, medical therapy, previous surgery, kind of surgery and the findings at surgery and results of previous imaging examinations. Information regarding the presence of diabetes, renal impairment (risk of neph-rogenic systemic fibrosis) and magnetic metal implants are mandatory. Please see also pertinent parts in the cor-responding paragraph regarding CT.

Examination Technique In order to optimise image quality, the field of view

should be kept as small as possible and the thinnest sec-tions available should be chosen. No slice gap should be used if it can be avoided. In contrast to CT, i.v. adminis-tration of an anti-peristaltic drug (e.g. butylscopolamine 20 mg i.v.) is recommended to optimise MRI examination of the pancreas and bowel.

MRI is generally not optimal for thorough examina-tion of extended body areas. In order to allow for a high-quality MRI, including all proper sequences and dynam-ic imaging during i.v. contrast enhancement, only a lim-ited part of the body can be examined within a reasonable period of time. In addition to this fact and due to the gen-erally more limited availability of MRI compared to CT, MRI is best used as a ‘problem-solving tool’. It can be ap-plied when there is strong suspicion for a NET not docu-mented by other imaging modalities and when the results of these are equivocal or contradicting. Conversely, if ex-tended body areas are included, there is usually no time to apply the most optimal technique and the examination needs to be performed with thicker sections, fewer se-quences and without applying proper contrast-enhance-ment techniques.

The MRI sequences that are generally recommended for the detection of NETs are fat-saturated transaxial T 1 -weighted (if available water selected) and fat-saturated T 2 -weighted sequences (if available spectral inversion re-covery SPIR) and optionally fat-saturated transaxial in and out of phase T 1 -weighted sequences. For MRI of the pancreas, MRCP should also be performed by coronal radiated T 2 -weighted thick slice (25 mm) radiated se-quences with two ranges including the pancreatobiliary junction and the pancreatic body, respectively, to better evaluate the regional anatomy and the relation of the EPT to the pancreatic duct and the main bile duct. T 2 thin slices MRCP with 3D acquisition is also accurate.



Short breath-hold sequences are recommended when ‘moving targets’ such as liver, pancreas and bowel are ex-amined. Transaxial dynamic Gd contrast-enhanced MRI should be applied. This involves acquisition at 30, 70 and 120 s and at 3–5 min after injection start. 3D acquisitions are recommended, particularly for dynamic examina-tions, which can be reconstructed in various anatomical planes and not only to produce transaxial sections.

The conventional extracellular Gd-based MRI CM, with a pharmacokinetic pattern similar to that of iodine CM used for CT, remains the standard for i.v. contrast-enhanced MRI. Liver-specific i.v. CM for characterisa-tion of liver lesions are optional.

Some Gd chelates (Gd-DTPA, Gd-EOB-DTPA) imme-diately after injection act as extracellular contrast agents but are not eliminated with glomerular filtration. Instead they accumulate in the hepatocytes during a relatively long period of time following injection (approximately 15–120 min depending on the chelate) and thereby make tumor tissue appear hypointense. Mn-DPDP is a manga-nese-based hepatocyte-specific contrast agent that re-tains a strong paramagnetic effect approximately 15 min to 4 h following injection producing an increased signal in the normal liver parenchyma. Mn-DPDP may also be used for MRI of the pancreas.

Superparamagnetic iron oxide particles are composed of iron oxide crystals coated with dextran or carboxydex-tran and are taken up by the Kupffer cells but are not re-tained in tumor tissue. The particles induce strong relax-ation effects in the normal liver parenchyma, which be-comes hypointense, while tumors appear hyperintense relative to the liver parenchyma, thereby increasing tissue contrast.

Image Findings At MRI, a NET appears typically as a low signal lesion

in T 1 - and a high signal lesion in T 2 -weighted images.The MRI appearances of NETs are similar to those of CT concerning tumor delineation, contrast-enhancement characteristics and various morphologic patterns. Al-though spatial resolution is poorer with MRI than CT, the better soft tissue contrast of MRI facilitates the detec-tion of small NETs.

Detection of small EPTs is favorable with MRI ( fig. 8 ), particularly with T 1 water selected and T 2 SPIR thin slic-es. EPT typically is not associated with main pancreatic duct stenosis and upstream enlargement ( fig. 8 ), and this fact is particularly underlined by the findings at MRCP.

Depiction of small liver metastases is also favorable by MRI using these signal sequences and lesions that are

equivocal or contradictory at CT and CEUS may better be characterised by using the various MRI sequences and should also include dynamic examination with i.v. CM.

Although EPT liver metastases commonly show very high signal intensities on T 2 -weighted images, making their distinction from cavernous haemangioma difficult, Gd-enhanced hepatic arterial dominant-phase imaging facilitates their differentiation. Thus, liver metastases regularly show heterogeneous intense enhancement while a haemangioma during the arterial dominant con-trast-enhancement phase typically displays globular pe-ripheral skip enhancement. In the haemangioma the con-trast enhancement will subsequently gradually extend towards the lesion center, and during the late contrast-enhancement phase a complete filling of the haemangio-ma is regularly seen. The haemangioma will then appear hyperintense compared to the normal liver whereas the washout of the CM from a liver metastasis regularly will make the lesion appear relatively hypointense [26] . Danet et al. [27] , who evaluated MR imaging findings on 512 metastatic lesions in 165 patients with NETs, reported that ring enhancement was observed in 72% of patients during the hepatic arterial dominant phase. Peripheral low intensity area signs were observed in the post-con-trast late phase, and perilesional enhancement in the por-tal-venous phase was found in 92% of hypovascular me-tastases.

Fig. 8. Coronal T 2 -weighted MR image showing a hypersignalling EPT in the pancreatic head (arrowhead). The common bile duct can be clearly delineated (arrow) and is not compromised by the tumor.



Fig. 9. Sagittal T 1 -weighted MR image of the spine showing hy-pointense midgut carcinoid bone metastases most evident in the vertebral bodies of thoracic vertebra 10 and lumbar vertebrae 3 and 5.

Fig. 10. Transaxial MR image of the brain during i.v. Gd contrast enhancement in the venous dominant phase showing contrast-enhancing cerebellar metastases (arrows) from a midgut carci-noid.

Table 3. US, EUS, IOUS and CEUS diagnosis of NETs

Type of NET and US method

Sensitivitymean (range)




Reference

Endocrine pancreatic tumorUS 39% (17–79) 153/6 28–33EUS 90% (77–100) 261/10 10, 29–31, 33–38

93% 95% 75/1 39IOUS 92% (74–96) 127/4 28, 31, 40, 41

InsulinomaEUS 92% (88–94) 86/4 10, 30, 37, 39IOUS 92% (84–96) 109/3 28, 40, 41

Duodenal tumors and lymph node metastasesUS 18% 25/1 33EUS 63% 59/2 33, 36

Liver metastasesUS 88% 95% 131/1 12CEUS 82% 48/1 42

Data in the literature on the sensitivity, specificity and detection rate for NET diagnosis by US, EUS, IOUS and CEUS.



The application of MRI for locoregional staging of rec-tal NETs is mentioned earlier in the CT section of this paper. Imaging of distant metastases in bone ( fig. 9 ) and brain ( fig. 10 ) is advantageous by MRI.

Documentation and Reporting of Results The documentation and reporting of results of MRI is

similar to that of CT. The standardised report used for rectal cancer, according to the consensus conferences, must be used.

Ultrasound

Sensitivity, Specificity and Detection Rates US is known to be an operator-sensitive modality lead-

ing to wide variation regarding sensitivity and specificity of the reported series. The US-, EUS-, IOUS- and CEUS-acquired sensitivity, specificity and detection rate (mean and range based on the number of patients and studies) for NETs at various anatomical sites is presented in ta-ble 3 .

For EPT diagnosis, a mean 39% (range 17–79%) detec-tion rate was found in 6 studies including 153 patients [28–33] . EUS is the most sensitive method for diagnosing EPTs and a mean 90% (range 77–100%) detection rate was shown in 10 studies comprising 261 patients [10, 29–31, 33–38] . In a study on 75 patients the sensitivity was 93% and the specificity 95% [39] . IOUS is also a sensitive meth-od for detecting EPTs with a mean 92% (range 74–96%) detection rate reported in 4 studies that included 127 pa-tients [28, 31, 40, 41] . When insulinomas are considered separately, the mean detection rate of EUS was 92% (range 88–94%) in 4 studies including 86 patients [10, 30, 37, 39] and that of IOUS, 92% (range 84–96%) in 3 studies on 109 patients [28, 40, 41] .

For duodenal tumors and lymph node metastases, the detection rate of US was 18% in a study on 25 patients [33] and that of EUS 63% in 2 studies comprising 59 patients [33, 36] .

Studies reporting on US for the detection of liver me-tastases exclusively from NETs are scarce. However, in one study including 131 patients with various NETs, US exhibited an 88% sensitivity and 95% specificity, whereas in a subgroup of 87 patients with carcinoid tumors the corresponding figures were 82 and 92%, respectively [12] . CEUS has been shown to be more sensitive for the diag-nosis and characterisation of liver lesions than conven-tional US. In 48 patients with NETs and suspicion of liv-er metastases, the sensitivity of CEUS was 82% [42] . The

diagnostic yield of US-guided biopsies in 129 patients was shown to improve by CEUS compared to conventional US [43] . Liver haemangiomas were easier to characterise by CEUS than by pre-contrast US [44] .

Hard- and Software Requirements The possibility of using different transducers with ap-

propriate ultrasound frequencies is important. The deep-er portions of the abdomen require better penetration of a low-frequency transducer than more superficial areas where a high frequency transducer is preferred. With the recent development of US transducer, the frequency in one single transducer may be adjusted according to the different needs during the examination. By harmonic imaging technique the sensitivity of US can be improved. The use of i.v. CM for US is an important development of the technique, and preferably the US equipment software should allow for CEUS.

Patient Information and Preparation The patient needs to be informed that the examination

generally lasts 15–30 min, unless CEUS, which lasts lon-ger, is performed. During US of the abdomen patients may repeatedly need to hold their breath for a few sec-onds, and the insertion of an i.v. catheter before CEUS may cause some discomfort.

Information Provided by the Clinician US of the abdomen in obese patients is difficult to per-

form and tends to be unreliable as abdominal organs can-not be sufficiently penetrated. These patients are better candidates for CT or MRI examination. An exception from this rule is US-guided biopsy, which can always be tried and, if needed, converted into a CT-guided proce-dure. The referring physician needs to provide informa-tion regarding the patient’s diagnosis, kind of medical therapy, previous surgery, kind of surgery and the find-ings at surgery and results of previous imaging examina-tions. If CEUS is contemplated, information should be provided regarding previous insertion of cardiac valve prosthesis since the use of i.v. CM for US in these patients presently is not accurate (bubbles are broken by such prosthesis), and recent cardiac angina is a contraindica-tion due to the risk of acute cardiac insufficiency. Please see also pertinent parts in the corresponding paragraph regarding CT and MRI.

Examination Technique As opposed to CT, which allows detailed examination

of the whole abdomen and of additional body regions



(thorax, neck) at the same session, US is better suited for examination of limited parts of the abdomen, for exam-ple the pancreas and the liver.

Because US is an operator-dependent procedure, an op-timal examination technique is essential. Examination by using different transducer frequencies is important. Low frequencies (about 3 MHz) better penetrates tissues, but high frequencies (approx. 5 MHz) allow for higher spatial resolution. The advantage and drawback of the high and low frequencies must be considered during the examina-tion and used accordingly for examination of deep and superficial parts of the abdominal organs, respectively. Abdominal organs are generally easier to examine during a breath hold, and it is often advantageous to place the pa-tient in different positions on the examination couch and perform US while the patient is standing up or during a Valsalva manoeuvre enlarging the abdominal wall. This can be especially helpful for the examination of the pan-creas, when bowel gas, especially in the transverse colon, prevents accurate ultrasound penetration.

Doppler techniques (power Doppler, colour-coded Doppler) are valuable in order to evaluate the tumor vas-cularity and are helpful in distinguishing vascular from non-vascular tubular structures.

By dynamic CEUS the temporal and spatial pattern of tumor uptake and washout (in- and outflow) of the CM

may be evaluated. CEUS may therefore be considered for localisation of EPTs and NET liver metastases. By CEUS, liver metastases in the 2- to 3-mm range may be readily detected and previously equivocal tumor findings at un-enhanced US, or CT, may be characterised. CEUS is man-datory when percutaneous radiofrequency ablation of liver metastases is considered. A limitation of the tech-nique, however, is that the whole liver may not be evalu-ated by US during all phases of contrast enhancement.

In case of negative preoperative US in patients with the Zollinger-Ellison syndrome, peroperative US is recom-mended by which the duodenal wall and pancreatic head can be explored.

Image Findings Abdominal ultrasound and CT are complementary

radiological methods used to diagnose EPTs, liver metas-tases, lymph node and mesenteric metastases and these are an excellent tool for guiding the biopsy needle to ob-tain a tumor tissue specimen ( fig. 11 ). By US, the bile ducts, the pancreatic duct and vessels may be evaluated for dilatation and tumor invasion and free fluid in the abdomen and pleural spaces may be detected.

Intestinal tumors are rarely detected but are occasion-ally seen as a low echogenic wall thickening or polypoid tumor, which is well vascularised. A large locally advanced intestinal NET infiltrating the surrounding tissues is more easily detected. The ability of US to differentiate an adeno-carcinoma of the colon from a NET is poor.

An EPT is typically a low echogenic and hypervascu-lar lesion. As with CT and MRI, the local extent of the tumor should be assessed. The relation of the EPT to the pancreatic duct and the common bile duct should be de-termined as well as any encasement or invasion of the splenic vein and the superior mesenteric artery and vein.

Mesenteric metastases from a midgut carcinoid and mesenteric and retroperitoneal lymph node metastases are seen as low echogenic masses. The desmoplastic reac-tion, which by CT and MRI is a characteristic feature of a mesenteric metastasis from a midgut carcinoid, cannot be detected by US.

NET liver metastases cannot be differentiated from any other type of liver metastases. Small ( ! 1 cm) metas-tases generally appear as low echogenic rounded lesions, whereas large ( 1 1 cm) metastases usually are highly echo-genic ( fig. 11 ) with a low echogenic halo and may have central low echogenic necrosis. These lesions often ap-pear hypervascular by Doppler techniques and CEUS. In patients with fatty infiltration of the liver, resulting in a

Fig. 11. Transabdominal US image showing a high echogenic liv-er metastasis of an EPT. The white track lines for the US-guided biopsy of the metastasis are displayed in the image.



high echogenic normal parenchyma, the NET metastases may instead appear low echogenic.

Documentation and Reporting of Results The documentation and reporting of results by US is

similar to that of CT and MRI. However, for therapy monitoring, the reported lesion sizes by US are generally difficult to compare with those measured by CT and MRI. This is because the size of the lesions, according to the WHO and RECIST criteria, are measured in the transaxial CT and MRI images whereas by US these tu-mors are measured in undefined anatomical imaging planes. Usually the US measurement is performed in the plane in which the lesions by US appear largest. Also, an overview of the tumor load is generally difficult to make by US in patients with extended disease. For example, the assessment of the tumor burden by US in a patient in whom the normal liver is almost replaced by metastases is generally unreliable. Therefore, US is not employed for initial diagnosis or therapy monitoring in clinical trials (except to evaluate superficial tumor lesions as an adjunct to estimating the lesion size by palpation). However, in the clinical setting, US is an excellent method for diagno-sis and characterisation of NETs. Since CT and US are complementary imaging methods, they may both be ad-vantageous for using therapy monitoring in order to de-crease the radiation dose to the patient, particularly to those who are young and have a long life expectancy.

List of Participants

List of Participants of the Consensus Conference on the ENETS Guidelines for the Standard of Care for theDiagnosis and Treatment of Neuroendocrine Tumors,Held in Palma de Mallorca (Spain), November 28 toDecember 1, 2007 Göran Åkerström, Department of Surgery, University Hospi-

tal, Uppsala (Sweden); Bruno Annibale, University Sa pienza Roma, Rome (Italy); Rudolf Arnold, Department of Internal Medicine, Philipps University, Munich (Germany); Emilio Bajet-ta, Medical Oncology Unit B, Istituto Nazionale Tumori, Milan (Italy); Jaroslava Barkmanova, Department of Oncology, Univer-sity Hospital, Prague (Czech Republic); Yuan-Jia Chen, Depart-ment of Gastroenterology, Peking Union Medical College Hospi-tal, Chinese Academy of Medical Sciences, Beijing (China); Fre derico Costa, Hospital Sirio Libanes, Centro de Oncologia, São Paulo (Brazil); Anne Couvelard, Service de Gastroentérologie, Hôpital Beaujon, Clichy (France); Joseph Davar, Department of Cardiology, Royal Free Hospital, London (UK); Wouter de Herd-er, Department of Internal Medicine, Section of Endocrinology, Erasmus MC, Rotterdam (The Netherlands); Gianfranco Delle Fave, Ospedale S. Andrea, Rome (Italy); Barbro Eriksson, Medical

Department, Endocrine Unit, University Hospital, Uppsala (Sweden); Massimo Falconi, Medicine and Surgery, University of Verona, Verona (Italy); Diego Ferone, Departments of Internal Medicine and Endocrinological and Metabolic Sciences, Univer-sity of Genoa, Genoa (Italy); David Gross, Department of Endo-crinology and Metabolism, Hadassah University Hospital, Jeru-salem (Israel); Ashley Grossman, St. Bartholomew’s Hospital, London (UK); Björn Gustafsson, Medi sinsk avd, Gastroseksjon, St Olavs Hospital, Trondheim (Norway); Rudolf Hyrdel, II. Inter-nal Medical Department, University Hospital Martin, Martin (Slovakia); Diana Ivan, Endocrinology and Diabetology, Klini-kum der Philipps-Universität, Marburg (Germany); Reza Kian-manesh, UFR Bichat-Beaujon-Louis Mourier, Service de Chirur-gie Digestive, Hôpital Louis Mourier, Colombes (France); Günter Klöppel, In stitut für Patho logie, TU München, Munich (Germa-ny); Ulrich-Peter Knigge, Department of Surgery, Rigshospitalet, Copenhagen (Denmark); Paul Komminoth , Institute for Pathol-ogy, Stadtspital Triemli, Zürich (Switzerland); Beata Kos-Kudła, Slaska Akademia Medyczna Klinika Endo krynologii, Zabrze (Poland); Dik Kwekkeboom, Department of Nuclear Medicine, Erasmus University Medical Center, Rotterdam (The Nether-lands); Rachida Lebtahi, Nuclear Medicine Department, Bichat Hospital, Paris (France); Val Lewington, Royal Marsden, NHS Foundation Trust, Sutton (UK); Anne Marie McNicol, Division of Cancer Sciences and Molecular Pathology, Pathology Depart-ment, Royal Infirmary, Glasgow (UK); Emmanuel Mitry, Hepa-togastroenterology and Digestive On cology, Hôpital Ambroise-Paré, Boulogne (France); Ola Nilsson, Department of Pathology, Sahlgrenska sjukhuset, Gothenburg (Sweden); Kjell Öberg, De-partment of Internal Medicine, Endocrine Unit, University Hos-pital, Uppsala (Sweden); Juan O’Connor, Instituto Alexander Fleming, Buenos Aires (Argentina); Dermot O’Toole, Department of Gastroenterology and Clinical Medicine, St. James’s Hospital and Trinity College Dublin, Dublin (Ireland); Ulrich-Frank Pape, Department of Internal Medicine, Division of He patology and Gastroenterology, Campus Virchow-Klinikum, Charité-Uni ver-si täts me dizin Berlin, Berlin (Germany); Mauro Papotti, Depart-ment of Biological and Clinical Sciences, University of Turin/St. Luigi Hospital, Turin (Italy); Marianne Pavel, Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité-Universitätsme dizin Berlin, Berlin (Germany); Aurel Perren, Institut für Allgemeine Pathologie und Pathologische Anatomie der Technischen Universität München, Klinikum r.d. Isar, Munich (Germany); Marco Platania, Istituto Nazionale dei Tumori di Milano, Milan (Italy); Guido Rindi, Department of Pa-thology and Laboratory Medicine, Università degli Studi, Parma (Italy); Philippe Ruszniewski, Service de Gastroentérologie, Hôpi-tal Beaujon, Clichy (France); Ramon Salazar, Institut Català d’Onco logia, Barcelona (Spain); Aldo Scarpa, Department of Pa-thology, University of Verona, Verona (Italy); Klemens Scheid-hauer, Klinikum rechts der Isar, TU München, Munich (Germa-ny); Jean-Yves Scoazec, Anatomie Pathologique, Hôpital Edouard-Herriot, Lyon (France); Waldemar Szpak, Westville Hospital, Mayville (South Africa); Babs Taal, Netherlands Cancer Centre, Amsterdam (The Netherlands); Pavel Vitek, Institute of Radia-tion Oncology, University Hospital, Prague (Czech Republic); Bertram Wiedenmann, Department of Internal Medicine, Divi-sion of Hepatology and Gastroenterology, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin (Germa-ny).



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ENETS Consensus Guidelines for the Standards of Care in ...ic resonance imaging (MRI), ultrasonography (US), con-trast-enhanced US (CEUS), endoscopic US (EUS) and intraoperative US