2012 ISSUE 6 Newsletter

EFSUMB Newsletter

EFSUMB Newsletter European Federation of Societies for Ultrasound in Medicine and Biology

Ultrasound Learning Centre at the 20th United European Gastroenterology Week in Amsterdam from 20–23 October, 2012 Despite its tremendous diagnostic and therapeutic potential, ultrasound is still performed by only a minority of Gastroenterologists in Europe and all over the World.

The reasons for this serious diagnostic and therapeutic deficit in international Gastroenterology is caused by numerous factors such as unavailability of ultrasound machines, introduction of sonographers in many countries and lack of educational opportunities. This unacceptable situation led Lucas Greiner and others 15 years ago to introduce ultrasound into an international gastroenterological organisation, the United European Gastroenterology (UEG) in favour of our patients. The UEG turned out to be the perfect partner in order to advance the idea of gastroenterologists performing ultrasound on a high professional level. Hence, an Ultrasound Learning Centre (ULC) was established at the annual meetings of the UEG. Since then an international faculty from various European countries was prepared to teach doctors from all over the world basic and advanced ultrasound. The idea of including ultrasound into the triad of firstly taking patients history, secondly performing clinical examination and thirdly performing ultrasound at the same time was then called “Clinical ultrasound”. This approach offers fundamental advantages over performing ultrasound investigations rather statically.

However, in order to be able to further develop this issue, gastroenterologists are needed and in demand to perform clinical ultrasound everywhere in the world.

ween EFSUMB and the UEG allowing for optimal support and improvement of the teaching programme. This positive development explains why the meeting was so successful.

The ULC at the 20th UEG Week 2012 for the first time took place with a contract bet-

Special topics in abdominal ultrasound were dealt with on day 2. Abdominal

We had the opportunity to meet physicians from all over the world: Arab Emirates, ­Bulgaria, Greece, Russia, Israel, Lithuania, Mongolia, Norway, Poland, Romania, Russia, South Africa and many other countries.

More than 360 colleagues attended the ULC to increase their knowledge on clinical gastroenterological ultrasound (60 basic courses, 100 postgraduate courses and more than 200 individual trainings).

On day one the programme offered basics and an introduction in abdominal ultrasound. Ultrasound anatomy was presented organ by organ in numerous lectures followed by intense hands-on training on patient models with ultrasound machines kindly provided by Hitachi Medical Systems.

blood vessel pathology, intestinal pathology, diffuse and focal liver pathology, bile duct and gallbladder pathology, pancreas pathology, contrast enhanced ultrasound and many other topics were highlighted by an international faculty from France, Germany, Lithuania, Norway and Romania. The lectures were complemented by more sophisticated abdominal ultrasound hands-on training.

On 22 and 23 October Noon Lectures with topics in “Ultrasound for the Gastroenterologist” were held (for programme and lectures visit www.efsumb.org or www. ultraschalltagung-bb.de). Complex issues in gastroenterology were dealt with in close association with guidelines and recommendations of our national and international gastroenterological organisations. New developments in ultrasound were brought closer to our colleagues and case-movie quizzes challenged the auditorium. In the morning and in the after-

Hands-on-training

EFSUMB Lynne Rudd 26 Portland Place, London W1B 1LY, United Kingdom Tel: +44 (0) 20 7099 7140 Email: efsumb@efsumb.org

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EFSUMB Newsletter noon intense hands-on training was offered to the many participating colleagues in the ULC. Looking back on the 15th ULC at the 20th UEG Week we are convinced that we should continue to spread the idea of gastroenterologists utilizing ultrasound to

obtain diagnoses and perform ultrasound guided interventions for the benefit of our patients. We received very positive feedback from colleagues from all over the world and we were unanimously motivated to intensify our efforts to push ultrasound forward in order to achieve the goal that gastroenterological ultrasound per-

Contrast Enhanced Ultrasound Guided Biopsies. An Increasing Role in Clinical Practice Introduction ▼▼

In spite of dramatic improvement in imaging and tumoral markers over the last ­years, ­percutaneous biopsy continues to be used for tumor diagnosis.

With all the advantages offered by ultrasound guidance, the overall sensitivity of this method in the diagnosis of tumor remained around 90 %. Consistent progress has been made in recent years in terms of needle design [1] or ultrasound ­ methods with complementary role in guidance (Color or Power Doppler, 3D / 4D ultrasound, navigation systems) [2–4].

The performance of percutaneous guided puncture biopsy in the tumoral diagnosis is limited by several factors, among which tumor characteristics such as tumor type, size and location play an important role.

The performances are lower for large tumors due to the existence of tumoral necrosis or fatty changes. Necrotic tissue cannot be identified on B-mode sonography, especially before liquefaction has occurred, possibly leading to an unsuccessful biopsy or a false-negative diagnosis [5].

In larger lesions biopsy is performed therefore in the peripheral zone or a hypervascular area of the tumors.

Due to difficulties of visualization and targeting, small lesions represent another cause of false negative result of percutaneous biopsy. Lesions deep located or in risky locations (i. e. near major vascular structures, gallbladder, colon or pancreas) and those with low visibility on B-mode ultrasound are other factors responsible for failures or increased complication rate [5, 6]. Peculiarities of tumors, where lesions are often invisible in B-mode ultra-

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sound (often multifocal lesions of adenocarcinoma of the prostate, small liver metastasis) or their distribution is unequal (i. e. in tumoral lymph nodes) require the use of special techniques, which require multiple, systematic passages with scanning of the whole parenchyma. This approach inevitably increases labor costs, risk of complications and degree of acceptance by the patient [7].

Contrast Harmonic Ultrasound ▼▼

Beside the well accepted use of CEUS in detection and characterization of various tumors, especially those located in the liver, this technique has enabled the delimitation of the avascular, necrotic areas from the viable, active, vascularized regions of the tumors. The necrotic areas usually present no enhancement in all vascular phases of CEUS and may appear echo free or slightly hypoechoic in the background of enhanced liver parenchyma.

First data published in literature have reported that using CEUS it may be possible to increase the accuracy of percutaneous needle biopsy in the tumoral diagnosis by targeting hyperperfused tumor areas or increasing the conspicuity of liver metastasis [8, 9].

The potential added value of CEUS in tumor diagnosis by means of percutaneous biopsy may be related to several factors: a) targeting of the needle in the vascular, viable areas of several tumors b) avoiding avascular areas (truly necrosis) in larger tumors (retroperitoneal, renal, adrenal) [8] or in those with frequent necrosis (kidney, liver metastases, especially the larger

formed by gastroenterologists will be ­accepted in Europe and all over the world.

Klaus Schlottmann (Germany) Alina Popescu (Romania) Dieter Nürnberg (Germany) (Course Directors)

ones – i. e. those arising from colon or renal ­cancer) c) avoiding hypovascular areas in certain tumors. The hypovascularity may be explained by the presence of marked fibrosis in pancreatic adenocarcinoma (and in liver metastasis from those tumors), fat areas in hepatocellular carcinomas (HCCs) and desmoplastic tissue in sarcomas or pancreatic tumors d) directing the needle in the tumor-­ affected areas of an organ (ganglion, prostate) in case of patchy involvement e) targeting of otherwise invisible ­lesions or those hardly visible (small ­nodules of HCC on cirrhosis, adenocarcinoma’s areas in the prostate, lung tumors in anatelectatic consolidation) [9–11].

Technique ▼▼

CEUS guided biopsy may be performed using an ultrasound system able to scan at low MI (0.06–0.1) and several transducers for abdominal, small parts and endocavitary applications. An attached needle guide is not mandatory but should be used especially for biopsies performed in arterial phase. For prostate biopsy an endocavitary transducer 5–10 MHz with a needle guide is used.

When using hexafluoride microbubbles (SonoVue®, Bracco, Italy) a pre procedural planning CEUS is performed. If the lesion shows an homogenous enhancement in arterial phase the biopsy is done with conventional US guidance. If unenhanced necrotic areas are present the puncture may be done either by CEUS guidance or, if the necrosis is not so large, by US guidance in areas previously selected by CEUS. For liver tumors, scanning in portal (30– 120 s after injection) and parenchymal phase (120–600 s after injection) is important to detect invisible or poorly visib-

EFSUMB Newsletter le lesions, to characterize them and to select a proper one for a subsequent CEUS biopsy.

Using the 2–9 MHz transducer ultrasound was performed in a split-screen mode, which displays the CEUS image on the right side and the background B-mode US image on the left side, simultaneously, on a single monitor.

In cases where large unenhanced areas were found on the planning CEUS, the needle is directed in arterial phase into the enhanced, perfused areas. For poorly visible tumoral lesions in B mode ultrasound the biopsy is performed in parenchymal phase when the lesions wash out and the tissue to lesion contrast ratio is maximal.

The biopsy needles are well visible under CEUS conditions due to the fact that the needle causes tissue motion in the vicinity of the needle which generates harmonic signals, detected by the transducer. For automatic TruCut needle (i. e. Bard type) the presence of air in the side notch is ea-

sily visible after the automatic tissue retrieval [12]. Sometimes the bright contrast enhancement in the surrounding parenchyma masks the echogenic biopsy needle in CEUS image [13].

One technical difficulty is related to the short period of arterial enhancement available for puncture. If the tip of the needle is lost it may take some time to find it and to perform the biopsy without losing the arterial enhancement. This limitation may be overcome by the use of needle guides and an appropriate selection of the needle path in the planning CEUS.

Applications And Results of CEUS Guided Biopsy in Tumoral Diagnosis.

Liver Tumors. ▼▼

This technique allows targeting a viable, enhanced area in large hepatic tumors and to sample a non-necrotic specimen (q Fig. 1). Less defined or invisible lesions in conventional ultrasound become well demarcated in portal and parenchymal phases and can be easily punctured.

Fig. 1 Large hepatic ­tumor with extensive necrosis. CEUS guided liver biopsy. The specimen was sampled from an enhanced marginal area. The entire length of the needle is seen (arrowhead).

In a recent study published in 2006 it has been shown that using CEUS the diagnostic accuracy of percutaneous biopsy in the diagnosis of liver tumors (both benign and malignant ones) increases from 87 % (obtained by classical guided technique) to 95.3 %. The excess of accuracy is even greater in lesions less than 2 cm, 97.1 % versus 78.8 % [11]. Another consequence of using CEUS in that study was the decrease of number of passages. This study was, however, conducted on different patient groups.

Pulmonary Tumors ▼▼

The US-guided percutaneous biopsy in pulmonary tumors may lead to sampling of tissue from necrotic areas with consecutive decreased sensitivity. Although sonography can depict liquefaction necrosis inside the tumor and can guide the needle in the periphery in order to avoid necrotic tissue, inadequate specimens can be sampled in 9 % to 26 % of cases when necrosis is large [14,15].

This is the case mostly in tumors larger than 5 cm [16].

In the clinical practice the use of CEUS guidance allowed the puncture of vascularized, active tumoral areas thus avoiding the sampling of a necrotic fragment [15] (q Fig. 2). On the other hand it delineates the tumor embedded in atelectatic tissue [17].

In a series of 40 patients with subpleural pulmonary lesions larger than 4 cm the sensitivity of CEUS guided biopsy in diagnosing malignancy was 100 % [18].

Fig. 2 Subpleural lung tumor, arterial phase.

The needle (>) is ­guided into an ­enhanced area. Histo­ logy: epidermoid ­cancer.

In a recent published study comparing the CEUS guided biopsy with conventional biopsy in the diagnosis of pulmonary lesions it was shown that the use of CEUS guidance increases the efficacy of the biopsy from 77.08 % to 96.1 % [17]. Kidney and adrenal tumors. Generally these tumors may grow very large with frequent and extensive necrosis so they would be very suitable for this technique [19–21] (q Fig. 3). There are no studies regarding the benefits of CEUS guided biopsy in the kidney and adrenal tumors, although an experience in the use of CEUS in renal tumors is quite important.

In our experience with 28 renal and 10 adrenal large tumors the sensitivity reached 100 % [22].

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Fig. 3 Large renal ­tumor with extensive necrotic areas. CEUS guided biopsy. Note the tip of the needle in an enhanced, peripheral area. Histology: ­renal carcinoma, clear cell type.

Retro and intraperitoneal tumors may reach important sizes and are easily punctured with US guidance. Due to the presence of necrosis the sensitivity of US guided biopsy is around 80 %. CEUS guidance may increase the accuracy of percutaneous biopsy by sampling tissue from vascularized, active tumoral areas [6].

There are several studies regarding the ­diagnosis of prostate adenocarcinoma (PADK) using CEUS guided biopsy in targeting the tumoral areas in the peripheral zone [23, 24]. The optimized technique ­detects 15.6 % of all cancers compared to 6.8 % for systematic biopsy [25]. The ­advantage is more pronounced in PADK located on small glands and with lower PSA values [24].

Soft tissue tumors. In the diagnosis of these tumors, cutting needle biopsy is a minimally invasive approach with high accuracy regarding the diagnosis of malignant versus benign lesions ranging from 94–95 %. However the accuracy in establishing the histological subgroup and grading is lower, ranging from 68–80 % [26].

In a recent study CEUS guided CNB yielded a sensitivity and specificity of 97.1 % and 92.5 % respectively. In specific pathological sub-grouping and grading definition the sensitivity and specificity were 100 % and 100 % and 96.8 % respectively [26].

Conclusions, Perspectives ▼▼

CEUS guided percutaneous biopsy is a relatively new, feasible technique that ­ should be applied in large tumors with consistent necrosis, in hypovascular tumors or in those invisible or poorly visib-

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le to conventional ultrasound. The increasing use of CEUS in various tumors may select certain cases where CEUS guided biopsy may be needed.

The quality of specimen sampled by means of percutaneous biopsy could also be dramatically improved. Demonstrating some biological features on certain tissue samples (i. e. VEGF, EGREF, among others) which are helpful in assessing prognosis in various tumors need very good quality specimens that can be sampled by means of CEUS guided biopsy.

References 1 Diederich S, Padge B, Vossas U, Hake R, Eidt S. Application of a single needle type for all image-guided biopsies: results of 100 consecutive core biopsies in various organs using a novel tri-axial, end-cut needle. Cancer Imaging 2006; 6: 43–50.

2 Lencioni R, Caramella D, Bartolozzi C. Percutaneous biopsy of liver tumors with color Doppler US guidance. Abdom Imaging 1995; 20: 206–208.

3 Polaków J, Janica J, Serwatka W, Ladny JR, Zukowska-Serwatka K. Value of three-dimensional sonography in biopsy of focal liver lesions. J Hepatobiliary Pancreat Surg 2003; 10: 87–89.

4 Bang N, Bachmann Nielsen M, Vejborg I, Mellon Mogensen A. Clinical report: contrast enhancement of tumor perfusion as a guidance for biopsy. Eur J Ultrasound 2000; 12: 159–161.

5 Meuwly JY, Schnyder P, Gudinchet F, Denys AL. Pulse-inversion harmonic imaging improves lesion conspicuity during US-guided biopsy. J Vasc Interv Radiol 2003; 14: 335– 341.

6 Schlottmann K, Klebl F, Zorger N, Feuerbach S, Schölmerich J. Contrast-enhanced ultrasound allows for interventions of hepatic ­lesions which are invisible on conventional B-mode. Z Gastroenterol 2004; 42: 303–310.

7 Wu W, Chen MH, Yin SS, et al. The role of contrast-enhanced sonography of focal liver lesions before percutaneous biopsy. AJR Am J Roentgenol 2006; 187: 752–761.

8 Sartori S, Nielsen I, Trevisani L, Tombesi P, Ceccotti P, Abbasciano V. Contrast-enhanced sonography as guidance for transthoracic biopsy of a peripheral lung lesion with large necrotic areas. J Ultrasound Med 2004; 23: 133–136.

9 Yeow KM, Tsay PK, Cheung YC, Lui KW, Pan KT, Chou AS. Factors affecting diagnostic ­accuracy of CT-guided coaxial cutting needle lung biopsy: retrospective analysis of 631 procedures. J Vasc Interv Radiol. 2003; 14: 581–588.

10 Cao BS, Wu JH, Li XL, Deng J, Liao GQ. Sonografically guided transthoracic biopsy of peripheral lung and mediastinal lesions: role of contrast-enhanced sonography. J Ultrasound Med. 2011; 30: 1479–1490.

11 Sparchez Z, Radu P, Pop M, Zaharie T, Todea D, Pop M. Utility of CEUS guided biopsy in subpleural pulmonary tumors. Ultrasound Med Biol 2011; 37: S30 12 Xu ZF, Xu HX, Xie XY, et al. Renal cell carcinoma: real-time contrast-enhanced ultrasound findings. Abdom Imaging 2010; 35: 750–756.

13 Dietrich CF, Ignee A, Barreiros AP, et al. Contrast-enhanced ultrasound for imaging of adrenal masses. Ultraschall Med 2010; 31: 163–168.

14 Sparchez Z, Radu P, Kacso G, et al. Performance of CEUS guided biopsy in large renal and adrenal tumors. Ultrasound Med Biol 2011; 37: S33 15 Mircea P, Pop S, Chira R, Valean S, et al. Echoguide biopsy in abdominal tumors. Factors influencing overall results, other than the type and size of the biopsy needle. Rev Rom Ultrasonografie 2001; 3: 39–47.

16 Heijmink SW, Barentsz JO. Contrast-enhanced versus systematic transrectal ultrasound-guided prostate cancer detection: an overview of techniques and a systematic review. Eur J Radiol 2007; 63: 310–316.

17 De Marchi A, Brach del Prever EM, Linari A, et al. Accuracy of core-needle biopsy after contrast-enhanced ultrasound in soft-tissue tumours. Eur Radiol. 2010; 20: 2740–2748.

Zeno Spârchez “Iuliu Hatieganu” University of Medicine and Pharmacy, Institute for Gastroenterology and ­Hepatology, Cluj Napoca, Romania Address for corespondence: Assoc. Prof.

Zeno Spârchez: Institute for Gastroenterology and ­Hepatology, Croitorilor 19–21 Cluj Napoca, Romania Email:zsparchez@yahoo.co.uk

EFSUMB Newsletter

More information on all Schools can be found on www.efsumb.org

New Technologies

Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy: Using the Optical Needle into the Acoustic Haystack Endoscopic Ultrasound, Confocal Laser Endomicroscopy, ­Optical Biopsy Both transcutaneous ultrasound (TUS) and endoscopic ultrasound (EUS) are intensively used in state-of-the-art gastrointestinal (GI) units, for early detection, characterisation, staging and follow-up of lesions located within the vicinity of the GI tract (thus including esophageal, gastric, intestinal, colorectal, but also pancreatic, biliary, adrenal, liver, mediastinal lesions, etc.). Even more important, different ultrasound techniques are necessary for guidance of interventional procedures used for cytological and histological diagnosis [1]. TUS and EUS have distinct advantages as compared to CT-guided procedures, related to high accuracy and precision, cost-effectiveness, lack of ionising radiation and low complication rates. Nevertheless, both techniques have certain caveats including a long learning curve (especially for EUS), sampling errors, necessity of trained cytopathology personnel and delays in the final cytopathological diagnosis, which still relies on TUS or EUS-guided fine needle aspiration biopsy.

“Optical biopsies” are being increasingly studied and investigated in gastroentero-

logy. These include a plethora of biophysical methods like autofluorescence endoscopy, narrow band imaging, optical coherence tomography or confocal laser microscopy [2]. Point methods still under development include laser-induced fluorescence spectroscopy, elastic light scattering or Raman spectroscopy, and these methods are currently tested in various preclinical research protocols [3]. Even ultrasound entered this field by the development of photoacoustic imaging which is a hybrid of optical and ultrasound techniques [4]. The term “optical biopsy” is thus defined as a method that uses light to enable visualisation of tissue details and thus allow the operator to make an instant diagnosis, which was previously available only by histology or cytology [5]. Most of these techniques might generate a huge advantage through usage of molecular imaging approaches based on various targeted fluorescent molecules, thus allowing disease- and patient-specific targeted treatment, as well as followup of specific effects of the treatment [6].

The term “translational imaging” was further coined to describe the availability

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Fig. 1 ab Representa­ tive image of the nCLE fiber (AQFlex,Mauna Kea Technology, Paris, France) inserted into a 19G EUS-FNA needle (courtesy of Mauna Kea Technology, Paris, France).

of various techniques that might simultaneously offer structural and functional information at subcellular resolutions, while being translated into current clinical practice [7].

Confocal laser endomicroscopy (CLE) has recently been introduced for in vivo microscopy (optical biopsies) of the gastrointestinal mucosa [8–10]. Based on various fluorescent contrast agents, the mucosal structure, but also the microvessels can be examined in vivo. Thus, microscopical images of the pit patterns, surface epithelial cells, connective tissue matrix of the lamina propria, blood vessels and red blood cells, can easily be obtained during conventional endoscopic examinations.

The technique uses dedicated endoscopes (eCLE), but also miniprobes (pCLE) which can be passed through a usual endoscope, for e. g. inside the pancreatic or biliary ducts. Further developments of this exciting technology include the evaluation of an optic fiber that can be passed through a 19 Gauge needle to examine solid organs like the liver, pancreas and / or lymph nodes (qFig. 1a, b). The technique thus opens a window for real-time functional and structural imaging in human patients, as well as molecular imaging through the use of targeted antibodies linked with fluorescent compounds.

Methods ▼▼

EUS procedures are carried out in the conventional way, with a linear array EUS endoscope, inserted into the esophagus, stomach or duodenum, until the localisation and visualisation of a lesion of interest.

These lesions might include any cystic or solid lesion located adjacent to the GI tract (pancreas, lymph nodes, etc.) which has to

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be detected, characterised and / or staged.

All EUS techniques (elastography, color Doppler, contrast enhancement, etc.) can be employed in the usual way in order to select a target for EUS–guided fine needle aspiration biopsy. Special care should be taken in order to avoid interposed vessels in the needle tract.

Needle-based CLE (nCLE) probes, thin enough to pass through 19 G and 22 G needles, were recently approved (CE marked) for human use, in order to enable in vivo microscopic analysis during ongoing EUS-guided sampling procedures. The probe-based CLE system consists of a thin probe (AQ-Flex, Mauna Kea Technology, Paris, France) consisting of a bundle of optical fibers linked to a micro-objective, a laser scanning unit and the related software (Cellvizio; Mauna Kea Technology, Paris, France). The principle of the technique is based on a 488 nm (blue light) laser beam being split and focused towards the targeted tissue in a single transverse plane located at different depths, while the recaptured signal is displayed as ‘optical biopsies’. nCLE is a contrast based technique, with i. v. fluorescein being the most frequently used in human studies [11], although other agents are in the preclinical stages (e. g. topical proflavine) [12]. Beside confocal systems, significantly cheaper approaches are currently available, although in the preclinical stage of development [13].

Clinical Applications ▼▼

Initial studies used the technology in experimental animal models, for real-time evaluation of in vivo histology of different intra-abdominal organs [14]. The minia-

ture confocal probe has been inserted through a 22 G needle and puncture of various intra-abdominal structures and organs was performed (liver, spleen, pancreas, lymph nodes, etc.) after i. v. injection of fluorescein. The imaging depth was fixed in between 30 and 150 μm, located at EUSguided puncture depths of 1 to 3 cm. The initial feasibility study proved that nCLE was possible in all study animals, without any relevant complications, yielding acceptable imaging quality sufficient for virtual optical biopsies similar to histopathological biopsies.

The in vivo porcine model was also used to show the feasibility of high-resolution microendoscopy imaging through a 19 G needle, for both liver and the pancreas [15]. The contrast agent was proflavine, used topically, which has the added advantage of labelling cell nuclei. Thus, the study was completed with an ex vivo analysis of explanted pancreatic and liver tissue, based on training and testing sets of images submitted blindly to several endosonographers. All optical imaging results were validated through corresponding histopathology sections. The median accuracy for identifying malignant versus benign tissue in the liver was 85 %, while for the pancreas the median accuracy for differentiation of malignant lesions was 90 %.

Recently, use of nCLE technology has been assessed during EUS-FNA in vivo, in human patients with pancreatic focal or cystic masses [16]. Thus, the feasibility of a 19G needle fibre probe was tested during EUS-guided procedures, after injection of i. v. fluorescein. Based on this feasibility trial, device integrity was observed in all cases, with higher image quality for the probes with fixed imaging depth at 50 μm. Some limitations can be acknowledged, as there is no way of to ensure co-registration to cytopathology images. Furthermore, an ongoing multicentric trial (INSPECT), will hopefully validate descriptive criteria for the diagnosis of pancreatic cystic neoplasms [17].

Also, further data concerning other solid lesions are eagerly awaited from several groups, including ours, as the technique is certainly feasible and ready to be translated into clinical practice (q Fig. 2–5).

Suggestive images based on the CLE system used with i. v. fluorescein and the HRMI system used with topical proflavine are also consistent with the initial descriptions of optical biopsies.

EFSUMB Newsletter

Fig. 2 EUS-guided nCLE image of normal pancreatic tissue, with acini, fibrous connective tissue and blood microvessels filled with fluorescein.

Fig. 3 EUS-guided nCLE image of a malignant lymph node in a patient with biopsy-proven colorectal adenocarcinoma, showing a clump of dark enlarged malignant cells.

Fig. 4 Malignant neuroendocrine tumor diagnosed by EUS-guided FNA with microhistology and immunohistochemistry of the cell blocks, with EUS-guided nCLE, showing disorganised structure with enlarged and tortuous microvessels.

Fig. 5 Normal duodenal mucosa visualised during EUS-guided nCLE withdrawal of the fiber, with microvilli and normal glands with a visible epithelial layer.

Conclusions ▼▼

EUS-guided CLE is an exciting technique which currently allows visualisation of high-resolution ”optical biopsies” inside cysts or solid masses. Development of new contrast agents and especially targeted fluorescent molecules or nanoparticles might further enhance imaging quality.

Moreover, the construction of other hybrid imaging combinations might further enhance the spectrum and quality of optical biopsies through co-registration of different structural and functional information in the same enhanced image [18].

All these methods will certainly allow real-time early diagnosis and accurate ­ staging, as well as follow-up during antiangiogenic and / or chemoradiotherapy treatment, thus enhancing the potential of imaging methods for development of personalised oncological treatment strategies. Further studies will have to clarify the potential and clinical impact of this novel techno­logy.

References 1 Khati NJ, Gorodenker J, Hill MC.Ultrasoundguided biopsies of the abdomen. Ultrasound Q. 2011; 27: 255–68.

2 Săftoiu A, Vilmann P. Imaging techniques used for the real-time assessment of angiogenesis in digestive cancers. World J Gastroenterol 2011; 17: 7–8.

3 DaCosta RS, Wilson BC, Marcon NE. Fluorescence and spectral imaging. ScientificWorldJournal 2007; 7: 2046–71.

4 Srivalleesha Mallidi, Geoffrey P. Luke, and Stanislav Emelianov. Photoacoustic imaging in cancer detection, diagnosis, and treatment guidance. Trends Biotechnol 2011; 29: 213–221.

5 Wang TD, Van Dam J. 1. Optical Biopsy: A New Frontier in Endoscopic Detection and Diagnosis. Clin Gastroenterol Hepatol 2004; 2: 744–753.

6 Pysz MA, Gambhir SS, Willmann JK. Molecular imaging: current status and emerging strategies. Clin Radiol 2010; 65: 500–16.

7 Taruttis A, Ntziachristos V. Translational optical imaging. AJR Am J Roentgenol. 2012; 199: 263–71.

8 Kiesslich R, Neurath MF. Endoscopic confocal imaging. Clin Gastroenterol Hepatol 2005; 3 (7 Suppl. 1): S58–60.

9 Goetz M, Watson A, Kiesslich R. Confocal laser endomicroscopy in gastrointestinal diseases. J Biophotonics 2011; 4: 498–508.

10 Gheonea DI, Cârţână T, Ciurea T, Popescu C, Bădărău A, Săftoiu A. Confocal laser endomicroscopy and immunoendoscopy for realtime assessment of vascularization in gastrointestinal malignancies. World J Gastroenterol 2011; 17 (1): 21–7.

11 Wallace MB, Meining A, Canto MI, Fockens P, Miehlke S, et al. The safety of intravenous fluorescein for confocal laser endomicrosco-

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12 Thekkek N, Muldoon T, Polydorides AD, Maru DM, Harpaz N, Harris MT, Hofstettor W, Hiotis SP, Kim SA, Ky AJ, Anandasabapathy S, Richards-Kortum R.Vital-dye enhanced fluorescence imaging of GI mucosa: metaplasia, neoplasia, inflammation. Gastrointest Endosc 2012; 75 (4): 877–87.

13 Pierce M, Yu D, Richards-Kortum R. High-resolution fiber-optic microendoscopy for in situ cellular imaging. J Vis Exp 2011; 11 (47) e2306: 1–4.

14 Becker V, Wallace MB, Fockens P, et al. Needle-based confocal endomicroscopy for in vivo histology of intra-abdominal organs: first results in a porcine model (with videos) Gastrointestinal Endoscopy. 2010; 71 (7): 1260–1266.

15 Regunathan R, Woo J, Pierce MC, Polydorides AD, Raoufi M, Roayaie S, Schwartz M, Labow D, Shin D, Suzuki R, Bhutani MS, Coghlan LG, Richards-Kortum R, Anandasabapathy S, Kim MK. Feasibility and preliminary accuracy of high-resolution imaging of the liver and pancreas using FNA compatible microendoscopy (with video). Gastrointest Endosc 2012; 76 (2): 293–300.

16 Konda VJ, Aslanian HR, Wallace MB, Siddiqui UD, Hart J, Waxman I. First assessment of needle-based confocal laser endomicroscopy during EUS-FNA procedures of the pancreas (with videos). Gastrointest Endosc. 2011 Nov; 74 (5): 1049–60. Epub 2011 Sep 15.

17 Konda VJ, Meining A, Jamil LH, Giovannini M, et al. An International, Multi-Center Trial on Needle-Based Confocal Laser Endomicroscopy (nCLE): Results From the In Vivo CLE Study in the Pancreas With Endosonography of Cystic Tumors (INSPECT). Gastroenterology May 2012 Vol. 142, Issue 5, Supplement 1, Pages S-620-S-621 [Abstract for DDW 2012].

18 Dobre GM, Podoleanu AG, Rosen RB. Simultaneous optical coherence tomography -Indocyanine Green dye fluorescence imaging system for investigations of the eye’s fundus.

Opt Lett 2005; 30 (1): 58–60

Adrian Săftoiu1,2, Peter Vilmann2, Manoop S. Bhutani3 1

Research Center of Gastroenterology and Hepatology Craiova, University of Medicine and Pharmacy of Craiova, Romania

2

Gastrointestinal Unit, Copenhagen University Hospital Herlev, Denmark 3 Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, ­Texas, USA Correspondence: Adrian Săftoiu, MD, PhD, MSc Professor of Diagnostic and Therapeutic Techniques in Gastroenterology Research Center of Gastroenterology and Hepatology University of Medicine and Pharmacy Craiova, Romania Address: str. Petru Rares nr. 4, Craiova, Dolj, 200 349, Romania Mobile: + 40 744 823 355 and Fax: +40 251 310 287 E-mail: adrian.saftoiu@webmail.umfcv.ro or adriansaftoiu@aim.com