Advice

Technology overview

Technology overview

This briefing describes the regulated use of the technology for the indication specified, in the setting described, and with any other specific equipment referred to. It is the responsibility of healthcare professionals to check the regulatory status of any intended use of the technology in other indications and settings.

About the technology

CE marking

Mauna Kea Technologies received CE marking for the Cellvizio 100 Series F400‑v2 Laser Scanning Unit (LSU; wavelength 488 nm) system (from here onwards referred to as 'Cellvizio system') in April 2011 and for the AQ‑Flex 19 Confocal Miniprobe (from here onwards referred to as the AQ‑Flex 19) in September 2011. In Europe, the Cellvizio system with AQ‑Flex 19 is regulated as a class IIa medical device (within the scope of Directive 2007/47/EC).

The AQ‑Flex 19 is designed to be advanced through an endoscopic ultrasound (EUS) needle and, combined with the 488 nm excitation wavelength of the Cellvizio system, is used specifically for the characterisation of pancreatic cysts.

Description

The Cellvizio system is a probe-based confocal laser endomicroscopy (CLE) system. When combined with the AQ‑Flex 19, the system allows CLE imaging of tissues through an endoscopic needle, a technique also known as needle-based CLE (nCLE). Using this method, the technology generates 'optical biopsies', providing endoscopists with real-time microscopic video images of tissues.

The Cellvizio system is composed of several components which are integrated into a cart. These are:

  • Main components:

    • Laser scanning unit (LSU; F400‑v2; 488 nm laser source). This is a software-operated device classified as a class 2M laser product. The LSU includes a Class IIIB laser source that produces continuous laser emission at 488 nm, a laser scanning module (to expand and deflect the laser beam), lenses (used to focus the light at the tissue area of interest and refocus reflected light onto the detector) and a detector (to collect the photons corresponding to the illumination of 1 given fibre at a time). Data acquired by the detector are transmitted to the processor.

    • AQ‑Flex 19. This carries the laser beam to the tissue and captures the light emitted back. It contains 10,000 optical fibres, and has a diameter of 0.85 mm with a length of 4 m. The AQ‑Flex 19 is compatible with a 19‑gauge endoscopic needle. Its imaging depth ranges from 40 to 70 micrometres and depth of focus is 30 micrometres. It has a maximal field of view of 325 micrometres, and a lateral resolution of 3.5 micrometres (at 1,000 times magnification). The AQ‑Flex 19 can be sterilised and reused for up to 10 examinations in multiple patients, but the locking devices used to secure its position inside the endoscopic needle are single-use only.

    • Confocal processor with Cellvizio software. This is a computer used to record and store images and video sequences. Cellvizio software 2.2 has a digital imaging and communications in medicine (DICOM) connection option, which is compatible with standard NHS systems for the export of images and reports. It includes the Endomicroscopy Virtual Assistant software, which provides reference videos to assist during procedures, identifies visually stable segments of videos and prepares images for printing.

  • Peripherals (included):

    • keyboard

    • pointing device (trackball)

    • footswitch (to start and stop the laser emission and imaging). A separate button switches the LSU on and off

    • screen

    • video converter

    • isolation transformer

    • printer.

  • Peripherals (optional):

    • sterilisation tray

    • external hard drive (for data transfer).

  • Accessories: These include the single-use confocal miniprobe locking device, Cletop‑S confocal miniprobe connector cleaning system, storage box, protective caps (intended to protect the connector of the AQ‑Flex 19 during sterilisation), spare fuses and user documentation.

Before the EUS with fine needle aspiration (FNA) procedure, the AQ‑Flex 19 is loaded into a standard 19‑gauge needle. The position of the AQ‑Flex 19 is secured using the locking device that attaches the probe to the inlet of the needle biopsy channel of the endoscope. Fluorescein dye (2.5 to 10 ml of 10% fluorescein sodium) is injected intravenously immediately before nCLE imaging and is taken up by the cells of the cyst wall. During EUS examination of the pancreas, cysts needing further investigation are identified. The preloaded needle is then used to puncture the target cyst and the tip of the AQ‑Flex 19 is moved through the needle and into the cyst, under EUS guidance, until the probe touches the cyst wall. The laser beam is then shone through the AQ‑Flex 19, onto the cyst wall to activate the fluorescein. The photons emitted are reflected back to the AQ‑Flex 19 and deflected to an ultra-sensitive detector. Software in the LSU reconstructs the image from the detector signal and passes it to the Cellvizio processor, which then projects the image as a 12‑frame per second video display. Images show details of the pancreas including vessels, cells, connective tissue and cysts. Real-time images of the tissue (which can be recorded and saved) are displayed on the screen to aid diagnosis. The average duration of an nCLE procedure is 7 minutes. The AQ‑Flex 19 is removed and a syringe is attached to the proximal end of the needle for cyst aspiration.

The Cellvizio system can also be used in other medical specialties including gastroenterology, pulmonology, and urology. Different indications need different types of confocal miniprobes and are outside the scope of this briefing.

Setting and intended use

The Cellvizio system is intended to be used with the AQ‑Flex 19 for confocal laser imaging of pancreatic cysts during a standard EUS‑FNA procedure.

The Cellvizio system is intended for use in secondary care by endoscopists who have been trained to use the system. Training is given by the manufacturer through onsite training courses and online resources. Except for allergy to fluorescein, there are no known contraindications associated with use of the Cellvizio system, as long as it is used according to the instructions provided by the manufacturer.

Current NHS options

There is currently no NICE guidance for pancreatic cysts and no definitive consensus on their management.

The NICE guideline on recognition and referral for suspected cancer recommends the referral of people for pancreatic cancer (for an appointment within 2 weeks) if they are aged 40 and over and have jaundice.

The guideline also recommends an urgent direct access CT scan within 2 weeks of referral (or an urgent ultrasound scan if CT is not available) to assess people aged 60 and over for pancreatic cancer if they have weight loss and any of the following symptoms:

  • diarrhoea

  • back pain

  • abdominal pain

  • nausea

  • vomiting

  • constipation

  • new-onset diabetes.

Abdominal CT or MRI scanning may indicate the presence of pancreatic cysts, whether carried out to investigate associated symptoms or for other indications. After a cyst is identified, further tests (EUS‑FNA as standard or CT‑guided FNA) are done to classify the cyst as benign or malignant. The results of these tests help to determine whether any follow‑up is needed (such as surgery or surveillance). Decisions are based on the risk of malignancy, and the presence and severity of any cyst-related symptoms. Provided the patient is deemed fit, surgery is considered the most appropriate treatment option if the cyst is confirmed as malignant.

NICE is aware of the following CE‑marked devices that appear to fulfil a similar function to the Cellvizio system:

Costs and use of the technology

Information on the price of the technology was provided by the manufacturer and has been converted from euros to GBP (at 1 euro to 0.78 GBP). All prices exclude VAT:

  • Cellvizio 100 series system: £79,000.

  • Installation, commissioning and initial training: £2,145.

  • Each AQ‑Flex 19 can be used up to 10 times and costs £4,000. After each use, the manufacturer recommends that the probes are sterilised with an enzyme detergent using a low temperature sterilisation system.

  • The optional DICOM connectivity module costs: £2,730.

According to the manufacturer, the technology has a lifespan of at least 10 years if routinely maintained by the end user. A survey reported by Meenan et al. (2011) suggests that around 85 EUS‑FNA procedures are done annually at each suitably equipped centre in the UK. Many of these procedures will be to investigate pancreatic cysts and given that the Cellvizio system is used during the EUS‑FNA procedure, this figure represents an estimate of potential annual Cellvizio usage. Using an annuity calculation and assuming a technology lifespan of 15 years with a discount rate of 3.5%, an estimate of (technology only) cost per procedure is £486. This includes the cost of the DICOM connectivity module. This does not include the cost of EUS‑FNA, NHS staff time, facility or capital costs.

The comparator treatment is EUS‑FNA alone. NHS reference costs list the average unit cost of 'Diagnostic Endoscopic Upper Gastrointestinal Tract Procedures with Biopsy, 19 years and over' as £469 (Department of Health 2015; code FZ61Z). In addition, Sharples et al. (2012) provides relevant cost and price information from the finance department of Papworth Hospital. This allows a calculation for the estimated unit cost of EUS‑FNA that is not as nationally representative as NHS reference costs but may be more precise. The calculation is inclusive of the following costed NHS resource use: annuitised, fixed and per treatment consumable clinical costs (EUS scope, ultrasound processor, aspiration needle etc.), consultant and nurse costs, hospital overheads and capital costs. This estimate gives an (inflation adjusted) unit cost of £932. Assuming a similar level of NHS labour time use, the unit cost of EUS‑FNA with Cellvizio is about £1,418 (£932+£486).

No other practical difficulties have been identified in using or adopting the technology.

Likely place in therapy

The Cellvizio system is designed to be used as an adjunct to the standard EUS‑FNA procedure for diagnosing and managing indeterminate pancreatic cysts.

Specialist commentator comments

One specialist commentator stated that Cellvizio should not be considered less invasive than an EUS‑FNA procedure because the Cellvizio procedure also involves puncturing the cyst. The same commentator suggested that the time the probe has contact with the pancreatic tissue in the Cellvizio procedure may be longer than with EUS‑FNA, because the time taken to image may be longer than the time taken to aspirate fluid.

One specialist commentator suggested that EUS‑FNA alone is not accurate enough to characterise all pancreatic cysts. Another specialist commentator suggested that the available evidence on the development of Cellvizio diagnostic criteria, especially for mucinous pancreatic cysts, is still limited and highlighted the need for more research to address this knowledge gap.

One specialist commentator mentioned that because intravenous administration of fluorescein is part of the nCLE process, allergy to fluorescein dye should be listed as a contraindication.

Equality considerations

NICE is committed to promoting equality, eliminating unlawful discrimination and fostering good relations between people with particular protected characteristics and others. In producing guidance, NICE aims to comply fully with all legal obligations to:

  • Promote race and disability equality and equality of opportunity between men and women.

  • Eliminate unlawful discrimination on grounds of race, disability, age, sex, gender reassignment, marriage and civil partnership, pregnancy and maternity (including women post-delivery), sexual orientation, and religion or belief (these are protected characteristics under the Equality Act 2010).

The prevalence of pancreatic cysts increases with age, which is a protected characteristic defined in the Equality Act 2010. Up to 90% of people with von Hippel-Lindau syndrome, a rare genetic disorder affecting around 1 in 36,000 people, develop serous cystadenoma (Jana et al. 2015).