Medical Device Daily National Editor

As a diagnostic procedure to identify a malignancy, biopsy is fairly definitive. Take a piece of tissue, put it under a microscope and you know what you’ve got.

“Taking” that material, of course, is a problem. It means invasiveness – perhaps even triggering disease in some cases, it is thought. And the whole procedure takes time, is expensive and delays treatment.

So how do you avoid biopsy?

Well, let’s say we add a microscope to the business end of an endoscope. That is one of the leading-edge strategies in the device world currently called probe-based confocal laser endomicroscopy (pCLE).

The technique was first introduced in 2004 by Optiscan Imaging (Melbourne, Australia) in an R&D collaboration/marketing partnership with Pentax (Tokyo). Pentax then was first to market in 2006 with its OptiScan device, a system integrated into Pentax instruments and used primarily for assessment in the gastrointestinal tract.

Pursuing broader pathways with this optical imaging approach is Mauna Kea Technologies (Paris), which last year launched its U.S. subsidiary CellVizio (Fort Washington, Pennsylvania).

Mauna Kea/Cellvizio has developed the Cellvizio, a pCLE system that can be used as an accessory to endoscopes made by many manufacturers, so that it can be used by a larger number of clinicians, in a broader number of applications.

The device is essentially an endoscopic accessory which, when placed against mucosal tissue, provides microscopic visualization of the tissue. The images obtained have a resolution 500 to 1000 times greater than a regular endoscope, and the system has been described as a disruptive technology in its clinical applications, after finding initial use in lab research in animals.

Cellvizio delivers up to 12 images per second and is designed to be used with almost any endoscope. It has 510(k) clearance and the CE mark for use in the gastrointestinal and pulmonary tracts.

While, like Pentax, Mauna Kea/Cellvizio also is focused on gastrointestinal applications, it is exploring various other uses for detection of cancer.

For instance, it recently reported the first patients enrolled in an international, multi-center study designed to assess the use of the Cellvizio to determine the condition of Barrett’s Esophagus, in particular whether or not it has progressed to a cancerous condition.

Importantly, the quick determination of cancer enables treatment more quickly, with fewer biopsies, and Mauna Kea/Cellvizio say that positive data in the Barrett’s trial will add confirmation to its overall clinical usefulness.

Chris Tihansky, president of Cellvizio, told Medical Device Daily, “We’re doing a fair amount of physician education – to help them understand what they’re looking at” with the device. A key strategy being used by the company is to place the device with “opinion leaders” in the field, with many of them doing their own trials.

Tihansky reported 80 installations of the system “worldwide.” While he declined to state the number of users in the U.S., he said that there is a “tremendous amount of interest in the U.S. We’re on track to meet our objectives with the company, and over the next several years, to make [the Cellvizio] a standard of care.”

More than 100 patients will be enrolled in the Detection Of Neoplastic Tissue in Barrett’s Esophagus with In vivO Probe-based Confocal Endomicroscopy (DON’T BIOPCE) study the at four sites: Columbia-Presbyterian Medical Center (New York), the Veteran Affairs Hospital (Kansas City, Missouri), Mayo Clinic (Jacksonville, Florida) and Klinikum rechts der Isar (Munich, Germany).

Collection of data for the primary outcome measure is expected in June, with study completion set for September of 2009.

Principal investigator Prateek Sharma, MD, professor of medicine in the Division of Gastroenterology and Hepatology at the University of Kansas School of Medicine and the Veteran Affairs Medical Center (both Kansas City, Missouri), said, “Until now, we haven’t been able to differentiate dysplastic and cancerous tissue within the Barrett’s segment, so we take random biopsies from the area in hopes that this will represent an accurate sample.”

Barrett’s occurs when gastroesophageal reflux disease (commonly called GERD) causes stomach acid to leak back into the esophagus, damaging the lining and increasing the risk of cancer of the esophagus (adenocarcinoma).

Besides exploring the esophageal application, the company is doing R&D for use of its systems in gastroenterology and hepatology, and the assessment of pancreatic cancer, lung cancer and bile duct cancer.

Tehansky acknowledges that the Optiscan system from Pentax is “a compelling technology,” but also that the pCLE sector will continue to grow and be available to the Cellvizio device “because of its compatibility with any endoscope on there on the market.”

Characterizing the Cellvizio as a platform opportunity he said is “a fair comment – it potentially has broad applications in detection of early-stage cancers across a number of specialties and some of those specialties are very encouraging to us.”

“We hope to reproduce the positive results of our earlier Barrett’s Esophagus studies in a wider group of physicians and patients,” said Sacha Loiseau, founder and president/CEO of Mauna Kea.

An earlier study demonstrating that use of the Cellvizio for assessing the progress of Barrett’s Esophagus was published in the December issue of GUT, the international journal of gastroenterology and hepatology.

In the study, two independent examiners evaluated 199 and 200 biopsy sites in respective multi-centric studies.

The blinded diagnostic assessments matched in 176 cases, the physicians coming to an accurate diagnosis in 93.3% of those 176 cases. They accurately determined which patients had pre-cancerous tissue 80% of the time and correctly differentiated the non-cancerous tissue 94.1% of the time. Of the lesions which tested negative, the physicians were 98.8% accurate (negative predictive value).

Lead author of the study, Heiko Pohl, MD, of the Dartmouth-Hitchcock Medical Center, said, “Traditional endoscopic cameras don’t differentiate cancerous or precancerous Barrett’s tissue, so we take random samples from sections of the region in hopes that it represents an accurate sampling. A more precise, real-time, microscopic imaging device will help us more accurately target dangerous Barrett’s tissue and remove or treat it immediately before it develops into esophageal cancer.”

The company cites estimates that since the 1980s, the rates of adenocarcinoma of esophagus (ACE) have been increasing in both genders in developed countries, is the fastest rising malignancy among white men in the U.S., and is increasing faster than breast cancer, malignant melanoma, or prostate cancer.

The company reports that more than 2,000 of these procedures to assess Barrett’s have been done, with publication of more than 25 peer-reviewed papers on the technology.

The company describes the in vivo cellular imaging market as focused on enabling the visualization, diagnosis and treatment of pathologies that can’t be seen with other imaging techniques, and the company this year won the Wall Street Journal Technology Innovation Award.

Founded in 2000, Mauna Kea/Cellvizio investors include the Psilos Group, Seventure and Creadev. The company in January reported the close of a $30 million financing, lead by the Psilos Group (Medical Device Daily, Jan. 24, 2008).