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Confocal applications

Monday, January 10, 2000

Pittsburgh Post-Gazette

A new type of microscope that can show individual cells moving and functioning inside living tissue is allowing researchers to imagine dramatically different ways of diagnosing and treating disease.

The obvious clinical application for the confocal endomicroscope would be as a substitute for skin biopsies normally required for diagnosing skin cancers, said Dr. Louis Falo, a UPMC dermatologist.

Rather than excising a suspicious lesion and examining it under a microscope, a dermatologist might simply swab the lesion with some fluorescent dye, press the microscope's hand-held probe against the skin and study the resulting images displayed on a computer monitor to see if abnormal cells are present.

"This could replace the biopsy," Falo said.

Moh's surgery, a technique for removing skin cancers completely while minimizing the loss of healthy tissue, requires multiple biopsies that must be studied under a microscope. By using the endomicroscope instead, what is now a full-day affair might become a short-term procedure, Falo suggested.

Because it is non-invasive and painless, the hand-held microscope might also be used by dermatologists to monitor treatments for skin disorders. In patients with psoriasis, for instance, the confocal endomicroscope could be used to see if steroid therapy has reduced the activity of immune system cells called T-cells; steroid doses could be adjusted rapidly, if necessary. It also could be used to check for T-cells in patients with malignant melanoma who are being treated with a cancer vaccine; in those cases, doctors would hope to see T-cells attacking melanoma cells.

The microscope might even be able to directly target cancer cells for destruction. Dr. John Comerci, a gynecologic oncologist at Magee-Womens Hospital, said it might allow him to focus a laser on groups of precancerous cells in the cervix and help spare healthy, surrounding tissue.

This spring, Comerci is beginning a National Cancer Institute-sponsored clinical trial evaluating the treatment of cervical and vulvar dysplasia -- a precancerous condition that can be identified with Pap smears -- using a technique called photodynamic therapy. This involves giving the patient a drug called Lutrin that is sensitive to light and tends to accumulate in abnormal tissue; when laser light is shined on these tissues, the Lutrin is activated and destroys those cells.

The common ways of eliminating these dysplastic cells include cauterizing, freezing or burning them off with a laser. But those techniques also remove large numbers of healthy cells. That is a concern because cervical dysplasia is associated with human papilloma virus infection, which can't be treated. Dysplasia thus tends to recur, leading to repeated treatments that eventually remove so much healthy tissue that some women are unable to reproduce.

Because Lutrin is concentrated in abnormal cells, photodynamic therapy should reduce the loss of healthy tissue, Comerci said. But the confocal endomicroscope might allow doctors to be even more selective by focusing the laser light only on groups of abnormal cells.

The two-year trial, which will include 54 patients, won't use the endomicroscope to target cells, but will use it to help evaluate the response of cervical and vulvar cells to Lutrin. Use of the microscope for aiming the laser might be considered in future studies if photodynamic therapy is shown to be beneficial.

Though clinical applications are limited for now to areas such as the skin or the cervix that are accessible to the cigar-size probe, Falo said it should also be possible to image internal organs and surfaces using viewing devices called endoscopes, though the images may be less sharp.

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