ATLANTAA fluorescent marker given 4 hours before surgery lights
up renal cell carcinoma cells and eliminates the need for frozen
sections to guarantee clean margins during kidney-preserving tumor
resection, German researchers reported in a poster presented at the 95th
Annual Meeting of the American Urological Association (AUA).
Gralf Popken, MD, told ONI in an interview that a single oral 20
mg/kg dose of 5-aminolevulinic acid (ALA) produces maximal
fluorescence 4 hours after administration and that this is enough to
identify the outer margins of renal cell tumors during resection. Dr.
Popken is assistant professor of urology, University of Freiburg, Germany.
ALA is converted to protoporphyrin IX (PPIX), which is eliminated
from normal cells, Dr. Popken said. In malignant epithelial tumors,
such as renal cell carcinoma, glioblastoma, and bladder cancer, this
enzymatic process is defective. PPIX accumulates in these cells.
Shining a blue light on these cells makes them fluoresce in the
visible red region of the spectrum. This fluorescence
distinguishes the tumor from the healthy surrounding tissue,
Dr. Popken said.
This process requires a xenon light system and a yellow filter, but
Dr. Popken said that existing endoscopic light systems could be
adapted easily for this use.
The process was tested first in an animal model in which human renal
cell carcinoma was xenotransplanted into nude mice. In this animal
model, the ALA marker was easily detectable both within the kidney at
operation and in the dissected tumor. Maximum tissue levels of the
marker were reached at 1.5 hours after intravenous administration and
at 4 hours after oral administration.
technique was then tested during resection in 35 patients with renal
tumors less than 4 cm in diameter. Patients received oral ALA 4 hours
before their surgery. A retroperitoneal approach was used, and the
tumor was excised under cold ischemia with a safety margin of 0.3 to
0.5 cm (see Figures).
In this pilot study, Dr. Popken said that good fluorescence appeared
in all 31 patients with renal cell tumors; there was no fluorescence
in the 4 benign tumors.
This was sufficient to identify outer margins of the tumors for
kidney-preserving tumor resection, he reported. There were no
local recurrences during the follow-up period of 18 months. The
investigators also observed no side effects of oral ALA as given in
Dr. Popken said that the ALA method, if further validated, is
expected to enable surgeons to do partial rather than full
nephrectomies for more patients who have renal cell carcinoma.
For physicians who see patients with kidney tumors, this will
increase the importance of sending these patients for surgery to
centers experienced in and potentially able to do partial
nephrectomies, he said.
Dr. Popken expects the new procedure to be particularly helpful in
the treatment of patients who have recurrent multiple tumors. He told ONI
that being able to identify and remove all tumors at the same time in
such patients will help surgeons reset the clock more
completely and potentially lengthen the interval between recurrences.