Abstract
AimTo determine a dose response relationship of disintegration of a hyaluronic acid (HA) and hyaluronidase (HAS) used in prostate cancer radiotherapy. Materials and methodsFive in-vitro models are applicated with 3 ml (ml) HA. For dissolution varying doses of HAS were used: 6 ml, 3 ml, 1.5 ml, and 0 ml. One ml contains 150 International Units (IU). Each HAS was added with saline till the complementary amount of 6 ml. One phantom was solely implanted with a HA 3 ml acting as a control. Length, width and height were measured on different time points: 1st day 4 times, 2nd day 3 times, third day 2 times, and then once daily during one week, with a final measurement 2 weeks after implantation. The experiments were performed in duplicate to exclude variations and confirm the results. ResultsThe fastest dissolution was observed with the highest concentration of HAS, already observed at the first time point 2 h after implantation, with volume decrease of 50% on the second day, and less than 1 ml residue (33%) on day 4. The 2 other concentrations of HAS also showed a volume decrease, with less than 2 ml (66%) on day 4. All the applied quantities of HAS are observed with a residue of less than 1 ml after 7 days. After 14 days the control phantom and the saline filled one remains on steady state volume (3 ml). ConclusionsA dose response was observed by HAS injection: highest volumes of HAS dissolute most swiftly. Using a ratio of HA:HAS of 1:2 results in a decrease to half of initial volume within 24 h. This is of special interest when used in clinical practice following erroneous positioning, and dissolution is urgently needed.
Highlights
Hyaluronic acid (HA) is one of the four commercialized implantable rectum spacers available on the market, besides hydrogel, saline filled balloon, and human collagen [1,2,3,4]
No knowledge is available on the dissolution of the HA used in prostate cancer radiotherapy in perspective of the timing and the required quantities of hyaluronidase (HAS), which is an enzyme that degrades HA
It has the capacity to hold water, which allows for reliable, reproducible injections which is of great interest in rectal spacing in prostate cancer radiotherapy to decrease radiation dose to the rectum
Summary
Hyaluronic acid (HA) is one of the four commercialized implantable rectum spacers available on the market, besides hydrogel, saline filled balloon, and human collagen [1,2,3,4]. These implantable rectum spacers are used to decrease rectal radiation dose in prostate cancer radio therapy to avoid rectal complications after prostate cancer radiotherapy. It can take 3 to 9 months for such spacers to resolve [7] Such a complication results in a significant treatment delay, since an immediate start of radiotherapy could increase the risk of fistula development. This invitro analysis was performed to determine a dose response relation ship of disintegration between HA and HAS
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