20 The Pros and Cons of a Bladder Thermotherapy Delivery System Any treatment given to a patient is always an amalgam of benets and side effects and intravesical bladder therapy is no exception. Advantages include rstly that by inserting a drug directly into the bladder lumen one then avoids all the side effects of the drug if given orally or by a parental route. For example, the patients’ hair does not fall out during intravesical Mitomycin C administration! A second positive is that the drug is not being metabolised and eliminated and the rst-pass effect of the oral route is eliminated. This means that lower concentrations of the dug can be used to achieve a desired result and the physician knows that the drug is reaching its intended target. Thirdly, the route allows within reason a predetermined time that the drug is in contact with the diseased tissues. The downside is rst off, the catheter used to access the bladder lining. Though we as urologists blithely insert catheters on a daily basis, we sometimes forget that it is an invasive process. It is uncomfortable and sometimes even downright painful despite the use of anaesthetic lubricants. For the patient, having a catheter inserted can be an embarrassing or degrading experience. The catheter breeches the body’s immune system and the plethora of bacteria in the genital region from E.coli to Pseudomonas aeruginosa can result in urinary infections. These bacteria induce biolms which can retard drug access to the tumour. A second issue is that the bladder is designed to be impervious to most biological molecules. Urine is a toxic substance and nature designed a bladder epithelium that not only can stretch but is very good at keeping toxins out. Additionally, there is the surface glycose amino glycan layer (GAG) that protects the urothelium. Urologists know only too well the problems that arise in patients when this barrier becomes leaky. The bladders’ primary role of urine storage does not stop during therapy. There is a continuous drainage of urine into the bladder from the kidneys which on a time-based formula gradually dilute the instilled drug so two hours is usually the maximum time period for effective therapy. One can of course increase successful therapy time by getting the patient to uid restrict. Lastly associated bladder pathology such as overactive bladder and interstitial cystitis can signicantly shorten the time period available for effective dosing. Conclusion After the rough ride that thermotherapy experienced at the turn of the century it would appear at least with bladder thermotherapy that the future is brighter. There is an air of quiet excitement as more centres turn their gaze on this form of treatment. I have now reached the end of this article on chemo thermotherapy of the bladder for NIMBC. I have truly only glanced over this subject and to those of you who are more knowledgeable I hope I did not disappoint too much. This technology is still in its infancy, and it still has a large clinical hurdle to climb before it gains wide acceptance. In my next article I will discuss all the important clinical papers documenting its efcacy and safety and how one day it may well replace BCG as a rst line therapy. BIBLIOGRAPHY 1) Recirculant hyperthermic IntraVEsical chemotherapy (HIVEC) in intermediate–high-risk non-muscle-invasive bladder cancer Alejandro Sousa,Idelfonso Piñeiro,Silvia Rodríguez,Vicente Aparici,Victor Monserrat,Pilar Neira: Journal of Hyperthermia; Pages 374-380 25 Feb 2016 2) The impact of temperature and urinary constituents on urine viscosity and its relevance to bladder hyperthermia treatment. Inman BA, Etienne W, Rubin R, Owusu RA, Oliveira TR, Rodriq ues DB, et al. Int J Hyperthermia 2013;29:206–10. 3) Pharmacokinetics of intravesical mitomycin C in supercial bladder cancer patients. J T Dalton 1, M G Wientjes, R A Badalament, J R Drago, J L Au: Cancer Res: . 1991 Oct 1;51(19):5144-52. 4) LONG-TERM RESULTS OF INTRAVESICAL THERAPY FOR SUPERFICIAL BLADDER CANCER. Donald L.LammMD1 et al: Urologic Clinics of North America: Volume 19, Issue 3, August 1992, Pages 573-580 5) FRI-10 MITOMYCIN-C: HISTORICAL ASPECTS OF THE DISCOVERY OF MOST COMMONLY USED CHEMOTHERAPY AGENT IN UROLOGY. Hemant Nemade, Hussein Tukmatchy, and Peter Thompson: Journal of Urology Volume 193 Issue 4S April 2015 6) The Role of Thiotepa Instillations in Bladder Cancer. Ralph J. Veenema, MD: JAMA. 1968;206(12):2725-2726. 7) A BCG success story: From prevention of tuberculosis to optimal bladder cancer treatment. Lamm DL, Morales A: Vaccine, 18 Aug 2021, 39(50):7308-7318 8) Intravesical gemcitabine for non?muscle invasive bladder cancer. Monitoring Editor: Cochrane Urology Group, Mi Ah Han, Philipp Maisch, Jae Hung Jung, Jun Eul Hwang, Vikram Narayan, Anne Cleves, Eu Chang Hwang, and Philipp Dahm : Cochrane Database Syst Rev. 2021; 2021(6) 9) Thiotepa. From Wikipedia, the free encyclopedia 10) Gemcitabine. From Wikipaedia, the free encyclopaedi 11) Neoadjuvant combined microwave induced local hyperthermia and topical chemotherapy versus chemotherapy alone for supercial bladder cancer. R Colombo 1, L F Da Pozzo, A Lev, M Freschi, G Gallus, P Rigatti: J Urol. 1996 Apr;155(4):1227-32. 12) Intravesical drug delivery approaches for improved therapy of urinary bladder diseases.Luca Palugan, Matteo Cerea, Micol Cirilli, Saliha Moutaharrik, Alessandra Maroni, Lucia Zema. Alice Melocchi, Marco UboldiIlaria Filippin, Anastasia Foppoli, Andrea Gazzaniga: International Journal of Pharmaceutics: X Volume 3, December 2021, 100100 13) Strategies to Get Drugs across Bladder Penetrating Barriers for Improving Bladder Cancer Therapy. Shupeng Wang, Shaohua Jin, Qinghai Shu, and Song Wu: Pharmaceutics. 2021 Feb; 13(2): 166. 14) COMBAT BRS COMBined Antineoplastic Thermotherapy. https://www.innomedicus.com UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
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