16 cellular metabolism as well as increasing resistance to chemotherapeutic drugs and radiotherapy. The better oxygenation can be directly toxic to the cancer cells; it improves tissue healing and reduces resistance to chemotherapy. Enhanced Immunity The level of immune system enhancement is determined by the temperature of the heated tissues and the duration of the thermal therapy. The consequence of heat therapy is that the immune system adapts to augment tumourocidal activity. The increased temperature stimulates increased activity of dendritic cells, natural killer cells and phagocytic cells. Dendritic cells can assimilate antigen to stimulate other cells useful in antitumour activity. Natural killer cells which obviously naturally seek out and destroy tumour cells become super killer cells and phagocytes function better to clear up cellular debris. There is upregulated production of heat shock proteins and chaperone tumour related antigens which are released by cancer cells in the presence of heat, radiotherapy, and chemotherapy. These proteins are taken up by dendritic cells which then present these antigens to CD8 T cells and Macrophages. This antigen interaction stimulates production of cytokines and interleukins. These released proteins are proapoptotic and proinammatory culminating in increased tumourocidal activity. The heat shock proteins attach to tumour cell walls like labels making easier identication for the immune system to target. These proteins can also enter tumour cells causing disruption and cell toxicity. Lastly for this article intercellular adhesion molecules have augmented production so that there is increased trafcking of lymphocytes to the target region. The story is actually more complicated but for brevity and clarity I have tried to depict the cellular effects of hyperthermia simplistically. The Physics of Bladder Hyperthermia The physics involved in bladder chemohyperthermia are wonderfully complicated but there are a few easy truths to assimilate. I will concentrate on only treatment for non-muscle invasive bladder tumours (NMIBC) for this article. Thermotherapy has been developed to treat muscle invasive disease but at present this falls outside the domain of the urologist. The understanding of thermodynamics for deep muscle thermotherapy brings to mind the cliché that it is outside of the scope of this article. Various institutions have vied to create mathematical models of the uid dynamics and heat transfer inside bladders but for multiple reasons of which I will mention a few the process is incredibly difcult. The above diagram will remind readers of the principles of heat transfer. These concepts are important to contemplate when one considers thermal therapy of any form. The bladder is an organ with a complex shape varying from an empty tetrahedron to a full pseudosphere. Its position and shape and dimensions all vary continuously depending on gender, the degree of lling and the state of adjacent organs. Trying to understand ow which is invariably turbulent as uid leaves and enters the bladder either from the kidneys or via the catheter in a constantly changing shape can be considered challenging. The changing volume during the therapy also affects heat transfer within the uid. Add to that the issue that thermal gradients can be non-uniform within the uid bathing the bladder wall due to salinity variances and bubbles of gas which have completely different heat transfer physics and one ends up with seriously complex mathematical models. The average bladder wall thickness in a healthy subject is 3.0 mm for a female and 3.3 mm for a male. The average depth of the urothelial layer and the lamina is about 1 mm. This is the depth that we focus on when treating NIMBC which includes Tis; Ta; and T1 tumours. The applied heat needs to penetrate to this depth to reach the goal of effective chemo thermotherapy. The technological hurdles are much easier to surmount with NMIBC using uncomplicated thermal conduction heating solutions. Heat applied to the wall of the bladder via warmed uid in the bladder is taken up by the process of conduction. This simply involves the transfer of heat energy from a region of higher temperature to a region of lower temperature. This process will continue until equilibrium is reached. UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
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