Indian Journal of Urology
: 2010  |  Volume : 26  |  Issue : 3  |  Page : 465--466

A minimally invasive non-thermal ablative modality for prostate: Histotripsy

Amod Kumar Dwivedi, Vengetsh K Sengottayan, Apul Goel 
 Department of Urology, C.S.M. Medical University (Upgraded king George's Medical College), Lucknow, Uttar Pradesh, India

Correspondence Address:
Apul Goel
Department of Urology, C.S.M. Medical University (Upgraded king George«SQ»s Medical College), Lucknow, Uttar Pradesh

How to cite this article:
Dwivedi AK, Sengottayan VK, Goel A. A minimally invasive non-thermal ablative modality for prostate: Histotripsy.Indian J Urol 2010;26:465-466

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Dwivedi AK, Sengottayan VK, Goel A. A minimally invasive non-thermal ablative modality for prostate: Histotripsy. Indian J Urol [serial online] 2010 [cited 2019 Nov 21 ];26:465-466
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Feasibility of histotripsy for ablation of prostatic tissue has been demonstrated in canine models in a previous study. [1] The current study is a continuation of a previous study and aims to define the dose to be given to develop it as a modality to be used in clinical practice. The study was conducted on 20 canines with prostates greater than 20ml. Histotripsy of variable doses were given to all subjects (56000, 160000 and 540000 pulse) and tissue response was objectively demonstrated at various intervals. Five subjects were euthanized immediately, seven at seven days, and eight at 28 days. Chronic canine models (canines that did not euthanized immediately but followed for a week or more and examined subsequently) were catheterized with a 12F urinary catheter placed immediately after treatment and left in place for 24 to 72 hours. After euthanasia, the prostate, bladder, and adjacent rectum were surgically removed en bloc and inspected grossly and microscopically for injury. The lowest dose (56000 pulses) applied was found to produce only scattered cellular disruption and necrosis, whereas higher doses produced more significant regions of tissue effect that resulted in sufficient fractionation so that the necrosed tissue could be voided with urination. Tissue responses in chronic canine models found that the targeted volume was replaced by collapsed cavity lined by transitional cells. Tissue lesions in histotripsy were quite sharply demarcated with very little surrounding tissue injury. The doses required for parenchymal tissue and urethra were defined; it was found that higher doses are required for urethra to create similar necrotic effect as in parenchyma. The study has practical implication regarding the optimal dose of histotripsy for treatment.[2]


There is a constant search for a non-invasive modality that has the benefit of rapid tissue debulking property of trans-urethral resection of prostate (TURP) and which is safe; histotripsy appears to fulfil both criteria. Almost all minimal invasive modalities developed for treatment of benign prostate hyperplasia (BPH), like trans-urethral needle ablation of prostate (TUNA), trans-urethral microwave therapy (TUMT) and high-intensity focused ultrasound (HIFU) work by heating of prostatic parenchyma which causes coagulative necrosis. Cells injured by this mechanism are gradually reabsorbed over two to three weeks. Prostatic edema due to thermal injury increases its size and poses risk of urinary retention, and so there is a need for urethral catheterization for two to four weeks. [3],[4]

Histotripsy, like HIFU, utilises the therapeutic potential of ultrasound waves. While ultrasound used in HIFU has a therapeutic effect by directly heating the tissue thereby causing coagulative necrosis, histotripsy immediately ablates tissue by liquefaction caused by the mechanical effect of highly vibrating micro bubbles created at focal region of histotripsy, causing adjacent tissue breakdown. In HIFU, energy is delivered in a continuous fashion or as long pulses (0.015 to 4 seconds) leading to energy absorption in the focal zone exceeding the ability of the tissue to dissipate heat, thus, resulting in a temperature increase causing coagulative necrosis. In contrast, ultrasound waves used in histotripsy have intermittent highly intense burst pattern with short duty cycle (per cent of time when ultrasound energy is delivered) of only 0.2% compared to 100% with HIFU. [5]

A short duty-cycle gives tissues time to dissipate heat and so minimizes heating of adjacent neurovascular bundles and sphincters. Liquefied tissue (prostate) is drained through urethra by creating a rent in the urethral wall by providing more intense energy at urethra. Histotripsy appears appealing due to rapid tissue debulking, highly accurate tissue ablation and non-thermal mode of tissue injury. To date, experience of histotripsy is limited to canine models only and no human trial has been conducted yet. This technology needs to be modified to be useful in humans, as prostate in humans is deeply seated in pelvis in comparison to canines and not amenable to be focused extra corporally through the abdomen. Canine prostate is also not equivalent to human prostate in BPH due to different stromal and glandular architecture. Further investigations and clinical trials are needed to make this highly fascinating modality clinically relevant.


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