Continued interest in finding more effective minimally invasive alternative therapies for prostate pathology along with new therapeutic agents supports the ongoing evolution of intraprostatic injection as a potentially viable treatment for various prostate diseases.1
The anatomical site of the prostate and refined imaging techniques make the prostate easily accessible via a transrectal route.
Our preclinical canine studies demonstrated that intraprostatic AE injection creates coagulative necrosis surrounded by acute and chronic inflammation with focal areas of hemorrhage and edema.14
Use of a single lumen needle was associated with varying degrees of injection resistance and significant backflow along the needle track.3
Our preclinical chronic study in 22 dogs confirmed that transurethral intraprostatic ethanol injections diffused irregularly with unpredictable resultant lesion size.5
In that study the extent of tissue necrosis after injection was 0% to 95% of prostate lobe volume.
Variability in clinical outcome was also noted in subsequent multicenter clinical trials of transurethral ethanol ablation of the prostate.6–8
Since the conclusion of these studies, new potential injectables suitable for intraprostatic injection have been introduced.15–18
By its nature transrectal intraprostatic injection compromises prostate capsule integrity. Potential backflow along the needle tract could result in injectable leakage into the periprostatic area. Thus, transrectal intraprostatic injection necessitates solid preclinical evidence showing the lack of back-flow. This was documented in our study.
Transrectal ultrasound guided intraprostatic injection is impossible in a dog due to prostate mobility. Our alternative method using direct injection into the exposed prostate allowed us to circumvent this limitation. The infusion rate of 250 μl per minute per cm, which was determined in prior ex vivo experiments, was the fastest flow rate that could be used without backflow.
Infusion pressure varied and lower pressure was associated with a larger diffusion area. The lower mean pressure noted for the MiHFC was expected, given that it has a substantively larger surface area than a standard needle. The estimated area of the approximately elliptical opening of a beveled 21 gauge needle is 40 to 80 times smaller than the surface area of the 1 to 2 cm hollow fibers. Thus, outflow velocity is 40 to 80 times slower for the hollow fiber than for needle infusion at the same flow rate. Interstitial uptake of the infused drug can occur at a slower rate, making it less likely that infusion velocity will exceed the interstitial flow velocity of the tissue. As a result, the MiHFC showed more uniform delivery.
In contrast to our previous study, we did not observe backflow along the needle tract during injections using the standard needle or the MiHFC. This may have been due to the slow, steady infusion rate controlled by the syringe pump, in contrast to the manual injection used in previous studies.
Methylene blue allowed us to evaluate the presence or absence of injected solution outside the prostate. AE injection led to histological changes in exposed tissue. We used hematoxylin and eosin staining to identify histological changes and quantify the volume of affected tissue. Three-dimensional reconstruction showed lesions of varying sizes and shapes. Each dog served as its own control since prostates were injected with an MiHFC or a control needle in the right and left prostate lobe, respectively.
Overall lesions of variable sizes were created. In all cases the lesion was larger on the side of MiHFC injection. On 3-dimensional reconstruction most lesions were oval with sides that ended abruptly in a flat plane. The distance of 2.5 mm between sections could account for this phenomenon. However, as evident on individual sections and gross specimens, this could have been due to a barrier function of the intraprostatic septa in the canine prostate. The canine prostate is composed of approximately 17% acini and ducts while the remaining 63% is solid glandular tissue.19
To some degree this limits its applicability as a surrogate of human prostates. The long, narrow lesions seen using the control needle suggest backflow (), given proximal tracking of the AEMB solution.