Abstract
The purpose of this publication is to document the evolution of a new surgical procedure for the treatment of carefully selected patients with organ confined localized prostate cancer. Natural orifice surgery represents a paradigm shift in the surgical approach to disease, although its adoption into clinical practice has been limited to date. This manuscript describes the development of natural orifice translumenal endoscopic surgical radical prostatectomy (NOTES RP). The laboratory, animal, preclinical and early clinical experiences are described and detailed. While the early experiences with this approach are promising and encouraging, more information is required. Despite the early successes with the procedure, long-term oncological and functional outcomes are essential and more work needs to be done to facilitate the teaching and ease of the NOTES RP.
Introduction
The dawn of a new age in medicine and surgery is upon us. The ever changing landscape of surgery has pushed new and innovative minimally invasive approaches to the forefront of surgical discovery. These radically new ideas and concepts have become commonplace and have dramatically changed teaching, expectations, and outcomes for patients across all surgical subspecialties. The goals of less-invasive surgical techniques, while maintaining sound surgical principles, have compelled technology and surgeons to achieve a new competence. Natural orifice translumenal endoscopic surgery (NOTES) and laparo-endoscopic single site (LESS) surgery represent the latest efforts to limit surgical morbidities while treating disease.
These approaches epitomize the far right portion in the spectrum of minimally invasive surgery. Early forays in laparoscopy began in 1901 with the first laparoscopic procedure performed by George Kelling in Germany, but because of equipment limitations the technique was slow to gain acceptance [O’Dowd and Philipp, 2000]. Ureteroscopy was first described by H.H. Young in 1912 when he inadvertently used a pediatric cystoscope to cannulate a ureter in a young male patient [Young and McKay, 1929]. Surgery largely remained relegated to open incisions until technological advancements allowed safe and reproducible procedures to be performed. In urology this began with the first laparoscopic nephrectomy in 1991 by Clayman and associates [Clayman et al. 1991]. This was followed by the initial description of the first laparoscopic prostatectomy by Schuessler and colleagues in 1992 [Schuessler et al. 1997]. The field of robotic-assisted surgery enabled open surgeons to transform into minimally invasive surgeons after the first robot-assisted laparoscopic prostatectomy was reported by Abbou and associates [Abbou et al. 2001] and Binder and coworkers [Binder and Kramer, 2001].
LESS is a hybrid technique, between conventional laparoscopy and NOTES, minimizing the number and often the size of the ports necessary for conventional laparoscopy. While the concept of NOTES may have begun as a specimen extraction portal (vaginal removal of an intact kidney reported in 1993) [Breda et al. 1993], the current practice represents a true paradigm shift in the conceptualization of surgery. The act of performing extirpative and reconstructive procedures without the need for any visible incisions and by taking advantage of the human bodies own natural orifices (mouth, anus, vagina, bladder) is rapidly turning science fiction into reality.
The challenges of NOTES are great, while the benefits are largely theoretical. Considerable work and effort has been done with these emerging techniques in the laboratory setting while clinical development, at least in urology, remains in its infancy. The most common NOTES procedures involve transvaginal techniques, which effectively excludes 50% of the world’s population. When the clinical implementation of NOTES in humans is examined in the field of urology, the progress to date has been modest. Kaouk and associates described the first pure transvaginal NOTES nephrectomy in a woman with an atrophic kidney [Kaouk et al. 2010]. The purpose of this report is to describe the rationale for NOTES RP and to chronicle its development and introduction into the clinical armamentarium.
The prostate
Prostate cancer is unlike other urologic malignancies as it has undergone significant shifts in treatment patterns not only in the United States, but worldwide. The multitude of treatment modalities and options provide many choices for consideration by both patient and physician. However, for young patients with organ confined disease the cornerstone of management for cure remains RP [Axelson et al. 2011]. Technology has made a major impact on the contemporary surgical treatment of prostate cancer, first with the introduction of laparoscopy and then with remote robot-assisted laparoscopic procedures. The outcomes of any new surgical procedure must equal or improve upon the standards of what is currently available. This is a lofty endeavor when it comes to prostate cancer. The ultimate arbitrator of success is disease-specific survival and biochemical-free recurrence survival, but given the natural history of prostate cancer these parameters can take decades to mature. Margin status is a commonly accepted surrogate of disease control [Lake et al. 2010; Emerson et al. 2005]. While debate in the literature exists about the importance of positive surgical margin (PSM) location, extent, and degree in organ confined disease (OCD) most agree that a PSM reflects technical failure. Therefore, in NOTES RP where long-term oncological outcomes are unknown, it is critical to at least estimate oncological efficiency by determining the surgical margin status.
The technique of NOTES RP is an extension of holmium laser enucleation of the prostate (HoLEP). In the experience of the senior author, during HoLEP, occasional forays through the surgical capsule into the periprostatic space spawned the concept that by extending the enucleation technique to include the surgical capsule complete removal of the prostate might be feasible. HoLEP involves separation of the lateral and median lobes of the prostate from the surgical capsule (Figures 1 and 2). With NOTES RP, the initial incisions between the lobes of the prostate which initiate the HoLEP technique are not needed. Rather the dissection is initiated lateral to and at the distal limit of the veru montanum (Figure 3). This dissection is carried from the 7 o’clock location circumferentially to the 5 o’clock location leaving the veru montanum intact for leverage purposes. This dissection in the periprostatic space is extended underneath the endopelvic fascia until the bladder is entered. This portion of the dissection is very similar to what is done with HoLEP. Once the bladder is entered, the lateral attachments of the prostate to the bladder neck are taken down. At this point, the veru montanum is divided (Figure 4) and the apex of the prostate is lifted up with the beak of the resectoscope as the posterior attachments and neurovascular bundles are dropped off of the prostate. The seminal vesicles and ampulla are divided. To minimize the risk of injury to the neurovascular bundles, no attempt is made to remove the entire seminal vesicle. Once the prostate has been detached completely, it is pushed up into the bladder.
Representation of the initial incisions, based on the presence or absence of a median lobe, into the prostate during a holmium laser enucleation of the prostate (HoLEP). In a HoLEP the transition zone is separated from the peripheral zone in order to treat benign prostatic hyperplasia.
Depiction of removal of the lateral lobe of the prostate during HoLEP, which served as a conceptual basis for NOTES RP.
The initial steps of NOTES RP. The periprostatic space is entered lateral to the veru montanum at the apex at 7 o’clock and the dissection is continued clockwise below the level of the dorsal venous complex. At the vesico-prostatic junction the bladder is entered at 12 o’clock and the lateral attachments of the prostate are precisely resected from the circular fibers of the bladder neck.
After the prostate has been freed from it surrounding attachments the seminal vesicles and vas deferens are transected allowing enough of each structure to remain with the prostate for final histopathological examination.
In the early cadaver work the periprostatic tissue was biopsied then later removed en bloc for histopathologic analysis. These methods require exact knowledge of where residual prostate tissue is or may be and would not be possible in a live human patient without resulting in significant morbidity. The prostate specimen mounted as a whole provides the most data about where margins are positive and to what extent. Three of the cadavers in our series actually had incidental prostate cancer and in each cadaveric specimen the prostate was removed entirely. In one cadaver a false anterior plane was seen violating the prostate capsule, but this was recognized and corrected during the procedure. It was the confidence in the determination of the surgical completeness and margin status of the prostate specimens that gave us assurance in proceeding with the clinical development of the procedure, albeit at least initially at the cost of a small suprapubic cystotomy.
Other techniques were attempted to remove the specimen without the need for a cystotomy. Attempts were made using a standard morcellator to remove the specimen; however, the pathologist was unable to determine the different anatomic areas of the prostate, definitively identify the prostate capsule, and differentiate portions of the seminal vesicles. Later, efforts to stain the resected prostate in vivo with a variety of agents and then complete morcellation met with failure. A concern was raised over the risk of retained tissue, especially if it harbored prostate cancer and the implications for those patients. Also, the potential spread of the cellular debris which could have prostate cancer cells present raises questions over the safety of in vivo morcellation. While the risks may be minimal based on historical prostate biopsy data, such concerns must be considered. At this time it is our belief that the cystotomy currently represents the best and safest way for specimen extraction.
The technique
Prostate resection
The initial series of cadavers were used as a proof of concept that the procedure could be accomplished. After obtaining institutional approval and funding, four fresh frozen male cadavers (two initially at Mayo Clinic and two subsequent at Indiana University Health) were used to develop the method of NOTES RP. Using a 100 W holmium:yttrium–aluminum–garnet (Ho:YAG) laser (Verapulse; Lumenis Inc, Santa Clara, CA), 550 µm end-firing quartz laser fiber (SlimLine 550 micron Reusable Fiber; Boston Scientific Corp, Natick, MA), continuous-flow 26F resectoscope with a laser bridge, 7F laser stabilizing catheter (Cook Medical Inc., Bloomington, IN), continuous saline irrigation, rigid offset 27F nephroscope with a 5-mm working channel, and tissue morcellator (Lumenis Inc., Santa Clara, CA), the procedures were performed as described in a previous publication [Humphreys et al. 2009].
After first surveying the genitourinary anatomy with a 22F rigid cystoscope the bladder was irrigated until free of debris. The resectoscope was then placed transurethrally and continuous flow (no active suction) was maintained by gravity. The prostate of the first cadaver was treated with laser setting of 2 J and 40 Hz which was decreased in subsequent cadavers (2 J and 20 Hz) due to the adequacy of resection at lower power levels. The initial power setting was adopted from our HoLEP experience, which was more than needed for dissection in the extraprostatic space. The initial incision was made lateral to the verumontanum (veru) at the apex of the prostate, separating the transition zone from the peripheral zone of the prostate. Once the tissue planes were identified the capsule was cut from the 7 to 9 o’clock position to begin the extraprostatic dissection. The dissection was performed circumferentially in a clockwise manor to approximately the 11 o’clock position visually ensuring that all of the prostatic tissue was being excised completely. This was confirmed by visualization of the levator ani muscles and extraprostatic fat.
The properties of the holmium laser are uniquely adapted to facilitate such a dissection because of the pulsed nature of the device with approximately 350 µs pulse duration and a high laser energy absorption in water [Marks and Teichman, 2007]. While the main lithotripsy effects of the 2100 µm wavelength are photothermal, the pulsed energy also generates an acoustical shock wave [Chan et al. 2001] that results in ‘acoustical dissection’ much like a water pick. This phenomenon helps to develop tissue planes causing tissue to separate without direct application of thermal energy thereby limiting the amount of peripheral heat distribution and theoretically limiting adjacent tissue injury and damage. This characteristic of the holmium laser facilitates the procedure, which still requires a thorough understanding of the anatomy, tissue planes, and laser tissue interactions.
After the lateral dissection on one side of the prostate was completed, the plane of resection was carried towards the bladder neck anterior to the prostate but below the level of the dorsal venous complex. Then once the bladder had been entered anteriorly, a second incision was made near the apex of the prostate and an identical dissection from 5 to 11 o’clock in a counterclockwise fashion was done connecting to the previous dissected extraprostatic space. The only remaining attachments at the apex was at the veru (5 to 7 o’clock position), which was initially maintained for orientation and traction purposes. The final tissue bridge was then divided and the plane posterior to the prostate above the rectum was developed. Next, the posteriolateral attachments of the neurovascular bundles were identified and dissected off the prostate, using blunt dissection with the beak of the resectoscope and minimal laser energy. The prostate attachments to the bladder neck were taken down circumferentially until the only remaining connection was posteriorly at the seminal vesicles and ampullas of the vas deferens. The beak of the scope was used to manipulate and facilitate exposure so the final tissue could be detached allowing the prostate to be delivered into the bladder.
In the first cadaver, several biopsies were endoscopically obtained at the bladder neck, apex and neurovascular bundles to assess the completeness of tissue removal with the margin status to be determined from the retrieved whole prostate specimen via a small cystotomy. In the second cadaver the prostate was morcellated and then the prostatic fossa was grossly biopsied during the postprocedure open exploration. Since the initial two cadavers, 10 additional cadaveric studies have been done. The aim of each was to gain familiarity, expertise, comfort and confidence with the technique, to perfect the understanding of the anatomic constraints, and most importantly to develop a reliable method of performing a NOTES vesicourethral anastomosis.
The vesicourethral anastomosis
The vesicourethral anastomosis was the major development making NOTES RP a reality. Once the potential of a complete endoscopic resection was realized, the next major hurdle was how to join the bladder and urethra back to one another. A considerable amount of time, effort, research and technological innovation was invested to achieve this goal. In the initial cadaver, the anastomosis was accomplished by placing a 20 Fr Foley catheter with a large capacity balloon (75 ml) in the bladder under direct vision and placing the catheter under tension. In the subsequent cadavers, various methods of placing interrupted or vest sutures were attempted. Starting with four sutures placed through the resectoscope sheath or the offset nephroscope with the SR5 suture device (LSI SOLUTIONS Inc., Victor, NY) proved problematic due to the confining geometry of the endoscopes. In addition, tying the sutures extracorporally and sliding them down the urethra with a laparoscopic knot pusher resulted in significant urethral trauma. Later, sliding the knots through the endoscopes was challenging without achieving adequate tension on the sutures and without getting good tissue to tissue apposition. In addition to poor tactile feedback, knot tying was done essentially blindly as the endoscopes could not visualize the tissue, the sutures, and the knot simultaneously. A new anastomotic scope was devised, the cannula scope (LSI SOLUTIONS Inc., Victor, NY) with a geometry designed to handle specially made variations of the suture device. It additionally provided offset optics in an attempt to allow complete visualization during the tensioning of the suture. Lastly, modifications were made to the Ti-Knot device (LSI SOLUTIONS Inc, Victor, NY) allowing ease of knot placement with adequate holding force, while at the same time cutting the suture. The equipment underwent several iterations until it was felt that the anastomosis system functioned well, was reproducible, and provided a hermetic tissue to tissue appositional seal. After being tested extensively in bench top models and cadavers, we determined that six interrupted sutures provided the best anastomosis.
Preclinical development: live animal validation
Dr Krambeck and Dr Lingeman championed the live animal development of NOTES RP. After obtaining IACUC and institutional approval they performed a NOTES RP in six male hounds, weighing from 50 to 70 lbs [Krambeck et al. 2010]. Owing to anatomic constraints they had to first perform perineal urethrostomies, and urethral dilatation to allow passage of the resectoscope. They demonstrated the adequacy of the dissection technique and found that the physiologic consequences were minimal. The laser controlled any bleeding without problem or compromise of visualization. They only achieved a successful vesicourethral anastomosis in one animal which required vest sutures to complete. However, it is important to consider that the canine prostate is an intra-abdominal organ, rather than retroperitoneal as in humans, and that the anastomotic difficulties arose when the prostate holding the bladder in the pelvis was finally detached allowing the bladder to float away. The intra-abdominal location was also the cause of the fluid extravasation that they noted during their experience. They concluded that the procedure was feasible with minimal bleeding that was easily controlled and did not impair visualization. This work helped to guide the future development and revision of the anastomotic equipment described previously. This work was also important in validating that the resection technique, the anastomosis, and bleeding concerns could all be overcome, making possible clinical consideration of the procedure.
The clinical experience
Prior to initial clinical activities, the NOTES RP procedure was presented to the institutional review board (IRB), local ethics committee, local surgical committee, and local clinical practice committee for peer review and approval at Mayo Clinic. It was and is our intention to hold ourselves to the highest ethical standards. During this preclinical work, contingencies were discussed and alternative plans were devised to account for any and all potential clinical outcomes in case of complication or concern at every stage of the proposed procedure. Informed consent was required and obtained from all patients that met the selection criteria for clinical application.
Patient selection
The selection criteria included the ability to provide informed consent, localized prostate cancer (cT1c disease, Gleason ≤ 3+4, low volume disease on biopsy, no core with more than 50% involvement, prostate-specific antigen [PSA] <10 ng/ml), no palpable disease, no previous lower urinary tract system surgery, no history of pelvic radiation, sexual health inventory for men (SHIM) score less than 10, prostate size less than 40 cm3 on transrectal ultrasound (TRUS) measurement, no significant lower urinary tract symptoms, and no requirement for perisurgical anticoagulation. The preoperative evaluation included review of all prostate biopsy data by a single genitourinary pathologist, detailed anatomic and apical survey with measurement of the prostate by TRUS, PSA, electrolyte panel, complete blood count, digit rectal examination (DRE), chest X-ray, uroflow with postvoid residual volume (PVR), cystoscopy, American Urological Association symptom score (AUA SS) and SHIM score. Patients were required to have at least three physician interactions prior to the procedure to discuss the operation, hospitalization, expectations, risks, benefits, alternatives, potential complications, conversion strategies, and to answer all questions and concerns. The two consenting patients underwent the identical procedure as described in the technique section by the same surgeon at Mayo Clinic without intraoperative complication or need for conversion.
Pathological results
The two patients underwent the surgical dissection in 37 and 94 minutes, respectively. Patient one was 71 years old and had a prostate size of 27 cm3 on preoperative TRUS, with a PSA of 2.47 ng/ml, and had Gleason 3+3 in two of 18 core biopsies, consistent with cT1c cancer. Patient two was 80 years old and had a prostate size of 38 cm3 on preoperative TRUS, with a PSA of 5.73 ng/ml, and had Gleason 3+4 in five of 12 cores, consistent with cT1c cancer as well. The pathologic examination of patient one’s surgical specimen revealed a single focus of Gleason 3+3 adenocarcinoma confined to the left side of the prostate, with no extraprostatic extension, lymphovascular involvement, negative seminal vesicles, and all margins negative consistent with pT2aNxMx disease. Patient two had Gleason 3+4 adenocarcinoma involving the right and left sides of the prostate from apex to base with greater involvement of the right side (estimated 25% involvement of the gland with adenocarcinoma), no extraprostatic extension, lymphovascular involvement, negative seminal vesicles, and all margins negative consistent with pT2cNxMx disease. The surgical procedure was longer in patient two which was attributed to the larger gland size which was actually 48 g on final pathology. This also required that the anastomosis had to transverse a larger empty prostatic fossa, but on immediate postoperative cystogram no extravasation was demonstrated.
Perioperative outcomes
Table 1 denotes the preoperative and postoperative data from both patients. Neither patient had any operative difficulty preventing the completion of the NOTES RP. The physiologic consequences of retroperitoneal normal saline irrigation during the operation were minimal. Neither patient experienced a significant change in their postoperative electrolyte lab values: patient one had a 2 mmol/l increase in serum sodium, while patient two had a 1 mmol/l increase. The estimated blood loss for each patient was 45 ml and 85 ml, respectively, and neither patient required a postoperative blood transfusion. The range of the change in preoperative compared with postoperative hemoglobin was 0.4–1.7 g/dl. Each patient’s hospital course was unremarkable and each went home on postoperative day two, with their drains removed prior to discharge.
Summary of perioperative patient data.
Patient one had his Foley catheter removed on postoperative day 10 without problem, while in patient two there was extravasation of contrast on the postoperative cystogram on day 10 into the empty prostatic fossa. Patient two’s Foley and suprapubic tube were left in place until postoperative days 19 (cystogram showed resolution of the extravasation) and 26, respectively.
Functional results
The long-term data are not available at this time, as this is a relatively new surgical technique and many of the most important follow-up parameters have yet to mature. However, each patient was contacted 30 days after their procedure by phone consultation (patients were not available for clinic visit) by one of the surgeons involved in the case. Patient one reported subjectively that he was doing well, with no pain or other symptoms. He stated that he was regaining continence and only required one security pad a day, was fully back at work 2 weeks after his procedure, and had engaged in successful sexual activity on three separate occasions without the need for medical intervention. Patient two reported that he was leaking some urine requiring 3–4 pads per day and that he had pain in his left buttock that was exacerbated by sitting for prolonged periods of time. He denied any hematuria, frequency, urgency, fevers or other constitutional symptoms. PSA and long-term data on both patients is pending and beyond the scope of this initial report.
Discussion
Treatment and subsequent outcomes for carcinoma of the prostate have improved steadily over time for this common neoplasm. NOTES RP appears to be a logical endpoint for surgical intervention if the initial experience is reproducible. Although significantly more experience will be necessary to confirm the adequacy of the dissection, if the technique can be refined to the stage that confidence exists as to the completeness of the surgical dissection then it seems realistic to move to a completely incisionless NOTES RP by performing morcellation of the prostate in the bladder following completion of the vesicourethral anastomosis. Based on our initial experience, the hemodynamic consequences of the NOTES RP dissection in the prevesical space are limited as evidenced in both the animal and clinical work. Further, with elimination of the suprapubic cystotomy, it seems reasonable to expect that postoperative morbidity from this approach will be very low, perhaps even allowing an outpatient procedure. In some ways, the NOTES RP dissection of the prostate is more straightforward than HoLEP as the distinction between capsule and adenoma can be considerably more subtle than the distinction between capsule and periprostatic fat. This technique, at least initially, is best suited for patients with early stage disease and prostates less than 50 cm3 (representing the vast majority of patients undergoing RP currently) but the true limits of the technique will only become apparent with time.
The experience of our first patient vis-à-vis sexual function is intriguing and also consistent with our experiences during the preclinical animal study. The mongrel dogs subjected to NOTES RP required creation of a perineal urethrostomy. The penile stimulation associated with creation of the perineal urethrostomy stimulated an erection in all of the animals that persisted throughout the entire dissection suggesting minimal effect on the neurovascular bundle. The early return of sexual function in our first patient is consistent with this observation and, further, is plausible given the physics of the energy source, the holmium laser, used for the dissection. The holmium wavelength is highly absorbed by water and only penetrates into tissues less than 0.4 mm. Further, the holmium laser used in our patients is pulsed, thereby generating very little collateral thermal effect. These attractive features of the energy source associated with the leverage that can be brought to bear by lifting up of the apex of the adenoma with the beak of the resectoscope during the dissection provides an ideal circumstance to drop the neurovascular bundle off of the capsule of the prostate with precision and with minimal thermal energy being transmitted to the neurovascular bundle. Dissecting the prostate away from the neurovascular bundles rather than putting traction on the neurovascular bundles themselves may be protective against mechanical injury. The magnified image provided by the resectoscope during this portion of the dissection also allows for precise handling of this critical feature of a potentially nerve-sparing approach. Although the potential benefits of NOTES RP vis-à-vis preservation of sexual function remains to be proved, this is potentially one of the most attractive features of this novel approach, at least to patients interested in the preservation of sexual function.
If the potential for NOTES RP is realized, it is likely that the attractiveness of a number of radiation-based approaches to treating adenocarcinoma of the prostate will be lessened. Many patients opt for radiation because of its reduced invasiveness, concern about sexual side effects, or because of advanced age or comorbidities. NOTES RP allays many of the concerns relative to current surgical approaches whether they be open, laparoscopic, or robot-assisted in nature and, thus, could hold the potential to significantly increase the percentage of patients with carcinoma of the prostate managed primarily by a surgical approach. Based on current instrumentation this could also represent a major cost savings to patients and health systems in terms of capital expenses, length of hospitalization, convalescence, and surgical morbidity
At this point, from the extensive preclinical and now early clinical experience reported, NOTES RP appears to be a feasible approach for carcinoma of the prostate. Only as clinical experience expands significantly will it be possible to understand the exact role that this novel technique will play in the management of this common disease. Further, time will be required to be certain about the oncologic outcomes but, of course, this is not unique to this particular approach. Obstacles to the establishment of NOTES RP focus primarily in two areas. First, the adequacy of the surgical dissection and, second, the ideal approach to creation of the vesicourethral anastomosis. In the report of Nagele and colleagues no anastomosis was performed and the surgeons merely relied on a Foley catheter [Nagele et al. 2011]. Such a minimalist approach will need further experience to see if this is truly feasible but it would seem likely in our view that a directly sutured anastomosis of some sort would be more reliable and, therefore, preferred. Historically, the importance of performing a mucosal to mucosal anastomosis during reconstruction has proven to decrease the likelihood of bladder neck contracture and stricture disease. Currently, instrumentation for performing a sutured anastomosis is somewhat problematic but we anticipate that as our industry colleagues develop interest in the approach of NOTES RP that there will likely be a number of techniques, technologies, and telescopes brought to bear on the problem.
Finally, the issue of the learning curve for NOTES RP will be significant. It seems to us that a prerequisite for performing NOTES RP is considerable familiarity and facility with HoLEP. Once this approach has been mastered then it may naturally be extended to NOTES RP. However, the technical challenges involved in performing HoLEP and ultimately NOTES RP are not trivial and one may anticipate a significant learning curve. Of course, this is not unexpected nor insurmountable as it has been established in a multicenter trial that approximately 200–250 cases are needed to overcome the learning curve associated with laparoscopic RP [Secin et al. 2010].
The future of NOTES RP will be based on partnership with industry to push innovation and to make the procedure easier to teach, perform, and reproduce. Technology may be of assistance as it could potentially aid with tissue manipulation and dissection or perhaps by providing the surgeon with some form of live intraoperative imaging to guide the dissection. New markers of prostate malignancy or specific tumor genetic markers may alleviate the need for determining margin status of the prostate as a surrogate for prognosis, making morcellation of the specimen more palatable without the loss of important disease-specific information. Instruments and tissue staining techniques may make it possible to determine margin status without the need for a cystotomy to remove the specimen. Now that NOTES RP has proven to be clinically feasible, additional research and efforts are needed to advance the technique so that it can be added to the surgical armamentarium for the treatment of localized prostate adenocarcinoma.
Conclusions and future directions
We have presented a summary of our preclinical cadaver and animal studies, as well as our initial clinical experience with a novel new technique for the treatment of carcinoma of the prostate, NOTES RP. The feasibility of NOTES RP has been established. Further experience will be necessary to understand the potential advantages, disadvantages, and ultimately the role of NOTES RP for the management of patients with carcinoma of the prostate.
Footnotes
Acknowledgements
The authors especially thank Desert Mountain C.A.R.E. for their support of prostate cancer research which has enabled research like this project to be accomplished. In addition, we would like to thank LSI SOLUTIONS Inc. for their contribution of time, instrument innovation, and material support of both the laboratory and clinical work.
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. The research was facilitated by institutional support of Mayo Clinic Arizona and Methodist Research Institute.
None of the authors have any relevant financial or industrial affiliations associated with this work. The authors declare that there are no conflicts of interest.