As minimally invasive surgery (MIS) increases in utility given the shorter hospital stays and the potentially lower surgical morbidity, surgeons will continue to strive for more efficacious techniques. This has been evidenced by the rapid shift away from open surgery and to laparoscopic and now robotic-assisted surgeries. The appeal towards MIS, particularly with the advent of robotics, has been the idea that improved visibility and the more precise surgical techniques will allow for (1) decreased postoperative morbidity, (2) shorter hospital stay and quicker recovery, and (3) potentially fewer complications.
In recent years, the adoption of newer technologies such as single-port (SP) robotic surgery performed by using a dedicated platform has shown promise in achieving these goals. Early evidence suggests that with the use of single-site surgery, postoperative morbidity in terms of the need for narcotics, hospital stay, and overall recovery would be significantly decreased. Concomitant with these advancements, the concept of scarless surgery has been always under investigation during the past two decades.
One such novel technique that has been viewed as predominantly experimental since its conception is natural orifice transluminal endoscopic surgery (NOTES). This technique is based on the principle of performing a surgery through a naturally hollow viscus, thereby essentially eliminating external scars for the patient, and potentially decreasing the morbidity associated with skin incisions. Ultimately, the goals are the same, namely the improved cosmesis, paired to less postoperative pain and shorter recovery time. Examples of entry points for NOTES procedures include transgastric, transvaginal (TV), transrectal, and transvesical.
In this chapter, we will review the background of NOTES procedures, and discuss some landmark experiments and studies regarding the application of NOTES procedures in urology, specifically focusing on the envelopes pushed in the field after the advent of the SP dedicated surgical platforms. Challenges and future directions will also be addressed.
Background—transition from laparoscopy to hybrid and pure NOTES
The first NOTES procedures were reported in the 1970s within the field of gynecology, where TV culdoscopic sterilization was described. However, the term NOTES was not coined until the early 2000s and gained a larger audience after the Natural Orifice Surgery Consortium for Assessment and Research was established, and their “White Paper” was published highlighting critical areas that required further research and analysis.
As various fields continued to advance NOTES techniques, it was quickly realized that standard laparoscopic instruments sometimes lacked the required flexibility and degrees of freedom to perform an entire operation safely and effectively. Therefore some surgeries would require at least one laparoscopic assistant port or a small laparotomy for assistance or specimen extraction (the so called “hand-assisted NOTES”). This required a distinction to be made between pure-NOTES (done solely through the incision of the viscus) versus the hybrid-NOTES (that required assistance via laparoscopy or laparotomy). In the pursuit of completing predominately pure NOTES procedures, many technological advances have been made to eliminate the ergonomic issues associated with standard laparoscopic instruments. For example, in 2006 Zeltser et al. developed a SP magnetic anchoring and guidance system that allowed them to successfully perform a standard laparoscopic nephrectomy with minimal difficulty in manipulating instruments compared to that encountered when using a standard equipment. Additionally, simple changes such as different surgical positioning has been shown to be effective. When implementing the use of robotics, it was found that pure NOTES procedures were highly impractical given the extensive extracorporeal instrument clashing in the confined surgical space in the lithotomy position. Laydner et al. found that repositioning to the prone-jack-knife position was able to mitigate the instrument clashing for performing NOTES nephrectomy ( Fig. 11.1 ).
NOTES in urology
In the field of urology, the concept of NOTES was first described by Breda et al. in 1993 with the vaginal extraction of an intact kidney after laparoscopic nephrectomy. It was not until 2002 that NOTES procedures were performed in live animal models by Gettman et al. In this small series of six TV laparoscopic nephrectomies in female farm pigs, five were hybrid NOTES and one was pure NOTES. All hybrid NOTES procedures were completed with only a single 5 mm trans-abdominal trocar with mean operative time of 210 minutes. For the pure NOTES procedures, the surgery took 360 minutes and the animal survived with no postoperative or intraoperative complications. These results were quite promising and emboldened surgeons to continue translational work.
Aminsharifi et al. expanded upon animal trials in TV NOTES nephrectomy using 10 female dogs for both right and left nephrectomies. Like Gettman et al., these surgeries showed great promise with minimal intraoperative blood loss (mean change in pre- and post-operative hemoglobin 0.31) and operative times ranging from only 75–135 minutes. Abdominal re-exploration 1 month postoperatively showed no significant intra-abdominal adhesions and complete healing of the colpotomy incision with this technique.
Continued experimental surgeries in both animal and cadaver models expanded the field with surgeries including NOTES radical prostatectomy and combined transgastric and transurethral NOTES partial cystectomy. In 2008, Branco et al. reported the first TV hybrid NOTES to be performed in a live patient ( Fig. 11.2 ).
In 2009, Kaouk et al. were the first to perform a TV pure NOTES nephrectomy. Currently, many groups have reported successful pure and hybrid NOTES surgeries in clinical practice with safe and effective outcomes. A cumulative retrospective analysis of NOTES and natural orifice specimen extractions (NOSE) was reported by Zou et al. including 35 animal and 305 clinical surgeries. Within this study, both pure and hybrid TV NOTES were included and procedure variety included nephrectomy, nephroureterectomy, partial nephrectomy, cystectomy, and adrenalectomy. These surgeries were undertaken for both malignant and benign conditions, with all oncologic surgeries having tumor size <7 cm (cT2a). In total, 12 TV-NOSE, 260 hybrid TV-NOTES, and 25 pure TV-NOTES were collected with major complications occurring in 7.2% of all cases. The causes of complications related to the learning curve, the presence of dense pelvic adhesions, or rectal injury ( n =1) during blind placement of the vaginal port. The procedures were tolerated well with minimal pain and similar preoperative and postoperative female sexual function index scores. Four patients were able to conceive naturally within 1 year of surgery. No complications with delivery secondary to previous vaginal access were observed. It must be emphasized that given the technical complexity and skillset required to achieve the aforementioned successes, these surgeries are still considered experimental and further research and analysis of clinical trials is required before implementing into standard practice.
Trans-vaginal access for NOTES nephrectomy
Nephrectomy is the most common urological NOTES. Branco et al. performed the first clinical TV hybrid NOTES nephrectomy in 2008 for a 23-year-old female with a nonfunctional right kidney secondary to chronic urinary tract infections. Their technique utilized two 5 mm abdominal trocars in addition to the TV ports. The operative time was 170 minutes and the patient was able to be discharged on postoperative day one and return to her daily routines on day three. This was a landmark report for the field of NOTES in urology and showed that it could be safely performed in the clinical setting.
The next advancement came in 2009 with successful pure TV NOTES nephrectomy in the clinical setting by Kaouk et al. ( Figs. 11.3 and 11.4 ).
Nephrectomy was done for a 58-year-old female with a history of right vesicoureteral reflux, recurrent urinary tract infections, and a resultant poorly functioning right kidney. The entirety of the procedure was completed trans-vaginally with operative time of 420 minutes and an estimated blood loss of only 50 cc. Importantly, the authors noted difficulties faced during this case were the close proximity of instrument ports resulting in extracorporeal clashing and poor tissue handling. Additionally, despite being able to complete the surgery completely through a vaginal access, the authors recommended that, atleast in early experience, the TV access should be done under direct visualization via a standard laparoscopic port camera to reduce the risk of visceral injury with a blind access through vagina.
As technique and experience continued to improve, another landmark case of hybrid TV NOTES nephrectomy was presented in 2012 when Kaouk et al. performed the first clinical TV hybrid NOTES transplant donor nephrectomy. Their technique was quite novel as they performed the surgery robotically, using the robotic arms for both the umbilical and the vaginal incisions ( Fig. 11.5 ).
This configuration allowed them to resolve the constraints of extra-corporeal clashing seen in TV pure NOTES. They were able to complete the procedure without the need for conversion to standard laparoscopy with an operative time of 240 minutes, a warm ischemia time of 5.8 minutes and an EBL of 75 cc. The patient tolerated the procedure well and was discharged after 48 hours of observation and required no intravenous pain medications. At follow-up of 4 weeks postoperatively, there were no complaints of vaginal pain or drainage, a well-healed vaginal incision, and patients were allowed resumption of regular sexual activity at that time. Although feasible, the author noted that further trials would have been necessary to evaluate safety and efficacy of this approach compared to standard laparoscopy.
Kaouk et al. actually paved the way for robotic NOTES. They were the first engrafting a robotic platform to the NOTES approach, trying to bridge the technology gap. Their hybrid approach using a robotic platform facilitated the surmounting of the technical challenges noted in both LESS (the instrument clashing) and NOTES. Nevertheless, the approach did not know further widespread diffusion.
Until this point, most renal surgeries performed via NOTES approach, whether hybrid or pure, were for benign indications. However, in 2014 Georgiopoulos et al. published their results on 38 hybrid TV-NOTES nephrectomies for tumor (23) and benign (15) indications. Their average demographics included average tumor size of 6 cm (largest of 7.5 cm) for renal cell carcinoma. Average operative time was 114.1 minutes with EBLs ranging from 50–150 cc. Intraoperative bladder injuries occurred in two patients that were closed primarily and two patients required transfusions postoperative. Notably, no positive surgical margins were noted after pathology reports.
Trans-rectal and trans-gastric access for NOTES nephrectomy
Trans-vaginal NOTES has been the most studied access point thus far given a sheer ease of access. Obviously, this would limit the use of NOTES procedures in male population.
Success with gastro-intestinal access has been demonstrated in several animal and cadaver model trials. In 2011, Bazzi et al. described the first attempts at transrectal NOTES via a hybrid transrectal approach in a porcine model. Access was obtained through a 2-cm incision above the dentate line under direct visualization via umbilical laparoscopic port. A total of three nephrectomies were performed with median operative time of 180 minutes (30 minutes for rectal access) and average blood loss less than 50 cc. The rectal incision was closed primarily without significant difficulty. Necropsy was performed 1 week postoperatively that noted no intra-abdominal injuries or signs of peritonitis. Similar results were seen in Park et al., where 15 female pigs were randomly divided into groups to undergo TV, transrectal, and standard laparoscopic nephrectomy. Mean operative times were significantly longer for TV and transrectal approaches (61 and 84 minutes, respectively) compared to conventional laparoscopy (24 minutes), but no evidence of visceral injury or peritonitis was noted on postmortem exams in all three groups.
Data on trans-gastric NOTES in urology is quite limited compared to trans-vaginal and even trans-rectal surgeries. In 2007, Lima et al. published their experience in a nonsurvival study of six trans-gastric and trans-vesical nephrectomies in porcine models. Median operative time was 120 minutes but notably decreased with experience per author report. Complications included hemorrhage during the dissection of the renal vasculature. Importantly, the specimens were not extracted from the pigs and the gastrotomy was not closed due to the lack of appropriate instrumentation. This topic was revisited in 2010 when Boylu et al. performed a pure transgastric NOTES partial nephrectomy in a single porcine model with specimen extraction and closure of the gastrotomy. They performed left upper pole nephrectomy with an operative time of 240 minutes and complete hemostasis was achieved with estimated blood loss of 240 cc. This was confirmed with direct visualization of the surgical site 4 hours postoperatively.
Trans-urethral approach for NOTES Prostatectomy
To expand the application of NOTES procedures in urology, Humphreys et al. tried to develop NOTES radical prostatectomy with the urethra as the natural access point. They applied the concept and principles of the Holmium laser enucleation of the prostate (HoLEP) for performing a radical prostatectomy. To prove this concept, this group performed NOTES radical prostatectomy in four male cadavers using a surgical set-up similar to that of HoLEP. Intraoperatively, they were able to preserve bilateral neurovascular bundles, the dorsal venous complex, the bladder neck, and the external sphincter. The vesicourethral anastomosis was completed using a laparoscopic suture device and knot pusher system. After excision of the prostate, the prostate was morcellated within the bladder. Negative margins were found at the NVB, bladder neck, and urethra. Despite the technical feasibility, questions about the possibility of cancer seeding in the bladder from the morcellation of cancerous prostatic tissue as well as the inability to perform appropriate lymph-nodes dissection when indicated remained.
In 2011 and 2012, two separate studies investigated the first clinical applications of NOTES radical prostatectomy. Humphreys et al. were the first who used their original technique on cadaver models. They extracted the en-bloc specimen via a small suprapubic cystotomy. This surgery was completed in two separate patients, one with Gleason 3+3=6, Stage pT2a Nx Mx and the other with Gleason 3+4=7, Stage pT2c Nx Mx. Negative margins did result after pathologic review. Patient one was able to have his catheter removed after 7–10 days. A similar concept was presented by Nagele et al. who reported a single NOTES radical prostatectomy (Gleason 4+3=7, Stage pT2c Nx Mx) using a thulium laser. They performed a sutureless vesicourethral anastomosis via traction with a Foley catheter and placement of a supra-pubic tube for improved drainage.
Trans-rectal approach NOTES prostatectomy
In 2015, Akca et al. reported successful trans-rectal NOTES radical prostatectomy in a cadaver model using SP robotics. Authors noted ease of exposure of the posterior prostate and seminal vesicles as well as extraction of an intact specimen through the trans-rectal port site. This is in stark contrast to the transurethral approach, which necessitates cystotomy to retrieve the prostate in the setting of oncologic surgery. There were no reported injuries to vascular, visceral, or neural structures during this procedure and the primary rectal incision was able to be closed securely.
NOTES in urology: challenges, limitations, and future directions
At the present time, there are very limited dedicated instruments and platforms for NOTES procedures. The use of standard minimally invasive instruments for NOTES can be challenging due to their limited degrees of freedom and maneuverability for surgery performed through natural orifices. For instance, Laydner et al. addressed how the poor flexibility, in addition to the close proximity of the ports resulted in extra-corporeal clashing in the dorsal lithotomy position. These constrains have thus far made TV surgery, even performed by using robotic platforms, highly impractical ( Fig. 11.6 ).