NOTES: A review

Quarterly Reviews

NOTES: A review

Magnus Jayaraj Mansard,¹ D Nageshwar Reddy², G Venkat Rao¹
Department of Surgical Gastroenterology¹ & Gastroenterology² Asian Institute of Gastroenterology Hyderabad-500082, India.

Corresponding Author: Dr. Magnus J Mansard
Email: jeymagnus@gmail.com,
jey_magnus@yahoo.com

Abstract

A few years ago a new approach to performing abdominal surgery was presented, i.e. via the natural body orifices using endoscopes. The interest and research in this approach progressed very rapidly, in spite of the initial skepticism. It was initially demonstrated in animal models, then in human beings and has now very nearly become routine practice. This article reviews the development of natural orifice transluminal endoscopic surgery (NOTES), its benefits and the hurdles we have yet to overcome.

There has been accelerated progress in the field of surgery. Laparoscopy was an improvement over conventional surgery as a small stab replaced the open abdominal laparotomy. The minimally invasive nature of this method resulted in the reduction of post-operative wound pain, shorter convalescence, and decreased wound infection and abdominal-wall herniae as well as the absence of scars. The next logical step in the evolution of minimally invasive surgery was to eliminate the abdominal incision altogether. Gastrointestinal tract endoscopy has also been witnessing major advances. Developing from flexible endoscopy to endoscopic retrograde cholangiopancreatography (ERCP) in the 1950’s and 70’s to endoscopic ultrasound in the 80’s, endoscopic technology has been transformed from serving purely diagnostic purposes to manifold therapeutic applications as well.

Natural orifice transluminal endoscopic surgery (NOTES) is an experimental surgical technique whereby “scarless” abdominal operations can be performed with an endoscope passed through a natural orifice (mouth, urethra, anus, etc.) avoiding an incision in the abdominal wall. It is in the developmental stage and several obstacles need to be overcome before the procedure can become part of routine clinical use. NOTES is potentially the next paradigm shift in minimally invasive surgery. It is safer, less invasive and possibly more cost-effective than the traditional open surgical or laparoscopic approach.

History

The origin of NOTES may be traced back to the year 2000 when Kalloo and colleagues[1] used a flexible endoscope through the gastrointestinal tract to enter the peritoneal cavity of a porcine model. They demonstrated the feasibility and safety of this approach and the report was published in 2004. Since then, there has been a surge in the number of different procedures performed with NOTES. Initial reports dealt with diagnostic procedures including endoscopic peritoneoscopy, liver biopsy, lymphadenectomy, and abdominal exploration. This was followed by a variety of successful transluminal procedures including oophorectomy, partial hysterectomy, transgastric jejunostomy, and gastrojejunostomy in both survival and non-survival porcine models.[2] In 2003, the first peroral appendectomy was carried out in a human subject, by the authors[1,3] The first clinical series of transgastric peritoneoscopy has recently been published.[4] Human NOTES has already been reported from numerous centres and the results are promising.[5,6] As expected, there are of course teething issues generating vigorous debate.

In order to prevent the premature adoption of NOTES in clinical practice, a rational framework to follow its development was proposed in 2005 by fourteen leaders from the American Society of Gastrointestinal Endoscopy (ASGE) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES).[7] This group published its deliberations as the NOTES Working Group White Paper.[8] The White Paper delineated the anticipated technical barriers to further development of NOTES, emphasised the need for development to be carried out by interdisciplinary teams of surgeons and gastroenterologists and asserted that any human procedures be performed only with IRB approval. Subsequently, the first international conference on NOTES was held in Scottsdale, Arizona in March 2006.

Transgastric NOTES

The peroral transgastric route using the anterior wall of the stomach was chosen to access the peritoneal cavity in initial trials because of the potentially lower risk for surrounding organ injury.[3] Also the gastric flora is less contaminating to the peritoneal cavity when compared to the intestinal flora. It has been shown in a recent study that transgastric instrumentation does contaminate the abdominal cavity however the pathogens do not mount a clinically significant response.[9] Techniques commonly used to reduce the bacterial load are: preoperative overnight fasting, antibiotic lavage of the stomach, perioperative intravenous antibiotic cover and use of a sterile overtube through the gastrotomy. The least vascular area, midway between the vascular arcades lying along the greater and lesser curvatures of the stomach, is chosen. The port is placed in the proximal body of the stomach for lower abdominal procedures like appendectomy. A similar site in the antrum, midway between the arcades, is chosen for upper abdominal procedures like cholecystectomy. A standard wire-guided needle knife, using blended current, is used to create a stab gastrotomy at the selected site. Adequate pneumoperitoneum is created through this stab which is further enlarged using a balloon or a sphincterotome for passage of the double channel endoscope. The most important issue in NOTES that is fiercely debated and is an area of active research is the safe closure of the gastric access.[1] Devices ranging from endoscopic clips to stapling devices have been used with considerable success in both animal and human studies.

Transvaginal and transanal NOTES

The transgastric route was used in the initial trials as experience from percutaneous endoscopic gastrotomy placements demonstrated the safety of his approach. The degree of convenience provided by the scope in performing upper abdominal procedures came to the fore when the scope needed to be retroflexed for performance of cholecystectomies and liver biopsies.[10] The transvaginal route, which provides a more direct view for these procedures, was used to obviate this disadvantage. A triangular area between the uterosacral ligaments which is avascular without innervation is chosen for the port placement. The difficulties of port closure are also averted as the port can be hand sewn under vision. A recent report of successful transvaginal liver resection in a human being speaks for this approach.[11] Potential ill effects of this route from the gynaecological point of view are formation of adhesions, spread of pre-existing endometriosis, infertility and dyspareunia.[12]

The transanal route was introduced subsequently to overcome the gender hurdle posed by the transvaginal route. Experience with transanal endoscopic microsurgery instrumentation was transferred to the performance of NOTES procedures.[13] In contrast to the transgastric method, a transcolonic approach provides more consistent identification of structures in the upper abdomen and provides better en face orientation and scope stability. Therapeutic intervention in the upper abdomen, including organ resection, may be more tenable by using a transcolonic method. Extra-long instruments are necessary for dissection from the pelvis. The potential disadvantages of the transanal route are also significant and include issues of sterility, the risk of inadvertent trauma to the adjacent organs during transmural puncture, and the risk of colonic wall shearing.[14] The transanal/ transvaginal route has also been called the transdouglas route in some series.[15]

Transesophageal NOTES

While the majority of the research in NOTES was limited to intra-abdominal surgery, some researchers evaluated its role inside the chest cavity.[16] Thoracoscopy and mediastinoscopy are common procedures with painful incisions and prominent scars. A natural orifice transesophageal endoscopic surgical (NOTES) approach could reduce pain, eliminate intercostals neuralgia, provide access to the posterior mediastinal compartment, and improve cosmesis. The submucosal endoscopy with mucosal flap safety valve (SEMF) technique is used to enter the chest transesophageally.[17] It as also called the STAT (self-approximating translumenal access technique).[18] High-pressure carbon dioxide injection and balloon dissection creates a large submucosal working space for the insertion of a cap-fitted endoscope. The muscularis propria is resected inside the submucosal space, and mediastinoscopy is performed by inserting the endoscope through the myotomy site. The muscular defect is sealed with the overlying mucosal flap, and the mucosal entry site is closed with clips. The SEMF technique provides safe entry into the mediastinum with a protective submucosal tunnel that prevents mediastinal soiling. The submucosal tunnel creates a flap-valve that alone, may be sufficient for preventing esophageal leak. Mid to distal esophageal access was demonstrated as safer than higher-level access. Transesophageal endoscopic mediastinoscopy, lymph node resection, thoracoscopy, pleural biopsy[19] and other complex operations including therapeutic procedures on the heart[20] and a complete Heller-type cardiomyotomy[21] have been shown as safe and feasible in animal models. Transesophageal endoscopic mediastinoscopy and thoracoscopy provide excellent visualization of mediastinal and intrathoracic structures that are difficult to appreciate using traditional cervical mediastinoscopy and thoracoscopy.

Single port NOTES

Use of the flexible scope, as has been discussed, results in various inconveniences including poor transfer of push and pull force and spatial incongruity. The TEM (transanal endoscopic microsurgery) technique, which has been in clinical use for more than 2 decades now, uses a single port that provides a stable platform for the passage of specialised rigid instruments capable of complex funtions like intraluminal suturing.[13] Similar single ports have been designed for NOTES having multiple channels and are capable of being locked into position.[22,23,24] NOTES peritoneal access, a peritoneoscopy, a liver biopsy, and colorectal resections have been carried out with relative ease transrectally and transvaginally.

Further the concept of E-NOTES has been developed, wherein the single port is introduced via the umbilicus, which is an embryonal (E) natural orifice.[25,26] It has also been termed NOTUS (natural orifice transumbilical surgery),[27] SILS (singleincision laparoscopic surgery),[28] SLIT (single laparoscopic incision transabdominal)[29] and TUES (transumbilical endoscopic surgery).[30] Single-port sleeve gastrectomy,adjustable gastric banding, donor nephrectomy, colorectal laparoscopic operations, bilateral single-session Anderson- Hynes pyeloplasty, ileal ureter, and ureteroneocystostomy with a psoas hitch have all been shown as feasible and safe in animal and human studies when performed by experienced laparoscopic surgeons. At the end of the procedure, the scar of the single port is hidden inside the umbilicus, thus achieving the “scarless” condition. Single port laparoscopic access could possibly reduce morbidity associated with additional trocar placement and, through the development of a hybrid intermediate, facilitate the clinical adoption of evolving techniques such as natural orifice transluminal endoscopic surgery. Advanced trocar technology, as much as adapted surgical technique, seems necessary to best facilitate this however.

Hybrid NOTES

The combind use of laparoscopy with NOTES is termed the hybrid technique.[31] It has also been termed MA-NO (minilaparoscopy assisted natural orifice surgery).[32] Guidance from the camera scope introduced through the laparocopic port allows the safe placement of the initial NOTES port through an avascular area away from the intestinal viscera.[33] Some have used the laparoscopic instruments for organ retraction as well.[34] Others have used the laparoscopic port as the working port while the ‘natural orifice’ has been used to extract the resected specimen.[35] The combined use of flexible and rigid scopes has special advantages. The use of rigid instruments has helped performance of complex surgeries like nephrectomy,[36] right hemicolectomy[37] and radical sigmoidectomy[32] in humans.

The ‘dual lumen’ technique is a variant of the hybrid technique where two ‘natural orifices’ are used for the surgery.[38] For example, the first hybrid sleeve gastrectomy was performed tranvaginally when the stomach was manipulated with a flexible peroral gastroscope.[39] It has also been termed the ‘rendezvous’ technique.[40] The hybrid technique serves as a temporary approach to aid in developing the NOTES technique. It has also been used to investigate the safety and feasibility of pure natural orifice surgery for complex interventions. The hybrid technique offers a superior vision source independent to the working endoscope. It may be used as an interim technique for developing NOTES until a novel imaging device becomes available, or serve as the final solution for accurate vision during this approach.[34]

R-NOTES (robotic natural orifice translumenal surgery)

One of the main limitations of NOTES is the lack of fine instruments. Robotics is one field where there has been active research and significant success in the development of instruments for minimally invasive surgery. Robot-assisted laparoscopic surgery has gained immense popularity with the development of master-slave prototypes like the da Vinci system. So, it was inevitable that this was utilised in NOTES as well.

Initial studies used robotics to manipulate the flexible endoscope in the peritoneal cavity or used magnets to guide a hook cautery supported by a robotic arm inside the abdominal cavity.[41] Further studies evaluated the feasibility of performing surgical procedures using the da Vinci system introduced into the abdominal cavity via natural orifices.[42] The constraints on visual feedback and dexterity of conventional NOTES were to a great extent surmounted by this system. Recently 30 complex reconstructive urologic procedures have been performed safely in a porcine model. Intracorporeal suturing was significantly enhanced using the robot, especially through the challenging transluminal natural orifice approach.[43]

The other field of research has looked into the use of miniature robots introduced into the peritoneal cavity to perform various tasks.[44] In a recent study, a two-armed dexterous miniature in vivo robot with stereoscopic vision capabilities successfully demonstrated various capabilities in a nonsurvival natural orifice surgical procedure in a porcine model.[44] The design and kinematic configuration of the robot allows for its complete insertion into the peritoneal cavity, and provides intuitive visualisation and sufficient force application for tissue manipulation within the dexterous workspace. In another study, a telecontrol system using high-speed data transmission from the master device to the robot has guided the performance of robotic NOTES by the telesurgery method.[45] The final goal of robotics is to allow safer and more homogeneous outcome with less variability of surgeon performance, as well as new tools to perform tasks on the basis of medical transcutaneous imaging, in a less invasive way, at lower costs. Further development of robots adaptive to NOTES would boost efforts toward clinical NOTES applications.

EUS-guided NOTES

The peritoneal cavity was initially entered transgastrically, given the safety of this technique from experience with percutaneous endoscopic gastrotomy (PEG) placements. With the use of transdouglas routes for the initial blind puncuture, accidental injury to adjacent viscera has become a major concern. Blind puncture of the gastric antrum has also been a cause for concern. Endoscopic ultrasound (EUS) guided access through these sites has been shown to substantially reduce this risk.[46] EUS appears promising as an adjunct to NOTES access, particularly as more experience is gained in definitively excluding the presence of at-risk extraluminal structures.[47] An animal study comparing plain NOTES with EUS guided NOTES concluded that EUS guidance is helpful in gaining access or identifying structures in areas anatomically difficult to reach, in NOTES procedures.[48]

Training

Performance of NOTES requires two sets of advanced skills, those of interventional gastrointestinal endoscopy and those of minimally invasive surgery. In the future, a new cadre of NOTES surgeons with proficiency in both these fields might develop. The ASGE/SAGES working group formed some guidelines for such training.[7] They recommended multidisciplinary team involvement, use of animal laboratory facilities and monitoring by an institutional review board. Some institutions are developing training programmes for digestivists incorporating both surgical and gastroenterologic training. A steep learning curve has been reported from one such training programme, despite the presence of an investigator familiar with the elementary NOTES procedures.[49] Surgical residency programmes integrating training in endoscopy has allowed early integration of surgery residents into research efforts in NOTES.[50] Technological innovations developed to help in training include augmented reality techniques using pre-procedure CT or MRI imaging, real time tracking and reference image registration, and display to theoperating physician. It is anticipated that such augmentation will make intra-cavitary interventional techniques easier to master and use in practice, and thus more likely to be widely adopted.

Benefits of NOTES

There are many potential advantages of NOTES over conventional surgery. Much like laparoscopy has demonstrated less physiologic impact than laparotomy NOTES may cause less physiologic insult than either laparoscopy or laparotomy. Absence of scar has obvious advantages. There is the lack of common complications of conventional surgery like wound infections and incisional hernia. It may probably reduce the formation of intra-abdominal adhesions.[51]

Cosmesis is the one area where NOTES scores without doubt over open and laparoscopic surgery. “Invisible mending” that NOTES offers means that patients do not have a visual reminder of their surgery every time they undress. It has been shown that young people prefer to undergo a scarless experimental procedure than a well-established conventional procedure even after being educated about the risks involved.[52]In another study NOTES was preferred to laparoscopy as the technique for cholecystectomy as long as the complication rates were comparable with the current standards of laparoscopic cholecystectomy.[53]

Given the portability of NOTES equipment, NOTES might relocate the surgeon from the operating theatre to the patient’s bedside. Major interventional procedures might be carried out in the future in an ICU setting. Moving the equipment to the patient, rather than vice versa, might reduce the resource requirements and potential complications of transporting a patient to the operating room. Moreover, NOTES could be performed under conscious sedation, rather than general anesthesia, again favoring intensive care unit (ICU)-based procedures.

NOTES offers specific advantages to select patient populations. Patients with no percutaneous access, as in the patient with abdominal wall burns who underwent the first NOTES appendectomy, will derive special benefit from NOTES.[3] Another group is the morbidly obese, who will benefit greatly from NOTES. The lack of even the small laparoscopic incisions, which are prone for complications in these patients with a thick layer abdominal fat, is an important advantage. The need for minimal anaesthesia and rapid postoperative convalescence are other advantages.[54] Studies have already demonstrated the feasibility of obesity surgeries, like sleeve gastrectomy by NOTES.

The interest in NOTES has motivated a great deal of flexible endosurgical device innovation and development among the major makers of laparoscopic and endoscopic instruments. [55] Current and future endoscopists and lapraoscopists will reap the benefit of this research because many techniques and devices that are developed for NOTES will be also put to use in conventional procedures.

Challenges

NOTES being a new technique requires refinement before it can be employed in daily clinical practice. It has its fair share of skeptics, faces various technical and intellectual challenges and several key issues need to be addressed.

Reliable closure of the transluminal incision is the crucial step in NOTES. The transvaginal approach does not necessitate any sophisticated devices for opening and closure of the posterior colpotomy, thus making it easy for the surgeon and safe for the patient. In contrast, the problem of transluminal access and closure represents significant obstacles in the transgastric approach and is still unresolved.[56] In order to achieve this goal, various surgical prototype devices have been developed.[57] These include the use of conventional endoscopic clips, newly designed clips or T-BARS in different shapes or more complicated devices such as linear endoscopic staplers and septal occluders, originally used for the treatment of cardiac septal defects.[58] Various stapling devices, that include the NDO Plicator[59] originally designed for endoscopic plication for GERD, the endoscopic tissue plicating devices (TPD),[60] the over-the-scope clip system (OTSC)[61] and the automated flexible stapling device (SurgASSIST)[56] among many others, have been evaluated and safety proved in various studies. A self-approximating extended submucosal tunnel, described for transesophaeal procedures, has also been evaluated for the stomach with some success.[62] Unless new safe and simple devices for endoscopic gastrotomy closure are available and have proven efficient, NOTES will remain in the hands of a few specialists at centres of excellence because the risk of complications due to insufficient gastrotomy closure will not be acceptable for the surgeon and gastroenterologist in general practice.

Infection of the peritoneal cavity by organisms carried in by the scope from the orifices has been an obvious area of concern. Extensive surgical experience with bacteriologic contamination of the peritoneum during bowel surgery shows that if gross spillage is avoided and appropriate antibiotic cover is provided, the contamination is well tolerated. Studies have shown that transgastric instrumentation in patients does contaminate the abdominal cavity but pathogens are clinically insignificant due to species or bacterial load.[63, 64] Patients on proton pump inhibitors have an increased bacterial load in the gastric aspirate, without clinically significant infection. On the other hand, NOTES transgastric ventral hernia repair with mesh showed a high rate of infection despite adequate antibiotic precautions and gastric irrigation.[65] Infection was the chief concern when experienced gynaecologists were querid about the safety of transvaginal NOTES.[12] Introduction of new organisms that are commensals of the mouth, anus or the vagina into the peritoneal cavity is another important issue.

Triangulation, tissue retraction and apposition are the fundamental principles in any laparoscopic procedure. The current endoscopes however have limited ability to manipulate the intra-abdominal organs. There is a fixed parallel orientation of the view and instrument axes reducing the ability for threedimensional assessment. They have insufficient angulation, tolerate very little push force and have a very narrow accessory channel. NOTES tools that are being developed are expected to address these issues soon.[66]

Working off the axis of the camera angle (i.e., off axis) as is routine in laparoscopic surgery is a problem surmountable with practice and a little mental exercise when rigid scopes are used.[67] However, when flexible scopes are used in NOTES, the off-axis view results in spatial incongruity requiring severe mental strain. This will prevent complex procedures from being performed with the speed and facility that in-line visualization would allow. Potential solutions include the use of multiple cameras to achieve the appropriate inline view of the working area[68] and the use of computer interface (live video manipulator)[69] between the video feed and the actual image of the end organ, which automatically adjusts the axis of the camera angle with every deviation. New instrument designs and clinical tricks combined can dramatically decrease the mental work needed and make this closer to a widely learnable access method.

Till date the advantages of NOTES have been only theoretical. No study has so far shown scientific evidence of the proposed benefits of a ‘scarless’ surgery. For wider acceptance of this technique in the scientific community, trials comparing NOTES to conventional surgery need to be undertaken.

The pursuit of establishing NOTES in any institute requires animal lab facilities and advanced tools and devices, which incur huge costs. However, when NOTES gains general acceptance the actual expenditure may be overshadowed by the benefits accrued due to the paradigm shift in management strategy.[70]

Conclusion

While natural orifice translumenal endoscopic surgery may represent a new era in surgery, it is still largely an experimental field. Although clinical NOTES is gaining momentum, the field should remain in check while rigorous laboratory work is performed and cogent clinical trials are undertaken. The zeal for NOTES should not take precedence over the welfare of the patient. Well-managed human studies need to be conducted to determine the safety and efficacy of NOTES in the clinical setting. Although many limitations need to be surmounted before NOTES can reach the human clinical trial stage, the prospect of safe, minimal invasive and scarless surgery appears very promising.

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