Current progress on natural orifice transluminal endoscopic surgery (NOTES)

Abstract

Natural orifice transluminal endoscopic surgery (NOTES) has received considerable interest in recent years as a novel surgical technique. Here, we aim to review the current progress on NOTES, particularly focusing on the advantages and complications related to NOTES, the recent advances of surgical approaches, new instruments for closure of the natural orifice incision, and the newly developed platform for NOTES. Finally, we make a prediction of the conceivable applications of NOTES on human subjects.

Keywords

natural orifice transluminal endoscopic surgery (NOTES) / laparotomy / laparoscopy

Introduction

Natural orifice transluminal endoscopic surgery (NOTES) has received considerable interest in recent years as a novel surgical technique. In 2004, NOTES was first performed on swine by Kalloo et al. [1] for diagnosis and abdominal pathology treatment by combining endoscopic and laparoscopic techniques. The combination of techniques was done to eliminate abdominal incisions and incision-related complications. Since then, extensive research has been undertaken focusing on transluminal access and peritoneal cavity surgical procedures [2]. NOTES was designed to avoid the need for abdominal incisions and to offer potential benefits such as reduced invasiveness and increase efficacy compared to traditional laparotomy or laparoscopic surgery for certain indications. The technique was gradually developed to perform intra-peritoneal operations by means of natural orifices such as the mouth, anus, or vagina.

Clearly, NOTES offers an opportunity for patients who undergo a surgery that could result in cosmetic alterations. A comparison with laparotomy and laparoscopy demonstrated the potential advantages of NOTES, including a reduction in post-operative pain, hernias, and wound infections. In addition, the need for anesthesia would be decreased, and hospital stay would be made shorter when employing NOTES. This technique could also offer benefits for select patients, especially those who may be at a high surgical risk with traditional operative methods (e.g., patients with former abdominal surgical wound infections or surgical interventions). Morbidly obese patients could also choose NOTES to avoid complications after laparotomy [3]. Close collaborations between surgeons and gastroenterologists have been increasing in recent years. To develop NOTES systematically, The Natural Orifice Surgery Consortium for Assessment and Research™ (NOSCAR™) in the US [4] and the EURO-NOTES Foundation were formed.

NOTES is currently performed mainly in animal models (Figs. 1-3). Surgical practices such as cholecystectomy [5,6], liver biopsy [7], appendectomy [8], gastrojejunostomy [9], splenectomy [10], and antireflux surgery [11] have been successfully performed in animals. In addition, gynecologic operations such as tubal ligation [12], oophorectomy, and partial hysterectomy [13] have been performed. Recently, the application of NOTES in retroperitoneal procedures such as nephrectomy has also been reported [14].

Although procedures on animals have provided basic experience, human case reports are rare. The scarcity of human case reports is likely due to the lack of key methods for the application of NOTES, including safe methods for the closure of the gastric incision, the ability to avoid infections, new instruments and a new platform. Some authors have stated that NOTES was not ready for widespread use on humans. Furthermore, in 2006, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Working Group has defined the hurdles and challenges suggested above in a white paper to allow for surgeons to address these key obstacles [15]. In the years that followed these white pages, significant progress has been made to overcome those obstacles, and the use of NOTES on humans has become more feasible than in earlier years. Here, we aim to review the current progress on NOTES, particularly focusing on the advantages and complications related to NOTES, the recent advances of surgical approaches, new instruments for closure of the natural orifice incision, and the newly developed platform for NOTES. Finally, we make a prediction of the conceivable applications of NOTES on human subjects.

Advantages of NOTES

As a novel technique, NOTES introduces new operative approaches and applies innovative instruments, which are incredible advances in the context of traditional operations. NOTES has presented the following advantages compared with traditional laparotomy: (1) NOTES involves no abdominal incision, and therefore leaves no scar. This characteristic affords NOTES cosmetic advantages, and without an incisal wound, patients will no longer suffer from post-operative pain. (2) Given that NOTES leads to less injury and pain, a reduced dosage of analgesic and anesthetic drugs is needed for patients. By using an endoscope, NOTES could be performed without the necessity of general anesthesia and may even become a bedside operation. (3) Patients who adopt NOTES could recover more quickly than those who use laparotomy, and the length of stay in the hospital could be shortened. (4) NOTES is performed without any puncture through the abdominal wall, unlike procedures with a laparoscope, and the occurrence of a wound infection and/or an operation-related hernia could be reduced. (5) Severe inflammatory reactions could also be reduced due to the decreased injury associated with NOTES, and the occurrence of complications is likely to decrease. (6) NOTES is a more reasonable method for patients who are at high risk and who have difficulties (e.g., adiposis) with laparoscopy or laparotomy [16].

Wound infection is a common post-operative complication. Patients adopting either clean extra-abdominal operations or intra-abdominal operations could suffer infectious complications at a rate of 2%-5% and 20%, respectively [17]. The skin is the most common source for bacterial infections. NOTES is performed without employing a transabdominal approach and is instead achieved without a skin incision. Some authors have suggested that NOTES is associated with lower rates of infection [18]. Studies in swine have demonstrated that by employing NOTES, no abdominal wall infections and a low rate of intra-abdominal infections occurred. Few trials, however, have provided sufficient numerical data regarding the rate of intra-abdominal infection following NOTES.

Incisional hernia is another post-operative complication related to traditional procedures that employ an abdominal incision. Among patients with an abdominal incision, 5%-15% suffer from incisional hernia within one year after operation, especially patients with post-midline vertical incisions [19, 20]. The laparoscopic operation is an efficient way to reduce the occurrence of a hernia; however, for special patients such as those with adiposis, trocar-involved hernias can occur in approximately 5% of patients [21]. In NOTES, the surgeon uses approaches to avoid the abdominal wall, which may decrease the formation of a hernia. Practice in animal models has indicated that NOTES may help to eliminate hernias.

The peritoneum is a smooth structure that prevents abdominal viscera adhesion. During a laparotomy, an incision is made in the abdominal wall, thereby decreasing the effectiveness of the peritoneum. This kind of incision is the common cause of intra-abdominal adhesion. A prospective study concluded that 93% of the patients who underwent a laparotomy were diagnosed with an intra-abdominal adhesion after surgery [22], and severe adhesion could induce visceral complications such as small bowel obstruction. It is clear that reducing the incision made in the abdominal wall could be useful for preventing intra-abdominal adhesion. NOTES is performed through natural orifices, which is advantageous over laparotomy because it eliminates the incision in the abdominal wall. To operate on an abdominal viscera using NOTES, however, damage to the peritoneum cannot be avoided. In one study in which transcolonic NOTES was performed, adhesions were observed in four out of six swine [23], indicating that NOTES may not be able to solve adhesion complications.

Transluminal approaches to the thoracic or peritoneal cavity

Traditional surgical approaches are restricted in some situations because of the barrier of visual angles and the limitations of certain patients (e.g., patients with serious complications or morbid obesity). NOTES employs approaches that are contraindicated in traditional surgery by using special instruments and the utilization of natural orifices. To access the thoracic or abdominal cavity and perform a NOTES operation, an endoscope is inserted into an orifice, and the mediastinum, thoracic or abdominal cavity is punctured. In mediastinal and thoracic NOTES, the thoracic esophagus is the only reasonable site for access, whereas for NOTES in the abdominal cavity, access to the peritoneal cavity can be obtained via the stomach, colon, bladder, and vagina.

The method of secure transluminal access represents an obstacle to NOTES. For instance, punctures to critical structures surround the thoracic esophagus, including the descending thoracic aorta, the heart, and the pulmonary veins, may result in serious complications. Locating the sites of safe puncture is an important subject in NOTES. Endoscopic ultrasound (EUS), which has been widely used during transthoracic, transgastric, transcolonic and tranvaginal surgeries [24], has been found to be an efficient tool for locating safe access points through natural orifices [25-27]. The transrectal approach could also draw assistance from a catheter by cutting the colon, for which no puncture-related complications have occurred [28,29]. Finally, using a cystoscope, a transurinary approach is also known to be safe [30].

Another problem for locating a safe puncture site is identifying a site that will minimize the amount of turning required of a retroflexed endoscope. Transluminal approaches should result in the ability for the endoscope and other instruments to arrive at the operative site. Clearly, the transgastric approach could provide a clear visualization and efficient access to pelvic structures, whereas the transrectal and transvaginal methods could provide access to upper abdominal structures.

When localization has been accomplished, special instruments are used to create a transluminal incision. The development of these instruments was performed in two steps. Previously, a surgeon would use a needle-knife to pierce the tissue and then enlarge the incision with a dilating balloon or sphincterotome [1,9]. This procedure requires puncturing the wall of the orifice, and it is necessary for the surgeon to change instruments after making the incision with the needle-knife and risk peritoneal contamination via the incision through the gastric tunnel. Recently, the instruments used for NOTES have been refined to make the puncture and enlargement in one step. The needle-knife and the pull-type sphincterotome were assembled on the same instrumental shaft, and the perforation of the site became faster without increasing the occurrence of complications [31]. In addition, a new method for access allowed a tunnel to be made throughout the tissue submucosally, and the difficulty in closure of the opening could be solved reasonably due to this submucosal tunneling technique [32-34]. With the submucosal tunneling technique, the surgeon will observe a leak pressure after closure equal to that observed following a hand-sewn closure, thereby decreasing the risk of leakage from the site.

Methods for natural orifice incision closure

Suturing and anastomotic instruments have been developed to solve the problem of natural orifice incision closure, which is critical for a successful NOTES. Leakage is a severe post-operative problem in NOTES and is related to morbidity and mortality. Gastric leakage is the most common cause of NOTES failure. Intra-abdominal infection and peritonitis could follow leakage, and severe infection could result in death.

Several devices have been designed and applied in a variety of studies. Clipping, stitching, stapling, and occluding devices have demonstrated the most efficient closing of gastric defects.

In the clipping method, the jumbo endoclip was employed first. This device could approximate the mucosal edge of the orifice incision using clips [35,36]. When the opening of the orifice is too large, however, jumbo endoclips are unable to clip the defect outside of the range of the jaws. In these cases, the jumbo endoclip should be replaced by another clip device, such as nitinol clips, which can revert to their original shape when released. This kind of clip could provide similar leak pressures compared to hand-sewn closures and also presents the advantage of seromuscular layer inversion, which is useful for preventing leakage [37,38].

Stitching methods include the eagle claw, T-tags, and the G-Prox needle. The eagle claw is named due to its shape. It utilizes an opposing jaw to draw the edge of the incision closed and eject a nylon stitch. Eagle claws have provided solid suture pressure in swine models such that none of the test models suffered from gastric leakage or peritonitis [39]. The T-tag is made of a couple of tags that can tighten when placed in opposing positions, allowing the tags to lock together. This method provides efficient closure of thick gastric muscles; however, injury of the viscera typically occurs when tags penetrate through the thick tissue [40]. The G-Prox needle is a device that works like T-tags. With this device, the surgeon first sutures the opposing edge of the incision and then tightens the string. Next, two hooks loaded on the device approximate and lock the tissue. The flexible stapling system consists of an automatic eject lever, which could form four linear rows of staples across the defect. Occluding methods were first designed for closure in cardiac operations but now contribute to closing gastric incisions and provide satisfactory outcomes in reducing post-operative leakage of NOTES [41].

A new platform for NOTES

NOTES is practiced based on the endoscopic and laparoscopic technologies. There are currently two types of NOTES being used: pure NOTES and hybrid NOTES.

Pure NOTES uses the flexible endoscopic technique [4] by assembling devices as one instrument. Thus, pure NOTES is desirable because it allows for single port surgery and effectively reduces the formation of pain, hernia, and wound infections. In addition, it fulfills a cosmetic function. During surgery, however, the surgeon does not have tactile feedback or the ability to triangulate because of the application of only one instrument, and these limitations have yet to be resolved.

Hybrid NOTES combines laparoscopic and endoscopic technologies and is commonly used because of its controllability. With the development of new techniques and instruments, however, the use of hybrid NOTES should gradually give way to pure NOTES. We believe that a multitasking flexible endoscope-based platform is needed for future NOTES applications.

The new platform aims at a flexible, stable, and systematic application of NOTES. Laparoscopic techniques can provide a stable image and comfortable operating view obtained by a monitor through the trocar, independent of other instruments. A multitasking platform should also provide high qualitative images throughout a single port with no intervention of tasking arms when NOTES is performed. In addition, a reasonable platform should be adaptable to different operative fields by adopting different transluminal approaches.

The number of types of robotic arms needed for an operation is another considerable subject. To perform complex motions under NOTES without involving multiple arms or altering the image quality, the arms should be more flexible and should move at various angles.

Corporations such as Olympus Corp. (Tokyo, Japan) and Boston Scientific (Massachusetts, USA) have made an effort to develop new platforms and have developed NOTES instruments, the EndoSAMURAI and the Direct Drive Endoscopic System (DDES), respectively with multitasking functions [42,43]. The DDES has the advantage of performing complex motions under the endoscope, including grasping, clamping, cutting, suturing, and knot tying. Importantly, this platform allows for solo operating [44].

Flexible instruments should meet the need of not only complex motions but also bleeding control. Homeostasis remains a challenging post-operative problem when blood pressure rises to 200 mmHg [45]. In various studies, some instruments such as monopolar forceps and flexible bipolar forceps and methods such as endoscopic suturing and argon plasma coagulation have been used to combat this problem. Argon plasma coagulation has allowed for quick hemostatic control [46], and flexible bipolar forceps were introduced as a secure method to control main branch vessels ranging from 1.5 to 6 mm in diameter [45].

Discussion

NOTES has developed quickly over recent years, and this technology makes minimally invasive operations possible. Although the obstacles that prevent the widespread application of NOTES in human subjects have been discussed since the procedure was first suggested in 1994 by Wilk, with the progression of both special instruments and the abilities of surgeons, NOTES presents significant advantages over traditional surgical procedures. Based on the support of the laparoscopic technique, NOTES is becoming a method that employs a minimal incision and provides high efficiency, a favorable cosmetic outcome, fewer complications (e.g., pain, infection, and adhesion) and a shortened hospital stay.

Due to animal research, many problems encountered with NOTES have been resolved, including the identification of better approaches to the thoracic and abdominal cavities, safer puncture sites through natural orifices and more efficient closure methods. Platforms are being designed for multiple tasks and have made significant progress. These advances suggest that it may be possible to utilize NOTES on humans; however, reports of NOTES procedures on humans are somewhat lacking and are limited to single or series case reports. Whether differences between swine and human in both anatomy and physiology could result in different outcomes remains uncertain.

Compared to the laparoscope, anatomical structures encountered during NOTES could cause more restriction because of the single approach procedure and the internal structures between the opening and the aimed region. In classic laparoscopic operations, the surgeon locates different positions on the abdominal wall and uses several trocars to arrive at a particular intra-abdominal site. The view of the intra-abdominal cavity can be adjusted through different trocars during one operation, and through the operating trocars, devices can help to reveal a particular site. In NOTES, display devices and operating devices are handled through a single opening; thus, the flexibility of devices is restricted. In addition, anatomical differences between males and females could provide different levels of effectiveness. For instance, with the development of secure closure devices, transcolonic and transurinary approaches could be safer. The risk of leakage and severe peritonitis following surgery, however, could be increased due to the patient’s nutritional state and ability to heal. The transvaginal approach could provide a reasonable linear position for the epigastric region, and contamination through the vagina is less than either transcolonic or transurinary approaches. In addition, digestive leakage could be effectively avoided. The closure of the incision in the vaginal wall is also relatively easier and more secure than those on the colon and bladder. With the advantage of reduced peritonitis resulting from leakage, adhesion, and reasonable linear anatomical position, the transvaginal approach could be a favorable method for most NOTES procedures, especially for the epigastric region. In addition, the healing of the vaginal wall can be quick, and an incision in the wall does not require restrictions in the post-operative diet because the operation is performed without the involvement of the digestive tract. Clearly, NOTES cannot be performed on male patients via a transvaginal approach. To this point, female patients have a greater advantage because of the extra orifice.

Studies employing NOTES have indicated some problems with the procedure that still remain. First, different devices and instruments need to be used on a large sample size to be compared and commented on such that the safer and more efficient tools among the prototypes can be chosen. Second, the limit of obtaining an optimum position could hinder handling abilities during a procedure such as a transluminal enterotomy. Unfortunately, the modus operandi of NOTES is relatively monotonous compared to laparoscopic operations. Since an appendectomy was performed by Reddy in 2004 as the first NOTES in a human, the main procedure used in humans to date is via transvaginal or transgastric cholecystectomy, despite the different types of procedures available. Third, the approaches used in NOTES are governed by the type of operation being performed. Whether these approaches could provide a particular position for a special intra-abdominal region via the determinatus approach should be studied in a large sample size. Fourth, the recently reported multitasking platforms should meet the needs of different approaches and different anatomic conditions because the situation when using NOTES in humans will be more complex and difficult to control. Perhaps cooperation is necessary between organizations and centers to promote finding solutions to these issues.

Another subject that should be discussed is the economic effectiveness of NOTES. Instruments and devices have been specially developed for use with NOTES. Because the procedure can be performed via natural orifices while limiting the incisions necessary, devices should meet the needs of both flexibility through single openings and stability when performing NOTES with multiple and complex motions that could result in deterioration. Designing instruments and devices for NOTES should focus on fragile assemblies and the efficient consolidation of devices, which could decrease the medical cost and be accepted by a greater proportion of the population. Conversely, surgeons who are trained to employ NOTES are rare. Successful NOTES procedures rely on not only the flexible instruments but also technical performers. Training on the laparoscopic technique could be long and depends on the individual surgeon’s learning curve. New simulation platforms could be an efficient method to expedite learning.

Conclusions

The results of NOTES research present a hopeful prospect for the widespread use in human patients. Most studies, however, have focused on small trial applications of this procedure, suggesting that whether favorable data can be consistently obtained in humans remains unclear. Since 2005, the NOTES white paper was announced and outlined, and obstacles remain for NOTES. In recent years, it is clear that progress has been made with the procedure, and many problems that were significant barriers for NOTES have been addressed. In addition, by using technology developed to date, human NOTES procedures are gradually emerging and are currently performed mainly in the form of hybrid NOTES. Although it remains necessary to develop special instruments to attempt pure NOTES, the feasibility of NOTES has been demonstrated and studies of the procedure have transitioned from animal models to humans.

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