Advances in Pediatric Minimal Access Therapy: A Cautious Journey From Therapeutic Endoscopy to Transluminal Surgery Based on the Adult Experience

Since the introduction of laparoscopic surgery by Kelling in 1901, minimal access surgery has developed into a safe and clinically comparable alternative to open surgery of the abdomen. It brings substantial benefits to patients, both adult and pediatric, including less pain, reduced risk of local and systemic complications (eg, ventral herniation, wound infection, adhesion formation), faster recovery, and superior cosmesis ⁽¹⁾.

In recent years, therapeutic endoscopy has entered the realm of minimal access surgery, motivated by the goal of further minimizing the invasiveness of abdominal access. With the focus mainly on gastroesophageal reflux disease (GERD), several innovative endoscopic tools have been developed in the attempt to replicate 1 or more of the features of a surgical fundoplication. The Wilson-Cook Endoscopic Sew-Right suturing device, the Bard EndoCinch, and the NDO full-thickness plicator are examples of devices now in clinical use. Alternatively, procedures such as the Stretta exploit the use of energy sources, in this case radiofrequency ablation, to bolster the lower esophageal valve mechanism.

Blurring the lines between endoscopy and minimal access surgery, a new surgical technique has emerged that uses the natural orifices of the body, such as the mouth, anus, and vagina, to access the peritoneal cavity and pelvis. This new paradigm, natural orifice transluminal endoscopic surgery (NOTES), is expected to further reduce the pain, scarring, and recovery time associated with intraperitoneal surgery.

For any of these procedures to be adopted into mainstream clinical practice, efficacy and safety equal to that of existing surgical approaches (ie, open and laparoscopic surgery) must be demonstrated to realize the benefits of the endoscopic approach. Literature to support this is limited for the adult population and nearly absent for the pediatric population. There is a danger that conceptually exciting therapies such as NOTES may be prematurely adopted and applied to pediatric populations before sufficient experimental evidence accumulates to demonstrate their safety and efficacy. Perhaps a greater danger, however, is to prematurely discredit these therapies or ignore their existence. It is likely that future therapies will incorporate elements of minimal access endoscopic approaches, and it behooves the pediatric medical community to play an active role in their development and ethical application.

This article explores the confluence of pediatric minimal access surgery and therapeutic endoscopy in a novel modality called transluminal surgery, or NOTES. The limitations of conventional pediatric minimal access surgery are briefly discussed, and existing therapeutic endoscopic procedures are reviewed. The concept of transluminal surgery, with its future directions and challenges, is introduced, and the emergence of a new type of minimal access surgical specialist is proposed. The goal is to raise awareness of these “fringe” technologies so that practitioners can understand better what the future may hold for pediatric minimal access therapy.

PEDIATRICS AND MINIMAL ACCESS SURGERY

Laparoscopy has gained firm ground in the adult population since the first laparoscopic cholecystectomy in 1985, and a large majority of abdominal and thoracic procedures are now routinely performed by the use of minimal access methods. Pediatric surgeons have taken a more cautious approach. They first applied laparoscopic techniques already developed in adults, such as cholecystectomy, fundoplication, and appendectomy, before proceeding to conditions unique to pediatrics such as imperforate anus, biliary atresia, and tracheoesophageal fistula. This careful approach is attributed to a reluctance to “test” novel procedures on children and to the recognition that children are in many ways unique from adults.

The most obvious hurdle is that infants and children are not merely small adults to whom adult techniques can be applied. Contained within the relatively small abdominal cavity of a child are a relatively large liver and spleen, a more horizontally oriented stomach, and an intraabdominal bladder. Consequently, the abdominal workspace is significantly smaller than in an adult. Furthermore, the thinner abdominal wall increases the potential for bowel or vessel injury during trocar placement, and it increases the chance for the development of port-site hernias, particularly in infants. In addition to the anatomic differences between pediatric and adult patients, there is also variability in physiology. In children, more so than in adults, insufflation-induced hypothermia is of concern and must be closely monitored ^(2,3). The hypercarbia induced by pneumoperitoneum in infants has been shown to be associated with changes in cardiac output and cerebral blood flow ^(3,4).

Similarly, for endoscopic therapies, the size limitations imposed by existing scope technology and the relative dearth and infrequency of pediatric pathology amenable to endoscopic therapy has limited the development of interventional endoscopy in children. It is likely that interventional endoscopy and NOTES development will take a path similar to laparoscopy. The safety and efficacy of these approaches will first need to be established in adults, at least for conditions not specific to age, then repeated in children. For conditions unique to pediatrics (typically occurring in infants and small children), endoscope technologies that address size limitations will need to be developed.

EXISTING ENDOSCOPIC THERAPEUTIC TECHNOLOGIES

Endoscopic therapies for GERD were the first to be widely developed for the adult population (Table 1). However, little literature exists about the pediatric application of these technologies. The following are descriptions of some of the more popular interventional endoscopic procedures, with some of the supporting literature, mainly from adult studies. Some of these procedures (Enteryx, Gatekeeper) have fallen out of favor, owing to safety concerns or lack of efficacy. Others (EndoCinch, Stretta, NDO plicator) have shown short-term improvements in GERD symptoms but without objective evidence of reduced lower esophageal acid exposure or long-term durability ⁽⁵⁾.

TABLE 1: Current therapeutic endoscopic procedures

Endoscopic Mucosal Resection

Originally described in 1984 by Tada et al ⁽⁶⁾, endoscopic mucosal resection (EMR) has mostly been used and perfected in Japan because of the high incidence of early gastric cancer and the wide use of early detection screening programs. Unlike colon cancers, which usually arise from polypoid masses, the flat configuration of early gastric cancer does not lend itself to simple wire snare resection. Instead, broad mucosal resection is necessary. With EMR, a suspect nodule or area of mucosa is raised with a submucosal injection of liquid (saline or hyaluronate) and removed by use of a wire loop and cauterization. Ono et al ⁽⁷⁾ treated 445 adult patients with EMR for early gastric cancer and observed no cancer recurrence over a median follow-up period of 38 months.

Although early gastric cancer is not a major concern in children, EMR in pediatrics has received some attention. In a working group report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition in 2004, the authors stated that “endoscopic mucosal resection of large sessile polyps is feasible and hence may have application in pediatric endoscopic practice” ⁽⁸⁾. However, to date there are no descriptions in the literature, as far as we are aware, of such a procedure performed on a child.

Stretta

The Stretta procedure (Curon Medical, Fremont, CA) was the first interventional endoscopic GERD therapy to gain approval by the US Food and Drug Administration (FDA), in 2000. Consisting of a catheter, soft guide wire tip, balloon basket assembly, and 4 electrode delivery sheaths positioned radially, the Stretta device uses radiofrequency energy to increase the tone of the lower esophageal sphincter. In adults, this outpatient procedure can be performed while the patient is under conscious sedation and completed in just 40 minutes. Its mechanism of action is unclear, but it is believed that the radiofrequency energy results in shrinkage of collagen fibers, resulting in elevation of postprandial lower esophageal sphincter pressure ⁽⁹⁾ and reduction of transient lower esophageal sphincter relaxations ⁽¹⁰⁾.

A large multicenter prospective trial by Triadafilopoulus and Utley ⁽¹¹⁾ of 118 patients undergoing Stretta with 1-year follow-up showed a reduction of proton pump inhibitor (PPI) use from 88% to 30%. The only sham-controlled randomized trial of Stretta in 64 adult GERD patients with 1 year follow-up demonstrated significant symptom (GERD health-related quality of life) and quality of life (Short Form-36) improvement but no significant change in distal esophageal acid exposure (24-hour pH study) ⁽¹²⁾.

Islam et al ⁽¹³⁾ studied the effects of Stretta in a small series of 6 pediatric patients (mean age 12 ± 4 years), also concluding that the procedure was safe and effective. Five of the 6 patients were asymptomatic at 3 months, and 3 were able to discontinue antisecretory medication. Mean reflux score improved significantly after 6 months; however, pH studies were not done. Clearly, further evidence from institutional review board–approved clinical trials is necessary before widespread application of Stretta in children. Without significant improvements in acid exposure, the benefit of this procedure in children is questionable because the common indications for surgical management of pediatric GERD consist mainly of complications of esophageal acid exposure such as esophagitis, pharyngitis, or aspiration, as opposed to minor GERD symptoms.

EndoCinch

Also approved for use by the FDA in 2000, the EndoCinch system (BARD Endoscopic Technologies, Billerica, MA) aims to reduce gastric reflux by pleating the gastroesophageal junction (GEJ). The 30- to 60-minute procedure begins with insertion of the EndoCinch device through an over-tube. Suction applied 1 to 2 cm below the squamocolumnar junction facilitates full-thickness placement of 2 adjacent sutures. The sutures are then “cinched” together, or brought into approximation, to create a pleat. Usually several pleats are created, significantly narrowing the lumen at the GEJ. The resulting rosette of tissue (gastroplication) is intended to prevent reflux of gastric contents into the esophagus.

Schwartz et al ⁽¹⁴⁾ randomized 60 patients to either gastroplication, sham procedure, or observation, with up to 1-year follow-up. Proton pump inhibitor use reduced by 65% in the gastroplication group, compared with 25% and 0% in the sham and observation groups, respectively. The EndoCinch group also showed significant improvement in symptoms; however, the reduction of distal esophageal acid exposure after gastroplication was not significantly greater than after the sham procedure. In a similar study, Montgomery et al ⁽¹⁵⁾ randomized 46 patients to EndoCinch versus sham procedure. Although after 3 weeks EndoCinch patients reported significantly less PPI use, this effect was lost after 6 weeks, which persisted for up to 1 year follow-up. This lack of durability of EndoCinch is a consequence of suture degradation and loss, as demonstrated on follow-up endoscopy ⁽¹⁶⁾.

Only 1 pediatric study to date, as far as we are aware, describes the effects of the EndoCinch system for treating GERD ⁽¹⁷⁾. Seventeen patients with a median age of 12.4 years (range, 6.1–15.9 years) underwent gastroplication. All of the patients showed significant improvement in early postoperative assessments of symptom severity, symptom frequency, and quality of life. These effects persisted at 1 year follow-up in the majority of patients and were reflected in reduced pH indices.

The reason for the longer durability of this procedure in children compared with adults is unclear, but it may be a consequence of a greater ability to achieve full-thickness esophageal bites in the smaller patients. Even with treatment effect lasting for just 1 year, the benefit of this procedure in children can be imagined. Infants with severe GERD undergo laparoscopic Nissen fundoplication, an essentially permanent alteration of their anatomy. A procedure that lasts 1 year may be more appropriate for many infants who could be expected to outgrow their GERD by this time. Unfortunately, the current technology is not appropriately sized for use in infants.

NDO Plicator

Based on principles similar to those of the EndoCinch system, the NDO plicator (NDO Surgical, Mansfield, MA) was FDA approved for use in 2003 for the relief of acid reflux through the insertion of full-thickness gastric sutures. The device consists of a 2-channel endoscope with retroflexive capabilities and a pediatric endoscope for viewing. Like the EndoCinch system, it is also introduced through an over-tube. The 20 minute procedure is completed by using the 2 distal arms of the device to grab a segment of gastric wall just below the GEJ. The device then places full-thickness gastric wall sutures that effectively cinch the gastric walls and narrow the diameter below the GEJ. This “plication” of the fundus is also thought to bolster the natural angle of His and thereby prevent reflux. This effect is difficult to explain because surgical experience suggests that such a plication performed by conventional surgical means would not effectively address reflux in the long term.

In a 12-month follow-up for a North American open-label trial, 70% of 64 adult patients were no longer taking a PPI, and 39% of the patients had normalized acid exposure at 1-year follow-up ⁽¹⁸⁾. At 3-year follow-up of 29 of the original patients, there was minimal deterioration of GERD-related quality of life ⁽¹⁹⁾. The long-term outcome in the remaining original patients is unknown. The experience with NDO plicator is limited (eg, patients with large hiatal hernia, erosive esophagitis, or nonresponse to antisecretory medications were excluded), and no clinical trials have explored the use of the NDO plicator in pediatric populations. The large apparatus associated with this technique precludes its use in small children.

Enteryx

The Enteryx system (Boston Scientific, Natick, MA), no longer available, used a biocompatible polymer to increase lower esophageal sphincter pressure. Ethylene vinyl chloride mixed with a fluoroscopic agent was injected under fluoroscopic guidance 1 to 2 mm below the GEJ into the submucosa in a circumferential fashion. Upon contact with the tissue, the liquid polymer hardened into a malleable form. The Enteryx system is mentioned here only to exemplify the potential for serious complications with novel technologies and to reinforce the need for proper efficacy and safety trials before their widespread application, particularly in the pediatric population.

In a 2005 publication, Cohen et al ⁽²⁰⁾ reported on a 24-month clinical trial in 144 patients. Of these patients, 67% continued not to use PPI medications 24 months after injection, and 72% had reduced their PPI use by at least 50%. Still, 26% of patients required additional injection treatments 1 to 3 months after the initial procedure. In addition, the authors noted increased severity of esophagitis in 32% of the patients. Use of Enteryx came to a halt in 2005, however, when the FDA requested a recall by Boston Scientific of all Enteryx systems after reports of adverse effects and cases of fatality caused by inadvertent Enteryx injection into the mediastinum, pleural space, and aorta (with consequent arterial embolism).

EsophyX

The latest transoral endoscopic device on the market is the EsophyX (Endogastric Solutions, Redmond, WA), which is designed to achieve transoral endoluminal full-thickness plication of the GEJ. The goal of this antireflux procedure is to create an anteriorly placed 3- to 5-cm, 200° to 270° valve at the distal esophagus secured by special fasteners (Fig. 1). The end result is creation of an antireflux barrier and re-establishment of the angle of His. Unlike the NDO plicator, the device does not have to be inserted and removed for each stitch, and its function allows reduction of the small hiatal hernia, although the crura remains unapproximated. In an initial European study ^(20a), 17 adult patients who had clinical GERD and PPI dependence successfully underwent the EsophyX procedure under general anesthetic. At 12-month follow-up, 82% of patients had completely discontinued PPI use, and 63% of patients had normal esophageal acid exposure. Preoperative pH studies were not reported due to patient refusal to stop PPI use before the studies.

FIG. 1: The EsophyX device for transoral endoluminal fundoplication. An endoscope is passed through the center channel for visualization. The instrument backend (1) controls the distal end (2), which forms a tissue valve by creating multiple plications at the GEJ (3).

Emerging

Several new antireflux technologies have emerged, including the Antireflux Device (Syntheon, Miami, FL) and 2 new tissue approximation devices, the Swain System (Ethicon, Piscataway, NJ) and the G-prox (USGI Medical, San Clemente, CA), which are expected to be introduced in the near future. Objective experimental evidence in support of these devices is pending.

Clinical researchers and device manufacturers continue to explore the possibilities of novel endoscopic systems that achieve intraperitoneal surgical manipulation but eliminate the need for transabdominal access. As noted above, the evidence thus far has not been conclusive, and laparoscopic procedures remain the gold standard. This is particularly the case in pediatrics. Enthusiasm for new technologies must be tempered by their critical appraisal, as in the case of Enteryx. As Walter J. Hogan pointed out in a 2006 editorial ⁽²¹⁾, recent minimally invasive GERD treatments have “improved GERD symptoms and well-being and decreased the patients' PPI requirement during follow-up period. However, none of the endoscopic procedures reduced acid reflux impressively or improved lower esophageal sphincter tone.”

NATURAL ORIFICE TRANSLUMENAL ENDOSCOPIC SURGERY

NOTES Concept

Whereas therapeutic endoscopy has focused largely on treatments for GERD, the introduction of the NOTES concept has opened the possibility for many other endoscopic procedures such as cholecystectomy, appendectomy, and enteroenterostomy. Using NOTES, the clinician aims to access the peritoneal cavity through the gastric, colonic, or vaginal wall, perform the necessary intraabdominal procedure, and finish by removing the specimen and closing the visceral defect used for access. NOTES proponents envision performing some of these procedures with the patients under sedation as same-day cases. In pediatrics, there is little likelihood of performing NOTES procedures without general anesthetic except in the oldest of children.

Natural Orifice Surgery Consortium for Assessment and Research

The early development of NOTES has differed in several key ways from that of conventional laparoscopy. Laparoscopy was developed by a few surgeons in a nonformalized way and was adopted into practice quickly despite lack of training and evidence. These factors resulted in unacceptably high rates of bile duct injuries after laparoscopic cholecystectomy. Delegates from the American Society of Gastrointestinal Endoscopy (ASGE) and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) have taken a more formalized approach to the development of this field with the establishment of the Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) ^(22,23). NOSCAR defines stringent criteria for the safe and ethical development of NOTES, including appropriate ex vivo and animal studies before the surgery is performed on humans. A second unique feature of NOTES is the early involvement of industry in device development. Unlike laparoscopic surgery, industry has taken an early interest in the NOTES approach, recognizing its potential for widespread application. Perhaps the most important feature of NOTES development is the collaborative effort between surgeons and gastroenterologists (therapeutic endoscopists). Both groups bring unique expertise to the field, and each recognizes that NOTES will ultimately be performed by a “NOTES MD” who is trained in both traditional minimal access techniques of peritoneal surgery and advanced therapeutic endoscopy.

Before such techniques can be adopted into mainstream clinical practice, several issues must be addressed. The NOSCAR group met in July 2005 to discuss the challenges associated with this novel approach to surgery. In a white paper ⁽²³⁾, the group identified infection prevention, secure gastric closure, maintenance of an adequate operating space with good visualization, and access to functional instrumentation as the most important challenges necessary for safe implementation of NOTES. Furthermore, at the second annual NOTES/NOSCAR meeting in Boston in July 2007 ⁽²⁴⁾, an expert panel of minimal access therapists as performed in adults asserted their belief that any NOTES therapy must be well established in adults before they can be considered for the pediatric population. More important, these therapies must undergo their own equivalent (and perhaps more stringent) assessment, first in animal models, then in institutional review board–approved pediatric clinical trials, before widespread application in children.

NOTES Procedure

Kalloo et al ⁽²⁵⁾ first reported on the safety of peroral transgastric peritoneoscopy in 2004, demonstrating the feasibility of performing surgery without perforating the abdominal wall. Since then, other investigators have gone on to demonstrate transluminal surgery on porcine models for the purposes of fallopian tube ligation ⁽²⁶⁾, cholecystectomy and cholecystogastric anastomosis ⁽²⁷⁾, gastrojejunostomy ⁽²⁸⁾, and organ resection ^(29,30). These experiments demonstrated the feasibility of transgastric surgery and peritoneal exploration ⁽²⁵⁾, with potential benefits of reduced wound healing time, no visible scarring to the abdomen, and increased postoperative patient comfort ^{(23,25,27,28)}.

Although unpublished reports of peroral appendectomy in India have been reported in video form with considerable attention at several surgical meetings ⁽³¹⁾, most of the procedures to date have been performed on a porcine model. The appendectomies have been performed on patients described as having chronic appendicitis, without the usual advanced inflammation seen in acute appendicitis. The first pediatric case involved a child with severe abdominal wall burns that precluded transabdominal access. To date, there are no published reports of a pure NOTES procedure, although laparoscopic-assisted transvaginal NOTES removal of the gallbladder has been reported in the media ⁽³²⁾.

The experimental porcine procedures are performed with the animals under general anesthesia. Liquid formula diet followed by a 24-hour fast is used. Intravenous antibiotics are administered, the stomach is irrigated with sterile water/antibiotic solution, and a sterilized double-channel endoscope (Olympus GIF 2T160) is passed into the stomach through a sterile over-tube, all in an effort to prevent peritoneal contamination with oral or gastric contents.

A 2-mm incision with an endoscopic needle knife (Olympus KD-10Q-1A) is made on the anterior wall of the stomach. The anterior wall is well vascularized (but without major feeding vessels) with little or no bowel or organs surrounding it, ensuring a high rate of healing and little collateral damage. Endoscopic ultrasound can be used to ensure that all major vessels and organs are protected. The anterior approach also minimizes the spillage of gastric contents into the peritoneal cavity.

The gastrotomy is enlarged in 1 of 2 ways. The first method involves using a pull-type sphincterotome (Boston Scientific) typically used in endoscopic retrograde cholangiopancreatography for sphincterotomy. This creates a larger incision, requiring secure gastric closure on completion of the procedure ^{(25,28,33,34)}. Alternatively, a balloon (Microvasive CRE esophageal balloon 5838) is advanced over a catheter, and the incision is radially dilated to minimize gastric wall trauma. The advantage to dilatation is that the defect readily reapproximates by radial contraction once the endoscope is removed ^{(25–27,29,30,35)}. This works well when the procedure is finished, but if for any reason the endoscope is removed, the access port may be difficult to relocate. Also, this method limits the size of tissue that can be removed.

Once a transgastric incision is made, the endoscope is advanced into the peritoneal cavity. A guide wire may be placed through the same gastric incision to mark the incision in case the endoscope is removed intentionally or accidentally. The abdomen is air-insufflated without pressure regulation by use of the endoscope. The animals are evaluated clinically for hemodynamic or pulmonary compromise to titrate the pneumoperitoneum. Some investigators place a percutaneous 16-gauge catheter through the abdominal wall to vent the insufflated gas ⁽³⁰⁾. Using any of several existing endoscopic tools such as polypectomy snares (Sensation M00562650, Boston Scientific), endoscopic biopsy forceps (Olympus FB-24K-1), endoscopic grasping forceps (Olympus FG-47L-1), endoloops (Olympus), and endoscopic clips (Resolution M00522610, Boston Scientific), various procedures can be performed in the peritoneal cavity. Most animals recover bowel function and normal eating within 24 hours.

Challenges of Advancing NOTES Therapy

Contamination Prevention

Contamination of the peritoneal space is a prime concern with transluminal access to this cavity. The natural orifices such as the mouth and anus are host to numerous bacteria. Although these bacteria are harmless in their natural niches, they can cause severe infections elsewhere in the body. In fact, perforation of the gastrointestinal lumen is traditionally considered a surgical emergency requiring immediate repair. To avoid the transfer of bacteria as equipment is inserted and withdrawn from these orifices, many endoscopists are using over-tubes. However, contamination cannot be completely avoided because the over-tube itself becomes contaminated upon oral/anal insertion. In the process, this over-tube can transport bacteria from the oral cavity to the intraperitoneal space ^(29,36). To counter this, Kalloo et al ⁽²⁵⁾ used gastric lavage with antibiotic solution to prevent peritoneal contamination.

NOTES pioneers have also suggested that transgastric surgery may be feasible without gastric wall closure ^(25–27). Despite preliminary results indicating adequate self-closure of the gastric wall, the medical community was quick to respond with concern about bacterial leakage into the peritoneum ⁽³⁷⁾. These fears were substantiated by Merrifield et al ⁽²⁹⁾ in studies of peroral transgastric organ resection in 5 porcine models. They observed that 2 of 5 animals had collections of pus around the gastric incision site and throughout the abdomen (with 1 animal requiring to be killed early after bacterial peritonitis developed). With these results, both SAGES and ASGE agreed that a secure water-tight gastric closure is necessary to ensure the safety of the patient ⁽²³⁾.

Visualization and Triangulation

Although the laparoscopic image limits field of view, in comparison with open surgery, it has the added benefit of significantly magnified images and ability to see around corners. Unfortunately, maintaining spatial orientation and triangulating instruments remains challenging while an endoscope is being used. Wagh et al ⁽³⁰⁾ found that despite adequate visualization of all of the lower abdominal and pelvic structures using a transgastric approach, they were able to visualize the gallbladder in only 55% of cases, and the entire spleen could not be evaluated in all of the cases. The latter procedures required the operator to retroflex the endoscope to gain proper visualization, and consequently produced an inverted image. The colon seems to hold promise as an alternative transluminal route for upper quadrant organ visualization ^(38,39). The only reported porcine transluminal cholecystectomy that allowed adequate visualization and triangulation was performed by use of 2 endoscopes delivered into the peritoneal cavity by a transgastric route ⁽²⁷⁾.

Insufflation

Current endoscopes are not equipped to provide CO₂ insufflation at regulated pressures. Studies of peritoneal air insufflation using standard endoscopes show wide fluctuations in intraperitoneal pressures, overdistension of the abdomen, and adverse hemodynamic effects ^(40,41). Laparoscopic surgeons have used CO₂ as an insufflation gas because of its high solubility in blood and consequent low risk of gas embolus. The use of air in place of CO₂ can predispose to potentially lethal venous air embolus. Furthermore, the air used to insufflate the peritoneal cavity can inadvertently insufflate the gastrointestinal tract, causing bowel distension and reduced workspace. It will be important to equip endoscopes with pressure-regulated CO₂ insufflation devices to perform advanced intraperitoneal surgical procedures.

Surgical Capabilities

The initial porcine procedures, which were severely limited by current endoscopic technology, highlighted the need for new endoscopic tools with expanded capability. An impetus has emerged to develop reliable tools for gastric closure, such as endoscopic suturing devices, and flexible, dexterous endoscopes for traversing the intestinal lumen and effecting surgical manipulation. Furthermore, the ASGE/SAGES white paper established that robotics will be necessary in the progression of NOTES ⁽²³⁾ to allow for a potentially more facile and safer alternative to manually performed gastrointestinal endoscopy.

The use of flexible endoscopes to conduct conventional surgical tasks presents some inherent limitations because of the lack of rigidity and anchoring points. The limited dexterity of the tip and the user interface design make it challenging to conduct surgical tasks that require fine control and complex manipulations. As a result, the core surgical tasks of dissection, tissue manipulation, and incision closure require innovative approaches. Available endoscopic instruments are unable to generate sufficient force to allow adequate blunt dissection because of lack of stiffness ⁽²⁷⁾. This may be less of a problem in small children, in whom smaller forces are necessary. Energy-driven devices such as wire loops, needle knives, lasers, and water jets are preferred because they do not require exertion of significant tissue forces.

The lack of rigidity of endoscopes also makes them ineffective at pushing, pulling, or applying lateral forces. Laparoscopic tools are able to do this because they pivot around a fulcrum (the abdominal wall), which provides countertraction, with the operator's hands providing an opposing force. Furthermore, instruments passed through the 2 working channels of the endoscope are parallel to each other, preventing instrument triangulation, which is an important arrangement when manipulating tissues. From a surgeon's point of view, anatomic exposure and safe tissue dissection form the basis of operative therapy. To date, demonstrations of NOTES in animals or humans have been in minimally inflamed tissue, a condition for which minimal forces are necessary to achieve exposure, traction, and dissection. Existing technologies are not capable of the forces and dexterity necessary to operate in a surgical field that has significant tissue inflammation.

Suturing is difficult with endoscopic tools because it requires high forces and dexterity, neither of which is offered by current endoscope technology. Some specialized endoscopic suturing devices have been developed, but they remain experimental. For endoscopy, closure clips are available but have proved inadequate, especially in the setting of large, widely spaced incisions and tissue edema. There are no commercially available simple, safe, and secure methods for closing gastrotomy sites intraluminally during endoscopy.

Endoscopic instrumentation for managing significant complications such as hemorrhage is needed. The only available methods for hemostasis are clips, conventional cautery, and the argon plasma coagulator ⁽²⁷⁾. If these fail, no effective endoscopic suturing or stapling method is available to manage severe bleeding complications. If NOTES is to be performed in patients under sedation, then conversion to a laparoscopic or open procedure may not be a ready option in the event that severe hemorrhage control is necessary.

NOTES and the Pediatric Patient

NOTES could conceivably be applied to a diverse range of common childhood conditions, including those not specific to pediatrics, such as gastroesophageal reflux, appendicitis, cholecystitis, trauma laparoscopy, Meckel diverticulum, and tumor biopsy. More exciting is the challenging possibility of addressing congenital lesions such as duodenal atresia, esophageal atresia, and urologic anomalies. Although these conditions could be treated with NOTES, whether they should be remains to be seen.

In addition to the technical challenges faced by therapeutic endoscopy, the application to the pediatric population presents some additional specific difficulties. In small children, the available workspace is limited, leaving insufficient space for the wide arcs created by existing endoscopes. The primary challenge is making the endoscopic tools of a narrow enough diameter, and a short turning radius, to be used in a small patient but still have the ability to generate sufficient forces and introduce adequate end-effector tools to perform effective tissue manipulation. Reducing the size of the tools while maintaining their functionality is among the most complicated challenges for engineers, resulting in high-cost development projects. Unfortunately, the size of the pediatric market does not typically support these projects; as a consequence, the tools and techniques used for the adult population are slow to be adapted to the pediatric population.

Pediatric specialists must also begin to assess the clinical implications of interventional endoscopy and NOTES on the pediatric population. Most important, do novel approaches such as NOTES, even if technically possible, really have a place in the clinical treatment of pediatric patients? Unlike in adults, NOTES probably will not eliminate the need for a general anesthetic in children. There may be a reduction in pain and scarring, but are these benefits worth the added risk of making an enterotomy to access the abdominal cavity (effectively converting some operations from “clean” to “clean-contaminated”)? How safe does the approach need to be to justify its use? If NOTES is used in adults, should it nevertheless be restricted from use in children? These provocative questions, to which the answers remain unclear, are countered by other undeniable forces such as those of the market and media. Similar circumstances were experienced during the laparoscopic revolution, which in large part was carried by patient demand, despite initial skepticism in the surgical community. As pediatric gastroenterologists and surgeons, who are the most likely delivery mechanism for these new technologies, we are the ones responsible for policing these developments to ensure their safe implementation into clinical practice.

FUTURE TECHNOLOGIES

To address the issue of site contamination, experts are exploring approaches such as prophylactic intravenous antibiotics, antibiotic and sterile water lavage, and proper incision closure using novel devices. The Eagle Claw VII (Fig. 2) (Olympus American, Center Valley, PA) has effectively demonstrated suturing for transgastric gastrojejunostomy ⁽²⁸⁾ and endoluminal gastroplasty. ⁽⁴²⁾ Another device (Wilson-Cook Medical, Winston-Salem, NC) was shown to be effective in both gastric closure and full-thickness resection of the gastric wall, and for creating gastrojejunostomies ^(33,43).

FIG. 2: Eagle Claw VII endoscopic suturing device (Olympus America, Center Valley, PA). The device uses a curved needle with a detachable tip. Once the needle is advanced through the tissue (A–C), it attaches to an opposing cartridge, leaving only the suture in place (D). The suture is then tightened by pushing the cartridge against the tissue while pulling the suture again, allowing for tissue approximation (E, F). (Eagle Claw VII courtesy of Olympus; Eagle Claw VII was designed and manufactured by the Apollo Group in collaboration with Olympus Medical Systems Corp, Tokyo, Japan).

The challenge of creating an adequate pneumoperitoneum using CO₂ through an endoscope is also being addressed. By adapting current endoscopes, McGee et al ⁽⁴⁴⁾ and Park et al ⁽⁴⁵⁾ have both presented devices that monitor pressures with a sensor on the tip of the endoscope. Both are as effective as the laparoscopic insufflators.

A team of engineers and physicians at USGI Medical (San Clemente, CA) have established several design requirements, including size, imaging, insufflation, maneuverability, triangulation, and stability, to develop 2 devices. The first, called ShapeLock (Fig. 3), serves as a sleeve through which endoscopes can be inserted and withdrawn. Once the scope is inserted to the desired location, the sleeve can be made rigid, allowing the surgeon to exert forces against tissues in the abdomen without pushing the instrument away. This device is adapted for use with a laparoscopic CO₂ insufflator. The second device contains independently movable arms at the tip of the endoscope (Fig. 4), helping to alleviate many of the problems of triangulation associated with current endoscopic instruments.

FIG. 3: ShapeLock Technology for endoscope rigidization (USGI Medical, San Clemente, CA). This device allows a flexible scope to be inserted and positioned onto the operative site and then locked into position. The device gives the clinician a stable platform, allows the scope to be used as a retraction device, and maintains the maneuverability of a flexible endoscope. The device has been adapted for use with a laparoscopic CO₂ insufflator to provide controlled precise pneumoperitoneum. (Image copyright USGI Medical; used with permission.)

FIG. 4: Transport apparatus for endoscopic tissue manipulation and improved instrument triangulation (USGI Medical, San Clemente, CA). This variation of the Shapelock device has 2 independently movable arms at its distal tip to allow triangulation and the production of traction and counter traction, particularly for transgastric procedures requiring retroflexion. (Image copyright USGI Medical; used with permission.)

Transluminal surgery presents several other difficulties that remain to be solved. First, achieving correct orientation can be challenging. It is frequently difficult to discern one's location in the peritoneal cavity and the position of the scope in relation to other abdominal structures. Whereas this difficulty is generally surmountable when one is operating within a lumen such as the bowel (where up and down do not really matter), it becomes far more relevant in the presence of complex anatomy. A closely related issue is that of an unstable horizon. Near-horizontal orientation of the image is critical for safe operative manipulation of complex anatomy. Second, a unique aspect of existing therapeutic endoscopic technologies (eg, the double-lumen endoscope) is the coupling of the optics and the instruments. Movement of one results in movement of the other, which makes for clumsy operating. Last, the greater complexity of complex endoscopic positioning and tissue manipulation requires some unusual contortions by the operator, including twisting the body and crossing one's arms to work the instruments (eg, when working retroflexed). Current procedures are performed by teams in which 1 person manages the scope and the other the catheter instruments; a single-operator system would be preferable.

Many of the above problems are potentially addressed by computer or robotic interface, but such solutions come at considerable cost, at least initially. Robotically controlled endoscopes capable of segmented movement have been produced ^(46–49); however, these devices have many weaknesses, including low maximum force generation, limited bending angles, and large diameter. A potential solution for the orientation problem is the use of augmented reality techniques using preprocedure computed tomography or magnetic resonance imaging, real-time tracking, and reference image registration, made available to the operator by graphical interface ⁽⁵⁰⁾. When possible, lower cost solutions should be searched for, but incorporating some degree of computer and robotic interface to future endoscopic technologies seems necessary.

After evolving in parallel for many years, endoscopy, minimal access surgery, and interventional radiology are converging to form sophisticated therapy delivery systems. We envision this environment to be radically different from the conventional operating room. Most notably, the surgeon's view of the surface of the operating field will be complemented by images showing what is beyond the visible surface, and instrumentation combining features of laparoscopic tools with endoscopic tools will be used, all under robotic guidance. The overall goal is to integrate preoperative and intraoperative imaging data with a robot-assisted platform into a unified surgical delivery system ^(51,52).

The union of image guidance and robotic surgery may eventually give rise to operative techniques that transcend human capability. Emerging developments include augmented reality visualization through fusion of multimodal imaging techniques, noninvasive energy-based therapies such as high intensity focused ultrasound, device miniaturization possibly even to a nanoscale level, and catheter- and cell-based robotic navigation. Such technologies may be incorporated into endoscopic platforms of the future, allowing therapists to carry out intricate tasks with greater precision and efficacy than a set of hands would be able to accomplish. These capabilities would change current surgical practice and enable new therapies.

MINIMAL ACCESS THERAPY: A MULTIDISICPLINARY COLLABORATIVE EFFORT

The successful deployment of the advanced therapy systems described above depends on a multidisciplinary team composed of therapeutic endoscopists, minimal access surgeons, and interventional imaging experts. These practitioners are wed on the basis of a belief in a minimal access approach to therapeutic intervention. It is foreseeable, then, that future generations of trainees will accumulate experience in surgery, endoscopy, and imaging to a sufficient extent that a new type of practitioner will emerge. In this spirit, MacFadyen and Cuschieri ⁽⁵³⁾ have proposed that the term “minimal access surgery” be replaced with “minimal access therapy.” A single practitioner with a diversity of expertise and an understanding of the capabilities and limitations of each field is more likely to deliver optimal care than several individuals with divided expertise. How such a “minimal access therapist” will be trained and credentialed remains to be seen, but the development of this field will require the cooperation of surgeons, endoscopists, and radiologists.

Conclusions

Minimal access surgery and endoscopic therapies have merged to offer some interesting new possibilities in surgical care, with NOTES as the most recent example. It will be several years, however, before the public has access to NOTES and the emerging technologies enabling its progress. First, clinicians must critically appraise its role in clinical care and determine its safety. In general, this will occur in adults before it is considered for pediatric use, but pediatric practitioners must take an early and active role in NOTES development, both to realize its benefits and prevent its unsafe use. A translational approach from animal studies to tightly controlled clinical trials serves as a good model. Engineers must tackle the many problems complicating the manipulation and control of current endoscopes, and the reduction of tool sizes, to allow for broader application in children. Finally, the medical community must determine who is best equipped to execute NOTES procedures. This will initially mean a multidisciplinary team–based approach but will ultimately result in the emergence of a new type of practitioner, the minimal access therapist.