Full-Thickness Endoscopic and Combined Laparoscopic-Endoscopic Techniques
Zaheer H. Rizvi, MD; Harangad S. Bhangoo, MBBS; Alyssa J. Meyer, MPH; G.V. Rao, MS, MAMS, FRCS; and Navtej S. Buttar, MD
Introduction
By virtue of large size, depth of involvement, and anatomically challenging locations, certain benign and neoplastic lesions of the gastrointestinal (GI) tract are not amenable to traditional endoscopic resections. In the recent past, there has been a rapid evolution of accessories, devices, and platforms to address this unmet need. From the luminal side, novel endoscopic approaches such as widefield mucosal resections or endoscopic submucosal dissection (ESD) can partially address this, whereas minimally invasive laparoscopic segmental resections have been introduced in parallel for the management of extraluminal disease. These novel approaches have their strengths and limitations, which brings us to the interface of these approaches at the level of the gut wall. There is a potential for collaboration of endoscopic-laparoscopic approaches to maximize the benefits of both fields, respecting oncologic principles of resection, while negating their limitations. In this chapter, we will focus on endoscopic full-thickness resection (EFTR) and hybrid endoscopic-laparoscopic approaches for the management of difficult lesions without subjecting patients to more invasive surgeries and associated complications.
Unmet Needs
The majority of GI lesions can be managed via conventional endoscopic approaches. A recent review1,2 of 1000 advanced endoscopic resections of gastric lesions showed a complete en bloc resection rate of 87.7% with minimal risk of significant bleeding (0.6%) or perforation (1.2%). Similar results were also noted in a recent comprehensive meta-analysis involving 29,506 tumors in 27,155 patients who underwent gastric ESD. R0 resection rate was 90%; en bloc and curative resection rates were 94% and 86%, respectively. Immediate and delayed perforation rates were 2.7% and 0.39% respectively while rates of immediate and delayed major bleeding were 2.9% and 3.6%. After an average follow-up of about 30 months, tumor recurrence was 0.02% among those with R0 resection and 7.7% among those without R0 resection.3 Similarly, in a meta-analysis4 of 50 studies including 6442 patients and 6779 large colonic polyps, endoscopic resection was successful in 90.3% with a mortality of 0.08%. In another meta-analysis5 for subepithelial tumors (SETs), complete resection rate was estimated to be 86.2%. Those arising from submucosa have 91.4% success while those arising from the muscularis propria were 84.4% successful. The procedure-related gastric perforation rate, however, was high at 13%. As supported by the growing evidence, endoscopic resection is successful in the majority of cases. Yet, there is a small subset of patients that at present require surgical management to definitively address the lesion. These lesions may include adenomatous tissue with extensive nonlifting/submucosal fibrosis, polyps involving diverticulum or appendix, incomplete resection with residual malignancy, large SETs with high-risk features (particularly when involving the deep muscle layer), or lesions that are difficult to access endoscopically.6 Undertaking endoscopic resection for these lesions runs the risk of immediate complications or recurrent disease and requires novel platforms to safely manage without surgery.
Challenges
Conventional flexible endoscopes are inadequate to perform complex transluminal surgical procedures. They lack a multitasking platform that allows more variety of surgical manipulation. Unlike any laparoscopic procedures, key elements for resection, such as: triangulation, establishing a stable dissecting space, and full-thickness suturing, are still being developed in endoscopy.7 While flexible endoscopic platforms allow navigation in tight workspaces, they often fail to achieve the desired forces at the distal tip for adequate tissue handling and dissection.8 Multiheaded scopes and extra working arms were felt to be exciting endeavors; however, they compromised the luminal maneuverability and the extent of the gut that can be reached with these scopes.9 Ideally, all lesions should be removed en bloc to improve histopathological assessment and limit the risk of recurrence. However, en bloc resection with endoscopic mucosal resection (EMR) or even ESD techniques may not be feasible in all lesions. Aggressive efforts to achieve this goal may potentially increase the risk of serious adverse events, including that of perforation. Smaller defects can be managed by the use of through- or over-the-scope clips (OTSC), but full-thickness repair of large defects still remains challenging because of the loss of insufflation and the risk of compartment syndrome in the extraluminal space compromising the operative field. Bacterial contamination of the peritoneal space is also a concern. Nevertheless, vigorous endoscopic irrigation with massive amounts of saline (2 to 3 L) mixed with antibiotics can be effective in preventing peritonitis.10 While these lesions can also be addressed laparoscopically, localization of luminal lesions from the serosal aspect pose a challenge and laparoscopic segmental resection has its own associated complications such as anastomotic leaks.11 A combined approach of laparoscopically assisted aggressive endoscopic resection and a laparoscopic repair of unintentional serosal injury could have the potential to effectively address those select lesions not amenable to EMR or ESD. In the subsequent sections, we will discuss the standalone and hybrid management platforms currently available.
Platforms and Devices
To add multitasking and advanced manipulations to flexible endoscopes, novel platforms are evolving so endoscopes or endoscopic accessories can perform surgical tasks like excision and approximation.7 These platforms are either integrated platforms or combine endoscopes with devices or accessories to enhance their function. EndoSamurai by Olympus and the Anubis scope by Karl Storz are integrated systems in which a single device provides visual as well as mechanical functions. EndoSamurai has 2 articulated independently movable arms and a nonarticulating arm. The arm movement is mechanical via cables (Figure 35-1A). These arms can provide triangulation to provide traction and countertraction for dissection. The Anubis scope similarly provides 2 instrument-carrying channels that can be deflected to triangulate (Figure 35-1B). Unlike these, the Incisionless Operating Platform (USGI Medical) and Direct-Drive Endoscopic System (Boston Scientific) (Figure 35-2A) have multiple operating channels for manipulations and they rely on a standard endoscope for visualization.7 The instrument-carrying sheaths in the Incisionless Operating Platform are unique because of their shape-lock design to facilitate stability. The Dual-channel endoscope and its modification (R-Scope, both by Olympus) have the ability to accept over-the-scope attachments and provide an additional channel to help with tissue anchoring as well as full-thickness stitching. Plication devices for gastroesophageal reflux have also been exploited to accomplish full-thickness repair of the gut wall to create pseudopolyps.6,12,13 The Plicator suturing device (NDO Surgical) worked by deploying transmural polytetraflourethylene is no longer commercially available. The GERDX device (G-Surg) plicates with absorbable sutures to accomplish a similar goal. While not approved for repair, GERDX is more compact and has an extended reach.6 The Master and Slave Transluminal Endoscopic Robot (Nanyang University, Singapore), the Endomina system (MEDI-LINE) (Figure 35-3A), and the ViaCath (Hansen Medical) are multifunctional platforms that use robotic axial movement-enhanced limbs to perform functions such as grasping, dissection, and hemostasis.14
Developing platforms or importing them from recent advances in Natural Orifice Transluminal Endoscopic Surgery or laparoscopy has the potential to overcome various challenges to meet the needs of endoscopic resection in the GI tract. An equally important aspect is the need for the development of parallel expansion for dissecting and defect closure devices. The development of dedicated endoscopic dissection knives and closure devices (eg, endoscopic clips, suturing devices) in recent years have helped expand the scope of endoscopic resection.7 Approaches As with any evolving field, at present there is no firm consensus on which particular resection technique is most suited for any given lesion. In general, these advanced techniques are most frequently reserved for lesions not amenable for conventional endoscopic resection approaches, such as SETs originating from the muscularis propria layer or recurrence of superficial neoplastic lesions following failed EMR or ESD. While EFTR is preferred at locations that are difficult to approach with laparoscopic techniques (such as at the esophagogastric junction), other alternative hybrid approaches are typically used for larger lesions or those for which endoscopic access is suboptimal. Neoplastic lesions associated with high risk of lymph node metastasis or intraperitoneal dissemination of carcinoma cells as well as lesions for which preoperative imaging or histology predict high risk for aggressive behavior should not be subjected to these less-invasive approaches.15 Here we will describe these advances procedures by first classifying the approaches proposed in the literature followed by preclinical and clinical data supporting the different approaches. It is important to highlight that meaningful comparisons among these approaches are limited by the scarcity of data and the heterogeneity of endpoints among the available studies. Endoscopic Full-Thickness Resection Full-thickness resection permits negative deep resection margins for select lesions usually not amenable to conventional endoscopic resection techniques (ie, SETs originating from the muscularis propria or lesions complicated by severe fibrosis). Here we will first classify various approaches followed by preclinical and clinical data highlighting the role of EFTR. The classification is based on how the lesion is approached, and it does require a different set of technical expertise, devices, procedure duration, and potential risk for complications as well as recurrence. Classification Exposed or Cut-First and Close-Later or Endoscopic Submucosal Excavation With this approach, the excision of lesions involving deeper layers of the muscularis propria or the removal of adherent lesions may result in a breach of the serosal layer. This approach follows the standard resection techniques using partial or full submucosal lift, cutting the mucosa around the lesion, submucosal dissection, and excision of the lesion along with muscularis propria with various ESD knifes. The risk of this technique is the exposure of the extraluminal space to luminal contents during the resection. Therefore, the success of this approach relies on prompt and effective wound closure following resection.10,16 a. Secure first and cut later: With this technique, a pseudopolyp is created by placing sutures, plication, or clips to potentially provide a proactive serosal approximation prior to resection. The advantage of this approach is that it reduces the risk of spillage of luminal contents or neoplastic cells outside the lumen. The key technical aspect here is to ensure adequate inversion of the entire GI tract wall without injuring adjacent structures while at the same time avoiding an inversion that is too shallow that may prevent complete resection of the entire lesion.6 b. Submucosal tunneling endoscopic resection: This technique is further detailed elsewhere in this book. In summary, a submucosal tunnel is created to reach the lesion. The target is then dissected and retrieved via the channel, followed by closure of the tunnel entry site, therefore, with no or minimal exposure of the extraluminal space to luminal contents.17 A summary of 113 procedures in 99 porcine models reviewed 4 EFTR techniques including endoscopic stapling devices, T-tags, compression closure, or laparoscopic assistance for defect closure before or after specimen resection. Overall success rate was 89% with 4% mortality. The intraoperative complication rate was 22%. Postresection closure methods more commonly resulted in failure to close the defect (5% to 55%) and a high incidence of abnormal findings at postmortem examination (84%). Significant heterogeneity was observed in procedure duration (median or mean 3 to 233 minutes) and size of the excised specimen (median or mean 1.7 to 3.6 cm). Anastomotic bursting pressures and specimen quality were poorly documented.11 To streamline the full-thickness resection, a new EFTR device (FTRD, Ovesco Endoscopy AG), which is a combination of a modified OTSC system with an electrocautery snare, has been tested in an experimental setting. In 11 pigs, the average diameter of the tissue resected with the FTRD was 3.1, 3.6, and 5.4 cm in the 3 groups using different clip sizes. On follow-up endoscopy 7 days after the intervention, fibrin coating and stool residues were found on all clips, causing minor inflammatory reactions. However, the colon wall under the clip was noninflamed. After 28 days, the serosa had primarily healed in all cases. There was also stool residue on all clips; however, no acute inflammatory reactions were seen anymore because of complete healing. This study demonstrated the safety and efficacy of the clip-and-cut technique using the new FTRD system prior to clinical use. Early attempts at EFTR used a band ligator and the endoscopic closure of the defect was accomplished with detachable snares.18 More recently, a study reported outcomes of 35 gastric SETs managed using the cut-first followed by closure or exposed technique. EFTR consisted of submucosal injection; precutting the mucosal and submucosal layers around the lesion; circumferential incision as deep as the muscularis propria around the lesion using ESD and an incision into the serosal layer around the lesion with a HookKnife (Olympus); a full-thickness resection of the tumor, including the serosal layer with a Hook or ITKnife (Olympus); and finally closing the gastric wall with metallic clips. EFTR removed all the SETs successfully, and the complete resection rate was 100%. The mean operation time was 90 minutes (60 to 155 minutes), the mean hospitalization time was 6.0 days (4 to 10 days), and the mean tumor size was 2.8 cm (2.0 to 4.5 cm). Pathological examination confirmed the presence of gastric stromal tumors in 25 patients, leiomyomas in 7, and gastric autonomous nerve tumors in 2. No gastric bleeding, peritonitis, or abdominal abscess occurred after EFTR. Postoperative imaging on the third day detected no contrast extravasation into the abdominal cavity. At a mean follow-up period of 6 months, no lesion residue or recurrence was noted. This initial study suggests that EFTR may be a safe, effective, and minimally invasive approach for patients with SETs arising from the muscularis propria.19 EFTR using a secure-first, cut-later or nonexposed approach was prospectively assessed in 12 patients (7 gastric and 6 duodenal with SETs < 20 mm). EFTR was performed using a flat-based OTSC (Padlock, US Endoscopy, Inc). Technical success was achieved in 11 cases (85%). In all 11 cases, R0 resection was achieved. In all 6 duodenal cases and in 1 gastric case, full-thickness resection was achieved (64%). Adverse events were more common after duodenal vs gastric EFTRs, including perforation (n = 1), microperforation (n = 3), and hemorrhage (n = 1). During follow-up endoscopy, the clip was no longer in situ in most patients (7 of 10; 70%).20 In a separate study using another type of OTSC (Ovesco Endoscopy AG) (see Figure 35-2B) in 8 patients with SETs (duodenum 4, rectum 1, stomach 2, and esophagus 1), Sarker et al21 achieved complete resection (R0) in 87.5% of the cases. The mean size of the lesions was 13.4 mm (range 9 to 20 mm) but full thickness resection was achieved in only 2/8. There were no complications reported. Subsequently, Al-Bawardy and colleagues22 reported outcomes in 9 patients with SETs in the duodenum (4), rectosigmoid colon (2), stomach (1), and postappendectomy appendiceal orifice polyps (2). R0 resection was confirmed in all cases performed with either the Padlock or Ovesco clip. No adverse events were noted and the mean procedure time was 53 ± 21 minutes. Mean lesion size was 8 ± 3 mm, likely limited by the size of the cap. We developed a novel technique (Xtender) that used multiple telescoping caps along with an OTSC to resect nonlifting lesions. The use of overlapping caps allowed more space for suctioning large lesions into the cap with sufficient healthy margins. Our bench top and preclinical work suggested that the resected full-thickness samples were up to 5 cm in diameter. In 2 patients with nonlifting GI polyps (duodenal 1 and colon 1) resection revealed muscularis propria and serosa and patients remained recurrence free.23 Technical challenges such as passage of this device through the hypopharynx, limited visibility, and potential for separation of the caps could certainly be addressed by developing telescoping caps, steerable caps, and methods to secure these caps. Other closures have also been reported following EFTR. Schmidt et al13 used full-thickness sutures underneath a SET with a device originally designed for endoscopic antireflux therapy. This alternate EFTR approach still used the secure-first cut-later or nonexposed principle in 31 patients. All tumors were resected successfully but a significant rate of bleeding was noted (38.7%). Perforation occurred in 3 patients (9.6%). All cases of bleeding and perforation were managed endoscopically. Complete resection was histologically confirmed in 28 of 31 patients (90.3%). Mean follow-up was 213 days (range, 1 to 1737 days), and no tumor recurrences were observed. Unfortunately, the Plicator suturing device is no longer commercially available; however, the GERDX device, which is more compact and has an extended reach, is available but not approved for EFTR (see Figure 35-3B).6 Following the successful preclinical testing of the dedicated FTRD, a series of publications have shown promising results in various settings and indications, including incompletely resected adenomas with nonlifting sign, adenomas involving the appendix or diverticulum, resection of incompletely removed intramucosal cancers, as well as full-thickness sampling in patients with suspected Hirschsprung disease.24–29 The FTRD has been subsequently evaluated in a prospective multicenter study encompassing 9 centers and 181 patients.30 Indications included difficult adenomas (nonlifting and/or at difficult locations), intramucosal cancers and SETs. EFTR was technically successful in 89.5%. In 127 patients with difficult adenomas and benign histology, the R0 resection rate was 77.7%. In 29 cases of suspected or known cancer, R0 resection was achieved in 72.4%; with 8 of these cases showing deep submucosal invasion. Therefore, curative resection could be achieved only in 13/29 (44.8%). In the subgroup with SET (n = 23), the R0 resection rate was 87.0%. In general, the R0 resection rate was higher for lesions smaller than 2 cm (81.2% vs 58.1%, P = .0038). The adverse event rate was 9.9% with a 2.2% rate of emergency surgery. Three-month follow-up was available for 154 cases and recurrent/residual tumor was evident in 15.3%. These findings suggest that EFTR has a reasonable technical efficacy, especially if the lesion is equal or less than 2 cm with acceptable complication rates. Given the low curative resection rate for early cancers, this technique should not be used for this indication. Further comparative studies have to show the clinical value and long-term outcome of EFTR in benign colorectal lesions.30 Combined Endoscopic-Laparoscopic Resection The ideal resection of premalignant or early-stage cancers requires careful consideration to resect the target lesion along with appropriate disease-free margins without complications while minimally disrupting the native anatomy of the organ from where the lesion is being resected. Although logistically challenging, a combined endoscopic-laparoscopic resection can certainly fulfill the aforementioned paradigm in select cases. Endoscopic visualization of the lesion can limit the extent of laparoscopic wedge resection or avert the need for segmental resection. Similarly, laparoscopic backup allows more extensive and confident endoscopic resection. The meeting of the endoscope and laparoscope at the interface of gut wall provides numerous permutations of approaches that are classified as follows. Classification To simplify, the broader classification is based on the active role that either endoscope and or laparoscope play during the resection. Therefore, it could be laparoscopic-assisted endoscopic resection (LAER) or endoscopic-assisted laparoscopic resection or cooperative laparoscopic endoscopic resection. Laparoscopic-Assisted Endoscopic Resection With LAERs, the role of the laparoscope is to assist only. The resection is performed endoscopically with potential manipulation of the bowel by the laparoscope. The LAER approach can be used as an alternative to colonic resection in the setting of inaccessible polyps or gastric lesions that only partially involve the muscular layer. In this approach, the abdomen is explored and adhesions are lysed as needed. The lesion is identified, the area is mobilized, and vascular structures are isolated and preserved. Typically 2 bulldog clamps are placed on the bowel laparoscopically to prevent the distention of the bowel. Colonoscopy is performed with laparoscopic manipulation of the sigmoid as needed. The polyp is located with the colonoscope and is mobilized through laparoscopic maneuvering. Polypectomy, EMR, or ESD is performed and the specimen is extracted via the lumen. Lee et al31 used this procedure in 5 patients and had 100% successful removal with no serious complications. Minor complications included wound infections, atelectasis, and urinary tract infections. This approach is advantageous because it may facilitate positioning of the lesion and scope stability for endoscopic resection while enabling real-time diagnosis of any complications, such as perforations or full-thickness injuries that could be immediately managed by the laparoscope. Laparoscopy-Assisted Endoscopic Full-Thickness Resection Unlike LAER, during which all efforts are made to prevent breaching of the serosa, during laparoscopy-assisted EFTR (LAEFR), the serosa is also excised. This is particularly relevant for SETs that originate from the muscularis propria. LAEFR consists of 4 steps: The first uses ESD techniques to make a circumferential incision as deep as the submucosal layer around the lesion, then under laparoscopic supervision an endoscopic full-thickness incision around the circumference of the submucosal incision is made followed by a full-thickness incision laparoscopically from inside the peritoneal cavity, and finally closure of the gut wall defect. Owing to limited extent of resection and by avoiding wedge or segmental resection, the anatomical structures (luminal deformity) as well as physiological functions (such as gastric emptying) of the gut are preserved.32 Hiki and colleagues33 used this technique for 7 patients. It resulted in complete resection and no complications with a mean operation time of 169 minutes and mean tumor diameter of 46 mm. The limitation of this approach is that it cannot be used for gastric cancer or SETs with mucosal ulceration given the risks of more advanced disease and metastasis.34 a. Endoscopic-assisted wedge resection: Conventionally, a lesion that is not amenable to endoscopic resection because of location, size, or extent is managed by laparoscopic resection. Using the endoscopic-assisted wedge resection (EAWR) approach, the extent of the resection can be minimized. The approach involves placing the patient in the standard laparoscopy position and ports are placed. A laparoscopic bowel clamp is positioned distal to the angle of Treitz to avoid insufflation of the small bowel.35 After laparoscopic visualization of the target lesion is confirmed and marked, and blood vessels supplying the tumor are dissected and controlled to avoid excessive blood loss. The target lesion along with the gastric wall are lifted with seromuscular sutures or traction from grasping forceps. The tumor as well as margin of normal gastric tissue is removed with a linear GI stapler. The staple line can be reinforced with a running suture. After removing the tumor via an enlarged port hole, endoscopy can confirm the complete resection and the absence of bleeding or leak. This approach is appropriate for tumors located on the anterior wall or for exophytic tumors. Privette et al36 used this approach in 5 patients. They had 100% complete resection with average operative time of 180 minutes, average of 80 mL of blood loss, and average of 1.2 days to oral intake. Advantages include shorter operative time, minimal blood loss, and a shorter recovery time. Disadvantages include hemorrhage, hypoperistalsis, bowel injury, staple or suture line insufficiency, and incomplete resection. b. Endoscopy-assisted transluminal resection: In principle the endoscopy-assisted transluminal resection approach is similar to EAWR. Here, once the laparoscopic team locates the lesion and the exact position of the lesion is confirmed via palpation or translumination by the endoscope,35 a laparoscopic incision is made. This incision overlies the lesion, and traction is applied on the adjacent mucosa. The lesion is delivered into the peritoneal cavity and resected with an inverted wedge excision and laparoscopic stapler. This technique is most commonly used to resect lesions in the posterior gastric wall or posterior duodenum. Sasaki and colleagues37 used this approach for 10 patients with 100% complete resection. Median blood loss was 10 mL. The limitation of the approach is that it can be utilized for tumors < 4 cm that are located on the posterior wall. The advantage of this procedure is that it rarely results in hemorrhage, leak, or surgical wound infection because it uses controlled nonexposed resection. c. Laparoscopic transgastric surgery: Laparoscopic transgastric surgery (LTGS) is an alternative approach by which the laparoscope as well as the endoscope both are in the gut lumen. It primarily utilizes the laparoscope with assistance from the endoscope. In this approach, a lesion such as a SET is grasped and resected with a linear cutting stapler placed through a 12-mm transgastric trocar.34 The tumor is placed in a retrieval bag upon completion of resection, and the endoscopic grasper is used to retrieve the specimen. The linear cutting stapler is again utilized to close the gastrostomies from within the peritoneal cavity. The gastric wall may be secured to the abdominal wall. Barajas-Gamboa et al38 performed LTGS on 8 patients with 100% complete resection, with 2 patients developing postoperative bleeding. Privette and colleagues36 performed this technique on 4 patients, had 100% complete resection, and 1 patient with postoperative bleeding. When compared to more traditional laparoscopic approach, this technique is less invasive. Using the endoscope for visualization can eliminate the need for an additional laparoscopic camera and decrease the complexity of the case. Smaller tumors (< 3 cm) can also be removed through the mouth in this approach to reduce abdominal wall trauma. LTGS is limited to SETs < 3 cm and is difficult to perform on tumors growing in an extraluminal direction. a. Combination of laparoscopic and endoscopic approaches to the treatment of neoplasia with a nonexposure technique: While combination of laparoscopic and endoscopic approaches to the treatment of neoplasia with a nonexposure technique (CLEAN-NET) suggests a combination of laparoscopic and endoscopic approaches, this technique is predominantly a laparoscopic procedure. To avoid peritoneal contamination by luminal contents or neoplastic cells, in the CLEAN-NET procedure the endoscope is used to mark the lesion with dye. Following this, laparoscopically placed 4 full-layer stay sutures fix the surrounding healthy mucosa to the seromuscular layer.34 Next, the seromuscular layer is selectively incised outside of these stay sutures with the laparoscopic electrocautery knife while endoscopically observing and protecting any mucosal injury (Figure 35-4). An endoscopic submucosal injection to separate the healthy mucosa from seromuscular layer may help protect from any mucosal injury. After dissection, the lesion along with the seromuscular layers is pulled up with the 4 stay sutures into the peritoneal cavity along with the intact surrounding mucosa. The laparoscopic stapling device is used to dissect the full-layer specimen that is retrieved laparoscopically. Inoue et al39 performed this approach on 24 patients. In 22/24 patients, resection was completely successful. There was no recurrence in any of the 24 cases. This approach is advantageous because it can be used for nonexposed removal of GI stromal tumors with ulceration that will not be amenable to ESD. However, the specimen size is limited to 3 cm to avoid mucosal laceration and since the incision line is decided from the serosal side, it makes it challenging to prevent mucosal injury that may restrict the applicability of the procedure. b. Nonexposed endoscopic wall-inversion surgery: Nonexposed endoscopic wall-inversion surgery (NEWS) is essentially the opposite of CLEAN-NET, in which the lesion is inverted into the lumen and then removed per orally. It involves both endoscopic and laparoscopic incisions (Figure 35-5). The first step is a laparoscopic selective seromuscular incision around the lesion while endoscopically observing to prevent any mucosal injury. Next, multiple seromuscular sutures are placed outside this incision line to invert the lesion along with its incised seromuscular layer into the gut lumen.34 The final steps involve endoscopic resection of the mucosa-covered inverted lesion along with its laparoscopically incised seromuscular layer and endoscopic clipping to approximate the mucosal wound. This excised lesion is then removed per orally. Mitsui and colleagues40 performed the NEWS technique on 6 patients with 100% complete resection. Two patients had periprocedural perforations, which were repaired, and no patients developed postoperative complications. This approach is theoretically an optimal method to prevent peritoneal seeding but has the same limitations of CLEAN-NET such as a 3 cm or smaller lesion and difficulties in delineating the laparoscopic incision. c. Full-thickness laparoendoscopic excision: Conceptually, the full-thickness laparoendoscopic excision (FLEX) procedure resembles the NEWS, in which an artificial polyp-like structure is created with the help of BraceBars (Olympus) followed by endoscopic resection of the inverted lesion in the colonic lumen34 (Figure 35-6). The steps here include argon plasma coagulation (APC) for marking an excision line, which is 1 cm lateral from the polyp. Hook diathermy 1 cm outside the APC mark is used to mark the BraceBar placement site. Laparoscopically, the BraceBars are placed and tightened to plicate the colon. After placing 3 BraceBars, they are cinched together to achieve inversion of a fold containing the pseudopolyp into the colonic lumen. With 2 layers of continuous laparoscopic sutures, the BraceBars are oversewn. EFTR can then be safely performed. This approach is advantageous for removing polyps greater than 2 cm without risk of contents spilling into the peritoneal cavity. Damage to the blood vessels is avoided in this approach, thus reducing the risk for postprocedure leak from the resection site and enhancing postoperative recovery. Current studies are limited to animal models for this approach. Differences in anatomy between porcine models and humans may hinder the procedure for humans, especially for polyps located near the mesentery. d. Eversion full-thickness laparoendoscopic excision: Like the FLEX, this approach is used to create an artificial polyp-like structure for resection but it differs from the FLEX in that it is completed with laparoscopic resection and requires the eversion of the lesion toward the extraluminal size of the colon.34 APC is used to mark the excision 1 cm laterally from the polyp. BraceBars here are endoscopically placed. Eversion of the bowel is achieved through tightening of the BraceBars. The everted polyp can then be resected laparoscopically. This is performed by placing the linear stapler below the BraceBars to ensure adequate clearance while simultaneously removing the defect. The advantages and limitations of this approach are similar to the FLEX procedure. Again, current studies are limited to animal models with no human studies to date.