Endoscopic full-thickness resection: the logical step toward more extended endoscopic oncologic resections?

Few other disciplines have undergone a more dynamic development in the short-term history of medicine than flexible endoscopic surgery. Endoscopic polypectomy and mucosal resection successfully replaced the surgical resection of mucosal neoplasia – a major step in the reduction of trauma. Furthermore, the popularity of endoscopic submucosal dissection (ESD) is increasing because en bloc resections and the complete resection of larger lesions can be achieved with this technique. However, ESD is one of the most complex endoscopic procedures and remains challenging because of the long procedure time required and the relatively high risk for complications, including bleeding and perforation. For both of these complications, the “over-the-scope clip” (OTSC) system offers effective treatment. Therefore, now that we have the means to close iatrogenic perforations reliably [1], the next logical step is to perform full-thickness resections. Adequate specimens can be obtained for precise histopathologic assessment, as with laparoscopic wedge resection.

However, before such procedures can be integrated into our daily practice, several questions should be answered:

1. Lymph nodes cannot be resected by endoluminal endoscopic surgery, so the following should be clarified: what tumors can be treated without taking into account the risk of distant metastasis?

2. Is there a risk of seeding of tumor cells when the gut wall is opened?

3. Is it indeed always feasible to close iatrogenic perforations?

4. Finally, what future developments can be anticipated that will overcome current limitations?

First of all, it should be determined whether carcinomas or mesenchymal tumors are being treated. For carcinomas that do not exceed a specified depth of malignant infiltration and tumor grade, there are sufficient data showing that endoluminal resection, with the muscle layer left intact, is sufficient [2]. Therefore, there is no need for full-thickness resection. If the infiltration is deeper, assessment of the lymph node status is mandatory. However, at present, lymph node resection is possible only by open or laparoscopic surgery. Therefore, endoscopic full-thickness resection must be regarded as highly experimental, with no proven benefits.

The situation may be different for the resection of subepithelial tumors. Most of these tumors carry negligible or no risk for malignancy, and even with gastrointestinal stromal tumors (GISTs) below a certain size, the risk for lymph node metastasis is very low. However, taking into account the uncertainties of the various diagnostic methods used to assess the malignant potential of subepithelial tumors, resection is recommended for tumors larger than 2 cm, those that become symptomatic, and those that have features on endoscopic ultrasound that are suspicious for GISTs [3]. Resection can then be diagnostic or possibly therapeutic. At present, these tumors have been considered an ideal indication for laparoscopic wedge resection. Now, with new endoscopic tools and techniques available, a purely intraluminal approach may be as feasible as laparoscopy.

Basically, three different approaches to the resection of subepithelial tumors can be distinguished:

1. submucosal tunneling [4];

2. a grasp-and-snare technique with subsequent closure of any secondary perforation [5];

3. snare resection after the use of a full-thickness suturing device (suture first, cut later).

All techniques have documented success rates. Nevertheless, several shortcomings should also be taken into account. Tunneling techniques are time consuming and technically difficult to perform. Tumors should be relatively small (maximum 2 cm) and located at the distal esophagus or proximal stomach. The grasp-and-snare technique with use of the OTSC system to close secondary defects is rather easy to perform but entails a possible risk of contamination of the abdominal cavity, and laparoscopic assistance is required in some cases. To overcome these shortcomings, the application of an OTSC system before resection has also been reported [6]. However, such an approach is possible only for small lesions because the diameter of the cap bearing the clip is small. Finally, with dedicated suturing systems, it has become possible to resect a subepithelial tumor after the placement of transmural sutures at the base of the tumor, so that the potential perforation site is closed before resection is performed [7].

In the current issue of Endoscopy, Schmidt et al. report on the use of such a suturing device. The authors retrospectively analyzed 31 patients who underwent endoscopic full-thickness resection of a subepithelial tumor. The device that was used was originally designed for the endoluminal therapy of gastroesophageal reflux disease, in which the gastric cardia is tightened by placing transmural suture bands [8]. Because this device can be steered in the gastric lumen to some extent, serosa-to-serosa (transmural) sutures can also be placed at other regions in the stomach, apart from the cardia. This approach appears to be very elegant because it avoids the previously mentioned shortcomings of other methods for endoscopic full-thickness resection. Nevertheless, in the study of Schmidt et al., some complications occurred (bleeding in 12 patients and perforation in 3); however, these were managed endoscopically in all cases. Histology revealed GIST in 58.0 % of all cases. An R0 resection was achieved in all but 2 patients. One patient with a completely resected GIST and an intermediate risk for progression received adjuvant therapy. The authors concluded that their approach is feasible, safe, and effective from an oncologic point of view.

The authors should be congratulated on their excellent results and their innovative approach to treating gastric subepithelial tumors. Is this now the next step toward more extended endoscopic oncologic resections? The answer is both yes and no! Yes, if only echo-poor subepithelial tumors between 2 and 3 cm in size are treated and GISTs are suspected. No, if the tumors are larger and en bloc resection and extraction for further histopathologic analysis are impossible. Also no, if the tumors are smaller but have features typical of lesions other than GISTs (e. g., ectopic pancreas, lipoma). In these cases, resection is not indicated and would be regarded as overtreatment.

Furthermore, endoluminal resection can be impossible in the case of tumors with mainly extraluminal growth. One can assume that there are also cases in which resection is technically hampered because the tumor is located in a region of the stomach that is difficult to reach. And what about epithelial tumors? For carcinomas, endoscopic oncologic resection does not necessarily imply full-thickness resection. As previously mentioned, anything that goes more deeply into the submucosal layer requires surgical resection that includes an assessment of lymph nodes. The only indication one might consider are the few small mucosal cancers that cannot be resected by endoscopic mucosal resection or ESD because significant lifting after submucosal injection leads to significant scarring.

Nevertheless, despite the small number of patients who are currently eligible for endoscopic full-thickness resection as it is performed today, the horizons of interventional endoscopy have again been broadened. The key issue in endoscopic intraluminal surgery is to compare endoscopic practice with surgical standards. The main advantage of surgery is that it enables precise resection with the reliable suturing and/or closure of leaks (with staplers or hand-sewn sutures). What can endoscopy offer with respect to these features? Advanced resection techniques (such as ESD and submucosal tunneling) were the first developments to enable closure of perforations, followed by dedicated clipping systems. The placement of suture bars before resection, as mentioned in the study of Schmidt et al., has been the next step, and now, what might come next? One can only speculate. A personal wish would be the ability to work from within the lumen in the same way that a surgeon does in the abdominal cavity – namely, with two arms that can be moved independently of each other; this would enable traction and countertraction for the full-thickness resection of larger submucosal lesions or the easier and faster submucosal dissection of mucosal lesions. Furthermore, such platforms might facilitate the reliable and easy closure of leaks with serosa-to-serosa sutures. Currently, no reliable endoscopic platform is available that will allow us to solve all these issues. Let’s see what the future brings that will indeed allow us to perform extended endoscopic oncologic resections from within the lumen, in a similar fashion as conventional surgery done from outside the lumen, and with similar results.

• References

• 1 Voermans RP, LeMoine O, von Renteln D et al. CLIPPER Study Group. Efficacy of endoscopic closure of acute perforations of the gastrointestinal tract. Clin Gastroenterol Hepatol 2012; 10: 603-608
• 2 Gotoda T. Endoscopic resection of early gastric cancer. Gastric Cancer 2007; 10: 1-11
• 3 Sepe PS, Brugge WR. A guide for the diagnosis and management of gastrointestinal stromal cell tumors. Nat Rev Gastroenterol Hepatol 2009; 6: 363-371
• 4 Lu J, Zheng M, Jiao T et al. Transcardiac tunneling technique for endoscopic submucosal dissection of gastric fundus tumors arising from the muscularis propria. Endoscopy 2014; 46: 888-892
• 5 Schlag C, Wilhelm D, von Delius S et al. EndoResect study: endoscopic full-thickness resection of gastric subepithelial tumors. Endoscopy 2013; 45: 4-11
• 6 Sarker S, Gutierrez JP, Council L et al. Over-the-scope clip-assisted method for resection of full-thickness submucosal lesions of the gastrointestinal tract. Endoscopy 2014; 46: 758-761
• 7 Schmidt A, Bauder M, Riecken B et al. Endoscopic full-thickness resection of gastric subepithelial tumors: a single-center series. Endoscopy 2015; 47: 154-158
• 8 Koch OO, Kaindlstorfer A, Antoniou SA et al. Subjective and objective data on esophageal manometry and impedance pH monitoring 1 year after endoscopic full-thickness plication for the treatment of GERD by using multiple plication implants. Gastrointest Endosc 2013; 77: 7-14