Minimally invasive surgery for submucosal (subepithelial) tumors of the stomach

Abstract

Minimally invasive surgery has become common in the surgical resection of gastrointestinal submucosal tumors (SMTs). The purpose of this article is to review recent trends in minimally invasive surgery for gastric SMTs. Although laparoscopic resection has been main stream of minimally invasive surgery for gastrointestinal SMTs, recent advances in endoscopic procedures now provide various treatment modalities for gastric SMTs. Moreover, investigators have developed several hybrid techniques that include the advantages of both laparoscopic and endoscopic procedure. In addition, several types of reduced port surgeries, modification of conventional laparoscopic procedures, have been recently applied to the surgical resection of SMTs. Meanwhile, robotic surgery for SMTs requires further evidence and improvement.

Key Words: Minimally invasive, Surgery, Submucosal tumor, Gastrointestinal tract

Core tip: Minimally invasive surgery has become common in surgical resection of gastrointestinal submucosal tumors (SMTs). Although laparoscopic resection has been the main stream of minimally invasive surgery for gastrointestinal SMTs, recent advance in endoscopic procedures also provide various modalities of treatment for gastric SMTs. Moreover, investigators developed several hybrid techniques, which include the advatages of the laparoscopic and endoscopic procedure. Additionally, reduced port surgeries, which is modified from the conventional laparoscopic procedures, have been recently applied to the surgical resection of SMTs. Meanwhile, the application of a robotic surgeries to the treatment of SMTs still request more evidence and improvement.

INTRODUCTION

Since Dubois et al[1] reported their experience with laparoscopic cholecystectomy in 1989, minimally invasive surgery has become common in all surgical fields. Surgical resection of gastrointestinal submucosal tumors (SMTs) is no exception. Laparoscopic partial gastrectomy is widely accepted for the treatment of gastric SMTs[2]. Moreover, with recent developments in endoscopic procedures, endoscopic resection and a hybrid approach that combines endoscopic and laparoscopic techniques have been applied to gastric SMTs. In addition, the laparoscopic approach is feasible for SMTs of the small bowel and other sections of the gastrointestinal tract, although this procedure is rarely performed due to the infrequency of these tumors[3-7].

The purpose of this article is to review recent trends in minimally invasive surgery for SMTs of the stomach.

ENDOSCOPIC RESECTION

Although the standard treatment for gastrointestinal SMTs is surgical resection[8], many reports have suggested that endoscopic resection can be applied to some gastric SMT cases. Even in cases of gastric gastrointestinal stromal tumors (GISTs), endoscopic treatment has been advocated in several reports. However, in these cases, tumor size must be small. Because malignant transformation has been reported in GIST, and R0 resection with a negative resection margin is generally required[9]. Moreover, since GISTs do not have a true capsule and often have a fragile consistency, the lesion is often incompletely removed[10-13].

Recent advances provide several modalities of endoscopic resection for gastric SMTs, including band ligation, snare polypectomy, unroofing, endoscopic submucosal dissection (ESD), endoscopic muscularis dissection (EMD), submucosal endoscopic tumor resection (SET), endoscopic submucosal tunnel dissection (ESTD), and endoscopic full-thickness resection (EFTR)[8,13-17].

Endoscopic band ligation[18-21], endoscopic snare polypectomy[22,23], and endoscopic unroofing[22,24] are indicated only for the treatment of small SMTs (diameter < 2 cm). In particular, the unroofing technique is usually applied for the diagnosis of SMTs to assess whether the tumor is a GIST or not[25-28]. However, for treatment purposes, the unroofing technique is applicable only to lipomas and cystic lymphangiomas, which may spontaneously resolve after this treatment. Although Hizawa et al[24] reported nine cases of cystic SMTs treated by this technique, some lipomas may require additional treatment (e.g., endoscopic mucosal resection)[29]. Therefore, more advanced techniques are indicated for wider lesions of unknown behavior.

Standard ESD procedures can be used safely for the resection of gastric SMTs in the submucosal layer[12,30,31]. This technique consists of a circumferential incision around the tumor as deep as the submucosal layer and subtumoral dissection of the submucosal layer[32]. However, it is challenging to resect tumors originating from the proper muscle layer. In these cases, including GISTs, subtumoral dissection should be as deep as the proper muscle layer; therefore, this procedure was named EMD[14]. As a result of the deeper dissection than in standard ESD, a rather high rate of gastric perforation has been reported[10-12,33-37]. Although a recent prospective study showed a relatively high success rate of 94.4%[13], this procedure should be performed by a well-experienced endoscopist.

Since ESD and EMD, endoscopic resection has evolved continuously. In 2012, Inoue et al[15] reported SET, and Gong et al[16] reported ESTD. These are similar procedures, in which the dissection of the muscularis layer is the main technique. However, in these procedures, submucosal tunneling is begun far away from the lesion and is followed by muscular dissection under the lesion (Figure 1). Although tunnel dissection maintains the integrity of the mucosal layer over the tumor[13], there is still a risk of gastric perforation. Meanwhile, Zhou et al[17] reported EFTR, which involves full-thickness resection and closing of the defect with metallic clips endoscopically.

Figure 1 Endoscopic submucosal tunnel dissection. A: After the mucosa is lifted by submucosal injection, a 2 cm mucosal incision is made approximately 5 cm proximal to the submucosal tumor (SMT); B: A submucosal tunnel is created using endoscopic submucosal dissection; C: The submucosal dissection is continued until the SMT is visible by endoscopy; D: Dissection is performed along the margin of the SMT with an endoscopic knife; E: The dissected SMT is removed through the mucosal defect.

It is necessary to consider the long-term oncological consequences of iatrogenic gastric perforation when using this procedure. A case was reported in which an asymptomatic pelvic mass was noted 3 years after gastric perforation had occurred during endoscopic resection of a GIST[38].

LAPAROSCOPIC SURGERY

For the treatment of SMTs, several studies[39-41] have reported that laparoscopic procedures have the following advantages over open surgery: less pain, less inflammation, less blood loss, earlier diet, and shorter hospital stay (Table 1). Nonetheless, several considerations are necessary when performing laparoscopic treatment of SMTs.

Table 1 Comparative analysis of open vs laparoscopic surgery for gastric gastrointestinal stromal tumor.

	Nishimura et al[39] (2007)			Karakousis et al[40] (2011)			De Vogelaere et al[41] (2013)
	OR	LR	P value	OR	LR	P value	OR	LR	P value
Number of patients	28	39		40	40		16	37
Operative time1 (min)	115	136	0.06	89 (30-249)	96 (48-200)	0.320	155 ± 48.1	48.5 ± 16.0	< 0.001
EBL (mL)	80	45	0.26	100 (5-400)	25 (5-200)	0.006
Hospital stay (d)				7 (4-25)	4 (2-7)	0.002	16.9 ± 10.6	8.2 ± 3.3	0.007
Morbidity				25%	15%	1%	18.9%	2.7%	0.077
Mortality	0	0		0%	0%		6.3%	0%

¹Regarding the operation time, Nishimura et al[39] and De Vogelaere et al[41] reported mean operation time, and Karakousis et al[40] reported median operation time. GIST: Gastrointestinal stromal tumor; OR: Open resection; LR: Laparoscopic resection; EBL: Estimated blood loss.

Indication of laparoscopic resection

Some SMTs have malignant potential, so there is a potential risk of intraperitoneal dissemination when manipulating the tumor during laparoscopic surgery[9]. In most SMTs with benign features, including leiomyomas, schwannomas, granular cell tumors, and lipomas, laparoscopic procedures are safe in terms of peritoneal dissemination because they seldom recur[8,42-46]. However, the possibility of GISTs should always be considered because some GISTs display malignant behavior. Although GISTs show acceptable survival and recurrence after laparoscopic resection[47-49], such favorable results cannot be expected if tumor rupture occurs. Therefore, many surgeons take the size of the tumor into consideration, with the assumption that larger tumors may require more manipulation, increasing the risk of rupture. For these reasons, laparoscopic surgery is only indicated for small GISTs (diameter ≤ 2 cm) according to the GIST Consensus Conference in 2004[50]. However, size cannot be the only factor used to determine the applicability of the laparoscopic procedure. Regardless of size, fragile or highly vascular tumors may require open surgery because of the increased risk of tumor rupture or bleeding. Therefore, it is important to manipulate a SMT without grasping it directly. This principle is widely accepted, and there are several techniques for handling the tumor without touching it. Yahchouchy-Chouillard et al[51] reported a “no-touch” technique that includes grasping the surrounding tissue, holding the threads sutured at the gastric wall around the tumor, and using a laparoscopic stapler or bag during laparoscopic resection. With this technique, the risk of tumor dissemination can be minimized. In addition, by extending the umbilical port incision, the resected tumor can be safely removed using the laparoscopic bag.

The tumor size limit, which was initially considered to be 2 cm, can be larger under certain conditions, on the basis of recent evidence. Otani et al[52] and Ryu et al[53] reported that laparoscopic resection of SMTs was feasible with tumors up to 5 cm. Moreover, some investigators have reported that laparoscopic resection of larger tumors (> 5 cm, but < 10 cm) is also possible[40,54-56]. It is likely that this size limitation will increase in the near future. Even in the current guidelines, no concrete indication of size is mentioned[57-59]. Compared to gastric SMTs, a size limit for laparoscopic surgery has not been established for SMTs in other sites (e.g., small bowel, colon, and rectum). However, since the intestinal tract is mainly a tubular structure, the “no-touch” technique can be applied easily by handling of segments near the segment involved.

Surgical strategies according to tumor site

The general principle of the treatment for SMTs is local resection with negative resection margin[2]. There is no exception to this principle, even with laparoscopic surgery; however, different surgical techniques are required depending on the location and configuration (i.e., endophytic or exophytic) of the tumor[2].

If exophytic tumors are located on the anterior wall of the stomach, the exogastric approach is the most widely used method[2,60,61]. In this situation, the tumor can be isolated by grasping the surrounding normal tissue with the laparoscopic instrument[9]. Then, the laparoscopic linear stapler is applied to the normal tissue to preserve the oncologic safety margin. However, this method could result in stenosis or deformity of the stomach by excessive gastric wall resection[2], so it is necessary to apply the linear stapler perpendicularly to the longitudinal axis of the stomach[9]. Another technique to prevent stenosis, the eversion method, was recently introduced[62,63]. If a large SMT is located on the anterior wall of the stomach, it is not easy to trace the tumor and avoid excessive resection of the gastric wall[62]. Firstly, a gastrotomy is made near the tumor site. Then, the tumor is everted out of the stomach, and a linear stapler is applied to the everted stalk of the tumor. The gastrotomy can be simultaneously closed with the linear stapler. Here, the direction of the linear stapler must be perpendicular to the longitudinal axis of the stomach.

For SMTs on the posterior wall of the stomach, the approaching method is selected based on whether the lesion is exophytic or endophytic. The exogastric approach, which was described earlier, can be used for an exophytic lesion if the tumor can be resected after mobilizing and rotating the stomach[63]. In the case of an endophytic lesion, the intragastric or transgastric approach is usually applied[64-67]. The intragastric approach involves resecting the tumor with the scope and instruments directly inserted into the gastric lumen[68-71]. With this procedure, minimal deformity and stenosis can be expected[2]. Balloon trocars are usually preferred for use in this procedure to prevent retraction of the trocars[64,72-74]. Recently, the single-incision intragastric approach has been introduced[75], whereby the stomach is brought out and opened through a single umbilical incision, which is kept open with a wound retractor. The intragastric resection is performed via a multi-channel port inserted through the gastrotomy. The transgastric approach, on the other hand, involves visualizing and resecting the tumor through an anterior gastrotomy[67,76]. The anterior gastrotomy should be closed with a linear stapler, perpendicularly to the longitudinal axis of the stomach, as for the exogastric approach or eversion method.

The management of SMTs at the esophagogastric junction is very challenging. If potentially malignant lesions are suspected, highly invasive procedures are often required[2]. Since the attempt to acquire an adequate resection margin can induce stenosis of this portion, radical procedures are safer than wedge resection or other local resection. Therefore, for such lesions, total gastrectomy is recommended in some institutions. Although laparoscopic proximal gastrectomy was reported in 1995[77], many surgeons have avoided this procedure because of serious complications, such as stricture and reflux esophagitis, related to esophagogastrostomy[2]. One potential solution for this problem is double tract reconstruction. Recently, Ahn et al[78] reported that laparoscopic proximal gastrectomy with double tract reconstruction results in less reflux and stricture. However, most SMTs, including some malignant lesions, do not require such an invasive procedure. Transgastric or intragastric resection can be a useful method for benign disease and even some malignant lesions. Enucleation is also a good option for certain benign lesions[69]. Also, this procedure could prevent stenosis of the esophagogastric junction.

Laparoscopic wedge resection of SMTs on the prepyloric antrum and lesser curvature are also technically demanding procedures[2]. There is a risk of stenosis of the gastric lumen because of the low distensibility of these areas, and a risk of vagus nerve injury, which could result in functional gastric outlet obstruction or delayed gastric emptying[2,9,72]. Therefore, many surgeons recommend full-thickness resection of the tumor following repair by hand sewing[2,79]. If deformity exists after resection of the tumor, distal gastrectomy can be considered.

Additionally, small bowel SMTs can be resected intracorporeally or extracorporeally depending on the surgeon’s preference. Either extracorporeal or intracorporeal resection can be performed through an umbilical port site even if the tumor is large[6,9], but surgeons should be careful to prevent iatrogenic spillage of tumors during the laparoscopic approach. If tumor invasion to an adjacent organ is suspected, open conversion should be seriously considered.

Reduced port surgeries for SMTs

Recently, laparoscopic surgeries have been modified to reduce invasiveness and improve cosmesis. With this paradigm, reduced port surgeries, including single-incision laparoscopic surgery, are applied to the surgical resection of SMTs[80-84]. As a transitional procedure from conventional laparoscopic surgery, Hirano et al[80] reported their experience with reduced port surgery, which requires a 25 mm umbilical incision and a 2 mm extra incision. In this procedure, a mini-loop retractor was inserted through the extra port. In comparison, Sasaki et al[82] reported single-incision laparoscopic surgery for three SMT cases. However, they only used conventional laparoscopic instruments, and this procedure can only be used for small lesions at favorable locations (e.g., the anterior wall or greater curvature of the body). In contrast, Henckens et al[81] carried out single-incision laparoscopic surgery for a tumor located on the posterior wall by using double-bended instruments. The double-bended shape makes it possible to perform manipulations with minimal conflict between instruments passing through the single incision. The single-incision laparoscopic intragastric approach was developed as another way to address the technically demanding location of the tumor[75]. Applying the intragastric approach to single-incision laparoscopic surgery makes it easier to access high-lying gastric SMTs (i.e., SMTs of the fundus, cardia, and esophagogastric junction)[64,68,70,85]. Despite these advances, however, reduced port surgery is still technically demanding, and great care must be taken against unwanted injury. At present, it is necessary to develop more innovative instruments and procedures to overcome the ergonomic difficulties of reduced port surgeries.

Hybrid approach (endoscopy and laparoscopy)

Laparoscopic resection is the main stream of minimally invasive surgery for gastrointestinal SMTs, but it is difficult to localize small endophytic tumors by laparoscopy[86,87]. In that sense, the endoscopic approach has advantages such as easy localization of the tumors and less invasiveness. However, it also carries a risk of bleeding, perforation, and less radicality[88]. Therefore, to overcome these problems, investigators have developed several hybrid techniques that combine the laparoscopic method with endoscopic procedures[70,71,86-91].

At the beginning, ESD was performed with laparoscopic instruments using the intragastric approach[70,71,90,91]. If perforation occurred, it was repaired by the laparoscopic hand-sewing technique. The specimen was retrieved by endoscopy.

Laparoscopic endoscopic cooperative surgery (LECS) is a sequential procedure in which, after ESD, the seromuscular layer is partially dissected laparoscopically[86-89]. Laparoscopic linear staplers are then applied for resection of the tumor and closure of the gastric wall simultaneously, as in the eversion method (Figure 2)[88].

Figure 2 Laparoscopic endoscopic cooperative surgery. A: Three-fourths of the circumference is cut in the endoscopic side; B: Laparoscopic seromuscular dissection is performed along the submucosal dissection line; C: With the tumor and the non-resected portion are lifted, the defect is closed with laparoscopic linear staplers; D: The direction of stapling should be perpendicular to the longitudinal axis of the stomach.

In laparoscopy-assisted endoscopic full-thickness resection (LAEFR), after full-layer dissection is performed by endoscopy, the gastric defect is repaired by a laparoscopic suture technique[92].

Recently, Goto et al[93] and Mitsui et al[94] reported non-exposed endoscopic wall-inversion surgery (NEWS) to prevent gastric luminal exposure, which can result in intra-abdominal contamination and peritoneal dissemination of the tumor. First, seromuscular dissection is performed laparoscopically, followed by closure of the dissection line by laparoscopic suturing. Consequently, the dissected seromuscular area is invaginated toward the inside. Finally, the invaginated tumor is resected by the ESD technique (Figure 3)[94].

Figure 3 Non-exposed endoscopic wall-inversion surgery. A: Laparoscopic seromuscular dissection is done after endoscopic submucosal injection. Then, laparoscopic seromuscular suture is performed around the dissected portion; B: Subsequently, the dissected portion is invaginated to the luminal side; C: The mucosal layer is cut with the endoscopic device.

Although all the cooperative procedures are a little different from each other, the common advantage is minimizing the loss of normal tissue by precise localization with endoscopy.

Robotic surgery

Although the role of robotic surgery using the da Vinci Surgical System (Intuitive Surgical Inc., Sunnyvale, CA) has been established for intra-abdominal procedures, few studies have evaluated the efficacy of robotic surgery for SMTs[95,96]. Moriyama et al[96] suggested that the benefit of robotic surgery is its ergonomic superiority, which permits more appropriate surgical margins. The articulated robotic arms are able to make even resection margins around the round shape of SMTs. If the tumor is located on the esophagogastric junction or the pylorus, an even resection margin can prevent stenosis of the gastric lumen. However, this advantage is not definitive[9], because experienced surgeons can make adequate and precise margins in the conventional laparoscopic setting[2]. In addition, several cooperative procedures can achieve the same benefit as robotic surgery with less cost.

Even regarding cosmesis, robotic surgery does not reduce the number of ports or the size of the trocar required. Moreover, if a stapling procedure is needed, another port must be established, because robotic stapling devices are not available yet[96].

To justify the application of a robotic surgical system to the treatment of SMTs, more evidence is needed and several problems, including the bulky size of the devices, the lack of a stapling instrument and the high cost, must be addressed.

CONCLUSION

With the development of minimally invasive surgery, including single-port surgery and hybrid techniques, the management of SMTs is advancing to preserve the volume and function of the stomach, even with malignant lesions.