Endoscopic Resection with One-Port Placement: A Newly Developed Technique for the Safe Management of Advanced Endoscopic Resection for Gastric Gastrointestinal Stromal Tumors

It is known that gastric gastrointestinal stromal tumors (GISTs) have some malignant potential. However, regional lymph node metastasis is unusual for GISTs. Hence, a complete surgical resection of the lesion is the standard treatment for localized gastric GISTs. Furthermore, in the case of localized gastric GISTs (<5 cm in size), depending on location and growth pattern, less invasive laparoscopic surgery involving laparoscopic and endoscopic cooperative surgery (LECS) procedures has been performed with an emphasis on improving the postoperative quality of life [1, 2].

Endoscopic pioneers in Japan have addressed various issues related to endoscopic treatment during the past two decades [3]. Endoscopic submucosal dissection (ESD) is a technique developed in the field of endoscopic treatments for gastrointestinal neoplasms. Recently, many endoscopic procedures derived from ESD have been successfully performed to remove gastric GISTs. Several authors in China have described favorable treatment outcomes for gastric GISTs using endoscopic full-thickness resection (EFTR) without laparoscopic support, namely pure EFTR [4‒8]. In contrast, only a few authors outside China have reported about this procedure. Our study focused on the following barriers that may have led to the non-implementation of pure EFTR in clinical practice outside China: management of the pneumoperitoneum and difficulty maintaining gastric intraluminal pressure, lack of experience in handling luminal collapse, and absence of reliable endoscopic full-thickness suturing devices [9‒11]. Since these concerns are directly related to safety, introducing this procedure to endoscopists who have no experience with pure EFTR is difficult. To address these issues, in November 2019, we introduced endoscopic resection with one-port placement (EROPP), which is a hybrid EFTR procedure that minimizes the intervention of laparoscopic procedures and is a newly developed technique for the safe management of advanced endoscopic resection for gastric GISTs. This study aimed to evaluate the efficacy and safety of EROPP for gastric GISTs.

This single-center retrospective study included a total of 17 patients with gastric GISTs, which originated from the muscularis propria, who underwent EROPP from August 2019 to September 2022 at Yokohama City University Medical Center. Before the treatment, all patients underwent esophagogastroduodenoscopy, computed tomography (CT), and endoscopic ultrasound (EUS) for the determination of the size, the layer of origin, and growth pattern of the tumors. We ensured that all patients met the following criteria before treatment: (i) histological diagnosis of GIST via EUS-guided fine-needle aspiration (EUS-FNA); (ii) intraluminal tumors without a massive extraluminal component; (iii) tumor size <35 mm; (iv) no tumor ulceration; and (v) no regional lymph node enlargement or distant metastasis on CT. All patients provided written informed consent before treatment. The Institutional Review Board of Yokohama City University approved this retrospective observational study (Facility IRB certification number: F210900029).

EFTR was performed in the operating room under general anesthesia with tracheal intubation by a skilled endoscopist (K.H.). A single-channel endoscope with water jet (GIF-Q260J, Olympus, Tokyo, Japan) or a 2-channel multi-bending endoscope (GIF-2TQ260 M, Olympus, Tokyo, Japan) was used with a high-frequency power supply unit (VIO 300 D, ERBE Elektromedizin, Tübingen, Germany) for electrocoagulation. The EFTR procedure was performed using a 1.5-mm Dual knife (KD650Q, Olympus Medical Systems, Tokyo, Japan). A 4-mm-long transparent hood was attached to the tip of an endoscope (D-201-11804 or D-201-13404, Olympus Medical Systems, Tokyo, Japan) to facilitate optimal field visualization. Carbon dioxide insufflation was used during all cases. Prior to performing the endoscopic procedure, a camera port was inserted by a certified laparoscopic surgeon in the umbilicus to avoid intra-abdominal compartment syndrome due to pneumoperitoneum. A laparoscope was used for exploration of intra-abdominal adhesions. In addition, the liver, serosal surfaces, peritoneum, omentum, and mesentery were systematically inspected. Pneumoperitoneum was maintained at 10 mm Hg during exploration. After ensuring the setup to convert to laparoscopic surgery immediately, the EFTR procedure was performed as follows (Fig. 1; online suppl. Video 1; for all online suppl. material, see https://doi.org/10.1159/000532012): (i) a saline or 10% glycerin solution mixed with sodium hyaluronate (MucoUp; Johnson & Johnson Medical Company, Tokyo, Japan) was injected into the submucosal layer after making markings around the lesion; (ii) circumferential incision of the mucosal and submucosal layers around the lesion was performed by typical ESD technique; (iii) intentional perforation and subsequent seromuscular resection using dental floss and an endo-clip as a traction method were completed; and (iv) the gastric full-thickness defect was closed using an over-the-scope clip (OTSC, Ovesco Endoscopy, Tübingen, Germany) after peroral retrieval of the specimen. Additional OSTCs or endo-clips were used to achieve a complete closure if the defect did not close completely using a single OTSC. After endoscopic closure, laparoscopic checks for air leaks were performed, taking advantage of the fact that the intra-abdominal pressure does not change even if the gastric lumen is inflated. A gastrointestinal decompression drainage tube was routinely inserted in all cases after completion of the procedure.

Postoperative treatment included gastrointestinal decompression, proton pump inhibitor (PPI) therapy, and antibiotics. The gastrointestinal decompression drainage tube was withdrawn within 24–48 h. Patients were kept on nothing per os for at least 48 h and second-look endoscopy was routinely performed on postoperative day (POD) 3 to check the condition of the endoscopic closure. Patients were then moved to liquid meals on POD 4, and they gradually returned to a normal diet on POD 8. All patients received a standard intravenous dose of PPI for 4 days and were switched to oral PPI for 4 weeks after EROPP. Antibiotics were prescribed for 3 days to prevent postoperative infection.

En bloc resection was defined as resection of the lesion in a single piece with no endoscopically visible residual tumor. R0 resection was defined as an en bloc resection wherein the lateral and vertical margins of the specimens were free of tumor cells. The procedure time was measured from the start of the submucosal injection to the removal of the lesion. The closure time was measured from the time of insertion of the OTSC device to the end of the procedure.

Simple descriptive statistics were used to report proportions and characteristics of the study using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA). Data are presented as mean, median, and range.

Clinicopathological characteristics and treatment outcomes are summarized in Table 1. All EROPP procedures were completed successfully without conversion to laparoscopic surgery. In 2 cases, an additional port was required to aspirate the leaked liquid or retract the liver to check the condition of the endoscopic closure via laparoscopic view. The median size of the resected tumors was 23 mm (range, 8–35 mm). The median resection time was 36 min (range, 22–95 min) and the median closure time was 18 min (range, 10–45 min). All tumors were removed en bloc endoscopically, and the gastric wall defects were successfully closed with OTSCs without the requirement for laparoscopic closure. No patient had an OTSC detachment on second-look endoscopy. The R0 resection rate was 88%: R0 classification could not be applied in the remaining 2 cases because the histological margin was unclear because of cauterization in a tiny area or physical damage. The final histological diagnosis in all cases was GIST. All patients followed an uneventful course without any postoperative adverse events. During the median follow-up period of 26 months (range, 3–41 months), there was no evidence of recurrence in any patient.

Herein, we reported a hybrid EFTR procedure with minimal surgical intervention (EROPP) for gastric GISTs. EROPP has the important advantage of being able to keep the intra-abdominal pressure constant. This eliminates concerns about intra-abdominal compartment syndrome arising from pneumoperitoneum and helps maintain a good visual endoscopic field. Consequently, we were able to obtain good treatment outcomes for gastric GISTs despite the lack of experience with pure EFTR.

EFTR has been introduced as a treatment option for gastric GISTs (<4 cm) originating from the muscularis propria, according to the American Society for Gastrointestinal Endoscopy (ASGE) guidelines [4]. However, pure EFTR has not been widely adopted in clinical practice. One of the concerns regarding pure EFTR is the management of pneumoperitoneum and prevention of collapse in the gastric lumen. Pure EFTR procedures can potentially cause dangerously high pneumoperitoneum. Additionally, the intentional perforation of the gastric wall leads to an unclear visual field due to the escape of intragastric gases into the peritoneal cavity [12]. To overcome this, we tend to insufflate the lumen continuously to maintain a good visual field. This may cause pneumoperitoneum, which gives rise to abdominal compartment syndrome. Although previous studies revealed that needle decompression can decompress the abdominal cavity, luminal collapse caused by intentional perforation can prevent a good endoscopic visual field [6, 11, 12]. In an experiment performed in pigs, Kamba et al. [10] reported that the intra-abdominal pressure and the intragastric luminal pressure during EFTR were in equilibrium. Consequently, it was concluded that when the abdominal cavity is collapsed with a puncture needle, the gastric luminal pressure also reduces significantly, which prevents securing of the endoscopic visual field. Especially for endoscopists with no experience with EFTR, collapse of the gastric lumen is a technical obstacle. In this case series, however, the intra-abdominal pressure was monitored and adjusted via a port during the procedure, thus enabling the procedure without any concern of excessive pneumoperitoneum. Additionally, maintaining a constant intra-abdominal pressure from the port also maintains the intragastric luminal pressure, which enables a good view of the endoscopic field during the procedure. For these reasons, en bloc resection could be achieved in all cases and R0 resection in most cases, which also resulted in a relatively short procedural time. In this study, 2 cases (case no. 9 and 13) were judged to be non-R0 resection histologically. In 1 case, adhesion to the lesser omentum was extensive, causing thermal degeneration of the tumor during ablation of the adipose tissue, which made evaluation of the tumor margin in the tiny area difficult. However, endoscopically, the tumor was resected with proper visualization with no possibility of residual tumor. In the other case, the specimen was damaged while it was being retrieved orally. To eliminate these problems, it is essential to resect the margin of the tumor at a distance that does not cause thermal damage and retrieve carefully without damage using a balloon or overtube.

Another barrier for using pure EFTR is the absence of reliable endoscopic full-thickness suturing devices. Various methods and devices are available for gastric wall closure [9, 13]. A recent report suggested that OTSCs can be used to perform EFTR with defect closure for gastric tumors in the muscularis propria (tumor diameter <2 cm) [14]. Similarly, this case series demonstrated that gastric full-thickness defects were successfully closed with OTSCs in all 17 cases. As shown in online supplementary Video 1, the OTSC closure system enables us to achieve inverted seromuscular apposition [15, 16]. A previous study indicated that inverted serosal apposition provides a more durable and reliable repair than everted mucosal apposition [17]. In this procedure, defect closure using OTSCs is more reliable than purse-string suturing using an endoloop and endo-clips. In addition, when large defects led to incomplete closures, additional OTSCs or endo-clips were used to close the remaining portions, resulting in robust closure. Therefore, given the uneventful postoperative course in this case series, OTSC may be used as a reliable endoscopic full-thickness suturing device. When tumors are positioned on the gastric posterior wall or the lesser or greater curvature sides, which are covered with fat tissue, the EFTR site may not be visible using one-port laparoscopic observation. Therefore, closing the defects with no visibility in one-port laparoscopy poses the risk of damaging adjacent organs. As a countermeasure, the adjacent organs towards the gastric wall defect were always checked on the endoscopic screen intraoperatively along with the surgeon. This was safer because OTSC closure was performed after confirming the situation outside the gastric wall with the surgeon, regardless of whether the site was covered with lesser omental or omental adipose tissue or communicated directly with the abdominal cavity. In addition, considering the thickness of the gastric wall, the possibility of involving adjacent organs is extremely low in our method of inversion and closure of the gastric wall with a twin grasper. Finally, a leak test can be performed by inflating the gastric lumen and confirming that the intra-abdominal pressure does not increase. In cases where the EFTR site can be seen with a laparoscopic camera, we can directly observe if the EFTR site is inverted and robustly closed. In this case series, all gastric wall defects were successfully closed with OTSCs without requiring laparoscopic closure. This could be explained by the fact that the control and monitoring of intra-abdominal pressure via a port contribute to maintaining a good endoscopic field of view during the closure procedure. In addition, as shown in online supplementary Video 1, when the liver interfered with the laparoscopic view, we could immediately check the condition of the endoscopic closure via the laparoscopic view by retracting the liver through an additional port. Furthermore, if the defects were technically difficult to close in EROPP, we could immediately convert it to a laparoscopic hand-sewn closure using additional port access.

Management of bleeding from subserosal or extragastric vessels is also a risk in the pure EFTR procedure [11]. Fortunately, in this study, we did not encounter severe bleeding which required hemostatic techniques using the laparoscope. To prevent such situations, care was taken to ensure a good field of view and perform treatment in a situation that can be handled. Specifically, we used countertraction, such as a clip with a thread to recognize the resection site well and did not perform the procedure in a blind field of view; we prevented damage to blood vessels and organs outside the gastric wall by gradually incising the inner circular muscle and outer longitudinal muscle layer by layer from the inside of the stomach toward the abdominal cavity to reach the serosa side; and at the site of adhesion to the lesser and greater omentum, the blood vessels in the adipose tissue were resected while being coagulated using a hemostatic forceps to prevent damage to the blood vessels. Furthermore, by limiting the indication for the procedure to intraluminal growth-type tumor only, it was ensured that the field of view for intraoperative tumor localization and resection was inside the stomach, eliminating events arising due to untreatable fields. Lastly, with regards to the field of view outside the gastric wall after full-thickness resection, receiving advice from the attending surgeon also ensured safety.

The LECS technique was developed in Japan as a gastric wedge resection procedure with minimal transformation of the stomach [1]. Since its inception, LECS-related procedures have developed rapidly, spreading not only in Japan but worldwide [2]. According to the ASGE guidelines, LECS is a hybrid EFTR which combines endoscopic and laparoscopic techniques [4, 8]. On the other hand, most studies of pure EFTR for gastric GISTs have been performed in China [5‒7]. A previous review article of pure EFTR reported that conversion to surgery due to either EFTR failure or adverse events was needed in only 0.8% of the procedures [18]. However, this procedure, which is dominated by experience from China, is still controversial in its global spread. In Japan, the concept of extraluminal support through the abdominal wall for endoscopic treatment was surprisingly reported about 20 years ago [3]. Inheriting such innovative challenges, our EROPP, hybrid EFTR with minimal laparoscopic intervention, is excellent not only in terms of safety but also in the introduction of EFTR procedures and has the potential to be globally accepted. Our EROPP procedure is minimally invasive compared to conventional hybrid EFTR as it requires less gastric wall resection and no omental resection, thereby preserving normal gastric emptying. In addition, our procedure is better than conventional hybrid EFTR in terms of cosmetic outcomes because the majority of the EROPP procedures were performed with only one port access in this case series. Although the indication for our EROPP is similar to that for conventional hybrid EFTR, the size of GISTs was maximally 35 mm in diameter in this case series, which is smaller than the indication for conventional hybrid EFTR, because it is challenging to remove tumors >35 mm in diameter through the oral cavity. Additionally, secure R0 resection was important in determining the indication. To perform an R0 resection, trying to obtain a sufficient margin in the EROPP (EFTR) procedure may increase muscle layer defects and increase the difficulty of closure. In this study, the muscle layer adhesive site was theoretically smaller than 35 mm because of the intraluminal growth type, and even if a margin is secured, all muscle layer defects of this size can be closed endoscopically. Indeed, all the cases with a tumor size <30 mm achieved R0 resection and were successfully closed with one OTSC. In contrast, in a few cases of tumor size >30 mm, R0 resection was not achieved or/and was successfully closed with two OTSCs. Our results suggest that pure EFTR may be directly applicable for feasible and safe treatment of intraluminal GISTs of size <30 mm. However, we believe that EROPP, which is a bridge treatment for GIST between LECS and pure EFTR, has allowed endoscopists who have no experience with pure EFTR to perform it. Further study is needed to confirm the upper limit in tumor size for EROPP to achieve reliable R0 resection and closure. In terms of damage to the abdominal wall, pure EFTR is a less invasive treatment compared with our EROPP. However, as previously stated, many concerns about pure EFTR have not yet been addressed with currently available methods and devices. Because the efficacy and safety of pure EFTR remain poorly understood in countries where pure EFTR has not been popularized, safety should be considered a top priority. Thus, a close collaboration between endoscopists and laparoscopic surgeons is important for the implementation of safe treatments. In 2 cases, an additional port was required to ensure the safety of the procedure in intraoperative discussions between endoscopists and laparoscopic surgeons. Our case series suggests that port assistance plays an important role in addressing many concerns about pure EFTR. Furthermore, after experiencing EROPP, we believe that inexperienced endoscopists were the catalyst for the introduction of EFTR, and more endoscopists could learn to safely perform the pure EFTR technique. Finally, the cost-effectiveness of this procedure needs to be considered. ESD devices and a one-shot OTSC cost less than a standard laparoscopic surgery, but using two or more OTSCs would increase the cost. Moreover, as a comparison with surgical stapling or suture, the intensity of the OTSC closure system for gastric wall defect has been rarely described. However, EROPP has a benefit of no resection of the perigastric tissue, ignorable gastric deformity, and no functional disturbance. Thus, further investigations are required in this field.

There are certain limitations to our study. First, this is a retrospective, single-center study. Second, the number of patients was small, requiring validation of our results in larger sample sizes. Third, endoscopic procedures in this case series were performed by an experienced endoscopist at a high-volume center.

EROPP may be a safe, less-invasive hybrid EFTR for gastric GISTs. The experience of EROPP may make pure EFTR more accessible to endoscopists with limited or no experience in pure EFTR.

We thank Nobutsugu Abe for his helpful advice on the idea and naming of EROPP.

This study was approved by the Ethics Committee of Yokohama City University (approval number: F210900029), and the study was conducted following the provisions of the Declaration of Helsinki. All patients provided written informed consent for the procedure. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

The authors have no conflicts of interest to declare.

This work was not funded.

K.H. and A.S. conceptualized and designed the study and performed statistical analysis; K.H., A.S., C.S., S.S., T.S., K.S., and C.K. acquired the data; K.H., A.S., and S.M. analyzed and interpreted the data; K.H. drafted the article; and K.H. and S.M. critically revised the article. All authors read and approved the final manuscript. All authors listed have contributed substantially to the design, data collection and analysis, and editing of the manuscript.

All data generated or analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.