Endoscopic full-thickness resection for gastric gastrointestinal stromal tumor originating from the muscularis propria

OBJECTIVE: This study retrospectively reviewed 46 cases of gastric gastrointestinal stromal tumors treated by endoluminal endoscopic full-thickness resection (EFR) microsurgery in our gastrointestinal endoscopy center. We aimed to evaluate the EFR for the treatment of gastric gastrointestinal stromal tumors originating from the muscularis propria. METHODS: A total of 46 patients with gastric gastrointestinal stromal tumors originated from the muscularis propria layer from January 2012 to June 2015 were treated with EFR. The patients were followed up with gastroscope and computed tomography (CT) for evaluation of therapeutic effect and safety. RESULTS: EFR was successfully accomplished to remove all tumors in 46 patients. The mean procedure time was 82.5±39.8min (56188min). Except in 3 leiomyomas, pathological examination confirmed gastrointestinal stromal tumor (GIST) in 43 cases. None of the patients had occurred bleeding, peritonitis and other complications after EFR. Thereafter, all patients were followed up with gastroscope after 1, 6, 12 months. CONCLUSIONS: EFR is effective and safe for patients with gastric gastrointestinal stromal tumors originated from muscularis propria layer and has the advantage of less invasive treatment and higher tumor resection rate. It should be considered for further application.


INTRODUCTION
The gastric submucosal tumor less than 3cm in most benign tumors, but gastrointestinal stromal tumor (GIST) currently regarded as a potentially malignant tumor.Stromal tumors arising from the muscularis propria are located in deeper layers, especially those that do not grow within cavities 1 .The main treatment is complete tumor resection 1-3 .Recently, endoscopic full-thickness resection (EFR) has been applied as a treatment for gastrointestinal submucosal tumors (SMTs).
We used EFR for complete resection of gastric gastrointestinal stromal tumors from the muscularis propria and have summarized the effect of treatment.

Patients
From January 2012 to June 2015, 46 cases of gastric gastrointestinal stromal tumors, originating from the muscularis propria layer, were confirmed by endoscopic ultrasound (EUS) and computed tomography (CT) at The Affiliated Yantai Yuhuangding Hospital of Qingdao University.No metastasis of gastric gastrointestinal stromal tumors was found.The patients consisted of 21 males and 25 females at ages 23-65 years (median age 47.6±13.2years).All the cases were single occurrences.The tumors were 1.2-4.5cm in size and located in the fundus (n = 36), the gastric corpus (n = 9), the gastric antrum (n = 1).Each patient's written informed consent was obtained.This retrospective study was approved by the Ethics Committee of The Affiliated Yantai Yuhuangding Hospital of Qingdao University.

EFR Method
EFR method was done as previously described 4,5 .Pneumoperitoneum will happen inevitably as gas will spill into the abdominal cavity in the process of tumor resection and suture of gastric defects in if EFR full-thickness resection of gastrointestinal mucosa lead to gastric perforation, the used of CO2 in solution in water can reduce postoperative abdominal distension.The key to successful treatment of EFR is the endoscopic therapeutic perforation occurred as a mend.Under endoscopic guidance, the incisions on the gastric body from the two ends to the middle were fully closed with titanium clips, and the gastric wound was sealed.For wounds that were too large to seal directly, negative pressure was applied to suck the omentum into the gastric cavity, and the titanium clips were used to seal the wound by clipping the omentum to the gastric mucosa (Figure 1).When the serosa was cut all around the GIST tumor, the lesion can fall within the peritoneal cavity.For tumors larger than 4 cm, we use double-channel gastroscope to avoid that.

Sample processing
Post-EFR pathological diagnosis was made by focusing on cell types.The immunohistochemical tests for CD34, CD117, Dog-1, S-100, and SMA.Mitotic counts per 50 highpower fields were evaluated in GISTs.

Postoperative treatment
After EFR surgery, a gastrointestinal decompression drainage tube was placed.Postoperative medication included nothing perorally, gastrointestinal decompression drainage for 24 hours, and drug therapy, such as a proton pump inhibitor and broad-spectrum antibiotic intravenous administration, for 3 days.Patients were discharged with proton pump inhibitor therapy for 2 months.

Statistical analysis
Statistical analysis was performed with SPSS for Windows Version 17.0 software (SPSS Inc., Chicago, IL, USA).Data were analyzed using the two-tailed Student's t test.P < 0.05 was considered significant.Data are expressed as mean ± standard error of the mean (SEM).I.Among all enrolled patients, 46 tumors were located in the gastric fundus with 36 cases, 9 cases were in the gastric corpus, and 1 case was in the gastric antrum.All lesions were confirmed as originating from the muscularis propria or close to the serosa by endoscopic ultrasonography examination.

Clinicopathological characteristics and outcomes of EFR are summarized in Table
The EFR success rate was 100%.The median operation time was 82.5 minutes (range, 56-188minutes; SD, 39.8minutes).Mean size (the maximum diameter) of resected tumors was 2.6 (range, 1.2-4.5)cm.Pathological diagnosis showed 43 GISTs, 3 leiomyomas.Among the 43 GISTs, 33 cases were benign, 8 cases were a very low risk of malignancy, and 2 were at low risk of malignancy (Mitotic counts per 50 highpower fields≤5).All specimens were border-free.
Effects of tumor sizes affecting the entire EFR process were then assessed by subgroup analysis (Table II).EFR for GISTs larger than 2 cm took longer times.
No procedure-related death was found.No single case had severe complications, such as GI bleeding, peritonitis, or abdominal abscess.The length of hospital stay in the EFR ranged from 4 to 11 d, with a mean of 5.5 ± 1.6 d.The mean follow-up time was 1,6,12 months.No tumor residual or recurrence has been found yet.

DISCUSSION
Most GISTs, including GISTs, grow intraluminally and rarely metastasize to local lymph nodes.Laparoscopic wedge resection with a linear stapler is the mainstay to manage those GISTs 6, 7 .
In recent years, based on endoscopic submucosal dissection and endoscopic submucosal excavation and due to improvements in the application of titanium clips under endoscopy, EFR treatment of gastrointestinal tumors arising from the muscularis propria has become possible.The key to EFR procedure is the successful closure of wall defect after resection to prevent peritonitis and surgical intervention.
In the present study, we retrospectively reviewed those cases of gastric gastrointestinal stromal tumors treated by EFR therapy in our center.
Successful treatment using EFR required successful repair of the perforation, thus avoiding the need for additional surgical repair and postoperative peritonitis (8-10).The most common method for re-  Immediate closure of the gastric wall defects using metallic clips was performed in all 46 patients who received EFR.Consistent with the reports of Liu et al. 13 gastric muscularis propria originating GISTs were mostly found at the gastric fundus.Also consistent with had been previously presented 4 .In addition, a novel over-the-scope clip (OTSC) system may be suitable for closure of various GI perforations 14 .OTSCs are increasingly used in the treatment of acute gastrointestinal perforations and fistulas 15, 16 .Furthermore, OTSCs are also used in submucosal tunneling endoscopy for resection of SMT in recent series 17 .
According to our experience, a too big GIST is not suitable for EFR.Incision of large lesions is associated with the potential high risk of suturing difficulty, long operative times, and complications during and after surgery.Preoperative computed tomography is very important, especially in patients with large lesions.In one patient with a partly nonintracavity GIST of 3.8 cm, EFR was successfully carried out in 138minutes; however, the tumor body was retrieved in a piecemeal manner.Outcomes of our study demonstrated that GISTs are most common in GISTs, which is similar to previous studies 18, 19 .
We found that the complete resection rate in our EFR group was 100%, with a 0% recurrence rate.Lying in a semi-reclining position, administration of an-tibiotics and proton-pump inhibitors and nasogastric decompression can prevent peritoneal infection effectively 20 .In the present study, none of the patients in our EFR group experienced peritonitis or intra-abdominal abscess.Our outcomes of EFR for gastric GISTs are encouraging, because of active perforation being performed and GISTs being successfully resected, as well as observing no severe post-EFR complications in all 46 patients.
Our study was limited by the Short-term follow-up.Because of the biological characteristics of GISTs, the follow-up period was relatively shorter in our study.Long-term follow-up is essential to assess complete removal and recurrence of GISTs.

CONCLUSION
In conclusion, we consider that in the treatment of the gastric gastrointestinal stromal tumor, full-thickness endoscopic resection is safe.We suggest that this technique can replace some surgical and it should be applied more widely in clinical practice to convey advantages.

FIGURE 1 :
FIGURE 1: PROCESSES OF EFR FOR GIST ORIGINATED FROM MUSCULARIS PROPRIA.

TABLE 1 :
CLINICOPATHOLOGICAL CHARACTERISTICS AND OUTCOMES OF EFR

TABLE 2 :
EFFECTS OF TUMOR SIZES AFFECTING THE ENTIRE EFR PROCESS pairing perforations was titanium clip repair.Several clips can close small defects 11,12 .