Submucosal tumor (SMT) is a rare esophageal disease, comprising <1.0% among esophageal tumors [
This study conducted a retrospective analysis of the data of 119 lesions from 115 patients with SMTs originating from the MP layer, who underwent STER between September 2011 and May 2018 at the Digestive Department of Nanfang Hospital, Shenzhen Hospital, and Shunde Hospital of Southern Medical University. Indications included (1) endoscopy showing esophageal SMTs, excluding malignant tumors, (2) EUS examination showing that the tumor originated from the MP layer and protruded into the lumen, and (3) patients who could tolerate anesthesia with tracheal intubation.
All patients underwent preoperative examination, including ECG, chest X-ray, routine blood test, and blood coagulation test. A CT scan was also performed to exclude the possibility of malignant tumors and distant metastasis. All patients were informed of the procedure and received detailed explanations about the treatment and complications, and informed consent was obtained before performing the STER procedures. All the operations were performed by endoscopy doctors experienced in endoscopy therapy. This study was approved by the ethics committee of the Nanfang Hospital, Southern Medical University (Guangzhou, China).
The endoscopic equipment primarily included an endoscope (GIF-Q260J; Olympus, Tokyo, Japan), a transparent distal cap (MH-588; Olympus), a high-frequency electrogenerator (VIO200D; Erbe, Germany), a carbon dioxide (CO2) insufflator (UCR; Olympus, Japan), and a snare (SD-210U-25; Olympus, Japan). A hybrid knife (Type-I; Erbe, Tübingen, Germany) was used to resect the tumors completely. A hemostatic forceps (Microclip; Olympus) was used to control bleeding, while endoscopic clips (Micro-Tech; Nanjing, China) were used for closure of the wound.
All patients had fasted for 8 h before the operation and underwent STER under general anesthesia with tracheal intubation. The STER procedures are described below (Figure
Case illustration of submucosal tunnel endoscopic resection for esophageal submucosal tumor (SMT). (a) A SMT located at the midesophagus shown by white light. (b) A 2 cm longitudinal mucosal incision was made using a hybrid knife, approximately 5 cm proximal to the SMT, and a straight submucosal tunnel was made until the tumor was visible. (c) Resection was done along the margin of the SMT using the hybrid knife. (d) The wound of the submucosal tunnel was checked after the removal of the tumor. (e) Metal clips were used to close the entrance of the tunnel. (f) The resected specimen was measured, and the final pathological diagnosis confirmed a 35 mm leiomyoma.
A mixture of 10 ml saline and 0.2% indigo carmine was injected 5 cm proximal to the SMT. When the mucosa was fully lifted, a 2 cm longitudinal mucosal incision was made on the mucosal layer and the submucosal layer was exposed to create a tunnel entrance.
A transparent cap was attached to the front of the endoscope; the mucosa was separated from the muscular layer, and then, a straight submucosal tunnel was established using a hybrid knife. The submucosal layer was gradually dissected until the tumor was exposed to the endoscopic view. Continuous dissection was performed until the tunnel was created 2 cm distal to the tumor. Timely electrocoagulation was used to stop bleeding during the operation.
When the tumor was fully exposed, a hybrid knife was used to gradually dissect the tumor along the tumor capsule, until it was completely resected, and then the specimen was removed.
The wound in the tunnel was flushed, and electrocoagulation was performed to prevent bleeding.
The tunnel was gradually closed by using metal clips to make a continuous chain suture from the bottom up.
All the patients were required to remain on nil per os for at least 24 h before resuming their diet and water after the operation. To prevent postoperative infection, patients were administered routine prophylactic antibiotics for 48 h as needed, which primarily included the first- or second-generation cephalosporin drug. Moreover, they must at least receive proton pump inhibitors for 3 days, and their vital signs were closely monitored to observe the occurrence of complications. Postoperative complications primarily included subcutaneous emphysema, pneumothorax, pulmonary infection, and hemorrhage.
Perforations could be identified by endoscopy or by the discovery of free gas in the X-rays or the CT scan. Therefore, when a perforation was detected, it was important to perform an endoscopic suture, extend the duration of fasting and water deprivation and the use of antibiotics, and provide gastrointestinal decompression if necessary. If the patients suffered from progressive dysphagia after the operation, it was necessary to consider the possibility of internal bleeding in the tunnel. Therefore, the use of coagulation forceps during the endoscopy was important to stop the bleeding. Additional surgery was necessary for uncontrolled perforations and bleeding.
All patients were recommended to be followed up with gastroscopy or endoscopic ultrasonography for 6 and 12 months after the operation. If there were no residual tumors or recurrences, the patients could be followed up by an endoscopic examination once a year.
Data were analyzed through descriptive statistics. Quantitative data were expressed by mean (±standard deviation) or median (range). Qualitative data were expressed as
The baseline characteristics of patients are shown in Table
Baseline characteristics of patients.
No. of patients | 115 |
No. of lesions | 119 |
Age, yr (range) | 49.7 ± 10.7 (26–71) |
Sex (female/male) | 39/76 |
Tumor location | |
Upper esophagus | 10 (8.4%) |
Median esophagus | 58 (48.7%) |
Lower esophagus | 51 (42.9%) |
Tumor distribution | |
Superficial MP | 87 (73.1%) |
Deep MP | 32 (26.9%) |
Tumor size, mm (range) | 19.4 ± 10.0 (8–60) |
No. of tumors of different sizes, | |
Φ ≤ 30 mm | 110 (92.4%) |
30 < Φ ≤ 40 mm | 5 (4.2%) |
Φ > 40 mm | 4 (3.4%) |
All patients were successfully treated with the STER procedure. All the esophageal SMTs originated from the MP layer, 87 of which were located in the superficial MP layer, while the remaining 32 were located in the deep MP layer. As shown in Table
Clinical and pathological outcomes of STER in patients with SMTs.
Overall | |
---|---|
Operation time, min (range) | 46.7 ± 25.6 (10–150) |
Insufflation, | |
Air | 4 (3.5) |
CO2 | 111 (96.5) |
En bloc resection, |
116 (97.5) |
Complete resection, |
119 (100) |
Complication, | |
Perforation | 9 (7.8) |
Pneumothorax | 2 (1.7) |
Subcutaneous emphysema | 9 (7.8) |
Pneumoperitoneum | 0 (0) |
Delayed bleeding | 0 (0) |
Delayed perforation | 0 (0) |
Pathological diagnosis, | |
Leiomyoma | 113 (95.0) |
Gastrointestinal stromal tumor | 5 (4.2) |
Granular cell tumor | 1 (0.8) |
Hospitalization time, days (range) | 5.9 ± 2.8 (3–15) |
Follow-up time, months (range) | 15 (1–71) |
Recurrence rate (%) | 0 |
The histopathological results revealed 113 (95.0%) cases of leiomyoma, 5 (4.2%) cases of gastrointestinal stromal tumors (GISTs), and 1 (0.8%) case of a granular cell tumor. Based on the modified National Institutes of Health (NIH) classification suggested by Joensuu, the GISTs were graded according to the tumor size, tumor location, and the number of mitosis per 50 high power fields. Five cases diagnosed as GISTs were at low or extremely low risk. During a median follow-up of 15 months (range: 1–71 months), there were no tumor recurrences or distant metastasis. Moreover, there were no cases of delayed perforation or bleeding, digestive tract leakage, or other serious complications.
Upper gastrointestinal SMTs are a type of tumors that are rarely encountered and generally an incidental finding in daily clinical practice owing to their nature of rarely causing clinical symptoms. The development of the endoscopic technique has significantly improved the detection rate of esophageal SMTs. Open surgery and thoracoscopic surgery have long been considered as standard methods for treating upper gastrointestinal SMTs [
Xu et al. of Shanghai Zhongshan Hospital first reported about the use of STER technique to treat upper gastrointestinal SMTs [
In the present study, we included 119 cases of SMTs from 115 patients who had been identified through endoscopic examination during a period of 7 years. All tumors were successfully removed. The mean operation duration was 46.7 min, which was found to be consistent with other studies that reported a range of 40–78.3 min. Domestic experts have reached consensus on endoscopic diagnosis management of gastrointestinal SMT [
The diameter of the 115 lesions, for which we chose to perform STER, was evaluated to be <4 cm by a common endoscope and EUS. We believe that it is difficult to dissect tumors measuring >4 cm because of the limited operating space within the tunnel, which makes it difficult to remove the tumor from the tunnel. In this study, we found four patients in our center with tumors measuring >4 cm as measured by EUS. The patients were fully informed of the risk of failure with the difficult procedure performed under the guidance of an endoscope and the possibility of surgical treatment; however, the patients still demanded endoscopic resection and signed the informed consents. Based on the general operation procedure, the tunnel was successfully constructed 2 cm distal to the tumor. The mucosa was incised longitudinally, and the incision length was about 3 cm to achieve tunnel decompression. Continuous dissection of the tumor was performed until the tumor was successfully removed out of the tunnel. The tunnel space became larger, and the tumors could be resected and removed easily. Endoscopic tunnel decompression is a new attempt for removing SMTs measuring >4 cm and was successfully used in one case. However, although the other three cases were also completely resected, the tumors were too large to be removed out of the tunnel. Therefore, these three tumors were cut into pieces using a snare. The fragmentation excision method might lead to the possibility of tumor recurrence, although there is no such report in the case of endoscopic tunnel treatment for upper gastrointestinal tumors. Moreover, these three patients were monitored more closely. Surveillance endoscopies were performed every 3–6 months over the first year postprocedure and then annually thereafter. Eventually, the pathological results revealed that all these four tumors were leiomyoma and there was no recurrence in these four patients during the 3-year follow-up.
We found multiple SMTs in three patients, all located in the adjacent esophagus. We successfully removed the tumor in a tunnel by establishing a long tunnel. There were no complications during and after the operation. Some researchers have also reported the possibility of using STER procedure to remove multiple SMTs in the upper digestive tract. Chen et al. reported the successful removal of SMTs in the esophagus and cardia in the meantime using STER [
The incidence of perforation in our three centers was 7.8% (9/115) in terms of intraoperative complications. All the lesions were quickly excised, and the tunnel entry was closed by metal clips. Intraoperative complications such as pneumothorax and subcutaneous emphysema occurred in the patients, but no surgical treatment was required after the treatment. During the operation, there were two patients with subcutaneous emphysema and pneumothorax. Another seven patients showed pure subcutaneous emphysema. Several researchers have also reported that STER was associated with a higher incidence of subcutaneous emphysema, but after closing the tunnel by the metal clips, no special treatment was required. There were nine cases of gas-related complications in our centers, three of which were air injection and six occurred during CO2 insufflation. CO2 has been fully confirmed to be a safe gas that can be rapidly absorbed by the body. CO2 cannot only significantly reduce postoperative pain and shorten the postoperative recovery time but can also effectively reduce the incidence of pneumomediastinum and air embolism [
After taking out the tumor, the wound was rinsed and observed carefully and electrocoagulation was applied to suspected bleeding spots. There was no delayed bleeding in all the patients after the operation. All the specimens were sent for pathological examination, and the results revealed that 113 cases were leiomyoma, 5 cases were GISTs, and 1 case was a granular cell tumor. Although there are no guidelines recommending endoscopic resection for treating GISTs, several studies have demonstrated that endoscopic resection was safe and effective for removing small GISTs. Small GISTs primarily have a low or extremely low risk. Joo et al. [
Compared with surgical intervention and other endoscopic resection methods, the STER technique had the following obvious advantages: (1) By establishing a submucosal tunnel, SMTs can be resected and the blood vessels of the wound can be treated under direct vision. (2) According to literature reports, ESD therapy was associated with a perforation rate of 6.1%–15% for SMTs originating from the MP layer, and several large metal clips or suture devices were needed for closing the wound, which might cause a gastrointestinal fistula. Tunnel technology can guarantee the integrity of the tumor mucosal layer, and thus, the integrity of the gastrointestinal mucosa could be maintained. (3) Only a few small metal clips are needed to close the tunnel entry; thus, the STER technique was found to be simple and practicable.
STER is a safe and feasible technique for treating esophageal SMTs originating from the MP layer. However, our study still had some limitations. First, the number of cases enrolled in our study was not adequate and the follow-up time was too short. Furthermore, we performed pieces’ resection for three large tumors, which may increase the risk of recurrence and metastasis. Finally, we successfully treated large esophageal SMTs using “tunnel decompression” for the first time; however, this was an attempt with only a few cases and more cases are needed to explore whether the technique is feasible. Future studies must enroll a larger number of patients with a longer follow-up period to confirm the long-term outcome. In addition, multicenter randomized controlled studies should be conducted to prove the efficacy and safety of STER.
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that there is no conflict of interest regarding the publication of this paper.
Sufang Tu, Silin Huang, and Guohua Li contributed equally to this work as first authors.
We acknowledge the funding supported by the Guangdong Gastrointestinal Disease Research Center (no. 2017B02029003) and all the authors for giving support and contributions.