Diagnosis and Endoscopic Treatment of Gastrointestinal Stromal Tumors Arising from Esophagus

Abstract

Aim:

The primary purpose of this study was to investigate the diagnosis and endoscopic treatment of gastrointestinal stromal tumors (GISTs) arising from esophagus.

Materials and Methods:

From January 2013 to December 2017, 16 cases of GISTs of esophagus were retrospectively identified from a total of >3000 GISTs treated in our center. Demographic characteristics, clinical data, endoscopic therapy outcomes, histopathology, and follow-up were analyzed.

Results:

The mean age of the patients was 53 years (range 35–71 years), mostly female (56.3%). Seven tumors were in the lower esophagus, five in the middle esophagus, and one in the upper esophagus. The most common symptom was abdominal discomfort (8/16; 50.0%), followed by acid reflux (6/16; 37.5%). All of the patients underwent CT scan, gastroscopy, and/or endoscopic ultrasound. Two patients were diagnosed with esophageal GISTs with a preoperative endoscopic biopsy. Tumors were resected completely in all patients by endoscopic surgery. The median operating time was 85 minutes (range 28–153 minutes), and the average tumor size was 11.6 mm (range 6–21 mm). Postoperative histopathology demonstrated esophageal GISTs were positive for CD117 and CD34. The mean length of postoperative hospital stay was 4.7 days (range 2–7 days). The median postoperative follow-up duration was 28 months (range 1–59 months).

Conclusion:

Endoscopic treatment seems to be safe and effective for tumors size <20 mm in diameter. However, long-term prospective randomized controlled trials are further needed.

Introduction

Gastrointestinal stromal tumors (GISTs) are the most common mesenchyme neoplasms of digestive tracts with incidence of 7–20 per million per year.¹ GISTs could arise anywhere throughout the gastrointestinal tracts and most commonly originates from either stomach (60%–70%) or small bowel (25%–30%). Furthermore, the sites of GISTs in the colo-rectum (5%–15%) and extra gastrointestinal manifestations (<5%) are less common,^1–3 whereas esophageal GISTs are very rare of the entire GISTs and represent <1% of all GISTs.

Diagnosis of esophageal GISTs may be difficult due to clinical manifestations that were easily mistaken for leiomyomas, leiomyosarcomas, and leiomyoblastomas. Preoperative biopsy could provide histopathological information, which may help guiding the treatment strategy. With the development of histopathology, immunohistochemical staining for CD34 and CD117 has successfully helped distinguishing them from other esophageal tumors.^4–6 Complete resection of tumors with free margins is the standard treatment for GIST^7,8; however, the optimal treatment procedures are still controversial.

Studies involving a mass of esophageal GISTs are lacking. Many questions need to be answered regarding optimal management and clinical outcomes. Therefore, the purpose of this study was to introduce our center experience with diagnosis and endoscopic treatment of esophageal GIST patients.

Materials and Methods

A database was established for all patients diagnosed with esophageal GISTs and received treatment between 2013 and 2017. This retrospective study was approved by the Ethics Committee of the hospital. The preparation, procedure, possible costs, and potential complications were explained to the patients or their family members in advance and all the participants provided written informed consent.

Information about age, gender, clinical manifestation, tumor size, location, operation time, and complications were recorded. En bloc resection was defined as the tumor was excised in a single piece, and the capsule is complete.⁹ All the specimens were resected by endoscopy and were stretched smoothly by pins on a corkboard and fixed with 10% formalin for pathological examination. Immunohistochemical staining (CD117, CD34, DOG1, S-100, DESMIN, and Ki 67) was performed and the immunohistochemical characteristics of these lesions were recorded, including mitotic index per 50 high-power fields of the microscope and risk degree. Every specimen was confirmed by 2 specialist gastrointestinal pathologists, providing an accurate diagnosis.

The evidence of fever, dyspnea, hematemesis, and chest pain after endoscopic surgery was recorded. Proton pump inhibitors were used for every patient. All patients who did not have the aforementioned symptoms had a liquid diet. All patients were followed up by endoscopy and/or detailed telephone interviews if they were not willing to come back for an examination. The interview's outline was clinical symptoms, outcomes of treatment, and tests performed at their local hospitals.

Results

Demographics and clinical data of the patients and data of endoscopic treatment are given in Table 1. There were 7 men (43.7%) and 9 women (56.2%) with age range from 35 to 71 years (mean, 53.8 years). More than half of the patients (68.8%) were <60 years, and 43.8% were <50 years. The common clinical symptom included abdominal discomfort (n = 8), acid reflux (n = 6), helium (n = 3), abdominal pain (n = 2), and pharyngeal abnormal sensation (n = 1). The most common location was lower esophagus (7/16, 43.75%), followed by middle esophagus (5/16, 31.25%), and upper esophagus (4/16, 25.00%).

Table 1.

Demographics and Clinical Data of Patients

Patients	n	%
Gender
Male	7	43.75
Female	9	56.25
Age (years)
<50	7	43.75
Between 50 and 60	4	25.00
>60	5	31.25
Clinical symptom
Abdominal discomfort	8	50.00
Regurgitation	6	37.50
Helium	3	18.75
Abdominal pain	2	12.50
Foreign body sensation	1	6.25
Tumor location
Upper	4	25.00
Middle	5	31.25
Lower	7	43.75
Layer of origin
Muscularis mucosae	6	37.50
Muscularis propria	10	62.50

All patients were evaluated preoperatively by endoscopy and computed tomography (CT). Procedural data and pathological characteristics are given in Table 2. For 2 patients, GIST was diagnosed preoperatively by biopsy and the remaining patients were diagnosed accurately by postoperative histopathology. Eight patients (50%) received endoscopic submucosal dissection (ESD) and others received submucosal tunneling endoscopic resection (STER) (50%). Given the lack of advice on endoscopic management of esophageal gastrointestinal stromal tumors (E-GISTs), the decision of operating methods was made by experts who will consider the preoperative examinations and intraoperative results. And all the lesions'margins were negative. The mean operation time was 85 minutes with a mean size of 11.56 mm (range 6–21 mm).

Table 2.

Procedural Data and Pathological Characteristics

Patients	n	%
Operative method
ESD	8	50.00
STER	8	50.00
Operating time (minutes)
<60	3	18.75
60–120	12	75.00
>120	1	6.25
Size of lesion (mm)
<10	8	50.00
10–20	7	43.75
>20	1	6.25
Postoperative hospital stay (days)
<3	1	6.25
3–5	9	56.25
>5	6	37.50
Complication
Perforation	3	18.75
Bleeding	1	6.25
Cellular pattern
Spindle	16	100.00
Mitotic index
<5/50 HPF	14	87.50
5–10/50 HPF	1	6.25
>10/50 HPF	1	6.25
Risk classification
Very low risk	12	75.00
Low risk	3	18.75
Middle risk	1	6.25
Immunohistochemistry
CD34	16	100.00
CD117	16	100.00
DOG-1	14	43.75
SMA	7
KI-67		75.00
<5	12	12.50
5–10	2	12.50
>10	2	37.50
DESMIN	6
Follow-up time (minutes)
Mean (m, ±sd)	(27.81, ±21.07)

ESD, endoscopic submucosal dissection; HPF, high power fields; STER, submucosal tunneling endoscopic resection.

Every specimen was confirmed by postoperative histopathology and immunohistochemistry. All specimens displayed spindle cell morphology. CD117 and CD34 positivity was detected in all specimens with 3–7 specimens positive in the DOG-1, SMA, Ki-67, DESMIN, S-100, respectively. For patients with E-GIST, 1, 3, and 12 tumors were in middle-risk grade, low-risk grade, and very low-risk grade, respectively. The mitotic index of 15 tumors was <5/50 HPF (15/16, 93.75%). No patients had lymph node and distant metastasis and no patients were analyzed for gene mutation status.

A total of 4 patients had complications during intraoperation and postoperation. Two patients had subcutaneous emphysema, 1 patient had pneumothorax, and 1 patient had delayed bleeding. All patients recovered. The average duration of hospital stay after endoscopic surgery was 4.7 days. After a mean follow-up of 28 months, neither recurrence nor death was observed.

Discussion

GISTs located in the esophagus are very rare with limited data on the clinicopathological features and clinical outcomes.^10,11 Therefore, we evaluated the data of 16 cases of esophageal GISTs from our center.

To our knowledge, E-GISTs account for <5% of primary GISTs. In this study, the most frequent location of esophageal GISTs was lower esophagus, followed by middle esophagus and upper esophagus, which was same to the results of previous studies on E-GISTs.¹²

Our study data revealed notable differences in the demographic features between patients with esophageal GISTs and those in another place of the gastrointestinal tract. Nine of sixteen patients (56.3%) with esophageal GISTs were female, whereas GISTs of non-esophagus of the gastrointestinal tract are more common in male.^1,13

There are limited data in the diagnostic literature of esophageal GISTs and endoscopic treatment strategy. Although some studies reported the surgical strategies on E-GISTs,^14,15 the endoscopic management was reported rarely and was still controversial.

In our series, esophageal GISTs were small mesenchymal neoplasms that had a mean diameter of 11.6 mm (range 6–21 mm). Although patients with larger esophageal GISTs were more likely to have symptoms, all of the 16 patients were symptomatic. It is difficult to differentiate to other esophageal tumors due to lack of typical symptoms.

In the early stages of E-GISTs, patients usually exhibit asymptomatic or have nonspecific clinical symptoms. As the tumor grows, there are some clinical symptoms that could occur independently, such as chest and upper abdomen discomfort, acid reflux, and progressive dysphagia. Unlike the benign esophageal tumors, E-GISTs have unpredictable biological behavior and malignant potential, which need to be considered seriously, including resection, targeted drug imatinib treatment, or a combination.^16,17 Therefore, relevant examinations are indispensable and E-GISTs could be a potential cause of aforementioned symptoms. CT reveals whether there are distant metastasis and lymph metastasis.¹⁸ The CT scan of a patient with E-GISTs showed thickness of the esophageal wall in our center. CT features may help differentiation of E-GISTs, esophageal leiomyosarcomas, and esophageal leiomyomas. Especially when scanning contrast-enhanced CT, E-GISTs were larger than esophageal leiomyoma, with uneven density and stronger enhancement.

Endoscopy and endoscopic ultrasound (EUS) could assess the location, size, adjacency, and infiltration level of the tumor, and it could be possible to determine whether a mass is benign or malignant using biopsy. E-GISTs were characterized by a hypothetic enveloped lesion located in the muscularis propria or mucosal muscle layer under the EUS.¹⁹ And a well-circumscribed hypoechoic mass, homogeneous with smooth borders on EUS examination, was helpful in the differential diagnosis with other malignant tumors.²⁰ In our study, endoscopy was performed in all patients and E-GISTs were mainly located in the muscularis propria, and benign stromal tumors were generally smaller such as esophageal leiomyomas. Therefore, it is difficult to distinguish between benign esophageal GISTs and leiomyomas in size. According to Abbey J. Winant,¹⁸ chest radiographs may reveal a posterior mediastinal mass and esophageal barium imaging perhaps indicated a smooth submucosal mass that compromised the lumen by >50% without causing obstruction.¹⁸ There was only 1 patient who performed barium imaging based on our study. The result indicated that the gastrointestinal tract was normal and without obstruction, which was compliance with literature reports.

Preoperative biopsy was helpful in diagnosing the esophageal submucosal tumor (SMT). Generally, biopsy was considered the gold standard for determining the nature of the lesion.²¹ Then, it could provide the information of lesion pattern, tissue type, degree of differentiation, and depth of infiltration, which could help choose appropriate therapy strategy. However, there were only 2 patients diagnosed by preoperative biopsy in our study. The rate is 12.5%, which is lower than other studies.^22,23 The gap between pre- and postoperative pathology was large, which was lower than clinical expectations. In addition, it would delay the treatment, even worse prognosis. The difference may be related to biopsy location, depth, or size. Thus, improving the accuracy of the biopsy pathology is further needed to work.

Sometimes esophageal tumors could show similar clinical characteristics, endoscopic features, and radiographic manifestation. Thus, histology and immunohistochemistry play an important role in the evaluation and diagnosis of E-GISTs. And it is the most significant examination for differentiating these tumors. CD117 has been found to be a highly sensitive diagnostic marker to date [16]. And there are plenty of diagnostic markers updating rapidly. In this study, every patient was positive for CD117 and CD34, and 87.5% of cases were positive for DOG-1. Nine of sixteen (56.25%) cases were negative for SMA. Thus, the presence of different immunohistochemical markers in E-GISTs could distinguish them from other masses.

After the diagnosis of E-GISTs, the determination of the biological behavior of benign and malignant is a vital problem. We could make a preliminary judgment according to the size of the tumor, the number of mitotic phases, infiltration, metastasis, cell atypia, and tissue damage.²⁴

At present, in terms of the fact that esophageal GIST is a potentially malignant tumor, it may develop into malignant tumor.²⁵ However, the indications and methods for surgical resection are not uniform. Therefore, it is necessary to strictly control the indications before surgery and adopt appropriate treatment methods. With the development of minimally invasive technology, surgery is increasing being performed by laparoscopy due to decreased blood and pain, short hospital stays, and long-term disease-free survival.²⁶ However, it is sometimes difficult to resect precisely and normal tissue is excised immoderately. Especially, laparoscopy surgery is difficult to operate if the tumor is located in the esophagus gastric junction or tumor growth into the lumen.²⁷ Therefore, for E-GISTs, laparoscopy treatment may have limitations in some situations. In recent years, with the development of endoscopic diagnosis, treatment technology, and the endoscopic equipment, the safety and effectiveness of endoscopic resection of the tumor have been verified.

Endoscopic resection is currently available for E-GISTs with a diameter <5 cm, clear boundaries, uniform texture, and no signs of invasion and metastasis.²⁷ ESD can be performed for esophageal GISTs originating from the submucosal or mucosal muscle layers with a diameter of not >2 cm and the tumor should be regular, solid, and uniform hypoechoic.²⁸ ESD or STER is available when the lesions derived from the muscularis propria. This provides a new minimally invasive and effective treatment for esophageal lesions. However, due to the special anatomical location of the esophagus, lack of serosal membrane, it is easy to lead to complications such as bleeding and perforation during the operation. In some cases, it even can endanger patient life. Therefore, endoscopists should be master of endoscopic hemostasis, suture, and other hemostatic techniques. Only in this way, it can help patients to relieve the disease.

Our endoscopy center has much experience in the treatment of digestive tract masses. Nearly 1000 patients with digestive tract tumors are resected each year. In previous studies, there were few reports of endoscopic techniques for the treatment of esophageal GISTs, and lack of relevant management experience. Therefore, we applied endoscopic resection techniques for E-GISTs to explore its effectiveness and safety. Thus, ESD or STER technique is applied to treat E-GISTs in our endoscopy center. ESD has become a therapy choice for esophageal SMT because of minimally invasive.²⁹ Moreover, ESD could achieve complete resection that could provide complete histopathological data. ESD was preferred for lesions originating from mucosa or submucosa layer. However, this technique still has a relatively high rate of complications. STER is a novel technique developed from ESD and per-oral endoscopic myotomy.^29,30

STER not only has the advantages of ESD but also maintains the integrity of the esophageal mucous membranes, while reducing gas-related complications and infections.^31,32 But as the technique is complex, the procedure should be performed by experienced endoscopists. In this retrospective study, all of the 16 cases were resected successfully without tumor rupture. Eight patients used ESD and the rest STER. Both have achieved good clinical outcomes.

Bleeding and perforation are common complications of endoscopic treatment during or after operation. In our study, the perforation rate was 18.75%, which was similar to the previous reports.²⁷ All the perforations were successfully cured by metal clips. Antibiotic was given to patients who had perforation during hospitalization. Supportive care for patients with subcutaneous emphysema, especially for patients with pneumothorax, needle puncture is used to relieve the symptoms. Patients with pneumothorax were discharged successfully after recovery.

The proportion of bleeding in this study was 6.25%. Endoscopic hemostasis was applied using a thermal biopsy forceps in case of intraoperative bleeding. Endoscopic hemostatic clips can also be used for exposed blood vessels with suspected hemorrhage.

In recent years, imatinib has been used in many tumors, including GISTs with remarkable efficacy, especially for high-risk GISTs.³³ The application of imatinib could reduce tumor volume, clinical stage, the scope of surgery, and improve the success rate of surgery.

Currently, the guidelines for all GISTs from National Comprehensive Cancer Network are to use imatinib as initial treatment if the tumor is unresectable or metastatic.¹⁶ Imatinib should be used immediately after operation if margins are positive or mitotic index is high. However, some patients are still not sensitive or resistant to imatinib, and further research needed.

In this group, 13 tumors were benign and 3 tumors were malignant. No patients in this study had a recurrence of malignant GIST during the 28 months of follow-up after endoscopic surgery.

Owing to the rarity of the disease, there is currently no uniform guide for the treatment of esophageal GISTs. Esophagectomy has been advocated for small stromal tumors.⁴ However, according to our limited single-center data, endoscopic resection of GISTs <2 cm can achieve low rate of recurrence and mortality. At the same time, endoscopic treatment preserves the integrity of the anatomy and the original function of the organ.

In conclusion, esophageal tumors can be resected through endoscopic management, which was successfully performed. The diagnosis of E-GISTs was determined based on immunohistochemical results or other imaging examination. Therefore, endoscopic treatment appears to be a safe effective method for GISTs in the esophagus with not >2 cm. However, it will cause large deviations because this is a single-center study with limited data, and we still need multicenter, more samples to verify the feasibility and effectiveness of endoscopic treatment. Meanwhile, the safety and efficacy of treatment require long-term randomized controlled trials due to the short follow-up time.

Footnotes

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

References

Lott

, Schmieder

, Mayer

, Henne-Bruns

, Knippschild

, Agaimy

, et al. Gastrointestinal stromal tumors of the esophagus: Evaluation of a pooled case series regarding clinicopathological features and clinical outcome. Am J Cancer Res, 2015; 5:333–343.

Miettinen

, Makhlouf

, Sobin

, Lasota

. Gastrointestinal stromal tumors of the jejunum and ileum: A clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol, 2006; 30:477–489.

Woodall

, 3rd, Brock

, Fan

, Byam

, Scoggins

, McMasters

, et al. An evaluation of 2537 gastrointestinal stromal tumors for a proposed clinical staging system. Arch Surg, 2009; 144:670–678.

Robb

, Bruyere

, Amielh

, Vinatier

, Mabrut

, Perniceni

, et al. Esophageal gastrointestinal stromal tumor: Is tumoral enucleation a viable therapeutic option?. Ann Surg, 2015; 261:117–124.

, Wang

, Ning

, Xu

. Clinicopathological characteristics of gastrointestinal mesenchymal tumors and diagnostic value of endoscopic ultrasonography. J Gastroenterol Hepatol, 2008; 23,(8 Pt 2):e318–e324.

Yangong

, Shi

, Shahbaz

, Zhengchuan

, Wang

, Liang

, et al. Diagnosis and treatment experience of rectal carcinoid (a report of 312 cases). Int J Surg, 2014; 12:408–411.

Casali

, Abecassis

, Bauer

, Biagini

, Bielack

, Bonvalot

, et al. Gastrointestinal stromal tumours: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2018; 29:(Suppl 4):iv68–iv78.

Duffaud

, Meeus

, Bertucci

, Delhorme

, Stoeckle

, Isambert

, et al. Patterns of care and clinical outcomes in primary oesophageal gastrointestinal stromal tumours (GIST): A retrospective study of the French Sarcoma Group (FSG). Eur J Surg Oncol, 2017; 43:1110–1116.

Chen

, Zhou

, Chu

, Zhang

, Chen

, Ji

, et al. Long-term outcomes of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors. Ann Surg, 2017; 265:363–369.

10.

Kafeel

, Cheedella

, Wang

. Esophageal gastrointestinal stromal tumors presenting as mediastinal mass. Case Rep Oncol, 2013; 6:579–584.

11.

Demetri

, Benjamin

, Blanke

, Blay

, Casali

, Choi

, et al. NCCN Task Force report: Management of patients with gastrointestinal stromal tumor (GIST)—update of the NCCN clinical practice guidelines. J Natl Compr Cancer Netw, 2007; 5,(Suppl 2):S1–S29; quiz S30.

12.

Feng

, Tian

, Liu

, Xu

, Liu

, Guo

, et al. Clinicopathologic features and clinical outcomes of esophageal gastrointestinal stromal tumor: Evaluation of a pooled case series. Medicine, 2016; 95:e2446.

13.

Pence

, Correa

, Chan

, Khaitan

, Hofstetter

, Kim

. Management of esophageal gastrointestinal stromal tumor: Review of one hundred seven patients. Dis Esophagus, 2017; 30:1–5.

14.

Zhang

, Shi

, Shu

, Shi

, Lu

, Zhang

, et al. Diagnosis and surgical treatment of esophageal gastrointestinal stromal tumors. World J Gastroenterol, 2015; 21:5630–5634.

15.

Dematteo

, Heinrich

, El-Rifai

, Demetri

. Clinical management of gastrointestinal stromal tumors: Before and after STI-571. Hum Pathol, 2002; 33:466–477.

16.

von Mehren

, Randall

, Benjamin

, Boles

, Bui

, Ganjoo

, et al. Soft tissue sarcoma, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Cancer Netw, 2018; 16:536–563.

17.

Blum

, Bilimoria

, Wayne

, de Hoyos

, Talamonti

, Adley

. Surgical considerations for the management and resection of esophageal gastrointestinal stromal tumors. Ann Thorac Surg, 2007; 84:1717–1723.

18.

Winant

, Gollub

, Shia

, Antonescu

, Bains

, Levine

. Imaging and clinicopathologic features of esophageal gastrointestinal stromal tumors. Am J Roentgenol, 2014; 203:306–314.

19.

Akahoshi

, Oya

, Koga

, Shiratsuchi

. Current clinical management of gastrointestinal stromal tumor. World J Gastroenterol, 2018; 24:2806–2817.

20.

Sakamoto

, Kitano

, Kudo

. Diagnosis of subepithelial tumors in the upper gastrointestinal tract by endoscopic ultrasonography. World J Radiol, 2010; 2:289–297.

21.

Szaloki

, Toth

, Nemeth

, Tiszlavicz

, Lonovics

, Czako

. Endoscopic mucosal resection: Not only therapeutic, but a diagnostic procedure for sessile gastric polyps. J Gastroenterol Hepatol, 2008; 23:551–555.

22.

, Yang

, Lu

, Zhou

, Yao

, Fei

, et al. Magnifying narrow-band imaging endoscopy is superior in diagnosis of early gastric cancer. World J Gastroenterol, 2015; 21:9156–9162.

23.

Akahoshi

, Sumida

, Matsui

, Oya

, Akinaga

, Kubokawa

, et al. Preoperative diagnosis of gastrointestinal stromal tumor by endoscopic ultrasound-guided fine needle aspiration. World J Gastroenterol, 2007; 13:2077–2082.

24.

Jiang

, Jiao

, Han

, Zhang

, Sun

, Su

, et al. Clinical characteristics and surgical treatment of oesophageal gastrointestinal stromal tumours. Eur J Cardiothorac Surg, 2010; 38:223–227.

25.

Kawamura

, Shibasaki

, Yoshida

, Homma

, Takahashi

, Taketomi

. Strategy of laparoscopic partial resection for gastric gastrointestinal stromal tumors according to the growth pattern. Surg Laparosc Endosc Percutan Tech, 2015; 25:e175–e179.

26.

Zhou

, Wang

, Shen

. Laparoscopic surgery as a treatment option for elderly patients with colon cancer. J BUON, 2017; 22:424–430.

27.

, Sun

, Zheng

, Yu

, Wang

, Chen

, et al. Endoscopic submucosal dissection of large gastrointestinal stromal tumors in the esophagus and stomach. J Gastroenterol Hepatol, 2013; 28:262–267.

28.

Huang

, Zhang

, Huang

, Yuan

. Endoscopy dissection of small stromal tumors emerged from the muscularis propria in the upper gastrointestinal tract: Preliminary study. World J Gastrointest Endosc, 2012; 4:565–570.

29.

Probst

, Golger

, Arnholdt

, Messmann

. Endoscopic submucosal dissection of early cancers, flat adenomas, and submucosal tumors in the gastrointestinal tract. Clin Gastroenterol Hepatol, 2009; 7:149–155.

30.

, Cai

, Zhou

, Qin

, Zhong

, Chen

, et al. Submucosal tunneling endoscopic resection: A new technique for treating upper GI submucosal tumors originating from the muscularis propria layer (with videos). Gastrointest Endosc, 2012; 75:195–199.

31.

, Zhang

, Mao

, Zhu

, Zhou

, Chen

. Submucosal tunneling endoscopic resection for small upper gastrointestinal subepithelial tumors originating from the muscularis propria layer. Surgical endoscopy, 2014; 28:524–530.

32.

Chen

, Wang

, Zhao

, Chen

, Liu

, Wang

, et al. The retrospective comparison between submucosal tunneling endoscopic resection and endoscopic submucosal excavation for managing esophageal submucosal tumors originating from the muscularis propria layer. Surg Endosc, 2020; 34:417–428.

33.

Pandey

, Kochar

. Management of gastrointestinal stromal tumors: Looking beyond the knife. An update on the role of adjuvant and neoadjuvant imatinib therapy. J Gastrointest cancer, 2012; 43:547–552.