TO THE EDITOR
The high-quality article by Xu et al[1] is a retrospective observational study including 32 patients with esophageal gastrointestinal tumors (EGISTs) treated by endoscopic resection (ER). Thirty-one patients underwent en bloc resection. There were 24 (75.0%) R0 resections in the analyzed group. The tumor size was 2.12 ± 1.88 (0.8-2.75) cm. The overall complication rate was 25%, including hydrothorax and post-endoscopic submucosal dissection (ESD) electrocoagulation syndrome, successfully treated with conservative management. The mean mitotic index (MI) was 3.34 ± 5.04 (1.00-4.00) (median, 1.50). There were 18 (56.3%), 6 (18.8%), 2 (6.3%), and 6 (18.8%) patients of very low, low, intermediate, and high risk in the analyzed group, respectively. Recurrence after a median follow-up of 64.69 ± 33.13 months was reported in 3 patients. The 5-year overall survival (OS) rate was 100%, and the disease-free survival (DFS) rate was 90.6%. Based on the above-mentioned good short- and long-term outcomes, the authors concluded that ER was safe and effective for patients with low-risk EGISTs. It is known that the low risk is related to the smaller tumor size and lower MI. Therefore, early detection of EGISTs is required in order to allow less invasive ER of EGISTs. The authors pointed that ER is minimally invasive and allows faster recovery compared to surgical treatment[1]. This paper has some strengths. The subject is extremely interesting and important for clinicians. This research is one of only a few cohort studies analyzing the short- and long-term outcomes of ER for EGISTs. The authors presented clinicopathologic and demographic features of the patients, including the tumor size and MI, the endoscopic technique (submucosal tunneling ER, STER), as well as post-procedure complications and patients’ survival. These results were compared to those in the literature. However, this study has some limitations. It is a small-cohort two-center retrospective study, which included only patients undergoing ER without comparing those undergoing surgical treatment. In my opinion, further large multi-center prospective randomized studies optimally comparing two treatment methods (surgery vs endoscopic treatment) with regard to short-term results (postoperative morbidity) and long-term results (OS and DFS) are needed. This is very important, as there are no guidelines on the management of patients with EGISTs. Thus, the treatment of these tumors is very difficult and challenging due to their rarity.
CURRENT SITUATION AND CHALLENGES IN THE TREATMENT OF EGISTs
The latest research by Xu et al[1] has sparked my observations and reflections on the current management of patients with EGISTs. Decisions regarding the treatment of patients with EGISTs are challenging, due to the lack of clear guidelines and the rarity of these tumors. Surgery remains the standard treatment; however, it is known that surgical procedures on the esophagus are related to a high risk of serious postoperative complications and impaired quality of life. On the other hand, not all patients are fit to undergo surgery because of their general condition. Therefore, a less invasive, but effective therapeutic option for patients with EGISTs is very important. ER seems to be a good therapeutic option, but selection criteria for this treatment method should be clearly described.
GISTs are rare tumors, with an incidence of approximately 1/100000/year. They are the most common mesenchymal gastrointestinal neoplasms[2]. EGISTs account for only 2%–5% of all GISTs[3,4]. Due to their very rare occurrence, to date, only case reports, case series and small-cohort studies on EGISTs have been published[5]. Complete resection is the standard treatment for non-metastatic GISTs[5]. Surgery is still the mainstay management. However, no standard procedure has been established for EGISTs. Decisions regarding the type of management are made individually in each patient, and the risk of tumor recurrence and the patient’s general condition should be taken into account. In patients with EGISTs, tumor size and MI are the most significant predictors of prognosis and survival[5].
As mentioned above, surgical resection is the standard management for primary EGISTs. Regarding the type of surgery for EGISTs, esophageal segmental and wedge resections are not usually performed due to the specific esophageal anatomy. Therefore, complete surgical resections, including both highly invasive esophagectomy and enucleation, drug therapy, and ablation may be considered in patients with EGISTs[6]. The choice of optimal surgery type for EGISTs is still under debate. Generally, enucleation of EGISTs is recommended for smaller tumors 2–5 cm in size, whereas more invasive esophagectomy is indicated for GISTs more than 9 cm in size[7-10]. According to Robb et al[8], enucleation is safe for EGISTs < 65 mm in size[8]. The choice between esophagectomy and enucleation for tumors between 60 and 90 mm requires further clarification, with the decision being potentially based on the patient’s comorbidities, tumor location, and risk of malignancy[10]. Routine lymphadenectomy is not recommended, due to infrequent metastasizing to lymph nodes. A more extensive and radical procedure is recommended for GISTs with higher National Institutes of Health (NIH) classification which is associated with a higher risk of recurrence[7]. In the past, thoracotomy was the most common surgical approach for esophageal tumors. Currently, thoracoscopy is performed, when possible, due to decreased pain and blood loss compared to the open approach[11].
There are no clear standards regarding the use of neoadjuvant imatinib therapy for EGISTs. Generally, the role of neoadjuvant imatinib is reduction of the extent of surgical resection, which is most important in patients with GISTs located within the esophagus, duodenum, and rectum, because wide resection (esophagectomy, pancreaticoduodenectomy, rectal resection) may be associated with a higher risk of serious postoperative complications and worse postoperative quality of life in these patients. The optimal duration of preoperative imatinib is 6-12 months. On the other hand, it should be pointed that preoperative imatinib therapy is associated with a higher risk of tumor rupture or bleeding due to tumor necrosis and cystic changes[7]. According to Kang et al[9], neoadjuvant imatinib therapy may be considered in patients with larger tumors and or high MI in order to obtain negative microscopic margins (R0 resection) and to decrease the risk of intraoperative complications, including tumor rupture[7,9]. In general, adjuvant imatinib therapy following GIST resection is indicated in order to prevent recurrences and improve patient survival[10]. According to the modified NIH risk classification, lower tumor location, larger tumor size, and higher tumor MI are risk factors for recurrence in patients with GISTs[12]. Due to the rarity of EGISTs, further investigations are required to assess the role of imatinib in these tumors[11].
Surgery, especially esophagectomy, is a very complex and invasive procedure associated with a high risk of postoperative complications and impaired quality of life. Recently, rapid advances in endoscopic technology and continuous development of endoscopic instruments have been observed, and endoscopic management of GISTs results in a high completion rate, long-term DFS, and a low recurrence rate[5]. In a study by Du et al[5], which included 20 patients, 11 patients received ER and 9 underwent surgical resection, and both the surgery and endoscopic treatments were successful[5]. The hospitalization medical costs were similar between the two groups. In this study, tumor enucleation and STER were associated with less damage to the esophageal mucosa and no alterations of the normal esophageal anatomy compared to esophagectomy. The authors reported reflux esophagitis secondary to the alteration of esophageal anatomy following esophagectomy. In the authors’ opinion, endoscopic treatment may be an option for the treatment of EGISTs < 5 cm in size with MI ≤ 5/50 high power field[5]. In another study by Zhu et al[13], which included 23 patients with EGISTs undergoing surgery and ER, the choice of ER method was based on the tumor size, location, origin, and growth pattern. ER techniques included STER, ESD, and endoscopic mucosal band ligation. In this study, ESD was performed in patients with small GISTs, including 8 patients (53.3%) with tumors ≤ 10 mm and 12 patients (80%) with tumors ≤ 30 mm. Three (20%) patients had tumors 50-80 mm in size, with the largest tumor measuring 75 mm × 55 mm × 25 mm. Patients undergoing surgery generally had larger tumors, including 2 tumors > 100 mm in size[13]. Zhu et al[13] recommended ESD for smaller EGISTs < 30 mm in size[13]. In another study by Lian et al[14], which included 23 patients undergoing ER for EGISTs, the average tumor size was 2.3 (1.0–4.0) cm, and these authors recommended ER for EGISTs ≤ 40 mm in size suggesting STER as the preferred approach[14]. Zhou et al[15], based on the analysis of 16 patients undergoing ER for EGISTs, indicated ER for tumors < 20 mm in size[15]. Thus, the maximal EGIST size treated by ER has gradually increased. This observation is very important, as in the past, surgical enucleation was the standard treatment for EGISTs 20-50 mm in diameter. Surgery is more invasive compared to ER. STER, which is more minimally invasive is characterized by a shorter procedure duration and hospitalization as well quick recovery compared to thoracic enucleation[14,16,17]. The most common potential complications following ER for EGISTs are as follows: Gastrointestinal bleeding, esophageal perforation, infection, and pneumothorax[13,14]. The most common potential complications following surgery for EGISTs are more numerous and serious and include the following: Gastrointestinal bleeding, esophageal perforation, infection, mediastinitis, peritonitis, hydrothorax, pneumothorax, abdominal wound dehiscence, anastomotic leakage and dehiscence of anastomosis, and vena azygos damage[18]. Taking into account the above-mentioned differences between endoscopic and surgical procedures, it is very important to extend the use of ER for EGISTs as it is a less invasive treatment associated with a lower risk of serious complications, but allowing complete tumor resection with a favorable prognosis.
