Risk factors related to endoscopic resection conversion to laparoscopic resection for gastric gastrointestinal stromal tumors

Abstract

Background: Endoscopic resection (ER) of gastric gastrointestinal stromal tumors (gGISTs) is a commonly used treatment; however, there is a risk of conversion to laparoscopic resection (LR). The purpose of this study was to determine factors influencing conversion from ER to LR, and the effects of such a conversion on outcomes.

Methods: From March 2010 to May 2021, patients with gGISTs were retrospectively reviewed at the First Affiliated Hospital of Soochow University, Suzhou, China. Patient’s clinicopathological features and endoscopic procedure information were collected. Endpoints included the determination of risk factors associated with ER conversion to LR, with comparisons of surgical outcomes with and without conversion.

Results：In total, 371 gGISTs were analyzed. Sixteen patients (4.3%) required conversion to LR during gGIST ER. Invasion depth (muscularis propria (MP)-ex: odds ratio (OR) 16.026, 95% confidence interval (CI): 2.949–87.092, p<0.001) and gGIST size (≥ 3 cm: OR 6.747, 95% CI: 2.062–22.071, p=0.002) were independent risk factors for LR conversion. Conversion reasons included technical difficulties (nine patients had severe intraoperative bleeding and five had failed gastric perforation closure) and ER accidents (two patients had tumors accidentally fell into the abdominal cavity). Procedure (median 160.5 vs. 58.0 min, p<0.001), postoperative hospitalization (median 8 vs. 6 days, p<0.001), and postoperative fasting times (median 5 vs. 3 days, p<0.001) were significantly longer in LR conversion patients.However, En bloc R0 resection (93.8 vs. 90.4%, p>0.999) and recurrence (0 vs. 0.6%, p>0.999) were no different in patients with or without LR conversion.

Conclusions: An increased awareness of conversion risk factors is important for better patient selection for gGIST ER. Accurate preoperative measurements of tumor size and invasion depth can help determine more appropriate surgical approaches for patients.

Introduction

In the past, typical treatments for gastric gastrointestinal stromal tumors (gGISTs) included gastrectomy or wedge resection [1, 2]. With advanced endoscopic techniques and accumulated surgical experience, gGIST endoscopic resection (ER) is increasingly performed. Several cohort studies reported that when compared with laparoscopic resection (LR), gGIST ER exerted less trauma, had faster postoperative recovery times, and lower hospitalization costs [3–7]. However, perioperative complications may occur even with experienced surgeons, and require time-consuming conversion to LR surgery or open laparotomy. Although many studies have reported complications such as perforation and hemorrhage [8, 9], few have outlined the risks of unintended conversion to LR surgery during gGIST ER. Therefore, we sought to identify the incidence and risk factors associated with conversion to LR surgery during gGIST ER, and elucidate clinical outcome in patients.

Methods

Results

Baseline characteristics of patients. 

A flow chart of the study protocol is shown in Figure 2. Patient characteristics and clinicopathology are also highlighted in Table 1. We included 146 men and 225 women with a median age of 60 years (IQR: 53–66 years). We observed that 309 (83.3%) patients had tumors < 3 cm, while 62 (16.7%) had tumors > 3 cm. Approximately 2/3 of gGISTs were located at the fundus of the stomach (64.4%). ESD and EFTR procedures were performed in 45.6% and 54.4% of patients, respectively. Approximately 50% of patients had a BMI within the normal range. The majority of gGISTs (87.6%) originated within the muscularis propria (MP), and 258 cases were performed by experienced endoscopists (69.5%). We noted that 91.1% of participants had mild to moderate systemic disease (ASA score ≤ 2), and the main reasons for gastroscopy were abdominal discomfort (50.9%) and physical examination (44.7%). 

Risk factors for LR conversion. 

Of 371 cases, 16 (4.3%) resulted in LR conversion. The most common reason for this was severe intraoperative bleeding that could not be controlled by endoscopy (56.3%), followed by failure to close a gastric perforation (31.3%), and the accidental dropping of a tumor into the abdominal cavity (12.5%) (Table 2). A summary of patient characteristics requiring LR conversion is shown in Table 3. 

Univariate analyses revealed that tumor size, invasion depth, endoscopic technique, and endoscopist experience were risk factors for LR conversion (Table 1). The proportion of tumors > 3 cm in the conversion group was significantly higher than in the non-conversion group (62.5% vs. 14.6%; p<0.001). Patients treated by EFTR were more prone to developing LR conversion (p=0.008). In terms of gGIST invasion depth, in the conversion group, 12 cases showed an invasion depth which reached the MP-ex, accounting for 75.0%. In the non-conversion group, 34 cases showed an invasion depth which reached the MP-ex, accounting for only 9.6%. This difference was statistically significant (p<0.001). In the conversion group, five cases were performed by experienced endoscopists, accounting for 31.3%, while 253 cases were performed by experienced endoscopists in the non-conversion group, accounting for 71.3%. These differences were statistically significant (p=0.002). Multivariate analyses (Table 4) showed that gGISTs originating from MP-ex exhibited a significantly higher possibility of conversion than superficial gGISTs (OR 16.026, 95% CI: 2.949–87.092, p<0.001), and also tumor size ≥ 3cm was an independent risk factor for LR conversion (OR 6.747, 95% CI: 2.062–22.071, p=0.002). 

Comparing operative data and postoperative outcomes in patients with or without LR conversion.

Comparisons between operative data and postoperative outcomes in both patient groups are shown in Table 5. No significant differences were identified between groups regarding postoperative complications, En bloc R0 resection, and recurrence. The procedure time was significantly longer for patients requiring LR conversion (a median of 160.5 vs. 58.0 min for patients not converting to LR, p<0.001). The proportion of patients with severe intraoperative bleeding was significantly higher in the former group (50% vs. 0.3%, p<0.001). The rate of intraoperative perforation in the conversion group was higher than in the non-conversion group (87.8% vs. 53.0%, p=0.008). Postoperative hospitalization (median 8 vs. 6 days, p<0.001) and postoperative fasting times (median 5 vs. 3 days, p<0.001) were significantly longer in the conversion group. In terms of modified NIH risk criteria, the conversion group was dominated by intermediate or high-risk cases (68.8%), and the non-conversion group was dominated by very low or low-risk cases (95.2%) (p<0.001). In total, 305 patients were successfully followed up (12 in the conversion group and 293 in the non-conversion group). No significant differences were identified between groups regarding follow-up duration (median 42 vs. 42 months, p=0.312). 

Distribution of clinical complications across different gGIST sizes and invasion depths.

Larger gGISTs (≥3 cm) were more vulnerable to severe intraoperative bleeding (9.7% vs. 1.0%, p=0.001), intraoperative perforation (74.2% vs. 50.5%, p<0.001), and delayed bleeding (6.5% vs. 1.6%, p=0.046) when compared with tumors < 3 cm (Table 6). However, no significant differences were observed in terms of delayed perforation, and postoperative infection (p>0.05). Also, the probability of severe intraoperative bleeding and perforation in gGISTs originating from MP-ex was higher than for superficial gGISTs (15.2% vs. 0.6%, p<0.001; 100.0% vs. 48.0%, p<0.001). No statistical differences were identified between groups in terms of postoperative complications (p>0.05).

 Table 1

Patient clinicopathologic characteristics (conversion vs. non-conversion group).

MP: muscularis propria; MP-ex:MP with exophytic growth. 

Table 2

 Main conversion reasons in 16 failed endoscopic resection patients

Table 3

Characteristics of patients requiring conversion to laparoscopic resection

M: male; F: female; T: technical difficulty-related; E: endoscopic resection accident; A: Severe intraoperative bleeding that could not be controlled by endoscopy; B: Failure to close the gastric perforation; C: The tumor accidentally fell into the abdominal cavity. 

Table 4

Multivariate analysis of laparoscopic resection conversion of gastric gastrointestinal stromal tumors

Table 5

 Operative data and postoperative outcomes(conversion vs. non-conversion group)

Table 6

Distribution of clinical complications in different gastric gastrointestinal stromal tumor sizes and invasion depths

Discussion

Due to GIST malignant potential, European and Japanese guidelines recommend resection once a GIST histological diagnosis is confirmed, regardless of diameter [15, 16]. With the improved development and application of endoscopic ultrasound and minimally invasive endoscopic technologies, more gGISTs are being detected and effectively treated [17, 18]. A recent Chinese consensus document provided endoscopic indications for gGIST treatment [19]: (1) GISTs ≤ 2 cm with a short period of tumor enlargement or a strong patient desire for resection and (2) 2 < GISTs ≤ 5 cm with low risk. However, gGIST ER is more challenging than a mucosal lesion and requires substantial skills due to LR conversion risks. Currently, few studies have reported risk factors associated with gGIST ER conversion to LR, therefore we identified and characterized these risk factors.

From previous studies, incidence rates of conversion to LR for gGIST ER were variable [20–23]. Jeong et al. [20] reported that 5/32 (15.6%) gGIST patients undergoing ER were converted to LR. Dai et al. [21] reported that the ER conversion rate was 0.8% (2/262) in their cohort. Huang et al. [22] and Wu et al. [23] reported that none of their patients experienced any LR conversion. In our study, the percentage of patients requiring conversion to LR was 4.3% in 371 patients. We identified two possible reasons for these incidence differences. Firstly, in Jeong et al., the ESD technique was used to remove tumors, while Huang et al. and Wu et al. used the EFTR technique. The EFTR technique has a wider range of indications, and even if the tumor adheres to the gastric wall, it does not require conversion to LR. Secondly, different incidence rates were possibly related to small sample sizes, thus increasing sample sizes may generate more accurate results.

In our study, gGISTs > 3 cm (OR 6.747, 95% CI: 2.062–22.071, p = 0.002) and the invasion depth to MP-ex (OR 16.026, 95% CI: 2.949–87.092, p = 0.001) were independent risk factors for LR conversion. We found that 16.1% (10/62) of gGISTs ≥ 3 cm were converted to LR. In contrast, this proportion was only 1.9% (6/309) in gGISTs < 3 cm. Also, larger gGISTs were more vulnerable to severe intraoperative bleeding and perforation than tumors < 3 cm (9.7% vs. 1.0%, p = 0.001, 74.2% vs. 50.5%, p < 0.001, Table 6). When severe intraoperative bleeding could not be endoscopically controlled and endoscopic intraoperative perforation repair failed, LR conversion was required. We observed that 26.1% (12/46) of patients with gGISTs originated from MP-ex converted to LR, while only 1.2% (4/325) of patients with gGISTs originated within MP converted to LR. When compared with gGISTs within MP invasion, gGISTs with an MP-ex invasion had a higher probability of severe intraoperative bleeding and perforation when undergoing ER (15.2% vs. 0.6%, p < 0.001, 100.0% vs. 48.0%, p < 0.001, Table 6). Deep gGISTs were removed using the EFTR technique and large perforation repairs were difficult which increased the risk of LR conversion.

Undoubtedly, learning curves can objectively reflect an endoscopist’s experience [24, 25]. Sun et al. [26] reported that for endoscopists competent with basic endoscopic intervention skills, learning curves for ESD of submucosal tumors (SMTs) should be achieved after approximately 32 cases. In our study, endoscopist experience was differentiated according to the number of surgical gGIST ER cases performed (50 cases). Although univariate analyses showed that endoscopist experience exerted effects on LR conversion, multivariate analyses showed previous experience was not an independent risk factor for LR conversion. It may be because when inexperienced endoscopists encounter intraoperative bleeding or perforation that cannot be resolved, they seek help from experienced endoscopists, thereby reducing LR conversion risks. Additionally, we observed that the endoscopic method was not related to LR conversion, although specific steps varied. Thus, even if an intraoperative perforation occurred, as long as the perforation was not too large and no serious bleeding occurred, it would be well-managed under the endoscope.

Wu et al. [27] reported that laparoscopic surgery had more conversion risks to open laparotomy when gGISTs were located in the posterior wall of the gastric fundus near the cardia. The location of gGIST is a key factor affecting LR difficulty. However, we observed that a requirement for gGIST ER conversion to LR had nothing to do with tumor location. The reasons for LR conversion were related to technical difficulties (n = 14, 87.5%) and endoscopic resection accidents (n = 2, 12.5%). In our study, nine patients had to be converted to LR due to difficulties with intraoperative bleeding control by endoscopy. Five patients were converted to LR due to a failure to close the perforation. In two cases, LR conversion was performed because the tumor accidentally fell into the abdominal cavity and could not be found by endoscopy. Jeong et al. [20] reported that 15.6% (5/32) patients with gGISTs treated with ESD were converted to LR because the tumor had adhered to the gastric wall. However, Huang et al. [22] and Wu et al. [23] reported no LR conversion for gGISTs with the EFTR approach. When compared with surgery, the EFTR technique is safe, generates less intraoperative blood loss, has a faster postoperative recovery of bowel function, and is relatively inexpensive [28, 29]. Therefore, with improved endoscopic technology development, tumor adhesion to the gastric wall is no longer a risk factor for GIST ER conversion to LR.

In our study, procedure, postoperative hospitalization, and postoperative fasting times were significantly longer in patients converting to LR (median 160.5 vs. 58.0 min, p < 0.001; 8 vs. 6 days, p < 0.001; and 5 vs. 3 days, p < 0.001, respectively). The proportion of patients with severe intraoperative bleeding was significantly higher in the conversion group than the non-conversion group (50% vs. 0.3%, p < 0.001). The intraoperative perforation rate in the conversion group was higher than in the non-conversion group (87.8% vs. 53.0%, p = 0.008). However, no differences were observed in postoperative complications, En bloc R0 resection, follow-up duration, and recurrence between conversion and non-conversion groups. Although the long-term clinical efficacy in both groups were comparable, the non-conversion group had obvious advantages in terms of short-term efficacy.

Our study had some limitations. Firstly, this was a single-center retrospective study with a relatively small sample size. Only 16 patients were included in the LR conversion group. As we reviewed medical records, recall bias affecting results may have existed. A prospective multicenter large cohort study will be required to validate our results. Secondly, the median follow-up time was 42 months (range 3–139 months), and only two recurrences were recorded during this period, therefore, it was not appropriate to draw conclusions related to recurrence.

In summary, ER is a common treatment strategy for patients with gGISTs. Because LR conversion can result in compromised surgical outcomes, an awareness of risk factors contributing to LR conversion is crucial for the surgical management of patients with gGISTs. Tumor size (≥ 3 cm) and invasion depth (MP-ex) were independent factors for LR conversion during gGIST ER. Our experience suggests that a precise preoperative assessment of tumor size and invasion depth is important to avoid a requirement for LR conversion.

Declarations

Ethics approval and consent to participate:The research was approved by the Ethics Committee of the First Affiliated Hospital of Soochow University.Written informed consent was obtained from individual or guardian participants.

Consent for publication:All authors gave their consent for publication.

Availability of data and materials:All data generated or analysed during this study are included in this published article.

Competing interests:The authors declare that they have no competing interests.

Funding:This work is financially supported by the Science and Technology Project of Jiangsu Province (BE2019667)

Authors' contributions:Luojie Liu and Ye Ye collected the data. Luojie Liu and Xiaodan Xu interpreted the data. Luojie Liu drafted the manuscript.Rui Li and Dongtao Shi revised it. Rui Li and Weichang Chen designed this project and mapped the structure. 

Acknowledgements:The authors would like to thank the patients with gastric stromal tumors for their participation and cooperation.

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