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A propensity score-matched analysis of laparoscopic versus open surgical radical resection for gastric gastrointestinal stromal tumor
ZhaoHui Xu1, Hui Qu1, YanYing Ren2, ZeZhong Gong1, George Kanani1, Fan Zhang2, Shuai Shao2, XiaoLiang Chen2, Xin Chen2
1 Department of Hernia and Colorectal Surgery, The Second Hospital of Dalian Medical University; Graduate School of Dalian Medical University, Dalian, China
2 Department of Hernia and Colorectal Surgery, The Second Hospital of Dalian Medical University, Dalian, China
|Date of Submission||16-Jun-2021|
|Date of Acceptance||30-Sep-2021|
|Date of Web Publication||08-Nov-2021|
Department of Hernia and Colorectal Surgery, The Second Hospital of Dalian Medical University, 467 Zhong Shan Road, Dalian 116023
Source of Support: None, Conflict of Interest: None
Background: Surgery is the mainstay of treatment for gastric gastrointestinal stromal tumours (GIST). However, the choice of surgical approach for gastric GIST remains controversial.
Aims and Objectives: To evaluate the short- and long-term efficacies of laparoscopic surgery versus conventional open surgery for gastric GIST.
Materials and Methods: We retrospectively reviewed 148 patients with gastric GIST at our hospital between January 2013 and January 2020. The patients were categorised into the following two groups based on the surgery performed: The laparoscopic surgery group (LG) and the open surgery group (OG). Differences in the tumour size, surgical procedures and modified National Institutes of Health classification were statistically significant. To balance the intergroup confounders, we performed 1:1 propensity score matching (PSM).
Results: A total of 104 patients were selected after PSM (52 in each group). We focused on the short- and long- term outcomes of patients. The baseline information was balanced between the two groups after PSM. The LG benefited from the advantages of a minimally invasive surgery (faster gastrointestinal function recovery, shorter time to drainage tube removal, less blood loss and shorter hospitalisation period), however, it also had high treatment costs. Moreover, both laparoscopic and open surgeries resulted in similar intra-operative and post-operative complications rates, overall survival time and disease-free survival time.
Conclusion: Laparoscopic resection is feasible and oncologically safe for GIST. However, more prospective studies are required to confirm the findings.
Keywords: Gastric gastrointestinal stromal tumour, laparoscopic surgery, open surgery, prognosis, propensity score matching
|How to cite this URL:|
Xu Z, Qu H, Ren Y, Gong Z, Kanani G, Zhang F, Shao S, Chen X, Chen X. A propensity score-matched analysis of laparoscopic versus open surgical radical resection for gastric gastrointestinal stromal tumor. J Min Access Surg [Epub ahead of print] [cited 2022 May 21]. Available from: https://www.journalofmas.com/preprintarticle.asp?id=330042
| ¤ Introduction|| |
Gastrointestinal stromal tumours (GISTs) are the most frequently occurring mesenchymal tumours of the digestive tract but remain rare in comparison with gastrointestinal carcinomas. They are thought to be derived from the interstitial cells of Cajal or their precursors. Most GISTs originate from the stomach (50%–60%), followed by the small intestines (20%–30%), and the rectum (approximately only 5%)., Surgical resection without regional lymphadenectomy is the preferred treatment for GIST because of a lower rate of lymph node metastasis.
With the development of minimally invasive techniques, laparoscopic surgery for GIST has developed rapidly in the past decades. However, laparoscopic surgery should be performed only in experienced medical centres based on the surgical site and size.,,, Blindly performing laparoscopic surgery may rupture the tumour capsule and cause intraperitoneal seeding because of the fragile texture of stromal tumours. Scholars from various countries have gained experience in this field and proved the safety and feasibility of laparoscopic surgery for GISTs; however, the oncological results and long-term prognosis of laparoscopic surgery have not been widely reported, and the sample size is relatively small. Most studies are retrospective, with confounders or a selection bias. Propensity score matching (PSM) may minimise confounding in observational studies. In this study, we retrospectively analysed 148 cases of gastric GISTs at our hospital to evaluate the short- and long-term efficacies of laparoscopic surgery versus conventional open surgery for gastric GISTs by using a PSM method.
| ¤ Materials And Methods|| |
The study was conducted according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for cohort studies.
The medical records of patients with gastric GIST at the Second Hospital of Dalian Medical University (Dalian, China) between January 2013 and January 2020 were retrospectively evaluated. The inclusion criteria were as follows: (1) The patients were definitively diagnosed with gastric GIST by clinical histopathological analysis and immunohistochemical staining; (2) The patients had complete clinical records including the demographic data, clinical and pathologic features, details of the surgery and follow-up records; (3) The post-operative follow-up time was not <6 months. The exclusion criteria were as follows: (1) The patients only received endoscopic resection or conservative treatment; (2) The patients had distant metastasis or unresectable gastric GISTs. The patients were divided into two groups: LG and OG. The study was approved by the institutional ethics committee of the Second Hospital of Dalian Medical University. All patients had signed informed consent forms before surgery.
Data were obtained from electronic medical records and pathological reports. The baseline data included age, sex, initial clinical manifestations, pre-operative comorbid diseases, family history of cancers, positive resection margin rate, tumour location, surgical procedures, tumour size, mitotic count, modified National Institutes of Health (NIH) classification (very low, low, intermediate or high), histopathological classification, Ki-67 index, immunohistochemical analysis (CD117, CD34, S100 and DOG1) and post-operative imatinib mesylate (IM) therapy.
Intermediate- and high-risk patients were recommended post-operative IM treatment. Post-operative follow-up was performed (at an interval of 3–6 months for the first 5 years and annually thereafter) through telephonic interviews or regular outpatient visits. Follow-up examinations consisted of chest-X-ray imaging, ultrasonography and contrast-enhanced abdominal/pelvic computed tomography or magnetic resonance imaging. The deadline for follow-up was August 2020.
The main endpoints of our study were disease-free survival (DFS) and overall survival (OS). The DFS time was defined as the time from initial surgical resection to clinically or radiologically proven disease relapse. The OS time was defined as the time from surgery to death owing to any cause or to the end of the follow-up period.
All patients underwent the same pre-operative preparation and were operated on by the same group of surgeons with 15–20 years of surgical experience complying with the following clinical practice guidelines: (1) Direct contact with the tumour surface was avoided to reduce any risk of tumour rupture; (2) Gross resection of the tumour was performed with a negative resection margin; (3) Lymph node resection was not routinely performed. The patients were under general anaesthesia in lithotomy or split-leg position. The surgeon stood on the left side of the patient, whereas the first assistant stood on the right, and the camera assistant between the patient's legs. Open surgery was performed by entering into the abdominal cavity through a 15- to 20-cm subxiphoid abdominal incision and was equipped with an incision protector. Laparoscopic surgery was performed using a four- or five-port trocar technique. Macroscopical abdominal examination was performed to confirm the tumour location and assess the invasion of the tumour into adjacent organs or distant metastasis. In laparoscopic surgery, a pre-operative or an intra-operative endoscopic approach is usually used to assist precise localisation and excision of ingrown or small gastric GISTs. The operation selection was similar in both LG and OG based on the tumour location and size. Masses located in the greater curvature and fundus of the stomach were easily amenable to wedge resection. Masses located near the pylorus or cardia were excised by partial gastrectomy. Total gastrectomy is generally performed for large gastric GISTs. No patients required conversion to laparotomy in the LG. All specimens were removed in a protective bag by creating small incisions in the abdomen.
Statistical analysis was conducted using SPSS, version 25.0 (Armonk, NY: IBM Corp.). Normally distributed continuous variables, expressed as mean ± standard deviation, were analysed using the independent-samples t-test. For non-normally-distributed continuous variables, the data were expressed as median with an interquartile range (IQR) and evaluated using the Mann–Whitney U-test. Categorical variables were reported as the number of individuals and percentages (%), and the Chi-squared test or Fisher's exact test was used for comparison. A 1:1 PSM method using nearest-neighbour matching without replacement was used to analyse the LG and OG. The standard calliper value was 0.2. The propensity scores were calculated using multivariable logistic regression with the following observed covariates: Age, sex, symptoms, pre-operative co-morbid diseases, family history of cancers, tumour location, surgical procedures, tumour size, mitotic count, modified NIH classification, histopathological classification, Ki-67 index and immunohistochemical staining. Statistical analyses were conducted using the paired t-test, Wilcoxon's signed-rank test and McNemar test for paired samples. Two-tailed P < 0.05 were considered statistically significant. The survival curves were estimated using the Kaplan–Meier method and analysed using the log-rank test.
| ¤ Results|| |
From 2013 to 2020, of the 273 patients, 20 with incomplete case information, 12 receiving conservative treatment, 12 with simultaneous metastasis, 72 receiving endoscopic treatment and 9 who were lost to follow-up were excluded. Eventually, 148 patients were enrolled in the study. A total of 84 and 64 patients were included in the LG and OG, respectively. A total of 104 patients were included after PSM (52 in each group) [Figure 1] for the flow diagram of the study.
Baseline variables before and after propensity score matching
Differences between the groups in terms of most demographic and clinical data were not statistically significant. However, differences in the tumour size and modified NIH classification were statistically significant (all P < 0.05). After PSM, the baseline information was balanced between the two groups [Table 1].
|Table 1: Baseline variables of the laparoscopic surgery group versus open surgery group before and after propensity - score matching|
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Intraoperative and post-operative outcomes before and after propensity score matching analysis
Complete resection (R0) was performed in both groups without tumour rupture [Table 1]. Both laparoscopic and open surgeries had a similar surgical time after PSM (125.00 min versus 140.00 min, P > 0.05), which was the opposite of the result obtained before PSM and may be affected by different tumour sizes (4.5 cm in the LG versus 6.0 cm in the OG, P = 0.001) and diverse surgical procedures. Intra-operative blood loss in the LG was 50.00 mL, which was significantly less than that in the OG (100 mL, P < 0.05). Moreover, the incision length was significantly shorter in the LG than that in the OG (P < 0.05).
Intraoperative complications in our study included intraoperative haemorrhage (blood loss >800 mL), organ injury and incomplete haemostasis. Post-operative complications included anastomotic leakage, delayed gastric emptying, post-operative bleeding, pulmonary and intraperitoneal infection and surgical site infections. No significant differences were found in the adverse events between the LG and OG before and after PSM [Table 2].
|Table 2: Intra-operative and post-operative outcomes in the laparoscopic surgery group versus open surgery group before and after propensity score matching|
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Gastrointestinal function recovery was faster in patients who underwent laparoscopic surgery than that in patients who underwent open surgery P < 0.05, [Table 2]. Furthermore, they had a shorter time to drainage tube removal and earlier hospital discharge P < 0.05, [Table 2]. However, expenditure in the LG was higher than that in the OG 47, 630 Yuan RMB versus 36, 950 Yuan RMB, respectively, P < 0.05, [Table 2].
Recurrence and survival before and after propensity score matching analysis
All 148 patients were regularly followed up, and the median follow-up time was 40 months (ranging from 7 to 124 months), 36 months in the LG (ranging from 7 to 124 months) and 44.5 months in the OG (ranging from 10 to 100 months). No statistical differences were observed between the LG and OG in 1-year OS (100% vs. 100%, respectively), 3-year OS (95.0% vs. 93.0%, respectively), 5-year OS (83.3% vs. 70.5%, respectively), 1-year DFS (98.0% vs. 100.0%, respectively), 3-year DFS (95.7% vs. 79.1%, respectively) and 5-year DFS (85.8% vs. 70.1%, respectively) the results are provided in [Figure 2]. In the OG, 8 patients had recurrence and metastasis (2 cases of gastric recurrence, 2 cases of liver metastasis, 1 case of colon metastasis and 3 cases of intra-abdominal metastasis). Of these 8 patients, 5 underwent second surgery along with IM therapy, 2 refused to continue further treatment and 1 was treated with oral IM. A total of 4 patients were found to have tumour recurrence in the LG at 20, 38, 40 and 55 months after surgery (2 cases of gastric recurrence, 1 case of multiple liver metastases and 1 case of multiple intra-abdominal metastases). Of these 4 patients, 1 was treated with oral IM after the second surgery, 1 was treated with oral IM, 1 refused to continue further treatment and 1 received interventional therapy along with IM for multiple intrahepatic metastases [Table 3].
|Figure 2: The Kaplan–Meier survival curves in the unmatched and matched cohorts. The graphs have showed the (a) disease-free survival rate and (b) overall survival rate of laparoscopic group versus open surgery group before propensity-score matching, (c) disease-free survival rate and (d) overall survival rate of laparoscopic group versus open surgery group after propensity-score matching|
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| ¤ Discussion|| |
Open surgery is the most frequently implemented treatment strategy for GISTs. With the development of minimally invasive technology, laparoscopic surgery has become one of the most important treatment methods for GIST in some experienced centres. We employed a 1:1 PSM method to balance a high number of confounding factors in the present study, which provided reliable results.
In a study by Nilsson et al., a total of 69% of GISTs were diagnosed based on clinical symptoms. Consistent with the results of their study, the most common initial clinical manifestations in our study were dyspepsia (40 cases, 27.0%), gastrointestinal bleeding (34 cases, 23.0%), abdominal pain (29 cases, 19.6%) and palpable mass (5 cases, 3.4%), whereas 40 cases were asymptomatic (27.0%).
In the current report, although intermediate- and high-risk patients were recommended post-operative IM treatment, only 40.5% of patients in the LG and 33.3% of patients in the OG accepted regular IM therapy. This was mainly owing to the following reasons: Long-term IM therapy is still a heavy economic burden for most patients; in addition, a small number of people who cannot use the drug regularly because of severe side effects. Based on the finding of a previous study, some patients do not want to take medicines every day.
In the present study, the LG was oncologically safe and the R0 resection rate of the primary tumour was 100%. Tumours within 5 cm can be safely removed using laparoscopy., Growing evidence suggests that laparoscopy is a technically feasible and oncologically safe technique for treating patients with large GISTs.,, In our study, only 1 patient received open total gastrectomy because of a large gastric GIST (diameter = 18.0 cm). Laparoscopic technology is not adopted mainly because of the following two reasons: First, in the case of large tumours, there is no minimally invasive effect because the auxiliary incision is too large; second, adhesion in the abdominal cavity may lead to tumour rupture. Actually, a pre-operative or an intraoperative endoscopic approach may usually assist precise localisation and excision of ingrown or small gastric GISTs in laparoscopic surgery. In our centre, we usually use dyes (methylene blue and nanocarbon), stitches and titanium clips around the tumour for precise marking. In this study, 7 patients were treated with a dual endoscopic technique (tumour diameter ≤4 cm). The hybrid dual-scope technique can not only avoid tumour rupture caused by incomplete resection but also check the conditions of the gastric cavity and wound surface, which has a positive application value.
Some studies,,, have reported that laparoscopic surgery for gastric GISTs has several advantages, including less intra-operative blood loss, a shorter time to the first flatus and oral intake and a shorter post-operative hospital stay. These advantages were equally significant in our study. The mean incision length in the LG was 6 cm shorter than that in the OG (9.00 cm vs. 15.00 cm, respectively, P < 0.05). Moreover, less blood loss was observed in the LG than in the OG (50.0 mL versus 100.0 mL, respectively). Furthermore, compared with the OG, the LG group had a faster bowel function recovery, shorter time to drainage tube removal and shorter post-operative hospital stays. These results were consistent with those of numerous studies mainly because laparoscopic surgery was performed with a better visual field, thus facilitating more accurate anatomical structures, which helped to reduce unnecessary bleeding., In the LG, there was little gastrointestinal intervention, earlier feeding and sooner independently walking, which were beneficial for faster recovery of gastrointestinal function and earlier discharge.
The median operative time was 125.00 min in the LG and 140.00 min in the OG; however, this difference was not statistically significant. Laparoscopic surgery for GIST only requires the removal of the primary lesion without time-consuming and laborious lymphadenectomy. It is not theoretically difficult to complete the procedure. We expect that the surgical time will be further shortened with the development of laparoscopic technology.
There were more intra-operative complications in the OG than in the LG, mainly manifest as intra-operative haemorrhage; however, no statistically significant difference was observed. No statistically significant intergroup difference was observed in post-operative complications. In the present study, the major post-operative complications included anastomotic leakage and delayed gastric emptying in the LG and OG, respectively. In case of anastomotic leakage, 1 patient was drained using a drainage tube and the condition improved after conservative treatment, and two patients underwent another surgical intervention. For patients with post-operative gastroparesis, we used acupuncture therapy, traditional Chinese medicine, erythromycin and oral gastrointestinal motility drugs, and evaluated the curative effect using upper gastrointestinal angiography. In two patients with surgical site infection, we strengthened the systemic anti-infective treatment; opened part of the incision sutures and used silver ion dressing, epidermal growth factor and negative pressure wound therapy. Adverse effects were rare and similar in both groups.
The cost of laparoscopic surgery was significantly higher than that of open surgery (47, 630 Yuan RMB vs. 36, 950 Yuan RMB, respectively) because of the luminal the Endo-GIA stapling devices and laparoscopic instruments.
No significant difference was observed in OS or DFS between the two groups, which was consistent with the results of previous studies.,, Based on these characteristics, laparoscopic surgery is considered technically feasible and safe. The short-term efficacy of laparoscopic GIST resection is better than that of open GIST resection and does not affect safety and long-term prognosis., The long-term survival status of patients is primarily based on the nature of the tumour itself.
The present study has a few limitations. The study was retrospective. Although we used PSM to balance numerous confounders, considerable inherent selection bias was observed. Some real data were discarded, and the universality of the real-world cases may be affected. More prospective studies are needed to confirm the findings.
| ¤ Conclusions|| |
Laparoscopic surgery is minimally invasive and offers several advantages (faster gastrointestinal function recovery, shorter time to drainage tube removal, less blood loss and shorter hospitalisation period); however, it also had a high treatment cost. Moreover, both laparoscopic and open surgeries had similar intra-operative and post-operative complications rates, OS time and DFS time. In conclusion, the present study demonstrated that laparoscopic surgery is feasible and oncologically safe for GIST.
The authors acknowledge the support of the Liaoning province science and Technology Agency (No. 2014023034).
Financial support and sponsorship
Liaoning province science and Technology Agency (No. 2014023034).
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]