Laparoscopic versus open wedge resection for gastrointestinal stromal tumors of the stomach: a single-center 8-year retrospective cohort study of 156 patients with long-term follow-up

Adenocarcinomas are the most common tumors of the stomach, whereas submucosal tumors of the stomach such as GISTs are rare. Unlike adenocarcinomas of gastrointestinal tract, GISTs showed that negative macroscopic margins only may portends a survival benefit [3]. Lymphatic spread is quite uncommon, and as such, systemic lymphadenectomy has been deemed unnecessary [2,3]. These characteristics, along with GISTs’ tendency to grow in an exophytic manner, led many surgeons prefer wedge resection rather than formal gastrectomy for gastric GISTs whenever feasible. Though laparoscopic wedge resection is expected to be a preferable choice for GISTs compared with traditional open wedge resection as previously reported [27,29-33,35,36], more convincing evidence is still needed to prove its safety and feasibility. This manuscript summarizes the outcomes of LWR of gastric GISTs in the relatively larger series of patients to date. Our data demonstrate that the patients who underwent LWR for gastric GISTs results in effective control of the disease with minimal perioperative morbidity and no mortality. Besides, a rapid systematic review with a meta-analysis was conducted to summarize all the published information. We believe this could help surgeons to share the optimal individualized decision for patients.

Our series of patients who underwent LWR had less intraoperative blooding than that in the OWR group. The reduced length of incision wound, accurate operation and the application of energy-dividing devices, contributed to the reduction of blood loss. Pain after surgery was milder in LWR than in OWR, reflecting as the shorter duration or the lower dosage of analgesic application [29,32]. The time to first flatus was also earlier in LWR than in OWR, which indicated more rapid recovery of gastrointestinal function after LWR. Reduced use of analgesic drugs, shortened time of abdominal cavity exposure, alleviated inflammatory reactions, and earlier postoperative activities are considered to be the main reasons for earlier gastrointestinal recovery from LWR; all of which may also contribute to shortening the duration of postoperative hospital stay. The meta-analysis also revealed these mini-invasive advantages of the LWR. Interestingly, the operative time in the LWR group did not longer than OWR which is different from many other type of laparoscopic surgery [37-42]. This is because the time-consuming laparoscopic lymphadenectomy is unnecessary for GISTs resection due to the fact that the lymphatic metastasis of GISTs is quite rare. As time spending on the establishment of pneumoperitoneum and the closure of the trocar incision and minilaparotomy is likely to shorter than the open and closure of laparotomy, it is possible that the operative time for the LWR will be shorter than OWR with the development of the surgical techniques and laparoscopic instruments.

Regarding the postoperative complication, the incidence was higher in the OWR group than the LWR group, but the difference did not reach statistical significance in our study. However, the meta-analysis indicated a significant reduction in the LWR group (P = 0.04). In our study, there was a high incidence of wound problem in the OWR group. This is also true in included trials which specified the morbidity [31,34]. It was conceivable that complications other than wound problem were similar between groups because LWR results in the same organ and tissue resection as OWR.

LWR for gastric GISTs seems to have become a popular technique, the indications for this procedure in relation to tumor size are still controversial. Large lesions increase the difficulty to resect using endoscopic linear staplers and the risk of tumor spillage when removal. It was previously suggested by the NCCN Guidelines updated in 2007 for Optimal Management of Patients with GIST that laparoscopic techniques could be approached for tumors less than 5 cm [2]. However, many investigators have reported successful and safe removal of larger GISTs [26,43-45]. In our series, 12 cases with tumor size larger than 5 cm underwent LWR successfully with no conversion, demonstrating its feasibility, though the mean tumor size of OWR group was slightly larger than LWR group (4.3 versus 3.5 cm). This observation was mainly biased by the inherent selection process for patients to undergo a laparoscopic approach. patients with smaller tumors may be more amenable to laparoscopy versus larger tumors, which may tend to treat with laparoscopy or laparotomy. There were 20 cases in our series with tumor located near the esophagogastric junction or the pylorus who were considered inappropriate to undergo LWR. Performing this procedure has a high possibility of stenosis or deformity in the gastric inlet or outlet because it is associated with excessive resection of the healthy tissue of the gastric wall by laparoscopic stapling [46]. If the tumor was extraluminal growth, we resected the tumor using ultrasonic scalpel, then used laparoscopic intracorporeal handsewn method to close the incision. With those intraluminal growth, the laparoscopic transgastric wedge resection, which provided direct vision of the lesion and inner stomach, and allows better control of the surgical margin, was introduced. Whereas, if the tumor was large, laparoscopic distal or total gastrectomy was performed instead of LWR which is impossible in such situation. After tumors removal, all these cases were confirmed by intraoperative gastroscope examination to avoid gastric inlet or outlet narrowing. Currently, there are still no clear consensus guidelines for gastric GISTs laparoscopic approach based on tumor size and location. We advocate that tumor size and location should not be an absolute contraindication to laparoscopic techniques. However, one thing should be in mind that regardless laparoscopy or open surgery, it must be avoid direct tumor manipulation in an effort to eliminate the incidence of tumor rupture since tumor spillage can results in shortened disease-free survival [47].

With recent trials confirming the short-term surgical safety and long-term survival efficacy of laparoscopic techniques in other gastrointestinal malignancy [48-53], the role of laparoscopic surgery in resection of GISTs of the stomach should be clarified. Long-term survival remain critical for all patients with GISTs regardless of a benign or malignant designation since these tumors have an uncertain biologic behavior. It is widely accepted that the tumor size and mitotic index are two key factors on GISTs long-term outcomes. Several recent reports have also detailed recurrence rates of patients with gastric GISTs after laparoscopic surgery ranging from 4.8 to 18% [11,26,29,54,55]. In our study, LWR group had a lower recurrence rate (1.1%) compared to previous reports. This result was mainly due to most of patients in LWR group with tumors at very low, or low malignant risk (73.1%), whose recurrence may be delayed for as long as 10 years [56]. Moreover, in our center patients with tumors at moderate, or high malignant risk are routinely recommended to continue treatment with imatinib after surgery, which can effectively improved recurrence-free survival and overall survival of GIST patients with a high risk of GIST recurrence [57,58]. Despite the fact that tumor size of OWR group was larger than LWR group, two groups were comparable with no significant difference according to Fletcher’s criteria. Our series demonstrates the oncologic safety of the laparoscopic approach, with efficacy and recurrence rates similar to open surgical controls. All the tumor-recurrent cases in our study developed recurrence in 2 years after surgery, once more proving that most of the GISTs recurrence occurs within the first 2 years after surgery [3,11,59].

As nonadenocarcinomas in the stomach are uncommon, the sample of 156 patients is considered large. But it is still small for definitive conclusions on the safety and effectiveness of LWR. Thus, our rapid systematic review and meta-analysis synthesized the existing observational studies with strictly limiting inclusion and exclusion criteria. The included studies were primarily derived from the countries with the most widespread use of laparoscopic gastrectomy (two from Japan, one from Korea, one from China, one from Singapore, and one from Italy), and the total number of cases incorporated in the study was 525. The larger the number of patients in a meta-analysis, the greater its power to detect a possible treatment effect. Therefore, our comprehensive meta-analysis will contribute to a more systematic and objective evaluation for the safety and effectiveness of LWR.

There are some limitations to our study. The major bias was derived from retrospective nature and lack of prospectively defined inclusion criteria for those undergoing LWR. Also, the majority of cases in our study are in the past 3 years, which is short for the low risk GISTs to develop recurrence, and the follow up will continue. Although the meta-analysis confirmed the mini-invasive benefits of LWR and the similar postoperative and oncological outcomes between LWR and OWR, the simple size of some articles included was quite small and there was no prospective or randomized study that can markedly undermine the strength of the analysis. Our results should be confirmed by further randomized controlled trials that compare the open versus laparoscopic approach for the treatment GISTs.