ESD is widely used to treat gastric tumors and is often performed under either anesthesia or traditional sedation, administered by endoscopists [1, 8, 10]. Previous studies have compared outcomes based on the sedatives or anesthetic methods used. However, there have been insufficient data comparing the anesthetic methods (GA and MAC) used during difficult gastric ESD cases. To the best our knowledge, this is the first study comparing the therapeutic outcomes and adverse events following ESD of tumors, performed under GA or MAC, in the upper region of the stomach.
In this present study, the en-bloc resection rates were > 98% for both anesthetic groups and the complete resection rates were > 82%; similar results were observed when the EGC cases were separately examined. In a previous meta-analysis of ESD clinical outcomes, the en-bloc resection rate for 1437 cases of EGC was 92.4% and the complete resection rate for 1495 cases of EGC was 82.4%, regardless of the anesthetic method or tumor location [11]. Thus, the en-bloc and complete resection rates in our study were above average. However, our curative resection rates, for EGC cases, were relatively low (GA, 61.0%; MAC, 70.1%). A previous study of post-ESD, short-term outcomes, involving 712 patients in a prospective multicenter cohort study in Korea, showed an en-bloc resection rate of 97.3% and a curative resection rate of 86.8%. The authors of that study suggested that non-curative resection were associated with large lesions, submucosal invasion, and moderately or poorly differentiated adenocarcinomas [12]. Also in that study, 26.1% of the patients had EGC lesions > 2 cm in size, 33.1% of the lesions were moderately or poorly differentiated adenocarcinomas, and 16.0% of the lesions had invaded the submucosal layer [12]. In our study, 35.1% of EGCs were > 2 cm in size, 63.6% were moderately or poorly differentiated adenocarcinomas, and 44.8% showed submucosal invasion. Thus, the lower curative resection rate, in our study, may have been due to the tumor characteristics of our study population.
In the present study, the rates of ESD-related perforations were 12.6% for patients receiving GA and 9.5% for those receiving MAC; the respective bleeding rates were 5.3% and 4.5%. Amongst EGC cases, the perforation rates were 13.0% for those receiving GA and 5.2% for those receiving MAC; the bleeding rates were 5.2% and 3.9%, respectively. In a previous meta-analysis of ESD adverse events, a perforation rate of 4.3% was observed among 1437 EGC cases and bleeding occurred in 9.4% of 876 EGC cases, regardless of the anesthetic method or tumor location [11]. The higher incidence of perforations, in our study, may also be related to the tumor characteristics of our study population, as described for the curative resection rates. ESD involving the upper part of the stomach is carries a higher risk of adverse events, such as perforations and bleeding, due to the difficulty of positioning the ESD knife, the relatively thin gastric wall, and the associated vasculature; therefore, the procedure requires longer procedure times and more advanced technical skills than procedures involving the lower portion of the stomach [4, 13, 14]. Moreover, EGC submucosal invasion occurs more frequently in the mid and upper parts of the stomach [5]. A previous study of the risk factors for procedure-related perforations demonstrated that longer procedure times are an associated risk factor. That study also showed that the perforation rate was higher when the upper stomach was involved (8% of 478 cases) than when the lower stomach was involved (0.5% of 478 cases) [15]. Another study showed that the perforation risk is 4.9-fold higher for procedures involving the upper stomach than for those involving other areas of the stomach, after adjusting for submucosal invasion and dyslipidemia [16]. In the present study, the procedure times were longer for patients receiving GA than for those receiving MAC. However, the perforation rates were not significantly different between the two anesthetic groups. The results show that the two anesthetic methods are not associated with ESD clinical outcomes or adverse events; thus, safe and efficacious ESD may be achieved using MAC in high-volume centers with specialized endoscopists.
To develop the hypothesis for our study, we presumed that ESD performed under GA would have better therapeutic outcomes and fewer adverse events than those not performed under GA, because GA would prevent patients from demonstrating even subtle movements during the procedure. As noted previously, previous study results involving esophageal or gastric ESD indicated that GA decreases the risk of adverse events, compared with traditional sedation administered by endoscopists [2, 17]. Further, a previous study of esophageal ESD procedures, conducted at our institute, showed that the en-bloc resection rate was significantly higher and perforation rate was significantly lower in patients receiving GA than in those receiving traditional sedation; GA was shown to be a factor associated with achieving complete resection and minimizing perforations [17]. Despite only a few studies comparing GA and MAC, MAC has been shown to provide more clinical benefits than GA. One retrospective study compared endovascular angioplasty outcomes, in patients with aortoiliac disease, according to the intra-operative use of GA or MAC. Interestingly, the post-operative adverse event rate was significantly lower for procedures performed using MAC than for those using GA [18]. Similarly, another retrospective study also suggested that MAC is a safe anesthetic method for mid-gestation pregnant women and its use is associated with a lower adverse event rate than GA [18].
Our study has limitations due to its retrospective design and its inclusion of procedures performed only at one medical center. However, as a high-volume center that employs several technically advanced endoscopists, many stomach ESD cases have been performed and were available for inclusion. Since 2012, when ESD was introduced at our center, most cases have utilized traditional sedation or MAC. However, a selection bias exists because endoscopists request specific anesthetic methods, before starting their procedures. Endoscopists tend to request GA for difficult cases, such as those involving tumors in the upper stomach or that are presumed to be more invasive, based on morphologic assessments. Moreover, procedures involving the mid to upper stomach are 5 times more likely to involve MAC than GA. To overcome this limitation, we applied PS matching.
In conclusion, our study results demonstrated that good clinical outcomes were achieved following ESD of tumors in the mid to upper stomach, regardless of the anesthetic method used in our high-volume center. Further, the results showed the non-inferiority of the safety and therapeutic outcomes following ESD procedures performed in conjunction with MAC, compared with those performed with GA. Regarding cost-effectiveness and less invasiveness, gastric ESD under MAC might be superior to ESD under GA.