The present study shows that larger lesion size, incomplete pathologic resection, undifferentiated carcinoma, scar deformity, and no evidence of surface erythema were associated with local recurrence after ESD for EGCs. Endoscopic resection of EGC without lymph node metastasis has been accepted as a definite treatment method with long-term outcomes comparable with those of surgical resection of EGC. However, some lesions show local recurrence at the artificial ulcer scar after ESD. One drawback of endoscopic resection compared with surgical resection is the higher rate of local recurrence . There has been no definite recommendation on whether to select surgical resection or endoscopic treatment for local recurrence of EGC after endoscopic resection. To date, additive surgical resection of locally recurrent EGC lesions is recommended first because the additional endoscopic curative resection of locally recurred EGC lesions is more difficult than that of naïve ESD lesions because of widespread submucosal fibrosis. However, some patients in the old age group with poor performance status and who refused to undergo surgical resection could be candidates for endoscopic treatment.
In the present study, the proportion of locally recurrent cases was 3.1%. The reported rates of locally recurrent EGC after ESD range from 0.7–3.7% [8, 9]. We defined a locally recurred lesion as the neoplastic lesion that developed at the post-ESD artificial ulcer scar. Some recurrent lesions may be metachronous or synchronous lesions in relation to the mucosa near the artificial ulcer scar. On endoscopic photo review, nine lesions were found mainly at the margin of the artificial ulcer. If the recurred lesions are located mainly at the margin of the tumor, endoscopic resection could be preferred to surgical resection. We performed successful additive endoscopic resection in six patients. Twelve patients received surgical resections with lymph node dissection (three patients showed lymph node metastasis), and one patient who refused surgical resection underwent argon plasma destructive therapy. During the period of the study, only one case of gastric cancer-related death was found where the patient had refused additional surgical resection for deep submucosal and lymphovascular invasive EGC after ESD. Therefore, if we had kept endoscopic treatment indications for EGC, the number of gastric cancer-related deaths would have been zero during the study period.
In the present study, incomplete pathologic resection was significantly associated with local recurrence after ESD. The reported incidence of local recurrence after incomplete resection was 4.2–30% [10, 11]. Incomplete resection is a result of piecemeal resection or marginal involvement of EGC after a one-piece resection. Piecemeal resection was not a significant association in the present study because most of the lesions were resected in one piece (97.8%). Only two lesions had recurred after piecemeal resection, and the macroscopic photographs showed no residual tumors in most of the piecemeal-resected specimens. In piecemeal-resected tumors, estimation of marginal status is difficult. Therefore, after pathological confirmation of the undetermined marginal status, a clean artificial ulcer bed and resection of the mucosa outside the marking made before mucosal incision may be important. In addition to the macroscopic findings after endoscopic resection, pathologic differentiation and depth of invasion of the resected specimen may be key factors in deciding whether to perform additional surgical resection. In our institution, additional operative treatment is recommended for piecemeal-resected tumors under the following conditions: remnant gastric cancer is highly suspected macroscopically after endoscopic resection (irregular ulcer bed or mucosal incision performed inside the mucosal marking during ESD) or undifferentiated histology, submucosal invasion, or lymphatic invasion is observed in the resected specimen. If the piecemeal-resected EGC lesion shows well-differentiated carcinoma, mucosal cancer in the resected specimen, and artificial ulcer bed and margin with no visible evidence of remnant EGC, a discussion with the multidisciplinary team, including gastroenterologists and surgical team, is undertaken to decide whether to perform surgical resection. Marginal status is important in predicting local recurrence. Since surgical resection was recommended for all the vertical marginal-positive patients in the present study, the lateral marginal status might be an important predictive factor. A previous study reported that a longer length of the involved lateral margin was important for predicting local recurrence .
Undifferentiated adenocarcinoma was associated with local recurrence after ESD. Undifferentiated gastric tumor cells originating in the neck of the gastric gland can spread to the submucosal space . Therefore, estimation of the resection margin of undifferentiated EGC during ESD is more difficult than that of differentiated EGC. Moreover, remnant EGC is not predictable based on endoscopic findings. In the present study, surface erythema was not a risk factor for local recurrence. Surface erythema is an important endoscopic finding associated with well-differentiated EGC . In contrast, undifferentiated EGC such as signet-ring cell carcinoma invades and spreads underneath the surface epithelium without destruction of the mucosal epithelium and subepithelial capillaries; therefore, no surface erythema is observed during endoscopic examination . In addition, EGC with fibrotic submucosa or scar does not show erythema.
Larger lesion size is an important factor for local recurrence after ESD. Because endoscopic snare has a size limitation, tumors more than 20 mm in size are difficult to resect by simple snaring with a safe lateral margin. Although ESD is a more effective treatment method regardless of tumor size than conventional EMR, a large tumor is more difficult to resect safely than a small tumor . Therefore, larger tumor size is highly associated with incomplete endoscopic resection of tumors. In addition, ulcer scar formation is associated with local recurrence. Because ulcer deformity represents extensive submucosal fibrosis, exact submucosal dissection beneath the EGC is difficult without direct visualization of the submucosal layer. In addition, if the EGC has existing deep ulceration, the estimation of the vertical marginal status might be inaccurate. The possible presence of remnant cancer cells beneath the dissected ulcer scar could be a risk factor for local recurrence.
Incomplete resection of the tumor is highly associated with procedural difficulty. Difficult ESD procedures are associated with several factors such as larger lesion size; location of the tumor, which is difficult to reach using endoscopic electrosurgical knives; submucosal fibrosis; submucosal invasive cancer; and expertise of endoscopists . It is challenging to predict the difficulty of the procedure because all procedural situations are not the same. When a difficult endoscopic procedure is expected, preparations for all possible methods to overcome the difficult situation should be considered, including consultations with more experienced endoscopists.
The present study had several limitations. First, because the present study was retrospective in a single referral medical cancer, there was inherent selective bias. Second, the sample of locally recurrent tumors might be too small to analyze the factors associated with local recurrence and generalize the results. However, the results of this study are informative and consistent with those of other studies [8, 9]. Third, some of the locally recurrent lesions might be metachronous or missed synchronous lesions, which could not be differentiated using retrospective endoscopic photograph reviews. Fourth, the length of submucosal fibrosis might be an important factor associated with the difficulty of ESD. A short length of submucosal fibrosis might be associated with repeated endoscopic forceps biopsy. However, because of the retrospective study design, we were unable to estimate the length of submucosal fibrosis. Therefore, further prospective studies should be considered. However, additive information of this present study would be helpful to the clinical practice after ESD for EGCs.