From June 2014 to July 2017, 341 consecutive patients with 377 superficial esophageal neoplasms were treated by ESD at the West China Hospital of Sichuan University. The indication criteria of ESD for superficial esophageal neoplasms were: (1) Intraepithelial neoplasia or carcinoma determined by biopsy, performed during chromoendoscopy with iodine staining; (2) Depth of invasion limited to within sm1, as assessed by endoscopic ultrasonography (EUS) and/or magnifying endoscopy with narrow-band imaging (ME-NBI); and (3) The absence of lymph node or distant metastasis confirmed by contrast-enhanced computed tomography (CT) of the chest and abdomen. Patients with a history of esophagectomy, proximal gastrectomy or total gastrectomy were excluded from this study. Additionally, all patients completed diagnostic endoscopies before treatment without an MWT occurring. Written informed consent was obtained from all patients before the procedures. The present study was reviewed and approved by the Ethics Committee of the West China Hospital of Sichuan University.

The ESD procedure was categorized as conventional ESD and endoscopic submucosal tunnel dissection (ESTD) (Figure 1). The conventional ESD procedure comprised four steps: (1) Marking the margin of the lesion; (2) Submucosal injection to elevate the lesion; (3) Mucosal incision around the lesion; and (4) Submucosal dissection. Regarding ESTD, one or more submucosal tunnels were established during the dissection step. The ESD procedure was decided by the endoscopist according to the size of the lesion.

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Figure 1 Mallory-Weiss Tear occurred during ESTD. A: The lesion of the esophagus after iodine staining; B: The submucosal tunnel created during ESTD; C: The artificial wound after ESTD; D: The mucosal laceration at the gastro-esophageal junction. ESTD: Endoscopic submucosal tunnel dissection.

ESD was performed with a single-accessory channel endoscope (GIF-Q260J, Olympus, Tokyo, Japan) with a transparent cap (D-201-10704, Olympus, Tokyo, Japan) attached to the front. Other equipment and accessories included: A high-frequency generator (VIO200D; ERBE ELEKTROMEDIZIN GMBH, Germany), argon plasma coagulation (APC) unit (APC-ICC200; ERBE ELEKTROMEDIZIN GMBH, Germany), IT knife (KD -611L, Olympus, Tokyo, Japan), Dual-knife (KD-650L/Q, Olympus, Tokyo, Japan), injection needle (NM-200U-0423, Olympus, Tokyo, Japan), and hemostatic forceps (FD-410 LR, Olympus, Tokyo, Japan).

All patients were under mechanically-ventilated general anesthesia, and in the supine position. ESD was performed by one experienced endoscopist (with 25 years of endoscopy experience and > 300 cases of esophageal ESD) and two less-experienced endoscopists (with 15 years of endoscopy experience and approximately 100 cases of esophageal ESD), and carbon dioxide was used for insufflation. After resection of the esophageal lesion, the gastrointestinal decompression tube was placed, and proton-pump inhibitors (PPI) and hemostatic drugs were used on all patients. Endoscopic follow up was scheduled at 1, 3, 6, and 12 mo after ESD, and then annually.

The decisions regarding the treatment strategy, including whether to treat the MWT endoscopically, were made by endoscopists according to the size of the laceration and the presence of active bleeding. Based on the endoscopic findings, APC, hemoclips or hemoclips combined with endoloop were used to treat the MWT.

MWT was defined as a mucosal tear at the esophagastric junction with or without active bleeding during the ESD procedure. Atrophic gastritis and hiatal hernia were diagnosed based on endoscopic findings. The longitudinal diameter of the esophageal lesion was measured from the oral edge to the anal edge of the resected specimens, and the circumferential diameter was determined based on the length of the vertical axis against the longitudinal axis. The circumferential extent of the mucosal defect was judged by the endoscopists. Curative resection was defined as en bloc resection with tumor-free horizontal and vertical margins, and met the following conditions simultaneously: Invasion depth limited in the submucosa < 200 μm without lymphovascular involvement.

Data pertaining to potential predisposing factors, such as age, sex, atrophic gastritis, hiatal hernia, characteristics of the esophageal lesions, and the experience of the endoscopists were collected from our prospectively maintained endoscopic database.

Variables are reported using the median (range) and simple proportion according to the type of data. The Mann-Whitney U test, chi-square test or Fisher’s exact test were used for univariate analysis, as appropriate. Clinically or statistically significant variables in the univariate analysis were included in the multivariate logistic regression analysis to assess the independent risk factors for an MWT. Differences with a P < 0.05 were considered significant. Statistical analysis was performed using SPSS version 23 for Windows.

The clinicopathological features of the patents and lesions are shown in Table 1. Overall, the median age of the patients was 62 years (range, 37-83 years), and the male proportion was 67.7%. Of the 373 lesions, 67.6% (252/373) were located in the middle esophagus, and 26.8% (100/373) were located in the lower esophagus. The median circumferential and longitudinal diameters of the specimen were 2.5 cm (range, 0.5-7.0 cm) and 4.0 cm (range, 1.0-14.0 cm), respectively. The median procedure time was 60 min (range, 12-240 min). The en bloc resection rate and curative resection rate were achieved in 96.2% (359/373) and 86.1% (321/373) of the lesions, respectively. The histology and invasion depth were as follows: Intraepithelial neoplasia, 131 (35.1%); mucosal invasion, 194 (52.0%); SM < 200 μm invasion, 21 (5.6%); and SM ≥ 200 μm invasion 26 (7.0%). Perforations developed in 6 (1.6%) cases, and the incidence of stenosis was 12.3% (46/373).

Twenty patients developed MWTs during the ESD procedure. The characteristics of the patients with or without MWTs are shown in Table 2. Predisposing factors[14,16] including atrophic gastritis, hiatal hernia, and a history of distal gastrectomy were not observed in the MWT cases. There was no significant difference in age, concomitant diseases, location, size, invasion depth, type of resection, or experience of the endoscopists between the two groups. However, in the MWT group, the proportion of female patients was much higher (70.0% vs 30.0%, P < 0.001), and the procedure time was longer (90 vs 58 min, P = 0.008) than the non-MWT group. Multivariate logistic regression analysis (Table 3) revealed that female sex was an independent risk factor for an MWT during esophageal endoscopic resection (OR = 5.27, 95%CI: 1.94-14.32, P = 0.001), and the procedure time longer than 88.5 mins was also an independent risk factor for an MWT during esophageal endoscopic resection (OR = 3.953, 95%CI: 1.497-10.417, P = 0.005). The association between MWT and procedure time was evaluated using receiver operating characteristic (ROC) curve analysis, and the cutoff value of the procedure time was 88.5 min (sensitivity, 65.0%; specificity, 70.8%), as calculated by the Youden index method. This result suggested that female patients with procedure times longer than 88.5 min were susceptible to MWTs during esophageal endoscopic resection.

Among the 20 patients with MWTs, 6 received endoscopic treatment for the laceration during the ESD procedure. Five patients with slight oozing were treated by APC or endoclips. One patient was treated with 9 endoclips and 1 endoloop to close the laceration, as the mucosal tear was deep and long, with visible vessel and errhysis. The remaining patients did not receive endoscopic hemostasis, and had a benign clinical course, with the exception of one patient (case 7, Table 4) who received a blood transfusion and emergency endoscopy due to delayed bleeding. In this patient, the laceration was not serious at the end of the ESD procedure. However, nausea and vomiting after ESD might have aggravated the laceration, and resulted in hematemesis. In the emergency endoscopy, longitudinal laceration was observed at the esophagastric junction, with visible vessel and blood oozing. After a sprinkle of epinephrine solution (1:10000) and APC, the active bleeding stopped.

Additionally, a severe gas-related adverse event, namely, gastric perforation, occurred in one patient (patient 9, Table 4). The perforation was closed endoscopically by hemoclips and endoloops using a double purse-string suture. As the MWT of the patient was relatively slight without active bleeding, no endoscopic treatment was performed.

In general, most of the patients had a benign clinical course, and no surgery was required for the MWT.

Endoscopic submucosal dissection (ESD) has been widely accepted as an effective treatment for superficial esophageal neoplasms when the risk of lymph node metastasis is diagnosed as being very low or negligible. With the development of endoscopic technology and growing emphasis on the diagnosis and endoscopic treatment of early esophageal cancer, the ESD-associated Mallory-Weiss Tear (MWT) is reported case by case.

Adverse events during ESD of superficial esophageal neoplasms, such as perforation and bleeding, have been well-documented. However, MWT during esophageal ESD remains under investigation. The present study was carried out to investigate the incidence and risk factors of MWT during esophageal ESD, since no literature has focused on the risk factors for an MWT during esophageal ESD.

The present study aimed to clarify the incidence of WMTs during esophageal ESD, and to evaluate the associated risk factors.

Patients with superficial esophageal neoplasms who received ESD in our institution were retrospectively analyzed. The clinicopathological characteristics of the patients were collected. Patients were divided into a MWT group and non-MWT group based on whether MWT occurred during ESD. The incidence of MWTs was determined, and the risk factors for an MWT were then further explored.

Twenty patients developed MWTs during ESD (5.4%). Multivariate analysis identified that female sex (OR = 5.36, 95%CI: 1.47-19.50, P = 0.011) and procedure time longer than 88.5 min (OR = 3.953, 95%CI: 1.497-10.417, P = 0.005) were independent risk factors for an MWT during ESD. The cutoff value of the procedure time for an MWT was 88.5 min (sensitivity, 65.0%; specificity, 70.8%).

The incidence of MWTs during esophageal ESD was much higher than expected. Although most cases have a benign course, fatal conditions may occur. We recommend inspection of the stomach during and after the ESD procedure for timely management in cases of bleeding MWTs or even perforation outside of the procedure region.

The present study aimed to clarify the incidence of WMTs during esophageal ESD, and to evaluate associated risk factors. In this work, we found that female sex and procedure time were independent risk factors for an MWT during ESD. For patients with such characteristics, clinicians must remain vigilant and perform careful observations after ESD.