This study reports the outcomes of endoscopic submucosal single-tunnel dissection or endoscopic submucosal multi-tunnel dissection for the treatment of esophageal neoplastic lesions of at least three-quarters of the esophageal circumference, including circumferential superficial esophageal neoplastic lesions. From July 2014 to February 2018, a total of 124 lesions underwent endoscopic submucosal tunnel dissection at our hospital. One to four submucosal tunnels were created in the oral to anal direction. Of the 124 lesions, there were 83 noncomplete circumferential lesions and 41 circumferential lesions. Endoscopic submucosal single-tunnel dissection was performed in 54 patients, two-tunnel dissection in 43 patients, three-tunnel dissection in 19 patients, and four-tunnel dissection in 8 patients. The mean dissection speed was
Endoscopic submucosal dissection (ESD) is recommended as the preferred treatment choice for early esophageal squamous cell carcinoma, adenocarcinoma, and precancerous lesions by the Chinese Society of Digestive Endoscopy (CSDE) [
Our previous article suggested that endoscopic submucosal multi-tunnel dissection (ESMTD) could be used for the dissection of circumferential esophageal lesions [
There are few reports, all with a small sample size, on the use of ESSTD or ESMTD for the treatment of esophageal neoplastic lesions. To provide more evidence regarding the outcomes of ESSTD and ESMTD in treating near-circumferential and circumferential esophageal lesions, we report 124 sequential cases of large esophageal neoplastic lesions that were at least three-quarters of the esophageal circumference.
From July 2014 to February 2018, 124 consecutive patients (aged 41-83 years; 76 males and 48 females) underwent ESSTD or ESMTD at our hospital. Esophageal neoplastic lesions involve at least three-quarters of the esophageal circumference. Written informed consent was obtained from all patients before the operation. This research was reviewed and approved by the Ethics Committee of the West China Hospital of Sichuan University. The inclusion criteria were as follows: (1) lesions involving at least three-quarters of the esophageal circumference, (2) post-ESTD pathological diagnosis of esophageal cancer or precancerous lesions, (3) no evidence of lymph node or distant metastasis, and (4) no prior treatment of chemotherapy or radiation.
Endoscopic ultrasonography (EUS) (Pentax EG-3830UT, Pentax EG-3630UR, Pentax, Japan) was performed to evaluate the depth of the lesions in all patients. Magnifying endoscopy with narrow-band imaging (ME-NBI) was used to assess the intrapapillary capillary loops (IPCL) and the lateral spread of the partial lesions before the ESSTD/ESMTD procedure. Contrast-enhanced computed tomography (CT) of the chest and abdomen was carried out to identify lymph node metastasis. A chromoendoscopy was carried out after direct spraying of 15-20 mL of 1.5% iodine solution through the biopsy channel of the endoscope before the endoscopic dissection procedure, a pink color sign was utilized to determine tumor borders.
Three principal endoscopists (Jin-Lin Yang, Jun-Chao Wu, and Tao Gan) that performed this technique had 15-25 years of experience as endoscopists. An endoscope with a water jet system (GIF-Q260J, Olympus, Tokyo, Japan) was used for the ESTD procedure and had a transparent cap (D-201-10704, Olympus, Tokyo, Japan) attached to its tip. An IT knife (KD-611L, Olympus, Tokyo, Japan), a Dual-Knife (KD-650L/Q, Olympus, Tokyo, Japan), an injection needle (NM-200U-0423, Olympus, Tokyo, Japan), and hemostatic forceps (FD-410 LR, Olympus, Tokyo, Japan) were used during the procedure. The VIO200D and APC-ICC200 (Erbe Elektromedizin GmbH, Germany) were set to the forced coagulation mode (effect 2, output 45 W) to incise the mucosal layer.
The standard ESSTD or ESMTD procedures for near-circumferential esophageal lesions were performed as previously reported [
Endoscopic submucosal single-tunnel dissection (ESSTD) or endoscopic submucosal multitunnel dissection (ESMTD) for near-circumferential esophageal lesions. (a) Iodine staining of the lesions. (b) Endoscopic ultrasound (EUS) imaging. (c, d) Magnifying endoscopy with narrow-band imaging (ME-NBI). (e) Marking the margin of the lesion with a Dual-Knife. (f) Posterior tunnel entrance creation by submucosal dissection with an IT knife. (g) Anterior incision after submucosal injection with a Dual-Knife. (h) Operation in three tunnels. (i) The resected posterior lesion specimen cut and flattened on a foam board after the operation. (j) The artificial wound after endoscopic submucosal tunnel dissection (ESTD). (k) Esophageal stricture. (l) Endoscopic water balloon dilation.
Bleeding related to the procedure was defined as requiring postoperative hemostatic treatment, such as endoscopic clipping or thermocoagulation. Perforation was diagnosed when the mechanical damage exceeded the muscularis propria or when mediastinal connective tissue was observed during the procedure. Mediastinal emphysema was diagnosed by the presence of air in the mediastinal space on plain radiography or subcutaneous emphysema of the neck or chest. Postoperative esophageal stricture was present when the gastroscope (diameter: 9.2 mm) could not be successfully passed. The management of esophageal stricture in all patients is mainly due to composite factors from both patients and physicians. (1) Clinicians advised the alternative treatment for postoperative esophageal stricture according to the severity of esophageal stenosis (Stooler score) and (2) patients preferred to take more convenient and cheap endoscopic treatment based on the economic conditions, the convenience degree of traffic.
R0 resection was defined as a lesion with a tumor-free lateral and basal margin; R1 resection was defined as tumor cells being present on the margin. The follow-up was routinely performed at months 1, 3, 6, 12, 18, and 24 after ESTD. The deadline for follow-up was March 2018. The first contrast-enhanced computed tomography (CT) of the chest and abdomen scans was performed at 3 months after ESTD for invasive cancer or at 6 months after ESTD for noninvasive cancer and then performed at 12 months to assess for distant metastasis. Local recurrence was diagnosed when an iodine-unstained area was detected adjacent to an ESTD scar, and cancer cells were histologically verified by a biopsy specimen. If cancer cells were found at the basal resection margin, an additional surgical esophageal resection or esophageal chemoradiotherapy was performed.
The chi-squared test was used for the comparison of categorical variables. Student’s
The baseline characteristics of the included lesions are described in Table
Clinicopathological characteristics of the patients.
Number of patients | 124 |
Age, |
|
Sex (male, female) | 76 (48) |
Size, mean (range) (cm2) | |
Circumferential extent ( | |
3/4 | 39 (31.4%) |
4/5 | 25 (20.2%) |
5/6 | 15 (12.1%) |
7/8 | 4 (3.2%) |
1 | 41 (33.1%) |
Macroscopic type ( | |
0-IIb | 28 (22.6%) |
|
39 (31.4%) |
|
3 (2.4%) |
|
44 (35.5%) |
0-IIa | 10 (8.1%) |
Multifocal lesions ( |
37 (29.8%) |
Number of tunnels ( | |
Single tunnel | 54 (43.5%) |
Two tunnels | 43 (34.7%) |
Three tunnels | 19 (15.3%) |
Four tunnels | 8 (6.5%) |
Depth of invasion ( | |
Low-grade intraepithelial neoplasia | 1 (0.8%) |
High-grade intraepithelial neoplasia | 9 (7.3%) |
M1 | 36 (29%) |
M2 | 27 (21.8%) |
M3 | 29 (23.4%) |
SM1 | 8 (6.4%) |
>SM1 | 14 (11.3%) |
In the 124 patients, the mean operative time was
Endoscopic features of the lesions.
Operative time, mean (min) | |
Dissection speed, mean (range) (mm2/min) | |
En bloc resection (%) | 124 (100%) |
R0 resection | 87 (70.2%) |
R1 resection | 37 (29.8%) |
Positive resection margins ( |
53 (42.7%) |
Follow-up, mean (range) (mon) | |
Additional esophagectomy ( |
11 (8.9%) |
Residual cancer | 1 |
Complications ( | |
Perforation | 1 (0.8%) |
Damaged of circular muscle | 60 (48.4%) |
Cardiac mucosal laceration | 7 (5.6%) |
Gastric fundus perforation patients | 2 (1.6%) |
Stenosis | 54 (43.5%) |
Comparison of endoscopic features between complete circumferential (CC) and noncomplete circumferential lesions (non-CC).
CC ( |
Non-CC ( |
||
---|---|---|---|
Operative time, mean (min) | ≤0.001 | ||
Dissection speed, mean (mm2/min) | 0.317 | ||
Size, mean (cm2) | ≤0.001 | ||
En bloc resection (%) | 41 (100%) | 83 (100%) | |
R0 resection | 27 (65.9%) | 60 (72.3%) | 0.461 |
R1 resection | 14 (34.1%) | 23 (27.7%) | |
Complications ( | |||
Perforation | 0 | 1 | |
Damage of circular muscle | 20 (48.8%) | 40 (48.2%) | 0.951 |
Stenosis | 34 (82.9%) | 20 (24.1%) | ≤0.001 |
Additional esophagectomy was required for 11 patients due to the depth of infiltration (beyond SM1) or the presence of cancer cells at the basal or lateral resection margin. However, only a single lesion in the resected specimen was found to be invasive (Table
En bloc dissection was achieved in all lesions. The R0 resection rate was 70.2% in our study. There were 53 lesions with positive resection margins, accounting for 42.7% of total cases, which included 15 cases of LGIN, 28 cases of HGIN, and 10 cases of invasive cancer at the lateral or basal cutting edge of the tissue specimen.
The R0 resection rate, R1 resection rate, and the circular muscle damage rate for complete circumferential lesions and noncomplete circumferential lesions were 65.9%, 34.1%, and 48.8%, respectively, and 72.3%, 27.7%, and 48.2%, respectively, with no statistically significant differences between them (
Intraoperative perforation occurred in 1 patient (1.7%). Subcutaneous emphysema and mediastinal emphysema were observed in this patient. This was a noncomplete circumferential lesion that was dissected by ESSTD. No serious immediate or delayed bleeding was found. Although the circular muscle of the muscularis propria was slightly damaged in 60 (48.4%) patients during the operation, no further management was required except for the use of titanium clips in 5 patients. A total of 7 patients (5.6%) suffered from cardiac mucosal laceration and 2 patients (1.6%) experienced gastric fundus perforation (corrected by endoscopic suture); no additional treatment was required for these cases.
All the patients were followed up for 1-44 months. The esophageal stricture rate was 37.1% in our study. The incidence of postoperative stricture was 3.2% (4/124) when the circumferential lesion was 3/4, 6.5% (8/124) when 4/5, 4.8% (6/124) when 5/6, 1.6% (2/124) when 7/8, and 27.4% (34/124) when circumferential lesions were complete. The stenosis rate of complete circumferential lesions was significantly higher than that of the noncomplete circumferential lesions (82.9% vs 24.1%,
Patients with post-ESTD stricture underwent a mean of 5.8 (1-18) esophageal balloon dilatation sessions (Boston Scientific Corp., Marlborough, America) with a diameter of 12-13.5 mm or required a Savary-Gilliard Dilator (Wilson-Cook Medical, America) with the largest diameter being 12.8 mm. Three patients with esophageal stricture underwent fully covered esophageal stent placement (retrievable esophageal stents; Micro-Tech Co., Nanjing, China), with a diameter of 20 mm and a length of 60-120 mm, into the stenosis site to resolve symptoms according to the composite factors from both patients and physicians.
An increasing number of studies have reported a case series of ESTD for the treatment of superficial esophageal squamous cell neoplasms [
As far as we know, our study includes the largest sample size of near-circumferential and circumferential superficial esophageal neoplastic lesions dissected by ESTD. The operation pattern involves not only a single tunnel but also multi-tunnel in more than half of the patients. The median procedure time was
The R0 resection rate was 70.2% in our study; previous studies report an 81.8%-100% resection rate [
Recently published studies of ESTD for the treatment of superficial esophageal squamous cell neoplasms [
Post-ESD esophageal stricture developed in 12-17% of patients, with risk factors including the circumference and length of the resection and the histological depth [
In summary, ESSTD or ESMTD is a time-saving dissection technique for near-circumferential and circumferential esophageal lesions and is associated with fewer long-term complications. Our results showed a high positive margin during this process; however, we considered that positive resection margins in any large and multifocal lesions are inevitable, regardless of the type of endoscopic procedure used. Moreover, no recurrence has been found so far. Therefore, we suggest that there is no need for unlimited extended resection areas for multifocal lesions to reduce the rate of positive resection margins. It is open to discussion whether additional surgery for such patients is required, and additional research is needed to sufficiently address this question. In conclusion, ESTD, especially ESMTD, is recommended for the treatment of large superficial esophageal neoplastic lesions that occupy more than three-quarters of the esophageal circumference, including circumferential superficial esophageal neoplastic lesions.
The data used to support the findings of this study are included within the article.
The authors declare no conflicts of interest.
Jin-Lin Yang and Yi-Ping Wang designed the research. Tao Gan, Jin-Lin Yang, and Jun-Chao Wu performed the research. Lin-Lin Zhu performed the follow-ups. Du He and Wen-Yan Zhang performed pathological analysis. Tao Gan, Jin-Lin Yang, and Lin-Lin Zhu analyzed the data. Lin-Lin Zhu wrote the paper.
This work was supported by the Science and Technology Department of Sichuan Province of China (Jin-Lin Yang, no. 2015SZ0123).