A single-center retrospective review of collected data was conducted, examining 74 consecutive patients with 101 esophageal lesions who underwent resection via SB-knife ESD between April 2010 and August 2016 at Kure Medical Center and Chugoku Cancer Center, Japan (Figure 1). All patients underwent resection using only SB-knife ESD during this time period. Approved by the National Hospital Organization Kure Medical Center and the Chugoku Cancer Center Institutional Review Board Ethics Committee on 3 October 2016, the study incorporated good clinical practice, conforming to Declaration of Helsinki principles. All lesions were diagnosed preoperatively during chromoendoscopy, identifying areas for biopsy through narrow-band imaging or iodine staining. Inclusion criteria were patients with superficial esophageal neoplasms (SENs), consisting of high-grade intraepithelial neoplasia or SCC. Exclusion criteria included patients with adenocarcinoma, non-epithelial tumors (i.e., granular cell tumors, leiomyomas, and neuroendocrine tumors) or undetermined tumors.

Open in New Tab   Full Size Figure   Download Figure

Figure 1 Study design, evaluating the use of the stag beetle knife for esophageal endoscopic submucosal dissection. ESD: Endoscopic submucosal dissection; HGIN: High-grade intraepithelial neoplasia; SCC: Squamous cell carcinoma.

All patients were informed of the risks and benefits of ESD and provided written informed consent. ESD was contraindicated in patients with serious comorbidities, distant metastasis, or massive submucosal invasion.

ESD procedures were performed by four board-certified endoscopists of the Japan Gastroenterological Endoscopy Society, three with no previous conventional esophageal ESD experience and one with low experience (10 cases). Patients received intravenous nitrazepam for sedation, and cardiorespiratory function was monitored throughout the procedure. A single-channel endoscope equipped with a water jet (GIF-H260Z; Olympus Corp, Tokyo, Japan) and attached transparent tip hood was routinely used, along with carbon dioxide insufflation. Initially, the outside margin of each lesion was marked using argon plasma coagulation in forced coagulation mode; the esophageal mucosa was injected with 0.4% sodium hyaluronate (MucoUp; Seikagaku Corp., Tokyo, Japan) mixed with a small amount of indigo carmine. Circumferential excision was then carried out with the SB Knife Jr (4.5-mm opening width, 3.5-mm length; Sumitomo Bakelite Co.) (Figure 2). For submucosal dissection, the SB Knife Short (6-mm opening width, 6-mm length) (Figure 2) was often preferred, because detachment/peeling of the submucosa was faster, and it was less likely to engage the muscular layer, given the curved shape of the blade. The SB knife allowed grasping of the targeted segment, which was then cut using a high-frequency generator (VIO300D; ERBE, Tubingen, Germany) in the endo-cut Q mode (effect 1) for incising mucosa and dissecting submucosa. The soft coagulation mode (effect 5.40 W) was used for hemostasis. If repeated coagulation was required, hemostatic forceps (Coagrasper; Olympus Corp.) were applied to facilitate endoscopic hemostasis. The procedure was continued until resection was completed (Figure 3).

Open in New Tab   Full Size Figure   Download Figure

Figure 2 Features of the stag beetle Knife Jr and short devices.

Open in New Tab   Full Size Figure   Download Figure

Figure 3 Stag beetle knife used for esophageal endoscopic submucosal dissection in a 79-year-old man. Endoscopic appearance of a 35-mm, depressed lesion in the middle one-third of the esophagus (A) under white light (B) on a scatter image with Lugol’s iodine applied (C) with argon plasma coagulation markings; D and E: Use of the SB Knife Jr for full-circumferential incision; use of the SB Knife Short for (F) submucosal dissection and (G) hemostasis; H: En bloc resection of the lesion; I: Ulcer floor after resection.

In instances of semi-circumferential or circumferential ESD, intralesional diluted triamcinolone acetonide injected on postoperative day 2 [Kenacort (40-80 mg); Bristol-Myers Squibb Co., New York, NY, United States] or oral prednisolone (30 mg/d) was prescribed and tapered gradually over several weeks[25] to prevent postoperative stricture[26,27].

Resected specimens were immediately fixed in 10% buffered formalin, with samples later selected for routine processing, embedding in paraffin, and slide preparation (3-4 μm, hematoxylin & eosin stain). The histotype, depth of invasion, and resection margins (vertical and lateral) of the lesions were assessed microscopically (Figure 4) using an optical micrometer to measure invasive areas. The tumor size, anatomic location (upper one-third, middle one-third, or lower one-third of the esophagus), and extent (%) of esophageal circumferential involvement were documented. Rates of en bloc resection, histologically complete resection (i.e., en bloc resection with negative lateral and vertical margins), and curative or non-curative resection served as indices of therapeutic success. Curative resection was defined as complete tumor resection with invasion ≤ 200 μm below the deep border of the lamina muscularis mucosae and no lymphovascular involvement[8].

Open in New Tab   Full Size Figure   Download Figure

Figure 4 Formalin-fixed specimen sliced at 2-mm intervals for routine processing and slide preparation (A); Evaluation of the histotype, invasion depth, and vertical/lateral resection margins (B-D).

Immediate adverse events such as perforation, delayed bleeding, and postoperative pneumonia and delayed adverse events such as esophageal stricture were recorded.

To monitor patients, esophagogastroduodenoscopy was performed 3-6 mo and 1 year following ESD and annually thereafter; computed tomography was also performed annually. Three- and 5-year overall survival rates were assessed for the entire study cohort. SENs detected > 1 year after curative resection by ESD were considered metachronous cancers. Cumulative overall metachronous cancer rates during the 3- and 5-year periods were also assessed.

Continuous variables were expressed as a mean ± standard deviation or median and range, as appropriate, and categorical variables as frequency or number of occurrences. Kaplan-Meier curves were generated to analyze survival and metachronous cancer rates. A log-rank test was used to evaluate the significance of differences between curves, and a P value of less than 5% was considered significant. All statistical analyses were performed using JMP software (SAS Institute, Inc., Cary, NC, United States).

A total of 96 SENs in 70 patients qualified for analysis. One subject was excluded, having received a final diagnosis of nonepithelial tumor, and 4 subjects were excluded, having received a final diagnosis of adenocarcinoma (Figure 1). Fifteen patients had multiple lesions, harboring two (n = 9), three (n = 3), four (n = 1), or five (n = 2) lesions. Mean age of the study population (n = 70; 84% men) was 67 ± 10 years (Table 1). By location, 11% of lesions involved the upper one-third of the esophagus, 55% the middle one-third, and 34% the lower one-third. Macroscopically, majority of the lesions were depressed (90%) rather than elevated (7%) or flat (2%).

Resected specimens measured 33 ± 14 mm on average, with a mean tumor size of 24 ± 13 mm. Most tumors (61%) involved < one-half of the esophageal luminal circumference. Histopathological diagnoses were as follows: dysplasia/intraepithelial neoplasia (22%), or SCC (78%). Typically, invasive SCCs were limited to the lamina propria mucosae (41%), with SM2 or deeper infiltration accounting for 19% (Table 1).

Short-term outcomes are summarized in Table 2. The median procedural time was 60 min (range, 25-305 min). Rates of en bloc resection, histologically complete resection, and curative resection were 100%, 95%, and 81%, respectively.

All lesions were safely resected without any unintentional incisions/perforations or delayed bleeding episodes. Pneumonia was observed in 3% of patients and managed through antibiotic treatment. To prevent postoperative stricture after semi-circumferential ESD, intralesional injection of triamcinolone acetonide (3 patients) or oral prednisolone (7 patients) was administered. Esophageal strictures were encountered in seven patients, one requiring balloon dilatation (Table 2).

Curative resection was achieved in 57 patients, three of whom received additional chemoradiotherapy (CRT). One of these three patients later developed metachronous cancer. Seven of the 54 patients who were given no additional treatment also developed metachronous cancers. The 3- and 5-year cumulative rates of metachronous cancer in patients with curative resections were 14% and 26%, respectively (Figure 5A). Non-curative resection was achieved in 13 patients, seven of whom underwent additional treatment, either surgery (n = 4), chemotherapy (n = 1), or CRT (n = 2). No instances of local recurrence or metastasis were observed in any patient during the mean follow-up period of 35 ± 23 mo.

Open in New Tab   Full Size Figure   Download Figure

Figure 5 Long-term outcomes and survival analysis. A: Cumulative metachronous cancer rates in patients with curative resection; B: Kaplan-Meier analysis of overall survival rates in all patients; C: Patients grouped according to curative and non-curative resection.

Three- and 5-year overall survival rates for the study cohort were 83% and 70%, respectively (Figure 5B), with corresponding rates of 85% and 75% in curative resections, and 74% and 49% in non-curative resections (Figure 5C). However, the difference in survival between curative and non-curative resections by ESD was not statistically significant. Eleven of 70 patients (curative resections, 8/57; non-curative resections, 3/13) died during follow-up. In patients with curative resections, causes of death included isolated instances of unknown primary cancer, hepatocellular carcinoma, lung cancer, pharyngeal carcinoma, drowning, and aspiration pneumonia, as well as two instances of interstitial pneumonia. Causes of death after non-curative resection were oropharyngeal carcinoma, liver cirrhosis, and aspiration pneumonia, each a single occurrence. None of the deaths was directly attributable to esophageal neoplasms.

Several conventional endoscopic submucosal dissection (ESD) devices have been utilized for esophageal ESD. The thin wall with no serosa and narrow lumen of the esophageal wall make ESD more challenging in the esophagus. The restricted endoscopic maneuvering required with conventional ESD devices is also problematic owing to lack of fixation to targets and the fact that these devices are partially or entirely uninsulated. These factors can lead to unintentional incisions, increasing the potential risk of adverse events such as perforation and mediastinal emphysema.

The stag beetle (SB) knife, with its ability to grasp, assess, and then cut the targeted tissue allows endoscopists to maintain adequate dissection planes, preventing inadvertent injury to the muscular layer for safe ESD. Because of these advantages, the SB Knife is gaining acceptance, but relevant long-term outcome data is limited.

The aim of this study was to investigate use of the SB knife for ESD of early esophageal neoplasms, assessing both feasibility and safety. The subsequent short- and long-term clinical outcomes were examined as well.

We retrospectively reviewed 70 consecutive patients with 96 early esophageal neoplasms (HGIN/SCC) treated using ESD. An SB knife was used routinely in all procedures. Clinicopathologic characteristics of the lesions and rates of procedural adverse events, en bloc and histologically complete resection, overall and tumor-specific survival, and local or distant recurrence were assessed.

The en bloc resection rate was 100%, with 95% and 81% of dissections deemed histologically complete and curative, respectively. All procedures were completed without accidental incisions/perforations or delayed bleeding. During follow-up (mean, 35 ± 23 mo), no local recurrences or metastases were observed. The 3- and 5-year survival rates were 83% and 70%, respectively. The 3- and 5-year cumulative rates of metachronous cancer in the patients with curative resections were 14% and 26%, respectively.

ESD procedures using the SB knife are feasible, safe, and effective for treating early esophageal neoplasms, yielding favorable short- and long-term outcomes. No perforation occurred in our study population, attesting to the innovative design of the SB knife, which allows better control for safer dissection.

The availability of this tool may promote widespread adoption of ESD to treat early-stage cancers of the esophagus. There is a need to conduct RCT studies to compare this new innovative device with established devices.