Clinical experience of using a novel self‐help inflatable balloon to prevent esophageal stricture after circumferential endoscopic submucosal dissection

Although endoscopic submucosal dissection (ESD) is gradually becoming a first‐line treatment for superficial esophageal neoplasms (SEN), strictures occur in almost 100% of cases after circumferential ESD. A standard method to prevent stricture has not been established. Thus, we propose a novel self‐help inflatable balloon to prevent stricture. The new balloon was used by the patients themselves at home (4–5 times a day, duration of each procedure was approximately 15–20 min), and was removed when the defects were almost healed. From January 2018 to September 2018, eight patients who received circumferential ESD for SEN and underwent a novel self‐help inflatable balloon to prevent stricture were enrolled. Median size of the mucosal defects was 76.3 mm (range: 50–90 mm). Median time for removing the self‐help inflatable balloon was 94.6 days (range, 71–119 days). Only one (12.5%) patient experienced stricture, and three endoscopic balloon dilation sessions were carried out for this patient. All patients tolerated the balloon well, and none experienced perforation or delayed bleeding. The self‐help inflatable balloon seems to show a high preventive effect against stricture in patients whose mucosal defect was no longer than 100 mm in length after esophageal circumferential ESD. This method is economic, feasible, and safe.     

Risk factors of postoperative stricture after endoscopic submucosal dissection for superficial esophageal neoplasms: A meta-analysis

Background:As larger-sized superficial esophageal neoplasms became candidates for endoscopic submucosal dissection (ESD), post-ESD esophageal stricture has inevitably developed into a significant complication during long-term follow-up.Method:The PubMed, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Web of Science, as well as China National Knowledge Infrastructure, the Wanfang Database, and the Chinese Biomedical Literature Database, were searched to identify all the appropriate studies published from January 2000 through October 2019. For risk factor assessment between postoperative stricture and control groups, pooled odds ratios (OR) and weighted mean differences (WMD) estimation was done. All meta-analytical procedures were conducted by using Stata version 15.1 software.Results:The results showed that 11 studies with 2248 patients (284 structure cases and 1964 controls) were eligible for this meta-analysis. Statistical results indicated 6 substantial risk factors: lesion characteristics involving the upper third of the esophagus (OR 1.51, [1.02–2.25]), macroscopic type of IIa/IIc (OR 2.76, [1.55–4.92]), tumor depth of invasion above m1 (OR 7.47, [3.31–16.86]), and m2 (OR 12.67, [4.00–40.10]), longitudinal length (WMD 13.75 mm, [7.76–19.74]), circumferential diameter (WMD 10.87 mm, [8.13–13.60]), and circumferential range >3/4 (OR 38.17, [9.94–146.52]). Each additional 10% of the circumferential range increased the risk of stricture by 149% (OR 9282.46, [978.14–88089.35]).Conclusions:Six risk factors were assessed to have a key role in the elevated risk levels of post-ESD esophageal stricture. The results can help doctors identify patients with increased risk and thus can guide management of the adequate period of surveillance after ESD and take available approaches of stricture prevention.     

Endoscopic radial incision and cutting method for refractory esophageal stricture after endoscopic submucosal dissection of superficial esophageal carcinoma

A 59‐year‐old woman and a 69‐year‐old man had esophageal strictures that were refractory to over 10 therapeutic attempts with endoscopic balloon dilation (EBD) after endoscopic submucosal dissections (ESD) for superficial esophageal carcinoma (SEC). The strictured lesions in both patients improved remarkably with a new endoscopic modality (endoscopic radial incision and cutting [ERIC]), which was carried out one to three times, and stricture recurrence was not noted throughout the follow‐up period. ERIC is a safe and efficient method for treating refractory strictures after EBD caused by ESD for SEC.     

Clinical experience of esophageal perforation occurring with endoscopic submucosal dissection

Esophageal perforation occurring during or after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is a rare, but serious complication. However, reports of its characteristics, including endoscopic imaging and management, have not been fully detailed. To analyze and report the clinical presentation and management of esophageal perforations occurred during or after EMR/ESD. Four hundred seventy‐two esophageal neoplasms in 368 patients were treated (171 EMR; ESD 306) at Northern Yokohama Hospital from 2003 to 2012. Esophageal perforation occurred in a total of seven (1.9%) patients, all of whom were male and had undergone ESD. The etiology of perforation was: three (42.9%) intraoperative; three (42.9%) balloon dilatation for stricture prevention; one (14.2%) due to food bolus impaction. All cases were managed non‐operatively based on the comprehensive assessment of clinical severity, extent of the injury, and the time interval from perforation to treatment onset. Conservative management included (i) bed rest and continuous monitoring to determine the need for operative intervention; (ii) fasting and intravenous fluid infusion/ tube feeding; and (iii) intravenous antibiotics. All defects closed spontaneously, save one case where closure was achieved by endoscopic clipping. Surgery was not required. Conservative management for esophageal perforation during advanced endoscopic resection is may be possible when there is no delay in diagnosis or treatment. Decision‐making should be governed purely by multidisciplinary discussion.     

Disseminated nocardiosis during systemic steroid therapy for the prevention of esophageal stricture after endoscopic submucosal dissection

An 85‐year‐old man underwent endoscopic submucosal dissection for a large superficial esophageal epithelial neoplasm, which required removal of 95% of the circumference of the esophageal mucosa. Steroids were given orally to prevent esophageal stricture starting on day 3 postoperatively. In the 6th week of steroid treatment, he developed high fever without other symptoms. Chest computed tomography revealed a nodular lesion in the lung. Sputum sample showed Gram‐positive, branching, filamentous bacteria, and a diagnosis of nocardiosis was suspected. Brain magnetic resonance imaging revealed multiple focal lesions which indicated dissemination of nocardiosis. Trimethoprim‐sulfamethoxazole was immediately started, which led to the disappearance of pulmonary and cerebral nocardiosis with alleviation of fever. Recently, oral steroid treatment has been widely used for the prevention of esophageal stricture. However, the present case indicates the risk of life‐threatening infection and the importance of close monitoring of this treatment.     

A reliable nomogram model for predicting esophageal stricture after endoscopic submucosal dissection

Currently, endoscopic submucosal dissection (ESD) has gradually become the diagnosis and treatment of choice for initial esophageal cancer. However, the formation of esophageal stricture after ESD is one of its important complications. In this paper, we intend to identify the risk factors of esophageal stricture to develop a nomogram model to predict the risk of esophageal stricture and validate this model.A total, 159 patients were included in this study, including 21 patients with esophageal stenosis. Multivariate analysis showed that age greater than 60 years, high neutrophil-to-lymphocyte ratio, the extent of esophageal mucosal defect greater than 1/2, and postoperative pathological type of early esophageal squamous cell carcinoma were independent risk factors for predicting esophageal stricture. We constructed a nomogram model to predict esophageal stenosis by these 4 independent predictors.The prediction performance of the model was verified by the area under the receiver operating characteristic curve, the area under the receiver operating characteristic curve of the model was 0.889, and the sensitivity and specificity were 80.00% and 91.28%, respectively, indicating that the prediction performance of the model was good; The calibration curve constructed by internal cross-validation suggested that the predicted results of the nomogram agreed well with the actual observed values.The nomogram model has a high accuracy for predicting esophageal stricture after esophageal ESD and is extremely important to reduce or avoid the occurrence of esophageal stricture. But it needs more external and prospective validation.     

Prevention of esophageal stricture after endoscopic resection

Stricture formation after esophageal endoscopic resection has a negative impact on patients’ quality of life because it causes dysphagia and requires multiple endoscopic dilations. Various methods by which to prevent stricture have recently been developed and reported. Among these methods, local steroid injection is the most commonly used and is currently considered the standard method for noncircumferential resection. However, local steroid injection has a limited effect on circumferential resection. Thus, oral steroid administration is used for such cases because it may have a stronger effect than local injection. Steroid treatment, both by local injection and oral administration, is effective and low‐cost; however, it may cause fragility of the esophageal wall, resulting in adverse events such as perforation during balloon dilatation. Many innovative approaches have been developed, such as tissue‐shielding methods with polyglycolic acid, tissue engineering approaches with autologous oral mucosal epithelial cell sheet transplantation, and stent insertion. These methods may be promising, but they are limited by a scarcity of data. Further investigations are needed to confirm the efficacy of these methods.     

Endoscopic submucosal tunnel dissection for large superficial esophageal squamous cell neoplasms

Endoscopic submucosal dissection (ESD) is a well-established treatment for superficial esophageal squamous cell neoplasms (SESCNs) with no risk of lymphatic metastasis. However, for large SESCNs, especially when exceeding two-thirds of the esophageal circumference, conventional ESD is time-consuming and has an increased risk of adverse events. Based on the submucosal tunnel conception, endoscopic submucosal tunnel dissection (ESTD) was first introduced by us to remove large SESCNs, with excellent results. Studies from different centers also reported favorable results. Compared with conventional ESD, ESTD has a more rapid dissection speed and R0 resection rate. Currently in China, ESTD for large SESCNs is an important part of the digestive endoscopic tunnel technique, as is peroral endoscopic myotomy for achalasia and submucosal tunnel endoscopic resection for submucosal tumors of the muscularis propria. However, not all patients with SESCNs are candidates for ESTD, and postoperative esophageal strictures should also be taken into consideration, especially for lesions with a circumference greater than three-quarters. In this article, we describe our experience, review the literature of ESTD, and provide detailed information on indications, standard procedures, outcomes, and complications of ESTD.     

Development of novel treatment with a bioabsorbable esophageal patch for benign esophageal stricture

Using a large animal model, we examined whether circumferential stricture after esophageal endoscopic submucosal dissection (ESD) can be treated by grafting a bioabsorbable esophageal patch. Circumferential ESD was performed on the thoracic esophagus in pigs (n = 6) to create a stricture, for which one of the following interventions was performed: (1) the stricture site was longitudinally incised, and an artificial esophageal wall (AEW) was grafted after placing a bioabsorbable stent (AEW patch group, n = 3); (2) endoscopic balloon dilation (EBD) was performed every other week after stricture development (EBD group, n = 3). In both groups, esophageal fluoroscopy was performed 8 weeks after the interventions, and the esophagus was excised for histological examination of the patched site. In the AEW patch group, esophageal fluoroscopy revealed favorable passage through the patched site. Histologically, the mucosal epithelium and lamina propria had regenerated as in the normal area. In the EBD group, the circumferential stricture site showed marked thickening, and there were hypertrophic scars associated with epithelial defects on the luminal surface. Histologically, defects of the mucosal epithelium and full‐thickness proliferation of connective tissue were observed. AEW patch grafting was suggested to be a potentially novel treatment strategy for post‐ESD esophageal circumferential stricture.     

Useful strategies to prevent severe stricture after endoscopic submucosal dissection for superficial esophageal neoplasm

The minimal invasiveness of endoscopic submucosal dissection (ESD) prompted us to apply this technique to large-size early esophageal squamous cell carcinoma and Barrett’s adenocarcinoma, despite the limitations in the study population and surveillance duration. A post-ESD ulceration of greater than three-fourths of esophageal circumference was advocated as an important risk factor for refractory strictures that require several sessions of dilation therapy. Most of the preoperative conditions are asymptomatic, but dilatation treatment for dysphagia associated with the stricture has potential risks of severe complications and a worsening of quality of life. Possible mechanisms of dysphasia were demonstrated based on dysmotility and pathological abnormalities at the site: (1) delayed mucosal healing; (2) severe inflammation and disorganized fibrosis with abundant extracellular matrices in the submucosa; and (3) atrophy in the muscularis proper. However, reports on the administration of anti-scarring agents, preventive dilation therapies, and regenerative medicine demonstrated limited success in stricture prevention, and there were discrepancies in the study designs and protocols of these reports. The development and consequent long-term assessments of new prophylactic technologies on the promotion of wound healing and control of the inflammatory/tumor microenvironment will require collaboration among various research fields because of the limited accuracy of preoperative staging and high-risk of local recurrence.     

Endoscopic submucosal dissection for superficial esophageal neoplasms using the stag beetle knife

Endoscopic submucosal dissection (ESD) is an accepted standard treatment for early gastric cancer but is not widely used in the esophagus because of technical difficulties. To increase the safety of esophageal ESD, we used a scissors‐type device called the stag beetle (SB) knife. The aim of this study was to determine the efficacy and safety of ESD using the SB knife. We performed a single‐center retrospective, uncontrolled trial. A total of 38 lesions were excised by ESD from 35 consecutive patients who were retrospectively divided into the following two groups according to the type of knife used to perform ESD: the hook knife (hook group) was used in 20 patients (21 lesions), and the SB knife (SB group) was used in 15 patients (17 lesions). We evaluated and compared the operative time, lesion size, en bloc resection rate, pathological margins free rate, and complication rate in both groups. The operative time was shorter in the SB group (median 70.0 minutes [interquartile range, 47.5–87.0]) than in the hook group (92.0 minutes [interquartile range, 63.0–114.0]) (P = 0.019), and the rate of complications in the SB group was 0% compared with 45.0% in the hook group (P = 0.004). However, the lesion size, en bloc resection rate, and pathological margins free rate did not differ significantly between the two groups. In conclusion, ESD using the SB knife was safer than that using a conventional knife for superficial esophageal neoplasms.     

Predictive factors for esophageal stenosis after endoscopic submucosal dissection for superficial esophageal cancer

Endoscopic submucosal dissection (ESD) has been utilized as an alternative treatment to endoscopic mucosal resection for superficial esophageal cancer. We aimed to evaluate the complications associated with esophageal ESD and elucidate predictive factors for post‐ESD stenosis. The study enrolled a total of 42 lesions of superficial esophageal cancer in 33 consecutive patients who underwent ESD in our department. We retrospectively reviewed ESD‐associated complications and comparatively analyzed regional and technical factors between cases with and without post‐ESD stenosis. The regional factors included location, endoscopic appearance, longitudinal and circumferential tumor sizes, depth of invasion, and lymphatic and vessel invasion. The technical factors included longitudinal and circumferential sizes of mucosal defects, muscle disclosure and cleavage, perforation, and en bloc resection. Esophageal stenosis was defined when a standard endoscope (9.8 mm in diameter) failed to pass through the stenosis. The results showed no cases of delayed bleeding, three cases of insidious perforation (7.1%), two cases of endoscopically confirmed perforation followed by mediastinitis (4.8%), and seven cases of esophageal stenosis (16.7%). Monovalent analysis indicated that the longitudinal and circumferential sizes of the tumor and mucosal defect were significant predictive factors for post‐ESD stenosis (P < 0.005). Receiver operating characteristic analysis showed the highest sensitivity and specificity for a circumferential mucosal defect size of more than 71% (100 and 97.1%, respectively), followed by a circumferential tumor size of more than 59% (85.7 and 97.1%, respectively). It is of note that the success rate of en bloc resection was 95.2%, and balloon dilatation was effective for clinical symptoms in all seven patients with post‐ESD stenosis. In conclusion, the most frequent complication with ESD was esophageal stenosis, for which the sizes of the tumor and mucosal defect were significant predictive factors. Although ESD enables large en bloc resection of esophageal cancer, practically, in cases with a lesion more than half of the circumference, great care must be taken because of the high risk of post‐ESD stenosis.     

The effects of oral steroid duration on stricture prevention after extensive endoscopic submucosal dissection for superficial esophageal cancer

BackgroundEsophageal stricture is a major complication of endoscopic submucosal dissection (ESD) in patients with superficial esophageal cancer (SEC). Oral steroids have been used to prevent esophageal stricture in patients with more than 75% of the esophageal circumference resected. However, there are no established guidelines regarding the optimal duration of steroid use. This retrospective observational study aimed to compare the incidence of esophageal stricture according to the period of prophylactic oral steroid use and to identify the risk factors for esophageal stricture.MethodsEighty-one patients who were prescribed prophylactic steroid after undergoing ESD for SEC with more than 75% of esophageal circumference resected were enrolled. Patients were classified into the four-week steroid group (n=72) or eight-week steroid group (n=9) to compare the incidence of esophageal stricture. In addition, the patients were subdivided into those who developed esophageal stricture (n=24) and those who did not (n=57) to identify the risk factors for esophageal stricture.ResultsTwenty patients (27.8%) in the four-week oral steroid group and four patients (44.4%) in the eight-week oral steroid group developed esophageal stricture (P=0.44). The univariable analysis identified tumor size, longitudinal length of semi-circumferential resection, and proportion of circumferential resection as risk factors of esophageal stricture. The multivariable analysis identified the proportion of circumferential resection as an independent risk factor. After adjusting for the proportion of circumferential resection, the incidence of stricture was marginally higher in the eight-week steroid group [P=0.05; odds ratio (OR): 5.69; 95% confidence interval (CI): 1.01–32.15].ConclusionsEight weeks of oral steroid prophylaxis does not reduce the risk of stricture after extensive ESD more than four weeks of oral steroid prophylaxis. The proportion of circumferential resection is the strongest risk factor for stricture in patients with SEC undergoing ESD.     

Usefulness of clip traction in the early phase of esophageal endoscopic submucosal dissection

Background: The usefulness of clip traction in endoscopic submucosal dissection (ESD) for early esophageal carcinoma was investigated. Methods: A total of 87 patients who underwent ESD for esophageal squamous cell carcinoma were included in the study. The hook knife method was used for ESD. Twenty patients underwent ESD without clip traction (non‐clip group) and 67 underwent procedures in which clip traction was used (clip group). A clip with a string was attached to the oral edge of the lesion after mucosal incision in the clip group. Results: ESD was successful in all cases. Wide exposure of the submucosal tissue below the lesion was obtained by applying tension to the clip traction. The duration of ESD was shorter in the clip group, and there was a significant difference in duration between the non‐clip and clip groups. There were no complications of ESD in the clip group, but muscle layer injury occurred in three patients in the non‐clip group. Conclusion: Clip traction shortens operating time and is safer in esophageal ESD. Clip traction is recommended as a useful auxiliary procedure.