To assess the efficacy and safety of fibrin sealant for closure of mucosal penetration at the cardia during peroral endoscopic myotomy (POEM).

Twenty-four patients who underwent POEM and experienced mucosal injury of the cardia during the procedure were retrospectively identified. Of the 24 patients, 21 had mucosal penetration and 3 had only slight mucosal damage without penetration. The 21 patients with mucosal penetration received fibrin sealant for closure at the site of penetration. Penetration-related characteristics, treatment, and recovery were reviewed for all 21 patients to assess the efficacy and safety of fibrin sealant for closure of mucosal penetration at the cardia. Clinical data, including general characteristics, procedure-related parameters, Eckardt scores, lower esophageal sphincter pressures (LESP), and esophagogastroduodenoscopy (EGD) results, were analyzed to determine their influence on treatment success after mucosal penetration during POEM.

All 21 patients had a solitary mucosal penetration in the cardia (12 in esophageal region of the cardia, 9 in the stomach region of the cardia, and 1 in both the esophageal and stomach regions). Twelve had a hole-like penetration and 9 had a linear penetration. For those with a hole-like penetration, the mean size was 0.14 cm² (0.02-0.32 cm²). For those with a linear penetration, the median size was 0.37 cm (0.10-1.00 cm). Closure of the mucosal penetration using fibrin sealant was performed successfully in all 21 patients (two patients required 5 mL fibrin sealant, and the remaining 19 patients required 2.5 mL). Two patients had a nasogastric tube placed for five days after POEM; the remaining 19 patients were kept fasting for 3 d. All 21 patients were discharged after a median of 5 d (range: 5-7 d) postoperatively. During a median 42 mo (range: 9-62 mo) follow-up, all 21 patients with a mucosal penetration successfully healed without the occurrence of infection, ulcer, or esophagitis. Furthermore, the median LESP decreased from 31.9 mmHg (range: 21.9-67.1 mmHg) preoperatively to 20.3 mmHg (range: 6.0-41.0 mmHg) postoperatively (P < 0.05). The median preoperative and postoperative Eckardt scores were 5.0 (range; 4-10) and 1.0 (range: 0-4), respectively (P < 0.05). Of the 21 patients with mucosal penetration, symptom remission, which is defined as a postoperative Eckardt score ≤ 3, was achieved in 20 patients (95.2%) indicating that mucosal penetration did not influence the success of POEM treatment if closed successfully using fibrin sealant.

Fibrin sealant is safe and effective for closure of mucosal penetration during POEM. Mucosal penetrations do not appear to influence the treatment success of POEM if closed successfully using fibrin sealant. Additional studies regarding the feasibility, efficacy, and safety of fibrin sealant for closure of larger mucosal penetrations is warranted.

Peroral endoscopic myotomy (POEM) is an effective and safe procedure for achalasia, and is becoming one of the first-line therapies to treat achalasia[1-4]. However, some major perioperative adverse events after POEM have been reported; mucosal penetration is one of the most dangerous adverse events[1,2,5,6]. Mucosal penetration has been reported to occur in 4.2%-17.3% of POEM procedures[1,2,5,7]. Different studies have reported on different treatment strategies, including observation without special treatment, sealing of the penetration injury by hemostatic clips, and closing the penetration defect using fibrin sealant[8,9]. Mucosal penetration usually occurs at the cardia, where a myotomy is performed during POEM. We previously reported the usage of fibrin sealant for mucosal penetration at the cardia in two cases in 2012[7]. However, long-term outcomes with a larger population are needed to further assess this treatment strategy. To the best of our knowledge, there is still no evidence regarding the treatment response to fibrin sealant for mucosal penetration during POEM in a larger cohort. The purpose of the present study was to evaluate the efficacy and safety of fibrin sealant for closure of mucosal penetration at the cardia during POEM.

Esophageal achalasia is an esophageal motility disorder of unknown cause and is characterized by failure of the LES to relax and impaired peristalsis of the esophageal body[10]. Conventional therapies for achalasia include pharmacological therapy, endoscopic balloon dilation, and Heller-Dor surgery. With recent advances in endoscopic treatment techniques and devices, Inoue et al[9] have developed peroral endoscopic myotomy, in which the myotomy is performed through a submucosal tunnel. Excellent long-term outcomes after POEM have been reported[1,2], and POEM is expected to become a first-line therapy for achalasia requiring surgical intervention. However, some major perioperative adverse events from POEM have also been reported, with mucosal penetration being one of the most dangerous adverse events[1,2,5,6]. Mucosal penetration during POEM occurs at a rate ranging from 4.2%-17.3% depending on the study[1,2,5,7]. Treatment for this complication has varied, with some patients undergoing observation without special treatment, being sealed by multiple clips or an endoscopic suture device (OverStitch™ Endoscopic Suturing System; Apollo Endosurgery Austin, Texas), or being treated with the defect being closed using fibrin sealant[11-15]. Closure using hemostatic clips is not an ideal method. Once target mucosa is clipped, adjacent mucosa has the tendency to spontaneously split, making it hard to completely seal the penetration. Using endoscopic suture with the OverStitch system is usually considered when the mucosal penetration is large and difficult to close using conventional clips.

We first reported the usage of fibrin sealant for closure of mucosal penetration at the cardia in two cases in 2012[7]. The present study further supports the efficacy and safety of fibrin sealant for closure of mucosal penetration, including long-term follow-up in a larger population (21 patients). The biggest risk of mucosal penetration is that the fluids from the stomach or the esophagus could flow into the submucosal tunnel or the mediastinum and cause tunnel-infection, ulceration, esophagitis, mediastinal leak, or peritoneal leak[15,16]. In our study, all 21 mucosal penetrations healed successfully without tunnel-infection, ulceration, esophagitis, mediastinal leak, or peritoneal leak occurring. Of note, all 21 mucosal penetrations in the present study occurred at the cardia; one explanation for this might be that the small operating space and abundant submucosal vessels that demand repeated electrocoagulation during the POEM procedure make the mucosa in this area vulnerable. We presented the healing process of the mucosa after being closed using fibrin sealant (Figure 4). During a median 42 mo (range, 9-62 mo) follow-up, all patients had completely healed.

The required amount of fibrin sealant to adequately cover the mucosal injury was based on the size of the penetration; the endoscopist must ensure that the penetration is fully covered. In this cohort, we utilized 5 mL of fibrin sealant in the first patient with penetration because of lack of experience using this technique. Another patient who had a longer linear penetration (1.0 cm) consumed 5 mL fibrin sealant. The remaining 19 cases only required 2.5 mL. Of note, for penetration injuries that create larger defects, which are difficult to close using only fibrin sealant, it is suggested that one or two hemostatic clips be used to make a preliminary clipping that approximates the edges of the mucosal defect before then using fibrin sealant to fully cover the hole. Nasogastric tubes were placed postoperatively in the first two cases with penetration, again due to lack of experience with patient recovery from this technique. However, the remaining 19 cases did not require a nasogastric tube and had excellent healing results, suggesting that the postoperative placement of a nasogastric tube is not necessary in cases with a relatively small penetration.

The treatment outcomes of POEM for the 21 patients with mucosal penetration were excellent, with a 95.2% treatment success (Eckardt score ≤ 3), a 14.3% rate of gas-related complications, and a 14.3% rate of post-POEM esophagitis, indicating that mucosal penetration did not influence the treatment success of POEM if closed successfully using fibrin sealant.

Given that the sizes of the mucosal penetrations in this study were all relatively small, it is not clear whether the defects could have been observed and would have closed spontaneously. Therefore, a prospective randomized controlled trial comparing observation without special treatment to treatment with fibrin sealant is warranted. In previous studies evaluating intraoperative mucosal penetration during POEM, the injured mucosa could be closed only by prolonged fasting in those who received inner circular muscle myotomy. In the present study, 10 patients had an inner circular muscle myotomy, 1 had a full-thickness myotomy, 1 had a glasses-style anti-reflux myotomy, and 9 had a progressive full-thickness myotomy. Further research is needed to determine if the injured mucosa was more likely to close spontaneously in those who received inner circular muscle myotomy than in those who received a full-thickness myotomy. Our study is not without limitations. One limitation was that the submucosal defects in our study were all relatively small, so we cannot draw conclusions regarding the feasibility, efficacy, and safety of fibrin sealant in closing large mucosal penetrations. Additionally, with a small sample size of only 21 patients, we were not able to stratify our results to draw conclusions regarding the required amount of fibrin sealant based on the penetration size. Another limitation is that this was a single center study, suggesting that our results may not be representative of findings in other hospitals. However, to the best of our knowledge, this is the largest published study regarding the treatment response to fibrin sealant for mucosal penetration during POEM, incorporating data from 21 patients. The present study also provides instruction regarding the usage of fibrin sealant for penetration closure for endoscopists, which may be especially helpful for those who are unfamiliar with the technique or who might be worried about mucosal penetrations during POEM.

In conclusion, the use of fibrin sealant to close mucosal penetration during POEM is safe and effective. Mucosal penetrations do not appear to influence the treatment success of POEM if closed successfully using fibrin sealant. However, further research regarding the feasibility, efficacy, and safety of fibrin sealant for closing larger mucosal penetrations is warranted.