| Background and Aims:With the development of digestive endoscopy and the emergence of novel ideas, endoscopic submucosal tunnel technique (ESTT) has become a new minimally invasive methods for treating gastrointestinal diseases. During recent years, ESTT has made great developments in clinical practice. The key step of ESTT is to create gastrointestinal submucosal tunnel using endoscopy, which allows for the treatment for lesions involving the mucosal layer, submucosal layer and muscularis propria layer, even organs outside the cavity. Presently, ESTT has increasingly been used for the treatment of esophageal achalasia and gastrointestinal submucosal tumors, the former one known as peroral endoscopic myotomy (POEM) and the latter one known as submucosal tunnel endoscopic resection (STER). With regard to POEM and STER, a few authors reported their clinical effectiveness and safety; and compared to laparoscopy and open surgery, these two techniques were performed through the mouth instead of creating skin wound. Therefore, they can be called more minimally invasive treatment. But because of its high technological demanding and high complication rates, only a few large digestive endoscopy center in the world can carry out these two operations. Based on that, this research was performed to assess the clinical effectiveness and safety of POEM and STER for achalasia and upper gastrointestinal submucosal tumors, explore a novel and applicable training methods for POEM procedure, compare different devices in POEM and STER operations, investigate the methods of shortening POEM operation time and decreasing the complications, and compare the safety and efficacy of STER and video-assisted thoracoscopic surgery in the treatment of esophageal submucosal tumors.Materials and Methods:1. Peroral Endoscopic Myotomy For Treating Achalasia Performed By a Gastroenterologist:4 Years’Experience From a Single Endoscopy CenterBetween June 2011 to November 2015, POEM was performed in 153 consecutive patients with achalasia. POEM procedure consisted of the following step: firstly, submucosal tunnel was created and extended below the lower esophageal sphincter (LES) onto the gastric cardia after a mucosal incision was made; then endoscopic myotomy of circular muscle bundles was done; finally, the mucosal entry was closed by hemostatic clips. The Eckardt score and manometry were used to evaluate the outcomes.2. Feasibility and Safety of Peroral Endoscopic Myotomy for Achalasia After Failed Endoscopic InterventionsData on all patients undergoing POEM treatment of achalasia were collected prospectively. We enrolled 61 patients who underwent peroral endoscopic myotomy for achalasia between July 2011 and January 2014. The preoperative intervention group included patients who had undergone botulinum toxin injection or pneumatic balloon dilation before peroral endoscopic myotomy. The preoperative, operative, and short-term outcome data between the groups were compared.3. Comparison of Conventional versus Hybrid Knife Peroral Endoscopic Myotomy Methods for Esophageal Achalasia:A Case-Control StudyBetween June 2012 and July 2014,31 patients underwent POEM using Hybrid knife in our department (HK group), and 36 patients underwent POEM using conventional method (injection needle and triangular tip knife, TT group). Procedure-related parameters, symptom relief, adverse events were compared between two groups.4. Peroral Endoscopic Short versus Long Myotomy For the Treatment of Achalasia:A Case-Control StudyBetween July 2011 and September 2014,20 patients underwent peroral endoscopic short myotomy (myotomy length≤ 7 cm) in our department. These patients were matched by age, gender, symptoms duration, Eckardt score, and LES pressure with 48 patients who underwent long myotomy (myotomy length> 7 cm). Procedure-related parameters, manometry outcomes and complications were compared between the two groups.5. Peroral Endoscopic Shorter Myotomy for the Treatment of Sigmoid-Type Achalasia:A Preliminary StudyBetween July 2012 and November 2014, four consecutive achalasia patients (4 male, with a median age of 41.5 years) with sigmoid esophagus underwent peroral endoscopic shorter myotomy (myotomy length< 7 cm) in our department. Diagnosis was based on symptoms, manometry, radiology and endoscopy. Preoperative and postoperative symptoms scores, manometry outcomes and quality of life scoring of achalasia were recorded and analyzed.6. Usefulness of Peroral Endoscopic Myotomy for Treating Achalasia in Children:Experience of A Single-Center in ChinaBetween July 2012 and August 2014, five consecutive pediatric patients (2 female and 3 male, with a median age of 15.2 years) with achalasia underwent POEM in our center. Diagnosis was based on symptoms, manometry, radiology and endoscopy. Preoperative and postoperative symptoms scores, and manometry outcomes were recorded and analyzed.7. Factors Predicting the Technical Difficulty of Peroral Endoscopic Myotomy for AchalasiaA total of 105 cases of achalasia treated by POEM from April 2011 to September 2014 were analyzed. Difficult cases of POEM were defined as procedure time> 90 min, occurrence of adverse events, including mucosal perforation, pneumothorax and major bleeding. Univariate and multivariate logistic regression analyses were performed to assess the predictive factors of difficult POEM.8. A stepwise approach of peroral endoscopic myotomy for treating achalasia: from animal models to patientsA total of five ex-vivo porcine esophagus-stomach training models were created and POEM was performed. Then,25 patients with achalasia were treated similarly. The Eckardt score, barium esophagram, and high-resolution manometry were used to evaluate its efficacy.9. Submucosal Tunnel Endoscopic Resection for Upper GI Submucosal Tumors Originating From the Muscularis Propria Layer:A Single-Center StudyBetween January 2012 and January 2015, patients with SMTs were enrolled in this study. Demographic data, clinical data, outcome of treatment were collected and analyzed.10. Submucosal Tunnel Endoscopic Resection of Upper Gastrointestinal Submucosal Tumors:A Comparative Study of Hook knife versus Hybrid knifeBetween August 2012 and February 2015, STER was performed for 61 upper GI submucosal lesions. Of these,24 lesions were treated by HO (HO group), whereas 37 lesions were treated by HK (HK group). Data regarding to patients baseline characteristics and clinical outcomes were compared between the two groups.11. Submucosal Tunnel Endoscopic Resection Versus Thoracoscopic Enucleation of Esophageal Submucosal Tumors:A Case-Control StudyThe medical records of 106 consecutive patients with esophageal SMTs, who underwent STER or TE in a single institution from Feb 2011 to Feb 2015, were retrospectively analyzed. The data regarding to clinical characteristics, histopathologic features, complications and others were assessed.Results:1. POEM was successfully performed in all cases. Mean procedure time was 51.3 ± 16.6 min and mean myotomy length was 8.4 ± 3.3 cm. Mucosal perforations occurred in 6 (3.9%) patients during submucosal tunnel creation, major bleeding occurred in 9 (5.9%) patients, and 7 (4.6%) patients suffered pneumothorax immediate after procedure. All the complications were managed conservatively. During a mean follow-up period of 25 months (range 6-59.4 months), treatment success was achieved in 124/133 patients (93.2%). Mean LES pressure was 45.1 mmHg and 15.3 mmHg before and after the procedure (P= 0.000), respectively. Mean Eckardt score was 8.3 and 1.4 before and after POEM, respectively (P= 0.000).23 patient (17.3%) developed mild reflux symptoms and required intermittent medication with proton pump inhibitors during the follow-up.2. Among preoperative intervention group, twenty-two patients received endoscopic therapy before being referred for operation (18 dilation only,2 botulinum toxin only, and 2 both treatments). Procedure time in the preoperative intervention group was similar to the non-preoperative intervention group (60.8 ± 30.9 vs.62.0± 21.0 min, P= 0.863). Both groups demonstrated significant improvement in Eckardt scores and manometric outcomes at 1 year follow-up. There were no significant differences in pre-and post-treatment D-values of symptom scores and lower esophageal sphincter pressures between groups (6.2±2.2 vs.6.1±1.8, P= 0.840; 27.9±17.6 vs.24.9±15.2; P= 0.569). There was also no significant difference in the incidence of intraoperative complications (P= 0.958) and gastroesophageal reflux rate (23.5% vs.20.0%, P= 0.771) between the two groups.3. There were no significant differences in the age, sex and other baseline characteristics between the two groups. The mean procedural times were significantly shorter in HK group than TT group (53.0 ± 17.2 min vs.67.6 ± 28.4 min, P=0.015). The mean frequency of devices exchange was 4.7 ± 1.7 in HK group and 10.9±1.8 in TT group (P=0.000). No serious adverse events happened postoperatively in both groups. At 1-year’ follow up, a total of 94.0% treatment success was achieved in all patients (93.5% in HK group and 94.4% in TT group, P=0.877).4. There was no significant differences in baseline characteristics between the two groups. Mean myotomy length was 6.0±0.6 cm in short myotomy group, and 11.3±2.7 cm in long myotomy group (P= 0.000). The mean operation time was significantly shorter in short myotomy group than long myotomy group (49.7 ± 19.6 min vs.66.3± 25.6 min, P= 0.011). During 1 year’follow-up, treatment success (Eckardt score≤ 3) was achieved in 90.0%(18/20) of patients in short myotomy group and 91.7%(44/48) of patients in long myotomy group (P= 0.827). There was also no statistical difference in the incidence of intraoperative complications (9.5% vs.10.7%, P= 0.211) and gastroesophageal reflux diseases (15.0% vs.12.5%, P= 0.728) between the two groups.5. All achalasia patients had dysphagia as their chief presenting complaint with a median duration of 23 (range 18-35) months. Procedure was performed successfully in all patients, and the median time required for the procedure was 53 minutes (range 45-70 minutes). There were no mortality and no major postoperative complications. The median length of myotomy was 5 cm (range 5-6 cm). At 1-year follow-up, treatment success (Eckardt score≤3) was achieved in all patients. There was a significant improvement of symptoms relief, lower esophageal sphincter pressure decrease and quality of life. Symptoms of gastroesophageal reflux occurred in no patient.6. Procedure was performed successfully in all patients, and the mean time required for the procedure was 56 minutes (range 40-90 minutes). There were no mortalities and no serious intraoperative and postoperative complications. The mean length of myotomy was 8.4 cm (range 6-11 cm). During a mean follow-up period of 18.6 months, treatment success (Eckardt score≤3) was achieved in all patients. There was a significant improvement of symptoms relief, dysphagia score and lower esophageal sphincter pressure decrease (all:P<0.01) after POEM. No patient developed gastroesophageal reflux disease.7. POEM was successfully completed in all the patients and no one was converted to laparoscopy. The number of cases with procedure time≥90 min was 17. Mucosal perforations occurred in 6 (5.7%) patients during submucosal tunnel creation, major bleeding occurred in 7 (6.7%) patients, and 6 (5.7%) patients suffered pneumothorax immediate after procedure. All the complications were managed conservatively. No other intraoperative and immediate postoperative complications, including infections, pneumoperitoneum, occurred. Multivariate analysis showed that early period (odds ratio [OR] 4.173,95% confidence interval [95% CI] 1.36-6.829, P= 0.023), and triangular tip knife ([OR] 6.712, [95% CI] 1.479-30.460, P= 0.014), were independent factors associated with technical difficulty regarding to longer procedure time (procedure time≥90 min).8. POEM procedures were completed in five stomach-esophagus models, with perforations in the initial three and success in the last two. A total of 36 achalasia patients (22 males,14 females) with achalasia successfully underwent POEM. The mean operation time was 72.8 min (range,45-180 min). There were major complications in three patients:one case of severe bleeding and two cases of pneumothorax, which were both treated successfully. During the follow-up period, the median Eckardt score decreased dramatically from 8 to 1 (p= 0.000). The lower basal esophageal sphincter pressure decreased markedly (36.1 ± 14.3 vs.11.9 ± 4.6 mmHg, p=0.000), as well as the 4-s integrated relaxation pressure (12.9 ± 13.0 vs. 6.6 ± 2.9 mmHg, p= 0.000).9.71 SMTs originating from the muscularis propria (MP) layer were identified in 70 patients. All patients underwent STER procedure successfully. Mean procedure time was 49.1 ± 29.3 minutes, and mean tumor size was 18.8 ± 7.2 mm. Among all lesions, the majority (69.0%) located in the esophagus,12.7% in the cardia and 18.3% in the stomach. Complete resection rate was achieved in 68 (95.8%) lesions. Perforation occurred in 3 patient (4.3%), which was treated by endoclips. Pneumothorax occurred in 2 patients (2.9%) and was managed by thoracic drainage successfully. During a median follow-up of 17.2 months, patients were free of local recurrence or distant metastasis.10. The mean procedure time was significantly shorter in HK group than HO group (42.7±22.5 min vs.57.5±25.7 min, P=0.026). The mean frequency of device exchange was 3.3±0.6 in HO group and 1.4±0.6 in HK group (P< 0.001). The complication rate was similar between two groups (P= 0.151). During the follow-up time, no recurrence occurred in two groups.11. There was no difference of sex ratio, age and other baseline characteristics between STER and TE group. All tumors were resected successfully in both groups. Mean tumor size in STER group was 17.7 ± 6.6 mm, which was smaller than TE group (26.1 ± 18.5 mm, P=0.004), and number of tumor larger than 20 mm in STER was also less than TE group (n=7 vs.25, P=0.008). However, the operation time in STER group was much shorter than TE group (47.5±28.5 min vs.128±53 min, P<0.000). Compared to STER, TE were associated with a higher complication rate (32.2% vs.4.2%, P=0.003), and longer hospital stays (13.9 ± 4.5 vs.5.5 ± 1.5, P<0.000).Conclusion:1. Our study demonstrated that POEM is a safe, and effective treatment for achalasia during the long-term follow-up. Further studies are warranted to evaluate the efficacy and to compare POEM with other treatment modalities.2. Our study demonstrated that POEM is safe and effective, even for treating achalasia in the setting of failed endoscopic interventions.3. Hybrid knife in POEM can shorten the procedural time, and achieve similar treatment success rate compared to TT.4. Peroral endoscopic short myotomy is comparable with long myotomy for achalasia with regard to clinical efficacy and safety, and can shorten the procedure time.5. In this study, peroral endoscopic shorter myotomy is effective and safe in patients with sigmoid-type achalasia. Further studies are warranted to prove its long-term efficacy in comparison to other treatment modalities.6. Our study suggests that POEM is a safe and effective technique for treating pediatric achalasia. Further studies with long-term follow up in large-volume pediatric patients are warranted to clearly define the durability of the procedure.7. POEM is safe for the treatment of esophageal achalasia. Triangular tip knife and early period were independent risk factors for longer procedural time.8. The ex-vivo porcine esophagus-stomach can be used as simple and cheap training model that mimics the POEM procedure. POEM is a safe and effective therapy for achalasia patients.9. Our results demonstrated the feasibility and safety of STER for treating upper GI SMTs originating from the MP layer. Large-scale comparative studies with other treatment methods should be conducted in the future.10. Our study demonstrated for the first time that HO and HK do not differ in terms of efficacy or complication rates, but HK can reduce frequency of device exchange and procedure time.11. Our results indicated that both of STER and TE techniques are effective and safe for treating esophageal SMTs, and TE is more useful for larger SMTs in comparison to STER, but accompanying with longer procedure time, higher complication rate and longer hospital stays. Further randomized trials are warranted to compare the long-term efficacy and safety of these two treatment methods. |
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