Mei-Dong Xu

Peroral endoscopic remyotomy for failed Heller myotomy: a prospective single-center study.

BACKGROUND AND STUDY AIMS Recurrence/persistence of symptoms occurs in approximately 20 % of patients after Heller myotomy for achalasia. Controversy exists regarding the therapy for patients in whom Heller myotomy has failed. The aim of the current study was to evaluate the efficacy and feasibility of peroral endoscopic myotomy (POEM), a new endoscopic myotomy technique, for patients with failed Heller myotomy. PATIENTS AND METHODS A total of 12 patients with recurrence/persistence of symptoms after Heller myotomy, as diagnosed by established methods and an Eckardt score of ≥ 4, were prospectively included. The primary outcome was symptom relief during follow-up, defined as an Eckardt score of ≤ 3. Secondary outcomes were procedure-related adverse events, lower esophageal sphincter (LES) pressure on manometry, reflux symptoms, and medication use before and after POEM. RESULTS All 12 patients underwent successful POEM after a mean of 11.9 years (range 2 - 38 years) from the time of the primary Heller myotomy. No serious complications related to POEM were encountered. During a mean follow-up period of 10.4 months (range 5 - 14 months), treatment success was achieved in 11/12 patients (91.7 %; mean score pre- vs. post-treatment 9.2 vs. 1.3; P < 0.001). Mean LES pressure was 29.4 mmHg pre-treatment and 13.5 mmHg post-treatment (P < 0.001). One patient developed mild reflux symptoms and required intermittent medication with proton pump inhibitors. CONCLUSIONS POEM seems to be a promising new treatment for failed Heller myotomy resulting in short-term symptom relief in > 90 % of cases. Previous Heller myotomy may make subsequent endoscopic remyotomy more challenging, but does not prevent successful POEM.

Submucosal tunneling endoscopic resection: a new technique for treating upper GI submucosal tumors originating from the muscularis propria layer (with videos)

U T t s u g e o i T ( a ( f Upper GI submucosal tumors (SMTs) 3 cm are generally considered benign tumors. However, some such umors, especially mesenchymal neoplasms (including GI tromal tumors originating from the muscularis propria MP]), do have malignant potential.2 If tissue diagnosis is ttempted, the most challenging aspect in the diagnosis of MTs by needle biopsy is the sampling error when taking iopsy specimens of GI stromal tumors, which may show nly focal areas of malignant change.2 Asymptomatic GI MTs 3 cm could be followed-up with periodic endoscopy nd/or EUS or resection.3 However, some patients become tressed when told that they require periodic follow-up. As a esult, they feel the urge to seek a safe and efficacious reatment during the follow-up time. Conventional endocopic resection of tumors originating from the MP layer used o be discouraged because of incomplete resections or risk of erforation during procedures. This left such patients with wo choices: surgical resection or endoscopic follow-up. Enoscopic submucosal dissection (ESD)2 and new, emerging endoscopic techniques such as endoscopic full-thickness resection4 are now options for these patients.

Peroral Endoscopic Myotomy for the Treatment of Achalasia: A Clinical Comparative Study of Endoscopic Full-Thickness and Circular Muscle Myotomy

BACKGROUND A circular muscle myotomy preserving the longitudinal outer esophageal muscular layer is often recommended during peroral endoscopic myotomy (POEM) for achalasia. However, because the longitudinal muscle fibers of the esophagus are extremely thin and fragile, and completeness of myotomy is the basis for the excellent results of conventional surgical myotomy, this modification needs to be further debated. Here, we retrospectively analyzed our prospectively maintained POEM database to compare the outcomes of endoscopic full-thickness and circular muscle myotomy. STUDY DESIGN According to the myotomy depth, 103 patients with full-thickness myotomy were assigned to group A, while 131 patients with circular muscle myotomy were assigned to group B. Symptom relief, procedure-related parameters and adverse events, manometry outcomes, and reflux complications were compared between groups. RESULTS The mean operation times were significantly shorter in group A compared with group B (p = 0.02). There was no increase in any procedure-related adverse event after full-thickness myotomy (all p < 0.05). During follow-up, treatment success (Eckardt score ≤ 3) persisted for 96.0% (95 of 99) of patients in group A and for 95.0% (115 of 121) of patients in group B (p = 0.75). There were no statistically significant differences in pre- and post-treatment D-value of symptom scores and lower esophageal sphincter pressures between groups (both p > 0.05). The overall clinical reflux complication rates were also similar (21.2% vs 16.5%, p = 0.38). CONCLUSIONS Short-term symptom relief and manometry outcomes of each method were comparable. Full-thickness myotomy significantly reduced the procedure time but did not increase the procedure-related adverse events or clinical reflux complications.

Submucosal tumors of the esophagogastric junction originating from the muscularis propria layer: a large study of endoscopic submucosal dissection (with video)

BACKGROUND Given the high morbidity and mortality rates for surgery and the diminishment of quality of life caused by operative resection of the gastric cardia, a minor invasive treatment without loss of curability is desirable for submucosal tumors (SMTs) of the esophagogastric junction (EGJ). Endoscopic submucosal dissection (ESD) has been used successfully for the removal of esophageal or gastric SMTs; however, the EGJ has been regarded as a difficult location for ESD because of its narrow lumen and sharp angle. OBJECTIVE To evaluate the clinical impact of ESD for SMTs of the EGJ arising from the muscularis propria layer. DESIGN Single-center, prospective study. SETTING Academic medical center. PATIENTS 143 patients with 143 SMTs of the EGJ originating from the muscularis propria layer. INTERVENTIONS ESD. MAIN OUTCOME MEASUREMENTS Complications, en bloc resection rate, local recurrence, and distant metastases. RESULTS The average maximum diameter of the lesions was 17.6 mm (range 5 - 50 mm). The en bloc resection rate was 94.4% (135/143). All en bloc resection lesions showed both lateral and deep tumor-free margins, including 20 GI stromal tumors. Perforations occurred in 6 patients (4.2%, 6/143), and metal clips were used to occlude the defect. Four pneumoperitoneum and 2 pneumothorax caused by perforations were resolved with nonsurgical treatment. Local recurrence and distant metastasis have not occurred during a 2-year follow-up. LIMITATIONS Single-center, short follow-up. CONCLUSIONS ESD appears to be a safe, feasible, and effective procedure for providing accurate histopathologic evaluations, as well as curative treatments for SMTs of the EGJ originating from the muscularis propria layer.

Endoscopic submucosal dissection for treatment of esophageal submucosal tumors originating from the muscularis propria layer.

BACKGROUND The technique of endoscopic submucosal dissection (ESD), which was developed for en bloc resection of large lesions in the stomach, has been widely accepted for the treatment of early gastric cancer. It is being used for muscularis propria tumors of the digestive tract and has produced positive therapeutic effects. OBJECTIVE To study the feasibility of ESD for the removal of esophageal muscularis propria tumors and to evaluate the efficacy and safety of ESD for this treatment. DESIGN Single-center, retrospective study. SETTING University hospital. PATIENTS Thirty esophageal muscularis propria tumors from 28 patients were treated with ESD between December 2008 and December 2010. We defined esophageal muscularis propria tumors as esophageal submucosal tumors originating from the muscularis propria layer. INTERVENTION ESD. MAIN OUTCOME MEASUREMENTS Tumor characteristics, complications, en bloc resection rate, and local recurrence rate were evaluated. RESULTS Among the 28 patients, 11 were women (39.3%). The median age was 49.32 years (range 22-62 years). Mean (± SD) tumor size was 1.25 ± 0.70 cm (range 0.5-3.0 cm). Except for 2 failed cases (one changed to surgery and the other changed to nylon ligation), 26 cases with 28 tumors (2 cases had 2 tumors) originating from the muscularis propria of the esophagus were successfully resected by ESD. The en bloc resection rate was 93.3% (28/30). The median ESD procedure time was 73.5 minutes (range 30-120 minutes). Perforation occurred in 2 cases during dissection of the lesion, which was closed with metal endoclips. Pneumothorax occurred after the treatment in both cases. Closed thoracic drainages were initiated, and the patients recovered quickly without surgery. Pathological examination confirmed 27 leiomyomas and 1 GI stromal tumor. The curative resection rate was 100% (28/28). There was no recurrence during a 3 to 27-month follow-up period. LIMITATIONS The limitation of the study was its retrospective design. CONCLUSION ESD offers the promise of localized treatment of esophageal muscularis propria tumors with relatively few complications and low mortality. It makes the resection of whole lesions possible and provides precise histologic information.

Complete closure of large gastric defects after endoscopic full-thickness resection, using endoloop and metallic clip interrupted suture

BACKGROUND AND STUDY AIM Successful closure of wall defects is the key procedure following endoscopic full-thickness resection (EFTR). In this report we describe a new method similar to interrupted suture to repair gastric defects by means of endoloops and metallic clips. PATIENTS AND METHODS We retrospectively analyzed 20 patients who presented at our institute between March 2011 and February 2012 with gastric submucosal tumors and who consequently underwent EFTR, with the resulting large gastric defects being closed using endoloops and metallic clips. Tumor characteristics, en bloc resection rates, and postoperative complications were evaluated in all the patients. RESULTS The median age of the 20 patients was 47 years. The mean maximum size of lesions was 1.47 ± 0.72 cm (range 0.4 - 3 cm). All lesions were diagnosed by endoscopic ultrasound as tumors in the muscularis propria layer. The en bloc resection rate was 100 %. Five patients developed fever and complained of slight abdominal pain in the first day after treatment. No patient had severe complications such as peritonitis or abdominal abscess. In all cases, wounds healed after 1 month. We observed the persistence of the clips for over 3 months in 6 out of 19 cases without any clinical manifestations or large injury to the intestine. CONCLUSIONS Our study provides evidence that the use of metallic clips and endoloops is a relatively safe, easy, and feasible method for repairing gastric defects resulting from EFTR.

Early diagnosis and management of delayed bleeding in the submucosal tunnel after peroral endoscopic myotomy for achalasia (with video)

Peroral endoscopic myotomy (POEM) has recently been described as a scar-free and less-invasive surgical myotomy option for treating achalasia. This procedure incorporates concepts of natural orifice transluminal endoscopic surgery and achieves endoscopic myotomy by using a submucosal tunnel as the operating space. Initial published experience in humans is more than encouraging despite a relatively short follow-up. Common complications of POEM include mucosal injury, subcutaneous emphysema, mediastinal emphysema, pneumothorax, pneumoperitoneum, and pleural effusion. Postoperative delayed bleeding in the submucosal tunnel is a rare complication after POEM, and only 1 patient with delayed bleeding has been reported in the literature to date. Despite its low incidence, delayed bleeding can result in serious conditions, such as massive bleeding, hemorrhagic shock, and death. Thus, early

Endoscopic submucosal dissection for foregut neuroendocrine tumors： An initial study

AIM To evaluate the feasibility and efficacy of endoscopic submucosal dissection (ESD) for foregut neuroendocrine tumors (NETs). METHODS From April 2008 to December 2010, patients with confirmed histological diagnosis of foregut NETs were included. None had regional lymph node enlargement or distant metastases to the liver or lung on preoperative computerized tomography scanning or endoscopic ultrasonography (EUS). ESD was attempted under general anesthesia. After making several marking dots around the lesion, a mixture solution was injected into the submucosa. The mucosa was incised outside the marking dots. Dissection of the submucosal layer beneath the tumor was performed under direct vision to achieve complete en bloc resection of the specimen. Tumor features, clinicopathological characteristics, complete resection rate, and complications were evaluated. Foregut NETs were graded as G1, G2, or G3 on the basis of proliferative activity by mitotic count or Ki-67 index. All patients underwent regular follow-up to evaluate for any local recurrence or distant metastasis. RESULTS Those treated by ESD included 24 patients with 29 foregut NETs. The locations of the 29 lesions are as follows: esophagus (n = 1), cardia (n = 1), stomach (n = 23), and duodenal bulb (n = 4). All lesions were found incidentally during routine upper gastrointestinal endoscopy for other indications, and none had symptoms of carcinoid syndrome. Preoperative EUS showed that all tumors were confined to the submucosa. Among the 24 gastric lesions, 16 lesions in 11 patients were type I gastric NETs arising in chronic atrophic gastritis with hypergastrinemia, while the other 8 solitary lesions were type III because of absence of atrophic gastritis in these cases. All of the tumors were removed in an en bloc fashion. The average maximum diameter of the lesions was 9.4 mm (range: 2-30 mm), and the procedure time was 20.3 min (range: 10-45 min). According to the World Health Organization 2010 classification, histological evaluation determined that 26 lesions were NET-G1, 2 gastric lesions were NET-G2, and 1 esophageal lesion was neuroendocrine carcinoma (NEC). Complete resection was achieved in 28 lesions (28/29, 96.6%), and all of them were confined to the submucosa in histopathologic assessment with no lymphovascular invasion. The remaining patient with NEC underwent additional surgery because the resected specimens revealed angiolymphatic and muscularis invasion, as well as incomplete resection. Delayed bleeding occurred in 1 case 3 d after ESD, which was managed by endoscopic treatment. There were no procedure-related perforations. During a mean follow-up period of 24.4 mo (range: 12-48 mo), local recurrence occurred in only 1 patient 7 mo after initial ESD. This patient successfully underwent repeat ESD. Metastasis to lymph nodes or distal organs was not observed in any patient. No patients died during the study period. CONCLUSION ESD appears to be a safe, feasible, and effective procedure for providing accurate histopathological evaluations and curative treatment for eligible foregut NETs.

Risk factors for postoperative stricture after endoscopic submucosal dissection for superficial esophageal carcinoma

BACKGROUND AND STUDY AIMS Endoscopic submucosal dissection (ESD) is accepted as an established treatment modality for superficial esophageal carcinoma (SEC). The aim of this study was to identify risk factors for postoperative stricture after ESD for SEC. PATIENTS AND METHODS This was a retrospective study at a single institution. A total of 362 patients with SEC treated by ESD at Zhongshan Hospital, Shanghai, were enrolled between January 2007 and February 2012. Demographic and clinical parameters, including patient-, lesion-, and procedure-related factors, were analyzed for postoperative stricture risk factors. RESULTS The postoperative stricture rate was 11.6 % (42/362). The mean and median time from ESD to stricture was 58.5 ± 12.3 days (range 21 - 90 days) and 28 days, respectively. Mild, median, and severe stricture were observed in 16.7 % (7/42), 38.1 % (16 /42), and 45.2 % (19/42) of patients, respectively. Multivariate analysis revealed that circumferential extension of > 3/4 (odds ratio [OR] 44.2, 95 % confidence interval [CI] 4.4 - 443.6) and the depth of invasion above m2 (OR 14.2, 95 %CI 2.7 - 74.2) were independent risk factors for stricture. The degree of stricture was also related to lesion circumferential extension (relational coefficient φ = 0.47; P < 0.05) and histological depth (relational coefficient φ = 0.647; P < 0.05). CONCLUSIONS Circumferential extension and histological depth were reliable risk factors for postoperative stricture.

SLIT2 inhibits cell migration in colorectal cancer through the AKT-GSK3β signaling pathway.

PurposeColorectal cancer is a common malignancy and one of the major causes of cancer-related deaths worldwide. Similar to other human cancers, tumor metastasis is the biggest obstacle in the clinical treatment of colorectal cancer. In this study, we explored the functional role of SLIT2 in colon tumor metastasis and the relevant molecular mechanisms.MethodsImmunohistochemistry, Western blotting, and quantitative reverse transcription-polymerase chain reaction were used to measure SLIT2 expression in colorectal tumor tissues in the presence or absence of metastasis. Wound-healing assays, Transwell assays, Western blotting, and immunofluorescence assays were used to examine the effects of SLIT2 on SW480 and NCM460 cell migration and the epithelial-to-mesenchymal transition (EMT). An AKT inhibitor was introduced to examine the mechanism underlying SLIT2-mediated suppression of NCM460 cell migration.ResultsHigher SLIT2 expression was detected in metastasis-positive tumor tissues, and this upregulation was beneficial for the overall survival of patients with colorectal cancer. Either the addition of purified SLIT2 or overexpression of SLIT2 inhibited SW480 cell migration, whereas the depletion of SLIT2 with shRNA enhanced the migratory ability of NCM460 cells. Meanwhile, SLIT2 depletion also induced β-catenin accumulation and altered the expression levels of several molecules related to EMT in NCM460 cells. AKT inhibition abrogated the effects of SLIT2 depletion on EMT and migration in NCM460 cells.ConclusionsSLIT2 suppresses colon tumor metastasis, and it exerts its suppressive activity against colorectal cancer metastasis by restraining AKT signaling and EMT, thus making it a potential clinical prognosis marker in colorectal cancer.