Statement for gastroesophageal reflux disease after peroral endoscopic myotomy from an international multicenter experience.

It has been 10 years since peroral endoscopic myotomy (POEM) was reported for the first time, and POEM has currently become the standard treatment for achalasia and related disorders globally because it is less invasive and has a higher curative effect than conventional therapeutic methods. However, there are limited studies comparing the long-term outcomes of POEM with those of conventional therapeutic methods, particularly in the occurrence of gastroesophageal reflux disease (GERD) after therapy. With this background, we held a consensus meeting to discuss the pathophysiology and management of GERD after POEM based on published papers and experiences of each expert and to discuss the prevention of GERD and dealing with anti-acid drug refractory GERD. This meeting was held on April 27, 2018 in Tokyo to establish statements and finalize the recommendations using the modified Delphi method. This manuscript presents eight statements regarding GERD after POEM.

In vivo histopathology using endocytoscopy for non-neoplastic changes in the gastric mucosa: a prospective pilot study (with video).

BACKGROUND: Endocytoscopy (EC), as a novel ultrahigh magnification technology, enables in vivo histopathological diagnoses of the GI tract. EC is particularly exceptional when comparing dysplastic and neoplastic tissue with normal tissue. There are, however, no detailed data for minute or minimal changes in the gastric mucosa. OBJECTIVE: To describe non-neoplastic EC patterns of the gastric mucosa correlated with histopathological findings and to determine any relationship with Helicobacter pylori (HP) infection. DESIGN: A pilot prospective study. SETTING: Tertiary care referral center. PATIENTS: Sixty-four participants undergoing upper endoscopy for various indications. METHODS: Antral mucosal patterns on EC were divided into 4 categories: type 1 (normal), each papilla/pit has round smooth structure; type 2 (gastritis), extended, notched, and distorted structure with some necrotic tissue; type 3(atrophy), neighboring papilla/pit take on a lobulated appearance; type 4 (intestinal metaplasia [IM]), goblet cells are identified in a completely stained crypt. Target biopsy specimens were obtained from the region identified with these patterns, and multiple HP tests were performed. RESULTS: HP positivity was 0%, 40.9%, 50.0%, and 58.3% in types 1, 2, 3, and 4, respectively. The sensitivity and specificity of types 2+3+4 for HP positivity were 100％ and 42.5%, respectively. The positive predictive values of type 1 for normal, type 2 for chronic gastritis, type 3 for atrophic gastritis, and type 4 for IM were 100%, 62.5%, 40.0%, and 100%, respectively. The sensitivity and specificity of types 3+4 for atrophic gastritis to IM were 87.0% and 95.1%, respectively. LIMITATIONS: Small, single-center, pilot study. CONCLUSIONS: EC can differentiate gastric mucosal patterns of minimal, non-neoplastic change and appears to reliably exclude HP infection.

Greater curvature myotomy is a safe and effective modified technique in per-oral endoscopic myotomy (with videos).

BACKGROUND: Per-oral endoscopic myotomy (POEM) for achalasia with esophagocardiomyotomy in the lesser curvature (LC myotomy) is now established and accepted widely. However, in some cases LC myotomy is precluded by previous procedures, such as Heller myotomy, or by other anatomic considerations that obscure the normal dissection planes. It may also be difficult to identify the esophagogastric junction (EGJ), which can result in an incomplete gastric myotomy and poor rates of symptom relief. On the other hand, the angle of His is always located in the greater curvature of the stomach and serves as a consistent, definite landmark of the gastric side. OBJECTIVE: To evaluate esophagocardiomyotomy in the greater curvature (GC myotomy) as an alternative POEM technique in cases where a prior LC myotomy or supervening anatomic constraints make identification of the EGJ technically challenging. DESIGN: Prospective. SETTING: Single-center study. PATIENTS: Twenty-one achalasia patients who received POEM with GC myotomy. INTERVENTIONS: POEM. MAIN OUTCOME MEASUREMENTS: Efficacy and safety of GC myotomy measured in terms of reduction in lower esophageal sphincter (LES) pressures, improvement in Eckardt scores, and development of intraoperative or postoperative adverse events. RESULTS: Identification of the EGJ was achieved in all cases, resulting in a mean gastric myotomy length of 2.6±1.1 cm. Mean LES pressure and Eckardt symptom scores decreased significantly (21.2±7.3 vs 10.5±2.7 mm Hg, 5 [2-8] vs 1 [0-5], respectively) (P<.01). Endoscopic evidence of gastroesophageal reflux was identified in 52% of patients (11/21) postmyotomy; however, only 9.5% (2/11) were symptomatic, and these patients were successfully controlled with proton pump inhibitors. No severe adverse events were encountered. LIMITATIONS: Single center. CONCLUSIONS: GC myotomy is a promising, safe modification of the POEM technique and may be especially useful in cases of redo POEM, POEM post-Heller myotomy, or when the EGJ is difficult to recognize because of supervening anatomic constraints.

Utility of intrapapillary capillary loops seen on magnifying narrow-band imaging in estimating invasive depth of esophageal squamous cell carcinoma.

BACKGROUND AND STUDY AIMS: Intrapapillary capillary loops (IPCLs) have been used to estimate histopathological atypia and the invasion depth of squamous cell carcinoma (SCC). The aim of this study was to evaluate the clinical significance of IPCLs. PATIENTS AND METHODS: A total of 358 consecutive patients with esophageal neoplasia on magnifying narrow-band imaging (M-NBI) were studied. The lesions were categorized according to the IPCL classification of Inoue et al. and were subsequently resected. Resected specimens were histopathologically analyzed to determine the invasion depth. The inter- and intraobserver agreements in the interpretation of IPCL images were also investigated. RESULTS: A total of 446 lesions were diagnosed on M-NBI as IPCL type V lesions, which were further classified as 185 IPCL type V1, 109 type V2, 104 type V3, and 48 type Vn. Sensitivity and specificity of IPCL type V1-2 for invasion confined to the epithelium or lamina propria mucosa (m1-2) were 89.5 % (95 % confidence interval [CI] 85.4 % - 92.7 %) and 79.6 % (95 %CI 72.3 % - 85.7 %), respectively. Sensitivity and specificity of IPCL type V3 for invasion confined to the muscularis mucosa or slight submucosal invasion (m3-sm1) were 58.7 % and 83.8 %, respectively. Sensitivity and specificity of IPCL type Vn for deeper invasion (sm2-3) were 55.8 % and 98.6 %, respectively. Interobserver agreement was substantial (κ = 0.609, 0.641, and 0.705), as was intraobserver agreement (κ = 0.705 and κ = 0.819). CONCLUSION: Changes in the morphology of IPCLs on M-NBI correlated with the depth of SCC invasion, and results were reproducible and reliable among observers. Identification of IPCL type V1-2 proved useful for the intraprocedural identification of m1-2 lesions, which are considered an absolute indication for endoscopic resection.

Control of severe strictures after circumferential endoscopic submucosal dissection for esophageal carcinoma: oral steroid therapy with balloon dilation or balloon dilation alone.

BACKGROUND: Recent technological advances have allowed superficially spreading intramucosal carcinomas of the esophagus to be successfully resected by circumferential endoscopic submucosal dissection (cESD). After this procedure, esophageal strictures develop in most patients and are mainly treated by endoscopic balloon dilation (EBD). OBJECTIVE: To compare oral steroids plus EBD with EBD alone for the management of benign esophageal strictures after cESD. DESIGN: Retrospective cohort study. SETTING: Tertiary-care referral center. PATIENTS: We studied 23 consecutive patients who underwent complete cESD for superficial esophageal carcinoma (22 squamous cell carcinomas and 1 adenocarcinoma associated with Barrett's esophagus). INTERVENTION: After cESD, patients were managed with EBD alone (EBD, n = 13) or with EBD and oral prednisolone (steroid + EBD, n = 10), 30 mg daily, started 2 days after cESD and gradually tapered and discontinued after 8 weeks. MAIN OUTCOME MEASUREMENTS: Total number of EBD sessions and total EBD period (months). RESULTS: Steroid + EBD patients required fewer sessions (13.8 ± 6.9 vs 33.5 ± 22.9; P < .001) and a shorter management period (4.8 ± 2.3 vs 14.2 ± 17.5 months, P = .005) compared with the EBD group. An additional 3 patients received oral steroids a mean interval of 158 days after cESD. These patients required more EBD sessions (46.3 ± 30.0; P = .002), and the EBD period was significantly longer (17.5 ± 13.0 months; P = .005) than in the early steroid + EBD group. LIMITATIONS: Nonrandomized study; retrospective analysis. CONCLUSION: After cESD, oral steroid therapy dramatically reduced the need for EBD. We conclude that oral steroid therapy after EBD is an effective strategy for the management of esophageal strictures after complete cESD.

Microvasculature of the esophagus and gastroesophageal junction: Lesson learned from submucosal endoscopy.

Advanced therapeutic endoscopy, in particular endoscopic mucosal resection, endoscopic submucosal dissection, per-oral endoscopic myotomy, submucosal endoscopic tumor resection opened a new era where direct esophageal visualization is possible. Combining these information with advanced diagnostic endoscopy, the esophagus is organized, from the luminal side to outside, into five layers (epithelium, lamina propria with lamina muscularis mucosa, submucosa, muscle layer, adventitia). A specific vascular system belonging to each layer is thus visible: Mucosa with the intra papillary capillary loop in the epithelium and the sub-epithelial capillary network in the lamina propria and, at the lower esophageal sphincter (LES) level with the palisade vessels; submucosa with the drainage vessels and the spindle veins at LES level; muscle layer with the perforating vessels; peri-esophageal veins in adventitia. These structures are particularly important to define endoscopic landmark for the gastro-esophageal junction, helpful in performing submucosal therapeutic endoscopy.

Endoscopic Ex Vivo Evaluation of Bile Concentrations by Narrow Band Imaging: A Pilot Study.

Background. Bile juice plays a major role in duodenogastroesophageal reflux (DGERD). Several devices to directly measure the bile concentration have been proposed. We aimed to ex-vivo evaluate the bile concentration by narrow band imaging (NBI). Method. From six surgical cholecystectomies, the content of the gallbladders was aspirated and the total biliary acid (TBA) concentration was evaluated. 2 mL was employed for serial twofold dilutions. Each dilution was scoped. Images on white light (WL) and NBI were captured and grouped accordingly to NBI-appearance and TBA-concentration. Results. Nondiluted bile had a TBA-concentration of 61965 ± 32989 µmol/L. Final dilution (1 : 4096) had 1.16 µmol/L. NBI and correspondent WL images were grouped into seven groups, and an NBI/Bile scale was created. Conclusion. The scale showed that not only NBI scale but also white light scale could be useful to predict the bile concentration. This initial study shows that NBI has a potential role in the detection of DGERD and further investigation is warranted to distinguish the presence and the concentration of bile, especially at very low TBA concentrations.

In vivo gastric mucosal histopathology using endocytoscopy.

AIM: To study the ability of endocytoscopy to identify normal gastric mucosa and to exclude Helicobacter pylori (H. pylori) infection. METHODS: Endocytoscopic examination of the gastric corpus and antrum was performed in 70 consecutive patients. Target biopsy specimens were also obtained from the assessed region and multiple H. pylori tests were performed. The normal endocytoscopy patterns of the corpus and antrum were divided into the normal pit-dominant type (n-Pit) or the normal papilla-dominant type (n-Pap), respectively characterized as either regular pits with capillary networks or round, smooth papillary structures with spiral capillaries. On the other hand, normal mucosa was defined as mucosa not demonstrating histological abnormalities, including inflammation and atrophy. RESULTS: The sensitivity and specificity of n-Pit for normal mucosa in the gastric corpus were 94.4% and 97.1%, respectively, whereas those of n-Pap for normal mucosa in the antrum were 92.0% and 86.7%, respectively. The positive predictive values of n-Pit and n-Pap for H. pylori-negative tissue were 88.6% and 93.1%, respectively, and their negative predictive values for H. pylori-negative tissues were 42.9% and 41.5%, respectively. The inter-observer agreement for determining n-Pit and n-Pap for normal mucosa were 0.857 and 0.769, respectively, which is considered reliable. CONCLUSION: N-Pit and n-Pap, seen using EC, are considered useful predictors of normal mucosa and the absence of H. pylori infection.

Magnification endoscopy in esophageal squamous cell carcinoma: a review of the intrapapillary capillary loop classification.

Recent developments in image-enhancement technology have enabled clear visualization of the microvascular structure of the esophageal mucosa. In particular, intrapapillary capillary loops (IPCLs) are observed as brown loops on magnification endoscopy with narrow-band imaging (NBI). IPCLs demonstrate characteristic morphological changes according to the structural irregularity of esophageal epithelium and cancer infiltration, summarized in the IPCL classification. In this review, the process from the first endoscopic description of IPCLs to the eventual development of the IPCL classification is described and discussed, particularly focusing on early stage squamous cell carcinoma of the esophagus.

Submucosal endoscopy: from ESD to POEM and beyond.

Peroral endoscopic myotomy (POEM) is an evolving minimally invasive endoscopic surgical procedure, with no skin incision, intended for long-term recovery from symptoms of esophageal achalasia. POEM was developed based on both the already established surgical principles of esophageal myotomy and the advanced techniques of endoscopic submucosal dissection. This article relates how POEM was developed, and its use in practice is reported and discussed. As an extension of the POEM technique, submucosal endoscopic tumor resection is introduced.

In vivo histopathological assessment of the muscularis propria in achalasia by using endocytoscopy (with video).

BACKGROUND: The histopathology of the muscularis propria (MP) is unknown in patients with achalasia. Endocytoscopy (EC) was developed as an ultra-high magnification endoscopy, and the submucosal tunnel created during peroral endoscopic myotomy (POEM) not only provides access to the MP but also enables subsequent endoscopic assessment of the MP. PATIENTS AND METHODS: In seven patients with achalasia (mean ±â€ŠSD; 35 ±â€Š18.1 years; men:women, 4:3) who underwent POEM (myotomy length: 12 ±â€Š2.2 cm), subsequent EC examination was performed from the mid-esophagus to the gastric side. EC images were compared to the results of histopathologic examination (two biopsies from the mid-esophagus and lower esophageal sphincter), which was the standard. RESULTS: In all patients, favorable EC images were obtained, and spindle-shaped smooth muscle cells were detected. In our series, we observed no notable features such as atrophy or hypertrophy of smooth muscle cells. In addition, the EC assessment was consistent with the results of biopsy. No complications were encountered during any of the procedures. CONCLUSION: In a clinical setting, real-time assessment of the MP using EC is feasible. This technique may play an important role in determining the pathology of achalasia and other diseases that affect gastrointestinal function.

Surgical outcomes and clinicopathological characteristics of patients who underwent potentially noncurative endoscopic resection for gastric cancer: a report of a single-center experience.

Background. Standard treatment of early gastric cancer (EGC) after endoscopic resection with risk factors of nodal metastases and incomplete resection is controversial. We investigated optimal management for the patients with potentially noncurative EGC after endoscopic resection. Methods. We retrospectively examined clinicopathological data and surgical outcomes of all patients with clinically solitary gastric adenocarcinoma who underwent curative surgery after a single peroral endoscopic resection at the Digestive Disease Center of Showa University Northern Yokohama Hospital between April 2001 and December 2012. Fisher's exact test was used for univariate analysis. For multivariate analysis, stepwise multiple linear regression was used to identify independent predictors related to lymph node metastasis and remnant of primary tumor. Results. A total of 41 patients were studied. Four patients (9.8%) had lymph node metastases. Primary tumors remained in 6 patients (14.6%). Only venous invasion was statistically significant to lymph node metastasis (P = 0.017). With respect to remnant of the primary tumor, pT1b2 tumor invasion (P = 0.015) and horizontal margin (P = 0.013) were statistically significant. Conclusions. Surgery with limited lymphadenectomy is recommended for tumors with venous invasion or pT1b2 tumor invasion, and additional endoscopic resection may be allowed for tumors with horizontal involvement.

Peroral endoscopic myotomy is a viable option for failed surgical esophagocardiomyotomy instead of redo surgical Heller myotomy: a single center prospective study.

BACKGROUND: Surgical Heller myotomy has high rates of successful long-term results, but failed cases still remain. Moreover, the treatment strategy in patients with surgical myotomy failure is controversial. Recently, peroral endscopic myotomy (POEM) was reported to be efficient and safe in primary treatment of achalasia. In this study, we aimed to evaluate the efficacy and safety of POEM for surgical myotomy failure as a rescue second-line treatment, and we discuss the treatment options adapted in achalasia recurrence. STUDY DESIGN: A total of 315 consecutive achalasia patients received POEM from September 2008 to December 2012 in our hospital. Eleven (3.5%) patients who had persistent or recurrent achalasia and had received surgical myotomy as a first-line treatment from other hospitals were included in this study. Patient background, barium swallow studies, esophagogastroduodenoscopy (EGD), manometry, and symptom scores were prospectively evaluated. In principle, all patients in whom surgical myotomy failed received pneumatic balloon dilatation (PBD) as the first line "rescue" treatment, and only if PBD failed were patients considered for rescue POEM. RESULTS: The PBD alone was effective in 1 patient, and in the remaining 10 patients, rescue POEM was performed successfully without complications. Three months after rescue POEM, significant reduction in lower esophageal sphincter (LES) resting pressures (22.1 ± 6.6 mmHg vs 10.9 ± 4.5 mmHg, p < 0.01) and Eckardt symptom scores (6.5 ± 1.3 vs 1.1 ± 1.3, p < 0.001) were observed. CONCLUSIONS: Short-term results of POEM for failed surgical myotomy were excellent. Long-term results are awaited.