Prognosis of incompletely resected small rectal neuroendocrine tumor using endoscope without additional treatment.

BACKGROUND: In recent years, the incidence of rectal neuroendocrine tumors (NET)s has markedly increased due to the widespread use of screening colonoscopy. However, many patients are referred from local clinics after undergoing conventional endoscopic mucosal resection (EMR) for polyps without perceived NET, with a pathological report of incomplete resection. We evaluated the prognosis of incompletely resected small rectal NET without additional endoscopic resection for small rectal NET less than 10 mm in diameter present within the submucosal layer showing good prognosis, due to its rare metastatic potential. METHODS: We retrospectively reviewed patients from 2008 to 2018 at a single center who had had small rectal NET (located in the rectum from the anal verge to 20 cm in proximity) and had undergone 'incomplete resection' using endoscopy with a positive deep margin or with a very small safe deep margin (< 100 um). A small rectal NET was defined as a tumor ≤ 10 mm in diameter, without lymph node nor distant metastasis, and with low grade (G1) according to the WHO grading system. RESULTS: Of 267 patients who were diagnosed with small rectal NET, 77 were diagnosed with incomplete resection or possible remnant NET. Of those, 55 patients (55/77, 71.4%) were referred from local clinics post EMR diagnosed as polyps. The rate of histologically incomplete resection was highest in endoscopic submucosal dissection (11/21, 52.4%) and lowest in surgical resection (0/9, 0%), while endoscopic submucosal resection with band ligation showed an incomplete resection rate of 4.4% (5/113). After exclusion of 36 patients, namely 21 patients had undergone additional surgical (n = 6) or endoscopic (n = 15) resection and 25 patients who were lost during the follow-up period of 2 years, 31 patients had undergone surveillance with endoscopic evaluation or either a biopsy or radiological evaluation for distant metastasis during a median follow-up duration of 2 years. None of the incompletely resected small rectal NET patients showed local or distant metastasis. CONCLUSION: Incomplete resection of small rectal NET with G1 grade has a good prognosis without additional treatment.

Diode Laser-Can It Replace the Electrical Current Used in Endoscopic Submucosal Dissection?

BACKGROUND/AIMS: A new medical fiber-guided diode laser system (FDLS) is expected to offer high-precision cutting with simultaneous hemostasis. Thus, this study aimed to evaluate the feasibility of using the 1,940-nm FDLS to perform endoscopic submucosal dissection (ESD) in the gastrointestinal tract of an animal model. METHODS: In this prospective animal pilot study, gastric and colorectal ESD using the FDLS was performed in ex vivo and in vivo porcine models. The completeness of en bloc resection, the procedure time, intraprocedural bleeding, histological injuries to the muscularis propria (MP) layer, and perforation were assessed. RESULTS: The en bloc resection and perforation rates in the ex vivo study were 100% (10/10) and 10% (1/10), respectively; those in the in vivo study were 100% (4/4) and 0% for gastric ESD and 100% (4/4) and 25% (1/4) for rectal ESD, respectively. Deep MP layer injuries tended to occur more frequently in the rectal than in the gastric ESD cases, and no intraprocedural bleeding occurred in either group. CONCLUSION: The 1,940-nm FDLS was capable of yielding high en bloc resection rates without intraprocedural bleeding during gastric and colorectal ESD in animal models.

Two-Stage Peroral Endoscopic Myotomy for Sigmoid-Type Achalasia.

Peroral endoscopic myotomy (POEM) has been recently considered as the first treatment option for achalasia. The standard POEM procedures are often successful in most patients, but sometimes technical challenges are encountered. We report a new technique that is divided between two tunneling sites in the esophagus for sigmoid-type achalasia. A 40-year-old male patient with dysphagia for 10 years was diagnosed with a sigmoid-shaped esophagus at our hospital. We devised a two-stage myotomy technique to treat sigmoidtype achalasia. The myotomy was first performed in the upper part of the greater flexion area and then in the lower part of the flexion. We termed this method "two-stage POEM", which was successfully performed without any complications. This new POEM method can also be used to improve symptoms in patients with achalasia who have a structural deformity that may result in a high change of treatment failure.

Anti-reflux mucosectomy using a cap-assisted endoscopic mucosal resection method for refractory gastroesophageal disease: a prospective feasibility study.

BACKGROUND AND AIMS: Endoscopic therapy of gastroesophageal reflux disease (GERD) overcomes the "treatment gap" for patients with refractory GERD, who are not willing to go into surgery. We propose an easy and efficient technique that is referred to as anti-reflux mucosectomy (ARMS) using cap-assisted endoscopic mucosal resection (EMR-C) which could be called ARMS-C. This study aimed to investigate the short-term outcomes of ARMS-C in GERD patients. METHODS: From December 2016 to February 2018, we performed ARMS-C in 33 patients with pathologic reflux disease and esophageal hypersensitivity. ARMS-C involved endoscopic mucosal resection at the circumference of the esophagogastric junction (EGJ), resulting in narrowing of the hiatal opening after healing. The GERD symptoms, 24-h pH monitoring results, manometry, endoscopy, and EGJ distensibility were compared before and after the procedure. RESULTS: Six months after ARMS-C, 63% of patients discontinued the use of pump inhibitors (PPIs), while 30% patients reduced their PPI dose. The GERD questionnaire scores significantly decreased after ARMS-C, from 11.0 to 6.0 (P < 0.001). The median DeMeester score and acid exposure time based on pH monitoring also improved after ARMS-C. Furthermore, the median flap valve grade and EGJ distensibility decreased from 3.0 to 1.0 (P < 0.001) and from 19.0 to 13.9 (P < 0.001), respectively. Two patients were treated with balloon dilation due to stricture, but no other serious adverse events were encountered. CONCLUSION: ARMS-C may be an effective and safe treatment method for GERD in terms of short-term outcomes.

Endoscopic Submucosal Dissection Followed by Concurrent Chemoradiotherapy in Patients with Early Esophageal Cancer with a High Risk of Lymph Node Metastasis.

Endoscopic submucosal dissection is recommended as an alternative therapy for early esophageal cancer. However, achieving curative resection in this procedure remains controversial since precise prediction of lymph node metastasis can be difficult. Here, we present the preliminary results of endoscopic submucosal dissection followed by concurrent chemoradiotherapy for early esophageal cancer with a high risk of lymph node metastasis. From May 2006 to January 2014, six patients underwent concurrent chemoradiotherapy after endoscopic submucosal dissection with a median follow-up period of 63 months. No complications were encountered during concurrent chemoradiotherapy. Although local recurrence did not occur in all patients, two patients were diagnosed with metachronous cancer. Overall, the survival rate was 100%. Thus, endoscopic submucosal dissection followed by concurrent chemoradiotherapy may be a feasible treatment for early esophageal cancer in patients with a high risk of lymph node metastasis. Future prospective large-scale studies are warranted to confirm our results.

Performance of disposable endoscopic forceps according to the manufacturing techniques.

BACKGROUND/AIMS: Recently, to lower the production costs and risk of infection, new disposable biopsy forceps made using simple manufacturing techniques have been introduced. However, the effects of the manufacturing techniques are unclear. The aim of this study was to evaluate which types of biopsy forceps could obtain good-quality specimens according to the manufacturing techniques. METHODS: By using an in vitro nitrile glove popping model, we compared the popping ability among eight different disposable biopsy forceps (one pair of biopsy forceps with cups made by a cutting method [cutting forceps], four pairs of biopsy forceps with cups made by a pressing method [pressing forceps], and three pairs of biopsy forceps with cups made using a injection molding method [molding forceps]). Using an in vivo swine model, we compared the penetration depth and quality of specimen among the biopsy forceps. RESULTS: In the in vitro model, the molding forceps provided a significantly higher popping rate than the other forceps (cutting forceps, 25.0%; pressing forceps, 17.5%; and molding forceps, 41.7%; p = 0.006). In the in vivo model, the cutting and pressing forceps did not provide larger specimens, deeper biopsy specimen, and higher specimen adequacy than those obtained using the molding forceps (p = 0.2631, p = 0.5875, and p = 0.2147, respectively). However, the molding forceps showed significantly more common crush artifact than the others (cutting forceps, 0%; pressing forceps, 5.0%; and molding forceps, 43.3%; p = 0.0007). CONCLUSION: The molding forceps provided lower performance than the cutting and pressing forceps in terms of crush artifact.

Clarithromycin resistance and female gender affect Helicobacter pylori eradication failure in chronic gastritis.

BACKGROUND/AIMS: The eradication rate of the first-line triple therapy (a proton pump inhibitor, clarithromycin, and amoxicillin) for Helicobacter pylori infection has gradually decreased in Korea. We evaluated whether clinical parameters, clarithromycin resistance, and CYP2C19 genotype can affect the eradication failure. METHODS: A total of 203 patients with H. pylori-positive chronic gastritis were consecutively enrolled. They received clarithromycin-based triple therapy for 7 days. A clarithromycin resistance test was performed by detection of A2142G and A2143G point mutations in H. pylori 23S rRNA. The CYP2C19 genotype was examined for polymorphism G681A of exon 5 and G636A of exon 4 by polymerase chain reaction with restriction fragment length polymorphism. Eradication was assessed by a 13C-urea breath test 4 weeks after treatment. RESULTS: Of 203 patients, 190 completed the study. The eradication rate was 64.0% according to intention-to-treat analysis and 68.4% by per-protocol analysis. CY-P2C19 genotypes were identified as follows: 75 poor metabolizers, 75 intermediate metabolizers, and 40 rapid metabolizers. Nonetheless, this polymorphism was not significantly associated with eradication failure (p = 0.682). Clarithromycin resistance was detected in 33/190 patients (17.4%), and their eradication rate was zero. Clarithromycin resistance (odds ratio [OR], 19.13; 95% confidence interval [CI], 9.35 to 35.09) and female gender (OR, 1.73; 95% CI, 1.15 to 4.25) were significantly associated with eradication failure. The other clinical parameters such as age, cigarette smoking, alcohol intake, the body mass index, hypertension, and diabetes were not significantly associated with eradication. CONCLUSION: Clarithromycin resistance and female gender are factors affecting H. pylori eradication failure in patients with chronic gastritis.

Clinical outcomes of minimally invasive treatment for early gastric cancer in patients beyond the indications of endoscopic submucosal dissection.

BACKGROUND: Endoscopic submucosal dissection (ESD) with laparoscopic sentinel lymph node dissection (ESN) and endoscopic full-thickness gastric resection with laparoscopic sentinel lymph node dissection (Hybrid-natural orifice transluminal endoscopic surgery, Hybrid-NOTES) are minimally invasive treatment options for early gastric cancer (EGC) beyond the indications of ESD. This study aimed to evaluate the short- and long-term clinical outcomes of ESN and Hybrid-NOTES. METHODS: We retrospectively analyzed patients who had undergone ESN or Hybrid-NOTES for EGC from January 2009 to March 2013. A total of 48 patients, including 21 undergoing ESN and 27 undergoing Hybrid-NOTES, were enrolled. All patients had cancer stage T1N0M0, EGC less than 5 cm in size, and suspected submucosal invasion according to imaging or biopsy-proven diffuse-type histology. RESULTS: In ESN and Hybrid-NOTES, the curative resection rates were 76.5% and 90.9% of patients, respectively. In the ESN group, 5 patients underwent an additional gastrectomy (1 for lymph node metastasis (LNM), 3 for surgical complications, and 1 for noncurative resection). In the Hybrid-NOTES group, 6 patients underwent additional gastrectomy, (1 for LNM, 3 for surgical complications, and 2 for noncurative resection). Of the 37 patients who were followed up in the long-term (a median follow-up of 59.8 months), one was found to have liver metastasis after ESN and received palliative chemotherapy. CONCLUSIONS: ESN and Hybrid-NOTES have shown favorable long-term outcomes despite their technical limitations. These methods may be utilized as a bridge between ESD and gastrectomy in cases of EGC with a high risk of LNM beyond the ESD indications.

Introduction to Endoscopic Submucosal Surgery.

The concept of using natural orifices to reduce the complications of surgery, Natural Orifices Transluminal Endoscopic Surgery, has also been applied to therapeutic endoscopy. Endoscopic submucosal surgery (ESS) provides more treatment options for various gastrointestinal diseases than traditional therapeutic endoscopy by using the submucosal layer as a working space. ESS has been performed in various fields ranging from transluminal peritoneoscopy to peroral endoscopic myotomy. With further advances in technology, ESS will be increasingly useful for diagnosis and treatment of gastrointestinal diseases.

Comparison of the Outcomes of Peroral Endoscopic Myotomy for Achalasia According to Manometric Subtype.

BACKGROUND/AIMS: We evaluated whether manometric subtype is associated with treatment outcome in patients with achalasia treated by peroral endoscopic myotomy (POEM). METHODS: High-resolution manometry data and Eckardt scores were collected from 83 cases at two tertiary referral centers where POEM is performed. Manometric tracings were classified according to the three Chicago subtypes. RESULTS: Among the 83 cases, 48 type I, 24 type II, and 11 type III achalasia cases were identified. No difference was found in pre-POEM Eckardt score, basal lower esophageal sphincter (LES) pressure, or integrated relaxation pressure (IRP) among the type I, type II, and type III groups. All three patient groups showed a significant improvement in post-POEM Eckardt score (6.1±2.1 to 1.5±1.5, p=0.001; 6.8±2.2 to 1.2±0.9, p=0.001; 6.6±2.0 to 1.6±1.4, p=0.011), LES pressure (26.1±13.8 to 15.4±6.8, p=0.018; 32.3±19.0 to 19.2±10.4, p=0.003; 36.8±19.2 to 17.5±9.7, p=0.041), and 4s IRP (21.5±11.7 to 12.0±8.7, p=0.007; 24.5±14.8 to 12.0±7.6, p=0.002; 24.0±15.7 to 11.8±7.1, p=0.019) at a median follow-up of 16 months. CONCLUSIONS: POEM resulted in a good clinical outcome for all manometric subtypes.

Gastroesophageal reflux after peroral endoscopic myotomy: a multicenter case-control study.

Background and study aims The variables associated with gastroesophageal reflux (GER) after peroral endoscopic myotomy (POEM) are largely unknown. This study aimed to: 1) identify the prevalence of reflux esophagitis and asymptomatic GER in patients who underwent POEM, and 2) evaluate patient and intraprocedural variables associated with post-POEM GER. Patients and methods All patients who underwent POEM and subsequent objective testing for GER (pH study with or without upper gastrointestinal [GI] endoscopy) at seven tertiary academic centers (one Asian, two US, four European) were included. Patients were divided into two groups: 1) DeMeester score ≥ 14.72 (cases) and 2) DeMeester score of < 14.72 (controls). Asymptomatic GER was defined as a patient with a DeMeester score ≥ 14.72 who was not consuming proton pump inhibitor (PPI). Results A total of 282 patients (female 48.2 %, Caucasian 84.8 %; mean body mass index 24.1 kg/m2) were included. Clinical success was achieved in 94.3 % of patients. GER evaluation was completed after a median follow-up of 12 months (interquartile range 10 - 24 months). A DeMeester score of ≥ 14.72 was seen in 57.8 % of patients. Multivariable analysis revealed female sex to be the only independent association (odds ratio 1.69, 95 % confidence interval 1.04 - 2.74) with post-POEM GER. No intraprocedural variables were associated with GER. Upper GI endoscopy was available in 233 patients, 54 (23.2 %) of whom were noted to have reflux esophagitis (majority Los Angeles Grade A or B). GER was asymptomatic in 60.1 %. Conclusion Post-POEM GER was seen in the majority of patients. No intraprocedural variables were identified to allow for potential alteration in procedural technique.

Evaluation and Endoscopic Management of Esophageal Submucosal Tumor.

Submucosal tumors (SMTs) originate from tissues that constitute the submucosal layer and muscularis propria, and are covered by normal mucosa. Esophageal SMTs are rare, accounting for <1% of all esophageal tumors. However, the recent widespread use of endoscopy has led to a rapid increase in incidental detection of SMTs in Korea. Esophageal SMTs are benign in ≥90% of cases, but the possibility of malignancies such as gastrointestinal stromal tumor and malignant leiomyosarcoma still exists. Therefore, patients undergo resection in the presence of symptoms or the possibility of a malignant tumor. For resection of esophageal SMTs, surgical resection was the only option available in case of possible malignancy, but minimally invasive surgery by endoscopic resection is becoming more preferable to surgical resection with the development of endoscopic ultrasonography, endoscopic techniques, and other devices.

Current Techniques for Treating Gastrointestinal Stromal Tumors in the Upper Gastrointestinal Tract.

Most gastrointestinal stromal tumors (GISTs) arise from the proper muscle layer of the upper gastrointestinal (GI) tract and have a low malignant potential. They are sometimes accompanied by symptoms, but in most cases are detected by chance. Endoscopic surgery of subepithelial tumors in the upper GI tract has been actively performed, and its merits include the need for fewer medical devices compared with other surgical procedures and post-resection organ preservation. However, because endoscopic procedures are still limited to small or pilot studies, a multidisciplinary approach combining laparoscopy and endoscopy is needed for more effective and pathologically acceptable management of GISTs. Many new endoscopic surgeries have been developed, and this review describes the current status of and the new approaches for endoscopic surgery of GISTs in the upper GI tract.

Tissue diagnosis of GI subepithelial tumor only through Trucut biopsy under a forward-viewing endoscope: applicability as newer diagnostic modality.

BACKGROUND: Trucut biopsy (TCB) has been proposed to overcome the limitations of endoscopic ultrasonography (EUS)-guided fine-needle aspiration for the pathologic diagnosis of upper gastrointestinal (GI) subepithelial tumor (SET); however, it can be difficult to perform because the Trucut biopsy needle is very stiff. Although technical failures have been reported with the use of TCB, recently the forward-viewing echoendoscope showed a high diagnostic accuracy. We hypothesized that TCB under a conventional forward-viewing endoscope can be applied with higher yield of tissue diagnosis. METHODS: To evaluate the feasibility of TCB under a forward-looking endoscopy without cumbersome EUS guidance, we introduced a 19-gauge TCB needle into the working channel of a conventional upper endoscope in 27 patients with GI SET to make tissue diagnosis. Prospectively collected data were analyzed, including technical success rate, pathologic result, and adverse events. RESULTS: Twenty-seven patients with GI SET (18 esophageal tumors and nine gastric tumors) underwent TCB under a forward-looking endoscope. All procedures were performed safely without any TCB-related complications. Subsequently, histopathology examination revealed gastrointestinal stromal tumors (GISTs) in three cases and leiomyomas in 21 cases. Histologic assessment was completed in 24 out of 27 patients (88.9 %) because tissue obtained from three patients, whose tumors were located in the stomach, was not sufficient for the pathologic diagnosis. CONCLUSIONS: TCB using a conventional forward-viewing endoscope without EUS guidance provided an excellent pathologic diagnosis of upper GI SET.

Korean red ginseng ameliorated experimental pancreatitis through the inhibition of hydrogen sulfide in mice.

AIM: Effective therapy to treat acute pancreatitis (AP) or to prevent its recurrence/complication is still not available. Based on previous results that suggest that: i) hydrogen sulfide (H2S) levels were significantly increased in pancreatitis and gastritis and ii) Korean red ginseng (KRG) efficiently attenuated Helicobacter pylori-associated gastritis through the suppressive actions of H2S, we hypothesized that KRG can ameliorate experimental pancreatitis through suppression of H2S generation. METHODS: C57BL/6 mice were pre-administered KRG and then subjected to cerulein injection or pancreatic duct ligation (PDL) to induce pancreatitis. Blood and pancreas tissues were collected and processed to measure serum levels of amylase, lipase and myeloperoxidase and the concentration of H2S and the levels of various inflammatory cytokine in pancreatic tissues of mice with induced AP. RESULTS: KRG significantly inhibited NaHS-induced COX-2 and TNF-α mRNA in pancreatic cells, but dl-propargylglycine did not. KRG ameliorated cerulein-induced edematous pancreatitis accompanied with significant inactivation of NF-κB and JNK in pancreatic tissues of C57BL/6 mice (p < 0.001) and also significantly ameliorated PDL-induced necrotizing pancreatitis (p<0.01); in both conditions, the significant suppression of H2S resulting from KRG pretreatment afforded rescuing outcomes. Along with suppressed levels of H2S consequent to depressed expressions of CBS and CSE mRNA, KRG administration efficiently decreased the serum level of amylase, lipase, and myeloperoxidase and the expression of inflammatory cytokines in animal models of mild or severe AP. CONCLUSIONS: These results provide evidence for the preventive and therapeutic roles of KRG against AP mediated by H2S suppression.

Double-Scope Peroral Endoscopic Myotomy (POEM) for Esophageal Achalasia: The First Trial of a New Double-Scope POEM.

With the accumulation of clinical trials demonstrating its efficacy and safety, peroral endoscopic myotomy (POEM) has emerged as a less invasive treatment option for esophageal achalasia compared with laparoscopic Heller myotomy. However, the difficulty in determining the exact extent of myotomy, a critical factor associated with the success and safety of the procedure, remains a limitation. Although the various endoscopic landmarks and ancillary techniques have been applied, none of these has been proven sufficient. As a solution for this limitation, the double-scope POEM technique with a second endoscope to assure the exact length of the submucosal tunnel has been applied since 2014. Before double-scope POEM was introduced, the second endoscope was applied only to confirm the accuracy of the procedure. In the present study, we performed double-scope POEM in the treatment of esophageal achalasia through a novel procedure of simultaneous application of the second endoscope to assist in the conventional POEM procedure.

Endoscopic resection of early gastric cancer: current status and new approaches.

Endoscopic resection (ER) of early gastric cancer (EGC) has been an optimal treatment for selected patients. As endoscopic submucosal dissection (ESD) has been widely used for treatment of EGC, concerns have been asked to achieve curative resection for EGC while guaranteeing precise prediction of lymph node metastasis (LNM). Moreover, a new microscopic imaging for precise endoscopic diagnosis of EGC is introduced. This review covers the current status and new approaches of ER of EGC.

Novel 3D-printing technique for caps to enable tailored therapeutic endoscopy.

BACKGROUND AND AIM: To evaluate the feasibility of a tailored endoscopic cap created using 3D-printing technology that is customized according to esophagogastric lesions of each patient. METHODS: Tailored endoscopic caps, which were designed and fabricated with a 3D printer, were inserted in 35 patients. The types of cap were side-hole cap made for cap-assisted endoscopic mucosal resection (EMRC), oblique-head cap designed for endoscopic submucosal dissection (ESD), wide-head cap used for Trucut biopsy (TCB), and narrow-tip cap to facilitate peroral endoscopic myotomy (POEM). RESULTS: EMRC in the esophagus and gastroesophageal junction was carried out using a side-hole cap in seven patients. Median total procedure time for successful removal of lesions was 14 min (range 8-50 min). Gastric ESD was carried out using with an oblique-head cap in 16 patients, for which the median total procedure time was 53 min. TCB in the esophagus was done using a wide-head cap in eight patients. While carrying out POEM for tunneling, a narrow-tip cap was used in four patients with achalasia. CONCLUSION: Based on the current proof-of-concept study, we anticipate that creating a tailored endoscopic cap is feasible for therapeutic endoscopy.

Long-term outcomes of endoscopic submucosal dissection for early gastric cancer: a comparison study to surgery using propensity score-matched analysis.

BACKGROUND: Endoscopic submucosal dissection (ESD) has been accepted as a standard treatment in early gastric cancer (EGC) patients with negligible risk of lymph node metastasis. However, there are limited data regarding the long-term outcomes of ESD in comparison with surgery. This study aimed to compare the overall, recurrence-free, and metachronous cancer-free survival rates after ESD and surgery. METHODS: From May 2003 to December 2007, 391 patients with 413 EGCs and 258 patients with 276 EGCs were treated by ESD and surgery, respectively. According to inclusion criteria, 288 patients in the ESD group and 173 patients in the surgery group were eligible for this study. Using propensity score matching, 88 patients were analyzed per group. RESULTS: The overall survival rates were 92.0 % in the ESD group and 90.2 % in the surgery group. Local recurrence was observed in five patients (1.7 %) in the ESD group and distant recurrence in one patient (0.6 %) in the surgery group. Metachronous gastric cancers were detected in 14 patients (4.9 %) in the ESD group, whereas no patient in the surgery group. Kaplan-Meier curves exhibited no significant differences in overall or recurrence-free survival between the two groups. However, metachronous cancer-free survival of the ESD group was significantly lower than that of the surgery group (p = 0.002). In the ESD group, the late complication rate was significantly lower (0 vs. 6.8 %, p = 0.029), and the duration of hospital stay was shorter (7.3 vs. 14.2 days, p < 0.001), compared with the surgery group. CONCLUSIONS: The overall survival was similar between the ESD and surgery groups. Compared with surgery, the benefits of ESD included fewer late complications and shorter hospital stay duration.