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The concept of submucosal space, or rather the "third space", located between the intact mucosal flap and the muscularis propria layer of the gastrointestinal tract, represents a tunnel that the endoscopist could use to perform interventions in the muscularis propria layer or breech it to enter the mediastinum or the peritoneal cavity without full thickness perforation. The tunnel technique can be used both for the removal of mucosal tumours, called endoscopic submucosal tunnel dissection (ESTD), for the removal of subepithelial tumours (SELs), called submucosal tunnelling endoscopic resection (STER), and for the removal of extra-luminal lesions (for example in the mediastinum or in the rectum), called submucosal tunnelling endoscopic resection for extraluminal tumours (STER-ET). Aim of this updated narrative review, is to summarize the evidences that analyses indications, and outcomes of tunnelling techniques for the treatment of above mentioned lesions.

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BACKGROUND AND AIMS: This pilot study aimed to evaluate safety and tissue sampling from subepithelial lesions (SEL) in the upper gastrointestinal tract with a novel electric motor driven endoscopic ultrasonography (EUS)-guided 17-gauge (G) size core needle biopsy (CNB) instrument. METHODS: An investigator-led prospective open label, performance and safety control study, including seven patients (female n = 4, median 71 y, range 28-75) with a determined SEL (median size 30 mm, range 17-150 mm) in the upper digestive tract (stomach n = 6, duodenum n = 1) were eligible and later followed up 14 days after index procedure. All investigations were completed according to protocol with three FNB 22-G passes with four fanning strokes and two EndoDrill® 17-G passes with three fanning strokes. RESULTS: Quality of samples as 'visible pieces' (>5 mm): FNB (n = 5/7) (fragmented/blood imbibed n = 1, poor tissue quantity n = 1) compared with 17-G CNB (n = 7/7). Histological result which led to final diagnosis (leiomyoma n = 2, adenocarcinoma n = 1, schwannoma n = 1, neuroendocrine tumour n = 1, desmoid tumour n = 1 and gastrointestinal stromal tumour (GIST) n = 1) could be obtained with the 17-G CNB instrument in all seven patients. FNB technique reached correct diagnosis in six patients. No serious adverse event were recorded. CONCLUSIONS: By using an electric driven 17-G biopsy device, a true cylinder of core tissue can be obtained in one single puncture from the area of interest reducing the need for a second sampling. The absolute benefit of EUS-guided CNB is that the sample can be handled and histologically prepared in the same manner as standard percutaneous core needle sample, e.g., breast and prostate cancer.

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Exposed endoscopic full-thickness resection (Eo-EFTR) has been recognized as a feasible therapy for gastrointestinal submucosal tumours (SMTs) originating deep in the muscularis propria layer; however, Eo-EFTR is difficult to perform in a retroflexed fashion in the gastric fundus. As a supportive technique, clip- and snare-assisted traction may help expose the surgical field and shorten the operation time in endoscopic resection of difficult regions. However, the application of clip- and snare-assisted traction in Eo-EFTR of SMTs in the gastric fundus is limited. Between April 2018 and December 2021, Eo-EFTR with clip- and snare-assisted traction was performed in 20 patients with SMTs in the gastric fundus at The First Affiliated Hospital of Soochow University. The relevant clinical data were collected retrospectively for all of the patients and analysed. All 20 patients underwent Eo-EFTR successfully without conversion to open surgery or severe adverse events. The en bloc resection rate and R0 resection rate were both 100%. Two patients had abdominal pain and fever after the operation, and five patients had fever, which recovered with medical therapy. No complications, such as delayed bleeding or delayed perforation, were observed. The postoperative pathology indicated that 19 cases were gastrointestinal stromal tumours and one case was leiomyoma. During the follow-up, no residual tumour, local recurrence or distant metastasis was detected by endoscopy or abdominal computed tomography. In conclusion, Eo-EFTR with clip- and snare-assisted traction appears to be a relatively safe and effective treatment for gastric SMTs in the fundus. However, prospective studies on a larger sample size are required to verify the effect of the clip- and snare-assisted traction in Eo-EFTR.

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Purpose: To investigate the clinicopathological characteristics, diagnosis and key points in the differential diagnosis of patients with gastric cancer (GC) with features of a submucosal tumour (GCSMT). Methods: The clinical presentation and imaging findings of four GCSMT cases diagnosed at our centre from 2016 to 2021 were observed and their clinicopathological outcomes were analysed. The related literature was reviewed. Based on our collected data and the related literature, a total of 31 cases of GCSMT can be summarized. Results: 22 out of 31 cases did not present obvious symptoms and were accidentally discovered during gastroscopic examination. Only 10 patients experienced symptoms such as gastric discomfort, upper abdominal swelling and pain, haematemesis, or haematochezia. The male to female ratio was 22:9 and the age of onset ranged from 40 to 81 years (median age: 63 years). Tumours were located in the upper and middle third of the stomach (24/31), and in the lower third(7/31). The tumour diameter ranged from 0.6 to 7.3 cm, with an average value of 2.5 cm. Endoscopically, the disease manifested as SMTs, with the gastric mucosal surface appearing normal. Most patients underwent radical gastrectomy for GC (80.6%, 25/31). The pathological diagnoses of the 31 cases of GCSMT included well- and moderately-differentiated adenocarcinoma (6/31), poorly differentiated adenocarcinoma or signet ring cell carcinoma 6/31), mucinous adenocarcinoma (9/31), lymphoepithelioma-like carcinoma (7/31), gastric adenocarcinoma of the fundic gland type (3/31). Stage T1b and T2 tumours accounted for 56.7% (17/30) and 26.7% (8/30) of all cases. Lymph node metastases were found in six cases (20.0%, 6/30), whereas distant metastasis was not observed in any of the cases. For the 16 patients whose follow-up data were available, the follow-up time was 5-66 months, during which recurrence or metastasis was not observed. Conclusion: GCSMT is a rare disease that is often difficult to accurately diagnose through endoscopic biopsy. The importance of gaining an understanding of this disease lies in differentiating it from other SMTs (mostly mesenchymal tumours) to avoid misdiagnosis and missed diagnosis and enable the early diagnosis and treatment of patients.

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Aims and Objectives: Although laparoscopic surgery for submucosal tumours (SMTs) may require multiple support threads, the traction direction of a single thread is only one option and cannot be freely changed. To solve this problem, we introduced a novel innovative technique for tumour handling, named 'the parachute method'. Subjects and Methods: Prior to suturing, the surrounding vessel was treated when the tumour was located near the lesser or greater curvature. A monofilament thread was ligated in the serous muscle layer along the peritumoural markings with approximately five stitches in a row, with moderate deflection. Next, the other monofilament thread was passed through the deflection and ligated; this resembled a parachute shape that could be pulled in any direction over the entire circumference with uniform tension. Results: We performed this procedure in three patients with extramural growth-type gastrointestinal stromal tumours of approximately 2-3 cm. The median suturing time was 10 minutes. Laparoscopic local resection of the stomach was safely performed, and the patients were discharged without any complications. Conclusion: In this study, we demonstrate a novel, simple, inexpensive, useful and reasonable technique for handling SMTs, named 'the parachute method'. We believe that this technique will have additional applications in cooperative surgery with endoscopy.

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BACKGROUND: The conventional near-infrared fluorescence clip (NIRFC): ZEOCLIP FS®, was difficult to observe using the Firefly on da Vinci. We improved the ZEOCLIP FS® and produced the da Vinci compatible NIRFC. In this report, we describe a robot-assisted wedge resection of a submucosal tumour (SMT) of the stomach using the da Vinci compatible NIRFC. PRESENTATION OF CASE: Surgery was performed for an enlarging SMT (from 18 to 22 mm with an intragastric growth type). Through endoscopy, four da Vinci-compatible NIRFCs were placed at the tumour edge two days prior to the surgery. The location of the NIRFC was confirmed when observed with the Firefly. The distal NIRFC site was incised with a monopolar shear blade to identify the NIRFCs and tumour base. The open area was sutured in two layers using a 3-0 V-Loc. The operation time was 83 min, and the amount of blood loss was 2 g. There were no complications or clip dropout. DISCUSSION: This method could be performed without intraoperative endoscopist. CONCLUSION: In this case, we were able to observe the position of the da Vinci-compatible NIRFC with Firefly on da Vinci. This technique may be an option as a simple procedure to minimize the resection area of the stomach.

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Oesophageal schwannomas are extremely rare tumours arising from Schwann cells of the neural sheath, with less than 115 cases reported in the English literature. These tumours are usually sporadic and account for about 2% of all stromal oesophageal tumours. Diagnosis is usually confirmed by the presence of positive immunohistochemical marker S-100 and absence of CD117, CD34, smooth muscle actine and Desmin. Treatment can vary from enucleation to oesophagectomy. Herein, we report a case of a 61-year-old woman who presented with progressive dysphagia. Computerized tomography scan revealed a 5 × 3 cm mass extending proximal to the azygos arch. Oesophagogastroduodenoscopy showed a submucosal mass at 20-24 cm from the incisors. Endoscopic ultrasound showed a 6 × 3 cm well-circumscribed mass originating from the fourth layer, suspicious for a gastrointestinal stromal tumour. The patient underwent thoracoscopic enucleation of the tumour in a semi-prone position. Final pathology was consistent with a completely resected benign oesophageal schwannoma, positive for S-100.

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BACKGROUND: Oesophageal submucosal tumours are usually benign. We report a rare case of esophageal squamous cell carcinoma presenting as a submucosal tumour. CASE PRESENTATION: A 58-year-old man undergoing screening oesophago-gastroduodenoscopy was found to have a smooth-surfaced 0.6-cm sized submucosal tumour in the oesophagus 30 cm from the incisor. Endoscopic ultrasonography showed the tumour to be located in the muscularis mucosa; the lesion was heterogeneously hypoechoic and had a clear boundary. With a provisional diagnosis of leiomyoma, the tumour was removed by endoscopic submucosal dissection. Pathological examination showed it to be a moderately differentiated infiltrating squamous cell carcinoma, with normal overlying squamous epithelium. Immunohistochemistry indicated that it was caused by malignant transformation in mucosal glandular duct epithelium. Positron emission tomography-computer tomography showed no tumour spread to any other site. The patient was treated by oesophageal resection. CONCLUSION: The clinician should be aware that oesophageal submucosal tumours with smooth overlying mucosa may not always be benign; malignancy must be ruled out.

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Gastric ectopic pancreas presenting as a submucosal tumour accounts for approximately 11% of all endoscopic ultrasonography (EUS) examinations. Definitive diagnosis through endoscopy is difficult, even with EUS-guided fine-needle aspiration biopsy for histological examination. For symptomatic patients or those with uncertain diagnosis, complete surgical resection is the primary strategy for treatment and diagnosis. Herein, we report a case of gastric ectopic pancreas treated using robotic surgery.

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BACKGROUND: Rectal submucosal tumours are rare. The purpose of this study was to evaluate the safety and feasibility of robot-assisted rectal surgery. METHODS: Patients who received robot-assisted intersphincteric resection (ISR) were included in the present study. Clinical outcomes, operating time, length of hospital stay and pathological status were analysed. RESULTS: There were three patients with gastrointestinal tumours and three patients diagnosed with neuroendocrine tumours. The mean operating time was 369.2 min and the estimated blood loss was 66.7 ml. There were neither intraoperative complications nor conversions. On pathological examination, the mean number of lymph nodes harvested was 10.3 (range 3-16), the mean distal resection margin was 1.1 (range 0.1-3) cm and all six patients had the circumferential resection margins clear. CONCLUSIONS: Our data show that robotic surgery is feasible and safe, with no morbidity or mortality, and that ISR provides bowel continuity and eliminates the need for colostomy. Copyright © 2015 John Wiley & Sons, Ltd.

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AIM: A ligation-assisted endoscopic enucleation (EE-L) technique was developed and was evaluated to determine its efficacy and safety for treating colorectal submucosal tumours (< 10 mm) originating in the muscularis propria. METHOD: EE-L was used to treat 13 patients between January 2011 and January 2014. The tumour was sucked into a transparent cap and ligated at its base by a rubber band ligature attached to the tip of the endoscope. With the creation of a pseudo-stalk, the tumour was then enucleated using endoscopic dissection and the wound was closed with clips. RESULTS: All tumours [median diameter 6.8 (4-10) mm] were successfully enucleated [procedure time 19 (11-27) min]. Histopathological examination identified 11 (84.6%) to be leiomyoma and 2 (15.4%) low-risk gastrointestinal stromal tumours. No perforations or massive haemorrhage occurred and there were no recurrences during a follow-up of 3-39 months. CONCLUSION: EE-L is a successful technique for the removal of small colorectal tumours in the muscularis propria with few complications and enables a histopathological diagnosis. In this study, all the resected lesions had a benign pathology.

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Over the last decade, the development of stabilised microbubble contrast agents and improvements in available ultrasonic equipment, such as harmonic imaging, have enabled us to display microbubble enhancements on a greyscale with optimal contrast and spatial resolution. Recent technological advances made contrast harmonic technology available for endoscopic ultrasound (EUS) for the first time in 2008. Thus, the evaluation of microcirculation is now feasible with EUS, prompting the evolution of contrast-enhanced EUS from vascular imaging to images of the perfused tissue. Although the relevant experience is still preliminary, several reports have highlighted contrast-enhanced harmonic EUS (CH-EUS) as a promising noninvasive method to visualise and characterise lesions and to differentiate benign from malignant focal lesions. Even if histology remains the gold standard, the combination of CH-EUS and EUS fine needle aspiration (EUS-FNA) can not only render EUS more accurate but may also assist physicians in making decisions when EUS-FNA is inconclusive, increasing the yield of EUS-FNA by guiding the puncture with simultaneous imaging of the vascularity. The development of CH-EUS has also opened up exciting possibilities in other research areas, including monitoring responses to anticancer chemotherapy or to ethanol-induced pancreatic tissue ablation, anticancer therapies based on ultrasound-triggered drug and gene delivery, and therapeutic adjuvants by contrast ultrasound-induced apoptosis. Contrast harmonic imaging is gaining popularity because of its efficacy, simplicity and non-invasive nature, and many expectations are currently resting on this technique. If its potential is confirmed in the near future, contrast harmonic imaging will become a standard practice in EUS.

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BACKGROUND: The true impact of surgery for small, asymptomatic and biopsy-negative gastric submucosal tumours (SMTs) with size enlargement during 'watchful waiting' period has not been fully understood. METHODS: From 2005 to 2012, 100 patients with gastric SMTs underwent surgery. Twenty-three of them with size enlargement during observation period were enrolled in the retrospective analysis. Data included clinicopathologic findings, genetic findings, operative outcomes and prognoses. RESULTS: All patients (13 males, 10 females), with median age of 54 (41-71), had their lesions detected by routine health check-up (n=21) or incidentally (2). The tumours were 1.8 (0.5-4.0)cm in size at their initial detection, and enlarged up to 3.2 (2.0-7.0)cm at the operation during 63.0 (14.6-233.7) months. As surgical procedure, laparoscopic partial gastrectomy accounted for the majority (78.3%). Histologic examination revealed gastrointestinal stromal tumour (GIST) (21) and schwannoma (2). Although 16 out of 21 GISTs were categorised into 'Very low' (1), and 'Low' (13) risk according to Fletcher's classification, 'Intermediate' (5) and 'High' (2) risk were identified in the series. No recurrences/metastases were noted in 23.2 (0.9-87) months of postoperative follow-up. CONCLUSION: Our study revealed the existence of high mitotic GISTs in asymptomatic, small gastric SMTs with size enlargement, and laparoscopic surgery was safely applied to majority of those cases. Prompt surgical intervention should therefore be considered for those lesions.

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