Modified Gastric Peroral Endoscopic Myotomy for the Treatment of Gastric Stenosis after Atypical Gastrectomy

The role of endoscopy in subepithelial lesions of the GI tract

Endoscopic tunneling and subserosal dissection using a natural orifice transluminal endoscopic surgery approach for a gastrointestinal stromal tumor.

Background Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors found throughout the gastrointestinal tract, with esophageal GISTs being particularly uncommon. Surgical resection is the standard treatment option, though it is associated with significant morbidity. Submucosal Tunneling Endoscopic Resection (STER) is a minimally invasive technique for per-oral subepithelial tumor removal with preservation of the surrounding esophagus and no need for thoracoscopy or mediastinoscopy. Herein, we report a successful case of STER for esophageal GIST in an elderly Canadian patient. Aims To present the successful management of an esophageal GIST using submucosal tunneling endoscopic resection. Methods Case report and literature review. Results: Case Report An 80-year-old man with dysphagia underwent an EUS for a 1.5 cm subepithelial lesion identified in his mid-esophagus on EGD. EUS showed a hypoechoic lesion arising from the muscularis propria. Biopsy confirmed a spindle cell tumor, C-KIT positive consistent with GIST. The patient was offered transthoracic surgical resection but declined given the associated risks and complications. An interval CT scan demonstrated a 4 mm increase in the size of the tumor. The patient was referred for consideration of endoscopic resection. He ultimately underwent submucosal tunneled endoscopic resection of the GIST with no complications. The procedure was performed by creating a mucosal flap over the GIST via submucosal tunnelling with subsequent traction assisted full thickness myotomy surrounding the lesion while preserving the capsule, followed by clip closure of the mucosotomy. Pathology confirmed R0 resection with low mitotic rate. A routine esophagram post-procedure showed no contrast leakage, and the patient was discharged the following day. Literature Review STER is a minimally invasive technique for resection of gastrointestinal subepithelial lesions first reported in 2012. It offers several advantages including preservation of GI tract function, rapid recovery time, and low adverse event rate but requires careful lesion selection and technical facility with endoscopic submucosal dissection, myotomy and defect closure. Studies have demonstrated high rates of complete resection with low complication risks, particularly in treating small to medium-sized tumors. To our knowledge, this case represents the first reported use of STER in Canada. Conclusions: Conclusions STER is a minimally invasive option for resection of subepithelial lesions. In this case it was used effectively with readily available equipment in a Canadian hospital. It reduces recovery time, preserves esophageal structure, and minimizes complications. Funding Agencies None

Dear Editor: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the digestive tract. Surgery and imatinib are the recommended treatments for advanced highrisk GIST. However, even in most patients showing an initial response, imatinib resistance is developed within a few years. After progression, current therapeutic options include the switch to other tyrosine kinase inhibitors (TKI) or surgical debulking. We here report long-term survival in a metastatic GIST patient treated with reiterated multimodal therapeutic approaches and as a fourth-line treatment, imatinib rechallenge. Molecular analysis of the tumors provided a framework for interpretation of the pattern of response observed. A 52-year-old man was referred to surgical intervention for an abdominal mass in January 2003. Surgery revealed a major (15 cm) intestinal tumor, together with other smaller peritoneal nodules, which were also resected. At pathological evaluation, the lesions displayed a spindle cell morphology, were CD117 (KIT) positive, CD34 positive, desmin negative, focally positive for smooth muscle actin and S100, and negative for cytokeratins, consistent with a diagnosis of metastatic, high-risk GIST. Six months later, the patient relapsed and underwent a II surgery with complete resection (R0) of a mass of 12 cm at the right iliac fossa, pathologically confirmed as GIST. Adjuvant imatinib (400 mg/day) was administered for 24 months, without evidence of recurrence. Eight months after imatinib discontinuation, a CT scan revealed a mass of 6 cm at the right iliac fossa and multiple peritoneal nodules without clinical symptoms. Imatinib was therefore resumed at the same dose. Radiological assessment showed an initial response, but 14 months later, disease progression was observed. Patient then underwent curative III surgery (R0) for a major mass (8 cm) proximal to the rectum and multiple peritoneal and omental nodules of smaller size. After surgery, imatinib was continued at 400 mg/day until, 8 months later, disease recurrence was documented by CT scan with a larger pararectal mass and multiple small peritoneal nodules. Patient was again subjected to tumor debulking (IV surgery) with microscopic residual disease (R=1). Patient resumed imatinib at a higher dose (800 mg/day). Due to disease progression, after 3 months, he was switched to sunitinib (50 mg/day), reducing the dosage (37.5 mg/day) after the first cycle because of poor tolerance. Treatment was continued for 15 months until pelvic progression was detected. For his third line treatment, the patient was enrolled in a clinical trial evaluating nilotinib efficacy in patients with unresectable/metastatic GIST and refractory to imatinib and/ or sunitinib. Nilotinib was given at 800 mg/day for 2 months, until CT scan showed abdominal progression. Surgical Gianmaria Miolo and Elena Torrisi contributed equally to this work.

Gastrointestinal stromal tumors (GISTs) and gastrointestinal leiomyomas (GILs) are the most common subepithelial lesions (SELs). All GISTs have malignant potential; however, GILs are considered benign. Current imaging cannot effectively distinguish GISTs from GILs. We aimed to develop an artificial intelligence (AI) system to differentiate these tumors using endoscopic ultrasonography (EUS). The AI system was based on EUS images of patients with histologically confirmed GISTs or GILs. Participants from four centers were collected to develop and retrospectively evaluate the AI-based system. The system was used when endosonographers considered SELs to be GISTs or GILs. It was then used in a multicenter prospective diagnostic test to clinically explore whether joint diagnoses by endosonographers and the AI system can distinguish between GISTs and GILs to improve the total diagnostic accuracy for SELs. The AI system was developed using 10 439 EUS images from 752 participants with GISTs or GILs. In the prospective test, 132 participants were histologically diagnosed (36 GISTs, 44 GILs, and 52 other types of SELs) among 508 consecutive subjects. Through joint diagnoses, the total accuracy of endosonographers in diagnosing the 132 histologically confirmed participants increased from 69.7 % (95 % confidence interval [CI] 61.4 %-76.9 %) to 78.8 % (95 %CI 71.0 %-84.9 %; P = 0.01). The accuracy of endosonographers in diagnosing the 80 participants with GISTs or GILs increased from 73.8 % (95 %CI 63.1 %-82.2 %) to 88.8 % (95 %CI 79.8 %-94.2 %; P = 0.01). We developed an AI-based EUS diagnostic system that can effectively distinguish GISTs from GILs and improve the diagnostic accuracy of SELs.

Background/Aims: Differentiating subepithelial tumor (SET) from non-neoplastic gastrointestinal subepithelial lesion (SEL) and gastrointestinal stromal tumor (GIST) from leiomyoma are very important for proper management. This study was conducted to analyze factors that could predict the presence of SET and GIST in patients with upper gastrointestinal (UGI) SELs. Methods: A total of 527 patients were diagnosed with UGI SELs endosonographically at Gyeongsang National University Hospital from January 2008 to June 2013. Among these patients, histologic diagnosis was made in 84 patients. Data were collected by retrospectively reviewing the medical records. Variables that could differentiate neoplastic from non-neoplastic SELs and GIST from leiomyoma were analyzed. Results: Among 84 patients with SELs, 64 (76.2%) had SETs including GIST (42.9%) and leiomyoma (19.0%). The patients’ mean age (p=0.047), peak age distribution (p=0.047), proportions of patient ≥50 years (p=0.015), and number of proper muscle-originated lesions (p=0.001) were higher in neoplastic than non-neoplastic group. There were no significant differences in gender (p=0.195), size (p=0.266) and echogenicity (p=0.051) of the lesions. Older age (57.7 vs. 47.0 years, p=0.049), age ≥50 years (p=0.016), location in gastric body (p＜0.001), and proper muscle origin (p=0.003) were significantly related to the presence of GIST compared to leiomyoma. Multiple regression analysis showed that the patients’ age ≥50 years, size ≥30 mm, and proper muscle-origin of lesion were independent predictors of SET; however, there were no predictive factors that could differentiate GIST from leiomyoma. Conclusions: In patients with SEL, the possibility of having SET should be considered for patients ≥50 years with UGI SELs ≥30 mm that arise from the proper muscle. Thorough monitoring and aggressive management is warranted for those with gastric muscular SET since factors predictive of GIST are lacking. (Korean J Gastroenterol 2014;64:189-197)

Our understanding of gastrointestinal stromal tumors (GIST) has evolved rapidly over the last few years. GISTs are now considered a distinct entity that arise from the interstitial cells of Cajal and exhibit a variable clinical course. One of the major breakthroughs was the discovery of CD117 antigen expression, also referred to as c-kit, on the tyrosine kinase receptor by GISTs. This antigen can be identified using immunohistochemistry (IHC), is expressed nearly universally by GISTs, and is critical in allowing differentiation of GISTs from myogenic, neurogenic, and other mesenchymal tumors. There has also been a paradigm shift in how the clinical behavior of GISTs is viewed; even though only 10–30% of GISTs are clinically malignant [1], all GISTs are now considered to have malignant potential with long-term follow-up [2]. This shift is based on a number of studies, one of which is a large series from Armed Forces Institute of Pathology (AFIP), where GISTs larger than 2 cm were found to have some finite risk of recurrence [3]. The natural history of smaller GISTs remains unclear at this point, though there have been reports of aggressive behavior in GISTs smaller than 2 cm in size [4]. Specific criteria that include size, mitotic count, and location of GISTs have been described to stratify risk of malignancy and tailor treatment [3, 5]. In this context, an accurate diagnosis, and if possible risk stratification of GISTs, is critical. Towards this end, endoscopic ultrasound (EUS) has become an important tool in our armamentarium. GISTs are typically seen to arise from the fourth layer of the gastric wall. While EUS imaging alone can accurately determine tumor size, wall layer of origin, echogenicity, and tumor margins, it is unable to reliably discriminate GISTs from other subepithelial tumors in all cases [6, 7]. Whether specific endosonographic features alone can help define low-risk and high-risk lesions also remains uncertain [8–10]. Consequently, many experts recommend EUSguided fine needle aspiration (EUS-FNA) for diagnostic sampling of subepithelial lesions when a diagnosis of GIST is being considered. However, in general, gastroenterologists continue to view EUS-FNA for subepithelial lesions with ambiguity. A recent survey of 134 members of the ASGE EUS special interest group found that only 58% believed that EUS combined with FNA was most predictive of a diagnosis of GIST [11]. This notion that EUSFNA is unrevealing in GISTs has been supported by reports of inadequate tissue acquisition with EUS-FNA with yields as low as 33.3% in all specimens [12]. Nevertheless, there is a growing body of more recent literature that has reported steadily improved diagnostic yields of EUS-FNA for GISTs. Watson et al. [13], in the current issue of Digestive Diseases and Sciences, provide additional data regarding the diagnostic yield and performance characteristics of EUS-FNA for GISTs. The authors retrospectively analyzed 65 consecutive patients who underwent EUS-FNA for 66 solid-appearing submucosal upper GI tract lesions over a 4-year period. A resection specimen was available and used as a reference in 28 patients. FNA was performed using either a 22-gauge or 19-gauge needle at the discretion of the endosonographer. A result was deemed diagnostic if a sufficient sample for cytopathologic evaluation and IHC analysis was obtained leading to a specific diagnosis. The authors found EUS-FNA to be diagnostic in 68%, V. Chandrasekhara N. A. Ahmad (&) HUP Division of Gastroenterology, Hospital of University of Pennsylvania, University of Pennsylvania School of Medicine, Ravdin 3 3400 Spruce Street, Philadelphia, PA 19104, USA e-mail: nuzhat.ahmad@uphs.upenn.edu

Background Surgical resection with laparoscopic gastric wedge resection is commonly conducted for local management of gastrointestinal stromal tumours (GIST). However, resection margins are often difficult to appreciate for lesions with larger endophytic components. As a result, tumour margins may be compromised or excess tissue resected. Laparoscopic endoscopic cooperative surgery (LECS) was developed in Japan to overcome these technical challenges in the resection of subepithelial lesions, including GISTs. Here, we present a case report of an early Canadian experience utilizing LECS in the management of gastric GIST. Aims To describe a case report of an early Canadian experience of LECS for the resection of a gastric GIST. Methods We performed a review of the literature and describe a case of LECS. Results We present a 70-year-old female referred to our centre for endoscopic resection of a 2.5x2.5cm histologically confirmed gastric GIST (low mitotic index and no known metastases). Repeat endoscopic evaluation at our centre confirmed a 25-30mm subepithelial lesion with both exophytic (small) and endophytic (large) components. After tumour board review, we opted for a LECS approach. In the OR, the lesion was identified endoscopically and marked with a Dual J-Knife (Olympus). The margins were injected with a combination of Voluven, methylene blue, and dilute epinephrine. A circumferential incision was then completed using standard ESD technique. The lesion was subsequently identified laparoscopically, with endoscopic guidance, along the lesser curvature. The lesser omentum was mobilized for clear visualization of the serosa around the lesion. A full thickness incision was made endoscopically along the distal aspect of lesion. Full thickness resection was continued endoscopically for one third of the circumference of the lesion until gastric insufflation became compromised. Full thickness resection was completed laparoscopically under endoscopic guidance with grossly negative margins. The defect was closed with running laparoscopic sutures. Endoscopic leak test was performed which was negative. The specimen was retrieved and follow up pathology demonstrated a GIST with low mitotic index and negative margins without tumour rupture. Conclusions In a review of the literature, LECS appears to minimize tissue resection while maintaining R0 resection rates. This technique is especially useful for subepithelial lesions with larger endophytic and transmural components. It has an excellent safety profile with a less than 5% anastomotic leak rate. As such, the literature supports LECS as a suitable procedure for gastric subepithelial lesions <50 mm. However, further studies are needed to compare it systematically to conventional laparoscopic wedge resection in addition to other innovative endoscopic techniques such as STER and EFTR. Funding Agencies None

Endoscopic ultrasonography (EUS) has been widely accepted in the diagnosis of all types of tumors, especially pancreatic tumors, lymph nodes, and subepithelial lesions (SELs). One reason is that the examination can provide a detailed observation, with tissue samples being immediately obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Many SELs are detected incidentally during endoscopic examinations without symptoms. Most SELs are mesenchymal tumors originating from the fourth layer, such as gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas. GISTs are potentially malignant. Surgical treatment is recommended for localized GISTs of ≥20 mm. However, the indications for the diagnosis and follow-up of GISTs of <20 mm in size are controversial. There are several reports on the rapid progression or metastasis of small GISTs. Therefore, it is important to determine whether a SEL is a GIST or not. The main diagnostic method is EUS-FNA. Recently, endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) using a new biopsy needle has been reported to obtain larger tissue samples. Additionally, various biopsy methods have been reported to have a high diagnostic rate for small GISTs. In local gastric SELs, regardless of the tumor size, EUS can be performed first; then, EUS-FNA/B or various biopsy methods can be used to obtain tissue samples for decision-making in relation to therapy and the follow-up period.

Efficacy of real-time artificial intelligence-aid endoscopic ultrasonography diagnostic system in discriminating gastrointestinal stromal tumors and leiomyomas: a multicenter diagnostic study

Objectives Recently, artificial intelligence (AI) has been applied to clinical diagnosis. Although AI has already been developed for gastrointestinal (GI) tract endoscopy, few studies have applied AI to endoscopic ultrasound (EUS) images. In this study, we used a computer-assisted diagnosis (CAD) system with deep learning analysis of EUS images (EUS-CAD) and assessed its ability to differentiate GI stromal tumors (GISTs) from other mesenchymal tumors and their risk classification performance. Materials and methods A total of 101 pathologically confirmed cases of subepithelial lesions (SELs) arising from the muscularis propria layer, including 69 GISTs, 17 leiomyomas and 15 schwannomas, were examined. A total of 3283 EUS images were used for training and five-fold-cross-validation, and 827 images were independently tested for diagnosing GISTs. For the risk classification of 69 GISTs, including very-low-, low-, intermediate- and high-risk GISTs, 2,784 EUS images were used for training and three-fold-cross-validation. Results For the differential diagnostic performance of GIST among all SELs, the accuracy, sensitivity, specificity and area under the receiver operating characteristic (ROC) curve were 80.4%, 82.9%, 75.3% and 0.865, respectively, whereas those for intermediate- and high-risk GISTs were 71.8%, 70.2%, 72.0% and 0.771, respectively. Conclusions The EUS-CAD system showed a good diagnostic yield in differentiating GISTs from other mesenchymal tumors and successfully demonstrated the GIST risk classification feasibility. This system can determine whether treatment is necessary based on EUS imaging alone without the need for additional invasive examinations.

Auxiliary diagnosis of subepithelial lesions by impedance measurement during EUS-guided fine-needle biopsy.

Gastrointestinal stromal tumors (GISTs) are common subepithelial lesions (SELs) and require treatment considering their malignant potential. We recently developed an endoscopic ultrasound-based artificial intelligence (EUS-AI) system to differentiate GISTs from non-GISTs in gastric SELs, which were used to train the system. We assessed whether the EUS-AI system designed for diagnosing gastric GISTs could be applied to non-gastric GISTs. Between January 2015 and January 2021, 52 patients with non-gastric SELs (esophagus, n = 15; duodenum, n = 26; colon, n = 11) were enrolled. The ability of EUS-AI to differentiate GISTs from non-GISTs in non-gastric SELs was examined. The accuracy, sensitivity, and specificity of EUS-AI for discriminating GISTs from non-GISTs in non-gastric SELs were 94.4%, 100%, and 86.1%, respectively, with an area under the curve of 0.98 based on the cutoff value set using the Youden index. In the subanalysis, the accuracy, sensitivity, and specificity of EUS-AI were highest in the esophagus (100%, 100%, 100%; duodenum, 96.2%, 100%, 0%; colon, 90.9%, 100%, 0%); the cutoff values were determined using the Youden index or the value determined using stomach cases. The diagnostic accuracy of EUS-AI increased as lesion size increased, regardless of lesion location. EUS-AI based on gastric SELs had good diagnostic ability for non-gastric GISTs.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms that typically present as subepithelial lumps. Mucosa-associated lymphoid tissue lymphoma (MALToma) is the most common gastric lymphoma, often a result of chronic Helicobacter pylori (H Pylori) infection. Endoscopic ultrasound (EUS) has an evolving role in diagnosing subepithelial lesions of the gastrointestinal tract. Few cases have been reported in the literature with GIST and MALToma presenting together in the stomach as “synchronous tumors”. We are reporting a patient with a gastric mass that was initially diagnosed as MALToma on gastric biopsies but core biopsies by EUS revealed underlying GIST as a synchronous tumor. 71-year-old woman presented with an incidental finding of a gastric mass measuring 23X27 mm on CT imaging. EGD showed 2x3 cm mass within the proximal stomach with central umbilication. Biopsies showed chronic active gastritis with evidence of H Pylori infection and a lymphoplasmacytic infiltrate; immunohistochemical staining for CD20 and CD3 shows increased B cells relative to T cells with a monoclonal B-cell population, consistent with a diagnosis of gastric MALToma. The patient was treated for H pylori with triple therapy. Follow up EGD confirmed eradication of H Pylori with persistence of the polypoid mass. EUS confirmed a sub epithelial mass measuring 2x1.5cm arising from the muscularis propria. Fine needle biopsy (FNB) showed neoplastic cells positive for CD117 confirming the diagnosis of GIST. He underwent curative laparoscopic wedge resection. GIST's and MALToma's are both rare tumors arising from the stomach. Gastroscopic biopsies can diagnose mucosal lesions like MALToma, but do not yield sufficient sub-epithelial tissue. MALToma's are a form of gastric lymphoma that usually responds to H pylori eradication in about 75% of cases. GIST's are subepithelial lesions with good outcomes following surgical resection if they have not metastasized. Our case represents a scenario where a superficial MALToma capped the underlying GIST lesion. Latter diagnosis was only obvious following EUS-FNB months after the initial diagnosis of GIST. In conclusion, persistence of an endophytic mass despite treatment of a superficial disease like MALToma in this case, should prompt referral for EUS to obtain sub-epithelial tissue looking for a synchronous tumor. This was a rare combination of two unusual gastric tumors-MALToma and GIST- with a good outcome.Figure: Abdominal CT (upper images) shows gastric mass on the greater curvature measuring 2.7X2.3 cm. EGD (bottom left) shows 2x3 cm mass within the proximal stomach with central umbilication. EGD biopsy from the mass (bottom right) shows lymphoplasmacytic infiltrate in the lamina propria consistent with MALToma as clonality studies showed monoclonal B cell population.Figure: EUS (left) shows sub epithelial mass measuring 2x1.5cm arising from the muscularis propria. EUS-guided FNB (right) showed uniform spindle cells in a fascicular growth appearance consistent with GIST as immunostaining was positive for CD117.

Subepithelial lesions (SELs) are gastrointestinal tumors with heterogeneous malignant potential. Endoscopic ultrasonography (EUS) is the leading method for evaluation, but without histopathological analysis, precise differentiation of SEL risk is limited. Artificial intelligence (AI) is a promising aid for the diagnosis of gastrointestinal lesions in the absence of histopathology. To determine the diagnostic accuracy of AI-assisted EUS in diagnosing SELs, especially lesions originating from the muscularis propria layer. Electronic databases including PubMed, EMBASE, and Cochrane Library were searched. Patients of any sex and > 18 years, with SELs assessed by EUS AI-assisted, with previous histopathological diagnosis, and presented sufficient data values which were extracted to construct a 2 × 2 table. The reference standard was histopathology. The primary outcome was the accuracy of AI for gastrointestinal stromal tumor (GIST). Secondary outcomes were AI-assisted EUS diagnosis for GIST vs gastrointestinal leiomyoma (GIL), the diagnostic performance of experienced endoscopists for GIST, and GIST vs GIL. Pooled sensitivity, specificity, positive, and negative predictive values were calculated. The corresponding summary receiver operating characteristic curve and post-test probability were also analyzed. Eight retrospective studies with a total of 2355 patients and 44154 images were included in this meta-analysis. The AI-assisted EUS for GIST diagnosis showed a sensitivity of 92% [95% confidence interval (CI): 0.89-0.95; P < 0.01), specificity of 80% (95%CI: 0.75-0.85; P < 0.01), and area under the curve (AUC) of 0.949. For diagnosis of GIST vs GIL by AI-assisted EUS, specificity was 90% (95%CI: 0.88-0.95; P = 0.02) and AUC of 0.966. The experienced endoscopists' values were sensitivity of 72% (95%CI: 0.67-0.76; P < 0.01), specificity of 70% (95%CI: 0.64-0.76; P < 0.01), and AUC of 0.777 for GIST. Evaluating GIST vs GIL, the experts achieved a sensitivity of 73% (95%CI: 0.65-0.80; P < 0.01) and an AUC of 0.819. AI-assisted EUS has high diagnostic accuracy for fourth-layer SELs, especially for GIST, demonstrating superiority compared to experienced endoscopists' and improving their diagnostic performance in the absence of invasive procedures.