Gastric Muscularis Propria Research Articles

Adeno-associated virus-9 reverses delayed gastric emptying of solids in diabetic mice.

Gastroparesis is defined by delayed gastric emptying (GE) without obstruction. Studies suggest targeting heme oxygenase-1 (HO1) may ameliorate diabetic gastroparesis. Upregulation of HO1 expression via interleukin-10 (IL-10) in the gastric muscularis propria is associated with reversal of delayed GE in diabetic NOD mice. IL-10 activates the M2 cytoprotective phenotype of macrophages and induces expression of HO1 protein. Here, we assess delivery of HO1 by recombinant adeno-associated viruses (AAVs) in diabetic mice with delayed GE. C57BL6 diabetic delayed GE mice were injected with 1 × 1012 vg scAAV9-cre, scAAV9-GFP, or scAAV9-HO1 particles. Changes to GE were assessed weekly utilizing our [13 C]-octanoic acid breath test. Stomach tissue was collected to assess the effect of scAAV9 treatment on Kit, NOS1, and HO1 expression. Delayed GE returned to normal within 2 weeks of treatment in 7/12 mice receiving scAAV9-cre and in 4/5 mice that received the scAAV9-GFP, whereas mice that received scAAV9-HO1 did not respond in the same manner and had GE that took significantly longer to return to normal (6/7 mice at 4-6 weeks). Kit, NOS1, and HO1 protein expression in scAAV9-GFP-treated mice with normal GE were not significantly different compared with diabetic mice with delayed GE. Injection of scAAV9 into diabetic C57BL6 mice produced a biological response that resulted in acceleration of GE independently of the cargo delivered by the AAV9 vector. Further research is needed to determine whether use of AAV mediated gene transduction in the gastric muscularis propria is beneficial and warranted.

Efficacy and feasibility of snare-assisted endoscopic resection of small submucosal gastric tumors: A retrospective analysis.

The prevalence of small submucosal gastric tumors is rising. Despite the fact that high success rate of endoscopic resection of small submucosal gastric tumors originating from the muscularis propria has been reported, the procedure is technically challenging and has a high rate of complications. In this study, we investigated the efficacy and feasibility of a novel snare-assisted endoscopic resection technique for small submucosal gastric tumors. This is a single-center consecutive study of 50 patients who were diagnosed with small submucosal gastric tumors originating from the muscularis propria and who subsequently underwent snare-assisted endoscopic resection between January 2019 and January 2021 at our hospital. Data on the demographic characteristics, procedural success rate, complications, recurrence rate, and histopathology of the resected specimen were collected and analyzed retrospectively. The majority of the patient's population was male (66%) with the mean age of 48.4 ± 9 years (range, 20-70 years). The mean size of the tumor confirmed by endoscopic ultrasonography was 6.4 ± 1.6mm (range, 3.1-9.8 mm). All the tumors were resected successfully using snare-assisted endoscopic resection technique. The mean procedure time was 22.8 ± 9.6 (range, 15-35 min). The technical (performed the procedure successfully without converting to surgery) and clinical (the patient fully recovered after the procedure without experiencing any complications) success rate of the procedure was 100%. Eighteen (24%) patients had very small amount of mucosal damage, and wound closure was not needed in these patients. During 6-24 months of follow-up, no recurrence or metastasis occurred. No adverse event was noted during the follow-up time. The novel approach of snare-assisted endoscopic resection is simple, feasible, and effective for tumors with small size and originating from the gastric muscularis propria. In addition, it offers a better alternative therapy for the complete resection of small submucosal gastric tumors. Its advantages compared with traditional endoscopic approaches such as endoscopic submucosal resection and endoscopic submucosal dissection include shorter procedure times, lesser cost, and a lower rate of complications (perforation, bleeding, and infection).

ID: 3527921 ENDOSCOPIC INTRAPERITONEAL SUBSEROSAL DISSECTION (EISD): BETTER VIEW, SAFER OPERATION

Gastric submucosal tumor (SMT) originated from deep layers of the gastric wall can be resected by EFTR or STER. However, the lesions are usually in a tangent position, and the endoscopic view from gastric lumen is inherent poor. In addition, the highly movable tumor with limited endoscopic exposure increases the difficulty in the en bloc resection as well as safe hemostasis. Herein, we developed a modified method, called endoscopic intraperitoneal subserosal dissection (EISD), for the removal of gastric SMT with predominately extraluminal growth pattern. The specific steps of our technique were as follows. First, 1.5-cm gastric mucosal incision was created about 4-cm proximal to the lesion after submucosal injection. Subsequently, a short submucosal tunnel was created, and the gastric muscularis propria was then intentionally perforated about 3-cm away from the lesion. After locating the lesion on the serosa from the abdominal cavity, the tumor was carefully dissected from the serosa and the underlying muscularis propria without interruption of the tumor capsule. Subserosal injection was performed when necessary to create working space or to identify the layer. Caution should be taken to avoid the damage of the integrity of the mucosa during the dissection. The lesion was then removed after full dissection. Finally, after careful hemostasis, the tunnel entrance was closed. The video showed the two EISD cases of stromal tumor in the gastric body originated from the deep muscularis propria with predominantly extraluminal growth. The operating time was 70 and 65 minutes, respectively. The follow-up endoscopy and CT showed satisfactory healing with no residual tumor.

Value and limitation of endoscopic ultrasonography on the diagnosis of gastrointestinal submucosal tumor prior to endoscopic resection

Objective To investigate the efficacy and limitation of endoscopic ultrasonography(EUS) on the diagnosis of gastrointestinal submucosal tumor (SMT) prior to endoscopic resection. Methods Data of 211 patients, who were confirmed as gastrointestinal SMT before operation and received endoscopic resection for gastrointestinal submucosal tumor at Department of Gastroenterology, Shanghai Ruijin Hospital from January 2016 to December 2018 were analyzed. The value and limitation of EUS for SMT were investigated according to the final pathology. Results For the lesion distribution, 66 were in esophagus, 108 in stomach, 2 in duodenum and 35 in rectum. The accuracy of tumor origin by EUS was 99.5% (210/211). The accuracy of tumor nature by EUS was 75.8% (160/211). For the lesions originated from different locations, the diagnostic accuracy for lesion originated from esophageal mucosa/submucosa, esophageal muscularis propria, gastric mucosa/submucosa, gastric muscularis propria, duodenal submucosa, rectal mucosa/submucosa by EUS were 90.0%(54/60), 83.3%(5/6), 31.0%(13/42), 89.4%(59/66), 50.0%(1/2), 82.9%(29/35), respectively. With respect to hypoechoic lesions, leiomyoma, leiomyoma/gastrointestinal stromal tumor, and neuroendocrine tumor were the predominant type of tumor originated from esophageal mucosa, gastrointestinal muscularis propria and rectal mucosa/submucosal, respectively. Conclusion Although EUS is indispensible for the diagnosis of gastrointestinal submucosal tumor, it plays a limited role in the differential diagnosis of various lesions originated from gastric mucosa and submucosa. Since part of the submucosal tumors may be potential for malignant development, an diagnosis made by EUS should be more careful. Key words: Endoscopy; Endoscopic ultrasonography; Submucosal tumor

Change in Populations of Macrophages Promotes Development of Delayed Gastric Emptying in Mice

Muscularis propria macrophages lie close to cells that regulate gastrointestinal motor function, including interstitial cells of Cajal (ICC) and myenteric neurons. In animal models of diabetic gastroparesis, development of delayed gastric emptying has been associated with loss of macrophages that express cytoprotective markers and reduced networks of ICC. Mice with long-term diabetes and normal gastric emptying have macrophages that express anti-inflammatory markers and have normal gastric ICC. Mice homozygous for the osteopetrosis spontaneous mutation in the colony-stimulating factor 1 gene (Csf1op/op) do not have macrophages; when they are given streptozotocin to induce diabetes, they do not develop delayed gastric emptying. We investigated whether population of the gastric muscularis propria of diabetic Csf1op/op mice with macrophages is necessary to change gastric emptying, ICC, and myenteric neurons and investigated the macrophage-derived factors that determine whether diabetic mice do or do not develop delayed gastric emptying. Wild-type and Csf1op/op mice were given streptozotocin to induce diabetes. Some Csf1op/op mice were given daily intraperitoneal injections of CSF1 for 7 weeks; gastric tissues were collected and cellular distributions were analyzed by immunohistochemistry. CD45+, CD11b+, F4/80+ macrophages were dissociated from gastric muscularis propria, isolated by flow cytometry and analyzed by quantitative real-time polymerase chain reaction. Cultured gastric muscularis propria from Csf1op/op mice was exposed to medium that was conditioned by culture with bone marrow-derived macrophages from wild-type mice. Gastric muscularis propria from Csf1op/op mice given CSF1 contained macrophages; 11 of 15 diabetic mice given CSF1 developed delayed gastric emptying and had damaged ICC. In non-diabetic Csf1op/op mice, administration of CSF1 reduced numbers of gastric myenteric neurons but did not affect the proportion of nitrergic neurons or ICC. In diabetic Csf1op/op mice given CSF1 that developed delayed gastric emptying, the proportion of nitrergic neurons was the same as in non-diabetic wild-type controls. Medium conditioned by macrophages previously exposed to oxidative injury caused damage to ICC in cultured gastric muscularis propria from Csf1op/op mice; neutralizing antibodies against IL6R or TNF prevented this damage to ICC. CD45+, CD11b+, and F4/80+ macrophages isolated from diabetic wild-type mice with delayed gastric emptying expressed higher levels of messenger RNAs encoding inflammatory markers (IL6 and inducible nitric oxide synthase) and lower levels of messenger RNAs encoding markers of anti-inflammatory cells (heme oxygenase 1, arginase 1, and FIZZ1) than macrophages isolated from diabetic mice with normal gastric emptying. In studies of Csf1op/op and wild-type mice with diabetes, we found delayed gastric emptying to be associated with increased production of inflammatory factors, and reduced production of anti-inflammatory factors, by macrophages, leading to loss of ICC.

Screening differentially expressed genes of gastric stromal tumors originated form the muscularis propria by gene chip technology

Objective To screen the related gene expression in gastric muscularis propria tumor by gene chip assay, and to guide the accurate diagnosis and targeted therapygastric of gastric stromal tumors originated form the muscularis propria. Methods 6 cases of samples with gastric muscularis propria mesenchymal tumor and peritumoral tissue were treated by endoscopic treatment and laparoscopic surgery. cDNA was synthesized by reverse transcription with total RNA, then by in vitro transcription synthesised of biotin labeling cRNA that was hybridizationed with the Affymetrix mRNA expression profile chip, screened differentially expressed genes with bioinformatics analysis using PANTHER/KEGG database and Gene Ontology software. Results 3 293 differentially expressed genes were detected in Gastric stromal tumor tissue, including 2 588 up-regulated, and 705 down-regulated genes, especially in DPP10, ETV1, DKK4, CXCL14, MT1M gene expression significantly. These genes were involved in multiple signaling pathways related to tumor, such as Wnt pathway, Rap1 pathway, ECM receptor interaction, Ras signaling pathway, P13K-AKT signaling pathway, and cell adhesion. Conclusion There are significant differences of gene expression between gastric stromal tumor and peritumoral tissue, the aitered expression of DPP10, ETV1, DKK4, CXCL14 and MT1M might be involved in the regulation of gastric stromal tumor, rarely reported before in the literature, and might be new molecular markers or treatment targets. To conduct in-depth study of these genes and related regulation pathways, will contribute to the diagnosis, treatment and prognosis of gastric stromal tumor. Key words: Gastric muscularis propria mesenchymal tumor; Gene chip; Differentially expressed genes

Ligation-Assisted Endoscopic Enucleation for the Resection of Gastrointestinal Tumors Originating from the Muscularis Propria: Analysis of Efficacy and Facility

Background: Gastrointestinal tumors originating from the muscularis propria are believed to have the potential to progress to malignant tumors. The efficacy of ‘pre-management' with elastic band or endoloop assistant ligation after initial submucosal dissection in endoscopic enucleation procedure of these tumors was investigated and evaluated. Methods: The study included 21 patients with small gastric stromal tumors arising in the gastric muscularis propria as determined by endoscopy (endoscopic ultrasonography). A standard endoscope with a transparent cap attached to the tip was used. The cap was placed over the lesion, after incision of the surrounding tissue, maximum sustained suction was applied. Then the elastic band or endoloop was released around the base. Circumference resection was performed with clips strengthening the defect closure. Results: The 22 gastrointestinal stromal tumors sloughed completely. The mean time required for the full-thickness resection was 48 min. Minor perforation occurred with metal clips closing the defect of the gastric wall. Follow-up ranged from 13 to 42 months, during which time no recurrence was observed postoperatively. Conclusions: The band or endoloop assistant endoscopic ligation technique is effective for the enucleation of deep gastric tumors. It may help avoiding disturbance the abdominal cavity hemostasis in traditional full-thickness enucleation procedure.

Intrinsic Gastrointestinal Macrophages: Their Phenotype and Role in Gastrointestinal Motility.

There is an increasing awareness of the role of macrophages in the regulation and maintenance of gastrointestinal function in health and disease. This work has proceeded in the context of an increased understanding of the complex phenotypic variation in macrophages throughout the body and has shown previously unidentified roles for macrophages in diseases such as gastroparesis, postoperative ileus, and inflammatory bowel disease. Opportunities for exploiting the phenotypic modulation of tissue resident macrophages have been identified as possible therapies for some of these diseases. In addition, macrophages are an established component of the innate immune system and can respond to variations and changes in the intestinal microbiome and potentially mediate part of the impact of the microbiota on intestinal health. We reviewed the latest work on novel concepts in defining macrophage phenotype, discuss possible mechanisms of action for tissue-resident macrophages in the gut, address the significance of microbiome effects on macrophage phenotype, and review the known and possible roles of macrophages in motility disorders of the gastrointestinal tract.

EUS-guided FNA biopsy of the muscularis propria of the antrum in patients with gastroparesis is feasible and safe

EUS-guided FNA biopsies of the muscularis propria of the gastric wall in patients with gastroparesis could replace the routine use of surgical full-thickness biopsies for assessing the loss of the interstitial cells of Cajal (ICCs) and cellular infiltrates in the myenteric plexus. We investigated the efficacy and safety of EUS-guided FNA biopsies of the muscularis propria of the gastric antrum in gastroparesis and compared the tissue with a surgically obtained full-thickness biopsy specimen in the same patient. This was a prospective, nonrandomized, feasibility trial. Patients with gastroparesis who were undergoing gastric neurostimulator placement were enrolled. Patients had a gastric wall measurement by radial EUS in the body and antrum of the stomach followed by linear EUS examination and FNA of the muscularis propria in the antrum by using a 19-gauge core needle. Within 24 hours, a full-thickness biopsy specimen of the antrum was obtained surgically during neurostimulator placement. Endoscopic and surgical specimens were compared for tissue morphology, number of ICCs (c-kit stain) and enteric neurons (S-100 stain), and fibrosis (trichome) for each patient. The correlation coefficient of the ICC count per high-power field was used to compare both specimens. Continuous data were compared by using a t test. Eleven patients (10 female, 1 male), with a mean age of 40.6 years, were enrolled in the trial. EUS-guided core biopsies were successful in obtaining sufficient tissue for the histologic assessment of ICCs in 9 patients (81%) and for the myenteric plexus in 6 patients (54%). There was a good correlation coefficient (0.65) when both surgical and endoscopic groups were compared for the loss of ICCs. Mild serosal bruising and/or localized hematoma formations were noted at the sites of EUS biopsies, but there were no serosal tears, perforations, or adverse effects on the hospitalization and outcomes. EUS-guided FNA of the gastric muscularis propria in patients with gastroparesis is safe and provides adequate tissue for full histologic assessment. (Clinical trial registration number: NCT01916460.).

Inclusion Bodies in the Gastric Muscularis Propria in Diabetic Gastroparesis: A Neglected Finding

Inclusion Bodies in the Gastric Muscularis Propria in Diabetic Gastroparesis: A Neglected Finding

The Frequency of Histological Abnormalities in the Muscularis Propria of the Antrum and Pylorus in Gastroparesis Patients

Introduction: Gastroparesis (GP) patients represent a heterogenous population with diabetes mellitus (DM-GP), idiopathic (ID-GP) and post-vagotomy etiologies. Structural studies of their gastric smooth muscle have shown reduced numbers of interstitial cells of Cajal (ICC) and enteric neurons in DM-GP, as well as immune responses and infiltrates in the myenteric plexus in ID-GP. Our goal was to investigate smooth muscle abnormalities in full thickness surgical biopsies of the antrum as well as the pylorus in GP patients. Methods: 16 patients (88% female, 10 DM-GP and 6 ID-GP), aged 20-63, underwent full-thickness antral biopsies during surgery, 15 to place the gastric electrical stimulator (Enterra) and perform a pyloroplasty, and 1 for jejunostomy tube placement. Full-thickness pyloric biopsies were also obtained in 5 of these patients. In addition, antral biopsies were obtained at surgery from 5 female non-GP chronically vomiting patients, aged 19-61 years. The biopsy samples were stained with H&E, trichrome for fibrosis, S100 for myenteric plexus, and C- Kit (CD117) for ICC, where less than 10 per high power field (HPF) was regarded as reduced and also examined for cellular or inflammatory infiltrates or fibrosis in the myenteric plexus. Results: One of 5 controls did have reduced ICC but otherwise all had normal histologic analysis while 6 of the 16 (38%) GP patients had depleted ICC in the antrum (3 DM-GP and 3 ID-GP). Of the 5 pyloric biopsies analyzed, 2 DM-GP patients had reduced ICC. Polymorphonuclear leukocytes (PMN) were noted in nerve bundles in 2 ID-GP patients and aggregates of CD3+ T-cells in nerves were found in 1 DM-GP and 1 ID-GP. Inclusion bodies in the smooth muscle were observed in 3 patients with DM-GP. One patient with DM-GP had decreased ICC in the antrum and pylorus, inclusion bodies, and aggregates of T-cells in nerves. Conclusion: Abnormalities are found in the gastric muscularis propria in the majority (69%) of GP patients. Specifically: 1.) reduced ICC in 38%, 2.) PMN and CD3+ cellular infiltrates in the myenteric plexus of ID-GP patients indicative of a post-infection neural injury in some patients termed “idiopathic,” 3.) inclusion bodies consistent with a smooth muscle myopathy only seen in diabetics, and 4.) decreased pyloric sphincter ICC not previously reported in GP patients.

Mo1293 Comparison of Histological Characteristics of the Gastric Wall Muscularis Propria in Gastroparetic Patients by Endoscopic Ultrasound (EUS) Fine Needle Aspiration (FNA) Technique Versus Full Thickness Surgical Biopsy

G A A b st ra ct s SIBO test results were related to (i) 4 hr gastric retention (mild 10-20%, moderate >2035%, severe >35%), (ii) retained gastric food on endoscopy, and (iii) etiology and opiate use. Results: Breath tests were positive in 52% (H2 41% > CH4 16%, P 50% of gastroparesis patients. Pronounced gastric emptying defects do not increase SIBO prevalence, but may worsen SIBO severity as reflected by increased H2 production. Retained food in the stomach increases hydrogen andmethane release, suggesting potential gastric microbial reservoirs that seed the small bowel. Postsurgical patients show increased predilection to SIBO. Opiate use promotes trends to increased hydrogen release. Methane production with retained food and in postsurgical patients suggests varying microbial profiles in SIBO. These findings define factors associated with the prevalence and severity of SIBO in gastroparesis. Table 1: Relation of Breath Testing to Gastric Emptying and Food Retention

Sa1572 Diagnostic and Therapeutic Efficacy of Endoscopic Enucleation for Small Gastric Muscularis Propria Layer Tumor

Sa1572 Diagnostic and Therapeutic Efficacy of Endoscopic Enucleation for Small Gastric Muscularis Propria Layer Tumor

Efficacy and safety of endoscopic submucosal dissection in treating gastric subepithelial tumors originating in the muscularis propria layer: a single-center study of 144 cases

Objective. Subepithelial tumors (SETs) in the stomach are usually considered benign. However, some do have potential for malignant transformation, especially when originating in the muscularis propria (MP). Our study aimed to evaluate the clinical efficacy and safety of endoscopic submucosal dissection (ESD) for gastric SETs originating in MP. Material and methods. A total of 145 gastric MP SETs in 144 patients were treated by ESD between September 2008 and December 2012. Characteristics of patients and SETs, therapeutic outcomes, pathologic characteristics, complications and follow-up outcomes were evaluated. Results. Among the 144 patients, 104 were female (72.22%) and 40 were male (27.78%), and the mean age was 55.75 ± 11.29 years (range 18–78 years). The mean size of the tumors determined by endoscopic ultrasound (EUS) was 15.14 ± 9.70 mm (range 3–50 mm). En bloc complete resection was achieved in 134 of 145 tumors, giving a complete resection rate of 92.41%. The final histopathologic diagnoses included 52 leiomyomas, 89 gastrointestinal stromal tumors, 3 neurogenic tumors and 1 lipoma. Perforations occurred in 21 patients (14.48%) and were endoscopically repaired with clips or nylon bands. Intraoperative bleeding occurred in seven patients (4.83%) and was corrected with argon plasma coagulation (APC) or hot biopsy forceps. No local recurrence or distant metastasis was detected during a mean follow-up of 19.14 ± 10.29 months (range 3–51 months). Conclusions. ESD appears to be an effective and safe treatment for gastric SETs originating in MP.

Endoscopic Submucosal Dissection for Treatment of Gastric Submucosal Tumors Originating from the Muscularis Propria Layer

We aimed to study the feasibility of endoscopic submucosal dissection (ESD) for the removal of gastric muscularis propria tumors and to evaluate the efficacy and safety of ESD for this treatment. Eighteen patients with gastric SMTs originating from the muscularis propria were treated by ESD between July 2008 and July 2011. Tumor characteristics, complications, en bloc resection rate, and local recurrence rate were evaluated. Among the 18 patients, 11 were women (61.1 %). The median age was 65.3 ± 6.3 years old (range 30-71 years old). Seventeen tumors were resected completely by ESD (success rate 94.4 %). The mean tumor size as determined by endoscopic ultrasound was 2.6 ± 1.2 cm (range 1.0-3.5 cm). The histological diagnosis was gastrointestinal stromal tumor for 13 lesions and leiomyoma for four tumors. The mean operation time was 90 ± 38 min (range 50-120 min), and the average blood loss was 20 ml. Two patients developed perforation, which was closed by endoscopic methods with metallic clips. The tumor was closely adhered to the muscularis propria and was convex to the enterocoelia in one case. No single case had severe complications, such as GI bleeding, peritonitis, or abdominal abscess, and there were no other immediate post-procedure complications. ESD is a safe, effective, well-tolerated, and minimally invasive therapy for the intraluminal SMTs originating from gastric muscularis propria with relatively few complications. Although there is a risk of perforation which has become manageable endoscopically.

Endoscopic full-thickness biopsy of the gastric wall with defect closure by using an endoscopic suturing device: survival porcine study

The pathogenesis of several common gastric motility diseases and functional GI disorders remains essentially unexplained. Gastric wall biopsies that include the muscularis propria to evaluate the enteric nervous system, interstitial cells of Cajal, and immune cells can provide important insights for our understanding of the etiology of these disorders. To determine the technical feasibility, reproducibility, and safety of performing a full-thickness gastric biopsy (FTGB) by using a submucosal endoscopy with mucosal flap (SEMF) technique; the technical feasibility, reproducibility, and safety of tissue closure by using an endoscopic suturing device; the ability to identify myenteric ganglia in resected specimens; and the long-term safety. Single center, preclinical survival study. Animal research laboratory, developmental endoscopy unit. Twelve domestic pigs. Animals underwent an SEMF procedure with gastric muscularis propria resection. The resultant offset mucosal entry site was closed by using an endoscopic suturing device. Animals were kept alive for 2 weeks. The technical feasibility, reproducibility, and safety of the procedure; the clinical course of the animals; the histological and immunochemical evaluation of the resected specimen to determine whether myenteric ganglia were present in the sample. FTGB was performed by using the SEMF technique in all 12 animals. The offset mucosal entry site was successfully closed by using the suturing device in all animals. The mean resected tissue specimen size was 11 mm. Mean total procedure time was 61 minutes with 2 to 4 interrupted sutures placed per animal. Histology showed muscularis propria and serosa, confirming full-thickness resections in all animals. Myenteric ganglia were visualized in 11 of 12 animals. The clinical course was uneventful. Repeat endoscopy and necropsy at 2 weeks showed absence of ulceration at both the mucosal entry sites and overlying the more distal muscularis propria resection sites. There was complete healing of the serosa in all animals with minimal single-band adhesions in 5 of 12 animals. Retained sutures were present in 10 of 12 animals. Animal experiment. FTGB by using the SEMF technique and an endoscopic suturing device is technically feasible, reproducible, and safe. Larger tissue specimens will allow improved analysis of multiple cell types.

Modified endoscopic submucosal dissection with ligation for small tumors originated from gastric muscularis propria

Objective To explore the therapeutic value of modified endoscopic submucosal dissec- tion with ligation （ESD-L） for small tumors originated from gastric museularis propria. Methods Total of 60 patients with tumors originated from gastric museularis propria, which was confirmed by endoscopic ultra- sonography and smaller than 12 mm and were recruited to the present study. The conventional ESD technique was used to dissect the tumor to the depth of muscularis propria. Then the bottom of the tumor and the be- neath museularis propria were ligated fully with a nylon loop. Further dissection was applied till the whole tumor was isolated. Results All 60 lesions were dissected completely with perforation occurred in 10 cases, which were managed successfully with metal hemoclip. Pathologic diagnosis was obtained in all lesions, and no recurrence was found during the follow-up. Conclusion Modified technique of ESD-L is effective for complete resection of small tumors originated from gastric museularis propria, which can also decrease the risk of stomach perforation. Key words: Ligation; Endoscopic submucosal dissection; Submucosal tumor; Inherent muscular layer; Therapy

Gastrointestinal stromal tumor presenting with prominent calcification

We present a rare case of a gastrointestinal stromal tumor (GIST) in the stomach with prominent calcification at presentation. A 61-year-old woman visited our hospital because of epigastric discomfort. A spherical calcified lesion with a diameter of about 30 mm was incidentally shown in the left upper quadrant on an abdominal X-ray. Computed tomography demonstrated that the tumor was growing from the upper gastric body, with calcification in the peripheral ring area. A laparoscopic partial gastrectomy was performed, and the resected specimen revealed a well-circumscribed tumor with exophytic growth from the gastric muscularis propria. Microscopic examination revealed spindle-shaped tumor cells with calcification and hemorrhage. Additionally, positive immunoreactivity of the tumor to KIT and CD34 and a low mitotic index resulted in the diagnosis of very low risk GIST. There are a few case reports of heavily calcified GIST, although solitary or punctate calcification of primary GIST has been reported in several case series. Dystrophic calcification of necrotic or degenerative tissue is the supposed cause of primary calcified GISTs. In contrast, appearance of calcification after administration of imatinib mesylate, which may be one indicator of disease response, is possibly caused by a different mechanism.

Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract

Populations of interstitial cells of Cajal (ICC) are altered in several gastrointestinal neuromuscular disorders. ICC are identified typically by ultrastructure and expression of Kit (CD117), a protein that is also expressed on mast cells. No other molecular marker currently exists to independently identify ICC. The expression of ANO1 (DOG1, TMEM16A), a Ca(2+)-activated Cl(-) channel, in gastrointestinal stromal tumors suggests it may be useful as an ICC marker. The aims of this study were therefore to determine the distribution of Ano1 immunoreactivity compared with Kit and to establish whether Ano1 is a reliable marker for human and mouse ICC. Expression of Ano1 in human and mouse stomach, small intestine, and colon was investigated by immunofluorescence labeling using antibodies to Ano1 alone and in combination with antibodies to Kit. Colocalization of immunoreactivity was demonstrated by epifluorescence and confocal microscopy. In the muscularis propria, Ano1 immunoreactivity was restricted to cells with the morphology and distribution of ICC. All Ano1-positive cells in the muscularis propria were also Kit positive. Kit-expressing mast cells were not Ano1 positive. Some non-ICC in the mucosa and submucosa of human tissues were Ano1 positive but Kit negative. A few (3.2%) Ano1-positive cells in the human gastric muscularis propria were labeled weakly for Kit. Ano1 labels all classes of ICC and represents a highly specific marker for studying the distribution of ICC in mouse and human tissues with an advantage over Kit since it does not label mast cells.

Endoscopic Ultrasound-Guided Gastric Botulinum Toxin Injections in Obese Subjects: A Pilot Study

Gastric injections of botulinum toxin A (BTA) may induce changes in gastric emptying and body weight, but results vary. BTA dose and depth of injection may affect efficacy. This study assessed changes in gastric emptying, satiation, symptoms, and body weight after endoscopic ultrasound (EUS)-guided injection of 100 or 300 U BTA into gastric antral muscularis propria of obese subjects. Open label study of ten healthy, obese adults (age = 29-49 years, body mass index = 31-54 kg/m(2)) who received 100 U (n = 4) or 300 U (n = 6) BTA and were followed for 16 weeks. Measures included gastric emptying of solids (by scintigraphy), satiation (by maximum tolerated volume [MTV] during nutrient drink test), gastrointestinal symptoms (by the Gastrointestinal Symptom Rating Scale), caloric intake (by food frequency questionnaire), and body weight. For the entire cohort, MTV decreased from 1,380 cc (range: 474-2,014) at baseline to 620 cc (range: 256-1,180) 2 weeks after BTA injection; decreases were statistically significant in the subjects receiving 300 U BTA (p = 0.03). Average body weight loss was 4.9 (+/-6.3) kg after 16 weeks. Gastric emptying T(1/2) was prolonged in the 300 U BTA group, but not significantly different from baseline (p = 0.17). BTA injections were well tolerated without significant adverse effects. EUS-guided injection of BTA into gastric muscularis propria can be performed safely with minimal adverse effects. A dose of 300 U BTA significantly enhances satiation, is associated with weight loss, and may slow gastric emptying. Further study of higher dose BTA in obese subjects is warranted.