Natural History of Small Gastric Subepithelial Lesions Less than 20 mm: A Multicenter Retrospective Observational Study (NUTSHELL20 Study).

BACKGROUND AND AIM: Small gastric subepithelial lesions (SELs) are sometimes encountered in daily esophagogastroduodenoscopy (EGD) practice, but whether once-annual or twice-annual endoscopy can provide sufficient follow-up remains unclear. Because follow-up based on small-SEL characteristics is important, this study clarified the natural history of gastric SELs less than 20 mm. METHODS: This retrospective multicenter observation study conducted at 24 Japanese hospitals during April 2000 to March 2020 examined small gastric SELs of ≤20 mm diameter. The primary outcome was the rate of size increase of those SELs detected using EGD, with growth times assessed irrespective of SEL pathological diagnoses. RESULTS: We examined 824 cases with tumors of 1-5 mm diameter in 298 (36.2%) cases, 6-10 mm in 344 (41.7%) cases, 11-15 mm in 112 (13.6%) cases, and 16-20 mm in 70 (8.50%) cases. An increase of small gastric SELs was observed in 70/824 patients (8.5%). The SELs larger than 6 mm increased, even after 10 years. No-change and increasing groups had no significantly different malignant findings at diagnosis. In cases of gastrointestinal stromal tumors (GISTs), internal cystic change in endoscopic ultrasound (EUS) is a risk factor for an increased tumor size. The predictive tumor growth cutoff size at initial diagnosis was 13.5 mm. CONCLUSIONS: Small gastric SELs less than 20 mm have an approximately 8.5% chance of increase. Predictive markers for GIST growth are tumor size ≥13.5 mm and internal cystic change in EUS.

Endoscopic submucosal dissection for superficial duodenal neoplasms.

Endoscopic submucosal dissection (ESD) has emerged as a novel technique for achieving en bloc resection for superficial neoplasms limited to the mucosa. ESD was originally developed in Japan as a method of endoscopic resection of superficial gastric cancers. In our hospital, ESD has been used concurrently in other parts of the gastrointestinal tract, including the esophagus and colorectum from the beginning of its development. However, ESD in the duodenum is considered more challenging than other parts. From August 2005 to March 2008, a total of 15 superficial duodenal neoplastic lesions in 14 patients were treated with endoscopic resection. Of these, nine underwent ESD. We report our experience with duodenal ESD with a combination of ST hood and hook knife.

A case of choledochocele mimicking choledocholithiasis on MR cholangiography: A new differential diagnosis of pseudo-filling defect.

We present the case of a 79-year-old female with acute cholangitis and cholecystitis who presented with right upper quadrant pain. Thin-collimation MR cholangiogram showed a filling defect measuring 1 cm, which was less prominent on single-slab images. Endoscopy showed dynamic ballooning and collapsing of the ampulla of Vater, and a cholangiogram showed characteristic bulging at the distal common bile duct, which led to the diagnosis of choledochocele. It is important to differentiate choledochocele as a cause of filling defect of the lower common bile duct on the MR cholangiogram.

Autocrine loop between TGF-beta1 and IL-1beta through Smad3- and ERK-dependent pathways in rat pancreatic stellate cells.

Pancreatic stellate cells (PSCs) are activated during pancreatitis and promote pancreatic fibrosis by producing and secreting ECMs such as collagen and fibronectin. IL-1beta has been assumed to participate in pancreatic fibrosis by activating PSCs. Activated PSCs secrete various cytokines that regulate PSC function. In this study, we have examined IL-1beta secretion from culture-activated PSCs as well as its regulatory mechanism. RT-PCR and ELISA have demonstrated that PSCs express IL-1beta mRNA and secrete IL-1beta peptide. Inhibition of TGF-beta(1) activity secreted from PSCs by TGF-beta(1)-neutralizing antibody attenuated IL-1beta secretion from PSCs. Exogenous TGF-beta(1) increased IL-1beta expression and secretion by PSCs in a dose-dependent manner. Adenovirus-mediated expression of dominant-negative (dn)Smad2/3 expression reduced both basal and TGF-beta(1)-stimulated IL-1beta expression and secretion by PSCs. Coexpression of Smad3 with dnSmad2/3 restored IL-1beta expression and secretion by PSCs, which were attenuated by dnSmad2/3 expression. In contrast, coexpression of Smad2 with dnSmad2/3 did not alter them. Furthermore, inhibition of IL-1beta activity secreted from PSCs by IL-1beta-neutralizing antibody attenuated TGF-beta(1) secretion from PSCs. Exogenous IL-1beta enhanced TGF-beta(1) expression and secretion by PSCs. IL-1beta activated ERK, and PD-98059, a MEK1 inhibitor, blocked IL-1beta enhancement of TGF-beta(1) expression and secretion by PSCs. We propose that an autocrine loop exists between TGF-beta(1) and IL-1beta in activated PSCs through Smad3- and ERK-dependent pathways.

[Ultrasonography with liquid type CalorieMate for gallbladder motility].

We usually use yolks to assess gallbladder motility by ultrasonography. In this study, we evaluated liquid type CalorieMate as a simple oral stimulus instead of yolks. The volunteers (n = 27) underwent ultrasonography before, 30 min after, and 60 min after taking liquid type CalorieMate. Gallbladder volume and the ejection fraction were measured by ellipsoid method. The mean fasting gallbladder volume, 30-min ejection fraction, and 60-min one were 13.5 ml, 53%, and 62%, respectively. These results were similar to the previous reports by yolks. If the fasting volume is lower than 4ml, they should take re-examination after longer fast to reduce the influence of the dinner the day before the exam. In conclusion, liquid type CalorieMate is useful stimulus to assess gallbladder motility.

A case of esophageal stricture due to metastatic breast cancer diagnosed by endoscopic mucosal resection.

Metastasis of breast cancer to the esophagus has been reported but is rare. It is often difficult to diagnose metastases of breast cancer to the esophagus because they are often located in the submucosa and covered with normal mucosa. Although several methods have been reported in order to obtain specimens for pathological diagnosis, the adverse effects including bleeding and perforation were considerable problems. We report a case of a patient with esophageal stricture due to metastatic breast cancer to the esophagus. Pathological diagnosis was successfully obtained using endoscopic mucosal resection of the esophagus.

Extremely well-differentiated adenocarcinoma of the gastric cardia: a unique case with columnar cells and laminated stones.

Extremely well-differentiated adenocarcinoma (EWDA) is an unusual gastric cancer that is histologically too bland to be diagnosed as malignant neoplasm, particularly using biopsy. EWDA may be a gastric counterpart of 'adenoma malignum' or minimal deviation adenocarcinoma (MDA) in the uterine cervix; however, the clinicopathological features of EWDA remain less apparent than those of MDA. A 60-year-old male was complaining of dysphagia. He had been made aware of a small submucosal tumor in the cardia 2 years before the onset of this symptom. Endoscopic ultrasonographic examination revealed a large cardiac tumor consisting of thickened layers, as observed in Borrmann type IV. Three mucosal biopsies suggested only benign changes including adenoma and hyperplastic polyps. At the fourth biopsy, cytologically bland columnar cells were located in the submucosa along with stromal fibrosis and laminated stones. The possibility that non-neoplastic aberrant pancreas with lithiasis formed the tumor was denied at laparotomy by a frozen section that revealed benign-looking glands invading the diaphragm. Immunohistochemically the cancer glands were positive for CA19-9 and human gastric mucin, but not for p53 or MUC2. To our knowledge, this is a previously unknown combination of EWDA and psammomatous calcification in the stomach.

Angiotensin II stimulates DNA synthesis of rat pancreatic stellate cells by activating ERK through EGF receptor transactivation.

Although angiotensin II (Ang II) is known to participate in pancreatic fibrosis, little is known as to the mechanism by which Ang II promotes pancreatic fibrosis. To elucidate the mechanism, we examined the action of Ang II on the proliferation of rat pancreatic stellate cells (PSCs) that play central roles in pancreatic fibrosis. Immunocytochemistry and Western blotting demonstrated that both Ang II type 1 and type 2 receptors were expressed in PSCs. [3H]Thymidine incorporation assay revealed that Ang II enhanced DNA synthesis in PSCs, which was blocked by Ang II type 1 receptor antagonist losartan. Western blotting using anti-phospho-epidermal growth factor (EGF) receptor and anti-phospho-extracellular signal regulated kinase (ERK) antibodies showed that Ang II-activated EGF receptor and ERK. Both EGF receptor kinase inhibitor AG1478 and MEK1 inhibitor PD98059 attenuated ERK activation and DNA synthesis enhanced by Ang II. These results indicate that Ang II stimulates PSC proliferation through EGF receptor transactivation-ERK activation pathway.

Distinct roles of Smad2-, Smad3-, and ERK-dependent pathways in transforming growth factor-beta1 regulation of pancreatic stellate cellular functions.

Pancreatic stellate cells (PSCs) play a major role in promoting pancreatic fibrosis. Transforming growth factor-beta(1) (TGF-beta(1)) regulates PSC activation and proliferation in an autocrine manner. The intracellular signaling pathways of the regulation were examined in this study. Immunoprecipitation and immunocytochemistry revealed that Smad2, Smad3, and Smad4 were functionally expressed in PSCs. Adenovirus-mediated expression of Smad2, Smad3, or dominant-negative Smad2/3 did not alter TGF-beta(1) mRNA expression level or the amount of autocrine TGF-beta(1) peptide. However, expression of dominant-negative Smad2/3 inhibited PSC activation and enhanced their proliferation. Co-expression of Smad2 with dominant-negative Smad2/3 restored PSC activation inhibited by dominant-negative Smad2/3 expression without changing their proliferation. By contrast, co-expression of Smad3 with dominant-negative Smad2/3 attenuated PSC proliferation enhanced by dominant-negative Smad2/3 expression without altering their activation. Exogenous TGF-beta(1) increased TGFbeta(1) mRNA expression in PSCs. However, PD98059, a specific inhibitor of mitogen-activated protein kinase kinase (MEK1), inhibited ERK activation by TGF-beta(1), and consequently attenuated TGF-beta(1) enhancement of its own mRNA expression in PSCs. We propose that TGF-beta(1) differentially regulates PSC activation, proliferation, and TGF-beta(1) mRNA expression through Smad2-, Smad3-, and ERK-dependent pathways, respectively.