A novel endoscopic artificial intelligence system to assist in the diagnosis of autoimmune gastritis: a multicenter study.

BACKGROUND & AIMS: Autoimmune gastritis (AIG), distinct from Helicobacter pylori-associated atrophic gastritis (HpAG), is underdiagnosed due to limited awareness. This multicenter study aims to develop a novel endoscopic artificial intelligence (AI) system assisting in AIG diagnosis. METHODS: Patients diagnosed with AIG, as well as HpAG and non-atrophic gastritis (NAG), were retrospectively enrolled from six centers. Endoscopic images with relevant demographic and medical data, were collected for the development of AI-assisted system, SEER-SCOPE AI, based on multi-site feature fusion model. The diagnostic performance of SEER-SCOPE AI was evaluated in the internal and external datasets. Endoscopists' performance with and without AI support was tested and compared using Mann-Whitney U test. Heatmap analysis was performed to interpret SEER-SCOPE AI. RESULTS: 1 070 patients (294 AIG, 386 HpAG, 390 NAG) with 18 828 endoscopy images were collected. SEER-SCOPE AI achieved strong performance for identifying AIG, with 96.9% sensitivity, 92.2% specificity and an AUROC of 0.990 internally, and 90.3% sensitivity, 93.1% specificity and an AUROC of 0.973 externally. The performance of SEER-SCOPE AI (sensitivity 91.3%) was comparable to experts (87.3%) and significantly outperformed non-experts (70.0%). With AI support, the overall performance of endoscopists was improved (sensitivity: 90.3% [95% CI 86.0%-93.2%] vs. 78.7% [95% CI 73.6%-83.2%], p=0.008). Heatmap analysis revealed consistent focus of SEER-SCOPE AI on regions corresponding to atrophic areas. CONCLUSIONS: SEER-SCOPE AI demonstrated expert-level performance in identifying AIG, and enhanced the diagnostic ability of endoscopists. Its application holds promise as a potent endoscopy-assisted tool for guiding biopsy sampling and early detection of AIG.

Conventional versus rubber band traction-assisted endoscopic submucosal dissection for rectal neuroendocrine tumors: a single-center retrospective study (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) is a safe and effective technique for the treatment of gastrointestinal tumors, including rectal neuroendocrine tumors (r-NETs). However, the relative advantages of traction-assisted ESD for the treatment of small rectal lesions are still debated. AIMS: We conducted a study to compare the efficacy and safety of rubber band traction-assisted ESD (RBT-ESD) to conventional ESD (C-ESD). METHODS: This study retrospectively analyzed consecutive patients with r-NET treated with ESD between October 2021 and October 2023. Our study assessed differences between the groups in the complete resection rate of lesions, muscular layer injury, surgical complications, operation time, resection speed, time to liquid diet, postoperative hospital stay, hospital cost, and recurrence rate. RESULTS: A total of 119 patients with r-NETs participated in this study (RBT-ESD group, n = 27; C-ESD group, n = 92). The operation time in RBT-ESD group was shorter than in C-ESD group, but the difference was not statistically significant (16.0 min [9.0-22.0 min] vs. 18.0 min [13.3-27.0 min], P = 0.056). However, the resection speed was significantly faster in the RBT-ESD group (6.7 vs. 4.1 mm2/min, P = 0.005). Furthermore, the RBT-ESD group showed significantly less muscular layer injury (P = 0.047) and faster diet recovery (P = 0.035). No significant differences were observed in the complete resection rate, surgical complications, postoperative hospital stay, hospital cost, or recurrence rate between the two groups. CONCLUSION: For r-NETs of < 2 cm in size, the RBT method did not significantly shorten the operation time but resulted in faster resection speed, less muscular layer injury, and earlier postoperative recovery to a liquid diet.

Qualitative study on the perception of good death in patients with end-stage cancer in oncology nurses.

OBJECTIVE: To explore the perception of good death of patients with end-stage cancer by nurses in the oncology department. METHOD: In the study we used a phenomenological approach and semi-structured interviews. A total of 11 nurses from the oncology department of a Grade A hospital in Taizhou were interviewed on the cognition of good death from July 1 to September 30, 2022. Colaizzi's analysis method was used to analyse the interview data. This study followed the consolidated criteria for reporting qualitative research (COREQ). RESULT: Four themes were identified: a strong sense of responsibility and mission; To sustain hope and faith; The important role of family members; Improve patients' quality of life. CONCLUSION: The nurses in the department of oncology have a low level of knowledge about the "good death", and the correct understanding and view of the "good death" is the premise of the realization of " good death". The ability of nursing staff to improve the "good death", attention, and meet the needs and wishes of individuals and families, is the guarantee of the realization of "good death".

Development and validation of LightGBM algorithm for optimizing of Helicobacter pylori antibody during the minimum living guarantee crowd based gastric cancer screening program in Taizhou, China.

Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45-70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.

Molecular design and rational optimization of synergistic effect between the two wings of a roughly orthogonal cation-π-π stacking system at nasopharyngeal carcinoma YAP1-TEAD4 parallel Helix-Helix interaction interface.

The Yes-associated protein-1 (YAP1) is an essential regulator of human Hippo signaling pathway and functions through interaction with TEA domain-4 (TEAD4) transcription factor involved in the tumorigenesis of nasopharyngeal cancer. Previously, a parallel helix-helix interaction (PHHI) was identified as the key hotspot at YAP1-TEAD4 complex interface and has been exploited as an attractive druggable target to disrupt the complex. In this study, we investigated a roughly orthogonal cation-π-π stacking system across the crystal PHHI packing interface by integrating computational modeling and binding assay, which forms between one YAP1 helical residue Phe69 and two TEAD4 helical residues Phe373/Lys376. A synergistic effect between cation-π and π-π interactions was observed; they separately represent two wings of the stacking system. The π-electron is primarily responsible for the synergistic effect. Combination between diverse aromatic/charged amino acids. as well as neutral alanine on the cation-π-π stacking, revealed that the presence of aromatic tryptophan and charged arginine at, respectively, the residues 373 and 376 of TEAD4 helix can considerably improve PHHI binding affinity by ~6-fold, whereas neutral alanine substitution on each residue and on both would reduce the affinity significantly, confirming a strong synergistic effect involved in the roughly orthogonal cation-π-π stacking system at YAP1-TEAD4 PHHI interface.

Application of a WeChat-based mini-app as a patient reminder in Helicobacter pylori eradication: a prospective multi-center randomized controlled study.

BACKGROUND: To improve the eradication rate of H. pylori, researchers have investigated the role of WeChat-based mini-app as an electronic reminding system in H. pylori treatment. METHODS: Subjects from three medical centers were divided into two groups. Patients in the daily mini-app-based notification system group received daily notifications via the WeChat mini-app. Patients in the control group received one-time verbal education on the first clinical visit. Both groups received a 14-day quadruple therapy to eradicate H. pylori infection. Eradication rate, compliance, adverse events and satisfaction were evaluated. RESULTS: Both intention-to-treat (ITT) and per-protocol (PP) analyses were conducted. The eradication rate in the daily mini-app-based notification system group was slightly higher compared with the control group (ITT analysis: 76.70% vs. 70.73%, p = 0.312; PP analysis: 85.87% vs. 82.86%, p = 0.562). The compliance was significantly higher in the daily mini-app-based notification system group (ITT analysis: 85.52% vs. 70.48%, p = 0.028; PP analysis: 92.39% vs. 81.90%, p = 0.030). The adverse event rates were similar between the two groups (PP analysis: 36.96% vs. 40.95%, p = 0.566). No significant difference in eradication rate was seen in each subgroup analysis by age, place of residence, grade of education, or endoscopic findings. CONCLUSION: The study showed that daily mini-app-based notification improved patient compliance but not H. pylori eradication rate. Trial registration The research was registered in the Chinese Clinical Trial Registry (ChiCTR2000031011, 21/03/2020).

Feasibility of endoscopic resection without laparoscopic assistance for giant gastric subepithelial tumors originating from the muscularis propria layer (with video).

BACKGROUND AND AIMS: Currently, published data of endoscopic resection (ER) for giant (≥ 6 cm) gastric subepithelial tumors originating from the muscularis propria layer (MP-SETs) are extremely rare and limited to only case reports. The aim of this study was thus to assess the feasibility of using ER for giant (≥ 6 cm) gastric MP-SETs in a case series. METHODS: Between July 2013 and December 2020, a total of 23 patients with giant (≥ 6 cm) gastric MP-SETs were treated with ER in the endoscopic center of Taizhou hospital. The study assessed outcomes of en bloc resection, complete resection, total complications, and local residual/recurrence of tumors. RESULTS: The mean procedure time was 112.2 min. En bloc resection was achieved in 22 tumors (95.7%). En bloc removal from the stomach and complete resection were achieved in 6 patients (26.1%). The rate of complete resection differed significantly depending on the minimum tumor diameter (P < 0.001). During hospitalization, 4 patients had complications, including localized peritonitis (3/23, 13.0%) and pulmonary infection (1/23, 4.3%). These 4 patients recovered successfully after conservative medical treatment. Histopathological examination revealed that 18 tumors were gastrointestinal stromal tumors (GISTs), and 5 tumors were leiomyoma. No patients were observed to have residual or recurrent tumors during the follow-up. CONCLUSIONS: Although ER for giant (≥ 6 cm) gastric MP-SETs was associated with several technical challenges and a relatively low complete resection rate, this technique was found to be a feasible therapeutic method for selected patients with a giant (≥ 6 cm) gastric MP-SETs when performed by an experienced endoscopic team.

Feasibility of transgastric endoscopic gallbladder-preserving surgery for benign gallbladder diseases (with video).

BACKGROUND: With the increasing realization of the importance of gallbladder function, choledochoscopic gallbladder-preserving surgery has been advocated for benign gallbladder diseases. However, limited information is available regarding the use of endoscopic gallbladder-preserving surgery (EGPS) for patients with benign gallbladder diseases. The aim of this study was to evaluate the feasibility of EGPS for benign gallbladder diseases. METHODS: Between June 2020 and January 2021, 22 patients with gallbladder stones and/or gallbladder polyps were treated with EGPS. The main outcome measures included the rate of complications, residual gallbladder stones, and gallbladder stone recurrence. RESULTS: In this study, transgastric EGPS was successfully performed in 22 patients (13 female, 9 male) with benign gallbladder diseases, and included 8 cases of multiple gallstones, 4 cases of gallbladder polyps with gallstones, 6 cases of multiple gallbladder polyps, 2 cases of single gallstone, and 2 case of singe gallbladder polyp. The median time of transgastric EGPS was 118 min. During hospitalization, 4 patients suffered localized peritonitis (4/22, 18.2%), and these patients successfully recovered after conservative medical treatment. None of the patients experienced massive bleeding, delayed bleeding, diffuse peritonitis, or any other serious complications. During the median follow-up of 4 months, 1 patient suffered residual gallstone, while no gallstone recurrence or deaths related to transgastric EGPS occurred in any patients. CONCLUSIONS: Transgastric EGPS appears to be a feasible treatment method in selected patients with benign gallbladder diseases. However, as it is a new technique, further studies are needed to explore the long-term effectiveness of transgastric EGPS.

Vitamin D receptor targets hepatocyte nuclear factor 4α and mediates protective effects of vitamin D in nonalcoholic fatty liver disease.

Epidemiological studies have suggested a link between vitamin D deficiency and increased risk for nonalcoholic fatty liver disease (NAFLD); however, the underlying mechanisms have remained unclear. Here, using both clinical samples and experimental rodent models along with several biochemical approaches, we explored the specific effects and mechanisms of vitamin D deficiency in NAFLD pathology. Serum vitamin D levels were significantly lower in individuals with NAFLD and in high-fat diet (HFD)-fed mice than in healthy controls and chow-fed mice, respectively. Vitamin D supplementation ameliorated HFD-induced hepatic steatosis and insulin resistance in mice. Hepatic expression of vitamin D receptor (VDR) was up-regulated in three models of NAFLD, including HFD-fed mice, methionine/choline-deficient diet (MCD)-fed mice, and genetically obese (ob/ob) mice. Liver-specific VDR deletion significantly exacerbated HFD- or MCD-induced hepatic steatosis and insulin resistance and also diminished the protective effect of vitamin D supplementation on NAFLD. Mechanistic experiments revealed that VDR interacted with hepatocyte nuclear factor 4 α (HNF4α) and that overexpression of HNF4α improved HFD-induced NAFLD and metabolic abnormalities in liver-specific VDR-knockout mice. These results suggest that vitamin D ameliorates NAFLD and metabolic abnormalities by activating hepatic VDR, leading to its interaction with HNF4α. Our findings highlight a potential value of using vitamin D for preventing and managing NAFLD by targeting VDR.

Endoscopic resection of large (≥ 4 cm) upper gastrointestinal subepithelial tumors originating from the muscularis propria layer: a single-center study of 101 cases (with video).

BACKGROUND AND AIMS: Although endoscopic resection (ER) is already established as a minimally invasive technique for small (< 4.0 cm) upper gastrointestinal subepithelial tumors originating from the muscularis propria layer (MP-SETs), published data of ER for large (≥ 4.0 cm) upper gastrointestinal MP-SETs are extremely rare and limited to case reports. This retrospective study aimed to evaluate the feasibility and safety of ER for large (≥ 4.0 cm) upper gastrointestinal MP-SETs in a large case series. METHODS: Between June 2012 and December 2018, 101 patients with large (≥ 4 cm) upper gastrointestinal MP-SETs were enrolled in this study. The main outcome measures included complete resection, total complications, and local residual or recurrent tumor. RESULTS: The rate of complete resection was 86.1%. Thirteen patients (12.9%) experienced complications including gas-related complications (6/101, 5.9%), localized peritonitis (4/101, 4.0%), esophageal/cardiac mucosal laceration (2/101, 2.0%), and delayed bleeding (1/101, 1.0%). These 13 patients recovered after endoscopic and conservative treatment. The independent risk factor for incomplete resection was tumor size (P = 0.005), and the independent risk factors for total complications were tumor size (P = 0.011) and tumor extraluminal growth (P = 0.037). During the median follow-up of 36 months, local residual tumor was detected in 1 patient. No local recurrence occurred in any patient. CONCLUSIONS: Despite being associated with a relatively low complete resection rate, ER is an alternative therapeutic method for large (≥ 4.0 cm) upper gastrointestinal MP-SETs when performed by an experienced endoscopist. This method is especially valuable for patients who are unwilling to undergo surgery.

MiR-542-3p controls hepatic stellate cell activation and fibrosis via targeting BMP-7.

There has been an increasing number of studies about microRNAs as key regulators in the development of hepatic fibrosis. Here, we demonstrate that miR-542-3p can promote hepatic fibrosis by downregulating the expression of bone morphogenetic protein 7 (BMP-7), which is known to antagonize transforming growth factor ß1 (TGFß1)-mediated fibrogenesis effect. The expression of miR-542-3p is increased in activated hepatic stellate cells (HSCs). Downregulation of MiR-542-3p by antisense inhibitors can inhibit HSCs activation markers, including α-smooth muscle actin (α-SMA) and collagen as well as TGFß signaling pathways. MiR-542-3p was significantly upregulated in carbon tetrachloride (CCl4 )-induced hepatic fibrosis in mice, and downregulation of miR-542-3p by lentivirus could prevent the development of hepatic fibrosis. In addition, miR-542-3p can directly bind to the 3'-untranslated region of BMP-7 mRNA, indicating that its profibrotic effect appears to be caused by its inhibition of BMP-7. Our results suggest that downregulation of miR-542-3p prevents liver fibrosis both in vitro and in vivo, highlighting its potential as a novel biomarker or therapeutic target for hepatic fibrosis.

Endoscopic retrograde appendicitis techniques for the treatment of patients with acute appendicitis.

OBJECTIVE: The purpose of this study was to demonstrate the feasibility of endoscopic retrograde appendicitis therapy (ERAT) in treating patients with acute appendicitis. MATERIALS AND METHODS: Between January 2014 and December 2014, 22 patients with acute appendicitis underwent ERAT. Patient demographics, colonoscopy findings, endoscopic retrograde appendiceal radiography (ERAR) findings, and treatment outcomes of the ERAT and adverse events associated with ERAT were analyzed. RESULTS: In this study, 22 patients with acute appendicitis underwent ERAT. The median age of the patients was 39.5 years. Colonoscopy findings included mucosal hyperemia and swelling of the appendiceal orifice and/or its surrounding mucosa (86.4 %, 19/22) and pus at the appendiceal orifice (40.9 %, 9/22). ERAR findings included irregular contour (76.2 %, 16/21), appendiceal lumen dilation (28.6 %, 6/21), appendiceal lumen stenosis (42.9 %, 9/21), and filling defect of the appendiceal lumen (23.8 %, 5/21). Deep intubation was successfully performed in 21 of the 22 patients (95.5 %). Sixteen patients underwent endoscopic appendiceal stent placement after endoscopic appendiceal irrigation (EAI) due to lumen stenosis of the appendiceal, excessive pus, or appendiceal fecalith, and the remaining 6 patients only underwent EAI. Among the 22 patients who underwent ERAT, their abdominal pain was noticeably relieved following the procedure. The main adverse events associated with ERAT were spontaneous discharge of the stent, recurrent abdominal pain, and recurrent appendicitis. During the follow-up (median 33 months), 2 patients underwent laparoscopic appendectomy. CONCLUSIONS: ERAT provide a new alternative therapeutic method for patients with acute appendicitis, particularly for certain patients who are unwilling to undergo an appendectomy.

Safety of endoscopic resection for duodenal subepithelial lesions with wound closure using clips and an endoloop: an analysis of 68 cases.

BACKGROUND: Endoscopic removal of a duodenal lesion is still considered to be a challenging procedure that can be fraught with potentially serious complications, specifically perforation or delayed bleeding. This study was to assess the safety of endoscopic resection for duodenal subepithelial lesions (SELs) with wound closure using clips and an endoloop. METHODS: From October 2010 to July 2015, a total of 68 consecutive patients with duodenal SELs were treated with endoscopic resection with wound closure using clips and an endoloop. The main outcome measures considered were the incidence of complete resection, perioperative perforation, delayed perforation, delayed bleeding, residual lesions, and lesion recurrence. RESULTS: Complete resection was successfully achieved for all 68 patients. The median lesion size was 1.7 cm. The median procedure time was 62 min. The mean hospital stay was 5.5 days. During the procedure, five patients developed perioperative perforations (7.4 %) and no patients developed delayed bleeding, delayed perforation, or other serious complications. The five patients with perioperative perforations recovered after conservative treatment. The perioperative perforation rate was significantly higher for lesions originating in the muscularis propria layer (18.2 %) than in the submucosal layer (2.2 %; p < 0.05). No residual or recurrent lesions were detected during the follow-up period (median: 27 months). CONCLUSIONS: Endoscopic resection with wound closure using clips and an endoloop is an effective and reasonably safe therapeutic method for treating/removing duodenal SELs when managed by an experienced endoscopic team, and it can provide an alternative treatment option for patients with duodenal SELs.

Submucosal tunneling endoscopic resection using methylene-blue guidance for cardial subepithelial tumors originating from the muscularis propria layer.

Submucosal tunneling endoscopic resection (STER) of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the cardia is rarely performed due to the difficulty of creating a submucosal tunnel for resection. The aim of this study was to evaluate the feasibility of STER using methylene-blue guidance for SETs originating from the MP layer in the cardia. From January 2012 to December 2014, 56 patients with SETs originating from the MP layer in the cardia were treated with STER using methylene-blue guidance. The complete resection rate and adverse event rate were the main outcome measurements. Successful complete resection by STER was achieved in all 56 cases (100%). The median size of the tumor was 1.8 cm. Nine patients (15.3%) had adverse events including subcutaneous emphysema, pneumoperitoneum, pneumothorax, and pleural effusion. These nine patients recovered successfully after conservative treatment without endoscopic or surgical intervention. No residual or recurrent tumors were detected in any patient during the follow-up period (median, 25 months). The adverse event rate was significantly higher for tumors originating in the deeper MP layers (46.7%) than in the superficial MP layers (4.9%) (P < 0.05), differed significantly according to tumor size (5.4% for tumors < 2.0 cm vs. 36.8% for tumors ≥ 2.0 cm; P < 0.05), and also differed significantly in relation to the tumor growth pattern (4.1% for the intraluminal growth vs. 100% for the extraluminal growth; P < 0.001). STER using methylene-blue guidance appears to be a feasible method for removing SETs originating from the MP layer in the cardia.

Safety of Endoscopic Resection for Upper Gastrointestinal Subepithelial Tumors Originating from the Muscularis Propria Layer: An Analysis of 733 Tumors.

OBJECTIVES: Although endoscopic resection is an accepted technique for upper gastrointestinal subepithelial tumors (SETs) originating from the muscularis propria (MP) layer, published data regarding its complications are highly variable and limited to small data series. This study aimed to analyze the safety of endoscopic resection in a large case series. METHODS: A total of 726 consecutive patients with 733 upper gastrointestinal SETs originating from the MP layer underwent endoscopic resection from June 2005 to December 2014. The complete resection rate, perioperative perforation rate, and perioperative bleeding rate were the main outcome measurements. RESULTS: The complete resection rate was 97.1%. Ninety-four patients had complications (12.9%), including 88 with perioperative perforations (12.1%), 13 with perioperative bleeding (1.8%), 5 with localized peritonitis (0.7%), and one with delayed bleeding (0.1%). Eleven patients required surgery; the others were treated endoscopically. Risk factors for incomplete resection were extensive connection of the tumor to the MP layer (P=0.007) and extraluminal growth (P=0.048). Risk factors for perioperative perforation were larger tumor size (≤2.0 cm vs. 2.1-3.0 cm vs. >3.0 cm, P=0.021), extraluminal growth (P=0.046), and extensive connection (P<0.001). A risk factor for perioperative bleeding was larger tumor size (P=0.045). No residual or recurrent lesions were detected during the follow-up period (median: 28 months). CONCLUSIONS: Endoscopic resection is an effective and reasonably safe therapeutic method for treating/removing upper gastrointestinal SETs originating from the MP layer when managed by an experienced endoscopic team.

Complete circular endoscopic resection using submucosal tunnel technique combined with esophageal stent placement for circumferential superficial esophageal lesions.

BACKGROUND AND AIMS: At present, removing a circumferential superficial esophageal lesion (SEL) via en bloc resection is still a great challenge. Based on the previous success of submucosal tunneling endoscopic resection, this study aimed to evaluate the safety and effectiveness of complete circular endoscopic resection (CER) using a submucosal tunnel technique combined with esophageal stent placement for patients with circumferential SELs. METHODS: From August 2012 to June 2014, 23 patients with circumferential SELs were treated by CER using a submucosal tunnel technique combined with esophageal stent placement. The following steps were performed: (1) circular mucosa incisions were made at the anal and oral side of the lesion after marking the margin, (2) two submucosal tunnels were created from the oral to anal side using a hybrid knife, which was followed by submucosal dissection, and (3) following the completion of CER, a retrievable esophageal stent was placed to prevent postoperative stricture. RESULTS: CER using the submucosal tunnel technique combined with esophageal stent placement was successfully performed for all 23 cases. The complete resection and success rate were 100%, while the mean longitudinal diameter of the lesions was 65 mm. Mediastinal emphysema, pneumothorax, and postoperative stenosis were detected in 8.7% (2/23), 4.3% (1/23), and 17.4% (4/23) of the cases, respectively. Pathological diagnoses of the lesions included carcinomas (13/23) and high-grade intraepithelial neoplasias (10/23). No residual or recurrent tumors were detected in any patient during the follow-up period. CONCLUSIONS: CER using the submucosal tunnel technique combined with esophageal stent placement seems to be a safe and effective procedure for treating patients with SELs that result in a higher en bloc resection rate with fewer or minor complications.

Rational Molecular Design of Potent PLK1 PBD Domain-binding Phosphopeptides Using Preferential Amino Acid Building Blocks.

Polo-like kinase 1 (PLK1) is an important regulator in diverse aspects of the cell cycle and proliferation. The protein has a highly conserved polo-box domain (PBD) present in C-terminal noncatalytic region, which exhibits a relatively broad sequence specificity in recognizing and binding phosphorylated substrates to control substrate phosphorylation by the kinase. In order to elucidate the structural basis, thermodynamic property, and biological implication underlying PBD-substrate recognition and association, a systematic amino acid preference profile of phosphopeptide interaction with PLK1 PBD domain was established via virtual mutagenesis analysis and mutation energy calculation, from which the contribution of different amino acids at each residue position of two reference phosphopeptides to domain-peptide binding was characterized comprehensively and quantitatively. With the profile, we are able to determine the favorable, neutral, and unfavorable amino acid types for each position of PBD-binding phosphopeptides, and we also explored the molecular origin of the broad sequence specificity in PBD-substrate recognition. To practice computational findings, the profile was further employed to guide rational design of potent PBD binders; three 6-mer phosphopeptides (i.e., IQSpSPC, LQSpTPF, and LNSpTPT) were successfully developed, which can efficiently target PBD domain with high affinity (Kd = 5.7 ± 1.1, 0.75 ± 0.18, and 7.2 ± 2.6 µm, resp.) as measured by a fluorescence anisotropy assay. The complex structure of PLK1 PBD domain with a newly designed, potent phosphopeptide LQSpTPF as well as diverse noncovalent chemical forces, such as H-bonds and hydrophobic interactions at the complex interface, were examined in detail to reveal the molecular mechanism of high affinity and stability of the complex system.

Endoscopic excavation for the treatment of small esophageal subepithelial tumors originating from the muscularis propria.

BACKGROUND/AIMS: This study was designed to evaluate the safety and efficacy of endoscopic excavation for esophageal subepithelial tumors originating from the muscularis propria. METHODOLOGY: Forty-five patients with esophageal subepithelial tumors originating from the muscularis propria were treated with endoscopic excavation between January 2010 and June 2012. The key steps were: (1) making several dots around the tumor; (2) incising the mucosa along with the marker dots, and then seperating the tumor from the muscularis propria by using a hook knife or an insulated-tip knife; (3) closing the artificial ulcer with clips after the tumor was removed. RESULTS: The mean tumor diameter was 1.1 ± 0.6 cm. Endoscopic excavation was successfully performed in 43 out of 45 cases (95.6%), the other 2 cases were ligated with nylon rope. During the procedure perforation occurred in 4 (8.9%) patients, who recovered after conservative treatment. No massive bleeding or delayed bleeding occurred. Histologic diagnosis was obtained from 43 (95.6%) patients. Pathological diagnoses of these tumors were leiomyomas (38/43) and gastrointestinal stromal tumors (5/43). CONCLUSIONS: Endoscopic excavation is a safe and effective method for the treatment of small esophageal subepithelial tumors originating from the muscularis propria.