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Developments of endoscopic techniques brought the possibility of endoscopic resection for gastrointestinal stromal tumors (GISTs) of larger sizes. We aim to compare safety and short-term outcomes between endoscopic and laparoscopic resections of gastric GISTs with a diameter of 2-5 cm.This is a single-center, retrospective cohort study. The clinical data, perioperative conditions, and the adverse events of patients who underwent endoscopic or laparoscopic resection for gastric GIST of 2-5 cm in Zhongshan Hospital, Fudan University, from January 2016 to December 2020 were retrospectively reviewed.A total of 346 patients were reviewed; 12 patients who failed to accomplish the planned procedure were excluded; 182 underwent laparoscopic resection; and 152 underwent endoscopic resection. Significant differences exist in the tumor size between the laparoscopic group (3.43 ± 0.86 cm) and the endoscopic group (2.78 ± 0.73 cm) (P 0.01). Compared with laparoscopic resection, endoscopic resection was associated with faster recovery (P 0.01), shorter hospital stays (P 0.01), and lower cost (P 0.01). The incidence of Clavien-Dindo grade II-V adverse events in the endoscopic group (3/152) was significantly lower than that in the laparoscopic group (12/182) (P = 0.04). After a propensity score matching analysis, the endoscopic group showed similar incidences of complications with the laparoscopic group, while the advantages over laparoscopic resection in postoperative hospital stay, time to first oral intake, and hospitalization expenses remained significant (P 0.01).Endoscopic resection is a safe and cost-effective method for 2-5 cm of gastric GISTs compared with laparoscopic resection.

The small molecule chemical compound cinobufotalin (CB) is reported to be a potential antitumour drug that increases cisplatin (DDP) sensitivity in nasopharyngeal carcinoma. In this study, we first found that CB decreased DDP resistance, migration and invasion in lung adenocarcinoma (LUAD). Mechanistic studies showed that CB induced ENKUR expression by suppressing PI3K/AKT signalling to downregulate c-Jun, a negative transcription factor of ENKUR. Furthermore, ENKUR was shown to function as a tumour suppressor by binding to β-catenin to decrease c-Jun expression, thus suppressing MYH9 transcription. Interestingly, MYH9 is a binding protein of ENKUR. The Enkurin domain of ENKUR binds to MYH9, and the Myosin_tail of MYH9 binds to ENKUR. Downregulation of MYH9 reduced the recruitment of the deubiquitinase USP7, leading to increased c-Myc ubiquitination and degradation, decreased c-Myc nuclear translocation, and inactivation of epithelial-mesenchymal transition (EMT) signalling, thus attenuating DDP resistance. Our data demonstrated that CB is a promising antitumour drug and may be a candidate chemotherapeutic drug for LUAD patients.

Integrins, a family of cell adhesion transmembrane receptors, mediate cell adhesion, migration, proliferation, apoptosis, and phagocytosis. In the present study, an integrin ChIntα 4 from Crassostrea hongkongensis was characterized to investigate its role in defensing against pathogenic bacterium Vibrio alginolyticus. The full-length cDNA sequence of ChIntα 4 was 3572 bp with an open reading frame (ORF) of 3168 bp, which encoded a polypeptide with 1055 amino acids. The mRNA expression of ChIntα 4 in the hemocytes was significantly up-regulated at 6 h and 24 h post V. alginolyticus stimulation (p 0.01). The recombinant ChIntα 4 protein could agglutinate the rabbit red blood cells and Gram-negative bacteria V. alginolyticus and Escherichia coli. Moreover, the phagocytic activity of the hemocytes was significantly down-regulated from 46.9% to 32.7% when blocked with anti-ChIntα 4 antibody, and it was significantly up-regulated from 42.7% to 59.5% post transfection with pCI-neo-ChIntα 4 plasmid (p 0.05). In conclusion, these findings demonstrated that ChIntα 4 might be involved in resisting V. alginolyticus infection and regulating phagocytosis as a cell adhesion receptor in C. hongkongensis.

Gastrointestinal stromal tumors (GIST) are mostly seen in the stomach. Clinical data on GISTs ≤ 2 cm with 5 mitosis/50 HPFs are limited. This study aimed to analyze small GISTs with high histological grades to gain a more comprehensive understanding of their clinical characteristics with long-term follow-up.This was a nested cohort study of patients with gastric GISTs ≤ 2 cm and 5 mitosis/50 HPFs. Individuals with endoscopically resected gastric specimens diagnosed as GISTs between January 2008 and July 2019 were enrolled. We analyzed baseline clinicopathological characteristics, perioperative characteristics, risk of recurrence, and metastasis during follow-up.A total of 55 patients diagnosed with gastric GISTs ≤ 2 cm and 5 mitosis/50 HPFs were enrolled. The mean tumor size was 1.6 ± 0.4 cm (median 1.7 cm, range 0.8-2.0 cm). ESD was performed in 33 patients (60.0%) and EFTR in 22 patients (40.0%). Mean mitotic figures were 8.9/50 HPFs. Postoperative bleeding in one patient (1.8%) was the only severe adverse event. The mean follow-up period was 61.2 ± 33.9 months (median 53 months, range 13-133 months). Five patients (5/55, 9.1%) received additional therapies, including partial gastrectomy and adjuvant Imatinib. Only two patients (2/55, 3.6%) showed signs of recurrence. We observed no significant difference regarding baseline clinical characteristics and recurrence among GISTs with mitosis 10/50 HPF and ≥ 10/50 HPF. No patient had signs of metastasis during follow-up.Endoscopic resection of gastric GISTs ≤ 2 cm with 5 mitosis/50 HPFs has a low risk of recurrence and metastasis in the long term. Endoscopic resection of GISTs is safe and feasible.

Supplementary Tables A-F from Rapid Identification of UCA1 as a Very Sensitive and Specific Unique Marker for Human Bladder Carcinoma

Purpose: The most common genitourinary malignancy in China is bladder transitional cell carcinoma (TCC). Early diagnosis of new and recurrent bladder cancers, followed by timely treatment, will help decrease mortality. There are currently no satisfactory markers for bladder cancer available in clinics. Better diagnostic methods are highly demanded.Experimental Design: In this research, we have used comprehensive expressed sequence tag analysis, serial analysis of gene expression, and microarray analysis and quickly discovered a candidate marker, urothelial carcinoma associated 1 (UCA1). The UCA1 gene was characterized and its performance as a urine marker was analyzed by reverse transcription-PCR with urine sediments. A total of 212 individuals were included in this study, 94 having bladder cancers, 33 ureter/pelvic cancers, and 85 normal and other urinary tract disease controls.Results:UCA1 was identified as a novel noncoding RNA gene dramatically up-regulated in TCC and it is the most TCC-specific gene yet identified. The full-length cDNA was 1,439 bp, and sequence analysis showed that it belonged to the human endogenous retrovirus H family. Clinical tests showed that UCA1 assay was highly specific (91.8%, 78 of 85) and very sensitive (80.9%, 76 of 94) in the diagnosis of bladder cancer and was especially valuable for superficial G2-G3 patients (sensitivity 91.1%, 41 of 45). It showed excellent differential diagnostic performance in various urinary tract diseases without TCC.Conclusions: UCA1 is a very sensitive and specific unique marker for bladder cancer. It could have important implications in postoperative noninvasive follow-up. This research also highlights a shortcut to new cancer diagnostic assays through integration of in silico isolation methods with translational clinical tests based on RNA detection protocols.

PDF file - 179K, Includes HEPA analysis data, Calculation of DP score, and supplementary references

PDF file - 66K, Detailed information for the adult somatic tissues and cancer tissues from the five Affymetrix U133 plus2 gene expression datasets compiled for HEPA analysis

PDF file - 104K, Literature references reporting the clinical applications of known TSAs and the top 100 genes nominated by HEPA analysis

PDF file - 504K, 1) The principle and algorithm of HEPA analysis; 2) The parameters of HEPA analysis; 3) The HEPA score and expression profile of the TSA genes identified in this study; 4) Comparing PARSE and ELISA assay using IGF2BP3 antigen, and detecting autoantibody responses in an independent cohort of 149 lung cancer patients and 123 healthy individuals with PARSE assay; 5) The application of HEPA analysis in discovering therapeutically relevant overexpressed antigens

PDF file - 56K, Age and sex distribution of the lung patient and healthy cohorts, and the autoantibody responses in lung cancer patients at different clinical stages

PDF file - 98K, The detailed information and RT-PCR validation results for the TSA candidates nominated by HEPA analysis

PDF file - 41K, The weights for normal adult somatic tissues for the calculation of Depreciatory Penalty score

Immune-mediated neuroinflammation has been proposed to underlie the loss of lower esophageal sphincter (LES) myenteric neurons in achalasia. However, the immune status and key pathogenic immune subpopulations remain unclear. This study aims to evaluate the inflammatory status of patients with achalasia and their correlation with clinical characteristics, and further explore the key pathogenic subpopulations.We investigated the complete blood cell count and inflammatory markers in a large population of patients with achalasia (n=341) and healthy controls (n=80). The subpopulations of lymphocytes were analyzed by flow cytometry. Immunofluorescence was used to determine immune cell infiltration in the LES. Transcriptome changes of the key subpopulation were determined by RNA sequencing analysis.NLR, MLR, CRP, globulin, IL-6 and IL-10 were significantly elevated in patients with achalasia. MLR and globulin were positively correlated with disease duration. The absolute count and percentage of CD8+ T cells in peripheral blood and its infiltration around ganglion in the LES were significantly increased in achalasia. Transcriptome analysis indicated that CD8+ T cells were activated and proliferative. In addition to multiple inflammatory pathways, regulation of neuroinflammatory response pathway was also significantly up-regulated in achalasia. GSEA analysis revealed a close association with autoimmune diseases.Patients with achalasia suffered from chronic low-grade inflammation with dysregulated immune cells and mediators associated with disease duration. CD8+ T cells might be the key pathogenic subpopulation of achalasia. Our results provide an important immune cell signature of the pathogenesis of achalasia.

PurposeThis study aims to investigate the dual effects of commitment-based governance on the relationship between formal control and public–private partnership (PPP) project performance. Formal control and relationship governance are two primary forms of inter-organizational governance that affect project performance. However, little is known about the interplay between formal control and commitment and its effect on PPP projects. More specifically, previous studies have failed to distinguish the function routes of relationship governance resulting from different types of formal control (process and outcome control).Design/methodology/approachThis study adopts a questionnaire survey to empirically investigate the mechanism that commitment-based governance influences the relationship between formal control and PPP performance. After collecting data from public and private sector professionals involved in 101 Chinese PPP projects, the theoretical framework proposed in this paper is verified by the empirical results of the hierarchical multiple regression analysis.FindingsThe results show that process control has an inverted U-shaped effect and outcome control has a significant positive influence on PPP project performance. Furthermore, commitment moderates the effect of formal control on PPP project performance by increasing the relevance of outcome control and mediates the inverted U-shaped relationship between process control and PPP project performance.Practical implicationsManagers should recognize that process control is a double-edged sword and prevent the overuse of process control. Managers should direct their attention toward efforts to improve the commitment, which allows for the effectiveness of outcome control strategies. Additionally, this study new measurement method for relationship governance suggests that managers should be aware of the difference in parties' perceptions of the relationship.Originality/valueThis study allows for a comprehensive understanding of the relationship governance-control nexus from a commitment perspective. The authors bring into light the dual role of commitment-based governance in the relationship between the two types of formal control and PPP project performance. Moreover, the new approach to measure relationship governance offers valuable insight into the measurement of variables about individual's perception.

We aim to evaluate the efficacy and safety of endoscopic radial incision (ERI) versus endoscopic balloon dilation (EBD) treatment of naïve, recurrent, and refractory benign esophageal anastomotic strictures.One hundred and one ERI, 145 EBD, and 42 ERI combined with EBD sessions were performed in 136 consecutive patients with benign esophageal anastomotic stricture after esophagectomy at Zhongshan Hospital from January 2016 to August 2021. Baseline characteristics, operational procedures, and clinical outcomes data were retrospectively evaluated. Parameters and recurrence-free survival (RFS) were compared between ERI and EBD in patients with naïve or recurrent or refractory strictures. Risk factors for re-stricture after ERI were identified using univariate and multivariate analyses.Twenty-nine ERI versus 68 EBD sessions were performed for naïve stricture, 26 ERI versus 60 EBD for recurrent strictures, and 46 ERI versus 17 EBD for refractory stricture. With comparable baseline characteristics, RFS was greater in the ERI than the EBD group for naïve strictures (P = 0.0449). The ERI group had a lower 12-month re-stricture rate than the EBD group (37.9% vs 61.8%, P = 0.0309) and a more prolonged patency time (181.5 ± 263.1 vs 74.5 ± 82.0, P = 0.0233). Between the two interventions, recurrent and refractory strictures had similar RFS (P = 0.0598; P = 0.7668). Multivariate analysis revealed initial ERI treatment was an independent predictive factor for lower re-stricture risk after ERI intervention (odds ratio = 0.047, P = 0.001). Few adverse events were observed after ERI or EBD (3.0% vs 2.1%, P = 0.6918).ERI is associated with lower re-stricture rates with better patency and RFS compared with EBD for naive strictures.

To summarize the endoscopic and clinicopathological features of gastric adenocarcinoma of the fundic gland type(GA-FGs), and to evaluate the safety and efficacy of endoscopic submucosal dissection(ESD) for GA-FGs.From September 2017 to August 2021, patients treated with endoscopic resection and with pathological confirmed diagnosis of GA-FGs were included. Lymph node or distal metastasis was excluded before endoscopic resection. Medical records were retrospectively reviewed to obtain information regarding patient demographics, clinicopathological features, tumor characteristics, complete resection rate and complications. All patients underwent regular follow-up to evaluate for any local recurrence or distant metastasis.15 patients were included in this study, among which 11 were males and 4 were females. The average age of the patients was 56.9±10.7 years. Lesions were found at upper third(n=13,86.7%)or middle third(n=2,13.3%) of the stomach. The average size was 9.1±4.8mm. Lesions presented as flat elevated type with erosion on top(n=7,46.7%), depression type with pale color(n=5,33.3%) or submucosal tumor-like(SMT-like) appearance type(n=3,20%), macroscopiclly. 14(93.3%) patients reached en bloc resection, 13 (86.7%)patients had complete resection, and 11(73.3%) patients got curative resection, respectively. 9(60%)of the lesions had submucosal invasion. One patient accepted additional surgery. No local recurrence or metastasis was detected during follow-up.GA-FGs present with various endoscopic features. ESD appears to be a safe and effective choice for early-stage GA-FGs. This article is protected by copyright. All rights reserved.

There is accumulating evidence suggesting that an autoimmune component is involved in esophageal achalasia. An increase in immune cells, cytokines, chemokines, and autoimmune antibodies in serum and infiltration of immune cells in tissues support the view that immune-mediated inflammation is a crucial pathogenesis of inhibitory neuron degeneration in the lower esophageal sphincter. Infection of viruses such as the herpes virus family has been suspected of provoking the autoimmune reaction. Meanwhile, previous reports on immunogenetics have proposed that specific risk alleles on the human leukocyte antigen complex define the susceptible population to achalasia. In this study we reviewed current knowledge regarding the immune-related factors of achalasia, including immunology, viral infection and immunogenetic variations.

The surgery for esophageal cancer arising after prior gastrectomy is technically difficult with high morbidity and mortality. Endoscopic submucosal dissection (ESD) is a minimally invasive endoscopic treatment for superficial SCC with high curative resection rate. But few studies are concerned about ESD under these circumstances. The aim of this study was to elucidate the short- and long-term outcomes of ESD for superficial esophageal squamous cell cancer (SCC) in patients with prior gastrectomy. From January 2009 to January 2019, 37 patients with prior gastrectomy who underwent ESD for superficial esophageal SCC were retrospectively enrolled at the Zhongshan Hospital, Fudan University in Shanghai, China. Rates of en bloc resection, complete resection, curative resection, incidence of postoperative bleeding, perforation and postoperative stricture were evaluated as short-term outcomes. Overall survival, and local recurrence-free survival were evaluated as long-term outcomes. The rate of en bloc resection, complete resection and curative resection were 94.6%, 86.5% and 78.4%, respectively. No perforation was observed. 1 (2.7%) patient experienced postoperative bleeding. During the median observation of 43 months, 3 (8.6%) patients experienced esophageal stricture, successfully managed by balloon dilation. 3(8.6%) patients had local recurrence after ESD with 5-year local recurrence-free survival rate of 91.4%. During the observation period, 4 patients died of other reasons. The 1, 3, 5-year overall survival rates were 97.1%, 97.1% and 91.4%. The short-term outcomes indicate ESD is technically difficult with lower resection completeness in patients after gastrectomy, while the long-term outcomes are rather favorable.

Endoscopic resection is a feasible treatment for GI extraluminal tumors but remains a challenging procedure with limited data. In this study, we assessed the safety and efficacy of endoscopic resection for extraluminal tumors in the upper GI tract.From May 2016 to December 2021, 109 patients undergoing endoscopic resection for extraluminal tumors in the upper GI tract were retrospectively included. Clinicopathologic characteristics, procedure-related parameters, adverse events (AEs), and follow-up outcomes were analyzed.The en-bloc tumor resection rate was 94.5% and en-bloc retrieval rate 86.2%. Statistical analysis revealed tumor size ≥3.0 cm and irregular shape as significant risk factors for piecemeal extraction. Resection time and suture time were 46.8 ± 33.6 minutes and 20.6 ± 20.1 minutes, respectively. Large tumor size was significantly associated with a longer procedure duration. Five patients (4.6%) experienced major AEs, including recurrent laryngeal nerve injury, hydrothorax, major bleeding, local peritonitis, duodenal leakage, and repeat endoscopic surgery for tumor extraction. Minor AEs occurred in 13 patients (11.9%). Irregular tumor shape and tumor location (duodenum) were significantly associated with AE occurrence. Mean postoperative hospital stay was 4.7 ± 3.3 days. No recurrence or metastasis was observed during the mean follow-up period of 31.8 ± 15.2 months.Endoscopic resection is a safe and feasible therapeutic approach for upper GI extraluminal tumors. Tumor size, shape, and location impact the difficulty and safety of the procedure. Endoscopic resection of duodenal tumors is also feasible but associated with an increased risk of AEs compared with tumors in other locations.

Background Submucosal tunneling endoscopic resection (STER) and non-tunneling techniques are two alternative options for the treatment of cardial submucosal tumors (SMTs). We aimed to establish a regression model and develop a simple scoring system to help clinicians make surgical decisions for cardial submucosal tumors. Methods A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this study. All of them were randomized into the training cohort (n = 147) or internal validation cohort (n = 99). Then, the scoring system was proposed based on multivariate logistic regression analysis in the training cohort and assessed in the validation cohort. Results Of 246 patients, 97 were treated with STER, and the others with non-tunneling endoscopic resection. In the training stage, four factors were weighted with points based on the β coefficient from the regression model, including irregular morphology (-2 points), ulcer (2 points), the direction of the gastroscope (-2 points for reversing direction and 1 point for entering direction), and originating from the muscularis propria (-2 points). The patients were categorized into low-score (< -4), medium-score (-4 - -3) and high-score (> -3) groups, and those with low scores were more likely to be treated with STER. Our score model performed satisfying discriminatory power in internal validation (Areas under the receiver-operator characteristic curve (AUC), 0.829; 95% confidence interval (CI), 0.694-0.964) and goodness-of-fit in the Hosmer-Lemeshow test (P = .4721). Conclusions This scoring system could provide clinicians the references for making decisions about the treatment of cardial submucosal tumors.