Deep learning assists detection of esophageal cancer and precursor lesions in a prospective, randomized controlled study.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system's sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

The Effects of Programmed Cell Death of Mesenchymal Stem Cells on the Development of Liver Fibrosis.

Mesenchymal stem cells have shown noticeable potential for unlimited self-renewal. They can differentiate into specific somatic cells, integrate into target tissues via cell-cell contact, paracrine effects, exosomes, and other processes and then regulate the target cells and tissues. Studies have demonstrated that transplantation of MSCs could decrease the expression and concentration of collagen in the liver, thereby reducing liver fibrosis. A growing body of evidence indicates that apoptotic MSCs could inhibit harmful immune responses and reduce inflammatory responses more effectively than viable MSCs. Accumulating evidence suggests that mitochondrial transfer from MSCs is a novel strategy for the regeneration of various damaged cells via the rescue of their respiratory activities. This study is aimed at reviewing the functions of MSCs and the related roles of the programmed cell death of MSCs, including autophagy, apoptosis, pyroptosis, and ferroptosis, as well as the regulatory pathogenic mechanisms of MSCs in liver fibrosis. Research has demonstrated that the miR-200B-3p gene is differentially expressed gene between LF and normal liver samples, and that the miR-200B-3p gene expression is positively correlated with the degree of liver fibrosis, suggesting that MSCs could inhibit liver fibrosis through pyroptosis. It was confirmed that circulating monocytes could deliver MSC-derived immunomodulatory molecules to different sites by phagocytosis of apoptotic MSCs, thereby achieving systemic immunosuppression. Accordingly, it was suggested that characterization of the programmed cell death-mediated immunomodulatory signaling pathways in MSCs should be a focus of research.

Clinical manifestation and treatment of small intestinal lymphangioma: A single center analysis of 15 cases.

Background: Small intestinal lymphangioma is a very rare benign lesion. Thus far, the literature on small intestinal lymphangioma has mainly involved case reports. The present study retrospectively examined the clinical features of patients with a pathological diagnosis of small intestinal lymphangioma. Materials and methods: From January 2010 to January 2021, 15 patients were pathologically diagnosed with small intestinal lymphangioma. The age, gender, clinical manifestation, computed tomography (CT) findings, endoscopic findings, localization of the lesion, treatment method, complications, and follow-up were retrospectively analyzed. Results: Most of the patients had no symptoms, and those with symptoms had melena or abdominal pain. Lymphangioma was located in the duodenum in nine cases (60.0%), jejunum in two (13.3%), jejunal-ileal junction with mesentery involvement in one (6.7%) and ileum in three (20.0%). Three cases (20.0%) had multiple lesions, and the other 12 (80.0%) had single lesions. The median size of the lesions was 0.8 cm. Thirteen cases were found by endoscopy, and nine cases of them had white-colored spots on the surface. Ten cases (66.7%) underwent endoscopic treatment, three (20.0%) underwent surgical treatment, and two (13.3%) were followed up. Postoperative acute pancreatitis developed in one patient after endoscopic resection of duodenal papillary lymphangioma; postoperative abdominal bleeding occurred in one patient with jejunal lymphangioma who underwent partial small bowel resection. Conclusion: Small intestinal lymphangioma is extremely rare, and its clinical manifestations are non-specific. Endoscopy is of great value in the diagnosis of small intestinal lymphangioma. Depending on the clinical manifestations, the size, location and scope of the lesions, follow-up, endoscopic treatment and surgery can be selected.

Cost-effective low-coverage whole-genome sequencing assay for the risk stratification of gastric cancer.

BACKGROUND: Gastric cancer (GC), a multifactorial disease, is caused by pathogens, such as Helicobacter pylori (H. pylori) and Epstein-Barr virus (EBV), and genetic components. AIM: To investigate microbiomes and host genome instability by cost-effective, low-coverage whole-genome sequencing, as biomarkers for GC subtyping. METHODS: Samples from 40 GC patients were collected from Taizhou Hospital, Zhejiang Province, affiliated with Wenzhou Medical University. DNA from the samples was subjected to low-coverage whole-genome sequencing with a median genome coverage of 1.86 × (range: 1.03 × to 3.17 ×) by Illumina × 10, followed by copy number analyses using a customized bioinformatics workflow ultrasensitive chromosomal aneuploidy detector. RESULTS: Of the 40 GC samples, 20 (50%) were found to be enriched with microbiomes. EBV DNA was detected in 5 GC patients (12.5%). H. pylori DNA was found in 15 (37.5%) patients. The other 20 (50%) patients were found to have relatively higher genomic instability. Copy number amplifications of the oncogenes, ERBB2 and KRAS, were found in 9 (22.5%) and 7 (17.5%) of the GC samples, respectively. EBV enrichment was found to be associated with tumors in the gastric cardia and fundus. H. pylori enrichment was found to be associated with tumors in the pylorus and antrum. Tumors with elevated genomic instability showed no localization and could be observed in any location. Additionally, H. pylori-enriched GC was found to be associated with the Borrmann type II/III and gastritis history. EBV-enriched GC was not associated with gastritis. No statistically significant correlation was observed between genomic instability and gastritis. Furthermore, these three different molecular subtypes showed distinct survival outcomes (P = 0.019). EBV-positive tumors had the best prognosis, whereas patients with high genomic instability (CIN+) showed the worst survival. Patients with H. pylori infection showed intermediate prognosis compared with the other two subtypes. CONCLUSION: Thus, using low-coverage whole-genome sequencing, GC can be classified into three categories based on disease etiology; this classification may prove useful for GC diagnosis and precision medicine.

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.

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.

Transplantation of acellularized dermis matrix (ADM) plus fully covered metal stent to prevent stricture after circumferential endoscopic submucosal dissection of early esophageal cancer (with video).

BACKGROUD AND STUDY AIMS: Esophageal stricture is a serious adverse event occurring after circular endoscopic submucosal dissection (ESD) involving the whole esophagus. However, there is still a lack of effectively preventive methods. The main purpose of this study is to evaluate the efficacy of application of acellularized dermis matrix (ADM) for the prevention of post-ESD esophageal stricture. The main objective of this study was to evaluate the use of decellularized dermal matrix (ADM) in the prevention of post-esophageal ESD strictures. PATIENTS AND METHODS: A pilot, single-center, prospective study was conducted. The study enrolled seven patients who had high-risks with extended resection of developing post-ESD esophageal stricture. After undergoing ESD, we attached different size of ADM patches to the mucosal defects using titanium clips then fixed with a metal mesh stent. The stent covered with metal mesh was removed at the median time of 27 days after the endoscopic procedure. Follow-up and repeated outpatient endoscopic screening were performed at appropriate scheduled times. RESULTS: The average longitudinal diameter of the resected specimens was 58.3 mm (range 38-90 mm). There were three patients developing strictures postoperatively at a mean time of 87 days (range 42-140). The median number of postoperative endoscopic balloon dilatation (EBD) in patients with stenosis was 2 (range 2-9). There were no deaths during a median follow-up period of 6 moths (range 1-12). CONCLUSIONS: This study was performed to assess the efficacy and safe method of relieving the severity of esophageal stricture after ESD through transplantation of ADM.

Effectiveness and safety of over-the-scope clip in closing perforations after duodenal surgery.

BACKGROUND: Endoscopic resection of duodenal subepithelial lesions (SELs) is a difficult procedure with a high risk of perforation. At present, dealing with perforation after endoscopic resection of duodenal SELs is still considered a great challenge. AIM: To evaluate the effectiveness and safety of an over-the-scope clip (OTSC) in the treatment of perforation post-endoscopic resection of duodenal SELs. METHODS: From May 2015 to November 2019, 18 patients with perforation following endoscopic resection of duodenal SELs were treated with OTSCs. Data comprising the rate of complete resection, closure of intraprocedural perforation, delayed bleeding, delayed perforation, and postoperative infection were extracted. RESULTS: The rate of complete removal of duodenal SELs and successful closure of the perforation was 100%. The median perforation size was 1 cm in diameter. Seventeen patients had minor intraoperative bleeding, while the remaining 1 patient had considerable amount of bleeding during the procedure. Seven patients had postoperative abdominal infections, of which 1 patient developed an abscess in the right iliac fossa and another patient developed septic shock. All 18 patients recovered and were discharged. No delayed bleeding or perforation was reported. The mean time taken to resume normal diet after the procedure was 6.5 d. The mean postoperative hospital stay was 9.5 d. No residual or recurrent lesions were detected during the follow-up period (15-66 mo). CONCLUSION: Closing a perforation after endoscopic resection of duodenal SELs with OTSCs seems to be an effective and reasonably safe therapeutic method.

The Immunomodulatory Properties of Mesenchymal Stem Cells Play a Critical Role in Inducing Immune Tolerance after Liver Transplantation.

Although liver transplantation is considered to be the best choice for patients with end-stage liver diseases, postoperative immune rejection still cannot be overlooked. Patients with liver transplantation have to take immunosuppressive drugs for a long time or even their entire lives, in which heavy economic burden and side effects caused by the drugs have become the major impediment for liver transplantation. There is a growing body of evidences indicating that mesenchymal stem cell (MSC) transplantation, a promising tool in regenerative medicine, can be used as an effective way to induce immune tolerance after liver transplantation based on their huge expansion potential and unique immunomodulatory properties. MSCs have been reported to inhibit innate immunity and adaptive immunity to induce a tolerogenic microenvironment. In in vitro studies, transplanted MSCs show plasticity in immune regulation by altering their viability, migration, differentiation, and secretion in the interactions with the surrounding host microenvironment. In this review, we aim to provide an overview of the current understanding of immunomodulatory properties of MSCs in liver transplantation, to elucidate the potential mechanisms behind MSCs regulating immune response, especially in vivo and the influence of the microenvironment, and ultimately to discuss the feasible strategies to improve the clinical prognosis of liver transplantation. Only after exhaustive understanding of potential mechanisms of the MSC immunomodulation can we improve the safety and effectiveness of MSC treatment and achieve better therapeutic effects.

Use of Artificial Intelligence to Improve the Quality Control of Gastrointestinal Endoscopy.

With the rapid development of science and technology, artificial intelligence (AI) systems are becoming ubiquitous, and their utility in gastroenteroscopy is beginning to be recognized. Digestive endoscopy is a conventional and reliable method of examining and diagnosing digestive tract diseases. However, with the increase in the number and types of endoscopy, problems such as a lack of skilled endoscopists and difference in the professional skill of doctors with different degrees of experience have become increasingly apparent. Most studies thus far have focused on using computers to detect and diagnose lesions, but improving the quality of endoscopic examination process itself is the basis for improving the detection rate and correctly diagnosing diseases. In the present study, we mainly reviewed the role of AI in monitoring systems, mainly through the endoscopic examination time, reducing the blind spot rate, improving the success rate for detecting high-risk lesions, evaluating intestinal preparation, increasing the detection rate of polyps, automatically collecting maps and writing reports. AI can even perform quality control evaluations for endoscopists, improve the detection rate of endoscopic lesions and reduce the burden on endoscopists.

Prediction of Re-positivity for Coronavirus Nucleic Acid Among COVID-19 Patients in the Recovery Phase.

Background and Objectives: Although the pathogenesis and treatment of coronavirus disease 2019 (COVID-19) have been gradually revealed, the risk for re-emergence of coronavirus nucleic acids in recovered patients remains poorly understood. Hence, this study evaluated the risk predictors associated with re-positivity for virus nucleic acid. Methods: Between February 1 and March 20, 2020, we retrospectively reviewed the clinical epidemiological data of 129 COVID-19 patients who were treated at Zhongxiang People's Hospital of Hubei Province in China. Subsequently, a risk prediction model for the re-positivity of virus nucleic acid was developed, and a receiver operating characteristic (ROC) curve was drawn for further validation. Results: In this study, the rate of re-positivity for virus nucleic acid was 17.8% (23/129) where all re-positivity cases were asymptomatic. The median time interval from discharge to nucleic acid re-positivity to discharge after being cured again was 11.5 days (range: 7-23 days). Multivariate logistic regression analysis showed that leukocytopenia [odds ratio (OR) 7.316, 95% confidence interval (CI) 2.319-23.080, p = 0.001], prealbumin < 150 mg/L (OR 4.199, 95% CI 1.461-12.071, p = 0.008), and hyperpyrexia (body temperature >39°C, OR 4.643, 95% CI 1.426-15.117, p = 0.011) were independent risk factors associated with re-positivity. The area under the ROC curve was 0.815 (95% CI, 0.729-0.902). Conclusion: COVID-19 patients with leukocytopenia, low prealbumin level, and hyperpyrexia are more likely to test positive for virus nucleic acid after discharge. Timely and effective treatment and appropriate extension of hospital stays and quarantine periods may be feasible strategies for managing such patients.

Progress of esophageal stricture prevention after endoscopic submucosal dissection by regenerative medicine and tissue engineering.

Endoscopic submucosal dissection (ESD) has been widely accepted as an effective treatment for early esophageal cancer. However, post-ESD esophageal stricture remains a thorny issue. We herein review many strategies for preventing post-ESD esophageal stricture, as well as discuss their strengths and weaknesses. These strategies include pharmacological prophylaxis, esophageal stent and tissue engineering and regenerative medicine treatment. In this review, we summarize these studies and discuss the underlying progress and future directions of tissue engineering and regenerative medicine treatment.

Identification and Validation of a Novel DNA Damage and DNA Repair Related Genes Based Signature for Colon Cancer Prognosis.

Backgrounds: Colorectal cancer (CRC) with high incidence, has the third highest mortality of tumors. DNA damage and repair influence a variety of tumors. However, the role of these genes in colon cancer prognosis has been less systematically investigated. Here, we aim to establish a corresponding prognostic signature providing new therapeutic opportunities for CRC. Method: After related genes were collected from GSEA, univariate Cox regression was performed to evaluate each gene's prognostic relevance through the TCGA-COAD dataset. Stepwise COX regression was used to establish a risk prediction model through the training sets randomly separated from the TCGA cohort and validated in the remaining testing sets and two GEO datasets (GSE17538 and GSE38832). A 12-DNA-damage-and-repair-related gene-based signature able to classify COAD patients into high and low-risk groups was developed. The predictive ability of the risk model or nomogram were evaluated by different bioinformatics- methods. Gene functional enrichment analysis was performed to analyze the co-expressed genes of the risk-based genes. Result: A 12-gene based prognostic signature established within 160 significant survival-related genes from DNA damage and repair related gene sets performed well with an AUC of ROC 0.80 for 5 years in the TCGA-CODA dataset. The signature includes CCNB3, ISY1, CDC25C, SMC1B, MC1R, LSP1P4, RIN2, TPM1, ELL3, POLG, CD36, and NEK4. Kaplan-Meier survival curves showed that the prognosis of the risk status owns more significant differences than T, M, N, and stage prognostic parameters. A nomogram was constructed by LASSO regression analysis with T, M, N, age, and risk as prognostic parameters. ROC curve, C-index, Calibration analysis, and Decision Curve Analysis showed the risk module and nomogram performed best in years 1, 3, and 5. KEGG, GO, and GSEA enrichment analyses suggest the risk involved in a variety of important biological processes and well-known cancer-related pathways. These differences may be the key factors affecting the final prognosis. Conclusion: The established gene signature for CRC prognosis provides a new molecular tool for clinical evaluation of prognosis, individualized diagnosis, and treatment. Therapies based on targeted DNA damage and repair mechanisms may formulate more sensitive and potential chemotherapy regimens, thereby expanding treatment options and potentially improving the clinical outcome of CRC patients.

MiR-103 protects from recurrent spontaneous abortion via inhibiting STAT1 mediated M1 macrophage polarization.

Recurrent spontaneous abortion (RSA) is a common complication of early pregnancy. Excessive M1 macrophage was found to be involved in RSA, but the underlying mechanisms remains unclear. MicroRNAs play critical roles in RSA as well as the polarization of macrophages; however, the regulatory effect of miRNAs on M1 differentiation in RSA has not been fully investigated. In this study, miRNA microarray assay revealed that miR-103 was significantly decreased in RAW264.7-derived M1 macrophages upon IFNγ and LPS stimulation. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that in RSA patients, miR-103 expression was decreased substantially, and negatively correlated with that of STAT1. Moreover, down-regulation of miR-103 could sensitively discriminate RSA patients from normal pregnancies (NP) subjects. Experiments in vitro showed that overexpression of miR-103 suppressed M1 polarization by inhibiting STAT1/IRF1 signaling pathway and vice versa. miR-103 regulated STAT1 expression by direct binding to its 3'-UTR. Moreover, our in vivo study demonstrated that overexpressed miR-103 could reduce mice embryo resorption and M1 polarization effectively. Overall, the results suggested that decreased miR-103 was involved in RSA by increasing M1 macrophage polarization via promoting STAT1/IRF1 signaling pathway. miR-103 may be explored as a promising diagnostic marker and therapeutic target for RSA.

Long-term outcomes of endoscopic resection for small (≤ 4.0 cm) gastric gastrointestinal stromal tumors originating from the muscularis propria layer.

AIM: To evaluate the long-term efficacy of endoscopic resection (ER) for small (≤ 4.0 cm) gastric gastrointestinal stromal tumors (GISTs) originating from the muscularis propria layer. METHODS: Between June 2005 and February 2015, we retrospectively analyzed 229 consecutive patients with gastric MP-GISTs who underwent ER with a follow-up at least 36 mo. The main outcome measurements included complete resection rate, complications, and long-term follow-up outcomes. RESULTS: ER included endoscopic muscularis excavation in 179 cases, endoscopic full-thickness resection in 32 cases, and submucosal tunneling endoscopic resection in 18 cases. The median size of GISTs was 1.90 cm. Of the 229 GISTs, 147 were very low risk, 72 were low risk, 8 were intermediate risk, and 2 were high risk. Short-term outcomes showed the complete resection rate was 96.5%, and 8 patients (3.5%) had complications. Of the 8 patients with complications, only one patient required surgical intervention. Long-term outcomes showed 225 patients were actively followed-up until composition of this manuscript. The remaining 4 patients were lost because of unrelated death. During the follow-up period (median, 57 mo), no residual, recurrent lesions, or distant metastasis were detected in any patients. Binary logistic regression analysis showed tumor size was a risk factor associated with a high mitotic index (≥ 5/50 HPF) of GISTs (P = 0.002). CONCLUSION: ER seems to be an effective and safe method for gastric MP-GISTs ≤ 4.0 cm, and, for some intermediate or high risk GISTs, adjuvant therapy and/or additional surgery might be required to reduce the risk of recurrence or metastasis.

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.

Recovery Profiles of T-Cell Subsets Following Low-Dose Total Body Irradiation and Improvement With Cinnamon.

PURPOSE: Inefficient T-cell reconstitution from x-ray-induced immune damage reduces antitumor response. To understand the profile of T-cell reconstitution after irradiation will overcome the barrier of antitumor immunity. This study aimed to identify the recovery profile of T-cell subsets following x-ray irradiation and to highlight the role of cinnamon on efficient T-cell restoration postexposure in the antitumor response. METHODS AND MATERIALS: CD3(+), CD8(+), and CD4(+) T cells and Th1, Th2, Th17, and regulatory T (Treg) cells were evaluated at different time points after single low-dose total body irradiation (SLTBI) with or without cinnamon treatments. T-bet, GATA3, RORγt, and Foxp3 signaling specific for Th1, Th2, Th17, and Treg were also analyzed by RT-PCR assay. The effects of cinnamon on efficient T-cell subset reconstitution was confirmed in a lung melanoma model in irradiated mice. RESULTS: Reconstitution of CD4(+) T cells was delayed more than that of CD8(+) T cells in T-cell restoration after SLTBI. The production of IFNγ by Th1 or Tc1 cells was sharply decreased and was accompanied by reduced T-bet mRNA, even when total T-cell numbers had recovered; the frequencies of Th17 and Treg cells and their specific transcription factors (RORγt and Foxp3, respectively) were obviously increased. Irradiation-induced inefficient T-cell reconstitution impaired the antitumor capacities in the lung melanoma model. Pretreatment with cinnamon in irradiated mice accelerated the generation of Th1 and reduced the differentiation of Treg cells by activating T-bet and limiting transcriptions of Foxp3. Improvement resulting from cinnamon pretreatment on the efficient T-cell recovery profile from SLTBI promoted antitumor immunity in the lung melanoma model. CONCLUSIONS: T-cell reconstitution from SLTBI was characterized by impaired Th1 and elevated Th17 and Treg cells. Cinnamon effectively improved the imbalance of T-cell subsets by promoting the proliferation of Th1 and by suppressing expansions of Th17 and Tregs. The role of cinnamon in efficient T-cell reconstitution from SLTBI is effective in antitumor immunity.