A single-cell transcriptional landscape of immune cells shows disease-specific changes of T cell and macrophage populations in human achalasia.

Achalasia is a rare motility disorder of the esophagus caused by the gradual degeneration of myenteric neurons. Immune-mediated ganglionitis has been proposed to underlie the loss of myenteric neurons. Here, we measure the immune cell transcriptional profile of paired lower esophageal sphincter (LES) tissue and blood samples in achalasia and controls using single-cell RNA sequencing (scRNA-seq). In achalasia, we identify a pattern of expanded immune cells and a specific transcriptional phenotype, especially in LES tissue. We show C1QC+ macrophages and tissue-resident memory T cells (TRM), especially ZNF683+ CD8+ TRM and XCL1+ CD4+ TRM, are significantly expanded and localized surrounding the myenteric plexus in the LES tissue of achalasia. C1QC+ macrophages are transcriptionally similar to microglia of the central nervous system and have a neurodegenerative dysfunctional phenotype in achalasia. TRM also expresses transcripts of dysregulated immune responses in achalasia. Moreover, inflammation increases with disease progression since immune cells are more activated in type I compared with type II achalasia. Thus, we profile the immune cell transcriptional landscape and identify C1QC+ macrophages and TRM as disease-associated immune cell subsets in achalasia.

Clinical outcomes of endoscopic resection for the treatment of esophageal gastrointestinal stromal tumors: a ten-year experience from a large tertiary center in China.

BACKGROUNDS: Esophageal gastrointestinal stromal tumors (E-GISTs) are extremely rare and surgical resection is the recommended approach. However, surgical resection usually causes severe trauma that may result in significant postoperative morbidity. Endoscopic resection (ER) has developed rapidly in recent years and has been widely used in gastrointestinal lesions. Nevertheless, the feasibility and efficacy of ER in the management of E-GISTs are unknown. METHODS: Retrospective data were collected from January 2011 to December 2020 in a large tertiary center of China. Twenty-eight patients with E-GISTs treated by ER were included in the study. RESULTS: Of the 28 patients, there were 21 males and 7 females, with a median age of 55 years (40-70 years). The median tumor size was 15 mm (5-80 mm). The technical success rate was 100% (28/28), while the en bloc resection rate was 96.4% (27/28). The median operation time was 35 min (10-410 min). Sixteen (57.2%) tumors were categorized into very low risk group, six (21.4%) into low risk group, and six (21.4%) into high risk group. Pathologists carefully examined margins of each lesion. There were 11 lesions (39.3%) determined as R0 resection and 17 lesions (60.7%) as R1 resection with positive margins. The median hospital stay was 2 days (range, 1-8 days). One patient suffered from hydrothorax and required drainage, leading to a major adverse event rate of 3.6% (1/28). There was no conversion to surgery, and no death occurred within 30 days after the procedure. Imatinib was given to two patients after ER under multidisciplinary team surveillance. During follow-up (median of 54 months, 9-122 months), no recurrences or metastasis were observed. CONCLUSION: ER is safe and effective for E-GISTs and might become an optional choice in the future. Multicenter, prospective, large samples with long-term follow-up studies are still needed.

Single-cell transcriptomic analysis deciphers key transitional signatures associated with oncogenic evolution in human intramucosal oesophageal squamous cell carcinoma.

BACKGROUND AND AIMS: The early diagnosis and intervention of oesophageal squamous cell carcinoma (ESCC) are particularly important because of the lack of effective therapies and poor prognosis. Comprehensive research on early ESCC at the single-cell level is rare due to the need for fresh and high-quality specimens obtained from ESD. This study aims to systematically describe the cellular atlas of human intramucosal ESCC. METHODS: Five paired samples of intramucosal ESCC, para-ESCC oesophageal tissues from endoscopically resected specimens and peripheral blood mononuclear cells were adopted for scRNA-seq analysis. Computational pipeline scMetabolism was applied to quantify the metabolic diversity of single cells. RESULTS: A total of 164 715 cells were profiled. Epithelial cells exhibited high intra-tumoural heterogeneity and two evolutionary trajectories during ESCC tumorigenesis initiated from proliferative cells, and then through an intermediate state, to two different terminal states of normally differentiated epithelial cells or malignant cells, respectively. The abundance of CD8+ TEX s, Tregs and PD1+ CD4+ T cells suggested an exhausted and suppressive immune microenvironment. Several genes in immune cells, such as CXCL13, CXCR5 and PADI4, were identified as new biomarkers for poor prognosis. A new subcluster of malignant cells associated with metastasis and angiogenesis that appeared at an early stage compared with progressive ESCC was also identified in this study. Intercellular interaction analysis based on ligand-receptor pairs revealed the subcluster of malignant cells interacting with CAFs via the MDK-NCL pathway, which was verified by cell proliferation assay and IHC. This indicates that the interaction may be an important hallmark in the early change of tumour microenvironment and serves as a sign of CAF activation to stimulate downstream pathways for facilitating tumour invasion. CONCLUSION: This study demonstrates the changes of cell subsets and transcriptional levels in human intramucosal ESCC, which may provide unique insights into the development of novel biomarkers and potential intervention strategies.

Endoscopic mucosal resection of gastrointestinal polyps with a novel low-temperature plasma radio frequency generator: a non-inferiority multi-center randomized control study.

BACKGROUND: To evaluate the efficacy and safety of novel plasma radio frequency generator and its single-use polypectomy snares for endoscopic mucosal resection (EMR) of gastrointestinal (GI) polyps. METHODS: A total of 217 patients with 413 GI polyps were recruited from four centers in China. Patients were assigned to experimental or control groups using a central randomization method. The experimental group used the novel plasma radio frequency generator and its matched single-use polypectomy snares (Neowing, Shanghai), while the control group used the high-frequency electrosurgical unit (Erbe, Germany) and disposable electrosurgical snares (Olympus, Japan). The primary endpoint was the en bloc resection rate, and the non-inferiority margin was set at 10%. Secondary endpoint included operation time, coagulation success rate, intraoperative and postoperative bleeding rate, and perforation rate. RESULTS: The en bloc resection rate was 97.20% (104/107) in the experimental group and 95.45% (105/110) in the control group (P = 0.496). The operation time was 29.14 ± 20.21 min in the experimental group and 30.26 ± 18.74 min in the control group (P = 0.671). The average removal time of a single polyp in the experimental group was 7.52 ± 4.45 min, which was slightly shorter than that in the control group 8.90 ± 6.67 min, with no statistical difference (P = 0.076). The intraoperative bleeding rates of the experimental group and control group were 8.41% (9/107) and 10.00% (11/110), respectively (P = 0.686). No intraoperative perforation occurred in either group. The postoperative bleeding rates of the experimental group and the control group were 1.87% (2/107) and 4.55% (5/110), respectively (P = 0.465). No postoperative perforation occurred in the experimental group (0/107), while one case of delayed perforation occurred in the control group (1/110, 0.91%). There was no statistical difference between the two groups. CONCLUSIONS: Endoscopic mucosal resection of GI polyps with the novel plasma radio frequency generator is safe and effective, and non-inferior to the conventional high-frequency electrosurgical system.

Improving bowel preparation for colonoscopy with a smartphone application driven by artificial intelligence.

Optimal bowel preparation is a prerequisite for a successful colonoscopy; however, the rate of inadequate bowel preparation remains relatively high. In this study, we establish a smartphone app that assesses patient bowel preparation using an artificial intelligence (AI)-based prediction system trained on labeled photographs of feces in the toilet and evaluate its impact on bowel preparation quality in colonoscopy outpatients. We conduct a prospective, single-masked, multicenter randomized clinical trial, enrolling outpatients who own a smartphone and are scheduled for a colonoscopy. We screen 578 eligible patients and randomize 524 in a 1:1 ratio to the control or AI-driven app group for bowel preparation. The study endpoints are the percentage of patients with adequate bowel preparation and the total BBPS score, compliance with dietary restrictions and purgative instructions, polyp detection rate, and adenoma detection rate (secondary). The prediction system has an accuracy of 95.15%, a specificity of 97.25%, and an area under the curve of 0.98 in the test dataset. In the full analysis set (n = 500), adequate preparation is significantly higher in the AI-driven app group (88.54 vs. 65.59%; P < 0.001). The mean BBPS score is 6.74 ± 1.25 in the AI-driven app group and 5.97 ± 1.81 in the control group (P < 0.001). The rates of compliance with dietary restrictions (93.68 vs. 83.81%, P = 0.001) and purgative instructions (96.05 vs. 84.62%, P < 0.001) are significantly higher in the AI-driven app group, as is the rate of additional purgative intake (26.88 vs. 17.41%, P = 0.011). Thus, our AI-driven smartphone app significantly improves the quality of bowel preparation and patient compliance.

Endoscopic submucosal dissection for gastric adenocarcinoma of the fundic gland type (chief cell predominate type): Four years' experience from a tertiary hospital.

OBJECTIVE: To summarize the endoscopic and clinicopathological features of gastric adenocarcinoma of the fundic gland type (GA-FG), and to evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of GA-FGs. METHODS: From September 2017 to August 2021, patients treated with ESD who were pathologically confirmed to have GA-FGs were included. Those with lymphovascular and distal metastasis were excluded before ESD. The medical records were retrospectively reviewed to obtain information regarding patient demographics, clinicopathological characteristics, tumor features, complete resection rate, and complications, etc. All patients underwent follow-up for at least 12 months to evaluate any local recurrence or distant metastasis. RESULTS: A total of 15 patients with an average age of 56.9 ± 10.7 years were recruited, including 11 men and 4 women. Lesions were found at the upper third (13 [86.7%]) or middle third (2 [13.3%]) of the stomach. The average lesion size was 9.1 ± 4.8 mm. Macroscopically, lesions presented as a flat elevated type with reddish or erosion on top (n = 7, 46.7%), depressed type with pale color (n = 5, 33.3%), or submucosal tumor (SMT)-like appearance type (n = 3, 20.0%). En bloc resection, complete resection and curative resection were achieved in 14 (93.3%), 13 (86.7%), and 11 (73.3%) patients, respectively. Nine (60.0%) of the lesions had submucosal invasion. One patient underwent additional surgery. No local recurrence or metastasis was detected during the follow-up duration. CONCLUSIONS: GA-FGs present with various endoscopic features. ESD appears to be effective and safe for treating early-stage GA-FGs.

Endoscopic Submucosal Dissection for a Giant Well-Differentiated Liposarcoma Originated from Hypopharynx.

Hypopharyngeal liposarcoma is an extremely rare entity, and yet fewer than 40 cases have been reported in the literature. Lacking the possibility of distant metastases, local surgical resection with a clear margin can achieve the purpose of treatment. Endoscopic submucosal dissection has been widely used in the treatment of early upper gastrointestinal cancer and superficial hypopharyngeal cancer. Here, we present a case of a giant tumor originated from the hypopharynx that received primary resection by endoscopic submucosal dissection using a flexible upper gastroscope.

Landscape of esophageal submucosal tunneling endoscopic resection-related adverse events in a standardized lexicon: a large volume of 1701 cases.

BACKGROUND: Submucosal tunneling endoscopic resection (STER) has been widely applied for esophageal submucosal tumors. This large volume study aims to provide a standard landscape of STER-related AEs for reference. METHODS: 1701 patients with esophageal SMTs undergoing STER were included at Zhongshan Hospital, Fudan University. Data of clinical characteristics and adverse events were collected and analyzed in depth. Adverse events were recorded by ASGE lexicon and graded by ASGE grading/Clavien-Dindo system. Risk factors for major AEs were analyzed by univariate and multivariate logistic regression. RESULTS: Three hundred and twenty (18.8%) patients with 962 cases of adverse events were observed. Accordingly, 84 (5.0%) were classified as major AEs (moderate and severe) by ASGE grading and 37 (2.2%) were classified as major AEs (grades III-V) by Clavien-Dindo grading. First 1 year operation, distance > 6 cm from incision to tumor, piecemeal resection, partially extraluminal location, mucosal injury, and operation time > 60 min were included in the risk score model for major AEs of STER, with 57.1% sensitivity and 87.5% specificity. CONCLUSIONS: STER was a safe procedure for diagnosis and treatment of esophageal SMTs with a total 18.8% incidence of AEs, among which only 5.0% were major AEs requiring therapeutic measurements.

Comparison of safety and short-term outcomes between endoscopic and laparoscopic resections of gastric gastrointestinal stromal tumors with a diameter of 2-5 cm.

BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Endoscopic resection is a safe and cost-effective method for 2-5 cm of gastric GISTs compared with laparoscopic resection.

Utility of endoscopic ultrasound-guided fine-needle aspiration in pancreatic cancer patients who failed to obtain a pathological diagnosis in surgical exploration.

Background: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) allows for the analysis of diagnostic tissue specimens from various regions. For pancreatic tumors, especially un-resectable ones, how to obtain pathological confirmation is important for determining sub-sequent treatment. The purpose of this study is to investigate the clinical utility of EUS-FNA in patients who failed to obtain a pathological diagnosis in surgical exploration. Methods: Patients who underwent EUS-FNA due to unsuccessful biopsy in surgical exploration in our center were retrospectively reviewed. All of the patients were diagnosed with resectable disease before surgery but were found to be unresectable during surgery. The positive rate of pathological diagnosis of EUS-FNA was analyzed. Results: A total of 11 patients were included in this study, among which 8 were males and 3 were females. The median age of the patients was 55 years (range, 48 to 73 years). The median lesion size was 34 mm (range, 25 to 44 mm). The median number of needle passes was 3 (range, 1 to 3). Two patients underwent biliary stent implantation while 3 patients underwent gastrojejunostomy before EUS-FNA. The technical success rate of EUS-FNA was 100% (11/11); 10 (90.9%, 10/11) samples were positive and 1 was negative (being inadequate). Conclusions: Intraoperative biopsy is the first choice diagnostic modality for unresectable pancreatic neoplasms. However, for patients who fail to obtain a pathological diagnosis in surgical exploration, EUS-FNA is still worth an attempt.

Long-term prognosis of small gastric gastrointestinal stromal tumors with high histological grade: a longitudinal nested cohort study.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Endoscopic submucosal dissection for giant esophageal lipomatous tumors.

BACKGROUND AND AIM: Thoracotomy is the foremost choice of giant esophageal lipomatous tumors in previous studies, but it is highly traumatic and possibly diminishes the quality of patients' lives. To minimize such impacts, a minimally invasive method without loss of curability is desirable for giant lipomatous tumors of the esophagus. With recent progress in endoscopic techniques and devices, endoscopic submucosal dissection (ESD) has been successfully used to remove esophageal or gastric submucosal tumors. In our study, we aimed to evaluate the clinical impact of ESD for giant esophageal lipomatous tumors. METHODS: Design, single-center, retrospective study; setting, academic medical center; patients, six patients with six giant lipomatous tumors of the esophagus between February 2013 and December 2020; interventions, ESD; and main outcome measurements, procedure duration, en bloc resection rate, complications, local recurrence, and distant metastases. RESULTS: Endoscopic en bloc resections of esophageal lipomatous tumors were successfully performed in all patients, with a mean duration of 56.5 ± 26.0 min. All en bloc resection lesions showed both lateral and deep tumor-free margins. The average maximum diameter of the esophageal lipomatous tumors was 171.7 ± 66.2 mm. No complications such as bleeding and perforations happened during hospitalization with 4.0 ± 1.6 days. Besides, local recurrence and distant metastasis have not occurred during the follow-up period. CONCLUSIONS: Endoscopic submucosal dissection is a safe and effective way to dissect giant lipomatous tumors of the esophagus thoroughly.

Endoscopic removal of entirely embedded esophagus-penetrating foreign bodies (with video).

BACKGROUND AND AIM: Traditionally, surgery is the only choice for esophageal foreign bodies (FBs) penetrating into the mediastinum or cervical para-esophageal space. Recent progress in endoscopic techniques and devices has made it possible to perform endoscopic procedures in the mediastinum. Here, we describe a novel method to remove the entirely embedded esophagus-penetrating FBs through an endoscopic approach. METHODS: Patients who underwent endoscopic removal of entirely embedded esophagus-penetrating FBs were prospectively enrolled between December 2018 and June 2020. All procedures were performed by using five major steps: localization of the FB; mucosal incision; wound debridement, myotomy, and FB exposure; FB extraction; and closure of the esophageal wound. RESULTS: A total of five cases of entirely embedded esophagus-penetrating FBs were evaluated, two in children and three in adults. All FBs were successfully removed and extracted using a therapeutic endoscope and a hook knife or a hybrid knife and a grasping forceps as accessories. The average procedure time was 19.0 ± 12.4 min (range 10-40 min). The major surgical procedure was avoided in all patients. The average length of hospital stay was 3.8 ± 2.5 days (range 2-8 days). There were no severe short-term adverse events after all procedures. During the 1 month and 3 months follow-up, no patient developed long-term adverse events including stenosis of the esophagus and fistula formation. CONCLUSIONS: Endoscopic approach was a safe and effective way to remove entirely embedded esophagus-penetrating FBs.

Multiplex immunoassays reveal increased serum cytokines and chemokines associated with the subtypes of achalasia.

BACKGROUND: Achalasia is an esophageal motility disorder with unknown etiology. Previous findings indicate that immune-mediated inflammatory process causes inhibitory neuronal degeneration. This study was designed to evaluate levels of serological cytokines and chemokines in patients with achalasia. METHODS: We collected information from forty-seven patients with achalasia who underwent peroral endoscopic myotomy. Control samples were collected from forty-seven age- and sex-matched healthy people. The concentrations of serological cytokines and chemokines were analyzed by Luminex xMAP immunoassay. Serological and clinical data were compared between groups. KEY RESULTS: Compared with healthy controls, achalasia patients had significantly increased concentrations of eleven cytokines and chemokines, namely, TGF-ß1 (P < .001), TGF-ß2 (P < .001), TGF-ß3 (P < .001), IL-1ra (P < .001), IL-17 (P = .005), IL-18 (P < .001), IFN-γ (P < .001), MIG (P < .001), PDGF-BB (P < .001), IP-10 (P = .003), and SCGF-B (P < .001). Gene ontology (GO) and network functional enrichment analysis revealed regulation of signaling receptor activity and receptor-ligand activity were the most related pathways of these cytokines and chemokines. Levels of twelve cytokines and chemokines were significantly increased in type III compared with I/II achalasia, namely, TGF-ß2, IL-1ra, IL-2Ra, IL-18, MIG, IFN-γ, SDF-1a, Eotaxin, PDGF-BB, IP-10, MCP-1, and TRAIL. CONCLUSIONS AND INFERENCES: Patients with achalasia exhibited increased levels of serological cytokines and chemokines. Levels of cytokines and chemokines were significantly increased in type III than in type I/II achalasia. Cytokines and chemokines might contribute to the inflammatory development of achalasia.

Retrospective study of the efficacy and toxicity of lobaplatin in combined chemotherapy for metastatic breast cancer.

OBJECTIVE: To study the efficacy and adverse reactions of lobaplatin combined with other chemotherapy drugs in the treatment of metastatic breast cancer. METHODS: This retrospective analysis enrolled 114 patients who were diagnosed with advanced breast cancer from January 2010 to December 2015. Lobaplatin and another chemotherapeutic agent were given to patients. The efficacy and side effects were evaluated after at least two cycles of chemotherapy. RESULTS: Therapeutic efficacy and adverse reactions could be evaluated in 112 patients with 2 complete response (CR) patients, 31 cases of partial response (PR), 52 cases of stable disease (SD) and 27 cases of progressive disease (PD). The overall response rate (ORR) was 29.5% and the disease control rate (DCR) was 75.9%. The median time to progression (TTP) was 7.7 months, and the median overall survival (OS) was expected to be 28.0 months. The main side effects were myelosuppression. Twenty five patients (21.9%) had grade 3/4 neutrophil suppression, 18 patients (15.8%) had grade 3/4 thrombocytopenia. Other toxicities included gastrointestinal reaction, peripheral neuropathy, stomatitis, hepatic dysfunction, fatigue and skin rashes, which were alleviated by symptomatic treatment. CONCLUSION: Lobaplatin-based regimen chemotherapy for advanced metastatic breast cancer patients is effective and well tolerated.

A novel injectable thermo-sensitive binary hydrogels system for facilitating endoscopic submucosal dissection procedure.

Background and aims: Making an optimal and lasting submucosal cushion is critical for endoscopic submucosal dissection. The thermo-sensitive binary hydrogels system composed of poloxamer 407 and poloxamer 188 might be an excellent submucosal injection solution considering the unique feature that it remains liquid at room temperature and becomes gelatinous after being injected in the submucosa of the digestive tract. The present study focuses on preparing the thermo-sensitive binary hydrogels system and testing its capacity in mucosal lifting and its role in the endoscopic submucosal dissection procedure. Methods: Various concentrations of poloxamer 407 and poloxamer 188 were added to normal saline. The gelation temperature viscosity of the thermo-sensitive binary hydrogels system was measured to choose the best formula. The thermo-sensitive binary hydrogels system and normal saline were first compared in extracted porcine stomach. For in vivo study, the thermo-sensitive binary hydrogels system and normal saline were compared for facilitating the endoscopic submucosal dissection procedure. Results: Among the 46 kinds of thermo-sensitive binary hydrogels system, gelation temperatures of the thermo-sensitive binary hydrogels system I (poloxamer 407/poloxamer 188, 17%/0.5%, w/w) and the thermo-sensitive binary hydrogels system II (poloxamer 407/poloxamer 188, 18%/2%, w/w) were among the ideal range of gelation temperature. The injecting pressure in vitro study of thermo-sensitive binary hydrogels system II was significantly higher than that of thermo-sensitive binary hydrogels system I and normal saline (p < 0.001). Sixteen gastric endoscopic submucosal dissection procedures were performed in a porcine model. The initial volume of normal saline injection (13.88 ± 3.91 ml vs 5.88 ± 3.44 ml, p = 0.001) was significantly larger than the thermo-sensitive binary hydrogels system group. The postoperative wound showed a significant difference in the two groups (p = 0.023) indicating that the thermo-sensitive binary hydrogels system can create a cleaner wound. Conclusions: Considering the gelation temperature, viscosity, injection pressure, and the height of the mucosal elevation, the thermo-sensitive binary hydrogels system I was the better submucosal injection solution.

Mast cell infiltration associated with loss of interstitial cells of Cajal and neuronal degeneration in achalasia.

BACKGROUND: Achalasia is a motility disorder of unknown etiology. Previous studies supported the hypothesis that autoimmune-mediated inflammatory responses produce inhibitory neuronal degeneration. This study was designed to explore the role of mast cells in achalasia. METHODS: We collected information from 116 patients with achalasia who underwent peroral endoscopic myotomy between December 2016 and May 2017. Lower esophageal sphincter (LES) muscle biopsy was performed in all patients with achalasia, as well as 20 control subjects. The number of mast cells, interstitial cells of Cajal (ICCs), nNOS-positive cells, and S-100-positive cells in the LES were evaluated by immunohistochemistry. Pathological and clinical data were compared between groups. KEY RESULTS: Compared with controls, the LES of patients with achalasia had significantly fewer ICCs, nNOS-positive cells, and S-100-positive cells and a higher number of mast cells (all P < 0.001). Furthermore, the increased mast cell infiltration was significantly associated with decreased ICCs, nNOS-positive cells, and S-100-positive cells in patients with achalasia (all P < 0.05). Clinically, the number of strongly positive mast cells was highest in patients with type I achalasia and lowest in those with type III achalasia (P < 0.001). In addition, patients with a history of autoimmune disease or viral infection had greater mast cell infiltration in the LES muscle (P = 0.040). CONCLUSIONS & INFERENCES: In patients with achalasia, mast cell infiltration in the LES muscle is increased, in association with loss of ICCs and neuronal degeneration. Mast cells may thereby play a crucial role in the development of achalasia.

Glutathione S-transferase π: a potential role in antitumor therapy.

Glutathione S-transferase π (GSTπ) is a Phase II metabolic enzyme that is an important facilitator of cellular detoxification. Traditional dogma asserts that GSTπ functions to catalyze glutathione (GSH)-substrate conjunction to preserve the macromolecule upon exposure to oxidative stress, thus defending cells against various toxic compounds. Over the past 20 years, abnormal GSTπ expression has been linked to the occurrence of tumor resistance to chemotherapy drugs, demonstrating that this enzyme possesses functions beyond metabolism. This revelation reveals exciting possibilities in the realm of drug discovery, as GSTπ inhibitors and its prodrugs offer a feasible strategy in designing anticancer drugs with the primary purpose of reversing tumor resistance. In connection with the authors' current research, we provide a review on the biological function of GSTπ and current developments in GSTπ-targeting drugs, as well as the prospects of future strategies.