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Background: Endoscopic resection (ER) for jejunoileal lesions (JILs) has been technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and safety of ER for JILs. Method: We retrospectively investigated 52 patients with JILs who underwent ER from January 2012 to February 2022. We collected and analyzed clinicopathological characteristics, procedure‐related parameters, outcomes, and follow‐up data. Results: The mean age was 49.4 years. Of the 52 JILs, 33 ileal tumors within 20 cm from the ileocecal valve were resected with colonoscopy, while 19 tumors in the jejunum or the ileum over 20 cm from the ileocecal valve received enteroscopy resection. The mean procedure duration was 49.0 min. The en bloc resection and en bloc with R0 resection rates were 86.5% and 84.6%, respectively. Adverse events (AEs) included one (1.9%) major AE (delayed bleeding) and five (9.6%) minor AEs. During a median follow‐up of 36.5 months, two patients had local recurrence (3.8%), while none had metastases. The 5‐year recurrence‐free survival (RFS) and disease‐specific survival (DSS) were 92.9% and 94.1%, respectively. Compared with the enteroscopy group, overall AEs were significantly lower in the colonoscopy group (P < 0.05), but no statistical differences were observed in RFS (P = 0.412) and DSS (P = 0.579). There were no significant differences in AEs, RFS, and DSS between the endoscopic submucosal dissection (ESD) and the endoscopic mucosal resection (EMR) group. Conclusions: ER of JILs has favorable short‐term and long‐term outcomes. Both ESD and EMR can safely and effectively resect JILs in appropriately selected cases. [ABSTRACT FROM AUTHOR]

This article discusses the case of a 54-year-old woman with Peutz-Jeghers syndrome who underwent endoscopic resection (ER) for a massive small bowel tumor causing intussusception and incomplete obstruction. The patient had previously undergone multiple surgeries for ileus. The ER procedure involved the use of colonoscopy and enteroscopy to visualize and resect the tumor. Ligation at the neck of the tumor with a nylon loop was performed to block the blood supply and reduce bleeding risk. The procedure was successful, and there were no adverse events or complications. The authors suggest that ER may be a promising alternative to surgery for certain populations, such as elderly patients or those unwilling to undergo surgery. They also propose that the indications for endoscopic treatment of large small bowel tumors may expand with advancements in procedural techniques and equipment. [Extracted from the article]

Objectives: Delayed bleeding is a rare but important major adverse event (mAE) after endoscopic submucosal tunneling procedures (ESTP), which is scarcely reported. We aimed to characterize the clinical characteristics of delayed bleeding and provide better management of this mAE. Method: From August 2010 to October 2022, we reviewed 3852 patients with achalasia receiving peroral endoscopic myotomy (POEM) and 1937 patients with upper gastrointestinal tumors receiving submucosal tunneling endoscopic resection (STER). Among these, records of 22 patients (15 POEM, 7 STER) with delayed bleeding were collected. Clinical characteristics, treatment, and outcomes of delayed bleeding were analyzed. Results: The mean age was 43.6 years. Ten patients (45.5%) were intratunnel bleeding, seven (31.8%) were intratunnel bleeding accompanied by mucosal bleeding, and five (22.7%) were mucosal bleeding. The most common accompanied symptoms were hematemesis, fever, and melena. The most common accompanied mAEs were fistula, pulmonary inflammation, and pleural effusion with atelectasis. The mean duration from ESTP to endoscopic intervention was 5.3 ± 4.9 days. Active bleeding was identified in 21 patients (95.5%). The bleeding was successfully controlled by electrocoagulation (19 cases), endoscopic clipping (six cases), and Sengstaken–Blakemore tube insertion (three cases), and no patient required surgical intervention. The mean hemostatic procedure duration was 61.8 ± 45.8 min. The mean post‐bleeding hospital stay was 10.0 ± 6.2 days. A brief meta‐analysis of previous studies showed the pooled estimate delayed bleeding rate after POEM, STER, and G‐POEM was 0.4%. Conclusions: Delayed bleeding is uncommon and could be effectively managed by timely emergency endoscopic procedures without requiring subsequent surgical interventions. [ABSTRACT FROM AUTHOR]

Background and Aim: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

Background and aims: Endoscopic submucosal dissection (ESD) for anastomotic lesions is technically challenging due to severe fibrosis, deformity, staples, and limited space for procedure. We aimed to characterize the clinicopathological characteristics, feasibility, and effectiveness of ESD for anastomotic lesions of the upper gastrointestinal tract. Methods: We retrospectively investigated 43 patients with lesions involving the anastomoses of the upper GI tract who underwent ESD from April 2007 to February 2021. We collected clinicopathological characteristics, procedure‑related parameters and outcomes, and follow‑up data and analyzed the impact of anastomotic involvement. Results: The median duration from previous upper GI surgery was 60 months and the median procedure duration was 30 min. The rate of en bloc resection and en bloc with R0 resection was 90.7% and 81.4%, respectively. Two patients (4.7%) experienced major adverse events, including delayed bleeding and febrile episode. During a median follow-up of 80 months, 3 patients had local recurrence and 4 patients had metastases. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 89.6% and 95.1%, respectively. Compared with the unilaterally involving group, the straddling anastomosis group had significantly longer procedure duration, larger specimen, lower rates of en bloc resection and en bloc with R0 resection, and shorter DFS and OS (all P < 0.05). However, rates of adverse events did not differ significantly between the two groups. Conclusions: The short‑ and long-term outcomes of ESD for upper GI anastomotic lesions were favorable. Although with technically challenging, ESD could be performed safely and effectively for anastomotic lesions. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) for anastomotic lesions is technically challenging. We aimed to characterize the clinicopathologic characteristics, feasibility, and effectiveness of ESD for anastomotic lesions of the lower gastrointestinal tract. Method: We retrospectively investigated 55 patients with anastomotic lesions of the lower gastrointestinal tract who underwent ESD from February 2008 to January 2021. The lesions involving one or both sides of anastomoses were classified into the unilaterally involving anastomosis (UIA) or straddling anastomosis (SA) group, respectively. We collected clinicopathological characteristics, procedure‐related parameters and outcomes, and follow‐up data and analyzed the impact of anastomotic involvement. Results: The mean age was 62.5 years, and the median procedure duration was 30 min. The rates of en bloc resection and R0 resection were 90.9% and 85.5%, respectively. Four patients (7.3%) experienced major adverse events (AEs). During a median follow‐up of 66 months (range 14–169), seven patients had local recurrence, and six patients had metastases. The 5‐year disease‐free survival and overall survival rates were 82.4% and 90.7%, respectively. The 5‐year disease ‐specific survival (DSS) rate was 93.3%. Compared with the UIA group, the SA group had significantly longer procedure duration, larger specimen, lower rates of en bloc resection and R0 resection, and shorter disease‐free survival (all P < 0.05). However, rates of AEs did not differ significantly between the two groups. Conclusions: The short‐term and long‐term outcomes of ESD for colorectal anastomotic lesions were favorable. Although with technically challenging, ESD could be performed safely and effectively for lesions at the anastomoses. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Peroral endoscopic myotomy (POEM) is a treatment option for patients with previous surgical or endoscopic treatment. We aimed to evaluate the influence of prior treatment on perioperative and follow-up outcomes in patients undergoing POEM.Methods: From August 2010 to December 2014, a total of 1384 patients with achalasia underwent POEM at our center. We retrospectively reviewed 849 patients who completed follow-up. Patients with an Eckardt score ≥ 4 after POEM were considered to have a clinical failure. We compared variables between patients with and without prior treatment. We analyzed risk factors for perioperative major adverse events, and clinical reflux and failure during follow-up.  RESULTS:  245 patients (28.9 %) had undergone prior treatment, and 34 patients (4.0 %) experienced a major adverse event associated with the POEM procedure. During a median follow-up of 23 months (range 1 - 71), clinical reflux occurred in 203 patients (23.9 %) and clinical failure was recorded for 94 patients (11.1 %). Patients with prior treatment had a longer procedure duration (P = 0.001) and longer hospital stay after POEM (P = 0.001). Prior treatment was not an independent risk factor for major adverse events or clinical reflux (odds ratio [OR] 1.19, P = 0.65; OR 1.26, P = 0.19; logistic regression), but it did increase the rate of clinical failure during follow-up (hazard ratio 1.90, P = 0.002; Cox regression).Conclusions: POEM was performed safely with a low rate of major adverse events in patients with achalasia who had undergone prior surgical or endoscopic treatment. However, prior treatment increased the risk of clinical failure after POEM. [ABSTRACT FROM AUTHOR]

Watch a video of this article. [ABSTRACT FROM AUTHOR]

Because the tumor was located on the posterior wall of the duodenal bulb near the pylorus and had predominantly extraluminal growth, it would have been difficult to perform endoscopic full-thickness resection and close the wound. The tumor was gradually separated with an IT knife combined with a hook knife, then the tumor was removed en bloc with a snare. The tunnel was extended to the duodenal bulb and we observed that the tumor originated from the deep layer of the muscularis propria with extraluminal growth (Fig. [Extracted from the article]

The second gastroscopy (POD 7) revealed an esophageal fistula with 1.0 cm mucosal defect at the lower esophagus (Fig. 2 The third and fourth gastroscopies. a The third gastroscopy showed that the residual cavity was obviously smaller than before drainage. b The fourth gastroscopy showed that the esophageal wounds near the cardia were almost healed. After entering the thoracic cavity through the esophageal fistula, the necrotic tissue was cleaned and a gastric tube was placed into the cavity for drainage through the esophageal mucosal defect (Fig. [Extracted from the article]

A computed tomography scan revealed a linear foreign body (FB) perforation in the posterior part of the duodenal bulb, with adjacent inflammatory effusion and encapsulated abscess ( B a b ). Long-term embedded FB leads to chronic inflammatory fibrosis and abscess; therefore, perforation and diffuse peritonitis are not likely to occur when incision is made at the thickest part of the abscess, which avoids major surgery. Given that the thick abscess and the consistency of the position of the FB on the computed tomography scan and endoscopic findings, we decided to remove the FB by endoscopic dissection. [Extracted from the article]

None Infantile hypertrophic pyloric stenosis (IHPS) is the most common condition requiring surgical treatment in infants [1]. Here, we report on the use of peroral pyloromyotomy (POP), also called gastric peroral endoscopic myotomy (G-POEM), which has shown promising results in the treatment of adult gastroparesis [3], for a novel application, the treatment of IHPS. In this video, we report the first application of POP in IHPS, which may indicate that POP is a minimally invasive, safe, and effective alternative for treating infants with IHPS. [Extracted from the article]

Abstract: The HIV-1 gp41 core, a six-helix bundle formed between the N- and C-terminal heptad repeats, plays a critical role in fusion between the viral and target cell membranes. Using N36(L8)C34 as a model of the gp41 core to screen phage display peptide libraries, we identified a common motif, HXXNPF (X is any of the 20 natural amino acid residues). A selected positive phage clone L7.8 specifically bound to N36(L8)C34 and this binding could be blocked by a gp41 core-specific monoclonal antibody (NC-1). JCH-4, a peptide containing HXXNPF motif, effectively inhibited HIV-1 envelope glycoprotein-mediated syncytium-formation. The epitope of JCH-4 was proven to be linear and might locate in the NHR regions of the gp41 core. These data suggest that HXXNPF motif may be a gp41 core-binding sequence and HXXNPF motif-containing molecules can be used as probes for studying the role of the HIV-1 gp41 core in membrane fusion process. [Copyright &y& Elsevier]

Abstract: Endosomal trafficking of EGF receptor (EGFR) upon stimulation is a highly regulated process during receptor-mediated signaling. Recently, the sorting nexin (SNX) family has emerged as an important regulator in the membrane trafficking of EGFR. Here, we report the identification of a novel interaction between two members of the family, SNX1 and SNX5, which is mediated by the newly defined BAR domain of both SNXs. We have also shown that the PX domain of SNX5 binds specifically to PtdIns other than to PtdIns(3)P. Furthermore, the BAR domain but not the PX domain of SNX5 is sufficient for its subcellular membrane association. Functionally, overexpression of SNX5 inhibits the degradation of EGFR. This process appears to be independent of its interaction with SNX1. However, overexpression of SNX1 is able to attenuate the effect of SNX5 on EGFR degradation, suggesting the two proteins may play antagonistic roles in regulating endosomal trafficking of the receptor. [Copyright &y& Elsevier]

Monoclonal antibody 2F5 recognizing ELDKWA-epitope on HIV-1 gp41 has significant neutralization potency against 90% of the investigated viruses of African, Asia, American and European strains, but antibodies responses to ELDKWA-epitope in HIV-1 infected individuals were very low. Based on the epitope-vaccine strategy suggested by us, a recombinant glutathione S-transferase (GST) fusion protein (GST-MELDKWAGELDKWAGELDKWAVDIGPGRAFYGPGRAFYGPGRAFY) as vaccine antigen containing three repeats of neutralizing epitope ELDKWA on gp41 and GPGRAFY on gp120 was designed and expressed in Escherichia coli. After vaccination course, the recombinant multi-epitope vaccine could induce high levels of predefined multi-epitope-specific antibodies in mice. These antibodies in sera could bind to both neutralizing epitopes on gp41 peptide, V3 loop peptide and recombinant soluble gp41 (aa539–684) in ELISA assay (antisera dilution: 1:1600–25 600), while normal sera did not. Moreover, these antibodies in sera could recognize the CHO-WT cells which expressed HIV-1 envelope glycoprotein on the cell surfaces, indicating that the predefined epitope-specific antibodies could recognize natural envelope protein of HIV-1 though these antibodies were induced by recombinant multi-epitope-vaccine. These experimental results suggested a possible way to develop recombinant multi-epitope vaccine inducing multi-antiviral activities against HIV-1. [Copyright &y& Elsevier]

Background and aims: Chronic appendicitis is a condition with chronic abdominal pain or mild attacks of appendicitis, seriously affecting the patient's quality of life. Endoscopic retrograde appendicitis therapy (ERAT) has emerged as a promising, non-invasive treatment for acute uncomplicated appendicitis. Here, we aim to assess the safety and efficacy of ERAT for chronic fecalith appendicitis. Methods: We retrospectively reviewed the medical records of consecutive patients who underwent ERAT for chronic fecalith appendicitis at Zhongshan Hospital, Fudan University, Shanghai, China between December 2017 and June 2023. Clinicopathological characteristics, procedure-related parameters, AEs, and follow-up outcomes were analyzed. Results: A total of 60 patients were included. ERAT intubation was successfully performed in all patients (100%). The median procedure time was 15 min (IQR, 12–25 min). The postoperative abdominal pain scores were significantly reduced (P < 0.0001). Short-term adverse events included 5 cases of abdominal pain (8.3%) and 2 cases of fever (3.3%). Long-term adverse events included recurrent abdominal pain in 3 cases (5.0%) and recurrent appendicitis in 2 cases (3.3%). The median time to recurrence was 5 months (IQR, 2–12 months). Logistic regression analysis revealed appendiceal stenosis (OR 25.000, 95% CI 1.114–561.281, P = 0.043) and distorted appendix lumen (OR 12.500, 95% CI 1.373–113.806, P = 0.025) as significant risk factors for long-term adverse events. Conclusions: ERAT may be a safe, effective and minimally invasive alternative approach for chronic fecalith appendicitis. Appendix lumen stenosis and distortion are risk factors of recurrence. Further large-scale prospective studies are necessary to assess the efficacy and safety of ERAT compared with antibiotic therapy and surgery. [ABSTRACT FROM AUTHOR]

Background: Achalasia is a rare motility disorder of the esophagus often accompanied by immune dysregulation, yet specific underlying mechanisms remain poorly understood. Methods: We utilized Mendelian randomization (MR) to explore the causal effects of cytokine levels on achalasia, with cis-expression/protein quantitative trait loci (cis-eQTLs/pQTLs) for 47 cytokines selected from a genome-wide association study (GWAS) meta-analysis and GWAS data for achalasia obtained from FinnGen. For cytokines significantly linked to achalasia, we analyzed their plasma concentrations and expression differences in the lower esophageal sphincter (LES) using enzyme-linked immunosorbent assay and single-cell RNA sequencing (scRNA-seq) profiling, respectively. We further employed bioinformatics approaches to investigate underlying mechanisms. Results: We revealed positive associations of circulating Eotaxin, macrophage inflammatory protein-1b (MIP1b), soluble E-selectin (SeSelectin) and TNF-related apoptosis-inducing ligand (TRAIL) with achalasia. When combining MR findings with scRNA-seq data, we observed upregulation of TRAIL (OR = 2.70, 95% CI, 1.20–6.07), encoded by TNFSF10, in monocytes and downregulation of interleukin-1 receptor antagonist (IL-1ra) (OR = 0.70, 95% CI 0.59–0.84), encoded by IL1RN, in FOS_macrophages in achalasia. TNFSF10high monocytes in achalasia displayed activated type I interferon signaling, and IL1RNlow FOS_macrophages exhibited increased intercellular communications with various lymphocytes, together shaping the proinflammatory microenvironment of achalasia. Conclusions: We identified circulating Eotaxin, MIP1b, SeSelectin and TRAIL as potential drug targets for achalasia. TNFSF10high monocytes and IL1RNlow macrophages may play a role in the pathogenesis of achalasia. [ABSTRACT FROM AUTHOR]

Background: Transcolonic endoscopic appendectomy (TEA) is rapidly evolving and has been reported as a minimally invasive alternative to appendectomy. We aimed to characterize the feasibility and safety of a novel unassisted single-channel TEA. Method: We retrospectively investigated 23 patients with appendicitis or appendiceal lesions who underwent TEA from February 2016 to December 2022. We collected clinicopathological characteristics, procedure‑related parameters, and follow‑up data and analyzed the impact of previous abdominal surgery and traction technique. Results: The mean age was 56.0 years. Of the 23 patients with appendiceal lesions, fourteen patients underwent TEA and nine underwent traction-assisted TEA (T-TEA). Eight patients (34.8%) had previous abdominal surgery. The En bloc resection rate was 95.7%. The mean procedure duration was 91.1 ± 45.5 min, and the mean wound closure time was 29.4 ± 18.6 min. The wounds after endoscopic appendectomy were closed with clips (21.7%) or a combination of clip closure and endoloop reinforcement (78.3%), and the median number of clips was 7 (range, 3–15). Three patients (13.0%) experienced major adverse events, including two delayed perforations (laparoscopic surgery) and one infection (salvage endoscopic suture). During a median follow-up of 23 months, no residual or recurrent lesions were observed, and no recurrence of abdominal pain occurred. There were no significant differences between TEA and T-TEA groups and between patients with and without abdominal surgery groups in each factor. Conclusion: Unassisted single-channel TEA for patients with appendiceal lesions has favorable short- and long-term outcomes. TEA can safely and effectively treat appendiceal disease in appropriately selected cases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Former investigations demonstrated that the envelope glycoprotein E2 could protect pigs from classical swine fever virus (CSFV). Based on these findings, we prepared synthetic peptide vaccine using E2 N-terminal antigenic units B/C and hoped to induce protective activity against lethal challenge of virulent CSFV strain Shimen. Five overlapped peptides sequence-covering amino acids 693–777 on E2 of Shimen were synthesized and then conjugated with bovine serum albumin (BSA), respectively. In the vaccination course, the candidate peptide vaccines in combination (multi-peptide vaccine (MPV)) were applied for immunization of pigs (n=10) and induced strong antibody response against CSFV. It is subsequently demonstrated that this peptide vaccine could provide immunized pigs complete protection against lethal CSFV challenge as C-strain does, while all non-immunized pigs in negative control group manifested obvious typical symptoms and died during the second and third weeks after viral challenge. In order to confirm the neutralizing activity of the polyclonal antibodies induced by MPV, neutralization assay were carried out on rabbits. The live C-strain alone could ordinarily induce typical fever on rabbits. The typical fever of rabbits induced by the live C-strain could be inhibited by pre-incubation with the anti-sera (dilution 1:4 and 1:16) induced by MPV, but not inhibited by pre-incubation with the same anti-sera from which the antibodies against five peptides were removed by peptide-specific affinity chromatography, which indicates that these peptide-specific antibodies in the anti-sera induced by MPV provided protective activity against CSFV. Our finding provides a new way to develop marker vaccine against CSFV. [Copyright &y& Elsevier]

Background: Peroral endoscopic myotomy (POEM) is a safe and effective approach for achalasia. However, the safety, feasibility, perioperative and long-term efficacy in treating geriatric patients has not been well evaluated.Methods: Data of 2367 patients diagnosed with achalasia and treated with POEM in the Endoscopy Center, Zhongshan Hospital, Fudan University from August 2010 to December 2017 were retrospectively reviewed. Last follow-up was in December 2018. Propensity score matching based on baseline characteristics was used to adjust for confounding. With a caliper of 0.01 in propensity scoring, 139 patients aged ≥ 65 years were matched at a 1:2 ratio with 275 patients aged < 65 years. Perioperative complications and long-term outcomes were compared between the two groups.Results: After propensity score matching, the two groups had similar baseline clinical characteristics and distribution of propensity scores. The mean age was 70.22 years in geriatric patients and 42.02 in younger patients. Technical failure occurred in one geriatric and one non-geriatric patients (p = 0.485). The procedural time in geriatric patients was similar to younger patients [50 (interquartile range (IQR) 36-76) vs. 50 (IQR 36-70) min, p = 0.398]. There were also no significant differences in major perioperative adverse events (2.88% vs. 2.18%, p = 0.663) and hospitalization length (median 3 vs. 3 days, p = 0.488). During a median follow-up period of 41 months (IQR 26-60), mean decrease in Eckardt score and pressure of the LES were 6.63 and 11.9 mmHg in geriatric patients, which were similar to the change in non-geriatric patients (6.49 and 11.6 mmHg, p = 0.652 and 0.872, respectively). Clinical reflux occurred in 23.53% geriatric patients and 21.59% non-geriatric patients (p = 0.724). 5-year success rate of 92.94% was achieved in geriatric patients and 92.61% in younger patients (log-rank p = 0.737).Conclusions: POEM is a safe and reliable treatment in geriatric achalasia patients with confirmed short-term and long-term efficacy compared with those in non-geriatric patients. [ABSTRACT FROM AUTHOR]

The gut microbiota plays a critical role in the appropriate development and maintenance of the enteric nervous system (ENS). Esophageal achalasia (EA) is a rare motility disorder characterized by the selective degeneration of inhibitory neurons in the esophageal myenteric plexus. This study aimed to evaluate the composition of the esophageal microbiota in achalasia and explore the potential microbial mechanisms involved in its pathogenesis. The lower esophageal mucosal microbiota was analyzed in patients with achalasia and control participants using 16 S rRNA sequencing. The association between the esophageal microbiota and achalasia was validated by inducing esophageal dysbiosis in C57BL/10 J and C57BL/10ScNJ (TLR4KO) mice via chronic exposure to ampicillin sodium in their drinking water. The esophageal microbiota in EA patients had lower diversity and a predominance of Gram-negative bacteria (Type II microbiota) compared to that in the healthy controls. Additionally, the relative abundance of Rhodobacter decreased significantly in patients with achalasia, which correlated with an enrichment of lipopolysaccharide (LPS) biosynthesis based on the COG database. Antibiotic-treated mice showed an esophageal microbiota characterized by increased abundance of Gram-negative bacteria (Type II microbiome), decreased abundance of Rhodobacter, and enriched LPS biosynthesis. Compared to the control and TLR4KO mice, the antibiotic-treated wild-type mice had higher LES resting pressure, increased LES contraction rate after carbachol stimulation, and decreased relaxation response to L -arginine. Moreover, the number of myenteric neurons decreased, while the number of lamina propria macrophages (LpMs) increased after antibiotic exposure. Furthermore, the TLR4-MYD88-NF-κB pathway was up-regulated, and the production of TNF-α, IL-1β, and IL-6 increased in the antibiotic-treated mice. Patients with achalasia exhibit esophageal dysbiosis, which may induce aberrant esophageal motility. [ABSTRACT FROM AUTHOR]

Abstract: A multi-center population-based study in Shanghai, China was performed to explore the implications for the management of pancreatic cancer by comparing diagnosis and survival rates. Novel imaging modalities including MRI (13.9%), PET/CT (1.8%), and EUS (5.6%) were not widely used in our population. Only 39.7% of cases were histologically verified (surgery with histologic diagnosis 31.0%, cytological diagnosis 8.7%, surgery without histologic diagnosis 12.1%, and clinical diagnosis 48.2%). Overall, 30.0% of patients underwent curative-intent operation, and only 9.8% of patients received comprehensive treatment. The prognosis of pancreatic cancer patients was significantly better for patients who were treated in high-volume centers than in low-volume centers. We propose that more effort should be put on novel diagnostic modalities, histological confirmation, and comprehensive treatment in China. Multidisciplinary teams specialized in pancreatic cancer therapy in high-volume centers are urgently needed. [Copyright &y& Elsevier]