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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: 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]

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

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]

Primary mediastinal cysts are infrequent lesions derived from a variety of mediastinal organs or structures. Complete surgical resection is the treatment of choice even in asymptomatic patients to prevent severe adverse events (AEs) and to establish the diagnosis. Transesophageal endoscopic resection of benign mediastinal tumors has been proven feasible. The aim of this study was to evaluate the feasibility, safety, and efficacy of transesophageal endoscopic surgery for mediastinal cysts. From January 2016 to May 2021, patients with mediastinal cysts who underwent transesophageal endoscopic resection were retrospectively included. Clinicopathologic characteristics, procedure-related parameters, AEs, and follow-up outcomes were analyzed. Ten patients with mediastinal cysts were included in this study. The mean cyst size was 3.3 ± 1.3 cm. Histopathology revealed 3 bronchogenic cysts (30.0%), 4 esophageal duplication cysts (40.0%), 2 gastroenteric cysts (20.0%), and 1 lymphatic cyst (10.0%). All procedures were performed uneventfully without conversion to traditional surgery. En-bloc resection was achieved in 6 patients (60.0%). Aggressive resection was avoided to prevent damage to the surrounding vital organs. Mean resection time and suture time were 58.0 ± 36.4 minutes and 5.4 ± 1.0 minutes, respectively. No major pneumothorax, bleeding, mucosal injury, or fistula occurred. One patient had a transient febrile episode (>38.5°C). Mean postoperative hospital stay was 2.7 ±.9 days. No residual or recurrent lesions were observed in any patient during a mean follow-up period of 29.8 ± 19.5 months. Transesophageal endoscopic surgery appears to be a feasible, safe, effective, and much less invasive approach for mediastinal cyst resection. Larger prospective studies are required to fully assess the efficacy and safety of this novel technique. [ABSTRACT FROM AUTHOR]

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: 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]