Relationship between plasma cyclin-dependent kinase 5 levels and local immunoglobulin levels in patients with nasal polyps

Nasal polyps are the most common benign nasal tumors that can lead to nasal obstruction and other annoying problems for the patient. Several hypotheses have been proposed as the basic mechanism of nasal polyps. In order to investigate one of the possible causes that can be a disorder in the regulation of systemic immune responses, the present study was designed to investigate the relationship between plasma cyclin-dependent kinase 5 (CDK5) levels and local immunoglobulin levels in patients with nasal polyps. A cross-section study was used to evaluate concentrations of local immunoglobulin levels (IgE, IgM, IgA, and IgG) on blood and polyp specimens from 60 patients with nasal polyps, and 60 control groups. Western Blot Analysis was done for CDK5 in plasma cells. IgA, IgG and IgE concentrations were significantly higher in polyp tissue specimens, but not in blood, of nasal polyp patients compared to the control group. Furthermore, plasma CDK5 levels were significantly higher in nasal polyp tissue compared with control. The difference in IgA, IgE and IgG expression between nasal polyp tissue and blood, supported by increased numbers of plasma cells, suggests a local production of these local immunoglobulins in nasal polyps in response to chronic antigens. Among local immunoglobulins, only there was a significant correlation between CDK5 with IgG (positive correlation) and IgE (negative correlation). The exact explanation for the relationship between plasma CDK5 and local immunoglobulins in nasal polyps needs further studies.

GASTRIN IN SERUM AND MORPHOLOGICAL STATE OF GASTRIN-SECRETING CELLS IN PATIENTS WITH GASTRIC POLYPOSIS

Objective. Numerous studies regarding gastric hormones and their regulation have been performed until now. However, the effect of the hormones on the formation and malignisation of gastric polyps still remains not clear. Our aim was to identify the relation between the level of gastrin in the blood, gastric mucosa, polyp tissue, gastric juice and pathogenesis of gastric polyposis. Materials and methods. A thorough investigation of gastrointestinal hormones in serum and gastric juice, in polyp’s tissue and mucosa, gastrin-secreting cells and proteolytic activity of gastric juice was carried out in 40 patients with gastric polyps. These patients were divided into groups, depending on the location, number, and malignancy of the polyps. As a control group, 10 healthy individuals were used to determine the normal values of the studied indicators. Results: A significant increase (more than two times) in the gastrinemia level before the surgery was noted in patients with polyp recurrence, and gastrin level increased to more significant digits of 227.0+37.4 pg/ml (p<0.05) in one year after polypectomy. Conclusion. Gastrin is apparently involved in the process of polyp formation since polyp’s growth is accompanied by elevation of serum gastrin. This is confirmed by a response of gastrin in the blood to a test meal in individuals with different duration of the disease: a marked increase in gastrinemia appears in patients suffering from gastric polyposis for more than three years. Therefore, evaluation of gastrin level in the patients’ blood can be used to predict a recurrence potential of polyps. This is evidenced by more pronounced hypergastrinemia before polypectomy in patients who had a further recurrence of the disease within one year after the surgery

Efficacy and safety of cap-assisted endoscopic mucosal resection for treatment of nonlifting colorectal polyps

Background Suboptimal lifting increases complexity of endoscopic mucosal resection (EMR) for benign colorectal polyps. Cap-assisted EMR (EMR-C) may allow fibrotic polyp tissue to be captured in the snare. This study evaluated the efficacy and safety of EMR-C for benign nonlifting colorectal polyps. Methods This was a multicenter study, which prospectively registered all EMR-C procedures (2016–2018) for presumed benign nonlifting colorectal polyps. Results 70 nonlifting polyps with a median size of 25 mm (interquartile range [IQR] 15–40) were treated with EMR-C. Complete polyp removal was achieved in 68 (97.1 %), including 47 (67.1 %) with EMR-C alone. Overall, 66 polyps showed benign histology, and endoscopic follow-up after a median of 6 months (IQR 6–10) showed recurrence in 19.7 %. First (n = 10) and second (n = 2) benign recurrences were all treated endoscopically. Deep mural injury type III–V occurred in 7.4 % and was treated successfully with clips. Conclusion EMR-C may be an alternative therapeutic option for removal of benign nonlifting polyp tissue. Although recurrence still occurs, repeat endoscopic therapy usually leads to complete polyp clearance.

A randomized, double-blind placebo-controlled study to investigate the bacteriophages in patients with сhronic rhinosinusitis with nasal polyps

Background A randomized, double-blind placebo-controlled study investigated the use of bacteriophages in the treatment of chronic rhinosinusitis with nasal polyps. Materials and Methods 40 adult patients with сhronic rhinosinusitis with nasal polyps were examined. All patients underwent functional endoscopic sinus surgery. After the surgery, 20 patients got the intranasal gel with a bacteriophages mixture (Otofag, Micromir, Russia) twice a day for ten weeks, and 20 patients got a placebo. Results On the 10th day, IL-1β secretion diminished (63 mg/ml versus 440 mg/ml in control). There was a decrease in the total number of microorganisms and Enterobacteriaceae (5.7 x 106 CFU/ml versus 1.2 x 109 CFU/ml in control), and the absence of Streptococci (versus 2.1 x 109 CFU/ml in control) on the 30th day of the treatment in the group with the bacteriophages. On the 10th day, a decrease in the activity of secretory IL-1β and IL-8 strongly and very strongly correlated with a total number of microorganisms (r = 0.7; r = 0.9 respectively), as well as secretory IL-8 with Enterobacteriaceae (r = 0.72) and Staphylococci (r = 0.65) in the active group treated with the bacteriophages. On the 30th day, the decrease in serum IL-1β significantly correlated with the total number of microorganisms (r = 0.80) and enterobacteria (r = 0.90) in the active group. Conclusions The administration of bacteriophages restored the balance of microorganisms in the nasal cavity and decreased the inflammatory response in chronic rhinosinusitis with nasal polyps. These changes, such as an inflammation dampening, could theoretically reduce the recurrent growth of polyp tissue in the future.

The influence of nasal microbiome diversity and inflammatory patterns on the prognosis of nasal polyps

To understand the inflammatory microenvironment and microbiome factors for prognosis of chronic rhinosinusitis with polyps (CRSwNP), we explored the difference in characteristics of the microbiome of the nasal sinuses and inflammatory cytokines between recurrent and non-recurrent groups. We collected nasal secretions and polyp tissue from 77 CRSwNP patients. Then, we extracted microbial DNA from cotton swabs, performed high-throughput sequencing based on 16S rRNA to detect bacterial community composition, and analyzed cytokines such as IL-5, IL-8, IL-17a, IL-17e, IL-18, IL-27 and INF-gamma from polyp tissue using Luminex. The eosinophil and neutrophil cells in the peripheral blood and polyp tissue were counted. Postoperative follow-up of patients with CRSwNP for 1 year was conducted to record the recurrence of nasal polyps and analyze the correlation between the recurrence of nasal polyps and the characteristics of inflammatory cytokines, inflammatory cell count and nasal microbial diversity. After 1 year of follow-up, there were 12 recurrent patients, including 5 males and 7 females. Postoperative recurrence of nasal polyps was not significantly correlated with age, sex, asthma, allergic rhinitis or other allergic diseases in CRSwNP patients. In terms of the total nasal symptom score, the recurrent group was significantly higher than the non-recurrent group. In nasal polyp tissues, eosinophils (40.83/HP) and neutrophils (30.83/HP) in patients with CRSwNP in the recurrent group were significantly higher than those in the non-recurrent group (13.72/HP), and neutrophils (18.5/HP) were also significantly higher in the recurrent group than the non-recurrent group. The expression levels of IFN-, IL-17A, IL-17E and IL-18 were significantly higher in the recurrent group than in the non-recurrent group, and the positive rates were not different. In Southwest China, Enterobacteria and anaerobic bacteria may be correlated with the inflammatory pattern expression of nasal polyps. The neutrophil-mediated inflammatory response plays an important role in patients with CRSwNP in Southwest China and is correlated with nasal polyp recurrence. Recurrence of nasal polyps after endoscopic sinus surgery may be potentially associated with a reduced abundance of protective microorganisms and an increased number of pathogenic microorganisms.

Pathogenetic molecular mechanisms of chronic rhinosinusitis with nasal polyps associated with asthma

The combination of bronchial asthma (BA) and chronic rhinosinusitis with nasal polyps (CRSwNP) is currently considered a separate phenotype wit1 dysregulation of pro- and anti-inflammatory cytokines as one of t1e leading causes of inflammation. The aim of this study was to investigate the local and systemic inflammatory process in patients with BA associated with CRSwNP. Methods. The study enrolled 96 volunteers divided into 4 groups: the 1st was healthy control (Normal); the 2nd had allergic BA associated with CRSwNP; the 3rd had nonallergic BA associated with CRSwNP; the 4th had CRSwNP without BA. All participants of the study underwent clinical, laboratory, instrumental, and histological examinations. The expression of il-1β, il-4, il-,5 il-6, il-13, il-37, il-17f, ifn-γ, tnf-α and tgf-β genes was assessed in the peripheral blood mononuclear cells - PBMC and in the polyp tissue using RT-PCR. We also estimated the expression of tslp, il-25 and il-33 in the polyp tissue and expression of GATA3 and RORgt transcription factors in PBMC. Results. The pathogenesis of BA associated with CRSwNP is characterized by the dys-regulation of the local pro- and anti-inflammatory cytokines of the Th1-, Th2-, Th17- immune response. Moreover, the high expression of il-37 gene in patients with BA associated with CRSwNP, and especially in patients with not-allergic BA associated with CRSwNP, probably indicates the «inclusion» of the compensatory mechanism. In addition, BA associated with CRSwNP is characterized by severe course of both diseases. A nonallergic BA associated with CRSwNP is characterized by more pronounced eosinophilic inflammation, which is an unfavorable prognostic factor. Conclusion. Thus, a comparison of the levels of local and systemic cytokine expression in patients with BA associated with CRSwNP led to the conclusion that CRSwNP affects the local immunity more than systemic immunity. However, the latter is affected to some extent in the long-term as well.

Safety and efficacy of band ligation and auto-amputation as adjunct to EMR of colonic large laterally spreading tumors, and polyps not amenable to routine polypectomy

Introduction: The safety and efficacy of colonic band ligation and auto-amputation (1) as adjunct to endoscopic mucosal resection of large laterally spreading tumors and (2) for polyps not amenable to routine polypectomy due to polyp burden or difficult location remain unknown. Methods: An institutional review board–approved retrospective single-institution study was undertaken of patients undergoing colonic band ligation and auto-amputation from 2014 to date. Patients with indications of ‘endoscopic mucosal resection for laterally spreading tumors’ and ‘polyp not amenable to snare polypectomy’ were included in the study. Data were collected on patient demographics, colonoscopy details (laterally spreading tumors/polyp characteristics, therapies applied, complications), pathology results, and follow-up (polyp eradication based on endoscopic appearance and biopsy results). Results: Patients undergoing endoscopic mucosal resection for laterally spreading tumors: Thirty-two patients (31 males, aged 68 ± 9.17 years) underwent endoscopic mucosal resection-band ligation and auto-amputation of 34 laterally spreading tumors (40 ± 10.9 mm). A median of 2 ± 1.09 bands were placed. Follow-up colonoscopy and biopsy results confirmed complete eradication in 21 laterally spreading tumors (70%). Nine (30%) laterally spreading tumors required additional endoscopic therapy to achieve complete eradication. Four (13%) patients underwent surgery for cancer, and two of them had resection specimens negative for cancer or residual adenoma. One patient suffered post-polypectomy syndrome. Patients undergoing band ligation and auto-amputation for polyps not amenable to snare polypectomy: Seven patients underwent band ligation and auto-amputation due to serrated polyposis syndrome (one patient) and innumerable polyps, or polyps in difficult locations (extension into diverticula: two patients; terminal ileum: two patients; appendiceal orifice: one patient; anal canal: one patient). The patient with serrated polyposis syndrome achieved dramatic decrease in polyp burden, but not eradication. Follow-up in five of the six remaining patients documented polyp eradication. The patient with serrated polyposis syndrome suffered from rectal pain and tenesmus following placement of 18 bands. Conclusions: Band ligation and auto-amputation in the colon may be a safe and effective adjunct to current endoscopic mucosal resection and polypectomy methods and warrants further study. Plain Language Summary Colonoscopy with rubber band placement to aid in complete removal of large polyps and polyps in technically challenging locations Colonoscopy is a commonly performed procedure for the early detection of colon and rectal cancer, and prevention through polyp removal.During colonoscopy, sometimes situations are encountered making polyp removal difficult. These can include the presence of larger polyps or the location of a polyp in an area that makes removal technically challenging or high risk.A particularly challenging situation arises when after extensive effort there is still polyp tissue remaining that cannot be removed using routine techniques. We are interested in exploring a technique which involves the placement of a rubber band after sucking a small area of the colon lining into a cap loaded onto the tip of the colonoscope. With time the rubber band strangulates the tissue and falls off along with captured tissue and passes out of the colon naturally.To assess the effectives of this technique we studied patients that have undergone this procedure at our GI unit. We identified 32 patients with 34 large polyps between 4cm to 6cm that we placed rubber bands on polyp tissue after we were unable to completely remove the polyp. On their follow up colonoscopy, complete polyp removal was successful in 21 polyps. We were also able to achieve complete polyp removal in 9 of the remaining large polyps after additional treatment. Four patients underwent surgery because cancer was found in analysis of polyp tissue.In 5 of 6 patients with polyps in difficult locations (e.g. partly within the lumen of the appendix), placement of a rubber band led to complete removal of polyp tissue.Two patients in our study population had mild adverse events that were managed with simple measures.We believe our results show promise for our described technique and this technique should be tested in larger studies.

Black Lentil Water Extract Inhibited Inflammatory Cytokines in a Colitis-Associated Colon Carcinogenesis Model

Objectives The objective was to compare the impact of black lentil water extract (BL) and delphinidin 3-O-(2-O-β-d-glucopyranosyl-α-l-arabinopyranoside) (D3G)-rich lentil extract on tumor development and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) model. Methods C57BL/6 mice were randomly separated into four groups: healthy control (n = 6), AOM/DSS control (n = 14), AOM/DSS + BL (600 mg/kg body weight, n = 12), and AOM/DSS + D3G (41 mg/kg body weight, equivalent to D3G concentration in BL, n = 12). Mice were given treatments for 11 weeks using a voluntary oral jelly administration. Fecal samples were collected three times: after one week of treatments prior to the first AOM injection, after the first (of three) DSS cycle, and at the time of euthanasia. Secretory leukoprotease inhibitor (SLPI) expression was evaluated by qPCR, calprotectin by ELISA and fecal metabolite profiles by Agilent GC-MS system. Results AOM/DSS + BL presented a lower (p &lt; 0.05) disease activity index, throughout and at the end (2.4) compared to AOM/DSS control (6.3). AOM/DSS + BL mice had an average of 7.8 neoplasms/mouse vs. 12.8 for the AOM/DSS (p &lt; 0.05). Pro-inflammatory cytokines were downregulated in the colon mucosa in AOM/DSS + BL and AOM/DSS + D3G: interleukin 1β (−77.5%, −70.7%), interleukin 6 (−44.4%, −44.9%), respectively, compared to the AOM/DSS control. In non-polyp tissue, SLPI expression was higher compared to the healthy (1.0) and AOM/DSS control (5.0), AOM/DSS + BL (14.6) and AOM/DSS + D3G (10.3) groups. In polyp tissue, SLPI expression was highest in the AOM/DSS + BL group (24.3) versus the AOM/DSS control (9.3) and AOM/DSS + D3G (10.0). At the time of euthanasia, fecal calprotectin concentration was low for the healthy control (1.6 µg/g), AOM/DSS + BL (1.8 µg/g), and AOM/DSS + D3G (2.4 µg/g), but increased dramatically for the AOM/DSS control (4.1 µg/g) (p &lt; 0.05). Gallic and protocatechuic acids and epicatechin were found in feces; the concentration of amino acids such as alanine, isoleucine, and leucine was lower, and unsaturated fatty acids were higher for AOM/DSS + BL and AOM/DSS + D3G versus the AOM/DSS control. Conclusions BL and D3G-rich extracts showed anti-inflammatory effects and modified fecal metabolites while BL additionally prevented growth of neoplasia. Funding Sources US Department of Agriculture Hatch 1,014,457.