Search Results (243)

Endometriosis is a chronic, estrogen-dependent disorder associated with the presence of endometrial cells mainly in the pelvic cavity, causing systemic immune inflammation, infertility, epigenetic dysregulation of differential DNA methylation, coelomic metaplasia, and pain. It affects approximately 10–12% of women. Despite decades of research, full pathophysiology, a diagnostic roadmap, and clinical management strategies for endometriosis are not yet fully elucidated. Cell-free DNA (Cf-DNA) in the peripheral blood of diseased and healthy individuals was discovered in the 1950s. Quantifying peripheral Cf-DNA and the specific differential methylation of a group of genes have been proposed as potential non-invasive diagnostic biomarkers for somatic and constitutional genetics and for various other pathological disorders. In this study, we investigated the Cf-DNA levels of 78 young women, 38 of whom had endometriosis confirmed via laparoscopy and 40 of whom were healthy. We found a significant difference between the two groups when Cf-DNA was quantified, with 3.9 times more Cf-DNA in the serum of women with endometriosis. We also identified nine target genes potentially involved in the pathogenesis of endometriosis, with a different methylation profile between the two groups. Our data suggest that the combination of cell-free DNA quantification and the assessment of the epigenetic signature of differential methylation of nine genes can be proposed as a non-invasive predictive and diagnostic test for endometriosis. Full article

Studies on the gastric microbiota associated with gastric precancerous lesions remain limited. This study aimed to profile the gastric mucosal microbiota in patients with Helicobacter pylori-negative precancerous lesions. Gastric mucosal samples were obtained from 67 H. pylori-negative patients, including those with chronic gastritis (CG), intestinal metaplasia (IM), and dysplasia. The V3–V4 region of the 16S rRNA gene was sequenced and analyzed. No significant difference was observed in the alpha or beta diversity of the gastric microbiota among the groups. However, a taxonomic analysis revealed a significant enrichment of Lautropia mirabilis and the depletion of Limosilactobacillus reuteri, Solobacxterium moorei, Haemophilus haemolyticus, and Duncaniella dubosii in the IM and dysplasia groups compared to those in the CG group. Prevotella jejuni and the genus Parvimonas were enriched in the IM group. A predictive functional analysis revealed enrichment of the ornithine degradation pathway in the IM and dysplasia groups, suggesting its role in persistent gastric mucosal inflammation associated with gastric precancerous lesions. The gastric microbiota associated with H. pylori-negative gastric precancerous lesions showed an increased abundance of oral microbes linked to gastric cancer and a reduction in anti-inflammatory bacteria. These alterations might contribute to chronic gastric mucosal inflammation, promoting carcinogenesis in the absence of H. pylori infection. Full article

Background/Objectives: Gastric intestinal metaplasia (GIM) is considered an irreversible preneoplastic precursor for gastric adenocarcinoma in adults. However, its significance in children and the long-term outcome remain poorly understood. Methods: All children diagnosed with GIM between 2000 and 2020 were identified at a large tertiary referral centre. Upon reaching adulthood (≥18 years), the patients were invited to undergo follow-up esophagogastroduodenoscopy (using narrow-band imaging additionally to high-definition white light endoscopy), with gastric biopsies obtained according to the updated Sydney protocol. Childhood and adulthood gastric biopsies were re-evaluated by two experienced gastrointestinal pathologists using Kreyberg staining. Results: Paediatric GIM was diagnosed in 178/14,409 (1.2%) esophagogastroduodenoscopies performed during the study period. Fifty adult patients with childhood GIM agreed to participate in the study. The mean age at childhood and adulthood endoscopies were 14.3 years (median 15) and 25.2 years (median 24), respectively. The mean follow-up interval was 10.5 years. All childhood GIM cases were classified as complete-type. Notably, GIM completely resolved in 41/50 of patients (82%) by the time of adulthood follow-up. No dysplasia or carcinoma was detected in any patient. Childhood Helicobacter pylori infection, similar to other evaluated host-related factors, was not significantly associated with the persistence of GIM into adulthood (11.2% vs. 29.3%, p = 0.41). Conclusions: Childhood GIM was a rare finding but demonstrated a high rate of reversibility by adulthood regardless of Helicobacter pylori status, with no cases of dysplasia or carcinoma observed during long-term follow-up. Full article

Background/Objectives: Gastric cancer (GC) incidence remains high worldwide, and the survival rate is poor. GC develops from atrophic gastritis (AG), associated with Helicobacter pylori (Hp) infection, passing through intestinal metaplasia and dysplasia steps. Since Hp eradication does not exclude GC development, further investigations are needed. New data suggest the possible role of unexplored gastric microbiota beyond Hp in the progression from AG to GC. Aimed to develop a score that could be used in clinical practice to stratify GC progression risk, here was investigate gastric microbiota in AG Hp-negative patients with or without high-grade dysplasia (HGD) or GC. Methods: Consecutive patients undergoing upper endoscopy within an endoscopic follow-up for AG were considered. The antrum and corpus biopsies were used to assess the microbiota composition along the disease progression by sequencing the 16S ribosomal RNA gene. Statistical differences between HGD/GC and AG patients were included in a multivariate analysis. Results: HGD/GC patients had a higher percentage of Bacillus in the antrum and a low abundance of Rhizobiales, Weeksellaceae and Veillonella in the corpus. These data were used to calculate a multiparametric score (Resident Gastric Microbiota Dysbiosis Test, RGM-DT) to predict the risk of progression toward HGD/GC. The performance of RGM-DT in discriminating patients with HGD/GC showed a specificity of 88.9%. Conclusions: The microbiome-based risk prediction model for GC could clarify the role of gastric microbiota as a cancer risk biomarker to be used in clinical practice. The proposed test might be used to personalize follow-up program thanks to a better cancer risk stratification. Full article

The role of microbiota in human health and disease is becoming increasingly clear as a result of modern microbiome studies in recent decades. The gastrointestinal tract is the major habitat for microbiota in the human body. This microbiota comprises several trillion microorganisms, which is equivalent to almost ten times the total number of cells of the human host. Helicobacter pylori is a known pathogen that colonizes the gastric mucosa of almost half of the world population. H. pylori is associated with several gastric diseases, including gastric cancer (GC) development. However, the impact of the gastric microbiota in the colonization, chronic infection, and pathogenesis is still not fully understood. Several studies have documented qualitative and quantitative changes in the microbiota’s composition in the presence or absence of this pathogen. Among the diverse microflora in the stomach, the Firmicutes represent the most notable. Bacteria such as Prevotella sp., Clostridium sp., Lactobacillus sp., and Veillonella sp. were frequently found in the healthy human stomach. In contrast, H.pylori is very dominant during chronic gastritis, increasing the proportion of Proteobacteria in the total microbiota to almost 80%, with decreasing relative proportions of Firmicutes. Likewise, H. pylori and Streptococcus are the most abundant bacteria during peptic ulcer disease. While the development of H. pylori-associated intestinal metaplasia is accompanied by an increase in Bacteroides, the stomachs of GC patients are dominated by Firmicutes such as Lactobacillus and Veillonella, constituting up to 40% of the total microbiota, and by Bacteroidetes such as Prevotella, whereas the numbers of H. pylori are decreasing. This review focuses on some of the consequences of changes in the gastric microbiota and the function of probiotics to modulate H. pylori infection and dysbiosis in general. Full article

Objective: We previously developed artificial intelligence (AI) diagnosis algorithms for predicting the six classes of stomach lesions. However, this required significant computational resources. The incorporation of AI into medical devices has evolved from centralized models to decentralized edge computing devices. In this study, a deep learning endoscopic image classification model was created to automatically categorize all phases of gastric carcinogenesis using an edge computing device. Design: A total of 15,910 endoscopic images were collected retrospectively and randomly assigned to train, validation, and internal-test datasets in an 8:1:1 ratio. The major outcomes were as follows: 1. lesion classification accuracy in six categories: normal/atrophy/intestinal metaplasia/dysplasia/early/advanced gastric cancer; and 2. the prospective evaluation of classification accuracy in real-world procedures. Results: The internal-test lesion-classification accuracy was 93.8% (95% confidence interval: 93.4–94.2%); precision was 88.6%, recall was 88.3%, and F1 score was 88.4%. For the prospective performance test, the established model attained an accuracy of 93.3% (91.5–95.1%). The established model’s lesion classification inference speed was 2–3 ms on GPU and 5–6 ms on CPU. The expert endoscopists reported no delays in lesion classification or any interference from the deep learning model throughout their exams. Conclusions: We established a deep learning endoscopic image classification model to automatically classify all stages of gastric carcinogenesis using an edge computing device. Full article

Background/Objectives: Since 2013, eradication therapy for Helicobacter pylori gastritis (Hp-ET) has been covered by the National Health Insurance of Japan. Recently, the risk of post-eradication gastric cancer (pE-GC) has increased. pE-GC includes cancers that develop immediately and several years after Hp-ET. Therefore, we aimed to clarify the endoscopic and histological characteristics of late types of pE-GCs. Method: One hundred patients with differentiated cancers detected after Hp-ET who underwent endoscopic submucosal dissection from 2015 to 2023 were compared. Patients were divided into two groups; the immediate group (n = 69), with cancer detected within 6 years, and the delayed group (n = 31), with cancer detected within >6 years after Hp-ET. The background mucosa and tumor mucosa were examined individually. The endoscopic findings were as follows: enlarged folds, map-like redness, intermediate zone irregularity, and the presence of a regular arrangement of collecting venules and a light blue crest (background); an irregular surface structure, an irregular vascular pattern, an irregular surface pattern, and a gastritis-like appearance (tumor). The histological findings were as follows: a low remnant rate of the fundic glands, intestinal metaplasia (IM), crypt enlargement, and neutrophil infiltration (background); mosaicism, the elongation of noncancer ducts, and an overlying non-neoplastic epithelium (tumor). Results: There was no significant difference regarding the background mucosa and tumor mucosa between the two groups. In the delayed group, the remnant rate of the fundic glands was 19.8 ± 15.6%, and IM was 87.1% (27/31). Further, 90.3% (28/31) of the patients exhibited persistent neutrophil infiltration. Conclusion: This study suggested that patients with a low remnant rate of the fundic gland and IM and persistent mucosal inflammation were at high risk for developing pE-GCs. Full article

Helicobacter pylori (H. pylori), one of the most prevalent pathogenic bacteria worldwide, is the leading cause of gastritis, gastric intestinal metaplasia, and gastric cancer. Antibiotics, the conventional treatment for eliminating H. pylori, often lead to severe bacterial resistance, gut dysbiosis, and hepatic insufficiency and fail to address the inflammatory response or gastric mucosal damage caused by H. pylori infection. In this study, based on 10-week animal experiments, two models of L. salivarius NCUH062003 for the prophylaxis and therapy of H. pylori infection in C57BL/6 mice were established; a comprehensive comparative analysis was performed to investigate the anti-H. pylori effect of probiotics, the reduction in inflammation, and repair of gastric mucosal damage. ELISA, immunohistochemistry, and pathology analyses showed that NCUH062003 decreased the expression of pro-inflammatory cytokine interleukins (IL-1β, IL-6) and myeloperoxidase (MPO) and reduced neutrophil infiltration in the gastric mucosa lamina propria. Immunofluorescence and biochemical analysis showed that NCUH062003 resisted gastric epithelial cell apoptosis, increased the level of superoxide dismutase (SOD) in gastric mucosa, and promoted the expression of tight junction protein ZO1 and Occludin. In addition, through high-throughput sequencing, in the probiotic therapy and prophylactic mode, the diversity and composition of the gut microbiota of HP-infected mice were clarified, the potential functions of the gut microbiota were analyzed, the levels of short-chain fatty acids (SCFAs) were measured, and the effects of L. salivarius NCUH062003 on the gut microbiota and its metabolites in HP-infected mice treated with amoxicillin/metronidazole were revealed. This study provides functional strain resources for the development and application of microbial agents seeking to antagonize H. pylori beyond antibiotics. Full article

In addition to chronic hrHPV anogenital infection, continuing inflammatory cervical changes are intrinsic in the development of precancerous lesions. In younger women, much of this inflammatory background parallels the progressive maturation of squamous metaplasia, often rendering treatment interventions redundant; however, patients with persistent cervical precancer, as well as those harboring invasive bacterial pathogens, might benefit from controlling the active inflammatory process by shortening the HPV natural cycle and avoiding subsequent cervical surgery. In a colposcopy population of 336 predominantly young asymptomatic individuals, we explored the impact of molecularly detected bacterial STIs on HPV DNA and APTIMA positivity rates using validated assays. In the multivariable analysis, several largely anticipated epidemiological factors were related to STI positivity. In this cohort, the HPV DNA test illustrated better performance for the prediction of STI positivity than the corresponding APTIMA test (sensitivity 52.94% vs. 33.82%), while inversely, the APTIMA test was more indicative of bacterial STI negativity than the HPV DNA test (specificity 77% vs. 60%). In addition, no significant differences between these two molecular assays were documented in terms of PPV, NPV, and overall accuracy. Despite the high Ureaplasma urealyticum and low Chlamydia trachomatis prevalence recorded in this study’s population, which is among the first assessing the co-variation of bacterial STI expression with established HPV biomarkers, the APTIMA assay did not predict concurrent bacterial STIs superiorly compared with an established HPV DNA assay. Full article

Introduction: Performing a tandem endoscopy and colonoscopy in selected individuals has advantages, such as the early detection of benign and/or precancerous foregut diseases; it is efficient, and it may allow added therapies. It may also have disadvantages, such as generating anxiety from false-positive screening, possible harm from further testing, and unproven cost-effectiveness. Aims: We aimed to examine the prevalence of foregut endoscopic and histologic abnormalities in subjects referred for screening/surveillance colonoscopy who also underwent a tandem endoscopy. We wanted to (1) assess implications for cancer detection, intervention, and surveillance of precancerous foregut abnormalities, (2) identify benign foregut lesions, and (3) generate data on the utilities of this tandem approach. Patients and Methods: A retrospective cohort study of consecutive subjects referred for screening or surveillance colonoscopy who also underwent an endoscopy. Based on national screening guidelines, responses to prompting questions, personal or family history, or other risk factors, subjects were assigned to tandem endoscopy with biopsies (modified Seattle and Sydney protocols), under one anesthesia. Results: Of the 1004 patients referred for colonoscopy, 317 (32%) underwent tandem endoscopy. There were 214 women and 103 men. There were 237 Whites, 16 Asians, 40 Blacks, and 24 Hispanics. Median age was 59 (range 19–85). At endoscopy, we identified actionable benign (45%) peptic, inflammatory, and H. pylori-related abnormalities, and premalignant findings (i.e., intestinal metaplasia, 27%, dysplasia, 2%, and cancer 0.9%), comparable to the premalignant (40.3%) and malignant (0.6%) colonoscopy yield. Conclusions: When implemented based on national screening guidelines, tandem EGD and colonoscopy combines Barrett’s esophagus and gastric cancer screening in one examination, and it has a high yield in a diverse US population. Full article

Respiratory infections caused by RNA viruses are a major contributor to respiratory disease due to their ability to cause annual epidemics with profound public health implications. Influenza A virus (IAV) infection can affect a variety of host signaling pathways that initiate tissue regeneration with hyperplastic and/or dysplastic changes in the lungs. Although these changes are involved in lung recovery after IAV infection, in some cases, they can lead to serious respiratory failure. Despite being ubiquitously observed, there are limited data on the regulation of long-term recovery from IAV infection leading to normal or dysplastic repair represented by inflammation-to-metaplasia transition in mice or humans. To address this knowledge gap, we used integrative bioinformatics analysis with further verification in vivo to elucidate the dynamic molecular changes in IAV-infected murine lung tissue and identified the core genes (Birc5, Cdca3, Plk1, Tpx2, Prc1. Rrm2, Nusap1, Spag5, Top2a, Mcm5) and transcription factors (E2F1, E2F4, NF-YA, NF-YB, NF-YC) involved in persistent lung injury and regeneration processes, which may serve as gene signatures reflecting the long-term effects of IAV proliferation on the lung. Further analysis of the identified core genes revealed their involvement not only in IAV infection but also in COVID-19 and lung neoplasm development, suggesting their potential role as biomarkers of severe lung disease and its complications represented by abnormal epithelial proliferation and oncotransformation. Full article

Crohn’s disease (CD) is a chronic inflammatory bowel condition with increasing global incidence. Diagnosing CD is challenging and requires close collaboration between clinicians and pathologists due to the lack of specific diagnostic criteria. Histologically, CD is characterized by transmural inflammation, crypt distortion, metaplasia, and granulomas, although granulomas are not always present. Schaumann bodies (SB), initially described in sarcoidosis, are rare in CD but have been reported in about 10% of cases. This case report presents a 4-year-old female with chronic hemorrhagic diarrhea, severe anemia, and elevated inflammatory markers. Endoscopic and histological evaluations suggested CD, with the presence of SB in the gastric mucosa. Further investigations ruled out sarcoidosis, confirming a diagnosis of multi-segmental, very early onset CD with atypical histological features. SB are inclusions composed of calcium carbonate crystals and conchoid bodies, typically found within giant cells. The presence of SB in the mucosa is rare, limiting their diagnostic significance in endoscopic biopsies. Differential diagnosis should exclude other granulomatous diseases such as intestinal tuberculosis and sarcoidosis. This case highlights the importance of considering SB in the diagnosis of CD, particularly in pediatric patients. Full article

Background and Objectives: Empty nose syndrome (ENS) is a debilitating condition that often results from traumatic or iatrogenic causes, such as nasal surgery. There are various conservative and surgical treatments for ENS, but their effectiveness remains uncertain. Therefore, the development of animal models that accurately mimic human ENS is essential for advancing effective treatment strategies. Materials and Methods: To investigate ENS development, turbinoplasty was performed in the nasal cavity of swine, entailing partial removal of the ventral turbinate using turbinectomy scissors followed by electrocauterization. After 56 days, samples were obtained for histological and morphological analyses. Results: A significant reduction in the volume of the ventral turbinate in the ENS model led to an expansion of the nasal cavity. Histological analysis revealed mucosal epithelial changes similar to those observed in ENS patients, including squamous cell metaplasia, goblet cell metaplasia, submucosal fibrosis, and glandular atrophy. Biomarkers related to these histopathological features were identified, and signals potentially contributing to squamous cell metaplasia were elucidated. Conclusions: The swine ENS model is anticipated to be instrumental in unraveling the pathogenesis of ENS and may also be useful for evaluating the effectiveness of various treatments for ENS. Full article

The primary pre-neoplastic lesion of the lower esophagus in the vicinity of the gastroesophageal junction (GEJ) is any Barrett’s esophageal lesions (BE), and esophageal neoplasia has increased in the US population with predispositions (Caucasian males, truncal obesity, age, and GERD). The responses to BE are endoscopic and screening cytologic programs with endoscopic ablation of various forms. The former have not been proven to be cost-effective and there are mixed results for eradication. A fresh approach is sorely needed. We prospectively followed 2229 mostly male veterans at high risk for colorectal cancer in a 27-year longitudinal long-term study, collecting data on colorectal neoplasia development and other preneoplastic lesions, including BE and spontaneous regression (SR). Another cross-sectional BE study at a similar time period investigated antigenic changes at the GEJ in both BE glandular and squamous mucosa immunohistochemistry and the role of inflammation. Ten of the prospective cohort (21.7%) experienced SR out of a total of forty-six BE patients. Significant differences between SR and stable BE were younger age (p < 0.007); lower platelet levels (p < 0.02); rectal p87 elevation in SR (p < 0.049); a reduced innate immune system (InImS) FEREFF ratio (ferritin: p87 colonic washings) (p < 0.04). Ancillary testing showed a broad range of neoplasia biomarkers. InImS markers may be susceptible to intervention using commonplace and safe medical interventions and encourage SR. Full article

Unsuccessful tendon healing leads to fibrosis and occasionally calcification. In these metaplastic drifts, the mouse AT preclinical injury model represents a robust experimental setting for studying tendon calcifications. Previously, calcium deposits were found in about 30% of tendons after 28 days post-injury. Although a neuromediated healing process has previously been documented, the expression patterns of NF200, NGF, NPY, GAL, and CGRP in mouse AT and their roles in metaplastic calcific repair remain to be explored. This study included a spatiotemporal analysis of these neuromarkers during the inflammatory phase (7 days p.i.) and the proliferative/early-remodelling phase (28 days p.i.). While the inflammatory phase is characterised by NF200 and CGRP upregulation, in the 28 days p.i., the non-calcified tendons (n = 16/24) showed overall NGF, NPY, GAL, and CGRP upregulation (compared to 7 days post-injury) and a return of NF200 expression to values similar to pre-injury. Presenting a different picture, in calcified tendons (n = 8), NF200 persisted at high levels, while NGF and NPY significantly increased, resulting in a higher NPY/CGRP ratio. Therefore, high levels of NF200 and imbalance between vasoconstrictive (NPY) and vasodilatory (CGRP) neuromarkers may be indicative of calcification. Tendon cells contributed to the synthesis of neuromarkers, suggesting that their neuro-autocrine/paracrine role is exerted by coordinating growth factors, cytokines, and neuropeptides. These findings offer insights into the neurobiological mechanisms of early tendon healing and identify new neuromarker profiles predictive of tendon healing outcomes. Full article