Evaluation of MMP-12 expression in chronic rhinosinusitis with nasal polyposis

Background: The purpose of this study was to evaluate the expression of MMP-12 in patients with chronic rhinosinusitis with polyps (CRSwNP). Methodology: Tissue samples from 37 patients with CRSwNP undergoing functional endoscopic sinus surgery and healthy mucosa specimens from 12 healthy controls were obtained intraoperatively. The mRNA and protein expression levels of MMP-12 were quantified by real-time polymerase chain reaction and Western blotting, respectively. Results: mRNA levels of MMP-12 were significantly elevated in the CRSwNP tissue samples compared to those in control ones. The protein levels of MMP-12 showed a trend of increasing but with no statistical significance. Conclusions: Elevation of MMP-12 in patients with CRSwNP suggests its potential implication in the pathogenesis of the disease. The difference in the expression profile observed between mRNA and protein levels could be due to post-translational gene expression regulation. Our findings provide evidence that MMP-12 along with other MMPs may serve as a biomarker and therapeutic target in the management of the disease.

Higher Proportions of a Healthy Gastric Mucosa in Healthy Japanese Adults with Later Birth Year: Analysis of 41,957 Participants

Purpose: In Japan, most gastric cancers are associated with gastric mucosal atrophy caused by chronic infection with Helicobacter pylori (H. pylori). To recognize the condition of the gastric mucosa and to determe the infection status of H. pylori are important for predicting the individual risk of gastric cancer. The present study aimed to determine the proportion of Japanese adults with a healthy gastric mucosa (without H. pylori infection) among 12 birth-year groups encompassing 1935 to 1990.Methods: The gastric mucosa was classified as healthy or having gastritis based on routine double-contrast upper gastrointestinal barium X-ray radiopgraphy examination (UGI-XR). The participants were 41,957 healthy Japanese adults. Serum or urine H. pylori antibody levels were also assessed.Results: In total, 25,424 participants had a healthy mucosa without a history of H. pylori eradication. The proportions of participants with a healthy mucosa by birth year were 19.8% (57/288), 27.1% (306/1,128), 32.4% (569/1,756), 37.6% (1,808/4,811), 49.2% (3,207/6,522), 60.1% (3,966/6,550), 71.2% (5,224/7,342), 77.2% (5,114/6,624), 80.6% (3,342/4,149), 85.0% (1,404/1,652), 85.3% (302/354), and 94.7% (125/132) in 1935, 1940, 1945, 1950, 1955, 1960, 1965, 1970, 1975, 1980, 1985, and after 1990, respectively (p for trend < 0.01). All participants with a healthy mucosa showed negative results in H. pylori antibody tests.Conclusion: The proportion of participants with a normal gastric mucosa increased linearly with birth years. Prevalence of a morphologically healthy gastric mucosa may have been increasing, in parallel with prevalence of H. pylori infection has been decreasing.

Oral ulceration and vesiculobullous conditions in the paediatric patient

Deviations from the normal appearance of pale, pink and healthy mucosa require close monitoring or intervention and may be a sign of an underlying systemic disorder. Therefore, it is important that there is timely identification of abnormalities, appropriate management in primary care and onward referral for investigation to specialist services when required. Oral ulceration is the most common soft tissue abnormality in children, with recurrent aphthous stomatitis being the most common type of ulceration. This article discusses the various causes of oral ulceration in addition to vesiculobullous conditions, which may affect the paediatric patient. CPD/Clinical Relevance: It is important that GDPs are aware of the range of causes of ulcers and blisters presenting in children and are aware of when to refer.

Revisiting colorectal cancer tumorigenesis with spatially-resolved gene expression profiling

Early detection and treatment are paramount to the clinical outcome of patients with colorectal cancer (CRC). Deciphering the dynamic interactions that occur between epithelial cells and stromal cells during tumorigenesis requires in-depth analyses of early-stage CRC lesions in spatial context. Here we employed spatially-resolved gene expression profiling to dissect molecular processes that associate with malignant transformation in CRC. We provide the transcriptional landscapes of colorectal cancer tumorigenesis from healthy mucosa, through different degrees of dysplasia, to cancer. The complementary examination of epithelial and stromal fractions allowed us to define whether specific oncogenic processes involved cancer cells, stromal cells, or the tumor microenvironment as a whole. We identified several genes that were consistently deregulated during CRC onset that could serve as clinical biomarkers for early-stage CRC. Furthermore, we uncovered an essential role for the innate immune system during CRC tumorigenesis.

Integrative genomics analysis of nasal intestinal-type adenocarcinomas demonstrates the major role of CACNA1C and paves the way for a simple diagnostic tool in male woodworkers

Background Nasal intestinal-type adenocarcinomas (ITAC) are strongly related to chronic wood dust exposure: The intestinal phenotype relies on CDX2 overexpression but underlying molecular mechanisms remain unknown. Our objectives were to investigate transcriptomic and methylation differences between healthy non-exposed and tumor olfactory cleft mucosae and to compare transcriptomic profiles between non-exposed, wood dust-exposed and ITAC mucosa cells. Methods We conducted a prospective monocentric study (NCT0281823) including 16 woodworkers with ITAC, 16 healthy exposed woodworkers and 13 healthy, non-exposed, controls. We compared tumor samples with healthy non-exposed samples, both in transcriptome and in methylome analyses. We also investigated wood dust-induced transcriptome modifications of exposed (without tumor) male woodworkers’ samples and of contralateral sides of woodworkers with tumors. We conducted in parallel transcriptome and methylome analysis, and then, the transcriptome analysis was focused on the genes highlighted in methylome analysis. We replicated our results on dataset GSE17433. Results Several clusters of genes enabled the distinction between healthy and ITAC samples. Transcriptomic and IHC analysis confirmed a constant overexpression of CDX2 in ITAC samples, without any specific DNA methylation profile regarding the CDX2 locus. ITAC woodworkers also exhibited a specific transcriptomic profile in their contralateral (non-tumor) olfactory cleft, different from that of other exposed woodworkers, suggesting that they had a different exposure or a different susceptibility. Two top-loci (CACNA1C/CACNA1C-AS1 and SLC26A10) were identified with a hemimethylated profile, but only CACNA1C appeared to be overexpressed both in transcriptomic analysis and in immunohistochemistry. Conclusions Several clusters of genes enable the distinction between healthy mucosa and ITAC samples even in contralateral nasal fossa thus paving the way for a simple diagnostic tool for ITAC in male woodworkers. CACNA1C might be considered as a master gene of ITAC and should be further investigated. Trial registration: NIH ClinicalTrials, NCT0281823, registered May 23d 2016, https://www.clinicaltrials.gov/NCT0281823.

Motiro: a unified automatic framework for statistical analysis of probe-based confocal laser endomicroscopy videos of colorectal mucosa

Probe-based Confocal Laser Endomicrocopy (pCLE) enables imaging the colorectal mucosa for screening and surveillance of cancer. Analyzing acquired videos relies on subjectivity of the endomicroscopists. Quantitative criteria are needed to enhance the diagnostics obtained using pCLE. We present Motiro, an automatic framework to extract features of the colorectal mucosa imaged by pCLE. Morphometric features of the crypts of the healthy colorectal mucosa are analysed and their variability quantified using the Shannon entropy. Hellinger distance compares the statistics of a morphometric parameter in multiple mucosas (or mucosas&apos; regions). Quantification of variability of the healthy mucosa is a prerequisite for pCLE-based early diagnostics of colorectal cancer.

Immunohistochemical evaluation of survivin in oral lichen planus and oral squamous cell carcinoma - a retrospective study

Introduction. Oral cancer is a multistep process involving enhanced activation of proto-oncogenes. Survivin (anti-apoptotic protein) is one of such proto-oncogenes that contribute to the carcinogenesis by deregulating cell proliferation. Expression of these proteins in cancerous and pre-cancerous lesions helps a better understanding of the etiology, treatment and prognosis. Aim. To evaluate qualitative and quantitative expression of survivin in healthy mucosa, oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC). Methods. A total of 70 cases of formalin fixed paraffin embedded blocks, of which 20 healthy mucosa, 20 OSCC and 30 OLP were included in the study and stained immunohistochemically using antibodies against survivin monoclonal antibody. 4μm sections were stained immunohistochemically, both nuclear and cytoplasmic staining was considered as positive for survivin. Positive and negative stained cells were counted with the help of Olympus BX51 rarefaction microscope and were analyzed quantitatively using image analysis pro plus software. Representative fields were randomly selected at 40X high power magnification. Values obtained were evaluated and tabulated for statistical analysis. Results. There was a statistically significant relation between the expressions of survivin among healthy mucosa, OLP, OSCC with a p value of 0.001. Conclusion. Presence of survivin expression in healthy mucosa, OLP and OSCC, which is an inhibitor of apoptosis protein, can be identified as a useful diagnostic tool for the identification of precancerous lesions and conditions which are at higher risk for progression into invasive carcinoma.

Discrimination of Cancer Stem Cell Markers ALDH1A1, BCL11B, BMI-1, and CD44 in Different Tissues of HNSCC Patients

Cancer stem cells (CSCs) are accountable for the progress of head and neck squamous cell carcinoma (HNSCC). This exploratory study evaluated the expression of molecular CSC markers in different tissues of HNSCC patients. Tissue specimens of primary tumor, lymph node metastases and macroscopically healthy mucosa of 12 consecutive HNSCC patients, that were treated with surgery and adjuvant radio(chemo)therapy upon indication, were collected. Samples were assessed for the expression of p16 as a surrogate for HPV-related disease and different molecular stem cell markers (ALDH1A1, BCL11B, BMI-1, and CD44). In the cohort, seven patients had HPV-related HNSCC; six thereof were oropharyngeal squamous cell carcinoma. While expression of BMI-1 and BCL11B was significantly lower in healthy mucosa than both tumor and lymph node metastasis, there were no differences between tumor and lymph node metastasis. In the HPV-positive sub-cohort, these differences remained significant for BMI-1. However, no significant differences in these three tissues were found for ALDH1A1 and CD44. In conclusion, this exploratory study shows that CSC markers BMI-1 and BCL11B discriminate between healthy and cancerous tissue, whereas ALDH1A1 and CD44 were expressed to a comparable extent in healthy mucosa and cancerous tissues.

Impact of intraepithelial capillary loops and atypical vessels in confocal laser endomicroscopy for the diagnosis of laryngeal and hypopharyngeal squamous cell carcinoma

Purpose Confocal laser endomicroscopy (CLE) allows surface imaging of the laryngeal and pharyngeal mucosa in vivo at a thousand-fold magnification. This study aims to compare irregular blood vessels and intraepithelial capillary loops in healthy mucosa and squamous cell carcinoma (SCC) via CLE. Materials and methods We included ten patients with confirmed SCC and planned total laryngectomy in this study between March 2020 and February 2021. CLE images of these patients were collected and compared with the corresponding histology in hematoxylin and eosin staining. We analyzed the characteristic endomicroscopic patterns of blood vessels and intraepithelial capillary loops for the diagnosis of SCC. Results In a total of 54 sequences, we identified 243 blood vessels which were analyzed regarding structure, diameter, and Fluorescein leakage, confirming that irregular, corkscrew-like vessels (24.4% vs. 1.3%; P < .001), dilated intraepithelial capillary loops (90.8% vs. 28.7%; P < .001), and increased capillary leakage (40.7% vs. 2.5%; P < .001), are significantly more frequently detected in SCC compared to the healthy epithelium. We defined a vessel diameter of 30 μm in capillary loops as a cut-off value, obtaining a sensitivity, specificity, PPV, and NPV and accuracy of 90.6%, 71.3%, 57.4%, 94.7%, and 77.1%, respectively, for the detection of malignancy based solely on capillary architecture. Conclusion Capillaries within malignant lesions are fundamentally different from those in healthy mucosa regions. The capillary architecture is a significant feature aiding the identification of malignant mucosa areas during in-vivo, real-time CLE examination.

Precision silver nitrate cautery of the posterior nasal cavity

Background This technical note describes a novel method of cauterising the posterior nasal cavity through the use of a plastic straw and silver nitrate. Objective This technique aims to prevent unwanted damage to surrounding nasal mucosa. Methods Once the nasal cavity has been prepared for cauterisation, the silver nitrate stick is navigated to the bleeding point covered by the plastic straw. The silver nitrate stick is then advanced onto the bleeding point allowing precise cauterisation of the nasal mucosa, without effecting surrounding healthy mucosa.