Squamous Cell Metaplasia Research Articles

Development of a New Swine Model Resembling Human Empty Nose Syndrome.

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.

Pseudoinvasion and squamous metaplasia/morules in colorectal adenomatous polyp: a case report and literature review

BackgroundSubmucosal pseudoinvasion and squamous metaplasia (SM) are incidental and special morphological findings in colorectal adenomas, and both can mimic invasive carcinoma. The coexistence of these two findings further increases the risk of misdiagnosis, posing a great diagnostic challenge to pathologists. From 1979 to 2022, only 8 cases have been reported, which was extremely rare. In this report, we presented a case of sigmoid colon adenoma accompanied by pseudoinvasion and SM. Additionally, relevant literature was analyzed to summarize the clinical and pathological characteristics.Case presentationA 51-year-old Chinese male patient presented with fresh blood after defecation. Electronic colonoscopy revealed multiple polyps, which were removed using a snare and subjected to high-frequency electrocoagulation resection. The largest polyp, located in the sigmoid colon, was a thick pedunculated and lobulated polyp with a maximum diameter of 2.8 cm. The surface of the polyp showed slight ruggedness and redness, and it was sent for pathological examination. Grossly, the polyp had a lobulated and slightly rough surface. Microscopically, it showed a tubulovillous adenoma with focal high-grade dysplasia and mucosal muscle hyperplasia. Glandular elements were observed in the submucosal layer, forming a well-defined lobular structure. Some of the glands displayed cystic change, and focal SM could be seen within the adenoma. SM could manifest as discrete solid cell nests of varying sizes or cribriform-morular-like structures. Immunohistochemical staining showed that SM cells were diffusely positive for cytokeratin 5/6 (CK5/6); p40, p63, and cytokeratin 20 (CK20) were negative; while caudal type homeobox 2 (CDX2) was weakly positive. β-catenin showed abnormal nuclear expression, and an extremely low Ki67 proliferation index was observed.ConclusionsCoexistence of SM and pseudoinvasion in colorectal adenomas is highly rare. It is more commonly observed in males and tends to occur in the sigmoid colon. It primarily manifests in tubulovillous adenoma and tubular adenoma, with a majority of cases exhibiting a pedicle. Histologically, it is similar to invasive lesions. The cystic dilation of the submucosal glands, hemosiderin deposition, and the presence of a lamina propria around the submucosal glands without adjacent desmoplastic reaction, suggest pseudoinvasion rather than cancer. The bland cytological morphology and Immunohistochemical markers play a crucial role in distinguishing SM from true invasive lesions.

Exploring the DNA Methylation Profile of Genes Associated with Bladder Cancer in Bladder Tissue of Patients with Neurogenic Lower Urinary Tract Dysfunction.

DNA methylation is an epigenetic process that commonly occurs in genes' promoters and results in the transcriptional silencing of genes. DNA methylation is a frequent event in bladder cancer, participating in tumor initiation and progression. Bladder cancer is a major health issue in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD), although the pathogenetic mechanisms of the disease remain unclear. In this population, bladder cancer is characterized by aggressive histopathology, advanced stage during diagnosis, and high mortality rates. To assess the DNA methylation profiles of five genes' promoters previously known to be associated with bladder cancer in bladder tissue of NLUTD patients, we conducted a prospective study recruiting NLUTD patients from the neuro-urology unit of a public teaching hospital. Cystoscopy combined with biopsy for bladder cancer screening was performed in all patients following written informed consent being obtained. Quantitative methylation-specific PCR was used to determine the methylation status of RASSF1, RARβ, DAPK, hTERT, and APC genes' promoters in bladder tissue samples. Twenty-four patients suffering from mixed NLUTD etiology for a median duration of 10 (IQR: 12) years were recruited in this study. DNA hypermethylation was detected in at least one gene of the panel in all tissue samples. RAR-β was hypermethylated in 91.7% samples, RASSF and DAPK were hypermethylated in 83.3% samples, APC 37.5% samples, and TERT in none of the tissue samples. In 45.8% of the samples, three genes of the panel were hypermethylated, in 29.2% four genes were hypermethylated, and in 16.7% and in 8.3% of the samples, two and one gene were hypermethylated, respectively. The number of hypermethylated genes of the panel was significantly associated with recurrent UTIs (p = 0.0048). No other significant association was found between DNA hypermethylation or the number of hypermethylated genes and the clinical characteristics of the patients. Histopathological findings were normal in 8.3% of patients, while chronic inflammation was found in 83.3% of patients and squamous cell metaplasia in 16.7% of patients. In this study, we observed high rates of DNA hypermethylation of genes associated with bladder cancer in NLUTD patients, suggesting an epigenetic field effect and possible risk of bladder cancer development. Recurrent UTIs seem to be associated with increased DNA hypermethylation. Further research is needed to evaluate the impact of recurrent UTIs and chronic inflammation in DNA hypermethylation and bladder cancer etiopathogenesis in NLUTD patients.

Analysis of Methylome of Different Forms of Basal Cell Hyperplasia and Squamous Cell Metaplasia of Bronchial Epithelium.

Squamous cell lung cancer (SCLC) occurs as a result of dysregenerative changes in the bronchial epithelium: basal cell hyperplasia (BCH), squamous cell metaplasia (SM), and dysplasia. We previously suggested that combinations of precancerous changes detected in the small bronchi of patients with SCLC may reflect various "scenarios" of the precancerous process: isolated BCH→stopping at the stage of hyperplasia, BCH+SM→progression of hyperplasia into metaplasia, SM+dysplasia→progression of metaplasia into dysplasia. In this study, DNA methylome of various forms of precancerous changes in the bronchial epithelium of SCLC patients was analyzed using the genome-wide bisulfite sequencing. In BCH combined with SM, in contrast to isolated BCH, differentially methylated regions were identified in genes of the pathogenetically significant MET signaling pathway (RNMT, HPN). Differentially methylated regions affecting genes involved in inflammation regulation (IL-23, IL-23R, IL12B, IL12RB1, and FIS1) were detected in SM combined with dysplasia in comparison with SM combined with BCH. The revealed changes in DNA methylation may underlie various "scenarios" of the precancerous process in the bronchial epithelium.

Histologic Alterations in Salivary Glands Post Fine Needle Aspiration Cytology – A Diagnostic Challenge

Fine-needle aspiration (FNA) is used widely in the initial workup and diagnosis of both palpable and deep-seated masses. Salivary glands are among the most commonly aspirated locations in the head and neck area. Fine-needle aspiration cytology (FNAC) is a simple, safe and non-invasive ancillary diagnostic method that is relatively atraumatic. However, it can lead to histologic changes that may obscure the underlying pathology or mislead the unwary to render an erroneous diagnosis of malignancy. The tissue changes after FNAC include haemorrhage, squamous cell metaplasia, infarction and necrosis and needle track tumour seeding. Although tissue changes induced by FNAC are rare and account for only 7% and 10 % cases, awareness of these alterations will prevent the pathologist from overestimating the diagnosis. The aim of this review is to emphasize the importance of recognizing the histologic changes induced by FNAC and of obtaining the clinical history of a preoperative FNA procedure to avoid potential misdiagnosis.

Nasal Cytology Changes in Head and Neck Cancer Treatment: A Systemic Review.

Nasal cytology is a non-invasive, low-cost exam that can help physicians in the diagnosis of allergic and nonallergic rhinitis, discriminating between different nasal disorders. The aim of this review is to summarize and analyze the current knowledge about nasal cytological examination in head and neck cancer, with a specific focus on the effects of different treatments. Indeed, nasal cytology is important to choose the best treatment for nasal complaints in each patient. A review of the English literature (PubMed, Scopus, Cochrane) was performed (5404 records screened). The inclusion criteria were clinical trials, cohort studies, case-control studies, case series, and case reports regarding nasal cytology in head and neck cancer treatment. Exclusion criteria were as follows: non-human studies, non-English literature, non-cytological evaluations. Two independent reviewers, working separately, extracted the data from all the eligible studies, which were subsequently cross-checked. Five studies were included in qualitative synthesis: three assessed mucosal disorders after radiation therapy and two after total laryngectomy. Radiotherapy can determine mucous or squamous cell metaplasia and neutrophil inflammation. Laryngectomees show hyperplasia of the basal zone cells and mucous cell metaplasia, and they do not develop inflammatory changes. The main limitation of this review is the low number and heterogeneity of studies present in the literature. In conclusion, nasal cytology is useful and allows for identifying mucosal disorders of the nasal cavities after surgery and/or radiotherapy for head and neck cancer. This can help physicians to better treat the nasal complaints of such patients.

Molecular and Histological Changes in Airway Basal Stem Cells on Chronic Obstructive Pulmonary Disease

Airway basal stem cell changes in COPD including hyperplasia, squamous cell metaplasia, epithel-mesenchymal transision, impairment of cillia and secretoric non mucosal cell differentiation, and junctional barrier integrity disturbances that lead to histological changes. There are also molecular changes such as disturbances in gene expresion, cytokines, inflamation factor and dysregulation of basal cell transcriptome in locus 19q13.2. This article is aimed to review airway basal cell changes in COPD. By understanding initial changes of airway basal stem cell in COPD, hopefully can help to develop stem cell therapy in COPD treatment. The research aims to explore molecular and histological changes in airway basal stem cells on chronic obstructive pulmonary disease. The researchers used literature review as the way to verify their arguments on the issue discussed by analyzing the results of scientific sources, especially from trusted sources such as Google Scholar and Science Direct. The study continues by stating that regenerative therapy using stem cells has started to evolve with the advancement of stem cell technology and is anticipated to improve and treat this illness. Only preclinical and phase 2 clinical trials have seen recent advancements in the use of stem cells for treating COPD.

Sperm protein antigen 17 and Sperm flagellar 1 cancer testis antigens are expressed in a rare case of ciliated foregut cyst of the common hepatic duct

IntroductionCiliated foregut cysts (CFCs) are frequently described in liver, pancreas and gallbladder and generally considered benign although one case of squamous cell metaplasia and five cases of squamous cell carcinoma arising from a ciliated hepatic foregut cyst have been reported. Here we explore two cancer-testis antigens (CTAs), Sperm protein antigen 17 (SPA17) and Sperm flagellar 1 (SPEF1) expression in a rare case of CFC of the common hepatic duct Materials and Methods3 µm-thick CFC sections were immunohistochemically treated with antibodies raised against human SPA17 or SPEF1. In silico Protein-Protein Interaction (PPI) network and differential protein expression were also investigated ResultsImmunohistochemistry revealed SPA17 and SPEF1 in the cytoplasm of ciliated epithelium. SPA17, but not SPEF1, was also detected in cilia. The PPI networks demonstrated that other CTAs are significantly predicted functional partners with SPA17 and SPEF1. The differential protein expression demonstrated that SPA17 was higher in breast cancer, cholangiocarcinoma, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, gastric adenocarcinoma, cervical squamous cell carcinoma, bladder urothelial carcinoma. SPEF1 expression was higher in breast cancer, cholangiocarcinoma, uterine corpus endometrial carcinoma and kidney renal papillary cell carcinoma ConclusionsOur study suggests that further characterization of SPA17 and SPEF1 in patients with CFCs might provide significant insights to understand the mechanisms underlying their potential to malignant transformation.

Mire and Pelage-Mucoepidermoid Carcinoma Salivary Gland

Mucoepidermoid carcinoma of salivary gland is a frequently encountered, malignant neoplasm arising from salivary gland epithelium constituted of mucous cells, intermediate cells and epidermoid cells. Tumefaction is associated with specific chromosomal translocation t(11;19)(q14-21;p12-13) and CRTC1(MECT1)-MAML2 genetic fusion. Median age of disease emergence is 49 years and a mild female preponderance is observed. Neoplasm predominantly incriminates major salivary glands as the parotid gland. Tumefaction depicts a solid, cystic or dual configuration and is composed of neoplastic epidermoid cells demonstrating solid nests, sheets or cellular cords along with varying proportion of epidermoid cells, intermediate cells or mucocytes. Tumour cells appear immune reactive to pan-cytokeratin, CK5/6, p63, p40, epithelial membrane antigen(EMA), CK7 or CK14. Membrane bound mucins appear immune reactive to MUC1, MUC2, MUC4, MUC5AC and MUC5B. Mucoepidermoid carcinoma requires segregation from neoplasms such as pleomorphic adenoma with squamous cell and mucinous cell metaplasia, necrotizing sialometaplasia, Warthin tumour with squamous metaplasia, acinic cell carcinoma, mammary analogue secretory carcinoma (MASC), primary or secondary squamous cell carcinoma or salivary duct carcinoma. Preoperative assessment with ultrasonography or fine needle aspiration cytology may be beneficially employed. Tumefaction may be subjected to comprehensive surgical eradication with excision of broad perimeter of uninvolved, circumscribing soft tissue.

Efficacy of preoperative therapy in patients with high and low risk of distant metastasis in non-small cell lung cancer

Background. To select the optimal treatment for non-small cell lung cancer (NSCLC), it is important to predict the risk of distant metastasis and the effectiveness of therapy. The effect of neoadjuvant chemotherapy (NAC) on distant metastasis remains poorly understood. In this study we evaluated the feasibility of predicting the risk of distant metastasis and effectiveness of various treatment options for pre- and intraoperative therapy in NSCLC patients with high and low risk of distant metastasis, divided based on the assessment of morphological changes in the epithelium of small bronchi located near the primary tumor.Material and Methods. The study included 171 patients with NSCLC (T1-4N0-3M0). Various premalignant lesions: isolated basal cell hyperplasia (BCH+SM-D-), basal cell hyperplasia with squamous cell metaplasia (BCH+SM+D-) and squamous cell metaplasia with dysplasia (BCH-SM+D+) were identified in the bronchial epithelium of small bronchi taken at a distance of 3–5 cm from the tumor. Preliminary studies have shown that the detection of BCH+SM-D- or BCH-SM+D-in small bronchi are the markers of high risk of NSCLC distant metastasis, and the detection of BCH+SM+D- and BCH-SM-D- are the markers of low risk of NSCLC distant metastasis. 52.6 % of patients (90/171) received 2–3 courses of neoadjuvant chemotherapy (NAC), 41.1 % (37/90) of patients underwent intraoperative radiation therapy (IORT) at a single dose of 10–15 Gy and 47.4 % (81/171) of patients received platinum-based adjuvant chemotherapy (AC).Results. Both treatment options (NAC+IORT+ and NAC+IORT–) effectively reduced the incidence of distant metastases in the high-risk group patients during the first 2 years of follow-up compared with the high-risk group patients who did not received therapy. In the low-risk group patients, distant metastases rarely occurred, regardless of the treatment option. Adjuvant chemotherapy was found to have no influence on the frequency of distant metastases. Metastasis-free and overall survival rates were better in the low-risk group patients or in patients who received the NAC+IORT+ regimen.Conclusion. Combination of NAC and IORT resulted in the increase in metastasis-free and overall survival rates.

SARS-CoV-2 Associated Pulmonary Pathology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel entry in the betacoronaviridae group of coronaviruses. This is the second member of this group, and the third of the family overall to emerge in the last 20 years, which has caused significant health concerns due to the clinical severity and spread of the disease it causes—coronavirus disease identified in 2019 (COVID-19). While initially emerging as a respiratory disease, and while most cases experience symptoms predominantly from this system, SARS-CoV-2 has emerged as a multisystem pathogen. From a pathomorphological point of view, the severity of changes in the respiratory system can be summed up as diffuse alveolar damage—desquamation of the alveolar epithelium with exudative and proliferative changes—pulmonary hyaline membranes, Clara cell hyperplasia, squamous cell metaplasia, and fibrosis. The second most prominent way the disease affects the lung is through endotheliitis—damage to the endothelial cells of the pulmonary vasculature, predominantly affecting the medium and large caliber blood vessels that cause the well-established clinical phenomenon of thrombosis/thromboembolism of the pulmonary vasculature. As the spread of the disease continues with the emergence of new variants and the number of cases continues to grow, including a large percentage of recurrent cases, it is essential to remember that the viral effects are not only acute but, due to the proliferative phenomena, can produce chronic sequelae. Therefore, in the background of dwindling publication interest, it is critical to focus on the histopathological aspects of the pulmonary disease, with the goal of better understanding the effects of the virus on the organism and identifying probable future complications after infection.

428. CHARACTERIZATION OF CD82/KAI1 IN ESOPHAGEAL ADENOCARCINOMA

Abstract The incidence of esophageal adencocarcinoma (EAC) has increased in last decades. Regardless to improved perioperative chemotherapies and surgical approaches, the prognosis for EAC in advanced stages is poor. CD82 is a tumor suppressor gene, and its downregulation correlates with invasive growth, metastases formation and advanced clinical stages. CD82 might influence the Wnt/ß-catenin signaling pathway. We used an in vitro Barrett’s esophagus cell culture model, represented by esophageal squamous cell epithelium (EPC1, EPC2), metaplasia (CP-A), dysplasia (CP-B) and esophageal adenocarcinoma (OE33, OE19, SKGT4, FLO1). Antisense LNA Oligonucleotides (GapmeRs, Qiagen) were used to achieve a transient knockdown of CD82 in OE33 and OE19 cells. mRNA and proteins were analyzed by q-RT-PCR and western blot analyses, respectively. A fluorescence antibody specific to CD82 was used for flow cytometry analysis. Proliferation assay, colony formation assay and boyden chamber assay were performed after CD82-knockdown to further analyze cell proliferation, cell growth and survival, colony forming and cell migration. CD82 was expressed in all investigated cell lines by flow cytometry with a significant overexpression in OE19 and FLO1 cells. A stable downregulation of CD82 was achieved in OE33 and OE19 cells. Proliferation assays showed a significantly higher proliferation rate at 72 hours after CD82-knockdown in OE33 cells. A significantly higher mRNA expression of vimentin was observed after CD82-knockdown in OE33. Colony formation assay showed a significantly higher colony count after CD82-knockdown in both cell lines. Cell migration was increased after CD82-downregulated in OE33 and OE19 cells. CD82 might influence the expression of mesenchymal marker proteins, cell migration abilities and the process of colony forming and thus enhance the metastatic potential of OE33 and OE19 cells. Low expression of CD82 could alter metastasis and cancer progression but further molecular characterizations are needed to elucidate the impact on carcinogenesis of EAC.

Colposcopic Findings for Detecting Pre-invasive Lesion of Cervix Among Visually Inspected Acetic Acid Positive Cases

Background: Cervical cancer-a preventable disease, is the second most commonly diagnosed cancer among women of developing countries. Paps smear is the gold standard screening method worldwide. But a low-cost test, visual inspection of cervix with acetic acid (VIA) has been emerged as an alternative for use in lowresource settings. VIA is simple and easy to perform by auxiliary health professionals. Colposcopy is an essential procedure in the evaluation of screen positive cervix though it requires considerable training and experience. Objective: The objective of this study was to evaluate the VIA positive cases by colposcopy, colposcopy guided biopsy and histopathological examination. Methods: This was a cross sectional observational study conducted among 100 VIA positive cases attended at GOPD of Dhaka Medical College Hospital from July 2014 to December 2014. Colposcopy was performed in all VIA positive cases. Subsequent biopsy and histopathological examinations were done for those with colposcopic abnormal findings. Results: The mean age of the study population was 37.9±9.3 years. Among VIA positive cases 66.0% had complaints of whitish vaginal discharge. Among the study population, colposcopically 46.0% had healthy cervix (normal) and 54.0% had abnormal findings. Colposcopy guided biopsy was taken from those with abnormal findings. Histopathological findings were normal in 38.9% cases, chronic cervicitis in 20.37% cases, squamous cell metaplasia in 3.7% cases, CIN I in 16.7%, CIN II in11.11%, CIN III in 5.6% and 3.7% cases were carcinoma cervix. True positive value was 20, false positive value 34 and positive predictive value of colposcopy was 37.03%. Conclusion: This study concluded that VIA is effective in detection of CIN and invasive carcinoma of cervix. It also suggests the role of colposcopy in the evaluation of CIN and other cervical diseases in screen positive cases. VIA can be used as a screening tool in low and middle income countries like Bangladesh, not only in rural areas and small health centres, but also in hospitals, cancer institutes, and other health facilities with better resources. Bangladesh Med Res Counc Bull 2022; 48(1): 27-32

The Role of Proprotein Convertases in Upper Airway Remodeling.

Chronic rhinosinusitis (CRS) is a multifactorial, heterogeneous disease characterized by persistent inflammation of the sinonasal mucosa and tissue remodeling, which can include basal/progenitor cell hyperplasia, goblet cell hyperplasia, squamous cell metaplasia, loss or dysfunction of ciliated cells, and increased matrix deposition. Repeated injuries can stimulate airway epithelial cells to produce inflammatory mediators that activate epithelial cells, immune cells, or the epithelial–mesenchymal trophic unit. This persistent inflammation can consequently induce aberrant tissue remodeling. However, the molecular mechanisms driving disease within the different molecular CRS subtypes remain inadequately characterized. Numerous secreted and cell surface proteins relevant to airway inflammation and remodeling are initially synthesized as inactive precursor proteins, including growth/differentiation factors and their associated receptors, enzymes, adhesion molecules, neuropeptides, and peptide hormones. Therefore, these precursor proteins require post-translational cleavage by proprotein convertases (PCs) to become fully functional. In this review, we summarize the roles of PCs in CRS-associated tissue remodeling and discuss the therapeutic potential of targeting PCs for CRS treatment.

Temporal Patterns of COVID-19-Associated Pulmonary Pathology: An Autopsy Study.

IntroductionThe novel coronavirus variant - severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes clinically (novel coronavirus disease 2019 or COVID-19) have placed medical science into a frenzy due to the significant morbidity and mortality, as well as the myriad of clinical complications developing as a direct result of infection. The most notable and one of the most severe changes in COVID-19 develops in the lungs.Materials and methodsAll cases of real-time polymerase chain reaction (rtPCR)-proved COVID-19 subjected to autopsy were withdrawn from the central histopathology archive of a single tertiary medical institution - St. Marina University Hospital - Varna, Varna, Bulgaria. Pulmonary gross and histopathology changes observed on light microscopy with hematoxylin and eosin as well with other histochemical and immunohistochemical stains were compared with the time from patient-reported symptom onset to expiration, to compare the extent and type of changes based on disease duration.ResultsA total of 27 autopsy cases fit the established criteria. All cases clinically manifested with severe COVID-19. From the selected 27 cases, n=14 were male and n=13 were female. The mean age in the cohort was 67.44 years (range 18-91 years), with the mean age for males being 68.29 (range 38-80 years) and the mean age for females being 66.54 (range 18-91 years). Gross changes in patients who expired in the first 10 days after disease onset showed a significantly increased mean weight - 1050g, compared to a relatively lower weight in patients expiring more than 10 days after symptom onset - 940g. Histopathology changes were identified as intermittent (developing independent from symptom onset and persisting) - diffuse alveolar damage with hyaline membranes - acute respiratory distress syndrome, endothelitis with vascular degeneration and fibrin thrombi; early (developing within the first week, but persisting) - type II pneumocyte hyperplasia, alveolar cell multinucleation and scant interstitial mononuclear inflammation; intermediate (developing within the late first and second weeks) - Clara cell hyperplasia and late (developing after the second week of symptom onset) - respiratory tract and alveolar squamous cell metaplasia and fibrosis.ConclusionCOVID-19-associated pulmonary pathology, both gross and histopathology, show a time-related dynamic with persistent early and a myriad of later developing dynamic changes in patients with severe disease. These changes underline both the severity of the condition, as well as the mechanisms and the probability of long-lasting severe complications in patients with post-COVID syndrome.

Premalignant Changes in the Bronchial Epithelium Are Prognostic Factors of Distant Metastasis in Non-Small Cell Lung Cancer Patients.

BackgroundThe study assessed the possibility of dividing patients into groups based on the assessment of morphological changes in the epithelium of small-caliber bronchi located near the primary tumor in order to predict high and low risks of distant metastasis of non-small cell lung cancer.MethodsIn 171 patients with non-small cell lung cancer (T1-4N0-3M0) in small-caliber bronchi taken at a distance of 3–5 cm from the tumor, various variants of morphological changes in the bronchial epithelium (basal cell hyperplasia (BCH), squamous cell metaplasia (SM), and dysplasia (D)) were assessed. Long-term results of treatment, namely, distant metastasis, were assessed after 2 and 5 years.ResultsDuring the follow-up period, distant metastases were found in 35.1% (60/171) of patients. Most often, they were observed in patients of the high-risk group: BCH+SM−D− (51.6%, 40/95) and BCH−SM+D+ (54.4%, 6/11). Less often, distant metastases were observed in low-risk group patients: BCH+SM+D− (6.7%, 3/45) and BCH−SM−D− (10.0%, 2/20). Tumor size, grade, and stage were significant predictors of metastasis only in the high-risk group. The 5-year metastasis-free survival was better in the low-risk group of distant metastases.ConclusionsIsolated BCH or dysplasia in small bronchi distant from foci of tumor is associated with a high-risk distant metastasis and less 5-year metastasis-free survival.

Squamous cell metaplasia of the rectum associated with a longstanding ulcerative colitis (clinical cases report)

INTRODUCTION: squamous cell metaplasia in the rectum is found in patients with longstanding inflammation or infectious lesions [1]. Colonoscopy plays a major role in the diagnostic of squamous cell metaplasia, especially with the use of Narrow Band Imaging (NBI) or Blue Light Imagining (BLI), which allows for targeted visualization of intraepithelial capillary loopspeculiar for the squamous epithelium [1,2]. The final conclusion cannot be reached without morphological diagnostics. We would like to show on two clinical cases of patients with a longstanding ulcerative colitis the occurrence of squamous cell metaplasia in the rectum. These areas of metaplasia may be the source of squamous cell cancer.CLINICAL CASES: a clinical cases of squamous cell metaplasia in the rectum in two patients with a longstanding ulcerative colitis (9 and 14 years) are presented. The total ulcerative colitis was verified in both patients by colonoscopy. Against the background of endoscopic remission, flat whitish areas of irregular shape, up to 3 cm in size, in the form of “tongues” of metaplastic epithelium with clear boundaries were found in the low rectum. When examined in a Narrow Band Imaging (NBI) and Blue Light Imagining (BLI), the microvascular pattern in the detected areas was identical in structure to the microvascular pattern of the squamous epithelium. The biopsies confirmed the presence of squamous cell epithelium.CONCLUSION: patients with a longstanding ulcerative colitis may have squamous cell metaplasia of the rectal mucosa, which can be detected by colonoscopy in white light. Using a Narrow Band Imaging (NBI) followed by a targeted biopsy allows the most accurate diagnosis to be established. Patients of this group require repeated colonoscopies using the above methods, since areas of metaplasia can be a source of squamous cell cancer of the rectum.

Squamous cell metaplasia of the rectum associated with a longstanding ulcerative colitis (clinical cases report)

INTRODUCTION: squamous cell metaplasia in the rectum is found in patients with longstanding inflammation or infectious lesions [1]. Colonoscopy plays a major role in the diagnostic of squamous cell metaplasia, especially with the use of Narrow Band Imaging (NBI) or Blue Light Imagining (BLI), which allows for targeted visualization of intraepithelial capillary loopspeculiar for the squamous epithelium [1,2]. The final conclusion cannot be reached without morphological diagnostics. We would like to show on two clinical cases of patients with a longstanding ulcerative colitis the occurrence of squamous cell metaplasia in the rectum. These areas of metaplasia may be the source of squamous cell cancer.CLINICAL CASES: a clinical cases of squamous cell metaplasia in the rectum in two patients with a longstanding ulcerative colitis (9 and 14 years) are presented. The total ulcerative colitis was verified in both patients by colonoscopy. Against the background of endoscopic remission, flat whitish areas of irregular shape, up to 3 cm in size, in the form of “tongues” of metaplastic epithelium with clear boundaries were found in the low rectum. When examined in a Narrow Band Imaging (NBI) and Blue Light Imagining (BLI), the microvascular pattern in the detected areas was identical in structure to the microvascular pattern of the squamous epithelium. The biopsies confirmed the presence of squamous cell epithelium.CONCLUSION: patients with a longstanding ulcerative colitis may have squamous cell metaplasia of the rectal mucosa, which can be detected by colonoscopy in white light. Using a Narrow Band Imaging (NBI) followed by a targeted biopsy allows the most accurate diagnosis to be established. Patients of this group require repeated colonoscopies using the above methods, since areas of metaplasia can be a source of squamous cell cancer of the rectum.

The diverse roles of YAP in the regulation of human nasal epithelial remodeling

Yes-associated protein (YAP) is essential in maintaining tissue size. Aberrant epithelial remodeling is a key pathological alteration in both inflammation and benign tumors in nasal mucosa. We sought to investigate the expression and localization patterns of YAP in remodeled nasal epithelium of basal cell hyperplasia, goblet cell metaplasia and squamous metaplasia. YAP expression patterns were evaluated in tissues obtained from patients with NP (n = 45) and IP (n = 27), and control subjects with septal deviation (n = 17) and tissue-derived primary cell cultures. Compared to the normal epithelium, expressions of YAP were significantly higher in basal cell hyperplasia (NP, 11.4-fold; IP, 19.6-fold), followed by squamous metaplasia (8.2-fold) and mild to moderate goblet cell metaplasia (2.9-fold); while their expression was lower in severe goblet cell metaplasia (3.3-fold). Our resultsshowed that: 1) ectopic nuclear YAP expression associated with p63+ basal cell hyperplasia and the high proliferative potential epithelial cells; 2) increase of cytoplasmic YAP correlated with mild to moderate goblet cell metaplasia; 3) increase of cytoplasmic YAP correlated with squamous cell metaplasia. The in vitro cell model also demonstrated almost concordant changes of YAP with the mucosa findings. Different YAP expression and localization patterns should play critical but differential roles in the nasal epithelial remodeling processes under mucosal inflammation and benign tumor formation.

Creation of Tissue-Engineered Urethras for Large Urethral Defect Repair in a Rabbit Experimental Model

Introduction: Tissue engineering is a potential source of urethral substitutes to treat severe urethral defects. Our aim was to create tissue-engineered urethras by harvesting autologous cells obtained by bladder washes and then using these cells to create a neourethra in a chronic large urethral defect in a rabbit model.Methods: A large urethral defect was first created in male New Zealand rabbits by resecting an elliptic defect (70 mm2) in the ventral penile urethra and then letting it settle down as a chronic defect for 5–6 weeks. Urothelial cells were harvested noninvasively by washing the bladder with saline and isolating urothelial cells. Neourethras were created by seeding urothelial cells on a commercially available decellularized intestinal submucosa matrix (Biodesign® Cook-Biotech®). Twenty-two rabbits were divided into three groups. Group-A (n = 2) is a control group (urethral defect unrepaired). Group-B (n = 10) and group-C (n = 10) underwent on-lay urethroplasty, with unseeded matrix (group-B) and urothelial cell-seeded matrix (group-C). Macroscopic appearance, radiology, and histology were assessed.Results: The chronic large urethral defect model was successfully created. Stratified urothelial cultures attached to the matrix were obtained. All group-A rabbits kept the urethral defect size unchanged (70 ± 2.5 mm2). All group-B rabbits presented urethroplasty dehiscence, with a median defect of 61 mm2 (range 34–70). In group-C, five presented complete correction and five almost total correction with fistula, with a median defect of 0.3 mm2 (range 0–12.5), demonstrating a significant better result (p = 7.85 × 10−5). Urethrography showed more fistulas in group-B (10/10, versus 5/10 in group-C) (p = 0.04). No strictures were found in any of the groups. Group-B histology identified the absence of ventral urethra in unrepaired areas, with squamous cell metaplasia in the edges toward the defect. In group-C repaired areas, ventral multilayer urothelium was identified with cells staining for urothelial cell marker cytokeratin-7.Conclusions: The importance of this study is that we used a chronic large urethral defect animal model and clearly found that cell-seeded transplants were superior to nonseeded. In addition, bladder washing was a feasible method for harvesting viable autologous cells in a noninvasive way. There is a place for considering tissue-engineered transplants in the surgical armamentarium for treating complex urethral defects and hypospadias cases.