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We aim aim to compare immunophenotypic charac-teritics of atypical epithelium (AE) with COVID-19-induced diffuse alveolar damage (DAD) and pulmonary lepidic-growth adenocarcinoma, accounting for cell cycle control, proliferation and differentiation]. Methods. We examined pulmonary tissue specimens from twenty-four fatal cases of CO VID-19-induced acute respiratory damage syndrome confirmed by autopsy (Group 1) and four cases of pulmonary lepidic-growth adenocarcinoma (Group 2). Perpendicular dimensions of 10 nuclei were measured on the H&E slides, means of their sums of products (SPNM) were calculated. We have used p53, Ki67, pi6, p63 antibodies for immunohistochemical staining in each case. We evaluate co¬lour intensity, rate of stained cells of AE and the product of these parameters. We evaluated separately Nuclear and cyto-plasmic staining (couple) and only cytoplasmic staining (cyt) for pi6 expression. We measured proliferative index only at KI-67 stained slides. U-test and Spearman rank correlation test were used for statistical analysis. Results. Expression of p63 was higher in group 1 (p=0.001), while pi6 was more frequently expressed in group 2 (p=0.002). We have found no statistically significant differences (p>0.1) in the p53 and Ki67 expression. Group 1 showed There was negative correlation between the number of days from onset of symptoms and the following variables: Ki67 (r=M).587, p=0.003);SPNM (r 0.406, p=0.049). Conclusion. The present study has shown heterogeneity in levels of cell cycle control expression, proliferation and differentiation of atypical epithelium in the pulmonary lep-idic-growth adenocarcinoma and CO VID-19-induced diffuse alveolar damage.
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Background: Poor prognosis of lung cancer is linked to its late diagnosis, typically in the advanced stage 4 in 50-70% of incidental cases. Lung Cancer Screening Programs provide low-dose lung CT screening to current and former smokers who are at high risk for developing this disease. Greece is an EU country, returning strong from a long period of economic recession, ranked 2nd place in overall age-standardized tobacco smoking prevalence in the EU. In December 2020, at the Metropolitan Hospital of Athens, we started the 1st Screening Program in the country. We present our initial results and pitfalls met. Method(s): A weekly outpatient clinic offers consultation to possible candidates. LDCT (<=3.0mGy), Siemens VIA, Artificial Intelligence multi-computer-aided diagnosis (multi-CAD) system and LungRADS (v.1.1) are used for the validation of any abnormal findings with semi-auto measurement of volume and volume doubling time. Patients get connected when necessary with the smoking cessation and Pulmonology clinic. USPSTF guidelines are used, (plus updated version). Abnormal CT findings are discussed by an MDT board with radiologists, pulmonologists/interventional pulmonologists, oncologists and thoracic surgeons. A collaboration with Fairlife Lung Cancer Care the first non-profit organization in Greece is done, in order to offer the program to population with low income too. An advertisement campaign was organized to inform family doctors and the people about screening programs, together with an anti-tobacco campaign. Result(s): 106 people were screened, 74 males & 32 females (mean age 62yo), 27/106 had an abnormal finding (25%). 2 were diagnosed with a resectable lung cancer tumor (primary adenocarcinoma) of early-stage (1.8%). 2 with extended SCLC (lung lesion & mediastinal adenopathy). 1 with multiple nodules (pancreatic cancer not known until then). 3 patients with mediastinal and hilar lymphadenopathy (2 diagnosed with lymphoma, 1 with sarcoidosis). 19 patients were diagnosed with pulmonary nodules (RADS 2-3, 17%) - CT follow up algorithm. Conclusion(s): We are presenting our initial results, from the first lung cancer screening program in Greece. Greece represents a country many smokers, who also started smoking at a young age, with a both public and private health sector, returning from a long period of economic recession. COVID-19 pandemia has cause practical difficulties along the way. LDCT with AI software, with an MDT board and availability of modern diagnostic and therapeutic alternatives should be considered as essential. A collaboration spirit with other hospitals around the country is being built, in order to share current experience and expertise. Copyright © 2022
ABSTRACT
Background: A 54-year- old male presented to our centre with a chronic non-productive cough and breathlessness. Recent history of COVID treated and resolved few months back. He had a history of brain surgery performed five years back but details not known. Physical examination revealed no oedema and bilateral coarse creps with bronchiolar breathing. Laboratory findings indicated neutrophilic leucocytosis, elevated inflammatory markers, with elevated troponin I and D dimers. Urine analysis suggested microscopic haematuria with sediments. While 24 hour quantification revealed sub nephrotic proteinuria. As auto immune workup and vasculitis profile was negative and patient has not improved in spite of standard of therapy hence we went ahead with CT-Chest indicating ground-glass opacities in bilateral lung parenchyma and prominent interlobular/intralobular septal thickening. Then Bronchoscopy done which revealed the blood-stained secretions in the main stem bronchi and diffuse alveolar haemorrhage in bilateral bronchial segments indicating an inflammatory study, while tuberculosis diagnostic panel and infective bio fire panel in BAL was negative. Meanwhile, his repeat BAL culture suggested Carbapenem resistant Acinetobacter baumannii complex infection. As the patient did not respond to the standard of care for vasculitis. Probability considered was a small vessel vasculitis (namely Granulomatous polyangiitis) was considered due to lung manifestation involving upper respiratory tract with epistaxis, neutrophilic leucocytosis, elevated acute reactive protein, and renal manifestation including microscopic haematuria and proteinuria. However he responded poorly to conventional standard of treatment including pulse steroids and IVIG. Hence after MDT discussion we proceeded with lung biopsy which showed linear cores of lung tissue infiltrated by a malignant neoplasm and acinar pattern suggesting Invasive mucinous adenocarcinoma. Hence we went ahead with the biopsy diagnosis for the treatment plan. As he was to be started on chemotherapy, but he suddenly collapsed and went into hypotension, bradycardia, and cardiac arrest. In spite of high supports and post 4 cycles of CPR, was unable to revive and sadly succumbed to his illness. Discussion(s): In this rare case, the original diagnosis pointed to the pulmonary-renal syndrome, an autoimmune disease characterized by diffuse pulmonary haemorrhage and glomerulonephritis. However, negative autoimmune antibodies and vasculitis profile along with lung biopsy results indicated an unusual case of malignant lung adenocarcinoma presented with pulmonary renal syndrome. Conclusion(s): In cases suggesting pulmonary-renal syndromes, if autoimmune work up is negative and response is suboptimal relook the diagnosis.
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A 40-year-old man was admitted with a diagnosis of COVID-19 pneumonia. Although most of multiple ground-glass opacities and consolidations on computed tomography improved, a round ground-glass opacity with consolidation remained unchanged and was suspected to be a part-solid nodule of lung adenocarcinoma. Pathologic diagnosis of resected tumor was papillary adenocarcinoma.
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BACKGROUND: Malignant polyps represent the early development of colorectal adenocarcinoma. During 2020, there was widescale rationing of health-care resources in response to the COVID-19 pandemic. In particular there was deferral of some colonoscopy procedures required for timely malignant polyp detection. This study sought to assess how these deferrals affected the diagnosis of malignant polyps. METHODS: A population wide analysis was performed of 2079 malignant polyps, diagnosed in Queensland, Australia from 2011 to 2020. A regression analysis, with 95% prediction intervals, was produced to determine whether there was a significant impact on the number of malignant polyps diagnosed in 2020 compared to previous years. Univariate statistical analysis of patient, procedural, and pathological variables was also performed. RESULTS: In 2020 there were 211 malignant polyps diagnosed, which was significantly lower than was predicted by the univariate regression analysis (r2 = 0.85, 95% prediction interval: 255.07-323.91, P < 0.001). These malignant polyps were less likely to be diagnosed in a private setting (P < 0.001), and exhibited significantly less depth of submucosal invasion (P = 0.017). There was no significant difference in the management strategy (polypectomy, resection or trans-anal resection) between 2011 and 2019 and 2020. CONCLUSION: Because of the significant decrease in the number of malignant polyps, and the natural history of the disease, it is expected that there will be an increase in more advanced colorectal adenocarcinomas presenting in 2021 and beyond. This has implications for healthcare resources, particularly in light of the ongoing strain on health departments as a result of the COVID-19 pandemic.
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Background: The coronavirus disease 2019 (COVID-19) pandemic resulted in enormous medical and economic burden worldwide during the past 3 years. The vaccination was deemed the effective option to prevent the severe symptoms, and especially recommended among cancer patients. Shanghai experienced the first lockdown during the recent Omicron pandemic since 2019. How patients with pancreatic adenocarcinoma (PAC) suffered from the pandemic and how vaccination influenced their oncological outcomes were unexplored yet. Method: The retrospective study was carried out in a high-volume referral center including 1157 consecutively enrolled patients with PAC experiencing the COVID-19 pandemic. The primary outcome was the overall survival (OS). Results: Limited postoperative patients (9.21%) received the vaccination. The lockdown in Shanghai (April to May, 2022) was not observed impacting the survival prognoses of patients with PAC. Though vaccination was not significantly associated with OS itself (adjusted hazard ratio (aHR): 2.032 [0.940-4.391], p = 0.071), it was discovered to synergistically improve the chemotherapy effect in the multivariate analyses (interaction p = 0.023). Conclusion: The vaccination itself did not influence the survival prognoses of patients with PAC. A potential positive interaction was observed between chemotherapy and vaccination despite the limited follow-up time. The postoperative patients should consider the vaccination more. The patients with PAC did not suffer worse prognostic outcomes from the strict sanitary policy during the wave of COVID-19 pandemic in Shanghai.
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The mRNA vaccine has provided a promising approach for cancer immunotherapies. However, only a few mRNA vaccines have been developed against colon adenocarcinoma (COAD). Screening potential targets for mRNA vaccines from numerous candidates is a substantial challenge. Considering the tumor heterogeneity, only a subset of patients might respond to vaccinations. This study was conducted to identify potential candidates for mRNA vaccines, and distinguish appropriate subgroups of COAD patients for vaccination. A total of five tumor antigens with prognostic values were identified, including IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5. The COAD patients were stratified into five immune subtypes (IS1-IS5), according to consensus clustering analysis. Higher tumor mutation burden (TMB) was observed in IS1 and IS5 subtypes. The IS1 and IS5 subtypes have shown the baseline of immune-hot tumor microenvironment, while other subtypes displayed immune desert phenotype. Distinct expressions of immune checkpoints (ICPs)-related genes and immunogenic cell death (ICD) modulators were observed among five immune subtypes. Finally, the immune landscape was conducted to narrow the immune components for better personalized mRNA-based vaccination. The IFIT3, PARP9, TAP1, STAT1, and OAS2 were confirmed as hub genes, and COAD patients with higher expressions of these genes might be more appropriate for mRNA vaccination. In conclusion, the IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5 were identified as potential candidates for developing mRNA vaccines against COAD, and patients in IS1 and IS5 subtypes might respond better to mRNA vaccination.
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Background: The incidence of respiratory diseases and the respiratory disease mortality rate have increased in recent years. Recent studies have shown that long non-coding RNA (lncRNA) MALAT1 is involved in various respiratory diseases. In vascular endothelial and cancer cells, MALAT1 expression triggers various changes such as proinflammatory cytokine expression, cancer cell proliferation and metastasis, and increased endothelial cell permeability. Methods: In this review, we performed a relative concentration index (RCI) analysis of the lncRNA database to assess differences in MALAT1 expression in different cell lines and at different locations in the same cell, and summarize the molecular mechanisms of MALAT1 in the pathophysiology of respiratory diseases and its potential therapeutic application in these conditions. Results: MALAT1 plays an important regulatory role in lncRNA with a wide range of effects in respiratory diseases. The available evidence shows that MALAT1 plays an important role in the regulation of multiple respiratory diseases. Conclusion: MALAT1 is an important regulatory biomarker for respiratory disease. Targeting the regulation MALAT1 could have important applications for the future treatment of respiratory diseases.