Трудности диагностики центральной эндофитной опухоли легкого, возникшей на фоне туберкулеза

Background: Liquid biopsy-based biomarkers present a promising approach for non-invasive risk assessment and early detection of lung cancer. Aim: To identify a miRNA signature in sputum and plasma samples as a non-invasive biomarker for early detection of non-small cell lung cancer (NSCLC). Methods: A case-control study was conducted within the Barretos Cancer Hospital Screening Program, utilizing a low-dose CT mobile unit. Sputum and plasma samples were collected from high-risk controls (NLST and/or PLCO criteria; n=61) and NSCLC patients (n=62), matched for age, sex, and smoking history. MiRNA expression was analyzed using the nCounter HumanV3 miRNA panel (Nanostring™). Counts were normalized by the top stable miRNAs, followed by differential expression analysis (p<0.05). MiRNA selection was conducted using Boruta and LASSO. Dataset was partitioned into training and validation sets (85/15 split). Machine learning models (ML) were conducted (Azure) and performance was assessed using AUC (Table 1). Results: In plasma, 68 miRNAs were identified as differentially expressed, and 8 miRNAs were retained following filtering. Among the all-tested models (Table 1), the best ML (Voting Ensemble) for the 8-miRNA plasma signature showed a high accuracy in both training (80.3%, AUC = 0.931) and validation set (73.3%, AUC = 0.892). In sputum, 46 miRNAs were identified as differentially expressed, and 7 miRNAs were retained. The best ML (SVD,Logistic Regression) for the 7-miRNA sputum signature showed a high accuracy in both training (81.42%, AUC = 0.943) and validation set (78.57%, AUC = 0.916). The two defined signatures exhibited no overlap in miRNAs between fluids. Conclusion: This study identified two distinct miRNA fluid-specific signatures in sputum and plasma as potential non-invasive biomarkers for the early detection of lung cancer, underscoring their potential to advance precision-based screening and improve clinical decision-making in lung nodules management. Citation Format: Alessandro Pascon Filho, Giovana M. Stanfoca Casagrande, Rodrigo Sampaio Chiarantano, Fabiana de Lima Vazquez, Rui Manuel Reis M. Reis, Leticia Ferro Leal. MiRNA signatures in liquid biopsy for early detection of non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4569.

Aim. To analyze the features of the simultaneous course of pulmonary aspergillosis and multidrug-resistant pulmonary tuberculosis (MDR-TB) on the background of type 1 diabetes mellitus, on the example of a clinical case of our practice. Materials and methods. Clinical case of our practice of simultaneous pulmonary aspergillosis and MDR-TB on the background of type 1 diabetes mellitus in a patient, who was treated in Pulmonary tuberculosis department No. 2 of clinical base of Phthisiatry and Pulmonology Department of Zaporizhzhia State Medical University at Communal Non-Commercial Enterprise of the “Zaporizhzhia Regional Clinical and Diagnostic Center of Phthisiatry and Pulmonology” of Zaporizhzhia Regional Council. Results. In the presented clinical case, the patient had been suffering from diabetes mellitus for 8 years and had been receiving insulin therapy for all these years. One year before the TB disease, he had contact with an index patient, but he categorically refused a course of preventive chemotherapy. Also, the patient did not make a comparison X-ray TCO after 6 months, as a contact person. MDR-TB and aspergilloma of the left lung of the patient were diagnosed simultaneously on the background of severe condition with decompensated form of type 1 diabetes mellitus, severe intoxication syndrome and inflammatory process, massive hemoptysis. Aspergilloma of the left lung was diagnosed using X-ray TCO and cultural examination of bronchial aspirate for Aspergillus, which was not difficult to diagnose. Diagnosis of MDR-TB was also not difficult, because the patient had MBT, which contributed to the timely and correct appointment of antimycobacterial therapy. Surgery for aspergilloma of the left lung was contraindicated, as the type 1 diabetes was in decompensation. Persistent hyperglycemia remained, despite the fact of antifungal therapy and constant correction of insulin therapy prescribed for the patient. Endocarditis quickly developed in the patient, which was the reason of patient’s death. Conclusions. The decompensated form of type 1 diabetes mellitus caused persistent hyperglycemia, which was the reason of immune disorders and this made the patient’s body susceptible to bacterial (MDR-TB) and fungal (aspergillosis) infections, which led to the development of the complication of endocarditis and death. A big mistake in his case, was a categorical refusal by the patient to receive a course of preventive chemotherapy, as a contact person with an index patient. In view of this, in the presence of type 1 diabetes, the patient should have not neglected it. And as a result, the patient had a MDR-TB, one year after. At the same time, the patient did not make a comparison X-ray TCO, after 6 months, as a contact person, which was a possible reason for the missing of early diagnosis of pulmonary aspergilloma. That’s why, a correct treatment of type 1 diabetes mellitus and timely preventive radiological examination of the thoracic cavity organs are especially important, as the diabetes mellitus is the most common premorbid background for TB and aspergillosis.

Objective — referring to literature data on the effectiveness of antibacterial therapy in multidrug-resistant tuberculosis (MDR TB) of lungs, to develop an algorithm for treating patients with such forms of tubercu-losis. It based on comparing the effectiveness of conservative antibiotic therapy and surgical treatment according to the methods, developed by the authors on the background of double collapse of the lungs.Materials and methods. Under the supervision of the authors during 2011—2017 there were two groups of patients. The comparison group included 1136 patients with multidrug resistant pulmonary tuberculosis treated only with antimycobacterial drugs. The main group consisted of 107 patients with multidrug resistant pulmonary tuberculosis, who were operated on according to the methods developed in the TB clinic of Sumy State University. The proposed technique is based on the double collapse of the operated lung. Observation in the remote period was conducted during 7 years.Results and discussion. The treatment of patients in the main group was more frequent than the comparison groups in 2.2 times. Among patients in the comparison group during the observation period, 20 % of patients died, in the main group — 3.7 %, which is less 5.4 times (p < 0.05); unsuccessful treatment with interrupted in the comparison group was fixed at 32.7 %, in the main group — 7.5 %, which is less 4.4 times (p < 0.05).Conclusions. Double collapse of the lungs is a reliable alternative to antibiotic therapy in the proposed methods of surgical treatment of MDR TB. Surgical treatment of patients with limited prevalence of MRI can be applied by the type of resection, and in common processes — by the type of extrapleural thoraco-plasty.Surgery for multidrug-resistant pulmonary tuberculosis, according to the proposed algorithm, contributes to a positive effect (negative smear conversion, closure of decay cavities), which exceeds that in conservative treatment by 1.9 times. The unsuccessful effect at conservative therapy occurs more often than at surgical intervention in 3.5 times, and dies of such patients more in 5.4 times.

This study was planned to estimate the proportion of confirmed multi-drug resistance pulmonary tuberculosis (TB) cases out of the presumptive cases referred to DTC (District Tuberculosis Center) Jodhpur for diagnosis; to identify clinical and socio-demographic risk factors associated with the multidrug-resistant pulmonary TB and to assess the spatial distribution to find out clustering and pattern in the distribution of pulmonary TB with the help of Geographic Information System (GIS). In the Jodhpur district, 150 confirmed pulmonary multi-drug resistant tuberculosis (MDR-TB) cases, diagnosed by probe-based molecular drug susceptibility testing method and categorized as MDR in DTC's register (District Tuberculosis Center), were taken. Simultaneously, 300 control of confirmed non-MDR or drug-sensitive pulmonary TB patients were taken. Statistical analysis was done with logistic regression. In addition, for spatial analysis, secondary data from 2013-17 was analyzed using Global Moran's I and Getis and Ordi (Gi*) statistics. In 2012-18, a total of 12563 CBNAAT (Cartridge-based nucleic acid amplification test) were performed. 2898 (23%) showed M. TB positive but rifampicin sensitive, and 590 (4.7%) showed rifampicin resistant. Independent risk factors for MDR TB were ≤60 years age (AOR 3.0, CI 1.3-7.1); male gender (AOR 3.4, CI 1.8-6.7); overcrowding (AOR 1.6, CI 1.0-2.7); using chulha (smoke appliance) for cooking (AOR 2.5, CI 1.2-4.9), past TB treatment (AOR 5.7, CI 2.9-11.3) and past contact with MDR patient (AOR 10.7, CI 3.7-31.2). All four urban TUs (Tuberculosis Units) had the highest proportion of drug-resistant pulmonary TB. There was no statistically significant clustering, and the pattern of cases was primarily random. Most of the hotspots generated were present near the administrative boundaries of TUs, and the new ones mostly appeared in the area near the previous hotspots. A random pattern seen in cluster analysis supports the universal drug testing policy of India. Hotspot analysis helps cross administrative border initiatives with targeted active case finding and proper follow-up.

Despite that confirmative diagnosis of pulmonary drug-sensitive tuberculosis (DS-TB) and multidrug resistant tuberculosis (MDR-TB) is determined by microbiological testing, early suspicions of MDR-TB by chest imaging are highly desirable in order to guide diagnostic process. We aim to perform an analysis of currently available literatures on radiological signs associated with pulmonary MDR-TB. A literature search was performed using PubMed on January 29, 2018. The search words combination was "((extensive* drug resistant tuberculosis) OR (multidrug-resistant tuberculosis)) AND (CT or radiograph or imaging or X-ray or computed tomography)". We analyzed English language articles reported sufficient information of radiological signs of DS-TB vs. MDR-TB. Seventeen articles were found to be sufficiently relevant and included for analysis. The reported pulmonary MDR-TB cases were grouped into four categories: (I) previously treated (or 'secondary', or 'acquired') MDR-TB in HIV negative (-) adults; (II) new (or 'primary') MDR-TB in HIV(-) adults; (III) MDR-TB in HIV positive (+) adults; and (IV) MDR-TB in child patients. The common radiological findings of pulmonary MDR-TB included centrilobular small nodules, branching linear and nodular opacities (tree-in-bud sign), patchy or lobular areas of consolidation, cavitation, and bronchiectasis. While overall MDR-TB cases tended to have more extensive disease, more likely to be bilateral, to have pleural involvement, to have bronchiectasis, and to have lung volume loss; these signs alone were not sufficient for differential diagnosis of MDR-TB. Current literatures suggest that the radiological sign which may offer good specificity for pulmonary MDR-TB diagnosis, though maybe at the cost of low sensitivity, would be thick-walled multiple cavities, particularly if the cavity number is ≥3. For adult HIV(-) patients, new MDR-TB appear to show similar prevalence of cavity lesion, which was estimated to be around 70%, compared with previously treated MDR-TB. Thick-walled multiple cavity lesions present the most promising radiological sign for MDR-TB diagnosis. For future studies cavity lesion characteristics should be quantified in details.

Computed Tomography (CT), Magnetic Resonance Imaging (MRI), and X-rays have been very disappointing in the detection and diagnosis of central (airways/endobronchial) lesions. Bronchoscopy with direct visualization and other supportive technologies has been the primary tool for the detection and surveillance of endobronchial precancerous and cancerous lesions. Early detection of lung cancer allows early interventions which has a survival benefit as shown by a 20% relative decrease in lung cancer specific mortality with low-dose computed tomography screening and high-risk groups [1]. CT screening of the thorax is able to detect lesions that are peripheral, central, and sub centimeter, however it is insensitive for detection of precancerous and early small cancerous lesions arising from the airways. The pathological progression from normal bronchogenic epithelium to squamous metaplasia followed by dysplasia and finally carcinoma in situ(CIS) is supported by sputum cytology studies as well as animal data [2,3], however other models such as multiple foci of precursor lesions that are produced throughout the respiratory epithelium may develop into carcinoma in situ as opposed to a stepwise progression of a single area [4]. Regardless, prompt detection of high-risk patients that offers early diagnosis of preinvasive lesions could allow for early intervention and improved survival. The use of white light bronchoscopy is the standard imaging tool for the diagnosis of central airway tumors. However, in the detection of precancerous lesions WLB has a low sensitivity and specificity [5,6]. Recent advances have allowed bronchoscopists to evaluate the airway with advanced high-resolution imaging modalities. The development of the ideal bronchoscopic imaging technique capable of detecting preinvasive lesions is ongoing. Currently autofluorescence bronchoscopy (AFB), narrow-band imaging(NBI), high magnification bronchovideoscopy (HMB), probe based confocal endomicroscopy (pCLE), optical coherence tomography (OCT), radial probe endobronchial ultrasonography (R-EBUS) and now high definition bronchoscopy (HD) with surface enhancement (i-scan) are all being studied or used in clinical practice to evaluate the airway. The ideal system would be able to detect and define preinvasive lesions so that not only are we able to preemptively treat these lesions but determine effectiveness of treatment with noninvasive or minimally invasive techniques. In this issue of Respiratory Research, van der Heijden and colleagues report a randomized blinded prospective study, which examined the use of 5 videobronchoscopy techniques in 29 patients in which the authors explore whether different modalities might lead to improved detection of suspicious vascular changes or suspected preinvasive lesions. In the previous literature, WLB combined with AFB increased the diagnostic accuracy for squamous dysplasia, CIS, and early lung cancer with a high sensitivity but resulted in a large number of false positives and unneeded biopsies [7,8]. Heijden and colleagues did show that HD bronchoscopy with i-scan improve detection of vascular changes over WLB and AFB however AFB did detect more preinvasive lesions over WLB and HD modes. Histological confirmation was not obtained in this study so it is difficult to discern whether there would be improved accuracy of HD modes over AFB. That said we agree that it is likely that improved images and image enhancement which are able to better identify vascular abnormalities could improve overall diagnostic yield. Further studies in which a potential combination of methods, which improve efficiency of the airway evaluation while also improving accuracy of diagnosis are needed to fully determine the clinical implications of these modalities. Finally, the bigger question remains, would early detection and treatment of precancerous lesions in the airway as a primary or a recurrent lesion changes the ultimate outcomes in patients.

Background Surgery may have a role when medical treatment alone is not successful in patients with multi-drug resistant (MDR) pulmonary tuberculosis (PTB). To document the role of resection in MDR PTB, we analyzed 4 years of our experience. Methods A retrospective review was performed on thirteen patients that underwent pulmonary resection for MDR PTB between May 1996 and February 2000. All patients had organisms resistant to many of the first-line drugs including isoniazid (INH) and rifampicin (RFP). Results The thirteen patients were 37.5±12.4 years old (mean±S.D.)(M:F=5:8), and their sputum was culture positive even with adequate medication for prolonged periods (109.7±132.0 months), resistant to 2-8 drugs including isoniazid and rifampin. All patients had localized lesion(s) and most (92.3%) had cavities. At least 3 sensitive anti-TB medications were started before surgery in all patients according to the drug sensitivity test. The preoperative FE1 was 2.37±0.83 L. Lobectomy was performed in 11 patients and pleuropneumonectomy in two. Postoperative mortality did not occur, but pneumonia occurred as a complication in one (7.7%). After 41.5±58.9 days (range 1~150 days) follow up, negative conversion of sputum culture was achieved in all patients within 5 months. Only one patient (7.7%) recurred 32 months after lung resection. Conclusion When medical treatment alone is not successful, surgical resection can be a good treatment option in patients with localized MDR PTB.

Detection and Localization of Early Lung Cancer by Imaging Techniques*

Background : Recently, medical treatment of multi-drug resistant pulmonary tuberculosis has been unsuccessful. Through analyzing the cases with surgical treatment, we hope to provide some help in treating multi-drug resistant pulmonary tuberculosis in the future. Material and Method : A retrospective review was performed with 138cases of surgical treatment of multi-drug resistant tuberculosis during 10years from January 1994 to December 2003 at National Masan Hospital. Results : The ratio of men to women, 5.1:1 indicates that there were more incidences in men. The number of the resistant drugs was 5.3 with a mean age of 42.6 years. Cavitary lesions on the plain chest X-rays were seen in 94cases (68.1%). 128cases had positive sputum culture preoperatively. Types of operations were 24 pnemonectomies, 83 lobectomies, 10 bilobectomies, 19 lobectomies with segmentectomies or wedge resections, 1 wedge resection, and 1 carvenoplasty. There was no death after operation. There were 6cases of air leakage over a week, 6cases of postoperative bleeding, 8cases of bronchopleural fistula and empyema, 16cases of dead space, 1case of atelectasis, 1case of wound infection, 1case of cyst as postoperative complication. Postoperative complication showed higher long-term negative conversion rate of 92.8%. Conclusion : There has been many discussions about operative indications, postoperative drug regimens, length of postoperative chemotherapy. In our study, we showed higher long-term success rate of postoperative chemotherapy with pulmonary resection on multi-drug resistant pulmonary tuberculosis.

Objective To explore the clinical effect of different scheme of moxifloxacin and levofloxacin for elderly multi drug resistant pulmonary tuberculosis. Methods 136 cases of elderly patients included in the study were randomly divided into the observation group 1 and observation group 2 with 68 cases in each group according to the sequence in group. The observation group 1 used moxifloxacin regimen for treatment of pulmonary tuberculosis while the observation group 2 used levofloxacin regimen. The two groups were treated for 18 months and observed the clinical curative effect, and the sputum negative, pulmonary lesions absorption, empty changes and adverse reactions. Results The total efficiency of the observation group 1 was 92.6%, which in the observation group 2 was 72.1%,the total efficiency of the two groups had a significant difference(χ2= 9.917,P= 0.002); the sputum negative conversion rate of the observation group 1 at the end of 3 months was significantly higher than that of the observation group 2(χ2= 4.115,P= 0.043),no significant difference was found at the other time points(all P> 0.05); after treatment, the obvious absorption+ absorption of lung lesion in the observation group 1 was 59 cases, accounting for 86.8%,that in observation group 2 was 48 cases, accounting for 70.6%,two groups of lung lesions absorption had significant difference(χ2= 5.303,P= 0.021); the pulmonary cavity closure+ reduced in the observation group 1 was 52 cases, accounting for 76.4%, that in the observation group 2 was 41 cases, accounting for 60.3%,with significant difference between the two groups(χ2= 4.115,P= 0.043);there was no significant difference in adverse reaction of the two groups(P> 0.05). Conclusion Moxifloxacin anti tuberculosis regimen has a better curative effect in treatment of elderly patients with multi drug resistant pulmonary tuberculosis, which should be expanded the application. Key words: Multidrug-resistant, tuberculosis; Moxifloxacin; Levofloxacin; Aged

Lung cancer remains the second most commonly diagnosed cancer globally and the leading cause of cancer-related deaths, a trend consistent in the United States as of 2023. One of the key reasons for the high mortality rate of lung cancer is its poor prognosis, with 75% of patients diagnosed at middle and advanced stages. Early detection of subclinical lung cancer, metastases, and their fibrotic stroma is crucial for enabling timely treatment, reducing reoccurrence, and stratifying patients. Current diagnostic methods, such as lung biopsy for patients with small nodules, are highly invasive and technically challenging. The radiological gold standard, computed tomography (CT), is associated with ionizing radiation. However, positron emission tomography (PET) and magnetic resonance imaging (MRI) have emerged as promising methodologies for lung cancer diagnosis. PET tracers with a variety of targeting mechanisms are currently under development in human trials. With advancements in hardware and software over the past decades, radiation-free MRI has been clinically and preclinically validated as an alternative to CT. Moreover, novel-targeted MRI contrast agents have been tested in animal models and show strong translational potential. In this review, we summarize the state-of-the-art progress in molecular imaging for the early detection of lung cancer and its potential biomarkers.

Lung cancer has the highest mortality rate among cancer patients in the world, in particular because most patients are only diagnosed at an advanced and noncurable stage. Computed tomography (CT) screening on high-risk individuals has shown that early detection could reduce the mortality rate. However, the still high false-positive rate of CT screening may harm healthy individuals because of unnecessary follow-up scans and invasive follow-up procedures. Alternatively, false-negative and indeterminate results may harm patients due to the delayed diagnosis and treatment of lung cancer. Noninvasive biomarkers, complementary to CT screening, could lower the false-positive and false-negative rate of CT screening at baseline and thereby reduce the number of patients that need follow-up and diagnose patients at an earlier stage of lung cancer. Lung cancer tissue generates lung cancer-associated proteins to which the immune system might produce high-affinity autoantibodies. This autoantibody response to tumor-associated antigens starts during early stage lung cancer and may endure over years. Identification of tumor-associated antigens or the corresponding autoantibodies in body fluids as potential noninvasive biomarkers could thus be an effective approach for early detection and monitoring of lung cancer. We provide an overview of differentially expressed protein, antigen, and autoantibody biomarkers that combined with CT imaging might be of clinical use for early detection of lung cancer.

P1.05-026 High Resolution Metabolomics on Exhaled Breath Condensate to Discover Lung Cancer's Biomarker

Blood-based liquid biopsy: Insights into early detection and clinical management of lung cancer.

Lung cancer continues to be the foremost cause of death in both women and men. Worldwide, lung cancer kills over 1 million peoples a year. The major cause of lung cancer is smoking. In India each year it is estimated that about 80% of male lung cancer deaths and 70% of lung cancer deaths are caused by smoking. Undoubtedly, lung cancer is a major threat to human beings and also a widespread disease which constitutes a major public health problem. Other possible factors for lung cancer are increased air pollution by dusts and gases released by industry, automobile traffic etc. Hence, lung cancer detection is one of the major needs of the day. Several researchers developed Image Processing Techniques (IPT) for the detection of Lung Cancer [, , , , , , , ]. Earlier researchers employed the methods like Discrete Cosine Transform (DCT), Auto Enhancement Algorithm (AEA), Fast Fourier Transform (FFT), for image enhancement. These approaches are time consuming and less accurate. Some of the researchers are also used Kalman Filters, Hessian Based Filters (HBF), but these filters have drawbacks like, varying contrast; poor and non-uniform response for images of varying sizes [, ]. Some of other researchers used interpolation techniques, which is complex and time consuming []. So, to overcome the drawbacks of these earlier approaches, a new image enhancement technique is proposed with modifications in Gabor Filters which will help in early and efficient detection of lung cancer. This Modified Gabor Filter (MGF) approach has been validated using CT (Computer Tomography) and X-ray lung images which are collected from a hospital and they are analysed. The results obtained are comparable with real time analysis of medical practitioners. Hence, this new technique for Image Enhancement using MGF Approach can be employed for early detection of lung cancer and this technique is also suitable for development of new medical equipment’s for better detection of lung cancer.