Premalignant changes in the bronchial epithelium are prognostic factors of distant metastasis in non-small cell lung cancer patients

Background: The 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. Methods: In 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. Results: During 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. Conclusions: Isolated BCH or dysplasia in small bronchi distant from foci of tumor isassociated with a high-risk distant metastasis and less 5-year metastasis-free survival

Пульмональный Лангергансоклеточный гистиоцитоз легких: клиническое наблюдение в стадии раннего поражения

Histocytosis X is a rare disease of unknown etiology involving the reticuloendothelial system. We present a case of a 32 year-old man diagnosed with Pulmonary Histocytisis X. The CT image of the lungs showed disseminated disease with the formation of cyst-like cavities, which were histologically verified using lung biopsy. Лангергансоклеточный гистиоцитоз (гистиоцитоз Х) – заболевание ретикулогистиоцитарной системы неизвестной этиологии. Представлен клинический случай данной патологии у мужчины 32 лет с характерной компьютерно-томографической картиной легких в виде диссеминированного процесса с формированием кистозных полостей, который верифицирован морфологически с помощью биопсии легких.

Pulmonary histocytosis X: clinical observation of early-stage disease

Histocytosis X is a rare disease of unknown etiology involving the reticuloendothelial system. We present a case of a 32 year-old man diagnosed with Pulmonary Histocytisis X. The CT image of the lungs showed disseminated disease with the formation of cyst-like cavities, which were histologically verified using lung biopsy

Personalized Prescription of Chemotherapy Based on Assessment of mRNA Expression of BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBβ3, TYMS, and GSTP1 Genes in Tumors Compared to Standard Chemotherapy in the Treatment of Non-Small-Cell Lung Cancer

Objectives: A growing body of evidence suggests the important role of chemosensitive gene expression in the prognosis of patients with lung cancer. However, studies on combined gene expression assessments for personalized prescriptions of chemotherapy regimens in patients have not yet been conducted. The aim of this work was to conduct a prospective study on the appointment of personalized chemotherapy in patients with non-small-cell lung cancer. Materials and methods: The present study analyzed 85 patients with lung cancer (stage IIB-IIIB). Within this group, 48 patients received individualized chemotherapy, and 37 patients received classical chemotherapy. In the individualized chemotherapy group, the mRNA expression levels of ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 in lung tissues were measured by quantitative real-time PCR (qPCR), and an individual chemotherapy regimen was developed for each patient according to the results. Patients in the classical chemotherapy group received the vinorelbine/carboplatin regimen. Survival analyses were performed using the Kaplan–Meier method. Prognostic factors of metastasis-free survival (MFS) and overall survival (OS) of patients were identified via Cox’s proportional hazards regression model. Results: MFS and OS were significantly better in the personalized chemotherapy group compared to the classic chemotherapy group (MFS, 46.22 vs. 22.9 months, p = 0.05; OS, 58.6 vs. 26.9 months, p < 0.0001). Importantly, the best metastasis-free survival rates in the group with personalized ACT were achieved in patients treated with the paclitaxel/carboplatin regimen. Based on an assessment of chemosensitivity gene expression in the tumors, the classical chemotherapy strategy also increased the risk of death (HR = 14.82; 95% CI: 3.33–65.86; p < 0.000) but not metastasis (HR = 1.95; 95% CI: 0.96–3.98; p = 0.06) compared to the group of patients with chemotherapy. Conclusions: The use of combined ERCC1, RRM1, TUBB3, TYMS, TOP1, TOP2α, BRCA1, and GSTP1 gene expression results for personalized chemotherapy can improve treatment efficacy and reduce unnecessary toxicity

Dynamic changes in circulating miRNA levels in response to antitumor therapy of lung cancer

<p><b>Purpose:</b> Expression levels of cancer-associated microRNAs were reported to be altered in serum/plasma samples from lung cancer patients compared with healthy subjects. The purpose of this study was to estimate the value of five selected miRNAs plasma levels as markers of response to antitumor therapy in lung cancer patients. <b>Materials and Methods:</b> Expression levels of miR-19b, miR-126, miR-25, miR-205, and miR-125b have been evaluated by quantitative reverse transcription PCR versus control miR-16 in blood plasma samples from 23 lung cancer (LC) patients. Plasma samples were obtained from LC patients before treatment (untreated-UT), within 30 days after completing two courses of chemotherapy (postchemotherapy-PC) and 15 days after surgery (postoperative-PO). <b>Results:</b> Repeated Measures ANOVA demonstrated that miR-19b expression levels were decreased in PC and increased in PO samples. These changes were characterized by a significant quadratic trend (<i>p</i> = 0.03). Expression levels of miR-125b increased both after chemotherapy and again after surgery and demonstrated a significant linear trend (<i>p</i> = 0.03). The miR-125b/miR-19b ratio changed during the course of the antitumor treatment with a significant linear trend (<i>p</i> = 0.04). Individual analysis in the groups of patients with partial response to chemotherapy and patients with stable or progressive disease showed different trends for miR-19b, miR-125b, and miR-125b/miR-19b ratio between the groups. The Kaplan–Meier survival curves demonstrated an association of miR-125b/miR-19b ratio value with the survival time without the tumor relapse (<i>p</i> < 0.1). <b>Conclusions:</b> Dynamic change of trends for miR-19b and miR-125b expression levels and miR-125b/miR-19b ratio in the blood plasma have shown a potentiality to discriminate types of response to antitumor therapy in lung cancer patients. Further in-depth investigation is needed to establish a direct link the miRNAs expression levels in blood plasma with therapy response and patient's survival.</p