Surgical resection and survival of patients with unsuspected single node positive lung cancer (NSCLC) invading the descending aorta

Background: Surgical treatment of non-small cell lung cancer (NSCLC) with aortic invasion is still debated

Исследование процесса и разработка методологических основ безаварийного бурения под интервалы направлений и кондукторов на скважинах Восточно-Сибирского региона (на примере Куюмбинского ГКМ)»

Научный доклад содержит сформулированные выводы на основе реальных производственных результатов, а также разработаны обоснованные рекомендации по безаварийному строительству секций направлений и кондукторов для геологических условий Куюмбинского месторождения.The paper contains formulated conclusions based on real production results, and well-grounded recommendations for accident-free construction of sections of directions and conductors for the geological conditions of the Kuyumbinskoye field

Pulmonary cancers across different histotypes share hybrid tuft cell/ionocyte-like molecular features and potentially druggable vulnerabilities

Tuft cells are chemosensory epithelial cells in the respiratory tract and several other organs. Recent studies revealed tuft cell-like gene expression signatures in some pulmonary adenocarcinomas, squamous cell carcinomas (SQCC), small cell carcinomas (SCLC), and large cell neuroendocrine carcinomas (LCNEC). Identification of their similarities could inform shared druggable vulnerabilities. Clinicopathological features of tuft cell-like (tcl) subsets in various lung cancer histotypes were studied in two independent tumor cohorts using immunohistochemistry (n = 674 and 70). Findings were confirmed, and additional characteristics were explored using public datasets (RNA seq and immunohistochemical data) (n = 555). Drug susceptibilities of tuft cell-like SCLC cell lines were also investigated. By immunohistochemistry, 10–20% of SCLC and LCNEC, and approximately 2% of SQCC expressed POU2F3, the master regulator of tuft cells. These tuft cell-like tumors exhibited “lineage ambiguity” as they co-expressed NCAM1, a marker for neuroendocrine differentiation, and KRT5, a marker for squamous differentiation. In addition, tuft cell-like tumors co-expressed BCL2 and KIT, and tuft cell-like SCLC and LCNEC, but not SQCC, also highly expressed MYC. Data from public datasets confirmed these features and revealed that tuft cell-like SCLC and LCNEC co-clustered on hierarchical clustering. Furthermore, only tuft cell-like subsets among pulmonary cancers significantly expressed FOXI1, the master regulator of ionocytes, suggesting their bidirectional but immature differentiation status. Clinically, tuft cell-like SCLC and LCNEC had a similar prognosis. Experimentally, tuft cell-like SCLC cell lines were susceptible to PARP and BCL2 co-inhibition, indicating synergistic effects. Taken together, pulmonary tuft cell-like cancers maintain histotype-related clinicopathologic characteristics despite overlapping unique molecular features. From a therapeutic perspective, identification of tuft cell-like LCNECs might be crucial given their close kinship with tuft cell-like SCLC

WNT4 overexpression and secretion in thymic epithelial tumors drive an autocrine loop in tumor cells in vitro

BackgroundWNT4-driven non-canonical signaling is crucial for homeostasis and age-related involution of the thymus. Abnormal WNT signaling is important in many cancers, but the role of WNT signaling in thymic tumors is largely unknown.Materials & MethodsExpression and function of WNT4 and FZD6 were analyzed using qRT–PCR, Western blot, ELISA, in biopsies of non-neoplastic thymi (NT), thymoma and thymic carcinomas. ShRNA techniques and functional assays were used in primary thymic epithelial cells (pTECs) and TC cell line 1889c. Cells were conventionally (2D) grown and in three-dimensional (3D) spheroids.ResultsIn biopsy, WHO classified B3 thymomas and TCs showed increased WNT4 expression compared with NTs. During short-term 2D culture, WNT4 expression and secretion declined in neoplastic pTECs but not in 3D spheroids or medium supplemented with recombinant WNT4 cultures. Under the latter condition, the growth of pTECs was accompanied by increased expression of non-canonical targets RAC1 and JNK. Down-regulation of WNT4 by shRNA induced cell death in pTECs derived from B3 thymomas and led to decreased RAC1, but not JNK protein phosphorylation. Pharmacological inhibition of NF-κB decreased both RAC1 and JNK phosphorylation in neoplastic pTECs.ConclusionsLack of the age-related decline of non-canonical WNT4 expression in TETs and restoration of declining WNT4 expression through exogeneous WNT4 or 3D culture of pTECs hints at an oncogenic role of WNT4 in TETs and is compatible with the WNT4 autocrine loop model. Crosstalk between WNT4 and NF-κB signaling may present a promising target for combined interventions in TETs

Evaluation of the Value of Contrast-Enhanced Ultrasound (CEUS) within Radiology Departments in Germany

Purpose Contrast-enhanced ultrasound (CEUS) has been established for many years and has become an increasingly important cornerstone of the diagnostic imaging of various organ systems. However, this modality is rarely performed by radiologists and is primarily employed by other medical disciplines. The goal of this questionnaire study is to present the current value of CEUS in radiology and to encourage reevaluation of the method within this medical discipline. Materials and Methods 560 directors of radiology departments throughout Germany were contacted and given a 3-page questionnaire. The questionnaire included 37 questions on 5 different topics (general structures, CEUS and interdisciplinarity, CEUS in pediatric radiology, education/professional development, outlook) to assess the value of ultrasound (US) and in particular CEUS in radiology. Results The response rate was 42.3 %. A statistical analysis of the answers was performed, including subgroup analysis. Overall, it could be shown that CEUS is performed in comparatively few radiology departments (26.6 %), while the current value of the modality is given an average to high range of importance even by radiologLs. More than half of all participating radiologists (54.9 %) would like this method to be included in the requirements catalog for the specialist examination. Conclusion The nationwide questionnaire to evaluate CEUS within radiology departments in Germany had a very high response rate, which reflects the assessment of this topic by radiologists. There is a substantial discrepancy between the currently low utilization of CEUS in radiology and the high ranking of CEUS by many radiologists. The analyses of the replies point out important aspects of professional policy regarding this topic within the radiology community

Analysis of vascularization in thyroid gland nodes with superb microvascular imaging (SMI) and CD34 expression histology: a pilot study

Background!#!The Doppler sonography technique known as 'superb microvascular imaging' (SMI) is advancing sonographic micro vascularization imaging in various disciplines. In this study, we aimed to determine whether SMI could reliably reproduce the blood flow in thyroid nodes and whether malignancy could be diagnosed, based on vascularization properties. Immunhistochemical staining by CD34 and SMI where used to determine the vascularization of nodes in terms of quantified vascularization parameters gained by computational evaluation.!##!Methods!#!We used image analysis programs to investigate whether the quantitative value for vascularization strength in the thyroid node, measured with SMI, was correlated with the actual degree of vascularization, determined microscopically. We included 16 patients that underwent thyroid resections. We prepared thyroid gland tissue slices for immunohistochemistry and labelled endothelial cells with CD34 to visualize blood vessels microscopically. We used image analysis programs, ImageJ, to quantify SMI Doppler sonographic measurements and CellProfiler to quantify CD34 expression in histological sections. We evaluated the numeric values for diagnostic value in node differentiation. Furthermore, we compared these values to check for correlations.!##!Results!#!Among the 16 nodes studied, three harboured malignant tumours (18.75%): two papillary and one follicular carcinoma. Among the 13 benign lesions (81.25%), four harboured follicular adenomas. Malignant and benign nodes were not significantly different in sonographic (0.88 ± 0.89 vs. 1.13 ± 0.19; p = 0.2790) or immunohistochemical measurements of vascularization strength (0.05 ± 0.05 vs. 0.08 ± 0.06; p = 0.2260).!##!Conclusion!#!We found a positive, significant correlation (r = 0.55588; p = 0.0254) between SMI (quantitative values for vascularization strength) and immunohistochemistry (CD34 staining) evaluations of thyroid nodes

Laser assisted pulmonary metastasectomy promises a low local recurrence rate

Abstract Pulmonary metastasectomy (PM) is consensually performed in a parenchyma-sparing manner to preserve functionally healthy lung tissue. However, this may increase the risk of local recurrence at the surgical margin. Laser assisted pulmonary metastasectomy (LPM) is a relatively recent innovation that is especially useful to resect multiple metastatic pulmonary nodules. In this study we investigated the rate of local recurrence after LPM and evaluated the influence of various clinical and pathological factors on local recurrence. Retrospectively, a total of 280 metastatic nodules with different histopathological entities were studied LPM from 2010 till 2018. All nodules were resected via diode-pumped neodymium: yttrium–aluminum-garnet (Nd:YAG) 1,318 nm laser maintaining a safety margin of 5 mm. Patients included were observed on average for 44 ± 17 months postoperatively. Local recurrence at the surgical margin following LPM was found in 9 nodules out of 280 nodules (3.21%). Local recurrence at the surgical margin occurred after 20 ± 8.5 months post operation. Incomplete resection (p =  < 0.01) and size of the nodule (p = < 0.01) were associated with significantly increased risk of local recurrence at the surgical margin. Histology of the primary disease showed no impact on local recurrence. Three and five-year survival rates were 84% and 49% respectively. Following LPM, the rate of local recurrence is low. This is influenced by the size of the metastatic nodules and completeness of the resection. Obtaining a safety margin of 5 mm seems to be sufficient, larger nodules require larger safety margins