Ki67 Tumor Expression Predicts Treatment Benefit Achieved by Macroscopic Radical Lung-Preserving Surgery in Pleural Mesothelioma-A Retrospective Multicenter Analysis.

Pleural mesothelioma (PM), linked to asbestos-induced inflammation, carries a poor prognosis. Therapy ranges from therapy limitation to aggressive multimodality treatment. Given the uncertainty about treatment benefits for patients, this study aimed to assess the role of Ki67 as a prognostic and predictive parameter in PM. Ki67 was measured in the specimens of 70 PM patients (17 female, 53 male) from two centers and correlated to overall survival (OS) and therapy outcome. The median OS was 16.1 months. The level of Ki67 expression was divided into low (≤15%) and high (>15%). A low value of Ki67 expression was associated with a longer OS (Ki67 ≤ 15%: 31.2 (95% CI 6.5-55.8) months vs. Ki67 > 15%: 11.1 (95% CI 7.7-14.6) months, p = 0.012). The 5-year survival represents 22% in the low Ki67 expression group, in contrast to 5% in the high Ki67 expression group. We found a significant interaction term of Ki67 with multimodality treatment (p = 0.031) translating to an OS of 48.1 months in the low expression Ki67 group compared to 24.3 months in the high Ki67 expression group when receiving surgery within multimodality therapy. Therefore, Ki67 stands out as a validated prognostic and, most importantly, novel predictive biomarker for treatment benefits, particularly regarding surgery within multimodality therapy.

Development of a localization-based algorithm for the prediction of leg ulcer etiology.

BACKGROUND: Diagnostic work-up of leg ulcers is time- and cost-intensive. This study aimed at evaluating ulcer location as a diagnostic criterium and providing a diagnostic algorithm to facilitate differential diagnosis. PATIENTS AND METHODS: The study consisted of 277 patients with lower leg ulcers. The following five groups were defined: Venous leg ulcer, arterial ulcers, mixed ulcer, arteriolosclerosis, and vasculitis. Using computational surface rendering, predilection sites of different ulcer types were evaluated. The results were integrated in a multinomial logistic regression model to calculate the likelihood of a specific diagnosis depending on location, age, bilateral involvement, and ulcer count. Additionally, neural network image analysis was performed. RESULTS: The majority of venous ulcers extended to the medial malleolar region. Arterial ulcers were most frequently located on the dorsal aspect of the forefoot. Arteriolosclerotic ulcers were distinctly localized at the middle third of the lower leg. Vasculitic ulcers appeared to be randomly distributed and were markedly smaller, multilocular and bilateral. The multinomial logistic regression model showed an overall satisfactory performance with an estimated accuracy of 0.68 on unseen data. CONCLUSIONS: The presented algorithm based on ulcer location may serve as a basic tool to narrow down potential diagnoses and guide further diagnostic work-up.

Validation of Inflammatory Prognostic Biomarkers in Pleural Mesothelioma.

Evoked from asbestos-induced inflammation, pleural mesothelioma represents a fatal diagnosis. Therapy ranges from nihilism to aggressive multimodality regimens. However, it is still unclear who ultimately benefits from which treatment. We aimed to re-challenge inflammatory-related biomarkers' prognostic value in times of modern immune-oncology and lung-sparing surgery. The biomarkers (leukocytes, hemoglobin, platelets, neutrophils, lymphocytes, monocytes, neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), C-reactive protein (CRP)) and clinical characteristics (age, sex, histology, therapy) of 98 PM patients were correlated to overall survival (OS). The median OS was 19.4 months. Significant OS advantages (Log-Rank) were observed in multimodal treatment vs. others (26.1 vs. 7.2 months, p < 0.001), surgery (pleurectomy/decortication) vs. no surgery (25.5 vs. 3.8 months, p < 0.001), a high hemoglobin level (cut-off 12 g/dL, 15 vs. 24.2 months, p = 0.021), a low platelet count (cut-off 280 G/L, 26.1 vs. 11.7 months, p < 0.001), and a low PLR (cut-off 194.5, 25.5 vs. 12.3 months, p = 0.023). Histology (epithelioid vs. non-epithelioid, p = 0.002), surgery (p = 0.004), CRP (cut-off 1 mg/dL, p = 0.039), and platelets (p = 0.025) were identified as independent prognostic variables for this cohort in multivariate analysis (Cox regression, covariates: age, sex, histology, stage, CRP, platelets). Our data verified the previously shown prognostic role of systemic inflammatory parameters in patients treated with lung-sparing surgery within multimodality therapy.

Lymph but Not Blood Vessel Invasion Is Independent Prognostic in Lung Cancer Patients Treated by VATS-Lobectomy and Might Represent a Future Upstaging Factor for Early Stages.

Lung cancer is the most frequent cause of cancer-related death worldwide. The patient's outcome depends on tumor size, lymph node involvement and metastatic spread at the time of diagnosis. The prognostic value of lymph and blood vessel invasion, however, is still insufficiently investigated. We retrospectively examined the invasion of lymph vessels and blood vessels separately as two possible prognostic factors in 160 patients who underwent a video-assisted thoracoscopic lobectomy for non-small-cell lung cancer at our institution between 2014 and 2019. Lymph vessel invasion was significantly associated with the UICC stage, lymph node involvement, tumor dedifferentiation, blood vessel invasion and recurrence. Blood vessel invasion tended to be negative prognostic, but missed the level of significance (p = 0.108). Lymph vessel invasion, on the other hand, proved to be a prognostic factor for both histological subtypes, adenocarcinoma (p < 0.001) as well as squamous cell carcinoma (p = 0.018). After multivariate analysis apart from the UICC stage, only lymph vessel invasion remained independently prognostic (p = 0.018). Remarkably, we found analogue survival curve progressions of patients with stage I, with lymph vessel invasion, compared to stage II non-small-cell lung cancer. After further validation in prospective studies, lymph vessel invasion might be considered as an upstaging factor in resectable lung cancer. Especially in the early-stage of the disease, it might represent an additional risk factor to consider adjuvant therapy after surgical resection.

Transbronchial lung cryobiopsy: prospective safety evaluation and 90-day mortality after a standardized examination protocol.

BACKGROUND: Transbronchial lung cryobiopsy (TBLC) is a new method of bronchoscopic tissue sampling in patients with unclear diffuse parenchymal lung disease (DPLD). While not the gold standard, TBLC has a good diagnostic correlation with surgical lung biopsy, and retrospective analyses of peri-interventional complications and mortality are promising. However, prospective reports on 90-day mortality are lacking. OBJECTIVES: This study addresses morbidity and 30- and 90-day mortality in TBLC after a standardized protocol. METHODS: In this prospective study, 75 patients with DPLD requiring tissue sampling were included. A standardized protocol (including prophylactic use of an endobronchial balloon, postinterventional observation, and minimum sampling requirements) was used in all patients. Adverse events (pneumothorax, bronchial bleeding, premature discontinuation, prolonged monitoring at ICU, and fatal outcome) and 30- and 90-day mortality rates were recorded. RESULTS: A total of 308 cryobiopsies were performed in 75 patients. Peri- and postinterventional pneumothorax were observed in 20% (9.3% mild and 10.7% moderate with the necessity of chest drainage), and bronchial bleeding was found in 29.3% (22.7% moderate and 6.7% severe). Total lung capacity below normal value was associated with the risk of pneumothorax (p = 0.009), and diffusion limitation for carbon monoxide below normal value was associated with the risk of bronchial bleeding (p = 0.044). No fatal events were observed within 30 days, and the 90-day mortality rate was 1.3%, but not related to the procedure itself. CONCLUSION: As it gradually becomes the invasive procedure of choice in unclear DPLD, TBLC is a safe procedure with a low 30- and 90-day mortality.Trial registration ID: DRKS00026746 (German Clinical Trial Register).

Tumour cell PD-L1 expression is prognostic in patients with malignant pleural effusion: the impact of C-reactive protein and immune-checkpoint inhibition.

Malignant pleural effusion (MPE) confers dismal prognosis and has limited treatment options. While immune-checkpoint inhibition (ICI) proved clinical efficacy in a variety of malignancies, data on the prognostic role of PD-L1 in MPE is scarce. We retrospectively studied PD-L1 tumour proportion score and Ki-67 index in pleural biopsies or cytologies from 123 patients (69 lung cancer, 25 mesothelioma, and 29 extrathoracic primary malignancies). Additionally, the impact of C-reactive protein (CRP) and platelet count was also analysed. Median overall survival (OS) after MPE diagnosis was 9 months. Patients with PD-L1 positive tumours (≥1%) had significantly shorter OS than patients with negative PD-L1 status (p = 0.031). CRP and Ki-67 index were also prognostic and remained independent prognosticators after multivariate analysis. Interestingly, Ki-67 index and CRP influenced the prognostic power of PD-L1. Finally, patients receiving ICI tended to have a longer median OS and CRP - but not PD-L1 - was a significant prognosticator in this subgroup. In summary, histological and circulating biomarkers should also be taken into account as potential biomarkers in ICI therapy and they may have an impact on the prognostic power of PD-L1. Our findings might help personalizing immune-checkpoint inhibition for patients with MPE and warrant further prospective validation.

First record of the genus Echthronomas Forster, 1869 (Hymenoptera, Ichneumonidae, Campopleginae) for the fauna of Ukraine.

The genus Echthronomas Forster, 1869 and two species, Echthronomasfacialis (Thomson, 1887) and Echthronomasquadrinotata (Thomson, 1887), are recorded for the fauna of Ukraine for the first time. Descriptions and photographs of species are provided.

A review of the subfamily Acaenitinae Förster, 1869 (Hymenoptera, Ichneumonidae) from Ukrainian Carpathians.

Ichneumonid wasps of the subfamily Acaenitinae Förster, 1869 are reviewed for the first time from the Ukrainian Carpathians. Two species, Coleocentrusexareolatus Kriechbaumer, 1894 and Coleocentrusheteropus Thomson, 1894 are new records for Ukraine. Arotesannulicornis Kriechbaumer, 1894 is considered to be a junior synonym of Arotesalbicinctus Gravenhorst, 1829 (syn. nov.). A key to species of Coleocentrus of the Carpathians is provided.