Primary mediastinal germ cell tumors are a rare finding, and one third of them are seminomas. Seminomas are found in the anterior mediastinum, whereas they are extremely rare within the posterior ...compartment. Most clinicians would not consider a primary seminoma in the differential diagnosis of a posterior mediastinal mass, as only two cases have been reported in literature. Here we present the case of a 57-year-old male with a primary seminoma arising in the left posterior mediastinum. He was asymptomatic and the mass was an incidental finding. Positron emission tomography (PET) revealed a small area with an avid tracer uptake. Transthoracic needle aspiration led to a non-diagnostic result. Due to the strong suspect of malignancy, a surgical excision was chosen to obtain a diagnosis. He underwent complete excision, and pathology report demonstrated a mediastinal seminoma. Subsequent further staging did not reveal any other location of the disease. Given the complete excision of the primary tumor, active surveillance was the treatment of choice. The patient is free of disease 48 months after diagnosis.
Background
In advanced non–small cell lung cancer (NSCLC), cytologic specimens from transbronchial needle aspiration (TBNA) or transthoracic needle aspiration are often the only cancer tissue ...material available for the analysis of programmed death ligand 1 (PD‐L1) expression. This study was aimed at assessing the concordance of PD‐L1 expression in histologic and cytologic samples and at evaluating interobserver agreement on specimens in this setting.
Methods
One hundred and thirty‐eight specimens from 60 patients with NSCLC were analyzed. Histologic specimens were represented by endoscopic samples obtained with forceps (biopsies), whereas cytologic specimens were from TBNA and bronchial lavage (BL). PD‐L1 expression was quantified with the immunohistochemistry (IHC)‐based Ventana SP263 assay. For cytologic specimens, IHC was performed on cell block sections. Two independent pathologists who were blinded to the clinical data evaluated partial or complete membrane IHC staining. Concordance between 2 methods and between 2 pathologists was evaluated with normal and weighted Cohen's κ coefficients, overall agreement, and Bland‐Altman plots.
Results
PD‐L1 expression was quantified in 138 specimens from 60 patients. Concordance between cytologic and histologic approaches was moderate (κ = 0.56; weighted κ = 0.55). Also, concordance in the biopsy‐TBNA and biopsy‐BL subgroups was moderate (κ = 0.43 and κ = 0.47, respectively), whereas interobserver agreement was substantial (weighted κ = 0.72). A Bland‐Altman plot showed an underestimation in PD‐L1 values from cytologic samples in comparison with histologic ones.
Conclusions
The results demonstrate that in the absence of available histologic specimens, PD‐L1 positivity in cytologic samples could be a reliable data for the oncologist to consider immune checkpoint inhibitor therapy. However, a comparison of cytologic and histologic samples has shown an underestimation of PD‐L1 values in cytologic samples.
Cytologic samples from transbronchial needle aspiration and bronchial lavage are valid for determining programmed death ligand 1 (PD‐L1) expression. However, cytologic PD‐L1 assessment should be used only when histologic specimens are not available because of difficulties in interpretation and possible underestimation.
Aims
High mobility group box 1 (HMGB1) is a chromatin structural protein, expressed ubiquitously in the nuclei of mammalian cells. When transported extracellularly, it acts as a tumour suppressor and ...oncogenic protein. In malignant pleural mesothelioma (MPM), high serum levels of HMGB1 have been related to a poor prognosis. Conversely, the significance of HMGB1 expression in MPM tissues is still unclear.
Methods and results
Biopsy samples from 170 patients with MPM were assessed by immunohistochemistry and reverse transcription–polymerase chain reaction (RT–PCR) to evaluate HMGB1 protein and gene expression. The expression level of HMGB1 protein was scored using a semiquantitative system that sums the intensity (0–3) and the percentage (from 0 to 4) of positively stained cells in nuclei, cytoplasm and in both. The final score was considered as high (>3) or low (<3) expression. Gene expression levels were calculated using the ΔΔCt method. High expression levels of HMGB1 as total (P = 0.0011) and cytoplasmic score (P = 0.0462) were related to a worse disease‐specific survival (DSS) in the entire cohort and in the clinicopathological subgroups. No significant correlation was found between HMGB1 gene expression and DSS.
Conclusions
These findings indicate that HMGB1 may be a useful prognostic biomarker in MPM when detected by immunohistochemistry. Conversely, as it is also expressed in normal and reactive mesothelial cells, HMGB1 cannot be considered a diagnostic biomarker in histological samples of mesothelioma.
Boosting antitumor immunity has emerged as a powerful strategy in cancer treatment. While releasing T‐cell brakes has received most attention, tumor recognition by T cells is a pre‐requisite. ...Radiotherapy and certain cytotoxic drugs induce the release of damage‐associated molecular patterns, which promote tumor antigen cross‐presentation and T‐cell priming. Antibodies against the “do not eat me” signal CD47 cause macrophage phagocytosis of live tumor cells and drive the emergence of antitumor T cells. Here we show that CXCR4 activation, so far associated only with tumor progression and metastasis, also flags tumor cells to immune recognition. Both CXCL12, the natural CXCR4 ligand, and BoxA, a fragment of HMGB1, promote the release of DAMPs and the internalization of CD47, leading to protective antitumor immunity. We designate as Immunogenic Surrender the process by which CXCR4 turns in tumor cells to macrophages, thereby subjecting a rapidly growing tissue to immunological scrutiny. Importantly, while CXCL12 promotes tumor cell proliferation, BoxA reduces it, and might be exploited for the treatment of malignant mesothelioma and a variety of other tumors.
Synopsis
Induction of antitumor immunity is a successful strategy in cancer treatment. This study reports that BoxA, a fragment of the alarmin HMGB1, induces tumor remission and antitumor immunity in mouse models of mesothelioma and colon carcinoma.
Both BoxA and the chemokine CXCL12 bind the G‐Protein Coupled Receptor CXCR4.
CXCR4 and CD47 are in contact on the surface of tumor cells and co‐internalize upon CXCR4 engagement by either BoxA or CXCL12.
Both CXCL12 and BoxA induce the phagocytosis of tumor cells by macrophages.
BoxA inhibits tumor cell growth and induces antitumor immunological memory in syngeneic mouse models of mesothelioma or colon carcinoma.
CXCL12 is suggested to mediate a similar response (Immunogenic Surrender) in a fraction of untreated tumor‐bearing mice.
Induction of antitumor immunity is a successful strategy in cancer treatment. This study reports that BoxA, a fragment of the alarmin HMGB1, induces tumor remission and antitumor immunity in mouse models of mesothelioma and colon carcinoma.
Sarcopenia is a skeletal muscle disorder characterized by reduced muscle mass, strength, and performance. Muscle ultrasound can be helpful in assessing muscle mass, quality, and architecture, and ...thus possibly useful for diagnosing or screening sarcopenia. The objective of this study was to evaluate the reliability of ultrasound assessment of tibialis anterior muscle in sarcopenia diagnosis. We included subjects undergoing total or partial hip replacement, comparing measures with a healthy control group. We measured the following parameters: tibialis anterior muscle thickness, echogenicity, architecture, stiffness, skeletal muscle index (SMI), hand grip strength, and sarcopenia related quality of life evaluated through the SarQoL questionnaire. We included 33 participants with a mean age of 54.97 ± 23.91 years. In the study group we found reduced tibialis anterior muscle thickness compared to the healthy control group (19.49 ± 4.92 vs. 28.94 ± 3.63 mm, p < 0.05) with significant correlation with SarQoL values (r = 0.80, p < 0.05), dynamometer hand strength (r = 0.72, p < 0.05) and SMI (r = 0.76, p < 0.05). Moreover, we found reduced stiffness (32.21 ± 12.31 vs. 27.07 ± 8.04 Kpa, p < 0.05). AUC measures of ROC curves were 0.89 predicting reduced muscle strength, and 0.97 predicting reduced SMI for tibialis anterior muscle thickness, while they were 0.73 and 0.85, respectively, for muscle stiffness. Our findings showed that ultrasound assessment of tibialis anterior muscle might be considered a reliable measurement tool to evaluate sarcopenia.
Despite the use of robotics becoming increasingly popular among thoracic surgeons worldwide, there remains debate over the best robotic approach for lung resections. In this paper, we delineated the ...main port placement strategies and discussed their advantages and disadvantages.
A PubMed literature review was performed using key phrases such as "robotic lobectomy technique", "RATS lobectomy", and "port placement robotic lobectomy". After the final review, 22 articles were included as references, of which 10 described common robotic port mapping techniques.
Several port strategies for robot-assisted pulmonary lobectomies have been proposed and described in the literature, each showing its own limitations and advantages.
New robotic surgeons may choose their port strategy according to personal preference and previous surgical experience, especially regarding open or VATS resections. Robust data comparing different port placements in robotic surgery are lacking. Further research should be directed toward comparisons of clinical outcomes with different robotic approaches.
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs ...(miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort, we screened the whole miRNome in serum extracellular vesicles (EVs) of preclinical MPM cases. In a subgroup of 20 preclinical samples collected five years prior MPM diagnosis, we observed an upregulation of miR-11400 (fold change (FC) = 2.6, adjusted
-value = 0.01), miR-148a-3p (FC = 1.5,
-value = 0.001), and miR-409-3p (FC = 1.5,
-value = 0.04) relative to matched controls. The 3-miRNA panel showed a good classification capacity with an area under the receiver operating characteristic curve (AUC) of 0.81 (specificity = 0.75, sensitivity = 0.70). The diagnostic ability of the model was also evaluated in an independent retrospective cohort, yielding a higher predictive power (AUC = 0.86). A signature of EV miRNA can be detected up to five years before MPM; moreover, the identified miRNAs could provide functional insights into the molecular changes related to the late carcinogenic process, preceding MPM development.
Abstract The effects on long-term post-operative quality of life (QoL) and disease-control in malignant pleural mesothelioma (MPM) of extrapleural pneumonectomy (EPP) and pleurectomy/decortication ...(P/D) are compared. Seventy-seven patients affected by early-stage MPM received EPP (40) or P/D (37) associated with multimodal treatment between 1998 and 2009 at our institution. The last consecutive 39 (19 EPP and 20 P/D) were asked to answer the EORTC-QLQ-C30 questionnaire at baseline and at 6- and 12-months after treatment completion to evaluate the impact on QoL of both procedures. QoL evaluation was stopped at recurrence demonstration. Twenty-five (62%) EPP vs 9 (24%) P/D patients ( p = 0.002) had in-hospital major complications, and 2/40 (5%) EPP vs no one P/D patients died after surgery. Both procedures caused a significant impairment of all the considered variables of the EORTC-QLQ-C30 questionnaire after treatment completion; only P/D patients returned at baseline levels after12 months. EPP patients had a worse long-term post-operative QoL when compared with P/D. Median post-operative disease-free period was longer for EPP patients (14 vs 11 months) whereas the residual life to death period after recurrence detection was significantly longer for P/D patients (13 vs 9 months) ( p = 0.01). Median long-term survival was longer, even not significant, for P/D patients (25 vs 20 months). MPM patients submitted to EPP had a higher post-operative complication rate, a worse long-term QoL, a shorter residual life time after recurrent disease, despite a similar long-term survival when compared to P/D.
Malignant Pleural Mesothelioma (MPM) is a heterogeneous disease. Morphologically, three different phenotypes are distinguishable: epithelioid (e-), sarcomatoid (s-) and biphasic (biph-) MPM, the ...latest, being a mixture of e- and s-MPM cells. Being an intermediate entity, management of biph-MPM, remains debatable and controversial, with different guidelines recommending distinct approaches. Identification of biph-MPM associated genetic alterations, through deep sequencing analysis, may provide useful tools to understand these lesions. A retrospective cohort of 69 surgically resected MPMs, 39 biph-MPMs (56.5%) and 30 e-MPMs (43.5%) was selected. A separate set of 16 biph-MPM was used as validation set. Deep sequencing analysis on an MPM-specific custom panel (MPM_geneset) comprising 1041 amplicons spanning 34 genes was performed. A total of 588 variants and 5309 mutational events were detected. In total, 91.3% of MPMs showed at least one mutation and 76.8% showed co-occurrence of more than one alteration. Mutations in MXRA5 (p = 0.05) and NOD2 (p = 0.018) were significantly associated with biph-MPM both in the training and validation cohort and correlated with the extent of the sarcomatoid component. Mutations in NOD2 and XRCC6 correlated with patients’ survival. We demonstrated that biph-MPM are associated with a specific mutation set, and that genetic analysis at diagnosis may improve patients’ risk stratification.
Background To investigate the prognostic effect of persistent lung expansion after pleural talcage and other variables in non-surgically resected malignant pleural mesothelioma (MPM) patients. ...Methods All consecutive patients submitted to video-assisted thoracoscopic (VAT) pleurodesis by talc poudrage for MPM between 2006 and 2011 were studied. The following parameters were prospectively recorded: age; sex; smoking history; asbestos exposure; C-reactive protein (CRP) levels; platelet (PLT) count; Eastern Cooperative Oncology Group performance status (ECOG PS); histologic subtype; clinical stage (cStage); chemotherapy; pleural fluid volume; and persistence of lung expansion at 3 months follow-up. Survival was assessed in June 2013. Results A total of 172 patients were considered; 146 of 172 patients demonstrated a complete lung expansion at discharge, whereas only 85 of 172 patients had persistent expanded lung on the affected side at the 3-month follow-up chest x-ray. Median survival was 11.5 months (95% confidence interval CI, 10% to 14%) and 2-year disease-specific survival was 13% (95% CI, 7% to 24%) for the entire cohort. Multivariate analysis showed that non-epithelioid histology (hazard ratio HR, 2.81; 95% CI, 1.82% to 5.09%), pleural fluid recurrence (HR 2.54; 95% CI, 1.73% to 4.40%), cStage greater than II (HR 2.36; 95% CI, 1.50% to 4.32%), ECOG PS greater than 1 (HR 2.19; 95% CI, 1.26% to 4.23%), CRP greater than 5 mg/L (HR 2.01; 95% CI, 1.18% to 4.12%), and PLT count greater than 400,000 (HR 1.76; 95% CI 1.14% to 3.92%) were independent predictors of poor prognosis. Conclusions Persistent lung expansion after pleural talc poudrage and absence of fluid recurrence is demonstrated to be a stronger factor in predicting survival rather than clinical stage and other clinical variables in not surgically resected MPM patients.
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