Acrometastasis from an epidermal-growth-factor-receptor (EGFR) mutation-positive lung adenocarcinoma

AbstractWe report the first case of epidermal-growth-factor-receptor (EGFR) mutation-positive lung adenocarcinoma with acrometastasis in a 51-year-old woman who presented with a swelling on her right hand. Magnetic resonance imaging revealed an expansile lesion at the base of the 5th metacarpal bone of her right hand with cortical erosion and patchy enhancement suggestive of a malignant transformation of a giant-cell tumor. A core needle biopsy of this lesion showed a metastatic adenocarcinoma on histopathological examination which was immunoreactive to cytokeratin (CK) 7 and thyroid transcription factor (TTF)-1 but not to CK20 suggesting a lung primary. A chest radiograph and computed tomography (CT) scan revealed a right upper lobe lung mass. Fluoro-deoxyglucose hypermetabolism was noted in the lung mass and the right 5th metacarpal bone lesion but not elsewhere on positron-emission-tomography/CT scan. Needle biopsy of the lung mass showed adenocarcinoma with histopathological and immunohistochemical features similar to that of the right 5th metacarpal bone lesion. Both the primary lung adenocarcinoma and the acrometastatic lesion were tested positive for EGFR mutation in exon 21 (L858R substitution). She underwent R0 resection of her right upper and middle lobes with systematic mediastinal lymph nodes resection and wide excision of the metacarpal metastasis followed by cytotoxic chemotherapy. A curative approach with complete resection of the primary tumor and oligometastastic site in Stage IV non-small cell lung carcinoma (NSCLC) followed by additive cytotoxic chemotherapy has not been reported to date and as such there is still no data on disease-free survival with this approach

Quality Of Life Of Patients With Chronic Obstructive Pulmonary Disease Based On Clinical Phenotypes

Background and Aims: Spanish chronic obstructive pulmonary disease (COPD) guideline classifies COPD into 4 clinical phenotypes: nonexacerbator (A), asthma-COPD overlap (B), exacerbator with emphysema(C) and exacerbator with bronchitis (D). Methods: A cross-sectional study of quality of life (QOL) based on COPD phenotypes utilizing St George’s Respiratory Questionnaire (SGRQ-c) conducted in University Malaya Medical Center from 1 June 2017 – 31 May 2018. Results: Of 220 patients, 189 patients with post bronchodilator force expiratory volume in 1 second (FEV1)/force vital capacity (FVC) of <0.70 were recruited. Their demographic, clinical characteristics and SGRQ-c score are as shown in Table 1. Patients with phenotype C and D had poorer modified medical research center (MMRC) performance status and global initiative for COPD (GOLD) class based on FEV1. Nevertheless, only patients with phenotype D had significant higher total SGRQ-c score than others. They also scored significant higher in sub-components of COPD symptoms, activities and impacts. Patients with phenotypes B had numerically higher SGRQ-c total and symptoms score than those with phenotype A and C. The total and sub-components SGRQ-c score of patients with phenotype A and C were almost similar. Conclusion: Patients with phenotype D had poorest QOL, followed by phenotype B. These groups of patients need additional medical attention, in terms of pharmacology treatment, physiotherapy and rehabilitation

Comparison of pattern of disease progression and prevalence of acquired T790M mutation in Malaysia patients with EGFR mutant lung adenocarcinoma upon failure of first-line afatinib, gefitinib and erlotinib

Abstract Background Patients receiving first-line afatinib, gefitinib or erlotinib for epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer develop progression of disease (PD) after an average of 9-13 months. Methods A retrospective analysis of PD pattern and prevalence of acquired T790M mutation among patients failing first-line afatinib versus gefitinib or erlotinib at University Malaya Medical Centre from 1st January 2015 to 31th December 2018. Results Of 87 patients who developed PD while on first-line EGFR-tyrosine kinase inhibitor (TKI) treatment, 19 (21.8%) were on afatinib, 49 (56.3%) were on gefitinib, and 19 (21.8%) were on erlotinib. The median progression-free survival (mPFS) of these patients is as shown in the table. Of 20 patients (23.0%) who developed new symptomatic brain metastases, one (5.0%) had new leptomeningeal metastases, three (15.0%) had both new leptomeningeal metastases and solid brain metastases, and the remaining 16 (80.0%) had new solid brain metastases only. New leptomeningeal metastases occurred in one patient treated with afatinib and three patients treated with gefitinib. Forty-nine patients (56.3%) were investigated for acquired T790M mutation either by plasma biopsy or tissue biopsy or both. The prevalence of acquired T790M mutation was 61.2%. There was no difference in the pattern of PD or prevalence of acquired T790M mutation among patients treated with afatinib, gefitinib or erlotinib. Conclusions New leptomeningeal metastases were uncommon in patients receiving first-line EGFR-TKI. The choice of first-line first- or second generation EGFR-TKI did not influence the pattern of PD and prevalence of acquired T790M mutation. However, patients receiving afatinib appeared to have longer mPFS than those on gefitinib or erlotinib

COVID-19, Suffering and Palliative Care: A Review

According to the WHO guideline, palliative care is an integral component of COVID-19 management. The relief of physical symptoms and the provision of psychosocial support should be practiced by all healthcare workers caring for COVID-19 patients. In this review, we aim to provide a simple outline on COVID-19, suffering in COVID-19, and the role of palliative care in COVID-19. We also introduce 3 principles of palliative care that can serve as a guide for all healthcare workers caring for COVID-19 patients, which are (1) good symptom control, (2) open and sensitive communication, and (3) caring for the whole team. The pandemic has brought immense suffering, fear and death to people everywhere. The knowledge, skills and experiences from palliative care could be used to relieve the suffering of COVID-19 patients

Epithelial‐to‐mesenchymal transition (EMT) to sarcoma in recurrent lung adenosquamous carcinoma following adjuvant chemotherapy

Adjuvant chemotherapy has long been indicated to extend survival in completely resected stage IB to IIIA non-small cell lung cancer (NSCLC). However, there is accumulating evidence that chemotherapy or chemoradiotherapy can induce epithelial-to-mesenchymal transition (EMT) in disseminated or circulating NSCLC cells. Here, we describe the first case of EMT as the cause of recurrence and metastasis in a patient with resected stage IIB lung adenosquamous carcinoma after adjuvant chemotherapy. We review the literature and explore the possible mechanisms by which EMT occurs in disseminated tumor cells (DTC) or circulating tumor cells (CTC) in response to adjuvant chemotherapy (cisplatin) as a stressor. We also explore the possible therapeutic strategies to reverse EMT in patients with recurrence. In summary, although adjuvant cisplatin-based chemotherapy in resected NSCLC does extend survival, it may lead to the adverse phenomenon of EMT in disseminated tumor cells (DTC) or circulating tumor cells (CTC) causing recurrence and metastasis. © 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Lt

Pterostilbene Simultaneously Induced G0/G1-Phase Arrest and MAPK-Mediated Mitochondrial-Derived Apoptosis in Human Acute Myeloid Leukemia Cell Lines

<div><p>Background</p><p>Pterostilbene (PTER) is a dimethylated analog of the phenolic phytoalexin, resveratrol, with higher anticancer activity in various tumors. Herein, the molecular mechanisms by which PTER exerts its anticancer effects against acute myeloid leukemia (AML) cells were investigated.</p><p>Methodology and Principal Findings</p><p>Results showed that PTER suppressed cell proliferation in various AML cell lines. PTER-induced G0/G1-phase arrest occurred when expressions of cyclin D3 and cyclin-dependent kinase (CDK)2/6 were inhibited. PTER-induced cell apoptosis occurred through activation of caspases-8-9/-3, and a mitochondrial membrane permeabilization (MMP)-dependent pathway. Moreover, treatment of HL-60 cells with PTER induced sustained activation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK)1/2, and inhibition of both MAPKs by their specific inhibitors significantly abolished the PTER-induced activation of caspases-8/-9/-3. Of note, PTER-induced cell growth inhibition was only partially reversed by the caspase-3-specific inhibitor, Z-DEVE-FMK, suggesting that this compound may also act through a caspase-independent pathway. Interestingly, we also found that PTER promoted disruption of lysosomal membrane permeabilization (LMP) and release of activated cathepsin B.</p><p>Conclusion</p><p>Taken together, our results suggest that PTER induced HL-60 cell death via MAPKs-mediated mitochondria apoptosis pathway and loss of LMP might be another cause for cell apoptosis induced by PTER.</p></div

Effect of pterostilbene (PTER) on alterations of cell-cycle regulatory proteins in HL-60 cells.

<p>Proteins were extracted from cultured HL-60 cells at 24 h after PTER treatment and probed with proper dilutions of specific antibodies. (A and B) PTER at a concentration of 100 µM induced significant decreases in protein levels of cyclin D3, CDK2, and CDK6. Upper panels: Representative results of cyclins and cyclin-dependent kinase (CDK) protein levels as determined by a Western blot analysis. Lower panels: Quantitative results of cyclin and CDK protein levels, which were adjusted to the β-actin protein level and expressed as multiples of induction beyond its own control. Values are presented as the mean ± SE of three independent experiments. *<i>p</i><0.05, compared to the vehicle control group. (C) There were no significant differences in protein levels of p15 INK4B, p21 Cip1, or p27 Kip1 between control and PTER-treated HL-60 cells. Upper panel: Representative results of p15, p21, and p27 protein levels as determined by a Western blot analysis. Lower panel: Quantitative results of p15, p21, and p27 protein levels, which were adjusted with the β-actin protein level and expressed as multiples of induction beyond its own control. (D) Cyclin D3, CDK2, and CDK6 peotein expression were downregulated in a concentration-dependent fashion after PTER treatment in HL-60 cells. Left panel: Representative results of cyclin D3, CDK2, and CDK6 protein levels as determined by a Western blot analysis. Right panel: Quantitative results of cyclin D3, CDK2, and CDK6 protein levels, which were adjusted with the β-actin protein level and expressed as multiples of induction beyond its own control. *<i>p</i><0.05, compared to the vehicle control group.</p