An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches.

Hepatocellular carcinoma (HCC) constitutes a frequent highly malignant form of primary liver cancer and is the third cause of death attributable to malignancy. Despite the improvement in the therapeutic strategies with the exploration of novel pharmacological agents, the survival rate for HCC is still low. Shedding light on the multiplex genetic and epigenetic background of HCC, such as on the emerging role of microRNAs, is considered quite promising for the diagnosis and the prediction of this malignancy, as well as for combatting drug resistance. MicroRNAs (miRNAs) constitute small noncoding RNA sequences, which play a key role in the regulation of several signaling and metabolic pathways, as well as of pivotal cellular functions such as autophagy, apoptosis, and cell proliferation. It is also demonstrated that miRNAs are significantly implicated in carcinogenesis, either acting as tumor suppressors or oncomiRs, while aberrations in their expression levels are closely associated with tumor growth and progression, as well as with local invasion and metastatic dissemination. The arising role of miRNAs in HCC is in the spotlight of the current scientific research, aiming at the development of novel therapeutic perspectives. In this review, we will shed light on the emerging role of miRNAs in HCC.

Positron Emission-Computed Tomography, Cryobiopsy versus Bronchoalveolar Lavage and Computed Tomography Findings for Interstitial Lung Disease: A Long-Term Follow-Up.

Background and Objectives: Interstitial lung diseases have always been an issue for pulmonary and rheumatology physicians. Computed tomography scans with a high-resolution protocol and bronchoalveolar lavage have been used along with biochemical blood tests to reach a diagnosis. Materials and Methods: We included 80 patients in total. First, all patients had their diagnosis with computed tomography of the thorax, serological/ immunological blood tests and bronchoalveolar lavage. However; after 3 months, all were divided into 2 groups: those who had bronchoalveolar lavage again and those who had cryobiopsy instead of bronchoalveolar lavage (40/40). Positron emission-computed tomography was also performed upon the first and second diagnosis. The patients' follow-up was 4 years from diagnosis. Results: Patients suffered most from chronic obstructive pulmonary disease (56, 70%), while lung cancer was rarely encountered in the sample (7, 9.75%). Age distribution ranged between 53 and 68 years with a mean value of 60 years. The computed tomography findings revealed 25 patients with typical diagnosis (35.2%), 17 with interstitial pulmonary fibrosis (23.9%) and 11 with probable diagnosis (11%). The cryobiopsy technique led to a new diagnosis in 28 patients (35% of the total sample). Patients who had a new diagnosis with cryobiopsy had a mean survival time of 710 days (<1460). Positron emission-computed tomography SUV uptake was positively associated with the cryobiopsy technique/new disease diagnosis and improved all respiratory functions. Discussion: Positron emission-computed tomography is a tool that can be used along with respiratory functions for disease evaluation. Conclusions: Cryobiopsy is a safe tool for patients with interstitial lung disease and can assist in the diagnosis of interstitial lung diseases. The survival of patients was increased in the cryobiopsy group versus only bronchoalveolar lavage for disease diagnosis.

Epithelial Ovarian Cancer: A Five Year Review.

Ovarian cancer is a malignant disease that affects thousands of patients every year. Currently, we use surgical techniques for early-stage cancer and chemotherapy treatment combinations for advanced stage cancer. Several novel therapies are currently being investigated, with gene therapy and stem cell therapy being the corner stone of this investigation. We conducted a thorough search on PubMed and gathered up-to-date information regarding epithelial ovarian cancer therapies. We present, in the current review, all novel treatments that were investigated in this field over the past five years, with a particular focus on local treatment.

Changes in Body Weight, Body Composition, Phase Angle, and Resting Metabolic Rate in Male Patients with Stage IV Non-Small-Cell Lung Cancer Undergoing Therapy.

Background and Objectives: Cancer treatments can adversely influence body weight status, body composition, phase angle (PhA), and resting metabolic rate (RMR), which could possibly affect disease course. Τhe aim was to assess differences in body composition, PhA, RMR, and related parameters in non-small-cell lung cancer (NSCLC) patients after treatment. Methods: The sample consisted of 82 NSCLC (stage IV) male patients (chemotherapy (C) 15.7%; immunotherapy (I) 13.3%; C + I 25.3%; (C) + radiotherapy (R) 22.9 %; and other 15.5%). Body weight and body composition, PhA, RMR, oxygen consumption (VO2), ventilation rate, and diet were assessed at baseline and at 3 months after initiation of therapy. Results: Reductions in PhA, RMR, VO2, ventilation rate, and intracellular water were observed at follow up. Weight loss was evident for 45% of patients who also had a reduction in lean body mass. In the group under C, lean mass was reduced at follow up (55.3 ± 11.53 vs. 52.4 ± 12.6, p = 0.04) without significant weight changes. In subjects with a low adherence to the Mediterranean diet (MedDietScore < 30), RMR (1940 ± 485 vs. 1730 ± 338 Kcal, p = 0.001), VO2 (277.1 ± 70.2 vs. 247 ± 49.1 mL/min, p = 0.001), and ventilation rate (10.1 ± 2.28 vs. 9. ± 2 2.2 L/min, p = 0.03) were significantly reduced. The changes in body weight were positively related to % of change in fat mass (rho = 0.322, p = 0.003) and absolute lean mass change (rho = 0.534, p < 0.001) and negatively associated with % of change in total body water (rho = −0.314, p = 0.004) (Spearman correlation coefficients). Conclusions: In conclusion, cancer therapy related to reductions in PhA and RMR, while lean mass reduction may be related to the type of treatment. Our results emphasize the importance of a more holistic nutritional and body composition assessment beyond body weight, to better address patients' needs in clinical practice.

Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo.

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5µm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

Ablation for Single Pulmonary Nodules, Primary or Metastatic. Εndobronchial Ablation Systems or Percutaneous.

Single pulmonary nodules are a difficult to diagnose imagining artifact. Currently novel diagnostic tools such as Radial-EBUS with or not C-ARM flouroscopy, electromagnetic navigation systems, robotic bronchoscopy and cone beam-compuer tomography (CBCT) can assist in the optimal guidance of biopsy equipment. After diagnosis of lung cancer or metastatic disease as pulmonary nodule, then surgery or ablation methods as local treatment can be applied. The percutaneous ablation systems under computed tomography guidance with radiofrequency, microwave, cryo and thermosphere have been used for several years. In the past 10 years extensive research has been made for endobronchial ablation systems and methods. We will present and comment on the two different ablation methods and present up to date data.

Simultaneous Resection for Colorectal and Liver Metastases, new equipment and personalized medicine.

Nowadays we perform synchronous colorectal cancer resection along with synchronous liver metastases. We investigated whether colon resection first is safer than liver resection first and if simultaneous surgeries are in general safe. Patients and Methods: Twenty patients were included in our multicenter study. In our study patients had simultaneous laparoscopic resection of primary colorectal cancer and liver metastases. The patients included were divided into two groups based on their first surgery. Group A had colon resection first (n = 10) and group B had liver resection first (n = 10). All adverse effects and outcomes were compared after the first day of hospitalization. Results: The only difference between the two groups was the operative blood loss. It was observed to be less in group B. Conclusion: In our study we did not observe any significant difference regarding the order of the operation.

Microsatellite Instability Is Insufficiently Used as a Biomarker for Lynch Syndrome Testing in Clinical Practice.

PURPOSE: The pan-cancer presence of microsatellite instability (MSI)-positive tumors demonstrates its clinical utility as an agnostic biomarker for identifying immunotherapy-eligible patients. Additionally, MSI is a hallmark of Lynch syndrome (LS), the most prevalent cancer susceptibility syndrome among patients with colorectal and endometrial cancer. Therefore, MSI-high results should inform germline genetic testing for cancer-predisposing genes. However, in clinical practice, such analysis is frequently disregarded. METHODS: A next-generation sequencing (NGS)-based technique was used for MSI analysis in 4,553 patients with various tumor types. Upon request, somatic BRAF gene analysis was conducted. In addition, hereditary testing of cancer-associated genes was performed in MSI-high cases using a capture-based NGS protocol. MLH1 promoter methylation analysis was conducted retrospectively in patients with colorectal and endometrial cancer to further investigate the origin of MSI at the tumor level. RESULTS: The MSI positivity rate for the entire cohort was 5.27%. Endometrial, gastric, colorectal, urinary tract, and prostate cancers showed the highest proportion of MSI-high cases (15.69%, 8.54%, 7.40%, 4.55%, and 3.19%, respectively). A minority of 45 patients (22.73%) among the MSI-high cases underwent germline testing to determine whether the mismatch repair pathway deficiency was inherited. 24.44% of those who performed the genetic test carried a pathogenic variant in an LS-associated gene. Three MSI-high individuals had non-LS gene alterations, including BRCA1, BRCA2, and CDKN2A pathogenic variants, indicating the presence of non-LS-associated gene alterations among MSI-high patients. CONCLUSION: Although MSI analysis is routinely performed in clinical practice, as many as 77% of MSI-high patients do not undergo LS genetic testing, despite international guidelines strongly recommending it. BRAF and MLH1 methylation analysis could shed light on the somatic origin of MSI in 42.50% of the MSI-high patients; however, MLH1 analysis is barely ever requested in clinical practice.

Sotorasib after immune checkpoint inhibitor administration induces hepatotoxicity. True, false or just another adverse effect of NSCLC treatment.

Non-small cell lung cancer is still diagnosed at a late disease stage and systematic therapy is necessary. Currently we have three main treatment modalities; chemotherapy, targeted with tyrosine kinase inhibitors and immune check point inhibitors. In the recent years and based on new studies we can administer combination of chemotherapy and immunotherapy, or radiotherapy and immunotherapy. Every treatment approach is based on the specific gene expression of the tumor. Tyrosine kinase inhibitors have been used for more than a decade for epidermal growth factor positive tumors, the same for anaplastic lymphoma kinase and proto-oncogene 1. Programmed death-ligand 1 expression has been found to be associated with the efficiency of immune checkpoint inhibitors. However; there are still several subpopulations in non-small cell lung cancer patients. We will comment on the group with KRAS G12C mutation and the targeted therapy with sotorasib for its efficiency and toxicity based on new studies.

Immunotherapy for the elderly. Maybe the best option for lung cancer?

Lung cancer is usually diagnosed at advanced stage and systematic therapy is administered. New current diagnostic techniques such as the convex-endobronchial ultrasound, radial endobronchial ultrasound, cone beam ct, electromagnetic navigation and robotic bronchoscopy provide us with a high diagnostic yield. These techniques are minimal invasive and patients with comorbidities such as chronic obstructive pulmonary disease and heart failure can be diagnosed with minimal adverse effects. All these techniques provide sufficient sample for molecular investigation. Since immunotherapy was first administered, we have more and more information regarding the appropriate patient target group. Several published studies divided patients as elderly ≥75 and non-elderly ≤74 and investigated the adverse effects of different drugs and survival. In our current commentary we present information on patients receiving immunotherapy versus chemoimmunotherapy in two groups of elderly and non-elderly. Elderly patients can receive both combinations without differences between the two groups, however; more studies are needed to clarify certain aspects.