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.

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.

Endobronchial Radiofrequency Ablation for pulmonary nodules with Radial-Ebus and Navigation: Pros and Cons.

Introduction: Pulmonary nodules are common in the everyday clinical practice. There is always a diagnostic issue with this imaging finding. Based on the size we can use a variety of imaging and diagnostic techniques. Moreover; in the case of primary lung cancer or metastasis we can use radiofrequency ablation endobronchially. Patients and Methods: We used the radial-endobronchial ultrasound with C-arm and Archemedes, Bronchus electromagnetic navigation in order to acquire biopsy sample and we also used rapid on-site evaluation as a rapid diagnosis for pulmonary nodules. After rapid diagnosis we used the radiofrequency ablation catheter in order to ablate central pulmonary nodules. Results: Both techniques provide efficient navigation, however, with the Bronchus system less time is needed. The new radiofrequency ablation catheter provides efficient results in central lesions with low watts ≤40. Conclusion: We provided in our research a protocol to diagnose and treat such lesions. Future larger studies will provide more data on this subject.

Case Report: Endoscopic radiofrequency ablation with radial-EBUS and ROSE.

Background: Single pulmonary nodules are a common issue in everyday clinical practice. Currently, there are navigation systems with radial-endobronchial ultrasound and electromagnetic navigation for obtaining biopsies. Moreover, rapid on-site evaluation can be used for a quick assessment. These small lesions, even when they do not have any clinically significant information with positron emission tomography, are important to investigate. Case description: Radiofrequency and microwave ablation have been evaluated as local treatment techniques. These techniques can be used as therapy for a patient population that cannot be operated on. Currently, one verified operating system is used for endoscopic radiofrequency ablation through the working channel of a bronchoscope. Conclusion: In our case, a new system was used to perform radiofrequency ablation with long-term follow-up.

Molecular Epidemiology and Treatment Patterns of Patients With EGFR Exon 20-Mutant NSCLC in the Precision Oncology Era: The European EXOTIC Registry.

Introduction: Real-world evidence regarding molecular epidemiology and management patterns of patients with EGFR exon-20 mutated, advanced NSCLC outside the context of clinical trials is lacking. Methods: We created a European registry for patients with advanced EGFR exon 20-mutant NSCLC diagnosed from January 2019 to December 2021. Patients enrolled in clinical trials were excluded. Clinicopathologic and molecular epidemiology data were collected, and treatment patterns were recorded. Clinical end points according to treatment assignment were assessed using Kaplan-Meier curves and Cox regression models. Results: Data on 175 patients from 33 centers across nine countries were included in the final analysis. Median age was 64.0 (range: 29.7-87.8) years. Main features included female sex (56.3%), never or past smokers (76.0%), adenocarcinoma (95.4%), and tropism for bone (47.4%) and brain (32.0%) metastases. Mean programmed death-ligand 1 tumor proportional score was 15.8% (range: 0%-95%) and mean tumor mutational burden was 7.06 (range: 0-18.8) mutations per megabase. Exon 20 was detected in the tissue (90.7%), plasma (8.7%), or both (0.6%), using mostly targeted next-generation sequencing (64.0%) or polymerase chain reaction (26.0%). Mutations were mainly insertions (59.3%), followed by duplications (28.1%), deletions-insertions (7.7%), and the T790M (4.5%). Insertions and duplications were located mainly in the near loop (codons 767-771, 83.1%) and the far loop (codons 771-775, 13%) and only in 3.9% within the C helix (codons 761-766). Main co-alterations included mutations in TP53 (61.8%) and MET amplifications (9.4%). Treatment on mutation identification included chemotherapy (CT) (33.8%), CT-immunotherapy (IO) (18.2%), osimertinib (22.1%), poziotinib (9.1%), mobocertinib (6.5%), mono-IO (3.9%), and amivantamab (1.3%). Disease control rates were 66.2% with CT plus or minus IO, 55.8% with osimertinib, 64.8% with poziotinib, and 76.9% with mobocertinib. Corresponding median overall survival was 19.7, 15.9, 9.2, and 22.4 months, respectively. In multivariate analysis, type of treatment (new targeted agents versus CT ± IO) affected progression-free survival (p = 0.051) and overall survival (p = 0.03). Conclusions: EXOTIC represents the largest academic real-world evidence data set on EGFR exon 20-mutant NSCLC in Europe. Indirectly compared, treatment with new exon 20-targeting agents is likely to confer survival benefit than CT plus or minus IO.

Non-Small-Cell Lung Cancer Immunotherapy and Sleep Characteristics: The Crossroad for Optimal Survival.

INTRODUCTION: Non-small-cell lung cancer is still diagnosed at an inoperable stage and systematic treatment is the only option. Immunotherapy is currently considered to be the tip of the arrow as the first-line treatment for patients with a programmed death-ligand 1 ≥ 50. Sleep is known to be an essential part of our everyday life. PATIENTS AND METHODS: We investigated, upon diagnosis and after nine months, 49 non-small-cell lung cancer patients undergoing immunotherapy treatment with nivolumab and pemprolisumab. A polysomnographic examination was conducted. Moreover, the patients completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), the Fatigue Severity Scale (FSS) and the Medical Research Council (MRC) dyspnea scale. RESULTS: Tukey mean-difference plots, summary statistics, and the results of paired t-test of five questionnaire responses in accordance with the PD-L1 test across groups were examined. The results indicated that, upon diagnosis, patients had sleep disturbances which were not associated with brain metastases or their PD-L1 expression status. However, the PD-L1 status and disease control were strongly associated, since a PD-L1 ≥80 improved the disease status within the first 4 months. All data from the sleep questionnaires and polysomnography reports indicated that the majority of patients with a partial response and complete response had their initial sleep disturbances improved. There was no connection between nivolumab or pembrolisumab and sleep disturbances. CONCLUSION: Upon diagnosis, lung cancer patients have sleep disorders such as anxiety, early morning wakening, late sleep onset, prolonged nocturnal waking periods, daytime sleepiness, and unrefreshing sleep. However, these symptoms tend to improve very quickly for patients with a PD-L1 expression ≥80, because disease status improves also very quickly within the first 4 months of treatment.

Cryo-Biopsy versus 19G needle versus 22G needle with EBUS-TBNA endoscopy.

Introduction: We have been using cryo-biopsy for endobronchial lesions for lung cancer diagnosis and debulking. Cryo-biopsy is also known to be an excellent tool for diagnosis of lung interstitial disease. Recently cryo-biopsy with the 1.1mm probe was used for lymphnode biopsy. Patients and Methods: 311 patients participated with lymphadenopathy and at least one lung lesion. The following tools were used for diagnosis; 22G Mediglobe Sonotip, 22G Medigolbe, 21G Olympus, 19G Olympus and 1.1mm cryo probe ERBE CRYO 2 system (3 seconds froze). A PENTAX Convex-probe EBUS was used for biopsy guidance. Results: Cell-blocks slices had a higher number in the 19G needle group (19G> Cryo Probe>22G Mediglobe Sonotip >21G Olympus >22G Mediglobe). Conclusion: Cryo biopsy of the lymphnodes is safe with the 1.1mm cryo probe. Further studies are needed in order to evaluate new probes and the technique specifications.

"One Shot" Sample Evaluation of 22G, 22G upgraded, 21G and 19G needle for Endobronchial Ultrasound-EBUS-TBNA.

Background: There are still diagnostic issues with lung cancer and mediastinum lymphadenopathy. Endobronchial ultrasound (EBUS) is a state of the art equipment for the diagnosis of lymphadenopathy and central lesions. Objective: To investigate the sample size with one pass. Patients and Methods: 248 Stage IV patients were included in our study. All patients had a CT of the thorax with either lymphadenopathy or lyphadenopathy plus pulmonary lesions. Patients had a biopsy with endobronchial ultrasound with 22G Mediglope, 22G Mediglope Sonotip, 21G Olympus and 19G Olympus needle. We collected information regarding the cancer type, cell block, tissue, age, sex, lesion size and needle type. Results: The cancer type diagnosis was associated with the needle diameter. The number of cell-blocks were associated with the lesion size and needle diameter. Slices from the tissue and cell-blocks were again associated with the lesion size and needle diameter. Conclusion: One pass is enough for cancer diagnosis, however; careful selection has to be made among patients regarding the needle diameter. In the case of lymphoma suspicion we should use 19G needle.

Validation of Patras Immunotherapy Score model for prediction and prognosis of patients with advanced NSCLC treated with nivolumab or pembrolizumab: results from a European multicentre study.

Background: Recently, the Patras Immunotherapy Score (PIOS) has been developed to estimate the survival benefit of patients with advanced non-small-cell lung cancer (aNSCLC) treated with nivolumab or pembrolizumab. The aim of this study was to validate the clinical value of PIOS in an external cohort of aNSCLC patients. Methods: PIOS is a baseline formula produced by the combination of performance status, body mass index, age and line of treatment. In this multicentre study, 626 patients with confirmed NSCLC pathology, who had been treated with nivolumab or pembrolizumab, as well as 444 patients with aNSCLC, who had been managed with chemotherapy alone, were retrospectively enrolled. Predictive and prognostic values of PIOS were finally evaluated. Results: Patients treated with immunotherapy and higher PIOS score had an improved progression-free survival not only in univariate [hazard ratio (HR) = 0.621, p = 0.001], but also in multivariable analysis (HR = 0.651, p = 0.003). In addition, improved overall survival with increasing PIOS score was also observed (HR = 0.608, p < 0.001) with this association remaining statistically significant after adjusting for programmed-cell death ligand 1 (PD-L1) expression (HR = 0.620, p < 0.001). In addition, patients with disease progression (PD) had lower scores compared to those with stable disease (SD), partial response (PR) or complete response (CR) in a two-tier model (p < 0.001) as well as in a four-tier model (PD, SD, PR and CR; p < 0.001). Prognostic significance of PIOS score also persisted using a binary logistic regression analysis, adjusted for disease stage and PD-L1 status (p = 0.002, odds ratio: 0.578). Contrarily, PIOS had no prognostic significance in the chemotherapy group; however, upon combined analysis of the two cohorts, PIOS was found to have a significant interaction with the type of treatment (HR = 0.066 with p < 0.001), confirming its predictive value for immunotherapy. Conclusions: This study provides further validation of PIOS in aNSCLC patients treated with anti-PD-1 monotherapy.

Cryobiopsy for pneumonitis diagnosis in NSCLC immunotherapy.

Nowadays immunotherapy is considered the tip of the arrow as treatment for non-small cell lung cancer for inoperable patients. Programmed death-ligand 1 is considered a valuable marker for the success of immunotherapy. The higher the score ≥50% the more successful the treatment will be. However; previous studies have presented favorable data even for those patients where the programmed death-ligand 1 was ≤50% or even 0%, therefore it can be administered as first line treatment in these patients with the addition of chemotherapy or radiotherapy. Other treatment modalities are tested as surrogates like gene therapy with immunotherapy to improve the results in patients with programmed death-ligand 1 was ≤50% or even 0%. The main issue for these patients is an adverse effect pneumonitis, in case we will present the valuable method of lung parenchyma sampling with cryobiopsy for early diagnosis of immunotherapy induced pneumonitis.

Factors Affecting the Nuclei in Newborn and Children.

It is known that children are more sensitive to the effects of medical treatments and environment than adults. Today there is limited information regarding the differences in genotoxic effects in children. The micronucleus assay is a method that is used to monitor genotoxicity, and it was validated several years before. Today there is international interest for exfoliated buccal cells. Most of the micronuclei studies in children have been performed with the analyses of lymphocytes. However, there is vast interest in using exfoliated cells from the oral cavity. The reason is that other type of cells are acquired non-invasively, this is an important issue in paediatric cohorts. Unfortunately a limitation of measuring micronuclei frequency is that it has been observed to be low in newborns and on the other hand there are a large number of patients and cell sample counts. It has been observed that radiation exposure and environmental pollutants increase the micronuclei frequency in newborn and children. Regarding the medical treatments, there is little data and several studies are needed to optimise the doses. There is the need to observe if there is a relationship between micronuclei in lymphocytes and exfoliated cells and to identify the baseline of the micronuclei levels. Moreover, we evaluate the changes in response to the toxic agents. Prospective cohorts studies will clarify the predictive value of micronuclei for cancer and chronic diseases for both children and adults. Novel molecular technologies will assist in the elucidation of different biological pathways and molecular mechanisms connected with the micronulcei levels in newborn and children.

Radial-EBUS: CryoBiopsy Versus Conventional Biopsy: Time-Sample and C-Arm.

INTRODUCTION: Diagnosis of lung nodules is still under investigation. We use computed tomography scans and positron emission tomography in order to identify their origin. PATIENTS AND METHODS: In our retrospective study, we included 248 patients with a single lung nodule or multiple lung nodules of size ≥1 cm. We used a radial-endobronchial ultrasound and a C-Arm. We used a 1.1 mm cryoprobe versus a 22G needle vs. forceps/brush. We compared the sample size of each biopsy method with the number of cell-block slices. RESULTS: Central lesions indifferent to the method provided the same mean number of cell-block slices (0.04933-0.02410). Cryobiopsies provide less sample size for peripheral lesions due to the higher incidence of pneumothorax (0.04700-0.02296). CONCLUSION: The larger the lesion ≥2 cm, and central, more cell-blocks are produced indifferent to the biopsy method (0.13386-0.02939). The time of the procedure was observed to be less when the C-Arm was used as an additional navigation tool (0.14854-0.00089).

A Real-World, Observational, Prospective Study to Assess the Molecular Epidemiology of Epidermal Growth Factor Receptor (EGFR) Mutations upon Progression on or after First-Line Therapy with a First- or Second-Generation EGFR Tyrosine Kinase Inhibitor in EGFR Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer: The 'LUNGFUL' Study.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform cobas®EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

Connection between PD-L1 expression and standardized uptake value in NSCLC: an early prognostic treatment combination.

Objectives: Lung cancer is still diagnosed at advanced stage and early treatment initiation is needed. Therefore, we need biomarkers or clusters of information that can provide early treatment prognosis.Methods: Biopsies were acquired from 471 patients-lung masses with CT-guided biopsy, convex probe transthorasic biopsy, and EBUS-TBNA convex probe with 18 G needles and 19 G needles.Results: Standardized uptake value (SUV) measurement is associated with female, smoking status, hepatic metastasis, adenocarcinoma and programmed death-ligand 1 (PD-L1). In specific we expect that SUV ≥ 7 is associated with PD-L1 ≥ 50.Conclusions: Lung masses indifferent of size that have SUV ≥ 7 will also have PD-L1 expression ≥ 50. Also, it is likely that these patients will be female with intense smoking habit and hepar or multiple metastasis.

Lung cancer biopsies: Comparison between simple 22G, 22G upgraded and 21G needle for EBUS-TBNA.

Introduction: Novel technologies are currently used for lung cancer diagnosis. EBUS-TBNA 22G is considered one of the most important tools. However; there are still issues with the sample size.Patients and Methods: 223 patients underwent EBUS-TBNA with a 21G Olympus needle, 22GUS Mediglobe and 22GUB Mediglobe. In order to evaluate the efficiency of 22GUB novel needle design. In order to evaluate the sample size of each needle, we constructed cell blocks and measured the different number of slices from each biopsy site. Results: The 22GUB novel needle had similar and larger number of slices from each biopsy site compared to 21G needle. Discussion: Firstly as a novel methodology we used the number of slices from the constructed cell blocks in order to evaluate the sample size. Secondly, we should seek novel needle designs and not only concentrate on the volume of the sample size.

The development of bronchoscopy in China: a national cross-sectional study.

Objective: To investigate the development of bronchoscopy in China and compare it with its application in the early 21st century. Methods: The data collection was based on questionnaires. Three hundred and nineteen hospitals, which distributed across 30 provinces and 130 cities, were included in the study. Data about the application of bronchoscopy in Shanghai and Hunan province in the early 21st century are also involved for comparison. Results: The median period of performing diagnostic and therapeutic bronchoscopy was 19.7±11.0 and 7.4±7.0 years, respectively. On average, about 155.2 cases and 28.4 cases received diagnostic and therapeutic bronchoscopy in each hospital per month. The average area and number of the examination room was 122.7m2 and 2.2m2, respectively. More examination items were performed in specialty hospitals than those in general hospitals (P<0.05) and specialty hospitals owned more rooms exclusively for bronchoscopy (P<0.05), while no difference of the number of allocated doctors was found (P>0.05). On the other side, the whole amount of diagnosis and therapeutic items in teaching hospitals was slightly higher than that in non-teaching hospitals (P<0.01). Comparison of diagnosis and therapeutic endoscopy in Shanghai and Hunan province shows that the number of flexible bronchoscopy increased by 5.8 times in Shanghai from 2002 to 2017, while that increased by 3.4 times in Hunan province from 2005 to 2017. Furthermore, the average number of allocated doctors increased by 0.85 times in Shanghai, which was more rapidly compared with that of Hunan province (0.66 times) (P<0.05). Besides, the development rate of the diagnosis and therapeutic projects in Shanghai was significantly higher than that in Hunan province (P<0.05). Conclusion: All different classes of hospitals in China are capable of carrying out conventional bronchoscopy diagnosis and therapeutic projects, and newly developed bronchoscopy technology has gradually spread in high-level hospitals since 21st century. The higher class the hospital was, the earlier bronchoscopy was performed. Respiratory endoscopy in China has developed rapidly since the early 21st century and the construction of respiratory endoscopy center and the personnel training are on the right track, but it is also faced with inadequate equipment, unbalanced regional development and insufficient personnel allocation.

Infections Due to Multidrug-Resistant Bacteria in Oncological Patients: Insights from a Five-Year Epidemiological and Clinical Analysis.

Bacterial infections are frequent complications in cancer patients. Among them, those caused by multidrug-resistant (MDR) bacteria increase morbidity and mortality mainly because of limited therapeutic options. Current knowledge regarding MDR infections in patients with solid tumors is limited. We assessed the epidemiology and risk factors of increased mortality in these patients. In this retrospective five-year single cohort observational study, we included all oncological patients with MDR infections. Cancer-related parameters, comorbidities, prior use of antibiotics, previous surgical interventions and hospitalization, as well as the use of invasive procedures were investigated as potential risk factors causing adverse outcomes. Seventy-three patients with MDR infection were included: 37% with carbapenem-resistant Klebsiella pneumoniae, 24% with oxacillin-resistant Staphylococcus aureus (MRSA) and 21% with carbapenem-resistant Acinetobacter baumanni. Previous colonization with MDR bacteria was detected in 14% patients, while 20% of the patients presented MDR colonization or infection at ward admission. Mortality during the infection episode was 32%. Duration of hospitalization and CRP were statistically significant risk factors of mortality, whereas administration of guided antibiotics was a protective factor. Knowledge of local epidemiology of MDR bacteria can help physicians promptly identify cancer patients at risk of MDR infections and initiate timely effective empirical antibiotic treatment that can eventually improve the overall therapeutic management.