Intratumoral Treatment with Chemotherapy and Immunotherapy for NSCLC with EBUS-TBNA 19G.

Introduction: Immunotherapy is being used for the past five years either as first line or second line treatment with great results. Chemotherapy and radiotherapy have been also used as combination to immunotherapy to further enhance this type of treatment. Intratumoral treatment has been previously proposed as a treatment option for certain non-small cell lung cancer patients. Patients and Methods: We recruited in total seventy four patients with non-small cell lung cancer in their second line treatment who received only chemotherapy in their first line treatment with programmed death-ligand-1 ≤ 50. Only adenocarcinoma or squamous cell carcinoma, and all negative for epidermal growth factor receptor, anaplastic lymphoma kinase, proto-oncogene tyrosine-protein kinase-1 and proto-oncogene B-Raf. Data were first examined with descriptive statistics choosing frequencies for categorical variables and histograms for the continuous ones. Twenty five received only intravenous immunotherapy and forty-nine intravenous cisplatin with immunotherapy. Data were first examined with descriptive statistics choosing frequencies for categorical variables and histograms for the continuous ones. Results: The relationships between changes of performance status and disease progression were examined via a single correspondence analysis. The two-dimensional scores (coordinates) derived from the correspondence analysis were then regressed against the predictors to form distinct splits and nodes obtaining quantitative results. The best fit is usually achieved by lowering exhaustively the AICc criterion and looking in parallel the change of R2 expecting improvements more than 5%. both types of therapy are capable of producing best ameliorative effects, when either the programmed death-ligand-1 expression or parenchymal site in joint with low pack years are present in the sampling data. Conclusions: Intratumoral treatment combination with cisplatin plus immunotherapy indifferent of nivolumab or pembrolizumab combination is an effective choice. In specific for those with endobronchial lesions. Moreover; patients with programmed death-ligand-1 ≥ 50 had their performance status and disease progression improved over the eight month observation.

The Fluctuations of Melatonin and Copeptin Levels in Blood Serum During Surgical Stress Regarding the Pediatric Population.

INTRODUCTION: Copeptin is known to be associated with heart damage, while melatonin is a regulatory hormone related to circadian rhythm and represents the levels of inflammation in the body. METHODS AND PATIENTS: The aim of the study was to measure in different surgeries the levels of copeptin and melatonin at different times before and after surgery in 56 patients aged from 5 days to 13.6 years. We measured copeptin in 50-microL serum and plasma samples from patients before surgery, immediately after surgery, and 24 hours after surgery. The measured levels are aligned with the published GC / MS data, and the sensitivity of the analysis is such that serum and plasma levels can only be measured by rapid extraction. The measurement was made before surgery, immediately after surgery, and 24 hours after surgery. RESULTS: The multifactorial statistical analysis revealed a statistically significant difference between the 24-hour postoperative copeptin values in group 1 (mild-moderate gravity surgery) and group 2 (severe surgery) of the severity of the surgery. Post-hoc tests with Tukey correction for age groups in multiple comparisons of the multifactorial analysis revealed a statistically significant difference (p <0.05) between 24-hour postoperative melatonin values in age groups 3 (3-6 years) and 5 (6-12 years old). The age group 3 showed significantly (p <0.05) lower 24 hours postoperative melatonin values compared to the age group 5 (6-12 years). Again, these 3-6-year-olds were more likely to have inflammation due to the severity of the surgery and the presence of inflammation after the surgery. DISCUSSION: In summary, copeptin is a reliable biomarker for assessing a patient's health both preoperatively and postoperatively. Copeptin and melatonin are two independent agents and are not related to each other, and more studies will be needed with more patients of the same age and with the same underlying disease to assess their diagnostic value. Finally, melatonin could be considered an indicator of inflammation on its own and based on pre-and post-surgery values to determine a patient's health status and take appropriate actions.

Bronchogenic cyst or lung cancer. Only biopsy can tell.

Bronchogenic cysts are rare congenital malformations which derive from primitive ventral foregut. They are usually observed in intrathoracically. A fifty year old male was admitted for the investigation of a three month chest pain. Computed tomography scan of the thorax revealed a lesion around the esophagus and left stem bronchus. Endobronchial ultrasound with convex probe and a 19G needle biopsy revealed a bronchogenic cystic which was removed with video assisted thoracic surgery. Initial radiologic assessment although was thought to be lung cancer because of the smoking habit it turned out to be benignancy. EBUS-TBNAB with 10G needle is safe and absolutely necessary for these lesions, as they take large samples.

The lengths of trachea and main bronchus in Chinese Shanghai population.

The knowledge of airway length is the theoretical basis in the diagnosis and management of airway disease. The objective of this study is to measure the length of trachea and left and right main bronchus in Chinese Shanghai population. A total of 153 consecutive adult patients with minor pulmonary disease in Xinhua hospital were enrolled for bronchoscopy examination. Measurements were conducted on head and neck neutral position and height, weight and age for each patient were recorded either. Student t test and multiple linear regression was used to compare means between males and females and to analyze correlation among height, weight, sexual dimorphism and the lengths of the trachea and bronchus. The lengths of the trachea and left main bronchus are significantly different between male and female patients (P < 0.01), but not for the lengths of right main bronchus between man and woman. Multiple linear regression analysis showed that height but not sexual dimorphism and weight correlated with the lengths of the trachea and right main bronchus. The lengths of the trachea and left main bronchus are significantly longer in males than in females. Moreover, height but not sexual dimorphism and weight influenced the length of airway.

Acute pneumothorax due to immunotherapy administration in non-small cell lung cancer.

Nowadays we have novel therapies for advanced stage non-small cell lung cancer. Immunotherapy has been introduced in the market for several years and until now its administration is mostly based on the programmed death-ligand 1. First line treatment with immunotherapy can be administered alone if programmed death-ligand 1 expression is ≥ 50%. All therapies for advanced stage disease have advantages and disadvantages, immunotherapy until now has presented mild adverse effects when compared to chemotherapy. However; it is known to induce inflammatory response to different tissues within the body. In our case acute pneumothorax was induced after immunotherapy administration.

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.

Vapor for lung volume reduction; pros and cons.

INTRODUCTION: Bronchoscopic lung volume reduction (BLVR) is a novel approach for treatment of emphysema. Several techniques are available to accomplish BLVR including Bronchoscopic Vapor Thermal Ablation (BVTA). This technique is easy to perform and considered safe due to its gradual effect. We discuss BTVA in detail in this editorial. AREAS COVERED: We discuss our experience with BTVA in detail including patient selection, equipment, procedure, post-procedural care and complications. We also review the literature to determine the pros and cons for its use. Other modalities such as endobronchial valves, coils and lung sealants are also briefly discussed. EXPERT OPINION: Vapor ablation is a novel and safe approach in inducing lung volume reduction in emphysema patients. The effects are gradual, and therefore potentially making it safer than other minimally invasive modalities. Pneumonitis and infection are common side effects. Just as in other BLVR techniques, a case by case evaluation is needed to determine the right candidate for BTVA. Further larger studies are needed before BTVA becomes standard of care in treatment of patients with emphysema.

Acute Effects of a Heat-Not-Burn Tobacco Product on Pulmonary Function.

Background and objectives: During the last decade, conventional tobacco smoking is experiencing a decline and new smoking products have been introduced. IQOS ("I-Quit-Ordinary-Smoking") is a type of "heat-not-burn" (HNB) tobacco product. The impact of IQOS on respiratory health is currently not defined. The objectives of this study were to evaluate the acute effects of IQOS on pulmonary function in non-smokers and current smokers. Materials and Methods: Fifty male healthy non-smokers and current smokers with no known co-morbidity underwent an exhaled CO measurement, oximetry (SaO2%), pulmonary function tests (flows, volumes and diffusion capacity), and a measurement of respiratory resistances with an impulse oscillometry system (IOS) before and immediately after IQOS use. Results: In the whole group of 50 participants, SaO2%, forced expiratory flow at 25% and 50% of vital capacity (FEF 25%, FEF 50%, respectively), peak expiratory flow (PEF), and diffusion lung capacity for carbon monoxide/VA (KCO) decreased significantly after IQOS use, whereas exhaled CO and airway resistance (R5 Hz, R10 Hz, r15 Hz, R20 Hz, R25 Hz, R35 Hz) increased. When the groups of smokers and non-smokers were compared, in both groups (all males, 25 smokers and 25 non-smokers), exhaled CO increased and SaO2% decreased after IQOS use (p < 0.001). In the group of non-smokers, PEF (pre 8.22 ± 2.06 vs. post 7.5 ± 2.16, p = 0.001) and FEF 25% (pre 7.6 ± 1.89 vs. 7.14 ± 2.06, p = 0.009) decreased significantly; respiratory resistances R20 Hz (pre 0.34 ± 0.1 vs. post 0.36 ± 0.09, p = 0.09) and R25 Hz (pre 0.36 ± 0.1 vs. post 0.38 ± 0.09, p = 0.08) increased almost significantly. In smokers, PEF (pre 7.69 ± 2.26 vs. post 7.12 ± 2.03, p = 0.007) and expiratory reserve volume (ERV) (pre 1.57 ± 0.76 vs. post1.23 ± 0.48, p = 0.03) decreased and R35 Hz (pre 0.36 ± 0.11 vs. post 0.39 ± 0.11, p = 0.047) increased. The differences in the changes after the use of IQOS did not differ between groups. Conclusions: IQOS had an impact on exhaled CO, SaO2%, and airways function immediately after use. Even though these changes were rather small to be considered of major clinical importance, they should raise concerns regarding the long-term safety of this product. Further research is needed for the short- and long-term effects of IQOS, especially in patients with respiratory disease.

Late results of a randomized trial on the role of mild hypofractionated radiotherapy for the treatment of localized prostate cancer.

Background: Prostate cancer is considered to be highly sensitive to changes in radiation therapy dose per fraction, specifically to hypofractionation. An increase in the fractionation dose could cause a higher increase to the prostate than to the normal tissues leading to better disease control with less toxicity. Here we present the results of a randomized trial comparing mild hypofractionation to conventional fractionation after a median of 3,6 years follow up. Patients and Methods: 139 patients were randomized to receive either hypofractionated radiotherapy with 2,25 Gy/fr to a total of 72 Gy (arm 1) or conventionally fractionated treatment with 2Gy/fr to a total of 74 Gy (arm 2). 72 patients were assigned to arm 1 and 67 to arm 2. Results: After a median follow up of 3,6 years, 23 patients (31,9%) from arm 1 developed grade≥ 2 acute genitourinary toxicity and 21 (31,3%) from arm 2 (p=0,79). The corresponding values from gastrointestinal were 15 (20,8%) and 12 (17,9%) (p=0,6). For late toxicity from GU, 8 patients (11,1%) developed grade≥ 2 symptoms in arm 1 and 7 (10,4%) in arm 2 (p=0,92). late GI toxicity grade≥ 2 was observed in 8 (11,1%) patients in arm 1 and 8 (11,9%) in arm 2 (p=0,88). In multivariate analysis, hormone therapy was significantly associated with late GI events, while acute toxicity from both GU and GI was a prognostic factor of late adverse reaction. Conclusion: No difference in the toxicity profile could be identified between hypofractionation and conventional fractionation. Our schedule of 2,25Gy/fr seems safe and tolerable by the patients with acceptable rates of acute and late toxicity.

The role of hypofractionated radiotherapy for the definitive treatment of localized prostate cancer: early results of a randomized trial.

Background: Prostate cancer is considered to have a special biology which could affect the radiation therapy result based on the selected fractionation scheme. We present the preliminary results of a randomized trial comparing conventionally and hypofractionated radiation therapy for prostate cancer. Methods: Patients included in the study had localized prostate cancer (cT1c-T3bN0M0) and were randomly assigned to mild hypofractionated (72 Gy in 32 fractions, arm1) or conventionally fractionated (74 Gy in 37 fractions, arm2) radiation therapy treatment with Volumetric Arc Therapy technique. The treatment was delivered only to the prostate with or without the seminal vesicles according to physician's discretion and hormone therapy was optional according to the disease stage and comorbidities. Here we present the preliminary results of acute toxicity from the gastrointestinal (GI) and genitourinary (GU) system. Results: Between 2015 and 2016, 139 patients were enrolled. 67 patients were treated with conventional fractionation and 72 were treated with hypofractionation. Grade≥ 2 toxicity from GU and GI was observed in 23 and 21 patients (31,9% vs 31,3%, p=0,79) and 15 and 12 (20,8% vs 17,9%, p=0,6) for arm1 and arm2 respectively. No statistically significant differences were observed between arms in the incidence of early toxicity. There was no correlation observed between patient characteristics and toxicity from either GU or GI. Conclusions: Hypofractionated radiotherapy appears to be equally tolerated compared to conventional fractionation in the early setting. Longer follow up is needed to assess the late toxicity profile of the patients and any potential differences between the control and experimental arm.

Extending 2-D Convolutional Neural Networks to 3-D for Advancing Deep Learning Cancer Classification With Application to MRI Liver Tumor Differentiation.

Deep learning (DL) architectures have opened new horizons in medical image analysis attaining unprecedented performance in tasks such as tissue classification and segmentation as well as prediction of several clinical outcomes. In this paper, we propose and evaluate a novel three-dimensional (3-D) convolutional neural network (CNN) designed for tissue classification in medical imaging and applied for discriminating between primary and metastatic liver tumors from diffusion weighted MRI (DW-MRI) data. The proposed network consists of four consecutive strided 3-D convolutional layers with 3 × 3 × 3 kernel size and rectified linear unit (ReLU) as activation function, followed by a fully connected layer with 2048 neurons and a Softmax layer for binary classification. A dataset comprising 130 DW-MRI scans was used for the training and validation of the network. To the best of our knowledge this is the first DL solution for the specific clinical problem and the first 3-D CNN for cancer classification operating directly on whole 3-D tomographic data without the need of any preprocessing step such as region cropping, annotating, or detecting regions of interest. The classification performance results, 83% (3-D) versus 69.6% and 65.2% (2-D), demonstrated significant tissue classification accuracy improvement compared to two 2-D CNNs of different architectures also designed for the specific clinical problem with the same dataset. These results suggest that the proposed 3-D CNN architecture can bring significant benefit in DW-MRI liver discrimination and potentially, in numerous other tissue classification problems based on tomographic data, especially in size-limited, disease-specific clinical datasets.

Apparent Diffusion Coefficient Quantification in Determining the Histological Diagnosis of Malignant Liver Lesions.

PURPOSE: Diffusion Weighted Imaging is an established diagnostic tool for accurate differential diagnosis between benign and malignant liver lesions. The aim of our study was to evaluate the role of Histogram Analysis of ADC quantification in determining the histological diagnosis as well as the grade of malignant liver tumours. To our knowledge, there is no study evaluating the role of Histogram Analysis of ADC quantification in determining the histological diagnosis as well as the grade of malignant liver tumours. METHODS: During five years, 115 patients with known liver lesions underwent Diffusion Weighted Imaging in 3Tesla MR scanner prior to core needle biopsy. Histogram analyses of ADC in regions of interest were drawn and were correlated with biopsy histological diagnosis and grading. RESULTS: Histogram analysis of ADC values shows that 5th and 30th percentile parameters have statistically significant potency of discrimination between primary and secondary lesions groups (p values 0.0036 and 0.0125 respectively). Skewness of the histogram can help discriminate between good and poor differentiated (p value 0.17). Discrimination between primary malignancy site in metastases failed for the present number of patients in each subgroup. CONCLUSION: Statistical parameters reflecting the shape of the left side of the ADC histogram can be useful for discriminating between primary and secondary lesions and also between well differentiated versus moderate or poor. For the secondary malignancies, they failed to predict the original site of tumour.

DDMC-p53 gene therapy with or without cisplatin and microwave ablation.

Lung cancer remains the leading cause of death in cancer patients. Severe treatment side effects and late stage of disease at diagnosis continue to be an issue. We investigated whether local treatment using 2-diethylaminoethyl-dextran methyl methacrylate copolymer with p53 (DDMC-p53) with or without cisplatin and/or microwave ablation enhances disease control in BALBC mice. We used a Lewis lung carcinoma cell line to inoculate 140 BALBC mice, which were divided into the following seven groups; control, cisplatin, microwave ablation, DDMC-p53, DDMC-p53 plus cisplatin, DDMC-p53 plus microwave, and DDMC-p53 plus cisplatin plus microwave. Microwave ablation energy was administered at 20 W for 10 minutes. Cisplatin was administered as 1 mL/mg and the DDMC-p53 complex delivered was 0.5 mL. Increased toxicity was observed in the group receiving DDMC-p53 plus cisplatin plus microwave followed by the group receiving DDMC-p53 plus cisplatin. Infection after repeated treatment administration was a major issue. We conclude that a combination of gene therapy using DDMC-p53 with or without cisplatin and microwave is an alternative method for local disease control. However, more experiments are required in a larger model to identify the appropriate dosage profile.

Value of 3 Tesla diffusion-weighted magnetic resonance imaging for assessing liver fibrosis.

BACKGROUND: Limited data are available regarding the role of magnetic resonance imaging (MRI), particularly the new generation 3 Tesla technology, and especially diffusion-weighted imaging (DWI) in predicting liver fibrosis. The aim of our pilot study was to assess the clinical performance of the apparent diffusion coefficient (ADC) of liver parenchyma for the assessment of liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: 18 patients with biopsy-proven NAFLD underwent DWI with 3 Tesla MRI. DWI was performed with single-shot echo-planar technique at b values of 0-500 and 0-1000 s/mm2. ADC was measured in four locations in the liver and the mean ADC value was used for analysis. Staging of fibrosis was performed according to the METAVIR system. RESULTS: The median age of patients was 52 years (range 23-73). The distribution of patients in different fibrosis stages was: 0 (n=1), 1 (n=7), 2 (n=1), 3 (n=5), 4 (n=4). Fibrosis stage was poorly associated with ADC at b value of 0-500 s/mm2 (r= -0.30, P=0.27). However it was significantly associated with ADC at b value of 0-1000 s/mm2 (r= -0.57, P=0.01). For this b value (0-1000 s/mm2) the area under receiver-operating characteristic curve was 0.93 for fibrosis stage ≥3 and the optimal ADC cut-off value was 1.16 ×10-3 mm2/s. CONCLUSION: 3 Tesla DWI can possibly predict the presence of advanced fibrosis in patients with NAFLD.