Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Neoplasms

Pleural Effusion

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Patients who need removal of excess pleural effusion and assessed for the possibility of lung cancer.

Pleural effusion removed as part of standard care is fractionized and analyzed by mass spectrometry

Proteomics analysis of pleural effusion

Rune Matthiesen, PhD

Ana S Carvalho, PhD

The excessive accumulation of fluid between the membranes surrounding the lung, a clinical condition commonly referred to as "pleural effusion", is caused by one of three factors: increased production of pleural fluid, decreased ability to reabsorb pleural fluid or a mixture both.

The basis of pleural effusion accumulation may originate from multiple pathologies: from benign and extrapulmonary conditions to intrinsic pleural pathology (inflammatory or neoplastic primary or metastatic) in which the accumulation of fluid in the pleural space is mainly due to changes in the structure of the pleural membrane (loss of integrity and / or infiltration by neoplastic cells).

An example of extrapulmonary conditions is the pleural effusion observed in patients with congestive heart failure in which there is increase in hydrostatic capillary pressure, due to failure of the cardio circulatory pump.

The distinction between benign and malignant causes is currently a diagnostic challenge that usually requires the collection of material (cells immersed in the pleural fluid or even a histological sample).

The first step of this investigation is currently the cytological evaluation of the pleural fluid, that is, the observation of cells, of an initial sample of the pleural fluid. This procedure is associated with an average sensitivity of 62% while a second sample through thoracentesis improves the sensitivity of the diagnosis by 10%. In certain cases, however, it is not possible to diagnose by analyzing the pleural fluid and, as a rule, a more invasive diagnostic method is recommended, such as pleural biopsy (collected by puncture with a "blind" needle, echo guided or computed tomography guided or obtained by means of direct visualization of the pleural cavity through pleuroscopy).

The diagnostic yield of this approach can reach up to 97% (in the case of pleural biopsy obtained by medical thoracoscopy). However, it implies greater morbidity and greater consumption of resources (material and human). The development of a more sensitive and specific and at the same time less invasive diagnostic method for pleural fluid may contribute to a more effective screening of patients, limiting the use of more invasive methods to only patients with a higher risk of malignant pathology.

The excessive accumulation of fluid between the membranes surrounding the lung, a clinical condition commonly referred to as "pleural effusion", is caused by one of three factors: increased production of pleural fluid, decreased ability to reabsorb pleural fluid or a mixture both.

The basis of pleural effusion accumulation may originate from multiple pathologies: from benign and extrapulmonary conditions to intrinsic pleural pathology (inflammatory or neoplastic primary or metastatic) in which the accumulation of fluid in the pleural space is mainly due to changes in the structure of the pleural membrane (loss of integrity and / or infiltration by neoplastic cells).

An example of extrapulmonary conditions is the pleural effusion observed in patients with congestive heart failure in which there is increase in hydrostatic capillary pressure, due to failure of the cardio circulatory pump.

The distinction between benign and malignant causes is currently a diagnostic challenge that usually requires the collection of material (cells immersed in the pleural fluid or even a histological sample).

The first step of this investigation is currently the cytological evaluation of the pleural fluid, that is, the observation of cells, of an initial sample of the pleural fluid. This procedure is associated with an average sensitivity of 62% while a second sample through thoracentesis improves the sensitivity of the diagnosis by 10%. In certain cases, however, it is not possible to diagnose by analyzing the pleural fluid and, as a rule, a more invasive diagnostic method is recommended, such as pleural biopsy (collected by puncture with a "blind" needle, echo guided or computed tomography guided or obtained by means of direct visualization of the pleural cavity through pleuroscopy).

The diagnostic yield of this approach can reach up to 97% (in the case of pleural biopsy obtained by medical thoracoscopy). However, it implies greater morbidity and greater consumption of resources (material and human). The development of a more sensitive and specific and at the same time less invasive diagnostic method for pleural fluid may contribute to a more effective screening of patients, limiting the use of more invasive methods, only for patients with a higher risk of malignant pathology.

Study Objectives:

This project consists of a preclinical study where we will explore new methodologies for clinical evaluation, based on proteomic analysis of the immunological characteristics and the microenvironment of the tumor in the pleural fluid of patients whose diagnosis has not been confirmed. The results obtained will be used in the implementation of an algorithm for the classification of pleural fluid in the following groups: a) low risk or benign; b) high risk or malignant. If the algorithm has good sensitivity and specificity for malignant diagnoses, it may be useful to distinguish patients in to the groups: a) postpone the invasive test and do active imaging surveillance; b) proceed to invasive testing.

Benefit / Risk Assessment:

The collection of the pleural fluid will be carried out by procedures used in standard care and diagnosis of the disease, thus not constituting additional risks to the participants. The results of this investigation do not bring clinical effects directly applicable to the participants involved. However, in the future the results obtained may benefit other users through improved understanding the tumor microenvironment.

Modalities of Recruitment:

Through an interview with the investigating doctor, the participant in this study becomes aware of the terms of the treatment of his personal data in the scope of the research project. In addition, data subjects sign informed consent for participation in the study. The notification includes an explanation of the procedures involved in the investigation and the role of personal data collected in the context of the investigation. In an interview with the investigating doctor and by signing the informed consent for participation in the study, the data subject becomes aware of his right to withdraw from the study and / or to withdraw his informed consent.

The collection of biological samples for the comparative prospective cohort study will be carried out in all collaborative hospitals in this project in a period of two to three years. Based on the variance and statistical power observed in a previous study of the pulmonary fluid exosome proteome, 200 samples were estimated as the minimum number for the classification of biological samples. The analysis of statistical power is based on the variance observed in 10 samples in which approximately 3500 proteins were identified and quantified in pulmonary fluids. The statistical power analysis considers the correction for multiple tests according to the number of proteins identified and quantified.

Data collection specifications:

During the consultation, a clinical interview will be conducted, which will allow the collection of personal data, namely genetic data, data related to health and racial or ethnic origin. An objective exam will also be carried out to assess weight, height, blood pressure and heart rate. Data relating to the results of complementary diagnostic tests will be collected, namely: 1. Chest X-ray (location, extent and characteristics of the pleural effusion); 2. chest ultrasound (location, extent, characterization of the ecostructure - homogeneous / heterogeneous; with / without visible septations); 3. Thoracic Computed Tomography (location, extent, morphological aspect of the pleura - thickness increase, nodules, etc.); 4. Cytological evaluation of the pleural fluid; 5. Serum biochemical study: blood glucose level; assay of total proteins and serum albumin; lactate dehydrogenase level.

The reference diagnostic method will be based on histological evaluation of the tissue. The results of the proteomics analysis obtained in this project will not be taken into account for the final diagnosis of the participants.

Specification of collection and final destination of biological samples:

According to the clinician's decision, pleural fluid will be obtained for diagnosis (through thoracentesis or during the course of pleural biopsy or pleuroscopy). The sample obtained will follow the usual clinical investigation pathway (cytological and / or histopathological evaluation, biochemical evaluation, microbiological evaluation) as registered in each institution. For patients who agree to participate in the study, only an additional sample of pleural fluid will be sent for the study that we propose to carry out. These last samples will be stored at CEDOC.

Text of information to be provided to volunteers:

The study for which we ask for your consent aims to develop a diagnostic method with greater specificity and sensitivity in identifying different pathologies associated with excessive accumulation of pleural fluid (a condition commonly known as pleural effusion). Currently, the cytological evaluation, that is, the observation of cells, of an initial sample of the pleural fluid has an average sensitivity of 62% while a second sampling through thoracentesis (consists of aspiration of the liquid from the pleura through the puncture of the chest wall) improves the sensitivity of the diagnosis by 10%. In certain cases it is not possible to diagnose by analyzing the pleural fluid and as a rule a more invasive diagnostic method is recommended, such as pleural biopsy or pleuroscopy (surgical technique that allows you to directly view the inside of the rib cage) with pleural biopsy (sensitivity 98%). The development of a diagnostic method with greater specificity and sensitivity of the pleural fluid, thus avoiding invasive methods, can improve the efficiency in screening patients with pleural effusion, limiting the invasive study to a selected portion of patients with an effectively higher risk of malignant pathology. Your participation in this study does not involve additional procedures beyond those that your doctor considers necessary for the diagnosis of the disease or prescription of specific drugs for the study in question. The collected samples will be anonymized with a code, that is, it will not be possible for the researchers to match the samples with the personal data of the respective patients. Any of the data collected will be confidential, in accordance with the new General Data Protection Regulation (GDPR) that came into force last May 2018 (Regulation (EU) No. 2016/679).

PATIENT'S INFOMRED CONSENT:

(NAME) _____________________________________________________, I voluntarily agree to take part of the research project entitled "Clinical study in the context of the diagnosis of patients with pleural effusion".

I declare that I was informed about the objectives and methodology of this study, as well as about the conditions of participation, having received oral and written information, which I heard, read and understood.

This document was signed after all doubts were clarified with the investigating physician and after reflecting on this proposal for participation with unlimited time.

The samples and data will be encrypted, to protect my identity. I am free to refuse to donate my samples and, even after I have given my consent, I will be able to withdraw it at any time if that is my wish. My decision will in no way affect the quality of my clinical follow-up nor will it change my rights as a patient of the ________________________________________________________ (hospital unit).

At any time, I can request generic information about the study for which samples are being used. However, I will not be informed of the concrete results obtained in my samples, since these data are not relevant for my clinical follow-up.

I also authorize the use of biological samples and data collected, anonymously and confidentially, in subsequent research projects, provided they are authorized by the appropriate Ethics Committee.

Signature of Participant: ______________________________________

Date: __ / __ / _____

Investigator's Signature: ______________________________________

Date: __ / __ / _____

Ownership and data protection of participants / confidentiality:

The security measures in the protection of personal data that will be implemented include 1. Pseudonymization and encryption of personal data; 2. Ability to restore availability and access to personal data in a timely manner in the event of an incident; 3. Process for testing, assessing and regularly evaluating the effectiveness of technical and organizational measures to ensure the security of data processing.

Pleural effusion contains cells. We aim to both characterize the proteome of protein fractions of the acellular pleural effusion and the cellular component. DNA is not the target of the study.

Immune- and Microenvironment- Proteogenomics Profiling for Classifying Lung Cancer Patients

In case of publication, clinical parameters will be listed as overall summaries rather than for each individual.

diagnosis of lung cancer by histological examination of surgically-excised nodules

Fundação para a Ciência e a Tecnologia

Hospital Cuf Descobertas

Universidade Nova de Lisboa

Principal Investigator

Collection of sputum, blood, urine, and a small amount of lung tissue.

comparative genomic hybridization

gene expression microarray analysis

proteomic profiling analysis

biologic sample preservation procedure

Using a brush, superficial cells are removed from the nose.

nasal brushing

Blood draw

Subjects will be asked to provide a urine specimen.

Urine collection

Prior to their bronchoscopy, subjects will be asked for a sputum specimen. This is a collection of mucous that you cough up.

sputum sample

A flexible tube attached to a fluorescent light source will be inserted into the subject's mouth or nose to reach the airway. Samples of the lining of the airway will be taken, as well as bronchial secretions and epithelial cell from brushings of the lining of the airway.

fluorescence bronchoscopy with airway biopsy

A small needle is inserted into the lung to collect tissue. This procedure will only be performed if the patient's physician orders it.

fine needle aspiration of the lung

A small needle is inserted into the patient's lung cavity and a small amount of fluid is collected. This procedure will only be performed if the patient's physician orders it.

thoracentesis

Vanderbilt Ingram Clinical Trials Information Program

VICC Clinical Trials Information Program

Pierre Massion, MD

Research Office

Rena Burns, RN

Fabien Maldonado, MD

RATIONALE: Using samples of blood, urine, sputum, and lung tissue from patients at high risk of cancer for laboratory studies may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer.

PURPOSE: This research study is looking at molecular predictors of cancer in patients at high risk of lung cancer.

OBJECTIVES:

* To use fixed lung tissue for histological evaluation and fresh tissue samples for molecular studies to study DNA, RNA, and protein abnormalities in lung preneoplastic and neoplastic lesions.
* To use proteomic techniques, including matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS), to develop a method of diagnosing and staging both pre-invasive and invasive lesions, using less invasive methods.

OUTLINE: Blood, urine, nasal cell, and sputum samples are collected. Lung tissue samples are also collected using fluorescence bronchoscopy and epithelial cell collection.

Samples are studied by genetic and proteomic analyses, including comparative genomic hybridization, expression microarray, and protein profiling.

Blood, urine, nasal cells, sputum, bronchal epithelial cells, airway tissue, and lung tissue

Molecular Predictors of Cancer in Patients at High Risk of Lung Cancer

Molecular Predictors of Lung Cancer Behavior

As a part of the study nasal brushing specimens, sputum, blood, urine, and a small amount of other tissue will be collected during standard of care procedures (bronchial epithelial, trans-thoracic fine needle aspiration (FNA) and thoracentesis as part of patient work up.

Clinical diagnosis is the primary goal of the procedure. All the research specimens are collected after the primary goal of the procedure is met.

Use of proteomic techniques in the laboratory to find a method of diagnosing lung tissue as benign or malignant rather than relying on invasive open-chest surgery for a diagnosis

National Cancer Institute (NCI)

Vanderbilt-Ingram Cancer Center

Professor of Medicine and Thoracic Surgery

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Ascites

Fallopian Tube Neoplasms

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Patients with a diagnosis of malignant solid tumor

Kevin C Conlon, M.D.

Background:

Researchers want to study fluids and blood of people with cancer. The fluids are from the abdomen and around the lungs. Studying these might help researchers learn about the biology of cancer. This may lead to better ways to treat cancer.

Objectives:

To study the biology of cancer.

Eligibility:

Adults 18 and older with malignant solid tumors.

Design:

Participants will be screened with medical history, blood tests, and confirmation of diagnosis.

Participants will have samples taken at regularly scheduled procedures. Fluids from the abdomen and/or lungs will be taken as part of the procedures. Blood will be taken separately.

Participants may be asked to give more samples at future procedures.

Background:

-Malignant ascites or pleural effusions are often seen in patients with solid tumor

malignancies.

-Malignant ascites is proinflammatory with many cytokines present and acts to promote

tumor cell growth.

-The cellular composition of malignant ascites consists of lymphocytes, macrophages and

monocytes.

-Serum monocytes and lymphocytes play a role in the native host anti-tumor immune

mediated mechanisms.

-A paracentesis or thoracentesis is often done for symptomatic relief from the malignant

fluid collection.

Primary Objective:

-To obtain blood samples and ascites and pleural effusion samples from patients with solid

tumor malignancies, with the intent of performing translational studies related to cancer.

Eligibility:

* Patients greater than or equal to 18 years of age.
* Diagnosis of malignant solid tumor.
* Patients must be able and willing to provide informed consent.

Design:

-We will collect approximately 200cc-5L ascites from patients that are undergoing a

therapeutic paracentesis or thoracentesis. No thoracentesis or paracentesis will be

performed solely for research purposes.

-The fluid will be collected during the medical procedure and may be collected at more

than one time point.

-We will also collect 30ml of peripheral blood. This will be from patients who are being

seen in follow up, consultation, or presenting for enrollment on a clinical trial.

Collection of Malignant Ascites, Pleural Fluid, and Blood From People With Solid Tumors

Collection of Malignant Ascites, Pleural Fluid and Blood From Patients With Solid Tumors

.All IPD recorded in the medical record will be shared with intramural investigators upon request.

Experimental - Translational study outcomes from the collection/analysis of blood samples; and ascites and pleural effusion samples from patients with solid tumor malignancies.

Pleural Effusion, Malignant

Pleural Diseases

Pleural Neoplasms

Anti-Arrhythmia Agents

Channel Blockers

Central Nervous System Depressants

All Drugs and Chemicals

Vasoconstrictor Agents

Respiratory System Agents

Anti-Infective Agents

Lidocaine

Anesthetics

Epinephrine

Racepinephrine

Epinephryl borate

Disinfectants

Ultrasound-guided biopsy of the parietal pleura is taken through the same incision as the optimal site for thoracentesis and immediately prior to ultrasound-guided thoracentesis

Using ultrasound the optimal point of entry for thoracentesis is located. Local anesthesia is obtained with 10 mL of 2% lidocaine with adrenalin injected in cutis, subcutis, muscle and pleura. Before removing the syringe, aspiration of pleural fluid confirms the relevance of the chosen site . Again, the area is wiped with disinfectant and a millimeter small skin incision is made with a pointed scalpel. Six US-guided biopsies of 1.2 millimetres using closed needle biopsies (Quick-core Biopsy Needle 18G, COOK Medical, Bloomington, Indiana, USA or Bard Max Core needle 18G, Temple, Arizona, USA). ) are taken from the parietal pleura. Thoracentesis is performed as described above using the same incision as the pleural biopsy.

ultrasound-guided pleural biopsy

The optimal point of entry (the largest distance between parietal and visceral pleura) is identified using ultrasound. This is usually on the lower, dorsal side of the chest. Local anesthesia is obtained with 10 mL of 2% lidocaine with adrenalin injected in cutis, subcutis, muscle and pleura. Before removing the syringe, aspiration of pleural fluid confirms the relevance of the chosen site. The area is wiped with disinfectant and a millimeter skin incision is made with a pointed scalpel. A 7 French (or up to 16 French, to the choice of the clinician) pigtail catheter is inserted and connected to sealed bag. Fluid is aspirated via a 3-way valve, and transferred to relevant bottles for culture, analysis of albumin and LDH, protein, and for cytology.

Thoracentesis

Uffe Bødtger, MD, PhD,

The research group will investigate the diagnostic effect of early introduction of ultrasound guided pleural biopsy in the work-up of patients with one-sided pleural effusion, suspected of malignant pleural effusion.

Patients with unilateral pleural effusion with high protein content (exudative pleural effusion) are likely to have malignant pleural effusion. In the Danish guidelines, patient undergo two thoracentesis before more invasive procedures, due to the relatively low incidens of pleural TB and mesothelioma. The aim of the research group is to investigate the effect of early introduction of ultrasound-guided pleural biopsy taken at the optimal sport for thoracentesis. The research group will randomise half of our patients with unilateral pleural exudate to up-front ultrasound-guided biopsy and the other half usual care eg. a second thoracentesis, to see if there is a benefit of early pleural biopsy in the work-up of patients with unilateral pleural effusion, suspected of malignant pleural effusion.

Ultrasound-guided Biopsy of the Pleura as a Supplement to Extraction of Fluid in Patients With One-sided Fluid in the Pleura

Ultrasound-guided Pleural Biopsy as a Supplement to Thoracentesis: A Randomised Study

Our primary endpoint includes both patients who will receive palliative care and patients who will receive active treatment. For patients receiving palliative care, the presence of malignant cells is sufficient. However, for patients receiving active treatment, the primary endpoint is defined as a definite and treatment-guiding pathological result (immunohistochemistry, mutations, oncodrivers, culture and biochemistry) as decided by a multidisciplinary team conference.

mortality, pneumothorax, haemoptysis, local bleeding, infections and hospital admissions

measured by 5Q-5D-5L (2009 EuroQol Group EQ-5D™ Danish version).

Measured by Edmonton Symptom Assessment System (ESAS), scale 1-10, 0 being no symptoms, 10 being the worse symptoms

VAS score (visual analogue scale) for cough, 0-10, 0 being no cough, 10 being the worse cough

Measured by VAS score (visual analogue scale) for pain, 0-10, 0 being no pain, 10 being the worse pain

Measured by 5-point Likert scale,scale 1-5, 1 being definitely willing to have the procedure again, 5 being definitely not willing to have the procedure performed again

iMeasured by Edmonton Symptom Assessment System (ESAS) and VAS score (visual analogue scale) for cough

Measured by Edmonton Symptom Assessment System (ESAS) and VAS score (visual analogue scale) for cough and health measured by 5Q-5D-5L (2009 EuroQol Group EQ-5D™ Danish version).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Immune- and Microenvironment- Proteogenomics Profiling for Classifying Lung Cancer Patients	NCT04887545	Lung Cancer Malignancy	Proteomics anal...	18 Years -	Universidade Nova de Lisboa
Molecular Predictors of Cancer in Patients at High Risk of Lung Cancer	NCT00898313	Lung Cancer	comparative gen... gene expression... proteomic profi... biologic sample... nasal brushing Blood draw Urine collectio... sputum sample fluorescence br... fine needle asp... thoracentesis	18 Years -	Vanderbilt-Ingram Cancer Center
Collection of Malignant Ascites, Pleural Fluid, and Blood From People With Solid Tumors	NCT03189108	Ovarian Cancer Primary Periton... Fallopian Tube ... Cancer		18 Years -	National Institutes of Health Clinical Center (CC)
Molecular Predictors of Cancer in Patients at High Risk of Lung Cancer	NCT00898313	Lung Cancer	comparative gen... gene expression... proteomic profi... biologic sample... nasal brushing Blood draw Urine collectio... sputum sample fluorescence br... fine needle asp... thoracentesis	18 Years -	Vanderbilt-Ingram Cancer Center
Ultrasound-guided Biopsy of the Pleura as a Supplement to Extraction of Fluid in Patients With One-sided Fluid in the Pleura	NCT04236037	Malignant Pleur... Exudative Pleur...	ultrasound-guid... Thoracentesis	18 Years -	Naestved Hospital

Spots Global Cancer Trial Database for thoracentesis