Blood and Lymph Conditions

Diseases and Abnormalities at or Before Birth

All Conditions

Nutritional and Metabolic Diseases

Rare Diseases

Anemia, Sickle Cell

Thalassemia

Iron Overload

Hemochromatosis

Hemosiderosis

Metabolic Diseases

Iron Metabolism Disorders

Sickle Cell Anemia

Hemochromatosis Type 3

Micronutrients

All Drugs and Chemicals

Hematinics

Iron

Liver Extracts

Patients with iron overload or excessive body iron burden, a serious condition resulting from increased dietary gastro¬intestinal absorption, multiple erythrocyte transfusions, or both.

Interventions: R2\*-UTE, R2\*-GRE, and if clinically indicated, liver biopsy.

Ultra short echo time (UTE) magnetic resonance imaging (MRI). Study participants will undergo an MRI examination of the liver on a 1.5T MRI and a 3T MRI scanner each. Because liver biopsy metal needle fragments could interfere with the MRI measurements, the MRI exams will always precede liver biopsy. Multi-echo GRE sequences will be used to acquire images with increasing TEs. Images of the liver will be obtained in transversal slice orientation through the center of the liver at the level of the origin of the main portal vein. At equivalent slice locations R2\*-UTE scans will be performed.

R2*-UTE

Gradient-echo (GRE) magnetic resonance imaging (MRI). Study participants will undergo an MRI examination of the liver on a 1.5T MRI and a 3T MRI scanner each. Because liver biopsy metal needle fragments could interfere with the MRI measurements, the MRI exams will always precede liver biopsy. Multi-echo GRE sequences will be used to acquire images with increasing TEs. Images of the liver will be obtained in transversal slice orientation through the center of the liver at the level of the origin of the main portal vein. At equivalent slice locations R2\*-UTE scans will be performed.

R2*-GRE

Indications for liver biopsy include, but are not limited, to the need to quantify liver tissue iron and the need to obtain histopathological information of the liver tissue. Liver biopsies will only be performed if clinically indicated and will be done only once per patient. The technique to be used is coaxial percutaneous (transcapsular) technique; however, a coaxial transjugular technique may be performed in subjects with increased bleeding diathesis, since it is associated with less hemorrhagic risk. Healthy volunteers will not undergo liver biopsy.

Liver biopsy

Jane Hankins, MD, MS

Iron overload is a severe complication of multiple blood transfusions. As the body has no physiologic mechanism for clearing iron, repeated transfusions cause iron accumulation in organs and lead to iron toxicity. Accurate assessment of iron overload is paramount to quantify excessive iron accumulation and to monitor response to iron chelation therapy. Magnetic resonance imaging (MRI) methods have been used to noninvasively measure hepatic iron concentration (HIC). Although MRI-based measurements of transverse relaxation rates (R2 and R2\*) accurately predict biopsy-proven HICs below 15 mg Fe/g, previous studies have shown that their precision is limited for HICs above 15 mg Fe/g and inaccurate above 25 mg Fe/g. Current R2\* gradient-echo (GRE) MR techniques fail occasionally for very high iron overloads (HIC \~ 15-25 mg Fe/g) and always for massive iron overloads (HIC \> 25 mg Fe/g) because R2\* is so high that the MR signal decays before it can be measured accurately.

Overall accrual: 200 patients

Purpose: To determine if a new MRI (UTE) can measure the amount of iron in the liver of people with large amounts of iron and compare the results with the same patient's liver bx. Estimated patient accrual is 150. It is estimated that 41 of these patients will have clinical indication for liver biopsy.

The MIDAS study is a prospective and non-therapeutic study that will test a new MRI technique for the assessment of iron overload in the liver: the newly developed ultra short echo time (UTE), R2\*-UTE. The R2\*-UTE technique, developed by St. Jude investigators from the Department of Radiological Sciences, will be first tested in healthy volunteers for feasibility and implementation of the technique. The technique will then be tested in research participants, who will have both the R2\*-GRE and the R2\*-UTE techniques performed, in addition to a liver biopsy for liver iron quantitation if clinically indicated. Quantitation of liver tissue iron will be done at Mayo Clinic Laboratory in Rochester, Minnesota.

Primary Objective:

* To test the association of hepatic iron content (HIC) measured with the newly developed 1.5T R2\*-UTE technique and HIC quantified by liver biopsy in subjects with iron overload.

Secondary Objectives:

* To explore the relationship between 1.5T R2\*-UTE and 1.5T R2\*-GRE measurements in subjects with iron overload.
* To explore the relationship between 1.5T R2\*-UTE measurements with iron studies (serum iron and transferrin saturation) in subjects with iron.

Massive Iron Deposit Assessment

Hepatic iron content in the liver using liver biopsy

Hepatic iron content of the liver using MRI-derived 1.5T R2\*-UTE measurement, with results in Hz. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every "picture taken", this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.

MRI-derived R2\* Using 1.5T GRE Technique in Hz. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every "picture taken", this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.

MRI-derived R2\* value using 1.5T R2\*-UTE in Hz. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every "picture taken", this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.

MRI-derived R2\* value using 1.5T R2\*-UTE in Hz for patients who have had serum iron and transferrin saturation measurements. R2\* is a measure obtained with MRI, i.e., MRI R2\*. It is measured in hertz (Hz). In lay terms, the MRI machine picks up a signal back from the tissue during the process of scanning the tissues. With every "picture taken", this signal is strong in the beginning and then wanes off. R2\* reflects how fast the signal wanes off. If there is too much iron in the tissue, the signal disappears faster, making the T2\* value low. T2\* is the reciprocal of R2\* (R2\*= 1/T2\*). So, if the signal drops fast, the T2\* is low and the R2\* is high. In this study, we are measuring the R2\* value. The higher the R2\*, the more iron in the liver tissue. We can compare the R2\* value with that of a liver biopsy to then use the R2\* value to tell us how much iron is in the liver without having to biopsy the liver.

Serum iron measurements from eligible patients had 1.5T R2\*-UTE and serum iron and transferrin saturation measurements.

Iron Transferrin Saturation in % measurements Transferrin Saturation measurements from eligible patients had 1.5T R2\*-UTE and serum iron and transferrin saturation measurements.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Regional One Health

St. Jude Children's Research Hospital

Eligible iron-overloaded patients with both liver biopsy measurement and 1.5T R2\*-UTE measurement

Iron-overloaded Patients

All eligible patients with history of 12 or more lifetime erythrocyte transfusions, and need for liver iron content assessment

Arm 1

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Asian

Black or African American

White

More than one race

Unknown or Not Reported

Race/Ethnicity, Customized

United States

Region of Enrollment

Jane Hankins, MD

Eligible iron-overloaded patients with both liver biopsy measurement and 1.5T R2\*-UTE measurement.

Hepatic Iron Content in the Liver Using Liver Biopsy

MRI-derived R2* Values Using 1.5T UTE Technique

Iron-overloaded patients defined as having more than 12 transfusions in their lifetime as measured with R2\* using 1.5T GRE.

Iron-overloaded patients had 1.5T R2\*-GRE measurements.

MRI-derived R2* Using 1.5T GRE Technique

Iron-overloaded patients with R2\* using 1.5T UTE

Iron-overloaded patients had 1.5T R2\*-UTE-measurement.

MRI Derived R2* Using 1.5T UTE Technique

1.5T R2\*-UTE from eligible patients who had 1.5T R2\*-UTE, serum iron, and transferrin saturation measurements.

R2* Using 1.5T UTE Technique for Patients With Serum Iron and Transferrin Saturation Measurements

Serum Iron Measurements

Iron-overloaded patients had 1.5T R2\*-UTE and serum iron and transferrin saturation measurements.

Serum Iron Measurements Compared With 1.5T R2* UTE

Iron-overloaded patients with 1.5T R2\*-UTE and serum iron and transferrin saturation measurements.

Transferrin Saturation Measurements

All eligible patients with history of 12 or more lifetime erythrocyte transfusions, and need for liver iron content assessment.

Overall Study

Digestive System Diseases

Symptoms and General Pathology

Neoplasms

Behaviors and Mental Disorders

Liver Cirrhosis

Metabolic Syndrome

Syndrome

Carcinoma

Carcinoma, Hepatocellular

Liver Diseases

Fatty Liver

Alcohol Drinking

Non-alcoholic Fatty Liver Disease

Fibrosis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Insulin Resistance

Hyperinsulinism

Glucose Metabolism Disorders

Drinking Behavior

Chronic Graft Versus Host Disease

Visceral Steatosis

Anti-Infective Agents

Central Nervous System Depressants

Ethanol

The patients included in this observational study are patients with hepatic steatosis either related to NAFLD or to alcohol-related liver disease.

Patients included in the study may have hepatocellular carcinoma.

Thus, 4 groups of patients can be recruited:

* patients with NAFLD without hepatocellular carcinoma,
* patients with NAFLD with hepatocellular carcinoma,
* patients with alcohol-related liver disease without hepatocellular carcinoma, -patients with alcohol-related liver disease with hepatocellular carcinoma.

Liver biopsy planned as part of routine care. Clinical-biological characterisation with bio collections.

Rodolphe Anty, MD, PhD

The aim is to determine the metabolic factors, host immune factors, and medical imaging data associated with the development of HepatoCellular Carcinoma (HCC) in patients with alcohol-related liver disease or dysmetabolic steatosis/Non-Alcoholic SteatoHepatitis.

The investigators will include patients with and without cirrhosis in order to identify early molecular mechanisms involved in the development of HCC especially in non-cirrhotic patients.

Type and methodology of the research:

Within the framework of the usual management of the patient's pathology, a clinico-biological characterization (dietary and physical activity questionnaires, "performans status", anthropometric measurements, usual blood biology characterizing the hepatic, renal and inflammatory function, the carbohydrate and lipid metabolism, the non invasive test for liver fibrosis ELF etc.) will be carry out. In order to collect radiomic data, liver imaging (particularly in case of HCC) will be done.

A liver biopsy and constitution of a biobank (samples of plasma, sera, DNA and leucocyte pellets) will be performed.

The elements necessary for the classification of possible hepatocellular carcinomas (BCLC classification) will be collected.

Anticipated research schedule:

* The duration of inclusion in this research will be 10 years.
* The duration of the patient's participation will be from 1 day (if the consent is signed and the biopsy is performed on the same day) to 2 months (maximum reflection period is 8 weeks between the signature of the consent and the taking of samples).
* The total duration of the research (from the first inclusion, to the last visit of the last participant) will be 10 years and 2 months.

standard liver biopsy (for immunocytochemistry), frozen liver biopsy, frozen serum, frozen plasma, DNA

CHronic Hepatopathies Associated With ALcohol Consumption aNd metAbolic Syndrome

The primary endpoint will be the study of variations in metabolic gene markers (i.e. mRNA of genes implicated in inflammation or metabolism assessed in qPCR, using a housekeeping gene such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH)), in patients with and without hepatocellular carcinoma with different levels of severity of liver damage.

Secondary endpoint will include variations in other gene markers (e.g. genes implicated in the regeneration, cell deaths and tumor, assessed in qPCR, using a housekeeping gene such as glyceraldehyde-3-phosphate dehydrogenase (GAPDH)) in patients with and without hepatocellular carcinoma with different levels of severity of liver damage.

3th endpoint will include variations in genetic markers (Single Nucleotide Polymorphisms (SNPs)), in patients with and without hepatocellular carcinoma with different levels of severity of liver damage.

The frequency of SNPs will be compared to that found in the UK biobank cohort.

4th endpoint will include variations in epigenetic markers (histone methylation, micro RNA), in patients with and without hepatocellular carcinoma with different levels of severity of liver damage.

5th endpoint will include variations in tissue proteins (including tumor and non tumor tissue), in patients with and without hepatocellular carcinoma with different levels of severity of liver damage. Western blots will be quantified and compared in an automated way.

6th endpoint will include variations in specific markers or markers derived from analysis via platforms (OMICS), in patients with and without hepatocellular carcinoma with different levels of severity of liver damage.

7th endpoint will include variations in radiomics (radiomics is a method that extracts a large number of features from medical images using data-characterisation algorithms), in patients with and without hepatocellular carcinoma with different levels of severity of liver damage.

Centre Hospitalier Universitaire de Nice

Institut National de la Santé Et de la Recherche Médicale, France

Professor

Coagulants

Hemostatics

Blood collection (50 ml) will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Following analysis should be performed with

* serum for protein assays and characterization analysis of cytokines, new tumor markers and micro-RNA ...;
* plasma for protein assays and characterization analysis of micro-RNA, VEC (the content of proteins, RNA, micro-RNA and DNA) and metabolomics;
* PBMC for flow cytometry analysis, isolation macrophages;
* whole blood for circulating tumor DNA (mutations by NGS, ddPCR,...; methylation) and circulating tumor cells.

Blood sampling

An intraoperative liver biopsy will be performed at free edge of liver with a triangular sample for local resected patients.

This biopsy will be done with scissors, then patients will receive intraoperative hemostasis with mono- or bipolar coagulation. This procedure will be under laparoscopy or laparotomy without extending standard processing time.

This biopsy seeks to allow the evaluate liver modifications testifying the preparing for premetastatic niche, which would allow to identify the patients with risk for hepatic relapsing; the same analysis on the tumors will be performed.

Stool collection will be performed for all patients at baseline, at 1 month post-operative for resected patients (+ at the end of neoadjuvant treatment / before surgery if patient receives neoadjuvant treatment), and at 2-3 months after the beginning of the treatments in patients with metastases (+ at each progression).

Analysis will be performed for microbiota and metabolism analysis.

Stool collect

Frédérique PESCHAUD, MD, PhD

Cindy NEUZILLET, MD

The primary objective: association study of characteristics of tumoral microenvironment and immunity of digestive cancers with patients' overall survival (OS).

The study aims to explore relationship between the molecular subgroups (DNA and RNA analysis), tumor microenvironment, host (immunity system, premetastatic niche, microbiota, metabolism) and survival (prognostic value), response (predictive value) and tolerance (toxicities) to conventional treatments or immunotherapies in digestive cancers, in particular, in colorectal cancer and pancreaticobiliary cancer.

This is a prognostic monocentric study which includes 2 parts:

* one retrospective observational cohort for which 150 eligible patients (who have being diagnosed between 1998 to 2020) will be entered in the cohort per year during 22 years targeting 3300 patients and
* one prospective interventional cohort in which 3000 patients (diagnosis will be done between 2020-2030) will be enrolled during 10 years. 10 years of follow-up for all patients. This cohort is non comparative, non randomized, non control.

The enrollment will last 10 years in Digestive Surgery Department, Ambroise Paré Hospital, APHP.

There is any change in management of patients' care who will participate to the study, all of the treatment modalities (i.e. surgery, chemotherapy, radiotherapy, immunotherapy, intra-arterial treatments and supportive care) are possible and choice of treatment will be made by investigator physician, after multidisciplinary meeting validation, and according to referential and recommendations of practice in department.

Statistic analysis

The statistic analysis will be performed and reported according to the international guidelines STROBE for the observational studies.

Interaction Between Host, Microenvironment and Immunity on Gastrointestinal Neoplasms

Interaction Between Host, Microenvironment and Immunity on Gastrointestinal Neoplasms: A Retro-prospective Cohort Study

The OS is defined as timeframe between beginning of treatment (date of surgery or 1st cure of chemotherapy/immunotherapy) and death (regardless of reason).

The SWD is defined as timeframe between date of surgical treatment and appearance of cancer relapse, 2nd cancer diagnosis or death (regardless reason).

The SWP is defined as timeframe between the beginning of treatment (date of 1st cure of chemotherapy/immunotherapy or date of 1st session of radiotherapy) and the 1st progression or death (regardless reason).

The response of tumor will be evaluated according to the RECIST v1.1, Choi (intra-arterial treatments, antiangiogenic therapy) and/or iRECIST (immunotherapies) and/or imaging examinations depending on the given treatments.

Assistance Publique - Hôpitaux de Paris

Carcinoma, Ductal

Bile Duct Cancer

Intrahepatic Cholangiocarcinoma

Prior to PVE, patients undergo CT perfusion scan of the liver and liver biopsy over 15 minutes. Patients undergo a second CT perfusion scan immediately after PVE and a third CT perfusion scan 3-6 weeks post PVE.

Computed Tomography Perfusion Imaging

Liver Biopsy

Steven Y Huang, MD

Steven Y. Huang, MD

This trial studies the use of computed tomography (CT) perfusion scans in detecting changes in blood flow to the liver after portal vein embolization in patients with liver cancer. CT perfusion scans use a standard contrast drug given by vein to measure blood flow to the liver. CT perfusion scans may predict the rate and amount of growth of new, healthy tissue on one side of the liver after a portal vein embolization and detect change to the size of the liver tumor as result of the procedure.

PRIMARY OBJECTIVES:

I. To assess whether perfusion changes to the liver following portal vein embolization (PVE) correlate with hypertrophy of the future liver remnant (FLR).

SECONDARY OBJECTIVES:

I. To assess perfusion changes to liver tumors following PVE. II. To assess whether PVE may affect tumor growth.

OUTLINE:

Prior to PVE, patients undergo CT perfusion scan of the liver and liver biopsy over 15 minutes. Patients undergo a second CT perfusion scan immediately after PVE and a third CT perfusion scan 3-6 weeks post PVE.

CT Perfusion Scans in Detecting Changes in Blood Flow to the Liver After Portal Vein Embolization

To Evaluate Perfusion Changes to the Liver Following Pre-Operative Portal Vein Embolization for Patients With Liver Cancer

Will assess whether perfusion changes to the liver following PVE correlate with hypertrophy of the future liver remnant (FLR). Perfusion and FLR hypertrophy are two continuous variables. Each patient will serve as his/her own control. Perfusion to the liver (1) before PVE, (2) immediately after PVE, and (3) 3-6 weeks following PVE will be measured and compared. The changes in perfusion will be compared with FLR hypertrophy at the 3-6 week time point to assess correlation.

Will assess perfusion changes to liver tumors following PVE and whether this may affect tumor growth kinetics. Each patient will serve as his/her own control. Perfusion to the liver tumor(s) (1) before PVE, (2) immediately after PVE, and (3) 3-6 weeks following PVE will be measured and compared. Since a percutaneous biopsy will be performed of a single liver tumor before PVE and the tumor explant will be available following surgical resection, changes to tumor cellular proliferation following PVE can be assessed.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

liver tissue will be collected via core biopsy during liver resection surgery and post-operatively by fine needle aspiration biosy

Mamatha Bhat, MD

The liver is the only visceral organ with a tremendous capacity to regenerate. We don't yet understand how normal liver regeneration occurs (on a molecular level) or how to distinguish between normal and "abnormal"/neoplastic regeneration. This study will characterize the role of the different liver cell types in the regeneration process and will examine gene expression changes in the various liver cell types.

New studies are demonstrating that rodent models of the liver and liver disease are inadequate. The human liver is quite different and needs to be studied directly. The cell expression of human liver cells during regeneration has many implications for treatment of patients with cirrhosis and cancer.

This study will characterize the role of the different liver cell types in the regeneration process and will examine gene expression changes in the various liver cell types. We hypothesize that there is significant crosstalk among hepatocytes, macrophages, and T-cell subsets in the human liver, stimulating the regenerative process.

Tissue will be obtained from serial biopsies of "healthy" liver that is regenerating in patients who undergo liver resection for metastatic colorectal cancer. All participants must first provide written informed consent and meet study eligibility criteria. The first tissue sample will be collected intraoperatively, then serial fine-needle aspiration biopsies (FNAB) will be performed approx. 1 week following surgery, and 1 month following surgery. Liver regeneration will also be assessed using routine imaging of the liver at approx. 3 months.

Retrospective (previously collected diagnostic or biobanked) tissue is also being included for study, given lower than anticipated enrollment.

Liver Regeneration

Understanding the Molecular Basis of Normal Liver Regeneration

University Health Network, Toronto

Quantitative Ultrasound

B-mode US performed according to the clinical standard of care.

B-mode Ultrasound

The composite reference standard includes MRI performed according to the clinical standard of care or histopathology when available.

Magnetic Resonance Imaging

An Tang, MD, MSc

Casey Bourdeau Caporuscio, MSc

Worldwide, liver cancers are the third most common cause of cancer mortality. Even when liver cancer is suspected by blood tests, imaging is required to determine the location, size, and extent of disease. Medical societies therefore recommend surveillance with ultrasound every 6 months in at-risk patients. However, a key challenge to improving the survival is that ultrasound may miss half of early-stage liver cancers, thus diagnosis must rely on additional tests such as computed tomography (CT), magnetic resonance imaging (MRI), or biopsy. Hence, there is a clear need to improve the ability to detect liver cancers, especially with ultrasound. The investigator's team proposes novel ultrasound approaches to detect cancer nodules invisible on conventional ultrasound based on differences in mechanical and structural properties between liver and tumor. Improving detection is critical because liver cancer can be cured only if detected at an early stage, as shown by improvements in survival rates in patients enrolled in surveillance programs. The investigator's multi-disciplinary, national, and international team includes experts in clinical fields (hepatology, oncology, radiology, pathology), basic sciences (engineering, medical physics, machine learning, biostatistics), and patient partnership. The investirgator will apply the methodology of patient partner recruitment and collaborate with the Centre of Excellence on Partnership with Patients and the Public to select potential new collaborators. This will permit this project to be informed at every stage by patient and family perspectives, ensuring that the results of this project will be more robust, impactful, and aligned with the priorities, needs and experiences of those who live with liver cancer. The investigator submits a research proposal focused on advanced imaging techniques because imaging constitutes a foundation for surveillance, diagnosis, staging, treatment selection and assessment of treatment response in patients with liver cancer.

BACKGROUND Worldwide, liver cancers are the third most common cause of cancer mortality. In Canada, hepatocellular carcinoma (HCC) is one of the few cancers for which mortality is increasing. Early detection of HCC improves the likelihood of curative treatment and survival. Systematic HCC surveillance with ultrasound (US) is recommended by practice guidelines. However, conventional (B-mode) US suffers from low sensitivity (47%) for detecting early-stage HCC due to fatty liver, obesity, and cirrhosis. Once a suspicious nodule is detected by US, guidelines recommend contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) to confirm cancer. Hence, there is an urgent need to improve the ability to detect and diagnose HCC early. Members of the investigator's team have developed innovative quantitative ultrasound (QUS) techniques (including shear wave viscoelastography \[SWV\] and sub-resolution cellular imaging) that have a high diagnostic potential. The investirgator hypothesizes that a combination of QUS techniques offering complementary assessment of tissue characteristics will improve our ability to detect liver nodules and diagnose HCC.

METHODOLOGY Design: Prospective, cross-sectional imaging trial comparing head-to-head B-mode US and research QUS acquired within one month to the composite reference standard. Reference standard: MRI will be used as the non-invasive ground truth for liver nodules detection and classification except when biopsy is available. Data analysis: Lesion detectability will be measured by contrast-to-noise ratio on US and QUS maps for different size thresholds (\<10 mm, 10-20 mm, \>20 mm) used in diagnostic algorithms. Diagnostic performance will be measured by receiver operating characteristic curve analysis on the training and test sets for different size thresholds. The diagnostic accuracy of US and QUS + B-mode US will be compared by using the DeLong method.

RATIONALE AND IMPACT Early detection through systematic US surveillance translates into curative therapy in a higher proportion of patients and into improvements in survival rates. This imaging trial will provide a low-cost imaging technique to identify liver cancers earlier and from a single exam. Unlike some other imaging techniques, US is widely available throughout Canada. A major impact of this work, for patients and medical institutions, will be to lower the need for liver biopsy, the risk of complications and the cost for HCC diagnosis. This trial will position Canada as a leader in HCC diagnosis as new QUS and SWV biomarkers will be tested.

Early Detection of Liver Cancer by QUS

Quantitative Ultrasound to Improve Detection and Diagnosis of Liver Cancer

Lesion detectability will be measured by contrast-to-noise ratio on US and QUS maps for different size thresholds (\<10 mm, 10-20 mm, \>20 mm) used in diagnostic algorithms

Diagnostic performance will be measured by receiver operating characteristic curve analysis on the training and test sets for different size thresholds

The diagnostic accuracy of US and QUS + B-mode US will be compared by using the DeLong method

Centre de Recherche du Centre Hospitalier de l'Université de Montréal

Canadian Institutes of Health Research (CIHR)

Centre hospitalier de l'Université de Montréal (CHUM)

Participants undergo to a liver biopsy, a venous blood sampling and a fecal sample collecting

The liver biopsy is ultrasound-guided and target the hepatic lesions. It is performed with 18G or 19G Menghini needle. A part of bioptic sample will be used for genomic analysis. An other part of sample will be cultured to create the organoid. The organoid's cultures will be integrated with the host gut microbiota (collected by a fecal sample) and peripheral blood mononuclear cells (from venous blood sample) and they will be used for research such as molecular analysis and pharmacological tests.

Francesca Ponziani, MD

The goal of this interventional study is to create hepatocellular carcinoma organoids from liver bioptic samples of individuals with hepatocellular carcinoma. The main questions it aims to answer are:

* the feasibility of hepatocellular carcinoma organoids integrated with host gut microbiota and peripheral blood mononuclear cells
* the molecular pattern of the organoid tumor microenvironment
* the in vitro therapeutic response of hepatocellular carcinoma organoids

Hepatocellular Carcinoma Liver Organoids

Hepatocellular Carcinoma Organoids to Explore Tumor Microenvironment and Test Treatment Efficacy - Hepatocellular Carcinoma Liver Organoids (HELIO)

Number of successfully created organoids from all hepatocellular carcinoma samples

Comparison between organoids transcriptome and data from The Cancer Genome Atlas

DNA organoids and original tumor sample sequencing and comparison between the somatic genetic mutations found in both models

Definition of microbiota composition via DNA and RNA sequencing and correlation between specific bacteria abundance and successful organoids growth

Evaluation of organoids' tumor cells survival after 5 days of chemotherapy treatment.

Treatment will include different concentrations of sorafenib, lenvatinib, atezolizumab, bevacizumab, tremelimumab, durvalumab, regorafenib, cabozantinib. Tumor cells vitality will be assessed trough Cell TitelGlo3D Cell Viability Assay.

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Respiratory Tract (Lung and Bronchial) Diseases

Respiratory Aspiration

Patients with HCC or metastatic liver lesions who are refered to the abdominal imaging and biopsy clinic will have a liver biopsy performed. 3-5 days after a clinical MRI indicating a cancerous lesion, patients will return for the free-breathing MRI and a liver biopsy. These images will be compared to the clinical MRI and to images of the benign lesions.

Patients with benign liver lesions will be referred to the study team. 3-5 days after a clinical MRI an experimental, free-breathing MRI will be performed on these patients. The results will be compared to their clinical MRI images and to images of HCC or metastatic lesions

patients with HCC or metastatic lesions will have a liver biopsy performed after the experimental MRI. This biopsy will be examined to confirm the imaging results

liver biopsy

All patients will be asked to come in for an MRI scan using techniques developed which minimize the time a patient has to hold their breath to image the liver to \<8 seconds and validate quantifiable techniques which improve liver image quality

free-breathing MRI

Vikas Gulani, MD

The primary objective of this study is to develop and validate simultaneous free-breathing 4D fat and water quantification and quantitative dynamic contrast enhanced perfusion in the liver. Secondary aims include developing and validating free breathing quantification of relaxation parameters T1 and T2, and developing and validating a minimal breath-hold (\< 8 s) high quality diffusion exam using highly accelerated steady state diffusion imaging sequences. Investigators aim to scan 100 subjects receiving liver biopsies as a part of their standard care and another 70 subjects with known benign lesions. The study is greater than minimal risk.

The investigators hypothesize that a quantitative and near free-breathing MRI approach with Hepatocellular carcinoma (HCC) patients will lead to improved tissue characterization, resulting in fewer ambiguous readings and thus fewer biopsies. As each component of the proposed methodology has been experimentally validated in the investigators preliminary work, the next appropriate step would be to evaluate the clinical feasibility of the exam. The investigators goal is to test the ability of quantitative MRI techniques to provide high quality images of the liver and to differentiate liver lesions from one another in a time frame shorter than a current clinical exam.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Massive Iron Deposit Assessment	NCT01572922	Iron Overload Excessive Body ...	R2-UTE R2-GRE Liver biopsy	-	St. Jude Children's Research Hospital
CHronic Hepatopathies Associated With ALcohol Consumption aNd metAbolic Syndrome	NCT05623150	Non-Alcoholic F... Non-Alcoholic S... Alcohol-related... Cirrhosis, Live... Hepatocellular ...	Liver biopsy	18 Years -	Institut National de la Santé Et de la Recherche Médicale, France
Interaction Between Host, Microenvironment and Immunity on Gastrointestinal Neoplasms	NCT04363983	Gastrointestina...	Blood sampling Liver biopsy Stool collect	18 Years -	Assistance Publique - Hôpitaux de Paris
CT Perfusion Scans in Detecting Changes in Blood Flow to the Liver After Portal Vein Embolization	NCT03990623	Liver and Intra...	Computed Tomogr... Liver Biopsy	18 Years -	M.D. Anderson Cancer Center
Massive Iron Deposit Assessment	NCT01572922	Iron Overload Excessive Body ...	R2-UTE R2-GRE Liver biopsy	-	St. Jude Children's Research Hospital
Liver Regeneration	NCT03396705	Liver Diseases Liver Cancer	Liver Biopsy	18 Years -	University Health Network, Toronto
Early Detection of Liver Cancer by QUS	NCT06345508	Hepatocellular ... Liver Cancer	Quantitative Ul... B-mode Ultrasou... Magnetic Resona... Liver Biopsy	18 Years -	Centre hospitalier de l'Université de Montréal (CHUM)
Hepatocellular Carcinoma Liver Organoids	NCT06355700	Hepatocellular ...	Liver biopsy	18 Years -	Fondazione Policlinico Universitario Agostino Gemelli IRCCS
CHronic Hepatopathies Associated With ALcohol Consumption aNd metAbolic Syndrome	NCT05623150	Non-Alcoholic F... Non-Alcoholic S... Alcohol-related... Cirrhosis, Live... Hepatocellular ...	Liver biopsy	18 Years -	Institut National de la Santé Et de la Recherche Médicale, France
Assessment of Novel MRI Quantification Free Breathing Technique in Evaluation of Liver Lesions	NCT02095678	Hepatocellular ...	liver biopsy free-breathing ...	18 Years - 100 Years	Case Comprehensive Cancer Center
Boramae Hospital Liver Cirrhosis Patient Cohort Study	NCT01943318	Liver Cirrhosis Hepatocellular ...	Liver biopsy Hepatic venous ...	19 Years -	Seoul National University Boramae Hospital
Treatment Response Evaluation in Patients With Non-resectable Colorectal Liver Metastases A Feasibility Study	NCT03444194	Liver Metastasi...	liver biopsy	18 Years -	Odense University Hospital
Identification of Liver Tumours Using BIP - Biopsy System	NCT02620228	Liver Biopsy	BIP Biopsy Syst...	18 Years -	Injeq Ltd

Spots Global Cancer Trial Database for liver biopsy

Every month we try and update this database with for liver biopsy cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.