Neoplasms

All Conditions

Digestive System Diseases

Heart and Blood Diseases

Carcinoma

Carcinoma, Hepatocellular

Thrombosis

Venous Thrombosis

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Operation for clinically evaluated resectable hepatocelluar carcinoma. Compare the different expression of protein between tumor, non-tumor and tumor with vascular invasion part.

Operation

This is a pilot study to evaluate the difference between the protein expression between hepatocellular carcinoma and tumor with vessel invasion in Asian patients with hepatocellular carcinoma.

Proteomic Analysis of Human Hepatocellular Carcinoma

Proteomic Analysis of Human Hepatocellular Carcinoma Associated With Portal Vein Thrombosis

Evidence of clinically definite vascular invasion of hepatocellular carcinoma. Confirmed by operation. Compare the proteomic expression of tumor, non-tumor ans tumor tissue in vascular part.

Far Eastern Memorial Hospital

Physician

Symptoms and General Pathology

Neoplastic Cells, Circulating

Observational study of CTC microemboli in portal vein blood samples.

During Endoscopic UltraSound guided-Fine Needle Aspitation (EUS-FNA) a curvilinear echoendoscope is advanced to the distal stomach or duodenal bulb to provide a window of access to a branch of the PV. After verifying venous flow by Doppler signal, a 19-gauge EUS-FNA needle is advanced transhepatically into the portal vein branch. With the needle in the portal vein, the stylet is removed and negative-pressure suction is applied to aspirate blood. A transhepatic approach for portal vein branch access is an absolute requirement of this technique in order to minimize the risk of bleeding. The puncture site is monitored under EUS for complications.

Portal vein sampling

This is a research study in which bio-specimens (whole blood, plasma and serum from peripheral circulation and portal vein) will be collected from patients with pancreatic adenocarcinoma for translational research. These samples will be used for (but not limited to) identification and characterisation of blood-borne biomarkers at the genomic and protein expression level. Examples of such biomarkers are circulating tumour cells (CTCs), CTC clusters and circulating DNA (which can be tumour derived, or from unaffected/normal cells). CTC-enriched blood samples may also be used to generate CTC-derived tumour explant (CDX) models in immunocompromised mice in order to produce suitable disease models in which to test novel therapies and identify new molecular targets. In addition, permission will be sought from study participants for the research team to access clinical information from medical notes to aid in determining the clinical relevance of biomarkers identified during the course of this study. Validated biomarkers are anticipated to be used in designing future biomarker-directed clinical trials in these disease groups.

Pancreatic Ductal Adenocarcinoma (PDAC) presents an urgent medical need. Approximately 9000 new cases of pancreatic cancer are diagnosed every year in the United Kingdom (UK) and worldwide it is projected to become the second most common cause of cancer related death by 2030. Currently the diagnostic pathway starts with pancreatic protocol Computed Tomgraphy (CT) scan which demonstrates sensitivity of 90% and specificity of 99% in diagnosis of pancreatic cancer. Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) can assist with ambiguous masses. Despite the high sensitivity and specificity of imaging modalities, definitive diagnosis is routinely obtained only by endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). During this procedure four "passes" (biopsies) on average are required to obtain sufficient tissue for diagnosis.

Patients usually present with locally advanced or metastatic disease and are offered standard of care chemotherapy, which has only a limited impact on overall survival. Consequently the 5-year overall survival (OS) is only 2% with no significant improvement over the last 40 years. Approximately only 20% of the patients are eligible for surgical resection which is followed by adjuvant chemotherapy. However, 66% of these patients will experience local or distant recurrence, leading to a median overall survival in the range of 28 months. Improved stratification of patients for existing treatments may thus avoid unnecessary overtreatment and associated side effects to improve quality of life; conversely, it may also enable selection for a more appropriate treatment.

A significant reason for the lack of progress in tackling metastatic disease is the poor understanding of the biology and pathophysiology of metastasis. Studying the biology of PDAC metastasis is hampered by the fact that it is difficult to obtain tissue from the primary and metastatic sites. Moreover, serial biopsies following progression during treatment is largely not feasible, further hindering insight into the mechanisms of development of treatment resistance. The only easily-accessible blood-borne biomarker that is currently used in clinic is the serum marker carbohydrate antigen (CA) 19-9. However, its clinical use is limited firstly by the fact that 5-10% of the population are Lewis blood group negative and do not express CA19-9. Furthermore it is elevated in non-malignant pancreatic and extra-pancreatic diseases. Finally, CA19-9 cannot provide information about the genetic landscape that drives PDAC metastasis.

Metastatic spread is primarily haematogenous whereby tumour cells enter the circulation to metastasize mainly to the liver and lung. Such tumour cells have been shown to travel either as single circulating tumour cells (CTCs) or as groups of cells termed Circulating Tumour Microemboli (CTM). Heterogeneous CTM composed of cells expressing either epithellial or mesenchymal markers were isolated from patients with pancreatic cancer using a filtration-based method, the Isolation by Size of Epithelial Tumour cells platform (ISET), in a study performed at the Christie NHS Foundation Trust. As such, isolation and characterisation of CTCs and CTM will provide new insight into the underlying biological dependencies of metastasizing tumour cells and may thus provide opportunities to develop better and more accurate diagnostic and prognostic assays as well as opportunities to treat metastatic disease.

Detection and isolation of CTCs and CTM is limited by the fact that they represent very rare events compared to other cellular elements in the circulation. To this end, methods exploiting characteristics that differentiate CTCs from blood cells have been developed to overcome this obstacle. These CTC workflows usually start by enriching CTCs from a blood sample utilizing either surface markers present exclusively on CTCs, or their unique physical properties such as size, inertia, dielectric charge and density. Following enrichment, CTCs are isolated and can be simply enumerated or they are used for more advanced downstream analysis including genomic, transcriptomic and proteomic analysis as well as in vivo applications in cell culture and mouse models, with the aim of gaining insight into their function as metastatic seeds and biomarker development.

In the clinical setting, CTCs can be used to aid decision making. Indeed, enumeration of CTCs detected by the CellSearch platform has been FDA approved for prognosis and monitoring of metastatic breast, colorectal and prostate cancer. However, isolation and enumeration of CTCs in pancreatic cancer has given inconsistent results between studies as to whether CTCs can be used as prognostic biomarkers. These studies analysed CTCs isolated from peripheral blood. However, as the main venous drainage of the pancreas is through the portal vein to the liver, it may be hypothesized that CTCs could be filtered and removed as they pass through the liver capillaries. Hence, in order to define the biological and prognostic role of CTCs in pancreatic adenocarcinoma, it is critical to initiate studies with blood isolated from the portal vein to bypass confounding effects. Indeed, detection of CTCs in portal vein (PV) blood acquired at operation was recently reported by Bissolati et al.. By obtaining peripheral vein samples at the same time, this study confirmed that CTC number was greater in portal compared to peripheral samples and also demonstrated significant correlation between CTC positivity in portal vein samples and frequency on liver metastasis. However, it failed to show significant correlation with OS or Disease Free Survival (DFS). PV sampling has been performed safely; in December 2015 Catenacci et al. reported collection of PV blood from 18 patients with pancreatobilliary cancers by EUS-FNA with no complications during the procedure. PV puncture has also been previously reported for islet cell transplantation in patients with Type 1 Diabetes Mellitus. This procedure has low morbidity and also, potential complications, such as portal vein thrombosis, perihepatic or intraparenchymal hepatic haemorrhage and haemothorax are reported at a low rate.

During EUS-FNA a curvilinear echoendoscope is advanced to the distal stomach or duodenal bulb to provide a window of access to a branch of the PV. After verifying venous flow by Doppler signal, a 19-gauge EUS-FNA needle is advanced transhepatically into the portal vein branch. With the needle in the portal vein, the stylet is removed and negative-pressure suction is applied to aspirate blood. A transhepatic approach for portal vein branch access is an absolute requirement of this technique in order to minimize the risk of bleeding. The puncture site is monitored under EUS for complications. As tumour tissue will be obtained at the same time, a potential risk is the introduction of cancer cells into the circulation as the needle is withdrawn from the tumour. This risk however is circumvented as the route of the needle into the portal vein would avoid the primary mass.

The primary reason for drug failure in PDAC is the failure to identify predictive biomarkers for treatment response which would allow enrichment of patient sub-groups most likely to benefit from an individual therapy. This is in contrast to other major cancer types, in which advances in development of new cancer therapeutics and resulting improvement in survival outcomes are mainly due to the use of predictive biomarkers to select patients who will derive differential benefit from a particular therapeutic agent. Trastuzumab in breast cancers over-expressing HER-2, cetuximab for KRAS wild-type colorectal cancer, and gefitinib and erlotinib for Epidermal Growth Factor Receptor (EGFR) mutant non-small cell lung cancer best exemplify this therapeutic paradigm. By providing greater numbers of CTCs and CTM, analysis of PV sample will enable studies of their biology as well as development of cell lines and CDX models to allow identification of novel biomarkers and targets for new treatments.

Considering current gaps in knowledge of tumour biology of PDAC and the lack of progress in therapeutics, there is an urgent clinical need to develop a research strategy that will allow the discovery and validation of new biomarkers in this group of patients, and inform on biomarker-directed clinical trials to ultimately improve survival. To initiate such a research strategy, there is a need for systematic, prospective collection and analysis of blood samples acquired from peripheral and portal vein circulation to identify blood-borne surrogate tumour markers that will enable physicians to obtain relevant information for making personalised therapeutic decisions, in a minimally-invasive way.

PDAC Peripheral and Portal Vein Sampling

A Research Protocol for Collection of Peripheral and Portal Vein Blood From Patients With Pancreatic Adenocarcinoma for Translational Research

Identifiable personal data (IPD) will be reviewed by the investigators listed on the trial delegation log at the stage of reviewing the medical records during the hepatopancreatobiliary (HPB) MultiDisciplinary Team (MDT) meeting at Manchester University Foundation Trust where the recruitment process will start. The medical notes will also be reviewed to correlate biomarker research with clinical outcomes. However, no participants' identifiable information will be shared with anyone outside the clinical or research team.

To prospectively collect paired peripheral and portal vein serum, plasma and whole blood samples for translational research at various time points. To investigate the presence of Circulating Tumour Cells and Circulating Tumour Microemboli and their biological significance. To investigate potential prognostic and predictive blood-borne genetic, protein and/or messenger ribonucleic acid biomarkers using the collected specimens.

To prospectively collect progression free and overall survival data so that correlation between biomarker parameters and clinical parameters can be examined.

Investigation of potential predictive blood germline genetic biomarkers using the collected specimens.

Manchester University NHS Foundation Trust

The Christie NHS Foundation Trust

Professor of Medical Oncology

Neoplasm Metastasis

Colorectal Neoplasms

Intestinal Neoplasms

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Hematinics

All Drugs and Chemicals

Liver Extracts

In-situ liver split at time when portal vein ligature is performed

Intervention: Preoperative portal embolization (+/-ablation) followed by liver resection, or local resections and/or ablations followed by lobectomy, two-stage hepatectomy

The portal branches to the diseased side should be completely divided. The bile duct to the diseased side should not be divided. The parenchyma should be transected all the way through the transection plane and place a plastic sheet on the diseased transection surface.

In-situ split

Portal vein embolization is performed according to the intervention used at the different sites.

Portal embolization or ligation

Per Sandstrom, MD, PhD

Magnus Rizell, MD, Phd

Peter Noergard Larsen, PhD

Bard Rosak, MD, PhD

Bard Rosok, MD, PhD

Magnus Rizell

Magnus Rizell, MD, PhD

Per Sandstrom, PhD, MD

Gert Lindell, MD, PhD

Bengt Isaksson, MD, PhD

Bjarne Andnor, MD

Study Title Comparison of two different models of liver growth stimulation in advanced colorectal liver metastatic disease, (LIGRO Trial) enabling liver resection

Methodology Scandinavian Multiple Center Randomized Registry Based Clinical Trial

Study duration The planned duration of study participation for an individual subject from inclusion to follow-up are 3 years

Primary investigator:

Per Sandstrom (Linköping)

Number of subjects 100 patients randomized in a 1:1 randomization

Diagnosis and main inclusion criteria Patients with colorectal liver metastasis requiring liver resection, but are not resectable in one step because of a future liver remnant/standardized total liver volume of \< 30 % extrahepatic metastatic disease is not an exclusion criteria if they can be addressed surgically in the future

Overall goal To evaluate if the ALPPS approach is superior to PVE in enabling patients, primarily unresectable due to inadequate FLR, to be resected and reach an R0 situation with an acceptable level of complications and perioperative mortality.

To evaluate if the ALPPS approach increases the growth rate of the liver compared to portal embolization or portal ligation leading to a shorter treatment period.

In addition the investigators aim to study if ALPPS may reach these goals without detectable or improved differences in tumor activity (PFS and OS), but with a shorter recovery and a higher proportion of patients reaching R0.

Hypothesis A higher proportion of patients can be resected with ALPPS counted as rate resected compared to the previously established methods with portal ligation or embolization.

This increased resection rate will not reduce the R0 rate, or increase the rate of Clavien grade 4 complication or higher (H0).

The ALPPS approach will increase the growth rate compared to portal embolization/ligation measured one week after the primary intervention.

ALPPS Versus PVE/PL

Comparison of Two Different Models of Liver Growth Stimulation in Advanced Colorectal Liver Metastatic Disease, (LIGRO Trial) Enabling Liver Resection

Radical resection at resection line according to histopathology

Overall complications will be analysed as a composite endpoint (CEP) including: ascites, postresectional liver failure, bile leak, intra abdominal bleeding, intraabdominal abscess and mortality, all with a Clavien score of at least 3

Treatment time in days from PVE/PL or date of ALPPS op 1 until date of leaving hospital after final surgery.

Progression free survival according to randomization group.

Quality of life is measured by EORTC QLQ C-30 EQ5D ar 1,6,12,24 months.

An analysis with regard to hospitalisation rate and number of days in-ward between randomization arm.

For both the ALPPS and the portal vein embolization/ligation arm, resection is not allowed within the study if the patient is not reaching a future liver remnant of 30%.

For both groups carcinomatosis or more metastases making aiming radical resections impossible will be seen as failures.

Liver growth is measured with regard to the future liver remnant by measuring the kinetic growth rate by performing repeated CT or MRI at one week after portal vein embolization/ligation or after the first step of the ALPPS procedure.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Proteomic Analysis of Human Hepatocellular Carcinoma	NCT01177631	Carcinoma, Hepa...	Operation	18 Years - 75 Years	Far Eastern Memorial Hospital
PDAC Peripheral and Portal Vein Sampling	NCT04289961	Pancreatic Aden...	Portal vein sam...	18 Years - 80 Years	The Christie NHS Foundation Trust
PDAC Peripheral and Portal Vein Sampling	NCT04289961	Pancreatic Aden...	Portal vein sam...	18 Years - 80 Years	The Christie NHS Foundation Trust
ALPPS Versus PVE/PL	NCT02215577	Colorectal Canc... Liver Metastase...	In-situ split Portal emboliza...	18 Years -	Regionalt Cancercentrum Väst

Spots Global Cancer Trial Database for portal vein

Every month we try and update this database with for portal vein 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.

Spots Global Cancer Trial Database for portal vein

Every month we try and update this database with for portal vein 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.

Every month we try and update this database with for portal vein 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.