Neoplasms

All Conditions

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Digestive System Diseases

Carcinoma

Hypertrophy

Carcinoma, Hepatocellular

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Pathological Conditions, Anatomical

Hematinics

All Drugs and Chemicals

Liver Extracts

All prospective patients who undergo unilobar SIRT for HCC at SGH or NCC are potential candidates for this study. The study aims to recruit 25 subjects and it is anticipated that 50% will be from SGH and 50% will be from NCC

Liver volume will be measure at 3 time points. All patients will undergo CT volumetry at baseline, 4-6 weeks and 8-12 weeks after SIRT. The images are then measured using a commercially available 3D software (Vital's Vitrea Advanced CT Liver Oncology package) and manually corrected, reviewed and resected by a single senior radiologist to ensure consistency in following the same anatomical landmarks.

CT volumetric measurement after Y90 radioembolization

Brian Goh, MBBS

Patients undergoing Y90 radioembolization to will be followed prospectively with CT volumetry to determine post-Y90 rate of liver hypertrophy.

Study protocol: Prospective study of early contra-lateral liver lobar hypertrophy after unilobar Y-90 selective internal radiation therapy (SIRT) in patients with hepatocellular carcinoma (HCC)

All patients scheduled to undergo unilobar (Right or left) SIRT with Y-90 for HCC at the Singapore General Hospital or the National Cancer Center Singapore during the study period may be enrolled. The target sample size is 25 over 2 years

Information on baseline demographics and disease staging, as well as pre- and post-treatment tumour and liver dimensions would be prospectively obtained.

The diagnosis of HCC is made based on current accepted diagnostic criteria ie. a characteristic appearance on contrast-enhanced quadriphasic CT scan and/or MRI, raised serum AFP levels and the presence of known risk factors. The RECIST criteria will be used to evaluate tumour response and disease progression at the time of the final volume determination.

Patients scheduled for unilobar SIRT will be consented for the study and enrolled into the study.

Liver volume will be measured at 3 time points.

CT volumetry will be performed at: 1) prior to treatment; 2) 4 to 6 weeks and 3) 8 to12 weeks after SIRT.

Administration of Y90 SIRT

This is based on our current institution practice. All patients would be reviewed with regards to suitability for Y90 SIRT and given appropriate counselling and advice regarding the angiographic procedures and the Y90 SIRT procedure, including potential side-effects. The patients undergo baseline blood investigations, typically liver function tests, renal function tests as well as full blood counts and coagulation profiles. All prior imaging CT and MRI were reviewed. Mapping hepatic angiography and 99mTc-MAA (micro-aggregated albumin) injection are performed according to standard technique. Prophylactic coil embolization of vessels at risk are performed either at mapping hepatic angiography or at 90Y radioembolization, at the discretion of the interventional radiologist. The catheter tip position for 99mTc-MAA injection is decided by consensus between the interventional radiologist and nuclear medicine physician during mapping hepatic angiography. 99mTc-MAA is slowly hand-injected through the indwelling catheter. Patients are subsequently immediately transferred to the gamma-camera suite for planar liver-to-lung shunt scintigraphy and SPECT/CT of the abdomen. Y90 microspheres treatment is planned by artery-specific SPECT/CT partition modelling as described in the literature.

All treatments are planned by a team of experienced nuclear medicine physicians. Y90 SIRT is performed using resin microspheres (SIR-Spheres; Sirtex Medical Ltd.) within 2 weeks of mapping hepatic angiography. Catheter tip placement is the same as that for the 99mTc-MAA injections. In accordance with our institutional protocol, all patients are observed overnight after treatment. They are discharged the following day after Bremsstrahlung planar scintigraphy of the lung and SPECT/CT of the abdomen were performed.

Measurement of liver volume

Liver volume will be measure at 3 time points. All patients will undergo CT volumetry at baseline, 4-6 weeks and 8-12 weeks after SIRT. Multiphasic dynamic contrast-enhanced hepatic CT scans are obtained with either a Dual Source CT (Siemens Medical) or Brilliance iCT (Philips Medical System). Scans will be obtained using a standard four phase liver protocol with a multidetector CT system with at least 64-channel detectors. Contrast medium is administered to the patients for acquisition of arterial-phase and portal-venous-phase and equilibrium CT images. The CT scanning parameters included collimation of 0.625-1.2mm. The reconstructed slice thickness for the scans are 0.8 - 1.5 mm and reconstruction intervals of 0.4 - 1 mm. Reconstructed CT slices have a matrix size of 512×512 pixels. The images are then measured using a commercially available 3D software (Vital's Vitrea Advanced CT Liver Oncology package) and manually corrected, reviewed and resected by a single senior radiologist to ensure consistency in following the same anatomical landmarks. The software allows saving of the work performed in order to allow reviewing and rechecking of the final measurements.

If the patients' pretreatment CT scans were performed at SGH or NCC, they need not undergo additional baseline CT scan and volumetry may be performed on these the existing imaging data. However, they will need to undergo a baseline CT scan if the pretreatment scan was performed outside the campus.

Subsequently, the patient's will need to undergo 2 follow-up CT scans at 4 to 6 weeks and 8 to 12 weeks after administration of SIRT.

Primary outcomes:

1. The change in volume of the contralateral liver volume from baseline
2. Change in volume of the ipsilateral liver from baseline
3. HCC tumor response or progression after treatment according to RECIST criteria.

Follow-up

Other than the 2 additional follow-up CT scans, patient's will undergo follow-up as per any regular non-study patient who was treated with SIRT.

Prospective Post Y90 Liver Hypertrophy

Prospective Study of Early Contra-lateral Liver Lobar Hypertrophy After Unilobar Y-90 Selective Internal Radiation Therapy (SIRT) in Patients With Hepatocellular Carcinoma (HCC)

Primary outcomes:

The rate of change in volume of the contralateral liver volume from baseline

Singapore General Hospital

Rare Diseases

Cholangiocarcinoma

Klatskin Tumor

Bile Duct Cancer

Acute Graft Versus Host Disease

PVE with coils proximally plus TAGM distally and subsequent major hepatectomy

PVE with multiple coils and subsequent major hepatectomy

PVE with TAGM distally and coils proximally and subsequent scheduled major hepatectomy. Sequential transcatheter arterial chemoembolization and PVE for patients with HCC. Selective biliary drainage on future liver remnant (FLR) side for patients with pCCA when obstructive jaundice is present.

PVE with coils plus TAGM

Procedure: PVE with multiple coils PVE with multiple coils proximally and distally and subsequent scheduled major hepatectomy. Sequential transcatheter arterial chemoembolization and PVE for patients with HCC. Selective biliary drainage on FLR side for patients with pCCA when obstructive jaundice is present.

PVE with multiple coils

Feng SHEN, MD, PhD

Bin YI, MD, PhD

Bin YI, MD

The aim of this study is to investigate the differences of safety and liver hypertrophy between portal vein embolization (PVE) using coils plus tris-acryl gelatin microspheres (TAGM) and multiple coils in patients with perihilar cholangiocarcinoma (pCCA) or with hepatocellular carcinoma (HCC).

Perihilar cholangiocarcinoma (pCCA) and hepatocellular carcinoma (HCC) both are common primary hepatobiliary tumors, which often require extensive hepatic resection and challenge perioperative management as surgery remains the only chance of long-term survival for such patients. PVE induces effective hypertrophy on one side of the liver parenchyma ahead of a planned liver resection of the other side which becomes atrophic.

Technically, the percutaneous transhepatic approach becomes the standard of care for PVE. PVEs themselves with different embolization materials could vary in the degree of liver hypertrophy, though some techniques, such as TAE, HVE and stem cell, have been already used in combination with PVE and could promote the hypertrophy. Several aspects on the use of PVE are insufficiently studied and most recommendations are based on low-grade evidence. Large clinical studies that compare the effect of different embolic materials on the hypertrophy response are lacking. PVE using multiple coils to completely occlude all the target segmental and sectional branches is a conventional and fundamental approach in our center, which ensured a reliable hypertrophy response with a low PVE-related morbidity and post-hepatectomy liver failure rate in the past decades. PVE using with tris-acryl gelatin microspheres (TAGM) distally and coils proximally, which needs more interventional experience, has become one of standard approaches in our center. However, the study of high-grade evidence regarding the hypertrophy effect of PVE with TAGM and coils is still lacking.

In this randomized study, the investigators aim to compare PVE using TAGM plus coils to PVE using coils alone, in term of PVE-related complications, hypertrophy degree, hepatectomy completion rate, post-hepatectomy liver failure rate, features of immunohistochemical examination on parenchyma, for patients stratified by either pCCA or HCC.

Portal Vein Embolization Using Coils Plus TAGM vs Multiple Coils for Patients With Perihilar Cholangiocarcinoma or Hepatocellular Carcinoma

Preoperative Portal Vein Embolization Using Coils Plus TAGM vs Multiple Coils for Patients With Perihilar Cholangiocarcinoma or Hepatocellular Carcinoma: a Randomized Controlled Study

The rate of major and minor PVE-related complications

The difference of standardized FLR ratios before and 2 weeks after PVE

The rate of completed major hepatectomy in each Arm group

The rate of liver failure measured by 50-50, TB peak 7mg, and ISGLS criteria

Immunohistochemical stainings of hypertrophic and atrophic parenchyma including anti-albumin, anti-PCNA, TUNEL staining, etc.

Eastern Hepatobiliary Surgery Hospital

Professor and Chief Surgeon, Principal Investigator

Neoplasm Metastasis

Patients allocated to the PVE group will receive pre-intervention blood tests and a contrast enhanced CT scan of the abdomen. They will then have their portal vein embolized radiologically once their pre-intervention investigations have been completed and reviewed by the clinical team.

Post-intervention investigations (blood tests and CT scan) will take place 4 weeks after the completion of the PVE. At this point, they will be listed to receive their definitive surgical hepatectomy.

Patients allocated to the RALPP group will receive pre-intervention blood tests and a contrast enhanced CT scan of the abdomen. They will then have their right portal vein surgically ligated followed by radiofrequency ablation in situ splitting of the liver. Certain patients may additionally have a tumourectomy or wedge resection of the left liver lobe if clinically indicated. The RALPP procedure will occur once the patient's pre-intervention investigations have been completed and reviewed by the clinical team.

Post-intervention investigations (blood tests and CT scan) will take place 2 weeks after the completion of the RALPP. At this point, they will be listed to receive their definitive surgical hepatectomy.

Radiofrequency assisted liver partition with portal vein ligation (RALPP)

Portal vein embolization (PVE)

Long R Jiao, MD, FRCS

The aim of this study is to compare two different techniques (portal vein embolization and radiofrequency assisted liver partition with portal vein ligation) for increasing liver volume prior to major liver resection.

Liver resection remains the gold standard treatment for patients with liver tumours providing them the only chance for long-term survival. In up to 45% of cases that are amenable to surgical resection, an extended hepatectomy (removal of part of the liver) is usually necessary to achieve a clear resection margin. However, there must be enough liver left behind to meet the demands of the body. Indeed, liver failure due to insufficient remnant liver volume is still the principal cause of postoperative death following a major liver resection.

The liver receives its main blood supply from two vessels (the portal vein and the hepatic artery). In order to decrease the complications and improve the safety of extensive liver surgery in patients with insufficient future liver remnant volume (FLRV), pre-operative embolization (i.e. blockage) of part of the portal vein can be undertaken.

This has the effect of inducing growth of the liver on the unaffected side. Thus, when the resection is carried out, an increased FLRV (of around 12%) reduces post-operative liver failure. An alternative technique is to perform surgical ligation of the portal vein along with splitting of the liver.

The diseased portion of liver is left in the body for 7-10 days while the healthy side is induced to grow. During this time, the diseased portion continues to support the body's requirement for liver function and reduces the risk of liver failure. FLRV has been shown to increase by around 74% with this technique.

However, there are more postoperative complications with the alternative technique such as bile leaks. The aim of this study is to test a new way of splitting the liver so that the increased FLRV can be achieved without the increased complication rate.

Regeneration of Liver: Portal Vein Embolization Versus Radiofrequency Assisted Ligation for Liver Hypertrophy (REBIRTH)

Liver Regeneration: a Single-centre, Prospective, Randomised Controlled Trial Comparing Radiofrequency Assisted Liver Partition With Portal Vein Ligation (RALPP) With Portal Vein Embolization (PVE) for Preoperative Induction of Liver Hypertrophy in Patients With Insufficient Future Liver Remnant Volume for Major Liver Resection.

Percentage change in remnant liver volume following intervention. This will be measured by volumetric analysis of CT scan. Positive number represents increases and negative number represents decreases.

As defined by Dindo Clavien classification of surgical complications (≥grade 3b).

Imperial College London

Patients allocated to the PVE group received pre-intervention blood tests and a contrast enhanced CT scan of the abdomen. They then had their portal vein embolized radiologically once their pre-intervention investigations were completed and reviewed by the clinical team.

Post-intervention investigations (blood tests and CT scan) occurred 4 weeks after the completion of the PVE. At this point, they were listed to receive their definitive surgical hepatectomy.

Portal vein embolization (PVE)

Portal Vein Embolization (PVE)

Patients allocated to the RALPP received pre-intervention blood tests and a contrast enhanced CT scan of the abdomen. They then had their right portal vein surgically ligated followed by radiofrequency ablation in situ splitting of the liver. Certain patients may also have had a tumourectomy or wedge resection of the left liver lobe if clinically indicated. The RALPPS procedure occurred once the patient's pre-intervention investigations were completed and reviewed by the clinical team.

Post-intervention investigations (blood tests and CT scan) occurred 2 weeks after the completion of the RALPPS. At that point, they were listed to receive their definitive surgical hepatectomy.

Radiofrequency assisted liver partition with portal vein ligation (RALPPS)

Radiofrequency Assisted Liver Partition and Ligation (RALPPS)

Total

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Prospective Post Y90 Liver Hypertrophy	NCT02783261	Hepatocellular ... Liver Hypertrop...	CT volumetric m...	21 Years - 99 Years	Singapore General Hospital
Portal Vein Embolization Using Coils Plus TAGM vs Multiple Coils for Patients With Perihilar Cholangiocarcinoma or Hepatocellular Carcinoma	NCT04386772	Portal Vein Occ... Cholangiocarcin... Hepatocellular ... Liver; Hypertro...	PVE with coils ... PVE with multip...	18 Years - 70 Years	Eastern Hepatobiliary Surgery Hospital
Portal Vein Embolization Using Coils Plus TAGM vs Multiple Coils for Patients With Perihilar Cholangiocarcinoma or Hepatocellular Carcinoma	NCT04386772	Portal Vein Occ... Cholangiocarcin... Hepatocellular ... Liver; Hypertro...	PVE with coils ... PVE with multip...	18 Years - 70 Years	Eastern Hepatobiliary Surgery Hospital
Portal Vein Embolization Using Coils Plus TAGM vs Multiple Coils for Patients With Perihilar Cholangiocarcinoma or Hepatocellular Carcinoma	NCT04386772	Portal Vein Occ... Cholangiocarcin... Hepatocellular ... Liver; Hypertro...	PVE with coils ... PVE with multip...	18 Years - 70 Years	Eastern Hepatobiliary Surgery Hospital
Prospective Post Y90 Liver Hypertrophy	NCT02783261	Hepatocellular ... Liver Hypertrop...	CT volumetric m...	21 Years - 99 Years	Singapore General Hospital
Regeneration of Liver: Portal Vein Embolization Versus Radiofrequency Assisted Ligation for Liver Hypertrophy (REBIRTH)	NCT02216773	Liver Resection Cancer	Radiofrequency ... Portal vein emb...	18 Years -	Imperial College London

Spots Global Cancer Trial Database for liver hypertrophy