Portal vein embolization

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Portal vein embolization
Specialty Interventional radiology

Portal vein embolization (PVE) is a preoperative procedure performed in interventional radiology to initiate hypertrophy of the anticipated future liver remnant a couple weeks prior to a major liver resection procedure. The procedure involves injecting the right or left portal vein with embolic material to occlude portal blood flow. By occluding the blood flow to areas of the liver that will be resected away, the blood is diverted to healthy parts of the liver and induces hyperplasia. This may allow for a more extensive resection or stage bilateral resections that would otherwise be contraindicated resulting in better oncological treatment outcomes. [1]

Contents

Medical uses

Indications for PVE depend on the ratio of future liver remnant (FLR) to total estimated liver volume (TELV) and liver condition. Although there is no consensus to the absolute minimum liver volume required for adequate post-resection liver function, a FLR/TELV ratio of at least 25% is recommended in patients with otherwise normal livers. [2] The recommendation for those with chronic liver disease such as cirrhosis is a FLR/TELV ratio of at least 40%. In these patients a PVE may be indicated to increase the FLR and the FLR/TELV ratio. Preoperative patients receiving extensive chemotherapy with a FLR/TELV less than 30% should also receive PVE prior to resection; conversely, chemotherapy does not preclude subsequent PVE.

Other important considerations before a PVE include co-morbidities such as diabetes, procedure type and the extent of planned resection. Insulin resistance has been associated with slower rates of regeneration and higher likelihood of inadequate FLR growth after PVE. [2] Additionally, if the resection requires more extensive surgery such as a resections of the pancreas or small bowel, a greater FLR/TELV ratio may be needed for safe recovery. [2]

Outcomes

Preoperative PVE is a very well tolerated procedure with extremely low mortality rates (0.1 percent) and technical failure rates (0.4 percent). [3] Complication rates from the procedure are low as well (2 – 3 percent) and include portal vein thrombosis, liver infarction, necrosis, infection, pneumothorax, and other risks as listed above. [3] Success of PVE is determined by degree of regenerative response, which again depends on factors such as baseline liver condition, technical approach and pre-existing co-morbidities. 5-year survival in patients with originally unresectable tumors as a result of inadequate future liver remnant and received PVE with subsequent resection was found in one study to be 29%. [4]

Originally, there was concern that PVE could promote tumor growth and increase recurrence rates, however a systematic review has found that there was no significant difference observed in postoperative hepatic recurrence or 3 and 5 year overall survival rates. [5] This suggests that PVE does not have any significant adverse effects on the risk of oncogenesis. Overall, PVE is an important technique that can allow for patients with inadequate predicted FLR/TELV ratios an opportunity for resection and potential cure of their liver conditions.

Contraindications

Portal hypertension is an absolute contraindication, as these patients are not surgical candidates and are at higher risk of significant complications from PVE. Additionally, complete lobar portal vein occlusion of either lobe would preclude expected increases in FLR from PVE due to already existing diversion of portal flow. Patients with extrahepatic metastatic disease are also not candidates for resection, and therefore PVE is contraindicated. In the past patients with bi-lobar disease were not considered for PVE, however now there may be a role of PVE in combination with a two-stage hepatectomy. [2] [6] Additionally, patients who have an inadequate predicted FLR post PVE should not be considered. Other contraindications include any conditions that make a patient unfit for surgery or intervention (poor cardiopulmonary status, sepsis, kidney failure, etc.).

Risks and Benefits

PVE has been shown to have the following risks: [1]

  1. Portal vein thrombosis, liver infarction, necrosis and portal hypertension.
  2. Risks related to any percutaneous transhepatic procedures such as bleeding and infection.
  3. Accelerated tumor growth due to compensatory hepatic arterial flow and in cases when all of the tumor-bearing areas are not properly embolized.

PVE has been shown to have the following benefits:

  1. Decrease post-resection morbidity by decreasing number of complication and length of hospital stay.
  2. Patients initially with unresectable tumors due to inadequate FLR/TELV are able to have resections.
  3. Decrease post-resection mortality by increasing the volume of functional liver parenchyma.
  4. Poor regenerative response to PVE predicts poor compensatory regeneration following liver resection and can help identify patients unsuitable for resection.

Mechanism

Portal vein embolization is a preoperative procedure performed in interventional radiology to initiate hypertrophy of the anticipated future liver remnant a couple weeks prior to a major liver resection procedure. Future liver remnant (FLR) is defined as the predicted volume of functional liver after resection. There are specific FLR thresholds depending on the status of the liver (otherwise normal, chronic hepatitis, cirrhosis, etc.) that are required for safe liver resection. When the predicted FLR is below threshold, portal vein embolization may increase the FLR and bring it to threshold. [1] The majority of preoperative PVEs usually target the right portal vein in preparation of a major right-sided resection. Though rare, the left portal vein may be embolized prior to a left-sided resection.

The increase in FLR is a result of cellular hyperplasia and not cellular hypertrophy. This means that it is an increase in the number of hepatocytes that accounts for the growth rather than the increase in size of existing hepatocytes. The liver is unique in that it is an organ with regenerative potential. When blood flow to one section of the liver is occluded in PVE, the flow is diverted to other areas and this increase in blood flow stimulates the regenerative response. [7] Regeneration begins within hours of occlusion and factors important to this response include hepatocyte growth factor, epidermal growth factor, insulin, IL-6 and TNF-alpha, among others. [7] [8] The expected increase in FLR is approximately 10 percent; greater increases after four to six weeks can be observed, albeit at a lower rate of growth. An increase in FLR of greater than five percent for a normal liver and 10 percent for a cirrhotic liver is considered adequate and is associated with a reduced risk of post-resection liver failure. [9]

Method

PVE was originally performed using an open approach, but the majority is now done percutaneously under conscious sedation and local anesthesia by an interventional radiologist. This can be done using either a transjugular or transhepatic approach. The most commonly used method is the direct transhepatic puncture of the portal vein. [10] Several different embolization agents can be used and the choice of agents often depend on the expertise of the physician, availability and cost. As the agents differ in size, occlusive properties and side effect profiles, the choice of agent will also depend on the anatomy and locations of the tumors in a specific case. Some commonly used agents include cyanoacrylate, sodium tetradecyl sulfate foam, gelatin, metallic spherical particles, coils and absolute alcohol. [2]

Liver volumetry

To determinate whether there is a need for PVE the FLR needs to be measured. There are various imaging methods used in order to measure the liver volume such as contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) [11] and the FLR can be traced either manually or using automatic or semi-automatic segmentation tools. FLR is measured with the chosen imaging method before PVE and then again 1–4 weeks after PVE calculating the hypertrophy of the FLR.

Future directions [8]

Transarterial PVE

A technique tested so far in pigs in which a 3:1 mixture of iodinated oil and absolute ethanol was infused via lobar hepatic artery branches and into the portal system via the peribiliary plexus. The degree of FLR hypertrophy seen in the pigs with transarterial PVE compared to traditional percutaneous PVE were found to be nearly double. No significant adverse events were noted. The advantage to this new approach is a better safety profile (does not require direct hepatic puncture). However, this approach may be limited by the amount of embolic agent needed for successful embolization, as the amount needed for humans may exceed the threshold for pulmonary complications.

Reversible PVE

There are times when a patient who has undergone a PVE is no longer able to undergo a resection. In these instances, the patients are left with a permanently occluded portal vein that can exclude them from receiving other therapies. Therefore, PVE with absorbable materials such as powdered gelatin sponge dissolved in a 4:1 mixture of iodinated contrast medium and saline has been used and shown induce FLR hypertrophy. However, whether it can provide the comparable response to traditional PVE must still be studied. In the future, reversible PVE may also play a role in treating patients with chronic hepatic insufficiency to increase functional liver tissue, as opposed to just being used as an adjuvant therapy for liver resection.

PVE with Adjuvant Stem Cell Transplantation

Studies have shown that bone marrow-derived stem cells (specifically CD133+) play a role in liver regeneration. A study done by Esch, et al. [12] showed that patients who received stem cells in addition to PVE had significant increases in both absolute and relative FLR growth than in patients who received PVE only. They found no significant differences between the groups in regards to major complications and mortality. This suggests that adjuvant stem cell transplantation can increase the efficacy of PVE without increasing risk.

Related Research Articles

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<span class="mw-page-title-main">Hepatocellular carcinoma</span> Medical condition

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.

Liver tumors are abnormal growth of liver cells on or in the liver. Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. Liver tumors can be classified as benign (non-cancerous) or malignant (cancerous) growths. They may be discovered on medical imaging, and the diagnosis is often confirmed with liver biopsy. Signs and symptoms of liver masses vary from being asymptomatic to patients presenting with an abdominal mass, hepatomegaly, abdominal pain, jaundice, or some other liver dysfunction. Treatment varies and is highly specific to the type of liver tumor.

<span class="mw-page-title-main">Interventional radiology</span> Medical subspecialty

Interventional radiology (IR) is a medical specialty that performs various minimally-invasive procedures using medical imaging guidance, such as x-ray fluoroscopy, computed tomography, magnetic resonance imaging, or ultrasound. IR performs both diagnostic and therapeutic procedures through very small incisions or body orifices. Diagnostic IR procedures are those intended to help make a diagnosis or guide further medical treatment, and include image-guided biopsy of a tumor or injection of an imaging contrast agent into a hollow structure, such as a blood vessel or a duct. By contrast, therapeutic IR procedures provide direct treatment—they include catheter-based medicine delivery, medical device placement, and angioplasty of narrowed structures.

<span class="mw-page-title-main">Embolization</span> Passage and lodging of an embolus within the bloodstream

Embolization refers to the passage and lodging of an embolus within the bloodstream. It may be of natural origin (pathological), in which sense it is also called embolism, for example a pulmonary embolism; or it may be artificially induced (therapeutic), as a hemostatic treatment for bleeding or as a treatment for some types of cancer by deliberately blocking blood vessels to starve the tumor cells.

Transcatheter arterial chemoembolization (TACE) is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply. Small embolic particles coated with chemotherapeutic drugs are injected selectively through a catheter into an artery directly supplying the tumor. These particles both block the blood supply and induce cytotoxicity, attacking the tumor in several ways.

<span class="mw-page-title-main">Transjugular intrahepatic portosystemic shunt</span>

Transjugular intrahepatic portosystemic shunt is an artificial channel within the liver that establishes communication between the inflow portal vein and the outflow hepatic vein. It is used to treat portal hypertension which frequently leads to intestinal bleeding, life-threatening esophageal bleeding and the buildup of fluid within the abdomen (ascites).

<span class="mw-page-title-main">Uterine artery embolization</span>

Uterine artery embolization is a procedure in which an interventional radiologist uses a catheter to deliver small particles that block the blood supply to the uterine body. The procedure is done for the treatment of uterine fibroids and adenomyosis. This minimally invasive procedure is commonly used in the treatment of uterine fibroids and is also called uterine fibroid embolization.

Autotransplantation is the transplantation of organs, tissues, or even particular proteins from one part of the body to another in the same person.

<span class="mw-page-title-main">Percutaneous transhepatic cholangiography</span>

Percutaneous transhepatic cholangiography, percutaneous hepatic cholangiogram (PTHC) is a radiological technique used to visualize the anatomy of the biliary tract. A contrast medium is injected into a bile duct in the liver, after which X-rays are taken. It allows access to the biliary tree in cases where endoscopic retrograde cholangiopancreatography has been unsuccessful. Initially reported in 1937, the procedure became popular in 1952.

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<span class="mw-page-title-main">Metastatic liver disease</span> Medical condition

A liver metastasis is a malignant tumor in the liver that has spread from another organ affected by cancer. The liver is a common site for metastatic disease because of its rich, dual blood supply. Metastatic tumors in the liver are 20 times more common than primary tumors. In 50% of all cases the primary tumor is of the gastrointestinal tract; other common sites include the breast, ovaries, bronchus and kidney. Patients with Colorectal cancer will develop liver metastases during the disease

<span class="mw-page-title-main">Selective internal radiation therapy</span>

Selective internal radiation therapy (SIRT), also known as transarterial radioembolization (TARE), radioembolization or intra-arterial microbrachytherapy is a form of radiation therapy used in interventional radiology to treat cancer. It is generally for selected patients with surgically unresectable cancers, especially hepatocellular carcinoma or metastasis to the liver. The treatment involves injecting tiny microspheres of radioactive material into the arteries that supply the tumor, where the spheres lodge in the small vessels of the tumor. Because this treatment combines radiotherapy with embolization, it is also called radioembolization. The chemotherapeutic analogue is called chemoembolization, of which transcatheter arterial chemoembolization (TACE) is the usual form.

PVE may refer to:

Hepatic artery embolization, also known as trans-arterial embolization (TAE), is one of the several therapeutic methods to treat primary liver tumors or metastases to the liver. The embolization therapy can reduce the size of the tumor, and decrease the tumor's impact such its hormone production, effectively decreasing symptoms. The treatment was initially developed in the early 1970s. The several types of hepatic artery treatments are based on the observation that tumor cells get nearly all their nutrients from the hepatic artery, while the normal cells of the liver get about 70-80 percent of their nutrients and 50% their oxygen supply from the portal vein, and thus can survive with the hepatic artery effectively blocked. In practice, hepatic artery embolization occludes the blood flow to the tumors, achieving significant tumor shrinkage in over 80% of people. Shrinkage rates vary.

Interventional oncology is a subspecialty field of interventional radiology that deals with the diagnosis and treatment of cancer and cancer-related problems using targeted minimally invasive procedures performed under image guidance. Interventional oncology has developed to a separate pillar of modern oncology and it employs X-ray, ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) to help guide miniaturized instruments to allow targeted and precise treatment of solid tumours located in various organs of the human body, including but not limited to the liver, kidneys, lungs, and bones. Interventional oncology treatments are routinely carried out by interventional radiologists in appropriate settings and facilities.

<span class="mw-page-title-main">Cantlie line</span> Anatomical line dividing the liver

In human anatomy, the Cantlie line or Cantlie's line is an imaginary division of the liver. The division divides the liver into two planes, extending from the middle hepatic vein to the middle of the gallbladder. It is useful for performing hepatectomies.

Radiation lobectomy is a form of radiation therapy used in interventional radiology to treat liver cancer. It is performed in patients that would be surgical candidates for resection, but cannot undergo surgery due to insufficient remaining liver tissue. It consists of injecting small radioactive beads loaded with yttrium-90 into the hepatic artery feeding the hepatic lobe in which the tumor is located. This is done with the intent of inducing growth in the contralateral hepatic lobe, not dissimilarly from portal vein embolization (PVE).

Transarterial bland embolization is a catheter-based tumor treatment of the liver. In this procedure, a variety of embolizing agents can be delivered through the tumor’s feeding artery in order to completely occlude the tumor’s blood supply. The anti-tumor effects are solely based on tumor ischemia and infarction of tumor tissue, as no chemotherapeutic agents are administered. The rationale for the use of bland embolization for hepatocellular carcinoma(HCC) and/or other hyper-vascular tumors is based on the fact that normal liver receives a dual blood supply from the hepatic artery (25%) and the portal vein (75%). As the tumor grows, it becomes increasingly dependent on the hepatic artery for blood supply. Once a tumor nodule reaches a diameter of 2 cm or more, most of the blood supply is derived from the hepatic artery. Therefore, bland embolization and transarterial chemoembolization (TACE) consist of the selective angiographic occlusion of the tumor arterial blood supply with a variety of embolizing agents, with or without the precedence of local chemotherapy infusion. The occlusion by embolic particles results in tumor hypoxia and necrosis, without affecting the normal hepatic parenchyma.

References

  1. 1 2 3 Abdalla, E. K.; Hicks, M. E.; Vauthey, J. N. (2001-02-01). "Portal vein embolization: rationale, technique and future prospects". British Journal of Surgery. 88 (2): 165–175. doi:10.1046/j.1365-2168.2001.01658.x. ISSN   1365-2168. PMID   11167863. S2CID   22645135.
  2. 1 2 3 4 5 Loffroy, Romaric; Favelier, Sylvain; Chevallier, Olivier; Estivalet, Louis; Genson, Pierre-Yves; Pottecher, Pierre; Gehin, Sophie; Krausé, Denis; Cercueil, Jean-Pierre (2015-10-15). "Preoperative portal vein embolization in liver cancer: indications, techniques and outcomes". Quantitative Imaging in Medicine and Surgery. 5 (5): 730–739. doi:10.3978/j.issn.2223-4292.2015.10.04. PMC   4671969 . PMID   26682142.
  3. 1 2 Lienden, K. P. van; Esschert, J. W. van den; Graaf, W. de; Bipat, S.; Lameris, J. S.; Gulik, T. M. van; Delden, O. M. van (2013-02-01). "Portal Vein Embolization Before Liver Resection: A Systematic Review". CardioVascular and Interventional Radiology. 36 (1): 25–34. doi:10.1007/s00270-012-0440-y. ISSN   0174-1551. PMC   3549243 . PMID   22806245.
  4. ↑ Azoulay, D; et al. (2000). "Resection of nonresectable liver metastases from colorectal cancer after percutaneous portal vein embolization". Ann Surg. 231 (4): 480–486. doi:10.1097/00000658-200004000-00005. PMC   1421022 . PMID   10749607.
  5. ↑ Giglio, Mariano Cesare; Giakoustidis, Alexandros; Draz, Ahmed; Jawad, Zaynab A. R.; Pai, Madhava; Habib, Nagy A.; Tait, Paul; Frampton, Adam E.; Jiao, Long R. (2016-10-01). "Oncological Outcomes of Major Liver Resection Following Portal Vein Embolization: A Systematic Review and Meta-analysis". Annals of Surgical Oncology. 23 (11): 3709–3717. doi:10.1245/s10434-016-5264-6. hdl: 10044/1/31671 . ISSN   1068-9265. PMID   27272106. S2CID   22655871.
  6. ↑ Madoff, David C.; Hicks, Marshall E.; Vauthey, Jean-Nicolas; Charnsangavej, Chusilp; Morello, Frank A.; Ahrar, Kamran; Wallace, Michael J.; Gupta, Sanjay (2002-09-01). "Transhepatic Portal Vein Embolization: Anatomy, Indications, and Technical Considerations". RadioGraphics. 22 (5): 1063–1076. doi: 10.1148/radiographics.22.5.g02se161063 . ISSN   0271-5333. PMID   12235336.
  7. 1 2 Denys, A. L.; Abehsera, M.; Leloutre, B.; Sauvanet, A.; Vilgrain, V.; O'Toole, D.; Belghiti, J.; Menu, Y. (2000-10-01). "Intrahepatic hemodynamic changes following portal vein embolization: a prospective Doppler study". European Radiology. 10 (11): 1703–1707. doi:10.1007/s003300000577. ISSN   0938-7994. PMID   11097391. S2CID   23986141.
  8. 1 2 May, Benjamin J.; Talenfeld, Adam D.; Madoff, David C. (February 2013). "Update on Portal Vein Embolization: Evidence-based Outcomes, Controversies, and Novel Strategies". Journal of Vascular and Interventional Radiology. 24 (2): 241–254. doi:10.1016/j.jvir.2012.10.017. PMID   23369559.
  9. ↑ Ribero, D.; Abdalla, E. K.; Madoff, D. C.; Donadon, M.; Loyer, E. M.; Vauthey, J.-N. (2007-11-01). "Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome". British Journal of Surgery. 94 (11): 1386–1394. doi: 10.1002/bjs.5836 . ISSN   1365-2168. PMID   17583900. S2CID   38615358.
  10. ↑ Imamura, Hiroshi; Shimada, Ryo; Kubota, Mitsuru; Matsuyama, Yutaka; Nakayama, Ataru; Miyagawa, Shin-ichi; Makuuchi, Masatoshi; Kawasaki, Seiji (1999-04-01). "Preoperative portal vein embolization: An audit of 84 patients". Hepatology. 29 (4): 1099–1105. doi: 10.1002/hep.510290415 . ISSN   1527-3350. PMID   10094953.
  11. ↑ Ribero, D; Chun, YS; Vauthey, JN (June 2008). "Standardized liver volumetry for portal vein embolization". Seminars in Interventional Radiology. 25 (2): 104–9. doi:10.1055/s-2008-1076681. PMC   3036478 . PMID   21326551.
  12. ↑ am Esch, Jan Schulte; Knoefel, Wolfram Trudo; Klein, Michael; Ghodsizad, Ali; Fuerst, Guenter; Poll, Ludger W.; Piechaczek, Christoph; Burchardt, Elmar R.; Feifel, Niko (2005-04-01). "Portal Application of Autologous CD133+ Bone Marrow Cells to the Liver: A Novel Concept to Support Hepatic Regeneration". Stem Cells. 23 (4): 463–470. doi: 10.1634/stemcells.2004-0283 . ISSN   1549-4918. PMID   15790766.
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