The new startegies described currently for treatment of various liver diseases including cancer, have led to perfectioning the technique for major liver resections.
Complications of these resections are rare, but can contribute to prolonged recovery time, hospitalization and costs. Of these complications, the most feared is postoperative liver failure as a result of insufficient volume of the remnant liver.
Patients who are at increased risk of liver failure are those with normal livers who will be subjected to resections of more than 70% of the functional liver mass, or cirrhotic patients with resection of more than 60% of the liver’s functional mass.
Portal Vein Embolization redirects blood flow to the future liver remnant, initiating a hypertrophy of nonembolized segments, augmenting the preoperative functional hepatocellular mass. This technique, used in many hepatobiliary centers worldwide, can reduce the morbidity and enables the possibility of curative resections in not previously considered candidates for resection.
Mechanisms of Liver Regeneration
The liver’s capacity for replication is about 0.001% of hepatocytes undergoing mitosis at any time. This low cell turnover can be dramatically altered with toxic injury or surgical resection. This stimuli provoke a massive hepatocyte proliferation that can recover the functional liver mass within 2 weeks of the initiating event.
Certain hormones and growth factors mediate this hepatic regeneration. Hepatocyte Growth factor, the most potent mitogen for hepatocyte replication, in association with Epidermal Growth Factor and Transforming Grwoth Factor-a, induce citokine production and activate gene responses that favors hepatocyte replication.
Insulin is synergistic with HGF, the reason why liver regeneration is much slower in diabetics. These mediators travel to the liver via the Portal Vein and not the hepatic artery.
The amount of hepatocyte regeneration is proportional to the stimulus. Any injury greater than 10%, will induce cellular proliferation throughout the liver. In contrast hepatocyte regeneration is delayed 3 to 4 days when apoptosis is produced during PVE. This suggests that hepatocyte removal is a stroger stimulus.
Chronically diseased livers regenerate at a much slower rate, maybe because of a diminished capacity from hepatocytes to respond to hepatotropic factors in relation to dominished portal blood flows caused by fibrosis.
Non-cirrhotic liver regenerate at rates of 21 cm3/day at two weeks, while cirrhotic liver do so at 9 cm3/day.
Clinical Use
The first clinical experiences with PVE were done by Rous and Larimore in 1920, who first studied the consequences od segmental portal vein occlusion in rabbits. They found atrophy of the occluded segments and hypertrophy of the segments with patent PV.
Makuuchi decribed for the first time in 1990 PVE to induce left liver hypertrophy before right hepatectomy. Their procedure is now used widely.
Following PVE, alterations of liver function tests are usually minor and transient with many experiencing no changes. When transaminase levels rise, they generally peak at levels less than three times baseline 1 to 3 days after PVE
and return to baseline within 7 to 10 days. Slight changes in white blood cell count and total serum bilirubin level may be seen. Synthetic functions of the liver are almost never affected.
PVE is much less toxic than Arterial embolization, this because there is no distortion of the hepatic anatomy, just inflammation and theres is little tumor necrosis. The abscence of systemoc symptoms has been demostrated by hepatocyte apoptosis rather than necrosis.
Computed tomography (CT) with volumetry is essential for planning hepatic resection. Three-dimensional CT volumetric measurements are acquired by outlining the hepatic segmental contours and calculating the volumes
from the surface measurements from each slice. Contrast enhanced CT scans must be performed to demarcate the vascular landmarks of the hepatic segments. There are two techniques of CT volumetry.
In cirrhotic patients, a liver function assessment must be carried out. This is best done with the indocyanine green retention to determine the extent of safe resection.
PVE Approaches
There are three basic approaches. These approaches are chosen on the basis of operator preference, type of hepatic resection planned, extent of embolization, and type of embolic agent used.
Transhepatic contralateral
Was described by Kinoshita and is the most widely used. A left segmental branch, usually segment III, is used to advance a catheter into the right PV for PVE.
The ipsilateral approach
Described by Nagino and a catheter is placed in a peripheral right portal vein branch and advanced to the right PV and segment IV, with either ethanol or fibrin glue.
Intraoperative cannulation of the ileocolic vein
Embolic Material
Many materials have been used. Makuuchi in their initial experience used gelatin sponge but recanalization was observed at 2 weeks and appears to induce less hypertrophy at 4 weeks.
N-butyl-2-cyanoacylate (NCBA) was used but it induced too much inflammation and was not too efficient in patients with reduced hepatopetal flow.
Ethanol was first used by Shimamura owing to its strong coagulation effect. He described the procedure using 20 ml of ethanol, inducing a right PV occlusion. Ogasawara demonstrated doubling of left liver volume after 4 weeks for patients with chronic liver disease and HCC.
Fibrin glue is another commonly used agent with a 75% portal occlusion at 2 weeks and less tan 25% occlusion at 4 weeks.
Newer agents continue to be developed that may provide more complete and permanent occlusions in an attempt to reduce recanalization and ultimately provide better and faster hypertrophy.
Complications
The rate of portal embolization goes from 9.1% o 12.8%. The most commonly reported by Kodama are: subcapsular hematoma, hemoperitoneum, hemobilia, pseudoaneurysm, arteriovenous fistula, arterioportal shunts, PV thrombosis, transient liver failure, pneumothorax and sepsis.
Indications
Many factors should be kept in mind when proposing liver surgery to a patient. The presence or absence of liver disease will impact on liver remnant volume needed. Second, patient size must be considered, this is because larger patients will require larger remnant liver volumes and third the surgeon should always have in mind that there could be nonhepatic surgery at the time of the liver resection.
Quality of iver parenchyma is another factor that should be taken into account. Normal livers can withstand a resection of up to 90%, but cirrhotic livers with more than 60% volume resections will surely not survive. Lethal hepatic failure is common in cirrhotic patients. Retrospective data have shown that patients after systemic or local chemotherapy are at increased risk of surgical complications, so that experts have recommended a minimum of 40% functional liver remnant volume in these patients.
Contraindications
Absolute
1. Overt Portal Hypertension
2. Portal Vein tumoral invasion. This because portal flow is already diverted.
Relative
1. Tumor invasion to the functional liver remnant or extrahepatic metastases
2. Uncorrectable coagulopathy
3. Tumor precluding safe transhepatic access
4. Biliary dilation in the liver remnant (Previous drainage is recommended)
5. Mild Portal hypertension
6. Renal Failure
J Am Coll Surg. 1999;188:304-309; Ann Surg. 2000;231:480-486; Surgery.
1990;107:521-527; Surgery. 1995;117:677-681; Surgery. 2000;127:155-160.
Hepatology. 1995;21:434-439; Surgery. 1997;121:135-141; Surgery.
1997;121:135-141; Hepatology. 1999;29:1099-1105; Surg Today. 1995;25:43-48.
Semin Surg Oncol. 1993;9:298-304; Radiology.1996:200;559-563; Ann Surg. 2000;32:665-672; Br J Surg. 2000;87:879-882.
Complications of these resections are rare, but can contribute to prolonged recovery time, hospitalization and costs. Of these complications, the most feared is postoperative liver failure as a result of insufficient volume of the remnant liver.
Patients who are at increased risk of liver failure are those with normal livers who will be subjected to resections of more than 70% of the functional liver mass, or cirrhotic patients with resection of more than 60% of the liver’s functional mass.
Portal Vein Embolization redirects blood flow to the future liver remnant, initiating a hypertrophy of nonembolized segments, augmenting the preoperative functional hepatocellular mass. This technique, used in many hepatobiliary centers worldwide, can reduce the morbidity and enables the possibility of curative resections in not previously considered candidates for resection.
Mechanisms of Liver Regeneration
The liver’s capacity for replication is about 0.001% of hepatocytes undergoing mitosis at any time. This low cell turnover can be dramatically altered with toxic injury or surgical resection. This stimuli provoke a massive hepatocyte proliferation that can recover the functional liver mass within 2 weeks of the initiating event.
Certain hormones and growth factors mediate this hepatic regeneration. Hepatocyte Growth factor, the most potent mitogen for hepatocyte replication, in association with Epidermal Growth Factor and Transforming Grwoth Factor-a, induce citokine production and activate gene responses that favors hepatocyte replication.
Insulin is synergistic with HGF, the reason why liver regeneration is much slower in diabetics. These mediators travel to the liver via the Portal Vein and not the hepatic artery.
The amount of hepatocyte regeneration is proportional to the stimulus. Any injury greater than 10%, will induce cellular proliferation throughout the liver. In contrast hepatocyte regeneration is delayed 3 to 4 days when apoptosis is produced during PVE. This suggests that hepatocyte removal is a stroger stimulus.
Chronically diseased livers regenerate at a much slower rate, maybe because of a diminished capacity from hepatocytes to respond to hepatotropic factors in relation to dominished portal blood flows caused by fibrosis.
Non-cirrhotic liver regenerate at rates of 21 cm3/day at two weeks, while cirrhotic liver do so at 9 cm3/day.
Clinical Use
The first clinical experiences with PVE were done by Rous and Larimore in 1920, who first studied the consequences od segmental portal vein occlusion in rabbits. They found atrophy of the occluded segments and hypertrophy of the segments with patent PV.Makuuchi decribed for the first time in 1990 PVE to induce left liver hypertrophy before right hepatectomy. Their procedure is now used widely.
Following PVE, alterations of liver function tests are usually minor and transient with many experiencing no changes. When transaminase levels rise, they generally peak at levels less than three times baseline 1 to 3 days after PVE
and return to baseline within 7 to 10 days. Slight changes in white blood cell count and total serum bilirubin level may be seen. Synthetic functions of the liver are almost never affected.
PVE is much less toxic than Arterial embolization, this because there is no distortion of the hepatic anatomy, just inflammation and theres is little tumor necrosis. The abscence of systemoc symptoms has been demostrated by hepatocyte apoptosis rather than necrosis.
Computed tomography (CT) with volumetry is essential for planning hepatic resection. Three-dimensional CT volumetric measurements are acquired by outlining the hepatic segmental contours and calculating the volumes
from the surface measurements from each slice. Contrast enhanced CT scans must be performed to demarcate the vascular landmarks of the hepatic segments. There are two techniques of CT volumetry.
In cirrhotic patients, a liver function assessment must be carried out. This is best done with the indocyanine green retention to determine the extent of safe resection.
PVE Approaches
There are three basic approaches. These approaches are chosen on the basis of operator preference, type of hepatic resection planned, extent of embolization, and type of embolic agent used.
Transhepatic contralateral
Was described by Kinoshita and is the most widely used. A left segmental branch, usually segment III, is used to advance a catheter into the right PV for PVE.
The ipsilateral approach
Described by Nagino and a catheter is placed in a peripheral right portal vein branch and advanced to the right PV and segment IV, with either ethanol or fibrin glue.
Intraoperative cannulation of the ileocolic vein
Embolic Material
Many materials have been used. Makuuchi in their initial experience used gelatin sponge but recanalization was observed at 2 weeks and appears to induce less hypertrophy at 4 weeks.N-butyl-2-cyanoacylate (NCBA) was used but it induced too much inflammation and was not too efficient in patients with reduced hepatopetal flow.
Ethanol was first used by Shimamura owing to its strong coagulation effect. He described the procedure using 20 ml of ethanol, inducing a right PV occlusion. Ogasawara demonstrated doubling of left liver volume after 4 weeks for patients with chronic liver disease and HCC.
Fibrin glue is another commonly used agent with a 75% portal occlusion at 2 weeks and less tan 25% occlusion at 4 weeks.
Newer agents continue to be developed that may provide more complete and permanent occlusions in an attempt to reduce recanalization and ultimately provide better and faster hypertrophy.
Complications
The rate of portal embolization goes from 9.1% o 12.8%. The most commonly reported by Kodama are: subcapsular hematoma, hemoperitoneum, hemobilia, pseudoaneurysm, arteriovenous fistula, arterioportal shunts, PV thrombosis, transient liver failure, pneumothorax and sepsis.
Indications
Many factors should be kept in mind when proposing liver surgery to a patient. The presence or absence of liver disease will impact on liver remnant volume needed. Second, patient size must be considered, this is because larger patients will require larger remnant liver volumes and third the surgeon should always have in mind that there could be nonhepatic surgery at the time of the liver resection.
Quality of iver parenchyma is another factor that should be taken into account. Normal livers can withstand a resection of up to 90%, but cirrhotic livers with more than 60% volume resections will surely not survive. Lethal hepatic failure is common in cirrhotic patients. Retrospective data have shown that patients after systemic or local chemotherapy are at increased risk of surgical complications, so that experts have recommended a minimum of 40% functional liver remnant volume in these patients.
Contraindications
Absolute
1. Overt Portal Hypertension
2. Portal Vein tumoral invasion. This because portal flow is already diverted.
Relative
1. Tumor invasion to the functional liver remnant or extrahepatic metastases
2. Uncorrectable coagulopathy
3. Tumor precluding safe transhepatic access
4. Biliary dilation in the liver remnant (Previous drainage is recommended)
5. Mild Portal hypertension
6. Renal Failure
J Am Coll Surg. 1999;188:304-309; Ann Surg. 2000;231:480-486; Surgery.
1990;107:521-527; Surgery. 1995;117:677-681; Surgery. 2000;127:155-160.
Hepatology. 1995;21:434-439; Surgery. 1997;121:135-141; Surgery.
1997;121:135-141; Hepatology. 1999;29:1099-1105; Surg Today. 1995;25:43-48.
Semin Surg Oncol. 1993;9:298-304; Radiology.1996:200;559-563; Ann Surg. 2000;32:665-672; Br J Surg. 2000;87:879-882.
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