Lesions of the Liver Flashcards
- Which of the following tumor markers is elevated in the most common pediatric liver tumor?
A. β-hCG B. Urinary VMA C. AFP D. Carcinoembryonic antigen (CEA) E. Ferritin
ANSWER: C
COMMENTS: The most common liver tumor in children is hepatoblastoma, comprising about 80% of all pediatric liver tumors.
Hepatoblastoma generally affects children aged 3 years or younger.
Liver tumors in the pediatric population usually present as enlarged abdominal masses.
When a liver mass is encountered, laboratory tests can be extremely helpful in narrowing the differential diagnosis.
AFP is elevated in about 90% of patients with hepatoblastomas.
The second most common liver tumor in the pediatric population is the hepatocellular carcinoma (HCC).
These tumors generally affect older children.
Patients do not have an elevated AFP; however, they can have an elevated ferritin.
Hepatoblastomas are usually solitary lesions, whereas HCC may be multifocal.
Management of hepatoblastoma is based on the PRETEXT staging system, which takes into account the degree of involvement of the liver.
Surgical resection remains the only curative treatment.
Unfortunately, many of these tumors are not resectable at the time of diagnosis.
Hepatoblastomas are chemosensitive, and neoadjuvant therapy before resection has been shown to increase resectability and improve overall outcomes.
If the tumor remains unresectable, transplantation is another treatment option.
CEA is generally associated with colorectal cancers, and when elevated in the setting of a liver tumor, metastatic colorectal disease should be considered.
β-hCG is a tumor marker for germline tumors and not hepatoblastoma.
VMAs are elevated in patients with neuroblastomas.
What causes portal hypertension in infants and children?
Intrinsic liver disease with subsequent fibrosis and cirrhosis caused by biliary atresia, metabolic and autoimmune diseases, vascular causes including extrahe- patic portal vein occlusion, and rarely, post-hepatic Budd-Chiari syndrome and hepatic vein stenosis as well as high-flow intra-and extrahepatic arteriovenous communication.
How is portal hypertension defined?
Portal venous pressures exceeding 8–10 mmHg or a portal vein to hepatic pressure gradient greater than 5 mmHg.
Direct portal pressure measurement is difficult in children.
In children, indirect evidence of portal hypertension includes physical signs such as an enlarged spleen, caput medusa and thrombocytopenia.
Esophageal varices are also indirect evidence of portal hypertension.
What are the most common causes of portal hypertension in children?
Biliary atresia (BA) and extrahepatic portal vein obstruction (EPVO).
How do patients typically present?
Spontaneous hemorrhage from gastrointestinal sites, epistaxis, hematuria, menorrhagia, hypersplenism, thrombocytopenia, ascites.
What are key treatment goals for an acute gastrointestinal bleeding episode?
Volume resuscitation to restore hemodynamic stability with a target hemoglobin level of 8 mg/dl, platelet levels above 20,000, replacement of fresh frozen plasma, initiation of vasoactive intravenous medication such as octreotide or other somatostatin analogues, endoscopy with variceal banding (EVL) or sclerotherapy are the mainstays of initial therapy.
ICU admission is generally recommended.
Antibiotic prophylaxis is recommended in children with cirrhosis.
Is transjugular intrahepatic portosystemic shunts (TIPS) a treatment option?
Creation of a portosystemic shunt between portal and hepatic veins via inserted stent has limited use in children and is generally reserved for refractory treatment of variceal hemorrhage in patients with intrinsic liver disease as a bridge to transplantation.
What are surgical management options of portal hypertension?
Surgical treatment options are done to redirect portal hypertensive blood flow into the low pressure systemic venous circulation and need to consider underlying pathophysiology and severity of symptoms.
Shunt procedures can be divided into non-selective and selective shunts.
Mesocaval, proximal splenorenal and side-to-side porta-caval shunts essentially redirect the entire portal blood flow and are considered non-selective.
Selective shunts such as the distal splenorenal shunt divert only the splenic and gastroesophageal portion of portal blood flow.
The meso Rex shunt restores mesenteric venous circulation back to the intrahepatic portal circulation and as such, is more of a bypass than a shunt (MSB).
Non shunt options include extensive gastric devascularization with distal esophageal transection and reanastomosis (Sugiura procedure), splenic artery ligation as well as liver transplantation but are reserved for high risk patients that are not candidates for shunt surgery.
Splenectomy is NOT a surgical treatment option as it significantly reduces the chance of successful selective shunt surgery.
What diagnostic imaging should be considered in the workup?
Imaging objectives include confirming extrahepatic portal vein thrombosis and assessing size and patency of left portal vein and superior mesenteric vein for MRB feasibility.
Furthermore, evaluation of large collaterals as alternative conduits for MRB as well as inferior vena cava, renal and splenic veins for alternative porto-systemic shunt (PSS) are considered.
Abdominal ultrasonography with doppler can provide and assessment of the portal vein as well as liver parenchyma.
Both triphasic computed tomography (CT) or magnetic resonance (MR) angiography provide an excellent road map.
Transjugular wedged hepatic vein portography is the authors modality of choice to assess not only the patency of the left intrahepatic branch of the portal vein but also communication between left and right intrahepatic portal veins.
What are the indications for surgical treatment of extrahepatic portal vein thrombosis?
Failure of medical and endoscopic management of variceal hemorrhage, severe hypersplenism with thrombocytopenia below 50,000 and recurrent non-variceal bleeding, hepato-pulmonary syndrome and porto-pulmonary hypertension are considered absolute indications for shunt surgery.
Neurocognitive testing suggestive of encephalopathy, increased serum ammonium levels and growth retardation are relative indications.
How do treatment considerations differ for children with EHPVO as compared to those with Biliary Atresia?
Portal hypertension develops early in the disease course of EHPVO while in BA portal hypertension may rarely develop when liver function is generally well compensated and overall mortality is less than 1%.
However, unlike BA where the transplantation intervention prevents the disease progression, the natural course of PHT from EHPVO subjects children to a long variety of complications including splenomegaly, hypersplenism, spontaneous portosystemic shunting, encephalopathy, growth failure, coagulopathy and less commonly portal bilopathy and hepato- pulmonary syndrome.
Rather than serial symptomatic treatment, definite surgical correction should be considered.
When should MRB be considered preemptively?
There is expert consensus on the use of MRB as primary prophylaxis of PHT complications in EHPVO [1].
Favorable anatomy confirmed on wedge portography, patent superior mesenteric, splenic and bilateral internal jugular veins, negative coagulopathy work up, body weight greater than 8 kg, normal echocardiogram and a multidisciplinary team with MRB experience are prerequisite for a greater than 90% success rate.
What is the advantage of a MRB?
Both meso rex bypass and portosystemic shunt effectively relieve symptoms of portal hypertensive bleeding.
However meso rex bypass improves somatic growth, liver synthetic function, coagulopathy, neurocognitive function, prealbumin and insulin like growth factor as well as platelets to levels higher than portosystemic shunts [2, 3].
How did the Rex shunt get its name?
Hugo Rex, an Austrian anatomist, described the anatomic correlation of the intrahepatic left portal vein branch with the base of the falciform ligament and ductus venosus in 1888, later referred to as the Rex recessus.
Jean de Ville de Goyet first
described direct bypassing of an obstructed extrahepatic portal vein into the Rex
recessus in 1998 which became known as the Rex shunt or the meso Rex bypass [4].
What does the preoperative workup include?
In addition to preoperative imaging, liver function tests and biopsy must evaluate for intrinsic liver disease.
Echocardiogram and possibly cardiac catheterization is performed to assess operative risk particularly pulmonary hypertension and hepatopulmonary syndrome as both are contraindications for portosystemic shunts and relative indication for meso rex bypass.
Hematological workup should rule out a hypercoagulable state.
What are key technical components of a MRB?
The recessus of Rex is dissected following the round ligament maintaining vascular control of segmental feeding branches and assuring adequate lumen and backbleeding of the left portal vein.
Partial resection of liver segments III and IV allows wider exposure and passage of the subsequent vein graft.
Then, the superior mesenteric vein is exposed and controlled at the base of the small bowel mesentery and the jugular vein is harvested.
The narrower cephalic end is anastomosed to the exposed left portal vein and the wider thoracic end tunneled through the lesser sac over the pancreas posterior to the stomach and transverse mesocolon before anastomosing the distal wider end to the infrapancreatic superior mesenteric vein.
How are Rex shunt patients managed post operatively?
Systemic low level heparinization and transition to long-term antiplatelet therapy for 6 months.
If in the preoperative work-up a hypercoagulable condition has been identified, long term anticoagulation may be necessary.
How should patients be followed up?
Outpatient follow up includes doppler US every 3 months for the first year and then every 6 months for the second year and yearly after that.
What are complications of shunt surgery? How can they be managed?
Shunt thrombosis in the immediate postoperative period requires urgent thrombectomy, shunt revision and systemic anticoagulation.
If not salvageable alternative portosystemic shunts need to be considered.
Shunt stenosis can successfully be managed by percutaneous endovascular interventions in the majority of cases with excellent long term patency rates and resolution of clinical symptoms [5].
Failure of percutaneous therapy requires operative shunt revision.
Ascites from extensive dissection of retroperitoneal lymphatics resolves spontaneously in most cases but may require oral diuretics or reduced-fat diet.
What are the long-term outcomes of MRB?
Over 80% of patients with EHPVO can successfully be treated with MRB.
A patent MRB obviates the need for esophageal endoscopy, banding or use of non-selective beta blockade.
Age at the time of surgery does not appear to affect outcome but younger children tend to have shunt flows that are closer to normal portal flow when expressed per body surface area.
In management of portal hypertension, which of the following is false?
A. In endoscopic variceal ligation, the band and varices slough off in 5-7 days.
B. In proximal splenorenal shunt, splenectomy is required.
C. In portocaval shunt, side of portal vein and end of inferior vena cava is anastomosed.
D. In children, mesocaval and splenorenal shunts are commonly performed.
E. In mesocaval shunt, inferior mesenteric vein is dissected 5cm inferior to the pancreas.
C. In portocaval shunt, side of portal vein and end of inferior vena cava is anastomosed.
A 17-year-old male from Mexico presents with right upper quadrant pain and episodic diarrhea. He describes his pain as constant, dull, and aching. He says that he has not been feeling well for a few weeks, has no appetite, and has had a fever for the past 24 hours.
Bloodwork shows leukocytosis and elevated alkaline phosphatase. An enzyme-linked immunosorbent assay is positive for Entamoeba histolytica. What is the appropriate initial management?
Choices:
1. Amebicidal medication
2. CT scan in anticipation of needing percutaneous drainage
3. Open drainage and antibiotics
4. Observation
Answer: 1-Amebicidal medication
Explanations:
• The patient has an amebic liver abscess. The majority of amebic abscesses can be treated with amebicidal agents alone.
• After completion of treatment with tissue amebicides, an amebicidal drug that works inside the intestinal lumen, a lumicide, is administered. Failure to use lumicidal agents can lead to a relapse of the infection. Metronidazole, emetine, and dehydroemetine are such active agents.
• Treatment also entails the use of nitroimidazole, preferably metro-nidazole, at a dose of 500 mg to 750 mg by mouth three times per day for 10 days. Alternatively, tinidazole 2 grams by mouth daily for 5 days can be used. As parasites can persist in the intestine in 40% to 60% of patients, treatment with nitroimidazole should be followed with a luminal agent such as paromomycin. Metronidazole and paromomycin should not be given at the same time because diarrhea, a common side effect of paromomycin, can make assessing response to therapy difficult.
• Therapeutic aspiration, usually through image-guided percutaneous needle aspiration or catheter drainage, is occasionally required.
It should be considered in patients with no clinical response to antibiotics within 5 to 7 days; once an imaging exam shows an abscess with a high risk of rupture (cavitary diameter of more than 5 cm or presence of lesions in the left lobe; or in cases of bacterial confection of an amebic liver abscess.
StatPearls
A 2-year-old boy presents with right-sided abdominal swelling that his mother first noticed in the bathtub 2 months ago.
It has been increasing in size, and the boy now has a decreased appetite and mild pain in the area. Ultrasound and magnetic resonance imaging were performed and demonstrated a solitary liver mass. To stage this tumor, what is the best next step?
Choices:
1. Perform a biopsy
2. Screen for hepatitis
3. Chest CT
4. Perform liver function tests
Answer: 3 - Chest CT
Explanations:
• A chest CT can help detect lung metastases, as up to 20% of hepato-blastoma cases present with metastases.
• The lung is the most common site of metastases.
• Ultrasound and either CT or MRI are the imaging modalities used to define the extent of tumor involvement of the liver and aid in pre-surgical planning.
• The presence or absence of metastases is important in the staging process.
StatPearls
Which one of the following is the most common liver tumour?
A. Hepatocellular carcinoma.
B. Hepatoblastoma.
C. Sarcoma.
D. Mesenchymal hamartoma.
E. Adenoma.
B
Hepatoblastoma is the commonest (43 percent).
Hepatocellular carcinoma has 23 percent incidence, sarcoma 6 percent, mesenchymal hamartoma 6, percent and adenoma 2 percent.
Syed/MCQ
Regarding histological subtypes of hepatoblastoma, which of the following statements is correct?
A. Small cell is more common than foetal.
B. Macrotrabacular is more common than embryonal.
C. Teratoid is more common than non-teratoid.
D. Foetal is more common than teratoid.
E. Epithelial and mixed epithelial are not subtypes of hepatoblastoma.
D Histological subtypes of hepatoblastoma are as follows. 1. Epithelial
(a) Foetal 31 percent, (b) embryonal 19 percent, (c) macrotrabacular 05 percent, and (d) small cell 03 percent.
- Mixed epithelial/mesenchymal
(a) Teratoid 10 percent, (b) Nonteratoid 34 percent.
Syed/MCQ
With regard to hepatic tumour in children, which of the following is not true?
A. Primary tumour of liver is uncommon.
B. Forty per cent of primary liver tumours are malignant.
C. Hepatoblastoma is the most common primary liver tumour in children.
D. Hepatoblastoma affects boys as frequently as girls.
E. Right lobe is more commonly involved.
B Approximately 75 percent of primary liver tumours are malignant.
Syed/MCQ
Regarding liver abscess, which of the following statements is true?
A. Amoebic liver abscess is less common than pyogenic.
B. Left lobe is more commonly involved.
C. Indirect haemaglutination test (IHA) is positive in amoebic liver abscess.
D. Laparotomy and drainage is preferred mode of treatment.
E. Drainage is required if abscess is more than 2 cm.
C
Indirect haemagglutination test (IHA) is positive in amoebic liver abscess.
Amoebic liver abscess is more common than pyogenic, right lobe is much more commonly involved, and percutaneous needle aspiration under ultrasound guidance is preferred mode of treatment.
Drainage is generally required if abscess is above 5 cm.
Syed/MCQ
How is infantile hepatic hemangioma treated?
What is the PRETEXT system for hepatoblastoma?
Staging of HB tumors is, in part, based upon the Pretreatment Extent of Disease (PRETEXT) system developed in 1990 by the European International Society of Pediatric Oncology (SIOPEL).
Since their treatment protocols are based on primary treatment with chemotherapy followed by surgical resection, the PRETEXT staging system is based on the pretreatment anatomic location of the mass as determined by a high-quality axial imaging study (abdominal MRI or CT).
The liver is divided into four sectors based on its segmental anatomy as defined by Couinaud.
Within PRETEXT, the left hemi-liver is separated into the lateral sector, comprising Couinaud segments 2 and 3, and the medial sector comprising segment 4.
The right hemi-liver is an anterior sector made up of Couinaud segments 5 and 8, as well as a posterior sector made up of segments 6 and 7.
In PRETEXT I, three adjoining sectors are tumor free (tumor in only one sector).
In PRETEXT II, two adjoining sectors are tumor free (two sectors involved).
If only one sector is tumor free or a total of three nonadjoining sectors are involved (tumor involves two or three sectors), the tumor is designated PRETEX III.
For PRETEXT IV, there are no tumor-free sectors (tumor in all four sectors).
PRETEXT also takes into account additional criteria (annotation factors) including IVC or hepatic vein involvement (V), portal vein involvement (P), extrahepatic abdominal disease (E), tumor focality (F), tumor rupture (R), lymph node metastasis (N), caudate involvement (C), and distant metastasis (M).
The PRETEXT system is predictive of outcome and is being used by all multicenter HB trial groups.
The PRETEXT system is also used to reevaluate the tumor anatomy after adjuvant chemotherapy. In that setting, it is termed POST-TEXT and is determined approximately 10 days after every two cycles of chemotherapy.
In the most recent SIOPEL studies (SIOPEL 4 and 6), patients were stratified into the standard risk group if they were PRETEXT I, II, or III.
High-risk patients included those with AFP < 100 ng/mL, tumor rupture, SCU histology, and those positive for additional PRETEXT criteria; (V+, P+, E+, or M+).
Studies performed in North America through the Children’s Oncology Group (COG) use both the PRETEXT system and the Evans staging system, which take into account histology and the initial resectability of the tumor.
Under the Evans system, stage I tumors are localized and completely resected, stage II are tumors in which gross residual disease was present after resection, stage III tumors received preoperative chemotherapy, and IV are those tumors in which metastatic disease is present.
Determining the appropriate annotated PRETEX stage can be challenging in some cases. Staging of complex cases is facilitated by a central radiologic review process such as that used in COG studies.
The COG central review allows for accurate subcategorization of hepatic vein involvement (V0–V3) and portal vein involvement (P0–P3).
In the most recent COG study (AHEP-0731), patients were stratified into four groups: very low, low, intermediate, and high risk.
Patients at very low risk are those with PRETEXT I or II and with pure fetal histology (PFH).
Low-risk patients are PRETEXT I or II with any histology other than PFH who have undergone primary resection.
Intermediate-risk patients are PRETEXT II, III, or IV who are either unresectable at diagnosis, are V+, P+, or E+, or have SCU histologic subtype.
High-risk patients have metastatic disease or AFP less than 100 ng/mL.
A new risk stratification system has been developed through the global Children’s Hepatic Tumor International Collaboration (CHIC). Through this initiative, the data from eight (1605 patients) multicenter trials (SIOPEL-2, SIOPEL-3, COG INT-0098, COG P9645, GPOH HB89, GPOH HB99, JPLT-1, and JPLT-2) have been collected and recently reviewed.
Analysis of this data was used to determine the prognostic factors that correlated best with outcomes.
The factors with the highest correlation were found to be PRETEXT group,
age (<3, 3–7, and >7),
AFP (<100 ng/mL and 101–1000 ng/mL) at diagnosis, and
the presence/absence of PRETEXT annotation factors (V, P, E, F, R).
These factors were combined to create four clinically relevant “backbone” groups: very low, low, intermediate, and high risk.
H&A
What is the second most common Pediatric malignant liver tumor?
HCC is a relatively rare and highly malignant tumor that is more commonly seen in adults than in children. It is the second most common pediatric malignant liver tumor, constituting approximately 20% of the cases, but it makes up less than 0.5–1% of all pediatric tumors.
It occurs more commonly in boys and has an age-dependent incidence, with the peak between 10 and 15 years.
In the 1970s the EFS and overall survival (OS) were low, at approximately 30%. In the current era, the EFS and OS for patients with resectable HCC range from 70–90% due to improvements in chemotherapy and the operative technique.
The predisposing factors for HCC differ between children and adults. In adults, HCC is preceded by cirrhosis resulting from a spectrum of diseases causing hepatic inflammation and fibrosis. This spectrum includes hepatitis B and C viral infections, hemochromatosis, alcohol-related cirrhosis, nonalcoholic steatohepatitis, and primary biliary cirrhosis. Patients with these diseases are at a significantly increased risk for developing HCC, and it is recommended they undergo serial liver US and serum AFP screening levels every 6 months.
In contrast, pediatric HCC is not always preceded by cirrhosis. In most cases, no specific cause can be determined. Hepatitis B is linked to the development of HCC, and the risk in carriers is 10–25%.
In areas where hepatitis B is endemic, HCC ranks fifth in the causes of childhood malignancies and outnumbers HB by 3:1.
The importance of hepatitis B and the subsequent development of HCC in children is highlighted by the aggressive hepatitis B vaccination program that Taiwan initiated in 1984. When the mortality from pediatric (0–9 years old) HCC from 1984 was compared with 1993, there was a statistically significant decrease in HCC. Similar results have been found in Gambia. U.S.
Hepatitis C also has been linked to the development of HCC. In contrast to hepatitis B, the cirrhosis and the subsequent development of HCC in the hepatitis C population usually takes several decades to develop.
HCC in children has been associated with a variety of metabolic, familial, and infectious disorders, including tyrosinemia, α-1-antitrypsin deficiency, and hemochromatosis.
Patients with tyrosinemia are at a particularly high risk for developing HCC. Because of this high prevalence, it has been suggested that liver transplantation be performed before 2 years of age in these children.
HCC also has been seen in patients with type 1 GSD. Though most hepatic masses in patients with type 1 GSD are hepatic adenomas, carcinomas can occur as well.
Other noncirrhotic liver diseases that are associated with HCC include familial polyposis, Gardner syndrome, Sotos syndrome, Bloom syndrome, neurofibromatosis, Abernathy malformation, methotrexate therapy, and neonatal hepatitis.
Congenital hepatic inflammatory or fibrotic disorders associated with HCC include extrahepatic biliary atresia, congenital hepatic fibrosis, Alagille syndrome, and persistent familial intrahepatic cholestasis (PFIC).
This association between HCC and diseases that can lead to cirrhosis supports the practice of a screening protocol using liver US and AFP levels every 6 months.
Long-term use of total parenteral nutrition (TPN) is also associated with increased rates of pediatric HCC.
H&A
How is HCC diagnosed?
Clinical Presentation
Most patients with HCC present with an abdominal mass or abdominal pain. Other associated symptoms include nausea and vomiting, anorexia, malaise, and significant weight loss.
More than one-third of HCCs appear as multiple nodules rather than a single tumor.
In one study, 10% were seen initially with tumor rupture and hemoperitoneum.
Patients who experience spontaneous rupture of an HCC tumor present with acute right upper quadrant pain and can present with hypovolemic shock from intra-abdominal hemorrhage. The diagnosis of ruptured HCC can be made with US or abdominal CT.
If the patient is hemodynamically stable, treatment is conservative with volume resuscitation and correction of any associated coagulopathy. With a stable patient, a careful assessment of the tumor can be made with the goal of primary tumor resection.
In the patient with ongoing bleeding, transarterial embolization of the tumor can be performed to control the hemorrhage before proceeding to evaluation for resection.
Laboratory studies can reveal mild elevations in the asparate aminotransferase (AST) and lactic dehydrogenase (LDH) levels.
AFP is elevated in 85% of patients with HCC, but normal or only mildly elevated AFP values can be found in patients with the fibrolamellar variant. An elevated AFP is associated with an increased risk for recurrence and therefore reflects a poorer prognosis.l
Imaging CT and MRI are both helpful for delineating HCC masses and determining resectability. Just as with HB, intravenous contrast abdominal CT enables visualization of the hepatic and portal venous systems, thereby allowing assessment of any vascular involvement.
The American Association for the Study of Liver Diseases has published criteria for the noninvasive diagnosis of HCC.
In nodules less than 2 cm in diameter within a cirrhotic liver, the diagnosis of HCC can be made without biopsy of the lesion if two axial imaging studies (CT/MRI) reveal arterial-phase hypervascularity followed by washout in the portal venous phase (Fig. 66.18).
Fibrolamellar variant HCC appears as a hypodense, single or multilobed mass on noncontrast CT. A contrast CT of a fibrolamellar HCC reveals variable perfusion with hypervascularity. In addition, a central hypodense or hypervascular area can be seen to mimic a central scar. This can create confusion between the diagnosis of the fibrolamellar variant and FNH. MRI may be helpful in distinguishing between these two diagnoses.
Histology HCC can vary in size from 2–25 cm, and the surrounding liver exhibits either micronodular or macronodular cirrhosis in up to 60% of cases.
Microscopically, the tumor is made up of trabeculae that are 2–10 cell layers in thickness, with the larger trabeculae at times displaying central necrosis.
Individual tumor cells are usually larger than normal hepatocytes with nuclear hypochromasia and demonstrate frequent and bizarre mitosis.
Vascular invasion may be prominent.
Tumors less than 2 cm are generally well differentiated.
As the tumor grows, the original tumor cells are replaced by poorly differentiated cell clones. With further enlargement, its blood supply becomes dependent on newly formed arterial vessels and less dependent on the portal circulation, leading to the hypervascular pattern that is the radiologic hallmark for HCC.
In the fibrolamellar variant, the hepatocytes are large, deeply eosinophilic, and embedded within a lamellar fibrosis. Clusters of cells are often separated by broad bands of laminated collagen.
The presence of large amounts of fibrosis alone is not sufficient to make the diagnosis of fibrolamellar HCC.
H&A
What are indications for transplantation in HCC?
Transplantation for Hepatocellular Carcinoma
Just as in adults, liver transplantation has been found to be an effective curative therapy for management of pediatric HCC.
Two selection criteria are currently being used to evaluate the potential for recurrence after adult liver transplantation for HCC (Table 66.10).
The Milan criteria (tumor <5 cm diameter or a maximum of three tumors, none greater than 3 cm diameter, and no vascular invasion or extrahepatic involvement) is widely recognized as a good predictor of a low recurrence rate after transplantation.
However, since HCC can be a rapidly growing tumor, it is possible for the tumor to exceed these criteria before an organ becomes available.
Subsequently, The University of California at San Francisco (UCSF) developed expanded acceptable criteria for a liver transplant (tumor <6.5 cm diameter or a maximum of three tumors, with none greater than 4.5 cm diameter, and cumulative tumor diameter <8 cm) that allowed for a greater pretransplant tumor burden while still having a low post-transplant recurrence rate.
Several studies have supported the use of the UCSF criteria.
The Milan and UCSF criteria have not been verified in children.
The practice guidelines generated by both the American Association of Transplantation and the Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommend that liver transplantation be considered for any pediatric patient with unresectable HCC and no extrahepatic tumor or clear vascular invasion, without specific regard to the number and size of the HCC tumors.
The decision to proceed with liver transplant evaluation in pediatric patients with HCC has to be made on an individual, case-by-case basis.
Two absolute contraindications to transplantation for HCC in children are extrahepatic spread and macroscopic vascular invasion.
The SIOPEL-1 study reported no long-term survivors among those who failed to respond to chemotherapy.
Therefore, the lack of response to preoperative chemotherapy is a relative contraindication to transplantation.
Despite these constraints, liver transplantation in children with unresectable HCC has a very good 5-year survival rate between 63% and 89%.
Both adult and pediatric patients are afforded exception points for HCC in the UNOS matching system to enable transplantation before tumor progression.
In contrast to patients with HB, liver transplantation is an appropriate treatment option for patients with HCC who experience a recurrence after a resection.
Posttransplant survival after HCC recurrence is comparable to that of patients who underwent a primary transplant for HCC.
Patients who are not surgical or transplant candidates can potentially benefit from adjunctive interventional procedures that afford local tumor control.
Procedures such as percutaneous ethanol injection, radiofrequency ablation, or chemoembolization of the tumor have proven to be effective in decreasing or eradicating tumors, treating recurrent tumors, or shrinking tumors so that the patient again falls within the formal (Milan/UCSF) transplant criteria.
Though such interventional procedures can improve survival, they are not curative.
The outcome for patients with HCC, regardless of the treatment modality, is still not as good as the outcome for HB.
Further improvements in survival for HCC will come from advances in chemotherapy regimens that will prevent tumor recurrences.
H&A
