Hepatocellular carcinoma in children responds less to chemotherapy, so complete removal, or transplantation when removal is impossible, carries more of the weight. Benign tumors need surgery alone in most cases, and the operation can be smaller.
What do the international trials show?
We defined and adopted four risk groups.
Children's Hepatic tumors International Collaboration, Lancet Oncology, 2017
- The PRETEXT group, how much of the liver the tumor occupies.
- Age.
- Alpha-fetoprotein, where, unexpectedly, a very low level at diagnosis signals a more aggressive tumor that behaves differently from typical hepatoblastoma and needs the high-risk approach.
- Spread to the lungs, invasion of the main veins, multiple tumors or rupture.
Doxorubicin can be safely omitted from the treatment of standard-risk hepatoblastoma.
SIOPEL-3 trial of 255 children, New England Journal of Medicine, 2009
- Hearing loss from cisplatin, checked with hearing tests before each cycle.
- Low blood counts and infections between cycles.
- Kidney effects, monitored with blood tests.
Standard-risk hepatoblastoma
Standard-risk tumors leave at least one section of the liver free and produce plenty of alpha-fetoprotein. SIOPEL-3 asked whether one of the two drugs in the usual combination could be dropped, sparing children its side effects, and randomized 255 children to cisplatin alone or cisplatin with doxorubicin.
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SIOPEL-3, 255 children with standard-risk hepatoblastoma
| Outcome |
Cisplatin alone |
Cisplatin and doxorubicin |
| Complete resection |
95 percent |
93 percent |
| Event-free at 3 years |
83 percent |
85 percent |
| Alive at 3 years |
95 percent |
93 percent |
| Severe acute side effects |
20.6 percent |
74.4 percent |
High-risk hepatoblastoma
The SIOPEL-4 treatment regimen is feasible and efficacious for complete remission at the end of treatment for patients with high-risk hepatoblastoma.
SIOPEL-4 trial of 62 children, Lancet Oncology, 2013
SIOPEL-4 treated 62 children with high-risk tumors, 39 of them with lung metastases, using intensive cisplatin-based chemotherapy and surgery, including transplantation and removal of lung deposits when needed. Surgeons removed all tumor in 74 percent, 79 percent reached complete remission by the end of treatment, and 83 percent were alive at three years. The price was high. Almost every child had severe blood count problems, and half lost hearing to a moderate or severe degree.
Transplant when resection is impossible
Planning decides the result.
A review of the SIOPEL-1 study and the world experience compared children who had a transplant planned from the start with those who had one only after an attempted resection had failed or left tumor behind. Only invasion of the main veins changed survival among children with a primary transplant.
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Liver transplantation for hepatoblastoma, world experience
| Type of transplant |
Patients |
Survival |
| Primary transplant, planned instead of resection |
106 |
82 percent at 6 years |
| Rescue transplant, after a failed or incomplete resection |
41 |
30 percent at 6 years |
The operation
How a liver resection is done
Through an incision across the upper abdomen, the surgeon frees the liver, identifies the vessels and bile ducts of the part to be removed, and divides the liver tissue with instruments that seal small vessels as they go. Intraoperative ultrasound guides the cut. Depending on the tumor, the operation removes a segment, a lobe or an extended lobe, taking up to two thirds of the liver, and lasts three to six hours.
A tumor close to the main veins or the junction of the bile ducts needs particular experience. When the tumor cannot be removed with a clear margin, the team plans a transplant from the start, since a planned transplant gives far better results than a rescue transplant after a failed resection.
1
Intensive care
One to two days of close monitoring of blood sugar, clotting, liver tests and pain relief.
2
The ward
Feeding resumes within days. Drains come out once bile leakage is excluded. Home after seven to ten days in most children.
3
Further treatment
Postoperative chemotherapy starts two to three weeks later when planned, and alpha-fetoprotein is checked monthly at first.
Recovery and follow-up
Children bounce back. Most return to play within weeks. Complications include bleeding, bile leakage, infection and, rarely, temporary liver weakness after very large resections. After treatment, alpha-fetoprotein and ultrasound or MRI are checked regularly for several years, together with hearing and kidney tests for children who received cisplatin.
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A typical treatment timeline
| Stage |
Duration |
| Diagnosis and staging |
One to two weeks |
| Chemotherapy before surgery |
Two to four months |
| Surgery and hospital stay |
One to two weeks |
| Chemotherapy after surgery, if planned |
One to two months |
The length of stay in Istanbul depends on the plan. For the operation alone, plan two to three weeks. For the full treatment, the team works with your home oncology team so that chemotherapy takes place closer to home where possible, with the family coming to Istanbul for staging, surgery and key reviews.
Cost depends on the tests, the chemotherapy given in Istanbul, the operation, intensive care and the hospital stay. The coordinator explains each part once the plan is clear.
One coordinator supports the family through every visit, arranging the visa invitation letter ten days ahead, the transfer and an apartment near the hospital for the weeks of treatment. A parent stays with the child throughout. The team works in seven languages, with halal meals and a prayer room available. Back home, the pediatric oncology and surgery teams review alpha-fetoprotein results and scans sent by your local doctors and stay reachable on the same WhatsApp number, so that any rise in the marker is acted on early. Most recurrences show first as a rising alpha-fetoprotein, weeks or months before anything is visible on a scan, and that early warning gives the team time to find and treat a small deposit while it is still curable. Families keep a simple record of each result, and the coordinator makes sure every value reaches the surgeon and the oncologist within days, whatever the time difference. Flying home is safe once the wound has healed, the child eats well and blood counts allow it, two to three weeks after surgery for most children.
Liver resection in children FAQ
Can a child live normally after part of the liver is removed?
Yes. The remaining liver regrows within weeks to months and works normally.
What is the survival rate for hepatoblastoma?
In SIOPEL-3, 95 percent of children with standard-risk tumors were alive at three years. In SIOPEL-4, 83 percent of children with high-risk tumors were alive at three years.
Why is chemotherapy given before surgery?
It shrinks the tumor, in many children dramatically, which makes complete removal safer and preserves more healthy liver.
When is a liver transplant needed instead?
When the tumor involves all four sections of the liver or the main veins and cannot be removed safely. A planned transplant gives better results than a rescue transplant.
How long will we stay in Istanbul?
Two to three weeks for the operation. Your home team can give much of the chemotherapy.
Can a parent stay with the child?
Yes. A parent stays with the child throughout the hospital stay.
References
- Meyers RL, Maibach R, Hiyama E, et al. Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children's Hepatic tumors International Collaboration. Lancet Oncology. 2017;18(1):122-131.
- Perilongo G, Maibach R, Shafford E, et al. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. New England Journal of Medicine. 2009;361(17):1662-1670.
- Zsiros J, Brugieres L, Brock P, et al. Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncology. 2013;14(9):834-842.
- Roebuck DJ, Aronson D, Clapuyt P, et al. 2005 PRETEXT: a revised staging system for primary malignant liver tumours of childhood developed by the SIOPEL group. Pediatric Radiology. 2007;37(2):123-132.
- Otte JB, Pritchard J, Aronson DC, et al. Liver transplantation for hepatoblastoma: results from the International Society of Pediatric Oncology (SIOP) study SIOPEL-1 and review of the world experience. Pediatric Blood and Cancer. 2004;42(1):74-83.
