Liver transplant "excellent" option for kids with liver tumors

Last Updated: 2015-09-02

By Will Boggs MD

NEW YORK (Reuters Health) - Liver transplant combined with chemotherapy provides long-term disease-free survival in children with hepatoblastoma and hepatocellular cancer (HCC), according to a new study.

"Patients with metastatic hepatoblastoma (HBL) can have excellent results with transplantation," Dr. C. Andrew Bonham from Stanford University School of Medicine in Palo Alto, California, told Reuters Health by email. "Children with HCC have different outcomes (better) than adults."

Liver tumors in children are rare. The annual incidence of primary liver malignancies in children and adolescents is around one in 2 million, with HBL representing about two-thirds and HCC accounting for less than 25% of cases.

In order to clarify the long-term outcomes of liver transplant for unresectable HBL and HCC, Dr. Bonham's team reviewed their experience with 40 patients (30 with HBL and 10 with HCC) who underwent transplant from 1997 through 2014.

Disease-free survival 10 years after transplant was 82% in the HBL group and 78% in the HCC group. Overall 10-year survival was 84% in the HBL group and 72% in the HCC group, and graft survival was 83% in the HBL group and 85% in the HCC group.

Risk factors for HBL recurrence included having PRETEXT stage IV disease or tumor rupture and being older at the time of the transplant, the researchers report in JAMA Surgery, online August 26.

Children who developed HBL recurrence also spent about twice as long on the transplant waiting list as children without recurrence (mean 31 days vs 15 days, p<0.01).

In the HCC group, tumor size, vascular invasion, and time to transplant were not associated with recurrence, but being older at the time of transplant and having metastatic disease were significant risk factors for recurrence.

"HBL patients should be considered for transplant early," Dr. Bonham concluded. "Eradication of metastatic disease with chemotherapy and surgery should be followed by timely transplant. Prolonged waiting is associated with poorer prognosis and interrupts optimal chemotherapy. Children with HCC that develops in the absence of chronic viral hepatitis have a better prognosis, and should be transplanted regardless of Milan criteria if the tumor is confined to the liver and without vascular invasion."

Dr. Ronald W. Busuttil from David Geffen School of Medicine at UCLA, Los Angeles, California, who coauthored an invited commentary on the report, told Reuters Health, "Liver transplantation, either primary or salvage, has outstanding outcomes in this lethal cancer. Registry studies such as the pediatric liver unresectable tumor observatory (PLUTO) and single center experiences such as our own at UCLA have demonstrated an expected long-term liver survival of 80 to 90%. This is superior to what can be achieved with any other modality of therapy including chemotherapy, ablative therapy, or surgery alone."

"These data indicated that proper and timely referral is essential and liver transplantation for a child without significant extrahepatic disease should be considered as first-line therapy," Dr. Busuttil said.

A second report, also online August 26 in JAMA Surgery, describes damage control as a strategy to manage postreperfusion hemodynamic instability and coagulopathy after liver transplant.

The approach "includes completion of portal venous and hepatic arterial anastomoses for allograft reperfusion, deferral of biliary reconstruction, intra-abdominal packing, and resuscitation in the intensive care unit before packing removal, biliary reconstruction, and closure of the abdomen within 48 hours," Dr. Vatche G. Agopian from David Geffen School of Medicine at UCLA and colleagues write.

According to their review of 1,813 adult patients who underwent liver transplantation, 8.3% required damage control. These patients had longer hospital stay, higher infection rates, higher rates of graft nonfunction, and higher mortality within 30 days, compared with patients not requiring damage control.

"Despite recipients requiring damage control being significantly sicker to begin with compared to recipients who underwent 1-stage transplant, if only one additional operation was required, the outcomes were similar," Dr. Agopian told Reuters Health by email.

"As in trauma surgery, staying in the operating room can sometimes serve to worsen the cycle of bleeding, coagulopathy, acidosis, and hypothermia, and our study at least shows that this damage control strategy itself is not deleterious, and potentially mitigates the negative outcomes that may arise from staying in the operating room too long," he said.

SOURCE: http://bit.ly/1hU2AoK, http://bit.ly/1UmT4eQ and http://bit.ly/1L558XU

JAMA Surg 2015.