Liver malignancies account for approximately two percent of all pediatric cancers.1 Hepatoblastoma (HB) is the most common liver malignancy of childhood (∼67 percent), typically occurring in infants or toddlers.2 The incidence of HB is 1 to 2 per 1,000,000 live births and has increased significantly in recent decades.3,4 Hepatocellular carcinoma (HCC) is the second most common liver malignancy of childhood (∼31 percent) and most commonly occurs later in adolescence.2 Hepatocellular neoplasm not-otherwise-specified (HCN-NOS) represents a much rarer malignancy that displays histologic features of both HB and HCC and tends to occur in an intermediate age group.5,6 Biliary rhabdomyosarcoma, angiosarcoma, undifferentiated embryonal sarcoma of the liver, and rhabdoid tumor represent the majority of the remaining, very rare, primary pediatric liver malignancies.

Given the low incidence of pediatric liver cancer it is not uncommon for the practicing pediatric surgeon to encounter just one or two cases every few years. This chapter provides guidelines for resection based on contemporary evidence and expert opinion. These guidelines are divided into three critical elements: 1) Conventional Resection, 2) Extended or Extreme Resection, and 3) Liver Transplant. The foundation of these guidelines relies upon the Pre-Treatment Extent of Disease (PRETEXT) system described below. It is the authors’ general recommendation for any resection beyond the conventional wedge resection or hemi-hepatectomy consultation with a center capable of advanced hepatobiliary surgery and/or liver transplantation be initiated early in the diagnostic process.

The age of the patient, the alpha fetoprotein (AFP) value, and the initial radiographic evaluation are key factors in HB risk stratification. The current stratification algorithm was defined by the Children's Hepatic tumors International Collaborative (CHIC) and is currently the basis for the ongoing Pediatric Hepatic International Tumor Trial (PHITT).7, 8, 9 (Figure 1) The radiographic components of this risk stratification are based upon the PRETEXT system devised by Société Internationale d'Oncologie Pédiatrique – Epithelial Liver Tumor Study Group (SIOPEL) in the 1990s and adopted by the Children's Oncology Group (COG) for protocol AHEP-0731 which enrolled patients from 2009 to 2016. This system, through multiple iterations, has become the international language for describing the malignant liver tumors of childhood.

Founded upon the Brisbane nomenclature (hemi-liver, section, and segment), a patient's PRETEXT group is defined by contiguous tumor-free liver sections. A PRETEXT group is assigned at diagnosis; after neoadjuvant chemotherapy a POST-TEXT (POST-Treatment EXTent of tumor) group is assigned. PRETEXT I describes a liver with three adjacent sections free of tumor; PRETEXT II, two adjacent sections free of tumor; PRETEXT III, one section free of tumor; and IV, no tumor-free sections. (Figure 2). In addition to the initial PRETEXT group assignment, patients are evaluated for annotation factors. Annotation factor definitions have been updated for the current PHITT trial and require evaluation of the retrohepatic vena cava and hepatic veins (V) and the portal vein (P) and evaluation for extrahepatic contiguous disease (E), multifocal disease (F), tumor rupture (R), caudate involvement (C), lymph node involvement (N), and metastatic disease (M) (Table 1).10 C and N involvement do not upstage HB in the current risk stratification. N involvement is incredibly rare and usually reactive lymphadenopathy, and caudate involvement is usually a contraindication to upfront resection due to proximity to main portal vein and IVC. With HCC, N involvement is important as this can be a contraindication to transplantation. Chest computed tomography is an essential component of the initial evaluation as about 20% of children with HB and 50% of those with HCC will have lung metastasis at diagnosis.

Conventional resection of pediatric liver tumors at diagnosis

Extended liver resections and management of PRETEXT/POST-TEXT positive annotation factors for pediatric liver tumors

Liver Transplantation for the Treatment of Pediatric Liver Cancer

1. Conventional resection of pediatric liver tumors at diagnosis

Recommendation: Conventional resection either by wedge resection, sectionectomy, or hemi-hepatectomy with a negative margin is the goal of curative surgical treatment of PRETEXT I and II pediatric liver tumors, specifically hepatoblastoma. Resection at diagnosis is recommended for tumors that meet strict criteria, and biopsy followed by neoadjuvant therapy is recommended for tumors that do not meet these criteria

Type of data: Level 2 (prospective cohort studies)

Grade of recommendation: Strong recommendation, moderate quality evidence

Rationale: Resection at diagnosis is recommended for HB when a segmentectomy (one segment), sectionectomy (left lateral or right posterior) or a routine right or left hemi-hepatectomy can be performed with negative margins, as anticipated for PRETEXT I and II patients.11 Resectable PRETEXT II tumors require a ≥1cm margin from the portal vein bifurcation, the retro-hepatic inferior vena cava, and the middle hepatic vein. Primary resection may reduce total chemotherapy administered, as this limits neoadjuvant chemotherapy only to patients deemed unresectable and also may limit the number of cycles given in the adjuvant setting or abdicate chemotherapy all together. Children with pure fetal histology require no additional chemotherapy after complete surgical resection.12

Biopsy and neoadjuvant chemotherapy followed by delayed resection is the standard approach for PRETEXT III and IV lesions. Delayed resection is also appropriate for tumors with PRETEXT annotation factors. Biopsy of the tumor can be performed percutaneously, laparoscopically, or open through an incision. Percutaneous biopsy is the preferred method of tissue sampling as it is associated with less complications and equivalent to open and laparoscopic techniques for obtaining a diagnosis.13,14 Tract seeding causing local tumor recurrence is rare when performed properly. In carefully selected patients and in high volume centers, nonanatomic resections can be considered based on post chemotherapy evaluation of tumor relationship to vessels, the tumor location, and the chances of negative resection margins. Nonanatomic resections have been shown to be feasible with outcomes and complication rates comparable to standard anatomic resection.17