Introduction
Hepatoblastoma is the most frequent of the malignant paediatric liver tumors. HB comprises 1% of all pediatric malignancies. Its incidence is increasing by as much as 2.7% per year |
HB developes usually in the absence of underlying liver disease |
Typical clinical presentation: asymptomatic abdominal mass, with no associated systemic symptoms |
PRETEXT (PRETreatment EXtent of Disease) system is used to stratify tumours and plan the extent of resection |
Surgery remains the cornerstone of management and complete resection is crucial for cure |
Historical perspective
The first successful resection of a solid liver tumour was performed by Carl von Langenbuch in 1887 in Berlin [8] |
In 1898 the first case of HB was described in the English literature, but the term “hepatoblastoma” was introduced by Willis in 1962 [1]. He defined it as “an embryonic tumour that contains hepatic epithelial parenchyma.” |
In 1908 James Hogarth Pringle developed a technique to minimise blood loss during hepatic surgery by clamping the hepatic pedicle (now commonly known as the Pringle maneuver) [9] |
In 1951 O'Sullivan reported a successful left hepatic lobectomy in a 5-year-old girl with hepatoma. One month after the operation the patient developed metastases and she died one year after surgery [10] |
In 1954 Claude Couinaud published the report defining segmental liver anatomy, contributing majorlyed to a reduction in surgical morbidity [11] |
Introduction of cisplatin- and doxorubicin-containing chemotherapy regimens in the 1980s [12] |
Biopsy—yes or no?
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Biopsy should be performed before chemotherapy.
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Intraoperative, rapid pathological analysis should be avoided.
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Fine-needle aspiration biopsy should be avoided for diagnosis, as it does not provide enough tissue to evaluate tumour.
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As many as five, and preferably ten, cores of tumour should be obtained, where possible, from different regions of the tumour.
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A biopsy of the adjoining normal liver should be taken for molecular tests.
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To prevent tumour seeding along the needle tract, the biopsy technique should be coaxial and the needle should be passed through “healthy” liver, which will be resected at the definite tumor resection.
Planning of liver surgery. PRETEXT system
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Cavernous transformation of the main portal vein is classified as (evidence of) tumour thrombus.
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Extrahepatic disease is a rare situation, occuring in less than 5% of patients with HB. Simple ascites is not considered extrahepatic disease.
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Multifocal tumours are present in 20% of patients with HB.
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Rupture of the tumour during surgery is not considered tumour rupture.
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Lymph node metastases are uncommon in HB and require pathologic confirmation.
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HB metastastses occur most commonly to the lung; this happens in 20% of HB cases. Biopsy is not necessary for diagnosis, because it is unusual for other lesions to mimic metastases.
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Tumours close to hilar structures leading to compression of local structures may lead to classification challenges. Tumours that are pushing vascular structures aside may cause pressure changes that can mimic invasion on imaging [19].
Definition | |
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PRETEXT group | |
I | 1 section involved |
3 contiguous sections are tumour free | |
II | 1 or 2 sections involved |
2 contiguous sections are tumour free | |
III | 2 or 3 sections involved |
1 contiguous section is tumour free | |
IV | 4 sections involved |
Annotation factors | |
V | Venous involvement. V-positive tumour: (1) tumour obliteratinga or encasingb (> 50% or 180O) all 3 hepatic veins or IVC, (2) tumour thrombus in any one hepatic vein or IVCc |
P | Portal venous involvement. P-positive tumour: (1) tumour obliterating or encasing (> 50% or 180O) both portal veins or main portal vein, (2) tumour thrombus in either or both the right and left portal veins, or the main portal vein |
E | Extrahepatic disease contiguous with the main liver tumour |
F | Multifocality. Two or more hepatic tumours surrounded by normal liver tissue |
R | Tumour rupture. Free fluid in the abdomen or pelvis at diagnosis with 1 or more findings of haemorrhage on imaging: (1) septations within fluid, (2) high-density fluid on CT (> 25 HU), (3) blood on MRI, (4) visible rupture/hepatic capsular defect. Clinical findings of haemorrhage: HCT < 25%, HGB < 7 g/dl, blood pressure drop, requiring blood transfusion, acute abdominal signs |
C | Caudate: Involvement of the caudate lobe (segment 1) – the tumour is at least PRETEXT II |
N | Lymph node metastases: (1) Lymph node with a short-axis diameter of > 1 cm or a portocaval lymph node > 1.5 cm, (2) spherical lymph node with loss of fatty hilum. Definitive involvement of lymph nodes should be confirmed histologically |
M | Distant metastases. M-positive: One pulmonary nodule ≥ 5 mm, or 2 or more nodules, each ≥ 3 mm in diameter |
Tumour resection
The timing and extent of surgical resection. Primary or delayed surgery?
General principles and basic techniques of liver resection (Table 4)
The size of the tumour alone is not a contraindication to resection |
Tumour resectability depends upon surgical expertise |
Knowledge of liver anatomy, experience in liver surgery and specialised equipement are absolutely necessary |
The goal of surgery is to achieve complete tumour resection with negative margins. Incomplete macroscopic tumour resection is associated with worse outcome! |
Anatomic resections are usually recommended |
Types of liver resections
Anatomical term | Couinaud segments | Term for surgical resection |
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Right (hemi)liver | 5–8 (± seg.1) | Right hepatectomy/right hemihepatectomy (± seg.1) |
Left (hemi)liver | 2–4 (± seg.1) | Left hepatectomy/left hemihepatectomy (± seg.1) |
Right anterior section | 5.8 | Right anterior sectionectomy/sectorectomy |
Right posterior section | 6 and 7 | Right posterior sectionectomy/sectorectomy |
Left medial section | 4 | Left medial sectionectomy/segmentectomy 4 |
Left lateral section | 2 and 3 | Left lateral sectionectomy/bisegmentectomy 2,3 |
Right hemiliver + left medial section | 4 and 5–8 (± seg.1) | Right trisectionectomy/extended right hemihepatectomy/ extended right hepatectomy |
Left hemiliver + right anterior section | 2–5 and 8 (± seg.1) | Left trisectionectomy/extended left hemihepatectomy/ extended left hepatectomy |
Segments 1–8 | Any one of seg.1–8 | Segmentectomy |
2 contiguous segments | Any two of seg.1–8 | Bisegmentectomy |
Stages of liver resection
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Liver mobilisation. Triangular ligament ligated and transected, and the falciform ligament is incised until the subdiaphragmatic inferior vena cava (IVC) is reached. To mobilise the right lobe, the right triangular ligament is incised. On the left side, the left triangular ligament is transected.
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Intraoperative ultrasonography. It is very important to evaluate the resection margin from the point of view of oncological safety, particularly in the case of extensive tumour or multifocal lesions. It allows to reveal liver anatomy, locate lesions, and define tumour connections with portal pedicles and hepatic veins.
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Inflow control (hilar phase) (Fig. 4). The arterial and portal venous blood supply to the part of the liver to be removed can be controlled by extrahepatic or intrahepatic pedicle ligation. Knowledge of the anatomy of the portal vessels is crucial. The portal triad is composed of common hepatic duct, portal vein and hepatic artery. The arterial and portal venous blood supply to the part of the liver to be removed can be controlled by extrahepatic or intrahepatic pedicle ligation. Knowledge of the anatomy of the portal vessels is crucial. In children, the standard technique is to divide the hepatic artery and portal vein separately although mass transection with a stapler can be used, too. Control of the relevant biliary pedicle may accompany vascular dissection, but there is a risk of biliary injury. To avoid this, the biliary structures can be secured during parenchymal transection.
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Outflow control (venous phase). Extrahepatic isolation of the hepatic veins is possible in most cases. This technique allows for good control in case of haemorrhage during the next phase. In some situations hepatic veins can be transected during parenchymal transection. This particularly applies to the middle hepatic vein (MHV), as it is often involved in the surgical margin.
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Parenchymal transection. After inflow and outflow control, a clear line of ischemia is visible and parenchymal dissection is proceeded along this line. Methods of parenchymal transection are, inter alia: (1) finger or clampfracturing the tissue, (2) harmonic scalpel, (3) ultrasonic energy (Cavitron Ultrasonic Surgical Aspirator, CUSA), (4) radiofrequency energy (the salinelinked radiofrequency dissecting sealer), (5) water-jet dissection, (6) the application of surgical stapler. To minimize blood loss the Pringle maneuver (portal triad clamping) can be applied. It is worth remembering that intermittent clamping is better tolerated by the liver remnant than continuous occlusion [25]. When performed in intervals the portal triad is usually clamped for 10–15 min and unclamped for 3–5 min. This allows for a longer potential total occlusion time [22].
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Oozing control. After cutting the liver surface it can be secured with bipolar coagulation, LigaSure, argon beam, clips, and/or various topical hemostatic agents (Fig. 5).
Complete tumour resection—is it still the gold standard?
Laparoscopic liver resection
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Patients must be carefully selected.
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Specific training is needed and the accompanying learning curve should be taken into account (experience in both open hepatobiliary and laparoscopic surgery are crucial).
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The rules of safe oncological surgery must always be followed.
ALPPS (associating liver partition with portal vein ligation for staged hepatectomy)
Stages of ALPPS
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First operation: (1) portal vein ligation, (2) in situ splitting of the liver parenchyma (partial partition—dissection to the level of the MHV, total partition—dissection to the IVC), (3) eventual clearance of the FLR from satellite neoplastic lesions in case of multifocal tumour.
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Second operation: (1) transection of the hepatic artery and the bile duct, (2) transection of the hepatic vein, (3) appropriate part of the liver is removed.
Advantages
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Rapid hypertrophy of the future liver remnant—47–93% within 7–14 days [32].
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Increased likelihood of possible R0 resection in selected cases.
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Avoidance of postoperative liver failure.
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Reduced the interval between the 2 surgeries, and thus less chance of tumour progression.
Disadvantages
Extreme liver resections and with resection of adjacent organs/structures
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Cases of HB warranting extreme resections and vascular reconstructions, should be carried out in transplant centres of excellence in paediatric liver surgery.
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We recommend a combination of a surgeon well experienced in liver surgery and a liver transplant surgeon in the operating team for such HB cases.
Liver transplant for hepatoblastoma
Comments | |
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Indications | |
Multifocal PRETEXT IV | No active extrahepatic tumour sites (metastases or regional extension) |
Solitary PRETEXT IV | Potential downstaging to PRETEXT III after neoadjuvant chemotherapy |
If resection possible: only in very experienced hands | |
PRETEXT III with major vascular involvement (P + , V +) | Unresectable tumour after neoadjuvant chemotherapy |
Central tumours involving segments IV, V, VIII in close proximity to major vessels (main PV, PV bifurcation, hepatic veins) | Possible central hepatectomy (mesohepatectomy, middle lobectomy)† |
Tumours adjoining major vessels | If aggressive resection possible: only in very experienced hands |
Tumours invading major vessels | Resection is very risky (bleeding, tumour residual, compromise of vascular inflow/outflow) |
Contra-indications | |
Lung metastases or regional extension not completely cleared during preoperative chemotherapy and not resectable | Microscopic foci of chemoresistant tumor highly probable |
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It is important to note that hepatoblastoma patients who present with extrahepatic or metastatic active disease at diagnosis that fully clears with chemotherapy and/or surgery are still candidates for transplantation.
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Survival rates after primary transplantation are excellent: about 80–85% 5 years OS [46].
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However, it should be borne in mind that LTX has its own “dark side”: a relatively high complication rate leading to comorbidity and the need for immunosuppressive drugs and their side effects such as secondary neoplasms.
Preoperative tumour rupture
Resection of pulmonary metastases—before or after primary tumour resection?
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Children with resectable HB and synchronous lung metastases: pulmonary metastasectomy should be performed after the resection of the primary tumor, because the control of primary HB is associated with improved outcomes. After hepatectomy, pulmonary metastasectomy is usually preceeded by 1 or 2 chemotherapy courses.
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Patients with an indication for LTX: pulmonary metastases that persist after chemotherapy should be resected before transplantation.
The main hazards of hepatic resection (Table 7)
Surgical complication | Most common cause | Comments |
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Bleeding | Intra- and postoperative haemorrhage | Potentially life-threatening How to avoid this: (1) Meticulous oozing control at the end of resection if necessary with coagulant agents (2) Avoid aggresive dissection near large vessels |
Intraoperative cardiac arrest (incidence 1–2%) | Massive blood loss Air embolism | Good communication beetween surgeon and the anesthesiologist, for instance about timing of required low central venous pressure (parenchymal dissection), occurrence of bleeding, and signs of disturbed coagulation Application of PEEP (Positive End-Expiratory Pressure) during vein and IVC dissection |
Bile leakage (incidence 4–17%) | Bile duct injury at the level of the hilum Bile leakage from the cut surface | Definition: an increased bilirubin concentration (at least 3 times greater than serum bilirubin concentration) in the intra-abdominal fluid (drain) Avoid non-anatomic resections Sometimes drainage with Roux-en-Y limb of jejunum is necessary |
Post-hepatectomy liver failure | Small liver remnant Vascular flow disturbance Bile duct obstruction Viral infection Severe septic conditions | Depending on the etiology Liver transplantation may be needed |
Infection | Surgical site infection and wound dehiscence Pneumonia Hepatic or perihepatic abcess Cholangitis Peritonitis | Optimise anabolic state preoperatively Use antibiotic prophylaxis and repeat if the surgery takes > 6 h Use meticulous fascial suturing technique Optimise postoperative pain management and keep intubated period to a minimum Use respiratory physical therapy for post operative respiratory rehabilitation Be meticulous in postoperative follow up and consider draining larger abcesses with a low threshold Treat signs of cholangitis aggresively and promptly Perform urgent imaging and if indicated do not delay reoperation |
Other | Adhesive bowel obstruction Pleural effusion | No definitive measures to avoid these complications are known |
Unresectable and recurrent hepatoblastoma
Recurrences | 59/695 (8.4%) | |
Time to relapse from diagnosis | 12 months (4–115 months) Late relapse (> 3 years)—6 patients | |
Site of relapse | Local | 21 (36%) |
Metastatic | 32 (55%) | |
Combined | 5 (9%) | |
Unknown | 1 | |
Site of metastases | Lungs | 27 |
Peritoneum | 4 | |
Central nervous system | 1 | |
Treatment | Chemotherapy | 21 |
Chemotherapy + surgery | 25 | |
Surgery | 7 | |
Palliative care | 5 | |
Chemotherapy regimens | Carboplatin + etoposide | 13 |
Carboplatin + etoposide + doxorubicin | 6 | |
Irinotecan | 12 | |
High-dose cyclophosphamide | 6 | |
Resection | Local relapse | 16 (including 1 LTX) |
Lung metastasectomy | 15 | |
Peritoneal implants | 1 | |
Survival | 23 patients (39%) (18 in CR2 and 5 in CR3) are alive with no evidence of disease | |
3-year OS/EFS | 43%/34% |