Japanese classification (a) and the “French” classification (b) depending on the patency of both the gallbladder and common bile duct. Cystic BA is also included in this classification
Other surgical classifications are based on the on the patency of both the gallbladder and the common bile duct in order to perform rather a Kasai portocholecystostomy (KPC) than a Kasai portoenterostomy (KPE) (Fig. 26.1b) .
The UK group developed a clinical classification based on the outcome:
Cystic BA is that variant characterized by cystic change within otherwise obliterated ducts. The cyst communicates poorly with intrahepatic ducts, with a cloudy appearance on cholangiogram (Fig. 26.2). It should not be confused with true choledochal cysts. They usually have a better outcome than the isolated complete BA .
Cholangiogram of a cystic BA showing that the cyst (K) communicates with the intrahepatic bile ducts, although these latest have a cloudy appearance. This is rather the feature of BA than choledochal malformation
Biliary atresia splenic malformation (BASM) is a peculiar constellation of anomalies and occurs in ~10 % of Caucasian series; Table 26.1 illustrates the associated anomalies. There is a marked detrimental effect of age at Kasai in this subtype than the isolated type of BA .
Recognized anomalies in the biliary atresia splenic malformation syndrome
Preduodenal portal vein
Immotile cilia syndrome
CMV IgM positive associated biliary atresia is a recent entity with a poorer outcome than isolated BA .
Prenatal detection of BA is a rare situation, found on 20 patients over 15 years in our center (with about 20 pts/year referred for BA). Prenatal signs on ultrasound performed at the second trimester of gestation include:
Absence of the gallbladder: 35 % (although most of the prenatal absence of the gallbladder is benign and not related to BA)
Cyst located on the liver hilum: 50 % (differentials include choledochal cyst or duplication)
Elements of the splenic malformation syndrome: 15 % (situs inversus, polysplenia, etc.)
Great care should be deserved for the prenatal counseling regarding the likelihood of BA, although a complete and early postnatal assessment should be performed before the second week of life.
Infants with BA present with a conjugated jaundice, dark urine, and pale stools. These signs are usually present from birth. Initially the infants feed normally though their weight gain is subnormal due to their inability to digest fat and soluble vitamins. The liver is usually enlarged and firm in older infants (e.g., more than 10 weeks), and there may be ascites and or splenomegaly indicating the onset of portal hypertension along with cirrhosis.
The diagnosis of BA is an operative diagnosis, but is accurate when performed preoperatively in more than 90 % of cases. In our institution, this is achieved by exclusion of various medical causes of conjugated jaundice (Fig. 26.3). Ultrasonography is equivocal of BA if it excludes intrahepatic bile duct dilatation (found in choledochal malformation) and the absence, irregular, or very small gallbladder after a 4 hours long fasting, and the specific triangular cord sign (which corresponds to the fibrotic remnant at the hilum) is found in about 80 % of cases  (Fig. 26.4). In our center, ERCP is indicated if there is any doubt regarding the color of stools or the presence of a gallbladder without the triangular cord sign on US. ERCP showing stained bile at the papilla or intrahepatic bile ducts excludes BA .
Algorithm to achieve an accurate diagnosis of BA in our center. Abbreviations: PH portal hypertension, LFT liver function tests, CMV Cytomegalovirus, CF cystic fibrosis, ERCP endoscopic retrograde cholangiopancreatography
Sagittal view of a hepatic ultrasonography, the triangular cord sign (white arrow) is located above the portal vein; this sign corresponds to the biliary fibrous remnant
18.104.22.168 Surgery: The Kasai Operation
The first step is to formerly establish the operative diagnosis of BA, by either the mean of a limited incision or by laparoscopy. The gallbladder patency is checked to see whether it is atretic or normal. If normal the cholangiogram is performed and the steps are detailed in Fig. 26.5. Once the diagnosis of BA is confirmed (no opacification of the intrahepatic bile ducts), the scar is enlarged, the liver is exteriorized through the wound avoiding transection of the triangular ligaments, and the dissection is performed but only above the level of the portal and arterial bifurcation in order not to compromise both the arterial vascularization of the liver and a further transplantation. The remnant is excised leaving the liver capsule intact (Fig. 26.5). The third step is the reconstruction: mainly by a Roux-en-Y loop (Kasai portoenterostomy) performed at the level of the second jejunal limb, in an antegrade fashion, and should be long enough (45 cm), both to prevent ascending cholangitis especially when the child is transplanted, as the extremity is chopped out (Fig. 26.5). Elements of the splenic malformation syndrome are checked for, and a Meckel’s diverticulum should be resected during the surgery, anti-adhesive barriers could be used to facilitate a hypothetic liver transplantation. In case of a patent gallbladder and main bile duct, we would rather perform the less common Kasai portocholecystostomy (Fig. 26.5).
Operative algorithm for biliary atresia. GB gallbladder, KPE Kasai portoenterostomy, KPC Kasai portocholecystostomy, BA biliary atresia, HBD intrahepatic bile ducts, HA hepatic artery, PV portal vein
Referring the patient to a primary transplantation should probably only be considered when clinical imaging and biologic features of cirrhosis and portal hypertension are present (e.g., obvious ascites, widening of the small omentum, high figures of elastometry, parenchymal heterogeneity) especially when associated with signs of liver failure (raised INR and low albumin).
The role of the laparoscopy for BA is still controversial. Although laparoscopy for the diagnosis steps is not challenged, many high-volume centers, including those which have tried this technique, do not advocate using laparoscopy for the Kasai since the results have been proven to be worse compared to the open approach [40, 41]. However worldwide, in Japan and Brazil, some centers still use it with fair results, not comparative, though, and difficult to recommend for this rare disease, with a likely long learning curve .
22.214.171.124 Postoperative Complications
Ascending Bacterial Cholangitis
Cholangitis occurs most commonly in the days following primary surgery but can be delayed. It is recorded in about 40–50 % of cases in most series and almost always occurs in children with at least some degree of bile flow, not those with early failure. Clinically, it is characterized by worsening jaundice, fever, and acholic stools. The diagnosis may be confirmed by blood culture, but it is important to treat suspected cases early with broad-spectrum antibiotics effective against gram-negative organisms.
Bowel obstruction: It is difficult to diagnose as these infants do not have stained vomiting postoperatively. Pain, uncomfort, clear or bilious vomits, as well as high temperature (obstruction after the Roux-en-Y limb) should raise the diagnosis. Adherence-related bowel obstruction has become rare since the use of anti-adhesive barriers in our center; however, postoperative ileo-ileal intussusception is a rare cause of mechanic bowel obstruction and compromises both the bile flow and the Roux-en-Y sutures. Peritonitis by anastomotic leak at the bottom limb of the Roux-en-Y is very rare, but the diagnosis and the adequate treatment are delayed as it is confused with an ascending cholangitis.
Inguinal hernia, usually occurring in about 10 % of these infants, should be checked before discharge and repaired especially if the child has a successful Kasai .
Biliary leakage does not occur after Kasai portoenterostomy, but in Kasai portocholecystomy. This technique is given up by most of the teams, even though the risk of leakage should be balanced with the risk of cholangitis.
126.96.36.199 Results of the Kasai Operation
The earliest measurable outcome is clearance of jaundice to normal bilirubin values within 6 months in large; typically multicenter series have varied from 27 to 57 %, translation into a 5- (or 4)-year native liver survival of 37–52 % for the most recent cohorts [30, 44–46]. Uncorrected biliary occlusion causes progressive intrahepatic disease, and the longer this is allowed to persist, the more irreversible it becomes, explaining why age at surgery (especially before 6–8 weeks of age), although without obvious cutoff, has become the main prognosis factor. Series from France, the USA, and the UK suggest that about 30–45 % of the children may survive to reach 10 years of age with their native liver intact [33, 45, 46].
188.8.131.52 Indication for Liver Transplantation
Biliary atresia is still the commonest indication for liver transplantation during childhood and is indicated in case of:
Failure of Kasai (persistence or recurrence of jaundice) with any of the following:
Failure to thrive, liver failure which can be precipitated by infection, portal hypertension with uncontrolled esophageal varices, portopulmonary syndrome, onset of pulmonary hypertension, and recurrent cholangitis
In patients who have a sustainable successful Kasai, portal hypertension may benefit from either surgical or transjugular intrahepatic portosystemic shunts. Recurrent ascending cholangitis can be treated by the revision of Roux-en-Y which may be too short or having a mechanic chronic obstruction (role of a HIDA scan) .
26.3.3 Hepatic Trauma
The spleen and the liver are the most frequent solid organs involved in traumatology. Their damage is present in 5 % of pediatric blunt abdominal trauma with 52 % hepatic injury and 43 % splenic injury, and in 5 % both organs are injured . The most frequent mechanism is motorized vehicle accident, the child being either a pedestrian hit by car or a car passenger. Penetrating trauma is rare. Apparent benign blunt abdominal trauma occurring in a backyard or during sport activities can also lead to liver injury.
As for all patients presenting with abdominal trauma, ABC should be performed at the arrival in the trauma room . Two intravenous accesses is the rule. At the end of this first assessment, you should be able to know what exam to perform, either a FAST evaluation or a total body CT scan. Based on 136 papers accepted among 900 on pediatric abdominal trauma, Sang-Woo Pak speculated in 2013 that if the clinical exam shows abdominal wall or lower chest bruising, abdominal pain or tenderness, and/or low blood pressure without shock, a FAST scan and a blood work should be performed searching for liver enzyme increase. In case of anomalies, a CT scan can be discussed. If not, the patient can be admitted to the ward for monitoring .
The liver has a tremendous capacity of healing, and the success rate has been reported to be between 82 and 100 % . The treatment is mainly guided by the patient’s hemodynamic status more than by the liver injury scale . The initial management should follow the Advanced Trauma Life Support (ATLS) principles of aggressive fluid resuscitation, guided by monitoring of central venous pressure and urinary output . Actually, the only indication of surgery is the need for blood transfusion above 40 ml/kg (half body mass index). Nonoperative management involves admission to a unit and the monitoring of vital signs, with strict bed rest, frequent monitoring of hemoglobin concentration, and repeated abdominal examinations . In case of failure, angio-embolization can be an interesting option. A perfect collaboration between the anesthesiologist, the interventional radiologist, and the surgeon is therefore crucial. Angio-embolization can be necessary either in a high-grade liver injury (grade IV and V) associated to unstable hemodynamic or after a first surgical procedure such as a packing when the patient remains unstable . Success has been reported to be between 68 and 87 % . Complications can be related to the nonoperative management (liver hematoma, false aneurysm, biloma, or biliary ascites) or to angio-embolization (hepatic necrosis, liver abscess). Incidence increases accordingly with the grade of injury. In a series of 337 patients with liver injury grades III–V treated nonoperatively, those with grade III had a complication rate of 1 %, grade IV 21 %, and grade V 63 % . Patients with grades IV and V injuries are more likely to require surgery and to develop complications of nonoperative treatment.
If the patient requires surgery because of instability, laparoscopic approach has no place. Through a midline incision, after a complete exploration of the abdominal cavity, the surgeon should be able to see the liver fracture and starts by packing with surgical dress. Indeed, severe coagulopathy, acidosis, and hypothermia can occur in case of important hemorrhage and make the resuscitation challenging to save the patient. Initial control of hemorrhage and contamination followed by packing and temporary abdominal closure, ICU restoration of normal physiology, and delayed definitive repair is also well known as “the damage control” technic. The group at the University of Pennsylvania has popularized this technic in 1993 . If the patient remains unstable, an attempt to see where the bleeding comes from should be done carefully, especially in case of hepatic vein rupture. Indeed, if the surgeon tries to bring down the liver with his hand, the risk of aggravating the hepatic vein lesion is major. The next step would be the Pringle maneuver, which consists in clamping the whole hepatic pedicle. This maneuver is controversial, but it can be maintained up to 1 h without compromising the blood supply to the liver. Despite this, if the patient continues to be unstable, the next step is to clamp the inferior vena cava. After this, surgeon should consider performing a hepatic resection in case of continuous bleeding or repair a hepatic vein or vena cava injury.
The treatment of a bile leakage is most of the time a conservative treatment. A simple drainage of the ascites or a cholecystostomy can be done if the leak is heavy with a considerable amount of ascites. Stenting the bile duct through radiologist intervention is another interesting and valid option .
184.108.40.206 Posttrauma Care
For isolated liver injury, a guideline with the number of hospitalization days has been published depending on the grade of the injury from 2 to 5 days for grade I to grade IV . An even shorter hospital stay has been also reported with a discharge at day 1 or 2 after the trauma [61, 63]. Considering the risk of secondary bleeding, it could be safer to keep the patient to the hospital longer especially in case of high-grade liver injury.
Hepatoblastoma (HBL) is the most common malignant hepatic tumor in children typically seen in the first 3 years of life. Incidence is about 1.2–1.5 cases per million . Those that occur after 5 years of age, formerly called transitional hepatocellular carcinoma (HCC), tend to have a worse prognosis, probably because their behavior is similar to a HCC . Most HBLs do not have an abnormal genetic background, but predisposing factors include trisomy 18, Beckwith-Wiedemann syndrome, familial adenomatous polyposis, and prematurity .
220.127.116.11 Clinical Presentation
The most common presentation is an isolated abdominal mass. As some HBL found to have an HCG excretion, mild signs of virilization should be looked for. They rarely present signs of rupture, i.e., acute abdominal pain with guarding or contracture.
α-fetoprotein (α-FP) is the key marker in HBL and its level has a prognostic value. An abnormal level of α-FP (below 100 IU/l or higher than 1 million IU/l) predicts a poor outcome whether it correlates with tumor pathology or not. α-FP is excreted by the fetal liver and is increased at birth but should decrease to a normal level (i.e., 5 IU/l or ng/ml) after 1 year of age. In infants with a malignant liver tumor and a normal AFP, the diagnosis of a rhabdoid tumor of the liver should be evoked. α-FP may be increased in various other malignant or benign conditions (Table 26.2).
Elevation of α-fetoprotein (α-FP)
Newborn until 1 year
Congenital persistence of AFP
Mixed fibrolamellar carcinoma
Yolk sac tumors
Acinar cell carcinoma of the pancreas
Human chorionic gonadotropin (HCG) hormone is a marker, which might be raised in some HBL, although its prognosis value has not yet been determined.
Liver ultrasound with Doppler is used to assess the intrahepatic extent of the tumor and patency of the portal and hepatic veins.
Thoracoabdominal CT scan (with arterial and mixed portal and venous phases) is used to assess the input and output blood vessels of the liver and is sent for review in national referral centers in the SIOPEL or COG studies to set up the pretreatment extent (PRETEXT) of disease . The PRETEXT is used for locoregional involvement only. The PRETEXT relies on the Brisbane classification with sections (right posterior, right anterior, left anterior, and left lobe) outlined by the right, median hepatic veins and the umbilical fossa (Fig. 26.6). The PRETEXT formula is for numbers of adjacent tumor-free sections. Pulmonary lesions documented on the chest CT scan are considered as unequivocally metastatic if there is one nodule > 10 mm or several nodules with at least one > 5 mm. In the other cases, the metastases will be considered as doubtful, and a surgical biopsy of one of the nodules should be discussed. Patient with a PRETEXT equal or superior to III or/and with either P2 or V3 should be, before chemotherapy, referred for a possible liver transplant, which may happen promptly according to the extent of disease, after neoadjuvant chemotherapy.
The PRETEXT classification in the liver
Pretreatment biopsies are strongly recommended in European protocols and may exclude other differential diagnoses such as liver metastases of a yolk sac tumor, benign liver tumors, and HCC in older children. Biopsies are carried out with a minimum of 5 and preferably 10 cores and should also include a biopsy of the adjacent non-tumoral liver whenever possible.
Different pathologic subtypes consist of epithelial, fetal, or mixed fetal and epithelial hepatoblastoma. Small cell undifferentiated carcinoma (SCUD) is a special subtype with a worse prognosis . Transitional hepatoblastoma/carcinoma is defined by the age rather than by the pathology . Children are then classified into three risk groups according to outcomes identified in previous SIOPEL studies. This is based on clinical data, tumor biology, imaging, and pathology (Table 26.3).
Risk stratification in current SIOPEL studies
Expected CR, EFS, OS
M0 P and V in involved sectors, E0, N0
100 < AFP
3y CR = 99 %
3y EFS = 83 %
3y OS = 95 %
None of criteria of standard and very high risk groups
M0 or P2 or V3 or E+
SIOPEL 3 HR
3y CR = 89 %
3y EFS = 75 %
3y OS = 86 %
Very high risk
AFP < 100 IU/L (apart from very small tumors)
SIOPEL 4 HR
3y CR = 70 %
3y EFS = 77 %
3y OS = 79 %
18.104.22.168 Chemotherapy: The European Experience
The chemotherapy of hepatoblastoma is based on platin family and anthracyclines. Neoadjuvant chemotherapy has been administered to all patients in SIOPEL protocols as compared to the North American protocol, although this may change in the future. The type and frequency of drug administration are reported in Fig. 26.7, as well as the timing of surgery.
Current SIOPEL protocols: SIOPEL 6 protocol for standard risk: CDDP, cisplatin; STS, sodium thiosulfate (ear protection). SuperPlado protocol in SIOPEL 3: C = cisplatin, D = doxorubicin, CA = carboplatin, 1 arrow = 2 weeks. High-risk protocol in SIOPEL 4: C = cisplatin, D = doxorubicin, CA = carboplatin
Careful preoperative assessment is mandatory before surgery. Patients should be referred to a radiologist and a surgeon with expertise in liver resection and imaging. Early referral after diagnosis improves surgery planning. After the chemotherapy, preoperative assessment includes CT scan and post-neoadjuvant chemotherapy (POSTEXT) evaluation coupled with operative or preoperative Doppler ultrasound to carefully identify the limits of the tumor with the main hepatic vessels. α-FP decrease should be monitored and documented. Echocardiography is mandatory in order to assess both anthracycline-related toxicity and the tolerance to a potential hepatic vascular exclusion. For these large tumors with a poor prognosis in case of local relapse, both minimally invasive surgery and wedged surgical excision are not recommended. Transverse or subcostal laparotomy is performed. The abdominal cavity is inspected. The hepatic pedicle is encircled by a tape in prevision of a Pringle maneuver, triangular ligaments are sectioned, and total vascular exclusion of the liver is prepared. Anatomic resection of the liver is performed via vascular ligature of the inflow to the involved part of the liver. Transection is done with the help of either thermic or ultrasound sealing devices. The aim is complete microscopic resection of the tumor with minimum blood loss and avoiding air embolism via the main hepatic veins. This is why, in our experience, we perform a brief total vascular exclusion of the liver (i.e., less than 30 min) when the tumor borders are in the vicinity of the hepatic veins. Morbidity of this procedure is low given that the remaining liver parenchyma is healthy.