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Benign Liver and Biliary Tract Masses in Infants and Toddlers By Rebecka L. Meyers and Eric R. Scaife
,t LTHOUGH a biliary tract mass presenting in an ft infant is likely to be a choledochal cyst, there is a remarkable diversity of conditions encompassed by benign liver masses. Multiple surveys of primary liver tumors throughout childhood suggest that about three quarters of them are malignant (hepatoblastoma, hepatocellular carcinoma, sarcoma). Because hemangioendothelioma is the most common liver tumor in infants, a comparable distribution restricted to neonates and young infants shows an increased proportion of benign tumors at about 70%.1 Imaging techniques such as ultrasonography, computed tomography (CT), and angiography are not always reliable in differentiating benign from malignant tumors in these infants, and difficulty frequently is encountered differentiating hemangioendothelioma from hepatoblastoma, mesenchymal hamartoma, focal nodular hyperplasia, and even neuroblastoma IV-S.l The most common benign hepatic tumors of childhood are hemangioendothelioma, mesenchymal hamartoma, focal nodular hyperplasia, and adenoma. Hepatic adenoma is almost exclusively a disease of older children and therefore will not be discussed in this review. The extremely rare
From the Department of Surgery, University of Utah School of Medicine, Primary Children s Medical Center, Salt Lake City, UT.
Address reprint requests to Rebecka L. Meyers, MD, JOO N Medical Drive, Suite 2600, Salt Lake City, UT 84113.
primary hepatic teratoma is discussed briefly. Included in the differential diagnosis of these benign hepatic tumors are nonneoplastic cystic hepatic masses including biliary and simple hepatic cysts, hematoma, parasitic cysts, and pyogenic and amebic liver abscess.
BENIGN LIVER MASSES
Hemangioendothelioma
Hemangioendothelioma is the most common benign tumor of the liver in infancy. The mean age at presentation is 47 days (range 1 to 365 days),2 and more than 80% of these tumors are diagnosed within the first 3 months.3
Symptoms at presentation may include abdominal distension with hepatomegaly, congestive heart failure, vomiting, anemia, thrombocytopenia and consumptive coagulopathy, jaundice secondary to biliary obstruction, and associated cutaneous or visceral hemangiomas.2-5 Many of these lesions are discovered incidentally and are localized and small enough to be of no clinical significance. Alternatively, a large rapidly growing infantile hepatic hemangioendothelioma can produce life-threatening complications in the form of intractable high-output cardiac failure from significant arteriovenous shunting, Kasabach-Merritt syndrome, intraperitoneal hemorrhage, and respiratory distress as a result of pulmonary congestion and massive hepatomegaly (Table 1).3 The KasabachMerritt eponym refers to a localized intravascular coagulopathy associated with profound platelet trapping within the tumor and is to be differentiated from the more global form of disseminated intravascular coagulopathy that may develop in severe cases.
The diagnosis usually is straightforward and based on the combination of clinical symptoms and radiographic appearance on ultrasound scan and CT. Because of the severity of hemodynamic alteration in some infants and the protean nature of the symptoms in others, the diagnosis may be delayed. In one series, 5 of the 12 infants were misdiagnosed, in 3 the diagnosis was made on postmortem examination after cardiorespiratory arrest, in 1 the initial diagnosis was neuroblastoma, and in another a combination of pyloric stenosis and bronchiolitis was diagnosed.2 Once a dynamic CT scan has been obtained, however, the distinctive radiographic appearance of hepatic hemangioendothelioma usually is diagnostic. The unenhanced CT scan shows an area of diminished density and after bolus injection of intravenous contrast, there is contrast enhancement from the periphery toward the center of the lesion, and, after a short delay, there essentially is complete isodense filling of the lesion and
Seminars in Pediatric Surgery, Vol 9, No 3 (August), 2000: pp 146-155
BENIGN LIVER AND BILIARY TRACT MASSES
Table 1. Presenting Symptoms of Infantile Hepatic
Hemangioendothelioma
Samuel Davenport Daller et al Cohen et al and Spitz et al
liver.6 The various types of radionuclide scans have not been shown to be particularly helpful. Angiography will be necessary in infants with refractory symptoms in whom either hepatic artery ligation or embolization is considered.
If a definitive diagnosis is made radiographically, the initial management can be noninvasive because spontaneous regression occurs in many cases. Historically, the initial medical intervention for infantile hemangioendothelioma has been corticosteroids, often in combination with radiation? However, the effectiveness of steroids has not been established conclusively, and there is a growing consensus that radiation therapy is not indicated because of a relative lack of efficacy and the possible long-term damage to adjacent normal liver tissue.8 Notwithstanding, many steroid treatment regimens have been advocated, with most regimens recommending prednisone 2 to 5 mg/kg per day for 2 to 4 weeks followed by a 3- to 5-week taper.2.3.9,10 A steroid-sensitive hemangioendothelioma should begin to respond within a week. In general, after treatment with high-dose steroids, about 30% of tumors respond with accelerated regression, 40% respond equivocally, perhaps showing some stabilization of the congestive heart failure and coagulopathy, but more than 30% may not respond at all.3,5,11 High-dose steroids are not without complications; serious hypertension has been reported in at least half, and prolonged steroid administration may have deleterious effects on the infant's growth and development. 12
Many other medical treatment options exist, although no single treatment has been shown to be universally helpful. Congestive heart failure is treated with digitalis and diuretics. Anemia and coagulopathy are treated with corrective blood product replacement therapy. However, consensus ends here, and both success and complete failure have been reported variously with many other treatments including epsilon-aminocaproic acid, 13 tranexamic acid,14 low-molecular-weight heparin,15 interferon-
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a2A (IF-a2A), vincristine,16 and cyclophosphamide.17,18 The relatively weak angiogenesis inhibitor, IF-a2A, has been used most successfully in reports of diffuse cutaneous and visceral hemangiomas, and although there have been isolated case reports of its successful use in hepatic hemangioendothelioma, it is perhaps too early to draw conclusions on its efficacy.9.15 A more potent investigational angiogenesis inhibitor, AGM-1470, has been shown to prolong survival in a mouse model of induced hemangioendothelioma. 19 There are case reports of the successful use of chemotherapeutic agents such as vincristine18
and cyclophosphamide. 17 However, application of these agents has not been universally successful. Ultimately, we simply need a better understanding of the pathogenesis of these lesions if we are going to understand why the therapeutic response in any given child generally has been so unpredictable.
Dehner and Ishak20 described 2 basic histological subtypes of hepatic hemangioendothelioma. The classification depends on the degree of endothelial cell proliferation and the size of the vascular channels. When actively dividing, vasoformative cells are plentiful and are not quite organized into channels, these lesions are called type II hemangioendotheliomas and have been disseminated occasionally. Type I lesions are more bland, often calcified, and show few mitoses. Unfortunately, the histological subtype does not seem to predict the biological behavior. Most cases of both types regress spontaneously or respond to corticosteroid therapy. Some have suggested that the younger the age at presentation, the more likely the tumor is to be associated with hemodynamic symptoms.5
In infants who exhibit progressive respiratory instability secondary to upward pressure on the diaphragm from the enlarged liver, or who exhibit congestive heart failure and consumptive coagulopathy refractory to medical measures, invasive measures are indicated. Readily resectable solitary tumors probably are best treated by complete excision; however, in a majority of cases the huge size and diffuse nature of these tumors makes excision difficult if not impossible. Although potentially hazardous, hepatic arterial ligation or embolization can be life saving because they reduce dramatically the arteriovenous shunting. 21,22 Where technically feasible, hepatic arterial embolization may be favored as a minimally invasive alternative. An arteriogram must be obtained to evaluate the tumor's vascular supply because children with multiple large afferent feeding tumor vessels or no single vessel available for embolization are not good candidates for this technique.23,24 Additionally, large intrahepatic arteriovenous shunts must be excluded to avoid passage of embolized particles into the venous circulation.25 In cases of favorable vascular anatomy, the loss of arterial flow to the liver may be well tolerated if
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hepatic perfusion and oxygenation are maintained by adequate portal venous flow. On the contrary, if there is not sufficient collateral flow to maintain the health of the biliary tract, biliary necrosis, strictures, and secondary septic cholangitis may occur.s Despite potential complications and pitfalls, however, more than 80% of cases have had a successful outcome when ligation or embolization is reserved for young infants with large arteriovenous shunts.
Finally, there have been several reports of orthotopic liver transplantation for cases in which (1) the lesion is extensive and not amenable to surgical resection, (2) the child has not responded to medical management, and (3) the child either has failed or has unsuitable anatomy for embolization (Fig 1).4.10,26 In addition, some groups have even argued that resection, where feasible, is preferable to hepatic arterial embolization or ligation. A retrospective series from Pittsburgh has shown that patients who undergo resectional surgery, with or without orthotopic liver transplantation, had a lower 5-month mortality rate and a greater 2-year survival rate than did those who underwent hepatic arterial ligation or embolization.4
Early morbidity and mortality tended to be a consequence of the primary lesion, whereas late morbidity and mortality were reflective of the treatment modality used.
Perhaps most sobering, our group and others have seen perfectly unremarkable lesions that have undergone malignant transformation to angiosarcoma.27-29 The hepatic angiosarcoma usually, but not exclusively, presents as an apparent malignant transformation 2 to 3 years after the diagnosis of benign infantile hemangioendothelioma. Even after apparent change in the biological behavior of the tumor, a biopsy may continue to show "benign" hemangioendothelioma as a seeming contradiction to the previously quiescent and now clinically aggressive and enlarging tumor.28 There are no clear radiographic features that can differentiate benign from malignant histology. Neither chemotherapy nor radiotherapy has achieved effective tumor control in this small subset of children, and definitive surgical resection early, before the tumor becomes unresectable, has been the only modality with long-term survival. Most children who have undergone hepatic transplantation after malignant transformation have died of recurrent metastatic disease.4,26,28
Mesenchymal Hamartoma
Mesenchymal hamartoma of the liver is a benign developmental malformation of the liver rather than a true neoplasm. Historically, mesenchymal hamartoma has been described in the literature by various names including pseudocystic mesenchymal tumor, hepatic and giant cell lymphangioma, cystic hamartoma, bile cell fibroadenoma, hamartoma, and cavernous lymphangiomatoid tumor. 30 Edmondson recognized these to be similar
MEYERS AND SCAIFE
Fig 1. (A) Massive infantile hepatic hemangioendothelioma completely fills the abdomen on CT scan. (8) Same infant at 5 months of age with massive abdominal distension and persistent heart and respiratory failure despite maximal medical management. She is being prepared for tumor excision and liver transplantation. (C) Some tumor areas showed histology consistent with type I, whereas others were more consistent with type II.
lesions and described them as mesenchymal hamartoma in 1956.30 This tumor typically presents before 2 years of age with abdominal swelling as the initial symptom. Before the widespread and liberal use of sophisticated diagnostic imaging, most of these tumors became very large, eventually presenting with a mass effect such as vena caval compression, feeding difficulties, and respiratory distress secondary to upward pressure on the dia-
BENIGN LIVER AND BILIARY TRACT MASSES
phragms. With the more widespread use of ultrasound and CT, many tumors now are detected early as a palpable mass in an otherwise asymptomatic child. The child typically has a palpable right upper quadrant mass that usually is nontender with smooth borders and, occasionally, abdominal wall vein engorgement. The alpha-fetoprotein (AFP) may be variably elevated in this tumor confounding the differentiation from hepatoblastoma.
Mesenchymal hamartoma is more common in the right lobe of the liver. On ultrasonography one sees multiple echogenic cysts with thin echo genic septae and no debris within the cysts; although, if the cysts are small, the entire tumor may appear as an echogenic mass. Hepatic scintigraphy shows a mass lesion with poor tracer uptake. The typical CT scan features are that of a well-circumscribed, multilocular mass that contains low-density cysts separated by solid septae and stroma (Fig 2). The stroma and septae may be vascular and occasionally show contrast enhancement on CT scan similar to that seen in hemangioendothelioma. Histologically, mesenchymal hamartoma contains cystic areas with bile ducts, hepatocytes, mesenchyme, and multiple portal vein branches. Particularly when the cysts are small and mesenchymal hamartoma appears solid rather than the usual septated cystic appearance, biopsy may be required to eliminate the diagnosis of malignant neoplasm.? The tumor tends to increase in size during the first several months of life and subsequently may either stabilize, continue to grow or undergo spontaneous regression.30-32
Traditionally, the surgical treatment has been complete tumor excision, either nonanatomically with a rim of normal tissue or as an anatomic hepatic lobectomy. If the tumor is considered umesectable, the surgical options include enucleation and marsupialization. Management continues to evolve, however, and because of many reports of spontaneous regression, there is a growing debate in the literature regarding the feasibility of nonoperative management in the asymptomatic patient.32 If the lesion is not going to be excised, many have stressed the importance of a biopsy to definitively exclude malignancy, especially in cases of elevated AFP. Moreover, a careful review of the literature does not give unequivocal support to nonoperative management. Of special concern are several reports documenting massive local recurrence after subtotal excision. 1O•31 In 1 case, after a partial left lobectomy as an infant, a child presented at 4 years of age with an umesectable recurrent mass. In another, an attempt at marsupialization was complicated by the formation of a cystocutaneous fistula, which drained up to 4 to 5 L of ascites per day. The patient ultimately required liver transplantation. In a literature review of 133 reported cases of mesenchymal hamartoma, 17 were treated by biopsy or marsupialization, and the remainder
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Fig 2. (A) CT appearance of a mesenchymal hamartoma of the right lobe ofthe liver showing a well-circumscribed multilocular mass that contains multiple low density cysts. (B) Gross appearance of mesenchymal hamartoma after right hepatic lobectomy. (C) Histology shows cystic areas, biliary epithelium, hepatocytes, and mesenchymal elements.
were treated by complete eXCISiOn. There were no recurrences in patients who underwent total resection of the tumor. Of the 17 cases managed conservatively that were treated with biopsy or partial removal, there were 6 recurrences, 5 event-free survivals, and 6 patients in whom long-term follow-up was not reported.3! Therefore, although there is a growing body of evidence that the asymptomatic lesion may spontaneously regress, careful follow-up of any nomesected tumor is mandatory.
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Focal Nodular Hyperplasia
Focal nodular hyperplasia may be diagnosed at any age, from newborns to the elderly. In children, it usually is diagnosed between 2 and 5 years of age.33 It is a benign epithelial tumor that has been referred to by various names in the literature including benign hepatoma, solitary hyperplastic nodule, focal cirrhosis, cholangiohepatoma, and even mixed adenoma. Focal nodular hyperplasia is a well-circumscribed, lobulated lesion whose typical architecture on gross examination consists of bile ducts and a central stellate scar containing blood vessels that supply the hyperplastic process. Usually, there is no real capsule, but often the fibrous tissue surrounds the liver in lesions varying in size from a few millimeters to more than 20 cm in diameter and may be single or multiple. Microscopically, the proliferating cells are practically identical to the surrounding hepatocytes (Fig 3).
Like other benign liver tumors, small lesions may be asymptomatic incidental findings. Larger lesions eventually will present with mass symptoms, usually abdominal pain. The diagnosis of focal nodular hyperplasia is suggested by the ultrasonographic appearance of a well-
Fig 3. (A) Gross appearance of focal nodular hyperplasia with prominent central stellate scar. (B) Microscopically the proliferating cells of focal nodular hyperplasia are nearly identical to surrounding hepatocytes.
MEYERS AND SCAIFE
1 • .; ()
Fig 4. (A) CT appearance of focal nodular hyperplasia without intravenous contrast enhancement. (B) CT appearance of focal nodular hyperplasia with intravenous contrast enhancement. (C) •• mTC sulfur colloid scan showing good uptake of tracer by the tumor.
demarcated, hyperechoic and homogeneous lesion; the tumor may be much more evident on CT after intravenous contrast enhancement; and usually has normal accumulation of 99mTc sulfur colloid on liver scintigraphy (Fig 4). Although approximately 50% of tumors will have normal accumulation of 99mTc sulfur colloid, this finding is not universally specific and there have been case reports of scintigraphic findings suggestive of focal nodular hyperplasia in children who turned out to have hepatoblastoma.34 Another series of patients operated on for a preoperative diagnosis of benign liver tumor showed 3 patients with hepatocellular carcinoma diagnosed at the time of surgery.35 These data suggest that
BENIGN LIVER AND BILIARY TRACT MASSES
despite distinctive findings on radiographic imaging, liver biopsy or resection often is necessary to establish the diagnosis. To date, there have been no cases of malignant transformation of histologically proven focal nodular hyperplasia; however, there have been rare reports of focal nodular hyperplasia coexisting in patients whose dominant histology is hepatocellular carcinoma.36
Complete surgical resection of biopsy-proven focal nodular hyperplasia is not mandatory in asymptomatic patients. Because spontaneous regression has not been reported, symptomatic patients will require either surgical excision or ablative therapy with ligation or embolization of the feeding hepatic arterial supply.37 Reymund et aP3 summarized the long-term follow-up results of 31 pediatric cases reported in the literature. Complete tumor resection was performed in 18 cases (58%); of these, 3 died of postoperative complications, and 15 were symptom free at long-term followup. The deaths all occurred in children operated on in the 1960s and 1970s. A surgical biopsy was performed in 9 patients (29%); 1 died in the postoperative period, and 8 were symptom free. The last 4 children (13%) all did well with various approaches using hepatic arterial ligation or embolization, initial biopsy followed by embolization several months later, embolization followed by tumor resection, and another with hepatic arterial ligation followed by biopsy many years later.33 In a case report not included in the above review, open biopsy was followed by ethanol embolization. Reduction in tumor volume was not rapid, and the appearance of intralesional gas 1 month postembolization almost led to an incorrect diagnosis of abscess. However, with simple expectant management the tumor reduced to a small calcified nodule over the next 18 months.38
Unfortunately, long-term follow-up data are based on small numbers of patients, and to definitively understand the natural history and outcome, long-term prospective multigroup studies are recommended.33
Hepatic Teratoma
True hepatic teratoma is extremely rare. Twenty-four cases have been reported in the literature, 18 of whom were in children less than 3 years 0Id.39.40 About half of these tumors have been malignant, about half benign. The characteristic histological finding is the predominance of hepatic tissue in the resected specimen.39
Nonneoplastic Cystic Hepatic Masses
Simple hepatic cyst. Simple hepatic cysts are uncommon in children and may be congenital or acquired in origin. Unlike polycystic liver disease, which is seen in association with polycystic kidney disease, solitary hepatic cysts may occur at any age with most cases occurring in the 5th or 6th decade of life, but several having been reported in children and even in newborn
151
infants.41 Congenital solitary cysts are thought to arise from obstruction of aberrant bile ducts leading to stasis and retention and generally have a broad base along the inferior surface of the liver, most commonly in the right lobe. Because the liver tissue will almost never completely encircle the cyst, preoperative radiographic determination of hepatic origin can be difficult, although it may be suggested by a flattening of the inferior surface of the liver along the edge of the cyst. 42 Small asymptomatic cysts should be left alone. Large symptomatic hepatic cysts may require drainage, injection with sclerosing agents, marsupialization, or excision.43.44
Acquired or posttraumatic cysts may result from blunt trauma or birth trauma causing an intrahepatic hematoma. The hematoma eventually is resorbed leaving behind a cystic cavity. The cyst lining is of granulation tissue and fibrosis and rarely may communicate with the biliary tree. In newborns there may be no known history of trauma, as was the case of the child shown in Fig 5. Hepatomegaly in this child led to ultrasound screening of the liver, which showed a calcified semisolid cystic mass. The mass was managed expectantly and ultimately required biopsy to rule out malignancy. Biopsy results showed simple organizing hematoma.
Parasitic hepatic cyst. Parasitic cysts generally refer to echinococcosis or hydatid disease. These cysts are uncommon in newborns. The endemic areas of hydatid disease are in Greece, Eastern Europe, South America, Australia, and South Africa.43 Hydatid disease is rare in the United States and especially rare in children. Plain radiography shows egg shell calcifications, and ultrasound and CT scan can further define the anatomy and identify any daughter cysts. There is a risk of rupture with resultant anaphylaxis, thus surgical resection is advo-
Fig 5. Calcified hepatic hematoma in an infant with hepatomegaly.
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cated.45 Surgery is by controlled aspiration and flushing of the cavity with hypertonic saline followed by removal of the laminated membrane from the adventitial outer wall. If the wall itself is removed completely, there is a risk of bleeding and bile leak.
Pyogenic liver abscess. In young infants, pyogenic liver abscess is most commonly a complication of peritoneal infection in premature infants with necrotizing enterocolitis, omphalitis, or an infected umbilical venous catheter (pyelephlebitis). Multiple organisms have been reported with Escherichia coli, Staphylococcus sp., and Candida sp., the most common.46 It is diagnosed easily with ultrasound scan or CT scan. Treatment is with antibiotics targeted at the organisms obtained by percutaneous or open surgical drainage. Antibiotics should be continued for at least 2 to 3 weeks after successful drainage. Chronic granulomatous disease should be ruled out with a nitroblue tetrazolium test,47 because it has frequently been documented as a risk factor for the development of liver abscess. One should be aware of the possibility of pyogenic liver abscess as a complication associated with a ventriculoperitoneal (VP) shunt. This complication is rather unusual, with 7 cases in the literature.48 The mechanism is direct erosion of the liver by the VP shunt causing an intrahepatic cyst, which becomes secondarily infected. Treatment is externalization of the shunt, drainage of the cyst, and appropriate antibiotics.
Amebic liver abscess. As with hydatid disease, amebic liver abscess is quite rare in the United States. A report from Pakistan documented cases as young as 3 weeks of age, with 80% of cases occurring between 2 years and 10 years of age.49 Unlike adults, these children did not present with jaundice. Symptoms at the time of presentation included fever, right upper quadrant pain, hepatomegaly, and feeding difficulties. Laboratory evaluation found leukocytosis, an elevated sedimentation rate, and an elevation in the indirect hemagglutination titer. Although the risk of developing disseminated disease from entomoeba histolytica is quite low, localized disease in the form of amebic hepatic abscess is prevalent in endemic areas of the world such as Mexico, Western South America, South Asia, and West and Southeastern Africa.43 In about one half of patients, the abscess remains small and confined to the liver and is treated effectively with dehydroemetine and metronidazole. However, the other half will require percutaneous aspiration or surgical drainage because of persistent abdominal pain, persistent sepsis, an abscess cavity greater than 6 cm, or an abscess that has ruptured or is at risk for rupture.50
Forty-seven percent of cases reported by Porras-Ramirez et apo were complicated by rupture; 11 ruptured into the pleura, 3 into the peritoneum, and 1 into the pericardium. Findings at surgery include the classic "anchovy paste"
MEYERS AND SCAIFE
pus, and surgery should be directed at thorough lavage and drainage. Although death has been reported secondary to sepsis, a 96% survival rate is expected with appropriate treatment.
BILIARY TRACT MASSES
Choledochal Cyst
The incidence of choledochal cyst disease has not been well defined, and estimates range from 1 in 13,000 to 1 in 2,000,000.51.52 There is a female predominance (3:1) and they are more common in Asians, with a large majority of the reported cases originating from Japan.53.54 Although a choledochal cyst may present throughout life, they are most commonly discovered during childhood.
The classic presentation of a choledochal cyst is the triad of abdominal pain, jaundice, and an abdominal mass, although the complete triad proves to be the exception rather than the rule. Ultrasonography is increasingly responsible for detecting choledochal cysts in the fetus.55 Neonates more commonly present with asymptomatic jaundice or an abdominal mass. As children grow older the cyst may become painful or infected. In adults, an abdominal mass is appreciated rarely, and patients present more commonly with symptoms of cholangitis or pancreatitis. 56 Rarely a child may have bile peritonitis secondary to perforation of a choledochal cYSt.57
Vater brought the diagnosis of choledochal cyst to the attention of the medical community in 1723.58 AlonzoLej et aP9 introduced the modem medical community to 3 anatomic subtypes in 1959, and since then, 2 additional types have been described (Fig 6). Type I are fusiform dilations of the extrahepatic bile duct. Type II are saccular outpouchings of the main bile duct, mimicking an accessory gallbladder. Type III are referred to as choledochoceles and present as a wide-mouthed dilation of the
, Type II
Fig 6. Choledochal cyst is classified anatomically into 5 types. Reprinted with permission.74
BENIGN LIVER AND BILIARY TRACT MASSES
common duct at its confluence with the duodenum. Todani et aP8 added type IV in 1977 describing cystic dilations of both the intra- and extrahepatic bile ducts. Type V consists of lakes of multiple intrahepatic cysts with no extrahepatic component, and when Type V is associated with hepatic fibrosis it commonly is termed Caroli's disease. Type I and type IV are the most common. Type III almost never presents during childhood and may differ from the other types in its etiology and natural history.60 Caroli's disease associated with type V appears to be a congenital syndrome and often follows an autosomal recessive pattern of inheritance in association with various other anomalies such as polycystic kidney disease and renal tubular ectasia.61
Several theories have emerged to explain the development of the common forms of choledochal cysts. The female and East Asian predominance suggests a genetic influence. However, familial cases have not been described. Some believe that the cystic dilation is a result of embryological obstruction of the bile duct. In this theory, the fetal bile duct becomes temporarily plugged with protein, pressurizing the immature duct and resulting in expansion of the fragile fetal biliary tissue into a cyst. 62 Another popular theory postulates an anomalous, extrasphincteric confluence of the pancreatic duct and the common bile duct resulting in a long common channe1.63-65 The long common channel proximal to the sphincter of Oddi promotes reflux of activated pancreatic enzymes into the bile duct partially digesting the biliary epithelium allowing it to dilate gradually into a cyst. Although the long common channel theory is attractive, the abnormal long common channel anatomy has been shown by cholangiography in only 65% to 80% of patients, and it is likely that a combination of etiologic factors may be at work.51
Bile is meant to flow, not stagnate, and within a choledochal cyst a static pond of bile accumulates proteinaceous debris leading to bacterial overgrowth, cholangitis, or chronic inflammatory fibrosis. If left untreated, it may progress to biliary cirrhosis and over years to epithelial dysplasia and, finally, cholangiocarcinoma. The risk of cholangiocarcinoma in the first decade oflife is only 0.7%; however, this increases to about 14% at 20 years and is postulated to increase even further throughout life.66 It has been suggested that type III cysts, or choledochoceles, represent a form of duodenal duplication and therefore do not share the malignant potential of the other bile duct cysts.60
The newborn most often presents with a right upper quadrant cystic mass and an elevated conjugated bilirubin level. In many cases ultrasonography may be the only diagnostic test necessary. In other cases, in which more anatomic detail is needed, supportive studies may include a DIS IDA scan or a cholangiogram. Cholangio-
153
grams historically have been obtained by endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography. More recently, magnetic resonance cholangiopancreatography has been applied to children as young as 3 years of age in the literature and as young as 3 months at our institution (Fig 7).54.67,68 The anatomic detail provided by a preoperative cholangiogram might document an anomalous pancreaticobiliary junction and usually will rule out biliary atresia. If a preoperative cholangiogram has not been obtained, a cholangiogram should be performed at the time of operation.
Historically, choledochal cysts were treated with internal drainage by anastomosis of the cyst wall to the stomach, duodenum, or small bowel. Internal drainage procedures were soon recognized to have an unacceptably high morbidity rate including persistent biliary stasis with the development of sludge, stones, cholangitis, chronic inflammatory fibrosis, and anastomotic stricture. Reoperation rates were reported as high as 73%69 and, more ominously, the unresected cyst proved capable of malignant degeneration.
In the mid-1960s, surgeons began to favor complete cyst excision, and today cyst excision with Roux-en-Y hepaticojejunostomy is the procedure of choice. Distally, the common bile duct is transected just above the pancreatic duct, limiting the amount of residual biliary tissue at risk for malignancy. The cyst is dissected carefully off of the portal vein and hepatic arteries, a process sometimes complicated by dense pericystic in-
Fig 7. Preoperative magnetic resonance cholangiogram in a 3-month-old child with cholestatic jaundice and a type I choledochal cyst.
154
flammation and fibrosis. To safely deal with this problem, Lilly70 described intramural resection of the posterior cyst wall eventually leaving the outer portion of the posterior cyst wall in place to avoid dangerous dissection and bleeding in the region of the hepatic artery and portal vein. Usually, however, the entire cyst can be excised to the hepatic bifurcation and a mucosa-to-mucosa anastomosis created between the hepatic ducts and Roux-en-Y limb of jejunum. A liver biopsy should be performed to document the presence or absence of biliary cirrhosis.
Early surgical treatment of choledochal cysts is supported by the observation that children have lower postoperative morbidity rates than adults after cyst excision. Although it may seem that an older child would allow a technically easier operation because of the larger hepatic ducts, in fact, the chronic inflammation present in older patients makes the operation more difficult. Not only does cyst excision in children less than 5 years of
MEYERS AND SCAIFE
age seem to have the lowest incidence of anastomotic stricture, but equally importantly the intrahepatic biliary ductile dilatation of a type IV cyst may be reversible if the procedure is performed early.?! In children in whom the diagnosis was established prenatally, cyst excision has been performed as early as 4 days of life (c. Albanese, personal communication).
The results of choledochal cyst excision with hepaticojejunostomy reconstruction have been consistently excellent, but these children do require lifelong follow-up for the risk of anastomotic stricture and intrahepatic stones. Saing et al72 followed up with a series of 84 patients in Hong Kong who had anastomotic strictures up to 8 and 11 years postoperatively. There have been case reports of children in whom cholangiocarcinoma developed years after cyst excision; however, a compiled review of recent series, including long-term follow-up of over 400 children, showed no cases of cancer.66.7!-73
REFERENCES
1. VonSchweinitz D, Dammeier B, Gluer S: Mesenchymal hamartoma of the liver: New insight into histiogenesis. J Pediatr Surg 34:1269-1271, 1999
2. Cohen R, Myers N: Diagnosis and management of massive hepatic hemangiomas in childhood. J Pediatr Surg 21:6-9,1986
3. Samuel M, Spitz L: Infantile hepatic hemangioendothelioma: The role of surgery. J Pediatr Surg 30:1425-1429, 1995
5. Davenport M, Hansen L, Heaton N, et al: Hemangioendothelioma of the liver in infants. J Pediatr Surg 30:44-48, 1995
6. O'Neill J: Vascular disorders involving the liver, in WA Walker, PR Durise, JR Hamilton, et al (eds): Pediatric Gastrointestinal Disease. Philadelphia, PA, BC Becker, II: 1075-1080, 1991
7. Stanley P, Geer G, Miller J: Infantile hepatic hemangioma. Cancer 64:936-949,1989
8. Howard E: Surgery of Liver Disease in Children. Oxford, Butterworth-Heinemann, 1991
9. Woltering M, Robben S, Egeler R: Hepatiac hemeangioendothelioma of infancy: Treatment in interferon alfa. J Pediatr Gastroent Nutr 24:348-351,1997
10. Egawa H, Berquist W, Garcia-Kennedy R: Respiratory distress from benign liver tumors: A report of two unusual cases treated with hepatic transplantation. J Pediatr Gastroenterol Nutr 19:114-117, 1994
11. Enjolras 0, Wassef M, Mazoyer E, et al: Infants with KasabachMerritt syndrome do not have "true" hemangiomas. J Pediatr 130:631,
infancy and childhood. Arch Surg 125:1017-1021, 125 13. Warrell R, Kemping J: Treatment of severe coagulopathy in
Kasabach Merritt syndrome with amino-caproic acid and cryoprecipitate. N EnglJ Med 313:309-312,1985
14. Morad A, McClain K, Ogden A: The role of tranexamic acid in the treatment of giant hemangiomas in newborns. J Pediatr Hematol OncoI15:383-385, 1993
15. Teillac-Hamel D, DeProst Y, Bodemer C, et al: Serious childhood angiomas: Unsuccessful alfa interferon treatment report of four cases. Br J DermatoI129:473-476, 1993
ment of life threatening hemangiomas with vincristine. N Engl J Med 333:69,1985
17. Manglani M, Chari G, Shama U, et al: Successful treatment with syclophosphamide in a large hepatic hemangioendothelioma. Indian Pediatr 31 :875-877, 1994
18. AI-Rashid R: Cyclophosphamid and radiation therapy in the treatment of disseminated intravascular clotting. Cancer 27:364-368, 1971
19. O'Reilly M, Brem H, Folkman J: Treatment of murine hemangioendothelioma with angiogenesis inhibitor AGM-1470. J Pediatr Surg 30:325-330,1995
20. Dehner L, Ishak K: Vascular tumors of the liver in infants and children. Arch Pathol 92: 10 I-Ill, 1971
21. deLorimier A, Simpson E, Baum R, et al: Hepatic arterial ligation for hepatic hemangiomatosis. N Engl J Med 277:333-337, 1967
22. Hazebrook F, Tibboel D, Robben S, et al: Hepatic artery ligation for hepatic vascular tumors with arteriovenous and arterioportal venous shunts in the newborn: Successful management of two cases and review of the literature. J Pediatr Surg 30: 1127 -1130, 1995
23. Burrows P: Variations in the vascular supply to infantile hepatic hemangioendothelioma. Radiology 181:631-6332, 1991
24. Fellows K, Hoffer F, Markowitz R, et al: Multiple collaterals to infantile hepatiac hemangioendotheliomas and arteriovenous malformations: Effect on embolization. Radiology 181:813-818, 1991
25. Tegtmeire C, Smith J, Shaw A: Renal infaction: A complication of gelfoam embolization of an hemangioendothelioma of the liver. AIR 128:305-307, 1977
26. Achilleos 0, Buist L, Kelly D, et al: Unresectable hepatiac tumors in childhood and the role of liver transplantation. J Pediatr Surg 31:1563-1567,1965
27. Alt B, Hafez G, Trigg M: Angiosarcoma of the liver and spleen. Pediatr PathoI4:331, 1985
28. Awan S, Davenport M, Portmann B, et al: Angiosarcoma of the liver in children. J Pediatr Surg 31: 1729-1732, 1996
29. Kirchner S, Heller R, Kasselbert A, et al: Infantile hepatic hemangioendothelioma with subsequent malignant degeneration. Pediatr Radiol 11 :42-45, 1981
30. Barnhart D, Hirschi R, Garver K, et al: Conservative management of mesenchymal hamartoma of the liver. J Pediatr Surg 32: 1495-1498, 1997
31. Meinders A, Simons M, Heij H, et al: Mesenchymal hamartoma
BENIGN LIVER AND BILIARY TRACT MASSES
of the Ii ver: Failed management by marsupialization. J Pediatr Gastroenterol Nutr 26:353-355, 1998
32. Leary D, Weiskittel D, Blane C, et al: Follow-up imaging of benign pediatric liver tumors. Pediatr RadioI19:234-236, 1989
33. Reymond D, Plaschkes J, Ridolfi-Luthy A, et al: Focal nodular hyperplasia of the liver in children: Review of follow-up and outcome. J Pediatr Surg 30:1590-1593,1995
34. Tanasecu D, Hurwitz C, Waxman A: Scintigraphic findings mimicking focal nodular hyperplasia in a case of hepatoblastoma. Clin Nucl Med 16:236-238, 1991
35. Belghiti J, Paterson D, Panis y, et al: Resection of presumed benign liver tumors. Br J Surg 80:380-383, 1993
36. Muguti G, Tait N, Richardson A, et al: Hepatic focal nodular hyperplasia: A benign incidenteloma or a marker of serious hepatic disease? HPB Surg 5:171-180,1992
37. Pain J, Gimson A, Howard E: Focal nodular hyperplasia of the liver: Results of treatment and options in management. Gut 32:524-527, 1991
38. Soucy P, Rasuli P, Chou S, et al: Definitive treatment of focal nodular hyperplasia of the liver by ethanol emgolization. J Pediatr Surg 24:1095-1097,1989
39. Todani T, Tabuchi K, Watanabe Y, et al : True hepatic teratoma with high serum alpha fetoprotein in serum. J Pediatr Surg 12:591-592, 1977
40. Kononenko N: Benign neoformations of the liver in children. Klin Khir (Ukraine) 6:71-72,1994
41. Merine D, Nussbaum A, Sanders R: Solitary nonparacytic hepatic cyst causing abdominal distension and respiratory distress in a newborn. J Pediatr Surg 25:349-350, 1990
42. Athey P, Lauderman J, King V: Massive congenital solitary nonparacytic cyst of the liver in infancy. J Ultrasound Med 5:585-587, 1986
44. Yamada N, Shinzawa H, Ukaj K, et al: Treatment of symptomatic hepatic cysts by percutaneous instillation of minocycline hydrochloride. Dig Dis and Sci 39:2503-2509, 1994
45. Eyal I, Zveibil F, Stambler B: Anaphylactic shock due to rupture of a hepatic hydatid cyst into a pericystic blood vessel following blunt abdominal trauma. J Pediatr Surg 26:217-218, 1991
46. Doerr C, Demmler G, Garcia-Prats J, et al: Solitary pyogenic li ver abscess in neonates: Report of three cases and review of the literature. Pediatr ID J 13:64-69, 1994
47. Pineiro-Carrero V, Andres J: Morbidity and mortality in children with pyogenic liver abscess. Am J Dis Child 143:1424-1427, 1989
48. Huang L, Chen C, Ko S, et al : Pyogenic liver abscess complicating a ventriculoperitoneal shunt. Pediatr Surg Int 13:6-7, 1998
49. Nazir Z, Moazam F: Amebic liver abscess in children. Pediatr ID J 12:929-932, 1993
patients in the Japanese literature. Am J Surg 140:653-657, 1980 54. Yamataka A, Kuwatsuru R, Shima H, et al: Initial experience
with nonbreath-ho1d magnetic resonance cholangiopancreatography: A new noninvasive technique for the diagnosis of choledochal cyst in children. J Pediatr Surg 32: 1560-1562, 1997
155
55 . Lugo-Vicente H: Prenatally diagnosed choledochal cysts: Observation or early surgery? J Pediatr Surg 30: 1288-1290, 1995
56. Lipsett P, Pitt H, Colombani p, et al: Choledochal cyst disease: A changing pattern of presentation. Ann Surg 220:644-652, 1994
57. Moss L, Musemeche C: Successful management of ruptured choledochal cyst by primary cyst excision and biliary reconstruction. J Pediatr Surg 32:1490-1491, 1997
58. Todani T, Watanabe Y, Narusue M, et al: Congenital bile duct cysts: Classification, operative procedures, and review of 37 cases including cancer arising from choledochal cyst. Am J Surg 134:263-269, 1977
59. Alonzo-Lej F, Revor W, Pessagno D: Congenital choledochal cyst, with report of 2, and analysis of 94 cases. Surg Gynecol Obstet Abst Surg 108:1-30, 1959
60. Spier L, Crystal K, Kase D, et al: Choledochocele: Newer concepts of origin and diagnosis. Surgery 117:476-478, 1998
61. Pinto R, Lima J, Silveira Td, et al: Caroli's disease: Report of 10 cases in children and adolescents in Southern Brazil. J Pediatr Surg 33:1531-1535, 1998
62. Ando H, Kaneko K, Takahiko S, et al: Surgical removal of protein plugs complicating choledochal cysts: Primary repair after adequate opening of the pancreatic duct. J Pediatr Surg 33:1265-1267,
1998 63. Han S, Hwang E, Chung K, et al : Acquired choledochal cyst
64. Babbitt D: Congenital choledochal cysts: New etiologic concepts based on anomalous relationships of the CBD and pancreatic bulb. Am RadioI12:231-240,1969
65. Ono J, Sakoda K, Akita H: Surgical aspect of cystic dilatation of the bile duct. An anomalous junction of the panacreaticobiliary tract in adults. Ann Surg 195:203-208, 1982
66. Shian W, Wang Y, Chi C: Choledochal cysts: A nine-year review. Acta Paediatr 82:383-386, 1993
67. Sugiyama M, Baba M, Alomi T, et al : Diagnosis of anomalous pancreaticobiliary junction: Value of magnetic resonance cholangiopancreatography. Surgery 123:393-397, 1998
68. Matos C, Nicaise N, Deviere J, et al: Choledochal cysts: Comparison of findings at MR cholangiopancreatography and endoscopic retrograde cholangiopancreatography. Radiology 209:443-448, 1998
69. Stain S, Guthrie C, Yellin A, et al: Choledochal cyst in the adult. Ann Surg 222:128-133,1995
70. Lilly J: Total excision of choledochal cyst. Surg Gynecol Obstet 146:254-256, 1978
71 . Yamataka A, Ohshiro K, Okada Y, et al : Complications after cyst excision with hepaticoenterostomy for choledochal cysts and their surgical management in children versus adults. J Pediatr Surg 32: 1097-1102,1997
72. Saing H, Han H, Chan K, et al: Early and late results of excision of choledochal cysts. J Pediatr Surg 32: 1563-1566, 1997
73. Ohi R, Yaoita S, Kamiyama T, et al: Surgical treatment of congenital dilation of the bile duct with special reference to late complications after total excisional operation. J Pediatr Surg 25:613-617,1990
74. Taylor LA, Ross AJ: Abdominal mass, in Walker WA, Durie PR, Hamilton JR (eds): Pediatric Gastrointestinal Disease. Philadelphia, PA, Decker, 1991, pp 132-145