Benign Liver and Biliary Tract Masses in Infants and Toddlers By Rebecka L. Meyers and Eric R. Scaife

Salt Lake City, Utah

There is a remarkable diversity of conditions encompassed by benign liver masses in infants and toddlers. The most common benign hepatic tumor in this age group is infantile hepatic hemangioendothelioma. Other commonly seen be­nign tumors are mesenchymal hamartoma and focal nodular hyperplasia. Hepatic adenoma is almost exclusively a dis­ease of older children; primary hepatic teratoma is exceed­ingly rare. There are several distinguishing characteristics of these benign tumors on radiographic evaluation; however, imaging techniques such as ultrasound scan, computed tomography, and angiography are not always reliable in differentiating benign from malignant tumors. The differen­tial diagnosis of benign hepatic tumors includes nonneoplas­tic cystic masses including biliary and simple hepatic cysts, hematoma, parasitic cysts, and pyogenic and amebic liver abscess. Choledochal cyst presents with a classic triad of abdominal pain, cholestatic jaundice, and a palpable abdomi­nal mass. They are classified anatomically into 5 subtypes with the most popular types being type I and type IV. Treatment is with complete cyst excision with hepaticojeju­nostomy reconstruction. Copyright © 2000 by W.B. Saunders Company

,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.

Copyright © 2000 by WE. Saunders Company 1055-8586/00/0903-0006$10.00/0 doi: JO.J053/spsu.2000. 7562

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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

1999' 1986' 1995' 19955

Hepatomegaly (%) 71 83 Skin/visceral heman-

giomas (%) 57 33 62 55 Congestive heart failure

(%) 50 75 68 82 Kassabach-Merritt syn-

drome or consumptive

coagulopathy (%) 29 42 75 Anemia (%) 21 75 Feeding difficulties/vom-

iting (%) 21 50 Jaundice (%) 42 33

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

149

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.

152

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

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