Portal Vein Embolization BeforeExtended Hepatectomy in a ToddlerWith Mesenchymal HamartomaSylvain Terraz, MDa,b, Maxime Ronot, MD, PhDa,c, Romain Breguet, MDa,b,c, Mehrak Anooshiravani, MDa,Laura Rubbia-Brandt, MDb,d, Christoph D. Becker, MDa,b, Barbara E. Wildhaber, MDe,f

abstractPortal vein embolization is widely used to induce hypertrophy of the futureliver remnant before extended hepatectomy, decreasing the risk ofpostoperative liver failure. However, this percutaneous procedure has notbeen previously reported in a young child. The present report describes thecase of a 14-month-old patient with a large multifocal mesenchymalhamartoma of the entire right liver, successfully resected after induction offuture liver remnant hypertrophy by portal vein embolization.

Mesenchymal hamartoma of the liver(MHL) is the second most commonbenign hepatic tumor in childhood andis typically discovered as a large mixedsolid-multicystic mass in patientsyounger than 3 years.1 Even thoughMHL is considered to be a congenitalmalformation, cytogenetic data haverecently demonstrated translocationsand aneuploidy, suggesting that theselesions are neoplastic. Interestingly,similar anomalies have also beendescribed in undifferentiatedembryonal sarcoma of the liver.2

Therefore, although MHL has beenclassically considered to present nopotential for malignant transformation,several common pathologic,immunohistochemical, and cytogeneticfeatures suggest a possible relationbetween these 2 entities and justifyradical treatment.3

The preferred treatment option forMHL is primary complete excision byhepatic resection. Large or multifocallesions may be sometimesunresectable, because insufficientfuture liver remnant (FLR) volumecould lead to postoperative liverfailure. Portal vein embolization (PVE)is a well-established percutaneous

procedure, which stimulates growth ofthe FLR.4 Various techniques have beendescribed, using different embolicagents. Overall, the technical andclinical success of PVE is very high inexperienced hands.5 However,published data and accumulatedexperience come exclusively from adultstudies.

The present report describes the caseof a 14-month-old patient with largehepatic mesenchymal hamartomasuccessfully resected after FLRhypertrophy induced by percutaneousPVE.

PATIENT PRESENTATION

A 14-month-old girl was referred toour hepatobiliary pediatric center forthe management of a growing cysticmass in the liver. Imaging workup afterbirth (34 weeks of amenorrhea) hadrevealed multiple cystic lesions in theright liver, suggesting mesenchymalhamartoma.

At admission, the patient wasasymptomatic, fed normally, and hadregular bowel habits. Her weight was6.9 kg (22 SD) and her height was68 cm (22 SD), whereas her vital signs

Departments of aRadiology, dPathology, and ePediatrics,bHepato-Pancreato-Biliary Centre, fSwiss Centre for LiverDiseases in Children, University Hospitals of Geneva,Geneva, Switzerland; and cDepartment of Radiology,University Hospitals of Beaujon, Paris, France

Dr Terraz performed the portal vein embolization, playeda central role in diagnosis and management of thepatient before the hepatic resection, conceptualized anddesigned the study, coordinated and supervised datacollection, drafted the initial manuscript, and revised themanuscript; Dr Ronot drafted the initial manuscriptand revised the manuscript; Dr Breguet played a centralrole in diagnosis and management of the patient beforethe hepatic resection and revised the manuscript;Dr Anooshiravani played a central role in diagnosisbefore the hepatic resection, coordinated datacollection, and revised the manuscript; Dr Rubbia-Brandtperformed the histopathological study of thehepatectomy specimen and revised the manuscript;Dr Becker revised the manuscript; Dr Wildhaberperformed the hepatic resection, managed the patientfrom the hospital admission to the present, and revisedthe manuscript; and all authors approved the finalmanuscript as submitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2015-0179

DOI: 10.1542/peds.2015-0179

Accepted for publication Jun 8, 2015

Address correspondence to Sylvain Terraz, MD,Department of Radiology, University Hospitals ofGeneva, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva14, Switzerland. E-mail: sylvain.terraz@hcuge.ch

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,1098-4275).

Copyright © 2015 by the American Academy ofPediatrics

FINANCIAL DISCLOSURE: The authors have indicatedthey have no financial relationships relevant to thisarticle to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors haveindicated they have no potential conflicts of interestto disclose.

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were normal. Physical examinationrevealed an abdominal distensionwith a painless, firm, and smoothliver mass, palpable 7 cm below theright costal margin. Laboratorystudies revealed a prothrombin time-international normalized ratio of 1.15and normal liver function tests,including albumin (38 g/L [normal:35–48 g/L]) and total bilirubin(8 mmol/L [normal: 7–25 mmol/L]).The serum a-fetoprotein was slightlyelevated (28 mg/L [normal:,15 mg/L]),and b-human chorionic gonadotropin(,1 U/L) was within normal range.Ultrasonography and MRI revealed 2predominant complex cystic masseswith multiple small cystic satellitesthroughout the parenchyma of theright hepatic lobe (Fig 1). The firstmass was located in segments 4b, 5,and 6, measuring 8.9 3 7.8 3 6.9 cm3,whereas the second one was insegments 4a and 8, measuring 6.6 36.0 3 6.1 cm3. A contrast-enhancedcomputed tomography (CT) wasperformed to assess the hepaticvessels. The volume of the FLR,including segments 1, 2, and 3,measured 104 cm3. Thiscorresponded to 1.6% ofbody weight and 21.5% of the livervolume, excluding the volume of alltumors.

Clinical presentation, imaging, andevolution were sufficiently suggestiveof MHL, to avoid biopsy of the tumor.During a multidisciplinary meeting,right hepatectomy extended to

segment 4 was considered as the besttreatment option, because of tumorprogression, mild failure to thrive,and potential for malignanttransformation. Preoperativeembolization of the right portal veinwas considered necessary to reducethe probability of postoperative liverfailure. The risk of a small-for-sizeliver was weighted with the risk ofcomplications related to PVE, whichcould potentially render a resectablepatient unresectable.

PVE was performed under generalanesthesia (2 hours and 10 minutes)and after intravenous infusion of50 mg/kg ceftriaxone (Rocephin,Roche Pharma, Switzerland). Afterlocal anesthesia with 3 mL 1%lidocaine (Rapidocain, Sintetica,Switzerland), the portal branch ofsegment 7 was punctured with a 22-G

needle under ultrasound guidance. A4-F introducer sheath was placed atthe splenomesenteric confluence, and200 mg heparin was injected. Thebasal portal pressure was 9 mmHg,whereas the central venous pressurewas 6 mmHg. Digital subtractedportography was performed to assessportal anatomy (Fig 2). After selectivecatheterization with a 4-F Simmons 1catheter (Radiofocus, Terumo,Belgium), the portal branches ofsegments 5, 6, 7, and 8 weresuccessively embolized, under pulsedfluoroscopic guidance. Segment 4 wasnot embolized, because the 3 feedingbranches were considered too small.A total of 2.8 mL of ethylene-vinylalcohol copolymer (Onyx 18, ev3,France) was injected downstreamthrough a 2.4-F microcatheter (Rebar 18,ev3), previously flushed with 1.5 mLdimethyl sulfoxide solution. The finalportal pressure was 8 mmHg, and thecontrol portography confirmeda complete occlusion of the right portalvein (Fig 2). The puncture track wasembolized with Onyx (ev3). A total of30 mL of iohexol 270 mg I/mLcontrast media (Visipaque, GEHealthcare, Switzerland) wasinjected, and the total delivered dosewas 11 Gy·cm2.

No complication was observed duringthe 4-day hospital stay. Dopplerultrasound study revealed a normalhepatopetal flow in the portal veinand left portal branch. During

FIGURE 1Mesenchymal hamartoma of the right hepatic lobe. A, Ultrasonography reveals multiloculated cystswith anechoic cavities, sometimes containing a few debris, and regular thin septae. B, CoronalT2-weighted MRI reveals the hyperintense signal of cystic portions. C, Coronal gadolinium-enhancedT1-weighted image reveals a mild enhancement of the peripheral stroma and internal septationswith regard to surrounding parenchyma. The dashed lines depict the borders of the FLR.

FIGURE 2PVE of the right liver. A, Portogram after insertion of a 4-Fr catheter demonstrates the modalanatomy of the portal vein and a compression of the right branch by the cystic mass. B, Radio-graphic image after embolization reveals a complete filling of the right portal vein by Onyx (ev3). C,Postprocedural portogram confirms the occlusion of the right portal vein 1.5 cm beyond portalbifurcation and the patency of all segmental branches on the left. LPV, left portal vein; PV, portal vein;RPV, right portal vein.

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12 days, the patient receivedsubcutaneous enoxaparin (Clexane,Sanofi-Aventis, Switzerland) 23 500 Uper day for thromboprophylaxis. After

35 days, FLR volume grew to 216 cm3

corresponding to 3.0% of body weightand 42.6% of the liver volume,excluding the volume of all tumors. Therelative volume gain of FLR was 108%,and the kinetic growth rate was 4.22%per week, which was above thethreshold of 2% per week (Fig 3).6 Thenonembolized segment 4 had a relativevolume gain of 8% and a kineticgrowth rate of 0.02% per week.

Right hepatectomy extended tosegment 4 was performed. Afterdissection and ligation of the righthepatic duct and right hepatic artery,the parenchymal transection wasdone by clamp crushing along thedescending left hepatic vein. Pringlemaneuver and caval exclusion werenecessary to control a small tear ofthis vessel. The integrity of the left

bile duct and bile confluence werecontrolled at the end of the operation.The 12-day recovery of the patientwas uneventful. The total bilirubin(16 mg/L [normal: 7–25 mmol/L])and V factor activity (100% [normal:.70%]) stayed within normal ranges.The right lobectomy specimenweighted 533 g. On cut section, therewere multiloculated cysts containingserous fluid and separated bytrabecular walls with some hyalinizedor myxoid nodules (Fig 4).Microscopically, the cysts were linedby biliary-type epitheliumexpressing cytokeratins 7 and 19and were surrounded bya mesenchymal stroma, confirmingthe diagnosis of MHL. No malignantcells were observed, and themargins of resection in the liverparenchyma were at least 5 mm.The portal vein branches wereoccluded by embolization material.The venous wall was partiallydestroyed and was surrounded bygigantocellular reaction of theforeign body type.

Four years postoperatively, the childwas thriving and doing well. YearlyDoppler-US studies revealeda normal liver parenchyma andnormal flow of the hepatic vessels,without bile duct dilatation. Biologicalparameters were normal.

DISCUSSION

MHL is the second most frequentbenign tumor of the liver in children,developing in most cases beforethe age of 3, with a boy to girl ratio of2:1.7. The preferred treatmentoption for MHL is primary completeexcision with hepatic lobectomy ornonanatomic resection, because ofthe potential risk of malignanttransformation. Other alternatives areincomplete resection,marsupialization, and decompressiondrainage, although all of these carrya risk of tumor recurrence.3 Livertransplantation may becomenecessary if the above options cannotbe performed.8

FIGURE 3CT-based volumetry. A and B, Axial and coronal contrast-enhanced CT images before PVE: the volumeof the FLR (dashed lines) is 104 cm3. C and D, Axial and coronal contrast-enhanced CT images (sameplanes than in A and B) 5 weeks after PVE: the volume of the FLR is 216 cm3. The left portal vein(black arrow) and their branches are still patent. Both coronal images reveal a compression of thedescending left hepatic vein by the medial border of the cystic mass (white arrow).

FIGURE 4On cut section of the right lobectomy specimen,there are multiloculated cysts (C) containingserous fluid and separated by trabecular wallswith some hyalinized or myxoid nodules. Seg-mental branches of the right portal vein areoccluded by blackish embolization material(arrows).

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When performed, hepatic resectionshould preserve enough functionalliver parenchyma, leading to minimalpostoperative morbidity. However, incase of large or multifocal lesions, theFLR volume may be too small andpatients may be deemed initiallyunresectable. Before resection of livermalignancies, PVE has beenextensively used in adults forpromoting preoperative hypertrophyof the FLR, increasing the resectionrate and limiting the risk ofpostoperative liver failure.5 PVE leadsto apoptotic necrosis of the embolizedliver and triggers hepatocellularregeneration of the FLR, by means ofgrowth factor production andredirection of portal flow towardthe FLR.

Numerous technical variants havebeen described, but in all cases, thefinal end point is the completeobstruction of the targeted branchesand redistribution of flow to the FLRbranches only. PVE procedure ismainly performed witha transhepatic approach, the portalbranches being generallycatheterized with 5-F or morediameter materials. Various embolicagents have been used for PVE,including gelatin sponge, glue, beads,alcohol, coils, and plugs.9 Themixture of n-butyl cyanoacrylate andiodized oil seems to have a greatereffect on hypertrophy.5 However, useof the latter is more difficult andrequires more experience of theradiologist, because delivery must bevery precise to prevent embolizationof nontargeted branches. Overall,both reported technical and clinicalsuccess rates of PVE are very high,ranging from 95% to 100%, withcomplication rates lower than 1%.4

Nevertheless, all these results comefrom adult populations.

No consensus exists on the minimalvolume of functional liverparenchyma that should be left inplace after an extendedhepatectomy.10,11 In the present case,preoperative PVE was decided to stay

on the safe side. Consequently, similarthreshold as those applied to adultswere considered (ie, a FRL volume atleast 25% to 30% of the liver volumeor at least 2% of body weight).Overall, hypertrophy of the FLR wasconsidered satisfactory, whereas nocomplication occurred.

Reported cases of portal veinocclusion before hepatic resection inpediatric population are veryscarce.12 To our knowledge, there iscurrently no published case of PVEperformed in an infant. The mainreasons are technical limitationsrelated to the small body size of thispopulation and the absence oftailored materials to pediatricpatients in interventional radiology.The first challenge is to geta percutaneous access to smallcaliber portal vessels. Thepuncture should be performed witha thin 22-G needle under ultrasoundguidance, whereas portal branchesshould be catheterized with thesmallest materials possible, such asmicrocatheters. The second issue isto prevent any embolization ofnontarget portal branches, whichcould be achieved with the use of anembolic agent, such as ethylene vinylalcohol copolymer (Onyx; ev3). Thisproduct is delivered with veryaccurate control, because it isa liquid nonadhesive to cathetermaterials and it has an optimalradiopacity for visualization underfluoroscopy. This reduces the risk ofunintentional reflux and preventsembolization of nontargetedbranches.13,14 Its use as an embolicagent in PVE procedures needsfurther validation on larger clinicalseries.15

CONCLUSIONS

PVE is feasible in very youngchildren when an extended liverresection is indicated. However,there is a need to developappropriate materials for pediatricpatients, to warrant the safety profileof this procedure.

ABBREVIATIONS

CT: computed tomographyFLR: future liver remnantMHL: mesenchymal hamartoma of

the liverPVE: portal vein embolization

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DOI: 10.1542/peds.2015-0179 originally published online September 21, 2015; 2015;136;e1055Pediatrics 

Rubbia-Brandt, Christoph D. Becker and Barbara E. WildhaberSylvain Terraz, Maxime Ronot, Romain Breguet, Mehrak Anooshiravani, Laura

Mesenchymal HamartomaPortal Vein Embolization Before Extended Hepatectomy in a Toddler With

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Mesenchymal HamartomaPortal Vein Embolization Before Extended Hepatectomy in a Toddler With

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