Hepatobiliary Surgery - part 4 pot

of different types of liver tumors is not well understood, but suffice it to say, farmore than 50% of all hepatic lesions are either hemangiomas or benign cystsTable 6.2.. Benign solid t

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Ascites

Ascites manifests as a result of:

1) impaired albumin and protein synthesis,

2) increased hydrostatic pressure in hepatic sinusoids and splanchniccapillaries,

3) over-production, transudation and low reabsorption of lymph into theperitoneal space,

4) renal sodium retention and,

5) impaired renal water excretion, partially due to increased concentrations

of antidiuretic hormone (ADH) Albumin infusion has no beneficial effecteven in the presence of severe hypoalbuminemia The treatment of ascitesunderscores bed rest and sodium restriction, to be followed by spirono-lactone if a spontaneous diuresis is not restored If life threatening com-plications such as cardiac or respiratory compromise occur, these patientsrequire hemodynamic monitoring Paracentesis should be attempted incase ascites persists

Renal Failure

Following hepatobiliary surgery, rapidly progressive renal failure may occur Thedifferential diagnosis includes acute tubular necrosis, prerenal azotemia andhepatorenal syndrome Hepatorenal syndrome is the development of otherwiseunexplained renal failure with urine sodium < 10 meq/l, hyperosmolar urine, olig-uria (< 400 ml/24hrs), fractional excretion of sodium (FeNa+) < 1, and urine creati-nine to plasma creatinine ratio > 30:1 in patients with advanced liver disease Thepathophysiology of hepatorenal syndrome is based on the pooling of blood in thesplanchnic bed and the resultant decrease in plasma volume The kidney perceives adecreased glomerular filtration rate and causes a vasoconstriction that shunts bloodaway from the renal cortex There is no specific treatment for hepatorenal syndrome.Dopamine (1-2.5 mcg/kg/min) may help maintain urine output Although sponta-neous recovery has been reported, mortality is very high These patients, generallycirrhotic, may benefit from liver transplant

Pulmonary Care

Hepatopulmonary syndrome is defined by liver disease, increased alveolar rial gradients, and evidence of reduced intrapulmonary vascular resistance In cir-rhotic patients, an increased synthesis of nitric oxide has been demonstrated thatmay lead to arteriovenous shunts in the lungs The resulting hypoxemia requiresoxygen supplementation and may progress to respiratory failure

arte-Glucose Metabolism

We might expect the postoperative patient to be prone to hypoglycemia ary to diminished glycogen reserves, increased insulin levels, and impaired gluco-neogenesis Yet, dangerous hypoglycemia is rare Routine (5%) dextrose solutionsshould be infused while monitoring glucose serum levels

Coagulation

Hypocoagulability derives from thrombocytopenia or reduced synthesis of min K dependent factors; cholestasis also decreases vitamin K absorption and hepaticstores Improvements in coagulation may be achieved with vitamin K 10 mg/day.Another cause of bleeding is fibrinogen deficiency; this situation may benefit fromfresh frozen plasma transfusion Decreased serum concentration of protein S, protein

vita-C and antithrombin III result in hypercoagulable states that can lead to disseminatedintravascular coagulation (DIC)

Sepsis

Abdominal sepsis is the most common cause of mortality after hepatic resection.Preoperative biliary manipulation, infected bile, biliary stones, ascites, and bloodloss may all predispose to abdominal sepsis Other sources of sepsis include therespiratory and urinary systems Wound infection and a central line catheter shouldalso be considered as possible sources of infection

Gastrointestinal Bleeding

The incidence of GI bleeding is 5%, with a mortality reaching 50% The ing site can usually be identified by endoscopy Treatment includes transfusions,antacids and H2 blockers All postoperative hepatobiliary patients should be treatedprophylactically About 30% of cirrhotic patients have esophageal varices The emer-gent treatment should combine blood product transfusion to correct the coagulopathy,gastric endoscopy with variceal banding or sclerotherapy, and possibly, octreotide25-100 mcg/min to control bleeding Life saving procedures may include compres-sion of the varices via a Sengstaken-Blakemore tube As rebleeding occurs in 50% ofpatients, a definitive surgical treatment should be pursued

bleed-Encephalopathy

Hepatic encephalopathy may be precipitated by GI bleeding, infection, drugs,diet or dehydration It manifests as a sudden change in a patient’s mental status orthe onset of asterixis The precise pathogenesis remains unknown The historicalpostulate has been the accumulation of endogenous ammonia Other etiologies havebeen suggested, including changes in the blood-brain barrier permeability, abnor-mal neurotransmitter balance, altered cerebral metabolism, impairment of neuronal

Na+-K+ ATPase activity, and increased endogenous benzodiazepines Standard therapy

is devised to reduce levels of ammonia and other potentially toxic metabolites.Flumazenil has been administered with some improvement; however, proteinrestriction and lactulose administration are still practiced

8 Goldman L, Caldera DL, Nussbaum SR et al Multifactorial index of cardiac risk

in noncardiac surgical procedures New Engl J Med 1997; 297:845-50

9 Habib N, Zografos G, Dalla Serra G et al Liver resection with total vascular sion for malignant tumors Br J Surg 1994; 81:1181-4

exclu-10 Hannoun L, Borie D, Delva E et al Liver resection with normothermic ischemiaexceeding 1 h Br J Surg 1993; 80:1161-5

11 Krowka MJ, Cortese DA Hepatopulmonary syndrome Current concepts in nostic and therapeutic considerations Chest 1994; 105:1528-1537

diag-12 Melendez JA, Arslan V, Fischer M et al Peri-operative outcome of major hepaticresections under low central venous pressure anesthesia—blood loss, blood trans-fusion and the risk of postoperative renal dysfunction J Am Coll Surg 1998;178:620-25

of different types of liver tumors is not well understood, but suffice it to say, farmore than 50% of all hepatic lesions are either hemangiomas or benign cysts(Table 6.2) Focal nodular hyperplasia (FNH), metastatic tumors from an undiag-nosed primary cancer site, hepatic adenomas, focal fatty infiltration, and hepatocel-lular carcinomas are the next most common diagnoses in descending order offrequency Additional benign tumors have also been described; however, most if notall, are sufficiently rare as to be labeled medical “fascinomas.”

The infrequency of symptoms associated with most benign and many malignantliver tumors complicates the process of establishing a firm diagnosis when hepatictumors are identified incidentally Despite significant advances in a variety of diag-nostic imaging modalities, the appearance of these lesions is often not clear-cut andbiopsy or resection is indicated as diagnosis is mandatory Indeed, the most com-mon indication for surgical management of “benign” liver tumors is the inability toexclude a possible malignancy Table 6.3 reviews an MSKCC experience in treating

152 patients with “presumably” benign liver tumors between 1995 and 1998 four percent of patients underwent operation, in part or solely to exclude a potentialmalignant diagnosis Less common indications for surgical management included:

Fifty-1 Relief of debilitating symptoms

2 To reduce the risk of rupture (a rare event), or potential for malignanttransformation

3 To treat life-threatening complications of rupture or hemorrhage

Evaluation

The most “appropriate” work-up for an asymptomatic patient with a newly tified solid liver tumor is unclear and it is difficult to recommend precise algo-rithms In general, the workup should be individualized based upon patient age,sex, personal medical and social history, as well as the stage and suspected histology

iden-of the tumor in question Physical examination is typically unrevealing unless thetumor is expansive, and in this setting, pain or abdominal discomfort is normally

Hepatobiliary Surgery, edited by Ronald S Chamberlain and Leslie H Blumgart.

©2003 Landes Bioscience

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Table 6.1 Benign solid tumors of liver

Cell of origin Tumor

Epithelial

Hepatocellular Focal nodular hyperplasia (FNH)

Hepatocellular adenoma (HA)Regenerative noduleCholangiocellular Biliary adenoma

InfantileMesothelial Solitary fibrous tumor

Other names: benign mesothelioma or fibroma

MyelolipomaAngiomyelipomaMiscellaneous

Pseudotumors Focal fatty infiltration

Adrenal neoplasmInflammatory pseudotumorChronic abscess

Table 6.2 Incidental solid liver tumors: Diagnostic frequency for various histologies 3

(e.g., abscess, adrenal tumor)

as alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), and CA-19-9, arerarely elevated in benign liver tumors and should suggest the likelihood of an under-lying malignancy.

In most instances, radiologic studies can provide a precise diagnosis based on thecharacteristic appearance of the tumor; however multiple studies yielding comple-mentary data are required (Table 6.4) In Chapter 4, Decorato and Schwartz pro-vide a detailed discussion of the advantages and disadvantages of various hepatobiliaryimaging techniques

In brief, ultrasonography is the most common initial study since it can tively differentiate between cystic and solid neoplasms Contrast-enhanced com-puted tomography (CT) with delayed imaging, a so-called “triple phase CT scan”,can provide precise diagnostic information while also determining the number, size,and location of these tumor(s) Magnetic resonance imaging (MRI) is the mostuseful imaging modality with regard to differentiating between “indeterminate” and

Table 6.4 The radiographic appearance of common benign liver tumors

Increased vascular flow Contrast: Irregular peripheral Hyperdense on T2 Blood pooling of

Delayed central filling scan shows similar

findings to contrast CT

Nonspecific

and Kupffer cellsNonspecific

* Tc 99 RBC scan—Technetium–labeled red blood cell scan; HIDA—Hepatic aminodiacetic acid scan; Tc 99 SC—Technetium sulfur colloidscan

malignant tumors Although many liver tumors have a characteristic angiographicappearance, the information it provides can currently be obtained by noninvasiveimaging modalities in most situations Laparoscopy can be used as a diagnostic tool

in some patients by allowing the surgeon to obtain a reliable tissue biopsy usingminimally invasive techniques In rare cases, the surgical management may be car-ried out laparoscopically as well

Benign Liver Tumors

Hemangioma

Hemangiomas are the most common benign solid tumors of the liverand occur

in two variants, capillary hemangiomas and cavernous hemangiomas Capillary mangiomas are the most common, but are clinically insignificant They are typicallysmall, hypervascular lesions (< 2 cm) encountered at the time of laparotomy andmay be the source of considerable diagnostic uncertainty Establishing the diagnosisand excluding a malignancy is all that is required

he-Cavernous hemangiomas are clinically more relevant because of the potential forcomplications and associated symptoms Cavernous hemangiomas have been reported

in up to 7% of patients at autopsy and occur more commonly in adults than inchildren The etiology of cavernous hemangiomas remains uncertain; however, theymost likely represent benign congenital hamartomas Although the incidence ofcavernous hemangioma has been reported as 1.3-6 times higher in women than inmen, the higher incidence of hemangioma in females is likely a reflection of referralbias rather than a true difference in incidence Sex hormones have not been linkedetiologically to the development of hemangiomas Cavernous hemangiomas mayvary in size from less than 1 cm, to “giant hemangiomas” which may be greater than30-40 cm The size of a hemangioma correlates with symptoms, as it is usually largepedunculated tumors that are encountered at surgery.These tumors are often sharplydemarcated from surrounding liver tissue, have a spongy appearance, and may bepartly necrotic or fibrotic Occasionally, infarct of the hemangioma may cause it to

be completely fibrosed and, in rare cases, calcified When this occurs, these tumorscan be extremely difficult to distinguish from other benign and malignant tumors.The acute nature of some symptoms related to hemangioma may, in fact, not berelated to increase in size, but rather thrombosis and infarct that lead to focal fibrosisand obliteration of vascular channels in part or whole

Clinical Presentation

Symptoms from hemangiomas of the liver are generally attributed to rapidexpansion in the size of the lesion or to thrombosis and infarct that lead to stretch-ing or inflammation of Glisson’s capsule Occasionally, a large hemangioma maypresent as a nontender mass in the right upper quadrant, but more often the physi-cal examination reveals only vague upper abdominal tenderness with no mass Itmay be possible to auscultate a bruit over a large hemangioma, but this is not pathog-nomonic Rarely, a hemangioma may rupture resulting in a hemoperitoneum andshock requiring emergency surgical care

Severe thrombocytopenia and the development of a consumptive coagulopathyhave been associated with cavernous hemangiomas of the liver Although the

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Kasabach–Merritt syndrome was initially used to describe thrombocytopenia andafibrinogenemia associated with hemangiomas of the skin and spleen in infants, thisterm is often used to describe similar coagulopathies in children and adults (rare)with hemangiomas of the liver

Pathology

Historically, hemangiomas are typically well demarcated and distinct from thesurrounding hepatic parenchyma The sharp interface between hemangioma andnormal liver parenchyma permits surgical enucleation in most cases However, notall hemangiomas are enucleable, and the histologic features of the tumor-liver inter-face define how easily a parenchymal-sparing technique may be utilized (Figs 6.1A,B).Four variants of the interface between the hemangioma and liver have beendescribed A “fibrolamellar interface”, characterized by a capsule-like fibrous ring ofvariable thickness, is most common The normal hepatic parenchyma is often atro-phic, and a plane between the hemangioma and the normal liver tissue can be welldefined A second variant, the “interdigiting” pattern, is marked by the lack of afibrous lamella surrounding the hemangioma which is replaced by an ill-definedplane between normal liver tissue and the vascular channels of the hemangioma.These tumors can be quite hazardous to remove without a formal resection Twoadditional histologic variants have been identified, including a “compression” inter-face, in which the periphery of the tumor is well demarcated in the absence of afibrous lamella and an “irregular or spongy” variant which appears to intercalateinto the surrounding liver parenchyma making complete excision hazardous andunnecessary Note, despite the invasive appearance of this histologic variant,hemangiomas are not premalignant lesions and do not invade or metastasize.The diagnosis of a cavernous hemangioma is generally clear-cut on both macro-scopic and microscopic examination In rare instances, an atypical hemangiomamay be confused for other liver conditions including peliosis hepatis, hemorrhagictelangiectasia (Osler–Rendu–Weber), hemangioendothelioma and other malignantvascular tumors As a rule, percutaneous biopsy of a suspected hemangioma should

be avoided as this may result in unnecessary and uncontrollable hemorrhage tomatic lesions, large lesions, or indeterminate lesions should be managed surgically

Symp-Radiologic Evaluation

The initial radiologic evaluation of a suspected hemangioma is often dictated bythe clinical presentation In most instances, hemangiomas are discovered inciden-tally on a study performed for other reasons and the degree of diagnostic certaintyprovided by this study may obviate the need for additional imaging If a patientpresents with dull, nonspecific right upper quadrant complaints, ultrasonography istypically the first study performed On ultrasound (US), a hemangioma appears as ahyperechoic mass well demarcated from the surrounding liver The number andlocation of the lesion(s) can be precisely defined on B-mode ultrasound, and theaddition of duplex ultrasonography can provide information with regard to peripheralblood flow and central pooling of venous blood On a noncontrast CT scan,hemangiomas appear as a hypodense mass which exhibits a characteristic pattern ofirregular peripheral nodular enhancement after initial injection of contrast material.Delayed CT scanning, several minutes after contrast injection, demonstrates central

6Fig 6.1A, B Cavernous hemangioma A, The gross appearance of a cavernoushemangioma on cut section is shown B, A sponge-like architecture with venouslakes is characteristic of these lesions

filling of the hypoechoic lesion which persists for some time and is felt to be nostic of hemangioma (Figs 6.2 and 6.3) MRI is the most sensitive and specificmeans to detect hepatic hemangiomas The T-2 weighted image demonstrates acharacteristic hyperechoic pattern The administration of gadolinium results in similarperipheral enhancement with delayed central filling as was described with CT scan-ning Although a technetium-99 labeled red blood cell scintigram (Tc99 RBC scan)has historically been considered the “gold standard” diagnostic evaluation forhemangiomas (Fig 6.4) Technologic advances in axial imaging diagnostic tech-niques, such as MRI and CT, combined with the additional staging informationthese studies provide, have led to less reliance upon RBC scintigrams Selective hepaticangiography demonstrates a characteristic neovascularity to these lesions oftendescribed as “corkscrewing.” Rapid filling of the central portion of hemangiomasfrom the neovascular periphery yields a “cottonwool” appearance to these lesions.Despite this characteristic finding, the diagnostic yield of less invasive studies

diag-is such that arteriography diag-is unnecessary in the evaluation of most patients As

a rule, biopsies, by whatever means, are unnecessary unless a histologic diagnosiswill alter planned therapy

Treatment

Observation is the most appropriate treatment for nearly all asymptomatichemangiomas To date, there are no documented instances in which a hemangiomahas spontaneously ruptured while being observed Trastek et al followed 36 patientswith a cavernous hemangioma for up to 15 years (mean 5.5).Among this groupwere two infants who were treated with steroids; one child responded One adultpatient was also treated with external beam radiation and showed marked reduction

in the size of the lesion The other 33 patients were observed with no other ment There were no spontaneous ruptures and, most importantly, no changes in

Fig 6.2 Cavernous hemangioma An MRI with gadolinium is shown below (A) The precontrast study demonstrates multiple

hypodense lesions within Segments 4, and 6 of the liver (B) One minute after gadolinium administration early peripheral

enhancement of the lesion is seen (C) Three minutes after gadolinium is provided, contrast material is seen to fill the lesion from

the periphery (D) Five minutes after gadolinium administration the center of the hemangioma retains the contrast material

symptoms over the course of follow up In four patients the size of the hemangiomaincreased and in three patients the size decreased Foster followed 44 patients withhemangiomas for a period ranging from 2 months to 12 years There were no reports

of rupture, death, or change in clinical symptoms in their series.In the absence ofclinical symptoms, the careful observation of all asymptomatic hemangiomas is therecommendation of most experienced liver surgeons

Hepatic resection for a hepatic hemangioma should be approached no differentlythan surgery for other tumors of the liver The surgeon should have extensive knowl-edge of the anatomy and vascular supply of the liver The extent of the liver resectionrequired for removal is directly related to the anatomic location of the lesion and itsproximity to major blood vessels In patients with symptomatic hemangiomas, someform of treatment is often necessary Patients with disabling pain, pressure symptoms,

or acute symptoms related to the hemangioma should undergo surgical resection Thelocation of the hemangioma is critical to planning surgical resection Large centrallesions that abut the portal vein, hepatic outflow tract, or inferior vena cava over a longdistance may pose a prohibitive surgical risk even in experienced hands In these situa-tions, alternative therapeutic modalities should be considered Unlike malignant le-sions, the resection of a hemangioma does not require the surgeon to remove a margin

of normal tissue with the tumor As such, the most appropriate treatment for mosthemangiomas is enucleation In some cases, however, it may be safer and more rational

to perform formal lobectomy or extended resection

The effectiveness of hepatic artery ligation as a treatment for hemangioma hasbeen described anecdotally; however, its benefit is likely transient Hepatic arterialFig 6.3 Sagittal view of a large cavernous hemangioma as visualized on T1 andT2 weighted images

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ligation or embolization does play a pivotal role in temporarily controlling hemorrhagefrom a hemangioma to permit transfer of a patient to an institution where experi-enced surgical help is available Radiotherapy has been used successfully to treatsymptoms and induce involution of hemangiomas in some situations, but the rarity

of this occurrence makes the results difficult to interpret On the whole, data

justi-Fig 6.4 Cavernous hemangioma A techntium-99 red blood cell scan is shown.The heart (top center) and spleen are bright on radionucleotide scanning The liverretains some contrast but is significantly less intense than the spleen and heart Acavernous hemangioma is seen arising from the left lobe of the liver

fying the use of radiotherapy in hemangiomas is scant However, if surgical therapy

is not possible, radiotherapy seems a reasonable alternative approach to the ment of symptomatic hemangiomas

treat-Special Issues: Hemangiomas in Children

Hepatic hemangiomas of infancy and childhood are different lesions from thoseseen in adults These lesions are typically large, and if so, their symptoms are rarelysubtle The vast venous lakes within these lesions can function as tremendous siphonsfor a large amount of the total cardiac output leading to severe congestive heartfailure and death In children who develop high output cardiac failure, the initialtreatment usually consists of digitalis, diuretics, oxygen, corticosteroids and hepaticartery ligation Radiation treatment is often employed and may result in improvedcardiac performance In contrast to adults, the risk of spontaneous rupture of hepatichemangiomas that occur in infancy is great Similarly, Kasabach-Merritt syndrome

in association with life-threatening thrombocytopenia and afibrinogenemia, occursmore frequently and may result in death in a high proportion of affected infants Asopposed to the conservative approach to treatment of hemangiomas recommendedfor adults, hemangiomas of infancy and early childhood frequently require life-sav-ing surgical treatment and should be referred immediately to an experienced pediat-ric tertiary center

Focal Nodular Hyperplasia

Focal nodular hyperplasia (FNH) is the second most common benign tumor ofthe liver.Up to 90% of both FNH and hepatic adenomas occur in women of men-strual age FNH tumors are almost always asymptomatic lesions discoveredincidentally during a radiological work-up for other reasons In rare instances, theymay present as a palpable abdominal mass on physical examination Although a raretumor prior to the 1960s, the incidence of FNH has increased markedly in the lastthree decades Notably, the increased incidence in FNH has occurred concurrentwith the introduction and widespread use of ultrasound and CT scanning in clinicalpractice, as well as the development and acceptance of the oral estrogen contraceptivepill (OCP) Whether the increased reporting of FNH tumors represents a true change

in incidence or merely reflects the proficiency of scanning in identifying these lesions

is unclear, but the latter is probably the case Klatskin and Vana et al reported rate series of patients with FNH tumors in which they suggested an etiologic rela-tionship between OCP usage and the development of both FNH and hepaticadenoma However, numerous reports of FNH prior to the 1960s, and its frequentoccurrence in individuals who have never used OCP, cast significant doubt on theexistence of any etiologic association between OCP use and FNH The potentialeffect of pregnancy on FNH (as well as hepatic adenomas) remains poorly under-stood Scott et al have reported a single case of a female who had used OCPs for 11years prior to developing an FNH After stopping the OCP, the tumor regressed; itsubsequently increased in size during a later pregnancy Although their report isprovocative, data linking pregnancy and changes in the size or symptoms of anFNH tumor are scant As opposed to hepatic adenoma, there are no reports ofspontaneous rupture of FNH during pregnancy Importantly, although it may beimpossible (without surgical resection) to distinguish an FNH from a well differen-

a “central scar”; however, the core of these lesions is neither necrotic nor fibrotic.Rather, the central portion of an FNH is composed of a round cell infiltrate andprominent thick-walled blood vessels divided by fibrous septae.

Clinical Presentation

Most FNH tumors are solitary, although 20% may be multiple when identified.FNH often occurs in association with other benign hepatic tumors such as heman-giomas.These lesions are small (< 3 m), and intraoperatively they appear as pale red

to brown, firm nodules with prominent blood vessels on the surface Larger lesionscan be particularly difficult to distinguish from well-differentiated hepatocellularcarcinoma (HCC) Nearly all FNH tumors are asymptomatic, and unlike otherbenign liver tumors, spontaneous rupture is extremely rare In our experience inmanaging 33 patients with FNH tumors, there were no spontaneous ruptures, andthe most common indication for surgical resection was the inability to exclude apotential hepatic malignancy

Fig 6.5 Focal nodular hyperplasia (FNH) A, On cross-section this FNH appears asyellow-tan lesion that is sharply demarcated from the normal liver in the absence of atrue capsule The gross and microscopic architecture of these lesions, B, suggests aregenerative rather than a neoplastic process Bile duct hyperplasia and Kuppfer cellsare prominent